CONFIRMATION OF A CARBOXYLIC-ACID METABOLITE OF POLYCHLOROTRIFLUOROETHYLENE AND A METHOD FOR ITS GC-ECD ANALYSIS IN BIOLOGICAL MATRICES

3.1 Oil, referred to as polychlorotrlfluoroethylene (pCTFE), Is a polymeric mixture consisting primarily of trlmers and tetramers of chlorotrlftuoroethylene (CTFE) end-capped with chlorine. Inhalation studies have associated dose-related body weight loss, increased organ weights, and abnormal hepatic enzyme activities with exposure to pCTFE. The carboxylic acid metabolites of pCTFE have been shown to cause hepatotoxlclty In rats, which Is manifested by Increased liver weights and the proliferation of hepatic peroxlsomes. A method was developed to derivatize these carboxyllc acid metabolltes. Tissue homogenates and feces were extracted with methanol, and urinary metabolltes were extracted on octadecylsllane (ODS) solid-phase extraction columns. AIIquots of the extracts and whole blood were methylated with 3N methanollc HCI to transesterlfy the carboxyllc acid metabolites to volatile methyl esters. The pCTFE methyl esters were analyzed by gas chromatography (GC) with electron capture detection (ECD). The on-column limit of detection was 5 pg for each methyl ester. Solid-phase extraction of spiked urine gave extraction efficlencies of 90.4% for the trlmer acid and 84.7% for the tetramer acid. This method was successfully applied to toxicity studies In rats and nonhuman primates. The IdentlUes of the derlvatized metabolltes were confirmed by GC/MS. © 1992, Oxford University Press. All rights reserved.