Differential toxicity of trans-permethrin in rainbow trout and mice : II. Role of target organ sensitivity

Abstract

Previous studies demonstrated that even when trans-permethrin ester hydrolysis was inhibited in mice and the toxicity of trans-permethrin was increased at least 1.6 times by tri- o-tolyl phosphate (TOTP), the toxicity of trans-permethrin remained 60 times greater in the rainbow trout than in the mouse. This information suggested that factors other than metabolism, such as target organ sensitivity, may play a role in the differential toxicity of trans-permethrin between rainbow trout and mice. Since the brain of both the fish and the mouse is believed to be a site of action of the pyrethroids, the concentration of permethrin in the brains of these two species at the onset of signs of pyrethroid toxicity was measured in an attempt to establish a correlation between permethrin brain levels and toxicity in the fish and mammal. Signs of pyrethroid toxicity, such as intense whole body twitches and loss of equilibrium, were observed in rainbow trout when 14C- trans-permethrin brain levels exceeded 1.5 μg/g brain, regardless of whether the compound was administered iv or ip. Pyrethroid toxicity signs, such as intense tremors and loss of righting, were not observed in mice until 14C- trans-permethrin levels reached 25 to 30 μg/g brain. Thin-layer chromatographic analysis indicated that 85 to 95% of the 14C was parent compound in the rainbow trout brains compared to 60 to 70% in the mouse brains. 14C- cis-Permethrin produced lethality in trout and mice when the 14C- cis-permethrin brain concentrations were 2 and 6 μg/g, respectively. The results suggest that the rainbow trout may be physiologically more sensitive to the action of permethrin than is the mouse. In the trout, the cis and trans isomers appear to be equal in toxicity while in the mouse the cis isomer is more active than the trans isomer. The difference in isomer sensitivity between the trout and mouse may suggest differences in specificities at the site of pyrethroid action. The physiologic basis for this difference in pyrethroid toxicity is not understood.