The impact of vehicle on assessment of relative skin sensitization potency of 1,4-dihydroquinone in the local lymph node assay

Abstract

Background: The murine local lymph node assay (LLNA) has been validated as an alternative method for the identification of skin sensitization hazards. Contact allergens are identified as a function of proliferative responses induced in draining lymph nodes. The quantitative nature of the LLNA data also provides the opportunity of assessing relative potency by reference to dose response analyses. Objective: In the current investigations, the influence of vehicle on the skin sensitization potency of a known skin sensitizer (1,4-dihydroquinone) was assessed. Methods: 1,4-dihydroquinone was tested in the LLNA using 7 different vehicle systems in each of 2 independent laboratories. Results: Results from the 2 laboratories were almost identical. LLNA dose response data were interpolated to derive the estimated concentration (EC) of 1,4-dihydroquinone necessary to cause a three-fold stimulation of proliferation compared with controls, the EC3 value. The vehicles used and mean EC3 values obtained were: methyl ethyl ketone 0.07%, acetone 0.08%, acetone/olive oil ( 80 20 v/v) 0.15%, dimethyl formamide 0.22%, dimethyl sulfoxide 0.4%, and propylene glycol and acetone/saline ( 50 50 v/v) vehicles gave negative results. However, when tested at higher concentrations, positive results were obtained in these vehicles. Conclusion: These data reveal that the vehicle in which a chemical is encountered in the skin can have a significant impact on a quantitative measure of skin sensitization potency. The implication is that accurate assessment of risk to humans will require an understanding of the matrix in which skin exposure is likely to occur.