Table 1.

Definitions of strength-of-evidence descriptors for the evidence streams

Strength-of-Evidence descriptor	Evidence stream
	Cancer in humans	Cancer in experimental animals	Mechanistic evidence
Sufficient (or Strong for mechanistic evidence)	A causal association has been established: a positive association has been observed in the body of evidence on exposure to the agent and cancer in studies in which chance, bias, and confounding were ruled out with reasonable confidence.	A causal relationship has been established between exposure to the agent and cancer in experimental animals based on an increased incidence of malignant neoplasms or of an appropriate combination of benign and malignant neoplasms in (a) two or more species of animals or (b) two or more independent studies in one species carried out at different times or in different laboratories and/or under different protocols or (c) in both sexes of a single species in a well-conducted study.	Results in several different experimental systems are consistent, and the overall mechanistic database is coherent. Further support can be provided by studies that demonstrate experimentally that the suppression of key mechanistic processes leads to the suppression of tumour development. Typically, a substantial number of studies on a range of relevant end-points are available in one or more mammalian species*
Limited	A causal interpretation of the positive association observed in the body of evidence on exposure to the agent and cancer is credible, but chance, bias, or confounding could not be ruled out with reasonable confidence.	The data suggest a carcinogenic effect but are limited for making a definitive evaluation because, for example, (a) evidence of carcinogenicity is restricted to a single experiment; (b) the agent increases the incidence only of benign neoplasms or lesions of uncertain neoplastic potential; (c) the agent increases tumour multiplicity or decreases tumour latency but does not increase tumour incidence; (d) the evidence of carcinogenicity is restricted to initiation–promotion studies.	The evidence is suggestive, but, for example, (a) the studies cover a narrow range of experiments, relevant end-points, and/or species; (b) there are unexplained inconsistencies in studies of similar design; and/or (c) there is unexplained incoherence across studies of different end-points or in different experimental systems.
Inadequate	No data are available, or the available studies are of insufficient quality, consistency, or statistical precision to permit a conclusion to be drawn about the presence or the absence of a causal association between exposure and cancer.	The studies cannot be interpreted as showing either the presence or the absence of a carcinogenic effect because of major qualitative or quantitative limitations, or no data are available on cancer in experimental animals.	Few or no data are available; there are unresolved questions about the adequacy of the design, conduct, or interpretation of the studies; and/or the available results are negative.

^*Quantitative structure–activity considerations, in vitro tests in non-human mammalian cells, and experiments in non-mammalian species may provide corroborating evidence but typically do not in themselves provide strong evidence. However, consistent findings across a number of different test systems in different species may provide strong evidence