Capillary Bed Bioreactor: Improved Estimation of Dermal Bioavailability

Project: Research council

Description

Historically, animal testing has been used to support risk assessment for a variety of toxicological endpoints related to cosmetic ingredients, including the local lymph node assay (LLNA) to assess the sensitization potential and potency of a chemical. However, in recent years, there has been a continuous drive to reduce the level of animal testing undertaken to support risk assessments for new cosmetic products, and a move towards a mechanistic understanding of human exposure. Consequently, the development of mechanistic/biologically relevant in vitro, in chemico or in silico models for predicting the sensitising potential and/or potency of new chemicals is necessary to generate data leading to increased confidence in predictions of in vivo scenarios. The chemical and biological events driving the induction of human skin sensitisation are now well understood and companies such as Unilever use this information in non-animal models to test the safety of new compounds. Discs of ex vivo skin (from cosmetic surgery procedures) are mounted in diffusion cells and the permeation of a test item through the skin is monitored over time. While this has proved to be an adequate model, it does not truly represent living skin. At present, little is known regarding chemical clearance via dermal capillaries, and this is a gap in our mechanistic understanding of the bioavailability of a topically applied chemical in the elicitation of skin sensitisation. The proposed capillary bed bioreactor (CBB) better replicates the in vivo environment of the skin and its blood supply by providing a bed of pseudovascularisation in the form of hollow fibre membranes. Therefore it should more accurately predict permeation of chemicals through the skin, and provide data that more closely resembles that of the in vivo scenario. The new bioreactor will be more physiologically accurate than the current model and can therefore potentially refine inputs to our mechanistic models for skin sensitisation, to give us more accurate predictions of adverse outcomes. This in turn will give greater confidence in our ability to risk assess new ingredients in the future without the requirement for animal testing.
StatusFinished
Effective start/end date1/10/1430/06/16

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Bioreactors
Biological Availability
Skin
Cosmetics
Local Lymph Node Assay
Dermatologic Surgical Procedures
Plastic Surgery
Computer Simulation
Toxicology
Safety
Membranes