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Refinement of the relative alkylation index (RAI) model for skin sensitization and application to mouse and guinea-pig test data for alkyl alkanesulphonates by D. W. Roberts; R. Fraginals; J. -P. Lepoittevin; C. Benezra is a Medicine article available to read on EtoBox.

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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 alkane-sulphonates, 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 'over-load 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 t

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Author

D. W. Roberts; R. Fraginals; J. -P. Lepoittevin; C. Benezra

Publisher

Springer-Verlag; Springer Verlag; Springer Science and Business Media LLC (ISSN 0340-3696)

Published

1991

Language

EN

Field

Medicine (Health Sciences)