Background. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin), is commonly considered the most toxic man-made substance. We have previously shown that high serum concentrations of TCDD in parents from Seveso, Italy, were linked to their having a relative increase in the number of female births after the parents exposure to a release of dioxin in 1976. We have continued the study to determine whether the parents' sex and/or age at exposure affected the sex ratio of their children. Methods. We measured the TCDD concentrations in serum samples from potentially exposed parents collected in 1976 and 1977, and investigated the sex ratio of their offspring. Findings. Serum samples were collected from 239 men and 296 women. 346 girls and 328 boys were born to potentially exposed parents between 1977 and 1996, showing an increased probability of female births (lower sex ratio) with increasing TCDD concentrations in the serum samples from the fathers (p = 0.008). This effect starts at concentrations less than 20 ng per kg bodyweight. Fathers exposed when they were younger than 19 years of age sired significantly more girls than boys (sex ratio 0.38 [95% CI 0.30-0.47]). Interpretation. Exposure of men to TCDD is linked to a lowered male/female sex ratio in their offspring, which may persist for years after exposure. The median concentration of dioxin in fathers in this study is similar to doses that induce epididymal impairments in rats and is about 20 times the estimated average concentration of TCDD currently found in human beings in industrialised countries. These observations could have important public-health implications.
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