Identify Data from Studies Used to Develop Non-Cancer Health Guidelines

This section describes the process for reviewing the studies used to develop health guidelines for non-cancer health effects. Using a fictional example, it describes key resources you will use and walks you through the process.

Important: Health assessors need to examine key studies when a non-cancer health guideline is exceeded, but this is not a required step when a cancer risk estimate exceeds a level of concern. For cancer risk, health assessors are only required to quantitatively estimate the cancer risk (when a contaminant has a CSF or an IUR) and interpret that risk. In rare cases, a review of the original study could be useful, but this is not typically recommended. Consult an ATSDR toxicologist if you need assistance.

Remember: Simply being exposed to a contaminant does not make it a hazard. The magnitude, frequency, timing, and duration of exposure and the toxicity characteristics of individual contaminants affect the degree of hazard, if any.

Tip: Always start this step of identifying key studies for non-cancer by looking at ATSDR’s Toxicological Profiles and EPA’s IRIS Database.

This figure illustrates how the dose response looks following a BMD analysis, and allows scientists to examine the entire dose-response curve. The BMD analysis differs from the NOAEL/LOAEL approach, which looks not at the whole dose-response curve but instead at individual study doses to see if they are different than the control. Using this example, you can see that we do not have study results below the NOAEL (100 mg/kg/day) or between the NOAEL and LOAEL (150 mg/kg/day).

The BMD analysis allows us to examine what exposure gives a threshold of effect (i.e., the benchmark response, or BMR) instead of being able to use only the NOAEL or LOAEL. The BMD analysis applies a statistical model to the dose-response data (shown by the red line going through the points that fit to the data) that allows scientists to incorporate uncertainty into the experimental study results. The example figure shows that the corresponding dose that would result in 10% of animals affected (i.e., the benchmark dose) is somewhere between 70 and 80 mg/kg/day. The analysis allows us to closely estimate the level at which this response would be seen (the BMD), and then calculate a 95% lower confidence limit on the estimated BMD, called the BMDL. We want to make sure not to just assume the mean effect of the benchmark dose, but to use the lower bound to that estimate and be reasonably confident that the benchmark dose is not lower than the BMDL.

BMD modeling is often used to identify the point of departure in deriving the health guideline. The BMDL is also an effect level that health assessors can compare their site-specific doses and concentrations to when deciding the possibility of harmful effects. In some studies, ATSDR and EPA will use dosimetric methods to convert the BMDL to a human equivalent dose (HED). If an HED is available, health assessors will use that over the BMDL when deciding the possibility of harmful effects. This is discussed further in the Evaluate the Evidence to Examine Non-Cancer Effects section.