Table 9.

Guidance for Consideration of Evidence in Support of Cancer Descriptors (Adapted from EPA 2005 Guidelines for Carcinogen Risk Assessment)

Cancer Descriptor	Sufficient Evidence
Carcinogenic to humans	Convincing evidence of causal association between human exposure and cancer (e.g., from well conducted cohort study[ies]).
	OR
	Strong evidence of association between human exposure and cancer or key precursor events AND extensive evidence of carcinogenicity in animals AND mode(s) of action identified in animals AND strong evidence that mode(s) of action identified in animals occur in humans.
Likely to be carcinogenic to humans	Plausible (but not definitively causal) association between human exposure and cancer in most cases with some supporting biological and experimental evidence (not necessarily carcinogenicity data from animal experiments).
	OR
	An agent that has tested positive in animal experiments in more than one species, sex, strain, or exposure route, with or without evidence of carcinogenicity in humans.
	OR
	A positive tumor study that raises additional biological concerns beyond that of a statistically significant result, e.g., a high degree of malignancy, or an early age at onset.
	OR
	A rare animal tumor response in a single experiment that is assumed to be relevant to humans.
	OR
	A positive tumor study that is strengthened by other lines of evidence, e.g., either plausible association between human exposure and cancer or evidence that the agent or an important metabolite causes events generally known to be associated with tumor formation or likely to be related to the tumor response in the this particular case.
Suggestive evidence of carcinogenic potential	A small and possible not statistically significant increase in tumor incidence observed in a single animal or human study that does not reach the weight of evidence for “Likely to be carcinogenic to humans”. The study findings would generally not be contradicted by other similar studies of equal quality.
	OR
	A small increase in tumor with a high background rate in that sex and strain when there is some evidence that the observed tumors may be due to intrinsic factors that cause background tumors and not due to the agent being assessed.
	OR
	Evidence of a positive response in a study whose power, design, or conduct limits the ability to draw a confident conclusion, but where the carcinogenic potential is strengthened by other lines of evidence (e.g., structure activity relationships).
	OR
	A statistically significant increase at one dose only, but no significant response at other doses and no overall trend.
Inadequate information to assess carcinogenic potential	Little or no pertinent information
	OR
	Conflicting evidence in studies of equal quality
	OR
	Negative results that are not sufficiently robust to support “Not likely to be carcinogenic to humans”
Not likely to be carcinogenic to humans	Animal evidence that demonstrates lack of carcinogenic effect in both sexes in at least two appropriate animal species (in absence of other animal or human data suggesting a potential for cancer effects)
	OR
	Convincing and extensive experimental evidence showing that the only carcinogenic effects observed in animals are not relevant to humans
	OR
	Convincing evidence that carcinogenic effects are not likely by a particular exposure route
	OR
	Convincing evidence that carcinogenic effects are not likely below a defined dose range