Postnatal development of rat pups after maternal low-dose exposure to the carbamate insecticide carbaryl during gestation.

FUCHS J; WOLANSKY MJ; KANDEL GAMBARTE P; KRISTOFF G; RUEDA L; LONGONI V; ROVEDATTI MG

Baltimore

Encuentro; 2017 SOT Annual Meeting; 2017

Society of Toxicology

Regulatory decisions on pesticide classification by hazard may be challenged by the fact that daily exposure to multiplepesticides acting by dissimilar modes of action occurs throughout a person′s lifetime as a rule rather than an exception. Thepersistent nervous system alterations caused by exposure to one pesticide during critical periods of early development may bepotentially attenuated or exacerbated by concurrent exposures to other pesticides. There is little data available to estimatepesticide threshold levels for developmental neurotoxicity (DNT) after coexposure to relevant combinations of insecticides. In thiswork 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. 0.5-3 mg CBL/kg was daily administered to pregnantrats from gestational day (GD) 2 to 20. These doses were below CBL NOAEL estimates for maternal toxicity in rat, and above itsADI (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 pertreatment have been evaluated to date. The offspring was monitored for body weight (bw) and developmental landmarks such aseye opening, fur appearance, anogenital distance (AGD) and righting reflex. Pups were then evaluated using an associative-spatiallearning assay with circling velocity as a motor endpoint (Circling Training Test, CTT) at adolescence to assess enduring effects onfine nervous system function. There were no evident alterations observed in dams during gestation. CBL-treated pups showed atrend for a dose-related decrease in AGD and bw gain at the highest dose. Moreover, CBL treated pups showed suboptimalperformance in the righting reflex test. Last, no marked difference between treatment groups was evident in the CTT. Thus, theselected CBL dose scheme appears adequate for low-dose DNT studies using environmentally relevant combinations ofinsecticides and herbicides (work in progress).