ment that tetrachloroethylene induces MCL or a related form of leukemia. In addition, those studies investigated tetrachloroethylene exposure in mice, a species in which MCL has never been observed. The only evidence that tetrachloroethylene induced MCL comes from exposure studies with F344 rats. Nevertheless, the effects of tetrachloroethylene on hemolysis in mice and on bone marrow function provide the basis of a hypothesis that could be explored to demonstrate the mechanism by which tetrachloroethylene could, within some dose range, affect the spleen.
The majority of the committee finds that EPA has not adequately justified the use of MCL data over the evidence for liver or kidney cancer in its cancer risk assessment. Evidence of tetrachloroethylene-induced leukemia from epidemiologic studies is limited and inconsistent. The NTP (1986) and JISA (1993) study results of increased MCL incidences in F344 rats given tetrachloroethylene by inhalation are also questionable because of the high background rates of MCL in control animals. More thorough statistical evaluation of the data, such as the life-table analysis proposed by Thomas et al. (2007), could provide a stronger basis for drawing conclusions. However, MCL resulting from tetrachloroethylene exposure has not been observed in other strains of rats or other animal species, and no definitive evidence is available to support a hypothesized MOA by which tetrachloroethylene increases MCL in F344 rats. Those are all sources of uncertainty surrounding the relevance of MCL to human cancer risk. The information is considered in the context of the other evidence on carcinogenicity in Chapter 11, where EPA’s assessment of carcinogenic risks of tetrachloroethylene is evaluated.