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NIOSH Home > Safety and Health Topics >Skin Exposures and Effects >Occupational & Environmental Exposures of Skin to Chemicals- 2005> Abstracts

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Abstract for Poster 42

 

 

Development of a physiologically-based pharmacokinetic model for dermal absorption and penetration of methyl tertiary butyl ether in humans

D. Kim1, L.A. Nylander-French*1, J.D. Pleil2, J.D. Prah3
1Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, United States
2National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency. Research Triangle Park, United States
3National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, United States

Background

Methyl tertiary butyl ether (MTBE) is a volatile organic chemical that is added to gasoline as an octane booster and to reduce vehicular emissions of carbon monoxide. MTBE is introduced into the environment through fuel spills, leakage of storage tanks, and evaporation during auto refueling, leading to contamination of ambient air and water supplies.  MTBE has been linked to toxicity and cancer in animals. The main route of human exposure to MTBE is from inhalation of gasoline vapors; however, dermal exposures may also be significant. The objective of this study is to construct a skin model that adequately describes dermal absorption of MTBE in humans.

Methods

Physiologically-based pharmacokinetic (PBPK) models developed previously were modified to include a two-compartment model for the skin. The initial model contained compartments for skin (stratum corneum and viable epidermis), blood (arterial and venous), brain, kidney, fat, liver, gastrointestinal tract, rapidly perfused tissues, and slowly perfused tissues. The parameters describing the skin compartment were estimated using blood data collected from humans following 1-h exposure to MTBE in water. Sensitivity analysis was implemented to identify parameters that could be adjusted.

Results

The following skin parameters were estimated: permeability coefficients across the stratum corneum (PERM1) and the viable epidermis (PERM2), partition coefficients for vehicle to stratum corneum (PD), stratum corneum to viable epidermis (PE), and viable epidermis to venous blood (PEB). The estimated values are PERM1=0.023 cm/hr, PERM2=0.0037 cm/hr, PD=3.0, PE=70.9, and PEB=23.9.

Conclusions

The model demonstrates that the process of dermal absorption and penetration by MTBE can be described and quantified using a two-compartment model of the skin. Estimation of the skin parameters suggests that the diffusion of MTBE across the stratum corneum is more rapid than across the viable epidermis.

Content last modified: 18 May 2005

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