The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 1999-2000

A New Approach to Modeling Allergic Contact Dermatitis

Philip S. Magee, PhD
BIOSAR Research Project, Vallejo, California

During the past two years, a broad spectrum of electrophilic haptens that cause sensitization and subsequent contact dermatitis have been modeled for reactivity with protein end-groups. This key reaction with the cell surface identity molecules of several allergen presenting cells, especially the epidermal Langerhans cells is the initiating step in sensitization. The computational database now in hand allows the estimation of reactivity for many new haptens and the method permits the direct evaluation of specific new haptens where this is not possible.

At the end of the second grant year, a data set of 25 haptens evaluated by the guinea pig maximization test (GPMT) at 4 levels (1 = non or very weak; 2 = weak; 3 = moderate; 4 = strong or severe) was compared with computed values of the same haptens. The agreement was excellent and fully consistent with the GPMT. Although more work needs to be done to expand this comparison between live animal and computational results, it is clear that the method has commercial value in providing companies with rapid and low-cost information to enable the setting of priorities.

During our third year study, many more haptens will be studied will be studied in direct comparison with lab animal results to fully validate the method. In addition, the large amount of computational data we now have will be used to construct a convenient scale of reactivities that will allow the rapid classification of new haptens and provide descriptors for future structure-activity studies.