Modeling of human dermal absorption of octamethylcyclotetrasiloxane (D(4)) and decamethylcyclopentasiloxane (D(5)).
In this study, data for human dermal absorption of octamethylcyclotetrasiloxane, D(4), and decamethylcyclopentasiloxane, D(5), 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., D(4) and D(5) concentrations in exhaled air and plasma) were used to estimate model parameters. In volunteers exposed to either D(4) or D(5), 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 D(4) that was absorbed into systemic circulation for men and women was 0.12 and 0.30%, respectively; for D(5) about 0.05% of the applied dose was absorbed for both men and women. For both D(4) and D(5), 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.
Reddy
Micaela B
MB
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523, USA. micaela.reddy@roche.com
Looney
Richard John
RJ
Utell
Mark J
MJ
Plotzke
Kathleen P
KP
Andersen
Melvin E
ME
D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D012833:Siloxanes / Q000493:pharmacokinetics*; D012869:Skin Absorption
D012833:Siloxanes; C114768:decamethylcyclopentasiloxane; C024064:octamethylcyclotetrasiloxane