Dermal penetration and models
Micaela B. Utell, Kathleen P. Plotzke, Melvin E. 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.
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Many studies have used pharmacokinetic compartment models for skin to predict or analyze dermal absorption of chemicals. Comparing these models is difficult because the relationships between rate constants and the physicochemical parameters were not always defined clearly, simplifying assumptions built into models sometimes were not stated, and which skin layers were included often were not specified. In this paper we review and compare published one- and two-compartment models for which rate constants were expressed in terms of the physicochemical and physical properties of the skin i. Nine one-compartment and two two-compartment models are presented with a consistent nomenclature and clearly defined assumptions.
Dermal penetration studies are conducted to determine how much of a chemical penetrates the skin, and thereby whether it has the potential to be absorbed into the systemic circulation. Dermal penetration is considered to occur by passive diffusion; however, biotransformation of the test substance within the deeper viable regions of the skin metabolism prior to systemic absorption can occur OECD, a. It may provide an indication that the substance penetrates the skin if it produces systemic toxicity, but the amount of chemical absorbed is not quantified by dermal toxicity testing. One of the primary roles of the skin is to act as a barrier to protect humans from substances contacted in the environment. Permeation of a substance through the skin depends upon a number of factors, including: the formulation or vehicle in which it is presented to the skin; physicochemical properties of the test substance such as lipophilicity fat solubility , molecular weight, charge, and concentration of the test substance; and area and duration of exposure.