摘要：

A derivation, more rigorous than hitherto, of the Relative Alkylation Index (RAI) as a quantifier of carrier protein haptenation in skin sensitization tests is presented. It is shown that the RAI, which is a composite parameter made up of dose, reactivity and lipophilicity terms, is likely to require a higher weighting for the reactivity term in the case of non-adjuvant tests than in the case of Freund's adjuvant-based tests. Methyl alkanesulphonates, R SO 3 Me with R ranging from n -C 6 H 13 to n -C 16 H 33 , were found to be skin sensitizers in a mouse ear swelling test, in agreement with published findings in a guinea-pig adjuvant model. A structure-activity relationship consistent with the published RAI model was observed whereby, in tests at fixed molar induction (0.1 m M ) and challenge concentrations (0.025 m M ), the level of sensitization response at first increased with increasing chain length of R , then showed a reversal of this trend at the highest chain length ( R = n -C 16 H 33 ). That this is a genuine 'overload effect', as reported for several other series of compounds examined in guinea-pig adjuvant models, is indicated by the finding that on reducing the induction concentration for the R = n -C 16 H 33 compound the sensitization response was increased. Alkyl and alkenyl methanesulphonates, MeSO 3 R ( R = n -C 12 H 25 , n -C 18 H 37 and R =oleyl) did not give significant sensitization in the mouse ear test. Although they are chemically less reactive than methyl alkanesulphonates, these compounds are reported to be strong sensitizers in guinea-pig adjuvant tests and to fit a common quantitative sensitization — structure — dose relationship with the methyl alkanesulphonates. This difference between the murine and the guinea-pig adjuvant tests is attributed to the sensitization potential being more sensitive in the murine test to differences in chemical reactivity, as predicted by the more rigorously derived RAI model.

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