Sex-related effects of imidacloprid modulated by piperonyl butoxide and menadione in rats. Part II: genotoxic and cytotoxic potential

Abstract

Despite its intended use, imidacloprid causes genotoxic and cytotoxic effects in mammals, especially in the presence of metabolic activation systems. The aim of this study was to determine to which extent these effects are sex related and how its metabolism modulators piperonyl butoxide and menadione affect its toxicity. Male and female Sprague-Dawley rats were injected with the intraperitoneal LD₅₀ dose of imidacloprid alone (170 mg/kg) or pretreated with piperonyl butoxide (100 mg/kg) and menadione (25 mg/kg) for 12 and 24 h. Structural chromosome aberrations, abnormal cells and mitotic index were determined microscopically in bone marrow cells. Male rats showed susceptibility to the genotoxic effects of imidacloprid. Piperonyl butoxide was effective in countering this effect only at 24 h, whereas menadione exacerbated imidacloprid-induced genotoxicity. Piperonyl butoxide and menadione pretreatments increased the percentage of structural chromosome aberrations and abnormal cells in females. Imidacloprid decreased the mitotic index, whereas pretreatment with piperonyl butoxide and menadione showed improvement in both sexes. We believe that CYP450-mediated metabolism of imidacloprid is under the hormonal control and therefore that its genotoxicity is sex related. Piperonyl butoxide pretreatment also showed sex-related modulation. The hormonal effects on imidacloprid biotransformation require further investigation.

Keywords:

• Cytotoxicity
• genotoxicity
• imidacloprid
• menadione
• piperonyl butoxide
• rats
• sex
• structural chromosomal aberrations

Acknowledgements

We wish to thank Dado Cakalo for having edited the manuscript to read better.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. We wish to thank the Adiyaman University Scientific Research Commission for supporting this study (project grant no. FEFBAP2011/007).