Skin sensitisation, vehicle effects and the local lymph node assay.
Accurate risk assessment in allergic contact dermatitis is dependent on the successful prospective identification of chemicals which possess the ability to behave as skin sensitisers, followed by appropriate measurement of the relative ability to cause sensitisation; their potency. Tools for hazard identification have been available for many years; more recently, a novel approach to the quantitative assessment of potency--the derivation of EC3 values in the local lymph node assay (LLNA)--has been described. It must be recognised, however, that these evaluations of chemical sensitisers also may be affected by the vehicle matrix in which skin exposure occurs. In this article, our knowledge of this area is reviewed and potential mechanisms through which vehicle effects may occur are detailed. Using the LLNA as an example, it is demonstrated that the vehicle may have little impact on the accuracy of basic hazard identification; the data also therefore support the view that testing ingredients in specific product formulations is not warranted for hazard identification purposes. However, the effect on potency estimations is of greater significance. Although not all chemical allergens are affected similarly, for certain substances a greater than 10-fold vehicle-dependent change in potency is observed. Such data are vital for accurate risk assessment. Unfortunately, it does not at present appear possible to predict notionally the effect of the vehicle matrix on skin sensitising potency without recourse to direct testing, for example by estimation of LLNA EC3 data, which provides a valuable tool for this purpose.
Basketter
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DA
SEAC Toxicology Unit, Unilever Research, Colworth House, Sharnbrook, MK44 1LQ, Bedford, UK. david.basketter@unilever.com
Gerberick
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GF
Kimber
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I
D000485:Allergens / Q000633:toxicity*; D001681:Biological Assay / Q000379:methods; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis* / Q000209:etiology; D015386:Hazardous Substances / Q000633:toxicity; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects*; D014677:Pharmaceutical Vehicles / Q000494:pharmacology*; D018570:Risk Assessment
D000485:Allergens; D015386:Hazardous Substances; D014677:Pharmaceutical Vehicles