Developmental neurotoxicity of pyrethroid insecticides in zebrafish embryos.
Pyrethroid insecticides are one of the most commonly used residential and agricultural insecticides. Based on the increased use of pyrethroids and recent studies showing that pregnant women and children are exposed to pyrethroids, there are concerns over the potential for developmental neurotoxicity. However, there have been relatively few studies on the developmental neurotoxicity of pyrethroids. In this study, we sought to investigate the developmental toxicity of six common pyrethroids, three type I compounds (permethrin, resmethrin, and bifenthrin) and three type II compounds (deltamethrin, cypermethrin, and lambda-cyhalothrin), and to determine whether zebrafish embryos may be an appropriate model for studying the developmental neurotoxicity of pyrethroids. Exposure of zebrafish embryos to pyrethroids caused a dose-dependent increase in mortality and pericardial edema, with type II compounds being the most potent. At doses approaching the LC(50), permethrin and deltamethrin caused craniofacial abnormalities. These findings are consistent with mammalian studies demonstrating that pyrethroids are mildly teratogenic at very high doses. However, at lower doses, body axis curvature and spasms were observed, which were reminiscent of the classic syndromes observed with pyrethroid toxicity. Treatment with diazepam ameliorated the spasms, while treatment with the sodium channel antagonist MS-222 ameliorated both spasms and body curvature, suggesting that pyrethroid-induced neurotoxicity is similar in zebrafish and mammals. Taken in concert, these data suggest that zebrafish may be an appropriate alternative model to study the mechanism(s) responsible for the developmental neurotoxicity of pyrethroid insecticides and aid in identification of compounds that should be further tested in mammalian systems.
Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, USA.
Amy
A
DeMicco
Keith R
KR
Cooper
Jason R
JR
Richardson
Lori A
LA
White
D000014:Abnormalities, Drug-Induced; D062365:Aminobenzoates / Q000494:pharmacology; D000818:Animals; D001681:Biological Assay; D019465:Craniofacial Abnormalities / Q000139:chemically induced; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000473:pathology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D007306:Insecticides / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000196:embryology / Q000209:etiology*; D011722:Pyrethrins / Q000633:toxicity*; D015203:Reproducibility of Results; D018570:Risk Assessment; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013035:Spasm / Q000139:chemically induced; D013723:Teratogens / Q000633:toxicity; D015027:Zebrafish / Q000196:embryology*
D062365:Aminobenzoates; D018756:GABA Antagonists; D007306:Insecticides; D011722:Pyrethrins; D026941:Sodium Channel Blockers; D013723:Teratogens; C003636:tricaine; D003975:Diazepam