Chain length and chlorine position affect biotransformation of chlorinated paraffins in an in vitro hepatic model.
Series / Report no.
Open Access
Type
Journal Article
Article
Article
Language
en
Date
2025-05-26
Research Projects
Organizational Units
Journal Issue
Title
Chain length and chlorine position affect biotransformation of chlorinated paraffins in an in vitro hepatic model.
Translated Title
Published in
J Hazard Mater 2025; 494:138746
Abstract
Chlorinated paraffins (CPs) are emerging environmental contaminants with limited biotransformation data because of the complexity of CP technical mixtures and the lack of single congener standards. In this study, novel single CP congeners, with similar chlorine patterns to those found in technical mixtures, were incubated for 60 min with rat hepatic subcellular fractions to evaluate their relative biotransformation extent and identify their potential metabolites. Results demonstrated that these CP congeners were metabolized by phenobarbital and 5,6-benzoflavone-induced rat liver S9, following 1st-order kinetics. The 1st-order rate constants were logarithmically inversely related to the chain lengths at a given number of chlorine atoms. In turn, the chlorine positions affected the biotransformation pathways, resulting in the formation of different metabolites. Metabolites identified by high-resolution mass spectrometric analysis included (multi-)hydroxylated, carbonyl, carboxylic, and chain-shortened products. Hydrolytic and oxidative dechlorination, stepwise hydroxylation/oxidation, and C-C bond cleavage were identified as potential biotransformation pathways. A notable transformation of initial hydroxylated metabolites further into aldehydes and carboxylic acids (ω-oxidation) was emphasized. The study's results fill the knowledge gap in CP biotransformation and provide structural information on potentially bioactive CP metabolites for future synthesis and toxicity studies.