In vitro and in ovo effects of four brominated flame retardants on toxicity and hepatic mRNA expression in chicken embryos

• Published in: Toxicology letters Vol. 207; no. 1; pp. 25 - 33
• Main Authors: Egloff, Caroline, Crump, Doug, Chiu, Suzanne, Manning, Gillian, McLaren, Kristina K., Cassone, Cristina G., Letcher, Robert J., Gauthier, Lewis T., Kennedy, Sean W.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10-11-2011; Elsevier
• Subjects: Animals; Aryl Hydrocarbon Hydroxylases - biosynthesis; Aryl Hydrocarbon Hydroxylases - genetics; BEHTBP; Biological and medical sciences; BTBPE; Cell Survival - drug effects; Chick Embryo; Chicken; Cytochrome P450 Family 3; DBDPE; Flame retardant; Flame Retardants - toxicity; Gene Expression Profiling; Gene Expression Regulation, Enzymologic - drug effects; HCDBCO; Hepatocytes - drug effects; Hepatocytes - metabolism; Iodide Peroxidase - biosynthesis; Iodide Peroxidase - genetics; Liver - cytology; Liver - drug effects; Liver - embryology; Liver - enzymology; Medical sciences; mRNA expression; Polybrominated Biphenyls - toxicity; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Statistics, Nonparametric; Toxicology; BEHTBP; DBDPE; Flame retardant; HCDBCO; Chicken; BTBPE; mRNA expression; Embryo; Digestive system; Toxicity; Liver; In vitro; Vertebrata; Messenger RNA; Animal; Bromine Organic compounds; Aves
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2011.08.015

► Effects of HCDBCO, BEHTBP, BTBPE, and DBDPE exposure are examined in chicken embryos. ► None of the chemicals are overtly toxic to chicken hepatocytes or chicken embryos. ► HCDBCO, BTBPE, and DBDPE altered mRNA expression of several target genes.
Some currently used brominated flame retardants (BFRs), such as hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO), bis(2-ethylhexyl)tetrabromophthalate (BEHTBP), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and decabromodiphenylethane (DBDPE), are persistent organic contaminants detected in various environmental matrices, including wild birds. Data on potential toxicological and molecular responses to exposure of these BFRs are lacking for avian species. A combined
in vitro/
in ovo approach was used to determine the concentration-dependent effects of these BFRs on overt toxicity and hepatic messenger RNA (mRNA) expression levels of 11 transcripts in (1) primary cultures of chicken embryonic hepatocytes (CEH; all four BFRs) and (2) chicken embryos (HCDBCO and BTBPE only). Neither hepatocyte viability nor embryonic pipping success were affected by the BFRs at any of the administered concentrations (CEH: 0.001–30
μM, egg injection: 0.1–10
μg/g nominal dose). In CEH, 10
μM HCDBCO induced cytochrome P450 2H1 (CYP2H1) and CYP3A37, while CYP1A4/5 were down-regulated at all tested concentrations. In contrast, only transthyretin was down-regulated by HCDBCO in embryonic liver. There was concordance between the BTBPE-induced transcriptional responses
in vitro and
in ovo for CYP1A4/5 (up-regulated) and type III iodothyronine 5′-deiodinase (DIO3; down-regulated). DBDPE induced CYP1A4/5 29- and 59-fold at 0.2
μM in CEH and increased DIO1. None of the gene targets were responsive to BEHTBP exposure in CEH. The multi-tiered
in vitro/
in ovo screening approach was effective for assessing toxicological and molecular biological effects of these BFRs in an avian species.