The Salmonella mutagenicity assay: the stethoscope of genetic toxicology for the 21st century.
OBJECTIVE
According to the 2007 National Research Council report Toxicology for the Twenty-First Century, modern methods (e.g., "omics," in vitro assays, high-throughput testing, computational methods) will lead to the emergence of a new approach to toxicology. The Salmonella mammalian microsome mutagenicity assay has been central to the field of genetic toxicology since the 1970s. Here we document the paradigm shifts engendered by the assay, the validation and applications of the assay, and how the assay is a model for future in vitro toxicology assays.


METHODS
We searched PubMed, Scopus, and Web of Knowledge using key words relevant to the Salmonella assay and additional genotoxicity assays.


METHODS
We merged the citations, removing duplicates, and categorized the papers by year and topic.


RESULTS
The Salmonella assay led to two paradigm shifts: that some carcinogens were mutagens and that some environmental samples (e.g., air, water, soil, food, combustion emissions) were mutagenic. Although there are > 10,000 publications on the Salmonella assay, covering tens of thousands of agents, data on even more agents probably exist in unpublished form, largely as proprietary studies by industry. The Salmonella assay is a model for the development of 21st century in vitro toxicology assays in terms of the establishment of standard procedures, ability to test various agents, transferability across laboratories, validation and testing, and structure-activity analysis.


CONCLUSIONS
Similar to a stethoscope as a first-line, inexpensive tool in medicine, the Salmonella assay can serve a similar, indispensable role in the foreseeable future of 21st century toxicology.
Claxton
Larry D
LD
Genetic and Cellular Toxicology Branch, Integrated Systems Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Umbuzeiro
Gisela de A
Gde A
DeMarini
David M
DM
D001681:Biological Assay / Q000379:methods*; D008861:Microsomes / Q000187:drug effects; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D012475:Salmonella / Q000187:drug effects* / Q000235:genetics
D009153:Mutagens