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EC number: 200-756-3
CAS number: 71-55-6
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).
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).
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).
did not increase unscheduled DNA synthesis in rat hepatocytes (Althaus
In a bone
marrow micronucleus test in the mouse (Gocke 1981) there was no increase
in micronuclei following intraperitoneal administration of up to 2000
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
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
was negative in the Drosophilia Basc test when tested at 25 mM (3.34
mg/mL), close to the LD50
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.
There is no clear evidence for the mutagenicity of 1,1,1
-trichloroethane. Therefore no classification is proposed.
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