Predicting vehicle effects on the dermal absorption of halogenated methanes using physiologically based modeling

Area of Science:

• Toxicology and Environmental Health
• Dermal Absorption and Pharmacokinetics

Background:

• Occupational and environmental exposures frequently involve dermal contact with chemicals diluted in various vehicles or mixtures.
• Understanding vehicle effects is crucial for accurate dermal risk assessment of industrial chemicals.

Purpose of the Study:

• To evaluate the influence of different vehicles (water, mineral oil, corn oil) on the dermal penetration of dibromomethane (DBM) and bromochloromethane (BCM).
• To determine dermal permeability coefficients and assess their relationship with vehicle properties for risk assessment.

Main Methods:

• In vivo dermal exposure studies using 15 vehicle combinations of DBM and BCM.
• Blood sampling at multiple time points (0.5-24 h) to quantify chemical absorption.
• Application of a physiologically based pharmacokinetic (PBPK) model to estimate absorbed doses and dermal permeability coefficients.

Main Results:

• Permeability coefficients for DBM and BCM were substantially higher in water compared to corn oil (73- and 40-fold, respectively).
• When normalized by the skin:vehicle partition coefficient, dermal permeability varied by less than a factor of two across vehicles.
• Aqueous vehicle permeability successfully predicted dermal permeability in a nonpolar vehicle (peanut oil).

Conclusions:

• Vehicle effects on dermal penetration are largely explained by the skin:vehicle partition coefficient.
• PBPK modeling and normalized permeability provide a robust method for predicting dermal absorption across different exposure scenarios.
• Findings support improved risk assessment for dermal exposure to halogenated hydrocarbons.