Opposing Visual Impairments Induced by Structurally Similar Organophosphate Flame Retardants TPHP and CDP in Zebrafish Larvae

Vision is the primary sensory function for most animals and is also a sensitive toxic target of environmental pollutants. A new class of organophosphate flame retardants (OPFRs) termed emerging OPFRs (eOPFRs) with limited toxicological information is rapidly developed into the substitutes of traditional OPFRs. In this study, we investigated the visual toxicity of triphenyl phosphate (TPHP, one traditional OPFR) and cresyl diphenyl phosphate (CDP, one emerging OPFR) on zebrafish larvae at environmentally relevant concentrations (3 and 30 nM). After 5 days of exposure, an opposite toxicity was found between the two OPFRs, manifested in the light perception and the gene expressions of visual opsins. CDP caused a weak reaction to light and overall inhibition of opsin expression (0.7- to 0.8-fold) in the larvae, while TPHP tended to stimulate these events (1.2- to 2.4-fold). Besides, we identified a key transcription factor, tbx2a, that was significantly disrupted in both OPFRs' exposure. The differing ways in which both OPFRs bind to Tbx2a may be the reason behind their opposite effects. These findings provided new clues for the toxicological mechanisms of OPFRs and revisited the question regarding safe substitutes for those emerging contaminants.