発癌物質の同定とリスク評価の新動向 : メカニズム知見を重視した個々の物質の個々人へのリスク評価

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Recent advanced knowledge in mechanism of multistage carcinogenesis is changing the way by which we identify carcinogens and estimate their risks to human. Thus, IARC monographs on carcinogen evaluation now incorporate mechanistic information as an important component for the final classification of agents for their carcinogenic risk to humans. The NTP and EPA of USA also consider full use of mechanistic information. These trends reflect the progress made not only in biological sciences, but also in regulatory sciences, both of which now realize that more solid scientific information and less default assumptions can be used for risk assessment of carcinogens. The use of mechanistic information on cancer hazard identification and risk assessment is often regarded as if a revolutionary step had been created. However, it is only in fact a form of evolution from earlier practice. In the past, we used data from mutation assays, as well as those derived from cytogenetic studies, for identifying carcinogens. These endpoints were based upon our mechanistic understanding of carcinogenesis at that time, according to which carcinogenesis involved gene and chromosomal mutations. We have thus been using mechanistic information for a long time. Then, why a seemingly new era is being welcomed? A major reason may stem from the fact that both scientists and regulators started to realize that we can do better than hazard identification based on"white"and"black"decisions. Thus, we started to characterize hazard, using mechanistic information so that we can provide better basis for risk assessment. At the same time, we started to realize that not all carcinogens are mutagenic and thus"non-genotoxic"mechanisms of carcinogenesis have attracted much attention. Since numerous cellular molecules are possible targets of non-genotoxic activities of agents, it is more practical to study various chemicals with working hypothesis rather than making efforts to establish short-term tests based on individual endpoints. There have been, and still are, attempts to categorize agents based on mechanistic information, in the hope that risk assessment will thus be simplified. Such categories include"genotoxix/nongenotoxic", "tumor-initiating/-promoting"and"peroxisome proliferation inducing"agents. It is my personal view that such categorization is not only useless, but sometimes impedes the conduct of meaningful risk assessment. Since we usually evaluate the possible risk of"individual"agents rather than as a"group"or a"category", there is no need to group agents. As we need to evaluate"individual"agents, risk assessment needs to be conducted also for"individuals"rather than for"general population";even if we are exposed to a given agent at a similar level, the actual risks we receive from it heavily depends on host factors of individuals. (This paper, chaired by Taijiro Matsushima, was presented as the special lecture at the 26th annual meeting of the Environmental Mutagen Society of Japan, and held at the Hadano Culture Hall in Hadano, Japan, December 3-5, 1997.)
日本環境変異原学会の論文
1998-10-31

発癌物質の同定とリスク評価の新動向 : メカニズム知見を重視した個々の物質の個々人へのリスク評価

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