Research in Veterinary Science /986. 4/, 336-339 Effect of pretreatment with hepatic microsomal enzyme inducers on the toxicity of diazinon in calves E. B. ABDELSALAM*, E. J. H. FORD, Department of Veterinary Clinical Science, University of Liverpool, Leahurst, Neston, South Wirral L64 7TE The pretreatment of calves with a single dose of 10 mg kg-I dieldrin or 21 daily doses of 10 mg kg-I pheno- barbitone increased the toxicity of diazinon as reflected by the development of more severe clinical signs and greater depression in whole blood cholin- esterase activity in the pretreated calves. Induction by dieldrin or phenobarbitone of the hepatic microsomal enzyme amidopyrine-N-demethylase was also accom- panied by a concurrent rise in the liver carboxyl- esterase activity. D1AZINON (O,O-diethyl 0-[2-isopropyl-4-methyl-6- pyrimidinyl) phosphorothioate) and other phospho- rothioate and phosphorothionate organophos- phorus compounds are indirect cholinesterase inhibitors which require previous biological activa- tion of their toxic oxygen analogues by the action of the liver microsomal enzymes (O'Brien 1959, Dahm et al 1962, Johnson and Dahm 1966). However, these mixed function enzymes are also involved in detoxi- fication reactions of many organophosphorus compounds (Neal 1967, O'Brien 1967). For this reason, the effect of hepatic microsomal enzyme induction on the toxicity of a particular organo- phosphorus compound is not always predictable. It depends on the nature of the compound or its metabolites and on the extent to which activation and degradation processes are affected. In addition, the administration of hepatic microsomal enzyme inducers was found to increase the liver carboxyl- esterase activity (Read et al 1964, Lundquist and Perlmann 1966, Schwark and Ecobichon 1968) and thereby reduce the toxicity of many organo- phosphorus compounds (Welch and Coon 1964, Triolo and Coon 1966, Brodeur 1967). However, most of these experiments were carried out in rats or mice, and the following experiment was, therefore, designed to study the effect of pretreatment with microsomal enzyme inducers (dieldrin and pheno- barbitone) on the toxicity of diazinon and their effect ·Present address: Department of Pathology, Faculty of Veterinary Science, PO Box 32, Khartoum North, Sudan on the activity of amidopyrine-N-demethylase and carboxylesterase in the liver of calves. Materials and methods Ten, three-month-old Guernsey calves weighing between 50 and 80 kg were housed in individual pens and fed on 2· 3 kg of calf nuts per day with free access to hay and water. Phenobarbitone sodium (BDH) dissolved in water, dieldrin (Shell Research) and diazinon (90 per cent Technical; Wellcome) were mixed in olive oil and administered by stomach tube to calves as follows (Table 1): group 1 (calves 63, 64) was given 120 mg kg-I of diazinon; group 2 (calves 65, 66, 67, 68) was pretreated with a single dose of 10 mg kg- I dieldrin three weeks before the administration of 120 mg kg "! of diazinon; group 3 (calves 69, 70, 71, 72) was pretreated with daily doses of 10 mg kg-I phenobarbitone for three weeks before the administration of 120mg kg-I of diazinon, Liver biopsy samples were collected before and three weeks after the administration of dieldrin and phenobarbitone for measurement of the liver micro- somal amidopyrine-N-demethylase and carboxyl- esterase activities. The animals were observed for clinical changes and blood samples-were collected four times before the administration of diazinon and at intervals thereafter for measurement of whole blood cholinesterase activity. Collection of liver biopsy samples, preparation of homogenates and measurement of liver microsomal amidopyrine-N- demethylase activity was performed as described by Ford et al (1972). This enzyme was chosen as an indicator of the activity of the group of mixed function oxidases that are stimulated by dieldrin and phenobarbitone although it may not be a direct activator of diazinon. The liver carboxyl esterase activity of the homogenate was measured spectro- photometrically by the method of Ecobichon (1970) using 0·01 M a-naphthyl acetate as the substrate. The total activity was measured in the crude homo- genate and the microsomal activity was measured in the supernatant fluid obtained after centrifugation at 336