Characterizing reproductive risks using biomarkers of reproductive toxicity.

Recently attention has been directed toward risks and risk factors which impair reproduction and development (Wilcox, et al., 1988; Wilcox, et al., 1990; Schardein, 1993).  For example, exposure in dental offices to scavanged
nitrous oxide (concentrations estimated between 100 and 1,000 ppm) for five or more hours per week decreases fertility to less than half that observed in dental offices where the anesthetic gas is scavenged (Rowland, et al., 1992). Several studies, including a recently concluded industry-wide evaluation, have demonstrated an increased risk of spontaneous abortion among women working in the fabrication of semiconductors (Eskenazi, et al., 1995a and b; Swan, et al., 1995; Schenker, et al., 1995).  The fertility among men working in semiconductor fabrication was also studied by these investigators and appears to be decreased in comparison to men in other work settings in the semiconductor industry (Samuels, et al., 1995).  For many years it has been observed that cigarette smoking decreases male and female fecundity as well as decreasing fertility and increasing the time needed to achieve pregnancy (Baird and Wilcox, 1985; Mattison, 1982; Weinberg, et al., 1989; Ratcliffe, et al.,
1992).  Recently, the US EPA, in its reanalysis of the human health risk assessment for dioxin has suggested that adverse reproductive and developmental effects may be the most critical and sensitive endpoints (EPA, 1997).  This article will present definitions of reproductive toxicology, describe biomarkers of reproduction, suggest an approach for characterizing reproductive toxicity in the context of risk assessment, and illustrate this approach
with a recently developed risk assessment approach using two reproductive biomarkers simultaneously.