Impurities in technical mixtures of chlorinated paraffins show AhR agonist properties as determined by the DR-CALUX bioassay

Yao Zhou, Stefan P.J. van Leeuwen, Marco Knobloch, Caroline Dirks, Yoran Weide, Toine F.H. Bovee*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Chlorinated paraffins (CPs) are produced at more than one million tons per year. Technical CPs mixtures may contain impurities, which end up in consumer products. In the present study, 17 technical CPs mixtures were investigated for the potential occurrence of potential impurities. By applying the DR-CALUX bioassay, 3 out of 17 technical mixtures were shown to elicit responses at 4 h exposure time, but much lower at 48 h. Constitutional defined CPs materials did not show responses. Subsequently different groups of known AhR-agonists and compounds suspected to be present in technical CPs mixtures were investigated. Benzene, (poly)chlorobenzene, non-dioxin like polychlorinated naphthalenes (PCNs), and three-ringed polyaromatic hydrocarbons (PAHs) did not result in a significant response at 4 h or 48 h. TCDD, non-ortho PCBs, dioxin-like PCNs, four or five ringed PAHs and their chlorinated analogues resulted in a significant response. TCDD and the non-ortho PCBs showed the highest potency and stability, while dioxin-like PCNs, PAHs, and the chlorinated PAHs were clearly inactivated (metabolized) at longer incubation. Altogether, the present findings substantiate that AhR-mediated responses of CPs technical mixtures in the DR-CALUX bioassay are caused by impurities, most likely some intermediate stable AhR-agonists such as dioxin-like PCNs or (chlorinated) PAHs. The current study shows that impurities in CPs technical mixtures need to be investigated for assessing the safety of technical CPs mixtures.

Original languageEnglish
Article number105098
JournalToxicology in Vitro
Volume72
DOIs
Publication statusPublished - Apr 2021

Keywords

  • Analytical toxicology
  • Contaminants of emerging concerns
  • Dose-response modeling
  • DR-CALUX
  • Metabolic stability

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