SIMULATION IN - Helmholtz Zentrum München€¦ · the American Journal of Epidemiology (Venero Fernandez, et al., 2011). In a recent paper, we offered a plausible explanation for

Herausgeber:

Jochen Wittmann

Mike Müller

SIMULATION IN

UMWELT- UND

GEOWISSENSCHAFTEN

Workshop Leipzig 2013

ASIM-Mitteilung AM 146

The human sex odds at birth in France - a preliminary geo-

spatial-temporal approach in the vicinity of three selected

nuclear facilities (NF): Centre de Stockage (CdS) de l'Aube,

Institute Laue-Langevin (ILL) de Grenoble, and Commissariat à

l'Énergie Atomique (CEA) de Saclay/Paris

Hagen Scherb, Ralf Kusmierz, Kristina Voigt

Institute of Biomathematics and Biometry, Helmholtz Zentrum Muenchen – German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764

Neuherberg, Germany [email protected]

Summary:

Epidemiological effects of environmental pollution can be assessed and modeled in many different ways. Sex odds in general is the ratio of male to female individuals in a population. An important genetic indicator is the human sex ratio or sex odds at birth (male/female). This is a simple and non-invasive measure to monitor the reproductive health or detriment of a population. Except in societies where selective abortion skews the sex odds (SO), approximately 104 to 106 boys are born for every 100 girls. In previous studies we found shifts in the sex odds in the vicinity of German and Swiss NF, especially around the nuclear storage site TBL Gorleben (Transport-behälterlager: nuclear waste shipping casks storage) in Lower Saxony, Germany. Therefore, the question arises concerning the behavior of the human birth sex odds around French NF. We received complete official birth statistics by gender and municipality (1968 - 2007) from the Centre Maurice Halbwachs, Partenaire du Reseau Quetelet in Paris, France. For geo-coding the municipalities in France, i.e., to determine those municipalities distances from NF, the Lambert-93 coordinate reference system (CRS) is well suited. To assess time trends in the occurrence of boys among all live births, and to investigate whether there have been changes in the trend functions after distinct events, e.g. commissioning of NF or nuclear accidents, we apply ordinary linear logistic regression. This involves considering the male proportion among all male (m) and female (f) births: pm=m/(m+f). Two Important and useful parameters in this context are the sex odds (SO=pm/(1- pm)=m/f), and the sex odds ratio (SOR=SO1/SO0=(m1/f1)/(m0/f0)), which is the ratio of two interesting sex odds if those two sex odds have to be compared, e.g. in exposed (SO1) versus non-exposed (SO0) populations. To allow for changing sex odds trend slopes (broken sticks), we use dummy coding of time windows and interactions of those time windows with time. We found distinct significant sex odds increases around the CdS de l’Aube from 2000 onward, around the ILL de Grenoble from 1968 to 2007, and within 5 km from the CEA de Saclay after a nuclear accident in July 1979. These preliminary results for France corroborate the previous findings obtained for Germany and Switzerland, namely a significant increase in the human birth sex odds in the vicinity of NF.

Scherb / Kusmierz / Voigt 24

1 Introduction and Motivation

France is currently one of the largest producers of nuclear energy. Its 59 nuclear reactors generate 78 percent of the entire country’s electricity, and France is also the largest exporter of nuclear electricity in the European Union. France is second in the world (behind the United States) in terms of total nuclear power production, contributing 16 percent of the world’s nuclear electricity. Similar to Gorleben in Germany, France operates a nuclear storage site Centre de Stockage (CdS) near l'Aube, Champagne, about 200 km east of Paris. We analyze the sex odds around the CdS de l’Aube. Furthermore, we chose the Institute Laue-Langevin (ILL) in Grenoble for studying possible sex odds increases around a significant neutron emitting source. Finally, we take a closer look at the CEA de Saclay as an example of a nuclear accident (in July 1979) in a highly populated area near Paris.

Over the past decades, animal experiments and epidemiological studies have revealed the vulnerability of living beings exposed to adverse chemical, physical, or social conditions. The sex odds at birth is an important epidemiological indicator of genetic health in humans. Sex odds in general is the ratio of males to females in a population. The primary sex odds is the ratio at the time of conception, the secondary sex odds is the ratio at birth, and the tertiary sex odds is the ratio in mature organisms. For methodological reasons, we prefer "sex odds" over the usual term "sex ratio" in order to be able to utilize the methodologically appropriate and convenient statistical terms “odds” and “odds ratio”, in this case: sex odds (SO) and sex odds ratio (SOR). An increase in the sex odds means a drift in the direction of relatively more boys and/or less girls, whereas a decrease means a drift in the direction of relatively fewer boys and/or more girls. This is why changes in the sex odds are rather difficult to interpret.

According to Neel and Schull (1991), the sex odds is unique among the genetic indicators. Its uniqueness arises from the fact that maternal exposure is expected to produce sex odds different from sex odds after paternal exposure. Therefore, the odds of male to female offspring at birth may be a simple and non-invasive way to study and monitor the reproductive status or health of a population. According to Scholte and Sobels (1964), one of the few methods available for studying the genetic effects of ionizing radiation in man is the observation of changes in the sex odds among offspring from irradiated parents. Lethal factors of varying degree of dominance on the X chromosome, depending on whether an impaired X chromosome is derived from the mother or the father, impact the formation and the survival probability of the female zygote, entailing more or less girls at birth. According to theory, Cox found reduced offspring sex odds in irradiated women, and James, on the other hand, states, “ionizing radiation is the only reproductive hazard, which causes men to sire an excess of sons”(Cox, 1964, James, 1997, Vogel and Motulsky, 1986). In addition to lethal factors on the X chromosome, Scholte and Sobels (1964) allude to nondisjunction resulting in X0 genotypes, which are non-viable in man and, thus, may also distort the birth sex odds. As Down syndrome is a

The human sex odds at birth in France 25

well-known consequence of meiotic nondisjunction in man, evidence of increased nondisjunction across Europe after Chernobyl is obtained from increased Down syndrome prevalence at birth (Sperling, et al., 2012).

Except in societies where selective abortion skews the sex odds, approximately 104 to 106 boys are born for every 100 girls. In humans, on the one hand, the sex odds at birth is constant at the secular population level (Ein-Mor, et al., 2010), but on the other hand, considerable variability may be observed under a variety of specific circumstances. A lot of hypothetical sex odds determinants and methodological challenges assessing them have been discussed in the literature (James, 2012). However, Steiner (2012) points out that proposed determinants showed associations in small samples that could not be replicated in larger populations. This, of course, may be due to insufficient statistical power due to small effects and/or small study-populations.

Anthropogenic chemicals and ionizing radiation are determinants of the human sex odds at birth (secondary sex odds). From animal experiments it has been known for long that exposure to mutagenic chemicals or ionizing radiation can alter the natural sex odds of living beings (Muller, 1918, Muller, 1927, Muller, 1950). Stevenson and Bobrow (1967) provide a detailed account of methodological issues relevant for the assessment of determinants of the sex odds in man with special emphasis on the impact of male fetal mortality dynamics on the sex odds. Terrell et al. (2011) reviewed approximately 100 publications on possible environmental and occupational determinants of the sex odds. They concluded: “Limitations in study design and methodological issues make it difficult to draw firm conclusions from the existing sex ratio literature”. This highlights the difficulties in generating firm knowledge on sex odds determinants in man. Since recently, we put research emphasis on the effect of chemicals on the human secondary sex odds. In our first evaluation approach around chemical plants, we considered the influence of chemical accidents on the sex odds. We took a closer look at the live birth sex odds in the vicinity of Hoechst – Griesheim, where an accident occurred in 1993 spreading tons of nitroarenes into the environment (Heudorf, et al., 1994). Here, we detected a remarkable decrease in the sex odds after the chemical accident (Voigt, et al., 2012). Sociological influences, like e.g. stress, have also been reported. We just name the sex odds studies after earthquakes in Chile (Torche and Kleinhaus, 2012) and Italy (D'Alfonso, et al., 2012). In accordance with the Trivers-Willard hypothesis (Trivers and Willard, 1973), the results of these studies suggest decreases of the human sex odds at birth under adverse living conditions. However, the most dramatic influence on the human sex odds at birth is man-made, namely sex selective abortion, which poses a problem for example in China (Hesketh and Xing, 2006, Zhou, et al., 2012, Zhou, et al., 2011) and in India (Manchanda, et al., 2011, Sahni, et al., 2008). The mere appraisal of increased abortions as such due to difficult living conditions of a population does not provide convincing evidence for sex odds changes as those abortions are unlikely to be gender specific in general.


We have been investigating the influence of ionizing radiation on the human birth sex odds for several years, since we had found increased stillbirths and birth defects after Chernobyl (Scherb and Weigelt, 2003, Scherb and Weigelt, 2004, Scherb, et al., 1999). By an initial pilot study, we assessed the trends in the human sex odds of live births and stillbirths combined in several selected European countries with emphasis on the Chernobyl Nuclear Power Plant accident (Scherb and Voigt, 2007). As this study yielded positive results, we investigated the behavior of the human sex odds of live births after the atmospheric atomic bomb tests and after Chernobyl more thoroughly on a global scale. This comprehensive investigation (Scherb and Voigt, 2011) fully confirmed our opening study (Scherb and Voigt, 2007). During our research, we also detected increased sex odds near NF in Germany and Switzerland (Kusmierz, et al., 2010). The continuous discussion about the nuclear waste shipping casks storage (in German: Transportbehälterlager, TBL) in Gorleben, Lower Saxony in Germany, increased our interest in taking a closer look at this location. A spatial-temporal data analysis discloses a significant sex odds increase within 40 km distance from the TBL after the first Castor was transported to Gorleben in 1995: SOR 1.0838, (1.0391, 1.1305), and p-value = 0.0002 (Scherb and Voigt, 2012a, Scherb, et al., 2011). An intriguing new example of increased sex odds after Chernobyl is the long term sex odds trend in Cuba from 1960 to 2008, published in the American Journal of Epidemiology (Venero Fernandez, et al., 2011). In a recent paper, we offered a plausible explanation for the increase in the secondary sex odds in Cuba based on our experiences concerning the evaluation of human sex odds at birth in the light of the Chernobyl accident in single European countries and in Europe as a whole (Scherb and Voigt, 2012): We conjecture that radioactively contaminated food imported to Cuba from Chernobyl affected countries caused the sudden sex odds increase from 1987 onward in Cuba.

2 Data and statistical Methods

Complete annual French mainland gender specific birth data at the municipality level from 1968 till 2007 were provided by the Centre Maurice Halbwachs, Partenaire du Reseau Quetelet in Paris, France. The data set obtained accounts for 36 561 different municipalities giving rise to 1 281 729 individual municipality-years with 30 018 962 total births, 15 386 928 male births, and 14 632 034 female births, respectively. For geo-coding the municipalities in the German and Swiss evaluation studies, the geographic coordinates given in the Gauss–Krüger coordinate system are used. The Gauss–Krüger coordinate system is a special transverse Mercator map projection used in Germany, Austria and Finland rather than the UTM-system but similar to this. For France we used LRGF93/Lambert-93. Lambert-93 is a projected CRS last revised on 04/22/2008 that is suitable for use in France - onshore and offshore, mainland and Corsica. RGF93/Lambert-93 uses the RGF93 geographic 2D CRS as its base CRS and the Lambert-93 (Lambert Conic Conformal (2SP)) as its projection. RGF93/Lambert-93 is a CRS for large and medium scale topographic


mapping and engineering survey. It was defined by information from IGN - Paris. Lambert-93 is well suited for our purposes of determining the distances of municipalities from NF in France.

To assess spatial-temporal trends in the occurrence of boys among all live births in the vicinity of French NF (NF), and to investigate whether there have been changes in the trend functions after those NF went on stream, we applied ordinary linear logistic regression. This involves considering the male proportion among male (m) and female (f) births combined: pm=m/(m+f). Two Important and useful parameters in this context are the sex odds (SO=pm/(1-pm)=m/f), and the sex odds ratio (SOR=SO1/SO0=(m1/f1)/(m0/f0)), which is the ratio of two interesting sex odds if those two sex odds have to be compared, e.g. in exposed (SO1) versus non-exposed (SO0) populations. We used dummy coding for single points in time and for time periods as well. For example, the dummy variable for the time window from T onward is defined as dT(t)=0 for t<T and dT(t)=1 for t≥T. The simple and parsimonious logistic model for a trend and a jump in T has the following form:

Boyst ~ Binomial(LBt, πt) (t)d t intercept odds log Tt

where t: year; LBt: live births in year t; πt : Binomial probability male in year t.

The data in this study were processed with Microsoft Excel 2010. For statistical analyses, we used R 2.15.1, MATHEMATICA 9, and mostly SAS 9.2 (SAS Institute Inc: SAS/STAT User’s Guide, Version 9.2. Cary NC: SAS Institute Inc; 2003). Table 1 contains sample SAS code for testing a change-point in the sex odds trend function for a jump in the year 1996, which is suited for investigating the trend of the birth sex odds around the TBL Gorleben within 30 km distance, since the first highly active waste was transported to Gorleben in spring 1995.

3 Results

Gorleben, Lower Saxony in Germany, is known for a radioactive waste disposal facility (TBL – Transportbehälterlager), used for intermediate storage of highly radioactive waste (HAW). Previously, we have found increased human birth sex odds within 30 to 40 km distance from the TBL Gorleben right after the first HAW had arrived at Gorleben in Spring 1995 (Kusmierz, et al., 2012, Kusmierz, et al., 2010, Scherb and Voigt, 2012a, Scherb, et al., 2011, Scherb, et al., 2012). This result has been confirmed by an official investigation by the “Niedersächsisches Landesgesundheitsamt” in 2011 (NLGA, 2011), and has been discussed in a subsequent workshop in 2012 (NLGA, 2012). See Figure 1 for a possible alternative change-point model for Gorleben with a significant jump in 1998 instead of 1996. In contrast to Gorleben, Germany, it is less clear by when highly radioactive waste was first transported to the “Centre de Storage (CdS) de l’Aube” in France, see:


http://www.greenpeace.de/fileadmin/gpd/user_upload/themen/atomkraft/GPI_nucl_waste_crisis_in_France_briefing_30may06.pdf.

However, it is interesting to note that from 2000 onward there is a highly significant jump in the sex odds within the 30 km circular disc around the CdS de l’Aube similar to but somewhat stronger than the effect observed in Gorleben from 1996 or 1998 onward. Table 2 and Figures 1 and 2 display the basic birth data and the results of the trend analyses for Gorleben and de l’Aube in tabular and graphical form. Figure 3 shows the combined trend with a highly significant jump in 1998. Within 30 km from l’Aube and Gorleben combined there is a theoretical deficit of ca. 1200 girls from 1998 onward. One out of several possibilities of studying the spatial-temporal behavior of those sex odds increases near TBL Gorleben and CdS de l’Aube, is to consider the sex odds ratio within concentric 10 km distance rings around those nuclear storage sites 8 years after vs. 8 years before the temporal change-points in 1998 (TBL Gorleben: 1998 to 2005 vs. 1990 to 1997) and 2000 (CdS de l’Aube: 2000 to 2007 vs. 1992 to 1999), respectively. The reason for choosing those 8-year intervals is that the marked sex odds increase around l’Aube occurs in 2000 and we have French data not after 2007, i.e. only 8 exposed years. Therefore, it is temporally impartial to consider 8 years before and 8 years after the sex odds increase near l’Aube. Further, to make the Gorleben analysis as much as possible comparable to the l’Aube analysis, and to allow for a power increasing synoptic analysis in the end, we also consider two 8 year intervals for Gorleben from 1990 to 2005. By the way, this underpins the robustness of the Gorleben effect, as we initially considered the Gorleben change-point in 1996 rather than in 1998. The corresponding significant individual distance laws are presented in Figures 4 and 5. Figure 6 contains the significant distance law of the Gorleben and l’Aube data combined.

In our second French spatial example, we take a closer look at the Institute Laue-Langevin (ILL) in Grenoble. The ILL is a research center for neutrons, founded in 1967 in honor of the physicists von Laue and Langevin. The ILL hosts some of the most intense neutron sources in the world. In contrast to the storage of highly active waste at Gorleben and l’Aube, not before the middle or the end of the 1990ies, the operation of the neutron sources at the ILL has no clear cut start or end in the period 1968 to 2007, see Figure 7. To cope with this situation, it is possible to study the purely spatial behavior of the sex odds centered at the ILL by completely collapsing or disregarding the temporal dimension. The sex odds in 10 km and 1 km wide distance rings, centered at the ILL, are displayed in Figures 8 and 9, respectively. A Rayleigh function fitted to these 1 km data is significant according to the F-test (p=0.0162). The estimated sex odds peak is located at 32.2 km, 95% confidence interval (19.6, 44.9). The peak sex odds ratio at 32.2 km is 1.010, 95% confidence interval (1.002, 1.018). The sex odds increasing effect around Grenoble is, thus, on the one hand much weaker than the effects near Gorleben and l’Aube, but on the other hand it is acting at a larger distance in a higher populated area. Between 5 km and 70 km the sex odds ratio (SOR) is 1.008 (1.003, 1.013). Since in this large area 310 573 girls were born from 1968 to 2007, the increased sex odds corresponds to a


theoretical deficit of baby girls of 2484, 95%-confidence limits (932, 4037). A more precise deficit of girls is obtained by quantifying the gap between the bold line (Rayleigh function) and the dotted black base line in Figure 9. This yields a theoretical deficit of baby girls of 2994 around the ILL from 1968 to 2007 in France.

As a third example, we consider the CEA de Saclay in Paris. At the Saclay BL3 Reactor, on July 25 1979, radioactive fluids were released into drains designed for ordinary wastes, seeping into the local watershed. Figures 10 and 11 show the temporal and spatial trends, which demonstrate significant sex odds increases of 6% on average within 5 km from the CEA de Saclay from 1979 onward.

Table 1. SAS code for parallel trends with jump function in logistic regression.

*comment: m=male f=female births;

data a; set a; *addressing data set;

t=year-1970; *time with 1-digit origin;

km=d_TBL_Gorleben; *distance form TBL-Gorleben;

if km lt 30; *distance less than 30 km;

d1996=0; *dummy variable for period >= 1996;

if year >= 1996 then d1996=1;

run;

proc logistic data=a; *logistic regression;

model m/(m+f)= t d1996/scale=d; *model and checking heterogeneity;

run; *start procedure logistic;


Table 2. Gender specific live births within 30 km circular discs around the TBL Gorleben and the CdS

de l’Aube, within 5 km from the CEA de Saclay, and within 80 km from the ILL de Grenoble.

year total male female total male female total male female total male female

1968 . . . 1138 586 552 613 310 303 25407 13044 12363

1969 . . . 1119 591 528 743 361 382 25298 13032 12266

1970 . . . 1007 498 509 843 430 413 25837 13399 12438

1971 622 326 296 1127 571 556 952 485 467 26822 13699 13123

1972 478 226 252 1041 524 517 1084 561 523 26550 13642 12908

1973 443 240 203 1040 542 498 1202 581 621 26163 13452 12711

1974 454 236 218 903 479 424 1201 599 602 24636 12772 11864

1975 396 202 194 838 431 407 1219 614 605 22842 11667 11175

1976 375 198 177 819 421 398 1256 651 605 22240 11341 10899

1977 412 203 209 786 421 365 1274 643 631 23196 11860 11336

1978 391 211 180 797 432 365 1209 618 591 23246 12021 11225

1979 394 196 198 790 405 385 1356 707 649 24532 12685 11847

1980 398 202 196 900 452 448 1467 791 676 25586 13183 12403

1981 378 174 204 910 463 447 1360 703 657 25924 13318 12606

1982 378 178 200 855 440 415 1246 633 613 26013 13468 12545

1983 379 203 176 737 382 355 1227 602 625 24171 12283 11888

1984 345 175 170 759 383 376 1241 656 585 24747 12771 11976

1985 395 196 199 746 377 369 1281 632 649 25456 13067 12389

1986 383 192 191 783 395 388 1266 695 571 25628 13087 12541

1987 401 203 198 757 357 400 1294 660 634 25451 13272 12179

1988 362 187 175 778 381 397 1305 663 642 25879 13260 12619

1989 362 183 179 753 396 357 1387 701 686 25971 13253 12718

1990 734 355 379 717 357 360 1329 679 650 26035 13487 12548

1991 1126 567 559 666 342 324 1299 663 636 25907 13173 12734

1992 977 491 486 706 342 364 1255 653 602 25768 13144 12624

1993 953 509 444 663 343 320 1238 675 563 24476 12620 11856

1994 933 442 491 632 303 329 1294 648 646 24199 12301 11898

1995 872 418 454 657 311 346 1171 634 537 25150 12826 12324

1996 1002 506 496 671 336 335 1202 659 543 25779 13322 12457

1997 1018 516 502 704 346 358 1237 628 609 25361 12966 12395

1998 941 512 429 687 336 351 1210 642 568 25622 13186 12436

1999 1015 552 463 744 356 388 1201 637 564 25755 13138 12617

2000 1056 539 517 635 324 311 1240 655 585 27066 14142 12924

2001 1012 562 450 669 348 321 1186 587 599 27598 14171 13427

2002 929 489 440 679 362 317 1148 566 582 27105 13998 13107

2003 860 422 438 663 348 315 1122 590 532 27061 13878 13183

2004 871 439 432 708 368 340 1166 634 532 27636 14251 13385

2005 881 450 431 624 340 284 1174 607 567 27903 14435 13468

2006 787 441 346 675 369 306 1181 622 559 28750 14674 14076

2007 799 432 367 618 318 300 1126 579 547 28404 14521 13883

2008 746 388 358 . . . . . . . . .

2009 741 383 358 . . . . . . . . .

2010 849 442 407 . . . . . . . . .

2011 736 377 359 . . . . . . . . .

Total 27584 14163 13421 31501 16076 15425 47805 24654 23151 1027170 527809 499361

Births within 30 km

from the TBL Gorleben

Births within 5 km from

the CEA Saclay


the ILL Grenoble


the CdS de l'Aube


Figure 1. Trend of the live births sex odds around the TBL Gorleben, Germany, 1971 – 2011.

Figure 2. Trend of the live births sex odds around the CdS de l’Aube, France, 1968 – 2007.

Figure 3. Trend of the live births sex odds around Gorleben and l’Aube combined.


Figure 4. Spatial-temporal trend of the live births sex odds ratio in 10 km distance categories around

the TBL Gorleben.

Figure 5. Spatial-temporal trend of the live births sex odds ratio in 10 km distance categories around

the CdS de l’Aube.

Figure 6. Combined spatial-temporal trend of the live births sex odds ratio in 10 km distance

categories around the CdS de l’Aube (change-point: CP=2000) and the TBL Gorleben (CP=1998).


Figure 7. Constant time trend of the live births sex odds around the ILL de Grenoble, 1968 – 2007,

compared to the rest of France (thin broken straight line).

Figure 8. Spatial trend of the live births sex odds in 10 km distance categories around the ILL de

Grenoble 1968 – 2007.

Figure 9. Spatial trend of the live births sex odds in 1 km distance categories around the ILL de

Grenoble 1968 – 2007.


Figure 10. Trend of the live births sex odds around CEA de Saclay, 1968 – 2007.

Figure 11. Spatial trend of the live births sex odds in 1 km distance categories around the CEA de

Saclay 1979 – 2007.

4 Discussion

Human sex ratio at birth, conventionally expressed by the number of male live births per female live births, is about 1.05 - 1.06 and remarkably constant (Ein-Mor, et al., 2010). Some environmental hazards can alter the sex ratio at birth. We have been studying the effects of ionizing radiation on the sex odds for several years under various aspects. Scherb and Voigt (2007) investigated the trends in the sex odds before and after the Chernobyl accident. Gender-specific annual birth statistics were obtained from the Czech Republic, Denmark, Finland, Germany, Hungary, Norway, Poland, and Sweden between 1982 and 1992. For parts of Germany, annual birth statistics and fallout measurements after Chernobyl are available at the district level. The findings suggested a possible long-term chronic influence of the Chernobyl


Nuclear Power Plant accident on the human sex odds at birth in several European countries. Consequently, further studies were carried out to investigate the effect of running NF (Kusmierz, et al., 2010, Scherb and Voigt, 2011). In these studies, influences of ionizing radiation on the sex odds at birth were noticed. It has to be stressed that we evaluate large data sets in the range of tens to hundreds of millions of births. Only recently, the scope of interest has been amplified to the effects of chemical sites on the human sex odds at birth (Voigt, et al., 2012). Both, increases and decreases in the human sex odds provide a strong indication that there is an impact of man-made facilities on the human genome, be it chemical or physical agents. Further background concerning human reproductive vulnerability is given by Sperling et al. (2012). To date, the physical and biologic mechanisms behind the detected sex odds increases are not known. The second author has investigated the possibility of neutron activation near casks containing highly radioactive waste (Kusmierz, 2012). According to this analysis, the activation product 41Ar may play an underestimated role. Finally, as mentioned above, sex odds changes are difficult to interpret. We discussed this issue in some detail (Scherb and Voigt, 2011). It is possible that the odds of X and Y containing sperm is influenced during spermatogenesis or that female embryos get lost early and unnoticed entailing a shift in the gender proportion towards more males.

5 Conclusions and Outlook

In Europe, the nuclear facilities are built in populated regions. This does not only increase the risk of human exposure to the emissions of radioactive elements in the case of nuclear accidents, but it also increases the risk of being exposed to the continuous emissions of nuclear reactors and nuclear processing and storage sites. This has already been acknowledged by several European countries initiating studies on the occurrence of childhood cancer and leukemia in the vicinity of nuclear power plants (Sermage-Faure, et al., 2012, Spix, et al., 2008, Spycher, et al., 2011). Our work on the increase of the sex odds in the vicinity of nuclear facilities gives further evidence of detrimental genetic effects by ionizing radiation. We found significantly elevated human birth sex odds in France around the nuclear storage site CdS de l’Aube from the year 2000 onward, around the high energy neutron sources of the Institut Laue-Langevin (ILL) in Grenoble from 1968 to 2007, and around the CEA de Saclay from the 1979 accident onward. This adds convincing evidence to our previously published results. We are of the strong opinion that we have to extend our work to other data sets. We are planning to evaluate the complete German data set including the new German states (i.e. the former GDR from 1980 to 1989) with special focus on the former nuclear processing and disposal sites in Rhineland Palatinate, Saxony, and Thuringia. The difficulties in the data collection and geo-informatic aspects have been outlined at a previous iEMSS conference (Kusmierz, et


al., 2012). Furthermore, we will of course evaluate the human sex odds at birth more thoroughly around the multitude of nuclear facilities in France. We conclude that Europe as a highly populated area, with a dense collection of nuclear facilities, is a potentially dangerous continent (Lelieveld, et al., 2012). Unfortunately, this has not yet been acknowledged by most people.

6 References

Cox DW. An Investigation of Possible Genetic Damage in the Offspring of Women

Receiving Multiple Diagnostic Pelvic X Rays. American journal of human genetics 1964; 16:214-230.

D'Alfonso A, Patacchiola F, Colagrande I, D'Alessandro G, Di Fonso A, Palermo P and Carta G. A decrease in sex ratio at birth nine months after the earthquake in L'Aquila. TheScientificWorldJournal 2012; 2012:162017.

Ein-Mor E, Mankuta D, Hochner-Celnikier D, Hurwitz A and Haimov-Kochman R. Sex ratio is remarkably constant. Fertility and sterility 2010; 93:1961-1965.

Hesketh T and Xing ZW. Abnormal sex ratios in human populations: causes and consequences. Proc Natl Acad Sci U S A 2006; 103:13271-13275.

Heudorf U, Neumann HG and Peters M. [Accident in the Hoechst AG company 22 February 1993. 2. Public health evaluation]. Gesundheitswesen 1994; 56:405-410.

James WH. Ionizing radiation and offspring sex ratio. J Epidemiol Community Health 1997; 51:340-341.

James WH. Hypotheses on the stability and variation of human sex ratios at birth. Journal of theoretical biology 2012; 310:183-186.

Kusmierz R. Weshalb Zwischenlager Radioaktivität freisetzen. Strahlentelex 616-617. Strahlentelex. 2012. Herausgeber: Thomas Dersee, Berlin - Schöneiche.

Kusmierz R, Scherb H and Voigt K. Overview on data sources for modelling epidemiological effects of environmental pollution. In Seppelt R, Voinov AA, Lange S and Bankamp D (eds) International Environmental Modelling and Software Society (iEMSs) 2012. 2012, Leipzig, Germany.

Kusmierz R, Voigt K and Scherb H. Is the human sex odds at birth distorted in the vicinity of nuclear facilities (NF)? A preliminary geo-spatial-temporal approach. <http://www.helmholtz-muenchen.de/ibb/homepage/hagen.scherb/KusmierzVoigtScherb2010BonnProceedings%20short.pdf>, Accessed 8 May 2012. In Greve K and Cremers AB (eds) 24th EnviroInfo 2010. 2010. Shaker, Bonn and Cologne, Germany, pp. 616 - 626.

Lelieveld J, Kunkel D and Lawrence MG. Global risk of radioactive fallout after major nuclear reactor accidents. Atmospheric Chemistry and Physics 2012; 12: 4245-4258.

Manchanda S, Saikia B, Gupta N, Chowdhary S and Puliyel JM. Sex ratio at birth in India, its relation to birth order, sex of previous children and use of indigenous medicine. PloS one 2011; 6:e20097.

Muller HJ. Genetic Variability, Twin Hybrids and Constant Hybrids, in a Case of Balanced Lethal Factors. Genetics 1918; 3:422-499.

Muller HJ. Artificial Transmutation of the Gene. Science 1927; 66:84-87. Muller HJ. Our load of mutations. American journal of human genetics 1950; 2:111-176. Neel JV and Schull WJ. The Children of atomic bomb survivors: a genetic study, 1991.

National Academy Press, Washington, D.C.


NLGA. Niedersächsisches Landesgesundheitsamt (NLGA). Veränderungen beim sekundären Geschlechterverhältnis in der Umgebung des Transportbehälterlagers Gorleben ab 1995 - Analysen auf Basis der Geburtsstatistiken der Bundesländer Brandenburg, Mecklenburg-Vorpommern, Sachsen-Anhalt sowie Niedersachsen. Editor: Niedersächsisches Landesgesundheitsamt, Roesebeckstr. 4 - 6, 30449 Hannover, September 2011; überarbeitete Version, Erstellt von: M. Hoopmann und K. Maaser. http://www.nlga.niedersachsen.de/download/60794. Accessed 16 April 2012. 2011.

NLGA. Niedersächsisches Landesgesundheitsamt (NLGA). Fachgespräch Sekundäres Geschlechterverhältnis in der Umgebung des Transportbehälterlagers (TBL) Gorleben am 12. März 2012. Editor: Niedersächsisches Landesgesundheitsamt, Roesebeckstr. 4 - 6, 30449 Hannover. http://www.nlga.niedersachsen.de/download/65642/Sekundaeres_Geschlechterverhaeltnis_in_der_Umgebung_des_Transportbehaelterlagers_TBL_Gorleben_-_Fachgespraech_am_12_Maerz_2012.pdf. Accessed 16 April 2012. 2012.

Sahni M, Verma N, Narula D, Varghese RM, Sreenivas V and Puliyel JM. Missing girls in India: infanticide, feticide and made-to-order pregnancies? Insights from hospital-based sex-ratio-at-birth over the last century. PloS one 2008; 3:e2224.

Scherb H and Voigt K. Trends in the human sex odds at birth in Europe and the Chernobyl Nuclear Power Plant accident. Reprod Toxicol 2007; 23:593-599.

Scherb H and Voigt K. The human sex odds at birth after the atmospheric atomic bomb tests, after Chernobyl, and in the vicinity of nuclear facilities. Environmental science and pollution research international 2011; 18:697-707.

Scherb H and Voigt K. Response to F. Bochud and T. Jung: Comment on the human sex odds at birth after the atmospheric atomic bomb tests, after Chernobyl, and in the vicinity of nuclear facilities, Hagen Scherb & Kristina Voigt, Environ Sci Pollut Res (2011) 18:697-707 (DOI: 10.1007/s11356-012-0767-6). Environmental science and pollution research international 2012; 19:4234-4241.

Scherb H and Voigt K. Response to W. Kramer: The human sex odds at birth after the atmospheric atomic bomb tests, after Chernobyl, and in the vicinity of nuclear facilities: comment (doi:10.1007/s11356-011-0644-8). Environmental science and pollution research international 2012a; 19:1335-1340.

Scherb H, Voigt K and Kusmierz R. Fact Sheet Gorleben Version 3.0, December 2011: Gender specific live births in the vicinity of Gorleben, Germany: Lower Saxony (1971–2010), Mecklenburg-West Pomerania (1990-2010), Brandenburg (1991-2009), and Saxony Anhalt (1991-2009). http://www.helmholtz-muenchen.de/ibb/homepage/hagen.scherb/FactSheetGorleben.pdf. Accessed 16 April 2012 2011.

Scherb H, Voigt K and Kusmierz R. Modelling the human radiation risks around nuclear facilities in Germany and Switzerland: A case study. In Seppelt R, Voinov A, Lange S and Bankamp D (eds) International Environmental Modelling and Software Socienty (iEMSs) 2012. 2012. 978-88-9035-742-8, Leipzig, Germany.

Scherb H and Weigelt E. Congenital Malformation and Stillbirth in Germany and Europe Before and After the Chernobyl Nuclear Power Plant Accident. Environmental Science and Pollution Research, Special Issue 2003; 1:117-125.

Scherb H and Weigelt E. [Cleft lip and cleft palate birth rate in Bavaria before and after the Chernobyl nuclear power plant accident]. Mund Kiefer Gesichtschir 2004; 8:106-110.

Scherb H, Weigelt E and Brüske-Hohlfeld I. European stillbirth proportions before and after the Chernobyl accident. International journal of epidemiology 1999; 28:932-940.

Scholte PJ and Sobels FH. Sex Ratio Shifts among Progeny from Patients Having Received Therapeutic X-Radiation. American journal of human genetics 1964; 16:26-37.


Sermage-Faure C, Laurier D, Goujon-Bellec S, Chartier M, Guyot-Goubin A, Rudant J, Hemon D and Clavel J. Childhood leukemia around French nuclear power plants - the Geocap study, 2002-2007. Int J Cancer 2012.

Sperling K, Neitzel H and Scherb H. Evidence for an increase in trisomy 21 (Down syndrome) in Europe after the Chernobyl reactor accident. Genet Epidemiol 2012; 36:48-55.

Spix C, Schmiedel S, Kaatsch P, Schulze-Rath R and Blettner M. Case-control study on childhood cancer in the vicinity of nuclear power plants in Germany 1980-2003. Eur J Cancer 2008; 44:275-284.

Spycher BD, Feller M, Zwahlen M, Roosli M, von der Weid NX, Hengartner H, Egger M, Kuehni CE, Swiss Paediatric Oncology G and Swiss National Cohort Study G. Childhood cancer and nuclear power plants in Switzerland: a census-based cohort study. International journal of epidemiology 2011; 40:1247-1260.

Steiner AZ. Epidemiologic evidence for an ecological phenomenon. Fertility and sterility 2012; 98:819-820.

Stevenson AC and Bobrow M. Determinants of Sex Proportions in Man, with Consideration of the Evidence Concerning a Contribution from X-linked Mutations to Intrauterine Death. Journal of Medical Genetics 1967; 4:190–221.

Terrell ML, Hartnett KP and Marcus M. Can environmental or occupational hazards alter the sex ratio at birth? A systematic review. Emerging Health Threats Journal 2011; 4:1 - 18.

Torche F and Kleinhaus K. Prenatal stress, gestational age and secondary sex ratio: the sex-specific effects of exposure to a natural disaster in early pregnancy. Human reproduction 2012; 27:558-567.

Trivers RL and Willard DE. Natural selection of parental ability to vary the sex ratio of offspring. Science 1973; 179:90-92.

Venero Fernandez SJ, Medina RS, Britton J and Fogarty AW. The association between living through a prolonged economic depression and the male:female birth ratio--a longitudinal study from Cuba, 1960-2008. American journal of epidemiology 2011; 174:1327-1331.

Vogel F and Motulsky AG. Human Genetics, 1986. Springer, Berlin Heidelberg New York Tokyo.

Voigt K, Scherb H and Kusmierz R. Chemicals' risks versus radiation risks with respect to the alteration of human sex odds: a preliminary evaluation approach. In Seppelt R, Voinov A, Lange S and Bankamp D (eds) International Environmental Modelling and Software Socienty (iEMSs) 2012. 2012, Leipzig, Germany.

Zhou C, Wang XL, Zhou XD and Hesketh T. Son preference and sex-selective abortion in China: informing policy options. International journal of public health 2012; 57:459-465.

Zhou XD, Wang XL, Li L and Hesketh T. The very high sex ratio in rural China: impact on the psychosocial wellbeing of unmarried men. Social science & medicine 2011; 73:1422-1427.

Documents

SIMULATION IN - Helmholtz Zentrum München€¦ · the American Journal of Epidemiology (Venero Fernandez, et al., 2011). In a recent paper, we offered a plausible explanation for