Sex ratios of children of Russian pesticide producers exposed to dioxin.

Abstract

We investigated the sex ratio of children of pesticide workers who produced the biocide trichlorophenol and the herbicide 2,4,5-trichlorophenoxy acetic acid from 1961 to 1988 in the city of Ufa, Bashkortostan, Russia. We measured exposure of the two related cohorts to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxins by analyzing 84 blood samples, which produced median TCDD toxic equivalents blood lipid values of 240 ng/kg, which are more than 30 times higher than background or normal exposure from the region. The sex ratio (fraction male) of the combined cohort of 227 children from 150 male and 48 female workers was 0.40, significantly lower (z-test for proportions = 3.21; p < 0.001) than those for the city of Ufa (0.512) and elsewhere worldwide. When we analyzed the sex ratio of the children according to maternal or paternal exposure, we observed a decrease in the number of boys (ratio 0.38) for fathers and a normal number (ratio 0.51) for the mothers. Human exposure of these pesticide producers to high levels of dioxins is associated with the birth of more girls, but only for paternal exposures.

Dose Paternal Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) affect the Sex Ratio of Offspring?

“…To the best of our knowledge, this is the first experimental report to investigate the correlation between the sex ratio of offspring and the influence of direct TCDD exposure of the father in an animal experiment. The present study verifies the data obtained from TCDD-exposed humans in Seveso [15,16] and Ufa [20]. Because of the limited experimental data available on the (F1) sex ratio endpoint , our data set is advantageous due to its large sample size and its use of multiple dose levels.…”

“…We examined the sex ratio of offspring at PND 0 and used a relatively large number of animals. The human subjects at Seveso [15,16] and those at Ufa [20] were not exposed to TCDD in utero or lactationally but directly, and the male/female sex ratio of their offspring was found to be decreased. In the present study, we directly exposed male parent mice to TCDD by oral administration using a gastric sonde, finding that the TCDD-exposed groups showed a dose-related decrease in the male/female sex ratio of offspring.…”

“…In addition to these effects, a decreased male/female sex ratio among children born to males who were exposed to TCDD at a relatively young age compared with unexposed males has also been reported [15,16,20]. On the other hand, it was reported in a human cohort study that no association was found between paternal serum TCDD levels and the sex ratio of offspring [21].…”

“…It has been reported that the half-life of TCDD is approximately 7 years in humans [17] and 20 days in mice [12], and the Seveso and Russian data have shown that an increased probability of female births is related to increasing TCDD concentrations in fathers rather than in the mothers [15,16,20]. Based on these reports, we followed a modified version of Faqi's regimen of repeated exposure with low doses [4] in order to maintain a body TCDD burden in male mice as close to that of the human situation.…”

“…The Seveso data showed that an increased probability of female births is related to an increased TCDD concentration in fathers, and the altered sex ratio was especially pronounced in the children of men exposed to TCDD before age 19 [15,16]. Ryan et al [20], in a study conducted in Ufa, Russia, suggest that human exposure to high levels of dioxin is associated with the birth of more girls only in cases of paternal exposure. In contrast, the sex ratio among offspring is not markedly affected among humans exposed to a phenoxy herbicide containing TCDD and produced in the US factories which manufactured Agent Orange [21], and Yoshimura et al [25] found that the sex ratio was not significantly different from normal (0.513) in Yusho victims after accidental massive exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs).…”