A future approach to measuring relative skin sensitising potency: a proposal.
Current approaches to skin sensitisation risk assessment are dependent upon the availability of information regarding two fundamental parameters. Firstly, data relating to the relative skin sensitising potency of the chemical, and secondly, information regarding likely conditions of human exposure. During the past two decades, much has been achieved in terms of refining methods capable of informing these parameters. For example, the development of the local lymph node assay (LLNA) has made it possible to predict skin sensitising hazard, and to determine relative skin sensitising potency, in a way that was not possible previously. Taken together with accurate information about predicted exposure, such potency data can be used to facilitate the derivation of effective risk assessments. However, although the LLNA provides an integrated assessment of skin sensitising activity, it does require the use of experimental animals and there is growing enthusiasm for designing robust alternative approaches that will reduce or obviate that need. Progress is being made in defining alternative experimental strategies that avoid animal use, but it is clear that accurate characterisation of skin sensitisation hazards will require the effective integration of various sources of information. For this reason, we exemplify here one possible approach that, in theory, provides a framework for not only the identification of skin sensitising chemicals, but also the estimation of relative sensitising potency. This paradigm depends upon development of an understanding of the various biological, biochemical and chemical factors that impact on the allergenic properties of chemicals and the acquisition of skin sensitisation, and an ability to measure these in vitro.
Jowsey
Ian R
IR
Unilever Safety and Environmental Assurance Centre, Sharnbrook, Bedfordshire, UK. ian.jowsey@unilever.com
Basketter
David A
DA
Westmoreland
Carl
C
Kimber
Ian
I
D000826:Animal Testing Alternatives; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects*; D049109:Cell Proliferation; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D023381:Endpoint Determination / Q000379:methods; D006241:Haptens / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D023441:Local Lymph Node Assay; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012867:Skin / Q000187:drug effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*
D006241:Haptens; D009842:Oligopeptides