American consumers have no problem with carcinogens, but they will not purchase any product, including floor wax, that has fat in it.
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The lifetime feeding study of mice and rats appears to have less than a 50% probability of finding known human carcinogens. On the basis of probability theory, we would have been better off to toss a coin...The `definitive bioassay for carcinogenesis' as now designed has never been subjected to proper validation as an assay for human carcinogens. At attempt made in this paper to examine the literature suggests that it may have an unacceptably high false negative rate and that it produces so many contradictory answers as to suggest a very poor specificity.
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Our risk models are based on at least 50 assumptions, none of which has been scientifically demonstrated. For example, we assume that there is no difference between continuous (as in animal tests) or intermittent (as in human experience) dosages. But that ignores our growing knowledge of the way in which DNA repairs the human system . . .We feed rodents `all-you-can-eat' buffets every day, yet we know that caloric intake is the single greatest contributing cause of cancer [in rodents]. In fact, we found you can modify the cancer causing impact of one of the most potent carcinogens from 90% down to less than 3%, just by cutting caloric intake 20%.
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It has been conventional practice to test potential carcinogens using highly inbred strains of rodents. The rationale was the supposed superior reproducibility of results compared with those obtained from wild-type animals. However, that assumption can be questioned. At least three examples of genetic drift of inbred strains can be cited... Lifetime expectation [in an inbred strain of mice] of developing one or another form of neoplasm ['spontaneous tumour'] had risen from 10 to 80 percent.
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...of the 20 probable human non-carcinogens with conclusive animal bioassay results, only one, methotrexate, is negative, and the other 19 are positive... Thus, the standard interpretation of animal bioassay results provides essentially no differentiation between definite human carcinogens and probable human non-carcinogens.
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[Regarding tamoxifen, an anti-cancer drug] 'Experimentally, tamoxifen has carcinogenic potential. In some strains of rat, but not mouse or hamster, tamoxifen can cause liver cancers at doses as low as 5mg/kg per day... However, there are doubts about the correlation of [the results] with the risk of malignant disease even in rats, let alone in other rodents, mammals, or human beings. There are many uncertainties in extrapolating these experimental data from rats to women. The effect depends on bioavailability, hepatic [liver] blood flow, and hepatic [liver] metabolism to active genotoxic carcinogens, all of which differ enormously between rat and man.
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Warning is given not to carry over, without reservation, to man, the conclusions based on animal experiments. In monkeys none of the powerful carcinogens [of man] has been shown to produce cancers.
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The problem with animal carcinogenicity tests is not their lack of sensitivity for human carcinogens, but rather their lack of human specificity. A positive result has poor predictive value for humans.
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Let us look at some animal carcinogens – gold, DDT, clofibrate and bromocriptine. There is no doubt that all of these can rightly be regarded as carcinogenic for rodents, and yet there is really quite good evidence that they are not carcinogenic to man.
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