Paternal concentrations of dioxin and sex ratio of offspring

Background 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin), is commonl y considered the most toxic man-made substance. We have previously shown th at high serum concentrations of TCDD in parents from Seveso, Italy, were li nked to their having a relative increase in the number of female births aft er the parents exposure to a release of dioxin in 1976. We have continued t he study to determine whether the parents' sex and/or age at exposure affec ted the sex ratio of their children. Methods We measured the TCDD concentrations in serum samples from potential ly exposed parents collected in 1976 and 1977, and investigated the sex rat io 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 199 6, showing an increased probability of female births (lower sex ratio) with increasing TCDD concentrations in the serum samples from the fathers (p=00 08). This effect starts at concentrations less than 20 ng per kg bodyweight . Fathers exposed when they were younger than 19 years of age sired signifi cantly 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 s ex ratio in their offspring, which may persist for years after exposure. Th e median concentration of dioxin in fathers in this study is similar to dos es that induce epididymal impairments in rats and is about 20 times the est imated average concentration of TCDD currently found in human beings in ind ustrialised countries. These observations could have important public-healt h implications.