title: Developmental exposure to organophosphate flame retardants elicits overt toxicity and alters behavior in early life stage zebrafish (Danio rerio).
abstract: Organophosphate flame retardants (OPFRs) are common replacements for the phased-out polybrominated diphenyl ethers (PBDEs) and have been detected at high concentrations in environmental samples. OPFRs are structurally similar to organophosphate pesticides and may adversely affect the developing nervous system. This study evaluated the overt toxicity, uptake, and neurobehavioral effects of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP) in early life stage zebrafish. Chlorpyrifos was used as a positive control. For overt toxicity and neurobehavioral assessments, zebrafish were exposed from 0 to 5 days postfertilization (dpf). Hatching, death, or malformations were evaluated daily. Teratogenic effects were scored by visual examination on 6 dpf. To evaluate uptake and metabolism, zebrafish were exposed to 1 µM of each organophosphate (OP) flame retardant and collected on 1 and 5 dpf to monitor accumulation. Larval swimming activity was measured in 6 dpf larvae to evaluate neurobehavioral effects of exposures below the acute toxicity threshold. TDBPP elicited the greatest toxicity at >1 µM. TDCPP and chlorpyrifos were overtly toxic at concentrations ≥10 µM, TCEP, and TCPP were not overtly toxic at the doses tested. Tissue concentrations increased with increasing hydrophobicity of the parent chemical after 24 h exposures. TDCPP and TDBPP and their respective metabolites were detected in embryos on 5 dpf. For all chemicals tested, developmental exposures that were not overtly toxic significantly altered larval swimming activity. These data indicate that OPFRs adversely affect development of early life stage zebrafish.
authors.affiliation: *Nicholas School of the Environment, Duke University, Durham, North Carolina 27708 and Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Laura V
authors.initials: LV
authors.lastname: Dishaw
authors.affiliation: *Nicholas School of the Environment, Duke University, Durham, North Carolina 27708 and Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Hunter
authors.affiliation: *Nicholas School of the Environment, Duke University, Durham, North Carolina 27708 and Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Beth
authors.initials: B
authors.lastname: Padnos
authors.affiliation: *Nicholas School of the Environment, Duke University, Durham, North Carolina 27708 and Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Padilla
authors.affiliation: *Nicholas School of the Environment, Duke University, Durham, North Carolina 27708 and Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 heather.stapleton@duke.edu.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Stapleton
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D005411:Flame Retardants / Q000493:pharmacokinetics / Q000633:toxicity*; D015394:Molecular Structure; D009420:Nervous System / Q000187:drug effects / Q000196:embryology; D010755:Organophosphates / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D016019:Survival Analysis; D013550:Swimming; D015027:Zebrafish / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism
chemical_list: D005411:Flame Retardants; D010755:Organophosphates
keywords: TDCPP; development; flame retardant; neurotoxicity; organophosphate; zebrafish