Developmental neurotoxicity of organophosphate flame retardants in early life stages of Japanese medaka (Oryzias latipes)

Published: 05-01-2016 In Publication


As brominated flame retardants are being banned or phased out worldwide, organophosphate flame retardants (OPFRs) have been used as alternatives on a large scale and have thus become ubiquitous environmental contaminants; this raises great concerns about their environmental health risk and toxicity. Considering that previous research has identified the nervous system as a sensitive target, Japanese medaka were used as an aquatic organism model to evaluate the developmental neurotoxicity of four OPFRs, including triphenyl phosphate (TPHP), tri-n-butyl phosphate (TNBP), tris(2-butoxyethyl) phosphate (TBOEP) and tris(2-chloroethyl) phosphate (TCEP). The embryo toxicity test showed that OPFR exposure could decrease hatchability, delay time to hatching, increase the occurrence of malformations, reduce body length, and slow heart rate. Regarding locomotor behavior, exposure to the tested OPFRs (except TCEP) for 96 h resulted in hypoactivity for medaka larvae in both the free-swimming and the dark-to-light photoperiod stimulation test. The changes of acetylcholinesterase (AChE) activity and transcriptional responses of genes related to the nervous system likely provide a reasonable explanation for the neurobehavioral disruption. Overall, the present study clearly demonstrated the developmental neurotoxicity of various OPFRs with very different potency and contributed to the determination of which OPFRs are appropriate substitutes, as well as the consideration of whether regulations are reasonable and required.