ISSN:
1432-069X
Keywords:
RAI (relative alkylation index)
;
The mouse model in contact dermatitis
;
Alkyl methanesulphonates
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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, RSO3Me with R ranging from n-C6H13 to n-C16H33, 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 mM) and challenge concentrations (0.025 mM), 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-C16H33). 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-C16H33 compound the sensitization response was increased. Alkyl and alkenyl methanesulphonates, MeSO3 R (R=n-C12H25, n-C18H37 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00371821
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