Factors influencing the selective toxicity of cis‐ and trans‐cypermethrin in rainbow trout, frog, mouse and quail: Biotransformation in liver, plasma, brain and intestine

Abstract

AbstractThe biotransformation rates of cis‐ and trans‐cypermethrin, and their routes of metabolism have been studied in subcellular tissue fractions from rainbow trout, frog, mouse and quail to assess the role of detoxification in the selective toxicity of pyrethroid insecticides in these species. The liver was the principal site of biotransformation in mouse and quail, though intestine and plasma (not quail) were also active in hydrolysing cypermethrin isomers. In trout, plasma and intestine were more important sites than liver for the detoxification of tram‐cypermethrin. On the basis of total metabolism of cypermethrin isomers by liver per kilogram of body weight, mouse, quail and frog were respectively 27, 17 and 2 times more active than trout towards the cis‐isomers, and 87, 55 and 6 times more active in metabolising the trans‐isomers. Some of these differences were accounted for by variations in liver/body weight ratios. Extra‐hepatic tissues metabolised cypermethrin principally by ester hydrolysis with maximal activity towards the trans‐isomers, brain and gut contents possessing very low activities. In the presence of NADPH and UDPGA, cis‐ and trans‐cypermethrin were metabolised at very similar rates in frog, mouse and quail liver. Trout liver was more active towards the cis‐isomer forming 4′‐hydroxycypermethrin (aryl hydroxylation) and its glucuronide almost exclusively. Frog and mouse showed either aryl hydroxylation or aliphatic hydroxylation of one of the methyl groups at C‐2 of the cyclopropane ring of cis‐cypermethrin, while quail was unique amongst the four species in metabolising the cis‐isomers largely by oxidative de‐esterification. In all species, except trout, trans‐cypermethrin was rapidly hydrolysed by micro‐somal esterases. The presence of the phase II cofactor UDPGA increased the rate of biotransformation mainly through the glucuronidation of the products of oxidation. This investigation shows that, in addition to differences in target organ sensitivity, biotransformation accounts for some of the observed differences in the susceptibility of these four species to pyrethroids.