Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 200-864-0
CAS number: 75-35-4
Genetic toxicity in vitro
A high number of in vitro studies on the genotoxic potential of
1,1-dichloroethene in vitro are available. An extensive review of these
studies is provided in the CICAD report No 51 on 1,1-dichloroethylene
(Benson, 2003) which concluded that overall, 1,1-dichloroethene appears
to show genotoxic activity in in vitro testing systems, especially in
the presence of metabolic activation.
1,1 -dichloroethene induced mutations in Salmonella typhimurium (TA100
and TA1530) in Ames test conducted in desiccator, in the presence of an
exogenous metabolic activation system only (Bartsh et al., 1975). The
Ara forward mutation test performed using Salmonella typhimurium BA13
and BAL13 elicited positive response in the presence of an external
metabolizing system (Roldan-Arjona et al., 1991). In Saccharomyces
cerevisiae, 1,1 -dichloroethene induced reverse mutation in D7 strain
and aneuploidy in D61.M strain (Koch et al., 1988). In Aspergillus
nidulans, 1,1 -dichloroethene was found to be positive for the induction
of chromosome malsegregation (Crebelli et al., 1992). Chromosomal
aberrations and Sister Chromatid Exchanges in vitro were found in
Chinese Hamster lung fibroblast in the presence of metabolic activation
(Sawada et al., 1987). In a mouse lymphoma assay conducted with L5178Y
cells, 1,1 -dichloroethene showed positive response in the presence of
metabolic activation and ambiguous results without metabolic activation
(McGregor et al., 1991). However, in Chinese Hamster lung cells (V79),
no mutagenic activity was found either in the absence or presence of
metabolic activation (Bartsh et al., 1975). Result of Unscheduled DNA
Synthesis (UDS) in vitro assay showed a positive response using
hepatocytes from male Long-Evans rats.
Genetic toxicity in vivo
As indicated in 8.4.3. of Annex VIII, appropriate in vivo mutagenicity
studies shall be considered in case of a positive result in any of the
genotoxicity studies in Annex VII or VIII.
Several in vivo studies are available: Micronucleus studies (3 in mice,
1 in rats), Dominant Lethal assays (1 in rats, 1 in mice), and a
Sex-Linked Recessive Lethal Mutation assay in Drosophila melanogaster
addressing lethal mutations in germ cells. In addition 1 mechanistic
study investigating DNA replication and DNA repair in both rats and mice
and 1 gene profiling study in rats are provided. In 2016, an in vivo
Comet assay has been added to the genotoxicity dataset.
- Chromosome aberrations
The 4 micronucleus studies provide information on the tendency of
1,1-dichloroethylene to lead to chromosome aberrations. As all 4 studies
are negative, it can be concluded that 1,1-dichloroethylene does not
exert such effects.
- Gene mutations
Information on the tendency of 1,1 -dichloroethylene to lead to gene
mutations can be obtained from the 2 dominant lethal assays, although
these studies are primarily aimed at detecting chromosomal aberrations.
According to ECHA R7a guidance "The test identifies substances that
induce dominant lethal effects causing embryonic or foetal death
resulting from inherited dominant lethal mutations induced in germ cells
of an exposed parent, usually the male." Indeed, OECD guideline 478
states that “dominant lethals are generally accepted to be the result of
chromosomal aberrations (structural and numerical anomalies), but gene
mutations and toxic effects cannot be excluded”. It can be concluded
from this phrase that although chromosomal aberrations are the “main
target” of the assay, a (strong) gene mutation activity might well have
not gone undetected in the 2 dominant lethal assays performed with
1,1-dichloroethene. The 2 studies were however both negative.
- DNA damage
Information on the tendency of 1,1-dichloroethylene to incur DNA damage
is available from the Comet assay. In the Comet assay, statistical
significant and biologically relevant DNA damage without adverse
histopathological findings was observed for some of the tested
concentration in lung cells and kidney cells (lung: 1 mg/L (= 250 ppm;
1000 mg/m3); kidney: 1 mg/L (= 250 ppm;
1000 mg/m3) and 3 mg/L (= 750 ppm; 3000
mg/m3)) indicating that
1,1-dichloroethylene induced DNA damage in these cells. It has been
concluded that the increased DNA damage observed, under the conditions
of the test and in the absence of histopathological findings, is caused
by a genotoxic effect. Furthermore, DNA damage was found to occur
in combination with histopathological findings in lungs at and above 3
mg/L (750 ppm; 3000 mg/m3), in kidneys
at 25 mg/L (6350 ppm; 25000 mg/m3) and
in liver as of 1 mg/L (250 ppm; 1000 mg/m3).
- Germ cell mutagenicity
Information on the tendency of 1,1 -dichloroethylene to cause germ
cell mutagenicity can be obtained from the two Dominant Lethal
(DL) assays available, one in mice and another in rats. According
to OECD guideline 478 (Rodent Dominant Lethal test), "DL mutations
cause embryonic or fetal death. Induction of DL mutations after
exposure to a test chemical indicates that the chemical has
affected the germ cells of the test animal. A DL assay is useful
for confirmation of positive results of tests using somatic in
vivo endpoints, and is a relevant endpoint for the prediction of
human hazard and risk of genetic diseases transmitted through the
germline." As both DL assays available for 1,1 -dichloroethylene
are negative, it can thus be concluded that 1,1 -dichloroethylene
is not a germ cell mutagen.
As mentioned above, one Sex-Linked Recessive Lethal Mutation assay in
Drosophilia melanogaster is also available. The test addresses lethal
mutations in germ cells. The test showed no tendency of
1,1-dichloroethylene to cause germ cell mutations in insects, supporting
the above conclusion.
Finally, one study by Reitz et al. (1980), is also included in the
genotoxicity dataset. In this mechanistic study DNA replication and DNA
repair in both rats and mice after inhalation exposure is examined.
Reitz reported that exposure to tumorigenic doses of 1,1
-dichloroethylene resulted in massive tissue damage but induced minimal
DNA alkylation or DNA repair synthesis.
Short description of key information:
- Chromosome aberration: based on 4 negative in vivo micronucleus
tests it was concluded that 1,1 -dichloroethylene does not exert effects
of chromosome aberration.
- Gene mutations: based on 2 negative dominant lethal assays does not
exert a (strong) gene mutation activity.
- DNA damage: based on the in vivo Comet assay it was concluded that
1,1-dichloroethylene should be considered as genotoxic after a 3-day
inhalation exposure of male Wistar rats.
- Germ cell mutagenicity: based on the 2 negative dominant lethal assays
it was concluded that 1,1 -dichloroethylene is not a germ cell mutagen.
For the classification for germ cell mutagenicity, the possibility of
the test substance to induce heritable mutations in the germ cells of
humans has to be assessed.
Based on the positive in vivo Comet assay in male rats by inhalation, it
is concluded that 1,1 -dichloroethylene incurs DNA damage in somatic
cells. However, 1,1 -dichloroethylene did not induce dominant lethal
mutations in mice and rat after inhalation exposure. Therefore, it can
be concluded that 1,1 -dichloroethylene does not induce heritable
genetic damage, and thus classification is not warranted in accordance
with the EU regulation 1272/2008 on Classification, Labeling and
Packaging of substances and mixtures (CLP).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again