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Methylated PACs Are More Potent than Their Parent Compounds-A Study on AhR-mediated Activity, Degradability and Mixture Interactions in the H4IIE-luc Assay.

Author
Abstract
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In this study, 26 polycyclic aromatic compounds (PACs) including native polycyclic aromatic hydrocarbons (PAHs), hydroxylated PAHs, alkylated and oxygenated PAHs and (alkylated) heterocyclic compounds were investigated for their aryl hydrocarbon receptor (AhR)-mediated potencies in the H4IIE-luc bioassay. Potential degradabilities of PACs were investigated by use of various durations of exposure (24, 48 or 72 h). Furthermore, various mixtures of PACs including PAHs, alkylated and oxygenated PAHs and heterocyclic compounds were tested for their joint AhR-mediated potency. Additive behaviors of PACs in mixtures was studied by comparing observed mixture potencies to mixture potencies predicted by use of the concentration addition (CA) model. Methylated derivatives were more potent than their parent compounds in the H4IIE-luc assay. A time-dependent decrease in relative potency was observed for all AhR-active compounds, which may be indicative of in vitro biotransformation. Monomethylated compounds seemed to be more rapidly transformed than analogous unsubstituted compounds. In addition, results of this study showed that the predictive power of the CA model increased with the number of compounds, suggesting additivity in multicomponent mixtures. Due to greater potency of methylated derivatives and their ubiquitous occurrence, there is a need for further research on the toxicity and mixture behavior of those environmentally and toxicologically relevant compounds. This article is protected by copyright. All rights reserved.

Year of Publication
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2018
Journal
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Environmental toxicology and chemistry
Date Published
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2018
ISSN Number
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0730-7268
URL
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http://dx.doi.org/10.1002/etc.4087
DOI
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10.1002/etc.4087
Short Title
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Environ Toxicol Chem
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