Effect of oral administration of a mixture of pyrethroids at doses relevant to human exposure on the general and male reproductive physiology in the rat

Studies on the effects of unintentional intake of pyrethroid pesticides that are akin to actual human exposure settings are very rare. Such an exposure is primarily by consuming the food products as routine diet that contain residual levels of pyrethroids. In this study, rats were orally administered for 15 months with a mixture of pyrethroids at a dose that is one-fifth (high dose; HD) or one-twenty fifth (low dose; LD) of the residual levels commonly present in the average amount of rice and vegetables consumed by Indian population. Lipid profile, kidney and liver function were assessed. Lipid peroxidation, nitric oxide, antioxidant enzyme activities and histopathological changes were analyzed in the liver, lung, kidney, pancreas, testes, caput, cauda and prostate. The effect on the male reproductive system as a function of sperm count, enzyme activity of 3β-HSD and 17β-HSD and the expression profile of genes involved in spermatogenesis, steroidogenesis, genetic reprogramming and apoptosis of male gametes were evaluated. Significant increase in the relative organ weight, perturbations in the activities of antioxidant enzymes, lipid profile and liver function were observed in both LD and HD groups. Damage to the anatomical architecture was evident in all the tissues due to pyrethroid toxicity. Exposure to LD and HD of pyrethroid mixture resulted in decreased sperm count, activities of 3β-HSD and 17β-HSD, impaired capacitation and acrosome reaction and perturbations in the expression of genes that govern male gamete production. Results of our study indicate that exposure to pyrethroids for longer durations even at doses that are far below the residual levels present in the food consumed will result in severe damage to general physiological processes as well as reproductive function.