Neurological effects of long-term exposure to low doses of pesticides mixtures in male rats: biochemical, histological, and neurobehavioral evaluations

Humans are usually exposed to multiple pesticides in real life, but little is known as yet about the safety of low-dose pesticides mixtures. This study was conducted to evaluate the effects of long-term exposure to very low doses of pesticide mixtures on biochemical, histological, and neurobehavioral alterations in the rat model. For 90 days, four groups of male Wistar rats were given a mixture of five pesticides (in drinking water) in doses of 0, 0.25, 1 and 5 times the legally permitted levels (mg/kg body weight/day). After three-month exposure, the neurobehavioral effects of pesticide mixtures were evaluated by the Morris water maze, elevated plus maze and the open field tests. Then the biochemical and histopathological alterations in the hippocampus of studied animals were evaluated. Results showed that long-term exposure to a combination of five pesticides affected the nervous system in dose-dependent manner. As expected, nearly all of the parameters determined in this study were adversely changed in the high dose group. Exposure to medium dose (permitted level of pesticides mixture) was also able to induce oxidative stress and impaired memory and learning ability, although not all parameters were significantly changed in this group. It means that pesticides may behave differently when mixed. Interestingly, the administration of low doses of these chemicals induced an adaptive response by stimulating the redox system. In conclusion, it seems that the prolonged exposure to pesticide mixtures may cause adverse neurobehavioral effects, even at permitted levels.