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Toxicity studies in rats of simple mixtures of chemicals with the same or different target organs

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Author: Feron, V.J. · Groten, J.P. · Zorge, J.A. van · Cassee, F.R. · Jonker, D. · Bladeren, P.J. van
Institution: Instituut CIVO-Toxicologie en Voeding TNO
Source:Toxicology Letters, 82-83, 505-512
Identifier: 52806
doi: DOI:10.1016/0378-4274(95)03580-X
Keywords: Toxicology · Animals · Irritants · Kidney · Rats · Respiration · Toxicology


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 mixtures and exposure conditions the additivity assumption did not hold. However, the additivity rule appeared to be applicable to mixtures of chemicals with the same target organ and the same mechanism of action or receptor. Fractional 2-factorial study designs were found to be promising tools for examining possible combined actions or interactions of chemicals in a mixture.