Toxicants which affect the male reproductive system can act indirectly via alteration of the complex hormonal control of the testes, or directly by virtue of their chemical reactivity. Both categories of agents may require metabolic biotransformation to attain activity, and the site of activation may play a significant role in the modulation of testicular toxicity. The modes of action of 2 well known direct-acting male reproductive toxicants are discussed here. The use of a combination of in vivo and in vitro systems to distinguish the site and mechanism of action of these chemicals, ethylene glycol monomethyl ether and dinitrobenzene, is described. Because of the complexity of the reproductive process and of the interaction between gonadal and extragonadal metabolism, the use of multiple endpoints and multiple test systems can lend a greater degree of precision and confidence to our conclusions.
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