Androgen disruption from environmental contaminants interferes with the action of endogenous androgens and results in abnormal male development and reproductive function. The influence of chronic, low-level, micropollutant exposure on endocrine disruption in the androgen pathway, however, is not well understood. Disinfection by-products (DBPs) are chemicals formed during the production of microbially safe drinking water for which toxicological studies indicate a potential association with a number of cancers, as well as with developmental and reproductive effects. The relation between the physiological effects observed from exposure to DBPs and their toxicological results, however, has not been straightforward. In an effort to elucidate one possible mechanism through which these health effects are caused, a group of 21 DBPs were tested for their competitive binding ability in the androgen receptor binding assay, as measured by their IC50 values. Individual chemicals were evaluated in concentration ranges from 0.1 nM to 2 mM against a tritium-labeled reporter ligand. Of those tested, 17 bound to the androgen receptor with log(IC50) values in the range of 0.71 M to -4.86 M. The 10 strongest binders were then tested in binary mixtures with the positive control, 4-nonylphenol, where they exhibited non-additive binding capabilities when comparing log(IC50) values of the mixtures to those of the individual chemicals. Specifically, enhanced binding was observed for mucochloric acid and 2,3-dibromopropionitrile, while suppressed binding was measured for 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, more commonly referred to as mutagen X or MX. Importantly, the order of receptor binding affinity for the individual chemicals was not the same as those found in mixtures, with some weaker compounds found to exhibit stronger binding affinities when in the presence of 4-nonylphenol. These results indicate that drinking waters, which contain a mixture of DBPs, albeit at concentrations well below their measured log(IC50) value in this assay, could be a source of androgen disruption.

Identifying disinfection by-products (DBPs) capable of endocrine disruption through binding to the androgen receptor

249th National Meeting (2015)

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