METABOLISM OF TETRAMETHRIN ISOMERS IN RAT .4. TISSUES RESPONSIBLE FORFORMATION OF REDUCED AND HYDRATED METABOLITES

1. To identify the sites of formation of the reduced metabolites, 3-hy droxycyclohexane-1,2-dicarboximide (3-OH-HPI-1 and -2), 1,2-cyclohexan edicarboxylic acid (TCDA) and 1-hydroxy-1,2-cyclohexanedicarboxylic ac id (1-OH-HPA), in rat treated with C-14-labelied (1RS, trans)-tetramet hrin, [3,4,5,6-tetrahydrophthalimidomethyl (1RS, trans)-chrysanthemate ], bile-duct cannulated animals were orally or intravenously administe red C-14-labelled 3,4,5,6-tetrahydrophthalimide (TPI) dr 3,4,5,6-tetra hydrophthalic acid (THPA), precursors of these metabolites, and bile, urine and faeces were collected for analysis. 2. 3-OH-HPI-1 and 3-OH-H PI-2, which art cis-form reduced metabolites, and 1-OH-HPA were detect ed in bile and urine samples of the bile-cannulated rat treated intrav enously and orally with C-14-labelled TPI, indicating their formation in tissues or blood. TCDA, a trans-form reduced metabolite, was not de tected in bile, urine or faeces of the bile-cannulated rat treated int ravenously with C-14-THPA, but was found in the faeces after oral appl ication, indicating formation in the gastrointestinal tract. 3. To cla rify whether 1-OH-HPA is produced from THPA via TCDA (hydroxylation vi a reduction) or by direct addition of H2O to its double bond (hydratio n), rats were orally administered C-14-labelled TCDA, and metabolites in urine and faeces were analysed. The observed lack of 1-OH-HPA indic ated formation by direct addition of H2O to the double bond of THPA. 4 . To specify which tissues form reduced and hydrated metabolites, in v itro metabolism studies were carried out. Reduction to the cis-form wa s found to take place in blood cells, reduction to the trans-form took place in the gastrointestinal tract contents, and hydration took plac e in the liver and the intestinal tract contents.