The Redundancy of Mouse Carcinogenicity Bioassays

Wittenau, M. Schach von; ESTES, PAUL C.

doi:10.1093/toxsci/3.6.631

Cited by 7 publications

(6 citation statements)

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“…Despite this high concordance, however, we believe that both sexes of two rodent species should continue to be used, in most studies, to determine the long-term toxicology and carcinogenesis effects of chemical exposures. Although some investigators feel that this high concordance implies that the mouse is redundant and should not be used in determining the carcinogenicity of chemicals (16), most national and international scientific guidelines for laboratory animal carcinogenicity studies (17)(18)(19) recommend that at least two species be used. Further, for the NCI/NTP studies the similarity in carcinogenic response between sexes within a species was greater than the redundancy across species.…”

Section: Resultsmentioning

confidence: 99%

Comparative results of 327 chemical carcinogenicity studies.

Haseman

Huff

Zeiger

et al. 1987

Environ Health Perspect

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and the National Toxicology Program (NTP) have carried out a number of laboratory animal carcinogenicity studies and presented the results of these experiments in a series of Technical Reports. This paper tabulates the results of the 327 NCI/NTP studies carried out to date on 308 distinct chemicals, and discusses certain issues relevant to the evaluation of carcinogenicity in these experiments. This compilation of results from NCI/NTP carcinogenicity experiments provides a large database that can be used to study structure-activity correlations, interspecies concordance, and associations between laboratory animal carcinogenicity and other toxicological effects.

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Section: Resultsmentioning

confidence: 99%

Comparative results of 327 chemical carcinogenicity studies.

Haseman

Huff

Zeiger

et al. 1987

Environ Health Perspect

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“…The suggestion that a single species is adequate for detection of potential hazardous chemicals (41) minimizes the importance of negative results in 2-yr studies. Two recent chemical evaluations illustrate this point.…”

Section: Discussionmentioning

confidence: 99%

“…The potential for differences in target organ responses are not included in most risk assessment paradigms. The justification of a 2-rodent system for evaluating chemicals for potential hazard is also based on a paradox: if "carcinogens" possess an inherent property ofproducing cancer, then one species should be sufficient, but if the carcinogenic activity is species-specific, then one can question the models as surrogates for humans (41). In fact, the procedure has been to consider that a chemical causing cancer in any sexhpecies combination, even in one of the 4 sexhpecies combinations, is a "carcinogen."…”

Section: History Of Rodent Bioassaysmentioning

confidence: 99%

Rodent Carcinogenicity Bioassay: Past, Present, and Future

1994

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Toxicitykarcinogenicity studies in rodents have played a pivotal role in identifying chemicals that are potentially hazardous to humans. In fact, nearly all of the known human carcinogens are also carcinogenic in 1 or more rodent species. During the past 20 yr the quality and consistency of rodent studies has improved considerably, and much has been learned about mechanisms whereby chemicals initiate or promote the carcinogenic process in rats and mice. The process of identifying chemicals that cause toxicity or carcinogenicity in rodents is quite well established, but the procedures for extrapolating this data for risk management decisions in the protection of human health have lagged far behind. While many would accept the assumptions that genotoxic chemicals that cause cancer in animals pose a cancer risk to humans and that genotoxic chemicals causing cancer at high doses pose a risk at lower doses, there is much less certainty with respect to nongenotoxic chemicals. The confusion about risk extrapolation for nongenotoxic chemicals has often lead to criticism of the hazard identification process for chemicals in general. There is increasing awareness of the complexity of the carcinogenic process that has made species extrapolation and dose extrapolation from rodent studies to humans more complex. Although newer molecular biological techniques and cell kinetic measurements offer exciting possibilities for better risk assessment, it is the combination of welldesigned rodent studies with appropriate mechanistic studies that offers the best hope for regulatory decisions based on sound scientific principles._.

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“…Mouse only positive findings are typically due to the mouse liver tumor response (13 [Vainio et al (17)]. (6,10,16).…”

Section: Bioassaymentioning

confidence: 99%