of each section, an evaluation of the strength of the evidence of genotoxicity of a particular compound should be included by way of summarizing the totality of data available. Finally, there should be an integrative assessment, including species-specific kinetics and metabolism of tetrachloroethylene and of genotoxicity and mutagenicity in intact animals and humans.


Nonmammalian Systems

A considerable number of mutagenicity studies of pure tetrachloroethylene that used Salmonella strains, Escherichia coli, and Saccharomyces have been performed with and without exogenous metabolic activation by liver S9 fractions from rats, mice, and hamsters (including animals pretreated with Aroclor or phenobarbital). The results have been essentially negative. The studies should be documented in a table (see above for specific format suggestions). However, when tetrachloroethylene was incubated with purified glutathione S-transferase (GST), glutathione, and rat kidney fractions, formation of S-(1,2,2-trichlorovinyl) glutathione (TCVG) 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) of sex-linked lethal mutations in Drosophila.

Mammalian Cells in Vitro

EPA should describe the mutation study with mouse lymphoma L5178Y cells (NTP 1986), which appears to be the only available mammalian mutation test performed with tetrachloroethylene. This well-done study revealed that tetrachloroethylene at a variety of concentrations, with and without S9 for metabolic activation (but not with GST and rat kidney fractions), did not enhance the frequency of mutations at the thymidine kinase locus. Likewise, investigations of chromosomal aberrations and sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells (NTP 1986; Galloway et al. 1987) showed no evidence of tetrachloroethylene-induced genetic activity, although for technical reasons the weight of these studies was somewhat limited. In addition, the negative studies of chromosome aberrations in Chinese hamster lung cells by Sofuni et al. (1985) should be reported.

The work of Hartmann and Speit (1995) is addressed in the draft IRIS assessment, but it is incorrectly quoted in a statement that tetrachloroethylene induced genetic damage, which was not shown. Hartmann and Speit investigated SCEs and DNA integrity (by using the single-cell gel electrophoresis or comet assay) in human blood cells exposed to tetrachloroethylene in vitro. The study was well performed, with negative and positive controls, without and with

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