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.
|
The standard carcinogenicity bioassay, which involves treating two rodent species for a minimum of 2 years, at a range of doses, is acknowledged to be an insensitive tool because of the background `noise' of spontaneous disease. Most strains of rat used in such studies have high incidence of pituitary and mammary tumours; some inbred rat strains frequently develop leukaemia or testicular tumours; mice strains show high incidence of malignant lymphomas and liver tumours.
|
...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.
|