Extrapolation of carcinogenicity between species: Qualitative and quantitative factors

Journal Article · Tue Dec 01 04:00:00 EST 1992 · Risk Analysis; (United States)

DOI:https://doi.org/10.1111/j.1539-6924.1992.tb00714.x· OSTI ID:6899623

Gold, L S ^[1]; Manley, N B; Ames, B N ^[2]

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1. Lawrence Berkeley Lab., CA (United States) Univ. of California, Berkeley (United States)
2. Univ. of California, Berkeley (United States)

Prediction of human cancer risk from the results of rodent bioassays requires two types of extrapolation: a qualitative extrapolation from short-lived rodent species to long-lived humans, and a quantitative extrapolation from near-toxic doses in the bioassay to low-level human exposures. Experimental evidence on the accuracy of prediction between closely related species tested under similar experimental conditions (rats, mice, and hamsters) indicates that: (1) if a chemical is positive in one species, it will be positive in the second species about 75% of the time; however, since about 50% of test chemicals are positive in each species, by chance alone one would expect a predictive value between species of about 50%. (2) If a chemical induces tumors in a particular target organ in one species, it will induce tumors in the same organ in the second species about 50% of the time. Similar predictive values are obtained in an analysis of prediction from humans to rats or from humans to mice for known human carcinogens. Limitations of bioassay data for use in quantitative extrapolation are discussed, including constraints on both estimates of carcinogenic potency and of the dose-response in experiments with only two doses and a control. Quantitative extrapolation should be based on an understanding of mechanisms of carcinogenesis, particularly mitogenic effects that are present at high and not low doses.

• DOE Contract Number: AC03-76SF00098
• OSTI ID: 6899623
• Journal Information: Risk Analysis; (United States), Journal Name: Risk Analysis; (United States) Vol. 12:4; ISSN 0272-4332; ISSN RIANDF
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOASSAY
CARCINOGEN SCREENING
CARCINOGENESIS
CARCINOGENS
DISEASES
EXTRAPOLATION
HAMSTERS
MAMMALS
MAN
MICE
NEOPLASMS
NUMERICAL SOLUTION
PATHOGENESIS
PRIMATES
RATS
RISK ASSESSMENT
RODENTS
SCREENING
VERTEBRATES