Appropriate models and an understanding of carcinogenic mechanisms--requirements for hazard risk assessment

Given the immense variety of compounds developed for introduction into the human environment, appropriate carcinogen risk assessment is essential. One of the responsible international bodies recognized as providing a lead in this endeavour is the International Agency for Research on Cancer (IARC), primarily through the Monographs on the Evaluation of Carcinogenic Risks to Humans. However, serious allegations have recently been made that industry now has undue influence on the decisions of the IARC Workshops as to category assignment, especially concerning down-grading of risk. The contention is that too much stress is placed on mechanistic considerations which have not been sufficiently validated. Since avoidance of carcinogens in our environment is clearly of prime importance to cancer prevention, open discussion of how they should be identified is of essential significance to the APOCP. Clearly, decisions should be based solely on scientific evidence and there should be no place for politics or polemic. We have therefore looked, in what we hope is a dispassionate fashion, at the arguments offered in the recent literature, while admitting to a bias towards taking into account all the available knowledge on mechanisms of action of carcinogens and modulating agents. As scientists, generation of an understanding of this area is one of the main reasons why we receive our salaries. To blindly argue that carcinogenicity, for example at high dose in one strain of experimental animal, necessarily implies human risk at normal levels of exposure is obviously untenable. At the same time, precipitous conclusions regarding species-specific mechanisms must naturally be avoided. Both academic and industrial researchers need to apply a balanced judgement and to simply imply that any association with industrial concerns is likely to lead to irresponsible behaviour to the detriment of public health is not tenable. With regard to regulatory decision making, we should be concentrating more attention on mechanisms, rather than less, especially in light of recent findings pointing to hormesis at low doses of carcinogens, which will inevitably generate heated discussion and the charge of bias in favour of industry. The onus is on all members of the scientific community to impartially view all the epidemiological and experimental data which are available in decision-making.