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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
Örebro University, School of Science and Technology. (MTM Research Centre)
Örebro University, School of Science and Technology. (MTM Research Centre)
Örebro University, School of Science and Technology. (MTM Research Centre)ORCID iD: 0000-0001-7338-2079
Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Canada.
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2018 (English)In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 37, no 5, p. 1409-1419Article in journal (Refereed) Published
Abstract [en]

Twenty-six 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), and 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 were studied by comparing observed mixture potencies with mixture potencies predicted by use of the concentration addition 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, the results showed that the predictive power of the concentration addition model increased with the number of compounds, suggesting additivity in multicomponent mixtures. Due to the greater potency of methylated derivatives and their ubiquitous occurrence, there is a need for further research on the toxicity and mixture behavior of these environmentally and toxicologically relevant compounds.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018. Vol. 37, no 5, p. 1409-1419
Keywords [en]
Polycyclic aromatic compounds, Relative potency factors, In vitro bioassays, Mixture toxicity
National Category
Pharmacology and Toxicology Environmental Sciences
Identifiers
URN: urn:nbn:se:oru:diva-64509DOI: 10.1002/etc.4087ISI: 000430916000017PubMedID: 29334126Scopus ID: 2-s2.0-85044416468OAI: oai:DiVA.org:oru-64509DiVA, id: diva2:1177392
Funder
Knowledge Foundation
Note

Funding Agencies:

KK Foundation (SOILEFFECT)  2013/0157 

KK Foundation (EnForce)  20160019 

Canada Research Chair program  

"High Level Foreign Experts" program - People's Republic of China State Administration of Foreign Experts Affairs  

Einstein Professor Program of the Chinese Academy of Sciences  

Distinguished Visiting Professorship in the School of Biological Sciences of the University of Hong Kong 

Available from: 2018-01-25 Created: 2018-01-25 Last updated: 2018-09-11Bibliographically approved

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Lam, Monika M.Bülow, RebeccaEngwall, MagnusLarsson, Maria

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