arbete och hälsa | vetenskaplig skriftserie
isbn 978-91-85971-02-2 issn 0346-7821
nr 2008;42:2
Basis for skin notation. Part 1.Dermal penetration data for substances
on the Swedish OEL listGunnar Johanson, Matias Rauma
Arbete och Hälsa
Arbete och Hälsa (Work and Health) is a scien-tific report series published by Occupational and Environmental Medicine, Sahlgrenska Academy, Göteborg University. The series publishes scientific original work, review articles, criteria documents and dissertations. All articles are peer-reviewed.Arbete och Hälsa has a broad target group and welcomes articles in different areas. Instructions and templates for manuscript editing are available at http://www.amm/se/aohSummaries in Swedish and English as well as the complete originial text as from 1997 are also available online.
Arbete och HälsaEditor-in-chief: Kjell TorénCo-editors: Maria Albin, Ewa Wigaeus Tornqvist, Marianne Törner, Wijnand Eduard, Lotta Dellve and Roger PerssonManaging editor: Gunilla RydénEditorial assistant: Anna-Lena Dahlgren
© Göteborg University & authors 2008
Arbete och Hälsa, Göteborg University, S-405 30 Göteborg, Sweden
ISBN 978-91-85971-02-2ISSN 0346–7821 http://www.amm.se/aohPrinted at Elanders Gotab, Stockholm
Editorial Board: Tor Aasen, BergenBerit Bakke, OsloLars Barregård, GöteborgJens Peter Bonde, ÅrhusJörgen Eklund, LinköpingMats Eklöf, GöteborgMats Hagberg, GöteborgKari Heldal, OsloKristina Jakobsson, LundMalin Josephson, UppsalaBengt Järvholm, UmeåAnette Kærgaard, HerningAnn Kryger, KöpenhamnSvend Erik Mathiassen, GävleSigurd Mikkelsen, GlostrupGunnar D. Nielsen, KöpenhamnCatarina Nordander, LundKarin Ringsberg, GöteborgTorben Sigsgaard, ÅrhusStaffan Skerfving, LundKristin Svendsen, TrondheimGerd Sällsten, GöteborgAllan Toomingas, StockholmEwa Wikström, GöteborgEva Vingård, Uppsala
Preface
Skin notations are used by many organizations and in many countries including Sweden. Thus, substances that may easily be absorbed percutaneously are marked with an “H” in the Swedish provisions on occupational exposure limits (OELs) (AFS 2005). This procedure started already with the first list of OELs introduced in 1974. OELs are given for 368 substances or substance groups in the present provisions (AFS 2005). Out of these, 101 substances/groups (27%) have a skin notation.
No formal or quantitative criteria have been developed in Sweden. The intent was originally that the skin notation would give a qualitative indication of possible dermal absorption of the chemical at work. In other words, the attempt was mainly to evaluate the ability of penetration through intact “healthy” skin, i.e. the intrinsic properties of the chemical relative to skin.
In an international perspective the criteria for assigning a skin notation vary widely but are generally qualitative rather than quantitative in nature. During the last few years, however, focus has shifted towards more quantitative assessments, either by expressing the intrinsic properties of the chemical in numerical terms, such as dermal absorption rate (flux) at defined conditions or by expressing the systemic exposure (absorbed dose), i.e. a combination of the intrinsic properties and the exposure conditions (exposed skin area, exposure duration etc).
In view of the large and increasing numbers of H-labeled substances, there is a need for more formal criteria. There is also a risk that the warning effect of the label is diminished if too many substances are labeled.
In view of these concerns, the Swedish Work Environment Authority (SWEA) has initiated a project with the aim to develop new criteria and procedures for skin notation. As input for the project, SWEA requested the Division of Work Environment Toxicology at the Institute for Environmental Medicine, Karolinska Institutet to produce two reports on dermal absorption in relation to skin notations and OELs.
The aim of the first report, presented herein, is to describe methods used to measure dermal absorption and to compile and evaluate published quantitative data on dermal absorption focusing on substances listed in the ordinance on Swedish OELs (AFS 2005). The second report will address different approaches to skin notation.
Literature searches, compilations and writing of the report were carried out by MSc Matias Rauma and professor Gunnar Johanson at the Division of Work Environment Toxicology. The final literature search was performed in January 2007. The cited papers were to a large extent supplied by the library at the Swedish National Institute for Working Life.
The major sources used were:
- Medline,
- the EDETOX database on the web (www.ncl.ac.uk/edetox/),
- consensus reports and criteria documents (and publications cited therein) published by the Swedish Criteria Group for Occupational Standards at the National Institute for Working Life,
- criteria documents (and publications cited therein) published by the Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals (NEG),
- the documentation (and publications cited therein) published by the Chemical Substance - Threshold Limit Values (CS-TLV) Committee of the American Conference of Industrial Governmental Hygienists (ACGIH), and
- secondary sources, i.e. references given in the above sources. We wish to express our gratitude to associate professor Anders Boman (Occupational and Environmental Dermatology, Karolinska Institutet, Stockholm), professor Magnus Lindberg (Dermatology Unit, Örebro University Hospital), associate professor Pierre-Olivier Droz (Institute of Occupational Health, Lausanne), Dr. Karin Sørig Hougaard (National Research Centre for the Working Environment, Copenhagen) and associate professor Margareta Warholm (SWEA, Solna) for valuable comments on the manuscript. We are also grateful to MSc Tina Isaksson for compilation of some of the data. The investigation was financially supported by the Swedish Work Environment Authority.
Stockholm July 2007
Gunnar Johanson Matias Rauma
Contents
1. Introduction 1 2. Anatomy of the skin 2 3. Skin as a diffusion barrier 4 4. Fick’s law of diffusion 6 5. Factors affecting dermal penetration 7 Concentration 7 Properties of the chemical 8 Properties of the skin 8 Summary 11 6. Assessment of dermal penetration 12 In vivo tests 12 In vitro tests 13 Structure-activity based methods 15 7. Dermal penetration data for substances on the Swedish OEL list 17 Approach 17 Conclusions 19 8. Summary 31 9. References 32 Appendices A. Tabular data for individual substances A1-A181 B. References to individual substances Octanol:water partition coefficients B1 Other physical properties B1-B2 Scientific bases B2 Other physical properties B3 - B16
1
1. Introduction
The aim of this report is to review the published data on dermal penetration of workplace chemicals, as a basis for assignment of skin notations.
Dermal exposure is a major route of systemic exposure at work. Along with reductions in OELs and occupational exposure via air, the dermal route has become even more important.
Data on dermal absorption are input for so called skin notations. Skin notations are used as warning signals for chemicals that may easily be taken up via the skin, thereby causing - or increasing the risk of - systemic toxicity (see e.g. AFS 2005, SCOEL 1999). The decision to assign a skin notation is largely based on the ability of the chemical to penetrate skin. Sometimes experience from work practice is also considered, so that chemicals for which health effects have been seen at work after (presumed) dermal exposure are also assigned with a skin notation. Direct effects on the skin, such as irritation, corrosion and sensitization, are usually not considered.
The criteria for skin notations and their practical application are beyond the scope of the present report but will be described and discussed in a second report. Nevertheless, it should be mentioned that the relations between the presence of a chemical in the work environment and dermal dose, as well as that between dermal dose and systemic dose is very complex and highly variable. Thus, the first relationship is affected by a number of factors, such as the volatility and other properties of the chemical, how the chemical is used, the work process, the individual’s behavior and work practices, type of clothing and protective equipment, and so on. The influence of some of these factors may be highly variable and is often difficult to predict. The second relationship (and the focus of this report) depends on the properties of the chemical and the skin and is, at least in principle, more easily described and measured.
2
2. Anatomy of the skin
The skin provides a barrier between the human body and its environment. The major function is to prevent loss of water and heat to the environment. It also protects the body from mechanical, biological and chemical hazards.
The skin is the largest organ of the human body (15% of total adult body weight). The skin consists of three layers (from inside to outside): hypodermis, dermis, epidermis (figure 1). The hypodermis (subcutis) is the deepest part of the skin and contains mainly adipose tissue. The subcutaneous layer is important for protection from mechanical injuries, energy provision, thermoregulation and insulation.
Hair
Nerve
Capillaries
Epidermis
Dermis
Hypodermis
Sebaceousgland
Muscle
Sweatgland
VenuleArteriole
Hair
Nerve
Capillaries
Epidermis
Dermis
Hypodermis
Sebaceousgland
Muscle
Sweatgland
VenuleArteriole
Figure 1. Drawing of the skin (adapted from http://www.nku.edu/~dempseyd/SKIN.htm). The dermis contains connective tissue and provides elasticity, flexibility, strength and stability to the skin. The main cells are fibroblasts (synthesizing the collagen fibres), dermal dendrocytes and mast cells (belonging to the immune system). The dermis is in close contact with the abundant ridges and grooves of the epidermis. The ridges are enlarging the surface area between dermis and epidermis, allowing for a better adhesion and a more efficient exchange of nutrients and waste.
Both the dermis and hypodermis are richly innervated and vascularized. The skin appendages (hair, nails, sweat glands, sebaceous glands) originate in these parts of the skin, mostly in the dermis.
The epidermal layer consists mainly of keratinocytes (90-95%), Langerhan’s cells (skin immune response), melanocytes (skin color and UV protection) and Merkel cells (slow-adapting mechanoreceptors for touch). The keratinocytes are constantly being replaced. The shape of the cells changes during their migration from the innermost part of the epidermis towards the surface of the skin (figure 2).
3
Based on the appearance in the microscope, the epidermis is subdivided in five different layers (from inside to outside): stratum basale, stratum spinosum, stratum granulosum, stratum lucidum and stratum corneum (figure 3).
Cells flatten as they migrate toward the surface
Stratum basale with dividing stem cells
Stratum corneum, with dead keratinized cells at surface
Cells flatten as they migrate toward the surface
Stratum basale with dividing stem cells
Stratum corneum, with dead keratinized cells at surface
Figure 2. The maintenance of the epidermis (adapted from http://www.mhhe.com/biosci/ap /histology_mh/stratepi.html).
The stratum corneum consists of several layers of completely keratinized dead cells without a nucleus (corneocytes). The cells are stacked, leaving little space between them. Keratin is a tough, insoluble protein that is also the chief structural constituent of hair, nails, and hooves. Thus, the stratum corneum mainly consists of keratin and highly resistant to diffusion of water and other molecules (figure 3).
Thick skin has many layers of corneocytes cemented together. Thin skin has fewer layers of living and dead cells but the same overall structure.
Stratum corneum, 10-30 cell layers
Stratum lucidum, 1 cell layerStratum granulosum, 2-3 cell layers
Stratum spinosum, 2-7 cell layers
Basal membrane
Stratum basale, 1-2 cell layers
Dermis
Stratum corneum, 10-30 cell layers
Stratum lucidum, 1 cell layerStratum granulosum, 2-3 cell layers
Stratum spinosum, 2-7 cell layers
Basal membrane
Stratum basale, 1-2 cell layers
Dermis
Figure 3. The five layers of the epidermis (adapted from Forslind & Lindberg 2004).
4
3. Skin as a diffusion barrier
A major function of the skin is to prevent loss of water to the environment. The humidity in the ambient air is often low and without an effective barrier the organism would rapidly loose large amounts of water. This would preclude life on land.
The major diffusion barrier is the stratum corneum. However, this skin layer is not entirely impermeable. Water as well as other small molecules diffuse more or less slowly through the skin. Water is very important to maintain the flexibility of the skin. Dry skin becomes rough and flaky and completely dried stratum corneum is reduced to a very brittle, thin sheet. Water is also important for thermoregulation, as the heat used to evaporate the water excreted via sweat glands lowers the temperature of the skin.
In principle, there are three possible diffusion pathways through the skin. The major route, especially for fat soluble, nonpolar molecules, is likely to be the intercellular lipid pathway. Due to the brick and mortar structure (figure 4), the “true” diffusion path is very much longer than the thickness of the stratum corneum. The diffusional pathlength has been estimated to be as long as 500 µm for stratum corneum of 20 µm thickness (Hadgraft 2004). Further, since impermeable corneocytes make up most of the skin and intercellular lipids constitute only a small part, the area accessible for diffusion is very small compared to the total skin area. Another factor that complicates diffusion is that the intercellular spaces contain structured lipids and a diffusing molecule has to cross a variety of lipophilic and hydrophilic domains.
Corneocytes
Intercellular lipids
Diffusion pathway
Corneocytes
Intercellular lipids
Diffusion pathway
Figure 4. Brick and mortar structure of the stratum corneum showing dense, keratinized corneocytes, intercellular lipid layers and one of the diffusion pathways.
5
The second possibility is that of transcellular permeation, i.e. that the molecules diffuse through the corneocytes.
A third route of absorption is through the appendages (hair follicles). In most cases, this route is insignificant as the area of appendages is very small compared to the total skin area. However, in the initial phase of the absorption and for very slowly permeating chemicals, this route may be of importance.
The structure of the skin and the stratum corneum contrasts that of the lungs and the respiratory airways. Thus, whereas the skin is designed to resist diffusion (and loss of water) the lungs are built to facilitate diffusion (uptake of oxygen and release of carbon dioxide). In the skin, this is manifested by:
- a relatively small surface area (approximately 2 m2 in a human adult), and
- a stratum corneum consisting of several densely packed layers of cells filled with highly resistant protein (keratin), resulting in high resistance long diffusion pathways (figures 2-4).
In contrast, the alveolae in the lungs have:
- a relatively large surface area (approximately 80 m2 in a human adult), and
- only two thin cell layers (alveolar epithelium and capillary endothelium), resulting in a low resistance, short diffusion distance from ambient air to blood (figure 5).
Figure 5. Transmission electron micrograph of the lung showing as: the alveolar airspace and c: the capillary lumen, separated by two thin cell layers with a total thickness of about 1 µm (taken from http://www.cf.ac.uk/phrmy/PCB/PageLungAlveolarepithelium.htm).
6
4. Fick’s law of diffusion
The driving force for dermal absorption of practically all chemicals is diffusion, i.e. the spontaneous movement of molecules. The flux of molecules from the outer side to the inner side of a barrier (for example the skin) is proportional to the number of molecules at the outer side and the resistance of the barrier. Likewise, the flux from the inner to the outer side is proportional to the number of molecules at the inner side and the resistance of the barrier. The net flux is the difference between the two fluxes and can be described mathematically as: P = Kp x ( A1 – A2 ) (1)
Equation 1 is known as Fick’s first law of diffusion. The parameter P is the net flux (number of molecules per time unit) and Kp is the permeability coefficient (resistance to diffusion). A1 and A2 the number of freely moving molecules outside and inside the barrier, respectively. Chemical activity is a measure of how different molecules in a non-ideal gas or solution interact with each other. For very dilute gases and solutions, molecular interactions are negligible and activity is also proportional to concentration. For gases, activity is proportional to partial pressure. A can thus be substituted by thermodynamic activity, partial pressure or, for dilute solutions, concentration. Such substitution will only alter the value of Kp, as these parameters are directly proportional to the number of molecules.
In most cases with dermal exposure to chemicals, the concentration at the inner side (in the body) is negligible compared to the outer side (skin surface) and may be approximated to zero. In this case, the flux depends only on the Kp and the concentration at the outer skin surface.
Obviously, the value of, Kp depends on the properties of both the skin and the chemical. Further, the numerical value and units of Kp depend on the units chosen for P and A. It is common to express Kp in cm/h, from which follows that suitable units for P are µmol/h/cm2 or mg/h/cm2. A is then expressed as µmol/cm3 (mM) or mg/cm3.
7
5. Factors affecting dermal penetration
In this report the term dermal penetration is used for the amount of chemical that passes through the skin and reaches the systemic circulation. A synonymous term is percutaneous absorption. These two terms are different from dermal absorption which denotes the amount of chemical that has entered the skin from the outer environment. The dermally absorbed chemical may stay in the skin, diffuse back to the outer environment, be metabolized or pass on to the inner environment (penetration). If excess chemical is applied on the skin for a sufficiently long time (so that a steady-state is reached) and if metabolism in the skin is negligible, penetration equals absorption.
From equation 1 in Chapter 4 follows that the unit penetration rate (flux) across the skin is directly proportional to:
- the concentration (activity, partial pressure) of the chemical at the skin surface (provided that the inner concentration is negligible) of the chemical, and
- the permeability of the skin (expressed by Kp).
The permeability depends on the properties of the chemical as well as the properties of the skin. The total penetration is proportional to (in addition to concentration and permeability):
- the exposed area (since Kp is expressed per area unit), and
- the duration of exposure.
5.1 Concentration
Other factors held constant, the flux is always proportional to chemical activity (figure 6, left), the slope is determined by the permeability coefficient (Kp). At high concentrations, e.g. when the skin is exposed to neat chemical, the molecules begin to interact so that the concentration is no longer proportional to the number of freely moving “particles”. Hence, the relation between flux and concentration becomes sublinear at high concentrations (figure 6, right). In conclusion, dermal absorption rates cannot easily be translated from one concentration to the other and experimentally determined values for Kp are concentration-dependent.
8
Conc. gradient
Der
mal
abs
. rat
e
Activity gradient (A1-A2)
Der
mal
abs
. rat
e
Figure 6. According to Fick’s first law of diffusion (see also Chapter 4), the dermal absorption rate is proportional to the activity gradient (A1-A2) over the skin. The rate is further proportional to the concentration gradient for diluted, but not concentrated, chemicals.
5.2 Properties of the chemical
Molecular size and solubility are the major physical properties that determine the diffusion coefficient. Small molecules diffuse more easily through the skin than big molecules. Further, substances such as many organic solvents that easily dissolve in nonpolar (lipids) as well as polar (water) media, diffuse more easily through the skin. Conversely, substances that are either ionized, highly lipophobic or highly hydrophobic exhibit low skin permeability.
5.3 Properties of the skin
A thicker keratin layer of the stratum corneum will make the diffusion path length longer and, hence, the permeability lower (=higher resistance). Roughly, the Kp is inversely proportional to the thickness of the stratum corneum. The number of cell layers as well as the thickness varies widely between different parts of the body. At the extreme ends are the genitals with as little as 6 and the heels with as much as 86 cell layers (table 1).
9
Table 1. Number of stratum corneum cell layers at different locations (from Ya-Xian, Suetake et al. 1999).
Location Number of cell layers (mean±sd)
Genital 6±2 Ear 7±2 Eyelid 8±2 Face 9±2 Lip 10 Scalp 12±2 Trunk 13±4 Extremities 15±4 Dorsum of hand 25±11 Dorsum of foot 30±6 Palm 50±10 Sole 55±14 Heel 86±36
The palms and soles, and especially the heels, have the thickest stratum corneum of as much as 1.5 mm, whereas that of the eyelids is as little as 0.05 mm. Densely furred species such as rats and mice have a much thinner skin than hairless species, such as humans and pigs. This difference includes the stratum corneum, as well as the epidermis (figure 7).
0
10
20
30
40
50
60
Cat
Cow Dog
Hor
se
Hum
an
Mon
key
Mou
se Pig
Rab
bit
Rat
Thic
knes
s (µ
m)
0
1
2
3
4
5
No.
of e
pide
rmal
cel
l laye
rs
Stratum corneum thicknessEpidermal thicknessEpidermal cell layers
Figure 7. Thickness of stratum corneum and epidermis. The figure is based on measurements of the skin over the shoulder (animal data from Monteiro-Riviere, Bristol et al. 1990, human data from Sandby-Möller, Poulsen et al. 2003).
10
The stratum corneum is optimized to provide minimum permeability (maximum resistance) at “normal” conditions. Various conditions and factors may affect the structure of the stratum corneum, thereby increasing permeability. These conditions include skin damage caused, e.g. by disease, detergents or ultraviolet radiation, as well as temperature and humidity.
There is little data on the influence of skin lesions on dermal penetration in exposed human populations. A recent case report on four workers with different skin status (healthy, erythematous and burned skin and dishydrotic eczema) envolved in exposed to ortho-toluidine during rubber vulcanisation suggests that the absorption of o-toluidine is 1.5- to 2-fold higher through damaged than through healthy skin (Korinth, Weiss et al. 2006). In a follow-up study with 51 workers occupationally exposed to aniline and o-toluidine, the hemoglobin-aromatic amine-adduct levels in workers with erythema were on average 73% higher than in workers with healthy skin (Korinth, Weiss et al. 2007).
Similar results have been obtained in animal experiments. The permeation of hydrocortisone was studied in vitro using skin from a monkey diagnosed as having eczematous dermatitis. The permeation was approximately twice as high in eczematous skin, as compared to unaffected skin from the same individual. The absorption of another anti-inflammatory steroid, triamcinolone acetonide, was also enhanced through the eczematous skin (Bronaugh, Weingarten et al. 1986).
Soap washing and dermal exposure to solvents causes extraction of stratum corneum lipids, and increased permeability. Thus, for example, experimental 3-h treatment of human skin in vitro with 0.1% or 0.3% sodium lauryl sulphate caused an impaired barrier function as indicated by up to three-fold increases in the penetration of tritiated water and various pesticides (Nielsen 2005). In hairless mice topically treated with acetone, the permeation of hydrophilic substances (sucrose, caffeine, hydrocortisone) increased through stratum corneum as well as whole skin in vitro. In contrast, the permeation of lipophilic substances (propegesterone, estradiol) increased through stratum corneum but not whole skin (Tsai, Sheu et al. 2001).
Considering ultraviolet radiation, the permeation methanol and ethanol nearly tripled through UVA-treated as compared to untreated human human epidermis. In contrast, the permeation of higher, more lipophilic primary alcohols (propanol, butanol, hexanol, and heptanol) was not significantly altered (McAuliffe & Blank 1991).
Increased skin temperature increases the kinetic energy, .i.e. the movements, of the molecules, thereby affecting the lipid structure in the stratum corneum. Also, skin humidity increases as a result of sweating. All these factors may increase the dermal penetration. Johanson and Boman (1991) demonstrated that the percutaneous absorption of 2-butoxyethanol vapour was slightly increased at 33ºC ambient air temperature and 71% relative humidity, as compared to 23ºC and 29% relative humidity. In vitro experiments with freshly prepared human skin showed that the permeability coefficient of benzene in water nearly doubled at 50ºC and decreased slightly at 15ºC, as compared to 26ºC (Nakai, Chu et al. 1997).
11
5.4 Summary
The permeability of a given piece of skin for a specific substance is reflected by the permeability coefficient. The permeability coefficient is mainly determined by the:
- properties of the chemical,
- properties of the vehicles (if present),
- thickness of the keratin layer in stratum corneum,
- condition of the skin, e.g. skin damage.
The thickness of stratum corneum varies widely between species and between different parts of the body. The condition of the skin varies with, e.g. the temperature and the degree of hydration of the skin.
12
6. Assessment of dermal penetration
In principle, studies of dermal absorption measures the diffusion of the test substance from a test preparation placed on the skin through the stratum corneum and into the skin. The methods can be divided into two categories: in vivo and in vitro.
6.1 In vivo tests
The rat is the most commonly used species for in vivo testing. However, a wide variety of other species and strains are being used, including (hairless) rats, humans, monkeys, dogs, pigs, mini pigs, (hairless) guinea pigs, and (hairless) mice.
In vivo studies in laboratory animals are preferably conducted as described by OECD (2004). In brief, the exposed area, ideally about 10 cm2 in rats, should be defined by a device that is attached to the skin surface. The test sample is applied to the surface of skin and allowed to remain for a specified period of time, relevant to human exposure. At the end of the exposure period excess sample is removed. During the study, animals are housed individually in metabolism cages from which excreta are collected. If measurable volatile metabolites (such as radiolabelled carbon dioxide) are expected, exhaled breath is also collected. At the end of the study, the removable remains of the dose are washed from the skin surface. The animals are then killed and the amount of parent chemical and metabolites in skin, carcass and excreta is determined. These data allow for an estimate of the total recovery of the test substance.
Test chemical remaining in the skin after wash-off will disappear over time by four pathways, by diffusion into the environment, by desquamation (shedding of the outer layers of the skin), by ingestion when the animal grooms itself, and by diffusion into the systemic circulation. To avoid overestimation of the systemically absorbed dose, measures have to be taken to prevent grooming of the site of application, and to prevent desquamated skin from falling into the urine and fecal collection systems.
The skin absorption of the test substance can be expressed as the percentage of dose absorbed per unit time or, preferably, as an average absorption rate per unit area of skin, e.g. μg/cm2/h.
By necessity, in vivo studies in humans must use a different experimental protocol, as the total recovery cannot be directly determined. The dermal dose is thus determined indirectly, by comparison to a known dose, for instance the net uptake by inhalation exposure (Dinhaled), where the bioavailability is known to be 100%. The dermal uptake, or rather, the systemic dose via the dermal route (Ddermal), may then be calculated for example by comparing the urinary recoveries of the chemical or its metabolite(s) (R). Alternatively, since the area under of the
13
concentration-time curve (AUC) in e.g. plasma or blood is proportional to dose, dermal uptake may be obtained by comparing the two AUCs. Thus:
inhaled
dermalinhaleddermal
inhaled
inhaled
dermal
dermal
RRD
DRD
RD ⋅
=⇒= (2)
or
inhaled
dermalinhaleddermal
inhaled
inhaled
dermal
dermal
AUCAUCD
DAUC
DAUC
D ⋅=⇒= (3)
For examples of this approach, see e.g. studies by Johanson and colleagues (Johanson & Boman 1991, Johanson, Boman et al. 1988, Johanson & Fernström 1986, 1988). A different approach to measure dermal absorption is that of microdialysis. A small probe equipped with a semi permeable hollow fiber is inserted superficially into the dermis, parallel to the skin surface. A physiological solution is slowly pumped through the fiber, allowing the solutes of interest to equilibrate with the surrounding extracellular space. For overviews, see e.g. Anderson (2006), Schnetz & Fartasch (2001) or Stahl, Bouwet et al. (2002).
Human pharmacokinetic microdialysis has only been carried out for two decades and there is limited data, mainly on pharmaceutical drugs, on dermal absorption using this technique. There are several difficulties in obtaining quantitative measures, maybe the major one being that concentration and not flux is measured. The concentration will depend not only on influx via stratum corneum but also on outflux via the blood stream. Other related difficulties reside in determining the position of the probe (since the concentration decreases with distance from the skin surface) and in defining the exposed skin area.
6.2 In vitro tests
Skin from many mammalian species, including humans, as well as non-mammalian species, e.g. snakes, can be used. The receptor compartment of a so-called static diffusion cell or Franz cell (figure 8) is filled with a suitable fluid. An excised skin sample is mounted on top of the cell so that the inner side is in close contact with the receptor medium. The test sample is applied in the donor compartment so that it covers the skin surface. For more detailed descriptions, see e.g. the OECD guideline (2004).
14
Donor compartment containing chemical or preparation to be studied
Skin piece is mounted here
Sampling site
Magnetic stirrer.
Heated water compartment, connected to a thermostatted water bath
Receptor compartment containing buffered saline or other suitable medium
Donor compartment containing chemical or preparation to be studied
Skin piece is mounted here
Sampling site
Magnetic stirrer.
Heated water compartment, connected to a thermostatted water bath
Receptor compartment containing buffered saline or other suitable medium
Figure 8. Static diffusion cell for dermal absorption studies in vitro.
As in the in vivo studies, the exposure duration should be relevant for human situations. At the end of exposure, excess sample is removed from the skin by appropriate cleansing.
The receptor fluid is sampled at defined time points throughout the experiment and the concentration of the parent chemical as well as any significant metabolite(s) is determined by a suitable method, e.g. gas chromatography, to ascertain the mass of the test substance (including any significant metabolite) that has passed through the skin. At the end of the study, the dislodgeable dose, the amount contained in the skin and the amount in the receptor fluid are determined. These data are necessary to calculate the total skin absorption, and allow for an estimate of the total recovery of the test substance.
When calculating the dermal penetration rate, the concentration in the receptor fluid translated to absolute mass by multiplying with the volume. The absolute mass rate, i.e. the increase in mass with time during steady-state condition, is obtained as the slope of the linear part of the mass versus time curve (figure 9). Finally, the unit penetration rate or flux is obtained by dividing the mass rate by the exposed skin area.
15
0
5
10
15
20
25
0 10 20 30
Time
Mas
s
C
B
A
Figure 9. Mass of chemical versus time in the receptor medium static diffusion cell. A: Lag time of skin penetration, B: Steady-state, slope of increase equals penetration rate, C: Penetration rate decreases (curve levels off), either due to back diffusion (limited solubility in receptor medium) or depletion at donor site.
It has to be assured that the test chemical is sufficiently soluble in the receptor medium. For highly water soluble chemicals this is no problem and physiological saline or isotonic buffer are sufficient as solvents. However, if this kind of receptor medium is used with non-polar, poorly soluble chemicals such as hexane, an equilibrium will soon be established between the donor and the receptor compartment (phase C in figure 9). Thus, the net movement of chemical approaches zero and the flux and permeability coefficient may be seriously underestimated.
The static diffusion cells may be replaced by a flow-through, so-called Bronaugh cell. Advantages of the latter type of cell are that saturation of the receptor medium can be avoided and that the system can easily be automated by connecting to an autosampler.
6.3 Structure-activity based methods
Several regression equations have been developed that relates permeability coefficients to easily obtained chemical properties, such as the octanol:water partition coefficient (Kow) and molecular weight (MW). The Kow is thought to represent the solubility and MW the size and hence diffusivity of the molecule in the skin. The equations are often of the form (McCarley & Bunge 2001): MWcKbaK owp ⋅+⋅+= loglog (4)
16
The constants a, b, and c are determined by fitting the equation to specific experimental data sets. One of the most commonly referred equations was developed by Potts and Guy (1992): MWKK owp ⋅−⋅+−= 0061.0log71.072.2log (5) where Kp is expressed in cm/h. More complicated models have also been developed, e.g. the modified Guy (Wilschut, ten Berge et al. 1995), the Cleek and Bunge (1993), the McKone and Howd (1992), the modified Robinson (Wilschut, ten Berge, Robinson & McKone 1995) and the Frasch model (2002). The US National Institute of Occupational Safety and Health (NIOSH) has developed an on-line skin permeation calculator that makes use of the Potts and Guy, the modified Robinson and the Frasch models (figure 10).
These equations generally work well within homologous series and structurally related chemicals, but are often unreliable outside that range. The error may be up to one or two orders of magnitude, compared to experimental data.
Figure 10. Screen dump of the US NIOSH skin permeation calculator available at http://www.cdc.gov/niosh/topics/skin/skinPermCalc.html.
17
7. Dermal penetration data for substances on the Swedish OEL list
7.1 Approach
Published percutaneous absorption data were searched for 165 substances. The compilation includes all 117 substances denoted with “H”, i.e. a skin notation in the ordinance on Swedish OELs (AFS 2005). In addition, 50 listed substances without skin notation but with published quantitative data on dermal absorption were included. Detailed information on each substance is given in the Appendix.
All substances in the Appendix except nicotine correspond to a defined entry with its own value in the Swedish ordinance. For nicotine the indicative OEL value of the European Commission should be used as a recommendation pending the introduction of a Swedish OEL. A few closely related substances, e.g. the PCB congeners, the mercury salts and the dinitrotoluene, butyl amine and cresol isomers, are given a single OEL in the Swedish list. Thus, the 165 substances correspond to 150 OEL entries.
All published dermal uptake data were listed for each substance. The compilations include information on species, type of experiment (in vitro/in vivo), type of diffusion cell, skin location, thickness and area, vehicle, concentration, number of experiments, exposure duration, observation time, lag time of penetration and percent absorbed chemical. Abbreviations and terms are given in table 2. Flux and permeability (Kp) are either listed as stated by the authors or calculated by us (numbers in italic).
In addition, physico-chemical properties are provided for each substance. This includes molecular weight, density at 25ºC, melting and boiling points, vapor pressure at 25ºC and evaporation rate relative to n-butyl acetate. These properties were obtained from Chemfinder (http://chemfinder.cambridgesoft.com), Swedish consensus reports published in Arbete och Hälsa, the NIOSH Pocket Guide to Chemical Hazards, and data on the internet supplied by various companies and organizations (see Appendix for references). Octanol:water partition coefficients were obtained using the KowWin software from Syracuse Research Corporation (http://www.syrres.com/esc/kowwin.htm).
In cases with multiple data, a preferred data set (marked by dots in figure 12) was selected according to the following criteria:
1. Human skin preferred over animal skin
2. In vivo studies preferred over in vitro studies
3. Neat liquid preferred over vapor or diluted liquid
4. Water preferred over other vehicles
5. Infinite or large dose preferred over low dose
18
Infinite or large doses, although perhaps unrealistic considering workplace conditions, were preferred over low doses as they allow for assessment of steady-state fluxes.
Although experimental exposure to neat (pure) chemical may affect the skin barrier and may reflect reality less well than exposures to vapors and dilutions, the former type of studies was preferred for two reasons; (a) they are more common facilitating comparisons between and ranking of chemicals and (b) they are less dependent on exposure conditions and thus more closely reflect the intrinsic properties of the chemical. The motives for selecting the preferred study for each individual chemical are given in the Assessment section of each substance in Appendix A.
Based on the preferred Kp value, substances were grouped in seven categories, from “Extremely low” to “Extremely high” permeability, according to a logarithmic scheme (figure 11) slightly modified from Marzulli et al. (1965) and Barber et al. (1995).
Extremely high
10-2
100
10-3
10-4
10-5
10-7
10-1
10-6
Very high
High
Moderate
Low
Very low
Extremely low
Kp ,
cm/h
Figure 11. Grouping scheme according to skin permeability (Kp). The grouping does not take toxic potency into account.
For chemicals lacking quantitative data, indirect data such as comparisons between oral and dermal LD50 values and other statements on dermal penetration ability were identified in the documentation published by the Swedish Criteria Group and by the Threshold Limit Value Committee of the American Conference for Governmental Industrial Hygienists. These statements, if any, are also provided in the Assessment section.
19
7.2 Conclusions
Quantitative dermal penetration data were missing for 53 of the 165 substances, i.e. about one third of the substances. Figure 12 summarizes the permeability coefficients for the 108 substances where a permeability coefficient could be obtained (see appendix for details). As can be seen in the figure, there is a trillionfold (1012) range in permeability. Moreover, multiple Kp values are reported for many substances (represented by vertical lines in figure 12) and these within-substance deviations are sometimes several orders of magnitude.
The wide within-substance range of permeability indicates that experimental design is critical. Thus, the Kp depends on the type of skin (species, location etc.) as well as the exposure conditions (solid, liquid or vapor, neat or diluted, vehicle, exposure duration etc.).
One major issue is that of using concentrated versus diluted chemicals. Two concerns already mentioned above is that exposure to neat chemical may affect the skin barrier and may also be unrealistic from the occupational viewpoint. An additional concern is that, at least for some chemicals, the permeability is heavily influenced by dilution with water. Thus, the flux of 2-butoxyethanol reaches its maximum at about 50% dilution and the permeability coefficient increases approximately 100-fold moving from neat to very dilute aqueous solutions (Johanson & Fernström 1988, Korinth, Schaller et al. 2005).
Another aspect not covered by our preferred studies approach is that of evaporation. Thus, following exposures of short duration, such as when spills occur at a workplace, some chemical will evaporate back to the atmosphere. This reduces the amount available for dermal penetration. The extent of evaporation depends on the volatility and skin permeability of the chemical, the exposure duration, and the lag time of penetration (Kasting & Miller 2006, N’Dri-Stempfer & Bunge 2005). Theoretical calculations suggest that the fraction lost by evaporation may be significant for volatile chemicals. For example, it has been estimated that following a 1-h exposure to chloroform, 73% of the chemical in the skin evaporates (N’Dri-Stempfer & Bunge 2005). To date, no systematic evaluation of the impact of evaporation has been performed for industrial chemicals.
About two thirds of the chemicals with dermal permeability data have a skin notation (table 3 and figure 13). One might expect that skin notations would occur more frequently among chemicals with higher permeability. However, no clear relation between permeability and frequency of skin notation was seen (figure 13).
20
1E-1
1
1E-1
0
1E-0
9
1E-0
8
1E-0
7
1E-0
6
1E-0
5
1E-0
4
1E-0
3
1E-0
2
1E-0
1
1E+0
0
1E+0
1
1E+0
27439-97-6
75-21-888-06-275-15-079-11-8
151-67-780-62-6
1634-04-426675-46-7
106-44-595-48-767-68-579-09-4
108-39-410112-91-1
67-56-167-66-3
127-19-568-12-274-90-8
872-50-4108-10-1
64-17-575-01-454-11-5
6423-43-4598-56-1100-41-4
62-53-32807-30-9
420-04-2107-06-2108-95-2
75-09-271-23-8
102-71-6111-15-9124-17-4
10025-73-7628-96-6
7775-11-3107-13-1110-80-5
71-36-37487-94-7
50-00-059-50-7
107-98-2120-80-9
7646-79-9591-78-6
71-43-287-86-579-01-656-23-5
112-34-5111-76-2143-33-9108-38-3
71-55-6108-46-3
25013-15-4123-86-4
91-20-3121-14-2
67-63-0108-88-3
1303-96-41330-20-7
98-01-1606-20-2127-18-4111-90-0107-15-3118-96-7107-21-1
1327-53-3100-42-5
79-06-1108-94-1109-99-9141-43-5
78-93-3131-11-3111-42-2
95-47-67778-39-4
55-63-067-64-1
25167-83-384-66-2
123-31-97778-50-9
111-46-627323-18-825512-42-9
84-74-2110-54-3
26914-33-050-32-8
26601-64-9142-82-5107-83-5117-81-7
13463-67-77440-48-4
109-66-01327-41-9
111-65-9
CA
S n
umbe
r
Permeability coefficient (cm/h)
Fi
gure
12.
Sum
mar
y of
exp
erim
enta
lly d
eter
min
ed p
erm
eabi
lity
coef
ficie
nts (
Kp,
cm/h
) for
the
inve
stig
ated
che
mic
al. T
he c
hem
ical
s are
sorte
d in
dec
reas
ing
orde
r with
resp
ect t
o th
e pr
efer
red
valu
e (d
ots)
. Ran
ges o
f val
ues a
re g
iven
as v
ertic
al li
nes.
Not
e th
e lo
garit
hmic
scal
e of
the
y ax
is.
21
It should be pointed out that this grouping solely according to permeability (such as in figure 13) does not take toxic potency into account. The European Centre for Ecotoxicology & Toxicology of Chemicals has suggested a skin notation should be assigned when the amount of chemical absorbed upon exposure of both hands and lower arms (2000 cm2) for one hour is expected to contribute more than 10% to the systemic dose, compared to the amount absorbed via inhalation exposure at the OEL during a full work day (assuming that 10 m3 air is inhaled during an 8-h workday and that 50% is absorbed). This applies only for chemicals for which the OEL is based on systemic toxicity (ECETOC 1993).
0
10
20
30
40
50
60
No
conc
lusi
on
No
data
Ext
rem
ely
low
Very
low
Low
Mod
erat
e
Hig
h
Ver
y hi
gh
Ext
rem
ely
high
Skin permeability
Num
ber o
f sub
stan
ces
No skin notationSkin notation
Figure 13. Number of substances with and without a skin notation in the Swedish OEL list, grouped by experimentally determined skin permeability. This grouping does not take the toxic potency into account.
A comparison between the ECETOC criteria and the Swedish skin notations produces some interesting results (table 3 and figure 14). Thus, two (o-xylene and diethylene glycol) of 12 substances with a dermal/inhalation ratio of less than 0.1 (i.e. should not have a notation according to ECETOC) do have a skin notation in the Swedish list. For o-xylene this is maybe not so controversial, as another study with mixed xylenes in solution yields a ratio above 0.1. On the other hand, 6 out of 14 substances with a ratio between 0.1 and 1 lack a skin notation. Even more remarkable is that 30 out of 82 with a ratio above 1 lack the notation. For the latter chemicals the dermal route contributes to more than 90% of the total dose, according to the ECETOC calculation. For some substances (such as formaldehyde) it may be argued that the systemic dose, and hence the dermal/inhalation ratio, is irrelevant since the OEL is based on a non-systemic effect (such as irritation). Nevertheless these comparisons suggest that a revision of the Swedish skin notations would be appropriate.
22
0
20
40
60
80
100
<0.1 0.1-1.0 >1.0 No dataDermal/inhalation ratio
Num
ber o
f sub
stan
ces
No skin notationSkin notation
Figure 14. Number of substances with and without a skin notation in the Swedish OEL list, categorized by the ratio between dermal and inhalation uptake rate. As inhalation is calculated at the OEL, this ratio does take toxic potency into account. The ECETOC criterion for skin notation (>0.1) is marked by a dotted line.
23
Table 2. Abbreviations and terms as used in tables and appendix.
A Area of exposed skin Me Methanol Ab Abdomen Mon Monkey Abs Per cent absorbed chemical Mou Mouse Ac Acetone MP Minipig AoH Arbete och Hälsa n Number of experiments Ax Axilla NaCl Physiological saline (0.9% NaCl) Ba Back n-Bu n-Butanol Br Breast NC Nitrocellulose Bw Body weight Ne Neck C Concentration of chemical in vehicle Neat Undiluted chemical CAS Chemical Abstracts Service Registry No. DMF Dimethylformamide Chf Chloroform Oct Octane Der Dermis OiW Oil in water emulsion EB Elbow PB Phosfate buffer Epi Epidermis PCP Pentachlorophenol Et Ethanol PG Propyleneglycol FH Forehead Ph Phenol Fi Finger Ph/NaCl Phenol and saline Fk Flank PHD Permanent Hair Dye Fl Flow-through diffusion cell Pit Armpit FS Fore skin Pol fab Polyester fabric FS/TM Fore skin, cultured Rab Rabbit Full Full thickness skin Sat Vap Saturated vapour Gas Gasoline Sc Scalp GP Guinea pig SC Stratum corneum H:M Hexane:Methylene chloride Sn Snake Ha Hand Solv Solvent Ham Hamster Sp Examined species Has Hands SpSt Explosive (Sprengstoff in German) HD Hexadecane St Static diffusion cell HDP Hair Dye Precursors TCP Tetrachlorophenol Hep n-Heptane Texp Duration of exposure Hex n-Hexane Th Thigh HGP Hairless guinea pig Ti Tinker soil HM Hairless mouse Tlag Time lag for penetration HR Hairless rat Tobs Duration of observation Hum Human Tol Toluene JP-8 Jet fuel, type JP-8 V Applied volume Kp Permeability coefficient Vap Vapor L Thickness of exposed skin VIC Vaseline Intensive Care Loc Body location of the skin WB Whole body Log Kow Log octanol:water partition coefficient Yo Yolo soil Ma Marmoset
24
Tab
le 3
. Sum
mar
y de
scrip
tors
on
derm
al a
bsor
ptio
n fo
r the
inve
stig
ated
che
mic
als.
Q
uant
itativ
e da
ta
avai
labl
e on
ECET
OC
der
mal
/in
hala
tion
ratio
Skin
not
atio
na Su
bsta
nce
Y
ear o
f lis
ting
CA
S nu
mbe
r V
apor
pr
essu
re
Der
mal
ab
sorp
tion
Phys
ical
stat
e
<0.1
0.1-
1 >1
by
EC
ETO
C
in
Swed
en
A
ceto
ne
1993
67
-64-
1 Y
es
Yes
N
eat l
iqui
d X
N
o N
o A
ceto
nitri
le; m
ethy
l cya
nide
19
93
75-0
5-8
Yes
N
o
No
Acr
ylam
ide
1993
79
-06-
1 Y
es
Yes
A
q. so
l.
X
Y
es
Yes
A
cryl
onitr
ile
1993
10
7-13
-1
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Ally
l alc
ohol
; 2-p
rope
n-1-
ol
1993
10
7-18
-6
Yes
N
o
Yes
A
llyla
min
e; 3
-am
inop
rope
ne
1984
10
7-11
-9
Yes
N
o
Yes
A
llylc
hlor
ide;
3-c
hlor
opre
ne
1993
10
7-05
-1
Yes
N
o
Yes
A
lum
iniu
m c
hlor
ohyd
rate
19
96
1327
-41-
9 N
o Y
es
Aq.
sol.
X
No
No
Ani
line
1993
62
-53-
3 Y
es
Yes
A
q. so
l.
X
Y
es
Yes
A
rsen
ic a
cid
2004
77
78-3
9-4
No
Yes
A
q. so
l.
X
Y
es
No
Ars
enic
trio
xide
20
04
1327
-53-
3 N
o Y
es
Aq.
sol.
X
Yes
N
o B
enze
ne
1990
71
-43-
2 Y
es
Yes
N
eat l
iqui
d
X
Y
es
Yes
B
enzo
apyr
ene
1993
50
-32-
8 N
o Y
es
Nea
t sol
id
X
Yes
Y
es
Bor
ax
1978
13
03-9
6-4
No
Yes
A
q. so
l.
X
Y
es
Yes
B
utan
ol, i
so-
1987
78
-83-
1 Y
es
No
Y
es
But
anol
, n-
1989
71
-36-
3 Y
es
Yes
N
eat l
iqui
d
X
Y
es
Yes
B
utan
ol, s
ek-
1987
78
-92-
2 Y
es
No
Y
es
But
anol
, ter
t- 19
87
75-6
5-0
Yes
N
o
Yes
B
utyl
ace
tate
, n-
2000
12
3-86
-4
Yes
Y
es
Nea
t liq
uid
X
Yes
N
o B
utyl
amin
e, is
o-
1984
78
-81-
9 Y
es
No
Y
es
But
ylam
ine,
n-
1984
10
9-73
-9
Yes
N
o
Yes
B
utyl
amin
e, se
c-
1984
13
952-
84-6
Y
es
No
Y
es
But
ylam
ine,
tert-
19
84
75-6
4-9
Yes
N
o
Yes
C
arbo
n di
sulfi
de
1978
75
-15-
0 Y
es
Yes
A
q. so
l.
X
Y
es
Yes
a B
old
text
is u
sed
to h
ighl
ight
dis
cord
anci
es b
etw
een
the
Swed
ish
ordi
nanc
e an
d th
e EC
ETO
C p
ropo
sal
25
Q
uant
itativ
e da
ta
avai
labl
e on
ECET
OC
der
mal
/in
hala
tion
ratio
Skin
not
atio
n Su
bsta
nce
Y
ear o
f lis
ting
CA
S nu
mbe
r V
apor
pr
essu
re
Der
mal
ab
sorp
tion
Phys
ical
stat
e
<0.1
0.1-
1 >1
by
EC
ETO
C
in
Swed
en
Car
bon
tetra
chlo
ride
1978
56
-23-
5 Y
es
Yes
N
eat l
iqui
d
X
Y
es
Yes
C
atec
hol
1993
12
0-80
-9
Yes
Y
es
Solu
tion
X
Yes
Y
es
Chl
orin
ated
bip
heny
ls, p
oly-
(PC
B)
1978
13
36-3
6-3
No
No
Y
es
Chl
oro-
1,3-
buta
dien
e, 2
-; ch
loro
pren
e 19
90
126-
99-8
Y
es
No
Y
es
Chl
orob
iphe
nyl,
di- (
DC
B)
1978
b 25
512-
42-9
N
o Y
es
Nea
t sol
id
X
Yes
Y
esb
Chl
orob
iphe
nyl,
hexa
- (H
CB
) 19
78b
2660
1-64
-9
No
Yes
N
eat s
olid
X
Y
es
Yes
b C
hlor
obip
heny
l, m
ono-
(MC
B)
1978
b 27
323-
18-8
N
o Y
es
Nea
t liq
uid
X
Yes
Y
esb
Chl
orob
iphe
nyl,
tetra
- (TC
B)
1978
b 26
914-
33-0
N
o Y
es
Nea
t sol
id
X
Yes
Y
esb
Chl
oroc
reso
l; 4-
chlo
ro-3
-met
hylp
heno
l 19
93
59-5
0-7
Yes
Y
es
Aq.
sol.
X
Yes
N
o C
hlor
oeth
anol
, 2-
1981
10
7-07
-3
Yes
N
o
Yes
C
hlor
ofor
m; t
richl
orom
etha
ne
1978
67
-66-
3 Y
es
Yes
N
eat l
iqui
d
X
Y
es
No
Chr
omat
e, p
otas
sium
di-
2004
77
78-5
0-9
Yes
Y
es
Aq.
sol.
X
Yes
N
o C
hrom
ate,
sodi
um d
i- 20
04
7775
-11-
3 N
o Y
es
Aq.
sol.
X
Yes
N
o C
hrom
ic c
hlor
ide
2004
10
025-
73-7
N
o Y
es
Aq.
sol.
X
Yes
N
o C
obal
t 19
78
7440
-48-
4 N
o Y
es
Solu
tion
X
Yes
N
o C
obal
t dic
hlor
ide
1978
76
46-7
9-9
Yes
Y
es
Aq.
sol.
X
Yes
N
o C
reso
l, m
- 20
00
108-
39-4
Y
es
Yes
A
q. so
l.
X
Y
es
No
Cre
sol,
o-
2000
95
-48-
7 Y
es
Yes
A
q. so
l.
X
Y
es
No
Cre
sol,
p-
2000
10
6-44
-5
Yes
Y
es
Aq.
sol.
X
Yes
N
o C
yana
mid
e, h
ydro
gen
2000
42
0-04
-2
No
Yes
A
q. so
l.
X
Y
es
No
Cyc
lohe
xano
ne
2004
10
8-94
-1
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Di-(
2-et
hylh
exyl
)pht
hala
te (D
EHP)
19
87
117-
81-7
Y
es
Yes
N
eat l
iqui
d X
N
o N
o D
ibut
yl p
htha
late
(DB
P)
1987
84
-74-
2 Y
es
Yes
N
eat l
iqui
d
X
Y
es
No
Dic
hlor
oeth
ane,
1,2
- 19
81
107-
06-2
Y
es
Yes
N
eat l
iqui
d
X
Y
es
Yes
D
ieth
anol
amin
e 19
93
111-
42-2
Y
es
Yes
A
q. so
l.
X
Y
es
Yes
D
ieth
yl p
htha
late
(DEP
) 19
87
84-6
6-2
Yes
Y
es
Nea
t liq
uid
X
Yes
N
o
b R
efer
s to
PCB
, CA
S no
. 133
6-36
-3
26
Qua
ntita
tive
data
av
aila
ble
on
EC
ETO
C d
erm
al
/inha
latio
n ra
tio
Sk
in n
otat
ion
Subs
tanc
e
Yea
r of
listin
g C
AS
num
ber
Vap
or
pres
sure
D
erm
al
abso
rptio
n Ph
ysic
al st
ate
<0
.1
0.
1-1
>1
by
ECET
OC
in
Sw
eden
Die
thyl
amin
e 19
84
109-
89-7
Y
es
No
Y
es
Die
thyl
amin
oeth
anol
, 2-
1996
10
0-37
-8
Yes
N
o
Yes
D
ieth
ylen
e gl
ycol
19
93
111-
46-6
Y
es
Yes
N
eat l
iqui
d X
N
o Y
es
Die
thyl
ene
glyc
ol m
onob
utyl
eth
er (D
EGB
E)
1996
11
2-34
-5
Yes
Y
es
Nea
t liq
uid
X
Yes
N
o D
ieth
ylen
e gl
ycol
mon
obut
yl e
ther
ace
tate
(D
EGB
EA)
1996
12
4-17
-4
Yes
Y
es
Nea
t liq
uid
X
Yes
N
o D
ieth
ylen
e gl
ycol
mon
oeth
yl e
ther
(DEG
EE)
2000
11
1-90
-0
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Die
thyl
ene
glyc
ol m
onoe
thyl
eth
er a
ceta
te
(DEG
EEA
) 20
00
112-
15-2
Y
es
No
Y
es
Die
thyl
entri
amin
e 19
96
111-
40-0
Y
es
No
Y
es
Diis
opro
pyla
min
e 19
93
108-
18-9
Y
es
No
Y
es
Dim
ethy
l pht
hala
te
1987
13
1-11
-3
Yes
Y
es
Nea
t liq
uid
X
Yes
N
o D
imet
hyla
ceta
mid
e, N
- 19
96
127-
19-5
Y
es
Yes
N
eat l
iqui
d
X
Y
es
Yes
D
imet
hyla
nilli
ne, N
,N-
1993
12
1-69
-7
Yes
N
o
Yes
D
imet
hyle
thyl
amin
e 19
93
598-
56-1
Y
es
Yes
So
lutio
n
X
Y
es
No
Dim
ethy
lform
amid
e 19
87
68-1
2-2
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Dim
ethy
lsul
foxi
de
1993
67
-68-
5 Y
es
Yes
N
eat l
iqui
d
X
Y
es
Yes
D
initr
oben
zene
19
78
2515
4-54
-5
Yes
N
o
Yes
D
initr
otol
uene
19
93
2532
1-14
-6
Yes
N
o
Yes
D
initr
otol
uene
, 2,4
- 19
93
121-
14-2
Y
es
Yes
So
lutio
n
X
Y
es
Yes
D
initr
otol
uene
, 2,6
- 19
93
606-
20-2
Y
es
Yes
So
lutio
n
X
Y
es
Yes
D
ioxa
ne
1996
12
3-91
-1
Yes
N
o
Yes
D
ipro
pyle
ne g
lyco
l mon
omet
hyl e
ther
(D
PGM
E)
1993
34
590-
94-8
Y
es
No
Y
es
Epic
hlor
ohyd
rin
1978
10
6-89
-8
Yes
N
o
Yes
Et
hano
l 19
93
64-1
7-5
Yes
Y
es
Nea
t liq
uid
X
Yes
N
o Et
hano
lam
ine
1993
14
1-43
-5
Yes
Y
es
Aq.
sol.
X
Yes
Y
es
27
Q
uant
itativ
e da
ta
avai
labl
e on
ECET
OC
der
mal
/in
hala
tion
ratio
Skin
not
atio
n Su
bsta
nce
Y
ear o
f lis
ting
CA
S nu
mbe
r V
apor
pr
essu
re
Der
mal
ab
sorp
tion
Phys
ical
stat
e
<0.1
0.1-
1 >1
by
EC
ETO
C
in
Swed
en
Ethy
l 2-c
yano
acry
late
20
00
7085
-85-
0 Y
es
No
Y
es
Ethy
l acr
ylat
e 19
87
140-
88-5
Y
es
No
Y
es
Ethy
l ben
zene
19
87
100-
41-4
Y
es
Yes
N
eat l
iqui
d
X
Y
es
No
Ethy
l eth
er
1996
60
-29-
7 Y
es
No
N
o Et
hyla
min
e 19
84
75-0
4-7
Yes
N
o
Yes
Et
hyle
ne g
lyco
l 19
93
107-
21-1
Y
es
Yes
N
eat l
iqui
d
X
Y
es
Yes
Et
hyle
ne g
lyco
l din
itrat
e 19
90
628-
96-6
Y
es
Yes
So
lutio
n
X
Y
es
Yes
Et
hyle
ne o
xide
19
89
75-2
1-8
Yes
Y
es
Solu
tion
X
Yes
Y
es
Ethy
lene
diam
ine
1978
10
7-15
-3
Yes
Y
es
Aq.
sol.
X
Yes
Y
es
Ethy
lene
gly
col m
onob
utyl
eth
er (E
GB
E)
1993
11
1-76
-2
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Ethy
lene
gly
col m
onob
utyl
eth
er a
ceta
te
(EG
BEA
) 19
93
112-
07-2
Y
es
No
Y
es
Ethy
lene
gly
col m
onoe
thyl
eth
er (E
GEE
) 20
00
110-
80-5
Y
es
Yes
N
eat l
iqui
d
X
Y
es
Yes
Et
hyle
ne g
lyco
l mon
oeth
yl e
ther
ace
tate
(E
GEE
A)
2000
11
1-15
-9
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Ethy
lene
gly
col m
onoi
sopr
opyl
eth
er ( E
GiP
E)
1996
10
9-59
-1
Yes
N
o
Yes
Et
hyle
ne g
lyco
l mon
oiso
prop
yl e
ther
ace
tate
(E
GiP
EA)
1996
19
234-
20-9
N
o N
o
Yes
Et
hyle
ne g
lyco
l mon
opro
pyl e
ther
(EG
PE)
1996
28
07-3
0-9
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Ethy
l mor
phol
ine,
N-
1984
10
0-74
-3
Yes
N
o
Yes
Fo
rmal
dehy
de
1987
50
-00-
0 N
o Y
es
Aq.
sol.
X
Yes
N
o Fo
rmam
ide
1993
75
-12-
7 Y
es
No
Y
es
Furf
ural
19
90
98-0
1-1
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Furf
uryl
alc
ohol
19
90
98-0
0-0
Yes
N
o
Yes
H
alot
hane
19
90
151-
67-7
Y
es
Yes
V
apou
r
X
Y
es
No
Hep
tane
, n-
1989
14
2-82
-5
Yes
Y
es
Nea
t liq
uid
X
No
No
Hex
ane,
n-
1989
11
0-54
-3
Yes
Y
es
Nea
t liq
uid
X
No
No
Hex
anon
e, 2
-; m
ethy
l n-b
utyl
ket
one
1993
59
1-78
-6
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
28
Q
uant
itativ
e da
ta
avai
labl
e on
ECET
OC
der
mal
/in
hala
tion
ratio
Skin
not
atio
n Su
bsta
nce
Y
ear o
f lis
ting
CA
S nu
mbe
r V
apor
pr
essu
re
Der
mal
ab
sorp
tion
Phys
ical
stat
e
<0.1
0.1-
1 >1
by
EC
ETO
C
in
Swed
en
Hyd
roge
n cy
anid
e 19
74
74-9
0-8
Yes
Y
es
Vap
our
X
Yes
Y
es
Hyd
roqu
inon
e 19
93
123-
31-9
Y
es
Yes
A
q. so
l.
X
Y
es
No
Hyd
roxy
ethy
lacr
ylat
e, 2
-; pr
open
oic
acid
, 2-
1981
81
8-61
-1
Yes
N
o
Yes
Is
oflu
rane
19
90
2667
5-46
-7
Yes
Y
es
Vap
our
X
Yes
N
o Is
opro
pano
l 19
89
67-6
3-0
Yes
Y
es
Aq.
sol.
X
Yes
N
o Is
opro
pylb
enze
ne; c
umen
e 19
84
98-8
2-8
Yes
N
o
Yes
M
ercu
ry b
ichl
orid
e; d
ichl
orom
ercu
ry
1993
74
87-9
4-7
No
Yes
A
q. so
l.
X
Y
es
Yes
M
ercu
ry c
hlor
ide;
dim
ercu
ry d
ichl
orid
e
1993
10
112-
91-1
N
o Y
es
Aq.
sol.
X
Yes
Y
es
Mer
cury
, dim
ethy
l 19
93
593-
74-8
Y
es
No
Y
es
Mer
cury
, met
al
1993
74
39-9
7-6
Yes
Y
es
Vap
our
X
Yes
Y
es
Met
hano
l 19
90
67-5
6-1
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Met
hyl e
thyl
ket
one
(MEK
); 2-
buta
none
19
87
78-9
3-3
Yes
Y
es
Nea
t liq
uid
X
No
No
Met
hyl i
odid
e 19
81
74-8
8-4
Yes
N
o
Yes
M
ethy
l iso
buty
l ket
one
(MiB
K)
1989
10
8-10
-1
Yes
Y
es
Nea
t liq
uid
X
Yes
N
o M
ethy
l ter
t-but
yl e
ther
(MTB
E)
2000
16
34-0
4-4
Yes
Y
es
Aq.
sol.
X
Yes
N
o M
ethy
l-2-p
enta
nol,
4-
1996
10
8-11
-2
Yes
N
o
Yes
M
ethy
l-2-p
yrro
lidon
e, n
- (N
MP)
19
90
872-
50-4
Y
es
Yes
N
eat l
iqui
d
X
Y
es
No
Met
hyl a
cryl
ate
1987
96
-33-
3 Y
es
No
Y
es
Met
hyla
min
e 19
84
74-8
9-5
Yes
N
o
Yes
M
ethy
l bro
mid
e 19
90
74-8
3-9
Yes
N
o
Yes
M
ethy
lene
chl
orid
e; d
ichl
orom
etha
ne
1989
75
-09-
2 Y
es
Yes
N
eat l
iqui
d
X
Y
es
Yes
M
ethy
l met
acry
late
19
87
80-6
2-6
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Met
hyl m
orph
olin
e, N
- 19
84
109-
02-4
Y
es
No
Y
es
Met
hylp
enta
ne, 2
- 19
89
107-
83-5
Y
es
Yes
N
eat l
iqui
d X
N
o N
o M
onoc
hlor
oace
tic a
cid
1993
79
-11-
8 Y
es
Yes
So
lutio
n
X
Y
es
Yes
M
orph
olin
e 20
00
110-
91-8
Y
es
No
Y
es
Nap
htal
enes
, chl
orin
ated
19
78
1321
-65-
9 Y
es
No
Y
es
Nap
htha
lene
20
00
91-2
0-3
Yes
Y
es
Solu
tion
X
Yes
N
o
29
Q
uant
itativ
e da
ta
avai
labl
e on
ECET
OC
der
mal
/in
hala
tion
ratio
Skin
not
atio
n Su
bsta
nce
Y
ear o
f lis
ting
CA
S nu
mbe
r V
apor
pr
essu
re
Der
mal
ab
sorp
tion
Phys
ical
stat
e
<0.1
0.1-
1 >1
by
EC
ETO
C
in
Swed
en
N
icot
ine
54
-11-
5 Y
es
Yes
A
q. so
l.
X
Y
es
Yes
N
itrob
enze
ne
1974
98
-95-
3 Y
es
No
Y
es
Nitr
ogly
cerin
19
90
55-6
3-0
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Nitr
otol
uene
19
93
1321
-12-
6 Y
es
No
Y
es
Oct
anes
19
89
111-
65-9
Y
es
Yes
N
eat l
iqui
d X
N
o N
o Pe
ntac
hlor
ophe
nol
1974
87
-86-
5 Y
es
Yes
A
q. so
l.
X
Y
es
Yes
Pe
ntan
e 19
78
109-
66-0
Y
es
Yes
N
eat l
iqui
d X
N
o N
o Ph
enol
19
87
108-
95-2
Y
es
Yes
A
q. so
l.
X
Y
es
Yes
Pr
opan
ol, n
- 19
89
71-2
3-8
Yes
Y
es
Nea
t liq
uid
X
Yes
N
o Pr
opio
nic
acid
19
90
79-0
9-4
Yes
Y
es
Nea
t liq
uid
X
Yes
N
o Pr
opyl
ene
glyc
ol d
initr
ate
1987
64
23-4
3-4
Yes
Y
es
Solu
tion
X
Yes
Y
es
Prop
ylen
e gl
ycol
mon
omet
hyl e
ther
(P
GM
E); 1
-met
hoxy
-2-p
ropa
nol
1990
10
7-98
-2
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
-“- a
ceta
te (P
GM
EA)
1990
10
8-65
-6
Yes
N
o
Yes
R
esor
cino
l 19
93
108-
46-3
Y
es
Yes
A
q. so
l.
X
Y
es
Yes
So
dium
cya
nide
19
74
143-
33-9
N
o Y
es
Aq.
sol.
X
Yes
Y
es
Styr
ene
1990
10
0-42
-5
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Tetra
chlo
roet
hyle
ne
1989
12
7-18
-4
Yes
Y
es
Nea
t liq
uid
X
Yes
N
o Te
trach
loro
phen
ol
1990
25
167-
83-3
N
o Y
es
Aq.
sol.
X
Yes
Y
es
Tetra
ethy
l lea
d 19
81
78-0
0-2
Yes
N
o
Yes
Te
trahy
drof
uran
19
93
109-
99-9
Y
es
Yes
N
eat l
iqui
d
X
Y
es
No
Tetra
met
hyl l
ead
1981
75
-74-
1 Y
es
No
Y
es
Thio
glyc
olic
aci
d 19
96
68-1
1-1
Yes
N
o
Yes
Ti
tani
um d
ioxi
de
1990
13
463-
67-7
N
o Y
es
Aq.
sol.
X
No
No
Tolu
ene
1987
10
8-88
-3
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Trib
utyl
tin
1978
56
573-
85-4
Y
es
No
Y
es
Tric
hlor
etha
ne, 1
,1,1
- 19
89
71-5
5-6
Yes
Y
es
Nea
t liq
uid
X
Yes
N
o Tr
ichl
oroe
thyl
ene,
1,1
,2-
1989
79
-01-
6 Y
es
Yes
N
eat l
iqui
d
X
Y
es
No
30
Q
uant
itativ
e da
ta
avai
labl
e on
ECET
OC
der
mal
/in
hala
tion
ratio
Skin
not
atio
n Su
bsta
nce
Y
ear o
f lis
ting
CA
S nu
mbe
r V
apor
pr
essu
re
Der
mal
ab
sorp
tion
Phys
ical
stat
e
<0.1
0.1-
1 >1
by
EC
ETO
C
in
Swed
en
Tric
hlor
ophe
nol
1990
25
167-
82-2
N
o N
o
Yes
Tr
ichl
orop
heno
l, 2,
4,6-
19
90
88-0
6-2
Yes
Y
es
Solu
tion
X
Yes
Y
es
Trie
than
olam
ine
1984
10
2-71
-6
Yes
Y
es
Nea
t sol
id
X
Yes
N
o Tr
initr
otol
uene
, 2,4
,6-
1993
11
8-96
-7
Yes
Y
es
Solu
tion
X
Yes
Y
es
Turp
entin
e 19
90
8006
-64-
2 Y
es
No
Y
es
Vin
yl c
hlor
ide
1974
75
-01-
4 Y
es
Yes
G
as
X
Yes
Y
es
Vin
yl to
luen
e; m
ethy
l sty
rene
19
93
2501
3-15
-4
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Xyl
ene,
m-
1987
10
8-38
-3
Yes
Y
es
Nea
t liq
uid
X
Yes
Y
es
Xyl
ene,
o-
1987
95
-47-
6 Y
es
Yes
N
eat l
iqui
d X
N
o Y
es
Xyl
ene,
p-
1987
10
6-42
-3
Yes
N
o
Yes
X
ylen
es
1987
13
30-2
0-7
Yes
Y
es
Sol
utio
n
X
Y
es
Yes
31
8. Summary
Johanson G & Rauma M. Basis for skin notation. Part 1. Dermal penetration data for substances on the Swedish OEL list. Arbete och Hälsa 2008;42:2. The aim of this report is to review the published data on dermal penetration of workplace chemicals, as a basis for assignment of skin notations. Short chapters describe the anatomy of the skin, the skin as a diffusion barrier, Fick’s law of diffusion, factors affecting dermal penetration and methods to assess dermal penetration.
The major part of the report is devoted to compilation of data assessment of dermal penetration (fluxes and permeability coefficients) for 165 substances corresponding to 150 entries listed in the Swedish ordinance (AFS 2005) on Occupational Expsoure Limits (OELs). The compilation covers all 117 substances marked with an “H” in the ordinance and, in addition, 50 substances that have not been given a skin notation. The compiled data can be used in future revision of skin notations.
An analysis of the data shows that quantitative information on dermal penetration is lacking for 53 or about one third of the 165 substances. For those who have quantitative data, a variety of species and experimental techniques have been used. There is a trillion-fold (1012) span in permeability coefficients between the substances. Moreover, for many chemicals with several experimental data sets on permeability, there is a huge intra-chemical span, sometimes several orders of magnitude. In these cases, a preferred study was selected, mainly based on the following criteria: human skin, in vivo studies, neat liquid, water as vehicle and infinite or large dose were preferred over animal skin, in vitro studies, vapor or diluted liquid, other vehicles and low dose, respectively.
Notably, more than one third of the chemicals with high skin permeability and with a dermal/inhalation ratio higher than 0.1 according to the ECETOC criteria (1993) lacks a skin notation. This suggests a need for revision of all substances, including those without a skin notation, in the Swedish list.
32
9. References
AFS (2005) Hygieniska gränsvärden och åtgärder mot luftföroreningar, AFS 2005:17, Solna, Sweden, Arbetsmiljöverket.
Anderson CD (2006) Cutaneous microdialysis: Is it worth the sweat? Journal of Investigative Dermatology, 126, 1207-1209.
Barber ED, Hill T, Schum DB (1995) The percutaneous absorption of hydroquinone (hq) through rat and human skin in vitro. Toxicology Letters, 80, 167-172.
Bronaugh RL, Weingarten DP, Lowe NJ (1986) Differential rates of percutaneous absorption through the eczematous and normal skin of a monkey. Journal of Investigative Dermatology, 87, 451-453.
Cleek RL, Bunge AL (1993) A new method for estimating dermal absorption from chemical exposure. 1. General approach. Pharmaceutical Research, 10, 497-506.
ECETOC (1993) Strategy for assigning a "Skin notation", Report no. 31, Bruxelles, Belgium, European Centre for Ecotoxicology & Toxicology of Chemicals.
Forslind B, Lindberg M, eds. (2004) Skin, hair, and nails. New York: Marcel Dekker. Frasch HF (2002) A random walk model of skin permeation. Risk Analysis, 22, 265-276. Hadgraft J (2004) Skin deep. European Journal of Pharmaceutics & Biopharmaceutics, 58,
291-299. Johanson G, Boman A (1991) Percutaneous absorption of 2-butoxyethanol vapour in
human subjects. British Journal of Industrial Medicine, 48, 788-792. Johanson G, Boman A, Dynesius B (1988) Percutaneous absorption of 2-butoxyethanol in
man. Scandinavian Journal of Work, Environment & Health, 14, 101-109. Johanson G, Fernström P (1986) Percutaneous uptake rate of 2-butoxyethanol in the guinea
pig. Scandinavian Journal of Work, Environment & Health, 12, 499-503. Johanson G, Fernström P (1988) Influence of water on the percutaneous absorption of 2-
butoxyethanol in guinea pigs. Scandinavian Journal of Work, Environment & Health, 14, 95-100.
Kasting GB, Miller MA (2006) Kinetics of finite dose absorption through skin 2: Volatile compounds. Journal of Pharmaceutical Sciences, 95, 268-280.
Korinth G, Schaller KH, Drexler H (2005) Is the permeability coefficient kp a reliable tool in percutaneous absorption studies? Archives of Toxicology, 79, 155-159.
Korinth G, Weiss T, Angerer J, Drexler H (2006) Dermal absorption of aromatic amines in workers with different skin lesions: A report on 4 cases. Journal of Occupational Medicine and Toxicology, 1, 17.
Korinth G, Weiss T, Penkert S, Schaller KH, Angerer J, Drexler H (2007) Percutaneous absorption of aromatic amines in rubber industry workers: Impact of impaired skin and skin barrier creams. Occupational and Environmental Medicine, 64, 366-372.
Marzulli FN, Callahan JF, Brown DW (1965) Chemical structure and skin penetrating capacity of a short series of organic phosphates and phosphoric acid. Journal of Investigative Dermatology, 44, 339-344.
McAuliffe DJ, Blank IH (1991) Effects of uva (320-400 nm) on the barrier characteristics of the skin. Journal of Investigative Dermatology, 96, 758-762.
McCarley KD, Bunge AL (2001) Pharmacokinetic models of dermal absorption. Journal of Pharmaceutical Sciences, 90, 1699-1719.
McKone TE, Howd RA (1992) Estimating dermal uptake of nonionic organic chemicals from water and soil: I. Unified fugacity-based models for risk assessments. Risk Analysis, 12, 543-557.
Monteiro-Riviere NA, Bristol DG, Manning TO, Rogers RA, Riviere JE (1990) Interspecies and interregional analysis of the comparative histologic thickness and
33
laser doppler blood flow measurements at five cutaneous sites in nine species. Journal of Investigative Dermatology, 95, 582-586.
N’Dri-Stempfer B, Bunge AL (Year) How much can evaporation of dermally absorbed chemical reduce the systemically absorbed dose? International Conference on Occupational and Environmental Exposures of Skin to Chemicals (OEESC); 2005; Stockholm, Sweden; 2005.
Nakai JS, Chu I, Li-Muller A, Aucoin R (1997) Effect of environmental conditions on the penetration of benzene through human skin. Journal of Toxicology & Environmental Health, 51, 447-462.
Nielsen JB (2005) Percutaneous penetration through slightly damaged skin. Archives of Dermatological Research, 296, 560-567.
OECD (2004) Guidance document for the conduct of skin absorption studies, Report no. 28, Paris, France, Organisation for Economic Co-operation and Development.
Potts RO, Guy RH (1992) Predicting skin permeability. Pharmaceutical Research, 9, 663-669.
Sandby-Möller J, Poulsen T, Wulf HC (2003) Epidermal thickness at different body sites: Relationship to age, gender, pigmentation, blood content, skin type and smoking habits. Acta Dermato-Venereologica, 83, 410-413.
Schnetz E, Fartasch M (2001) Microdialysis for the evaluation of penetration through the human skin barrier - a promising tool for future research? European Journal of Pharmaceutical Sciences, 12, 165-174.
SCOEL (1999) Methodology for the derivation of occupational exposure limits: Key documentation, EUR 19253 EN, Luxembourg, European Commission. Directorate-General for Employment, Industrial Relations and Social Affaires.
Stahl M, Bouw R, Jackson A, Pay V (2002) Human microdialysis. Current Pharmaceutical Biotechnology, 3, 165-178.
Tsai JC, Sheu HM, Hung PL, Cheng CL (2001) Effect of barrier disruption by acetone treatment on the permeability of compounds with various lipophilicities: Implications for the permeability of compromised skin. Journal of Pharmaceutical Sciences, 90, 1242-1254.
Wilschut A, ten Berge WF, Robinson PJ, McKone TE (1995) Estimating skin permeation. The validation of five mathematical skin permeation models. Chemosphere, 30, 1275-1296.
Ya-Xian Z, Suetake T, Tagami H (1999) Number of cell layers of the stratum corneum in normal skin - relationship to the anatomical location on the body, age, sex and physical parameters. Archives of Dermatological Research, 291, 555-559.
App
endi
x A
Subs
tanc
e: A
ceto
neM
olec
ular
wei
ght:
58.1
CA
S: 6
7-64
-1D
ensi
ty:0
.786
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
8:32
Mel
ting
poin
t:-9
4.3°
CB
oilin
g po
int:
56.2
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:24
kPa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
Low
Eva
pora
tion
rate
:10
Log
Kow
:-0.
24
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
Fl28
00.
640.
2N
eat
524
240.
310.
050.
1310
Wilk
inso
n et
al.
(200
1)H
umB
rFl
280
0.64
0.2
H2O
3
524
240.
380.
4114
4.2
Wilk
inso
n et
al.
(200
1)
Hum
FiIn
fH
2O1%
1215
s0.
30.
280.
22N
aito
h et
al.
(200
2)H
umFi
Inf
H2O
1%12
15s
0.3
129.
5N
aito
h et
al.
(200
2)
The
only
ava
ilabl
e in
viv
o st
udy
is th
at o
f Nai
toh
et a
l. (2
002)
. An
unco
nven
tiona
l tec
hniq
ue w
as u
sed
in th
at o
ne th
umb
was
dipp
ed o
nce
or se
vera
l tim
es (1
5 se
c/oc
casi
on) i
n an
aqu
eous
solu
tion.
The
flux
was
cal
cula
ted
from
the
evap
orat
ion
from
the
thum
b.Th
e ev
apor
atio
n pr
ofile
was
bip
hasi
c, th
us tw
o di
ffer
ent f
luxe
s wer
e re
porte
d. T
he re
porte
d flu
xes r
efle
cts a
bsor
ptio
n in
to
(and
out
of)
rath
er th
an th
roug
h sk
in. T
hus t
he c
alcu
late
d K
p m
ay re
pres
ent a
n se
rious
ove
rest
imat
e of
the
"tru
e" v
alue
.
The
perm
eabi
lity
for n
eat a
ceto
ne (1
·10-5
) may
be
cons
ider
ed a
s "lo
w",
whe
reas
the
perm
eabi
lity
in w
ater
(1·1
0-3) i
s abo
ut
100-
fold
hig
her a
nd m
ay b
e co
nsid
ered
as "
high
". T
hus,
ther
e is
a st
rong
veh
icle
eff
ect o
f wat
er.
Bas
ed o
n ne
at so
lven
t, th
e pe
rmea
bilit
y is
con
side
red
"low
".
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A1
App
endi
x A
Subs
tanc
e: A
ceto
nitri
le; m
ethy
l cya
nide
Mol
ecul
ar w
eigh
t:41
.1C
AS:
75-
05-8
Den
sity
:0.7
857
g/cm
³Sc
ient
ific
basi
s: A
oH 1
991:
8M
eltin
g po
int:
-45°
CB
oilin
g po
int:
81.6
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:9.7
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:5.7
9L
og K
ow:-
0.34
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s rep
ort (
AoH
199
1:8)
doe
s not
men
tion
derm
al u
ptak
e of
ace
toni
trile
.
Acc
ordi
ng to
AC
GIH
(200
1), t
he o
ral L
D50
val
ue v
arie
s muc
h be
twee
n sp
ecie
s, i.
e. ra
t 650
0-24
000
mg/
kg b
w
and
mou
se 1
80 m
g/kg
bw
. The
bas
is fo
r ski
n no
tatio
n is
a c
ase
repo
rt w
here
a tw
o-ye
ar-o
ld c
hild
was
der
mal
ly e
xpos
ed
to 3
0 m
l of a
ceto
nitri
le n
ail p
olis
h re
mov
er (c
onc.
98-
100%
). Ei
ght h
ours
late
r, vo
miti
ng a
nd p
ain
appe
ared
.Th
e in
toxi
catio
n w
as re
solv
ed w
ith o
xyge
n an
d de
xtro
se su
ppor
t the
rapy
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A2
App
endi
x A
Subs
tanc
e: A
cryl
amid
eM
olec
ular
wei
ght:
71.1
CA
S: 7
9-06
-1D
ensi
ty:1
.13
g/cm
³Sc
ient
ific
basi
s: A
oH 1
992:
6M
eltin
g po
int:
84.5
°CB
oilin
g po
int:
192.
6°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.9 P
a (a
t 25°
C)
Skin
per
mea
bilit
y: L
owE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:-0.
67
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Arm
24H
2O50
% (2
.5 m
g/kg
bw
)5
7272
320.
6432
Fenn
ell e
t al.
(200
5)R
atB
a2.
5N
eat (
160
mg/
kg b
w)
424
2414
-30
0.85
-1.8
95-2
00Su
mne
r et a
l. (2
003)
Onl
y %
abso
rbed
dos
e ha
s bee
n re
porte
d.
The
rat a
nd h
uman
stud
ies a
re in
agr
eem
ent.
The
perm
eabi
lity
of a
cryl
amid
e m
ay b
e co
nsid
ered
as "
low
".
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A3
App
endi
x A
Subs
tanc
e: A
cryl
onitr
ileM
olec
ular
wei
ght:
53.1
CA
S: 1
07-1
3-1
Den
sity
:0.8
08 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
987:
39M
eltin
g po
int:
-83.
6°C
Boi
ling
poin
t:77
.3°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:1
3 kP
a (a
t 22.
8°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:5
.8L
og K
ow:0
.25
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Arm
Nea
t4
7.5
600
Rog
acze
wsk
a et
al.
(196
8)
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
as fo
und
in th
e lit
erat
ure,
exc
ept f
or R
ogac
zew
ska
et a
l. (1
968)
ci
ted
in W
HO
(198
3).
The
perm
eabi
lity
of a
cryl
onitr
ile m
ay b
e co
nsid
ered
as "
mod
erat
e".
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A4
App
endi
x A
Subs
tanc
e: A
llyl a
lcoh
ol; 2
-pro
pen-
1-ol
M
olec
ular
wei
ght:
58.1
CA
S: 1
07-1
8-6
Den
sity
:0.8
54 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
987:
39M
eltin
g po
int:
-129
°CB
oilin
g po
int:
97°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:3
.2 k
Pa (a
t 25°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:1
Log
Kow
:0.7
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
the
Swed
ish
cons
ensu
s rep
ort (
AoH
198
7:39
) the
LD
50 v
alue
in a
nim
al st
udie
s sho
w th
at
ally
l alc
ohol
is a
bsor
bed
via
the
skin
. No
furth
er d
etai
ls a
re g
iven
.
Smyt
h et
al.
(194
8) re
port
sim
ilar o
ral a
nd d
erm
al L
D50
val
ues (
oral
LD
50 in
rat 6
4 m
g/kg
bw
, de
rmal
LD
50 in
rabb
its 4
5 m
g/kg
bw
), su
gges
ting
effic
ient
der
mal
pen
etra
tion.
Theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
sugg
est t
hat t
he p
oten
tial f
or d
erm
alab
sorp
tion
and
resu
lting
toxi
city
is si
gnifi
cant
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A5
App
endi
x A
Subs
tanc
e: A
llyla
min
e; 3
-am
inop
rope
neM
olec
ular
wei
ght:
57.1
CA
S: 1
07-1
1-9
Den
sity
:0.7
61 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
983:
36M
eltin
g po
int:
-88°
CB
oilin
g po
int:
53°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:2
6 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.0
3
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
the
Swed
ish
cons
ensu
s doc
umen
t (A
oH 1
983:
36) s
kin
upta
ke m
ay o
ccur
with
mas
sive
exp
osur
e.N
o fu
rther
det
ails
are
giv
en.
Cla
yton
et a
l. (1
981)
(pag
e 31
46) r
efer
s to
a de
rmal
LD
50 o
f 27
mg/
kg b
w in
rabb
its. T
his v
ery
low
LD
50
is e
ven
low
er th
an th
e or
al L
D50
in ra
ts o
f 81
mg/
kg b
w.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A6
App
endi
x A
Subs
tanc
e: A
llylc
hlor
ide;
3-c
hlor
opre
neM
olec
ular
wei
ght:
76.5
CA
S: 1
07-0
5-1
Den
sity
:0.9
38 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
989:
32M
eltin
g po
int:
-134
.5°C
Boi
ling
poin
t:44
to 4
6°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:3
9 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:7
Log
Kow
:1.9
3 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
No
info
rmat
ion
rega
rdin
g de
rmal
toxi
city
is g
iven
in th
e sc
ient
ific
basi
s (A
oH 1
989)
.
The
prop
osal
of a
skin
not
atio
n by
AC
GIH
(200
1) is
bas
ed u
pon
an u
npub
lishe
d in
dust
rial r
epor
t.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A7
App
endi
x A
Subs
tanc
e: A
lum
iniu
m c
hlor
ohyd
rate
Mol
ecul
ar w
eigh
t:N
ot a
vaila
ble
CA
S: 1
327-
41-9
Den
sity
:1.1
5 g/
cm³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
Not
ava
ilabl
eB
oilin
g po
int:
Not
ava
ilabl
eSk
in n
otat
ion:
No
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Ext
rem
ely
low
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:N
ot a
vaila
ble
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Pit
770.
4H
2O
21%
(13m
g A
l)2
144
1272
~63.
6 µg
0.00
0015
0.00
032
Flar
end
et a
l. (2
001)
The
stud
y of
Fla
rend
et a
l. (2
001)
is p
erfo
rmed
on
hum
ans s
ubje
cts b
y ex
posi
ng th
em to
deo
dora
nts c
onta
inin
g al
umin
ium
.
The
perm
eabi
lity
corr
espo
nds t
o "e
xtre
mel
y lo
w".
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A8
App
endi
x A
Subs
tanc
e: A
nilin
eM
olec
ular
wei
ght:
93.1
CA
S: 6
2-53
-3D
ensi
ty:1
.022
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
9:32
Mel
ting
poin
t:-6
.2°C
Boi
ling
poin
t:18
4°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:4
0 Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Hig
hE
vapo
ratio
n ra
te:0
.048
Log
Kow
:0.9
0
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
320
Nea
t4-
69
927
1900
Bar
ry e
t al.
(198
5)H
umA
b32
0V
apSa
tura
ted
4-6
99
2426
0B
arry
et a
l. (1
985)
HM
Ba
0.8
0.01
Nea
t10
24
220
µg1.
314
0Su
sten
et a
l. (1
990)
Hum
Arm
260.
25N
eat
50.
524
39 m
g27
3000
Bar
anow
ska-
Dut
kiew
icz
(198
2b)
Hum
Arm
260.
25H
2O
97%
60.
524
33 m
g24
2500
Bar
anow
ska-
Dut
kiew
icz
(198
2b)
Hum
Ha
350-
460
Inf
H2O
2%
40.
524
230
mg
600
1220
Bar
anow
ska-
Dut
kiew
icz
(198
2b)
Hum
Ha
350-
370
Inf
H2O
2%
21
2430
0 m
g39
082
0B
aran
owsk
a-D
utki
ewic
z (1
982b
)H
umH
a35
0-42
0In
fH
2O
1%4
0.5
2458
mg
3232
0B
aran
owsk
a-D
utki
ewic
z (1
982b
)H
umH
a35
0-44
0In
fH
2O
1%4
124
80 m
g20
020
0B
aran
owsk
a-D
utki
ewic
z (1
982b
)
The
stud
ies w
ith m
inut
e vo
lum
es a
pplie
d (≤
0.2
5 m
l) ar
e ex
clud
ed si
nce
depl
etio
n m
ay h
ave
occu
rred
,re
sulti
ng in
und
eres
timat
es o
f flu
x an
d K
p.A
num
ber o
f qua
ntita
tive
stud
ies a
re a
vaila
ble,
ther
efor
e th
e hu
man
in v
ivo
stud
ies a
re p
refe
rred
.
The
Kp
valu
es o
f nea
t ani
line
rang
e fr
om 2
·10-3
to 3
·10-3
cm
/h, c
orre
spon
ding
to "
high
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A9
App
endi
x A
Subs
tanc
e: A
rsen
ic a
cid
Mol
ecul
ar w
eigh
t:14
1.9
CA
S: 7
778-
39-4
Den
sity
:2 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
984:
44M
eltin
g po
int:
35°C
Boi
ling
poin
t:16
0°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:N
ot a
vaila
ble
Skin
per
mea
bilit
y: L
owE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:-3.
14 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Fl50
01
Soil
0.6
µg/c
m²
924
240.
40.
0001
1W
este
r et a
l. (1
993a
)H
umFl
500
10.
01H
2O0.
429
2424
0.9
0.03
80.
0016
Wes
ter e
t al.
(199
3a)
Hum
Br
Fl0.
3240
0H
2O0.
011
>65-
62.
50.
310.
0003
1B
erns
tam
et a
l. (2
002)
Hum
Br
Fl0.
3240
0H
2O0.
11
>65-
61.
30.
160.
0016
Ber
nsta
m e
t al.
(200
2)H
umB
rFl
0.32
400
H2O
0.25
1>6
5-6
4.7
0.59
0.01
5B
erns
tam
et a
l. (2
002)
Hum
Br
Fl0.
3240
0H
2O0.
51
>65-
65.
40.
680.
034
Ber
nsta
m e
t al.
(200
2)H
umB
rFl
0.32
400
H2O
11
>65-
67.
53.
90.
39B
erns
tam
et a
l. (2
002)
Pig
Ab
Fl20
00.
640.
01Et
2.5
µg14
1616
0.4
0.03
90.
0009
8Tu
rkal
l et a
l. (2
003)
Mon
Ab
12So
il
424
168
3.2
Wes
ter e
t al.
(199
3a)
Mon
Ab
120.
06H
2O
0.42
324
168
20.
042
0.00
18W
este
r et a
l. (1
993a
)M
on10
00.
5H
2O2.
7 (1
430
µg)
38
962.
80.
180.
05Lo
wne
y et
al.
(200
5)M
on10
0So
il1.
4 m
g/g
(560
µg)
38
960.
10.
60.
0008
4Lo
wne
y et
al.
(200
5)R
atTa
ilH
2O0.
01-0
.2M
11
0.02
71.
1-33
Dut
kiew
icz
(197
7)
The
Kp
of D
utki
ewic
z (1
977)
was
cal
cula
ted
by B
erns
tam
et a
l. (2
002)
.B
erns
tam
et a
l. (2
002)
use
d ar
tific
ial h
uman
skin
(cul
ture
d ke
ratin
ocyt
es),
ther
efor
e th
e va
lidity
of t
he re
sults
is q
uest
iona
ble.
The
sam
e pr
oble
m a
pplie
s to
the
stud
ies b
y W
este
r et a
l. (1
993a
) tha
t use
d so
il as
"ve
hicl
e" o
r use
d a
very
smal
l ap
plie
d vo
lum
e of
0.0
1 m
l.Th
e pr
efer
red
stud
y is
that
of L
owne
y et
al.
(200
5) w
ho a
pplie
d an
aqu
eous
solu
tion
of a
rsen
ic a
cid
on th
e sk
in o
f R
hesu
s mon
keys
for 8
h. T
he 9
6-h
excr
etio
n in
urin
e an
d fa
eces
was
com
pare
d to
that
of a
kno
wn
i.v. d
ose
of a
rsen
ic.
The
perm
eabi
lity
of a
rsen
ic in
mon
keys
cor
resp
onds
to "
low
".
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A10
App
endi
x A
Subs
tanc
e: A
rsen
ic tr
ioxi
deM
olec
ular
wei
ght:
395.
7C
AS:
132
7-53
-3D
ensi
ty:3
.74
g/cm
³Sc
ient
ific
basi
s: A
oH 1
984:
44M
eltin
g po
int:
193°
CB
oilin
g po
int:
465°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:-0.
13 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
Fl0.
3240
0H
2O0.
11
>65-
60.
940.
0094
Ber
nsta
m e
t al.
(200
2)H
umB
rFl
0.32
400
H2O
0.25
1>6
5-6
0.96
0.02
4B
erns
tam
et a
l. (2
002)
Hum
Br
Fl0.
3240
0H
2O0.
51
>65-
60.
790.
04B
erns
tam
et a
l. (2
002)
Hum
Br
Fl0.
3240
0H
2O1
1>6
5-6
1.3
0.13
Ber
nsta
m e
t al.
(200
2)
N
o da
ta a
vaila
ble
The
only
foun
d st
udy
on a
rsen
ic tr
ioxi
de w
as th
e on
e by
Ber
nsta
m e
t al.
(200
2).
In th
e st
udy,
arti
ficia
l hum
an sk
in (c
ultu
red
kera
tinoc
ytes
) was
use
d, th
eref
ore
the
valid
ity o
f the
resu
lts a
re q
uest
iona
ble.
The
repo
rted
Kp
valu
es c
orre
spon
d to
"m
oder
ate"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A11
App
endi
x A
Subs
tanc
e: B
enze
neM
olec
ular
wei
ght:
78.1
CA
S: 7
1-43
-2D
ensi
ty:0
.879
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
8:32
Mel
ting
poin
t:5.
5°C
Boi
ling
poin
t:80
.1°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:7
.3 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:2
.13
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StEp
iIn
fH
2O1.
813
44
1100
0.19
Bla
nk e
t al.
(198
5)H
umA
bSt
Epi
Inf
HD
4414
09.
40.
044
Bla
nk e
t al.
(198
5)H
umA
bSt
Epi
Inf
Oct
4411
037
0.17
Bla
nk e
t al.
(198
5)H
umA
bSt
Epi
Inf
Hex
440
240.
11B
lank
et a
l. (1
985)
Hum
Ab
StEp
iIn
fG
as44
90
140.
061
Bla
nk e
t al.
(198
5)H
umA
bSt
40N
eat
44
2118
00B
lank
et a
l. (1
985)
Hum
Ab
St40
Vap
0.36
(Sa
tura
ted)
44
2500
091
0B
lank
et a
l. (1
985)
Hum
Ab
St40
H2O
1.
8 (2
µl/m
l)13
44
1100
190
Bla
nk e
t al.
(198
5)H
umB
rFu
ll0.
350.
035
Nea
t10
0.5
0.5
0.25
mg/
cm²
5.7
500
Lode
n (1
986a
)H
umB
rFl
Full
Nea
t7
13.5
13.5
~3.7
1.1
99Lo
den
(198
6b)
Hum
Ab/
Br
Fl20
0-40
00.
240
0H
2O15
-50
µg/l
210
88
0.8
600-
3300
Nak
ai e
t al.
(199
7)H
um5
µl/c
m²T
ol0.
44 µ
g/cm
² (0
.01%
)4
1-12
0.12
0.00
5-0.
060.
0000
44-0
.000
53W
este
r et a
l. (2
000)
Hum
5 µl
/cm
²Tol
4.4
µg/c
m²
(0.1
%)
41-
120.
110.
0004
6-0.
055
0.00
04-0
.004
8W
este
r et a
l. (2
000)
Hum
5 µl
/cm
²Tol
6.6
µg/c
m²
(0.1
5%)
41-
120.
10.
0042
-0.0
50.
0005
5-0.
0066
Wes
ter e
t al.
(200
0)H
um5
µl/c
m²T
ol22
µg/
cm²
(0.5
%)
41-
120.
080.
0034
-0.0
40.
0015
-0.0
176
Wes
ter e
t al.
(200
0)H
um5
µl/c
m²H
2O4.
4 µg
/cm
² (0
.1%
)4
1-12
50.
2-2.
50.
018-
0.22
Wes
ter e
t al.
(200
0)H
um5
µl/c
m²H
2O22
µg/
cm²
(0.5
%)
41-
123.
90.
16-2
0.07
2-0.
86W
este
r et a
l. (2
000)
Mon
Nea
t2.
52.
51.
816
0Fr
anz
(198
4)M
PFl
900
3.1
Nea
t6
1818
2.4
210
Jaco
bs e
t al.
(199
3)M
PFl
900
3.1
Vap
0.36
(Sat
urat
ed)
618
1838
0014
0Ja
cobs
et a
l. (1
993)
Rat
Ab
StFu
ll2.
61
Nea
t46
0.5-
2.5
0.5-
2.5
0.67
41-9
20 µ
g2.
219
0Ts
urut
a (1
982)
Rep
orte
d da
ta
In v
itro
A12
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
HM
Ba
0.8
0.00
45N
eat
752
s4
39 µ
g38
3400
Sust
en e
t al.
(198
5)H
MW
BV
ap0.
0097
(30
00pp
m)
62-
62-
662
005.
9Ts
urut
a (1
989)
HM
WB
Vap
0.00
32 (
1000
ppm
)6
2-6
2-6
6200
1.9
Tsur
uta
(198
9)H
MW
BV
ap0.
0006
4 (2
00pp
m)
62-
62-
662
000.
32Ts
urut
a (1
989)
Hum
Arm
35-4
5N
eat
52
2410
mg
2.8-
4.7
240-
400
Han
ke e
t al.
(200
0)M
onA
rm13
0.05
Nea
t (3.
4 m
g/cm
²)3
412
00.
170.
016
1.4
Mai
bach
et a
l. (1
981)
Mon
Arm
13N
eat (
68 m
g/cm
²)3
2.5
168
0.85
2.6
230
Mai
bach
et a
l. (1
981)
Rat
WB
Vap
0.13
(40
000
ppm
)5
44
0.8
1500
19M
cDou
gal e
t al.
(199
0)
Due
to la
ck o
f inf
orm
atio
n (n
o e.
g. a
rea,
vol
ume,
dur
atio
n) in
Wes
ter e
t al.
(200
0) th
e du
ratio
n of
the
expo
sure
was
ass
umed
to b
e be
twee
n 1
and
12h
due
to th
e sm
all a
mou
nt (5
µl/c
m²)
appl
ied,
resu
lting
in w
ide
span
s for
the
fluxe
s and
per
mea
bilit
ies.
The
perm
eabi
lity
thro
ugh
hum
an sk
in in
vitr
o va
ries t
rem
endo
usly
bet
wee
n st
udie
s, w
ith K
p va
lues
bet
wee
n 1·
10-4 c
m/h
for n
eat b
enze
ne a
nd 3
cm
/h fo
r sat
urat
ed v
apou
r. Th
e on
ly h
uman
in v
ivo
stud
y is
that
of H
anke
et a
l. (2
000)
(196
1, tr
ansl
ated
in 2
000)
, with
a K
p of
3·1
0-4 to
5·1
0-4 c
m/h
. Th
is is
in a
gree
men
t with
the
in v
itro
stud
ies u
sing
hum
an sk
in a
nd n
eat b
enze
ne (1
, 6 a
nd 2
1·10
-4 c
m/h
).
The
perm
eabi
lity
corr
espo
nds t
o "m
oder
ate"
.
In v
ivo
Ase
ssm
ent
A13
App
endi
x A
Subs
tanc
e: B
enzo
apyr
ene
Mol
ecul
ar w
eigh
t:25
2.3
CA
S: 5
0-32
-8D
ensi
ty:1
.351
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
176.
5°C
Boi
ling
poin
t:49
5°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:N
ot a
vaila
ble
Skin
per
mea
bilit
y: E
xtre
mel
y lo
wE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:6.1
3
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
GP
Ba
Fl50
00.
640.
01A
cN
eat (
13 µ
g/cm
²)4
2448
280.
0011
0.15
Moo
dy e
t al.
(199
5)G
PB
aFl
200
0.64
0.01
Ac
Nea
t (8
µg/c
m²)
524
2437
0.00
090.
12N
g et
al.
(199
2)G
PB
aFl
200
0.64
0.01
Ac
Nea
t (8
µg/c
m²)
524
2410
0.00
025
0.03
4N
g et
al.
(199
2)G
PB
aFl
200
0.64
0.01
Ac
Nea
t (74
µg/
cm²)
524
247.
20.
0016
0.22
Ng
et a
l. (1
992)
GP
Full
5N
eat (
10 µ
g)4
2424
0.33
0.00
0001
90.
0002
5K
ao e
t al.
(198
5)H
GP
Fl20
00.
640.
01A
c 0.
19 (
3µg/
cm²)
2-5
2424
4.6
0.31
0.00
58St
orm
et a
l. (1
990)
HM
Ba
FlFu
ll2
0.01
-0.0
2A
cN
eat (
2.5
µg/c
m²)
1016
162.
90.
0000
330.
0045
Kao
et a
l. (1
988)
HM
Ba
FlFu
ll2
0.01
-0.0
2A
cN
eat (
2.5
µg/c
m²)
916
162
0.00
0023
0.00
31K
ao e
t al.
(198
8)H
umA
bFl
500
0.64
0.01
Ac
Nea
t (9.
8 µg
/cm
²)4
2448
3.3
0.00
0096
0.01
3M
oody
et a
l. (1
995)
Hum
Ab
Fl50
00.
640.
01A
cN
eat (
8.4
µg/c
m²)
424
481.
50.
0000
390.
0053
Moo
dy e
t al.
(199
5)H
umFS
/TM
Fl30
00.
640.
01A
cN
eat (
9.1
µg/c
m²)
424
480.
20.
0000
056
0.00
076
Moo
dy e
t al.
(199
5)H
umSt
350
1.8
18 m
gSo
il92
0 m
g so
il/kg
4-5
9696
110
13St
roo
et a
l. (2
005)
Hum
St35
01.
818
mg
Soil
140
mg
soil/
kg4-
596
9654
6.7
Stro
o et
al.
(200
5)H
umSt
350
1.8
18 m
gSo
il17
00 m
g so
il/kg
4-5
9696
160
20St
roo
et a
l. (2
005)
Hum
St35
01.
818
mg
Soil
110
mg
soil/
kg4-
596
9627
3.3
Stro
o et
al.
(200
5)H
umSt
350
1.8
18 m
gSo
il38
mg
soil/
kg4-
596
9627
3.3
Stro
o et
al.
(200
5)H
umSt
350
1.8
18 m
gSo
il82
0 m
g so
il/kg
4-5
9696
160
20St
roo
et a
l. (2
005)
Hum
St35
01.
818
mg
Soil
630
mg
soil/
kg4-
596
9611
013
Stro
o et
al.
(200
5)H
umFl
500
140
mg
Soil
0.01
4 (1
0 pp
m)
624
240.
0112
0.01
7W
este
r et a
l. (1
990)
Hum
Fl50
01
0.6
Ac
Nea
t (5
8 µg
)6
2424
0.09
0.00
0016
0.00
22W
este
r et a
l. (1
990)
Hum
Fl20
00.
640.
01A
c 0.
19 (
3 µg
/cm
²)2-
524
240.
80.
053
0.00
1St
orm
et a
l. (1
990)
Hum
Ab
Fl10
000.
84
µg/c
m²
1H
awki
ns e
t al.
(198
6)H
umFu
ll5
Nea
t (10
µg)
424
242.
70.
0000
170.
0023
Kao
et a
l. (1
985)
Rep
orte
d da
ta
In v
itro
A14
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Mon
Full
5N
eat (
10 µ
g)4
2424
3.3
0.00
0021
0.00
28K
ao e
t al.
(198
5)M
ouB
aFl
Full
20.
01-0
.02
Ac
Nea
t (2.
5 µg
/cm
²)5
1616
6.8
0.00
0081
0.01
1K
ao e
t al.
(198
8)M
ouB
aFl
Full
20.
01-0
.02
Ac
Nea
t (2.
5 µg
/cm
²)10
1616
6.8
0.00
0081
0.01
1K
ao e
t al.
(198
8)M
ouB
aFl
Full
20.
01-0
.02
Ac
Nea
t (2.
5 µg
/cm
²)10
1616
9.4
0.00
011
0.01
5K
ao e
t al.
(198
8)M
ouB
aFl
Full
20.
01-0
.02
Ac
Nea
t (2.
5 µg
/cm
²)10
1616
9.2
0.00
010.
014
Kao
et a
l. (1
988)
Mou
Ba
FlFu
ll2
0.01
-0.0
2A
cN
eat (
2.5
µg/c
m²)
1016
164.
40.
0000
50.
0068
Kao
et a
l. (1
988)
Mou
Ba
FlFu
ll2
0.01
Ac
Nea
t (10
ng)
1717
150.
0000
0033
0.00
0044
Hol
land
et a
l. (1
984)
Mou
Ba
FlFu
ll2
0.01
Ac
Nea
t (10
0 ng
)17
1730
0.00
0006
0.00
088
Hol
land
et a
l. (1
984)
Mou
Ba
FlFu
ll2
0.01
Ac
Nea
t (10
00 n
g)17
1725
0.00
0054
0.00
73H
olla
nd e
t al.
(198
4)M
ouB
aFl
Full
20.
01A
cN
eat (
2500
ng)
1717
160.
0000
90.
012
Hol
land
et a
l. (1
984)
Mou
Ba
FlFu
ll2
0.01
Ac
Nea
t (50
00 n
g)17
1714
0.00
016
0.02
1H
olla
nd e
t al.
(198
4)M
ouB
aFl
Full
20.
01A
cN
eat (
5000
ng)
2016
1611
0.00
013
0.01
7H
olla
nd e
t al.
(198
4)M
ouB
aFl
Full
20.
01A
cN
eat (
1000
0 ng
)17
178
0.00
018
0.02
4H
olla
nd e
t al.
(198
4)M
ouFl
Full
0.64
0.01
Ac
0.19
(3µ
g/cm
²)2-
524
243.
10.
210.
0039
Stor
m e
t al.
(199
0)M
ouB
aFl
Full
0.8
4 µg
/cm
²6
Haw
kins
et a
l. (1
986)
Mou
Ba
Full
50.
02A
cN
eat (
5 µg
)4
2424
240.
0000
740.
01K
ao e
t al.
(198
4)M
ouB
aFu
ll5
0.02
Ac
Nea
t (10
µg)
424
2417
0.00
010.
014
Kao
et a
l. (1
984)
Mou
Ba
Full
50.
02A
cN
eat (
20 µ
g)4
2424
120.
0001
50.
02K
ao e
t al.
(198
4)M
ouB
aFu
ll5
0.02
Ac
Nea
t (30
µg)
424
247.
20.
0001
30.
018
Kao
et a
l. (1
984)
Mou
Full
5N
eat (
10 µ
g)4
2424
100.
0000
610.
0083
Kao
et a
l. (1
985)
Pig
Ba
Fl10
000.
84
µg/c
m²
0.6
Haw
kins
et a
l. (1
986)
Rab
Full
5N
eat (
10 µ
g)4
2424
1.7
0.00
001
0.00
14K
ao e
t al.
(198
5)R
atB
aFl
500
0.64
0.01
Ac
Nea
t (11
µg/
cm²)
424
4851
0.00
170.
23M
oody
et a
l. (1
995)
Rat
Fl20
00.
640.
01A
c 0.
19 (
3µg/
cm²)
2-5
2424
3.8
0.25
0.00
48St
orm
et a
l. (1
990)
Rat
Ba
St35
01.
8O
il10
0ppm
(90
µg/c
m²)
596
9638
0.27
0.36
Yan
g et
al.
(198
9)R
atB
aSt
350
1.8
Soil
1% (9
mg
soil/
cm²)
596
968.
40.
058
0.07
9Y
ang
et a
l. (1
989)
Rat
Ba
St32
01.
8So
lvN
eat (
9.3
- 9.9
µg/
cm²)
412
012
02.
10.
0000
130.
0017
Yan
g et
al.
(198
6)R
atB
aSt
Full
1.8
Solv
Nea
t (9.
3 - 9
.9 µ
g/cm
²)4
120
120
280.
0001
70.
023
Yan
g et
al.
(198
6)R
atB
aSt
350
1.8
Solv
Nea
t (9.
3 - 9
.9 µ
g/cm
²)4
120
120
500.
0003
0.04
Yan
g et
al.
(198
6)R
atFl
300
0.64
0.00
96A
cN
eat?
(2-
5 µg
/cm
²)3
168
168
3.7
0.00
0003
-0.0
0000
810.
0004
4-0.
0011
Bro
naug
h et
al.
(198
6)R
atFl
300
0.64
0.00
96A
cN
eat?
(2-
5 µg
/cm
²)3
168
168
560.
0000
5-0.
0001
30.
0067
-0.0
17B
rona
ugh
et a
l. (1
986)
Rat
Full
5N
eat (
10 µ
g)4
2424
20.
0000
130.
0017
Kao
et a
l. (1
985)
A15
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
GP
Ba
80.
1A
c N
eat (
17 µ
g/cm
²)4
66
4.1
0.00
090.
12C
hu e
t al.
(199
6)G
PB
a8
0.1
Ac
Nea
t (22
µg/
cm²)
424
2417
0.00
110.
15C
hu e
t al.
(199
6)G
PB
a8
0.1
Ac
Nea
t (32
µg/
cm²)
424
4823
0.00
220.
3C
hu e
t al.
(199
6)G
PB
a8
0.1
Ac
Nea
t (87
µg/
cm²)
424
168
240.
0065
0.87
Chu
et a
l. (1
996)
GP
Ba
4.2
0.05
Ac
Nea
t (9.
1 µg
/cm
²)4
2433
668
0.00
190.
26M
oody
et a
l. (1
995)
GP
Ba
40.
05A
c N
eat (
28 µ
g)5
2416
873
0.00
160.
22N
g et
al.
(199
2)M
onA
b12
480
mg
Soil
0.01
4 (1
0 pp
m)
424
144
131.
60.
0022
Wes
ter e
t al.
(199
0)M
onA
b12
Ac
Nea
t (5
8 µg
)4
2414
451
0.00
074
0.1
Wes
ter e
t al.
(199
0)M
ouB
a1.
8≤0
.015
Ac
15 (1
30 µ
g/cm
²)5-
624
2441
1.4
2.1
Sand
ers e
t al.
(198
4)M
ouB
a1.
8≤0
.015
Ac
15 (1
30 µ
g/cm
²)5-
624
2484
0.29
0.43
Sand
ers e
t al.
(198
4)M
ouB
a1.
8≤0
.015
Ac
15 (1
30 µ
g/cm
²)5-
624
2482
0.02
90.
043
Sand
ers e
t al.
(198
4)R
atB
a4.
20.
05A
c N
eat (
6.1
µg/c
m²)
424
336
690.
0013
0.17
Moo
dy e
t al.
(199
5)R
atB
a7
Oil
100p
pm (9
0 µg
/cm
²)5
9696
350.
240.
33Y
ang
et a
l. (1
989)
Rat
Ba
7So
il1%
(9 m
g so
il/cm
²)5
9696
9.2
0.06
40.
086
Yan
g et
al.
(198
9)R
atB
a1.
2N
eat (
9.2
µg/c
m²)
412
012
046
0.00
026
0.03
5Y
ang
et a
l. (1
986)
Rat
Ba
1.25
0.01
9A
cN
eat?
(2-
5 µg
/cm
²)5
2419
248
0.00
03-0
.000
740.
04-0
.1B
rona
ugh
et a
l. (1
986)
Nea
rly a
ll st
udie
s onl
y re
port
perc
ent a
bsor
bed
dose
. Flu
xes a
nd K
p va
lues
wer
e ca
lcul
ated
ass
umin
g co
nsta
nt
flux
durin
g th
e ex
posu
re.
The
in v
ivo
stud
y by
Chu
et a
l. (1
996)
is p
refe
rred
sinc
e a
rela
tivel
y la
rge
amou
nt o
f ben
zo[a
]pyr
ene
was
app
lied.
Furth
er it
repr
esen
ts th
e m
id-r
ange
of c
alcu
late
d K
p va
lues
.
The
Kp
of 1
·10-7
to 7
·10-7
cm
/h su
gges
ts "
extre
mel
y lo
w"
perm
eabi
lity
In v
ivo
Ase
ssm
ent
A16
App
endi
x A
Subs
tanc
e: B
orax
Mol
ecul
ar w
eigh
t:38
1.4
CA
S: 1
303-
96-4
Den
sity
:1.7
3 g/
cm³
Scie
ntifi
c ba
sis:
AoH
198
3:36
Mel
ting
poin
t:75
°CB
oilin
g po
int:
320°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:Not
ava
ilabl
e
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Leg
Fl50
01
1H
2O50
624
240.
411.
78.
5W
este
r et a
l. (1
998a
)
Hum
Ba
900
1.8
H2O
50
(2 µ
l/cm
²)8
2416
80.
210.
0018
0.00
9W
este
r et a
l. (1
998b
)
The
very
low
flux
and
Kp
in th
e in
viv
o st
udy
(Wes
ter e
t al.
(199
8b))
is li
kely
due
to th
e sm
all a
mou
nt a
pplie
d (2
µl/c
m² o
r 6 µ
g/cm
²).
The
perm
eabi
lity,
of t
he in
vitr
o st
udy
(Wes
ter e
t al.
(199
8a))
, cor
resp
onds
to "
mod
erat
e".
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A17
App
endi
x A
Subs
tanc
e: B
utan
ol, i
so-
Mol
ecul
ar w
eigh
t:74
.1C
AS:
78-
83-1
Den
sity
:0.8
02 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
984:
44M
eltin
g po
int:
-108
°CB
oilin
g po
int:
107.
9°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:1
.2 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:2
Log
Kow
:0.7
6
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
The
perm
eabi
lity
prop
ertie
s can
be
assu
med
to b
e si
mila
r to
that
of n
-but
anol
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A18
App
endi
x A
Subs
tanc
e: B
utan
ol, n
-M
olec
ular
wei
ght:
74.1
CA
S: 7
1-36
-3D
ensi
ty:0
.81
g/cm
³Sc
ient
ific
basi
s: A
oH 1
984:
44M
eltin
g po
int:
-89.
5°C
Boi
ling
poin
t:11
7.6°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.7
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:0
.46
Log
Kow
:0.8
8
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Dog
Br
StFu
ll1
5%5
55
2811
1M
ills e
t al.
(200
3)H
umA
bSt
26.6
2.5
H2O
7.
48
2519
Sche
uple
in e
t al.
(197
3)H
umA
bSt
2500
2.5
H2O
7.
43
300
220
Sche
uple
in e
t al.
(197
3)H
umA
bSt
26.6
2.5
Nea
t7
0.6
48Sc
heup
lein
et a
l. (1
973)
Hum
Ab
St25
002.
5N
eat
810
820
Sche
uple
in e
t al.
(197
3)H
umFl
250
10.
2-0.
3N
eat
324
241.
8 (9
h)4.
1-6.
233
0-50
0B
oman
et a
l. (2
000)
Hum
Fl25
01
0.2-
0.3
Tol
50%
521
2170
(10h
)14
0-20
056
00-8
400
Bom
an e
t al.
(200
0)H
umFl
250
10.
2-0.
3C
hf +
Me
50%
621
2122
21-3
284
0-13
00B
oman
et a
l. (2
000)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
40.
30.
365
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
44.
34.
382
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
47.
87.
812
0B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0001
M4
11.3
11.3
120
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
414
.314
.312
0B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0001
M1
26.3
26.3
120
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
40.
30.
342
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
45.
85.
868
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
49.
89.
873
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
413
.811
.375
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
417
.814
.373
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
426
.326
.379
Beh
l et a
l. (1
980)
Mou
Ab
StFu
ll0.
60.
2N
aCl
32
237
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
22
242
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
42
287
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
52
213
0B
ehl e
t al.
(198
4)
Rep
orte
d da
ta
In v
itro
A19
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Mou
Ab
StFu
ll0.
60.
2N
aCl
42
241
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
52
265
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
42
240
Beh
l et a
l. (1
984)
Mou
Ba
StFu
ll0.
60.
2N
aCl
32
287
Beh
l et a
l. (1
984)
Mou
Ba
StFu
ll0.
60.
2N
aCl
22
210
0B
ehl e
t al.
(198
4)M
ouB
aSt
Full
0.6
0.2
NaC
l2
22
170
Beh
l et a
l. (1
984)
Mou
Ba
StFu
ll0.
60.
2N
aCl
52
224
0B
ehl e
t al.
(198
4)M
ouB
aSt
Full
0.6
0.2
NaC
l4
22
62B
ehl e
t al.
(198
4)M
ouB
aSt
Full
0.6
0.2
NaC
l5
22
65B
ehl e
t al.
(198
4)M
ouB
aSt
Full
0.6
0.2
NaC
l5
22
51B
ehl e
t al.
(198
4)M
ouA
bSt
Full
0.6
NaC
l0.
0001
M5
22
76B
ehl e
t al.
(198
1)M
ouA
bSt
Full
0.79
NaC
l≤1
0-4M
22
29D
urrh
eim
et a
l. (1
980)
Mou
Ab
StFu
ll0.
79N
aCl
≤10-
4M2
244
Dur
rhei
m e
t al.
(198
0)M
ouA
bSt
Full
0.79
NaC
l≤1
0-4M
22
150
Dur
rhei
m e
t al.
(198
0)M
PFl
900
3.1
Nea
t6
17.5
17.5
3.7
300
Jaco
bs &
Pha
npra
sit (
1993
)M
PFl
900
3.1
Vap
0.02
6 (S
at.)
617
.517
.533
000
86Ja
cobs
& P
hanp
rasi
t (19
93)
Dog
Br
56N
eat
21
829
mg
6.5
530
DiV
ince
nzo
et a
l. (1
979)
Bas
ed o
n ne
at so
lven
t, th
e pe
rmea
bilit
y is
con
side
red
"mod
erat
e" w
ith K
p va
lues
of 4
·10-4
to 1
·10-3
cm/h
(h
uman
full
thic
knes
s ski
n in
vitr
o) a
nd 7
·10-4
cm
/h (d
og in
viv
o).
It sh
ould
be
note
d th
at th
ere
seem
s to
be a
stro
ng v
ehic
le e
ffec
t of w
ater
. Thu
s, th
e pe
rmea
bilit
yin
mou
se sk
in o
f n-b
utan
ol in
phy
siol
ogic
al sa
line
rang
es fr
om 4
·10-3
to 2
·10-2
cm
/h.
Sim
ilar v
alue
s (3·
10-3
for s
tratu
m c
orne
um a
nd 3
·10-2
cm
/h fo
r ful
l thi
ckne
ss sk
in) a
re re
porte
d fo
r hum
an sk
in.
In v
ivo
Ase
ssm
ent
A20
App
endi
x A
Subs
tanc
e: B
utan
ol, s
ek-
Mol
ecul
ar w
eigh
t:74
.1C
AS:
78-
92-2
Den
sity
:0.8
06 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
984:
44M
eltin
g po
int:
-115
°CB
oilin
g po
int:
99.5
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:1.6
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:1.3
Log
Kow
:0.6
1
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
The
perm
eabi
lity
prop
ertie
s can
be
assu
med
to b
e si
mila
r to
that
of n
-but
anol
.
Acc
ordi
ng to
theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
the
pote
ntia
l for
der
mal
abso
rptio
n an
d re
sulti
ng to
xici
ty is
sign
ifica
nt.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A21
App
endi
x A
Subs
tanc
e: B
utan
ol, t
ert-
Mol
ecul
ar w
eigh
t:74
.1C
AS:
75-
65-0
Den
sity
:0.7
86 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
984:
44M
eltin
g po
int:
25.5
°CB
oilin
g po
int:
82.2
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:3.4
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:1.1
Log
Kow
:0.3
5
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
The
perm
eabi
lity
prop
ertie
s can
be
assu
med
to b
e si
mila
r to
that
of n
-but
anol
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A22
App
endi
x A
Subs
tanc
e: B
utyl
ace
tate
, n-
Mol
ecul
ar w
eigh
t:11
6.2
CA
S: 1
23-8
6-4
Den
sity
:0.8
82 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
984:
44M
eltin
g po
int:
-106
.2°C
Boi
ling
poin
t:12
6.1°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:1.2
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:1
Log
Kow
:1.7
8
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
St30
0-60
00.
64N
eat
36
62.
220
0U
rsin
et a
l. (1
995)
N
o da
ta a
vaila
ble
Urs
in e
t al.
(199
5) st
retc
hed
the
skin
whe
n m
ount
ing
it in
the
diff
usio
n ce
ll, re
achi
ng a
fina
l thi
ckne
ss o
f abo
ut
one-
third
of t
he o
rigin
al th
ickn
ess.
This
pro
cedu
re m
ay g
ive
over
estim
ates
of t
he fl
ux a
nd K
p va
lues
.
The
perm
eabi
lity
corr
espo
nds t
o "m
oder
ate"
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A23
App
endi
x A
Subs
tanc
e: B
utyl
amin
e, is
o-M
olec
ular
wei
ght:
73.1
CA
S: 7
8-81
-9D
ensi
ty:0
.724
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
3:36
Mel
ting
poin
t:-8
5°C
Boi
ling
poin
t:66
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:13
kPa
(at 1
8.8°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.7
3
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
the
Swed
ish
cons
ensu
s doc
umen
t (A
oH 1
983:
36) s
kin
upta
ke m
ay o
ccur
with
mas
sive
exp
osur
e.N
o fu
rther
det
ails
are
giv
en.
See
also
info
rmat
ion
on n
-but
ylam
ine.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A24
App
endi
x A
Subs
tanc
e: B
utyl
amin
e, n
-M
olec
ular
wei
ght:
73.1
CA
S: 1
09-7
3-9
Den
sity
:0.7
41 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
983:
36M
eltin
g po
int:
-50°
CB
oilin
g po
int:
77°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:1
1 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:7
.3L
og K
ow:0
.97
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
the
Swed
ish
cons
ensu
s doc
umen
t (A
oH 1
983:
36) s
kin
upta
ke m
ay o
ccur
with
mas
sive
exp
osur
e.N
o fu
rther
det
ails
are
giv
en.
Cla
yton
et a
l. (1
981)
(pag
e 31
46) r
efer
s to
a th
e de
rmal
LD
50 o
f 370
mg/
kg b
w in
gui
nea
pig.
This
is lo
wer
than
the
oral
LD
50 in
rat (
500
mg/
kg b
w).
Theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
sugg
est t
hat t
he p
oten
tial f
or d
erm
alab
sorp
tion
and
resu
lting
toxi
city
is si
gnifi
cant
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A25
App
endi
x A
Subs
tanc
e: B
utyl
amin
e, se
c-M
olec
ular
wei
ght:
73.1
CA
S: 1
3952
-84-
6D
ensi
ty:0
.724
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
3:36
Mel
ting
poin
t:-8
5°C
Boi
ling
poin
t:66
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:18
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:0
.74
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
the
Swed
ish
cons
ensu
s doc
umen
t (A
oH 1
983:
36) s
kin
upta
ke m
ay o
ccur
with
mas
sive
exp
osur
e.N
o fu
rther
det
ails
are
giv
en.
See
also
info
rmat
ion
on n
-but
ylam
ine.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A26
App
endi
x A
Subs
tanc
e: B
utyl
amin
e, te
rt-M
olec
ular
wei
ght:
73.1
CA
S: 7
5-64
-9D
ensi
ty:0
.696
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
3:36
Mel
ting
poin
t:-6
7.5°
CB
oilin
g po
int:
44.4
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:48
kPa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:1L
og K
ow:0
.40
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
the
Swed
ish
cons
ensu
s doc
umen
t (A
oH 1
983:
36) s
kin
upta
ke m
ay o
ccur
with
mas
sive
exp
osur
e.N
o fu
rther
det
ails
are
giv
en.
See
also
info
rmat
ion
on n
-but
ylam
ine.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A27
App
endi
x A
Subs
tanc
e: C
arbo
n di
sulfi
deM
olec
ular
wei
ght:
76.1
CA
S: 7
5-15
-0D
ensi
ty:1
.263
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-110
°CB
oilin
g po
int:
46.2
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:35
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Ver
y hi
ghE
vapo
ratio
n ra
te:2
3L
og K
ow:1
.94
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Ha
Inf
H2O
0.
3-1.
721
18
7-37
mg
250-
830
20-9
6B
aran
owsk
a (1
965)
The
only
ava
ilabl
e st
udy
is th
at o
f Bar
anow
ska
(196
5) (i
n G
erm
an) w
ere
the
subj
ect p
lace
d on
e ha
nd in
an
aque
ous
carb
on d
isul
fide
solu
tion
for 1
hou
r. Th
e up
take
of t
he su
bsta
nce
was
mea
sure
d vi
a br
eath
mon
itorin
g.
The
repo
rted
Kp
valu
es ra
nge
betw
een
3·10
-2 a
nd 9
·10-2
cm
/h, s
ugge
stin
g "v
ery
high
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A28
App
endi
x A
Subs
tanc
e: C
arbo
n te
trach
lorid
eM
olec
ular
wei
ght:
153.
8C
AS:
56-
23-5
Den
sity
:1.5
94 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:-2
2.9°
CB
oilin
g po
int:
76.7
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:10
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:1
3L
og K
ow:2
.83
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Rat
Ab
StFu
ll3.
71
Nea
t24
2-4
2-4
1.4
52-2
10 µ
g0.
1321
Tsur
uta
(197
7)
Mou
Ab
0.5
Nea
t6
0.25
360
µg3.
149
0Ts
urut
a (1
975)
The
in v
itro
stud
y of
Tsu
ruta
(197
7) u
sed
phys
iolo
gica
l sal
ine
as th
e re
cept
or m
ediu
m, t
his i
s uns
uita
ble
for h
ighl
y lip
ophi
lic su
bsta
nces
.Ts
urut
a (1
975)
mea
sure
d ab
sorp
tion
by h
omog
eniz
ing
the
who
le a
nim
al.
Der
mal
upt
ake
of c
arbo
n te
trach
lorid
e ha
s als
o be
en sh
own
in h
uman
s (St
ewar
t et a
l. (1
964)
), ho
wev
er, t
hat s
tudy
do
es n
ot c
onta
in su
ffic
ient
dat
a to
cal
cula
te fl
ux o
f Kp.
The
pref
erre
d st
udy
is T
suru
ta (1
975)
, wer
e th
e ca
lcul
ated
Kp
valu
e su
gges
ts "
mod
erat
e" p
erm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A29
App
endi
x A
Subs
tanc
e: C
atec
hol
Mol
ecul
ar w
eigh
t:11
0.1
CA
S: 1
20-8
0-9
Den
sity
:1.3
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
2:47
Mel
ting
poin
t:10
4°C
Boi
ling
poin
t:24
5°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:6
60 P
a (a
t 104
°C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:0
.88
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
Fl20
0-32
00.
640.
01PH
D6
30.
524
0.4
1.6
0.98
Jung
et a
l. (2
003)
Hum
Ab
Fl20
0-32
00.
640.
01H
DP
60.
524
1.8
7.3
4.4
Jung
et a
l. (2
003)
Rat
Ba
Fl20
0-32
00.
640.
01PH
D6
0.5
240.
20.
810.
49Ju
ng e
t al.
(200
3)R
atB
aFl
200-
320
0.64
0.01
HD
P6
0.5
242
8.1
4.9
Jung
et a
l. (2
003)
Rat
Ba
Fl20
0-32
00.
640.
01Et
68
0.5
246.
928
17Ju
ng e
t al.
(200
3)R
atB
aFl
200-
320
0.64
0.01
Et6
2424
423.
52.
1Ju
ng e
t al.
(200
3)R
atB
aFl
200-
320
0.64
0.01
Et6
2472
494.
12.
5Ju
ng e
t al.
(200
3)R
atB
aFl
200-
320
0.64
0.01
Et6
424
2478
6.6
3.9
Jung
et a
l. (2
003)
Rat
Ba
Fl20
0-32
00.
640.
01Et
64
2424
554.
72.
8Ju
ng e
t al.
(200
3)R
atB
aFl
200-
320
0.64
0.01
Et40
924
2481
6.8
27Ju
ng e
t al.
(200
3)R
atB
aFl
200-
320
0.64
0.01
Et40
924
7281
6.9
27Ju
ng e
t al.
(200
3)
Rat
Ba
90.
18Et
40
324
2445
3.7
15Ju
ng e
t al.
(200
3)R
atB
a9
0.18
Et
403
2472
534.
418
Jung
et a
l. (2
003)
A n
umbe
r of d
iffer
ent e
xper
imen
ts y
ield
sim
ilar r
esul
ts.
The
hum
an in
vitr
o an
d ra
t in
vivo
exp
erim
ents
giv
e K
p va
lues
bet
wee
n 2·1
0-4an
d 7·
10-4
cm/h
, co
rres
pond
ing
to "
mod
erat
e" p
erm
eabi
lity.
It sh
ould
be
note
d th
at e
ither
eth
anol
or h
air d
ye c
hem
ical
s wer
e us
ed a
s veh
icle
s, th
is m
ay h
ave
alte
red
the
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A30
App
endi
x A
Subs
tanc
e: C
hlor
inat
ed b
iphe
nyls
, pol
y- (P
CB
)M
olec
ular
wei
ght:
291.
98 to
360
.86
CA
S: 1
336-
36-3
Den
sity
:1.4
to 1
.5 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:N
ot a
vaila
ble
Boi
ling
poin
t:34
0 to
375
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:6
.34
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
Swed
ish
cons
ensu
s doc
umen
t or T
LV d
ocum
enta
tion
is p
rese
nt.
Gar
ner e
t al.
(199
8) sh
owed
that
the
less
chl
orin
ated
PC
Bs p
enet
rate
the
skin
mor
e ra
pidl
y. H
owev
er th
e m
etab
olis
mis
mor
e ra
pid
for t
hese
smal
ler m
olec
ules
, res
ultin
g in
a h
ighe
r bod
y bu
rden
for t
he h
ighe
r chl
orin
ated
PC
Bs.
Dat
a on
four
con
gene
rs (s
ee m
ono-
, di-,
tetra
- and
hex
achl
orob
iphe
nyl)
sugg
ests
that
the
perm
eabi
lity
of P
CB
is "
extre
mel
y lo
w"
to "
very
low
".
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A31
App
endi
x A
Subs
tanc
e: C
hlor
o-1,
3-bu
tadi
ene,
2-;
chlo
ropr
ene
Mol
ecul
ar w
eigh
t:88
.5C
AS:
126
-99-
8D
ensi
ty:N
ot a
vaila
ble
Scie
ntifi
c ba
sis:
AoH
198
6:35
Mel
ting
poin
t:-1
30°C
Boi
ling
poin
t:59
.4°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:2
3 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:2.5
3 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
the
Swed
ish
crite
ria g
roup
(AoH
198
6) a
nd A
CG
IH (2
001)
an
old
stud
y (v
on O
ettin
gen
et a
l. (1
936)
)m
entio
ns th
at th
e su
bsta
nce
prob
ably
can
be
abso
rbed
thro
ugh
the
skin
in a
mou
nts l
arge
eno
ugh
to c
ause
acu
te e
ffec
ts.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A32
App
endi
x A
Subs
tanc
e: C
hlor
obip
heny
l, di
- (D
CB
)M
olec
ular
wei
ght:
Not
ava
ilabl
eC
AS:
255
12-4
2-9
Den
sity
:1.4
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
149°
CB
oilin
g po
int:
Not
ava
ilabl
eSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Ver
y lo
wE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:5.5
9 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Rat
Ba
1(0
.15
ml/k
g bw
)A
cN
eat (
0.4
mg/
kg b
w)
1848
336
85 (2
4h)
0.02
63.
5G
arne
r & M
atth
ews (
1998
)R
atB
a1
(0.1
5 m
l/kg
bw)
Ac
Nea
t (0.
4 m
g/kg
bw
)18
4833
666
(24h
)0.
022.
8G
arne
r et a
l. (2
006)
The
two
stud
ies b
y G
arne
r wer
e co
nduc
ted
in si
mila
r fas
hion
exc
ept f
or m
etho
d of
mea
surin
g ab
sorb
ed a
mou
nt.
This
was
don
e in
car
cass
(Gar
ner &
Mat
thew
s (19
98))
and
in u
rine
and
faec
es (G
arne
r et a
l. (2
006)
), re
spec
tivel
y.
The
two
stud
ies s
how
con
sist
ent r
esul
ts, w
ith th
e ca
lcul
ated
Kp
valu
es ra
ngin
g be
twee
n 2·
10-6
and
3·1
0-6 c
m/h
, sug
gest
ing
"ver
y lo
w"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A33
App
endi
x A
Subs
tanc
e: C
hlor
obip
heny
l, he
xa- (
HC
B)
Mol
ecul
ar w
eigh
t:36
0.9
CA
S: 2
6601
-64-
9D
ensi
ty:1
.8 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:20
1 to
202
°CB
oilin
g po
int:
Not
ava
ilabl
eSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Ext
rem
ely
low
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:7
.75
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Rat
Ba
1(0
.15
ml/k
g bw
)A
cN
eat (
0.4
mg/
kg b
w)
1848
336
9 (2
4h)
0.00
20.
38G
arne
r & M
atth
ews (
1998
)R
atB
a1
(0.1
5 m
l/kg
bw)
Ac
Nea
t (0.
4 m
g/kg
bw
)18
4833
619
(24h
)0.
0044
0.8
Gar
ner e
t al.
(200
6)
The
two
stud
ies b
y G
arne
r wer
e co
nduc
ted
in si
mila
r fas
hion
exc
ept f
or m
etho
d of
mea
surin
g ab
sorb
ed a
mou
nt.
This
was
don
e in
car
cass
(Gar
ner &
Mat
thew
s (19
98))
and
in u
rine
and
faec
es (G
arne
r et a
l. (2
006)
), re
spec
tivel
y.
The
two
stud
ies s
how
con
sist
ent r
esul
ts, w
ith th
e ca
lcul
ated
Kp
valu
es ra
ngin
g be
twee
n 2·
10-7
and
4·1
0-7 c
m/h
, sug
gest
ing
"ext
rem
ely
low
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A34
App
endi
x A
Subs
tanc
e: C
hlor
obip
heny
l, m
ono-
(MC
B)
Mol
ecul
ar w
eigh
t:N
ot a
vaila
ble
CA
S: 2
7323
-18-
8D
ensi
ty:1
.1 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:10
°CB
oilin
g po
int:
365°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Ver
y lo
wE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:4.5
8
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Rat
Ba
1(0
.15
ml/k
g bw
)Ac
Nea
t (0.
4 m
g/kg
bw
)18
4833
698
(24h
)0.
037
4.1
Gar
ner &
Mat
thew
s (19
98)
Rat
Ba
1(0
.15
ml/k
g bw
)Ac
Nea
t (0.
4 m
g/kg
bw
)18
4833
669
(24h
)0.
026
2.9
Gar
ner e
t al.
(200
6)
The
two
stud
ies b
y G
arne
r wer
e co
nduc
ted
in si
mila
r fas
hion
exc
ept f
or m
etho
d of
mea
surin
g ab
sorb
ed a
mou
nt.
This
was
don
e in
car
cass
(Gar
ner &
Mat
thew
s (19
98))
and
in u
rine
and
faec
es (G
arne
r et a
l. (2
006)
), re
spec
tivel
y.
The
two
stud
ies s
how
con
sist
ent r
esul
ts, w
ith th
e ca
lcul
ated
Kp
valu
es ra
ngin
g be
twee
n 3·
10-6
and
4·1
0-6 c
m/h
, sug
gest
ing
"ver
y lo
w"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A35
App
endi
x A
Subs
tanc
e: C
hlor
obip
heny
l, te
tra- (
TCB
)M
olec
ular
wei
ght:
292.
0C
AS:
269
14-3
3-0
Den
sity
:1.6
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
~170
°CB
oilin
g po
int:
~360
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Ext
rem
ely
low
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:6
.09
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Rat
Ba
1(0
.15
ml/k
g bw
)Ac
Nea
t (0.
4 m
g/kg
bw
)18
4833
637
(24h
)0.
0096
1.5
Gar
ner &
Mat
thew
s (19
98)
Rat
Ba
1(0
.15
ml/k
g bw
)Ac
Nea
t (0.
4 m
g/kg
bw
)18
4833
68
(24h
)0.
0019
0.3
Gar
ner e
t al.
(200
6)
The
two
stud
ies b
y G
arne
r wer
e co
nduc
ted
in si
mila
r fas
hion
exc
ept f
or m
etho
d of
mea
surin
g ab
sorb
ed a
mou
nt.
This
was
don
e in
car
cass
(Gar
ner &
Mat
thew
s (19
98))
and
in u
rine
and
faec
es (G
arne
r et a
l. (2
006)
), re
spec
tivel
y.
The
two
stud
ies s
how
rath
er c
onsi
sten
t res
ults
, with
the
calc
ulat
ed K
p va
lues
rang
ing
betw
een
2·10
-7 a
nd 1
·10-6
cm
/h, s
ugge
stin
g "e
xtre
mel
y lo
w"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A36
App
endi
x A
Subs
tanc
e: C
hlor
ocre
sol;
4-ch
loro
-3-m
ethy
lphe
nol
Mol
ecul
ar w
eigh
t:14
2.6
CA
S: 5
9-50
-7D
ensi
ty:0
.9 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:67
°CB
oilin
g po
int:
235°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:13
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:3
.10
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StEp
i2.
5In
fH
2O4
28
80.
355
022
0R
ober
ts e
t al.
(197
7)
GP
80.
2H
2O +
Gel
5% (1
0 m
g)19
2496
758.
739
And
erse
n et
al.
(198
5)G
P8
0.2
H2O
0.4%
(Sat
urat
ed. 0
.8 m
g)20
2496
545.
82.
3A
nder
sen
et a
l. (1
985)
GP
80.
2oi
l/ac
5% (1
0 m
g)20
2496
344
18A
nder
sen
et a
l. (1
985)
GP
80.
2PG
5% (1
0 m
g)20
2496
354
18A
nder
sen
et a
l. (1
985)
In th
e ex
perim
ents
by
Rob
erts
et a
l. (1
977)
, epi
derm
al sh
eets
wer
e se
para
ted
by e
xpos
ing
skin
to a
mm
onia
vap
our
for 3
0 m
in. A
mm
onia
is w
ell k
now
n to
cau
se se
vere
skin
dam
age
Am
shel
et a
l. (2
000)
. The
alk
alin
e na
ture
of
am
mon
ia q
uick
ly sa
poni
fies t
he e
pide
rmal
fats
, thu
s des
troyi
ng th
e pr
otec
tive
stru
ctur
e of
the
epid
erm
is.
Ther
efor
e, th
e m
etho
d us
ed b
y R
ober
ts e
t al.
(197
7) is
like
ly to
resu
lt in
seve
re o
vere
stim
ates
of t
he fl
ux a
nd K
pva
lue
of u
ndam
aged
skin
.
The
pref
erre
d in
viv
o ex
perim
ent i
s by
And
erse
n et
al.
(198
5) u
sing
wat
er a
s veh
icle
.
The
repo
rted
Kp
valu
e fo
r sat
urat
ed c
hlor
ophe
nol i
n w
ater
of 6
·10-4
cm
/h, s
ugge
sts "
mod
erat
e" p
erm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A37
App
endi
x A
Subs
tanc
e: C
hlor
oeth
anol
, 2-
Mol
ecul
ar w
eigh
t:80
.5C
AS:
107
-07-
3D
ensi
ty:1
.201
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-89°
CB
oilin
g po
int:
130°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.6
6 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.0
3
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
No
docu
men
tatio
n by
the
Swed
ish
cons
ensu
s gro
up o
r AC
GIH
was
foun
d fo
r thi
s sub
stan
ce.
The
acut
e de
rmal
toxi
city
is e
xtre
mel
y hi
gh. T
hus,
appl
icat
ion
of 2
ml o
n th
e sk
in c
ause
d 80
% m
orta
lity
in 1
hou
r and
a d
ose
of 1
ml c
ause
d 80
-100
% m
orta
lity
with
in 1
wee
k in
gui
nea
pigs
(Wah
lber
g et
al.
(197
9)).
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A38
App
endi
x A
Subs
tanc
e: C
hlor
ofor
m; t
richl
orom
etha
neM
olec
ular
wei
ght:
119.
4C
AS:
67-
66-3
Den
sity
:1.4
98 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:-6
3.7°
CB
oilin
g po
int:
61.7
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:18
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Ver
y hi
ghE
vapo
ratio
n ra
te:0
.09
Log
Kow
:1.9
7
Sp
Loc
C
ell
L
( µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
Fl30
00.
641
H2O
400
µg/l
(0.6
2 µg
/cm
²)4
44.
1 (2
h)32
00.
013
Dic
k et
al.
(199
5)H
umA
bFl
300
0.64
0.05
H2O
0.9
(70
µg/c
m²)
44
6.5
(2h)
262.
3D
ick
et a
l. (1
995)
Hum
Ab
Fl20
0-40
00.
2In
fH
2O14
0-29
0 µg
/l19
66
1400
Nak
ai e
t al.
(199
9)H
umA
bFl
200-
400
0.2
Inf
H2O
140-
290
µg/l
196
617
00N
akai
et a
l. (1
999)
HG
PW
B~3
00In
fH
2O19
-52
ppb
61.
22-
4w13
00B
ogen
et a
l. (1
992)
HR
WB
460
Inf
H2O
0.
443
0.5
0.5
20 m
g29
0013
0Is
lam
et a
l. (1
995)
HR
WB
510
Inf
H2O
0.
444
0.5
610
mg
900
40Is
lam
et a
l. (1
996)
HR
Ba
5.46
0.35
Nea
t3
1 m
in6
2.8
mg
210
3100
0Is
lam
et a
l. (1
999)
HR
Ba
5.46
0.35
Nea
t3
3 m
in6
3.5
mg
8513
000
Isla
m e
t al.
(199
9)H
RB
a5.
460.
35N
eat
38
min
613
mg
120
1800
0Is
lam
et a
l. (1
999)
Hum
Arm
3.1
0.05
H2O
1
(50
µg)
38
728.
21.
70.
17D
ick
et a
l. (1
995)
Hum
Arm
3.1
0.05
Et
5 (2
50 µ
g)4
872
1.7
0.34
0.17
Dic
k et
al.
(199
5)H
umW
BIn
fH
2O40
µg/
l6
0.5
2.5
150
0.00
06X
u et
al.
(200
5)H
umW
BIn
fH
2O60
-150
µg/
l(4
0-97
ppb
)9
0.5
~112
-44
µg60
00.
0036
-0.0
09C
orle
y et
al.
(200
0)M
ouA
b2.
90.
5N
eat
100.
2517
00 µ
g16
2400
Tsur
uta
(197
5)
The
expe
rimen
t usi
ng e
than
ol a
s veh
icle
is d
isre
gard
ed a
s ski
n pe
rmea
bilit
y m
ay b
e af
fect
ed.
The
in v
itro
Kp
valu
e of
Dic
k et
al.
(199
5) is
cal
cula
ted
durin
g th
e fir
st 2
h of
exp
osur
e, d
ue to
pos
sibl
e de
plet
ion.
The
in v
ivo
stud
y of
Dic
k et
al.
(199
5) w
as p
erfo
rmed
uno
cclu
ded,
hen
ce th
e lo
w a
bsor
ptio
n/K
p va
lues
.Ts
urut
a (1
975)
mea
sure
d ab
sorp
tion
by h
omog
eniz
ing
the
who
le a
nim
al. T
his m
etho
d m
ay se
vere
ly u
nder
estim
ate
skin
per
mea
bilit
y.Th
e pr
efer
red
expe
rimen
t is t
hat o
f Isl
am e
t al.
(199
9), u
sing
nea
t chl
orof
orm
and
hai
rless
rat i
n vi
vo a
nd th
e lo
nges
tex
posu
re d
urat
ion
(8 m
in).
The
Kp
valu
e of
1·10
-2 su
gges
t "ve
ry h
igh"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A39
App
endi
x A
Subs
tanc
e: C
hrom
ate,
pot
assi
um d
i-M
olec
ular
wei
ght:
294.
2C
AS:
777
8-50
-9D
ensi
ty:2
.676
g/c
m³
Scie
ntifi
c ba
sis:
AoH
200
0:22
Mel
ting
poin
t:39
8°C
Boi
ling
poin
t:50
0°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:N
ot a
vaila
ble
Skin
per
mea
bilit
y: V
ery
low
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:-
3.59
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StFu
ll0.
7/1.
855
6 µl
/cm
²H2O
0.5%
(0.0
34 M
)3
190
190
0.00
014
0.00
019
Gam
mel
gaar
d et
al.
(199
2)
Hum
WB
~130
00In
fH
2O0.
022
43
960.
068
0.00
015
Cor
bett
et a
l. (1
997)
Onl
y on
e st
udy
was
foun
d on
pot
assi
um d
ichr
omat
e. In
Gam
mel
gaar
d et
al.
(199
2), h
uman
abd
omin
alsk
in w
as e
xpos
ed to
aqu
eous
solu
tion.
The
repo
rted
Kp
valu
e su
gges
ts "
extre
mel
y lo
w"
perm
eabi
lity.
It sh
ould
be
note
d th
at th
e re
porte
d K
p va
lue
of so
dium
chr
omat
e is
two
orde
rs o
f mag
nitu
de h
ighe
r.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A40
App
endi
x A
Subs
tanc
e: C
hrom
ate,
sodi
um d
i-M
olec
ular
wei
ght:
162.
0C
AS:
777
5-11
-3D
ensi
ty:2
.7 g
/cm
³Sc
ient
ific
basi
s: A
oH 2
000:
22M
eltin
g po
int:
792°
CB
oilin
g po
int:
Not
ava
ilabl
eSk
in n
otat
ion:
No
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Hig
hE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:Not
ava
ilabl
e
Sp
Loc
C
ell
L
( µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
GP
Ba
FlFu
ll3.
1H
2O5.
5 (0
.034
M)
1048
4811
6.2
Wah
lber
g (1
965)
GP
Ba
Full
3.1
1H
2O2.
8 (0
.017
M)
524
2419
5.2
Wah
lber
g (1
970)
GP
Ba
Full
3.1
1H
2O13
(0.
080
M)
524
2415
20W
ahlb
erg
(197
0)G
PB
aFu
ll3.
11
H2O
39 (0
.239
M)
524
2414
54W
ahlb
erg
(197
0)G
PB
aFu
ll3.
11
H2O
65 (0
.398
M)
524
2412
75W
ahlb
erg
(197
0)H
umA
bFl
Full
3.1
H2O
5.5
(0.0
34 M
)10
4848
3.3
1.8
Wah
lber
g (1
965)
Hum
Ab
Full
3.1
1H
2O2.
8 (0
.017
M)
524
248.
72.
4W
ahlb
erg
(197
0)H
umA
bFu
ll3.
11
H2O
13 (
0.08
0 M
)5
2424
1317
Wah
lber
g (1
970)
Hum
Ab
Full
3.1
1H
2O39
(0.2
39 M
)5
2424
1454
Wah
lber
g (1
970)
Hum
Ab
Full
3.1
1H
2O65
(0.3
98 M
)5
2424
1597
Wah
lber
g (1
970)
GP
H2O
2.8-
65 (0
.017
-0.3
98 M
)20
55
17-1
84.
9-12
0W
ahlb
erg
et a
l. (1
965)
GP
Ba
3.1
H2O
5.5
(0.0
34 M
)10
4848
126.
8W
ahlb
erg
(196
5)G
PB
a1
H2O
2.8
(0.0
17 M
)5
2424
184.
9W
ahlb
erg
et a
l. (1
963)
GP
Ba
1H
2O13
(0.
080
M)
524
2413
17W
ahlb
erg
et a
l. (1
963)
GP
Ba
1H
2O42
(0.2
61 M
)5
2424
2611
0W
ahlb
erg
et a
l. (1
963)
GP
Ba
1H
2O65
(0.3
98 M
)5
2424
1812
0W
ahlb
erg
et a
l. (1
963)
Hum
Arm
H2O
1.
6 (0
.01M
)9
11
6.9
1.1
Bar
anow
ska-
Dut
kiew
icz
(198
1)H
umA
rmH
2O
16 (0
.1M
)9
11
4.1
6.5
Bar
anow
ska-
Dut
kiew
icz
(198
1)H
umA
rmH
2O
32 (0
.2M
)9
11
3.1
10B
aran
owsk
a-D
utki
ewic
z (1
981)
Hum
an a
nd g
uine
a pi
g da
ta su
gges
t "hi
gh"
perm
eabi
lity
of so
dium
dic
hrom
ate,
with
Kp
valu
es b
etw
een
3·10
-4 a
nd 3
·10-3
cm
/h.
It sh
ould
be
note
d th
at th
e re
porte
d K
p va
lue
for p
otas
sium
dic
hrom
ate
is tw
o or
ders
of m
agni
tude
low
er.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A41
App
endi
x A
Subs
tanc
e: C
hrom
ic c
hlor
ide
Mol
ecul
ar w
eigh
t:15
8.4
CA
S: 1
0025
-73-
7D
ensi
ty:2
.76
g/cm
³Sc
ient
ific
basi
s: A
oH 2
000:
22M
eltin
g po
int:
1152
°CB
oilin
g po
int:
Not
ava
ilabl
eSk
in n
otat
ion:
No
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Hig
hE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:1.1
6 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
GP
Ba
Full
3.1
1H
2O2.
7 (0
.017
M)
524
2420
5.5
Wah
lber
g (1
970)
GP
Ba
Full
3.1
1H
2O13
(0.
080
M)
524
2420
26W
ahlb
erg
(197
0)G
PB
aFu
ll3.
11
H2O
38(0
.239
M)
524
2421
81W
ahlb
erg
(197
0)G
PB
aFu
ll3.
11
H2O
63(0
.398
M)
524
2415
91W
ahlb
erg
(197
0)G
PB
aFl
Full
3.1
H2O
2.7
(0.0
17 M
)10
4848
154
Wah
lber
g (1
965)
GP
Ba
FlFu
ll3.
1H
2O13
(0.0
80 M
)10
4848
1013
Wah
lber
g (1
965)
GP
Ba
FlFu
ll3.
1H
2O20
(0.1
26 M
)10
4848
1224
Wah
lber
g (1
965)
GP
Ba
FlFu
ll3.
1H
2O38
(0.2
39 M
)10
4848
1350
Wah
lber
g (1
965)
GP
Ba
FlFu
ll3.
1H
2O41
(0.2
61 M
)10
4848
1352
Wah
lber
g (1
965)
Hum
Ab
Full
3.1
1H
2O2.
7 (0
.017
M)
524
2415
4W
ahlb
erg
(197
0)H
umA
bFu
ll3.
11
H2O
13 (
0.08
0 M
)5
2424
1316
Wah
lber
g (1
970)
Hum
Ab
Full
3.1
1H
2O38
(0.2
39 M
)5
2424
1140
Wah
lber
g (1
970)
Hum
Ab
Full
3.1
1H
2O63
(0.3
98 M
)5
2424
1275
Wah
lber
g (1
970)
N
o da
ta a
vaila
ble
The
calc
ulat
ed K
p va
lues
(tw
o st
udie
s onl
y) o
n ch
rom
ate
chlo
ride
are
cons
iste
nt.
The
pref
erre
d ex
perim
ents
are
thos
e on
hum
an sk
in, w
ith c
alcu
late
d K
p va
lues
cor
resp
ondi
ng to
"hi
gh"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A42
App
endi
x A
Subs
tanc
e: C
obal
tM
olec
ular
wei
ght:
58.9
CA
S: 7
440-
48-4
Den
sity
:8.9
2 g/
cm³
Scie
ntifi
c ba
sis:
AoH
200
4:16
Mel
ting
poin
t:14
95°C
Boi
ling
poin
t:28
70°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:N
ot a
vaila
ble
Skin
per
mea
bilit
y: E
xtre
mel
y lo
wE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.2
3 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StFu
ll1
NaC
l50
724
241.
550.
0025
0.01
2La
rese
Filo
n et
al.
(200
4)
Hum
Ha
390
Inf
Pow
der
5-15
% (0
.05-
0.25
mg/
m³)
41.
572
0.00
03-0
.000
90.
04Sc
anse
tti e
t al.
(199
4)
The
two
foun
d st
udie
s rep
ort f
airly
con
sist
ent K
p va
lues
, ran
ging
bet
wee
n 3·
10-7
and
3·1
0-8 c
m/h
.
The
pref
erre
d st
udy
is th
at o
f Sca
nset
ti et
al.
(199
4). T
he K
p va
lue
corr
espo
nds t
o "e
xtre
mel
y lo
w"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A43
App
endi
x A
Subs
tanc
e: C
obal
t dic
hlor
ide
Mol
ecul
ar w
eigh
t:12
9.8
CA
S: 7
646-
79-9
Den
sity
:3.3
56 g
/cm
³Sc
ient
ific
basi
s: A
oH 2
004:
16M
eltin
g po
int:
735°
CB
oilin
g po
int:
1049
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:5.3
kPa
(at 7
70°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.8
5 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
GP
Ba
FlFu
ll3.
1H
2O
5.0
(0.0
85M
)10
4848
126.
2W
ahlb
erg
(196
5)H
umA
b/B
rFl
Full
3.1
H2O
5.
0 (0
.085
M)
1048
484.
42.
2W
ahlb
erg
(196
5)
GP
Ba
3.1
H2O
5.
0 (0
.085
M)
1048
4813
-22
6.6-
11W
ahlb
erg
(196
5)H
amB
a0.
1N
aCl/E
t20
448
4860
Lacy
et a
l. (1
996)
The
stud
y by
Lac
y et
al.
(199
6) g
ives
no
area
of e
xpos
ure,
ther
efor
e no
Kp
or fl
ux v
alue
can
be
calc
ulat
ed.
The
high
abs
orpt
ion
show
s tha
t cob
alt d
ichl
orid
e re
adily
pen
etra
tes t
he sk
in.
The
thre
e st
udie
s of W
ahlb
erg
(196
5) sh
ow c
onsi
sten
t res
ults
. Th
e pr
efer
red
expe
rimen
t is t
hat w
ith h
uman
skin
. The
Kp
valu
e co
rres
pond
s to
"mod
erat
e" p
erm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A44
App
endi
x A
Subs
tanc
e: C
reso
l, m
-M
olec
ular
wei
ght:
108.
1C
AS:
108
-39-
4D
ensi
ty:1
.034
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
8:25
Mel
ting
poin
t:11
.5°C
Boi
ling
poin
t:20
2.2°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:13
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: V
ery
high
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:1
.96
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StEp
i2.
5In
fH
2O4
28
80.
2515
060
Rob
erts
et a
l. (1
977)
SnB
aSt
Full
1.8
PBS
1-3
46
699
9.9-
30Ito
h et
al.
(199
0)
N
o da
ta a
vaila
ble
In th
e st
udy
by It
oh e
t al.
(199
0), s
nake
skin
was
use
d. A
s thi
s is v
ery
diff
eren
t fro
m h
uman
skin
, thi
s dat
a is
dis
rega
rded
.
The
pref
erre
d st
udy
is th
at o
f Rob
erts
et a
l. (1
977)
, whe
re th
e re
porte
d K
p va
lue
of 2
·10-2
cm
/h su
gges
t "hi
gh"
perm
eabi
lity.
It sh
ould
be
note
d th
at in
the
expe
rimen
ts b
y R
ober
ts e
t al.
(197
7), e
pide
rmal
shee
ts w
ere
sepa
rate
d by
exp
osin
g sk
in to
am
mon
ia v
apou
r fo
r 30
min
. Am
mon
ia is
wel
l kno
wn
to c
ause
seve
re sk
in d
amag
e A
msh
el e
t al.
(200
0). T
he a
lkal
ine
natu
re
of a
mm
onia
qui
ckly
sapo
nifie
s the
epi
derm
al fa
ts, t
hus d
estro
ying
the
prot
ectiv
e st
ruct
ure
of th
e ep
ider
mis
. Th
eref
ore,
the
met
hod
used
by
Rob
erts
et a
l. (1
977)
is li
kely
to re
sult
in se
vere
ove
rest
imat
es o
f the
flux
and
Kp
valu
e of
und
amag
ed sk
in.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A45
App
endi
x A
Subs
tanc
e: C
reso
l, o-
Mol
ecul
ar w
eigh
t:10
8.1
CA
S: 9
5-48
-7D
ensi
ty:1
.048
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
8:25
Mel
ting
poin
t:30
.9°C
Boi
ling
poin
t:19
1°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:3
3 Pa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
Ver
y hi
ghE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:1.9
5
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StEp
i2.
5In
fH
2O4
28
80.
2516
064
Rob
erts
et a
l. (1
977)
N
o da
ta a
vaila
ble
Onl
y on
e st
udy
was
foun
d on
o-c
reso
l. Th
e st
udy
by R
ober
ts e
t al.
(197
7) re
porte
da
Kp
valu
e of
2·1
0-2 c
m/h
, sug
gest
ing
"hig
h" p
erm
eabi
lity.
It sh
ould
be
note
d th
at in
the
expe
rimen
ts b
y R
ober
ts e
t al.
(197
7), e
pide
rmal
shee
ts w
ere
sepa
rate
d by
exp
osin
g sk
in to
am
mon
ia v
apou
r fo
r 30
min
. Am
mon
ia is
wel
l kno
wn
to c
ause
seve
re sk
in d
amag
e A
msh
el e
t al.
(200
0). T
he a
lkal
ine
natu
re
of a
mm
onia
qui
ckly
sapo
nifie
s the
epi
derm
al fa
ts, t
hus d
estro
ying
the
prot
ectiv
e st
ruct
ure
of th
e ep
ider
mis
. Th
eref
ore,
the
met
hod
used
by
Rob
erts
et a
l. (1
977)
is li
kely
to re
sult
in se
vere
ove
rest
imat
es o
f the
flux
and
Kp
valu
e of
und
amag
ed sk
in.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A46
App
endi
x A
Subs
tanc
e: C
reso
l, p-
Mol
ecul
ar w
eigh
t:10
8.1
CA
S: 1
06-4
4-5
Den
sity
:1.0
34 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
998:
25M
eltin
g po
int:
32 to
34°
CB
oilin
g po
int:
201.
8°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:1
5 Pa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
Ver
y hi
ghE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:1.9
4
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StEp
i2.
5In
fH
2O4
28
80.
2718
072
Rob
erts
et a
l. (1
977)
N
o da
ta a
vaila
ble
Onl
y on
e st
udy
was
foun
d on
o-c
reso
l. Th
e st
udy
by R
ober
ts e
t al.
(197
7) re
porte
da
Kp
valu
e of
2·1
0-2 c
m/h
, sug
gest
ing
"hig
h" p
erm
eabi
lity.
It sh
ould
be
note
d th
at in
the
expe
rimen
ts b
y R
ober
ts e
t al.
(197
7), e
pide
rmal
shee
ts w
ere
sepa
rate
d by
exp
osin
g sk
in to
am
mon
ia v
apou
r fo
r 30
min
. Am
mon
ia is
wel
l kno
wn
to c
ause
seve
re sk
in d
amag
e A
msh
el e
t al.
(200
0). T
he a
lkal
ine
natu
re
of a
mm
onia
qui
ckly
sapo
nifie
s the
epi
derm
al fa
ts, t
hus d
estro
ying
the
prot
ectiv
e st
ruct
ure
of th
e ep
ider
mis
. Th
eref
ore,
the
met
hod
used
by
Rob
erts
et a
l. (1
977)
is li
kely
to re
sult
in se
vere
ove
rest
imat
es o
f the
flux
and
Kp
valu
e of
und
amag
ed sk
in.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A47
App
endi
x A
Subs
tanc
e: C
yana
mid
e, h
ydro
gen
Mol
ecul
ar w
eigh
t:42
.0C
AS:
420
-04-
2D
ensi
ty:1
.06
g/cm
³Sc
ient
ific
basi
s: A
oH 1
999:
25M
eltin
g po
int:
42°C
Boi
ling
poin
t:26
0°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:N
ot a
vaila
ble
Skin
per
mea
bilit
y: H
igh
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:-
0.82
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Arm
161
H2O
1% (1
0mg)
66
487.
7 (2
.3 m
g)24
24M
erts
chen
k et
al.
(199
1)
The
only
stud
y fo
und
on c
yana
mid
e w
as th
at b
y M
erts
chen
k et
al.
(199
1)w
here
the
calc
ulat
ed K
p va
lue
corr
espo
nds t
o "h
igh"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A48
App
endi
x A
Subs
tanc
e: C
yclo
hexa
none
Mol
ecul
ar w
eigh
t:98
.1C
AS:
108
-94-
1D
ensi
ty:0
.947
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
9:25
Mel
ting
poin
t:-4
7°C
Boi
ling
poin
t:15
5.6°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.6
9 kP
a (a
t 25°
C)
Skin
per
mea
bilit
y: L
owE
vapo
ratio
n ra
te:0
.23
Log
Kow
:0.8
1
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Ha
Inf
Nea
t3
0.5
720.
5956
Mra
z et
al.
(199
4)
A si
ngle
hum
an in
viv
o st
udy
was
foun
d (M
raz
et a
l. (1
994)
).Th
e flu
x w
as o
btai
ned
by a
naly
zing
the
urin
ary
excr
etio
n of
1,4
-cyc
lohe
xane
diol
afte
r bot
h de
rmal
and
inha
latio
nal e
xpos
ure.
The
calc
ulat
ed K
p va
lue
of 6
·10-5
cm
/h, s
ugge
sts "
low
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A49
App
endi
x A
Subs
tanc
e: D
i-(2-
ethy
lhex
yl)p
htha
late
(DEH
P)M
olec
ular
wei
ght:
390.
6C
AS:
117
-81-
7D
ensi
ty:0
.973
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
3:36
Mel
ting
poin
t:-5
0°C
Boi
ling
poin
t:28
6.9°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:1 P
a (a
t 20°
C)
Skin
per
mea
bilit
y: E
xtre
mel
y lo
wE
vapo
ratio
n ra
te:<
0.00
5L
og K
ow:7
.60
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
GP
Ba
Fl20
00.
640.
01A
c0.
895
2424
6.1
0.4
0.03
5N
g et
al.
(199
2)G
PB
aFl
200
0.64
0.01
Ac
0.89
524
245
0.33
0.02
9N
g et
al.
(199
2)G
PB
aFl
200
0.64
0.01
Ac
3.8
524
242.
40.
160.
06N
g et
al.
(199
2)G
PB
aFl
200
0.64
0.01
Ac
7.8
524
242.
50.
160.
12N
g et
al.
(199
2)H
umSt
Epi
0.64
/1.0
Nea
t4
3232
1-2
0.00
1110
0B
arbe
r et a
l. (1
992)
Hum
Ab
StEp
i1.
80.
5N
eat
972
723.
10.
057
5.6
Scot
t et a
l. (1
987)
Pig
Full
100.
05Et
3.7
58
80.
10.
0088
0.00
32W
este
r et a
l. (1
998d
)R
atSt
Full
0.64
/1.0
Nea
t11
3232
1-2
0.00
4342
0B
arbe
r et a
l. (1
992)
Rat
Ba
FlEp
i0.
640.
05A
c1.
68
7272
2.58
519.
51.
5Pe
lling
et a
l. (1
998)
Rat
Ba
FlD
erm
0.64
0.05
Ac
1.6
1172
721.
175.
60.
980.
15Pe
lling
et a
l. (1
998)
Rat
Ba
FlEp
i0.
640.
05A
c1.
69
7272
2.47
1.2
0.13
0.02
1Pe
lling
et a
l. (1
998)
Rat
Ba
FlD
erm
0.64
0.05
Ac
1.6
972
720.
911.
70.
480.
076
Pelli
ng e
t al.
(199
8)R
atB
aSt
Epi
1.8
0.5
Nea
t9
5353
3.9
0.23
22Sc
ott e
t al.
(198
7)
GP
Ba
80.
1A
c 9.
54
2424
130.
670.
63C
hu e
t al.
(199
6)G
PB
a8
0.1
Ac
8.6
424
4819
0.97
0.83
Chu
et a
l. (1
996)
GP
Ba
80.
1A
c 35
424
168
190.
983.
5C
hu e
t al.
(199
6)G
PB
a8
0.1
Ac
424
2433
69.
70.
512.
1C
hu e
t al.
(199
6)G
PB
a4
0.05
Ac
4.2
524
168
532.
81.
2N
g et
al.
(199
2)H
umA
rm10
0.05
Et
3.7
624
168
1.8
0.03
80.
014
Wes
ter e
t al.
(199
8d)
Rat
Ba
15Fi
lm40
0mg
424
240.
10.
0025
0.24
Dei
sing
er e
t al.
(199
8)R
atB
a1.
35-
8 m
g/cm
²3
168
168
70.
034
3.3
Elsi
si e
t al.
(198
9)
Rep
orte
d da
ta
In v
itro
In v
ivo
A50
App
endi
x A
The
derm
al a
bsor
ptio
n of
DEH
P sh
ows h
uge
varia
bilit
y be
twee
n st
udie
s with
Kp
valu
es ra
ngin
g fr
om 1·
10-7
to 2
·10-5
cm
/h
(dat
a w
ith n
eat D
EHP
only
).Sc
ott e
t al.
(198
7) u
sed
phys
iolo
gica
l sal
ine/
etha
nol (
50/5
0) a
s rec
epto
r med
ium
. The
eth
anol
may
seve
rely
aff
ect s
kin
perm
eabi
lity.
The
pref
erre
d st
udy
is th
at o
f Bar
ber e
t al.
(199
2) w
ho u
sed
buff
ered
isot
onic
wat
er w
ith a
n ad
ditio
n of
po
lyet
hyle
ne g
lyco
l 20
oley
l eth
er to
ach
ieve
suff
icie
nt so
lubi
lity
of D
EHP
in th
e re
cept
or m
ediu
m.
The
Kp
valu
e of
1·1
0-7 c
m/h
for h
uman
skin
cor
resp
onds
to "
extre
mel
y lo
w"
perm
eabi
lity.
Ase
ssm
ent
A51
App
endi
x A
Subs
tanc
e: D
ibut
yl p
htha
late
(DB
P)M
olec
ular
wei
ght:
278.
3C
AS:
84-
74-2
Den
sity
:1.0
43 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
983:
36M
eltin
g po
int:
-35°
CB
oilin
g po
int:
340°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:<10
Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Ver
y lo
wE
vapo
ratio
n ra
te:<
0.00
5L
og K
ow:4
.50
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
HR
Ba
StFu
ll1.
8In
fN
eat
924
240.
3739
Paya
n et
al.
(200
1)H
umA
bSt
Epi
1.8
0.5
Nea
t15
3030
2.9
0.02
30.
07Sc
ott e
t al.
(198
7)H
umLe
gSt
7.1
0.5
Ac
202
4848
3.1
0.2
0.4
Sher
ertz
et a
l. (1
988)
Mou
StFu
ll7.
10.
5A
c20
348
482.
333
8.5
17Sh
erer
tz e
t al.
(198
8)R
atB
aSt
Full
1.8
Inf
Nea
t9
2424
0.25
26Pa
yan
et a
l. (2
001)
Rat
Ba
StEp
i1.
80.
5N
eat
98
80.
40.
99.
3Sc
ott e
t al.
(198
7)
Hum
Arm
14-1
62-
6PG
+ H
2OSa
tura
ted
126
652
03.
8H
aged
orn-
Lew
eke
et a
l. (1
995)
Rat
Ba
100.
1N
eat
872
7274
1.1
110
Paya
n et
al.
(200
1)R
atB
a10
0.1
Nea
t8
4848
631.
314
0Pa
yan
et a
l. (2
001)
Rat
Ba
100.
1N
eat
824
2431
1.2
130
Paya
n et
al.
(200
1)R
atB
a10
0.1
Nea
t8
88
3.3
0.38
40Pa
yan
et a
l. (2
001)
Rat
Ba
100.
1N
eat
84
41.
90.
3840
Paya
n et
al.
(200
1)R
atB
a10
0.1
Nea
t3
22
1.1
0.57
60Pa
yan
et a
l. (2
001)
Rat
Ba
100.
1N
eat
31
10.
50.
5760
Paya
n et
al.
(200
1)R
atB
a10
0.1
Nea
t3
0.5
0.5
0.3
0.57
60Pa
yan
et a
l. (2
001)
The
mos
t rel
evan
t stu
dy is
that
of S
cott
et a
l. (1
987)
, usi
ng h
uman
skin
in v
itro.
The
othe
r stu
dies
use
d ro
dent
skin
and
/or v
ehic
les (
acet
one,
pro
pyle
ne g
lyco
l) th
at m
ay a
ffec
t ski
n pe
rmea
bilit
y.
The
Kp
valu
e of
2·1
0-6 c
m/h
for h
uman
skin
cor
resp
onds
to "
very
low
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A52
App
endi
x A
Subs
tanc
e: D
ichl
oroe
than
e, 1
,2-
Mol
ecul
ar w
eigh
t:99
.0C
AS:
107
-06-
2D
ensi
ty:1
.253
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
1:21
Mel
ting
poin
t:-3
5.3°
CB
oilin
g po
int:
83.5
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:8.7
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Hig
hE
vapo
ratio
n ra
te:6
.5L
og K
ow:1
.48
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Rat
Ab
StFu
ll3.
71
Nea
t27
1-3
1-3
0.6
1-9
mg
810
00Ts
urut
a (1
977)
Mou
Ab
2.9
0.5
Nea
t3
0.3
2100
µg
2328
00Ts
urut
a (1
975)
Phys
iolo
gica
l sal
ine
was
use
d as
rece
ptor
med
ium
in th
e in
vitr
o st
udy,
this
may
resu
lt in
und
eres
timat
es o
f flu
x an
d K
p.Th
e in
viv
o st
udy
with
mic
e is
pre
ferr
ed.
The
Kp
valu
e of
2·1
0-3 c
orre
spon
ds to
"hi
gh"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A53
App
endi
x A
Subs
tanc
e: D
ieth
anol
amin
eM
olec
ular
wei
ght:
105.
1C
AS:
111
-42-
2D
ensi
ty:1
.09
g/cm
³Sc
ient
ific
basi
s: A
oH 1
992:
47M
eltin
g po
int:
28°C
Boi
ling
poin
t:26
8.8°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:<2
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: L
owE
vapo
ratio
n ra
te:<
0.00
1L
og K
ow:-
1.43
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
FlFu
ll1.
80.
04N
eat
66
63.
20.
10.
055.
7Su
n et
al.
(199
6)H
umB
rFl
Full
1.8
0.1
H2O
20
mg/
cm²
66
62.
40.
20.
3413
Sun
et a
l. (1
996)
Hum
Br
St~1
000
10.
2H
2O1%
2224
24~6
0.4
0.5
0.55
Bra
in e
t al.
(200
5)H
umB
rSt
~100
01
0.2
H2O
1%20
2424
~80.
10.
088
0.09
6B
rain
et a
l. (2
005)
Mou
FlFu
ll1.
80.
04N
eat
36
60.
91.
30.
4246
Sun
et a
l. (1
996)
Mou
FlFu
ll1.
80.
1H
2O
20 m
g/cm
²3
66
0.8
6.7
7.6
290
Sun
et a
l. (1
996)
Rab
FlFu
ll1.
80.
04N
eat
36
61.
30
0.01
0.9
Sun
et a
l. (1
996)
Rab
FlFu
ll1.
80.
1H
2O
20 m
g/cm
²3
66
1.5
2.8
3.4
130
Sun
et a
l. (1
996)
Rat
FlFu
ll1.
80.
04N
eat
36
60.
60
0.02
1.8
Sun
et a
l. (1
996)
Rat
FlFu
ll1.
80.
1H
2O
20 m
g/cm
²3
66
0.8
0.6
0.6
23Su
n et
al.
(199
6)
Mou
10.
0295
% E
t 13
448
4858
2.4
3.2
Mat
hew
s et a
l. (1
997)
Mou
10.
0295
% E
t 38
548
4834
1.4
5.4
Mat
hew
s et a
l. (1
997)
Mou
10.
0295
% E
t 14
05
4848
2.9
0.12
1.6
Mat
hew
s et a
l. (1
997)
Rat
20.
0395
% E
t 14
548
482.
90.
091
0.13
Mat
hew
s et a
l. (1
997)
Rat
20.
0395
% E
t 50
548
4811
0.33
1.6
Mat
hew
s et a
l. (1
997)
Rat
20.
0395
% E
t 18
04
4848
160.
519.
2M
athe
ws e
t al.
(199
7)
The
in v
ivo
stud
ies (
Mat
hew
s et a
l. (1
997)
) use
d 95
% e
than
ol a
s veh
icle
and
can
not b
e us
ed.
The
repo
rted
perm
eabi
litie
s usi
ng n
eat d
ieth
anol
amin
e ar
e co
ntra
dict
ive
with
Kp
valu
es ra
ngin
g fr
om 1
·10-6
to 4
·10-5
cm
/h.
The
perm
eabi
lity
of d
ieth
anol
amin
e in
wat
er so
lutio
n is
hig
her w
ith K
p va
lues
bet
wee
n 1·
10-5
and
8·1
0-4 c
m/h
. Th
e pr
efer
red
stud
y is
that
of B
rain
et a
l. (2
005)
who
app
lied
exce
ss v
olum
e of
1%
die
than
olam
ine
in w
ater
usi
ng a
stat
ic
diff
usio
n ce
ll an
d fr
esh
or fr
ozen
hum
an b
reas
t.Th
e K
p va
lues
of 9
·10-6
(fre
sh sk
in) a
nd 5
·10-5
(fro
zen
skin
) cm
/h c
orre
spon
d to
"lo
w"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A54
App
endi
x A
Subs
tanc
e: D
ieth
yl p
htha
late
(DEP
)M
olec
ular
wei
ght:
222.
2C
AS:
84-
66-2
Den
sity
:1.1
18 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:-3
°CB
oilin
g po
int:
298°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:0.3
Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Low
Eva
pora
tion
rate
:<0.
005
Log
Kow
:2.4
2
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
GP
Ab
St35
00.
64In
fPB
0.44
65
50.
6721
09.
2Fr
asch
et a
l. (2
005)
Hum
Br
FlFu
ll0.
320.
01N
eat (
17m
g/cm
²)4
7272
0.09
811
Min
t et a
l. (1
994)
Hum
Ab
StEp
i1.
80.
5N
eat
1130
306
0.11
1.3
Scot
t et a
l. (1
987)
Hum
*B
rFl
Full
0.32
0.01
Nea
t (17
mg/
cm²)
372
720.
1314
Min
t et a
l. (1
994)
Rat
Ba
FlFu
ll0.
320.
01N
eat (
17m
g/cm
²)4
7272
0.84
94M
int e
t al.
(199
4)R
atB
aSt
Epi
1.8
0.5
Nea
t11
88
1.1
3.7
41Sc
ott e
t al.
(198
7)R
at*
Ba
FlFu
ll0.
320.
01N
eat (
17m
g/cm
²)3
7272
0.92
103
Min
t et a
l. (1
994)
N
o da
ta a
vaila
ble
Two
diff
eren
t stu
dies
(Min
t et a
l. (1
994)
, Sco
tt et
al.
(198
7)) u
sing
hum
an sk
in in
vitr
o, re
port
cons
iste
nt re
sults
.Th
e tw
o da
ta se
ts fr
om M
int e
t al.
(199
4) fo
r rat
and
hum
an sk
in re
pres
ent n
on-o
cclu
ded
(*) a
nd o
cclu
ded
appl
icat
ion
of
diet
hyl p
htha
late
.
The
Kp
valu
e of
1·1
0-5 c
orre
spon
ds to
"lo
w"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A55
App
endi
x A
Subs
tanc
e: D
ieth
ylam
ine
Mol
ecul
ar w
eigh
t:73
.1C
AS:
109
-89-
7D
ensi
ty:0
.707
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
3:36
Mel
ting
poin
t:-5
0°C
Boi
ling
poin
t:55
.5°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:2
6 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:1
7L
og K
ow:0
.58
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
derm
al L
D50
in ra
bbits
is 8
20 m
g/kg
bw
, as c
ompa
red
to a
n or
al L
D50
of 1
30 m
g/kg
bw
in m
ice
(AC
GIH
(200
1)).
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A56
App
endi
x A
Subs
tanc
e: D
ieth
ylam
inoe
than
ol, 2
-M
olec
ular
wei
ght:
117.
2C
AS:
100
-37-
8D
ensi
ty:0
.884
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
5:19
Mel
ting
poin
t:-7
0°C
Boi
ling
poin
t:16
2°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.19
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:0
.05
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
skin
not
atio
n by
AC
GIH
(200
1) is
bas
ed o
n th
e re
porte
d de
rmal
LD
50 o
f 0.9
g/k
g bw
in ra
bbits
.Fo
r com
paris
on, t
he o
ral L
D50
in ra
ts is
in th
e ra
nge
of 1
.3 to
5.7
g/k
g bw
.
Acc
ordi
ng to
theo
retic
al c
alcu
latio
ns (b
ased
on
the
phys
ical
pro
perti
es o
f the
subs
tanc
e)
by F
iser
ova-
Ber
gero
va e
t al.
(199
0), t
he p
oten
tial f
or d
erm
al a
bsor
ptio
n an
d re
sulti
ng to
xici
ty is
sign
ifica
nt.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A57
App
endi
x A
Subs
tanc
e: D
ieth
ylen
e gl
ycol
Mol
ecul
ar w
eigh
t:10
6.1
CA
S: 1
11-4
6-6
Den
sity
:1.1
18 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:-1
0°C
Boi
ling
poin
t:24
5°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.5 P
a (a
t 20°
C)
Skin
per
mea
bilit
y: V
ery
low
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:-
1.47
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Rat
Ba
120.
045
Nea
t (50
mg)
572
729.
10.
047
5.3
Mat
hew
s et a
l. (1
991)
Nea
t lab
elle
d di
ethy
lene
gly
col w
as a
pplie
d to
the
clip
ped
back
of r
ats a
nd to
tal r
adio
activ
ity w
as m
easu
red
in b
reat
h an
d ur
ine
up to
72h
.
The
calc
ulat
ed p
erm
eabi
lity
is c
onsi
dere
d as
"ve
ry lo
w".
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A58
App
endi
x A
Subs
tanc
e: D
ieth
ylen
e gl
ycol
mon
obut
yl e
ther
(DEG
BE)
Mol
ecul
ar w
eigh
t:16
2.2
CA
S: 1
12-3
4-5
Den
sity
:0.9
67 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
995:
19M
eltin
g po
int:
-68.
1°C
Boi
ling
poin
t:23
0.4°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:4.4
Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:0
.003
Log
Kow
:0.5
6
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
StEp
i0.
64/1
.0N
eat
108
81-
23.
129
0B
arbe
r et a
l. (1
992)
Hum
Ab
StEp
i1.
81-
5N
eat
98
82
0.36
35D
ugar
d et
al.
(198
4)R
atSt
Full
0.64
/1.0
Nea
t12
88
1-2
5.3
510
Bar
ber e
t al.
(199
2)
Rat
Ba
4.3
Nea
t4
2416
87.
7-16
730-
1500
Boa
tman
et a
l. (1
993)
All
thre
e st
udie
s use
d si
mila
r tec
hniq
ues;
stat
ic F
ranz
cel
ls, h
eat-s
epar
ated
epi
derm
is (6
0°C
in w
ater
), fr
ozen
and
thaw
ed h
uman
or
rat s
kin.
The
resu
lts o
f Bar
ber e
t al.
(199
2) a
nd B
oatm
an e
t al.
(199
3) a
re c
onsi
sten
t, w
here
as D
ugar
d et
al.
(198
4) re
ports
10
-fol
d lo
wer
flux
and
Kp.
The
pref
erre
d st
udy
is th
at o
f Bar
ber e
t al.
(199
2) u
sing
hum
an sk
in.
The
Kp
valu
e of
3·1
0-4 c
m/h
cor
resp
onds
to "
mod
erat
e" p
erm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A59
App
endi
x A
Subs
tanc
e: D
ieth
ylen
e gl
ycol
mon
obut
yl e
ther
ace
tate
(DEG
BEA
)M
olec
ular
wei
ght:
204.
3C
AS:
124
-17-
4D
ensi
ty:0
.98
g/cm
³Sc
ient
ific
basi
s: A
oH 1
995:
19M
eltin
g po
int:
-32°
CB
oilin
g po
int:
246°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:5.3
Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Hig
hE
vapo
ratio
n ra
te:0
.001
Log
Kow
:1.3
0 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Rat
Ba
4.3
Nea
t4
2416
813
-16
1300
-160
0B
oatm
an e
t al.
(199
3)
Onl
y ra
t in
vivo
dat
a ar
e av
aila
ble.
Not
ably
, the
flux
and
Kp
of D
EGB
EA is
sim
ilar t
o th
at o
f DEG
BE.
The
Kp
valu
e fo
r rat
skin
cor
resp
onds
to "
high
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A60
App
endi
x A
Subs
tanc
e: D
ieth
ylen
e gl
ycol
mon
oeth
yl e
ther
(DEG
EE)
Mol
ecul
ar w
eigh
t:13
4.2
CA
S: 1
11-9
0-0
Den
sity
:0.9
99 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
997:
24M
eltin
g po
int:
-76°
CB
oilin
g po
int:
197°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:19
Pa (a
t 25°
C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
:0.0
2L
og K
ow:-
0.54
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StEp
i1.
81-
5N
eat
108
8<1
1.3
130
Dug
ard
et a
l. (1
984)
N
o da
ta a
vaila
ble
The
only
stud
y fo
und
is th
at o
f Dug
ard
et a
l. (1
984)
wer
e hu
man
skin
was
exp
osed
to n
eat D
EGEE
in v
itro.
The
repo
rted
Kp
valu
e of
1·1
0-4 c
m/h
, cor
resp
onds
to "
mod
erat
e" p
erm
eabi
lity.
It sh
ould
be
note
d th
at D
ugar
d et
al.
(198
4) h
as a
lso
pres
ente
d K
p da
ta o
n so
me
rela
ted
glyc
ol e
ther
s, e.
g. D
EGB
E, th
at w
ere
appr
oxim
atel
y te
n tim
es lo
wer
that
that
of o
ther
inve
stig
ator
s.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A61
App
endi
x A
Subs
tanc
e: D
ieth
ylen
e gl
ycol
mon
oeth
yl e
ther
ace
tate
(DEG
EEA
)M
olec
ular
wei
ght:
176.
2C
AS:
112
-15-
2D
ensi
ty:1
.01
g/cm
³Sc
ient
ific
basi
s: A
oH 1
997:
24M
eltin
g po
int:
-25°
CB
oilin
g po
int:
210
to 2
20°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:7
Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:0.0
08L
og K
ow:0
.32
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s rep
ort (
AoH
199
7:25
) sta
tes t
hat "
… it
is re
ason
able
to a
ssum
e th
at (D
EGEE
A),
like
othe
r gly
col e
ther
s, ar
e ef
ficie
ntly
abs
orbe
d vi
a bo
th sk
in a
nd in
hala
tion"
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A62
App
endi
x A
Subs
tanc
e: D
ieth
ylen
triam
ine
Mol
ecul
ar w
eigh
t:10
3.2
CA
S: 1
11-4
0-0
Den
sity
:0.9
51 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
995:
19M
eltin
g po
int:
-33°
CB
oilin
g po
int:
207°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.0
5 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:0
.01
Log
Kow
:-2.
13 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s rep
ort (
AoH
199
5:19
) sta
tes t
hat t
he su
bsta
nce
can
be ta
ken
up b
y sk
in, w
ithou
t fur
ther
det
ails
.
The
oral
(2.3
3 an
d 1.
08 g
/kg
bw in
rats
, Sm
yth
et a
l. (1
949)
and
Hin
e et
al.
(195
8)) a
nd d
erm
al (1
.09
g/kg
bw
in ra
bbit,
Sm
yth
et a
l. (1
949)
) LD
50 a
re n
ot v
ery
diff
eren
t fro
m o
ne a
noth
er, s
ugge
stin
g ex
tens
ive
derm
al u
ptak
e.
Acc
ordi
ng to
theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
the
pote
ntia
l for
der
mal
abso
rptio
n an
d re
sulti
ng to
xici
ty is
sign
ifica
nt.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A63
App
endi
x A
Subs
tanc
e: D
iisop
ropy
lam
ine
Mol
ecul
ar w
eigh
t:10
1.2
CA
S: 1
08-1
8-9
Den
sity
:0.7
22 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
991:
8M
eltin
g po
int:
-61°
CB
oilin
g po
int:
84°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:8
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:1
.40
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s rep
ort (
AoH
199
1:8)
stat
es th
at d
iisop
ropy
lam
ine
can
be ta
ken
up b
y th
e sk
in. N
o fu
rther
det
ails
are
giv
en.
The
sour
ce (A
nder
sson
et a
l. (1
985)
) con
tain
s no
info
rmat
ion
on d
erm
al a
bsor
ptio
n.
Acc
ordi
ng to
theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
the
pote
ntia
l for
der
mal
abso
rptio
n an
d re
sulti
ng to
xici
ty is
sign
ifica
nt.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A64
App
endi
x A
Subs
tanc
e: D
imet
hyl p
htha
late
Mol
ecul
ar w
eigh
t:19
4.2
CA
S: 1
31-1
1-3
Den
sity
:1.1
9 g/
cm³
Scie
ntifi
c ba
sis:
AoH
198
3:36
Mel
ting
poin
t:2°
CB
oilin
g po
int:
283.
7°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:0
.8 P
a (a
t 20°
C)
Skin
per
mea
bilit
y: L
owE
vapo
ratio
n ra
te:<
0.00
5L
og K
ow:1
.60
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StEp
i1.
80.
5N
eat
1430
300.
10.
334
Scot
t et a
l. (1
987)
Rat
Ab
StEp
i1.
80.
5N
eat
88
0.5
3.5
42Sc
ott e
t al.
(198
7)
N
o da
ta a
vaila
ble
The
only
ava
ilabl
e st
udy
(Sco
tt et
al.
(198
7)) r
epor
ts 1
0-fo
ld d
iffer
ent p
erm
eabi
litie
s for
hum
an a
nd ra
t ski
n.H
uman
epi
derm
al m
embr
anes
wer
e pr
epar
ed b
y he
atin
g in
wat
er (6
0°C
), w
here
as ra
t mem
bran
es w
ere
prep
ared
usi
ng 2
M N
aBr.
How
ever
, the
aut
hors
cla
im th
at th
e tw
o pr
epar
atio
n te
chni
ques
giv
e th
e sa
me
perm
eabi
lity
prop
ertie
s.
The
hum
an in
vitr
o da
ta su
gges
ts "
low
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A65
App
endi
x A
Subs
tanc
e: D
imet
hyla
ceta
mid
e, N
-M
olec
ular
wei
ght:
87.1
CA
S: 1
27-1
9-5
Den
sity
:0.9
37 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
994:
30M
eltin
g po
int:
-20°
CB
oilin
g po
int:
166.
1°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.2 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: V
ery
high
Eva
pora
tion
rate
:0.1
4L
og K
ow:-
0.77
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
St30
0-60
00.
64N
eat
36
612
011
000
Urs
in e
t al.
(199
5)
N
o da
ta a
vaila
ble
The
only
stud
y fo
und
was
that
of U
rsin
et a
l. (1
995)
whe
re h
uman
skin
was
exp
osed
to n
eat n
-dim
ethy
lace
tam
ide
in v
itro.
The
repo
rted
Kp
valu
e of
1·1
0-2 c
m/h
, sug
gest
s "ve
ry h
igh"
per
mea
bilit
y
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A66
App
endi
x A
Subs
tanc
e: D
imet
hyla
nilli
ne, N
,N-
Mol
ecul
ar w
eigh
t:12
1.2
CA
S: 1
21-6
9-7
Den
sity
:0.9
56 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
991:
8M
eltin
g po
int:
2.5°
CB
oilin
g po
int:
194°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.0
67 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:<
1L
og K
ow:2
.31
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s rep
ort (
AoH
199
1:8)
stat
es th
at d
imet
hyla
nilin
e ca
n be
abs
orbe
d vi
a th
e sk
in.
No
addi
tiona
l dat
a ar
e gi
ven.
Acc
ordi
ng to
theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
the
pote
ntia
l for
der
mal
abso
rptio
n an
d re
sulti
ng to
xici
ty is
sign
ifica
nt.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A67
App
endi
x A
Subs
tanc
e: D
imet
hyle
thyl
amin
eM
olec
ular
wei
ght:
73.1
CA
S: 5
98-5
6-1
Den
sity
:0.6
75 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
992:
6M
eltin
g po
int:
-140
°CB
oilin
g po
int:
36°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:5
5 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: H
igh
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:0
.70
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
GP
FlFu
ll0.
1H
2O0.
676
4848
710
8Lu
ndh
et a
l. (1
997)
GP
FlFu
ll0.
1H
2O0.
676
4848
105
Lund
h et
al.
(199
7)G
PFl
Full
0.1
NaC
l0.
676
4848
340
25Lu
ndh
et a
l. (1
997)
GP
FlFu
ll0.
1N
aCl
0.67
648
488
209
Lund
h et
al.
(199
7)H
umFl
250
0.1
H2O
0.67
640
26Lu
ndh
et a
l. (1
997)
Hum
Fl25
00.
1H
2O0.
676
2011
Lund
h et
al.
(199
7)H
umFl
250
0.1
NaC
l0.
676
120
16Lu
ndh
et a
l. (1
997)
Hum
Arm
870
Inf
Vap
0.00
027
34
844
µg
500
0.01
3Lu
ndh
et a
l. (1
997)
Hum
Arm
870
Inf
Vap
0.00
053
34
864
µg
320
0.02
Lund
h et
al.
(199
7)H
umA
rm87
0In
fV
ap0.
001
34
888
µg
250
0.02
6Lu
ndh
et a
l. (1
997)
The
one
foun
d st
udy
by L
undh
et a
l. (1
997)
show
s con
sist
ent r
esul
ts b
etw
een
vapo
ur a
nd a
queo
us so
lutio
ns.
The
pref
erre
d ex
perim
ents
are
thos
e on
hum
an sk
in in
vitr
o w
ith re
porte
d K
p va
lues
bet
wee
n 2·
10-3
to 4
·10-3
cm
/h,
whi
ch c
orre
spon
ds to
"hi
gh"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A68
App
endi
x A
Subs
tanc
e: D
imet
hylfo
rmam
ide
Mol
ecul
ar w
eigh
t:73
.1C
AS:
68-
12-2
Den
sity
:0.9
44 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
983:
36M
eltin
g po
int:
-61°
CB
oilin
g po
int:
153°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.4
9 kP
a (a
t 25°
C)
Skin
per
mea
bilit
y: V
ery
high
Eva
pora
tion
rate
:0.1
7L
og K
ow:-
1.01
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StFu
ll3.
10.
2N
eat
6?4
41
9684
00La
rese
et a
l. (1
994)
Hum
Br
St30
0-60
00.
64N
eat
36
614
013
000
Urs
in e
t al.
(199
5)
Hum
Ha
Inf
Nea
t18
0.03
3-0.
3324
100
9400
Mra
z et
al.
(199
2)
The
thre
e di
ffer
ent s
tudi
es sh
ow c
onsi
sten
t res
ults
. The
pre
ferr
ed st
udy
is th
e hu
man
in v
ivo
stud
y by
Mra
z et
al.
(199
2).
The
Kp
valu
e of
1·1
0-2 c
m/h
cor
resp
onds
to "
very
hig
h" p
erm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A69
App
endi
x A
Subs
tanc
e: D
imet
hyls
ulfo
xide
Mol
ecul
ar w
eigh
t:78
.1C
AS:
67-
68-5
Den
sity
:1.0
96 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
992:
47M
eltin
g po
int:
18.5
°CB
oilin
g po
int:
189°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.0
49 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: V
ery
high
Eva
pora
tion
rate
:4.3
Log
Kow
:-1.
35
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
St30
0-60
00.
64N
eat
36
616
018
000
Urs
in e
t al.
(199
5)
Hum
EB25
088
0 (8
0%. 1
7 g)
0.5
504
25-4
038
0-61
033
000-
5300
0W
ong
et a
l. (1
971)
Hum
WB
2000
0H
2O77
0 (7
0%. 1
g/k
g B
W)
28
2013
0.74
57H
ucke
r et a
l. (1
967)
MP
Ba
250
880
(80%
. 17
g)4
144
100
190
1700
0W
ong
et a
l. (1
971)
Rat
Ab
25N
eat (
260
mg)
0.25
4837
140
1600
0M
cDer
mot
et a
l. (1
967)
Rat
Ab
25N
eat (
240
mg)
0.5
4867
120
1300
0M
cDer
mot
et a
l. (1
967)
Rat
Ab
25N
eat (
350
mg)
0.75
4890
160
1700
0M
cDer
mot
et a
l. (1
967)
Rat
Ab
25N
eat (
270
mg)
148
9492
1000
0M
cDer
mot
et a
l. (1
967)
The
diff
eren
t stu
dies
show
con
sist
ent r
esul
ts w
ith K
p va
lues
rang
ing
from
1·1
0-3 to
6·1
0-2 c
m/h
,w
ith a
pre
ferr
ed st
udy
of U
rsin
et a
l. (1
995)
wer
e hu
man
skin
was
exp
osed
to n
eat c
hem
ical
.
Thes
e K
p va
lues
cor
resp
ond
to "
high
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A70
App
endi
x A
Subs
tanc
e: D
initr
oben
zene
Mol
ecul
ar w
eigh
t:16
8.1
CA
S: 2
5154
-54-
5D
ensi
ty:1
.368
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
88 to
90°
CB
oilin
g po
int:
~300
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:<10
0 Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:N
ot a
vaila
ble
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
cont
ribut
ion
of d
erm
al e
xpos
ure
to th
e sy
stem
ic to
xici
ty o
f din
itrob
enze
ne is
wel
l est
ablis
hed
(AC
GIH
(200
1)).
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A71
App
endi
x A
Subs
tanc
e: D
initr
otol
uene
Mol
ecul
ar w
eigh
t:18
2.1
CA
S: 2
5321
-14-
6D
ensi
ty:1
.321
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
2:6
Mel
ting
poin
t:70
°CB
oilin
g po
int:
250°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:2.4
Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:2
.18
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Bio
mon
itorin
g st
udie
s in
wor
kers
show
hig
her u
rine
leve
ls o
f met
abol
ites t
han
wou
ld b
e ex
pect
ed fr
om in
hala
tion
expo
sure
only
(AoH
199
2:6,
AC
GIH
(200
1), T
chou
nwou
et a
l. (2
003)
).
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A72
App
endi
x A
Subs
tanc
e: D
initr
otol
uene
, 2,4
-M
olec
ular
wei
ght:
182.
1C
AS:
121
-14-
2D
ensi
ty:1
.521
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
2:6
Mel
ting
poin
t:69
°CB
oilin
g po
int:
300°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:130
Pa
(at 1
03°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:1.9
8
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Pig
Ba
St50
0-90
00.
811
mg/
cm²S
oil (
Ti)
0.93
(6.
8 µg
/cm
²)6
88
5.3
0.49
0.04
5R
eife
nrat
h et
al.
(200
2)Pi
gB
aSt
500-
900
0.8
12 m
g/cm
²Soi
l (Y
o)1.
5 (1
2 µg
/cm
²)6
88
141.
40.
21R
eife
nrat
h et
al.
(200
2)Pi
gB
aSt
500-
900
0.8
0.00
5A
c2.
4 (1
2 µg
/cm
²)6
88
342.
10.
49R
eife
nrat
h et
al.
(200
2)
N
o da
ta a
vaila
ble
The
only
foun
d st
udy
was
that
of R
eife
nrat
h et
al.
(200
2), w
here
pig
skin
was
exp
osed
to 2
,4-d
initr
otol
uene
and
2,
6-di
nitro
tolu
ene
with
soil
or a
ceto
ne a
s veh
icle
. It s
houl
d be
not
ed th
at th
e us
e of
ace
tone
as v
ehic
le
may
hav
e se
vere
ly a
ffec
ted
the
skin
pro
perti
es.
The
repo
rted
Kp
valu
es a
re c
onsi
sten
t bet
wee
n ex
perim
ents
and
isom
ers,
and
rang
e be
twee
n 1·
10-4
and
2·1
0-4 c
m/h
,su
gges
ting
a "m
oder
ate"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A73
App
endi
x A
Subs
tanc
e: D
initr
otol
uene
, 2,6
-M
olec
ular
wei
ght:
182.
1C
AS:
606
-20-
2D
ensi
ty:1
.283
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
2:6
Mel
ting
poin
t:65
°CB
oilin
g po
int:
300°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:130
Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:2.1
0
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Pig
Ba
St50
0-90
00.
817
mg/
cm²S
oil (
Ti)
0.47
(6.
1 µg
/cm
²)6
88
3.7
0.94
0.04
4R
eife
nrat
h et
al.
(200
2)Pi
gB
aSt
500-
900
0.8
11 m
g/cm
²Soi
l (Y
o)1.
1 (9
.7 µ
g/cm
²)6
88
151.
70.
2R
eife
nrat
h et
al.
(200
2)Pi
gB
aSt
500-
900
0.8
0.00
5A
c1.
9 (9
.6 µ
g/cm
²)6
88
221.
50.
29R
eife
nrat
h et
al.
(200
2)
N
o da
ta a
vaila
ble
The
only
foun
d st
udy
was
that
of R
eife
nrat
h et
al.
(200
2), w
here
pig
skin
was
exp
osed
to 2
,4-d
initr
otol
uene
and
2,
6-di
nitro
tolu
ene
with
soil
or a
ceto
ne a
s veh
icle
. It s
houl
d be
not
ed th
at th
e us
e of
ace
tone
as v
ehic
le
may
hav
e se
vere
ly a
ffec
ted
the
skin
pro
perti
es.
The
repo
rted
Kp
valu
es a
re c
onsi
sten
t bet
wee
n ex
perim
ents
and
isom
ers,
and
rang
e be
twee
n 1·
10-4
and
2·1
0-4 c
m/h
,su
gges
ting
a "m
oder
ate"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A74
App
endi
x A
Subs
tanc
e: D
ioxa
neM
olec
ular
wei
ght:
88.1
CA
S: 1
23-9
1-1
Den
sity
:1.0
33 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
992:
47M
eltin
g po
int:
11.8
°CB
oilin
g po
int:
101.
1°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:4
.9 k
Pa (a
t 25°
C)
Skin
per
mea
bilit
y: N
o co
nclu
sion
Eva
pora
tion
rate
:2.7
Log
Kow
:-0.
27
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Mon
Arm
3-15
Me
4 µg
/cm
²3-
624
120
2.3
0.00
0037
0.00
38M
arzu
lli e
t al.
(198
1)M
onA
rm3-
15C
ream
4 µg
/cm
²3-
624
120
3.4
0.00
57M
arzu
lli e
t al.
(198
1)
Mar
zulli
et a
l. (1
981)
stud
ied
derm
al u
ptak
e in
viv
o in
Rhe
sus m
onke
ys. T
he sm
all a
mou
nt a
pplie
d an
d th
e no
n-oc
clud
ed
cond
ition
mos
t pos
sibl
y le
d to
mas
sive
loss
es o
f dio
xane
via
eva
pora
tion.
Thu
s the
cal
cula
ted
fluxe
s and
Kp
valu
es a
re n
ot re
liabl
e.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A75
App
endi
x A
Subs
tanc
e: D
ipro
pyle
ne g
lyco
l mon
omet
hyl e
ther
(DPG
ME)
Mol
ecul
ar w
eigh
t:14
8.2
CA
S: 3
4590
-94-
8D
ensi
ty:0
.95
g/cm
³Sc
ient
ific
basi
s: A
oH 1
992:
6M
eltin
g po
int:
-83°
CB
oilin
g po
int:
190°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.0
5 kP
a (a
t °C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:0.0
2L
og K
ow:-
0.35
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
Sm
yth
et a
l. (1
962)
the
rat o
ral L
D50
is 5
.7 g
/kg
bw. F
or c
ompa
rison
, the
rabb
it de
rmal
LD
50 is
10
g/kg
bw
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A76
App
endi
x A
Subs
tanc
e: E
pich
loro
hydr
inM
olec
ular
wei
ght:
92.5
CA
S: 1
06-8
9-8
Den
sity
:1.1
83 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
981:
10M
eltin
g po
int:
-57°
CB
oilin
g po
int:
117.
9°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:1
.5 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.4
5
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
NEG
(198
1) e
pich
loro
hydr
in p
enet
rate
s the
skin
and
muc
ous m
embr
anes
. No
furth
er d
etai
ls a
re g
iven
.A
ccor
ding
to A
CG
IH (2
001)
the
rabb
it de
rmal
LD
50 is
755
mg/
kg b
w. F
or c
ompa
rison
, the
rat a
nd m
ouse
ora
l LD
50 v
alue
s ar
e 26
0 an
d 23
7 m
g/kg
bw
, res
pect
ivel
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A77
App
endi
x A
Subs
tanc
e: E
than
olM
olec
ular
wei
ght:
46.1
CA
S: 6
4-17
-5D
ensi
ty:0
.789
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
1:8
Mel
ting
poin
t:-1
14.1
°CB
oilin
g po
int:
78.3
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:6.7
kPa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
Hig
hE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:-0.
31
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Dog
Br
StFu
ll3.
11
PBS
55
56.
2M
ills e
t al.
(200
4)D
ogN
eSt
Full
3.1
1PB
S5
55
7.9
Mill
s et a
l. (2
004)
Dog
Ba
StFu
ll3.
11
PBS
55
59.
1M
ills e
t al.
(200
4)D
ogTh
StFu
ll3.
11
PBS
55
54.
8M
ills e
t al.
(200
4)D
ogA
xSt
Full
3.1
1PB
S5
55
8.4
Mill
s et a
l. (2
004)
GP
Ba
FlFu
ll5
0.1
Nea
t9
1919
272.
922
5G
umm
er e
t al.
(198
6)H
umA
bSt
272.
5H
2O
7.4
358
3.7
Sche
uple
in &
Bla
nk (1
973)
Hum
Ab
St25
002.
5H
2O
7.4
835
016
0Sc
heup
lein
& B
lank
(197
3)H
umA
bSt
272.
5N
eat
197.
257
0Sc
heup
lein
& B
lank
(197
3)H
umA
bSt
2500
2.5
Nea
t4
7055
00Sc
heup
lein
& B
lank
(197
3)H
umA
bSt
Full
2.5
0.1
H2O
56
63.
2Sc
ott e
t al.
(199
1)H
umB
rSt
300-
600
0.64
Nea
t3
66
1515
00U
rsin
et a
l. (1
995)
Hum
Ba
StSC
0.5
H2O
45-7
5%9
23-6
180
0-36
00B
erne
r et a
l. (1
989)
Hum
Ba
StSC
0.5
H2O
20%
925
400
Ber
ner e
t al.
(198
9)M
aA
bSt
Full
2.5
0.1
H2O
36
63.
8Sc
ott e
t al.
(199
1)M
aB
aSt
Full
2.5
0.1
H2O
36
63.
2Sc
ott e
t al.
(199
1)M
aA
rmSt
Full
2.5
0.1
H2O
66
68
Scot
t et a
l. (1
991)
Ma
Leg
StFu
ll2.
50.
1H
2O6
66
5.6
Scot
t et a
l. (1
991)
Ma
ScSt
Full
2.5
0.1
H2O
46
63.
9Sc
ott e
t al.
(199
1)M
aLe
gSt
Full
2.5
0.1
H2O
36
64.
1Sc
ott e
t al.
(199
1)M
aB
rSt
Full
2.5
0.1
H2O
36
65.
8Sc
ott e
t al.
(199
1)M
aA
rmSt
Full
2.5
0.1
H2O
56
66.
5Sc
ott e
t al.
(199
1)
Rep
orte
d da
ta
In v
itro
A78
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
80.
50.
521
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
85.
55.
522
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
810
.510
.523
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
815
.515
.522
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
820
.520
.521
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
825
.525
.520
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
829
.529
.519
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
40.
30.
320
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
45.
85.
820
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
49.
89.
821
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
413
.813
.823
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
417
.817
.821
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
01M
426
.326
.322
Beh
l et a
l. (1
980)
Mou
Ab
StFu
ll0.
60.
2N
aCl
32
29
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
22
29
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
42
225
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
52
235
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
62
213
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
42
29
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
52
212
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
60.
2N
aCl
52
29
Beh
l et a
l. (1
984)
Mou
Ba
StFu
ll0.
60.
2N
aCl
42
224
Beh
l et a
l. (1
984)
Mou
Ba
StFu
ll0.
60.
2N
aCl
22
229
Beh
l et a
l. (1
984)
Mou
Ba
StFu
ll0.
60.
2N
aCl
42
244
Beh
l et a
l. (1
984)
Mou
Ba
StFu
ll0.
60.
2N
aCl
52
275
Beh
l et a
l. (1
984)
Mou
Ba
StFu
ll0.
60.
2N
aCl
42
214
Beh
l et a
l. (1
984)
Mou
Ba
StFu
ll0.
60.
2N
aCl
52
212
Beh
l et a
l. (1
984)
Mou
Ba
StFu
ll0.
60.
2N
aCl
52
210
Beh
l et a
l. (1
984)
Mou
Ab
StFu
ll0.
6N
aCl
0.00
01M
52
232
Beh
l & B
arre
tt (1
981)
Mou
Ab
StFu
ll0.
79N
aCl
≤10-
4M2
27.
2D
urrh
eim
et a
l. (1
980)
Mou
Ab
StFu
ll0.
79N
aCl
≤10-
4M2
212
Dur
rhei
m e
t al.
(198
0)M
ouA
bSt
Full
0.79
NaC
l≤1
0-4M
22
48D
urrh
eim
et a
l. (1
980)
A79
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Pig1
Ba
FlFu
ll0.
390.
01N
eat
324
241
0.05
24.
1Pe
ndlin
gton
et a
l. (2
001)
Pig2
Ba
FlFu
ll0.
390.
01N
eat
324
2421
1.1
89Pe
ndlin
gton
et a
l. (2
001)
Rat
Ba
StFu
ll2.
50.
1H
2O8
66
4.2
Scot
t et a
l. (1
991)
Hum
FiIn
fH
2O1%
1215
s0.
30.
230.
18N
aito
h et
al.
(200
2)H
umFi
Inf
H2O
1%12
15s
0.3
3024
Nai
toh
et a
l. (2
002)
1 Non
occ
lude
d 2 O
cclu
ded
The
only
ava
ilabl
e in
viv
o st
udy
is th
at o
f Nai
toh
et a
l. (2
002)
. An
unco
nven
tiona
l tec
hniq
ue w
as u
sed
in th
at o
ne th
umb
was
di
pped
onc
e or
seve
ral t
imes
(15
sec/
occa
sion
) in
an a
queo
us so
lutio
n. T
he fl
ux w
as c
alcu
late
d fr
om th
e ev
apor
atio
n fr
om th
e th
umb.
The
evap
orat
ion
prof
ile w
as b
ipha
sic,
thus
two
diff
eren
t flu
xes w
ere
repo
rted.
The
repo
rted
fluxe
s ref
lect
s abs
orpt
ion
into
(a
nd o
ut o
f) ra
ther
than
thro
ugh
skin
. Thu
s the
cal
cula
ted
Kp
may
repr
esen
t an
serio
us o
vere
stim
ate
of th
e "t
rue"
val
ue.
Mos
t in
vitro
stud
ies r
epor
t Kp
valu
es in
the
rang
e 3·
10-4
to 8
·10-3
cm
/h, a
lthou
gh lo
wer
and
hig
her v
alue
s hav
e oc
casi
onal
ly
been
giv
en.
The
high
er e
nd, 7
·10-3
cm
/h, c
orre
spon
ds to
"hi
gh"
perm
eabi
lity.
In v
ivo
Ase
ssm
ent
A80
App
endi
x A
Subs
tanc
e: E
than
olam
ine
Mol
ecul
ar w
eigh
t:61
.1C
AS:
141
-43-
5D
ensi
ty:1
.012
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
2:47
Mel
ting
poin
t:10
.3°C
Boi
ling
poin
t:17
1°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.05
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Low
Eva
pora
tion
rate
:0.0
15L
og K
ow:-
1.31
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
FlFu
ll1.
80.
03H
2O
4 m
g/cm
²6
66
2.4
1.1
0.43
9.7
Sun
et a
l. (1
996)
Hum
Br
FlFu
ll1.
80.
01N
eat
66
63.
80.
60.
087.
9Su
n et
al.
(199
6)M
ouFl
Full
1.8
0.03
H2O
4
mg/
cm²
36
60.
125
4.6
170
Sun
et a
l. (1
996)
Mou
FlFu
ll1.
80.
01N
eat
36
60.
417
1.2
120
Sun
et a
l. (1
996)
Pig
Ba
Fl10
000.
80.
01Et
0.8
(4 µ
g/cm
²)50
505
0.06
30.
005
Kla
in e
t al.
(198
5)R
abFl
Full
1.8
0.01
Nea
t3
66
1.3
8.7
0.72
74Su
n et
al.
(199
6)R
abFl
Full
1.8
0.03
H2O
4
mg/
cm²
36
63.
11.
91.
125
Sun
et a
l. (1
996)
Rat
FlFu
ll1.
80.
01N
eat
36
61.
56
0.42
43Su
n et
al.
(199
6)R
atFl
Full
1.8
0.03
H2O
4
mg/
cm²
36
61.
71.
30.
5312
Sun
et a
l. (1
996)
N
o da
ta a
vaila
ble
The
stud
y by
Kla
in e
t al.
(198
5) u
sed
etha
nol a
s veh
icle
and
is th
eref
ore
disr
egar
ded
as it
may
aff
ect s
kin
perm
eatio
n.
The
stud
y by
Sun
et a
l. (1
996)
show
s con
sist
ent r
esul
ts c
onsi
derin
g kn
own
spec
ies d
iffer
ence
s and
eff
ect o
f dilu
tion.
The
expe
rimen
t usi
ng h
uman
skin
and
aqu
eous
dilu
tion
repo
rted
a K
p of
4·1
0-5 c
m/h
sugg
estin
g "l
ow"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A81
App
endi
x A
Subs
tanc
e: E
thyl
2-c
yano
acry
late
Mol
ecul
ar w
eigh
t:12
5.1
CA
S: 7
085-
85-0
Den
sity
:1.0
6 g/
cm³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-22.
5°C
Boi
ling
poin
t:N
ot a
vaila
ble
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:1
7 Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:1
.42
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
In O
uste
rhou
t et a
l. (1
968)
, the
radi
olab
elle
d ho
mol
ogou
s sub
stan
ces m
ethy
l α-c
yano
acry
late
and
n-b
utyl
α-c
yano
acry
late
wer
e st
udie
d. T
he n
eat s
ubst
ance
s (50
ml/5
00 0
00 µ
g) w
ere
plac
ed o
n th
e ba
ck o
f rat
s (29
cm
²) an
d th
e ur
ine
was
ana
lyze
d fo
r rad
ioac
tivity
.Th
e ex
posu
re a
nd o
bser
vatio
n tim
e w
as 6
day
s (14
4 h)
. Fro
m fi
gure
1, t
he %
radi
oact
ivity
in u
rine
was
~4
and
0.25
%, r
espe
ctiv
ely.
From
thes
e fig
ures
the
stea
dy-s
tate
flux
and
per
mea
bilit
y ca
n be
cal
cula
ted
(e.g
. for
met
hyl α
-cya
noac
ryla
te):
Flux
Con
c.
The
corr
espo
ndin
g va
lues
for n
-but
yl α
-cya
noac
ryla
te a
re 0
.3 µ
g/cm
²/h a
nd 3·
10-7
cm/h
.
Thes
e pe
rmea
bilit
ies c
orre
spon
d to
"ve
ry lo
w"
and
"ext
rem
ely
low
", re
spec
tivel
y.
=
5 µ
g/cm
²/hA
rea·
Dur
atio
n·10
029
·144
Kp
= =
4.8
=
5·10
-6 c
m/h
1000
000
Flux
=
%A
bsor
bed·
App
lied
amou
nt=
0.04
·500
000
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A82
App
endi
x A
Subs
tanc
e: E
thyl
acr
ylat
eM
olec
ular
wei
ght:
100.
1C
AS:
140
-88-
5D
ensi
ty:0
.924
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
5:32
Mel
ting
poin
t:-7
1.2°
CB
oilin
g po
int:
99.8
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:3.5
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:3.3
Log
Kow
:1.3
2
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
the
Swed
ish
cons
ensu
s rep
ort (
AoH
198
5:32
) acr
ylat
es a
re ta
ken
up fa
irly
slow
ly v
ia th
e sk
in.
No
furth
er d
etai
ls a
re g
iven
on
ethy
l acr
ylat
e.
The
rat o
ral L
D50
is re
porte
d to
be
appr
oxim
atel
y 10
20 m
g/kg
bw
. The
der
mal
LD
50 fo
r rab
bits
is in
the
sam
e ra
nge
(179
0 m
g/kg
bw
) sug
gest
ing
that
skin
abs
orpt
ion
may
be
exte
nsiv
e (A
CG
IH (2
001)
).
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A83
App
endi
x A
Subs
tanc
e: E
thyl
ben
zene
Mol
ecul
ar w
eigh
t:10
6.2
CA
S: 1
00-4
1-4
Den
sity
:0.8
67 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
987:
39M
eltin
g po
int:
-94.
9°C
Boi
ling
poin
t:13
6.2°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:2 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: H
igh
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:3
.15
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Rat
Ba
St56
04.
92
JP-8
0.15
%8
44
0.5
3.1
0.38
McD
ouga
l et a
l. (2
000)
Rat
Ab
StFu
ll2.
61
Nea
t31
3-6
3-6
218
-68
µg0.
076.
3Ts
urut
a (1
982)
HM
Ba
0.8
0.01
Nea
t11
0.08
34
3.4
(150
µg)
2622
00Su
sten
et a
l. (1
990)
Hum
Arm
170.
2N
eat
70.
17-0
.25
199
mg
320
2800
0D
utki
ewic
z et
al.
(196
7)H
umH
a40
0In
fH
2O
0.11
71
1439
mg
1100
012
0D
utki
ewic
z et
al.
(196
7)H
umH
a40
0In
fH
2O
0.16
71
1471
mg
1400
022
0D
utki
ewic
z et
al.
(196
7)H
umH
as80
0H
2O
0.14
52
2411
mg
500
7D
utki
ewic
z et
al.
(196
7)
Tsur
uta
(198
2) u
sed
phys
iolo
gica
l sal
ine
as th
e re
cept
or m
ediu
m, t
his i
s uns
uita
ble
for h
ighl
y lip
ophi
lic su
bsta
nces
like
et
hyl b
enze
ne. M
cDou
gal e
t al.
(200
0) u
sed
jet f
uel a
s veh
icle
, thi
s may
hav
e af
fect
ed th
e pe
rmea
tion
of e
thyl
ben
zene
.In
the
first
thre
e ex
perim
ents
by
Dut
kiew
icz
et a
l. (1
967)
, abs
orbe
d am
ount
was
obt
aine
d as
the
diff
eren
ce b
etw
een
appl
ied
and
rem
aini
ng a
mou
nt a
fter d
ippi
ng o
ne h
and
in a
bea
ker f
or 1
h. T
hese
mea
sure
s inc
lude
s abs
orpt
ion
into
the
skin
as w
ell a
s ev
apor
atio
n an
d m
ay h
eavi
ly o
vere
stim
ate
the
syst
emic
abs
orpt
ion.
In th
e 4t
h, a
bsor
ptio
n ra
te w
as o
btai
ned
from
mea
surin
gth
e m
etab
olite
man
delic
aci
d, in
urin
e. T
he e
xtre
mel
y hi
gh K
p va
lue
is u
nrea
listic
.
The
Sust
en e
t al.
(199
0) st
udy,
alth
ough
usi
ng h
airle
ss m
ice
in v
ivo,
is c
hose
n as
the
pref
erre
d st
udy.
The
Kp
valu
e of
3·1
0-3 c
m/h
cor
resp
onds
to "
high
" pe
rmea
tion.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A84
App
endi
x A
Subs
tanc
e: E
thyl
eth
erM
olec
ular
wei
ght:
74.1
CA
S: 6
0-29
-7D
ensi
ty:0
.713
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-116
.3°C
Boi
ling
poin
t:34
.6°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:4
8 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: N
o co
nclu
sion
Eva
pora
tion
rate
:38
Log
Kow
:0.8
9
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
FiIn
fH
2O0.
05%
1215
s0.
39.
80.
35N
aito
h et
al.
(200
2)H
umFi
Inf
H2O
0.05
%12
15s
0.3
210
7.6
Nai
toh
et a
l. (2
002)
The
only
ava
ilabl
e st
udy
is th
at o
f Nai
toh
et a
l. (2
002)
. An
unco
nven
tiona
l tec
hniq
ue w
as u
sed
in th
at o
ne th
umb
was
dip
ped
once
or s
ever
al ti
mes
(15
sec/
occa
sion
) in
an a
queo
us so
lutio
n. T
he fl
ux w
as c
alcu
late
d fr
om th
e ev
apor
atio
n fr
om th
e th
umb.
The
evap
orat
ion
prof
ile w
as b
ipha
sic,
thus
two
diff
eren
t flu
xes w
ere
repo
rted.
The
repo
rted
fluxe
s ref
lect
s abs
orpt
ion
into
(and
out
of)
rath
er th
an th
roug
h sk
in.
Thus
the
calc
ulat
ed K
p m
ay re
pres
ent a
n se
rious
ove
rest
imat
e of
the
"tru
e" v
alue
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A85
App
endi
x A
Subs
tanc
e: E
thyl
mor
phol
ine,
N-
Mol
ecul
ar w
eigh
t:11
5.2
CA
S: 1
00-7
4-3
Den
sity
:0.9
05 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:-6
3°C
Boi
ling
poin
t:13
8°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.8 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:0
.74
Log
Kow
:0.1
4 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
AC
GIH
has
ass
igne
d a
skin
not
atio
n by
ana
logy
with
mor
phol
ine
(AC
GIH
(200
1)).
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A86
App
endi
x A
Subs
tanc
e: E
thyl
amin
eM
olec
ular
wei
ght:
45.1
CA
S: 7
5-04
-7D
ensi
ty:0
.8 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
983:
36M
eltin
g po
int:
-81°
CB
oilin
g po
int:
16.6
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:120
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:-
0.13
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s doc
umen
t (A
oH 1
983:
36) s
tate
s tha
t der
mal
upt
ake
of a
min
es m
ay o
ccur
follo
win
g ve
ry h
igh
expo
sure
s, w
ithou
t fur
ther
spec
ifica
tion.
The
skin
not
atio
n by
AC
GIH
(200
1) is
bas
ed o
n th
e lo
w d
erm
al L
D50
in ra
bbits
of 3
90 m
g/kg
bw
, whi
ch is
sim
ilar t
o th
e or
al L
D50
(400
mg/
kg b
w in
rats
).
Acc
ordi
ng to
theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
the
pote
ntia
l for
der
mal
abs
orpt
ion
and
resu
lting
toxi
city
is si
gnifi
cant
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A87
App
endi
x A
Subs
tanc
e: E
thyl
ene
glyc
olM
olec
ular
wei
ght:
62.1
CA
S: 1
07-2
1-1
Den
sity
:1.1
16 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
982:
24M
eltin
g po
int:
-13°
CB
oilin
g po
int:
195°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:13
Pa (a
t 25°
C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
:0.0
1L
og K
ow:-
1.36
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
FlFu
llN
eat
816
.516
.5~0
.51.
112
0Lo
den
(198
6b)
Hum
Leg
Fl50
01
Ac
1.6
324
2418
0.56
0.09
Driv
er e
t al.
(199
3)H
umSt
900
0.64
0.13
H2O
10%
88
29
µg0.
212.
3K
orin
th e
t al.
(200
3)H
umSt
900
0.64
0.13
H2O
50%
88
230
µg
0.14
7.8
Kor
inth
et a
l. (2
003)
Mou
Ba
1N
eat (
10 m
g/kg
bw
)4
9696
770.
014
1.6
Fran
tz e
t al.
(199
6a)
Mou
Ba
1N
eat (
1000
mg/
kg b
w)
496
9684
1.6
180
Fran
tz e
t al.
(199
6a)
Mou
Ba
1H
2O50
% (1
000
mg/
kg b
w)
496
9660
2.2
130
Fran
tz e
t al.
(199
6a)
Rat
Ba
1N
eat (
10 m
g/kg
bw
)4
9696
320.
059
6.6
Fran
tz e
t al.
(199
6a)
Rat
Ba
1N
eat (
1000
mg/
kg b
w)
496
9629
5.5
610
Fran
tz e
t al.
(199
6a)
Rat
Ba
1H
2O50
% (1
000
mg/
kg b
w)
496
9626
9.7
540
Fran
tz e
t al.
(199
6a)
Rat
Ba
1N
eat (
10 m
g/kg
bw
)4
9696
320.
059
6.6
Fran
tz e
t al.
(199
6b)
Rat
Ba
1N
eat (
1000
mg/
kg b
w)
496
9636
6.6
740
Fran
tz e
t al.
(199
6b)
Rat
Ba
1H
2O50
% (1
000
mg/
kg b
w)
496
9622
8.3
460
Fran
tz e
t al.
(199
6b)
The
expe
rimen
t usi
ng a
ceto
ne a
s veh
icle
is d
isre
gard
ed, a
s ski
n pe
rmea
bilit
y m
ay b
e af
fect
ed.
The
pref
erre
d st
udy
is th
at o
f Lod
en (1
986b
) usi
ng n
eat e
thyl
ene
glyc
ol a
nd h
uman
skin
.Th
e K
p va
lue
of 1
·10-4
cm
/h, c
orre
spon
ds to
"m
oder
ate"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A88
App
endi
x A
Subs
tanc
e: E
thyl
ene
glyc
ol d
initr
ate
Mol
ecul
ar w
eigh
t:15
2.1
CA
S: 6
28-9
6-6
Den
sity
:1.4
9 g/
cm³
Scie
ntifi
c ba
sis:
AoH
198
5:32
Mel
ting
poin
t:-2
3°C
Boi
ling
poin
t:11
4°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:5
-6.6
Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Hig
hE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:1.1
6
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Arm
122
mg
SpSt
22%
67
72.
3-2.
8 m
g10
-12
330-
400
Gro
ss e
t al.
(196
0)R
atB
r/Ab
110
0 m
gN
C93
%36
192
192
35 m
g (1
2h)
2129
00G
ross
et a
l. (1
960)
Rat
Br/A
b1
200
mg
NC
93%
3619
219
243
mg
(12h
)26
3600
Gro
ss e
t al.
(196
0)R
atB
r/Ab
130
0 m
gN
C93
%36
192
192
59 m
g (1
2h)
3649
00G
ross
et a
l. (1
960)
Rat
Br/A
b1
400
mg
NC
93%
3619
219
260
mg
(12h
)36
5000
Gro
ss e
t al.
(196
0)R
atB
r/Ab
150
0 m
gN
C93
%36
192
192
80 m
g (1
2h)
4867
00G
ross
et a
l. (1
960)
Rat
Br/A
b1
600
mg
NC
93%
3619
219
285
mg
(12h
)51
7100
Gro
ss e
t al.
(196
0)
The
only
ava
ilabl
e st
udy
is a
Ger
man
pub
licat
ion
by G
ross
et a
l. (1
960)
wer
e th
e sk
in a
bsor
ptio
n in
viv
o in
rats
and
hum
ans
was
mea
sure
d af
ter a
pplic
atio
n of
eth
ylen
e gl
ycol
din
itrat
e in
"ge
latin
" (n
itroc
ellu
lose
, NC
) and
"sp
reng
stof
f" (S
pSt).
The
abso
rptio
n w
as o
btai
ned
as th
e di
ffer
ence
bet
wee
n ap
plie
d an
d re
cove
red
amou
nt. T
he c
alcu
late
d flu
xes (
and
Kp
valu
es)
incr
ease
d w
ith a
pplie
d do
se, i
n sp
ite o
f usi
ng th
e sa
me
conc
entra
tion
with
in th
e ex
perim
ent.
This
sugg
est t
hat
depl
etio
n of
eth
ylen
e gl
ycol
din
itrat
e oc
curs
in th
e la
yers
clo
sest
to th
e sk
in.
The
pref
erre
d ex
perim
ent i
s tha
t of h
uman
s in
vivo
, wer
e a
calc
ulat
ed K
p va
lue
of 1
·10-3
cm
/h c
orre
spon
ds to
"hi
gh"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A89
App
endi
x A
Subs
tanc
e: E
thyl
ene
glyc
ol m
onob
utyl
eth
er (E
GB
E)M
olec
ular
wei
ght:
118.
2C
AS:
111
-76-
2D
ensi
t y:0
.903
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
3:3 6
Mel
ting
poin
t:-7
0°C
Boi
ling
poin
t:17
1°C
Skin
not
atio
n: Y
esV
a pou
r pr
essu
re:0
.12
kPa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:0
.07
Lo g
Kow
:0.8
3
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
HR
Ba
StFu
ll5
0.03
Nea
t3
11
1912
1100
Bar
tnik
et a
l. (1
987)
HR
Ba
StFu
ll5
0.03
Nea
t3
11
5.6
3.4
303
Bar
tnik
et a
l. (1
987)
HR
Ba
StFu
ll5
0.03
H2O
10%
31
163
3834
0B
artn
ik e
t al.
(198
7)H
RB
aSt
Full
50.
03H
2O10
%3
11
106.
256
Bar
tnik
et a
l. (1
987)
HR
Ba
StFu
ll5
0.03
H2O
3.50
%3
11
4626
82B
artn
ik e
t al.
(198
7)H
RB
aSt
Full
50.
03H
2O3.
50%
31
111
6.3
20B
artn
ik e
t al.
(198
7)H
RB
aSt
Full
50.
05H
2O10
% (1
000
µg/c
m²)
31
111
2.4
22B
artn
ik e
t al.
(198
7)H
RB
aSt
Full
50.
05H
2O10
% (1
000
µg/c
m²)
31
143
9.6
87B
artn
ik e
t al.
(198
7)H
RB
aSt
Full
50.
03H
2O10
% (6
00 µ
g/cm
²)3
11
152
18B
artn
ik e
t al.
(198
7)H
RB
aSt
Full
50.
03H
2O10
% (6
00 µ
g/cm
²)3
11
638.
375
Bar
tnik
et a
l. (1
987)
Hum
Ab
StEp
i1.
81-
5N
eat
88
8<1
2.1
200
Dug
ard
et a
l. (1
984)
Hum
Br
Fl30
00.
640.
2H
2O
65
247
2318
011
0W
ilkin
son
et a
l. (2
002)
Hum
Br
Fl30
00.
640.
1H
2O
35
247
0.36
1610
031
Wilk
inso
n et
al.
(200
2)H
umB
rFl
300
0.64
0.2
H2O
3
524
240.
327
210
64W
ilkin
son
et a
l. (2
002)
Hum
Br
Fl30
00.
640.
011
Nea
t5
2424
9.5
851
Wilk
inso
n et
al.
(200
2)H
umA
rmSt
Full
30.
03H
2O10
% (1
000
µg/c
m²)
31
16.
92.
523
Bar
tnik
et a
l. (1
987)
Hum
Arm
StFu
ll3
0.03
H2O
10%
(100
0 µg
/cm
²)3
11
176.
458
Bar
tnik
et a
l. (1
987)
Hum
Br
Fl33
00.
640.
01M
e50
%5
2424
110.
4822
Lock
ley
et a
l. (2
004)
Hum
Br
Fl28
00.
640.
01N
eat
524
243.
90.
1918
Lock
ley
et a
l. (2
004)
Pig
Ba
StFu
ll5
0.03
Nea
t3
66
111.
110
1B
artn
ik e
t al.
(198
7)Pi
gB
aSt
Full
50.
03H
2O10
%3
66
373.
733
Bar
tnik
et a
l. (1
987)
Pig
Ba
StFu
ll5
0.03
H2O
3.50
%3
66
484.
414
Bar
tnik
et a
l. (1
987)
Pig
Ba
StFu
ll5
0.05
H2O
10%
(100
0 µg
/cm
²)3
11
8.6
1.9
17B
artn
ik e
t al.
(198
7)Pi
gB
aSt
Full
50.
05H
2O10
% (1
000
µg/c
m²)
31
118
3.9
35B
artn
ik e
t al.
(198
7)Pi
gB
aSt
Full
50.
03H
2O10
% (6
00 µ
g/cm
²)3
11
137.
816
Bar
tnik
et a
l. (1
987)
Pig
Ba
StFu
ll5
0.03
H2O
10%
(600
µg/
cm²)
31
121
2.8
25B
artn
ik e
t al.
(198
7)
Rep
orte
d da
ta
In v
itro
A90
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Rat
Ba
FlFu
ll0.
640.
01M
e50
%5
2424
150.
8137
Lock
ley
et a
l. (2
004)
Rat
Ba
Fl28
00.
640.
01M
e50
%5
2424
231.
464
Lock
ley
et a
l. (2
004)
Rat
Ba
FlFu
ll0.
640.
01N
eat
524
247.
90.
3229
Lock
ley
et a
l. (2
004)
Rat
Ba
Fl28
00.
640.
01N
eat
524
2416
0.92
83Lo
ckle
y et
al.
(200
4)R
atB
aFl
280
0.64
0.01
Nea
t5
2424
181.
199
Lock
ley
et a
l. (2
004)
GP
Ba
6.3
Nea
t10
24.
50.
35-1
2018
00Jo
hans
on e
t al.
(198
6)G
PB
a3.
11
H2O
5%
22
410
052
5Jo
hans
on e
t al.
(198
8c)
GP
Ba
3.1
1H
2O
10%
22
460
525
Joha
nson
et a
l. (1
988c
)G
PB
a3.
11
H2O
20
%2
24
4070
0Jo
hans
on e
t al.
(198
8c)
GP
Ba
3.1
1H
2O
40%
22
420
700
Joha
nson
et a
l. (1
988c
)G
PB
a3.
11
H2O
80
%2
24
860
0Jo
hans
on e
t al.
(198
8c)
GP
Ba
3.1
1N
eat
142
23
350
Joha
nson
et a
l. (1
988c
)H
umFi
79-1
90In
fN
eat
122
2415
-220
mg
1.5
50-6
80Jo
hans
on e
t al.
(198
8a)
Hum
WB
Vap
0.00
024
42
459
0000
14Jo
hans
on e
t al.
(199
1)H
umW
B20
000
49pp
m18
234
11Jo
nes e
t al.
(200
3)H
umA
rm40
H2O
50%
64
818
-30
920-
1340
Jaka
sa e
t al.
(200
4)H
umA
rm40
H2O
90%
34
88.
8-11
740-
920
Jaka
sa e
t al.
(200
4)H
umA
rm40
Nea
t6
48
2.9
260
Jaka
sa e
t al.
(200
4)H
umA
rm40
8H
2O50
%6
448
5324
00K
ezic
et a
l. (2
004b
)R
atB
a12
0.07
2N
eat
(200
mg/
kg B
W)
1248
4827
0.26
23B
artn
ik e
t al.
(198
7)R
atB
a9.
40.
09A
c0.
0001
6 (1
20 µ
mol
/rat)
472
7225
0.34
0.00
0005
4Sa
bour
in e
t al.
(199
2)R
atB
a9.
40.
09A
c0.
0004
8 (3
70 µ
mol
/rat)
472
7226
0.35
0.00
0017
Sabo
urin
et a
l. (1
992)
Rat
Ba
9.4
0.09
Ac
0.00
085
(650
µm
ol/ra
t)4
7272
210.
270.
0000
23Sa
bour
in e
t al.
(199
2)R
atB
a9.
60.
1N
eat
524
2428
1.2
111
Lock
ley
et a
l. (2
004)
The
stud
ies u
sing
ace
tone
or m
etha
nol a
s veh
icle
are
exc
lude
d as
they
may
aff
ect s
kin
perm
eatio
n.
The
Kp
for v
apou
r is a
n ov
eres
timat
e of
the
"tru
e" K
p, si
nce
EGB
E ha
s an
extre
mel
y hi
gh w
ater
:air
parti
tion
coef
ficie
nt
of 7
000
(Joh
anso
n et
al.
(198
8b))
and
is th
eref
ore
conc
entra
ted
on th
e sk
in.
The
pref
erre
d st
udy
is th
at o
f Jak
asa
et a
l. (2
004)
wer
e hu
man
skin
in v
ivo
is u
sed,
with
a re
porte
d K
p va
lue
of n
eat E
GB
E is
3·1
0-4 c
m/h
, whi
ch c
orre
spon
ds to
"m
oder
ate"
per
mea
bilit
y.It
shou
ld b
e no
ted
that
the
perm
eabi
lity
of E
GB
E in
aqu
eous
solu
tions
is a
ppro
xim
atel
y on
e or
der o
f mag
nitu
de h
ighe
r.
10-5
1
0-4
10-3
1
0-2
10-1
1
00
1
01
1
02
N
eat
Aq.
dilu
tion
V
apou
r
In v
ivo
Ase
ssm
ent
A91
App
endi
x A
Subs
tanc
e: E
thyl
ene
glyc
ol m
onob
utyl
eth
er a
ceta
te (E
GB
EA)
Mol
ecul
ar w
eigh
t:16
0.2
CA
S: 1
12-0
7-2
Den
sity
:0.9
4 g/
cm³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
5.5°
CB
oilin
g po
int:
192°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:31
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:0
.03
Log
Kow
:1.5
7 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
subs
tanc
e ha
s not
bee
n as
sess
ed b
y th
e Sw
edis
h C
riter
ia G
roup
, nor
the
AC
GIH
-TLV
com
mitt
ee.
Bas
ed o
n co
mpa
rison
bet
wee
n et
hyle
ne g
lyco
l mon
oeth
yl e
ther
(EG
EE) a
nd e
thyl
ene
glyc
ol m
onoe
thyl
eth
er a
ceta
te (E
GEE
A)
Joha
nson
(199
6), i
t may
be
assu
med
that
the
skin
per
mea
bilit
y of
eth
ylen
e gl
ycol
mon
obut
yl e
ther
ace
tate
(EG
BEA
)is
sim
ilar t
o th
at o
f eth
ylen
e gl
ycol
mon
obut
yl e
ther
(EG
BE)
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A92
App
endi
x A
Subs
tanc
e: E
thyl
ene
glyc
ol m
onoe
thyl
eth
er (E
GEE
)M
olec
ular
wei
ght:
90.1
CA
S: 1
10-8
0-5
Den
sity
:0.9
31 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
983:
36M
eltin
g po
int:
-90°
CB
oilin
g po
int:
135.
6°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.71
kPa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:0
.3L
og K
ow:-
0.32
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StEp
i1.
81-
5N
eat
118
8<1
8.4
800
Dug
ard
et a
l. (1
984)
Hum
Ab
FlFu
ll3.
10.
02N
eat
44
18.
882
0La
rese
et a
l. (1
994)
Hum
Ab
FlFu
ll3.
10.
02A
c27
9.3
44
0.72
7.4
3083
0La
rese
et a
l. (1
994)
Hum
Br
Fl28
00.
640.
01M
e93
524
247.
50.
595.
5Lo
ckle
y et
al.
(200
2)H
umB
rFl
280
0.64
0.01
Nea
t5
2424
8.3
0.74
69Lo
ckle
y et
al.
(200
2)H
umB
rFl
500
0.64
0.2
H2O
34
2424
5.1
4313
Wilk
inso
n &
Will
iam
s (20
02)
Hum
Br
Fl50
00.
640.
1H
2O3
524
2414
200
59W
ilkin
son
& W
illia
ms (
2002
)H
umB
rFl
500
0.64
0.2
H2O
66
2424
1816
098
Wilk
inso
n &
Will
iam
s (20
02)
Hum
Br
Fl50
00.
640.
2H
2O3
424
2411
8325
Wilk
inso
n &
Will
iam
s (20
02)
Hum
Br
Fl50
00.
640.
2H
2O3
524
2413
100
31W
ilkin
son
& W
illia
ms (
2002
)H
umB
rFl
500
0.64
0.2
H2O
35
2424
1280
24W
ilkin
son
& W
illia
ms (
2002
)H
umB
rFl
500
0.64
0.01
Nea
t5
2424
6.2
580
Wilk
inso
n &
Will
iam
s (20
02)
Hum
Br
Fl50
00.
640.
2N
eat
424
2412
1100
Wilk
inso
n &
Will
iam
s (20
02)
Rat
Ba
Fl33
00.
640.
01M
e93
524
2430
0.78
7.3
Lock
ley
et a
l. (2
002)
Rat
Ba
FlFu
ll0.
640.
01M
e93
524
2411
2.3
21Lo
ckle
y et
al.
(200
2)R
atB
aFl
330
0.64
0.01
Nea
t5
2424
201.
514
0Lo
ckle
y et
al.
(200
2)R
atB
aFl
Full
0.64
0.01
Nea
t5
2424
110.
7570
Lock
ley
et a
l. (2
002)
Rat
Ba
Fl33
00.
640.
01N
eat
524
2422
4.7
440
Lock
ley
et a
l. (2
002)
Hum
Arm
1000
Vap
0.00
375
0.75
100
58 m
g19
0000
Kez
ic e
t al.
(199
7)H
umA
rm27
Nea
t5
0.25
100
5.2
mg
7.5
700
Kez
ic e
t al.
(199
7)R
atB
a9.
60.
1N
eat
324
2425
1.1
100
Lock
ley
et a
l. (2
002)
Rat
Ba
9.4
0.09
Ac
0.00
012
(120
µm
ol/ra
t)4
7272
270.
360.
0000
044
Sabo
urin
et a
l. (1
992)
Rat
Ba
9.4
0.09
Ac
0.00
039
(390
µm
ol/ra
t)4
7272
170.
230.
0000
089
Sabo
urin
et a
l. (1
992)
Rat
Ba
9.4
0.09
Ac
0.00
088
(880
µm
ol/ra
t)4
7272
200.
260.
0000
23Sa
bour
in e
t al.
(199
2)
Rep
orte
d da
ta
In v
itro
In v
ivo
A93
App
endi
x A
The
stud
ies u
sing
ace
tone
or m
etha
nol a
s veh
icle
are
exc
lude
d as
they
may
aff
ect s
kin
perm
eatio
n.
How
ever
, the
Kp
for v
apou
r is a
n ov
eres
timat
e of
the
"tru
e" K
p, si
nce
EGEE
has
an
extre
mel
y hi
gh w
ater
:air
parti
tion
coef
ficie
nt o
f 230
00 (J
ohan
son
et a
l. (1
988b
)) a
nd is
ther
efor
e co
ncen
trate
d on
the
ski n
The
pref
erre
d st
udy
is th
at o
f Kez
ic e
t al.
(199
7) w
ere
hum
an sk
in in
viv
o is
use
d, w
ith a
repo
rted
Kp
valu
eof
nea
t EG
EE is
8·1
0-4 c
m/h
, whi
ch c
orre
spon
ds to
"m
oder
ate"
per
mea
bilit
y.
It sh
ould
be
note
d th
at th
e pe
rmea
bilit
y of
EG
EE in
aqu
eous
solu
tions
is o
ne o
r tw
o or
ders
of m
agni
tude
hig
her.
10-5
1
0-4
10-3
1
0-2
10-1
1
00
1
01
1
02
N
eat
Aq.
dilu
tion
Vap
our
Ase
ssm
ent
A94
App
endi
x A
Subs
tanc
e: E
thyl
ene
glyc
ol m
onoe
thyl
eth
er a
ceta
te (E
GEE
A)
Mol
ecul
ar w
eigh
t:13
2.2
CA
S: 1
11-1
5-9
Den
sity
:0.9
75 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:-6
1.7°
CB
oilin
g po
int:
156°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.2
7 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: H
igh
Eva
pora
tion
rate
:0.2
1L
og K
ow:0
.59
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Dog
Br
StFu
ll0.
9N
eat
97
71.
623
2200
Gue
st e
t al.
(198
4)H
umSt
Epi
0.64
/1.0
Nea
t12
88
1-2
1514
00B
arbe
r et a
l. (1
992)
Hum
Ab
StEp
i1.
81-
5N
eat
108
8<1
8.1
800
Dug
ard
et a
l. (1
984)
Rat
StFu
ll0.
64/1
.0N
eat
128
81-
225
2400
Bar
ber e
t al.
(199
2)
Dog
Br
56N
eat
50.
5-1
248.
886
0G
uest
et a
l. (1
984)
Hum
an, a
nim
al, i
n vi
tro a
nd in
viv
o da
ta sh
ow fa
irly
cons
iste
nt re
sults
in th
ree
diff
eren
t stu
dies
with
Kp
valu
es
betw
een
8·10
-4 a
nd 2
·10-3
cm
/h.
Thes
e va
lues
sugg
est "
high
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A95
App
endi
x A
Subs
tanc
e: E
thyl
ene
glyc
ol m
onoi
sopr
opyl
eth
er (E
GiP
E)M
olec
ular
wei
ght:
104.
1C
AS:
109
-59-
1D
ensi
ty:0
.903
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
5:19
Mel
ting
poin
t:-6
0°C
Boi
ling
poin
t:~1
40°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.69
kPa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:0
.05
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s rep
ort (
AoH
199
5:19
) sta
tes t
hat b
ased
on
anal
ogy
with
oth
er e
.g. e
ther
s, sk
in a
bsor
ptio
n m
ay b
e hi
gh.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A96
App
endi
x A
Subs
tanc
e: E
thyl
ene
glyc
ol m
onoi
sopr
opyl
eth
er a
ceta
te (E
GiP
EA)
Mol
ecul
ar w
eigh
t:14
6.2
CA
S: 1
9234
-20-
9D
ensi
ty:0
.95
g/cm
³Sc
ient
ific
basi
s: A
oH 1
995:
19M
eltin
g po
int:
Not
ava
ilabl
eB
oilin
g po
int:
164°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:1
.01
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s rep
ort (
AoH
199
5:19
) sta
tes t
hat b
ased
on
anal
ogy
with
oth
er e
.g. e
ther
s, sk
in a
bsor
ptio
n m
ay b
e hi
gh.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A97
App
endi
x A
Subs
tanc
e: E
thyl
ene
glyc
ol m
onop
ropy
l eth
er (E
GPE
)M
olec
ular
wei
ght:
104.
1C
AS:
280
7-30
-9D
ensi
ty:0
.931
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
4:30
Mel
ting
poin
t:-1
90°C
Boi
ling
poin
t:14
9°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:1
70-3
90 P
a (a
t 25°
C)
Skin
per
mea
bilit
y: H
igh
Eva
pora
tion
rate
:0.2
Log
Kow
:0.0
8
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
StEp
i0.
64/1
.0N
eat
58
81-
26.
458
0B
arbe
r et a
l. (1
992)
Rat
StFu
ll0.
64/1
.0N
eat
58
81-
225
2300
Bar
ber e
t al.
(199
2)
N
o da
ta a
vaila
ble
Qua
ntita
tive
upta
ke d
ata
on ra
t and
hum
an sk
in in
vitr
o ar
e av
aila
ble
(Bar
ber e
t al.
(199
2)).
Hum
an e
pide
rmis
was
pre
pare
d us
ing
hot (
60°C
) wat
er, w
hich
may
hav
e af
fect
ed th
e pe
rmea
tion
prop
ertie
s. Th
e pr
efer
red
stud
y is
the
one
usin
g in
tact
rat s
kin.
The
Kp
valu
e of
3·1
0-3 c
m/h
cor
resp
onds
to "
high
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A98
App
endi
x A
Subs
tanc
e: E
thyl
ene
oxid
eM
olec
ular
wei
ght:
44.1
CA
S: 7
5-21
-8D
ensi
ty:0
.882
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
2:24
Mel
ting
poin
t:-1
11.3
°CB
oilin
g po
int:
10.7
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:150
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Ext
rem
ely
high
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:-
0.30
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
St50
01
Pol f
ab0.
0033
(18
00pp
m)
224
241.
328
00.
0000
92W
este
r et a
l. (1
997)
Hum
St50
01
Pol f
ab0.
0033
(18
00pp
m)
224
2446
1000
00.
0033
Wes
ter e
t al.
(199
7)
N
o da
ta a
vaila
ble
The
skin
not
atio
n by
AC
GIH
(200
1) is
bas
ed o
n a
case
repo
rt (S
exto
n et
al.
(194
9)) w
here
thre
e w
orke
rs th
at
wer
e ac
cide
ntal
ly e
xpos
ed to
a 1
% E
O so
lutio
n de
velo
ped
naus
ea a
nd v
omiti
ng. I
t is h
owev
er u
ncle
ar to
wha
t ext
ent
inha
latio
n ex
posu
re c
ontri
bute
d.
In th
e fir
st e
xper
imen
t of W
este
r et a
l. (1
997)
, pol
yest
er fa
bric
(Pol
fab)
was
satu
rate
d w
ith e
thyl
ene
oxid
e. T
he sk
in p
iece
was
then
exp
osed
to th
e sa
tura
ted
fabr
ic in
an
non-
occl
uded
fash
ion.
Thu
s, m
ost o
f the
eth
ylen
e ox
ide
evap
orat
ed in
toth
e ai
r as s
een
in th
e lo
w a
bsor
ptio
n pe
rcen
tage
.
The
seco
nd e
xper
imen
t was
sim
ilar e
xcep
t tha
t the
pol
yest
er fa
bric
was
cov
ered
by
a do
uble
-laye
r lat
ex g
love
.Th
e 46
% a
bsor
ptio
n oc
curr
ed w
ithin
the
first
4h
sugg
estin
g hi
gh p
erm
eabi
lity
of e
thyl
ene
oxid
e.
The
fluxe
s and
Kp
valu
es in
the
tabl
e w
ere
calc
ulat
ed a
ssum
ing
a th
ickn
ess o
f the
fabr
ic o
f 0.5
mm
and
, hen
ce,
an a
pplie
d am
ount
of 1
7 ng
.
This
hig
hly
unce
rtain
exe
rcis
e su
gges
ts a
"ve
ry h
igh"
or e
ven
"ext
rem
ely
high
" pe
rmea
bilit
y of
eth
ylen
e ox
ide.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A99
App
endi
x A
Subs
tanc
e: E
thyl
ened
iam
ine
Mol
ecul
ar w
eigh
t:60
.1C
AS:
107
-15-
3D
ensi
ty:0
.899
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
3:36
Mel
ting
poin
t:8.
5°C
Boi
ling
poin
t:11
6.5°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:1.4
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:0
.91
Log
Kow
:-2.
04
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Rat
Ba
490.
2H
2O25
% (1
000
µg/c
m²)
4-6
2424
551
23Y
ang
et a
l. (1
987)
Rat
Ba
490.
2H
2O50
% (2
000
µg/c
m²)
4-6
2424
611.
252
Yan
g et
al.
(198
7)
Onl
y ra
t in
vivo
dat
a w
ere
foun
d. T
he K
p va
lue
of 1
·10-4
cm
/h su
gges
ts "
mod
erat
e" p
erm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A10
0
App
endi
x A
Subs
tanc
e: F
orm
alde
hyde
Mol
ecul
ar w
eigh
t:30
.0C
AS:
50-
00-0
Den
sity
:1.0
9 g/
cm³
Scie
ntifi
c ba
sis:
AoH
198
3:36
Mel
ting
poin
t:-1
18°C
Boi
ling
poin
t:-1
9.5°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.3
5
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
Full
0.35
0.03
5H
2O +
MeO
H (1
0-15
%)
370
110.
50.
50.
10 m
g/cm
²5.
721
0Lo
den
(198
6a)
Hum
Br
FlFu
ll0.
35H
2O +
MeO
H (1
-1.5
%)
375
2121
~1.4
4.6
17Lo
den
(198
6b)
Hum
Br
FlFu
ll0.
35H
2O +
MeO
H (1
0-15
%)
370
515
15~1
.48.
632
0Lo
den
(198
6b)
Rat
Ba
820
0 m
gC
ream
0.10
%8
4848
6.1
0.32
0.03
2B
artn
ik e
t al.
(198
5)R
atB
a8
200
mg
Cre
am0.
10%
448
489.
20.
480.
048
Bar
tnik
et a
l. (1
985)
Rat
Ba
820
0 m
gC
ream
0.10
%2
4848
3.4
0.18
0.01
8B
artn
ik e
t al.
(198
5)
The
in v
ivo
stud
y w
ith ra
t ski
n B
artn
ik e
t al.
(198
5) u
sed
skin
cre
am a
s veh
icle
, thi
s may
cha
nge
the
perm
eabi
lity
prop
ertie
s sig
nific
antly
. Th
e pr
efer
red
stud
y is
that
of L
oden
(198
6b),
usin
g hu
man
full
thic
knes
s ski
n in
vitr
o.
The
Kp
valu
es ra
nge
betw
een
5·10
-4 a
nd 9
·10-4
cm
/h, c
orre
spon
ds to
"m
oder
ate"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A10
1
App
endi
x A
Subs
tanc
e: F
orm
amid
eM
olec
ular
wei
ght:
45.0
CA
S: 7
5-12
-7D
ensi
ty:1
.134
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
1:8
Mel
ting
poin
t:2.
5°C
Boi
ling
poin
t:21
0°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.013
kPa
(at 3
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:0.0
04L
og K
ow:-
1.51
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
No
info
rmat
ion
rega
rdin
g sk
in u
ptak
e is
giv
en in
the
Swed
ish
cons
ensu
s rep
ort (
AoH
199
1:8)
.A
ccor
ding
to th
e A
CG
IH (2
001)
doc
umen
tatio
n, fo
rmam
ide
is re
lativ
ely
non-
toxi
c by
skin
app
licat
ion,
with
a d
erm
al L
D50
of 6
g/k
g in
rabb
its. H
owev
er, 3
mon
ths d
aily
der
mal
trea
tmen
t (5
d/w
k) w
ith 3
g/k
g pr
oduc
ed
gene
ral s
yste
mic
toxi
city
in ra
ts.
Acc
ordi
ng to
theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
the
pote
ntia
l for
der
mal
abso
rptio
n an
d re
sulti
ng to
xici
ty is
sign
ifica
nt.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A10
2
App
endi
x A
Subs
tanc
e: F
urfu
ral
Mol
ecul
ar w
eigh
t:96
.1C
AS:
98-
01-1
Den
sity
:1.1
59 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
984:
44M
eltin
g po
int:
-36.
5°C
Boi
ling
poin
t:16
7°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.14
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.4
1
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Ha
Nea
t6
0.25
2027
mg
1.6
180
Flek
et a
l. (1
978)
Hum
WB
Vap
30 m
g/m
³6
820
1800
000.
53Fl
ek e
t al.
(197
8)
The
flux
mea
sure
men
t is b
ased
on
reco
very
of f
urfu
ral m
etab
olite
in u
rine
afte
r dip
ping
one
han
d in
nea
t fur
fura
l. Th
is m
etho
d m
easu
res t
he ra
te o
f pen
etra
tion
into
skin
, rat
her t
han
the
stea
dy-s
tate
flux
, and
may
thus
be
an o
vere
stim
atio
n.
This
stud
y gi
ves a
Kp
valu
e of
2·1
0-4 c
m/h
, cor
resp
ondi
ng to
"m
oder
ate"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A10
3
App
endi
x A
Subs
tanc
e: F
urfu
ryl a
lcoh
olM
olec
ular
wei
ght:
98.1
CA
S: 9
8-00
-0D
ensi
ty:1
.128
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
5:32
Mel
ting
poin
t:-2
0.2°
CB
oilin
g po
int:
170°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.6
9 kP
a (a
t 25°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.2
8
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Ref
errin
g to
an
indu
stry
repo
rt, th
e Sw
edis
h co
nsen
sus d
ocum
ent (
AoH
198
5) st
ates
that
the
perc
utan
eous
upt
ake
has b
een
dem
onst
rate
d in
ani
mal
s. A
CG
IH (2
001)
giv
es a
sim
ilar s
tate
men
t with
the
addi
tiona
l inf
orm
atio
n of
dos
e-re
late
d m
orta
lity
in a
nim
als.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A10
4
App
endi
x A
Subs
tanc
e: H
alot
hane
Mol
ecul
ar w
eigh
t:19
7.4
CA
S: 1
51-6
7-7
Den
sity
:1.8
64 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
985:
32M
eltin
g po
int:
-118
°CB
oilin
g po
int:
50.2
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:32
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Ver
y hi
ghE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:2.3
0
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Rat
WB
Vap
5000
0ppm
44
40.
245
018
McD
ouga
l et a
l. (1
990)
The
only
stud
y fo
und
on h
alot
hane
is th
at o
f McD
ouga
l et a
l. (1
990)
wer
e ra
ts w
ere
expo
sed
to h
alot
hane
vap
our.
The
repo
rted
Kp
valu
e of
5·1
0-2 c
m/h
sugg
ests
a "
very
hig
h" p
erm
eabi
lity
It sh
ould
be
note
d th
at h
alot
hane
is v
ery
vola
tile.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A10
5
App
endi
x A
Subs
tanc
e: H
epta
ne, n
-M
olec
ular
wei
ght:
100.
2C
AS:
142
-82-
5D
ensi
ty:0
.684
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-90.
6°C
Boi
ling
poin
t:98
.4°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:4
.2 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: E
xtre
mel
y lo
wE
vapo
ratio
n ra
te:4
.3L
og K
ow:4
.66
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Rat
Ab
StFu
ll2.
61
Nea
t30
4-20
4-20
1-7
µg0.
0021
0.14
Tsur
uta
(198
2)
N
o da
ta a
vaila
ble
The
only
foun
d st
udy
on n
-hep
tane
is th
at o
f Tsu
ruta
(198
2) w
ere
rat s
kin
was
exp
osed
to n
eat n
-hep
tane
in v
itro.
The
calc
ulat
ed K
p va
lue
of 2
·10-7
cm
/h su
gges
ts a
n "e
xtre
mel
y lo
w"
perm
eabi
lity.
It sh
ould
be
note
d th
at h
epta
ne h
as v
ery
low
solu
bilit
y in
wat
er a
nd T
suru
ta (1
982)
use
d sa
line
as re
cept
or m
ediu
m.
Hen
ce, t
he K
p m
ay b
e an
und
eres
timat
e.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A10
6
App
endi
x A
Subs
tanc
e: H
exan
e, n
-M
olec
ular
wei
ght:
86.2
CA
S: 1
10-5
4-3
Den
sity
:0.6
55 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
986:
20M
eltin
g po
int:
-95°
CB
oilin
g po
int:
69°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:1
4 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: V
ery
low
Eva
pora
tion
rate
:9L
og K
ow:3
.90
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
FlFu
llN
eat
512
12~5
.20.
010.
83Lo
den
(198
6b)
Rat
Ab
StFu
ll2.
61
Nea
t51
2-22
2-22
0.4-
3 µg
0.00
092
0.06
1Ts
urut
a (1
982)
Hum
Arm
/Ha
1000
Vap
1.3
mm
ol/l
50.
56
130
1.5
Kez
ic e
t al.
(200
0)R
atW
BV
ap60
000p
pm5
44
0.1
310
6.5
McD
ouga
l et a
l. (1
990)
Ther
e is
a h
uge
diff
eren
ce in
Kp
valu
es b
etw
een
expe
rimen
ts in
viv
o an
d in
vitr
o.
Tsur
uta
(198
2) u
sed
salin
e as
rece
ptor
med
ium
, thi
s is l
ikel
y to
giv
e a
seve
re u
nder
est
imat
e of
the
flux
and
Kp
due
to th
e lo
w so
lubi
lity
of n
-hex
ane.
The
pref
erre
d st
udy
is th
at b
y Lo
den
(198
6b) w
ere
hum
an sk
in w
as e
xpos
ed to
nea
t n-h
exan
e.
The
calc
ulat
ed K
p va
lue
of 1
·10-6
cm
/h su
gges
ting
a "v
ery
low
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A10
7
App
endi
x A
Subs
tanc
e: H
exan
one,
2-;
met
hyl n
-but
yl k
eton
eM
olec
ular
wei
ght:
100.
2C
AS:
591
-78-
6D
ensi
ty:0
.811
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-57°
CB
oilin
g po
int:
127°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.3
3 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
:1.2
Log
Kow
:1.3
8
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Arm
5615
Nea
t4
112
19 m
g4.
234
0D
iVin
cenz
o et
al.
(197
8)
The
only
foun
d st
udy
is th
at o
f DiV
ince
nzo
et a
l. (1
978)
whi
ch w
as a
n in
viv
o st
udy
wer
e hu
man
skin
was
ex
pose
d to
nea
t 2-h
exan
one.
The
calc
ulat
ed K
p va
lue
corr
espo
nds t
o "m
oder
ate"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A10
8
App
endi
x A
Subs
tanc
e: H
ydro
gen
cyan
ide
Mol
ecul
ar w
eigh
t:27
.1C
AS:
74-
90-8
Den
sity
:0.6
9 g/
cm³
Scie
ntifi
c ba
sis:
AoH
200
1:19
Mel
ting
poin
t:-1
3.4°
CB
oilin
g po
int:
25.6
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:84
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Ver
y hi
ghE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:-0.
25
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
St40
1.8
Vap
1.3
(Sat
urat
ed)
0.1
100
13D
ugar
d (1
987)
N
o da
ta a
vaila
ble
The
sing
le st
udy
foun
d on
hyd
roge
n cy
anid
e w
as th
at o
f Dug
ard
(198
7) w
ere
hum
an sk
in w
as e
xpos
ed to
satu
rate
d cy
anid
e va
pour
(con
cent
ratio
n no
t giv
en, b
ut c
ould
be
calc
ulat
ed fr
om fl
ux a
nd K
p).
The
repo
rted
Kp
valu
e of
1·1
0-2 c
orre
spon
ds to
"ve
ry h
igh"
per
mea
bilit
y.
It sh
ould
be
note
d th
at th
e pe
rmea
bilit
y of
sodi
um c
yani
de is
two
orde
rs o
f mag
nitu
de lo
wer
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A10
9
App
endi
x A
Subs
tanc
e: H
ydro
quin
one
Mol
ecul
ar w
eigh
t:11
0.1
CA
S: 1
23-3
1-9
Den
sity
:1.3
32 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
991:
8M
eltin
g po
int:
170°
CB
oilin
g po
int:
285°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:0.0
024
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: V
ery
low
Eva
pora
tion
rate
:Neg
ligib
leL
og K
ow:0
.59
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
HG
PFl
250-
300
1.1
OiW
0.08
% (
2.5
µg/c
m²)
924
244.
30.
036
0.00
4H
ood
et a
l. (1
999)
Hum
Ab
StEp
iIn
fH
2O
569
88
0.09
30.
52B
arbe
r et a
l. (1
995)
Hum
Ab
Fl50
01
0.01
Cre
am2%
624
2434
1.1
2.9
Wes
ter e
t al.
(199
8c)
Rat
Ab
StFu
llIn
fH
2O
499
88
0.23
1.1
Bar
ber e
t al.
(199
5)R
atA
bSt
320
0.95
Cre
am50
(5%
)5
77
014
mg
3820
0M
atsu
baya
shi e
t al.
(200
3)
Hum
FH25
Cre
am2%
(2.5
mg)
624
9637
0.71
1.9
Wes
ter e
t al.
(199
8c)
Hum
Arm
25C
ream
2% (2
.5 m
g)6
88
450.
381
Wes
ter e
t al.
(199
8c)
The
stud
y by
Mat
suba
yash
i et a
l. (2
003)
seem
s unr
ealis
tic in
that
no
lag
time
was
obs
erve
d.Th
e ot
her i
n vi
tro st
udie
s are
in a
ccor
danc
e w
ith th
e in
viv
o st
udie
s.
The
in v
itro
stud
y us
ing
hum
an sk
in a
nd w
ater
as v
ehic
le (B
arbe
r et a
l. (1
995)
) is p
refe
rred
. Th
e K
p va
lue
of 9
·10-6
cm
/h c
orre
spon
ds to
"ve
ry lo
w"
perm
eabi
lity.
It sh
ould
be
note
d th
at K
p va
lues
cal
cula
ted
for a
queo
us so
lutio
ns a
re g
ener
ally
muc
h hi
gher
than
thos
e ob
tain
ed
for n
eat s
ubst
ance
s.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A11
0
App
endi
x A
Subs
tanc
e: H
ydro
xyet
hyla
cryl
ate,
2-;
prop
enoi
c ac
id, 2
-M
olec
ular
wei
ght:
116.
1C
AS:
818
-61-
1D
ensi
ty:1
.101
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-60.
2°C
Boi
ling
poin
t:21
0°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:7
Pa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:-
0.21
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
No
docu
men
tatio
n w
as fo
und
from
the
Swed
ish
crite
ria g
roup
or t
he A
CG
IH-T
LV c
omm
ittee
.
OEC
D (2
005)
repo
rts th
e fo
llow
ing
LD50
val
ues (
mg/
kg b
w):
oral
rat/m
ouse
601,
107
0, 1
040,
810
, 540
, 650
, 548
derm
al ra
bbit
250,
298
, 154
, >63
, 110
0, 3
000
derm
al ra
t>1
000
The
derm
al a
nd o
ral L
D50
val
ues a
re in
the
sam
e ra
nge,
sugg
estin
g th
at sk
in a
bsor
ptio
n m
ay b
e si
gnifi
cant
.
Als
o a
stud
y ci
ted
in O
ECD
(200
5) sh
owed
that
two
third
s (66
%) o
f der
mal
ly a
pplie
d ra
diol
abel
led
2-hy
drox
yeth
ylac
ryla
te (4
mal
e ra
ts, c
lippe
d fu
r, 12
.5 m
g/kg
bw
, exp
osed
are
a no
t giv
en) w
as re
cove
red
with
in 4
8h.
This
sugg
ests
ext
ensi
ve sk
in p
enet
ratio
n.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A11
1
App
endi
x A
Subs
tanc
e: Is
oflu
rane
Mol
ecul
ar w
eigh
t:18
4.5
CA
S: 2
6675
-46-
7D
ensi
ty:1
.45
g/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:~-
103°
CB
oilin
g po
int:
48.5
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:32
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Ver
y hi
ghE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:2.0
6
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Rat
WB
Vap
5000
0ppm
64
40.
125
09.
6M
cDou
gal e
t al.
(199
0)
The
only
foun
d st
udy
on is
oflu
rane
is th
at o
f McD
ouga
l et a
l. (1
990)
. Th
e re
porte
d K
p va
lue
of 3
·10-2
cm
/h su
gges
ts a
"ve
ry h
igh"
per
mea
bilit
y.
It sh
ould
be
note
d th
at v
apou
r exp
osur
e us
ually
yie
ld fo
r hig
her K
p va
lues
than
doe
s liq
uid
expo
sure
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A11
2
App
endi
x A
Subs
tanc
e: Is
opro
pano
lM
olec
ular
wei
ght:
60.1
CA
S: 6
7-63
-0D
ensi
ty:0
.785
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
2:24
Mel
ting
poin
t:-8
8.5°
CB
oilin
g po
int:
82.4
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:3.9
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:2
.9L
og K
ow:0
.05
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
St90
00.
640.
13H
2O10
%8
81
26 µ
g (4
h)1.
713
Kor
inth
et a
l. (2
003)
Hum
St90
00.
640.
13H
2O50
%8
81
430
µg2.
496
Kor
inth
et a
l. (2
003)
Rat
Ba
4.3
H2O
70
%4
4814
-15
780-
850
Boa
tman
et a
l. (1
998)
The
hum
an in
vitr
o an
d ra
t in
vivo
giv
e co
ncor
dant
resu
lts.
The
hum
an d
ata
yiel
d a
Kp
valu
e of
2·1
0-4 c
m/h
sugg
estin
g "m
oder
ate"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A11
3
App
endi
x A
Subs
tanc
e: Is
opro
pylb
enze
ne; c
umen
eM
olec
ular
wei
ght:
120.
2C
AS:
98-
82-8
Den
sity
:0.8
62 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
982:
24M
eltin
g po
int:
-96°
CB
oilin
g po
int:
151°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:610
Pa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:0.4
3L
og K
ow:3
.66
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
the
Swed
ish
cons
ensu
s rep
ort (
AoH
198
2), t
here
are
indi
catio
ns th
at it
is a
bsor
bed
by th
e sk
in.
Acc
ordi
ng to
AC
GIH
(200
1) th
e ci
ted
stud
y (V
alet
te e
t al.
(195
4)) d
id n
ot d
irect
ly d
emon
stra
te sk
in
abso
rptio
n of
isop
ropy
lben
zene
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A11
4
App
endi
x A
Subs
tanc
e: M
ercu
ry b
ichl
orid
e; d
ichl
orom
ercu
ryM
olec
ular
wei
ght:
271.
5C
AS:
748
7-94
-7D
ensi
ty:5
.44
g/cm
³Sc
ient
ific
basi
s: A
oH 1
984:
44M
eltin
g po
int:
277°
CB
oilin
g po
int:
302°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:-0.
22
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
GP
Ba
FlFu
ll3.
1H
2O
1-48
(0.
005-
0.24
M)
3048
4817
-20
2-81
Wah
lber
g (1
965)
Hum
Ab
FlFu
ll3.
1H
2O
1 (0
.005
M)
1048
488
0.8
Wah
lber
g (1
965)
Hum
Ab
FlFu
ll3.
1H
2O
16 (
0.08
0M)
1048
484.
57.
2W
ahlb
erg
(196
5)H
umB
rFl
Full
3.1
H2O
16
(0.
080M
)10
4848
9.4
15W
ahlb
erg
(196
5)H
umA
bFl
Full
3.1
H2O
48
(0.
24M
)10
4848
6.3
30W
ahlb
erg
(196
5)H
umSt
250
11.
5H
2O50
(5%
)10
17.5
17.5
92 µ
g1.
15.
3Pi
lgra
m e
t al.
(200
0)H
umA
bFl
300-
600
0.95
40 m
gSo
il0.
0088
nm
ol/c
m³
572
7214
00.
0000
32Sa
rtore
lli e
t al.
(200
3)H
umA
bFl
300-
600
0.95
40 m
gSo
il0.
061
nmol
/cm
³4
7272
300.
0000
49Sa
rtore
lli e
t al.
(200
3)Pi
gA
bFl
200
0.64
0.00
5Et
0.03
2 (1
60 n
g)16
160.
13 (1
h)0.
140.
0004
6Sk
owro
nski
et a
l. (2
000)
Hum
Arm
220.
3H
2O
27 (
0.1M
)3
0.08
11.
0 m
g21
056
0B
aran
owsk
a-D
utki
ewic
z (1
982a
)H
umA
rm22
0.3
H2O
27
(0.
1M)
30.
171
1.5
mg
150
400
Bar
anow
ska-
Dut
kiew
icz
(198
2a)
Hum
Arm
220.
3H
2O
27 (
0.1M
)3
0.25
11.
9 m
g13
034
0B
aran
owsk
a-D
utki
ewic
z (1
982a
)H
umA
rm22
0.3
H2O
27
(0.
1M)
40.
51
3.0
mg
100
280
Bar
anow
ska-
Dut
kiew
icz
(198
2a)
Hum
Arm
220.
3H
2O
27 (
0.1M
)3
11
3.2
mg
5615
0B
aran
owsk
a-D
utki
ewic
z (1
982a
)
The
stud
ies f
ound
on
mer
cury
bic
hlor
ide
expo
sing
hum
an sk
in to
aqu
eous
solu
tions
are
not
con
sist
ent.
The
rang
e fo
r the
cal
cula
ted
Kp
valu
es is
1·1
0-4 to
1·1
0-2 c
m/h
, i.e
. tw
o or
ders
of m
agni
tude
.Th
e pr
efer
red
stud
y is
that
of W
ahlb
erg
(196
5) w
ith c
alcu
late
d K
p va
lues
rang
ing
betw
een
5·10
-4 a
nd 9
·10-4
cm
/h, s
ugge
stin
g "m
oder
ate"
per
mea
bilit
y.Th
e in
viv
o st
udy
by B
aran
owsk
a-D
utki
ewic
z (1
982a
) sho
w th
at th
e pe
netra
tion
into
skin
is
appr
oxim
atel
y 20
tim
es h
ighe
r. Th
is su
gges
ts th
at a
dep
ot o
f dic
hlor
omer
cury
is c
reat
ed in
the
skin
that
m
ay la
ter b
ecom
e sy
stem
ical
ly a
vaila
ble.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A11
5
App
endi
x A
Subs
tanc
e: M
ercu
ry c
hlor
ide;
dim
ercu
ry d
ichl
orid
eM
olec
ular
wei
ght:
472.
1C
AS:
101
12-9
1-1
Den
sity
:7.1
5 g/
cm³
Scie
ntifi
c ba
sis:
AoH
198
4:44
Mel
ting
poin
t:40
0 to
500
°CB
oilin
g po
int:
Not
ava
ilabl
eSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Ver
y hi
ghE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:-0.
55 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StFu
ll0.
64C
ream
290
µg/l
1024
2427
00.
0078
Palm
er e
t al.
(200
0)H
umA
bSt
Full
0.64
H2O
290
µg/l
1024
2415
00.
0044
Palm
er e
t al.
(200
0)
N
o da
ta a
vaila
ble
The
only
stud
y fo
und
on m
ercu
ry c
hlor
ide
was
that
of P
alm
er e
t al.
(200
0).
The
pref
erre
d ex
perim
ent i
s the
one
usi
ng w
ater
as v
ehic
le. T
he re
porte
d K
p va
lue
of 2
·10-2
cm
/hsu
gges
ts a
"ve
ry h
igh"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A11
6
App
endi
x A
Subs
tanc
e: M
ercu
ry, d
imet
hyl
Mol
ecul
ar w
eigh
t:23
0.7
CA
S: 5
93-7
4-8
Den
sity
:2.9
6 g/
cm³
Scie
ntifi
c ba
sis:
AoH
198
4:44
Mel
ting
poin
t:-4
3°C
Boi
ling
poin
t:93
to 9
4°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:6
.7-1
0.9
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:2
.59
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
The
Swed
ish
skin
not
atio
n ap
plie
s to
orga
nic
mer
cury
com
poun
ds in
gen
eral
(inc
ludi
ng d
imet
hyl m
ercu
ry).
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
A c
ase
repo
rt (N
iere
nber
g et
al.
(199
8)) d
escr
ibes
the
deat
h of
a c
hem
ist 1
0 m
onth
s afte
r spi
lling
dim
ethy
l mer
cury
on th
e do
rsum
of h
er g
love
d ha
nd. T
he e
stim
ated
dos
e w
as 1
344
mg
corr
espo
ndin
g to
0.4
4 m
l nea
t dim
ethy
l mer
cury
.A
lthou
gh a
dditi
onal
exp
osur
e(s)
can
not b
e ex
clud
ed, t
his c
ase
stro
ngly
supp
orts
hig
h po
tent
ial f
or d
erm
al to
xici
ty.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A11
7
App
endi
x A
Subs
tanc
e: M
ercu
ry, m
etal
Mol
ecul
ar w
eigh
t:20
0.6
CA
S: 7
439-
97-6
Den
sity
:13.
53 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
984:
44M
eltin
g po
int:
-38.
9°C
Boi
ling
poin
t:35
6.5°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.1
6 Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Ext
rem
ely
high
Eva
pora
tion
rate
:4L
og K
ow:0
.62
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Arm
360-
430
Inf
Vap
0.88
-2.1
ng/
ml
50.
45-0
.72
60 d
220-
850
ng61
00-2
4000
0.00
1-0.
005
Hur
sh e
t al.
(198
9)
The
only
foun
d st
udy
on m
etal
mer
cury
was
that
of H
ursh
et a
l. (1
989)
wer
e a
hum
an a
rm w
as e
xpos
edto
mer
cury
vap
our.
The
repo
rted
rang
e of
Kp
valu
es su
gges
ts a
n "e
xtre
mel
y hi
gh"
perm
eabi
lity.
It sh
ould
be
note
d th
at st
udie
s on
vapo
ur e
xpos
ure
tend
to o
vere
stim
ate
the
Kp
valu
e.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A11
8
App
endi
x A
Subs
tanc
e: M
etha
nol
Mol
ecul
ar w
eigh
t:32
.0C
AS:
67-
56-1
Den
sity
:0.7
91 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
985:
32M
eltin
g po
int:
-98°
CB
oilin
g po
int:
64.6
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:13
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Ver
y hi
ghE
vapo
ratio
n ra
te:4
.6L
og K
ow:-
0.77
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
GP
Ba
FlFu
ll5
0.1
Nea
t9
1919
444.
736
8G
umm
er &
Mai
bach
(198
6)H
umA
bSt
272.
5H
2O
7.4
105
1.6
Sche
uple
in &
Bla
nk (1
973)
Hum
Ab
St25
002.
5H
2O
7.4
353
017
0Sc
heup
lein
& B
lank
(197
3)H
umA
bSt
272.
5N
eat
710
083
00Sc
heup
lein
& B
lank
(197
3)H
umA
bSt
2500
2.5
Nea
t2
230
1800
0Sc
heup
lein
& B
lank
(197
3)H
umA
bSt
Epi
10H
2O10
86
60.
3716
1300
Sout
hwel
l et a
l. (1
984)
Hum
Ab
St40
10H
2O3.
2 (0
.1M
)2
5-7
5-7
12-2
13.
8-6.
3So
uthw
ell e
t al.
(198
3)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
40.
30.
318
0.00
59B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
45.
85.
816
0.00
51B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
49.
89.
817
0.00
54B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
413
.813
.819
0.00
61B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
417
.817
.818
0.00
59B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
426
.326
.318
0.00
59B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
40.
30.
329
0.00
93B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
44.
34.
326
0.00
83B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
47.
87.
823
0.00
74B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
411
.311
.328
0.00
9B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
414
.314
.325
0.00
8B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
126
.326
.324
0.00
77B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
40.
30.
317
0.00
54B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
45.
85.
816
0.00
51B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
49.
89.
815
0.00
48B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
413
.813
.815
0.00
48B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
417
.817
.814
0.00
45B
ehl e
t al.
(198
0)
Rep
orte
d da
ta
In v
itro
A11
9
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
32 (
0.00
01M
)4
26.3
26.3
150.
0048
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
32 (
0.00
01M
)8
0.5
0.5
210.
0067
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
32 (
0.00
01M
)8
55
180.
0059
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
32 (
0.00
01M
)8
1010
190.
0061
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
32 (
0.00
01M
)8
1515
190.
0061
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
32 (
0.00
01M
)8
2020
190.
0061
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
32 (
0.00
01M
)8
2828
200.
0064
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
32 (
0.00
01M
)4
0.5
0.5
610.
02B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
45
557
0.01
8B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
410
1052
0.01
7B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
415
1560
0.01
9B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
420
2063
0.02
Beh
l et a
l. (1
980)
Mou
Ab/
Ba
StFu
ll0.
61.
4N
aCl
0.00
32 (
0.00
01M
)4
2525
620.
02B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
430
3058
0.01
9B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
80.
80.
823
0.00
74B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
86.
26.
222
0.00
7B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
810
1022
0.00
7B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
815
1523
0.00
74B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
822
2225
0.00
8B
ehl e
t al.
(198
0)M
ouA
b/B
aSt
Full
0.6
1.4
NaC
l0.
0032
(0.
0001
M)
827
2726
0.00
83B
ehl e
t al.
(198
0)M
ouA
bSt
Full
0.6
0.2
NaC
l3
22
10B
ehl e
t al.
(198
4)M
ouA
bSt
Full
0.6
0.2
NaC
l2
22
12B
ehl e
t al.
(198
4)M
ouA
bSt
Full
0.6
0.2
NaC
l4
22
26B
ehl e
t al.
(198
4)M
ouA
bSt
Full
0.6
0.2
NaC
l5
22
34B
ehl e
t al.
(198
4)M
ouA
bSt
Full
0.6
0.2
NaC
l5
22
13B
ehl e
t al.
(198
4)M
ouA
bSt
Full
0.6
0.2
NaC
l5
22
8B
ehl e
t al.
(198
4)M
ouB
aSt
Full
0.6
0.2
NaC
l4
22
27B
ehl e
t al.
(198
4)M
ouB
aSt
Full
0.6
0.2
NaC
l2
22
35B
ehl e
t al.
(198
4)M
ouB
aSt
Full
0.6
0.2
NaC
l4
22
43B
ehl e
t al.
(198
4)M
ouB
aSt
Full
0.6
0.2
NaC
l5
22
68B
ehl e
t al.
(198
4)M
ouB
aSt
Full
0.6
0.2
NaC
l5
22
11B
ehl e
t al.
(198
4)M
ouB
aSt
Full
0.6
0.2
NaC
l5
22
10B
ehl e
t al.
(198
4)M
ouA
bSt
Full
0.6
NaC
l0.
0032
(0.
0001
M)
52
254
Beh
l & B
arre
tt (1
981)
A12
0
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Mou
Ba
StFu
ll0.
6Ph
/NaC
l4.
0 (0
.5%
)6
2.5
2.5
2610
Beh
l et a
l. (1
983)
Mou
Ba
StFu
ll0.
6Ph
/NaC
l7.
9 (1
.0%
)6
2.5
2.5
3931
Beh
l et a
l. (1
983)
Mou
Ba
StFu
ll0.
6Ph
/NaC
l16
(2.
0%)
62.
52.
569
110
Beh
l et a
l. (1
983)
Mou
Ba
StFu
ll0.
6Ph
/NaC
l32
(4.
0%)
62.
52.
585
027
00B
ehl e
t al.
(198
3)M
ouB
aSt
Full
0.6
Ph/N
aCl
47 (
6.0%
)6
2.5
2.5
1700
8000
Beh
l et a
l. (1
983)
Mou
Ab
StFu
ll0.
79N
aCl
≤10-
4M2
24.
1D
urrh
eim
et a
l. (1
980)
Mou
Ab
StFu
ll0.
79N
aCl
≤10-
4M2
29.
3D
urrh
eim
et a
l. (1
980)
Mou
Ab
StFu
ll0.
79N
aCl
≤10-
4M2
226
Dur
rhei
m e
t al.
(198
0)
Hum
Ha
480
Inf
Nea
t65
0.03
-0.2
77
0.5
1200
mg
100
8100
Bat
term
an e
t al.
(199
7)H
umA
rm11
0.2
Nea
t3
0.25
822
-27
mg
110
8800
Dut
kiew
icz
et a
l. (1
980)
Hum
Arm
110.
2N
eat
30.
338
38-4
1 m
g14
011
000
Dut
kiew
icz
et a
l. (1
980)
Hum
Arm
110.
2N
eat
60.
58
65-8
1 m
g18
014
000
Dut
kiew
icz
et a
l. (1
980)
Hum
Arm
110.
2N
eat
30.
588
81-9
2 m
g16
013
000
Dut
kiew
icz
et a
l. (1
980)
Hum
Arm
110.
2N
eat
30.
758
92-1
10 m
g15
012
000
Dut
kiew
icz
et a
l. (1
980)
Hum
Arm
110.
2N
eat
41
812
0-13
0 m
g14
011
000
Dut
kiew
icz
et a
l. (1
980)
The
data
on
met
hano
l are
abu
ndan
t.
The
stud
y by
Sch
eupl
ein
& B
lank
(197
3) is
dis
rega
rded
sinc
e he
at-s
epar
ated
(60°
C) e
pide
rmis
was
use
d.
The
stud
y by
Beh
l et a
l. (1
983)
is a
lso
disr
egar
ded
as p
heno
l was
use
d as
a v
ehic
le.
The
rem
aini
ng st
udie
s sho
w a
con
sist
ent p
atte
rn w
ith K
p va
lues
rang
ing
betw
een
1·10
-3 a
nd 7
·10-3
cm
/h fo
r mou
se a
nd
hum
an sk
in a
nd a
queo
us so
lutio
ns o
f met
hano
l.
The
pref
erre
d st
udie
s are
thos
e of
Bat
term
an e
t al.
(199
7) a
nd D
utki
ewic
z et
al.
(198
0), s
ince
they
use
d hu
man
skin
in v
ivo
expo
sed
to n
eat m
etha
nol r
epor
ting
high
er K
p va
lues
of 1
·10-2
to 2
·10-2
cm
/h, s
ugge
stin
g "v
ery
high
" pe
rmea
bilit
y.
In v
ivo
Ase
ssm
ent
A12
1
App
endi
x A
Subs
tanc
e: M
ethy
l acr
ylat
eM
olec
ular
wei
ght:
86.1
CA
S: 9
6-33
-3D
ensi
ty:0
.956
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-76.
5°C
Boi
ling
poin
t:80
.5°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:9
.1 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.8
0
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
No
docu
men
t fro
m th
e Sw
edis
h C
riter
ia G
roup
was
foun
d on
met
hyl a
cryl
ate.
The
derm
al L
D50
val
ues f
or ra
ts a
nd ra
bbits
are
4-6
tim
es h
ighe
r tha
n th
e co
rres
pond
ing
oral
LD
50 v
alue
s, th
is fo
rms t
he b
asis
for a
skin
not
atio
n by
AC
GIH
(200
1).
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A12
2
App
endi
x A
Subs
tanc
e: M
ethy
l bro
mid
eM
olec
ular
wei
ght:
94.9
CA
S: 7
4-83
-9D
ensi
ty:1
.732
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
8:32
Mel
ting
poin
t:-9
3.7°
CB
oilin
g po
int:
3.6°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:200
kPa
(at 2
3.3°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:1.1
9
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Toxi
c am
ount
s can
be
abso
rbed
by
the
skin
, bot
h w
ith d
irect
con
tact
and
with
exp
osur
e to
hig
h ai
r con
cent
ratio
ns (J
ordi
(195
3)).
A c
ase
repo
rt (L
ongl
ey e
t al.
(196
5)) i
s als
o si
ted
in A
CG
IH (2
001)
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A12
3
App
endi
x A
Subs
tanc
e: M
ethy
l eth
yl k
eton
e (M
EK);
2-bu
tano
neM
olec
ular
wei
ght:
72.1
CA
S: 7
8-93
-3D
ensi
ty:0
.805
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
5:32
Mel
ting
poin
t:-8
6.3°
CB
oilin
g po
int:
79.6
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:11
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Low
Eva
pora
tion
rate
:5.7
Log
Kow
:0.2
9
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
St30
0-60
00.
64N
eat
36
666
5800
Urs
in e
t al.
(199
5)H
umB
rFl
280
0.64
0.2
Nea
t5
2424
0.33
0.13
0.41
33W
ilkin
son
& W
illia
ms (
2001
)H
umB
rFl
280
0.64
0.2
H2O
3
524
240.
350.
7728
8.4
Wilk
inso
n &
Will
iam
s (20
01)
N
o da
ta a
vaila
ble
Urs
in e
t al.
(199
5) st
retc
hed
the
skin
whe
n m
ount
ing
it in
the
diff
usio
n ce
ll, re
achi
ng a
fina
l thi
ckne
ss o
f abo
ut o
ne-th
ird o
f the
orig
inal
thic
knes
s. Th
is p
roce
dure
may
giv
e ov
eres
timat
es o
f the
flux
and
Kp
valu
es.
The
pref
erre
d ex
perim
ent i
s the
one
usi
ng n
eat M
EK (W
ilkin
son
& W
illia
ms (
2001
), da
ta o
nly
pres
ente
d at
a c
onfe
renc
e), w
ith a
repo
rted
Kp
valu
e 4·
10-5
cm
/h, s
ugge
stin
g "l
ow"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A12
4
App
endi
x A
Subs
tanc
e: M
ethy
l iod
ide
Mol
ecul
ar w
eigh
t:14
1.9
CA
S: 7
4-88
-4D
ensi
ty:2
.279
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
1:21
Mel
ting
poin
t:-6
6.5°
CB
oilin
g po
int:
42.4
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:50
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:1
.51
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s rep
ort (
AoH
198
1:21
) sta
tes t
hat m
ethy
l iod
ine
can
be a
bsor
bed
via
skin
, with
no
addi
tiona
l dat
a.
In A
CG
IH (2
001)
, no
dire
ct st
udie
s or c
ase
repo
rts o
n de
rmal
abs
orpt
ion
and
resu
ltant
syst
emic
toxi
city
are
giv
en.
The
skin
not
atio
n is
bas
ed o
n tw
o ca
se re
ports
of f
atal
and
acu
te, p
erm
anen
t CN
S da
mag
e fo
llow
ing
acci
dent
alex
posu
re to
met
hyl i
odin
e w
ith u
nkno
wn
air c
once
ntra
tions
(Gar
land
et a
l. (1
945)
, App
el e
t al.
(197
5)).
Acc
ordi
ng to
theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
the
pote
ntia
l for
der
mal
abso
rptio
n an
d re
sulti
ng to
xici
ty is
sign
ifica
nt.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A12
5
App
endi
x A
Subs
tanc
e: M
ethy
l iso
buty
l ket
one
(MiB
K)
Mol
ecul
ar w
eigh
t:10
0.2
CA
S: 1
08-1
0-1
Den
sity
:0.7
98 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:-8
0°C
Boi
ling
poin
t:11
7.4°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:0.6
3 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: H
igh
Eva
pora
tion
rate
:1.6
Log
Kow
:1.3
1
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
GP
Ba
3.1
Nea
t8
2.5
2.5
8366
00H
jelm
et a
l. (1
991)
The
only
ava
ilabl
e st
udy
is th
at o
f Hje
lm e
t al.
(199
1) w
ere
guin
ea p
ig w
as e
xpos
ed in
viv
o to
nea
t MiB
K.
The
repo
rted
Kp
valu
e of
8·1
0-3 c
m/h
, cor
resp
onds
to "
high
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A12
6
App
endi
x A
Subs
tanc
e: M
ethy
l met
acry
late
Mol
ecul
ar w
eigh
t:10
0.1
CA
S: 8
0-62
-6D
ensi
ty:0
.943
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
3:37
Mel
ting
poin
t:-4
8°C
Boi
ling
poin
t:10
0°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:3
.6 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: V
ery
high
Eva
pora
tion
rate
:3.1
Log
Kow
:1.3
8
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
1A
bSt
Epi
2.54
2.5
Nea
t6
11
0.17
0.48
110
110
Bet
ts e
t al.
(200
6)
Hum
1A
bSt
Epi
2.54
2.5
Nea
t6
1010
0.17
0.56
3.7
3.5
Bet
ts e
t al.
(200
6)
Hum
2A
bSt
Epi
2.54
2.5
Nea
t6
11
0.17
2.4
290
270
Bet
ts e
t al.
(200
6)
Hum
2A
bSt
Epi
2.54
2.5
Nea
t6
1010
0.17
1516
015
0B
etts
et a
l. (2
006)
N
o da
ta a
vaila
ble
1 Non
occ
lude
d 2 O
cclu
ded
The
only
stud
y fo
und
on m
ethy
l met
acry
late
was
that
by
Bet
ts e
t al.
(200
6) w
here
hum
an sk
in w
as e
xpos
ed to
nea
t MM
A.
The
1h o
cclu
ded
expo
sure
is p
refe
rred
and
the
calc
ulat
ed K
p va
lue
of 3
·10-2
cm
/h c
orre
spon
ds to
"ve
ry h
igh"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A12
7
App
endi
x A
Subs
tanc
e: M
ethy
l mor
phol
ine,
N-
Mol
ecul
ar w
eigh
t:10
1.1
CA
S: 1
09-0
2-4
Den
sity
:0.9
2 g/
cm³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-66°
CB
oilin
g po
int:
115°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:2.3
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:1.8
Log
Kow
:-0.
33
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
No
Swed
ish
cons
ensu
s or A
CG
IH re
port
was
foun
d on
n-m
ethy
l mor
phol
in.
The
Swed
ish
skin
not
atio
n is
like
ly b
ased
on
anal
ogy
with
the
clos
ely
rela
ted
subs
tanc
e m
orph
olin
e.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A12
8
App
endi
x A
Subs
tanc
e: M
ethy
l ter
t-but
yl e
ther
(MTB
E)M
olec
ular
wei
ght:
88.1
CA
S: 1
634-
04-4
Den
sity
:0.7
41 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
999:
25M
eltin
g po
int:
-109
°CB
oilin
g po
int:
55.2
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:33
kPa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
Ver
y hi
ghE
vapo
ratio
n ra
te:8
.1L
og K
ow:0
.94
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Ha
Inf
H2O
0.05
114
124
280
1400
Prah
et a
l. (2
004)
Rat
Ba
2-5
10 m
l/kgB
WN
aCl
4(4
0 m
g/kb
BW
)12
06
4516
110-
280
43-1
10M
iller
et a
l. (1
997)
Rat
Ba
2-5
10 m
l/kgB
WN
aCl
40(4
00 m
g/kb
BW
)12
06
4534
230-
580
910-
2300
Mill
er e
t al.
(199
7)
The
expo
sed
skin
are
a w
as n
ot g
iven
by
Mill
er e
t al.
(199
7). T
he v
alue
s in
the
tabl
e w
ere
ther
efor
e ca
lcul
ated
usi
ng a
n ar
ea
of 2
-5 c
m² a
nd a
ssum
ing
a bo
dyw
eigh
t of 2
00 g
. The
Kp
valu
es th
us o
btai
ned
agre
e w
ell w
ith th
at re
porte
d fo
r hum
an sk
in.
The
pref
erre
d st
udy
is th
at o
f Pra
h et
al.
(200
4) w
ere
hum
an sk
in in
viv
o w
as u
sed,
and
the
repo
rted
Kp
valu
e of
3·1
0-2 c
m/h
cor
resp
onds
to "
very
hig
h" p
erm
eabi
lity.
It sh
ould
be
note
d th
at th
e ex
perim
ent u
sed
MTB
E di
lute
d in
wat
er. T
his p
roce
dure
tend
s to
give
muc
h hi
gher
Kp
valu
e sth
an th
at o
btai
ned
usin
g ne
at su
bsta
nce.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A12
9
App
endi
x A
Subs
tanc
e: M
ethy
l-2-p
enta
nol,
4-M
olec
ular
wei
ght:
102.
2C
AS:
108
-11-
2D
ensi
ty:0
.807
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
3:37
Mel
ting
poin
t:-9
0°C
Boi
ling
poin
t:13
2°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.54
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:0.3
Log
Kow
:1.6
8 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
No
data
was
foun
d in
the
Swed
ish
cons
ensu
s rep
ort (
AoH
199
3:37
).
The
AC
GIH
(200
1) re
port
stat
es th
at th
e sk
in n
otat
ion
is b
ased
on
data
from
Sm
yth
et a
l. (1
951)
,su
gges
ting
sim
ilar d
erm
al (3
.6 g
/kg
bw in
rabb
its) a
nd o
ral (
2.6
g/kg
bw
in ra
ts) L
D50
val
ues.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A13
0
App
endi
x A
Subs
tanc
e: M
ethy
l-2-p
yrro
lidon
e, n
- (N
MP)
Mol
ecul
ar w
eigh
t:99
.1C
AS:
872
-50-
4D
ensi
ty:1
.033
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
7:39
Mel
ting
poin
t:-2
4°C
Boi
ling
poin
t:20
2°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:6
6 Pa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
Ver
y hi
ghE
vapo
ratio
n ra
te:0
.06
Log
Kow
:-0.
38
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
200-
400
0.64
Inf
Nea
t4-
6.5
4-6.
598
1000
0D
ick
et a
l. (2
001)
Hum
200-
400
0.64
Inf
H2O
30
%2-
82-
84.
111
0D
ick
et a
l. (2
001)
Hum
200-
400
0.64
0.00
6N
eat
33
1617
00D
ick
et a
l. (2
001)
Hum
200-
400
0.64
0.00
6H
2O
30%
33
1958
0D
ick
et a
l. (2
001)
Hum
Br
St30
0-60
00.
64N
eat
66
616
019
200
Urs
in e
t al.
(199
5)R
at20
0-40
00.
640.
006
Nea
t3
330
3100
Dic
k et
al.
(200
1)R
at20
0-40
00.
640.
006
H2O
30
%3
330
910
Dic
k et
al.
(200
1)R
atB
aSt
Full
1.8
0.04
5/0.
72N
eat
2624
2451
-54
5300
-560
0Pa
yan
et a
l. (2
003)
Rat
FkSt
Full
1.8
0.04
5/0.
72N
eat
2624
2458
-65
6000
-670
0Pa
yan
et a
l. (2
003)
Rat
Ba/
FkSt
Full
1.8
0.04
5N
eat
624
2491
2021
00Pa
yan
et a
l. (2
003)
Rat
Ba/
FkSt
Full
1.8
0.09
Nea
t6
2424
8933
3400
Paya
n et
al.
(200
3)R
atB
a/Fk
StFu
ll1.
80.
18N
eat
424
2451
5300
Paya
n et
al.
(200
3)R
atB
a/Fk
StFu
ll1.
80.
36N
eat
724
2468
6264
00Pa
yan
et a
l. (2
003)
Rat
Ba/
FkSt
Full
1.8
0.72
Nea
t16
2424
5373
7500
Paya
n et
al.
(200
3)R
atB
a/Fk
StFu
ll1.
80.
045
H2O
50%
624
2423
Paya
n et
al.
(200
3)R
atB
a/Fk
StFu
ll1.
80.
18H
2O50
%4
2424
50Pa
yan
et a
l. (2
003)
Rat
Ba/
FkSt
Full
1.8
0.36
H2O
50%
724
2443
-53
Paya
n et
al.
(200
3)R
atB
a/Fk
StFu
ll1.
80.
72H
2O50
%7
2424
51-5
3Pa
yan
et a
l. (2
003)
Rat
Ba/
FkSt
Full
1.8
1.4
H2O
50%
424
2447
Paya
n et
al.
(200
3)R
atB
a/Fk
StFu
ll1.
80.
18H
2O13
%3
2424
51Pa
yan
et a
l. (2
003)
Rat
Ba/
FkSt
Full
1.8
0.72
H2O
13%
324
2476
Paya
n et
al.
(200
3)R
atB
a/Fk
StFu
ll1.
80.
72H
2O6.
30%
324
2457
Paya
n et
al.
(200
3)R
atB
a/Fk
StFu
ll1.
80.
72H
2O3.
20%
324
2447
Paya
n et
al.
(200
3)
Rep
orte
d da
ta
In v
itro
A13
1
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ha
~500
Inf
H2O
5%1
0.17
485.
0 m
g12
60A
krill
et a
l. (2
002)
Hum
Ha
~500
Inf
H2O
5%2
0.25
486.
4 m
g10
52A
krill
et a
l. (2
002)
Hum
Ha
~500
Inf
H2O
10%
20.
2548
14 m
g11
110
Akr
ill e
t al.
(200
2)H
umH
a~5
00In
fH
2O15
%2
0.25
4832
mg
1726
0A
krill
et a
l. (2
002)
Hum
Ha
~500
Inf
H2O
20%
20.
2548
32 m
g13
260
Akr
ill e
t al.
(200
2)H
umH
a~5
00In
fH
2O25
%2
0.25
4852
mg
1742
0A
krill
et a
l. (2
002)
Rat
Ba
100.
2N
eat (
20 µ
l/cm
²)4
0.25
0.25
648
5000
Paya
n et
al.
(200
3)R
atB
a10
0.2
Nea
t (20
µl/c
m²)
40.
50.
518
7274
00Pa
yan
et a
l. (2
003)
Rat
Ba
100.
2N
eat (
20 µ
l/cm
²)4
0.75
0.75
2976
7900
Paya
n et
al.
(200
3)R
atB
a10
0.2
Nea
t (20
µl/c
m²)
41
136
7375
00Pa
yan
et a
l. (2
003)
Rat
Ba
100.
2N
eat (
20 µ
l/cm
²)4
22
6060
6200
Paya
n et
al.
(200
3)
The
in v
ivo
and
in v
itro
data
show
a c
onsi
sten
t pat
tern
for b
oth
neat
and
wat
er-d
ilute
d N
MP,
with
nea
rly a
ll K
p va
lues
bet
wee
n 2·
10-3
and
1·1
0-2 c
m/h
.
Mos
t exp
erim
ents
by
Dic
k et
al.
(200
1) a
nd A
krill
et a
l. (2
002)
with
hum
an sk
in a
lso
show
a c
onsi
sten
t pat
tern
with
Kp
valu
es b
etw
een
1·10
-3 a
nd 3
·10-3
cm
/h.
The
pref
erre
d ex
perim
ent i
s tha
t of D
ick
et a
l. (2
001)
usi
ng h
uman
skin
in v
itro.
The
Kp
valu
e of
1·1
0-2 c
m/h
cor
resp
onds
to "
very
hig
h" p
erm
eabi
lity.
In v
ivo
Ase
ssm
ent
A13
2
App
endi
x A
Subs
tanc
e: M
ethy
lam
ine
Mol
ecul
ar w
eigh
t:31
.1C
AS:
74-
89-5
Den
sity
:0.9
02 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
983:
36M
eltin
g po
int:
-38°
CB
oilin
g po
int:
48°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:3
1 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:-0.
57
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s rep
ort (
AoH
198
3:36
) sta
tes t
hat;
"With
mas
sive
exp
osur
e, a
min
es c
an b
e ab
sorb
ed v
ia th
e sk
in.
How
ever
we
foun
d no
upt
ake
via
inta
ct sk
in."
Acc
ordi
ng to
AC
GIH
(200
1), t
here
is in
suff
icie
nt d
ata
to a
ssig
n a
skin
not
atio
n, a
nd n
o ac
coun
ts o
f sys
tem
ic re
actio
nsha
ve b
een
repo
rted
in th
e lit
erat
ure.
Theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
show
ed th
at th
e po
tent
ial f
or d
erm
alab
sorp
tion
and
resu
lting
toxi
city
is si
gnifi
cant
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A13
3
App
endi
x A
Subs
tanc
e: M
ethy
lene
chl
orid
e; d
ichl
orom
etha
neM
olec
ular
wei
ght:
84.9
CA
S: 7
5-09
-2D
ensi
ty:1
.326
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
1:21
Mel
ting
poin
t:-9
6.7°
CB
oilin
g po
int:
39.8
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:47
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Hig
hE
vapo
ratio
n ra
te:2
8L
og K
ow:1
.25
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
St30
0-60
00.
64N
eat
36
618
2700
Urs
in e
t al.
(199
5)R
atA
bSt
Full
3.7
1N
eat
250.
5-3
0.5-
30.
55-
55 m
g44
5800
Tsur
uta
(197
7)
Mou
Ab
2.9
0.5
Nea
t0.
2550
6600
Tsur
uta
(197
5)
Urs
in e
t al.
(199
5) st
retc
hed
the
skin
whe
n m
ount
ing
it in
the
diff
usio
n ce
ll, re
achi
ng a
fina
l thi
ckne
ss o
f abo
ut
one-
third
of t
he o
rigin
al th
ickn
ess.
This
pro
cedu
re m
ay g
ive
over
estim
ates
of t
he fl
ux a
nd K
p va
lues
.
The
thre
e st
udie
s rep
ort f
airly
sim
ilar K
p va
lues
, ran
ging
bet
wee
n 2·
10-3
to 5
·10-3
cm
/h.
The
pref
erre
d st
udy
is th
at o
f Urs
in e
t al.
(199
5), w
ere
hum
an sk
in w
as u
sed
in v
itro.
The
repo
rted
Kp
valu
e of
2·1
0-3 c
m/h
cor
resp
onds
to "
high
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A13
4
App
endi
x A
Subs
tanc
e: M
ethy
lpen
tane
, 2-
Mol
ecul
ar w
eigh
t:86
.2C
AS:
107
-83-
5D
ensi
ty:0
.653
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-154
°CB
oilin
g po
int:
62°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:2
1 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: E
xtre
mel
y lo
wE
vapo
ratio
n ra
te:8
.3L
og K
ow:3
.21
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Rat
Ab
StFu
ll2.
61
Nea
t15
4-22
4-22
1-6
µg0.
0017
0.11
Tsur
uta
(198
2)
N
o da
ta a
vaila
ble
The
only
stud
y fo
und
sugg
est a
Kp
valu
e of
2·1
0-7 c
m/h
in ra
t ski
n, c
orre
spon
ding
to "
extre
mel
y lo
w"
perm
eabi
lity.
It sh
ould
be
note
d th
at T
suru
ta (1
982)
use
d ph
ysio
logi
cal s
alin
e as
rece
ptor
med
ium
, res
ultin
g in
low
solu
bilit
yfo
r lip
ophi
lic su
bsta
nces
. Thi
s may
lead
to u
nder
estim
ated
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A13
5
App
endi
x A
Subs
tanc
e: M
onoc
hlor
oace
tic a
cid
Mol
ecul
ar w
eigh
t:94
.5C
AS:
79-
11-8
Den
sity
:1.5
8 g/
cm³
Scie
ntifi
c ba
sis:
AoH
199
2:6
Mel
ting
poin
t:61
to 6
2°C
Boi
ling
poin
t:18
8°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.1 k
Pa (a
t 23°
C)
Skin
per
mea
bilit
y: V
ery
high
Eva
pora
tion
rate
:1L
og K
ow:0
.22
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Rat
Ba
0.79
0.5
ml/k
gBW
Ac
250
(130
mg/
kg B
W)
432
7648
012
000
Sagh
ir et
al.
(200
3)
The
only
ava
ilabl
e st
udy
is o
n m
onoc
hlor
oace
tic a
cid
is o
n ra
t ski
n in
viv
o w
ith a
ceto
ne a
s veh
icle
.
The
calc
ulat
ed K
p va
lue
sugg
ests
"ve
ry h
igh"
per
mea
bilit
y.
It sh
ould
be
note
d th
at a
ceto
ne m
ay d
amag
e th
e sk
in c
ausi
ng in
crea
sed
pene
tratio
n.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A13
6
App
endi
x A
Subs
tanc
e: M
orph
olin
eM
olec
ular
wei
ght:
87.1
CA
S: 1
10-9
1-8
Den
sity
:0.9
94 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
996:
25M
eltin
g po
int:
-4.9
°CB
oilin
g po
int:
128.
9°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:1
.1 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:0
.66
Log
Kow
:-0.
86
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Mor
phol
ine
is w
ell a
bsor
bed
via
inta
ct sk
in, w
here
as n
eutra
lized
mor
phol
ine
is n
ot (A
oH 1
996:
25, 1
982:
32).
The
skin
not
atio
n by
AC
GIH
(200
1) is
bas
ed o
n th
e lo
wer
der
mal
(0.5
g/k
g bw
) com
pare
d to
ora
l (1.
05 g
/kg
bw)
LD50
val
ue in
rats
.Th
ere
is a
lso
a re
port
of h
uman
der
mal
pen
etra
tion
(AC
GIH
(200
1)).
Acc
ordi
ng to
theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
the
pote
ntia
l for
der
mal
abso
rptio
n an
d re
sulti
ng to
xici
ty is
sign
ifica
nt.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A13
7
App
endi
x A
Subs
tanc
e: N
apht
alen
es, c
hlor
inat
edM
olec
ular
wei
ght:
231.
5C
AS:
132
1-65
-9D
ensi
ty:1
.58
g/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:93
°CB
oilin
g po
int:
304
to 3
54°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:<
0.1
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:5.1
0 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
WH
O d
ocum
ent o
n ch
loro
-nap
htal
enes
(WH
O (2
001)
) sta
tes t
hat:
"Der
mal
and
inha
latio
n ab
sorp
tion
of P
CN
s can
be
conc
lude
d fr
om sy
stem
ic e
ffec
ts in
ani
mal
s and
hum
ans.
A q
uant
ifica
tion
is n
ot p
ossi
ble.
"
The
Dut
ch c
omm
ittee
on
upda
ting
of O
ELs f
ound
no
data
rega
rdin
g de
rmal
upt
ake
of tr
ichl
oron
apht
alen
e.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A13
8
App
endi
x A
Subs
tanc
e: N
apht
hale
neM
olec
ular
wei
ght:
128.
2C
AS:
91-
20-3
Den
sity
:0.9
97 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
998:
25M
eltin
g po
int:
80.6
°CB
oilin
g po
int:
218°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:11
Pa (a
t 25°
C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
:<<1
Log
Kow
:3.3
0
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
St50
01.
1JP
-824
242.
20.
45K
anik
kann
an e
t al.
(200
1)M
onA
bSt
Full
1.8
0.03
Ac
150
nmol
/cm
²9?
7272
2.17
515.
7Sa
rtore
lli e
t al.
(199
8)M
PEa
rSt
500
1.1
JP-8
2424
1.8
0.38
Kan
ikka
nnan
et a
l. (2
001)
Pig
Ba
Fl20
0-30
00.
32JP
-81.
20%
45
52.
5-3
1.4
0.19
Bay
nes e
t al.
(200
0)Pi
gB
aFl
200-
300
0.32
JP-8
1.20
%4
55
2.5-
31.
40.
19B
ayne
s et a
l. (2
001)
Pig
Fl45
0-55
00.
640.
02JP
-811
(34
0 µg
/cm
²)5
55
2.1
2.2
Muh
amm
ad e
t al.
(200
4)R
atB
aSt
560
4.9
2JP
-80.
26%
84
40.
55.
11
McD
ouga
l et a
l. (2
000)
N
o da
ta a
vaila
ble
The
repo
rted
Kp
valu
es a
re fa
irly
cons
iste
nt, e
ven
betw
een
diff
eren
t spe
cies
.
The
pref
erre
d st
udie
s are
thos
e us
ing
jet f
uel,
rath
er th
at a
ceto
ne, a
s veh
icle
. Jet
fuel
may
als
o af
fect
skin
per
mea
tion,
alth
ough
pro
babl
y to
a le
sser
ext
ent t
han
acet
one.
Hum
an sk
in w
as u
sed
in o
ne e
xper
imen
t by
Kan
ikka
nnan
et a
l. (2
001)
.
The
repo
rted
Kp
valu
e of
2·1
0-4 c
m/h
sugg
ests
a "
mod
erat
e" p
erm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A13
9
App
endi
x A
Subs
tanc
e: N
icot
ine
Mol
ecul
ar w
eigh
t:16
2.2
CA
S: 5
4-11
-5D
ensi
ty:1
.01
g/cm
³Sc
ient
ific
basi
s: A
oH 2
004:
16M
eltin
g po
int:
-7.9
°CB
oilin
g po
int:
247°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:5.7
Pa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Hig
hE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:1.1
7
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StFu
ll1
1.5
H2O
372
7233
Deg
im e
t al.
(199
8)H
umA
b/B
rSt
410
1.8
PB20
(0.0
5 M
)9
2828
100
210
Qvi
st e
t al.
(200
0)H
umA
b/B
rSt
410
1.8
0.36
H2O
10
%6
1.5
1.5
0.13
8488
0Zo
rin e
t al.
(199
9)H
umA
b/B
rSt
410
1.8
0.36
H2O
20
%6
1.5
1.5
0.15
4388
0Zo
rin e
t al.
(199
9)H
umA
b/B
rSt
410
1.8
0.36
H2O
50
%6
1.5
1.5
0.16
2713
00Zo
rin e
t al.
(199
9)H
umA
b/B
rSt
410
1.8
0.1
Nea
t6
1.5
1.5
0.22
0.8
82Zo
rin e
t al.
(199
9)H
umA
bEp
i0.
791
PB1%
612
122.
15.
95.
9Po
ngja
nyak
ul e
t al.
(200
2)M
PB
aSt
770
1.8
PB20
(0.0
5 M
)9
2828
8717
0Q
vist
et a
l. (2
000)
MP
Ba
St77
01.
8PB
20 (0
.05
M)
928
2810
021
0Q
vist
et a
l. (2
000)
MP
Ba
St77
01.
8PB
20 (0
.05
M)
928
2810
020
0Q
vist
et a
l. (2
000)
Pig
Ba
St77
01.
8PB
20 (0
.05
M)
928
2811
022
0Q
vist
et a
l. (2
000)
Pig
Th1.
10.
643.
3PB
5030
3011
056
0N
air e
t al.
(199
7)Pi
gTh
1.1
0.64
3.3
PB50
3030
3618
0N
air e
t al.
(199
7)Pi
gEa
r0.
90.
643.
3PB
5030
3012
061
0N
air e
t al.
(199
7)Pi
gB
a1.
80.
643.
3PB
5030
3034
150
Nai
r et a
l. (1
997)
Pig
Ab
1.2
0.64
3.3
PB50
3030
170
850
Nai
r et a
l. (1
997)
SnSC
0.79
1PB
1%15
1212
0.55
3.5
3.5
Pong
jany
akul
et a
l. (2
002)
SnSC
0.79
1PB
1%15
1212
0.74
4.2
4.2
Pong
jany
akul
et a
l. (2
002)
Rep
orte
d da
ta
In v
itro
A14
0
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Rat
Ba
2.8
0.1
Ac
0.08
43
7272
442.
20.
018
Shah
et a
l. (1
987)
Rat
Ba
5.6
0.2
Ac
0.06
53
7272
673.
30.
022
Shah
et a
l. (1
987)
Rat
Ba
2.8
0.1
Ac
33
7272
120.
60.
18Sh
ah e
t al.
(198
7)R
atB
a5.
60.
2A
c 2.
43
7272
743.
70.
88Sh
ah e
t al.
(198
7)R
atB
a2.
80.
1A
c 12
372
7276
3.8
4.5
Shah
et a
l. (1
987)
Rat
Ba
5.6
0.2
Ac
123
7272
552.
73.
3Sh
ah e
t al.
(198
7)
The
only
exp
erim
ent f
ound
on
neat
nic
otin
e w
as th
at o
f Zor
in e
t al.
(199
9),
whi
ch re
porte
d a
Kp
valu
e of
8·1
0-5 c
m/h
, cor
resp
ondi
ng to
"lo
w"
perm
eabi
lity.
The
othe
r in
vitro
exp
erim
ents
usi
ng h
uman
skin
hav
e di
lute
d so
lutio
ns. T
he re
porte
d K
p va
lues
rang
ebe
twee
n 6·
10-4
and
1·1
0-2 c
m/h
, sug
gest
ing
"mod
erat
e-ve
ry h
igh"
per
mea
bilit
y.
The
pref
erre
d ex
perim
ents
are
thos
e by
Zor
in e
t al.
(199
9) w
hen
hum
an sk
in is
exp
osed
to d
ilute
d ni
cotin
e (1
0-50
%),
repo
rting
Kp
valu
es b
etw
een
3·10-3
and
8·1
0-3 c
m/h
, whi
ch c
orre
spon
ds to
"hi
gh"
perm
eabi
lity.
In v
ivo
Ase
ssm
ent
A14
1
App
endi
x A
Subs
tanc
e: N
itrob
enze
neM
olec
ular
wei
ght:
123.
1C
AS:
98-
95-3
Den
sity
:1.1
96 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:5.
7°C
Boi
ling
poin
t:21
0.8°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:20
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: N
o co
nclu
sion
Eva
pora
tion
rate
:0.0
29L
og K
ow:1
.85
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
St35
01.
1A
cN
eat
(4 µ
g/cm
²)6
2424
7.8
0.00
011
0.01
3B
rona
ugh
et a
l. (1
985a
)H
umA
bSt
350
1.1
Ac
Nea
t (4
µg/
cm²)
324
2441
0.00
056
0.06
7B
rona
ugh
et a
l. (1
985a
)H
umFl
350
0.64
Ac
Nea
t (4
µg/
cm²)
612
1210
0 ng
(2h)
0.00
067
0.08
Bro
naug
h et
al.
(198
5a)
Mon
Ab
St35
01.
1A
cN
eat
(4 µ
g/cm
²)6
2424
6.2
0.00
0083
0.01
Bro
naug
h et
al.
(198
5a)
Hum
Arm
13A
cN
eat
(4 µ
g/cm
²)6
2412
01.
50.
0000
210.
0025
Feld
man
n et
al.
(197
0)H
umW
B20
000
Vap
5-30
ng/
ml
126
244-
80 m
g17
000-
2000
00.
1-0.
5Pi
otro
wsk
i (19
67)
Mon
Ab
13A
cN
eat
(4 µ
g/cm
²)4
2412
04.
20.
0000
580.
007
Bro
naug
h et
al.
(198
5a)
The
Kp
valu
e ob
tain
ed u
sing
nitr
oben
zene
vap
our d
iffer
by
8-9
orde
rs o
f mag
nitu
de fr
om th
ose
obta
ined
usi
ng
nitro
benz
ene
diss
olve
d in
ace
tone
.Fu
rther
, the
Kp
valu
es in
ace
tone
are
abo
ut 4
ord
ers o
f mag
nitu
de lo
wer
than
for d
i- an
d tri
nitro
tolu
ene.
Thus
, the
Kp
valu
es fo
r nitr
oben
zene
seem
s unr
ealis
tic.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A14
2
App
endi
x A
Subs
tanc
e: N
itrog
lyce
rinM
olec
ular
wei
ght:
227.
1C
AS:
55-
63-0
Den
sity
:1.6
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
5:32
Mel
ting
poin
t:13
°CB
oilin
g po
int:
218°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.0
35 P
a (a
t 20°
C)
Skin
per
mea
bilit
y: L
owE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:1.6
2
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
HM
Ba
FlFu
ll0.
95H
2O
0.1
510
10~1
200
2K
ikko
ji et
al.
(199
1)H
MSt
Full
0.64
Nea
t?5
2424
0.19
31M
ingh
etti
et a
l. (1
999)
HM
Ba
FlFu
ll0.
951
H2O
0.1
66
645
-160
0.45
-1.6
Hig
o et
al.
(199
2a)
HM
Ba
FlFu
ll0.
951
H2O
0.1
810
1045
-190
0.45
-1.9
Hig
o et
al.
(199
2b)
Hum
Ab
StEp
i3.
1H
2O
231
4848
8517
Lang
guth
et a
l. (1
986a
)H
umTh
St20
00.
64N
eat?
524
240.
1422
Min
ghet
ti et
al.
(199
9)H
umTh
St20
00.
64N
eat?
524
240.
2133
Min
ghet
ti et
al.
(199
9)H
umTh
StEp
i0.
64N
eat?
524
240.
1423
Min
ghet
ti et
al.
(199
9)H
umA
bFl
Full
0.34
Patc
h6
2424
15R
ober
ts e
t al.
(199
0)H
umB
rSt
300
0.79
1Et
(5%
) + H
2O0.
05%
310
1047
3.5
Pone
c et
al.
(199
0)H
umB
rSt
SC0.
791
Et (5
%) +
H2O
0.05
%6
1010
413.
1Po
nec
et a
l. (1
990)
Hum
Ba
StSC
0.5
Et (4
0-80
%) +
H2O
10%
62-
1030
-150
Ber
ner e
t al.
(198
9)H
umA
bSt
Epi
3.1
11H
2O2
2548
4885
17La
nggu
th e
t al.
(198
6b)
Hum
824
246-
20N
oona
n et
al.
(198
9-19
90)
Mou
StFu
llN
eat
2424
<10.
2741
Chi
en e
t al.
(198
4)
N
o da
ta a
vaila
ble
The
expe
rimen
ts u
sing
eth
anol
as v
ehic
le a
re d
isre
gard
ed a
s it m
ay a
ffec
t ski
n pe
rmea
bilit
y.Th
ere
seem
s to
be a
veh
icle
eff
ect f
or n
itrog
lyce
rin. T
he re
porte
d K
p va
lues
for n
eat n
itrog
lyce
rin ra
nge
betw
een
1·10
-5 a
nd 3
·10-5
cm
/h, c
orre
spon
ding
to "
low
" pe
rmea
bilit
y.
It sh
ould
be
note
d th
at fo
r dilu
ted
nitro
glyc
erin
the
repo
rted
Kp
valu
es ra
nge
betw
een
5·10
-3 a
nd 2
·10-2
cm
/h,
corr
espo
ndin
g to
"hi
gh/v
ery
high
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A14
3
App
endi
x A
Subs
tanc
e: N
itrot
olue
neM
olec
ular
wei
ght:
137.
1C
AS:
132
1-12
-6D
ensi
ty:1
.16
to 1
.25
g/cm
³Sc
ient
ific
basi
s: A
oH 1
992:
6M
eltin
g po
int:
-10
to 5
4°C
Boi
ling
poin
t:22
2 to
238
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:16-
20 P
a (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:2.3
0
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s rep
ort (
AoH
199
2:6)
refe
rs to
Sax
(198
4), s
tatin
g th
at n
itrot
olue
ne c
an
be ta
ken
up b
y sk
in in
toxi
c am
ount
s.
Acc
ordi
ng to
AC
GIH
(200
1) n
o qu
antit
ativ
e da
ta o
n ni
troto
luen
e w
ere
foun
d. T
he sk
in n
otat
ion
is b
ased
on
anal
ogy
with
ani
line
and
nitro
benz
ene.
OEC
D S
IDS,
judg
e ni
troto
luen
e to
be
rapi
dly
abso
rbed
via
all
rout
es.
Theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
show
that
the
pote
ntia
l for
der
mal
abso
rptio
n an
d re
sulti
ng to
xici
ty is
sign
ifica
nt.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A14
4
App
endi
x A
Subs
tanc
e: O
ctan
esM
olec
ular
wei
ght:
114.
2C
AS:
111
-65-
9D
ensi
ty:0
.703
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-56.
8°C
Boi
ling
poin
t:12
6°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:1
.9 k
Pa (a
t 25°
C)
Skin
per
mea
bilit
y: E
xtre
mel
y lo
wE
vapo
ratio
n ra
te:1
.4L
og K
ow:5
.18
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Rat
Ab
StFu
ll2.
61
Nea
t14
23-5
123
-51
0.00
0008
0.00
06Ts
urut
a (1
982)
N
o da
ta a
vaila
ble
The
only
ava
ilabl
e st
udy
sugg
ests
a K
p va
lue
of 1
0-9 c
m/h
, cor
resp
ondi
ng to
"ex
trem
ely
low
" pe
rmea
bilit
y.
It sh
ould
be
note
d th
at T
suru
ta (1
982)
use
d ph
ysio
logi
cal s
alin
e as
rece
ptor
med
ium
, re
sulti
ng in
low
er so
lubi
lity
for l
ipop
hilic
subs
tanc
es. T
his m
ay h
ave
led
to a
und
eres
timat
ed K
p va
lue.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A14
5
App
endi
x A
Subs
tanc
e: P
enta
chlo
roph
enol
Mol
ecul
ar w
eigh
t:26
6.3
CA
S: 8
7-86
-5D
ensi
ty:1
.979
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
174°
CB
oilin
g po
int:
310°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.0
1 Pa
(at 2
5°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:5.1
2
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Pig
Fl5
0.1
Et0.
4 (4
0 µg
/cm
²)4
88
1.1
70.
28R
ivie
re e
t al.
(200
1)Pi
gFl
50.
1Et
(40%
) + H
2O (6
0%)
0.4
(40
µg/c
m²)
48
86.
943
1.7
Riv
iere
et a
l. (2
001)
Pig
Ab
50.
07Et
33
88
1.1
0.4
0.12
Qia
o et
al.
(200
2)H
umFl
500
1So
il17
ppm
(0.7
µg/
cm²)
615
150.
01-0
.07
0.00
28-0
.019
0.00
0004
7-0.
0000
33W
este
r et a
l. (1
993b
)H
umFl
500
1A
c17
ppm
(0.8
µg/
cm²)
615
150.
6-1.
50.
19-0
.47
0.00
032-
0.00
08W
este
r et a
l. (1
993b
)H
umA
bSt
Full?
10.
01H
2O +
TC
P4.
49
2424
0.8
0.03
30.
015
Hor
stm
an e
t al.
(198
9)H
umA
bSt
Full?
10.
01D
iese
l + T
CP
150
924
240.
140.
0058
0.08
8H
orst
man
et a
l. (1
989)
Pig
Ba
Fl20
0-30
00.
64H
2O
4 µg
/cm
²4
88
0.13
µg
1.7
0.03
1B
ayne
s et a
l. (2
002)
Pig
Ba
Fl20
0-30
00.
64H
2O
40 µ
g/cm
²4
88
2.2
2.2
µg3.
70.
92B
ayne
s et a
l. (2
002)
Pig
Ba
Fl20
0-30
00.
64Et
4 µg
/cm
²4
88
0.05
µg
0.5
0.01
4B
ayne
s et a
l. (2
002)
Pig
Ba
Fl20
0-30
00.
64Et
40 µ
g/cm
²4
88
1.8
0.39
µg
0.6
0.14
Bay
nes e
t al.
(200
2)Pi
gA
b50
00.
33Et
3 (4
0 µg
/cm
²)3
88
0.2
0.04
0.01
2Q
iao
et a
l. (2
002)
Mon
Ab
12So
il17
ppm
(0.
7 µg
/cm
²)4
2433
624
4.2
0.00
71W
este
r et a
l. (1
993b
)M
onA
b12
Ac
17pp
m (
0.8
µg/c
m²)
424
336
295.
70.
0097
Wes
ter e
t al.
(199
3b)
Pig
Ab
7.5
100
mg
Soil
40 µ
g/cm
² (30
0µg)
340
840
829
700.
21Q
iao
et a
l. (1
997)
Pig
Ab
7.5
0.1
Et3
326
426
450
0.25
0.07
6Q
iao
et a
l. (2
002)
The
expe
rimen
ts w
ith a
ceto
ne, e
than
ol, d
iese
l or t
etra
chlo
roph
enol
as v
ehic
les a
re d
isre
gard
ed a
s the
sk
in p
erm
eatio
n co
uld
be a
ffec
ted.
The
pref
erre
d st
udy
is th
at o
n pi
g sk
in in
vitr
o w
ith w
ater
as v
ehic
le (B
ayne
s et a
l. (2
002)
).
The
repo
rted
Kp
valu
e of
4·1
0-4 c
m/h
sugg
ests
a "
mod
erat
e" p
erm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A14
6
App
endi
x A
Subs
tanc
e: P
enta
neM
olec
ular
wei
ght:
72.1
CA
S: 1
09-6
6-0
Den
sity
:0.6
26 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:-1
29.7
°CB
oilin
g po
int:
36.1
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:48
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Ext
rem
ely
low
Eva
pora
tion
rate
:29
Log
Kow
:3.3
9
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Rat
Ab
StFu
ll2.
61
Nea
t39
2.5-
18.5
2.5-
18.5
3.11
5-89
µg
0.00
060.
04Ts
urut
a (1
982)
N
o da
ta a
vaila
ble
The
only
ava
ilabl
e st
udy
sugg
ests
a K
p va
lue
of 1
0-8 c
m/h
, cor
resp
ondi
ng to
"ex
trem
ely
low
" pe
rmea
bilit
y.
It sh
ould
be
note
d th
at T
suru
ta (1
982)
use
d ph
ysio
logi
cal s
alin
e as
rece
ptor
med
ium
, res
ultin
g in
lo
wer
solu
bilit
y fo
r lip
ophi
lic su
bsta
nces
. Thi
s may
hav
e le
d to
a u
nder
estim
ated
Kp
valu
e.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A14
7
App
endi
x A
Subs
tanc
e: P
heno
lM
olec
ular
wei
ght:
94.1
CA
S: 1
08-9
5-2
Den
sity
:1.0
7 g/
cm³
Scie
ntifi
c ba
sis:
AoH
198
5:32
Mel
ting
poin
t:40
.5°C
Boi
ling
poin
t:18
1.7°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:47
Pa (a
t 29°
C)
Skin
per
mea
bilit
y: H
igh
Eva
pora
tion
rate
:<0.
01L
og K
ow:1
.46
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Pig
Full
7.5
0.08
-0.1
Et0.
3 (4
µg/
cm²)
28
85.
52.
40.
072
Bro
oks e
t al.
(199
6)Pi
gFu
ll7.
50.
08-0
.1Et
0.3
(4 µ
g/cm
²)2
88
7.3
3.3
1B
rook
s et a
l. (1
996)
Pig
Full
7.5
0.08
-0.1
Et0.
3 (4
µg/
cm²)
48
89.
26
0.18
Bro
oks e
t al.
(199
6)Pi
gFu
ll7.
50.
08-0
.1Et
3 (4
0 µg
/cm
²)4
88
7.4
3.7
1.1
Bro
oks e
t al.
(199
6)Pi
gFu
ll7.
50.
08-0
.1A
c0.
3 (4
µg/
cm²)
28
82.
91.
30.
038
Bro
oks e
t al.
(199
6)Pi
gFu
ll7.
50.
08-0
.1A
c3
(40
µg/c
m²)
28
82
0.47
0.14
Bro
oks e
t al.
(199
6)Pi
gFu
ll7.
50.
08-0
.1A
c0.
3 (4
µg/
cm²)
48
815
50.
15B
rook
s et a
l. (1
996)
Pig
Full
7.5
0.08
-0.1
Ac
3 (4
0 µg
/cm
²)4
88
115
1.5
Bro
oks e
t al.
(199
6)H
umA
bFl
350
0.32
VIC
4 µg
/cm
²7
2472
260.
13B
rona
ugh
et a
l. (1
985b
)H
umA
bSt
Full
10.
01A
cN
eat
(4 µ
g/cm
²)7
4848
110.
0000
850.
0091
Fran
z (1
975)
Hum
Br
FlFu
ll0.
320.
005-
0.01
Et0.
27 (
2.7
µg/c
m²)
672
7219
-20
0.81
-0.8
90.
022-
0.02
4H
otch
kiss
et a
l. (1
992)
Hum
Br
FlFu
ll0.
320.
005-
0.01
Et0.
27 (
2.7
µg/c
m²)
372
7247
20.
055
Hot
chki
ss e
t al.
(199
2)H
umA
bSt
Epi
2.5
Inf
H2O
42
88
0.25
8233
Rob
erts
et a
l. (1
977)
Hum
Ab
StSC
1H
2O10
3310
100.
551.
51.
5So
uthw
ell e
t al.
(198
4)H
umA
bSt
SC1
H2O
101
1010
0.35
2.6
2.6
Sout
hwel
l et a
l. (1
984)
Hum
Ab
StSC
1H
2O10
210
100.
721.
71.
7So
uthw
ell e
t al.
(198
4)H
umA
bSt
SC1
H2O
101
1010
0.25
1.6
1.6
Sout
hwel
l et a
l. (1
984)
Hum
Ab
StSC
1H
2O10
210
100.
41.
41.
4So
uthw
ell e
t al.
(198
4)H
umA
bSt
SC1
H2O
102
1010
0.43
0.98
0.98
Sout
hwel
l et a
l. (1
984)
Hum
Ab
StSC
1H
2O10
910
100.
932.
22.
2So
uthw
ell e
t al.
(198
4)H
umA
bSt
SC1
H2O
103
1010
0.57
1.1
1.1
Sout
hwel
l et a
l. (1
984)
Hum
Ab
StSC
1H
2O10
410
100.
850.
890.
89So
uthw
ell e
t al.
(198
4)H
umA
bSt
SC1
H2O
104
1010
0.6
1.8
1.8
Sout
hwel
l et a
l. (1
984)
Hum
Ab
StSC
1H
2O10
310
100.
370.
590.
59So
uthw
ell e
t al.
(198
4)H
umA
bSt
Epi
Inf
H2O
1%
337-
107-
100.
551.
51.
5So
uthw
ell e
t al.
(198
4)
Rep
orte
d da
ta
In v
itro
A14
8
App
endi
x A
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Mou
Ba
StFu
ll0.
6N
aCl
0.50
%6
2.5
2.5
230
120
Beh
l et a
l. (1
983)
Mou
Ba
StFu
ll0.
6N
aCl
1.00
%6
2.5
2.5
310
330
Beh
l et a
l. (1
983)
Mou
Ba
StFu
ll0.
6N
aCl
2.00
%6
2.5
2.5
470
1000
Beh
l et a
l. (1
983)
Mou
Ba
StFu
ll0.
6N
aCl
4.00
%6
2.5
2.5
170
710
Beh
l et a
l. (1
983)
Mou
Ba
StFu
ll0.
6N
aCl
6.00
%6
2.5
2.5
2000
1300
0B
ehl e
t al.
(198
3)M
ouSt
Full
0.79
330.
1717
0056
00H
uq e
t al.
(198
6)M
ouSt
Full
0.79
Trac
e0.
1719
0H
uq e
t al.
(198
6)Pi
gA
bFl
200
0.64
0.01
EtN
eat
(5.5
µg/
cm²)
616
16~0
.556
0.00
180.
19Sk
owro
nski
et a
l. (1
994)
Rat
Ba
Fl35
00.
32V
IC4
µg/c
m²
624
7216
Bro
naug
h et
al.
(198
5b)
Rat
Ba
FlFu
ll0.
320.
005-
0.01
Et0.
13 (
1.3
µg/c
m²)
672
7236
0.5-
0.51
0.00
65-0
.006
6H
otch
kiss
et a
l. (1
992)
Rat
Ba
FlFu
ll0.
320.
005-
0.01
Et0.
14 (
1.4
µg/c
m²)
672
7225
-27
0.34
-0.3
70.
0048
-0.0
052
Hot
chki
ss e
t al.
(199
2)R
atB
aSt
350
0.64
0.00
5-0.
01Et
0.4
(4 µ
g/cm
²)7
7272
981.
40.
054
Hug
hes e
t al.
(199
3)R
atB
aFl
350
0.32
0.00
5-0.
01Et
0.4
(4 µ
g/cm
²)10
7272
951.
30.
053
Hug
hes e
t al.
(199
3)Sn
Ba
StFu
ll1.
8PB
S1-
34
66
525.
2-16
Itoh
et a
l. (1
990)
Hum
Arm
2.5
0.02
H2O
+Et
5%5
2416
834
2312
0B
ucks
et a
l. (1
989-
1990
)H
umA
rm2.
50.
02H
2O+E
t5%
524
168
2416
86B
ucks
et a
l. (1
989-
1990
)H
umA
rm13
Ac
Nea
t (4
µg/
cm²)
324
120
4.4
0.00
009
0.01
Feld
man
n &
Mai
bach
(197
0)H
umW
BV
ap5-
25 m
g/m
³12
624
5-65
mg
200.
1-0.
5Pi
otro
wsk
i (19
71)
Rat
Ba
2.54
0.02
EtN
eat
(2.4
µg/
cm²)
472
7267
0.00
150.
16H
ughe
s et a
l. (1
995)
The
expe
rimen
ts u
sing
eth
anol
, ace
tone
and
Vas
elin
e ar
e di
sreg
arde
d as
thes
e su
bsta
nces
may
aff
ect s
kin
perm
eabi
lity.
The
expe
rimen
ts u
sing
nea
t phe
nol c
anno
t be
used
, sin
ce th
e su
bsta
nce
appe
ars a
s sol
id c
ryst
als a
t ski
n te
mpe
ratu
re (m
.p. ~
40°C
).
The
pref
erre
d st
udy
is th
at o
f Buc
ks e
t al.
(198
9-19
90) u
sing
5%
phe
nol i
n w
ater
.
The
Kp
valu
e of
2·1
0-3 c
m/h
is c
onsi
sten
t with
the
full
thic
knes
s ski
n in
vitr
o m
ouse
stud
y by
(Beh
l et a
l. (1
983)
) and
sugg
est "
high
" pe
rmea
bilit
y.
In v
ivo
Ase
ssm
ent
A14
9
App
endi
x A
Subs
tanc
e: P
ropa
nol,
n-M
olec
ular
wei
ght:
60.1
CA
S: 7
1-23
-8D
ensi
ty:0
.803
g/c
m³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
-126
°CB
oilin
g po
int:
97.2
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:0.5
3 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: H
igh
Eva
pora
tion
rate
:1.3
Log
Kow
:0.2
5
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
St27
2.5
H2O
7.
421
127.
2Sc
heup
lein
& B
lank
(197
3)H
umA
bSt
2500
2.5
H2O
7.
49
310
190
Sche
uple
in &
Bla
nk (1
973)
Hum
Ab
St27
2.5
Nea
t20
1.6
130
Sche
uple
in &
Bla
nk (1
973)
Hum
Ab
St25
002.
5N
eat
718
1400
Sche
uple
in &
Bla
nk (1
973)
Mou
Ab
StFu
ll0.
79N
aCl
≤10-
4M2
254
Dur
rhei
m e
t al.
(198
0)
N
o da
ta a
vaila
ble
The
only
foun
d st
udy
is th
at o
f Sch
eupl
ein
& B
lank
(197
3), w
ere
hum
an sk
in w
as e
xpos
ed to
nea
t and
dilu
ted
n-pr
opan
ol. T
he p
refe
rred
exp
erim
ent i
s the
one
usi
ng fu
ll th
ickn
ess s
kin.
The
Kp
valu
e of
2·1
0-3 cm
/h, s
ugge
sts "
high
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A15
0
App
endi
x A
Subs
tanc
e: P
ropi
onic
aci
dM
olec
ular
wei
ght:
74.1
CA
S: 7
9-09
-4D
ensi
ty:0
.993
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
8:32
Mel
ting
poin
t:-2
1.5°
CB
oilin
g po
int:
140.
7°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:3
90 P
a (a
t 20°
C)
Skin
per
mea
bilit
y: V
ery
high
Eva
pora
tion
rate
:0.2
4L
og K
ow:0
.33
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
MP
Ba
FlFu
ll1
Hep
744
22
0.07
4000
3000
0Li
ron
et a
l. (1
984a
)M
PB
aFl
Full
1H
ep74
44
40.
1318
0080
00Li
ron
et a
l. (1
984a
)M
PB
aFl
Full
1H
ep74
48
80.
1798
073
00Li
ron
et a
l. (1
984a
)M
PB
aFl
Full
1H
ep74
37
70.
3375
056
00Li
ron
et a
l. (1
984a
)M
PB
aFl
Full
1H
ep74
37
70.
6749
036
00Li
ron
et a
l. (1
984a
)M
PB
aFl
Full
1N
eat
55
~0.5
160
3.3
Liro
n et
al.
(198
4b)
N
o da
ta a
vaila
ble
The
expe
rimen
ts u
sing
n-h
epta
ne a
s veh
icle
are
dis
rega
rded
, as t
he sk
in p
erm
eatio
n co
uld
be a
ffec
ted.
The
only
rem
aini
ng st
udy
is th
at o
f Liro
n et
al.
(198
4b).
The
repo
rted
Kp
valu
e of
2·1
0-2 c
m/h
sugg
ests
a "
very
hig
h" p
erm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A15
1
App
endi
x A
Subs
tanc
e: P
ropy
lene
gly
col d
initr
ate
Mol
ecul
ar w
eigh
t:16
6.1
CA
S: 6
423-
43-4
Den
sity
:1.2
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
3:36
Mel
ting
poin
t:-8
°CB
oilin
g po
int:
121°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:9 P
a (a
t 20°
C)
Skin
per
mea
bilit
y: H
igh
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:1
.59
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Rat
Ba
4C
orn
oil
10%
(50
mg/
kg b
w)
0.5
0.5
1053
630
Cla
rk &
Litc
hfie
ld (1
969)
Onl
y on
e st
udy
was
foun
d on
pro
pyle
ne g
lyco
l din
itrat
e. In
Cla
rk &
Litc
hfie
ld (1
969)
, rat
s wer
e ex
pose
d to
a
10%
solu
tion
of p
ropy
lene
gly
col d
initr
ate
in c
orn
oil.
The
calc
ulat
ed K
p va
lue
of 5
·10-3
cm
/h su
gges
ts a
"hi
gh"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A15
2
App
endi
x A
Subs
tanc
e: P
ropy
lene
gly
col m
onom
ethy
l eth
er (P
GM
E); 1
-met
hoxy
-2-p
ropa
nol
Mol
ecul
ar w
eigh
t: 9
0.1
CA
S: 1
07-9
8-2
Den
sity
:0.9
24 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
987:
39M
eltin
g po
int:
-97°
CB
oilin
g po
int:
119.
6°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re: 1
.2 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
: 0.7
1L
og K
ow:-
0.49
(est
imat
ed)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StEp
i1.
85
Nea
t8
813
1200
Dug
ard
et a
l. (1
984)
Hum
Ab
StEp
i1.
81-
5N
eat
118
8<1
1312
00D
ugar
d et
al.
(198
4)H
umA
bSt
Full
3.1
Nea
t8
44
0.5
5.1
470
Lare
se F
ilon
et a
l. (1
999)
Hum
Br
Fl50
00.
640.
2H
2O3
524
242.
314
4.3
Wilk
inso
n &
Will
iam
s (20
02)
Hum
Br
Fl50
00.
640.
01N
eat
424
240.
6560
Wilk
inso
n &
Will
iam
s (20
02)
Hum
Br
Fl50
00.
640.
2N
eat
524
246.
560
0W
ilkin
son
& W
illia
ms (
2002
)
N
o da
ta a
vaila
ble
The
expe
rimen
t with
a a
pplie
d am
ount
of 0
.011
ml (
Wilk
inso
n &
Will
iam
s (20
02))
is d
isre
gard
ed si
nce
depl
etio
n of
PG
ME
occu
rred
.
The
rem
aini
ng st
udie
s sho
w c
onsi
sten
t res
ults
with
Kp
valu
es ra
ngin
g be
twee
n 5·
10-4
to 1
·10-3
cm
/h.
The
pref
erre
d st
udie
s of W
ilkin
son
& W
illia
ms (
2002
) and
Lar
ese
Filo
n et
al.
(199
9) w
ith h
uman
skin
exp
osed
to
neat
PG
ME
in v
itro,
repo
rts K
p va
lues
cor
resp
ondi
ng to
"m
oder
ate"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A15
3
App
endi
x A
Subs
tanc
e: P
ropy
lene
gly
col m
onom
ethy
l eth
er a
ceta
te (P
GM
EA)
Mol
ecul
ar w
eigh
t:13
2.2
CA
S: 1
08-6
5-6
Den
sity
:0.9
69 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
987:
39M
eltin
g po
int:
-10°
CB
oilin
g po
int:
145.
8°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.5 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:0
.3L
og K
ow:0
.56
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Ther
e is
no
men
tion
rega
rdin
g sk
in u
ptak
e of
PG
MEA
in th
e Sw
edis
h co
nsen
sus d
ocum
ent (
AoH
198
7:39
).
No
docu
men
tatio
n ha
s bee
n pr
oduc
ed b
y A
CG
IH.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A15
4
App
endi
x A
Subs
tanc
e: R
esor
cino
lM
olec
ular
wei
ght:
110.
1C
AS:
108
-46-
3D
ensi
ty:1
.27
g/cm
³Sc
ient
ific
basi
s: A
oH 1
992:
47M
eltin
g po
int:
110°
CB
oilin
g po
int:
281°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:7.1
kPa
(at 1
90°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.8
0
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StEp
i2.
5In
fH
2O10
02
88
1.33
2.4
24R
ober
ts e
t al.
(197
7)
N
o da
ta a
vaila
ble
Onl
y on
e st
udy
was
foun
d on
reso
rcin
ol. R
ober
ts e
t al.
(197
7) e
xpos
ed h
uman
abd
omin
al sk
in to
an
aque
ous
solu
tion
of re
sorc
inol
.
The
repo
rted
Kp
valu
e of
2·1
0-4 c
m/h
, sug
gest
s a "
mod
erat
e" p
erm
eabi
lity.
It sh
ould
be
note
d th
at in
the
expe
rimen
ts b
y R
ober
ts e
t al.
(197
7), e
pide
rmal
shee
ts w
ere
sepa
rate
d by
exp
osin
g sk
in to
am
mon
ia v
apou
r fo
r 30
min
. Am
mon
ia is
wel
l kno
wn
to c
ause
seve
re sk
in d
amag
e A
msh
el e
t al.
(200
0). T
he a
lkal
ine
natu
re
of a
mm
onia
qui
ckly
sapo
nifie
s the
epi
derm
al fa
ts, t
hus d
estro
ying
the
prot
ectiv
e st
ruct
ure
of th
e ep
ider
mis
. Th
eref
ore,
the
met
hod
used
by
Rob
erts
et a
l. (1
977)
is li
kely
to re
sult
in se
vere
ove
rest
imat
es o
f the
flux
and
Kp
valu
e of
und
amag
ed sk
in.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A15
5
App
endi
x A
Subs
tanc
e: S
odiu
m c
yani
deM
olec
ular
wei
ght:
49.0
CA
S: 1
43-3
3-9
Den
sity
:1.6
g/c
m³
Scie
ntifi
c ba
sis:
AoH
200
1:19
Mel
ting
poin
t:56
3.7°
CB
oilin
g po
int:
1496
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:Not
ava
ilabl
eSk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:-1.
69 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
St40
1.8
H2O
0.
0012
(0.0
0025
%)
61.
53.
70.
0004
5D
ugar
d (1
987)
Hum
Ab
St40
1.8
H2O
5.
3 (1
%)
51.
54.
32.
3D
ugar
d (1
987)
Hum
Ab
St40
1.8
H2O
53
(10%
)11
1.5
1158
Dug
ard
(198
7)H
umA
bSt
401.
8H
2O
210
(40%
)9
1.5
2.9
62D
ugar
d (1
987)
N
o da
ta a
vaila
ble
Seve
ral i
n vi
tro e
xper
imen
ts w
ith h
uman
skin
exp
osed
to a
queo
us so
lutio
ns o
f sod
ium
cya
nide
are
repo
rted
(Dug
ard
(198
7)).
The
Kp
valu
e of
3·1
0-4 c
m/h
, cor
resp
onds
to "
mod
erat
e" p
erm
eabi
lity.
It sh
ould
be
note
d th
at th
e pe
rmea
bilit
y of
hyd
roge
n cy
anid
e is
two
orde
rs o
f mag
nitu
de h
ighe
r.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A15
6
App
endi
x A
Subs
tanc
e: S
tyre
neM
olec
ular
wei
ght:
104.
2C
AS:
100
-42-
5D
ensi
ty:0
.905
g/c
m³
Scie
ntifi
c ba
sis:
AoH
199
1:8
Mel
ting
poin
t:-3
0.6°
CB
oilin
g po
int:
145.
2°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.86
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Low
Eva
pora
tion
rate
:0.5
4L
og K
ow:2
.95
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Rat
Ab
StFu
ll2.
51
Nea
t28
2.5-
62.
5-6
1.67
43-3
30 µ
g0.
3330
Tsur
uta
(198
2)
Hum
Ha
500
Inf
Nea
t9
0.17
-0.5
215
mg
0.67
60B
erod
e et
al.
(198
5)H
umA
rm/H
aN
eat
10<0
.199
-170
9000
-150
00D
utki
ewic
z et
al.
(196
8b)
Hum
Arm
/Ha
H2O
0.
067-
0.27
101
6000
-670
040
-180
Dut
kiew
icz
et a
l. (1
968b
)H
umW
B19
000
Vap
0.00
26 (
600p
pm)
23.
524
60 m
g35
000.
9R
iihim
aki e
t al.
(197
8)R
atW
BV
ap0.
013
(300
0ppm
)5
44
1800
021
McD
ouga
l et a
l. (1
990)
Tsur
uta
(198
2) u
sed
phys
iolo
gica
l sal
ine
as re
cept
or m
ediu
m, r
esul
ting
in lo
wer
solu
bilit
y fo
r lip
ophi
lic su
bsta
nces
,th
us p
roba
bly
unde
rest
imat
ing
the
perm
eabi
lity.
The
vapo
ur st
udie
s are
als
o di
sreg
arde
d.Th
e st
udie
s by
Dut
kiew
icz
et a
l. (1
968b
) are
onl
y de
scrib
ed v
ery
brie
fly a
nd a
ppea
r to
give
unr
ealis
tic K
p va
lues
.
The
pref
erre
d st
udy
is th
e hu
man
skin
in v
ivo
stud
y w
ith n
eat s
tyre
ne o
f (B
erod
e et
al.
(198
5)).
The
Kp
valu
e of
7·1
0-5 c
m/h
sugg
ests
"lo
w"
perm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A15
7
App
endi
x A
Subs
tanc
e: T
etra
chlo
roet
hyle
neM
olec
ular
wei
ght:
165
.8C
AS:
127
-18-
4D
ensi
ty:1
.623
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
1:21
Mel
ting
poin
t:-2
2.3°
CB
oilin
g po
int:
121.
1°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re: 1
.9 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
: 2.8
Log
Kow
:3.4
0
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
Fl20
0-40
00.
2In
fH
2O0.
13-0
.31
µg/m
l35
66
160-
580
0.00
21-0
.018
Nak
ai e
t al.
(199
9)H
umA
bFl
200-
400
0.2
Inf
H2O
0.12
-0.2
9 µg
/ml
296
611
0-61
00.
0013
-0.0
18N
akai
et a
l. (1
999)
Rat
Ab
StFu
ll3.
71
Nea
t49
2-6
2-6
2.46
5-74
µg
0.03
5Ts
urut
a (1
977)
HG
PW
B~3
00In
fH
2O0.
044-
0.10
µg/
ml
(27-
64 p
pb)
51.
22-
4w37
000.
016-
0.03
7B
ogen
et a
l. (1
992)
HM
WB
Vap
0.00
69 (
1000
ppm
)6
2-6
2-6
1000
06.
9Ts
urut
a (1
989)
HM
WB
Vap
0.02
1 (3
000p
pm)
62-
62-
695
0020
Tsur
uta
(198
9)H
MW
BV
ap0.
0014
(20
0ppm
)6
2-6
2-6
7900
1.1
Tsur
uta
(198
9)H
umA
rm/H
a10
00V
ap1.
1 (6
.7 m
mol
/l)5
0.33
654
060
Kez
ic e
t al.
(200
0)H
umW
B19
000
Vap
0.00
42(6
00pp
m)
33.
524
48 m
g17
000.
72R
iihim
aki &
Pfa
ffli
(197
8)H
umH
a4
kgSo
il30
g/k
g so
il3
22
0.38
20 m
g9
Poet
et a
l. (2
002)
Mou
Ab
2.9
0.5
Nea
t3
0.25
180
µg1.
524
0Ts
urut
a (1
975)
Rat
WB
Vap
0.08
6 (1
2500
ppm
)4
44
6700
54M
cDou
gal e
t al.
(199
0)R
atB
a8
0.5
gSo
il4.
6 g/
kg so
il3
55
5790
0Po
et e
t al.
(200
2)R
atB
a8
0.5
gSo
il15
g/k
g so
il3
55
5588
0Po
et e
t al.
(200
2)R
atB
a8
0.5
gSo
il51
g/k
g so
il3
55
5186
0Po
et e
t al.
(200
2)R
atB
a5
5 g
Soil
16 g
/kg
soil
35
511
1100
Poet
et a
l. (2
002)
Rat
Ba
55
gSo
il53
g/k
g so
il3
55
8.7
1100
Poet
et a
l. (2
002)
Rat
Ba
55
gSo
il16
g/k
g so
il5
55
4911
00Po
et e
t al.
(200
2)R
atB
a5
5 g
Soil
50 g
/kg
soil
55
553
1100
Poet
et a
l. (2
002)
Rep
orte
d da
ta
In v
itro
In v
ivo
A15
8
App
endi
x A
The
in v
itro
stud
y of
Tsu
ruta
(197
7) u
sed
phys
iolo
gica
l sal
ine
as th
e re
cept
or m
ediu
m, t
his m
ay le
ad to
a se
vere
un
dere
stim
ate
of fl
ux a
nd K
p fo
r hig
hly
lipop
hilic
subs
tanc
es.
Bog
en e
t al.
(199
2) a
nd N
akai
et a
l. (1
999)
use
d di
lute
aqu
eous
solu
tion
of te
trach
loro
ethy
lene
.Th
e st
udie
s with
hum
an sk
in u
sed
aque
ous s
olut
ions
, vap
our o
r soi
l, le
adin
g to
ver
y hi
gh K
p va
lues
.
The
pref
erre
d st
udy
is th
at o
f Tsu
ruta
(197
5) u
sing
nea
t tet
rach
loro
ethy
lene
and
mou
se sk
in.
The
Kp
valu
e of
2·1
0-4 c
m/h
sugg
ests
"m
oder
ate"
per
mea
bilit
y.
Ase
ssm
ent
A15
9
App
endi
x A
Subs
tanc
e: T
etra
chlo
roph
enol
Mol
ecul
ar w
eigh
t:23
1.9
CA
S: 2
5167
-83-
3D
ensi
ty:1
.8 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
986:
35M
eltin
g po
int:
~70°
CB
oilin
g po
int:
150
to 2
00°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:N
ot a
vaila
ble
Skin
per
mea
bilit
y: L
owE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:4.4
5
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
StFu
ll?1
0.01
H2O
+ P
CP
169
2424
30.
130.
2H
orst
man
et a
l. (1
989)
Hum
Ab
StFu
ll?1
0.01
Die
sel +
PC
P9.
49
2424
0.5
0.02
10.
02H
orst
man
et a
l. (1
989)
N
o da
ta a
vaila
ble
The
only
stud
y th
at w
as fo
und
on te
trach
loro
phen
ol w
as H
orst
man
et a
l. (1
989)
,w
ere
dies
el a
nd/o
r pen
tach
loro
phen
ol a
s use
d as
veh
icle
.
The
pref
erre
d ex
perim
ent g
ives
a K
p va
lue
of 1
0-5 c
m/h
, sug
gest
ing
"low
" pe
rmea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A16
0
App
endi
x A
Subs
tanc
e: T
etra
ethy
l lea
dM
olec
ular
wei
ght:
323.
4C
AS:
78-
00-2
Den
sity
:1.6
59 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:-1
36.8
°CB
oilin
g po
int:
~200
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:27
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:4.1
5
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
No
cons
ensu
s doc
umen
t by
the
Swed
ish
Crit
eria
Gro
up.
Acc
ordi
ng to
AC
GIH
(200
1), t
etra
ethy
l lea
d ca
n be
abs
orbe
d pe
rcut
aneo
usly
in
amou
nts t
hat c
ause
syst
emic
poi
soni
ng.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A16
1
App
endi
x A
Subs
tanc
e: T
etra
hydr
ofur
anM
olec
ular
wei
ght:
72.1
CA
S: 1
09-9
9-9
Den
sity
:0.8
86 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
991:
8M
eltin
g po
int:
-108
.4°C
Boi
ling
poin
t:66
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:18
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Low
Eva
pora
tion
rate
:8L
og K
ow:0
.46
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
Fl28
00.
640.
2N
eat
524
240.
330.
20.
4641
Wilk
inso
n &
Will
iam
s (20
01)
Hum
Br
Fl28
00.
640.
2H
2O
35
2424
0.35
1.7
6118
Wilk
inso
n &
Will
iam
s (20
01)
N
o da
ta a
vaila
ble
The
only
ava
ilabl
e da
ta a
re th
ose
of W
ilkin
son
& W
illia
ms (
2001
), gi
ven
as a
con
fere
nce
pres
enta
tion.
Hum
an b
reas
t ski
n w
as e
xpos
ed in
vitr
o to
nea
t and
aqu
eous
solu
tions
of t
etra
hydr
ofur
an.
The
Kp
valu
e of
nea
t tet
rahy
drof
uran
cor
resp
onds
to "
low
" pe
rmea
bilit
y.
It sh
ould
be
note
d th
at th
e K
p m
easu
red
from
aqu
eous
solu
tions
is o
ver t
wo
orde
rs o
f mag
nitu
de h
ighe
r,su
gges
ting
a st
rong
veh
icle
eff
ect.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A16
2
App
endi
x A
Subs
tanc
e: T
etra
met
hyl l
ead
Mol
ecul
ar w
eigh
t:26
7.3
CA
S: 7
5-74
-1D
ensi
ty:2
.0 g
/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:-2
7.5°
CB
oilin
g po
int:
110°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:2.9
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
No
data
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:2
.97
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
AC
GIH
-TLV
com
mitt
ee (A
CG
IH (2
001)
) bas
e th
eir s
kin
nota
tion
on a
stud
y w
ith d
ogs
dem
onst
ratin
g to
xici
ty a
fter d
erm
al e
xpos
ure.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A16
3
App
endi
x A
Subs
tanc
e: T
hiog
lyco
lic a
cid
Mol
ecul
ar w
eigh
t:92
.1C
AS:
68-
11-1
Den
sity
:1.3
25 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
994:
30M
eltin
g po
int:
-16.
5°C
Boi
ling
poin
t:12
0°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:1
.3 k
Pa (a
t 18°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:0.0
9
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
skin
not
atio
n as
sign
ed b
y A
CG
IH-T
LV is
bas
ed o
n sy
stem
ic to
xici
ty in
ani
mal
s fol
low
ing
derm
al a
pplic
atio
n.
Acc
ordi
ng to
theo
retic
al c
alcu
latio
ns b
y Fi
sero
va-B
erge
rova
et a
l. (1
990)
the
pote
ntia
l for
der
mal
abso
rptio
n an
d re
sulti
ng to
xici
ty is
sign
ifica
nt.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A16
4
App
endi
x A
Subs
tanc
e: T
itani
um d
ioxi
deM
olec
ular
wei
ght:
79.9
CA
S: 1
3463
-67-
7D
ensi
ty:4
.26
g/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:18
55°C
Boi
ling
poin
t:29
00°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:N
ot a
vaila
ble
Skin
per
mea
bilit
y: E
xtre
mel
y lo
wE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:2.2
3 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Pig
Ab
St50
01
H2O
+ o
il10
% (2
40 µ
g/cm
²)3
2424
< 0.
10.
001
0.01
Gam
er e
t al.
(200
6)
N
o da
ta a
vaila
ble
Mic
ro fi
ne T
iO2 (
10 w
t%) i
n oi
l/wat
er e
mul
sion
was
app
lied
to th
e sk
in. M
ean
parti
cle
size
was
80
nm w
ith 9
0%
of th
e pa
rticl
es <
160
nm
. Der
mat
omed
pig
skin
was
use
d in
the
stat
ic c
ells
, and
bov
ine
seru
m a
lbum
in (5
%)
was
add
ed to
the
salin
e as
rece
ptor
med
ium
. Hig
h re
cove
ry ra
tes (
98-1
00%
) wer
e ac
hiev
ed,
still
no
TiO
2 was
det
ecte
d in
the
rece
ptor
med
ium
.Th
e re
porte
d de
tect
ion
limit
was
0.3
µg
Ti, c
orre
spon
ding
to 0
.1%
abs
orbe
d do
se.
Thus
, the
cal
cula
ted
Kp
valu
e is
low
er th
an 1
·10-7
cm
/h, s
ugge
stin
g "e
xtre
mel
y lo
w"
perm
eabi
lity
(or l
ower
).
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A16
5
App
endi
x A
Subs
tanc
e: T
olue
neM
olec
ular
wei
ght:
92.1
CA
S: 1
08-8
8-3
Den
sity
:0.8
67 g
/cm
³Sc
ient
ific
basi
s: A
oH 2
002:
18M
eltin
g po
int:
-93°
CB
oilin
g po
int:
110.
6°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:3
.7 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
:2.2
Log
Kow
:2.7
3
Sp
Loc
C
ell
L
( µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
St50
01.
1JP
-824
242
0.09
5K
anik
kann
an e
t al.
(200
1)H
umB
rSt
300-
600
0.64
Nea
t6
66
113
0U
rsin
et a
l. (1
995)
Hum
Br
Fl28
00.
640.
2N
eat
524
240.
010.
220.
1412
Wilk
inso
n &
Will
iam
s (20
01)
Hum
Br
Fl28
00.
640.
2H
2O
205
2424
079
830
1.7
Wilk
inso
n &
Will
iam
s (20
01)
Hum
Fl25
01
0.2-
0.3
Nea
t3
2424
1.9
1.6-
2.4
140-
210
Bom
an &
Mai
bach
(200
0)H
umFl
250
10.
2-0.
3n-
Bu
430
(50%
)4
2020
9.5
9.2-
1440
0-62
0B
oman
& M
aiba
ch (2
000)
Hum
Fl25
01
0.2-
0.3
Chf
+ M
e43
0(5
0%)
520
202
2-3
85-1
30B
oman
& M
aiba
ch (2
000)
MP
Fl90
03.
1N
eat
614
.514
.53.
732
0Ja
cobs
& P
hanp
rasi
t (19
93)
MP
Fl90
03.
1V
ap0.
12 (S
atur
ated
)6
14.5
14.5
1400
016
0Ja
cobs
& P
hanp
rasi
t (19
93)
MP
Ear
St50
01.
1JP
-824
242.
50.
12K
anik
kann
an e
t al.
(200
1)R
atB
aSt
560
4.9
2JP
-80.
06%
84
40.
511
0.54
McD
ouga
l et a
l. (2
000)
Rat
Ab
StFu
ll2.
61
Nea
t34
1-5
1-5
1.55
10-4
30 µ
g0.
5447
Tsur
uta
(198
2)
HM
Ba
0.8
0.00
45N
eat
120.
033
490
µg
3429
00Su
sten
et a
l. (1
990)
HM
WB
Vap
3000
ppm
62-
62-
612
000
14Ts
urut
a (1
989)
HM
WB
Vap
1000
ppm
62-
62-
612
000
4.6
Tsur
uta
(198
9)H
MW
BV
ap20
0ppm
62-
62-
612
000
0.9
Tsur
uta
(198
9)H
umA
rm17
0.2
Nea
t10
11
71 m
g21
018
000
Dut
kiew
icz
et a
l. (1
968a
)H
umH
aH
2O
0.19
-0.6
116
11
130
mg
6200
-200
0038
0D
utki
ewic
z et
al.
(196
8a)
Hum
Ha
Nea
t10
122
019
000
Dut
kiew
icz
& T
yras
(196
8b)
Hum
Arm
/Ha
1000
Vap
0.06
5 (0
.7 m
mol
/L)
50.
336
1400
9K
ezic
et a
l. (2
000)
Hum
WB
1900
0V
ap0.
0023
(60
0ppm
)2
3.5
2426
mg
1700
0.4
Riih
imak
i & P
faff
li (1
978)
Hum
FiIn
fH
2O1%
1215
s0.
30.
890.
77N
aito
h et
al.
(200
2)H
umFi
Inf
H2O
1%12
15s
0.3
2320
Nai
toh
et a
l. (2
002)
Hum
WB
Inf
H2O
0.00
056
0.3-
0.5
0.75
-130
-200
0.00
15-0
.01
Thra
ll et
al.
(200
2a)
Rep
orte
d da
ta
In v
itro
In v
ivo
A16
6
App
endi
x A
Sp
Loc
C
ell
L
( µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Mou
Ba
0.8
0.00
4N
eat
124
42.
10.
2723
Sust
en e
t al.
(199
0)M
ouA
b3.
10.
5N
eat
150.
25-1
0.01
69Ts
urut
a (1
996)
Mou
Ab
3.1
0.5
Me
50%
150.
25-1
0.1
260
Tsur
uta
(199
6)M
ouA
b3.
10.
5D
MSO
50
%15
0.25
-10.
1231
0Ts
urut
a (1
996)
Mou
Ab
3.1
0.5
DM
F15
0.25
-10.
0822
0Ts
urut
a (1
996)
Rat
WB
64
472
0021
McD
ouga
l et a
l. (1
990)
Rat
Ba
4.9
2H
2O0.
23
55
4576
015
Thra
ll et
al.
(200
2b)
Rat
Ba
4.9
2H
2O0.
53
55
4270
035
Thra
ll et
al.
(200
2b)
The
hum
an sk
in in
vitr
o st
udie
s with
nea
t tol
uene
show
rela
tivel
y co
nsis
tent
resu
lts w
ith K
p va
lues
rang
ing
from
1·1
0-5 to
2·1
0-4 c
m/h
. Th
e in
viv
o st
udie
s by
Dut
kiew
icz
et a
l. (1
968a
) and
Dut
kiew
icz
& T
yras
(196
8b) s
how
two
orde
rs o
f m
agni
tude
hig
her K
p va
lues
.
The
pref
erre
d ex
perim
ent i
s the
one
by
Bom
an &
Mai
bach
(200
0) w
here
hum
an sk
in w
as e
xpos
ed to
nea
t tol
uene
.
The
Kp
valu
e of
2·1
0-4 c
m/h
cor
resp
onds
to "
mod
erat
e" p
erm
eabi
lity.
It sh
ould
be
note
d th
at th
e K
p va
lue
of to
luen
e va
pour
and
in a
queo
us so
lutio
n is
aro
und
4 or
ders
of m
agni
tude
hi
gher
than
in th
e pr
efer
red
stud
y.
Ase
ssm
ent
A16
7
App
endi
x A
Subs
tanc
e: T
ribut
yltin
Mol
ecul
ar w
eigh
t:29
0.0
CA
S: 5
6573
-85-
4D
ensi
ty:N
ot a
vaila
ble
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
53°C
Boi
ling
poin
t:19
3°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:N
ot a
vaila
ble
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:4.7
6
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
The
Swed
ish
skin
not
atio
n ap
plie
s to
orga
notin
com
poun
ds in
gen
eral
(inc
ludi
ng tr
ibut
yltin
).
Der
mal
app
licat
ion
of v
ario
us o
rgan
otin
com
poun
ds c
ause
s sys
tem
ic to
xici
ty in
labo
rato
ry a
nim
als.
For e
xam
ple,
dai
ly a
pplic
atio
n of
10
mg/
kg tr
ibut
yltin
oxi
de to
the
shav
ed sk
in o
f mal
e gu
inea
pig
s cau
sed
redu
ced
body
wei
ght a
nd re
nal t
ubul
ar d
egen
erat
ion
(AC
GIH
(200
1)).
The
derm
al L
D50
val
ue in
rats
was
repo
rted
to 6
05 m
g/kg
(AC
GIH
(200
1)).
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A16
8
App
endi
x A
Subs
tanc
e: T
richl
oret
hane
, 1,1
,1-
Mol
ecul
ar w
eigh
t:13
3.4
CA
S: 7
1-55
-6D
ensi
ty:1
.338
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
2:9
Mel
ting
poin
t:-3
2.6°
CB
oilin
g po
int:
74.1
°CSk
in n
otat
ion:
No
Vap
our
pres
sure
:13
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:1
3L
og K
ow:2
.49
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Hum
Arm
/Ha
1000
Vap
1.6
mm
ol/L
50.
336
210
4.4
Kez
ic e
t al.
(200
0)H
umW
B19
000
Vap
600p
pm2
3.5
242
mg
900.
03R
iihim
aki &
Pfa
ffli
(197
8)M
ouA
b2.
90.
5N
eat
60.
2527
0 µg
2.7
370
Tsur
uta
(197
5)
The
stud
y by
Tsu
ruta
(197
5) su
gges
t "m
oder
ate"
per
mea
bilit
y of
nea
t 1,1
,1-tr
ichl
oroe
than
e.H
owev
er, a
bsor
ptio
n w
as m
easu
red
by h
omog
eniz
ing
the
who
le a
nim
al. T
his m
etho
d m
ay se
vere
ly
unde
rest
imat
e sk
in p
erm
eabi
lity.
The
rem
aini
ng e
xper
imen
ts e
xpos
ed th
e sk
in to
1,1
,1-tr
ichl
oroe
than
e va
pour
, whi
ch p
roba
bly
give
s ov
eres
timat
ed K
p va
lues
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A16
9
App
endi
x A
Subs
tanc
e: T
richl
oroe
thyl
ene,
1,1
,2-
Mol
ecul
ar w
eigh
t:13
1.3
CA
S: 7
9-01
-6D
ensi
ty:1
.462
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
1:21
Mel
ting
poin
t:-8
6°C
Boi
ling
poin
t:86
.7°C
Skin
not
atio
n: N
oV
apou
r pr
essu
re:7
.2 k
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
:6.4
Log
Kow
:2.4
2
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
Fl20
0-40
00.
2In
fH
2O32
-82
µg/l
236
612
000.
0038
-0.0
098
Nak
ai e
t al.
(199
9)H
umA
bFl
200-
400
0.2
Inf
H2O
34-7
9 µg
/l17
66
1100
0.00
37-0
.008
7N
akai
et a
l. (1
999)
Hum
Br
FlFu
ll0.
79H
2O7.
3 ng
/ml
(5pp
b)10
50-
10-
128
000.
002
Bog
en e
t al.
(199
8)R
atFk
StFu
ll0.
790.
005
Nea
t5
1010
1.3
0.08
212
McC
orm
ick
et a
l. (1
991)
Rat
FkSt
Full
0.79
0.00
5N
eat
56
101.
10.
1217
McC
orm
ick
et a
l. (1
991)
Rat
FkSt
Full
0.79
0.00
5N
eat
54
101
0.16
23M
cCor
mic
k et
al.
(199
1)R
atFk
StFu
ll0.
790.
005
Nea
t5
310
0.9
0.19
28M
cCor
mic
k et
al.
(199
1)R
atFk
StFu
ll0.
790.
005
Nea
t5
210
0.7
0.22
32M
cCor
mic
k et
al.
(199
1)R
atFk
StFu
ll0.
790.
005
Nea
t5
110
0.5
0.32
46M
cCor
mic
k et
al.
(199
1)R
atFk
StFu
ll0.
790.
005
Nea
t5
0.5
100.
30.
3855
McC
orm
ick
et a
l. (1
991)
Rat
FkSt
Full
0.79
0.00
5N
eat
510
102.
50.
1623
McC
orm
ick
et a
l. (1
991)
Rat
FkSt
Full
0.79
0.00
5N
eat
56
102.
20.
2334
McC
orm
ick
et a
l. (1
991)
Rat
FkSt
Full
0.79
0.00
5N
eat
54
101.
90.
344
McC
orm
ick
et a
l. (1
991)
Rat
FkSt
Full
0.79
0.00
5N
eat
53
101.
70.
3652
McC
orm
ick
et a
l. (1
991)
Rat
FkSt
Full
0.79
0.00
5N
eat
52
101.
40.
4565
McC
orm
ick
et a
l. (1
991)
Rat
FkSt
Full
0.79
0.00
5N
eat
51
101
0.63
92M
cCor
mic
k et
al.
(199
1)R
atFk
StFu
ll0.
790.
005
Nea
t5
0.5
100.
50.
6392
McC
orm
ick
et a
l. (1
991)
Rat
Ab
StFu
ll2.
60.
5N
eat
271-
51-
51.
10.
4668
Tsur
uta
(197
8)
HG
PW
B~3
00In
fH
2O28
-160
ng/
ml
(19-
110
ppb)
51.
22-
4w23
000.
0064
-0.0
37B
ogen
et a
l. (1
992)
HG
PW
B~3
00In
fH
2O0.
15 (
1000
00 p
pb)
51.
22-
4w21
0032
Bog
en e
t al.
(199
2)H
umA
rm/H
a10
00V
ap1.
3 m
mol
/L5
0.33
649
08.
4K
ezic
et a
l. (2
000)
Hum
Arm
5080
H2O
1
32
20.
33
mg
190
19Po
et e
t al.
(200
0)H
umH
a51
040
00H
2O
13
22
0.3
40 m
g15
015
Poet
et a
l. (2
000)
Mou
Ab
2.9
0.5
Nea
t21
0.08
3-0.
2591
-340
µg
3.2
470
Tsur
uta
(197
8)
A w
ide
rang
e of
Kp
valu
es a
re re
porte
d, d
epen
ding
on
vehi
cle
and
spec
ies.
The
pref
erre
d st
udy
is th
at o
f Tsu
ruta
(197
8), u
sing
mou
se sk
in in
viv
o w
ith n
eat t
richl
oroe
thyl
ene.
The
calc
ulat
ed K
p va
lue
of 3
·10-4
cm
/h, s
ugge
sts "
mod
erat
e" p
erm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A17
0
App
endi
x A
Subs
tanc
e: T
richl
orop
heno
lM
olec
ular
wei
ght:
197.
4C
AS:
251
67-8
2-2
Den
sity
:~1.
5 g/
cm³
Scie
ntifi
c ba
sis:
Not
ava
ilabl
e M
eltin
g po
int:
~70°
CB
oilin
g po
int:
150
to 2
00°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:N
ot a
vaila
ble
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:3.6
9
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
The
Swed
ish
cons
ensu
s rep
ort (
AoH
198
9:35
) sta
tes t
hat r
epor
ted
case
s of p
oiso
ning
indi
cate
that
the
chlo
roph
enol
s (tri
-, te
tra-,
pent
a-) c
an b
e ab
sorb
ed e
ffec
tivel
y th
roug
h th
e sk
in, a
nd th
at th
is is
pro
babl
y th
e m
ajor
exp
osur
e ro
ute
at sa
wm
ills.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A17
1
App
endi
x A
Subs
tanc
e: T
richl
orop
heno
l, 2,
4,6-
Mol
ecul
ar w
eigh
t:19
7.4
CA
S: 8
8-06
-2D
ensi
ty:1
.49
g/cm
³Sc
ient
ific
basi
s: N
ot a
vaila
ble
Mel
ting
poin
t:69
.5°C
Boi
ling
poin
t:24
4.5°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:133
Pa
(at 7
6.5°
C)
Skin
per
mea
bilit
y: E
xtre
mel
y hi
ghE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:3.6
9
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Mou
Full
0.79
0.5
0.5
1700
85H
uq e
t al.
(198
6)
N
o da
ta a
vaila
ble
Onl
y on
e st
udy
on 2
,4,6
-tric
hlor
ophe
nol w
as fo
und.
In H
uq e
t al.
(198
6) th
e re
porte
d K
p va
lue
sugg
ests
"ex
trem
ely
high
" pe
rmea
tion.
It sh
ould
be
note
d th
at fo
r phe
nol,
Huq
et a
l. (1
986)
repo
rted
a K
p va
lue
whi
ch w
as tw
o or
ders
of m
agni
tude
high
er th
an th
e pr
efer
red
valu
e.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A17
2
App
endi
x A
Subs
tanc
e: T
rieth
anol
amin
eM
olec
ular
wei
ght:
149.
2C
AS:
102
-71-
6D
ensi
ty:1
.126
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
3:36
Mel
ting
poin
t:21
.6°C
Boi
ling
poin
t:33
5.4°
CSk
in n
otat
ion:
No
Vap
our
pres
sure
:<1
Pa (a
t 20°
C)
Skin
per
mea
bilit
y: H
igh
Eva
pora
tion
rate
:<0.
005
Log
Kow
:-1.
00
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Mou
Ba
20.
04-0
.06
Nea
t (20
00 m
g/kg
bw
)24
4848
783.
741
0St
ott e
t al.
(200
0)M
ouB
a2
0.2
Ac
Nea
t (1
000
mg/
kg b
w)
324
2492
4.2
480
Stot
t et a
l. (2
000)
Mou
Ba
20.
2H
2O25
0(2
000
mg/
kg b
w)
324
2479
3382
0St
ott e
t al.
(200
0)M
ou1
Ac
209
2424
380
780
Kna
ak e
t al.
(199
7)M
ou1.
8H
2O23
2148
4817
041
0K
naak
et a
l. (1
997)
Mou
1.8
Nea
t3
2424
360
840
Kna
ak e
t al.
(199
7)M
ou2
Nea
t24
4848
200
410
Kna
ak e
t al.
(199
7)M
ou1.
8N
eat
2448
4818
042
0K
naak
et a
l. (1
997)
Rat
Ba
20.
4N
eat (
1000
mg/
kg b
w)
348
4876
1820
00St
ott e
t al.
(200
0)R
at1.
8N
eat
348
4819
025
00K
naak
et a
l. (1
997)
The
data
pre
sent
ed b
y K
naak
et a
l. (1
997)
are
bas
ed o
n an
indu
stry
repo
rt by
Wae
chte
r 198
8 (u
nava
ilabl
e).
The
orig
inal
dat
a ap
pear
to b
e th
e sa
me
as th
ose
pres
ente
d in
Sto
tt et
al.
(200
0), h
owev
er, t
he c
alcu
latio
nof
con
cent
ratio
n an
d, h
ence
, Kp
valu
es o
f Kna
ak e
t al.
(199
7) a
re se
emin
gly
erro
neou
s.
The
first
two
expe
rimen
ts b
y St
ott e
t al.
(200
0) a
re d
isre
gard
ed d
ue to
smal
l vol
ume
and
acet
one
as v
ehic
le, r
espe
ctiv
ely.
The
next
two
expe
rimen
ts a
re in
goo
d ag
reem
ent c
onsi
derin
g kn
own
spec
ies d
iffer
ence
s bet
wee
n m
ouse
and
rat s
kin.
The
rat s
kin
data
is p
refe
rred
as b
eing
clo
ser t
o hu
man
skin
. The
Kp
valu
e of
2·1
0-3 c
m/h
cor
resp
onds
to "
high
" pe
rmea
bilit
y.
How
ever
, the
exp
erim
ents
of S
tott
et a
l. (2
000)
hav
e hi
gh %
abso
rptio
n, w
hich
sugg
est t
hat t
he fl
uxes
and
Kp
valu
es
may
hav
e be
en u
nder
estim
ated
.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A17
3
App
endi
x A
Subs
tanc
e: T
rinitr
otol
uene
, 2,4
,6-
Mol
ecul
ar w
eigh
t:22
7.1
CA
S: 1
18-9
6-7
Den
sity
:1.6
54 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
992:
6M
eltin
g po
int:
80.9
°CB
oilin
g po
int:
240°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.0
04 k
Pa (a
t 80°
C)
Skin
per
mea
bilit
y: M
oder
ate
Eva
pora
tion
rate
:Not
ava
ilabl
eL
og K
ow:1
.60
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Pig
Ba
St50
0-90
00.
89.
9 m
g/cm
²Soi
l (Ti
)1.
5 (9
.5 µ
g/cm
²)6
88
1.3
0.09
50.
015
Rei
fenr
ath
et a
l. (2
002)
Pig
Ba
St50
0-90
00.
810
mg/
cm²S
oil (
Yo)
1.8
(11
µg/c
m²)
68
85
0.39
0.06
8R
eife
nrat
h et
al.
(200
2)Pi
gB
aSt
500-
900
0.8
0.00
5A
c2.
2 (1
1 µg
/cm
²)6
88
191.
20.
25R
eife
nrat
h et
al.
(200
2)
N
o da
ta a
vaila
ble
The
only
foun
d st
udy
was
that
of R
eife
nrat
h et
al.
(200
2), w
here
pig
skin
was
exp
osed
to 2
,4,6
-trin
itrot
olue
new
ith so
il or
ace
tone
as v
ehic
les.
It sh
ould
be
note
d th
at th
e us
e of
ace
tone
as v
ehic
le m
ay h
ave
seve
rely
affe
cted
the
skin
pro
perti
es.
The
pref
erre
d ex
perim
ent i
s tha
t with
ace
tone
, sug
gest
ing
a "m
oder
ate"
per
mea
bilit
y.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A17
4
App
endi
x A
Subs
tanc
e: T
urpe
ntin
eM
olec
ular
wei
ght:
Not
ava
ilabl
eC
AS:
800
6-64
-2D
ensi
ty:0
.9 g
/cm
³Sc
ient
ific
basi
s: A
oH 1
987:
39M
eltin
g po
int:
-50
to -6
0°C
Boi
ling
poin
t:15
0 to
180
°CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.6
6 kP
a (a
t 25°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:Not
ava
ilabl
e
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
No
quan
titat
ive
expe
rimen
tal d
ata
on d
erm
al u
ptak
e w
ere
foun
d in
the
liter
atur
e.
Acc
ordi
ng to
the
Swed
ish
Crit
eria
Gro
up, α
-pin
ene
(a m
ajor
com
pone
nt o
f tur
pent
ine)
is re
adily
ab
sorb
ed v
ia th
e sk
in (A
oH 1
987:
39).
AC
GIH
(200
1), m
entio
n th
at sk
in m
ay b
e a
sign
ifica
nt ro
ute
of e
xpos
ure
to tu
rpen
tine
but t
hat t
here
is n
o ev
iden
ce o
f org
an d
amag
e as
a re
sult
of th
is a
bsor
ptio
n.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A17
5
App
endi
x A
Subs
tanc
e: V
inyl
chl
orid
eM
olec
ular
wei
ght:
62.5
CA
S: 7
5-01
-4D
ensi
ty:0
.911
g/c
m³
Scie
ntifi
c ba
sis:
AoH
198
6:17
Mel
ting
poin
t:-1
53.7
°CB
oilin
g po
int:
-13°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:340
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Hig
hE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:1.6
2 (e
stim
ated
)
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
Mon
WB
Inf
Vap
0.01
8 (7
000
ppm
. 340
0 m
g)1
22
0.02
620.
11H
efne
r et a
l. (1
975)
Mon
WB
3500
Inf
Vap
0.00
21 (
800
ppm
. 390
mg)
12.
52.
50.
0366
0.01
4H
efne
r et a
l. (1
975)
The
only
foun
d st
udy
was
that
of H
efne
r et a
l. (1
975)
, wer
e a
mon
key
was
exp
osed
to
viny
l chl
orid
e va
pour
.
The
repo
rted
Kp
valu
es su
gges
t a "
high
" pe
rmea
bilit
y.
It sh
ould
be
note
d th
at v
inyl
chl
orid
e is
a g
as a
t ski
n te
mpe
ratu
re (b
.p. -
14°C
).
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A17
6
App
endi
x A
Subs
tanc
e: V
inyl
tolu
ene;
met
hyl s
tyre
neM
olec
ular
wei
ght:
118.
2C
AS:
250
13-1
5-4
Den
sity
:0.8
9 g/
cm³
Scie
ntifi
c ba
sis:
AoH
199
2:6
Mel
ting
poin
t:-7
7°C
Boi
ling
poin
t:17
0°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.15
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:N
ot a
vaila
ble
Log
Kow
:3.4
8
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Ab
St46
-63
0.64
0.06
4N
eat
648
4825
2.3
200
Fasa
no e
t al.
(200
6)H
umA
bSt
46-6
30.
640.
006
Nea
t6
0.2
0.2
0.74
66Fa
sano
et a
l. (2
006)
Hum
Ab
St46
-63
0.64
0.00
6N
eat
61
11.
110
0Fa
sano
et a
l. (2
006)
N
o da
ta a
vaila
ble
The
only
foun
d st
udy
was
that
of F
asan
o et
al.
(200
6), w
ere
hum
an sk
in w
as e
xpos
ed to
ne
at v
iny
ltolu
ene.
The
repo
rted
Kp
valu
es su
gges
t a "
mod
erat
e" p
erm
eabi
lity.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A17
7
App
endi
x A
Subs
tanc
e: X
ylen
e, m
-M
olec
ular
wei
ght:
106.
2C
AS:
108
-38-
3D
ensi
ty:0
.868
g/c
m³
Scie
ntifi
c ba
sis:
AoH
200
5:16
Mel
ting
poin
t:-4
7.9°
CB
oilin
g po
int:
139.
1°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.86
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:0
.51
Log
Kow
:3.2
0
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
Fl28
00.
640.
2N
eat
524
240.
220.
590.
326
Wilk
inso
n &
Will
iam
s (20
01)
Hum
Br
Fl28
00.
640.
2H
2O
205
2424
0.18
5859
00.
15W
ilkin
son
& W
illia
ms (
2001
)
Hum
WB
1900
0In
fV
ap0.
0080
(60
0ppm
)3
3.5
2444
mg
2400
1.9
Riih
imak
i & P
faff
li (1
978)
Hum
WB
1900
0In
fV
ap0.
0040
(30
0ppm
)2
3.5
2421
mg
2400
0.94
Riih
imak
i & P
faff
li (1
978)
Hum
Arm
/Ha
1000
Inf
Vap
0.07
3 (5
500p
pm)
50.
336
1200
8.8
Kez
ic e
t al.
(200
0)H
umH
as81
0-10
00In
fN
eat
90.
256
35 m
g1.
412
0En
gstro
m e
t al.
(197
7)H
umH
as81
0-10
00N
eat
100.
2522
4.4
380
Riih
imak
i (19
79)
Hum
Arm
1178
Inf
Vap
0.00
16
0.33
691
00.
091
Kez
ic e
t al.
(200
4a)
Hum
Arm
1178
Inf
Vap
0.00
16
0.75
672
00.
072
Kez
ic e
t al.
(200
4a)
Hum
Arm
1178
Inf
Vap
0.00
16
26
660
0.06
6K
ezic
et a
l. (2
004a
)H
umA
rm11
78In
fV
ap0.
001
63
661
00.
061
Kez
ic e
t al.
(200
4a)
Rat
WB
Vap
64
472
0015
McD
ouga
l et a
l. (1
990)
Ther
e is
a w
ide
rang
e of
Kp
valu
es (o
-, m
-, p-
xyle
ne a
nd x
ylen
e m
ixtu
re),
depe
ndin
g on
veh
icle
and
spec
ies.
The
pref
erre
d ex
perim
ents
are
thos
e w
ith n
eat x
ylen
e by
Riih
imak
i (19
79) a
nd E
ngst
rom
et a
l. (1
977)
.
The
Kp
valu
e of
4·1
0-4 c
m/h
sugg
ests
"m
oder
ate"
per
mea
bilit
y.
It sh
ould
be
note
d th
at th
e pe
rmea
bilit
ies o
f aqu
eous
and
vap
orou
s xyl
ene
are
seve
ral o
rder
s of m
agni
tude
hig
her.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A17
8
App
endi
x A
Subs
tanc
e: X
ylen
e, o
-M
olec
ular
wei
ght:
106.
2C
AS:
95-
47-6
Den
sity
:0.8
97 g
/cm
³Sc
ient
ific
basi
s: A
oH 2
005:
16M
eltin
g po
int:
-25.
2°C
Boi
ling
poin
t:14
4°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.66
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Low
Eva
pora
tion
rate
:0.5
1L
og K
ow:3
.12
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Hum
Br
Fl28
00.
640.
2N
eat
524
240.
30.
350.
2220
Wilk
inso
n &
Will
iam
s (20
01)
Hum
Br
Fl28
00.
640.
2H
2O
315
2424
0.3
2535
01.
1W
ilkin
son
& W
illia
ms (
2001
)R
atA
bSt
Full
2.6
1N
eat
373-
63-
62.
210
-59
µg0.
076.
2Ts
urut
a (1
982)
N
o da
ta a
vaila
ble
The
pref
erre
d st
udy
is th
e on
e us
ing
neat
o-x
ylen
e an
d hu
man
skin
.
The
Kp
valu
e of
2·1
0-5 c
m/h
, sug
gest
s "lo
w"
perm
eabi
lity.
It sh
ould
be
note
d th
at th
e pr
efer
red
stud
y of
m-x
ylen
e su
gges
t a K
p va
lue
that
is o
ne o
rder
of m
agni
tude
hig
her.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A17
9
App
endi
x A
Subs
tanc
e: X
ylen
e, p
-M
olec
ular
wei
ght:
106.
2C
AS:
106
-42-
3D
ensi
ty:0
.861
g/c
m³
Scie
ntifi
c ba
sis:
AoH
200
5:16
Mel
ting
poin
t:13
.3°C
Boi
ling
poin
t:13
8.3°
CSk
in n
otat
ion:
Yes
Vap
our
pres
sure
:0.7
9 kP
a (a
t 20°
C)
Skin
per
mea
bilit
y: N
o da
taE
vapo
ratio
n ra
te:0
.51
Log
Kow
:3.1
5
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
N
o da
ta a
vaila
ble
N
o da
ta a
vaila
ble
Bas
ed o
n si
mila
ritie
s in
chem
ical
stru
ctur
e an
d ph
ysic
al p
rope
rties
, p-x
ylen
e m
ay b
e as
sum
ed to
hav
e si
mila
r pe
rmea
bilit
y to
that
of o
- and
m-x
ylen
e.
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A18
0
App
endi
x A
Subs
tanc
e: X
ylen
esM
olec
ular
wei
ght:
106.
2C
AS:
133
0-20
-7D
ensi
ty:0
.862
g/c
m³
Scie
ntifi
c ba
sis:
AoH
200
5:16
Mel
ting
poin
t:-5
0°C
Boi
ling
poin
t:14
0°C
Skin
not
atio
n: Y
esV
apou
r pr
essu
re:0
.66
kPa
(at 2
0°C
)Sk
in p
erm
eabi
lity:
Mod
erat
eE
vapo
ratio
n ra
te:0
.7L
og K
ow:3
.12
Sp
Loc
C
ell
L
(µm
) A
(c
m²)
V
(ml)
Veh
icle
C
(m
g/m
l) n
TE
xp
(h)
TO
bs
(h)
TL
ag
(h)
Abs
(%
) K
P
(10-4
cm
/h)
Flux
(µ
g/cm
²/h) R
efer
ence
Rat
Ba
St56
04.
92
JP-8
5.1
(0.5
9%)
84
40.
51.
70.
8M
cDou
gal e
t al.
(200
0)
Hum
Arm
Nea
t10
152
-110
4500
-960
0D
utki
ewic
z &
Tyr
as (1
968b
)
No
info
rmat
ion
on th
e co
nten
t of t
he x
ylen
e m
ixtu
re w
as a
vaila
ble
in th
e tw
o st
udie
s.
The
resu
lts o
f the
stud
y by
Dut
kiew
icz
& T
yras
(196
8b) s
eem
s ver
y un
real
istic
. Xyl
ene
abso
rptio
n w
asca
lcul
ated
as d
iffer
ence
bet
wee
n ap
plie
d an
d re
cove
red
amou
nt. A
s xyl
ene
is n
onpo
lar a
nd v
olat
ile
this
met
hod
may
resu
lt in
sign
ifica
nt lo
sses
and
, hen
ce, o
vere
stim
ates
of f
lux
and
Kp.
The
pref
erre
d st
udy
is th
at o
f McD
ouga
l et a
l. (2
000)
, wer
e th
e re
porte
d K
p va
lue
of 2
·10-4
cm
/h su
gges
ts "
mod
erat
e" p
erm
eabi
lity.
It sh
ould
be
note
d th
at th
e pe
rmea
bilit
ies f
or n
eat o
- and
m-x
ylen
e w
ere
dete
rmin
ed a
s"l
ow"
and
"mod
erat
e", r
espe
ctiv
ely.
See
als
o da
ta o
n ea
ch x
ylen
e is
omer
(o-,
m-,
p-)
Rep
orte
d da
ta
In v
itro
In v
ivo
Ase
ssm
ent
A18
1
Appendix B
B1
References
Octanol:water partition coefficients
Syracuse Research Corporation, http://www.syrres.com/esc/kowwin.htm
Other physical properties
Acros Organics (1999) Material safety data sheet. Phenol. http://avogadro.chem.iastate.edu/MSDS/phenol.htm.
Chemfinder (2007) http://www.chemfinder.com/. Elmer's Products (2005) Material safety data sheet. Ethyl 2-cyanoacrylate.
http://krazyglue.com/products/msds/mkg0583_a.htm. Fisher Scientific (2004a) Material safety data sheet. Catechol.
http://www.catalogue.fisher.co.uk/scripts/search.dll?ViewMSDS&SheetNumber=04360. Fisher Scientific (2004b) Material safety data sheet. Hydroquinone.
https://fscimage.fishersci.com/msds/11230.htm. Fisher Scientific (2005) Material safety data sheet. 4-Chloro-m-cresol.
https://fscimage.fishersci.com/msds/90138.htm. Fisher Scientific (2006) Material safety data sheet. Carbon tetrachloride.
https://fscimage.fishersci.com/msds/90116.htm. Fisher Scientific (2007) Material safety data sheet. 2,6-Dinitrotoluene.
https://fscimage.fishersci.com/msds/71341.htm. Huntsman (1999) Comparative solvents data.
http://www.huntsman.com/performance_products/Media/JEFFSOL_Alkylene_Carbonates_Comparative_Solvents_Data.pdf.
Information CaOS (2005) Safety data for 2,4-dinitrotoluene. The Physical and Theoretical Chemistry Laboratory, Oxford University. http://www.physchem.ox.ac.uk/MSDS/DI/2,4-dinitrotoluene.html.
Intergas (2001) Material safety data sheet. Vinyl chloride. http://www.intergas.co.uk/pdf/VINYLCHLORIDE.PDF.
International Furan Chemicals (2003) Safety data sheet. Furfural. http://www.furan.com/_resources/downloads/10195en_rev6.pdf.
J.T. Baker (2004a) Material safety data sheet. 2-Butoxyethanol. http://www.jtbaker.com/msds/englishhtml/b6100.htm.
J.T. Baker (2004b) Material safety data sheet. 4-Methylmorpholine. http://www.jtbaker.com/msds/englishhtml/m5700.htm.
J.T. Baker (2004c) Material safety data sheet. Acetonitrile. http://www.jtbaker.com/msds/englishhtml/a0518.htm.
J.T. Baker (2004d) Material safety data sheet. N,N-Dimethylaniline. http://www.jtbaker.com/msds/englishhtml/d6040.htm.
J.T. Baker (2004e) Material safety data sheet. N,N-Dimethylformamide. http://www.jtbaker.com/msds/englishhtml/d6408.htm.
J.T. Baker (2004f) Material safety data sheet. n-Butylamine. http://www.jtbaker.com/msds/englishhtml/b6340.htm.
J.T. Baker (2004g) Material safety data sheet. tert-Butyl alcohol. http://www.jtbaker.com/msds/englishhtml/b6304.htm.
J.T. Baker (2005a) Material safety data sheet. Cobalt chloride. http://www.jtbaker.com/msds/englishhtml/C4928.htm.
Appendix B
B2
J.T. Baker (2005b) Material safety data sheet. Dimethyl sulfoxide. http://www.jtbaker.com/msds/englishhtml/d7120.htm.
J.T. Baker (2005c) Material safety data sheet. sec-Butyl alcohol. http://www.jtbaker.com/msds/englishhtml/b6302.htm.
J.T. Baker (2006a) Material safety data sheet. 1-Methoxy-2-propanol. http://www.jtbaker.com/msds/englishhtml/m2600.htm.
J.T. Baker (2006b) Material safety data sheet. Octane. http://www.jtbaker.com/msds/englishhtml/o1694.htm.
Mallinckrodt Baker (1999) Material safety data sheet. tert-Butylamine. http://www.rose-hulman.edu/class/cm/HTML/000000/000845.pdf.
NIOSH (2006) NIOSH Pocket guide to chemical hazards. Cincinnati, OH: National Institute for Occupational Safety and Health.
NTP (2006a) Benzene. National Toxicology Program, Department of Health and Human Services. http://ntp.niehs.nih.gov/index.cfm?objectid=E8824C59-BDB5-82F8-FD3636ECFCD0CE77.
NTP (2006b) Ethyl acrylate. National Toxicology Program, Department of Health and Human Services. http://ntp.niehs.nih.gov/index.cfm?objectid=E87DACAB-BDB5-82F8-FADF7FCCBCA3E273.
NTP (2006c) Ethylbenzene. National Toxicology Program, Department of Health and Human Services. http://ntp.niehs.nih.gov/index.cfm?objectid=E87B65AB-BDB5-82F8-FD9C26FAF198084F.
NTP (2006d) Naphthalene. National Toxicology Program, Department of Health and Human Services. http://ntp.niehs.nih.gov/index.cfm?objectid=E8841CC3-BDB5-82F8-F8FF6B2922FA31BA.
NTP (2006e) Pentachlorophenol. National Toxicology Program, Department of Health and Human Services. http://ntp.niehs.nih.gov/index.cfm?objectid=E869736C-BDB5-82F8-F94528D7F55ADC45.
OECD (2005) Hydroxyethyl acrylate. Paris, France: OECD SIDS. http://www.inchem.org/documents/sids/sids/818611.pdf.
OECD (2003) 1-Methoxy-2-propanol acetate. Paris, France. OECD SIDS. http://www.inchem.org/documents/sids/sids/108656.pdf.
Penglai Chemical (N/A) Material safety data sheet. Methyl Bromide. http://www.penglaichem.com/OLDPAGE/msds-methyl%20bromide-98.htm.
Schlessinger GG (1971) Vapor pressures, critical temperatures and critical pressures of organic solvents. In: Weast RC ed. Handbook of chemistry and physics. 51st edition. Pp D146-D172, Cleveland: The Chemical Rubber Co.
Scott Specialty Gases (2001) Material safety data sheet. 3-Chloro-1-propene. http://www.scottecatalog.com/msds.nsf/PrintView/3D1A8EB159DBF0F285256A0A004E1E68?OpenDocument.
Scientific bases
AoH. Arbete och Hälsa. http://www.medicine.gu.se/avdelningar/samhallsmedicin_folkhalsa/amm/aoh/.
Appendix B
B3
Dermal uptake data
ACGIH (2001) Documentation of the Threshold Limit Values and the Biological Exposure Indices. 7th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.
Akrill P, Cocker J & Dixon S (2002) Dermal exposure to aqueous solutions of N-methyl pyrrolidone. Toxicology Letters, 134:265-269.
Amshel CE, Fealk MH, Phillips BJ & Caruso DM (2000) Anhydrous ammonia burns case report and review of the literature. Burns, 26:493-497.
Andersen KE, Carlsen L, Egsgaard H & Larsen E (1985) Contact sensitivity and bioavailability of chlorocresol. Contact Dermatitis, 13:246-251.
Andersson K, Hallgren C, Levin J-O & Nilsson C-A (1985) Determination of ethylenediamine in air using reagent-coated adsorbent tubes and high-performance liquid chromatography on the 1-naphthylisothiourea derivate. American Industrial Hygiene Association Journal, 46:225-229.
Appel GB, Galen R, O'Brien J & Schoenfeldt R (1975) Methyl iodide intoxication. A case report. Annals of Internal Medicine, 82:534-536.
Baranowska B (1965) [Evaluation of skin absorption of carbon disulphide]. Internationales Archiv für Gewerbepathologie und Gewerbehygiene, 21:362-368.
Baranowska-Dutkiewicz B (1981) Absorption of hexavalent chromium by skin in man. Archives of Toxicology, 47:47-50.
Baranowska-Dutkiewicz B (1982a) Evaluation of the skin uptake of mercuric chloride in man. Journal of Applied Toxicology, 2:223-225.
Baranowska-Dutkiewicz B (1982b) Skin absorption of aniline from aqueous solutions in man. Toxicology Letters, 10:367-372.
Barber ED, Hill T & Schum DB (1995) The percutaneous absorption of hydroquinone (HQ) through rat and human skin in vitro. Toxicology Letters, 80:167-172.
Barber ED, Teetsel NM, Kolberg KF & Guest D (1992) A comparative study of the rates of in vitro percutaneous absorption of eight chemicals using rat and human skin. Fundamental and Applied Toxicology, 19:493-497.
Barry BW, Harrison SM & Dugard PH (1985) Vapour and liquid diffusion of model penetrants through human skin; correlation with thermodynamic activity. Journal of Pharmacy and Pharmacology, 37:226-236.
Bartnik FG, Gloxhuber C & Zimmermann V (1985) Percutaneous absorption of formaldehyde in rats. Toxicology Letters, 25:167-172.
Bartnik FG, Reddy AK, Klecak G, Zimmermann V, Hostynek JJ & Kunstler K (1987) Percutaneous absorption, metabolism, and hemolytic activity of n-butoxyethanol. Fundamental and Applied Toxicology, 8:59-70.
Batterman SA & Franzblau A (1997) Time-resolved cutaneous absorption and permeation rates of methanol in human volunteers. International Archives of Occupational and Environmental Health, 70:341-351.
Baynes RE, Brooks JD, Budsaba K, Smith CE & Riviere JE (2001) Mixture effects of JP-8 additives on the dermal disposition of jet fuel components. Toxicology and Applied Pharmacology, 175:269-281.
Baynes RE, Brooks JD, Mumtaz M & Riviere JE (2002) Effect of chemical interactions in pentachlorophenol mixtures on skin and membrane transport. Toxicological Sciences, 69:295-305.
Baynes RE, Brooks JD & Riviere JE (2000) Membrane transport of naphthalene and dodecane in jet fuel mixtures. Toxicology and Industrial Health, 16:225-238.
Behl CR & Barrett M (1981) Hydration and percutaneous absorption II: Influence of hydration on water and alkanol permeation through Swiss mouse skin; comparison with hairless mouse. Journal of Pharmaceutical Sciences, 70:1212-1215.
Appendix B
B4
Behl CR, Flynn GL, Kurihara T, Harper N, Smith W, Higuchi WI, Ho NF & Pierson CL (1980) Hydration and percutaneous absorption: I. Influence of hydration on alkanol permeation through hairless mouse skin. Journal of Investigative Dermatology, 75:346-352.
Behl CR, Flynn GL, Kurihara T, Smith WM, Bellantone NH, Gatmaitan O, Higuchi WI & Ho NFH (1984) Age And Anatomical Site Influences On Alkanol Permeation Of Skin Of The Male Hairless Mouse. Journal of the Society of Cosmetic Chemists, 35:237-252.
Behl CR, Linn EE, Flynn GL, Pierson CL, Higuchi WI & Ho NF (1983) Permeation of skin and eschar by antiseptics I: baseline studies with phenol. Journal of Pharmaceutical Sciences, 72:391-397.
Berner B, Mazzenga GC, Otte JH, Steffens RJ, Juang RH & Ebert CD (1989) Ethanol: water mutually enhanced transdermal therapeutic system II: skin permeation of ethanol and nitroglycerin. Journal of Pharmaceutical Sciences, 78:402-407.
Bernstam L, Lan CH, Lee J & Nriagu JO (2002) Effects of arsenic on human keratinocytes: morphological, physiological, and precursor incorporation studies. Environmental Research, 89:220-235.
Berode M, Droz PO & Guillemin M (1985) Human exposure to styrene. VI. Percutaneous absorption in human volunteers. International Archives of Occupational and Environmental Health, 55:331-336.
Betts CJ, Dearman RJ, Heylings JR, Kimber I & Basketter DA (2006) Skin sensitization potency of methyl methacrylate in the local lymph node assay: comparisons with guinea-pig data and human experience. Contact Dermatitis, 55:140-147.
Blank IH & McAuliffe DJ (1985) Penetration of benzene through human skin. Journal of Investigative Dermatology, 85:522-526.
Boatman RJ, Perry LG, Fiorica LA, English JC, Kapp RW, Jr., Bevan C, Tyler TR, Banton MI & Wright GA (1998) Dermal absorption and pharmacokinetics of isopropanol in the male and female F-344 rat. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 26:197-202.
Boatman RJ, Schum DB, Guest D & Stack CR (1993) Toxicology of Diethylene glycol butyl ether. 2.Disposition studies with 14C-Diethylene glycol butyl ether and 14C-Diethylene glycol butyl ether acetate after dermal application to rats. Journal of the American College of Toxicology, 12:145-154.
Bogen KT, Colston BW, Jr. & Machicao LK (1992) Dermal absorption of dilute aqueous chloroform, trichloroethylene, and tetrachloroethylene in hairless guinea pigs. Fundamental and Applied Toxicology, 18:30-39.
Bogen KT, Keating GA, Meissner S & Vogel JS (1998) Initial uptake kinetics in human skin exposed to dilute aqueous trichloroethylene in vitro. Journal of Exposure Analysis and Environmental Epidemiology, 8:253-271.
Boman A & Maibach HI (2000) Influence of evaporation and solvent mixtures on the absorption of toluene and n-butanol in human skin in vitro. Annals of Occupational Hygiene, 44:125-135.
Brain KR, Walters KA, Green DM, Brain S, Loretz LJ, Sharma RK & Dressler WE (2005) Percutaneous penetration of diethanolamine through human skin in vitro: application from cosmetic vehicles. Food and Chemical Toxicology, 43:681-690.
Bronaugh RL & Maibach HI (1985a) Percutaneous absorption of nitroaromatic compounds: in vivo and in vitro studies in the human and monkey. Journal of Investigative Dermatology, 84:180-183.
Bronaugh RL & Stewart RF (1985b) Methods for in vitro percutaneous absorption studies V: Permeation through damaged skin. Journal of Pharmaceutical Sciences, 74:1062-1066.
Bronaugh RL & Stewart RF (1986) Methods for in vitro percutaneous absorption studies. VI: Preparation of the barrier layer. Journal of Pharmaceutical Sciences, 75:487-491.
Brooks JD & Riviere JE (1996) Quantitative percutaneous absorption and cutaneous distribution of binary mixtures of phenol and para-nitrophenol in isolated perfused porcine skin. Fundamental and Applied Toxicology, 32:233-243.
Appendix B
B5
Bucks DA, Guy RH & Maibach HI (1989-1990) Percutaneous penetration and mass balance accountability: Technique and implications for dermatology. Journal of Toxicology: Cutaneous and Ocular Toxicology, 8:439-451.
Chien YW, Keshary PR, Tojo K & Huang YC (1984) Transdermal controlled administration of nitroglycerin. 11 th International Symposium of Controlled Release of Bioactive Materials.
Chu I, Dick D, Bronaugh R & Tryphonas L (1996) Skin reservoir formation and bioavailability of dermally administered chemicals in hairless guinea pigs. Food and Chemical Toxicology, 34:267-276.
Clark DG & Litchfield MH (1969) The toxicity, metabolism, and pharmacologic properties of propylene glycol 1,2-dinitrate. Toxicology and Applied Pharmacology, 15:175-184.
Clayton GD & Clayton FE eds. (1981) Patty's industrial hygiene and toxicology. Third ed. (Vol. 2B). New York, NY: John Wiley & Sons.
Corbett GE, Finley BL, Paustenbach DJ & Kerger BD (1997) Systemic uptake of chromium in human volunteers following dermal contact with hexavalent chromium (22 mg/L). Journal of Exposure Analysis and Environmental Epidemiology, 7:179-189.
Corley RA, Gordon SM & Wallace LA (2000) Physiologically based pharmacokinetic modeling of the temperature-dependent dermal absorption of chloroform by humans following bath water exposures. Toxicological Sciences, 53:13-23.
Degim IT, Pugh WJ & Hadgraft J (1998) Skin permeability data: anomalous results. International Journal of Pharmaceutics, 170:129-133.
Deisinger PJ, Perry LG & Guest D (1998) In vivo percutaneous absorption of [14C]DEHP from [14C]DEHP-plasticized polyvinyl chloride film in male Fischer 344 rats. Food and Chemical Toxicology, 36:521-527.
Dick D, Ng KM, Sauder DN & Chu I (1995) In vitro and in vivo percutaneous absorption of 14C-chloroform in humans. Human and Experimental Toxicology, 14:260-265.
Dick IP, Bounds SVJ, Parod RJ, Banton MI & Griffiths JC (2001) In vitro dermal absorption of N-methyl-2-pyrrolidone(NMP) through human and rat skin. Society of Toxicology 40th Annual Meeting., San Francisco, USA.
DiVincenzo GD & Hamilton ML (1979) Fate of n-butanol in rats after oral administration and its uptake by dogs after inhalation or skin application. Toxicology and Applied Pharmacology, 48:317-325.
DiVincenzo GD, Hamilton ML, Kaplan CJ, Krasavage WJ & O'Donoghue JL (1978) Studies on the respiratory uptake and excretion and the skin absorption of methyl n-butyl ketone in humans and dogs. Toxicology and Applied Pharmacology, 44:593-604.
Driver J, Tardiff RG, Sedik L, Wester RC & Maibach HI (1993) In vitro percutaneous absorption of [14C] ethylene glycol. Journal of Exposure Analysis and Environmental Epidemiology, 3:277-284.
Dugard PH (1987) The absorption of cyanide through human skin in vitro from solutions of sodium cyanide and gaseous HCN. In: Ballantyne B & Marrs TC eds. Clinical and Experimental Toxicology of cyanides. Pp 127-137. Bristol: Wright.
Dugard PH, Walker M, Mawdsley SJ & Scott RC (1984) Absorption of some glycol ethers through human skin in vitro. Environmental Health Perspectives, 57:193-197.
Durrheim H, Flynn GL, Higuchi WI & Behl CR (1980) Permeation of hairless mouse skin I: Experimental methods and comparison with human epidermal permeation by alkanols. Journal of Pharmaceutical Sciences, 69:781-786.
Dutkiewicz B, Konczalik J & Karwacki W (1980) Skin absorption and per os administration of methanol in men. International Archives of Occupational and Environmental Health, 47:81-88.
Dutkiewicz T (1977) Experimental studies on arsenic absorption routes in rats. Environmental Health Perspectives, 19:173-176.
Dutkiewicz T & Tyras H (1967) A study of the skin absorption of ethylbenzene in man. British Journal of Industrial Medicine, 24:330-332.
Appendix B
B6
Dutkiewicz T & Tyras H (1968a) The quantitative estimation of toluene skin absorption in man. Internationales Archiv fur Arbeitsmedizin, 24:253-257.
Dutkiewicz T & Tyras H (1968b) Skin absorption of toluene, styrene, and xylene by man. British Journal of Industrial Medicine, 25:243.
Elsisi AE, Carter DE & Sipes IG (1989) Dermal absorption of phthalate diesters in rats. Fundamental and Applied Toxicology, 12:70-77.
Engstrom K, Husman K & Riihimaki V (1977) Percutaneous absorption of m-xylene in man. International Archives of Occupational and Environmental Health, 39:181-189.
Exley C (2004) Aluminum in antiperspirants: more than just skin deep. American Journal of Medicine, 117:969-970.
Fasano WJ & Baer KN (2006) The in vitro permeability coefficient and short-term absorption rates for vinyl toluene using human cadaver skin mounted in a static diffusion cell model. Drug and Chemical Toxicology, 29:39-55.
Feldmann RJ & Maibach HI (1970) Absorption of some organic compounds through the skin in man. Journal of Investigative Dermatology, 54:399-404.
Fennell TR, Sumner SC, Snyder RW, Burgess J, Spicer R, Bridson WE & Friedman MA (2005) Metabolism and hemoglobin adduct formation of acrylamide in humans. Toxicological Sciences, 85:447-459.
Fiserova-Bergerova V, Pierce JT & Droz PO (1990) Dermal absorption potential of industrial chemicals: criteria for skin notation. American Journal of Industrial Medicine, 17:617-635.
Flarend R, Bin T, Elmore D & Hem SL (2001) A preliminary study of the dermal absorption of aluminium from antiperspirants using aluminium-26. Food and Chemical Toxicology, 39:163-168.
Flek J & Sedivec V (1978) The absorption, metabolism and excretion of furfural in man. International Archives of Occupational and Environmental Health, 41:159-168.
Frantz SW, Beskitt JL, Grosse CM, Tallant MJ, Dietz FK & Ballantyne B (1996a) Pharmacokinetics of ethylene glycol. II. Tissue distribution, dose-dependent elimination, and identification of urinary metabolites following single intravenous, peroral or percutaneous doses in female Sprague-Dawley rats and CD-1 mice. Xenobiotica, 26:1195-1220.
Frantz SW, Beskitt JL, Tallant MJ, Zourelias LA & Ballantyne B (1996b) Pharmacokinetics of ethylene glycol. III. Plasma disposition and metabolic fate after single increasing intravenous, peroral, or percutaneous doses in the male Sprague-Dawley rat. Xenobiotica, 26:515-539.
Franz TJ (1975) Percutaneous absorption on the relevance of in vitro data. Journal of Investigative Dermatology, 64:190-195.
Franz TJ (1984) Percutaneous absorption of benzene. In: McFarland HN ed. Applied toxicology of petroleum hydrocarbons. Pp 61-70. Princeton, NJ: Scientific publishers.
Frasch HF & Barbero AM (2005) Application of solid-phase microextraction to in vitro skin permeation experiments: example using diethyl phthalate. Toxicology In Vitro, 19:253-259.
Gamer AO, Leibold E & van Ravenzwaay B (2006) The in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin. Toxicology In Vitro, 20:301-307.
Gammelgaard B, Fullerton A, Avnstorp C & Menne T (1992) Permeation of chromium salts through human skin in vitro. Contact Dermatitis, 27:302-310.
Garland A & Camps FE (1945) Methyl iodine poisoning. British Journal of Industrial Medicine, 2:209-211.
Garner CE, Demeter J & Matthews HB (2006) The effect of chlorine substitution on the disposition of polychlorinated biphenyls following dermal administration. Toxicology and Applied Pharmacology, 216:157-167.
Garner CE & Matthews HB (1998) The effect of chlorine substitution on the dermal absorption of polychlorinated biphenyls. Toxicology and Applied Pharmacology, 149:150-158.
Gross E, Kiese M & Resag K (1960) [Absorption of ethylene glycol dinitrate through the skin.]. Archiv fur Toxikologie, 18:194-199.
Appendix B
B7
Guest D, Hamilton ML, Deisinger PJ & DiVincenzo GD (1984) Pulmonary and percutaneous absorption of 2-propoxyethyl acetate and 2- ethoxyethyl acetate in beagle dogs. Environmental Health Perspectives, 57:177-183.
Gummer CL & Maibach HI (1986) The penetration of [14C]ethanol and [14C]methanol through excised guinea-pig skin in vitro. Food and Chemical Toxicology, 24:305-309.
Hagedorn-Leweke U & Lippold BC (1995) Absorption of sunscreens and other compounds through human skin in vivo: derivation of a method to predict maximum fluxes. Pharmaceutical Research, 12:1354-1360.
Hanke J, Dutkiewicz T & Piotrowski J (2000) The absorption of benzene through human skin. International Journal of Occupational and Environmental Health, 6:104-111.
Hawkins GS & Reifenrath WG (1986) Influence of skin source, penetration cell fluid, and partition coefficient on in vitro skin penetration. Journal of Pharmaceutical Sciences, 75:378-381.
Hefner RE, Jr., Watanabe PG & Gehring PJ (1975) Percutaneous absorption of vinyl chloride. Toxicology and Applied Pharmacology, 34:529-532.
Higo N, Hinz RS, Lau DT, Benet LZ & Guy RH (1992a) Cutaneous metabolism of nitroglycerin in vitro. I. Homogenized versus intact skin. Pharmaceutical Research, 9:187-190.
Higo N, Hinz RS, Lau DT, Benet LZ & Guy RH (1992b) Cutaneous metabolism of nitroglycerin in vitro. II. Effects of skin condition and penetration enhancement. Pharmaceutical Research, 9:303-306.
Hine CH, Kodama JK, Anderson HH, Simonson DW & Wellington JS (1958) The toxicology of epoxy resins. A.M.A. Archives of Industrial Health, 17:129-144.
Hjelm EW, Boman A, Fernstrom P, Hagberg M & Johanson G (1991) Percutaneous uptake and kinetics of methyl isobutyl ketone (MIBK) in the guinea-pig. Toxicology Letters, 56:79-86.
Holland JM, Kao JY & Whitaker MJ (1984) A multisample apparatus for kinetic evaluation of skin penetration in vitro: the influence of viability and metabolic status of the skin. Toxicology and Applied Pharmacology, 72:272-280.
Hood HL, Kraeling ME, Robl MG & Bronaugh RL (1999) The effects of an alpha hydroxy acid (glycolic acid) on hairless guinea pig skin permeability. Food and Chemical Toxicology, 37:1105-1111.
Horstman SW, Rossner A & Kalman DA (1989) Penetration of pentachlorophenol and tetrachlorophenol through human skin. Journal of Environmental Science and Health, A24:229-242.
Hotchkiss SA, Hewitt P, Caldwell J, Chen WL & Rowe RR (1992) Percutaneous absorption of nicotinic acid, phenol, benzoic acid and triclopyr butoxyethyl ester through rat and human skin in vitro: further validation of an in vitro model by comparison with in vivo data. Food and Chemical Toxicology, 30:891-899.
Hucker HB, Miller JK, Hochberg A, Brobyn RD, Riordan FH & Calesnick B (1967) Studies on the absorption, excretion and metabolism of dimethylsulfoxide (DMSO) in man. Journal of Pharmacology and Experimental Therapeutics, 155:309-317.
Hughes MF & Hall LL (1995) Disposition of phenol in rat after oral, dermal, intravenous, and intratracheal administration. Xenobiotica, 25:873-883.
Hughes MF, Shrivastava SP, Fisher HL & Hall LL (1993) Comparative In Vitro Percutaneous Absorption Of P-Substitued Phenols Through Rat Skin Usimg Static And Flow-through Diffusion Systems. Toxicology In Vitro, 7:221-227.
Huq AS, Ho NF, Husari N, Flynn GL, Jetzer WE & Condie L, Jr. (1986) Permeation of water contaminative phenols through hairless mouse skin. Archives of Environmental Contamination and Toxicology, 15:557-566.
Hursh JB, Clarkson TW, Miles EF & Goldsmith LA (1989) Percutaneous absorption of mercury vapor by man. Archives of Environmental Health, 44:120-127.
Islam MS, Zhao L, McDougal JN & Flynn GL (1995) Uptake of chloroform by skin during short exposures to contaminated water. Risk Analysis, 15:343-352.
Appendix B
B8
Islam MS, Zhao L, Zhou J, Dong L, McDougal JN & Flynn GL (1996) Systemic uptake and clearance of chloroform by hairless rats following dermal exposure. I. Brief exposure to aqueous solutions. Risk Analysis, 16:349-357.
Islam MS, Zhao L, Zhou J, Dong L, McDougal JN & Flynn GL (1999) Systemic uptake and clearance of chloroform by hairless rats following dermal exposure: II. Absorption of the neat solvent. American Industrial Hygiene Association Journal, 60:438-443.
Itoh T, Xia J, Magavi R, Nishihata T & Rytting JH (1990) Use of shed snake skin as a model membrane for in vitro percutaneous penetration studies: comparison with human skin. Pharmaceutical Research, 7:1042-1047.
Jacobs RR & Phanprasit W (1993) An in vitro comparison of the permeation of chemicals in vapor and liquid phase through pig skin. American Industrial Hygiene Association Journal, 54:569-575.
Jakasa I, Mohammadi N, Kruse J & Kezic S (2004) Percutaneous absorption of neat and aqueous solutions of 2-butoxyethanol in volunteers. International Archives of Occupational and Environmental Health, 77:79-84.
Johanson G (1996) An overview of glycol ethers metabolism and toxicokinetics. In: Guillemin MP ed. Occupational Hygene - Risk Management of Occupational Hazards - Proceedings of the International Symposium on Health Hazards of Glycol Ethers - 19-21 April 1994 Pont á Mousson, France. Vol. 2. Pp 5-24. Amsterdam: Gordon and Breach Publishers.
Johanson G & Boman A (1991) Percutaneous absorption of 2-butoxyethanol vapour in human subjects. British Journal of Industrial Medicine, 48:788-792.
Johanson G, Boman A & Dynesius B (1988a) Percutaneous absorption of 2-butoxyethanol in man. Scandinavian Journal of Work, Environment and Health, 14:101-109.
Johanson G & Dynesius B (1988b) Liquid/air partition coefficients of six commonly used glycol ethers. British Journal of Industrial Medicine, 45:561-564.
Johanson G & Fernstrom P (1986) Percutaneous uptake rate of 2-butoxyethanol in the guinea pig. Scandinavian Journal of Work, Environment and Health, 12:499-503.
Johanson G & Fernstrom P (1988c) Influence of water on the percutaneous absorption of 2-butoxyethanol in guinea pigs. Scandinavian Journal of Work, Environment and Health, 14:95-100.
Jones K, Cocker J, Dodd LJ & Fraser I (2003) Factors affecting the extent of dermal absorption of solvent vapours: a human volunteer study. Annals of Occupational Hygiene, 47:145-150.
Jones RA, Strickland JA & Siegel J (1972) Toxicity of propylene glycol 1,2-dinitrate in experimental animals. Toxicology and Applied Pharmacology, 22:128-137.
Jordi AU (1953) Absorption of methyl bromide through the intact skin; a report of one fatal and two non-fatal cases. The Journal of Aviation Medicine, 24:536-539.
Jung CT, Wickett RR, Desai PB & Bronaugh RL (2003) In vitro and in vivo percutaneous absorption of catechol. Food and Chemical Toxicology, 41:885-895.
Kanikkannan N, Patel R, Jackson T, Shaik MS & Singh M (2001) Percutaneous absorption and skin irritation of JP-8 (jet fuel). Toxicology, 161:1-11.
Kao J, Hall J & Helman G (1988) In vitro percutaneous absorption in mouse skin: influence of skin appendages. Toxicology and Applied Pharmacology, 94:93-103.
Kao J, Hall J, Shugart LR & Holland JM (1984) An in vitro approach to studying cutaneous metabolism and disposition of topically applied xenobiotics. Toxicology and Applied Pharmacology, 75:289-298.
Kao J, Patterson FK & Hall J (1985) Skin penetration and metabolism of topically applied chemicals in six mammalian species, including man: an in vitro study with benzo[a]pyrene and testosterone. Toxicology and Applied Pharmacology, 81:502-516.
Kezic S, Janmaat A, Kruse J, Monster AC & Verberk MM (2004a) Percutaneous absorption of m-xylene vapour in volunteers during pre-steady and steady state. Toxicology Letters, 153:273-282.
Appendix B
B9
Kezic S, Mahieu K, Monster AC & de Wolff FA (1997) Dermal absorption of vaporous and liquid 2-methoxyethanol and 2- ethoxyethanol in volunteers. Occupational and Environmental Medicine, 54:38-43.
Kezic S, Meuling WJ & Jakasa I (2004b) Free and total urinary 2-butoxyacetic acid following dermal and inhalation exposure to 2-butoxyethanol in human volunteers. International Archives of Occupational and Environmental Health, 77:580-586.
Kezic S, Monster AC, Kruse J & Verberk MM (2000) Skin absorption of some vaporous solvents in volunteers. International Archives of Occupational and Environmental Health, 73:415-422.
Kikkoji T, Gumbleton M, Higo N, Guy RH & Benet LZ (1991) Percutaneous penetration kinetics of nitroglycerin and its dinitrate metabolites across hairless mouse skin in vitro. Pharmaceutical Research, 8:1231-1237.
Klain GJ, Reifenrath WG & Black KE (1985) Distribution and metabolism of topically applied ethanolamine. Fundamental and Applied Toxicology, 5:S127-133.
Knaak JB, Leung HW, Stott WT, Busch J & Bilsky J (1997) Toxicology of mono-, di-, and triethanolamine. Reviews of Environmental Contamination and Toxicology, 149:1-86.
Korinth G, Geh S, Schaller KH & Drexler H (2003) In vitro evaluation of the efficacy of skin barrier creams and protective gloves on percutaneous absorption of industrial solvents. International Archives of Occupational and Environmental Health, 76:382-386.
Lacy SA, Merritt K, Brown SA & Puryear A (1996) Distribution of nickel and cobalt following dermal and systemic administration with in vitro and in vivo studies. Journal of Biomedical Materials Research, 32:279-283.
Langguth P, Hildegard S & Mutschler E (1986a) Variations of in vitro nitroglycerine permeation through human epidermis. Pharmaceutical Research, 3:61-63.
Langguth P, Spahn H, Mutschler E & Hubner K (1986b) An approach to reduce the number of skin samples in testing the transdermal permeation of drugs. Journal of Pharmacy and Pharmacology, 38:726-730.
Larese F, Fiorito A, Dobetti L, Furlan G, Fernetich E & Bussani R (1994) Skin absorption of solvents: Evaluation in experimental conditions. Occupational Hygiene, 1:191-198.
Larese Filon F, Fiorito A, Adami G, Barbieri P, Coceani N, Bussani R & Reisenhofer E (1999) Skin absorption in vitro of glycol ethers. International Archives of Occupational and Environmental Health, 72:480-484.
Larese Filon F, Maina G, Adami G, Venier M, Coceani N, Bussani R, Massiccio M, Barbieri P & Spinelli P (2004) In vitro percutaneous absorption of cobalt. International Archives of Occupational and Environmental Health, 77:85-89.
Liron Z & Cohen S (1984a) Percutaneous absorption of alkanoic acids I: A study of operational conditions. Journal of Pharmaceutical Sciences, 73:534-537.
Liron Z & Cohen S (1984b) Percutaneous absorption of alkanoic acids II: Application of regular solution theory. Journal of Pharmaceutical Sciences, 73:538-542.
Lockley DJ, Howes D & Williams FM (2002) Percutaneous penetration and metabolism of 2-ethoxyethanol. Toxicology and Applied Pharmacology, 180:74-82.
Lockley DJ, Howes D & Williams FM (2004) Percutaneous penetration and metabolism of 2-butoxyethanol. Archives of Toxicology, 78:617-628.
Loden M (1986a) The effect of 4 barrier creams on the absorption of water, benzene, and formaldehyde into excised human skin. Contact Dermatitis, 14:292-296.
Loden M (1986b) The in vitro permeability of human skin to benzene, ethylene glycol, formaldehyde, and n-hexane. Acta Pharmacologica et Toxicologica, 58:382-389.
Longley EO & Jones AT (1965) Methyl Bromide Poisoning in Man. Industrial Medicine and Surgery, 34:499-502.
Lowney YW, Ruby MV, Wester RC, Schoof RA, Holm SE, Hui XY, Barbadillo S & Maibach HI (2005) Percutaneous absorption of arsenic from environmental media. Toxicology and Industrial Health, 21:1-14.
Appendix B
B10
Lundh T, Boman A & Akesson B (1997) Skin absorption of the industrial catalyst dimethylethylamine in vitro in guinea pig and human skin, and of gaseous dimethylethylamine in human volunteers. International Archives of Occupational and Environmental Health, 70:309-313.
Maibach HI & Anjo DM (1981) Percutaneous penetration of benzene and benzene contained in solvents used in the rubber industry. Archives of Environmental Health, 36:256-260.
Marzulli FN, Anjo DM & Maibach HI (1981) In vivo skin penetration studies of 2,4-toluenediamine, 2,4-diaminoanisole, 2-nitro-p-phenylenediamine, p-dioxane and N-nitrosodiethanolamine in cosmetics. Food and Cosmetics Toxicology, 19:743-747.
Mathews JM, Garner CE, Black SL & Matthews HB (1997) Diethanolamine absorption, metabolism and disposition in rat and mouse following oral, intravenous and dermal administration. Xenobiotica, 27:733-746.
Mathews JM, Parker MK & Matthews HB (1991) Metabolism and disposition of diethylene glycol in rat and dog. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 19:1066-1070.
Matsubayashi T, Sakaeda T, Kita T, Kurimoto Y, Nakamura T, Nishiguchi K, Fujita T, Kamiyama F, Yamamoto A & Okumura K (2003) Intradermal concentration of hydroquinone after application of hydroquinone ointments is higher than its cytotoxic concentration. Biological and Pharmaceutical Bulletin, 26:1365-1367.
McCormick K & Abdel-Rahman MS (1991) The role of testosterone in trichloroethylene penetration in vitro. Environmental Research, 54:82-92.
McDermot HL, Finkbeiner AJ & Zanette B (1967) The fate of dimethyl sulfoxide applied to the skin of the rat. Canadian Journal of Physiology and Pharmacology, 45:475-478.
McDougal JN, Jepson GW, Clewell HJ, 3rd, Gargas ML & Andersen ME (1990) Dermal absorption of organic chemical vapors in rats and humans. Fundamental and Applied Toxicology, 14:299-308.
McDougal JN, Pollard DL, Weisman W, Garrett CM & Miller TE (2000) Assessment of skin absorption and penetration of JP-8 jet fuel and its components. Toxicological Sciences, 55:247-255.
Mertschenk B, Bornemann W, Filser JG, von Meyer L, Rust U, Schneider JC & Gloxhuber C (1991) Urinary excretion of acetylcyanamide in rat and human after oral and dermal application of hydrogen cyanamide (H2NCN). Archives of Toxicology, 65:268-272.
Miller MJ, Ferdinandi ES, Klan M, Andrews LS, Douglas JF & Kneiss JJ (1997) Pharmacokinetics and disposition of methyl t-butyl ether in Fischer-344 rats. Journal of Applied Toxicology, 17 Suppl 1:S3-12.
Mills PC, Magnusson BM & Cross SE (2003) Effect of solute lipophilicity on penetration through canine skin. Australian Veterinary Journal, 81:752-755.
Mills PC, Magnusson BM & Cross SE (2004) The effect of region of application on absorption of ethanol and hexanol through canine skin. Research in Veterinary Science, 76:37-41.
Minghetti P, Casiraghi A, Cilurzo F, Montanari L, Marazzi M, Falcone L & Donati V (1999) Comparison of different membranes with cultures of keratinocytes from man for percutaneous absorption of nitroglycerine. Journal of Pharmacy and Pharmacology, 51:673-678.
Mint A, Hotchkiss SAM & Caldwell J (1994) Percutaneous absorption of diethylphthalate through rat and human skin in vitro. Toxicology In Vitro, 8:251-256.
Moody RP, Nadeau B & Chu I (1995) In vivo and in vitro dermal absorption of benzo[a]pyrene in rat, guinea pig, human and tissue-cultured skin. Journal of Dermatological Science, 9:48-58.
Mraz J, Galova E, Nohova H & Vitkova D (1994) Uptake, metabolism and elimination of cyclohexanone in humans. International Archives of Occupational and Environmental Health, 66:203-208.
Mraz J & Nohova H (1992) Percutaneous absorption of N,N-dimethylformamide in humans. International Archives of Occupational and Environmental Health, 64:79-83.
Appendix B
B11
Muhammad F, Brooks JD & Riviere JE (2004) Comparative mixture effects of JP-8(100) additives on the dermal absorption and disposition of jet fuel hydrocarbons in different membrane model systems. Toxicology Letters, 150:351-365.
Nair MK, Chetty DJ, Ho H & Chien YW (1997) Biomembrane permeation of nicotine: mechanistic studies with porcine mucosae and skin. Journal of Pharmaceutical Sciences, 86:257-262.
Naitoh K, Inai Y, Hirabayashi T & Tsuda T (2002) Exhalation behavior of four organic substrates and water absorbed by human skin. Biological and Pharmaceutical Bulletin, 25:867-871.
Nakai JS, Chu I, Li-Muller A & Aucoin R (1997) Effect of environmental conditions on the penetration of benzene through human skin. Journal of Toxicology and Environmental Health, 51:447-462.
Nakai JS, Stathopulos PB, Campbell GL, Chu I, Li-Muller A & Aucoin R (1999) Penetration of chloroform, trichloroethylene, and tetrachloroethylene through human skin. Journal of Toxicology and Environmental Health. Part A, 58:157-170.
Ng KM, Chu I, Bronaugh RL, Franklin CA & Somers DA (1992) Percutaneous absorption and metabolism of pyrene, benzo[a]pyrene, and di(2-ethylhexyl) phthalate: comparison of in vitro and in vivo results in the hairless guinea pig. Toxicology and Applied Pharmacology, 115:216-223.
Nierenberg DW, Nordgren RE, Chang MB, Siegler RW, Blayney MB, Hochberg F, Toribara TY, Cernichiari E & Clarkson T (1998) Delayed cerebellar disease and death after accidental exposure to dimethylmercury. New England Journal of Medicine, 338:1672-1676.
Noonan PK & Gonzalez MA (1989-1990) Pharmacokinetics and the variability of percutaneous absorption. Journal of Toxicology: Cutaneous and Ocular Toxicology, 8:511-516.
OECD (2005) Hydroxyethyl acrylate, CAS N°: 818-61-1. Paris, France: OECD SIDS. Ousterhout DK, Gladieux GV & Leonard F (1968) Cutaneous absorption of N-alkyl
alpha-cyanoacrylate. Journal of Biomedical Materials Research, 2:157-163. Palmer RB, Godwin DA & McKinney PE (2000) Transdermal kinetics of a mercurous chloride
beauty cream: an in vitro human skin analysis. Journal of Toxicology. Clinical Toxicology, 38:701-707.
Payan JP, Boudry I, Beydon D, Fabry JP, Grandclaude MC, Ferrari E & Andre JC (2003) Toxicokinetics and metabolism of N-[(14)C]N-methyl-2-pyrrolidone in male Sprague-Dawley rats: in vivo and in vitro percutaneous absorption. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 31:659-669.
Payan JP, Marty JP, Fabry JP, Beydon D, Boudry I, Ferrari E, Canel F, Grandclaude MC & Vincent CM (2001) In vivo and in vitro percutaneous absorption of [(14)C]di-N- butylphthalate in rat. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 29:843-854.
Pelling D, Phillips JC & Cunninghame ME (1998) Absorption Of Hydrophilic And Lipophilic Compounds Through Epidermal And Subepidermal Strata Of Rat Skin in Vitro. Toxicology In Vitro, 12:47-55.
Pendlington RU, Whittle E, Robinson JA & Howes D (2001) Fate of ethanol topically applied to skin. Food and Chemical Toxicology, 39:169-174.
Pilgram GS, Engelsma-van Pelt AM, Koerten HK & Bouwstra JA (2000) The effect of two azones on the lateral lipid organization of human stratum corneum and its permeability. Pharmaceutical Research, 17:796-802.
Piotrowski J (1967) Further investigations on the evaluation of exposure to nitrobenzene. British Journal of Industrial Medicine, 24:60-65.
Piotrowski JK (1971) Evaluation of exposure to phenol: absorption of phenol vapour in the lungs and through the skin and excretion of phenol in urine. British Journal of Industrial Medicine, 28:172-178.
Poet TS, Corley RA, Thrall KD, Edwards JA, Tanojo H, Weitz KK, Hui X, Maibach HI & Wester RC (2000) Assessment of the percutaneous absorption of trichloroethylene in rats and
Appendix B
B12
humans using MS/MS real-time breath analysis and physiologically based pharmacokinetic modeling. Toxicological Sciences, 56:61-72.
Poet TS, Weitz KK, Gies RA, Edwards JA, Thrall KD, Corley RA, Tanojo H, Hui X, Maibach HI & Wester RC (2002) PBPK modeling of the percutaneous absorption of perchloroethylene from a soil matrix in rats and humans. Toxicological Sciences, 67:17-31.
Ponec M, Wauben-Penris PJ, Burger A, Kempenaar J & Bodde HE (1990) Nitroglycerin and sucrose permeability as quality markers for reconstructed human epidermis. Skin Pharmacology, 3:126-135.
Pongjanyakul T, Prakongpan S, Panomsuk S, Puttipipatkhachorn S & Priprem A (2002) Shed king cobra and cobra skins as model membranes for in-vitro nicotine permeation studies. Journal of Pharmacy and Pharmacology, 54:1345-1350.
Prah J, Ashley D, Blount B, Case M, Leavens T, Pleil J & Cardinali F (2004) Dermal, oral, and inhalation pharmacokinetics of methyl tertiary butyl ether (MTBE) in human volunteers. Toxicological Sciences, 77:195-205.
Qiao GL, Brooks JD & Riviere JE (1997) Pentachlorophenol dermal absorption and disposition from soil in swine: effects of occlusion and skin microorganism inhibition. Toxicology and Applied Pharmacology, 147:234-246.
Qiao GL & Riviere JE (2002) Systemic uptake and cutaneous disposition of pentachlorophenol in a sequential exposure scenario: effects of skin preexposure to benzo[a]pyrene. Journal of Toxicology and Environmental Health. Part A, 65:1307-1331.
Qvist MH, Hoeck U, Kreilgaard B, Madsen F & Frokjaer S (2000) Evaluation of Gottingen minipig skin for transdermal in vitro permeation studies. European Journal of Pharmaceutical Sciences, 11:59-68.
Rajaniemi R, Pfaffli P & Savolainen H (1989) Percutaneous absorption of methyl methacrylate by dental technicians. British Journal of Industrial Medicine, 46:356-357.
Reifenrath WG, Kammen HO, Palmer WG, Major MM & Leach GJ (2002) Percutaneous absorption of explosives and related compounds: an empirical model of bioavailability of organic nitro compounds from soil. Toxicology and Applied Pharmacology, 182:160-168.
Riihimaki V (1979) Percutaneous absorption of m-xylene from a mixture of m-xylene and isobutyl alcohol in man. Scandinavian Journal of Work, Environment and Health, 5:143-150.
Riihimaki V & Pfaffli P (1978) Percutaneous absorption of solvent vapors in man. Scandinavian Journal of Work, Environment and Health, 4:73-85.
Riviere JE, Qiao G, Baynes RE, Brooks JD & Mumtaz M (2001) Mixture component effects on the in vitro dermal absorption of pentachlorophenol. Archives of Toxicology, 75:329-334.
Roberts ME & Mueller KR (1990) Comparisons of in vitro nitroglycerin (TNG) flux across yucatan pig, hairless mouse, and human skins. Pharmaceutical Research, 7:673-676.
Roberts MS, Anderson RA & Swarbrick J (1977) Permeability of human epidermis to phenolic compounds. Journal of Pharmacy and Pharmacology, 29:677-683.
Rogaczewska T & Piotrowski J (1968) [Routes of acrylonitrile absorption in man.]. Medycyna Pracy, 19:349-353.
Sabourin PJ, Medinsky MA, Thurmond F, Birnbaum LS & Henderson RF (1992) Effect of dose on the disposition of methoxyethanol, ethoxyethanol, and butoxyethanol administered dermally to male F344/N rats. Fundamental and Applied Toxicology, 19:124-132.
Saghir SA & Rozman KK (2003) Kinetics of monochloroacetic acid at subtoxic and toxic doses in rats after single oral and dermal administrations. Toxicological Sciences, 76:51-64.
Sanders CL, Skinner C & Gelman RA (1984) Percutaneous absorption of [7.10-14C]benzo[a]pyrene and [7,12-14C]dimethylbenz[a]anthracene in mice. Environmental Research, 33:353-360.
Sartorelli P, Aprea C, Cenni A, Novelli MT, Orsi D, Palmi S & Matteucci G (1998) Prediction of percutaneous absorption from physicochemical data: a model based on data of in vitro experiments. Annals of Occupational Hygiene, 42:267-276.
Appendix B
B13
Sartorelli P, Montomoli L, Sisinni AG, Barabesi L, Bussani R & Cherubini Di Simplicio F (2003) Percutaneous penetration of inorganic mercury from soil: an in vitro study. Bulletin of Environmental Contamination and Toxicology, 71:1091-1099.
Sax NI (1984) Dangerous properties of industrial materials. 6th ed. New York: Van Nostrand Reinhold.
Scansetti G, Botta GC, Spinelli P, Reviglione L & Ponzetti C (1994) Absorption and excretion of cobalt in the hard metal industry. Science of the Total Environment, 150:141-144.
Scheuplein RJ & Blank IH (1973) Mechanism of percutaneous absorption. IV. Penetration of nonelectrolytes (alcohols) from aqueous solutions and from pure liquids. Journal of Investigative Dermatology, 60:286-296.
Scott RC, Corrigan MA, Smith F & Mason H (1991) The influence of skin structure on permeability: an intersite and interspecies comparison with hydrophilic penetrants. Journal of Investigative Dermatology, 96:921-925.
Scott RC, Dugard PH, Ramsey JD & Rhodes C (1987) In vitro absorption of some o-phthalate diesters through human and rat skin. Environmental Health Perspectives, 74:223-227.
Sexton R & Henson E (1949) Dermatological injuries by ethylene oxide. Journal of Industrial Hygiene and Toxicology, 31:297-300.
Shah PV, Fisher HL, Sumler MR, Monroe RJ, Chernoff N & Hall LL (1987) Comparison of the penetration of 14 pesticides through the skin of young and adult rats. Journal of Toxicology and Environmental Health, 21:353-366.
Sherertz EF & Sloan KB (1988) Percutaneous penetration of squaric acid and its esters in hairless mouse and human skin in vitro. Archives for Dermatological Research. Archiv fur Dermatologische Forschung, 280:57-60.
Skowronski GA, Kadry AM, Turkall RM, Botrous MF & Abdel-Rahman MS (1994) Soil decreases the dermal penetration of phenol in male pig in vitro. Journal of Toxicology and Environmental Health, 41:467-479.
Skowronski GA, Turkall RM & Abdel-Rahman MS (2000) In vitro penetration of soil-aged mercury through pig skin. Journal of Toxicology and Environmental Health. Part A, 61:189-200.
Smyth HF, Jr. & Carpenter CP (1948) Further experience with Range-Finding Test in the Industrial Toxicology Laboratory. Journal of Industrial Hygiene and Toxicology, 30:63-68.
Smyth HF, Jr., Carpenter CP & Weil CS (1949) Range-finding toxicity data, List III. Journal of Industrial Hygiene and Toxicology, 31:60-62.
Smyth HF, Jr., Carpenter CP & Weil CS (1951) Range-finding toxicity data: List IV. A. M. A. Archives of Industrial Hygiene and Occupational Medicine, 4:119-122.
Smyth HF, Jr., Carpenter CP, Weil CS, Pozzani UC & Striegel JA (1962) Range-finding toxicity data: List VI. American Industrial Hygiene Association Journal, 23:95-107.
Southwell D & Barry BW (1983) Penetration enhancers for human skin: mode of action of 2-pyrrolidone and dimethylformamide on partition and diffusion of model compounds water, n-alcohols, and caffeine. Journal of Investigative Dermatology, 80:507-514.
Southwell D, Barry BW & Woodford R (1984) Variations in permeability of human skin and between specimens. International Journal of Pharmaceutics, 18:299-309.
Stewart RD & Dodd HC (1964) Absorption of carbon tetrachloride, trichloroethylene, tetrachloroethylene, methylene chloride, and 1, 1, 1-trichloroethane through the human skin. American Industrial Hygiene Association Journal, September-October:439-446.
Storm JE, Collier SW, Stewart RF & Bronaugh RL (1990) Metabolism of xenobiotics during percutaneous penetration: role of absorption rate and cutaneous enzyme activity. Fundamental and Applied Toxicology, 15:132-141.
Stott WT, Waechter JM, Rick DL & Mendrala AL (2000) Absorption, distribution, metabolism and excretion of intravenously and dermally administered triethanolamine in mice. Food and Chemical Toxicology, 38:1043-1051.
Appendix B
B14
Stroo HF, Roy TA, Liban CB & Kreitinger JP (2005) Dermal bioavailability of benzo[a]pyrene on lampblack: implications for risk assessment. Environmental Toxicology and Chemistry / SETAC, 24:1568-1572.
Sumner SC, Williams CC, Snyder RW, Krol WL, Asgharian B & Fennell TR (2003) Acrylamide: a comparison of metabolism and hemoglobin adducts in rodents following dermal, intraperitoneal, oral, or inhalation exposure. Toxicological Sciences, 75:260-270.
Sun JD, Beskitt JL, Tallant MJ & Frantz SW (1996) In vitro skin penetration of monoethanolamine and diethanolamine using excised skin from rats, mice, rabbits and humans. Journal of Toxicology: Cutaneous and Ocular Toxicology, 15:131-146.
Susten AS, Dames BL, Burg JR & Niemeier RW (1985) Percutaneous penetration of benzene in hairless mice: an estimate of dermal absorption during tire-building operations. American Journal of Industrial Medicine, 7:323-335.
Susten AS, Niemeier RW & Simon SD (1990) In vivo percutaneous absorption studies of volatile organic solvents in hairless mice. II. Toluene, ethylbenzene and aniline. Journal of Applied Toxicology, 10:217-225.
Tchounwou PB, Newsome C, Glass K, Centeno JA, Leszczynski J, Bryant J, Okoh J, Ishaque A & Brower M (2003) Environmental toxicology and health effects associated with dinitrotoluene exposure. Reviews on Environmental Health, 18:203-229.
Thrall KD, Weitz KK & Woodstock AD (2002a) Use of real-time breath analysis and physiologically based pharmacokinetic modeling to evaluate dermal absorption of aqueous toluene in human volunteers. Toxicological Sciences, 68:280-287.
Thrall KD & Woodstock AD (2002b) Evaluation of the dermal absorption of aqueous toluene in F344 rats using real-time breath analysis and physiologically based pharmacokinetic modeling. Journal of Toxicology and Environmental Health. Part A, 65:2087-2100.
Tsuruta H (1975) Percutaneous absorption of organic solvents. I) Comparative study of the in vivo percutaneous absorption of chlorinated solvents in mice. Industrial Health, 13.
Tsuruta H (1977) Percutaneous absorption of organic solvents. II) A method for measuring the penetration rate of chlorinated solvents through excised rat skin. Industrial Health, 15:131-139.
Tsuruta H (1978) Percutaneous absorption of trichloroethylene in mice. Industrial Health, 16:145-148.
Tsuruta H (1982) Percutaneous absorption of organic solvents. III. On the penetration rates of hydrophobic solvents through the excised rat skin. Industrial Health, 20:335-345.
Tsuruta H (1989) Skin absorption of organic solvent vapors in nude mice in vivo. Industrial Health, 27:37-47.
Tsuruta H (1996) Skin absorption of solvent mixtures--effect of vehicles on skin absorption of toluene. Industrial Health, 34:369-378.
Turkall RM, Skowronski GA, Suh DH & Abdel-Rahman MS (2003) Effect of a chemical mixture on dermal penetration of arsenic and nickel in male pig in vitro. Journal of Toxicology and Environmental Health. Part A, 66:647-655.
Ursin C, Hansen CM, Van Dyk JW, Jensen PO, Christensen IJ & Ebbehoej J (1995) Permeability of commercial solvents through living human skin. American Industrial Hygiene Association Journal, 56:651-660.
Wahlberg JE (1965) Percutaneous absorption of sodium chromate (51Cr), cobaltous (58Co), and mercuric (203Hg) chlorides through excised human and guinea pig skin. Acta Dermato-Venereologica, 45:415-426.
Wahlberg JE (1970) Percutaneous absorption of trivalent and hexavalent chromium (51Cr) through excised human and guinea pig skin. Dermatologica, 141:288-296.
Wahlberg JE & Boman A (1979) Comparative percutaneous toxicity of ten industrial solvents in the guinea pig. Scandinavian Journal of Work, Environment and Health, 5:345-351.
Wahlberg JE & Skog E (1963) The percutaneous absorption of sodium chromate (51Cr) in the guinea pig. Acta Dermato-Venereologica, 43:102-108.
Appendix B
B15
Wahlberg JE & Skog E (1965) Percutaneous Absorption of Trivalent and Hexavalent Chromium: A Comparative Investigation in the Guinea Pig by Means of 51cr. Archives of Dermatology, 92:315-318.
Valette G & Cavier R (1954) [Percutaneous absorption and chemical structure; the case for hydrocarbons, alcohols and esters.]. Archives Internationales de Pharmacodynamie et de Therapie, 97:232-240.
Verkkala E, Rajaniemi R & Savolainen H (1983) Local neurotoxicity of methylmethacrylate monomer. Toxicology Letters, 18:111-114.
Wester RC, Hartway T, Maibach HI, Schell MJ, Northington DJ, Culver BD & Strong PL (1998a) In vitro percutaneous absorption of boron as boric acid, borax, and disodium octaborate tetrahydrate in human skin: a summary. Biological Trace Element Research, 66:111-120.
Wester RC, Hartway T, Serranzana S & Maibach HI (1997) Human skin in vitro percutaneous absorption of gaseous ethylene oxide from fabric. Food and Chemical Toxicology, 35:513-515.
Wester RC, Hui X, Maibach HI, Bell K, Schell MJ, Northington DJ, Strong P & Culver BD (1998b) In vivo percutaneous absorption of boron as boric acid, borax, and disodium octaborate tetrahydrate in humans: a summary. Biological Trace Element Research, 66:101-109.
Wester RC & Maibach HI (2000) Benzene percutaneous absorption: dermal exposure relative to other benzene sources. International Journal of Occupational and Environmental Health, 6:122-126.
Wester RC, Maibach HI, Bucks DA, Sedik L, Melendres J, Liao C & DiZio S (1990) Percutaneous absorption of [14C]DDT and [14C]benzo[a]pyrene from soil. Fundamental and Applied Toxicology, 15:510-516.
Wester RC, Maibach HI, Sedik L, Melendres J & Wade M (1993a) In vivo and in vitro percutaneous absorption and skin decontamination of arsenic from water and soil. Fundamental and Applied Toxicology, 20:336-340.
Wester RC, Maibach HI, Sedik L, Melendres J, Wade M & DiZio S (1993b) Percutaneous absorption of pentachlorophenol from soil. Fundamental and Applied Toxicology, 20:68-71.
Wester RC, Melendres J, Hui X, Cox R, Serranzana S, Zhai H, Quan D & Maibach HI (1998c) Human in vivo and in vitro hydroquinone topical bioavailability, metabolism, and disposition. Journal of Toxicology and Environmental Health. Part A, 54:301-317.
Wester RC, Melendres J, Sedik L, Maibach H & Riviere JE (1998d) Percutaneous absorption of salicylic acid, theophylline, 2, 4-dimethylamine, diethyl hexyl phthalic acid, and p-aminobenzoic acid in the isolated perfused porcine skin flap compared to man in vivo. Toxicology and Applied Pharmacology, 151:159-165.
WHO (1983) International Programme on Chemical Safety Environmental Health Criteria 28 Acrylonitrile. Geneva: World Health Orgnization.
WHO (2001) Concise International Chemical Assessment Document 34, Chlorinated Naphthalenes. Geneva: World Health Orgnization.
Wilkinson SC & Williams FM (2001) Volatility, LogP, and vehicle effects on dermal absorption of a range of solvents. Poster 621. Society of Toxicology, 40th Annual meeting, San Francisco, Ca, U.S.A.
Wilkinson SC & Williams FM (2002) Effects of experimental conditions on absorption of glycol ethers through human skin in vitro. International Archives of Occupational and Environmental Health, 75:519-527.
von Oettingen WF, Hueper WC, Deichmann-Gruebler W & Wiley FH (1936) 2-Chloro-butadiene (Chloroprene): Its toxicity and pathology and the mechanism of its action. Journal of Industrial Hygiene and Toxicology, 18:240-270.
Wong KK, Wang GM, Dreyfuss J & Schreiber EC (1971) Absorption, excretion, and biotransformation of dimethyl sulfoxide in man and miniature pigs after topical application as an 80 per cent gel. Journal of Investigative Dermatology, 56:44-48.
Appendix B
B16
Xu X & Weisel CP (2005) Dermal uptake of chloroform and haloketones during bathing. Journal of Exposure Analysis and Environmental Epidemiology, 15:289-296.
Yang JJ, Roy TA, Krueger AJ, Neil W & Mackerer CR (1989) In vitro and in vivo percutaneous absorption of benzo[a]pyrene from petroleum crude-fortified soil in the rat. Bulletin of Environmental Contamination and Toxicology, 43:207-214.
Yang JJ, Roy TA & Mackerer CR (1986) Percutaneous absorption of benzo[a]pyrene in the rat: comparison of in vivo and in vitro results. Toxicology and Industrial Health, 2:409-416.
Yang RS, Anuszkiewicz CM, Chu SC, Garman RH, McKelvey JA & Tallant MJ (1987) Biochemical and morphological studies on the percutaneous uptake of [14C] ethylenediamine in the rat. Journal of Toxicology and Environmental Health, 20:261-272.
Zorin S, Kuylenstierna F & Thulin H (1999) In vitro test of nicotine's permeability through human skin. Risk evaluation and safety aspects. Annals of Occupational Hygiene, 43:405-413.