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 1998-1999

A New Approach to Modeling Contact Dermatitis

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

Successful equations have been developed for predicting allergens/haptens and non-allergens from molecular structure. These require that haptens be rated only as protein-reactive or non-reactive. Because this approach allows for only two possibilities, it does not work when the intensity of allergic response is measured at four levels: non-allergen, weak, moderate, or strong.

To resolve this problem, Magee and colleagues use computational chemistry to model the relative heats of reaction of the known haptens with protein end-groups from cysteine and serine. These groups are involved in the epidermal cell-mediated hapten-protein reaction that initiates the sensitization response of the immune system. Sensitized individuals are susceptible to massive delayed responses when a subsequent contact is made with the dame hapten. To calculate the reactivity of a hapten, the heat of formation of the compound is derived from the lowest energy structure of the molecule, a quantum chemical procedure. The same is done for the protein end-group and for the very first intermediate of the reaction. The difference between the heat of formation of the first intermediate and that of the reactants is the heat of reaction and this is the goal of the study. The relative heats of reaction provide a scale that covers the entire range of allergic potential and will allow development of equations that predict the severity of response from molecular structure. It is expected that these equations will greatly reduce the need for animal testing.