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EC number: 406-880-6
CAS number: 88917-22-0
ACETATE DPMA ACROSOLV; ACROSOLV DPMA ACETAT; ACROSOLV DPMA ACETATE; DOWANOL DPMA; DOWANOL DPMA GLYCOL ETHER; DOWANOL DPMA GLYKOL ETHER; ETHER DE GLYCOL DPMA DOWANOL
A GLP-study according to OECD guideline 407 is available for dipropylene glycol methyl ether acetate. This data is supported by GLP-studies equivalent to OECD guidelines 407 and 413 for dipropylene glycol methyl ether. Further, several studies according to or similar to OECD guidelines 411 and 413 are provided for propylene glycol methyl ether and dipropylene glycol methyl ether.
groups of Sprague- Dawley rats each containing 5 males and 5 females
received T- 4388 (colorless liquid) via oral route by steel cannula at
dose levels of 0,100, 250, 1000 mg/kg/day daily for 28 days. Rats were
received from Charles River (UK) and housed 2 or 3 of one sex per cage
in suspended polypropylene cages with stainless steel wire grid tops and
bottoms. Animals were kept for acclimatization for 8 days and provided
adlibitum feed and water. Temperature maintained in animal rooms was 18
°C - 22 °C with relative humidity of 45 - 65 % and 15-20 air changes.12
hour dark and 12 hour light photoperiod was maintained.
animals were monitored for toxic effects which included clinical
observations, body weights, organ weights, hematology, clinical
chemistry, macroscopic and microscopic evaluations.
Increased breathing and subdued
behavior were evident in the majority of animals of both sexes receiving
T-4388. There were no deaths found during 4 weeks of dosing period.
body weights and feed consumption, there were no notable intergroup
differences in either sex during 4 weeks of oral administration of
T-4388. In hematology and clinical chemistry, there were no notable
intergroup differences in either sex. In organ weights there was a
slight increase in liver in high dose females.
were no notable intergroup differences in either sex in gross pathology.
There were no microscopic findings
considered to be due to administration of the test material T-4388.
Based on the results of this study a dose of
1000 mg/kg/day was identified as no observed adverse effect level. Based
on a slight increase in liver weight which was not accompanied by
histopathologic changes and observed in females only. The no observed
effect level is 250 mg/kg/day.
Fischer – 344 (10/sex/exposure concentration
) and New Zealand white rabbits ( 7/sex/exposure
concentration ) were exposed to 0, 15,50,200 ppm (0,91,303,1212 mg/m3)
of dipropylene glycol monomethyl ether (colorless liquid DPGME) for 6
hrs/day, 5 days/week for 13 weeks.
Rats were received from Charles River
Breeding Laboratories (, ) and Rabbits were received from Langshaw
Rabbitry (, ).Rats and rabbits were kept for an acclimatization period
of 2 weeks and 4 weeks respectively. Rats were housed (2/cage) and
rabbits (1/cage) in stainless steel cages with wire bottoms. A standard
laboratory diet (Purina Certified laboratory Chow, Ralson Purina Co., .
MO) was supplied to rats and rabbits. Water also provided ad libitum to
rats and rabbits except during exposure. Housing conditions were
maintained at temperature of 20 -24 °C with relative humidity of 40-60 %.
Monitored for effects included general
observations, body weights, clinical chemistry, hematology, urinalysis
(Rats only), necropsy, organ weights and histopathology.
There were no exposure related adverse
effects on body weights in either species during the 13 week study.
There were no statistically significant differences from control body
weight means in male and female rats or in male rabbits. The mean body
weights of female rabbits in the 50 ppm group were slightly higher than
the controls at the beginning of the study and at various intervals
thereafter. This was not considered to be exposure related, due to
absence of any effect on body weights of female rabbits in the high
There were no apparent clinical effects and
mortality due to DPGME exposure. There were no exposure related effects
on any measured hematology parameters in either sex of rat and rabbit.
There were also no statistically significant differences from control
means. There were no apparent effects on any of urinalysis parameters of
male and female rats.
Clinical chemistry, hematology (PCV, Hgb,
RBC, WBC and Plat only), urinary specific gravity, organ weight, body
weight and organ to body weight ratio data were evaluated by ’s test for
the equality of variances.
All surviving animals underwent a gross
necropsy on the day following last exposure. Rats (but not rabbits) were
deprived of food overnight prior to necropsy. Rats were anesthetized
with methoxyflurane, and then decapitated. Rabbits were anesthetized
with CO2, and then decapitated. The trachea of all animals was clamped
after anesthesia to prevent aspiration of blood during decapitation.
Each animal was examined internally and externally for gross
pathological changes. The heart, liver, kidneys, brain, thymus (rats),
and testes (males) were removed from each animal and weighed. Eyes of
all animals were examined grossly using a microscope slide technique
with fluorescent illumination. Representative portions of the tissues
and organs were preserved in buffered 10% formalin.
One male rabbit from the 200 ppm exposure
group was sacrificed prior to scheduled termination of the study because
of a head tilt and disequlibirium.This animals was examined in a manner
similar to the other rabbits, except that organs were not weighed and
serum was not collected. A full set of tissues was prepared and examined
Liver samples from male rats and rabbits (3
exposure group) were fixed in a phosphate buffered 2%gluteraldehyde and
2% formaldehyde solution, then routinely processed and embedded in EPON
812 resin for possible electron microscopy.
There were no exposure related changes
observed at the necropsy in rats and rabbits. There were no DPGME
exposure related microscopically changes observed in rats and rabbits.
All histopathological observations were considered to be spontaneous
changes of minimal severity which were not treatment related.
Based on the results of this study NOAEL in
rat and rabbit was 200 ppm. Under conditions of this
study the low vapor pressure of DPGME, and results in this 13 week study
DPGME appears to have a low subchronic vapor inhalation toxicity hazard.
rats (8 animals/sex/dose) were exposed to 0,100 and 1000 mg/kg/day
(occluded and open) of DOWANOL DPM (colorless liquid) 5 days/week for 28
for effects included clinical observations, body weights, food
consumption, hematology, blood chemistry and, necropsy, organ weights,
gross pathology and histopathology.
animals were survived during 28 day exposure period.There
were no significant differences in body weights, food consumption
between control and exposed animals.There
were no statistically significant differences from control values with
respect to hematology and clinical chemistry DPGME exposed rats.
and microscopic examination of the tissues revealed no significance
findings attributable to DPGME exposure in rats.
on results of the study NOEL for rats via dermal route was > 1000
Based on toxicokinetics data summarized in IUCLID section 7.1.1,
dipropylene glycol methyl ether acetate (DPMA) rapidly hydrolyzes to
yield dipropylene glycol methyl ether in vivo. Thus, it is appropriate
to conclude that the acetate behaves in a similar way to the parent
ether due to the rapid conversion. Therefore, data on dipropylene glycol
methyl ether are used to characterise the hazards of DPMA. Supporting
data on PM and PMA are also provided.
Short-term repeated dose toxicity studies in rats (28-day), via
oral gavage, are available for propylene glycol methyl ether (PM),
propylene glycol methyl ether acetate (PMA), dipropylene glycol methyl
ether (DPM) and DPMA. The NOAELs (oral) are > 919 mg/kg bw/day for all 4
substances. No adverse effects have been observed at the highest dose
level tested. For the inhalation route, range-finding studies (up to
14-days) are available for PM and DPM. Repeated dose toxicity studies
(28- and 90-day) via the dermal route are available for PM and DPM.
Sub-chronic (90-day) inhalation studies in rats and in rabbits are
available for PM and DPM. The NOAEL for PM is 1000 ppm (3686 mg/m3), in
rats and rabbits. The NOAEL for DPM is 200 ppm (1212 mg/m3, the highest
attainable concentration), in rats and rabbits.
The only effects observed during the repeated dose toxicity study
with DPMA were increased liver weights, subdued behaviour and increased
breathing. The liver weight increase was very slight and only observed
in females of the highest dose group. There were no histopathological
changes accompanying this effect. There were no changes in clinical
chemistry (ALP, ASP) indicating any liver damage.
The same liver effects were observed with other structurally
related molecules, e.g. PM has been shown to cause liver weight
increases via a phenobarbital-like enzyme induction mode of action and
it is highly likely that DPMA liver weight increases occur via the same
mode of action. As this is an adaptive effect typical for many glycol
ethers, it is not considered as adverse. The toxicological significance
of the observed increased breathing and subdue behaviour is unclear. As
these observations were not accompanied by any significant effect, they
are considered as not relevant.
PM, PMA and DPM have been subjected to repeated dose toxicity
studies by at least one route of exposure. All studies indicate low
repeated dose toxicity for these glycol ethers. The NOAELs obtained in
the 90-day inhalation studies with PGME and DPGME were 1000 ppm (3686
mg/m3) and 200 ppm (1212 mg/m3, the highest attainable concentration),
respectively. For DPMA, this would (theoretically) be equivalent to
inhalation NOAELs of 7779 mg/m3 and 1556 mg/m3, respectively.
Extrapolation to the oral route would result in NOAELs of 2256 and 451
mg/kg bw/day, respectively. Conducting repeated dose toxicity studies
with DPMA via the oral route up to the limit dose of 1000 mg/kg bw/day
will unlikely results in any adverse effects. Therefore, the data from
DPM should be used to read-across, based on the rapid hydrolysis of
acetate moiety from DPMA to yield DPM.
Further support for read across is attached at section 13 of the
For the purposes of risk assessment, the inhalation 90 -day study
peformed using DPM with a NOEC of 200ppm will be taken as the starting
point for DNEL derivation. Converting this to mg/m3 of DPMA, this is
equivalent to 1556 mg/m3.
The no observed adverse effect levels for
dipropylene glycol methyl ether acetate exceed the values triggering
classification via all routes of exposure. Therefore no classification
for prolonged exposure is required.
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