1-3 Butadiene, an important industrial chemical and a common environmental air pollutant, has been shown to be a weak carcinogen in the rat, but a potent carcinogen in the B6C3F1 mouse. This species difference makes risk extrapolation to humans difficult, and the underlying mechanism must be clarified before meaningful risk extrapolation to humans can be made.
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Extrapolating from one species to another is fraught with uncertainty... For almost all of- the chemicals tested to date, rodent bio-assays have not been cost-effective. They give limited and uncertain information on carcinogenicity, generally give no indication of mechanism of action, and require years to complete.' [They are] 'rarely the best approach for deciding whether to classify a chemical as a human carcinogen.
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The principal method of determining potential carcinogenicity of substances is based on studies of daily administration of huge doses of chemicals to inbred rodents for a lifetime. Then by questionable models, which include large safety factors, the results are extrapolated to effects of minuscule doses in humans... The rodent MTD test that labels plant chemicals as cancer-causing in humans is misleading. The test is likewise of limited value for synthetic chemicals. The standard carcinogen tests that use rodents are an obsolescent relic of the ignorance of past decades.
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Even when there are common target sites for a given carcinogen, there are usually important differences, between man and animals, and between different species and strains of animals. These 'spontaneous' tumours in rats and mice... [vary] widely according to sex, strain, diet, conditions of maintenance, hormonal status, immunological status and latent virus infections.
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