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Effects of In Vivo Exposure to Tamoxifen on a Non-Target Species, the Marine Fish Cunner (Tautogolabrus adspersus)
Citation:
Mills, L., Saro Jayaraman, R. Gutjahr-Gobell, Doranne Borsay, G. Zaroogian, AND S. Laws. Effects of In Vivo Exposure to Tamoxifen on a Non-Target Species, the Marine Fish Cunner (Tautogolabrus adspersus). Presented at Society of Toxicology, Phoenix, AZ, March 24 - 27, 2014.
Impact/Purpose:
Tamoxifen is an endocrine-active pharmaceutical that is used world-wide to treat certain breast cancers. Because tamoxifen has been detected in aquatic environments, a study was undertaken to investigate its biological effects in a non-target species, the marine fish cunner (Tautogolabrus adspersus). This abstract is for a poster that will present the results of that study.
Description:
Tamoxifen is an endocrine-active pharmaceutical that is used world-wide to treat certain breast cancers. Because tamoxifen has been detected in aquatic environments, a study was undertaken to investigate its biological effects in a non-target species, the marine fish cunner (Tautogolabrus adspersus). Effects of a 17-day exposure to two different oral doses of tamoxifen (0.5 and 5 mg/kg fish weight) on reproduction in spawning cunner were examined relative to controls. Results show mean egg production in tamoxifen-treated cunner was significantly less than controls. No significant effects were observed in fertile or viable eggs relative to controls, although a downward trend for both endpoints was noted. After the 17-day exposure, activity of the steroidogenic enzyme aromatase in brains and ovaries from these fish was also evaluated. Ovarian aromatase activity was significantly increased in cunner treated with 5 mg/kg of tamoxifen. There were no significant differences in brain aromatase activity or gonadosomatic index in either sex compared to controls. In a separate experiment, formation of biologically active metabolites over time (from 1 to 72 hours) after a single oral dose of tamoxifen (25 mg/mg) was compared in Wistar rats versus cunner. The predominant metabolite in plasma from rats was N-desmethyltamoxifen, while in plasma from cunner it was 4-hydroxytamoxifen. This difference suggests that the effects of exposure to tamoxifen could be magnified in cunner, since 4-hydroxytamoxifen is considered to be about 100 times more efficacious than tamoxifen or N-desmethyltamoxifen. Overall, differences in circulating metabolites between species and a significant reduction in egg production in spawning cunner treated with tamoxifen both suggest that exposure to tamoxifen could present a tangible ecotoxicological risk to fish such as cunner. Disclaimer: This abstract does not necessarily reflect US EPA policy.