and renal tumors in laboratory animals and to a lesser extent from epidemiologic evidence. EPA’s decision to characterize tetrachloroethylene as likely to be a human carcinogen as opposed to “carcinogenic to humans” appropriately reflects that there could be deficiencies or potential inaccuracies in interpretation of the data. Some of those possible deficiencies and inaccuracies are discussed below for each of the data sets.

BOX 11-1

EPA Cancer Guidance for Concluding a Chemical Is Likely to Be Carcinogenic to Humans (EPA 2005)

This descriptor is appropriate when the weight of evidence is adequate to demonstrate carcinogenic potential to humans but does not reach the weight of evidence for the descriptor “Carcinogenic to Humans.” Adequate evidence consistent with this descriptor covers a broad spectrum. As stated previously, the use of the term “likely” as a weight of evidence descriptor does not correspond to a quantifiable probability. The examples below are meant to represent the broad range of data combinations that are covered by this descriptor; they are illustrative and provide neither a checklist nor a limitation for the data that might support use of this descriptor. Moreover, additional information, e.g., on mode of action, might change the choice of descriptor for the illustrated examples. Supporting data for this descriptor may include:

  • an agent demonstrating a plausible (but not definitively causal) association between human exposure and cancer, in most cases with some supporting biological, experimental evidence, though not necessarily carcinogenicity data from animal experiments;

  • an agent that has tested positive in animal experiments in more than one species, sex, strain, site, or exposure route, with or without evidence of carcinogenicity in humans;

  • a positive tumor study that raises additional biological concerns beyond that of a statistically significant result, for example, a high degree of malignancy, or an early age at onset;

  • 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, for example, either plausible (but not definitively causal) 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 (such as DNA reactivity or effects on cell growth control) likely to be related to the tumor response in this case.



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