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: 201-174-2
CAS number: 79-07-2
Chloroacetamide was administered to mice by oral gavage
twice at an interval of 24 h at doses of 0, 1, 10, 100 mg/kg bw, next to
a positive control (Cyclophophamide 100 mg/kg bw).Six hours after the
second administration, the animals were sacrificed and the bone marrow
obtained from the femurs was processed, smeared on slides and stained.
Thereafter, normocytes and polychromatic erythrocytes of each animal
were examined for the ratio immature cells / normocytes as well as the
number of micronucleated normocytes and polychromatocytes.
Chloroacetamide did not result in a significant increase in the number
of polychromatic erythrocytes with micronuclei under the conditions of
the experiment; the number of micronucleated normocytes also did not
show substance related changes. The ratio normocytes/polychromatic
erythrocytes in male and female animals in all dose groups was
unaffected. The present result do not indicate an induction of
chromosomal mutations by Chloroacetamide.
Cyclophosphamide produced a significant increase in the
number of micronucleated polychromatic erythrocytes in male and female
animals. As an expression of the cytostatic effect of Cyclophosphamide
also the ratio normocytes/polychromatic erythrocytes was shifted in
favor of the mature cells.
Both batteries of in vitro and in vivo
genetic toxicity studies were performed.
In a key in vitro bacterial reverse mutation study (plate
incorporation), Chloroacetamide solved in DMSO was tested
with Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537,
with and without metabolic activation (S9) at concentrations of 4 to
2500 µg/plate (Hoechst, 1979). There was no mutagenicity neither in
the presence nor absence of rat liver preparation up to 2500 µg/plate.
Supporting information for absence of mutagenicity potential was
available from an in vitro bacterial reverse mutation study (plate
incorporation) with Konservierungsmittel CA 24
(containing 70% Chloroacetamide) with S.typhimurium strains TA 98,
TA100, TA1535, TA1537 and TA1538 strains, with and without metabolic
activation (S9) at concentrations of 0.5 to 1000 µg ( IBR, 1979) and
from a published study with Chloroacetamide tested in S. typhimurium
strains TA 98, TA 100 and TA 1537 with and without S-9 mix at
concentrations ranging from 0.05 to 10 mg/plate (Voogd, 1989). A
concentration of 20 mg/plate stopped bacterial growth. Finally,
Chloroacetamide was also tested in a fluctuation test using K.
pneumoniae at concentrations of 0.1 to 2 g/L (Voogd et al., 1989),
showing some increased rate of mutation at and above 0.5 g/L and
demonstrating cytotoxicity at 2 g/L.
In a key in vitro chromosome aberration study,
Chloroacetamide was investigated in Chinese hamster lung V79 cells
(Aventis, 2001) at 100, 250 and 350 µg/mL (3h with and without S9). The
highest concentration produced distinct lowering (+- 50%) of the mitotic
index, without precipitation of the test substance. A significant
increase in the number of chromosome aberrations was induced at
cytotoxic concentrations both with and without metabolic activation,
however not below cytotoxic concentrations. In conclusion,
Chloroacetamide was considered to be clastogenic at cytotoxic
concentrations in this in vitro chromosome aberration assay with V79
Chinese hamster lung cells.
In a key in vitro mammalian gene mutation study (Aventis,
2001) Chloroacetamide was tested in HPRT V79 cells of Chinese hamster. Two
independent experiments were conducted both with and without an
exogenous rat liver microsomal activation system (S9-mix). In experiment
1, concentrations were 1 - 175 µg/mL without S9-mix and 5 - 225 µg/mL
with S9 -mix; in the second main experiment, concentrations were 10 -
200 µg/mL without S9-mix and 50 - 250 µg/mL with S9 -mix. The highest
concentrations showed toxic effects with and without metabolic
activation. In both experiments in the absence of S9 metabolic
activation no statistically significant increase in the mutant frequency
was found with any of the concentrations used. Slight and sporadic
statistically significant increases in the mutation frequency were found
in the presence of S9, however they were not significant.
Chloroacetamide did not induce gene mutations in this HPRT-test both in
the presence and absence of a metabolic activation system and is
considered to be non-mutagenic in this HPRT assay.
A supporting study was done with Chloroacetamide in an in
vitro Cell Transformation Assay in Syrian Hamster Embryo (SHE) cells
(CCR, 1987). Per test group 10 plates were exposed to the test article
for 4h and 48h in the absence and 4h in the presence of S9-mix. Within
10 days after initiation of the cell culture the cells were fixed,
stained and examined for morphological transformation. The test article
did not significantly increase the number of morphologically transformed
colonies up to cytotoxic concentrations in the absence of S9-mix for 4
and 48h, neither in the presence of S9-mix for 4h. Chloroacetamide did
not induce morphological transformations, therefore it was concluded to
have no transforming potential in this SHE cell transformation assay.
Additionally, in vivo studies were conducted. In a key
bone marrow micronucleus assay, Chloroacetamide was administered twice
to mice by oral gavage at an interval of 24 h at doses of 0, 1, 10, 100
mg/kg bw (Hoechst, 1982). Six hours after the second administration, the
animals were sacrificed and the bone marrow obtained from the femurs was
processed, smeared on slides and stained. Thereafter, normocytes and
polychromatic erythrocytes of each animal were examined for the ratio of
immature cells / normocytes as well as the number of micronucleated
normocytes and polychromatocytes. Chloroacetamide did not result in a
significant increase in the number of polychromatic erythrocytes with
micronuclei under the conditions of the experiment; the number of
micronucleated normocytes also did not show substance relevant changes.
The ratio normocytes/polychromatic erythrocytes in male and female
animals in all dose groups was unaffected. The present results do not
indicate an induction of chromosomal mutations by Chloroacetamide. In
a supporting study, Konservierungsmittel CA24 formulation (containing
70% Chloroacetamide) was tested for the influence on the chromosomes of
the bone marrow and the testicular tissue in the Chinese hamsters, as
well as induction of micronuclei in blood smears from bone marrow (IBR,
1979). Doses were given twice by intraperitoneal administration with 24h
interval: 12.5, 25 and 50 mg/kg bw, corresponding with 1/12, 1/6 and 1/3
of the LD50 (= 150 mg/kg bw). Under the given experimental conditions,
no increase in structural and numerical chromosome aberrations nor
micronuclei were observed in treated groups.
Finally a supporting study was conducted by
intraperitoneal administration of Konservierungsmittel CA 24 in a
dominant lethal test at 114 mg/kg bw (group 1) and 123 mg/kg bw (group
2) in male NMRI-mice (IBR, 1979). The treated male mice were each mated
with 3 virgin females per week over a period of 10 weeks. At autopsy of
the mated females, a marked inhibitory effect on fertility of the
treated males was observed, which was considered to be related to toxic
effects in the male reproductive system during the first 3 weeks of
testing. Since there were no changes in number of resorptions,
mutagenicity index and number of dead fetuses during the entire test
period, a mutagenic effect of the test substance under the given
experimental conditions cannot be assumed.
In conclusion, based on the in vitro and in vivo test
batteries, Chloroacetamide does not have a mutagenicity or chromosome
Based on the findings in the genotoxicity test batteries,
classification for genotoxicity is not warranted.
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.
Deze website maakt gebruik van cookies om het surfen zo aangenaam mogelijk te maken.
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