Table 8. LLNA Data for Salicylate Esters^a.

^aObserved EC3 values are taken from Belsito et al.³⁸ LogP values are calculated manually by the method of Leo and Hansch³⁴ starting from the experimental value of 2.55 for methyl salicylate³⁹ and agree within 0.2 log units with published values calculated by various computer methods.

^bFor benzyl salicylate, an alternative electrophilic mechanism involving S_N2 attack at the benzyl carbon, with the salicylate anion acting as the leaving group, is also possible. Benzyl benzoate is also proposed to sensitize via this mechanism⁴⁰ and has an EC3 value of 17%. Benzyl salicylate would be predicted to be a stronger sensitizer than benzyl benzoate if they both act as S_N2 electrophilic sensitizers. This is because the salicylate ion should be a better leaving group than the benzoate ion, since it is less basic (pK_a values of benzoic acid and salicylic acid are 4.20 and 2.97, respectively⁴¹).

^cBelsito et al.³⁸ summarize four LLNA assays on methyl salicylate with acetone/olive oil as the vehicle, all negative at concentrations up to 25%, and one test in dimethyl formamide giving an EC3 value of 25%.