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Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene (2010) / Chapter Skim
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7 Renal Toxicity and Cancer
Pages 68-74

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From page 68...
... Epidemiologic studies of the effects of tetrachloroethylene exposure on renal function have been reported, and EPA summarizes the findings in a table. The discussion focuses on urinary proteins that are indicative of tubular damage, because -lyase is found in the proximal tubule.
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From page 69...
... , including cohort mortality studies, casecontrol studies, and nested case-control studies. Ultimately, the methodologic challenges of studying such a rare cancer as RCC, assessing tetrachloroethylene exposure accurately, and evaluating inconsistencies in results among studies limit the conclusions that can be drawn from the epidemiologic data.
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From page 70...
... ANIMAL STUDIES Renal Toxicity The draft IRIS assessment summarizes the studies of tetrachloroethylene toxicity across species, sexes, and routes and durations of exposure. Significant renal toxicity has been observed in lifetime bioassays in rats and mice of both
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From page 71...
... Overall, the dose-dependent induction of renal tumors in one experiment against the low background incidence of renal tumors in rats exposed to tetrachloroethylene indicates that tetrachloroethylene can induce renal tumors in rats. After integrating the results of the studies, the committee concluded that tetrachloroethylene induces renal tumors in rats.
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From page 72...
... Thus, the type of renal damage seen is not consistent with an immunotoxic mode of action. The draft IRIS assessment notes that immunesystem-mediated effects of organic solvents and the formation of protein adducts are related to autoimmune diseases, not to immunosuppression and therefore inconsistent with immunosuppression as a mode of action.
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From page 73...
... SUMMARY AND RECOMMENDATIONS EPA concluded there is limited evidence that tetrachloroethylene causes cancer in humans, and the committee agrees with this assessment. EPA evaluated bioassay studies to provide evidence suggestive of an effect.
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From page 74...
... 74 Review of the EPA's Draft IRIS Assessment of Tetrachloroethylene are causing or contributing to the formation of renal tumors. Finally, a robust physiologically based pharmacokinetic model is needed to evaluate differences between humans and rats in their sensitivity to tetrachloroethylene.
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