Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Organophosphorus flame retardants (OPFRs) are increasingly used as a replacement for polybrominated diphenyl ethers, and thus, human exposure to OPFRs has been increasing. Epidemiological studies indicate possible effects of OPFRs on children’s health status such as rhinoconjunctivitis. The objective of the present study was to assess the developmental effects of OPFRs and their metabolites, and possible mechanisms underlying developmental toxicity using zebrafish as a model. Zebrafish embryos were exposed to OPFRs or their metabolites observations. Significant increases in circulatory failure including blood flow reduction and pericardial edema were detected in embryos exposed to TPHP, TDCIPP, EHDPHP, and some of their metabolites (HO-m/p-TPHP and 5-HO-EHDPHP). The chemicals with higher logKow induced greater severity of the circulatory failure. RNA-Seq results of embryos exposed to EHDPHP, 5-HO-EHDPHP, and EHPHP at the highest concentrations where no significant circulatory failure was observed showed that genes involved in glucose homeostasis and retinol metabolism, as well as GUCY-cGMP and calcineurin signalings, were significantly altered by EHDPHP and/or 5-HO-EHDPHP, while immunity-related genes were significantly altered by EHPHP. These results clearly indicate distinct potency for developmental toxicity among OPFRs and their metabolites. Transcriptomic data suggest differences in possible molecular mechanisms underlying the developmental effects of these compounds.
