Statistical issues in risk assessment of reproductive outcomes with chemical mixtures.

Establishing the relationship between a given chemical exposure and human reproductive health risk is complicated by exposures or other concomitant factors that may vary from pregnancy to pregnancy. Moreover, when exposures are to complex mixtures of chemicals, varying with time in number of components, doses of individual components, and constancy of exposure, the picture becomes even more complicated. A pilot study of risk of adverse reproductive outcomes among male wastewater treatment workers and their wives is described here. The wives of 231 workers were interviewed to evaluate retrospectively the outcomes of spontaneous early fetal loss and infertility. In addition, 87 workers participated in a cross-sectional evaluation of sperm/semen parameters. Due to the ever-changing nature of the exposure and the lack of quantification of specific exposures, six dichotomous variables were used for each specific job description to give a surrogate measure of exposure. Hence, no quantitative exposure-response relationships could be modeled. These six variables were independently assigned by two environmental hygienists, and their interrater reliability was assessed. Results are presented and further innovations in statistical methodology are proposed for further applications.