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EC number: 252-104-2
CAS number: 34590-94-8
For the oral route, a 28-day oral gavage study conducted under GLP and according to guideline (KANPOGYO No.700, YAKUHATSU No. 1039.61, and KIKYKU No. 1014) is available for dipropylene glycol methyl ether. For the dermal route two non-GLP studies equivalent to OECD guidelines 410 (in rats) and 411 (in rabbits) are available for dipropylene glycol methyl ether. For the inhalation route, GLP-studies in rats and rabbits according to OECD guideline 413 and 412 are available for dipropylene glycol methyl ether. In addition, several non-GLP studies in rats, rabbits, guinea pigs and monkeys, similar to OECD guideline 452 were conducted with dipropylene glycol methyl ether.
This study was performed to assess the
systemic toxicity of dipropylene glycol methyl ether (DPGME) to the rat
by oral administration, once daily for 28 days, to 3 groups of 5 male
and 5 female rats at dosage levels of 40, 200 and 1000 mg/kg/day. A
negative control group was provided. A recovery group of 5 males and 5
females were additionally assigned to the control group and high dose
All animals survived during the treatment
period of 28 days and the 2 weeks recovery period. There were no
significant differences between control group and treatment groups for
body weights and food consumption. Macroscopic examination performed at
the end of the 28 days treatment and the recovery period revealed no
Tentative salivation was recorded in the
male and female animals treated with the 1000 mg/kg from the day 11
onward, which appeared immediately after oral administration of test
substance. Relative liver weight of male and female animals treated with
the 1000 mg/kg at 28 days treatment increased with statistical
significance, while the male animals treated with 1000 mg/kg at recovery
group showed also a statistical significant increases in absolute and
relative livery weight. Upon histopathological examination centrilobular
hypertrophy of the liver was observed in the animals treated with 1000
There were no other changes that were
considered to be related to treatment of this test substance.
It is concluded that 200 mg/kg/day
represents the no-observed-effect level (NOEL) and that 1000 mg/kg/day
represents no-observed-adverse-effect level (NOAEL)for DPGME in the
rat. The only effects observed at 1000 mg/day were transient salivation
immediately after administration of the test material, increased liver
weight and centrilobular hypertrophy of the liver. The liver weight
increase (which was very minor, <10 %) and hypertrophy in the liver
observed at 1000 mg/kg/day was likely due to increased metabolism and
was not accompanied by an increase in liver enzymes.
rats (10/sex/exposure) were exposed to 0, 15, 50 and 200 ppm (0, 91, 303
and 1212 mg/m3) of dipropylene glycol monomethyl ether (DPGME) for 6
hr/day, 5 days /week for 13 weeks.
were no DPGME exposure related adverse effects on body weights in rats
during the 13 week study. There were no statistically significant
differences from control body weight means in male and female rats. There
were no exposure related effects on any of the measured hematology
parameters in either sex of rat. There were also no statistically
significant differences from control means. There
were no exposure related effects on any of the measured clinical
chemistry parameters in either sex of rat. The only statistically
significant difference was a slight decrease in BUN in female rats
exposed to 50 ppm, but this had no toxicological significance. There
were no apparent effects on any of the urinalysis parameters of male and
female rats. There
were also no statistically significant differences in absolute or
relative organ weights of rats exposed to DPGME, except for a slight
decrease in mean relative liver weight of 50 ppm exposed males.
gross and histopathologic observations were considered to be spontaneous
changes of minimal severity which were not treatment related. Based on
gross observations, liver from rats exposed to DPGME appeared to be
increased in size, however this observation was not supported by group
mean liver weights and there was no histopathologic evidence of
Based on the results of this study the NOAEL
for dipropylene glycol methyl ether for inhalation exposure of
Fischer-344 rats is 200 ppm.
DOWANOL 50B, the methyl ether of dipropylene
glycol, a colorless liquid was evaluated for chronic skin absorption in
Male rabbits were selected and divided into
groups of at least five animals each. Dipropylene glycol methyl ether
was applied over the abdominal skin using the following technique. A pad
of absorbent cotton about 3”×3” in size and sufficiently thick just to
absorb the volume of the test material was applied to the clipped
abdomen of the rabbit. The proper dose of the compound was added to the
cotton and the pad was then covered with an impervious saran film about
5”×5”. This saran film was covered with a heavy cloth, and the whole
application was then strapped onto the animal with adhesive tape.
Dipropylene glycol methyl ether was thus applied five times a week over
a period of three months at four dosage levels: 1.0, 3.0, 5.0 and 10.0
ml/kg. A separate group of five animals to which distilled water was
bandaged served as controls.
The rabbits received the stock diet of
commercial rabbit chow and water ad libitum. The rabbits were weighed
before the application of each daily dose of the test compound. Control
blood counts were taken before the start of the study and on the
thirtieth and ninetieth day of the application of the compound. Possible
significance between means was studied by students test of “t”. On the
ninetieth day the rabbits were autopsied and tissues taken from the
liver, kidneys, spleen, adrenal, heart, lung and occasionally stomach,
for histopathological examination. Such sections were stained with
haematoxylin and eosin.
Dipropylene glycol methyl ether at the 10
ml/kg and 5 ml/kg produced some narcosis. However narcosis was not
observed at lower dose levels (1.0 and 3.0 ml/kg). Mortality was high at
the 10.0 ml/kg dosage level, slight at 5.0 ml/kg and absent at the 1.0
and 3.0 ml/kg dose levels.
No adverse body weight changes occurred at
any level except just prior to death in those animals that succumbed,
presumably to the narcotic effects of the top dosage levels.
No haematological changes occurred at any
dosage level. No significant organ weight changes occurred at any dosage
level. Observations for gross pathology revealed only gastric distension
and occasional gastric irritation in those animals dying at the 10 ml/kg
Histopathological studies conducted on the
liver, lung, spleen, adrenal, heart, testes and stomach of those animals
receiving the 5.0 and 10.0 ml/kg dosage levels revealed no changes. The
kidneys of those animals on the 10.0 ml/kg level showed some granular
and some hydropic changes, at the 5.0 ml/kg same kidney abnormalities
were observed but they were of no greater intensity than those observed
in some of the controls.
The effect of severe (repeated and
prolonged) exposure to the skin was slight, being similar to that caused
by distilled water under similar conditions.
The 28-day oral gavage study in rats is of
high quality and considered to be reliable without restrictions
(Klimisch 1). The only effects observed during this study were
salivation and increased liver weights at the highest dose level. The
liver weight increase observed at the highest dose level was only slight
and no histopathologic changes, except for hypertrophy, accompanied this
effect. There were no changes in clinical chemistry (ALP, ASP)
indicating a liver damage. The same effect was observed with other
structurally related molecules, e.g. propylene glycol methyl ether has
been shown to cause liver weight increases via a phenobarbital-like
enzyme induction mode of action and it is highly likely that dipropylene
glycol methyl ether liver weight increases occur via the same mode of
action. As this is an adaptive effect typical for many glycol ethers, it
is not consered as adverse. Based on the results of this study a no
observed adverse effect level (NOAEL) of 1000 mg/kg bw/day and a no
observed effect level (NOEL) of 200 mg/kg/day can be established in rats
under the conditions of this study.
The two studies via the dermal route are
both reliable with restrictions as they were not conducted under GLP,
but are equivalent to OECD guidelines. No adverse effects were observed
up to 1000 mg/kg bw/day in a 28 -day study in rats. In a 90-day study in
rabbits dipropylene glycol methyl ether produced some narcosis at 10
ml/kg bw/day and 5 ml/kg bw/day. No narcosis was observed at lower dose
levels (1.0 and 3.0 ml/kg bw/day). Mortality was high at the 10.0 ml/kg
dose level, some mortality was observed at 5.0 ml/kg bw/day and no
mortality was observed at the 1.0 and 3.0 ml/kg bw/day dose levels. No
haematological changes occurred at any dosage level. No significant
organ weight changes occurred at any dosage level. Observations for
gross pathology revealed only gastric distension and occasional gastric
irritation in those animals dying at the 10 ml/kg dosage level.
Histopathological analysis done on the liver, lung, spleen, adrenal,
heart, testes and stomach of those animals receiving the 5.0 and 10.0
ml/kg bw/day dose levels revealed no changes. The kidneys of those
animals on the 10.0 ml/kg bw/day level showed some granular and some
hydropic changes, at the 5.0 ml/kg same kidney abnormalities were
observed but they were of no greater intensity than those observed in
some of the controls. The effect of severe (repeated and prolonged)
exposure to the skin was slight, being similar to that caused by
distilled water under similar conditions. Based on the results of this
study a NOAEL of 3.0 ml/kg bw/day (2850 mg/kg/day) was established for
dermal exposure to dipropylene glycol methyl ether.
No significant adverse effects were observed
in rats, rabbits, guinea pigs and monkeys after repeated inhalation
exposure to dipropylene glycol methyl ether at any of the test
concentrations. The 90 -day inhalation studies in rats and rabbits were
selected as key studies as these studies are reliable without
restrictions. The highest concentration tested in these studies were 200
ppm which was identified as the NOAEC. Based on a the molecular weight of
148, this converts to 1232 mg/m3 at 20 deg Celcius and 1 atm.
The no observed adverse effect levels for dipropylene
glycol methyl ether exceed the values triggering classification via all
routes of exposure. Therefore no classification for prolonged exposure
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