A physiologically based kinetic model for quantifying human exposure to DEET.

Area of Science:

• Toxicology
• Pharmacokinetics
• Environmental Health

Background:

• N,N-diethyl-3-methylbenzamide (DEET) is a key ingredient in insect repellents used against mosquitoes and ticks.
• A human pharmacokinetic-based (PBK) model was developed for DEET and its primary metabolite, 3-(diethylcarbamoyl)benzoic acid (DCBA).

Purpose of the Study:

• To develop and validate a human PBK model for DEET and DCBA.
• To interpret biomonitoring data from a DEET exposure study in children.

Main Methods:

• Integrated systemic and mechanistic dermal absorption models for DEET and DCBA.
• Utilized in vitro, in vivo, and in silico data for model development and optimization.
• Validated model predictions against human pharmacokinetic and biomonitoring study data.

Main Results:

• The integrated PBK model accurately predicted urinary DEET concentrations within a 2-fold range.
• Estimated typical DEET application at a summer camp was 69.0 mg over 24 hours, with 24.2% dermal bioavailability.
• Simulated DEET time-course profiles aligned with published pharmacokinetic data.

Conclusions:

• A validated human PBK model for DEET and DCBA was successfully developed using integrated data.
• The model enabled estimation of external DEET dose and confirmed a margin of exposure above the level of concern.