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HERO ID
195022
Reference Type
Journal Article
Subtype
Review
Title
Chemical structure, Salmonella mutagenicity and extent of carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested in rodents by the U.S. NCI/NTP
Author(s)
Ashby, J; Tennant, RW
Year
1988
Is Peer Reviewed?
1
Journal
Mutation Research
ISSN:
0027-5107
EISSN:
1873-135X
Report Number
EMICBACK/69987
Volume
204
Issue
1
Page Numbers
17-115
Language
English
PMID
3277047
DOI
10.1016/0165-1218(88)90114-0
Abstract
A survey has been conducted of 222 chemicals evaluated for carcinogenicity in mice and rats by the United States NCI/NTP. The structure of each chemical has been assessed for potential electrophilic (DNA-reactive) sites, its mutagenicity to Salmonella recorded, and the level of its carcinogenicity to rodents tabulated. Correlations among these 3 parameters were then sought. A strong association exists among chemical structure (S/A), mutagenicity to Salmonella (Salm.) and the extent and sites of rodent tumorigenicity among the 222 compounds. Thus, a approximately 90% correlation exists between S/A and Salm. across the 115 carcinogens, the 24 equivocal carcinogens and the 83 non-carcinogens. This indicates the Salmonella assay to be a sensitive method of detecting intrinsic genotoxicity in a chemical. Concordance between S/A and Salm. have therefore been employed as an index of genotoxicity, and use of this index reveals two groups of carcinogens within the database, genotoxic and putatively non-genotoxic. These two broad groups are characterized by different overall carcinogenicity profiles. Thus, 16 tissues were subject to carcinogenesis only by genotoxins, chief among which were the stomach, Zymbal's glands, lung, subcutaneous tissue and circulatory system. Conclusions of carcinogenicity in these 16 tissues comprised 31% of the individual chemical/tissue reports of carcinogenicity. In contrast, both genotoxins and non-genotoxins were active in the remaining 13 tissues, chief among which was the mouse liver which accounted for 24% of all chemical/tissue reports of carcinogenicity. Further, the group of 70 carcinogens reported to be active in both species and/or in 2 or more tissues contained a higher proportion of Salmonella mutagens (70%) than observed for the group of 45 single-species/single-tissue carcinogens (39%). 30% of the 83 non-carcinogens were mutagenic to Salmonella. This confirms earlier observations that a significant proportion of in vitro genotoxins are non-carcinogenic, probably due to their non-absorption or preferential detoxification in vivo. Also, only 30% of the mouse liver-specific carcinogens were mutagenic to Salmonella. This is consistent with tumors being induced in this tissue (and to a lesser extent in other tissues of the mouse and rat) by mechanisms not dependent upon direct interaction of the test chemical with DNA. Detection of 103 of the 115 carcinogens could be achieved by use of only male rats and female mice.(ABSTRACT TRUNCATED AT 400 WORDS)
Keywords
Animals; *Carcinogens; Human; *Mutagenicity Tests; *Mutagens; Rodentia; Salmonella typhimurium/*genetics; Structure-Activity Relationship
Tags
IRIS
•
BBP (Butyl benzyl phthalate)
Literature Search
LitSearch Dec 2012
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1,2-Dibromo-3-chloropropane
Litsearch 2018
Toxline
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Hexachloroethane (HCE) (Final, 2011)
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