The next "extrapolation" we make is from effects observed from animal testing to expected human effects. This is not an "extrapolation" in the scientific or mathematical sense of that word. It is an assumption based on the fact that many biological systems are the same among different species, and that the closer (philogenetically) the species are, the more biological systems are the same, and thus the effects observed would also be the same. While this is logical and often true, it is not a scientific law or principle. For example, of chemicals tested for cancer in both rats and mice, only about half were carcinogenic in both species. On the other hand, of the chemicals that are known to cause cancer in humans, almost all of them cause cancer in laboratory animals. While there is little scientific certainty in the "animal to human extrapolation," it is the best we can do.
This may be a good time to present the EPA "Weight of Evidence" carcinogen ranking scheme:
Carcinogenic To Humans: This descriptor is appropriate when there is convincing epidemiologic evidence demonstrating causality between human exposure and cancer, or exceptionally when there is strong epidemiological evidence, extensive animal evidence, knowledge of the mode of action, and information that the mode of action is anticipated to occur in humans and progress to tumors.
Likely To be Carcinogenic To Humans: This descriptor is appropriate when the available tumor effects and other key data are adequate to demonstrate carcinogenic potential to humans, but does not reach the weight-of-evidence for the descriptor “carcinogenic to humans.”
Suggestive Evidence of Carcinogenic Potential: This descriptor is appropriate when the evidence from human or animal data is suggestive of carcinogenicity, which raises a concern for carcinogenic effects but is judged not sufficient for a stronger conclusion.
Inadequate Information to Assess Carcinogenic Potential: This descriptor is used when available data are judged inadequate to perform an assessment.
Not likely To Be Carcinogenic To Humans: This descriptor is used when the available data are considered robust for deciding that there is no basis for human hazard concern. Dose-Response Assessment is the determination of the shape and form of the relationship.
[Here's more on the EPA Guidance, if you are interested.]
This is a "weight-of-evidence" ranking. It says nothing about the doses involved, just that there was sufficient scientific testing done and the effects were consistent enough such that the chemical could be described by one of those groups.
Here is the IARC classification scheme, and towards the bottom of this page, under (d) overall evaluation, (scroll way down) for an explanation of each class. The assignment to each class is built on the monographs, long documents that explain the research done and the basis of the conclusions. Here is a sheet with all the classification ordered by CAS number. Above to the right is a downloadable Excel sheet with that data. Here, I downloaded that for you and put it in order with the Group 1 at the top. [IARC used to have a link to the listing for each classifications, but I could not find those links.]International Agency for Research on Cancer (IARC, "eye ark") is the gold standard in cancer pronouncements. Note their classification scheme and how many chemicals are listed as "Group 1" which is analogous to EPA's Group A. How many are "mixtures" and how many are "exposure circumstances." Save this sheet for homework.