Metabolic androgenization of female Daphnia magna by the xenoestrogen 4-nonylphenol

Vrtebrates and invertebrates metabolize testosterone to a variety of less-polar derivatives that elicit varying degrees of androgenicity as well as polar elimination products. We have developed a model, using the cladoceran Daphnia magna, with which the ability of xenobiotics to alter steroid hormone metabolism can be assessed and possible physiologic consequences evaluated during a 3-week assay. This model was used to assess the effects of the xenoestrogen 4-nonylphenol on steroid-metabolic processes. Exposure of daphnids to 100 μg/L 4-nonylphenol for 48 h caused a significant increase in the accumulation of radioactivity derived from [14C]testosterone provided to the exposure media. More definitive analyses demonstrated that both 25 and 100 μg/L 4-nonylphenol disrupted components of the testosterone metabolic pathway that would lead to a decrease in the metabolic elimination of testosterone and an increase in the accumulation of androgenic derivatives. Exposure of daphnids to 100 μg/L 4-nonylphenol significantly decreased fecundity of the organisms while having no effect on survival of the parental organisms. Comparison of metabolic and reproductive effects of 4-nonylphenol revealed that 71 μg/L, the reproductive chronic value, would reduce the metabolic elimination of testosterone by approximately 50%. This relationship is consistent with that which we have reported for other toxicants and identifies a mechanism, in addition to estrogenicity, that may contribute to the reproductive toxicity of this compound.