A physiologically based kinetic model for quantifying human exposure to DEET

Abstract

Background

N,N-diethyl-3-methylbenzamide (DEET) is an active ingredient of insect repellents that are applied on skin against mosquitoes and ticks. We developed a human PBK model of DEET and 3-(diethylcarbamoyl)benzoic acid (DCBA, a primary metabolite of DEET). The PBK model was used to interpret a biomonitoring study of DEET in children.

Methods

The model was built in three steps. First, systemic models of DEET and DCBA were built and linked based on in vitro and in vivo data and in silico predictions. Second, a mechanistic dermal absorption model of DEET was developed and optimized based on in vitro permeation test (IVPT) data. Finally, the systemic model was linked to the dermal model. Predictions of the integrated model were evaluated using in vivo dermal exposure study data. This model was used to interpret urine concentrations of DEET following use of DEET containing repellents by children at a summer camp.

Results

The model (i.e., combined dermal and systemic models) whose urinary predictions were within the 2-fold range was used to simulate the time-course profile of DEET; results were compared against data from a previously published pharmacokinetic study. The estimated typical amount of applied DEET at the summer camp over 24 h was 69.0 mg with a predicted dermal bioavailability of 24.2 %.

Conclusion

A PBK model of DEET and DCBA was developed and validated in humans by integrating publicly available data. The external dose of DEET was estimated using the PBK model, and the calculated margin of exposure is above the level of concern.