Pure and Applied Chemistry

This review describes the role of metabolism with endocrine active substances. Many modern synthetic compounds are readily metabolized to more polar forms that often contain hydroxy groups. This presence of polar groups and aromatic moieties in the parent compound or metabolite can play an important role in the mechanism of endocrine disruption. In addition, phase II metabolism (e.g., glucuronidation) can also lead to deactivation of the endocrine properties. In the case of bisphenol A and alkylphenols, metabolism can be considered as a detoxification mechanism as glucuronides decrease of inhibit binding to the estrogen receptors. In the case of phthalate esters, the primary metabolites, the monoesters, and further degraded metabolites do not interact with the estrogen receptor either. In contrast, the demethylation of methoxychlor in fish and other vertebrate species leads to metabolites with an increased affinity for the estrogen receptor. Certain PCB metabolites with hydroxy groups on the para position without vicinal chlorines have estrogenic activity, but these metabolites are not relevant for the environment. PCB metabolites with methylsulfonyl groups are commonly found in environmental biota and have been associated with several endocrine, developmental, and reproductive effects. Some DDT metabolites bind weakly to the estrogen receptor, but the major biotransformation product p,p-DDE is an androgen receptor (AR) antagonist. Vinclozolin is an anti-androgen and this effect appears to caused by two of its more water-soluble metabolites. The chloro-s-triazines exhibit an in vitro induction of aromatase, but their dealkylated metabolites show a decrease or lack of this effect.

It is recognized that common metabolic processes can differ strongly among species that complicates ecotoxicological risk assessment of endocrine active substances. In conclusion, the testing of metabolites for endocrine-disrupting properties should be encouraged in the future to establish a better risk assessment process.

An appendix containing levels and half-lives of various endocrine-disrupting chemicals in the environment and in wildlife is included at the end of this article.