Analysis and interpretation of pharmacokinetic studies following DEET administration to rats, dogs, and humans

Abstract

Pharmacokinetic studies on the undiluted insect repellent active ingredient, DEET, were assessed for relevance to exposure assessment for humans. Five studies designed to define the DEET plasma concentration profiles of systemic exposure occurring at the respective NOAELs for two laboratory species using dermal and/or oral exposure scenarios and human volunteers at the 95th percentile of consumer use were undertaken to support EPA re-registration. The studies reported herein demonstrate that the DEET plasma concentration for Sprague-Dawley rats and Beagle dogs at the respective NOAELs following oral bolus dosing is much greater in terms of C max and AUC than that achieved following human dermal administration at the 95th percentile of consumer use. In addition, these plasma level data confirm that a high-dose rat subchronic dermal toxicity study with DEET is the most relevant model for human safety assessment of this topically applied insect repellent active ingredient. Therefore, utilization of pharmacokinetic plasma level data is important to exposure assessment of DEET and significantly reduces uncertainty in human health safety assessment.