ABSTRACT
The first structured approach to evaluation of skin sensitizing activity as a function of challenge-induced increases in ear thickness resulted in the
description of the mouse ear swelling test or MEST (Gad et al., 1986). In its original form the MEST incorporated a rigorous induction regime comprising the repeated application (daily for four consecutive days) of test material to tape-stripped abdominal skin, the treatment site having been prepared previously by the intradermal administration of Freund’s Complete Adjuvant to enhance immunogenicity. Control mice were treated in an identical manner with vehicle alone. Seven days following completion of the induction procedure both test and control animals were treated on the dorsum of one ear with the test material and on the contralateral ear with vehicle. Concentrations of the test agent used for challenge were selected on the basis of prior sighting studies for lack of irritant activity. Induced changes in ear thickness were measured 1 and 2 days after challenge (Gad et al., 1986). This method was used to evaluate more than 70 chemicals which, on the basis of guinea pig and/ or human studies, were known to display varying skin sensitizing potential. The results of this first validation study were encouraging, although with some sensitizing chemicals only modest changes in ear thickness were recorded (Gad et al., 1986). A similar method, also incorporating treatment with adjuvant, the mouse ear sensitization assay, was described by Descotes in 1988. In two subsequent investigations doubts were raised about the sensitivity of the MEST and its ability to identify chemicals with weak to moderate skin sensitizing activity (Cornacoff et al., 1988; Dunn et al., 1990). However, in at least one of these studies a modification of the original procedure was used (Cornacoff et al., 1988).
