Ex vivo gastrointestinal biotransformation of chlorothalonil in the germ-free and conventional rat

Abstract

1. The metabolism and absorption of chlorothalonil and corresponding diglutathione and dicysteine conjugates was studied using isolated everted gastrointestinal sacs of the conventional and germ-free rat. An HPLC method was used to analyse mucosal and serosal fluids. Thiol metabolites of chlorothalonil were determined by GC/MS. 2. Low absorption of the substrates was observed, with < 4% of the radioactivity being recovered from the serosal buffers and the digestive tissues. A major part of the radioactivity was recovered from the mucosal fluids and it corresponded to unchanged chlorothalonil. Traces of unchanged chlorothalonil and mono-, di- and trimethylthio metabolites were present in serosal fluids as well as unidentified polar peaks. An important transformation (> 75%) of the chlorothalonil conjugates was observed. The di- and trimethylthio metabolites of chlorothalonil were detected from both sides of the everted gut sac of rat incubated with the diglutathione and dicysteine conjugates. 3. Few differences were observed between the conventional and germ-free rat: absorption was higher in the duodenum of germ-free rat, but tissue retention was more significant in the duodenum of the conventional rat.