Review of the Potential Environmental and Human Health–Related Hazards and Risks from Long-Term Exposure to p-tert-Octylphenol

Para-tert-octylphenol (OP) is an important chemical intermediate mainly used for production of phenolic resins and lacquers. OP has weak estrogen-like activity in vitro, with induction of vitellogenin in fish hepatocytes and competitive estrogen receptor binding and estrogen-responsive gene expression in mammalian systems. Induction of vitellogenin in fish plasma and liver, in vivo, has also been measured and weak estrogen-like activity in rodent screening assays occurs but at much lower potency than predicted by the in vitro activity. Conventional aquatic wildlife toxicity testing shows effects on survival, growth and development, and reproduction occurring at concentrations lower than the estrogen-like responses predicted from screening assays. Studies in rodents have provided evidence of metabolic saturation at high doses of OP, and a multigeneration reproductive study confirms the lack of estrogen-like activity below this metabolic saturation as well as the lack of reproductive toxicity. This article reviews the weight of evidence for the aquatic and mammalian data and compares the results of the definitive assays to those of the screening tests. The results show that the estrogen-like activity in screening tests is not predictive of results from definitive testing, and that risk assessment decisions should be made using conventional toxicity endpoints.