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)

Environ Sci Technol. 2021 Apr 20;55(8):5056-5064. doi: 10.1021/acs.est.0c06809. Epub 2021 Mar 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biphenyl Compounds
  • Embryo, Nonmammalian
  • Female
  • Oryzias*
  • Phosphates
  • Receptors, Retinoic Acid
  • Water Pollutants, Chemical* / toxicity

Substances

  • Biphenyl Compounds
  • Phosphates
  • Receptors, Retinoic Acid
  • Water Pollutants, Chemical
  • diphenyl