Authors
Schnorr, T.M., Lawson, C.C., Whelan, E.A., Dankovic, D.A., Deddens, J.A., Piacitelli, L.A., Reefhuis, J., Sweeney, M.H., Connally, L.B., Fingerhut, M.A.

Title
Spontaneous abortion, sex ratio, and paternal occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Journal
Environmental Health Perspectives. 109(11):1127-1132. 2001.

Summary
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been suggested to increase the risk of spontaneous abortion, particularly in wives/partners of Vietnam veterans exposed to Agent Orange contaminated with TCDD. A cross-sectional medical study, conducted by the National Institute for Occupational Safety and Health (NIOSH), examined 281 male workers exposed to TCDD during the production of sodium trichlorophenol and its derivatives at two chemical manufacturing plants in New Jersey and Missouri. The referents (325) were selected from the workers' neighborhoods at the time of the study and matched on age, race and sex. TCDD serum levels at the time of conception were estimated using a pharmokinetic model which incorporated the following parameters: serum TCDD levels at the time of study, dates of employment in dioxin-related processes, body mass index (BMI) measured at time of study and from employment records. TCDD serum levels measured in referents at the time of the study were assumed to represent 'background' levels of TCDD in the unexposed population and were assigned to the pregnancies fathered by these referents.

The authors found no association between spontaneous abortions and paternal TCDD exposure. In the exposed group, pregnancies in 245 wives/partners totaled 632 - 300 pregnancies prior to paternal TCDD exposure with 25 spontaneous abortions and 332 during/following exposure with 35 spontaneous abortions. In the referent group, pregnancies in 215 wives/partners totaled 707 with 89 spontaneous abortions. Relevant confounding factors were maternal age, Hispanic origin and treatment with thyroid medication during first trimester. TCDD exposure was examined using a continuous model of exposure and using categorical TCDD levels (<20 ppt, 20 - <255 ppt, 255 - <1120 ppt, =1120 ppt). The risk of spontaneous abortion was not associated with paternal TCDD exposure using either model of analysis.

Sex ratio was unaffected by paternal TCDD exposure (male birth rate of 0.53 in 544 exposed pregnancies and 0.54 in 647 referent pregnancies). All live births (singletons and twins) were included in the study. Sex ratio was not associated with young paternal age (<20 years) at first TCDD exposure, though the sample size was small (17% workers exposed before age 20).

Dioxins, including TCDD, have long been associated with adverse health effects; however, many studies have been unable to demonstrate an increased risk of spontaneous abortion. The authors of this study conclude that paternal TCDD exposure does not increase the risk of spontaneous abortion or result in altered sex ratios. While other studies have examined this question, the design of this study including the large sample size, appropriately selected referent group and the use of employment medical records to validate TCDD exposure strengthens the conclusions the authors have drawn. Paternal TCDD exposure levels at time of conception reported here are much higher (3-16340 ppt) compared to exposure levels from other studies (0-1424 ppt), enabling the authors to conclude that there does not appear to be an increased risk of spontaneous abortion associated with high TCDD exposure. Although the overall quality of this study was very good, it would have been preferable to have independent medical documentation of the reproductive histories rather than relying on interviews with the wives/partners. The authors point out that this recall bias should be similar in both referent and exposed wives/partners. Similarly, it would have been preferable to have records of TCDD levels at the time of conception rather than relying on mathematical estimates. Future studies should examine prepubertal TCDD exposure, as early exposure may cause long term impairment of spermatogenesis that may be reflected in reduced fertility during adulthood.