Gestational Exposure to Cadmium and Dimethoate Mixture Modifies Fetal Programming in Rats During Development

The combined effects of environmental agents, as metals and pesticides, on human health, need be evaluated because human exposition occurs generally through mixtures, while regulatory assessment of neurotoxicity by these compounds is currently performed only on selected single substances. In the present study the effects of maternal exposure to 10 mg cadmium/l (as cadmium acetate) in drinking water and dimethoate 4 mg/kg (via gavage) during gestation on the development of motor activity (locomotion and motor coordination) and social behavior (anxiety-like behavior and aggressivity) were studied. The importance of the cholinergic system in the modulation of behaviors was studied using acetylcholinesterase (AChE) activity as a biomarker of effect. Cadmium (Cd) and dimethoate (DM) single exposition modified fetal programing for motor activity and social behavior at childhood and adulthood and leads to disturbs of the AChE activity. Exposition to the mixture of Cd and DM enhanced effects on fetal programing and AChE activity. The present results provide, for the first time, direct experimental evidence supporting that joint exposure to cadmium and dimethoate in uterus of rats seems additive and it is perturbs offspring development leading to harmful consequences on motor activity and social behavior, probably related to modulation of the cholinergic system. Our data suggest that added precautions regarding gestational exposure to metals and pesticide mixtures would be prudent to avoid the possibility of fetal programming.