Long-term exposure to cypermethrin and piperonyl butoxide cause liver and kidney inflammation and induce genotoxicity in New Zealand white male rabbits

Abstract

Cypermethrin (CY) is a frequently used class II pyrethroid pesticide, while piperonyl butoxide (PBO) plays a major role in the pesticide formulation of synthetic pyrethroids. Synthetic pyrethroids are metabolized in mammals via oxidation and ester hydrolysis. PBO can prevent the metabolism of CY and enhances its pesticide effect. While this potentiation effect reduces the amount of pesticide required to eliminate insects, it is not clear how this mixture affects mammals. In our in vivo experiment, New Zealand white male rabbits were exposed to low and high doses of CY, PBO, and their combinations, for 4 months. Genotoxicity and cytotoxicity were monitored by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the cytokinesis block proliferation index (CBPI) in lymphocytes. After two months of exposure, a statistically significant increase in the frequency of BNMN was observed for all exposed animals (p < 0.001) in a dose-dependent way. MN were significantly elevated compared to controls (p < 0.001), with high dose groups reaching a 442% increase when co-exposed. BNMN and MN continued to increase after four months. Histopathological examination of lesions showed damage involving inflammation, attaining lymphoplasmatocytic infiltration in the high dose groups. Both CY and PBO cause liver and kidney inflammation and induce genotoxicity.

Keywords: Cypermethrin; Cytotoxicity; Genotoxicity; Histology; Micronuclei; Piperonyl butoxide; Potentiation.