Evidence for Regulatory Cancer Risk Assessment

Determining whether an observed association (risk) is causal rather than spurious involves consideration of a number of factors. Sir Bradford Hill (Hill 1965) developed a set of guidelines for evaluating epidemiologic associations that can be used in conjunction with the discussion of causality.  

the EPA opts for a causal analysis (that parallels and updates Hill s initial work consisting of nine criteria) forjudging causation (EPA 2005)  

Specificity of the Observed Association. Based on our current understanding that many agents cause cancer at multiple sites, and many cancers have multiple causes, this is now considered one of the weaker guidelines for causality. Thus, although the presence of specificity may support causality, its absence does not exclude it. 

Temporal Relationship of the Observed Association. A causal interpretation is strengthened when exposure is known to precede development of the disease. This is among the strongest criteria for an inference of causality. 

Biological Plausibility. An inference of causality tends to be strengthened by consistency with data from experimental studies or other sources demonstrating plausible biological mechanisms. A lack of mechanistic data, however, is not a reason to reject causality. 

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