Dermatitis is an extremely important occupational disease which can make the life of a worker miserable and cost the economy millions of dollars a year in medical treatment and lost time. Dermatitis is the second most frequent occupational disease. Appropriate identification of chemical irritants and the contact time needed to cause irritancy would help ameliorate problems from dermal exposures. The broad, long-term objectives of this project are to develop a biologically based mathematical modeling approach that can be used to provide duration-based standards for dermal irritancy. The specific objective of this research is to mechanistically model the relationship between duration of solvent exposure on the skin and the degree of irritation produced by three occupationally important surfactants and solvents. The short-term (4-hour) distribution of chemical in the stratum corneum, viable epidermis and dermis will be determined and a predictive pharamacokinetic model in the skin will be developed for each of three chemicals (sodium lauryl sulfate, m-xylene and d-limonene). The cellular responses to these chemicals will be determined over the same period of time. The time-concentration profile of important cytokines, chemolines, vasoactive products and a quantitative assessment of edema and erythema will be measured. A biologically based model of the relationship between skin concentration and cellular response (pharmacodynamic model) will be developed. The pharmacokinetic and pharmacodynamic models will be combined to predict irritation from surface concentrations of the chemicals. The entire model will be validated by predicting irritation from another exposure scenario and predicting a duration of exposure which will provide a specific level of edema and erythema. This demonstration will have important applications in occupational health.
