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ToxSci Advance Access published online on July 14, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm174
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Human Dermal Absorption Modeling of Octamethylcyclotetrasiloxane (D4) and Decamethylcyclopentasiloxane (D5)

Micaela B. Reddy*,1, R. John Looney{dagger}, Mark J. Utell{dagger}, Kathleen P. Plotzke{ddagger} and Melvin E. Andersen§

* Colorado State University, Fort Collins, Colorado 80523 {dagger} University of Rochester Medical Center, Rochester, New York 14642 {ddagger} Dow Corning Corporation, Midland, Michigan 48686 § CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709

1 Current address of corresponding author: Micaela B. Reddy, Ph.D., DMPK Department, Roche Palo Alto, 3431 Hillview Avenue, S3/2, Palo Alto, CA 94304, Phone: (650) 855-5239, Fax: (650) 354-7363, Email: micaela.reddy{at}roche.com

Received December 22, 2006; revision received May 2, 2007; accepted June 18, 2007


  Abstract

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 PBPK 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 one hour following administration of the test chemical. Based on model calculations, the percent of applied dose of D4 that absorbed into systemic circulation for men and women was 0.12 and 0.30%, respectively; for D5 about 0.05% of the applied dose 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 hours. 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.


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[Abstract] [Full Text] [PDF]


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