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  • Title: [Assessment of cumulative risk of mixtures with multiple target organs].
    Author: Galli CL, Marinovich M.
    Journal: G Ital Med Lav Ergon; 2003; 25(3):328-9. PubMed ID: 14582250.
    Abstract:
    Humans are exposed to very complex environmental mixtures. In contrast to this reality, most laboratory investigations of mixtures, with exception of mutagenicity assays, have focused on mixtures comprised of a few chemicals. Component-based approaches that use information on the individual chemical contained in the mixture are not by themselves sufficient for complex, environmental mixtures because significant portions of the mixtures mass are unidentified. Assessment of the cumulative risk posed by exposure to multiple chemicals is a problem the USEPA's and FDA's program discuss regularly. In USA the Food Quality Protection Act of 1996 directs the Office of Pesticide Programs to include in its assessments the risk associated with the cumulative effects of pesticides that have a common mode of action. organophosphorus pesticides (OPs) have been the first class addressed, based on the common mechanism of acetylcholinesterase inhibition. Interestingly toxicity studies focussing on component-based analysis of mixtures indicated that for chemicals not sharing the same target and mechanism, the type of combined action or interaction found when each chemical in the mixture was present at clearly toxic effect levels did not predict the response observed when each chemical was present at or below the lowest observed adverse effect level (LOAEL). Moreover, mixtures of chemicals produced toxicity only for those chemicals that showed the same toxic effect on the same target organ when given singly at dose above the LOAEL values. However, end-points chosen in routine toxicity studies do not offer a wide dynamic range of testable, significant responses around and above the NOAEL. So far sensitive methods that detect low level changes have not yet been employed in mixtures testing protocol. Toxicogenomics integrated functional genomics with classical toxicology and we believe that it has great potential to revolutionize mixtures research.
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