期刊
TOXICOLOGY IN VITRO
卷 29, 期 8, 页码 2124-2132出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2015.09.001
关键词
Reporter assay; Flame retardants; Mode of action; Bacterial stress genes; Escherichia coli
类别
资金
- EU [264600]
- Agency for Innovation by Science and Technology (IWT)
Flame retardants are ubiquitously used chemicals that have been shown to contaminate environments. Toxicological data is largely limited, with little insight into their molecular modes of action that may give rise to their toxic phenotypes. Such insight would aid more effective risk assessments concerning these compounds, while also improving molecular design. We therefore used a bacterial stress-gene profiling assay to screen twelve currently-used flame retardants to obtain mechanistic insights of toxicity. Both brominated and organophosphate flame retardants were tested. All compounds showed statistically significant inductions of several stress genes when compared to control treatments. Triphenyl phosphate, tris(2-butoxyethyl) phosphate, tris(1,3-dichloro-2-propyl)phosphate, tris(butyl)phosphate, and tetrabromobisphenol A elicited (at least) twofold inductions for any of the stress genes. When looking at absolute induction levels, the promoters induced are indicative of protein perturbation, DNA integrity and membrane integrity. However, normalising for the different induction potentials of the different stress genes and clustering using hierarchical and k-means algorithms indicated that in addition to protein and DNA damage, some compounds also resulted in growth arrest and oxidative damage. This research shows that this assay allows for the determination of toxicological modes-of-action while clustering and accounting for induction potentials of the different genes aids better risk assessment. (C) 2015 Elsevier Ltd. All rights reserved.
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