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1. Pentachlorophenyl methyl sulphoxide and pentachlorophenyl methyl sulphone were found to be substrates for microsomal and cytosolic glutathione-S-transferase of rabbit, monkey, chicken and human liver, covalently immobilized on beaded sepharose. 2. Protein was immobilized with greater than 95% transferase activity, measured by dinitrochlorobenzene. Immobilized rabbit liver microsomal transferase activity was more stable than immobilized cytosolic activity. 3. The sulphoxide moiety was displayed by glutathione in the presence of chicken liver microsomal protein. The sulphone moiety was displayed by glutathione in the formation of a diglutathione under catalysis by rhesus monkey liver cytosolic and microsomal protein. 4. Chlorine was displaced by transferases from all species to form regioisomeric monoglutathiones. 5. Qualitative and quantitative differences were observed in product distributions between species and between microsomal and cytosolic protein.

1. Radioactivity from oral doses of N-isopropyl[1-14C]acetanilide was excreted in urine (53.5%), faeces (8.1%) and expired air (17.0%) of rat. 2. Enterohepatic circulation occurred during formation of approximately 34% of the metabolites. N-isopropylacetanilide was metabolized by oxidation in all moieties of the molecule with subsequent conjugation with glucuronic and sulphuric acids. 3. The sulphate ester of 4'-hydroxyacetanilide (acetaminophen) was the major metabolite (28 % of the dose).

1. [1-14C]Propachlor-GSH was perfused at 0.34, 3.4 and 34 mumol/h through the portal vein or the right renal artery of anaesthetized rats with biliary and ureteral cannulas. Urine was the predominant route for elimination of the 14C regardless of the route of perfusion. 2. Mercapturic acid conjugates were found to be the end-products of metabolism of the 14C-propachlor-GSH by rat kidneys and liver, indicating that all enzymes necessary for the catabolism of GSH conjugates to mercapturates were present in each of these tissues. 3. Perfusion of 14C-propachlor-GSH at 34 mumol/h appeared to exceed the metabolic capacity of both liver and kidneys for this substrate. At this dose, parent compound was detected in the bile of portally perfused rats, and the amounts of 14C recovered in bile, kidneys and carcasses of renally perfused rats were greater than when smaller dosages were perfused.

Conventional rats metabolize 2-chloro-N-isopropylacetanilide (propachlor) mainly to various 2-methylsulphonylacetanilides and to residues in the faeces that are unextractable. Mercapturic acid pathway (MAP) metabolites of propachlor are the source of the methylsulphonyl sulphur and the insoluble faecal residues. Germ-free and antibiotic-treated rats quantitatively metabolized propachlor only to MAP metabolites, which were excreted in the urine and faeces (all water-soluble). Germ-free rats given enemas of caecal contents from conventional rats were qualitatively similar to conventional rats with respect to the metabolism of propachlor within 56 days of the inoculations i.e. they excreted 2-methylsulphonyl acetanilides in the urine and insoluble residues in the faeces. They approached quantitative similarity within 180 days. Antibiotic-treated rats spontaneously recovered the ability to metabolize propachlor as conventional rats, qualitatively within 6 days and quantitatively within 21 days. While differences occurred in the faecal metabolites of propachlor, biliary secretion of metabolites by germ-free rats was not different from that of conventional or antibiotic-treated rats.

Sheep and rats metabolized single oral doses of O-O-dimethyl-O-(3,5,6-trichloro-2-pyridyl) phosphorothioate (I) to three major metabolites that were excreted in the urine (approximately 70% of the 14C). These were the glucuronide of 3,5,6-trichloro-2-pyridinol, O-methyl-O-(3,5,6-trichloro-2-pyridyl) phosphorothioate, and 3,5,6-trichloro-2-pyridinol. The latter two metabolites and the parent compound were isolated from sheep feces. Sheep plasma contained the same metabolites that were found in sheep urine, and no parent compound was detected in the plasma. Tissue residues from I were determined. Visceral fat contained the highest concentration of I-equivalents (11.8 ppm). Sheep excreted a single oral dose of 3,5,6-trichoropyridinol (II) unchanged in the feces and as II-glucuronide in the urine.

Metabolites in which the chlorine from propachlor has been replaced by a cysteine group or a methylsulfonyl group [-S(O2) CH3] are present in the urine of rats dosed orally with propachlor. In the present study, urine from rats given single oral doses of 35S-labeled cysteine conjugate of propachlor contained metabolites having the methylsulfonyl groups labeled with 35S. No metabolites containing 14C-labeled methylsulfonyl groups were isolated from urine of rats given single oral doses of the cysteine conjugate of propachlor in which the cysteine group was uniformly labeled with 14C. These findings show that the cysteine conjugate of propachlor is the source of sulfur in the methylsulfonyl-containing metabolites. Therefore, we suggest that a C-S lyase present in the animal cleaves the cysteine conjugate of propachlor and thus allows further metabolism of the sulfur to a methylsulfonyl moiety.

Sheep metabolized a single oral dose of 2‐chloro‐N‐isopro‐pylacetanilide (propachlor) to four urinary metabolites. These were 2‐(S‐cysteinyl)‐N‐isopropylacetanilide and 2‐[S‐(N‐acetyl) cysteinyl]‐N‐isopropylacetanilide and the glucuronide conjugates of 4'‐hydroxy‐N‐isopropyl‐2‐methylsulfonylacetanilide and N‐(1‐hydroxyisopropyl)‐2‐methylsulfonylacetanilide. Residues (ppb equivalents of propachlor) from [14C]‐propachlor in the milk from a goat given daily oral doses (1.3 mg of propachlor three times daily for 15 days) plateaued at about 2 to 4 ppb equivalents of propachlor. In goat tissue, residues ranged from 1 ppb (fat) to 20 ppb (liver). Fecal and tissue metabolites were not identified.