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Review Studies to Identify Other Health Effects
In this step, you will identify other health effects by identifying and reviewing studies that have doses or air concentrations similar to those doses or air concentrations for your site.
When a Toxicological Profile is available for a potential COC, health assessors should use the LSE tables and figures for a review of the health effects and to locate data for a specific exposure scenario. All entries in these tables and figures represent studies that provide reliable, quantitative estimates of NOAELs, LOAELs, or CELs. Also, when making decisions about health effects, you should always read the information provided in the MRL worksheet (Appendix A in the Toxicological Profiles). In addition to describing the toxicological basis for the principle study used to derive the MRL, the MRL worksheet (Appendix A) will often describe the health effects from other studies with similar doses or concentrations.
For reference, the doses from our example are shown below, and the doses from the LSE tables/figures (NOAELs, LOAELs, etc.) are shown in the LSE table image and LSE figure image below. You should compare the CTE and RME doses from the PHAST results table to doses and concentrations from the LSE figures and table. You will focus on the highest estimated doses, which is usually one of the preschool age children with RME exposures. In this example, the highest estimated dose is 0.037 mg/kg/day in children birth to less than 1 year.
ATSDR’s Toxicological Profiles use LSE tables and figures to summarize the exposure doses and concentrations associated with health effects reported in scientific studies.
These levels cover
- health effects observed at different doses or concentrations and durations (acute, intermediate, and chronic),
- differences in response by species,
- the study used to derive duration-specific MRLs,
- CELs from animal and human studies, and
- EPA’s estimated range for doses and concentrations associated with an upper-bound individual lifetime cancer risk of 1 in 10,000 to 1 in 1,000,000 (when CSFs or IURs are available).
After you’ve found the LSE tables and figures in the Toxicological Profile, compare your site doses or concentrations with those from the studies provided. Remember, if the NOAEL or LOAEL is based on an intermittent exposure (e.g., 5 days per week), you will need to convert the NOAEL or LOAEL to a continuous exposure by multiplying the dose or concentration by the appropriate exposure factor (in this case 5/7). This comparison can really provide perspective of where your site-specific doses or concentrations fall in relation to those seen in published scientific studies that show other health effects.
As we learned, ATSDR has no chronic MRL for carbon tetrachloride because the chronic oral studies identified were based only on serious effects. But there is a chronic oral exposure LSE table and figure in the Toxicological Profile that lists the studies that were available. So, let’s take a look at them so you will know how to use the LSE tables and figures for your sites.
The LSE table is below. For our case exercise, the highest chronic exposure dose was estimated to be 0.037 mg/kg/day. This table has no NOAEL, and the lowest LOAEL is 47 mg/kg/day. Because this LOAEL is based on 5 days exposure per week, it converts to a adjusted LOAEL of 33.6 mg/kg/day ((47*(5/7)). The MOE (margin of exposure) is calculated to be 907 (33.6/0.037). This means that the site-specific dose (0.037 mg/kg/day) is 907 times lower than the adjusted LOAEL (33.6 mg/kg/day).
For training purposes, the LSE figure below has been modified from the original figure in the Toxicological Profile. Again, for our case exercise, the highest chronic exposure dose from drinking carbon tetrachloride contaminated water was estimated to be 0.037 mg/kg/day. The LSE figure is helpful to see where your site-specific doses compare with those in the published studies.
You can see that our example dose is several magnitudes lower than the doses where effects were noted in the chronic, oral scientific studies reported on the Toxicological Profile LSE table. Note that the reported levels in the LSE table are based on serious effects—a dose for a less serious LOAEL could be much lower than those reported here.
For contaminants without an ATSDR Toxicological Profile, we recommend that you refer to the EPA IRIS Toxicological Reviews. Health assessors may also want to refer to EPA IRIS if the Toxicological Profile available for their contaminant was completed before EPA derived the RfD.
Also, even though a Toxicological Profile is available for our potential COC, our health guideline and cancer risk value are from EPA. At a real site, we would go to the EPA IRIS Toxicological Review next to see if there is more information that we might be interested in. Here, you will find tables to see where your doses fall compared to the doses EPA pulled from all the studies examined during its health guideline and cancer risk value development. For example, you might find a table that summarizes chronic and sub-chronic oral toxicity studies, such as Table 4–13 in EPA’s IRIS Toxicological Review for Carbon Tetrachloride.