Why the dog was ever considered as an appropriate animal for carcinogenicity testing is also not entirely clear... Despite the obvious problems of study design and interpretation, carcinogenicity tests in the dog, lasting 7 years, were requested by regulatory authorities from the late 1960s...One of the best known examples of the inappropriate use of the dog was the carcinogenicity testing of hormonal contraceptives. It is now understood that mammogenesis in the dog is very different from that in primates; quantitative and qualitative differences exist in the feedback control mechanisms, receptor content and behaviour, and target sensitivity and responsivity. As a result of this biological difference there was a high incidence of mammary tumours in long-term studies in dogs treated with progestagens/contraceptive steroids such as lynestrol. Ultimately pressure from the scientific community led, relatively recently, to the requirement for carcinogenicity studies in dogs being dropped.
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Data from dose-response relationships are sometimes employed to estimate the expected tumour incidence at dose levels very much lower than those which could possibly be employed in conventional [animal] experiments. A number of mathematical models have been employed in such estimates and the results obtained vary considerably. Despite these uncertainties - and the possibly greater ones in extrapolating from animals to man - such models are often employed in some quarters to estimate the likely risk to man.
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