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MECHANISMS OF MALE REPRODUCTIVE TOXICITY: BED, BATH AND BEYOND
Citation:
Darney, S P. MECHANISMS OF MALE REPRODUCTIVE TOXICITY: BED, BATH AND BEYOND. Presented at Society of Toxicology of Canada Annual Symposium, Montreal, Canada, December 6-7, 2004.
Description:
Male reproductive function depends upon the integration of a great number of highly complex biological processes and their endocrine support. Therefore it is not surprising that male reproductive health can be impaired by exposures to drugs and environmental toxicants that impact these processes in a variety of ways. Since the late 1970s when we realized that exposure to pesticides such as DBCP could result in male sterility, scientists in government, industry and academia have focused attention on improving ways of detecting male reproductive toxicants and understanding their mechanisms of action in test species and humans. Animal toxicology studies employ controlled exposure conditions and an increasingly sophisticated array of outcomes to characterize adverse reproductive effects of chemicals. Health outcomes of interest include not only fertility and reproductive performance, but also the possibility of sperm-mediated abnormal embryo development and adverse pregnancy outcomes. General principles have emerged regarding classes of chemicals such as phthalates, certain pesticides, and metals that may impact critical stages of reproductive development and/or target specific reproductive cells or hormones. For some chemicals the mode of action is well characterized facilitating quantitative risk assessments and regulations to control human exposure and thereby protect human health. We are currently entering a new era of toxicology in which gene expression, proteomic and metabalomic profiles may allow us to define molecular mechanisms of toxicity in animal (or in vitro) studies, information which aids in the prediction of risk to exposed humans. On the other hand, chemicals in the environment comprise constantly changing and increasingly complex mixtures to which we are exposed through multiple routes. Effects demonstrated in populations of exposed humans can confirm the predictive power of toxicology studies, and in turn, provide further hypotheses for testing in animal or in vitro systems. A major goal of our laboratory is to assess and evaluate the reproductive toxicity of chemical byproducts that result from the disinfection of drinking water by chlorination or chloramination. This talk will summarize the information we have gleaned regarding the male reproductive toxicity of these byproducts, specifically the haloacetic acids (HAA). We have characterized effects of HAA on spermatogenesis and sperm function in rodent models, discovering modes of action using both in vivo and in vitro approaches. We are currently embarking upon a human study designed to evaluate potential risks associated with chlorinated or brominated HAA at levels encountered in municipal drinking water systems. Together, results of these toxicology and epidemiology studies will inform the EPA's Office of Water in its rulemakings that set maximum concentration levels of disinfection byproducts in order to ensure safe drinking water.