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Evaluation of Triclosan in the Hershberger and H295R Steroidogenesis Assays
Citation:
Farmer, W., G. Louis, A. Buckalew, D. Hallinger, AND T. Stoker. Evaluation of Triclosan in the Hershberger and H295R Steroidogenesis Assays. TOXICOLOGY LETTERS. Elsevier Science Ltd, New York, NY, 291:194-199, (2018).
Impact/Purpose:
Triclosan is an antibacterial that has been shown previously in our laboratory to affect estrogen related reproductive responses and outcomes. Although previous studies in the literature have reported changes in male related reproductive outcomes, we did not see any changes in puberty or androgen dependent tissue growth in a previous study in the perijuvenile male rat. Therefore, in the present study, we evaluated triclosan for the first time in the male Hershberger assay and did not observe any changes in androgen dependent sex accessory gland growth in the presence or absence of testosterone. We also tested triclosan in the in vitro steroidogenesis assay (H295R human adrenocortical cell line) and found no changes in androgen production. There was an increase in estrogen production but this effect does not appear to be due to any changes in aromatase activity. In summary, triclosan did not androgen synthesis or androgen receptor activity.
Description:
Triclosan (TCS) is an antibacterial widely used in personal care products that exhibits endocrine disrupting activity in several species with reports of altered thyroid, estrogen and androgen signaling pathways. To evaluate the androgen mode of action, TCS was evaluated for androgen receptor mediated effects in the Hershberger assay and for altered androgen synthesis in the H295R steroidogenesis assay. For the Hershberger, prepubertal castrated males were dosed by oral gavage for 10 days with corn oil (vehicle) or TCS (50 or 200mg/kg/day) in the presence or absence of testosterone proprionate (TP, 0.2mg/kg/day) prior to assessing accessory sex tissues (ASTs) weights. TCS alone or in combination with TP did not alter androgen dependent AST weights. Additional assessment of serum thyroxine (T4) demonstrated a significant dose-dependent decrease by TCS (50 or 200 mg/kg/day) co-administered with TP and TCS (200 mg/kg) without TP. However, no differences in liver or thyroid weights were observed. In the H295R assay, TCS from 0.01 to 10µM had no effect on testosterone production but did induce a significant increase in estrogen (E) production above 3µM. At 10µM, TCS produced significant cytotoxicity which confounded the interpretation of the estrogenic effect at that concentration. Thus, TCS had no effect on androgen synthesis or activity in the models used, but did enhance estrogen production and suppress T4 similar to our previous studies.
