By National Research Council, Committee to Review EPA's Toxicological Assessment
Tetrachloroethylene is a unstable, chlorinated natural hydrocarbon that's common as a solvent within the dry-cleaning and textile-processing industries and as an agent for degreasing steel components. it's an environmental contaminant that has been detected within the air, groundwater, floor waters, and soil. In June 2008, the U.S. Environmental security company published its draft Toxicological assessment of Tetrachloroethylene (Perchloroethylene) (CAS No. 127-18-4) in help of precis details at the built-in probability info method (IRIS). The draft IRIS evaluation offers quantitative estimates of melanoma and noncancer results of publicity to tetrachloreothylene, so that it will be used to set up airquality and water-quality criteria to guard public healthiness and to set cleanup criteria for unsafe waste websites. on the request of EPA, the nationwide examine Council carried out an self sustaining medical evaluate of the draft IRIS evaluate of tetrachloroethylene from toxicologic, epidemiologic, and human scientific views. The ensuing booklet evaluates the adequacy of the EPA overview, the knowledge and strategies used for deriving the noncancer values for inhalation and oral exposures and the oral and inhalation melanoma unit hazards posed through tetrachloroethylene; evaluates no matter if the foremost reports underlying the draft IRIS evaluate are of needful caliber, reliability, and relevance to help the derivation of the reference values and melanoma hazards; evaluates even if the uncertainties in EPA's possibility evaluate have been correctly defined and, the place attainable, quantified; and identifies study which could decrease the uncertainty within the present realizing of human overall healthiness results linked to tetrachloroethylene publicity.
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Extra info for Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene
Dichloroacetate is produced primarily through the β-lyase pathway and produces liver cancer in rats. THE β-LYASE-INDEPENDENT PATHWAY TCVC undergoes acetylation to its mercapturate N-acetyl-TCVC and then sulfoxidation to N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine (N-Ac-TCVCS), which is mediated by CYP3A or flavin-containing monooxygenase (FMO). In addition, TCVC undergoes sulfoxidation to TCVC-sulfoxide (TCVCS); this is also mediated by CYP3A or FMO (Ripp et al. 1997). TCVCS is a more potent nephrotoxicant than TCVC in vivo (Elfarra and Krause 2007).
Even though a blood tetrachloroethylene concentration of over 2 g/L was required for entry into the study, no concentrations were reported for five subjects (subjects 10-14) taken in their apartments (Figure 1A of Altmann et al. ). Without those specifications, it is impossible to determine whether the sample was biased (that is, whether others were excluded for reasons other than study design). 4. Tetrachloroethylene was measured in air samples from homes for 7 days. Figure 1B of the paper purports to show indoor air concentrations for exposed participants and controls, but no concentrations are shown for the referent group.
127-18-4) in Support of Summary Information on the Integrated Risk Information System (IRIS), hereafter called the draft IRIS assessment. 6 × 10-2 mg/m3, an RfD of 4 × 10-3 mg/kg-day, a range of inhalation unit risks of 2 × 10-6 to 2 × 10-2 per mg/m3, and a range of oral slope factors of 1 × 10-2 to 1 × 10-1 per mg/kgday. EPA requested a review of those values and their scientific basis in 2006 but delayed public release of the draft IRIS assessment for additional evaluation within the agency. Therefore, the committee’s review did not begin until June 2008, when the draft was released.
Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene by National Research Council, Committee to Review EPA's Toxicological Assessment