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Phenone, hydroxybenzophenone, and branched phenone estrogen receptor binding and vitellogenin agonism in rainbow trout in vitro models
Citation:
Tapper, M., J. Denny, J. Serrano, Rick Kolanczyk, B. Sheedy, G. Overland, M. Hornung, AND P. Schmieder. Phenone, hydroxybenzophenone, and branched phenone estrogen receptor binding and vitellogenin agonism in rainbow trout in vitro models. Applied In Vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, 5(1):62-74, (2019). https://doi.org/10.1089/aivt.2018.0008
Impact/Purpose:
This study addresses the environmental and health problem of the effect on aquatic species of endocrine disrupting chemicals in the environment. An endocrine disrupting chemical interferes with the organism’s endocrine system by mimicking the activity of the normal hormones found with the organism. This may produce adverse reproductive, developmental and neurological effects. The current work used the rainbow trout liver slice and competitive estrogen receptor binding assays as tools to study the effect of phenones, and benzophenones on the production of vitellogenein (Vtg) mRNA expression in liver slices of immature rainbow trout and ability of these chemicals to bind to the rainbow trout estrogen receptor (rtER). Phenones and benzophenones are chemicals classes used in the production of UV blockers, insecticides and pharmaceuticals. Vtg is an egg yolk precursor protein that should be absent or expressed at very low levels in male trout. Cyclic phenones, branched phenones and hydroxybenzophenones bound to rtER, with relative potency ranging from non-binder to high binding affinities, and induced Vtg gene expression in rt liver slices. In addition, the non-rtER binding cyclic phenone, cyclohexylphenylketone, was biotransformed within liver tissue to a chemical capable of induction of Vtg expression. Ultimately, the information obtained from these assays will be used to define effects-based chemical categories to build an ER expert system (ERES) for predicting ER binding potential for large numbers of structurally diverse chemicals. Furthermore, the data from this study will be used in conjunction with data from other chemical classes to provide the experimental foundation upon which the prediction of the ERES are based. Information generated by such a database would be of value to inform toxicological risk assessors which chemicals may be an endocrine disruptor and should be prioritized for further testing.
Description:
Understanding the estrogenic potential of phenones and hydroxy benzophenones, which are widely used as UV radiation filters, and in the manufacturing of insecticides and pharmaceuticals, is of interest to the US and other international environmental organizations. The estrogenic potential of cyclic phenones, branched phenones and hydroxybenzophenones, along with potential metabolites was evaluated in this study. The few published studies of phenone estrogenic activity in fish have limited test concentration ranges and do not include chemical quantification. The current study has the advantages of sequentially combining complementary in vitro rainbow trout estrogen receptor (rtER) binding and liver slice vitellogenin (Vtg) mRNA induction assays in the context of a defined ER-mediated adverse outcome pathway (AOP) and quantitative chemical analysis of the test chemicals. Cyclic phenones, branched phenones and hydroxybenzophenones bound to rtER, with relative potency ranging from non-binder to high binding affinities, and induced Vtg gene expression in rt liver slices. In addition, the non-rtER binding cyclic phenone, cyclohexylphenylketone, was biotransformed within liver tissue to a chemical capable of induction of Vtg expression.
URLs/Downloads:
DOI: Phenone, hydroxybenzophenone, and branched phenone estrogen receptor binding and vitellogenin agonism in rainbow trout in vitro models