title: Relative developmental toxicities of pentachloroanisole and pentachlorophenol in a zebrafish model (Danio rerio).
abstract: Pentachloroanisole (PCA) and pentachlorophenol (PCP) are chlorinated aromatic compounds that have been found in the environment and in human populations. The objective of this study is to characterize the effects of PCA in comparison to those of PCP on development at environmental relevant levels using a fish model. Zebrafish embryos were exposed to 0.1, 1, 10, 100, 500, 1000 μg/L PCA and PCP respectively for 96 h. Malformation observation, LC50 testing for survival rate at 96 hours post fertilization (hpf) and EC50 testing for hatching rate at 72 hpf indicated that the developmental toxicity of PCP was about 15 times higher than that of PCA. PCP exposure at 10 μg/L resulted in elevated 3, 3', 5-triiodothyronine (T3) levels and decreased thyroxine (T4) levels, whereas PCA had no effects on T3 or T4 levels. PCP and PCA exposure at 1 and 10 μg/L showed possible hyperthyroid effects similar to that of T3, due to increased relative mRNA expression of synapsin I (SYN), iodothyronine deiodinase type III (Dio3), thyroid hormone receptor alpha a (THRαa) and thyroid hormone receptor beta (THRβ), and decreased expression of iodothyronine deiodinase type II (Dio2). The results indicate that both PCA and PCP exposure can cause morphological deformities, possibly affect the timing and coordination of development in the central nervous system, and alter thyroid hormone levels by disrupting thyroid hormone regulating pathways. However, the developmental toxicity of PCA is at least ten times lower than that of PCP. Our results on the relative developmental toxicities of PCA and PCP and the possible underlying mechanisms will be useful to support interpretation of envrionmental concentrations and body burden levels observed in human populations.
authors.affiliation: Center for Advanced Research in Environmental Genomics, University of Ottawa, 30 Marie Curie, Ottawa, ON, Canada K1N 6N5.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Center for Advanced Research in Environmental Genomics, University of Ottawa, 30 Marie Curie, Ottawa, ON, Canada K1N 6N5.
authors.forename: Marc
authors.initials: M
authors.lastname: Ekker
authors.affiliation: Center for Advanced Research in Environmental Genomics, University of Ottawa, 30 Marie Curie, Ottawa, ON, Canada K1N 6N5. Electronic address: laurie.chan@uottawa.ca.
authors.forename: Hing Man
authors.initials: HM
authors.lastname: Chan
mesh_terms: D000818:Animals; D000840:Anisoles / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D007928:Lethal Dose 50; D010416:Pentachlorophenol / Q000633:toxicity*; D013961:Thyroid Gland / Q000187:drug effects; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*; D015027:Zebrafish / Q000254:growth & development* / Q000378:metabolism
chemical_list: D000840:Anisoles; D004785:Environmental Pollutants; D014284:Triiodothyronine; C015421:pentachloroanisole; D010416:Pentachlorophenol; D013974:Thyroxine
keywords: Developmental Toxicity; Pentachloroanisole (PCA); Pentachlorophenol (PCP); Thyroid Hormone; Zebrafish (Danio rerio)