Comparative in Vitro Metabolism of Short Chain Chlorinated Paraffins (Sccps) by Human and Chicken Liver Microsomes: First Insight into Heptachlorodecanes

Abstract

Short chain chlorinated paraffins (SCCPs) are emerging persistent organic pollutants of great concern due to their ubiquitous distribution in the environment. However, little information is available on the biotransformation of SCCPs in organisms. In this study, a chlorinated decane: 1, 2, 5, 5, 6, 9, 10-heptachlorodecane (HepCD) was subjected to in vitro metabolism by human and chicken liver microsomes at environmentally relevant concentration. Using ultra-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry, two metabolites: monohydroxylated hexachlorodecane (HO-HexCD) and monohydroxy heptachlorodecane (HO-HeptaCD) were detected in human liver microsomal assays, while only one metabolite (HO-HexCD) was identified in chicken liver microsomal assays. The formation of HO-HexCD was fitted to a Michaelis-Menten model for chicken liver microsomes with a V max (maximum metabolic rate) value of 4.52 pmol/mg/min. Metabolic kinetic parameters could not be obtained for human liver microsomes as steady state conditions were not reached under our experimental conditions. Notwithstanding this, the observed average biotransformation rate of HeptaCD was much faster for human liver microsomes than for chicken liver microsomes. Due to the lack of authentic standards for the identified metabolites, the detailed structure of each metabolite could not be confirmed due to the possibility of conformational isomers. This study provides first insights into the biotransformation of SCCPs, providing potential biomarkers and enhancing understanding of bioaccumulation studies.

Keywords: SCCP, In vitro, Metabolism, liver microsome