Capillary Bed Bioreactor: Improved Estimation Of Dermal Bioavailability

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Historically, animal testing has been used to support risk assessment for a variety of toxicological endpoints related tocosmetic ingredients, including the local lymph node assay (LLNA) to assess the sensitization potential and potency of achemical. However, in recent years, there has been a continuous drive to reduce the level of animal testing undertaken tosupport risk assessments for new cosmetic products, and a move towards a mechanistic understanding of humanexposure. Consequently, the development of mechanistic/biologically relevant in vitro, in chemico or in silico models forpredicting the sensitising potential and/or potency of new chemicals is necessary to generate data leading to increasedconfidence in predictions of in vivo scenarios. The chemical and biological events driving the induction of human skinsensitisation are now well understood and companies such as Unilever use this information in non-animal models to testthe safety of new compounds. Discs of ex vivo skin (from cosmetic surgery procedures) are mounted in diffusion cells andthe permeation of a test item through the skin is monitored over time. While this has proved to be an adequate model, itdoes not truly represent living skin. At present, little is known regarding chemical clearance via dermal capillaries, and thisis a gap in our mechanistic understanding of the bioavailability of a topically applied chemical in the elicitation of skinsensitisation. The proposed capillary bed bioreactor (CBB) better replicates the in vivo environment of the skin and itsblood supply by providing a bed of pseudovascularisation in the form of hollow fibre membranes. Therefore it should moreaccurately predict permeation of chemicals through the skin, and provide data that more closely resembles that of the invivo scenario. The new bioreactor will be more physiologically accurate than the current model and can thereforepotentially refine inputs to our mechanistic models for skin sensitisation, to give us more accurate predictions of adverseoutcomes. This in turn will give greater confidence in our ability to risk assess new ingredients in the future without therequirement for animal testing.