Predicting the carcinogenicity of chemicals in humans from rodent bioassay data

Journal Article · Thu Aug 01 04:00:00 EDT 1991 · Environmental Health Perspectives; (United States)

DOI:https://doi.org/10.2307/3431313· OSTI ID:6097652

Goodman, G ^[1]; Wilson, R ^[2]

---

1. Harvard Univ., Cambridge, MA (United States) School of Public Health, Boston, MA (United States)
2. Harvard Univ., Cambridge, MA (United States)

Regulatory agencies currently rely on rodent carcinogenicity bioassay data to predict whether or not a given chemical poses a carcinogenic threat to humans. The authors argue that it is always more useful to know a chemical's carcinogenic potency (with confidence limits) than to be able to say only qualitatively that it has been found to be a carcinogen. In a typical bioassay, a chemical is administered to groups of 50 to 100 rodents at the highest feasible level (the maximum tolerated dose) and rarely at less than 1/10 this dose in order to maximize the statistical significance of any increase in tumors that might result. Recently, much experimental work has focused on the mechanisms by which site-specific toxicity arising from chronic administration at the maximum tolerated dose may lead to carcinogenicity. Extrapolation of high-dose results to low dose does not take into consideration the possibility of a threshold dose, below which the carcinogenic potency is much lower or even zero. Threshold dose-response phenomena may be much more relevant to the etiology of cancer in the rodent bioassays than was earlier realized; if so, there is an even greater need for establishing dose-dependent potency estimates. The emphasis of this review is in the interspecies comparison of high-dose potencies. The qualitative and quantitative comparison of carcinogenicities between mice and rats and between rodents and humans is reviewed and discussed. They conclude that there is a good qualitative (yes/no) correlation for both the rat/mouse and the rodent/human comparison.

• OSTI ID: 6097652
• Journal Information: Environmental Health Perspectives; (United States), Journal Name: Environmental Health Perspectives; (United States) Vol. 94; ISSN 0091-6765; ISSN EVHPA
• 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.
AMINES
ANIMALS
ANTINEOPLASTIC DRUGS
AROMATICS
ARSENIC COMPOUNDS
BENZENE
BENZIDINE
BIOASSAY
BIPHENYL
CARBOXYLIC ACIDS
CARCINOGENESIS
CARCINOGENS
CHLORAMBUCIL
CHLORINATED ALIPHATIC HYDROCARBONS
CHROMIUM COMPOUNDS
COAL TAR
CORRELATIONS
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EXTRAPOLATION
HALOGENATED ALIPHATIC HYDROCARBONS
HYDROCARBONS
MAMMALS
MAN
MONOCARBOXYLIC ACIDS
NEOPLASMS
NUMERICAL SOLUTION
ORGANIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
OTHER ORGANIC COMPOUNDS
PATHOGENESIS
PRIMATES
RISK ASSESSMENT
RODENTS
TAR
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES
VINYL CHLORIDE