Effects of Dioxin on Gender Ratios in Offspring of Exposed Men

PI: Paolo Mocarelli and Brenda Eskenazi
University Milano-Bicocca and University of California, Berkeley

Background: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is considered to be one of, if not the most toxic man-made substance. It causes cancer and disrupts multiple hormonal functions. TCDD is a by-product of several manufacturing processes such as paper production and pesticide formulation.

On July 10, 1976, an explosion occurred at an herbicide manufacturing facility in Seveso, Italy. Approximately 30 kg of dioxin was released into the environment. It contaminated the soil of the surrounding area and many people were exposed. Many of these people have been followed for adverse health effects following the accident.

Advance: This paper reports a follow-up study on previous work that demonstrated a significant increase in the number of female births after the accident. Serum samples taken at the time of the accident were analyzed for TCDD. The data indicate a positive correlation between increased probability of female births with increasing TCDD concentration in the sera of the fathers. The effect starts at concentrations less than 20 ng/kg bodyweight--a level about 20 times higher than the normal TCDD concentration in people. This level of contamination is similar to doses that cause epididymal impairments in rats.

Implication: Dioxin is a ubiquitous toxin in that all human beings have some exposure. The Seveso incident occurred over 20 years ago and the effects on offspring gender ratios are still present. This fact demonstrates the persistence of dioxin and its adverse effects following exposure. Also, the level of exposure compared to "unexposed" populations is relatively low, suggesting that these effects may also be seen in the general population or susceptible individuals. These observations could have profound public-health implications. [Area of Emphasis: New Preventive Strategies Against Disease; GPRA Goal: Develop new or improved approaches for preventing or delaying the onset or progression of disease or disability.]

Citation: Mocarelli P, Gerthoux PM, Ferrari E, Patterson DG Jr, Kieszak SM, Brambilla P, Vincoli N, Signorini S, Tramacere P, Carreri V, Sampson EJ, Turner WE, Needham LL: Paternal concentrations of dioxin and sex ratio of offspring. Lancet 355:1858-1863, 2000.