Photolytic degradation products of two highly brominated flame retardants cause cytotoxicity and mRNA expression alterations in chicken embryonic hepatocytes

Tetradecabromo-1,4-diphenoxybenzene (TeDB-DiPhOBz) and 2,2′,3,3′,4,4′,5,5′,6,6′-decabromodiphenyl ether (BDE-209) are photolytically unstable flame retarding chemicals. The present study assessed photocatalysed byproducts of TeDB-DiPhOBz and BDE-209 (i.e Br8- to Br11-PB-DiPhOBz congeners from TeDB-DiPhOBz, and Br6- to Br8-BDE congeners from BDE-209), formed after 21 days of natural sunlight irradiation (SI), for exposure effects on cytotoxicity and mRNA expression levels of selected genes in chicken embryonic hepatocytes (CEH). CEHs were exposed for 36 h to concentrations of SI- and nonirradiated (NI)-TeDB-DiPhOBz and BDE-209. Cytotoxic effects were observed only in CEH exposed to 50 ?M SI-BDE-209. Results from a custom-designed Avian ToxChip polymerase chain reaction array showed that NI-TeDB-DiPhOBz and NI-BDE-209, up to maximum concentrations of 1.9 and 9 ?M, respectively, caused limited changes in mRNA levels of 27 genes from toxicologically relevant pathways, including phase I/II metabolism, the thyroid hormone pathway, lipid/cholesterol metabolism, oxidative stress, immune response, and cell death. In contrast, 12 and 14 of the 27 genes were altered after exposure to 25 ?M SI-TeDB-DiPhOBz or 10 ?M SI-BDE-209, respectively. Aryl hydrocarbon receptor (AhR)-related CYP1A4 mRNA levels were the most altered on the PCR array with an induction of 560- and 5200-fold after exposure to 1 or 25 ?M SI-TeDB-DiPhOBz, respectively, and 2500-and 2300-fold after exposure to 1 or 10 ?M SI-BDE-209, respectively. A dioxin-responsive luciferase reporter gene assay confirmed that the CYP1A4 inductions were independent of the dissolution solvents used (tetrahydrofuran/n-hexane, n-hexane, or methanol) during photolysis. The authors concluded that overall, degradation of TeDB-DiPhOBz and BDE-209 by natural sunlight generates byproducts that affect in vitro expression of genes, especially the AhR-mediated CYP1A4.

Authors: Su G, Letcher RJ, Crump D, Farmahin R, Giesy JP, Kennedy SW. ;Full Source: Environmental Science & Technology. 2014 Oct 21;48(20):12039-46. doi: 10.1021/es503399r. Epub 2014 Sep 29. ;