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EC number: 203-794-9
CAS number: 110-71-4
There is a strong evidence in literature that
Diethyleneglycoldimethylether is metabolised to 2-Methoxyethanol .
Therefore, a read across to the 2 and 13-week drinking water study with
2 -Methoxyethanol in mice was conducted.
The animals were treated with 0, 200, 400, 600, 1000 or 1200 mg/kg bw/d
2 -Methoxyethanol for 2 weeks or with 0, 200, 4000, 6000, 8000 or 10000
ppm 2 -Methoxyethanol for 13 weeks via drinking water. All animals
2 weeks study:
The final mean body weight and mean body weight gain did not differ from
those of the control group. Average water consumption decreased for all
males and females treated with 200, 400, 1000 and 1200 mg/kg bw/d. The
only clincal observation noted in male mice was dehydration in 2 of 5
males in the 1200 mg/kg bw/d group. Dehydration was also noted in one
female each in the 0, 1000 and 1200 mg/kg bw/d groups and in 2 females
in the 600 mg/kg bw/d group. Changes in organ weights were minimal. For
male mice, absolute and relative testis and thymus weights decreased in
a dose-related fashion, and for female mice in the two highest dose
groups, absolute and relative thymus weights were lower than those of
the control group. No chemical-related gross lesions were noted in male
or female mice.
13 weeks study:
The mean body weight gains of male mice receiving 10000 ppm and female
mice receiving 8000 or 10000 ppm were notably lower than those of the
control group. There were no significant clinical observations in male
or female mice during the study. With exception of decreases in thymus
and testis weights, most changes in absolute and relative organ weights
could be attributed to low final mean body weights. Dose-related
decreases were noted for the absolute and relative testis weights of
male mice (4000 ppm and above) and the absolute and relative thymus
weights of male and female mice (8000 ppm and above). Chemical-related
gross lesions were identified in the testis and thymus. Testes from mice
in the 6000, 8000 and 10000 ppm groups were small. Thymuses of males in
the 8000 and 10000 ppm groups and females in the 10000 ppm group were
also smaller than those of the control group animals. In male mice,
degeneration of the testis was characterised microscopically by a
dose-related, minimal to marked degeneration of the germinal epithelium
in seminiferous tubules; at the higher doses, the lumen of many tubules
contained only Sertoli cells. In the thymus of most males from the two
highest dose groups and females in the high-dose group, there was
minimal to mild lymphoid depletion (atrophy) consisting of a reduction
in the thickness of the thymic cortex and in the number of thymocytes.
Histopathologic changes were also present in the spleen of male (4000
ppm and above) and female mice (2000 ppm and above) and in the adrenal
gland of female mice (2000 ppm and above). Increased hematopoesis was
present in the spleen of mice from all dosed groups, excluding male mice
in the lowest dose group (2000 ppm), and was characterised by a marked
increase in the number of megakaryocytes present in the red pulp. In
adrenal gland of female mice in all dosed groups, there was hypertrophy
of the X-zone. In dosed mice, there was a marked increase in the lipid
vacuolization normally present in this region of the adrenal gland in
young female mice. Sperm morphology evaluations were performed on male
mice treated with 0, 2000, 4000 or 6000 ppm 2-Methoxyethanol. Vaginal
cytology evaluations were performed on female mice treated with 0, 6000,
8000 or 10000 ppm. Results showed significant decreases in epididymal
and cauda epididymal weights for males in the 6000 ppm group and in
testicular weight for males in the 4000 and 6000 ppm groups. The values
for sperm motility were significantly less than controls for 2000 ppm
and 6000 ppm groups, as were sperm concentration measurements for males
treated with 2000 to 6000 ppm. Spermatid measurements were significantly
lower than controls for males receiving 4000 or 6000 ppm. For females,
all dose groups differed significantly from controls in the relative
frequency of time spent in estrous stages.
In summary, the major target organs for toxicity were testes in males
and the hematopoetic system in both sexes. 2 -Methoxyethanol appeared
primarily to act primarily as a spermatotoxic and immunotoxic agent.
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