title: Development of a modified in vitro skin absorption method to study the epidermal/dermal disposition of a contact allergen in human skin.
abstract: In vitro skin absorption methods exist in Organisation for Economic Co-operation and Development (OECD) guideline form (No. 428) and are used to estimate the degree of systemic penetration of chemicals through skin. More detailed kinetics of permeation through skin compartments are not described well by existing methods. This study was designed to assess the practical feasibility of generating compartmental (stratum corneum/epidermal/dermal) disposition and kinetic data of topically applied chemicals. For chemically induced effects initiated in the skin (e.g., skin allergy), the delivery of tissue concentrations of chemical will impact the incidence and severity of biological effect. Explicit data on the kinetics of chemical disposition in skin have not traditionally been needed for skin allergy risk assessment: current in vivo assays embody delivery implicitly. Under the 7th Amendment to the European Cosmetics Directive, in vivo assays (such as the local lymph node assay for skin sensitization) will not be permitted to assess cosmetic ingredients. New in vitro and in silico alternative approaches and ways of predicting risk of adverse effects in humans need to be developed, and new methods such as that described here provide a way of estimating delivered concentrations and the effect of formulation changes on that delivery. As we continue to deconstruct the contributing factors of skin allergy in humans, it will be useful to have methods available that can measure skin tissue compartment exposure levels delivered from different exposure use scenarios. Here we provide such a method. The method could also be used to generate useful data for developing in silico kinetic models of compartmental skin delivery and for refining data for skin delivery in relation to the evaluation of systemic toxicity.
authors.affiliation: Safety & Environmental Assurance Centre, Unilever Colworth, Sharnbrook, Bedford, UK.
authors.forename: Ruth U
authors.initials: RU
authors.lastname: Pendlington
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Minter
authors.forename: Leanne
authors.initials: L
authors.lastname: Stupart
authors.forename: Cameron
authors.initials: C
authors.lastname: MacKay
authors.forename: Clive S
authors.initials: CS
authors.lastname: Roper
authors.forename: David J
authors.initials: DJ
authors.lastname: Sanders
authors.forename: Camilla K
authors.initials: CK
authors.lastname: Pease
mesh_terms: D000096:Acetone; D000171:Acrolein / Q000031:analogs & derivatives* / Q000378:metabolism; D000328:Adult; D000485:Allergens / Q000378:metabolism*; D000431:Ethanol; D005260:Female; D006801:Humans; D008875:Middle Aged; D000069463:Olive Oil; D010938:Plant Oils; D019946:Propylene Glycol; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: D000485:Allergens; D000069463:Olive Oil; D010938:Plant Oils; D000096:Acetone; D000431:Ethanol; D019946:Propylene Glycol; D000171:Acrolein; C012843:cinnamaldehyde