Long-lasting developmental effects in rat offspring after maternal exposure to acetamiprid in the drinking water during gestation

Neonicotinoids (NNTs) are a class of insecticides proposed to be safe for pest control in urban, suburban, and agricultural applications. However, little is known about their developmental effects after repeated low-dose exposures during gestation. Here, we tested a dose considered subthreshold for maternal toxicity in rats (6 mg/kg/day) by assessing several morphological, biochemical, and neurobehavioral features in preterm fetuses and developing pups after maternal administration of the NTT acetamiprid (ACP) dissolved in the drinking water during gestational days (GD) 2-19. The exploratory evaluation included monitoring maternal body weight gain, fetal viability, body weight and sex ratio, cephalic length, neonatal body weight and sex ratio, metabolic enzymes in the placenta, maternal blood and fetal liver, and anogenital distance and surface righting response during infancy. We also used the circling training test to study the integrity of the associative-spatial-motor response in adolescence. Results showed no consistent findings indicating maternal, reproductive or developmental toxicity. However, we found ACP effects on maternal body weight gain, placental butyrylcholinesterase activity, and neurobehavioral responses, suggestive of a mild toxic action. Thus, our study showed a trend for developmental susceptibility at a dose so far considered subtoxic. Although the ACP concentration in environmental samples of surface water and groundwater has been mostly reported to be much lower than that used in our study, our results suggest that the ACP point of departure used in current guidelines aimed to prevent developmental effects may need to be verified by complementary sensitive multiple-endpoint testing in the offspring.