ToxSci Advance Access originally published online on July 14, 2007
Toxicological Sciences 2007 99(2):422-431; doi:10.1093/toxsci/kfm174
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Modeling of Human Dermal Absorption of Octamethylcyclotetrasiloxane (D4) and Decamethylcyclopentasiloxane (D5)
* Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523
Department of Medicine, University of Rochester Medical Center, Rochester, New York 14642
Department of Health and Environmental Sciences, Dow Corning Corporation, Midland, Michigan 48686
Computational Biology Division, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709
1 To whom correspondence should be addressed at Drug Metabolism and Pharmacokinetics Department, Roche Palo Alto, 3431 Hillview Avenue, S3/2 Palo Alto, CA 94304. Fax: (650) 852-1070. E-mail: micaela.reddy{at}roche.com.
Received December 22, 2006; accepted June 18, 2007
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Abstract |
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In this study, data for human dermal absorption of octamethylcyclotetrasiloxane, D4, and decamethylcyclopentasiloxane, D5, through axilla skin in vivo are interpreted using pharmacokinetic models of dermal absorption by adding the dermal exposure route to inhalation physiologically based pharmacokinetics models developed previously. The compartmental model describing dermal absorption of these compounds included volatilization of the applied chemical from the skin surface, diffusion of absorbed chemical back to the skin surface and evaporation of this chemical from the skin surface after the applied dose had cleared from the application site, uptake from the skin compartment into blood, and a storage compartment within the skin. Data from exposures in volunteers (i.e., D4 and D5 concentrations in exhaled air and plasma) were used to estimate model parameters. In volunteers exposed to either D4 or D5, the maximum concentration of chemical in exhaled air reached a maximum at or prior to 1 h following administration of the test chemical. Based on model calculations, the percent of applied dose of D4 that was absorbed into systemic circulation for men and women was 0.12 and 0.30%, respectively; for D5 about 0.05% of the applied dose was absorbed for both men and women. For both D4 and D5, model calculations indicate that more than 83% of the chemical that reached systemic circulation was eliminated by exhalation within 24 h. These whole-body pharmacokinetic models for dermal absorption of two semi-volatile compounds provide a valuable tool for understanding factors controlling their dermal absorption through axilla skin and for applying results from these studies in consumer product risk assessments.
Key Words: octamethylcyclotetrasiloxane (D4); decamethylcyclopentasiloxane (D5); dermal absorption; PBPK model.