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Following chronic inhalation exposure, PCE selectively induced liver tumors in mice. Understanding the mode of action (MOA) for PCE carcinogenesis in mice is important in defining its possible human cancer risk. The proposed MOA is based on the extensive examination of the peer-reviewed studies that have assessed the mouse liver effects of PCE and its major oxidative metabolite trichloroacetic acid (TCA). Similar to PCE, TCA has also been demonstrated to liver tumors selectively in mice following chronic exposure. The Key Events (KE) of the proposed PCE MOA involve oxidative metabolism of PCE to TCA [KE 1]; activation of the peroxisome proliferator-activated receptor alpha (PPAR\u03b1) [KE 2]; alteration in hepatic gene expression including cell growth pathways [KE 3]; increase in cell proliferation [KE 4]; selective clonal expansion of hepatic preneoplastic foci [KE 5]; and formation of hepatic neoplasms [KE 6]. The scientific evidence supporting the PPAR\u03b1 MOA for PCE is strong and satisfies the requirements for a MOA analysis. The PPAR\u03b1 liver tumor MOA in rodents has been demonstrated not to occur in humans; thus, human liver cancer risk to PCE is not likely.<\/jats:p>","DOI":"10.1177\/07482337241240188","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T03:23:35Z","timestamp":1711337015000},"page":"272-291","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of the mode of action of perchloroethylene-induced mouse liver tumors"],"prefix":"10.1177","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4736-2223","authenticated-orcid":false,"given":"James E","family":"Klaunig","sequence":"first","affiliation":[{"name":"School of Public Health, Indiana University, Bloomington, IN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Bevan","sequence":"additional","affiliation":[{"name":"Halogenated Solvents Industry Alliance, Inc., 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