EPA in the drat IRIS assessment. Two rodent bioassays have demonstrated that high doses of tetrachloroethylene produced liver tumors in mice. While there is clear evidence that this occurs, the basis for their occurrence is not clear and may actually involve more than one MOA. This makes the determination of the relevance to humans more difficult. This is particularly true with respect to the importance of PPARα as the predominant or sole MOA, which led to a split opinion among committee members and a dissenting statement (see Appendix B).
Further studies are needed to define the MOAs for tetrachloroethylene-induced liver tumors, with particular emphasis on the importance of PPARα and whether species difference might exist. In addition, further study is needed to determine the relative roles of metabolites of tetrachloroethylene in tumor development. This may require the development of better analytical methods to detect some metabolites.