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EC number: 254-996-9
CAS number: 40601-76-1
The in vitro mutagenicity of the test material was dermined in bacteria
and mammalian cells. An in vitro chromosomal aberration study was
conducted in mammalian cells.
The test material was examined for mutagenic activity according to OECD
TG 471 and under GLP conditions in the bacterial reverse mutation test
using the histidine-requiring Salmonella typhimurium strains TA 1535, TA
1537, TA 98 and TA 100, the tryptophan-requiring Escherichia coli strain
WP2 uvrA, and a liver fraction of Aroclor 1254-induced rats for
metabolic activation (S9-mix).
Two tests were performed with all strains in both the absence and the
presence of S9-mix with different concentrations of the test substance
formulation, ranging from 62 - 5000 µg/plate and 125 - 2000 µg/plate.
Negative controls (DMSO) and positive controls were run simultaneously
with the test substance.
The test material was not toxic to the Salmonella typhimurium strains TA
1535, TA 98, TA 100 and E. coli strain, as was evidenced by an absence
in decrease in the mean number of revertant colonies with increasing
concentration. S. typhimurium strain TA 1537 showed a decrease in the
mean number of revertant colonies at the four highest concentrations in
the first assay. However, this decrease was not observed in the second
In both assays, in the absence and the presence of S9-mix and in all
strains at any of the concentration of the test substance, the material
did not cause a two-fold or greater reproducible increase in the mean
number of revertant colonies appearing in the test plates compared to
the background spontaenous reversion rate observed in the negative
The positive controls gave the expected increase in the number of his+
or trp+ revertants in both the absence and the presence of the S9-mix.
It is concluded that the test material was not mutagenic under the
conditions employed in this study.
An in vivo mouse micronucleus study was conducted.
The test material was subjected to a micronucleus assay in mice to
detect potential chromosome breaking activity according to the method of
In the assay, 6 animals of each sex were included in each treatment
group and 8 animals of each sex in the negative control group (5 animals
in the treated groups and 8 animals in the control group were used for
Each mouse was medicated per gavage once daily on two consecutive days
with the vehicle used for the test material (negative control), with
cyclophosphamide at a concentration of 50 mg/kg bw (positive control) or
with the test material at one of three dose levels (200, 1000 or 5000
mg/kg bw). The test material and the controls were administered in a
standard volume of 20 ml/kg bw. This treatment schedule was selected to
expose a high proportion of the cell population to the test material
during two successive S-phases of the cell cycle.
24 Hours after the second treatment (48 hours after the first
treatment), the mice were sacrificed and bone marrow was removed from
the femora and prepared on slides for examination. One thousand
polychromatic erythrocytes (PCE) as well as one thousand normochromatic
erythrocytes (NCE) were scored. The ratio of PCE to NCE based on 1500
cells (PCE + NCE) counted per animal was used as a measure of the toxic
efficacy of the test material.
After treatment of the mice with the test material, no substance-related
increase of micronucleated erythrocytes was observed at any dose level
tested in comparison with the negative control group. No toxic effects
of the test material were observed. As expected, the positive controlg
roup showed a significant increase in the number of micronucleated
erythrocytes in comparison with the negative control group.
In conclusion, it can be stated that during this mouse micronucleus
assay with the test material no chromosome-breaking activity or damage
to the mitotic apparatus could be detected under the experimental
conditions reported and thus no evidence of any potential chromosome
mutagenic activity was demonstrable.
Additional information from genetic toxicity in vitro:
an OECD Guideline 471 study, the test material was negative for
mutagenicity inS. typhimuriumstrains TA 1535, TA 1537, TA 98 and
TA 100 and inE. colistrain WP2 uvr A either with or without
metabolic activation. In an OECD Guideline 476 study in mouse lymphoma
L5178Y cells, the test material was negative for mutagenicity. In an
OECD Guideline 473 study with cultured Chinese hamster ovary cells (CHO
K-1 line), the test substance did not produce chromosomal effects either
with or without metabolic activation.
test substance was negative for mutagenicity in a mouse micronucleus
study conducted with NMRI KFM mice following oral administration at dose
levels as high as 5000 mg/kg bw.
Justification for selection of genetic toxicity endpoint
Well conducted in vitro and in vivo genetic toxicity studies
Based on the universally negative results
obtained in adequate in vitro and in vivo test for mutagenicity, the
test material is not classifed.
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