Acute Alterations in Thermoregulatory Response after Single-Compound and Joint Oral Exposure to Pyrethroid Insecticides in Infant Rats

SOSA HOLT, C.S.; ULISES BARDULLAS; WOLANSKY, M.J.

Fenix, Arizona

Congreso; Annual Meeting; 2014

Society of Toxicology (USA)

Presentacion en modalidad poster, PS1847 (ver pag. 486 en documento adjunto). Most pyrethroid insecticides (PYRs) may be classified as type-I or type-II compounds based on acute neurobehavioral effects in adult rodents. In rats, PYRs produce alterations in thermoregulatory response (TR): i.e., hyperthermia (a type-I landmark) or hypothermia (type-II compounds). This dual classification clearly distinguishes high-dose oral syndromes. However, recent evidence suggest that realistic exposures in humans are well below acute dose levels used to classify PYRs, and a greater commonality of clinical effects is observed across PYRs at lower doses. In addition, while a greater vulnerability for pesticides has been generally recognized during early life, there is limited information on the age-related toxicity of subconvulsive doses of PYRs. In this study, two PYRs in corn oil (dose volume = 2 ml/Kg) are evaluated, cypermethrin (CYPM; a prototypical type-II compound) and bifenthrin (BIF, a potent tremorigenic type-I like compound), in single-chemical and binary mixture assays using TR as an endpoint in Sprague Dawley rat pups (P20). Repeated body temperature records were captured by using a radiotelemetric system capable of scanning body heat signals from subcutaneous-implanted microchip-transponders (BMDS, USA). Subcutaneous temperature was recorded before and after single-bolus oral dosing (gavage) at 30 min intervals for a total monitoring period of 5 h. Infants were slightly more sensitive than adults to both PYRs. Most important, BIF produced a biphasic response that was not observed in a previous study in adults (Wolansky et al., 2007), with an initial mild increase followed by an evident decline in body temperature at 2-4 h after dosing at doses above 12 mg/kg. A biphasic response was also observed after exposure to CYPM, consistent with previous data obtained in adults (McDaniel and Moser, 1993). When infants were administered a mixture of low-effective equipotent doses of both PIRs, an apparent summation of the initial body heating effect was observed, and no hypothermic action was evident afterwards. The results are discussed in the context of the relevance of the age-specific toxicodynamic and toxicokinetic factors influencing qualitative divergence in toxic responses to pesticides (UB and CSSH had an equal contribution to this work).