Partition coefficients for benzene in human skin

Area of Science:

• Toxicology
• Dermal Absorption
• Pharmacokinetics

Background:

• Benzene exposure standards primarily focus on inhalation, but skin absorption's contribution to body burden is not well-quantified.
• Accurate assessment of benzene's dermal absorption is necessary for comprehensive risk evaluation and standard setting.
• Physiological-based pharmacokinetic (PBPK) modeling requires specific partition coefficients for skin layers to simulate benzene's systemic uptake.

Purpose of the Study:

• To determine crucial partition coefficients for benzene across human skin's epidermal and dermal layers.
• To enable quantitative assessment of benzene's flow rate through intact skin into the bloodstream via PBPK modeling.
• To provide essential data for refining benzene exposure standards by accounting for dermal absorption.

Main Methods:

• Experimental determination of partition coefficients for benzene across different human skin layers (stratum corneum, viable epidermis, dermis).
• Utilized blood substitute and benzene: water/blood substitute systems for coefficient measurements.
• Calculated partition coefficients for blood substitute: viable epidermis (2.4) and blood substitute: dermis (11.2).

Main Results:

• Key partition coefficients for benzene across human skin layers were successfully determined.
• Measured coefficients include benzene: stratum corneum (4.2), whole skin: blood substitute (2.2), benzene: water (109/126), and benzene: blood substitute (55/59).
• The determined coefficients (2.4 and 11.2 for viable epidermis and dermis, respectively) are suitable for PBPK model integration.

Conclusions:

• This research provides essential quantitative data on benzene's dermal absorption properties.
• The determined partition coefficients will enhance the accuracy of PBPK models for benzene exposure.
• Findings support a more comprehensive understanding of benzene's total body burden, aiding in the development of robust exposure standards.