SAFETY EVALUATION OF THE MIXTURE OF CHEMICALS AT A SPECIFIC WORKPLACE- THEORETICAL CONSIDERATIONS AND A SUGGESTED 2-STEP PROCEDURE

Procedures for the selection of compounds with high health hazard pote ntial are reviewed, and major aspects of the assessment of health risk s associated with exposure to mixtures of chemicals are discussed. Exa mples are given of additivity and synergism of effects following expos ure to mixtures. Using these data from the literature a two-step proce dure for the safety evaluation of the mixture of chemicals occurring a t a specific workplace is suggested. The first step consists of estima ting the relative health risk associated with each chemical; the estim ation is based on the ratio between exposure level and degree of toxic ity. Those chemicals representing a high risk are then selected for fu rther consideration. The second step comprises the risk assessment, fo cusing on prediction of the risk associated with exposure to the mixtu re of selected chemicals. To allow such prediction the (presumable) mo de of action of the selected compounds should be considered. A practic al way to find out whether exposure to chemicals at a specific workpla ce is of serious health concern, could be the conduct of both a 4-week toxicity study in rats and 2 different types of genotoxicity studies with the mixture of selected chemicals, using exposure concentrations related to those occurring in practice.