Vj. Feron et al., TOXICITY STUDIES IN RATS OF SIMPLE MIXTURES OF CHEMICALS WITH THE SAME OR DIFFERENT TARGET ORGANS, Toxicology letters, 82-3, 1995, pp. 505-512
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.