Even a Houdini risk assessment finds risks in occupational environment - TCE

Even a Houdini risk assessment has a hard time making an occupational exposure risk disappear.  The OSHA PEL for TCE is 100 ppm, about 5,000 mg/M3.  
The authors, one from the Chemical Industry Institute of Toxicology, and the other from ENVIRON “Institute” approach the EPA risk assessment for TCE.  Without tracking down the full text and seeing the acknowledgements, BrooklynDodger wonders whether this is a grant from CIIT to Environ, sort of pro malo on CIIT’s part, or whether there was a specific sponsor.  The big money in TCE is drinking water disinfection products or groundwater contamination.  
The authors note that EPA’s quantitative risk assessment, based on mitogenicity [increased cell division] of TCE metabolites, finds a 1.5 per million cancer risk at 1 ug/M3 exposure. [If it’s all linear, that would say 1 mg/M3, or about 1/5 ppm would generate the canonical 1/1000 risk benchmark for OSHA carcinogens.]
The authors assert as true their preferred mechanism, and state:  “Based on consideration of the most plausible carcinogenic modes of action of TCE, a margin-of-exposure (MOE) approach would appear to be more appropriate. Applying an MOE of 1000, environmental exposures below 66 μg TCE per cubic meter in air…would be unlikely to present a carcinogenic risk to human health.”
Rounding, 66 ug/M3 is about 0.8 ppb in air.  Taking away the MOE, we get back to 1 ppm.  If 1000 fold below is “unlikely,” is 1 ppm “likely”?  Anyway, the number is still 100-fold below the PEL.
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Incidentally, the Dodger wondered what’s up with Ruston.  Ruston is east of Shreveport, the home of Louisiana Tech.  Prior to Environ, LT was on the map because of Terry Bradshaw:
When Bradshaw was a student at Louisiana Tech he joined the Tau Kappa Epsilon Fraternity. After graduating from Louisiana Tech, Bradshaw was the first player selected in the 1970 NFL draft. During his first several seasons, the 6'3" (190 cm), 215 lb. (97 kg) quarterback was erratic, and was ridiculed by the media for his rural roots and perceived lack of intelligence.
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Critical Reviews in Toxicology Volume 34, Issue 5 , 2004, Pages 385-445
Applying mode-of-action and pharmacokinetic considerations in contemporary cancer risk assessments: An example with trichloroethylene
Harvey J. Clewell1, and Melvin E. Andersen2 1ENVIRON Health Sciences Institute, Ruston, Louisiana, USA2CIIT Centers for Health Research, Research Triangle Park, North Carolina, USA Available online 23 September 2005. Abstract
The guidelines for carcinogen risk assessment recently proposed by the U.S. Environmental Protection Agency (U.S. EPA) provide an increased opportunity for the consideration of pharmacokinefic and mechanistic data in the risk assessment process. However, the greater flexibility of the new guidelines can also make their actual implementation for a particular chemical highly problematic. To illuminate the process of performing a cancer risk assessment under the new guidelines, the rationale for a state-of-the-science risk assessment for trichloroethylene (TCE) is presented. For TCE, there is evidence of increased cell proliferation due to receptor interaction or cytotoxicity in every instance in which tumors are observed, and most tumors represent an increase in the incidence of a commonly observed, species-specific lesion. A physiologically based pharmacokinetic (PBPK) model was applied to estimate target tissue doses for the three principal animal tumors associated with TCE exposure: liver, lung, and kidney. The lowest points of departure (lower bound estimates of the exposure associated with 10% tumor incidence) for lifetime human exposure to TCE were obtained for mouse liver tumors, assuming a mode of action primarily involving the mitogenicity of the metabolite trichloroacetic acid (TCA). The associated linear unit risk estimates for mouse liver tumors are 1.5 × 10−6 for lifetime exposure to 1 μg TCE per cubic meter in air and 0.4 × 10−6 for lifetime exposure to 1 μg TCE per liter in drinking water. However, these risk estimates ignore the evidence that the human is likely to be much less responsive than the mouse to the carcinogenic effects of TCA in the liver and that the carcinogenic effects of TCE are unlikely to occur at low environmental exposures. Based on consideration of the most plausible carcinogenic modes of action of TCE, a margin-of-exposure (MOE) approach would appear to be more appropriate. Applying an MOE of 1000, environmental exposures below 66 μg TCE per cubic meter in air and 265 μg TCE per liter in drinking water are considered unlikely to present a carcinogenic hazard to human health.
Keywords: Cancer risk assessment; Mode-of-action; Pharmacokinetics; Trichloroethylene (image placeholder)

Address correspondence to Harvey J. Clewell, ENVIRON Health Sciences Institute, Ruston, LA 71270, USA.

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