Percutaneous absorption studies of octamethylcyclotetrasiloxane using the human skin/nude mouse model.
Octamethylcyclotetrasiloxane (D(4)) has been used for more than 40 years in industrial applications and consumer products, including the personal care industry. D(4) possesses many properties suitable for personal care products, such as low surface tension, water repellency, and thermal and chemical stability. The skin is a major route of exposure to D(4 )for humans. The main objective of this study was to evaluate the percutaneous absorption of neat D(4) in human skin using the human skin/nude mouse model. This information is needed to aid in assessing potential risks associated with the intended use of D(4). To determine whether D(4) accumulates in adipose tissue of the skin, the distribution of D(4) in human skin layers following application of neat D(4) was also evaluated. In this study, a mean of 1.09 +/- 0.46% of the applied dose was absorbed by the animal under semioccluded conditions. Only about 0.02% of the applied dose remained in the skin after 24 h of exposure (or 72 h after application). The majority (94.59 +/- 12.28%) of the dose evaporated from the site. Excretion in the volatile trap (or expired volatiles) accounted for 42% of the radioactivity that was absorbed, while 49% were excreted in the urine and feces. Despite the lipophilic properties of D(4), a significant accumulation of D(4) in adipose tissue of the skin was not observed 24 h following application to the surface of the skin. The small amount of D(4) detected in the skin was distributed mainly in the epidermis (61%), with lower amounts in the dermis (29%) and subcutaneous adipose tissue (10%). Dermal absorption studies using human skin transplanted onto nude mice showed that this model could be successfully applied for in vivo percutaneous absorption studies of D(4), and presumably of other cyclic siloxanes. The fraction of the percutaneous dose of D(4) absorbed in this model was found to be consistent with results reported by others using different experimental approaches.
Zareba
Grazyna
G
Department of Environmental Medicine, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA. grazyna_zareba@urmc.rochester.edu
Gelein
Robert
R
Morrow
Paul E
PE
Utell
Mark J
MJ
D000279:Administration, Cutaneous; D000818:Animals; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012833:Siloxanes / Q000737:chemistry / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000187:drug effects*; D016038:Skin Transplantation / Q000379:methods; D014018:Tissue Distribution / Q000187:drug effects; D014183:Transplantation, Heterologous / Q000379:methods
D004968:Estrogens, Non-Steroidal; D012833:Siloxanes; C024064:octamethylcyclotetrasiloxane