Postnatal Development of Rat Pups after Maternal Low-Dose Exposure to the Carbamate Insecticide Carbaryl during Gestation

LIS RUEDA; PAULA KANDEL GAMBARTE; VICTORIA LONGONI; GISELA KRISTOFF; ROVEDATTI, M.G.; JULIO FUCHS; MARCELO WOLANSKY

Baltimore, Maryland

Congreso; Annual Meeting of the Society of Toxicology; 2017

Society of Toxicology

Background: Regulatory decisions on pesticide classification by hazard may be challenged by the fact that daily exposure to multiple pesticides acting by dissimilar modes of action occurs throughout a person′s lifetime as a rule rather than an exception. The persistent nervous system alterations caused by exposure to one pesticide during critical periods of early development may be potentially attenuated or exacerbated by concurrent exposures to other pesticides. There is little data available to estimate pesticide threshold levels for developmental neurotoxicity (DNT) after coexposure to relevant combinations of insecticides. In this work we assessed several landmarks of postnatal development after gestational exposure to the carbamate insecticide carbaryl (CBL) as part of an ongoing project on DNT of complex pesticide mixtures. Methods: 0.5-3 mg CBL/kg was daily administered to pregnant rats from gestational day (GD) 2 to 20. These doses were below CBL NOAEL estimates for maternal toxicity in rat, and above its ADI (0.01-0.1 mg/kg/day; WHO-USEPA). A stock solution of CBL in acetone was used to prepare dosing solutions of CBL in water. Dose volumes were adjusted as pregnant dams became heavier to maintain the target daily dose scheme. Three litters per treatment have been evaluated to date. The offspring was monitored for body weight (bw) and developmental landmarks such as eye opening, fur appearance, anogenital distance (AGD) and righting reflex. Pups were then evaluated using an associative-spatial learning assay with circling velocity as a motor endpoint (Circling Training Test, CTT) at adolescence to assess enduring effects on fine nervous system function. Results: There were no evident alterations observed in dams during gestation. CBL-treated pups showed a trend for a dose-related decrease in AGD and bw gain at the highest dose. Moreover, CBL treated pups showed suboptimal performance in the righting reflex test. Last, no marked difference between treatment groups was evident in the CTT. Thus, the selected CBL dose scheme appears adequate for low-dose DNT studies using environmentally relevant combinations of insecticides and herbicides (work in progress).