COMPARATIVE METABOLISM AND ELIMINATION OF ACETANILIDE COMPOUNDS BY RAT

1. C-14-labelled propachlor, alachlor, butachlor, metolachlor, methoxy propachlor and some of their mercapturic acid pathway metabolites (MAP ) were given to rat either by gavage or by perfusion into a renal arte ry. MAP metabolites were isolated from bile and urine. 2. Rat gavaged with propachlor and methoxypropachlor eliminated C-14 mostly in urine, whereas rat gavaged with alachlor, butachlor and metolachlor eliminat ed C-14 about equally divided between urine and faeces. When bile duct s were cannulated, the gavaged rat eliminated most of the C-14 in bile for all compounds. The amount of C-14 in bile from the propachlor-gav aged rat was less than that for the other acetanilides, with the diffe rence being in the urine. 3. The mercapturic acid metabolites lphinyl- N-(1-methylhydroxyethyl)-N-phenylacetamide and lphinyl-N-(1-methylmeth oxyethyl)-N-phenylacetamide were isolated from the urine and bile of t he methoxypropachlor-gavaged rat. 4. Bile was the major route for C-14 elimination when MAP metabolites of alachlor, butachlor and metolachl or were perfused into a renal artery. Urine was the major route for C- 14 elimination when MAP metabolites of propachlor and methoxypropachlo r were perfused. Mercapturic acid conjugates were major metabolites in bile and urine when MAP metabolites were perfused. 5. We conclude tha t alkyl groups on the phenyl portion of the acetanilide causes biliary elimination to be favoured over urinary elimination.