Effects of dietary 2-(2H-benzotriazol-2-yl)-4-methylphenol (UV-P) exposure on Japanese medaka (Oryzias latipes) in a short-term reproduction assay

Abstract

Benzotriazole ultraviolet stabilizers (BZT-UVs) are added to various products to prevent damage caused by UV light and have emerged as contaminants of concern. Although BZT-UVs are detected in aquatic biota globally, few studies have assessed their potential toxic effects. The objective of the present study was to assess effects of 2-(2H-Benzotriazol-2-yl)-4-methylphenol (UV-P) on reproductive success of Japanese medaka (Oryzias latipes) in a standard 21-day reproduction assay. Japanese medaka were exposed to dietary UV-P at concentrations of 0, 36, 158, and 634 ng UV-P/g food, for a total of 28 days which included 7 days of exposure prior to the start of the 21-day reproduction assay. No significant effect on egg production or fertilization success was observed. Abundances of transcripts of erα, vtgI, cyp1a, or cyp3a4 were not significantly different in livers from male or female fish exposed to UV-P. However, abundances of transcripts of cyp11a and cyp19a were significantly lower in gonads from female fish. There was a trend of increasing concentrations of E2 and a non-significant increase of T in the 634 ng/g treatment in plasma from female fish exposed to UV-P. Concentrations of 11-KT were unchanged in plasma from males exposed to UV-P. These responses suggest weak perturbation of steroidogenesis, consistent with an antiandrogenic mode of action. However, this perturbation was insufficient to impair reproductive performance. Metabolomics analysis of female livers suggests altered concentrations of various metabolites and biological pathways, including glutathione metabolism, suggesting that UV-P might cause responses related to oxidative stress or phase II metabolism. However, metabolomics revealed no obvious mechanism of toxicity. Overall, results of this study indicate that dietary exposure to UV-P up to 634 ng/g food does not significantly impact reproductive performance of Japanese medaka but impacts on steroidogenesis could indicate a potential mechanism of toxicity which might lead to reproductive impairment in more sensitive species.

Keywords: Anti-androgenicity; Endocrine disruption; Metabolomics; UV Stabilizer.