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1. Radiolabelled metabolites excreted in the urine of swine after an oral dose of 14C-propachlor were similar to those previously reported with rats and included methylsulphonyl (CH3SO2-)-containing metabolites. 2. A bile-duct-cannulated pig dosed orally with 14C-propachlor excreted 7.6% dose in the bile compared with approx. 75% dose with rats. Although enterohepatic circulation had been prevented with the bile-duct-cannulated pig. CH3SO3 metabolites of propachlor were excreted in the urine. Enterohepatic circulation had been reported to be necessary for formation of CH3SO2 metabolites of propachlor with rats. 3. Germ-free pigs dosed orally with 14-C-propachlor did not excrete urinary CH3SO2 metabolites, indicating involvement of the enteric flora in the production of these metabolites as shown previously with rats. 4. A g.l.c.-mass spectrometric specific ion monitoring technique indicated that trace amounts of CH3SO2 metabolites were present in the urine and bile of bile-duct-cannulated rats dosed orally with 14C-propachlor. This was confirmed by isolation and mass-spectral analyses. 5. It is concluded that after oral administration of propachlor to rats and swine, glutathione (GSH) conjugation and cysteine conjugate beta-lyase activity in the enteric flora are involved in formation of CH3SO2 metabolites. Presumably, the GSH conjugate is formed in mammalian tissue and must be returned to the lumen of the gut to be acted upon by the gut microflora. In rats this is accomplished primarily by biliary excretion, whereas in swine a non-biliary mechanism is much more important.


P W Aschbacher, C B Struble. Evidence for involvement of non-biliary excretion into the intestines in the formation of methylsulphonyl-containing metabolites of 2-chloro-N-isopropylacetanilide (propachlor) by swine and rats. Xenobiotica; the fate of foreign compounds in biological systems. 1987 Sep;17(9):1047-55

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PMID: 3687061

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