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40 Years of the Salmonella Mutagenicity Assay: Implications for 21st Century Toxicology
DEMARINI, D. M. 40 Years of the Salmonella Mutagenicity Assay: Implications for 21st Century Toxicology. Presented at Italian Environmental Mutagen Society (SIMA), Parma, ITALY, September 29, 2011.
The Salmonella mutagenicity assay now has the .largest data base of any mutagenicity assay, consisting of hundreds of thousands of compounds and mixtures. The assay is part of the standard battery of genetic toxicity testing for all drug and chemical regulatory agencies.
The Salmonella (Ames) mutagenicity assay was developed and introduced by Bruce Ames and colleagues in 1971. Since then, it has become the standard assay for hazard identification of mutagens worldwide. It is a first-tier test for mutagenic activity in the pharmaceutical and chemical industries, as well as for evaluating air, water, and other environmental samples for mutagenic activity. It is also used for human biomonitoring to assess mutagenic exposure by measuring urinary mutagenicity. The Salmonella mutagenicity assay now has the .largest data base of any mutagenicity assay, consisting of hundreds ofthousands of compounds and mixtures. The assay is part of the standard battery of genetic toxicity testing for all drug and chemical regulatory agencies. Recently, some states and countries have begun using the assay to regulate source water for drinking water and also industrial effluents. Molecular analyses of the mutants (revertants) have found a strong relationship between mutation spectra induced by environmental agents in Salmonella and those in other assays, including cancer genes in human tumors associated with exposure to those agents. Nearly all of the 103 IARC-declared Group 1 human are positive in this assay. The assay is ~70% predictive for carcinogenicity in rodents, which is similar to the correlation between mouse and rat carcinogenicity. For particular chemical classes, the assay is highly predictive of rodent carcinogenicity (~1 00% for aromatic amines or PAHs), but for other classes, such as chlorinated organics, it is poorly predictive (~20-40%). There is not yet a replacement assay for primary genetic toxicity testing that is as reliable, inexpensive, and rests on such a large data base as the Salmonella mutagenicity assay. However, exciting developments are underway involving systems biology, high-throughput screening, and toxicogenomics that hold the promise for assays that are faster, cheaper, and perhaps more informative than the Salmonella mutagenicity assay for screening mutagenic and potential carcinogenic agents. Until that time, however, the Salmonella mutagenicity assay will continue to be used for genetic toxicity testing and environmental and human biomonitoring well into the 21st century. [Abstract does not necessarily reflect the policy ofthe US EPA.]
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
GENETIC AND CELLULAR TOXICOLOGY BRANCH