Evaluate the Evidence: Cancer

Steps for Cancer Effects

For cancer effects, ATSDR uses the information gathered from the exposure pathway analyses and exposure estimates to get a range of cancer risks that represent typically and highly exposed groups.
Health assessors estimate the theoretical increased risk of cancer in an exposed population by multiplying the site-specific exposure dose estimate by the oral CSF or the site-specific air concentration by the IUR.
Health assessors will need to discuss the types of cancer that might be possible and should keep in mind that some cancers might be route specific.
Health assessors should not do the following:
- Conduct a comparison between the cancer effect level (CEL; the lowest dose level observed to produce a significant increase in the incidence of cancer or tumors) and site exposure dose to assess cancer effects.
  - This is because cancer risk is a linear response without a threshold and very low doses can still cause an increased risk of cancer.
  - One exception to this rule is oral exposure to chloroform where EPA has stated that cytotoxicity is necessary before chloroform will cause cancer from ingestion. EPA has stated that their RfD can be considered protective against cancer from oral exposure. More information about chloroform and cancer is available in IRIS.
- Use a CEL to make a health hazard conclusion.
  - This is because you need to know the numerical cancer risk to decide whether exposure could cause a significant cancer risk.
A health assessor might look at the CEL if the risk is very high. The purpose would be to see if the site-specific dose or concentration is at cancer effect levels. When site doses approach or exceed the CEL reported in the Toxicological Profile, you can place greater emphasis on the cancer risk estimate.
When communicating the potential for cancer hazards, be sure to state how strongly associated a contaminant is with cancer outcomes. Using plain language, include the cancer classifications in your evaluation to describe the cancer-causing potential of a contaminant. Refer to ATSDR’s Cancer Classification System document for more information.
A decision about whether the estimated cancer risk is a health concern depends in part upon the numerical cancer risks. Estimated risks less than 1E-6 are generally not a concern. Estimated risks greater than 1E-4 are usually a concern. Health assessors should use professional judgement when determining whether cancer risks between 1E-4 and 1E-6 are a health concern. More information to help you make this decision can be found in PHAGM’s section titled Evaluate the Evidence to Examine Cancer Effects under “Describing Cancer Risk”.
For suspected or known carcinogens that don’t have CSFs or IURs, health assessors need to indicate in their documents that quantitative risk estimates aren’t possible. You can provide some context in your documents as noted below.
- Include highlights from studies supporting the contaminant being a carcinogen.
- Include information on how you identified the contaminant as a carcinogen (e.g., NTP or IARC cancer classification).
- Indicate what is known in a qualitative way. Provide a paragraph that explains why EPA hasn’t developed CSFs or IURs based on available data (if known), clearly states uncertainty, and includes other relevant information.
- Note that cancer risk estimates do not estimate actual cancer cases, but rather provide information to ATSDR when making determinations about actions needed to protect the public’s health.
- Consult with a toxicologist if there is information on human or animal exposure doses that caused cancer to see if it is appropriate to compare them to site-specific doses.

Practice

Let’s look at examples of information we might collect to examine potential cancer effects using our carbon tetrachloride example.

Cancer information can be found in ATSDR’s chemical-specific Toxicological Profiles (Chapter 7, Regulations and Guidelines), in EPA’s Integrated Risk Information System (IRIS), and in ATSDR’s PHAST database (CVs and Health Guidelines module). For access to PHAST, send a request to PHAST@cdc.gov.

You would pull all relevant information at your real sites. The table below has types of information you might want to gather, using the carbon tetrachloride example.

We examined and collected the following information:

Quality of study: we know a peer-reviewed study was deemed sufficient by EPA to use for the basis of an oral CSF, but the study used a relatively small group size and investigation of only two target organs (kidney and liver)
Cancer classification of contaminant: likely to be carcinogenic to humans (EPA), reasonably anticipated to be a carcinogen (NTP), possibly carcinogenic to humans (IARC), and occupational carcinogen (NIOSH)

**Identify data from key studies and other information for cancer effects–carbon tetrachloride**
Parameter	Data for Cancer Effects
Cancer risk value	CSF: 0.07 mg/kg/day^-1
Information source for cancer risk value	EPA IRIS (PHAST CVs and Health Guideline Module)
Study reference	JBRC, 1998; Nagano et al., 2007
Study exposure route and duration evaluated	Inhalation, chronic
Observed effect for cancer risk value	Liver cancer (hepatocellular adenoma or carcinoma)
Species cancer risk value is based on	Mice
Dosing method and exposure medium in study	Inhalation bioassay
Point of departure in study	LED₁₀: 1.54 mg/kg/day
Cancer classification(s)	Likely to be carcinogenic to humans (EPA), reasonably anticipated to be a carcinogen (NTP), possibly carcinogenic to humans (IARC), and occupational carcinogen (NIOSH)

LED₁₀= the lower 95% bound on the exposure associated with a 10% extra cancer risk; the CSF is obtained by dividing the risk (as a fraction) by the LED₁₀

Back Next