Guidance for Air
The following guidance was developed by the Health Risk Assessment Unit (HRA) of the Minnesota Department of Health (MDH) at the request of the Site Assessment and Consultation Unit of MDH and the Minnesota Pollution Control Agency.
Note: This information pertains to the chronic health-based value for trichloroethylene only. MDH also has developed an acute Health Risk Value for this chemical.
Trichloroethylene: Chronic Health-Based Value for Air
December 28, 2007
Chemical: Trichloroethylene (TCE)
CAS Number: 79-01-6
Chronic Value: 3µg/m3
Sources: 2001 U.S. EPA draft guidance for TCE; California EPA’s OEHHA, 2005; and NRC, 2006
The MDH has developed a chronic Health-Based Value (HBV) of 3 µg/m3 for inhalation exposures to TCE. A description of the techniques, assumptions and caveats used in developing this number follows.
There is a large and still growing body of experimental and epidemiological information concerning the toxicity of TCE. Rather than increasing the confidence in the ability of risk assessors to develop a protective number for TCE, the accumulated research has resulted in a great deal of controversy regarding the level of exposure required to produce effects in humans. Research, and the evaluation of this research, is continuing and it is likely that as new information and EPA’s reevaluation become available the HBV that has been developed will need to be reevaluated.
At this point it is clear that TCE is capable of inducing several types of tumors in different organs in experimental animals. Experimental information also indicates that TCE likely operates by multiple modes of action, including genotoxicity, to induce cancers.
Following a review of the available literature, including the 2001 U.S. EPA draft guidance for TCE (U.S. EPA, 2001) and the National Academy of Sciences report generated in response to EPA’s draft guidance (NRC, 2006), HRA has developed an HBV for TCE. Given the increased weight of evidence (discussed in the NAS report) indicating the potential for carcinogenicity in humans it is prudent to develop an HBV for TCE using cancer as an endpoint.
As pointed out by the NAS panel, epidemiological evidence accumulated to date indicates that TCE is likely to be carcinogenic in humans. In addition, epidemiological studies have associated TCE exposure to the induction of multiple types of cancer in humans. However, these data are insufficient to support quantitative dose response modeling for TCE and cancer. The committee recommended the toxicologic data be used to fit the primary dose response models and that the available epidemiological data be used only for validation.
Based on these comments HRA has elected to use an analysis of rodent cancer data posted on the California EPA’s OEHHA website as the basis for the HBV (California EPA, 2005). The California Department of Health Services used data from four studies in male and female mice to generate independent estimates of unit risk. For this analysis they used:
- PBPK modeling to adjust the applied dose for metabolism
- Surface area scaling to account for interspecies variation
- Linearized multistage modeling for low dose risk assessment
A best estimate of unit risk was obtained by taking the geometric mean of the independent unit risks from the four studies.
This approach is consistent with recommendations from the NRC report which suggested that, because the available information is insufficient to determine the best dose response curve model for TCE, a linear extrapolation between zero and the modeled point of departure is acceptable and consistent with current techniques suggested in EPA’s 2005 cancer guidelines (U.S. EPA, 2005a).
California EPA’s analysis produced a unit risk of 2.0 x 10-6 (µg/m3)-1. Because it is likely that at least some types of cancer induced by TCE are produced via a mutagenic mode of action, HRA has utilized the U.S. EPA method of adjusting cancer potency estimates for early life exposure (U.S. EPA, 2005b). Age specific adjustments for exposure are currently unavailable. The equation used follows:
Age Adjusted Unit Risk (AAUR) = 2/70 [(2 x 10-6) x 10] + 13/70 [(2 x 10-6) x 3] + 55/70 [(2 x 10-6 x 1] = 3.3 x 10-6 (µg/m3)-1
Consistent with MDH policy an additional lifetime risk level of 1 x 10-5 was used with the AAUR of 3.3 x 10-6 (µg/m3)-1 to calculate an exposure level.
1 x 10-5 = 3.03 (rounded to 3 µg/m3)
3.3 x 10-6
TCE is toxic to a number of organs and several other non-cancer endpoints have been used to develop health-based numbers. The U.S. EPA’s draft guidance for TCE developed a reference concentration for TCE of 40 µg/m3 based on CNS, liver and endocrine system toxicity (U.S. EPA, 2001). The California EPA’s OEHHA has developed a chronic reference exposure level (REL) of 600 µg/m3 based on CNS effects in workers (California EPA, 2005). The HBV developed for cancer would be adequately protective of these non-cancer endpoints.
U.S. EPA (2005a). Guidelines for Carcinogen Risk Assessment, March 2005, EPA/630/P-03/001B
U. S. EPA (2005b). Supplemental Guidance for Assuming Susceptibility from Early-Life Exposures to Carcinogens, EPA/R-03/0003F.
California EPA (2005). Chronic Toxicity Summary: Trichloroethylene.
California EPA (2005). Air Toxics Hot Spots Program Risk Assessment Guidelines for Describing Available Potency Factors, May 2005, California EPA, Office of Environmental Health Hazard Assessment.
U. S. EPA (2001). Trichloroethylene Health Risk Assessment: Synthesis and Characterization, August 2001, EPA/600/P-01/0002A – External Review Draft.
NRC (2006). Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues, National Academies Press, Washington, D.C.