IDENTIFICATION OF BIOMARKERS OF EXPOSURE AND EFFECT OF 1,4-DICHLOROHEXAFLUOROBUTENE-2

Abstract

Using gas and high-performance liquid chromatography with mass-selective detection (GC/MS and HPLC/MS, respectively), the metabolism of previously unstudied freon RL316 (1,4-dichloro-1,1,2,3,4,4-hexafluorobutene-2, hereinafter - DCHF) has been investigated. Two volatile metabolites, which are products of reductive replacement of chlorine atoms: 1-chloro-1,1,2,3,3,4,4,4-octafluorobutane and 1-chloro-1,1,2,3,4,4-hexafluorobutene-2, have been detected and identified in the blood and urine samples of rats. In total 15 different previously unknown metabolites have been revealed and identified. The main direction of metabolism of DCHF is the formation of adducts with glutathione and their further degradation to cysteine and acetylcysteine adducts. Among all metabolites 4-methylsulfyl-1-chloro-1,1,2,3,4,4-hexafluorobutene-2, 4-methylsulfynyl-1-chloro-1,1,2,3,4,4-hexafluorobutene-2 and 1,1,3,4,4-pentafluoro-1,4-dichlorobutanethion-2 were found to be the most sensitive biomarkers. The intake of DCHF in the body does not lead to its bioactivation with the formation of labile thioketenes which are the main cause of mutagenic and carcinogenic effects of some halocarbons. Metabolic profiling of blood plasma revealed potential metabolic markers of exposure to D CHF at a concentration of 18,8 mg/ m 3 : the ratio of concentrations of gulonic acid and myo-inositol phosphate. The combination of the determination of the chemical markers - nonmetabolic forms of DCHF and 1,4-dichloro-1,1,3,4,4-butanthione-2 with the definition of discovered metabolic markers allows to estimate more accurately the dose or level of exposure of DCHF on the body of people in contact with it.