Vj. Feron et al., SAFETY EVALUATION OF THE MIXTURE OF CHEMICALS AT A SPECIFIC WORKPLACE- THEORETICAL CONSIDERATIONS AND A SUGGESTED 2-STEP PROCEDURE, Toxicology letters, 76(1), 1995, pp. 47-55
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.