Maternal Transfer of 2‑Ethylhexyl Diphenyl Phosphate Leads to Developmental Toxicity Possibly by Blocking the Retinoic Acid Receptor and Retinoic X Receptor in Japanese Medaka (Oryzias latipes)

• Published in: Environmental science & technology Vol. 55; no. 8; pp. 5056 - 5064
• Main Authors: Li, Yu, Ma, Haojia, Chen, Ruichao, Zhang, Hong, Nakanishi, Tsuyoshi, Hu, Jianying
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20-04-2021
• Subjects: Animals; Biphenyl Compounds; Ecotoxicology and Public Health; Embryo, Nonmammalian; Embryos; Female; Fertilization; Fish; Fish populations; Larvae; Lipids; Maternal transfer; Oryzias; Phosphates; Receptors; Receptors, Retinoic Acid; Retinoic acid; Retinoic acid receptors; Retinoid X receptors; Toxicity; Transcription; Water Pollutants, Chemical - toxicity
• ISSN: 0013-936X; 1520-5851
• DOI: 10.1021/acs.est.0c06809

2-Ethylhexyl diphenyl phosphate (EHDPP) has been detected in wild fish with high concentrations, which may pose a risk in the embryo development considering its potential maternal transfer. In this study, EHDPP was demonstrated to elicit antagonistic activity to medaka retinoic acid receptor (mRAR) and retinoic X receptor (mRXR) with 50% inhibitory concentration of 18 and 36 μM, respectively. After adult female medaka were exposed to EHDPP at 156, 405, and 1161 ng/L for 35 days, the embryonic EHDPP concentrations (364–4824 ng/g lipid weight (lw)) were higher than those in the maternal tissues (15.0–4166 ng/g lw), showing notable maternal transfer. The embryonic concentration of EHDPP decreased limitedly during 1-2 day post-fertilization (dpf, the main developmental window of eye) but then decreased sharply after 2 dpf. The transcript abundance of cyp26a1 was inhibited and subsequent increasing embryonic all-trans RA level was observed in embryos, showing RAR/RXR antagonistic activity. These results may specifically contribute to the increased eye deformity incidences in all exposure groups (up to 8.0%; 51/637) relative to the control (1.0%, 7/733). The response behavior of the larvae to light stimulation was impaired in a dose-dependent manner, demonstrating a vision disorder. Because such developmental toxicities were observed at the environmental level, EHDPP may pose a threat to the survival of wild larvae and therefore a population risk for wild fish.