TOXICITY STUDIES IN RATS OF SIMPLE MIXTURES OF CHEMICALS WITH THE SAME OR DIFFERENT TARGET ORGANS

Mixtures of chemicals with different target organs or the same target organ but different target sites or different modes of action did not appear to be distinctly more hazardous than the individual chemicals, provided the dose level of each chemical in the mixture did not exceed its own 'No-Observed Adverse-Effect Level'. Clearly, for such mixture s and exposure conditions the additivity assumption did not hold. Howe ver, the additivity rule appeared to be applicable to mixtures of chem icals with the same target organ and the same mechanism of action or r eceptor. Fractional 2-factorial study designs were found to be promisi ng tools for examining possible combined actions or interactions of ch emicals in a mixture.