The redundancy of mouse carcinogenicity bioassays

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

doi:10.1016/s0272-0590(83)80114-6

Cited by 36 publications

(6 citation statements)

References 17 publications

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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: Discussionmentioning

confidence: 99%

Comparative Results of 327 Chemical Carcinogenicity Studies

Haseman¹,

Huff²,

Zeiger³

et al. 1987

Environmental Health Perspectives

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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: Discussionmentioning

confidence: 99%

Comparative Results of 327 Chemical Carcinogenicity Studies

Haseman¹,

Huff²,

Zeiger³

et al. 1987

Environmental Health Perspectives

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“…Some authors (Von Wittenau and Estes, 1983) have suggested that carcinogenicity testing in the mouse is "redundant" and that male and female rats are sufficient for the detection of most carcinogens. The present data suggest that if one wishes to halve the number of sex-species groups tested, a better choice would be male rats in conjunction with female mice.…”

Section: Discussionmentioning

confidence: 99%

Results from 86 two‐year carcinogenicity studies conducted by the national toxicology program

Haseman

Crawford

Huff

et al. 1984

Journal of Toxicology and Environmental Health

100

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Five categories of evidence of carcinogenicity in rats and mice were used to group interpretative results on 86 chemicals studied in recent carcinogenicity tests carried out by the National Toxicology Program (NTP). Of these studies, 50% (43/86) were regarded as showing carcinogenic effects, 42% (36/86) gave no evidence of carcinogenicity, 6% (5/86) showed equivocal evidence of carcinogenicity, and 2% (2/86) were regarded as inadequate experiments. The liver was the most frequent site of cancer in male and female Fischer-344 rats and in male and female B6C3F1 mice. Male rats appeared more sensitive than female rats to the induction of neoplasia, while for mice the females seemed more responsive. The routes of administration yielding the highest percentage (80-83%) of positive studies were gavage and inhalation; approximately one-third of the feed, drinking water, and dermal studies showed carcinogenic effects. In feeding studies, overall survival in dosed and control groups were similar, while the majority of gavage studies showed significantly reduced survival in one or more dosed groups relative to the corresponding controls. The overall percentage of studies showing carcinogenic effects (50%) agrees closely with the rate reported by other investigators for nearly 200 earlier carcinogenicity experiments conducted by the National Cancer Institute.

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“…The Fischer inbred (F344) rat and the B6C3F1 hybrid mouse are commonly chosen for carcinogen bioassay, in large part because of the experience gained by the NCI from their use (488,503,511). Despite its long history, the continued use of the B6C3F1 hybrid mouse by the NTP is currently under review because of the difficulty in interpreting the significance of proliferative liver lesions (488,492,493,503,512,514). The merits of using only a rat strain instead of both a rat and a mouse strain have also been recently discussed (514).…”

Section: Ad Hoc Panel On Chemical Carcinogenesis Testing Andmentioning

confidence: 99%

“…Despite its long history, the continued use of the B6C3F1 hybrid mouse by the NTP is currently under review because of the difficulty in interpreting the significance of proliferative liver lesions (488,492,493,503,512,514). The merits of using only a rat strain instead of both a rat and a mouse strain have also been recently discussed (514). This issue and others relating to species selection are considered in the NTP Ad Hoc Panel's Report (503).…”

Section: Ad Hoc Panel On Chemical Carcinogenesis Testing Andmentioning

confidence: 99%

Chemical carcinogens: a review of the science and its associated principles. U.S. Interagency Staff Group on Carcinogens

1986

Environ Health Perspect

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In order to articulate a view of chemical carcinogenesis that scientists generally hold in common today and to draw upon this understanding to compose guiding principles that can be used as a bases for the efforts of the regulatory agencies to establish guidelines for assessing carcinogenic risk to meet the specific requirements of the legislative acts they are charged to implement, the Office of Science and Technology Policy, Executive Office, the White House drew on the expertise of a number of regulatory agencies to elucidate present scientific views in critical areas of the major disciplines important to the process of risk assessment. The document is composed of two major sections, Principles and the State-of-the-Science. The latter consists of subsections on the mechanisms of carcinogenesis, short-term and long-term testing, and epidemiology, which are important components in the risk assessment step of hazard identification. These subsections are followed by one on exposure assessment, and a final section which includes analyses of dose-response (hazard) assessment and risk characterization. The principles are derived from considerations in each of the subsections. Because of present gaps in understanding, the principles contain judgmental (science policy) decisions on major unresolved issues as well as statements of what is generally accepted as fact. These judgments are basically assumptions which are responsible for much of the uncertainty in the process of risk assessment. There was an attempt to clearly distinguish policy and fact. The subsections of the State-of-the-Science portion provide the underlying support to the principles articulated, and to read the "Principles" section without a full appreciation of the State-of-the-Science section is to invite oversimplification and misinterpretation. Finally, suggestions are made for future research efforts which will improve the process of risk assessment.

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The redundancy of mouse carcinogenicity bioassays

Cited by 36 publications

References 17 publications

Comparative Results of 327 Chemical Carcinogenicity Studies

Comparative Results of 327 Chemical Carcinogenicity Studies

Results from 86 two‐year carcinogenicity studies conducted by the national toxicology program

Chemical carcinogens: a review of the science and its associated principles. U.S. Interagency Staff Group on Carcinogens

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