1,1,1-trichloroethane

Endpoint summary

Additional information

1,1,1-trichloroethane was one of 42 substances used in a multi-laboratory collaborative study assessing the predictability and reliability of the Ames and other in vitro tests; it was, initialy, selected as an example of a non-genotoxic substance.  The design used in these studies was very similar to the OECD 471 guideline, and the tests were conducted at respected laboratories.  In the standard Ames test 1,1,1-trichloroethane was found to be negative (Brooks 1981, Gatehouse 1981, Richold 1981, Rowland 1981 and Vennitt 1981).  This is supported by a number of other researchers, not part of the inter-laboratory assessment but also recorded negative results (Chan 2000, Longstaff 1984, Nestmann 1980, and Simmons 1977).  However, when the study was modified to account for the volatility of 1,1,1-trichloroethane by incubating the plates in a desiccator or air-tight container with an open volume of 1,1,1-trichloroethane some positive results were recorded for the S. typhimurim strains TA 100 and TA1535 only (Gocke 1981, Nestmann 1980 and Simmons 1977).  In these latter studies no measurement of actual exposure was made. However, the results indicate that in the Ames test, when conducted in an enclosed environment, there is evidence of weak mutagenicity. 

There was no increase in the induction of sfiA in E.coli when assessed using the SOS colorimetric assay (Quillardet 1985).

The potential for 1,1,1-trichloroethane to induce gene mutations was also assessed in mammalian cells using the mouse lymphoma assay in two independent laboratories at concentrations up to 0.4 μL/mL (Chan 2000).  In one laboratory the results were negative (Mitchell 1988), in the second laboratory the results with metabolic activation were deemed to be equivocal (Myhr 1988).

In an assessment of chromosomal aberrations, a positive response was observed with Chinese Hamster Ovary cells in the absence of metabolic activation and an equivocal response in the sister chromatid exchange assay (Galloway 1987 and also reported by Chan 2000).  A chromosomal aberration test using Chinese hamster lung fibroblasts, using a direct method as well as with and without metabolic activation was negative (Sofuni 1985).

1,1,1-trichloroethane did not increase unscheduled DNA synthesis in rat hepatocytes (Althaus 1982)

In a bone marrow micronucleus test in the mouse (Gocke 1981) there was no increase in micronuclei following intraperitoneal administration of up to 2000 mg/kg  1,1,1-trichloroethane to a limited (2 males + 2 females per group) number of animals.  Similarly a negative result was recorded in groups of 5 mice following intraperitoneal injection of up to 80 % of the LD₅₀ (Salmone 1981).  In an unpublished ICI micronucleus evaluation (IUCLID 4) following inhalation exposure, 1,1,1-trichloroethane was considered not to be clastogenic.  At the end of a 13 week dietary study conducted on behalf of the National Toxicology Programme (Chan 2000) examination of peripheral blood cells from 5 male and 5 female mice in each group resulted in a statistically significant dose-related trend in males only.  None of the group mean values were statistically significantly greater than the vehicle or untreated control, but the report considered the male results to be equivocal but concluded that there was no clear evidence of mutagenicity.

1,1,1trichlorethane was negative in the Drosophilia Basc test when tested at 25 mM (3.34 mg/mL), close to the LD₅₀

Evaluation of the in vitro genotoxicity indicates that 1,1,1-trichloroethane, dependent on the conditions of the in vitro test, does have some limited mutagenic potential; observed only in strains TA 100 and TA 1535 when the volatility of the test substance is taken into account.  Mammalian in vitro cell systems found no clear evidence of mutagenicity, but equivocal or positive results were observed in one mouse lymphoma assay, a sister chromatid exchange assay and in Chinese hamster ovary cells. This potential is not clearly supported by in vivo data, where exposure and metabolism are assured and the majority of results were negative.  On balance, there is no clear or consistent evidence that 1,1,1-trichloroethane is mutagenic.

Short description of key information:
1,1,1-trichloroethane has been extensively tested in a full range of in vitro and in vivo mutagenicity tests. The majority of these tests are negative, but there are a number of positive or equivocal results, in all test systems; the potential for mutagenicity cannot be excluded under certain test conditions, but neither is there clear evidence of mutagenicity..

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

There is no clear evidence for the mutagenicity of 1,1,1 -trichloroethane. Therefore no classification is proposed.