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Interspecies extrapolation in carcinogenesis: prediction between rats and mice.
Open accessAbstract
Interspecies extrapolation in carcinogenesis is studied by evaluating prediction from rats to mice and from mice to rats. The Carcinogenic Potency Database, which includes 3500 cancer tests conducted in rats or mice on 955 compounds, is used for the analysis. About half of the chemicals tested for carcinogenicity are positive in at least one test, and this proportion is similar when rats and mice are considered separately. For 392 chemicals tested in both species, 76% of the rat carcinogens are positive in the mouse, and 70% of mouse carcinogens are positive in the rat. When compounds composed solely of chlorine, carbon, hydrogen, and, optionally, oxygen are excluded from the analysis, 75% of mouse carcinogens are positive in the rat. Overall concordance (the percentage positive in both species plus the percentage negative in both) is 76%. Three factors that affect prediction between rats and mice are discussed: chemical class, mutagenicity in the Salmonella assay, and the dose level at which a chemical is toxic. Prediction is more accurate for mutagens than non-mutagens and for substances that are toxic at low (versus only at high) doses. Species differences are not the result of failure in the bioassay to attain the maximum tolerated dose in the negative species or of more frequent testing in the positive species. An analysis of the predictive value of positivity for the 10 most common target sites indicates that most sites are good predictors of carcinogenicity at some site in the other species; the poorest predictors among these common sites are the rat urinary bladder and the mouse liver.
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“For many toxicological endpoints, even closely related species such as the mouse and rat do not predict effects in each other (Gold et al., 1989; Tomatis et al., 1973).”
From The use of whole food animal studies in the safety assessment of genetically modified crops: Limitations and recommendations (2013) · cites this paper as Gold et al., 1989
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Metadata
- Authors
- Gold, L. S., Bernstein, L., Magaw, R., & Slone, T. H.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- ORCID
- Bernstein, L
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 1989-05
- Volume
- 81
- Pages
- 211-219
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- OpenAlex
- W2101380195
- Cited by
- 131
- References
- 29
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 7.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy
- National Institute of Environmental Health Sciences (222-Y01-ES-10066)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Life Sciences › Agricultural and Biological Sciences › Food Science › Agricultural safety and regulations
- Keywords
- interspecies extrapolation, carcinogenesis, carcinogenicity prediction, chemical classes, Salmonella mutagenicity, dose levels, target sites, urinary bladder, liver, species differences
- MeSH terms
- Animals, Carcinogens, Female, Male, Neoplasms, Experimental, Predictive Value of Tests, Species Specificity, Carcinogenicity Tests, Mice, Rats
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