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Description of key information

Several non-GLP studies in rats and dogs equivalent to OECD guidelines 401 are available for dipropylene glycol methyl ether. For the inhalation route three non-GLP studies in rats equivalent or similar to OECD guideline 403 are available. For the dermal route three non-GLP studies (one in rats and two in rabbits) equivalent or similar to OECD guideline 403 are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Method: BASF-Test
TEST PROCEDURE
In principle, the methods described in OECD Guideline 401 were used.
Young adult laboratory rats were purchased from a breeder. Several groups of 5 to 10 rats per sex and dose were treated simultaneously by gavage with preparations of the test substance in a suitable vehicle. The concentrations of these preparations were usually adjusted to achieve comparable volumes (e.g. 10 ml) per kg body weight.
Group-wise documentation of clinical signs was performed over the 7- to 14 -day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose.
The clinical signs and findings were reported in summary form.
On the basis of the observed lethality, the LD50 value was estimated or determined using a graphical evaluation of the dose response curve on probability paper.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Mean weight at study initiation: 220 g (male) and 170 g (female)
- Fasting period before study: 15-20 hours before application
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50%

MAXIMUM DOSE VOLUME APPLIED
- Dose: 5000 mg/kg bw
- Applied volume: 10 ml/kg bw
Doses:
5000 mg/kg
No. of animals per sex per dose:
5 male and 4 female
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: days 1, 2, 3, 7 and 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
0%
(no animal died after application of the TS and during the observation period)
Clinical signs:
dyspnea, apathy, abnormal position, stagger, atony, loss of pain reflex, narcosis-like state, spastic gait, scrubby fur, exsiccosis, salivation, poor general condition
Body weight:
see table in the "remarks on results"-field
Gross pathology:
organs were without findings

 Number of animals     Male   Female
5 4
 dead animals after: 1 hour 0
 1 day 0
 2 days 0
 7 days 0
 14 days 0

 Mean weight (g)   Male    Female
 before application of TS  220  170
 after 2 -4 days  226  177
 after 7 days  266  199
 after 14 days (male) after 13 days (female)  304  213
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Dipropylene glycol methyl ether is not acutely toxic via the oral route. Based on the oral LD50 > 5000 mg/kg no classification is required according to EU criteria.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Good (Klimisch 2)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
PROCEDURE
This test (also called inhalation risk test) was performed in principle as described in OECD Guideline 403.
It demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at the temperature chosen for vapor generation (usually 20 °C).

Young adult laboratory rats were purchased from a breeder. In general, the source and strain of the animals were not documented.
Several groups of usually 3 rats per sex were exposed sequentially to the vapors, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for different time periods (e.g. 3 min, 10 min, 1, 3 or 7 or 8 hours). The exposure time not causing lethality was usually tested twice.

No analytical determination of the atmosphere concentrations was performed. The nominal concentration usually can be calculated as quotient of the amount of test substance weight loss during the exposure, which is given in the raw data, and the amount of air used during the exposure.

Group-wise documentation of clinical signs was performed over the 7- to 14-day study period. Body weight of groups was determined before the start of the study and at the end of the observation period in the surviving animals.
The clinical signs and findings were reported in summarized form.

The study allows for an estimate of the length of time required to cause severe toxic effects resulting from exposure to an atmosphere saturated with vapours of the test substance. The exposure time causing 50 % lethality (LT50) can be estimated from such a study as described for the LD50. Furthermore, using the nominal concentration, vapour pressure and LT50, in many cases a 4-hour LC50 can be estimated using Haber's law.

(Inhalation Risk Test (IRT) in the rat: method according to Smyth et al., Am.Ind.Hyg. Ass.J. 23, 1962)
GLP compliance:
no
Test type:
other: Inhalation Risk Test (IRT)
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
TEST ATMOSPHERE
- mean concentration of TS: 1.66 mg/l (275 ppm)
Duration of exposure:
7 h
No. of animals per sex per dose:
12 animals were used
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 275 ppm
Exp. duration:
7 h
Mortality:
0%
(no animal died after application of the TS and during the observation period)
Clinical signs:
irritation of the mucosa: wiping of the snout, watery nose secretion, dyspnea, scrubby fur
Gross pathology:
no findings
No mortalities (0/12) after 7-hour exposure to an atmosphere enriched with the test substance vapour at 20°C.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Dipropylene glycol methyl ether is not acutely toxic via the inhalation route. Based on the LC0 > 275 ppm (1667 mg/m3) no classification is required according to EU criteria.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
9 510 mg/kg bw

Additional information

Majority of the acute toxicity studies available for dipropylene glycol methyl ether were conducted prior to GLP and OECD guidelines. However, the studies are well documented and are considered to be reliable. Several independent studies are available for each route of exposure reporting consistent results.

Oral - All acute toxicity studies via the oral route reported LD50 values greater than 5000 mg/kg for dipropylene glycol methyl ether. The key study identified for acute oral toxicity is the BASF (1979) study in rats with a reported LD50 of greater than 5000 mg/kg body weight.

Inhalation - Via the inhalation route no mortality was observed at the highest attainable concentration (i.e. LC0 values > ca. 552.6 ppm, 3404.47 mg/m3) in three independent studies. The key study identified is the BASF (1979) study in rats with a LC0 greater than 275 ppm (duration 7 hours) which would be equivalent to approximately 1.69422 mg/l (based on conversion equation at 20 degree celsius and 1 atmosphere). Using Haber's law for converting this 7 -hour exposure to a 4 -hour exposure, the equivalent LC0 value is greater than 2.04 mg/l or 2040 mg/m3.

Dermal - For the dermal route, two studies reported no mortality up to the highest dose tested (20 ml/kg bw) in rats and rabbits. One study in rabbits reported a dermal LD50 of 10 ml/kg bw (9510 mg/kg bw). The lowest LD50 will be taken into account for the risk assessment. The key studies identified are the Dow/UCC (1961) study in rabbits and the UCC (1961) study in rats with reported LD50 values of 9510 mg/kg body weight for rabbits and greater than 19020 mg/kg body weight in rats.


Justification for selection of acute toxicity – oral endpoint
Acceptable, well-documented study report which meets basic scientific principles

Justification for classification or non-classification

LD50 values for oral and dermal route are greater than 2000 mg/kg/bw. The LC0 value for inhalation is greater than 3404.47 mg/m3 (3.40447 mg/l), the highest attainable concentration.

According to the EU criteria for classification and labeling, dipropylene glycol methyl ether is not classified for acute toxicity for any route of exposure. Although there was some transient narcosis observed in some of the acute toxicity studies, this occurred at high doses and in the absence of human data would not lead to a classification for STOT SE Cat 3.