Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene (2010) / Chapter Skim
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5 Genotoxicity
5 Genotoxicity
Pages 50-58
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From page 50... ...
The draft IRIS assessment predominantly reports positive studies, whereas good studies that had negative results are not mentioned or in some cases are incorrectly described as having had positive results. The committee therefore recommends that a more balanced, transparent, and inclusive approach be used to consider the evidence.
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From page 51... ...
was found, and mutagenic activity in Salmonella was clearly demonstrated as correctly described in the EPA draft. The committee recommends that EPA also consider the negative results in the National Toxicology Program study (NTP 1986)
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From page 52... ...
and epoxide hydrolase stably. The committee recommends that EPA acknowledge that those cell lines were not validated as test systems and that other compounds tested in the study, such as hexane and toluene, that are generally regarded as nongenotoxic also led to formation of micronuclei -- an indication that the new cell lines may be oversensitive and may provide false-positive results.
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From page 53... ...
, the high doses necessary to enhance micronucleus formation must have been severely toxic to the residual hepatocytes and to the whole organism. The toxic load on the residual liver would have been aggravated by the intraperitoneal tetrachloroethylene application and by the likely release of cytokines and reactive oxygen species.
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From page 54... ...
as bacterial mutagens that act either directly or after activation by rat renal microsomes. It also mentions the induction of unscheduled DNA synthesis by TCVC in a porcine renal-cell line and the key role of renal ß-lyase in the final activation step as demonstrated in these studies.
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From page 55... ...
The committee recommends integration of the data on single-strand breaks into a balanced review of all available genotoxicity studies of TCA (including a table and a discussion of the studies' strengths and weaknesses) to support the conclusion that TCA exhibits little if any evidence of genotoxicity by an evaluation of the weight of evidence.
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From page 56... ...
Comparing binding in rat kidney and rat liver subfractions, the dichloro adduct (indicating the GSH conjugation pathway) predominates in the kidney with only faint bands in liver; the trichloro adduct (indicating the oxidative pathway)
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From page 57... ...
When injected after partial hepatectomy, tetrachloroethylene slightly increased micronucleus formation, but this effect may be nonspecific because of severe liver toxicity caused by the high doses of tetrachloroethylene and the intraperitoneal application of this irritant substance. A study with 14C-labeled tetrachloroethylene suggested a low level of binding to mouse liver DNA and even less to rat liver DNA and mouse and rat kidney, lung, and stomach DNA.
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From page 58... ...
58 Review of the EPA's Draft IRIS Assessment of Tetrachloroethylene separate discussion of the genotoxic evidence on tetrachloroethylene and its metabolites, and by a more critical analysis of the studies.
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