title: Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations in chicken embryos.
abstract: The organophosphate flame retardants tris(2-butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP) are used in a wide range of applications to suppress or delay the ignition and spread of fire. Both compounds have been detected in the environment and TBOEP was recently measured in free-living avian species. In this study, TBOEP and TEP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 45,400 ng/g and 0 to 241,500 ng/g egg, respectively. Pipping success, development, hepatic mRNA expression of 9 target genes, thyroid hormone levels, and circulating bile acid concentrations were determined. Exposure to the highest doses of TBOEP and TEP resulted in negligible detection of the parent compounds in embryonic contents at pipping indicating their complete metabolic degradation. TBOEP exposure had limited effects on chicken embryos, with the exception of hepatic CYP3A37 mRNA induction. TEP exposure decreased pipping success to 68%, altered growth, increased liver somatic index (LSI) and plasma bile acids, and modulated genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Plasma thyroxine levels were decreased at all TEP doses, including an environmentally-relevant concentration (8 ng/g), and gallbladder hypotrophy was evident at ≥ 43,200 ng/g. Tarsus length and circulating thyroxine concentration emerged as potential phenotypic anchors for the modulation of transthyretin mRNA. The increase in plasma bile acids and LSI, gallbladder hypotrophy, and discoloration of liver tissue represented potential phenotypic outcomes associated with modulation of hepatic genes involved with xenobiotic and lipid metabolism.
authors.affiliation: National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Egloff
authors.affiliation: National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada. Electronic address: doug.crump@ec.gc.ca.
authors.forename: Doug
authors.initials: D
authors.lastname: Crump
authors.affiliation: National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada.
authors.forename: Emily
authors.initials: E
authors.lastname: Porter
authors.affiliation: National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada.
authors.forename: Kim L
authors.initials: KL
authors.lastname: Williams
authors.affiliation: National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Letcher
authors.affiliation: National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada.
authors.forename: Lewis T
authors.initials: LT
authors.lastname: Gauthier
authors.affiliation: National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada; Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
authors.forename: Sean W
authors.initials: SW
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002642:Chick Embryo; D047108:Embryonic Development / Q000187:drug effects*; D005411:Flame Retardants / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000378:metabolism*; D010755:Organophosphates / Q000493:pharmacokinetics / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019849:Sex Determination Processes; D013963:Thyroid Hormones / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D001647:Bile Acids and Salts; D005411:Flame Retardants; D010755:Organophosphates; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; D013963:Thyroid Hormones; D013974:Thyroxine; C009549:triethyl phosphate; C013320:tris(2-butoxyethyl) phosphate
keywords: Avian embryonic development; Bile acids; TBOEP; TEP; Thyroid hormone; mRNA expression