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Administrative data

Description of key information

GLP guideline studies for acute toxicity via oral, dermal and inhalation exposure are available for propylene glycol methyl ether. These studies are supported by several non-GLP studies equivalent or similar to OECD guidelines 401, 402 and 403. The studies rated as Klimisch 1 (reliable without restrictions) have been selected as as key studies for the  hazard assessment.

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:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to EU Method B.1 and in accordance with the Principles of GLP
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 180-250 g (male) and 110-170 g (female)
- Fasting period before study: overnight fasting (18 hours)
- Housing: 2-3 rats/cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not specified in the report

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): not specified in the report
- Air changes (per hr): not specified in the report
- Photoperiod (hrs dark / hrs light): 12 hours light:dark cycle
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test material was administered undiluted.
Doses:
2500, 3150, 3970 and 5000 mg/kg
No. of animals per sex per dose:
5 males + 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: initial, day 7 and day 14
- Necropsy of survivors performed: yes
Statistics:
probit analysis
Sex:
female
Dose descriptor:
LD50
Effect level:
4 277 mg/kg bw
95% CL:
3 478 - 5 572
Sex:
male
Dose descriptor:
LD50
Effect level:
3 739 mg/kg bw
95% CL:
2 573 - 7 986
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 016 mg/kg bw
95% CL:
3 503 - 4 915
Mortality:
Refer to Table 1 for further details.
Clinical signs:
Refer to Tables 2 and 3 for further details, rats in all the dose groups were overtly affected, the commonest clinical signs being gait abnormalities, chromodacryorrhoea and piloerection. The majority of the rats that died were comatose prior to death - in some cases they were unconscious for 48 hours or more before death. Four rats from the 3970 mg/kg dose group and one male from the 5000 mg/kg dose group were comatose for part or all of day 2 but recovered
Body weight:
All surviving animals had gained weight relative to their day 0 body weights by the end of the 14-day observation period
Gross pathology:
Refer to Tables 2 and 3 for further details
Other findings:
- Organ weights: no data
- Histopathology: no data
- Potential target organs: no data

Table 1: Mortality Table

Dose (mg/kg)        Cummulative mortality (14 days)
   Male  Female  Total
 2500 1/5  0/5  1/10 
 3150 1/5  0/5  1/10 
 3970 3/5  2/5  5/10 
 5000 4/5  4/5  8/10 
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, the LD50 for methyl proxitol to rats (combined) was 4016 mg/kg (3503-4915 mg/kg), for females was 4277 mg/kg (3478-5572 mg/kg) and for males was 3739 mg/kg (2573-7986 mg/kg)
Executive summary:

The acute oral toxicity of methyl proxitol was evaluated in groups of rats (5 males + 5 females) at doses of 2500, 3150, 3970 and 5000 mg/kg. Mortality was observed in all the dose groups. Rats in all the dose groups were overtly affected, the commonest clinical signs being gait abnormalities, chromodacryorrhoea and piloerection. The majority of the rats that died were comatose prior to death - in some cases they were unconscious for 48 hours or more before death. Four rats from the 3970 mg/kg dose group and one male from the 5000 mg/kg dose group were comatose for part or all of day 2 but recovered. All surviving animals had gained weight relative to their day 0 body weights by the end of the 14-day observation period. Based on the results of the study, the LD50 for methyl proxitol to rats (combined) was 4016 mg/kg (3503-4915 mg/kg), for females was 4277 mg/kg (3478-5572 mg/kg) and for males was 3739 mg/kg (2573-7986 mg/kg)

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
4 016 mg/kg bw
Quality of whole database:
Good (Klimisch 1)

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to OECD TG and was conducted in accordance with the Principles of GLP.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: approximately 8-9 weeks
- Weight at study initiation: not specified in the report
- Fasting period before study: not specified in the report
- Housing: two/cage in stainless steel wire cages
- Diet (e.g. ad libitum): Purina certified Rodent Chow #5002 available ad libitum, except during exposure
- Water (e.g. ad libitum): Municipal tap water available ad libitum, except during exposure
- Acclimation period: one week prior to exposure


ENVIRONMENTAL CONDITIONS
- Temperature (°C): standard conditions
- Humidity (%): standard conditions
- Air changes (per hr): standard conditions
- Photoperiod (hrs dark / hrs light): standard conditions
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel and glass Rochester-type inhalation chamber (50 x 50 x50 cm) with a pyramidal top, under dynamic conditions
- Exposure chamber volume: 157 liter stainless steel
- Method of holding animals in test chamber: whole-body exposure
- Source and rate of air: ambient
- Method of conditioning air: not specified in the report
- Treatment of exhaust air: not specified in the report
- Temperature, humidity, pressure in air chamber: 22 °C and 50%


TEST ATMOSPHERE
- Brief description of analytical method used: The analytical concentration of DOWANOL PM in the breathing zone of the animals was determined continuously with a Miran 1A infrared (IR) spectrophotometer at a wavelength of 8.9 microns. The IR was calibrated and a standard curve compiled, prior to start of the study, with air standards of DOWANOL PM, prepared by vaporizing measured volumes of DOWANOL PM into Saran fim bags containing metered volumes of dry, compressed air. The analytical concentration during each exposure was interpolated from a standard curve. The analytical system was checked prior to each exposure with at least one standard of known concentration. The nominal concentration of the test material in the chamber was calculated based on the amount of test material used and the total amount of air passed through the chamber during the exposure period.
- Samples taken from breathing zone: not specified in the report
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
6 h
Concentrations:
6000 ppm nominal (6038 ppm analytical), 7000 ppm nominal (7559 ppm analytical)
No. of animals per sex per dose:
5 male + 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observation and animals weighed on days 1, 2, 4, 8, 11 and 15
- Necropsy of survivors performed: yes
Statistics:
Descriptive statistics - means and standard deviations of body weights, chamber concentration (time-weighted average, only), temperatures, relative humidity and air-flows were calculated
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 7 000 ppm
Exp. duration:
6 h
Remarks on result:
other: 7559 ppm (analytical)
Mortality:
No mortalities observed
Clinical signs:
6000 ppm: All rats were generally unresponsive to noise with only staggered movement the last three and one half hours of the exposure. Upon removal from the chamber, all rats were laterally recumbent with sporadic, staggered movement. By day 2, all male rats appeared normal, however, three of five females were still inactive with some staggered movement. All rats appeared normal by day 3 and survived the 2-week post-exposure period
7000 ppm: All rats were mostly inactive and unresponsive to noise the last three and one half hours of the exposure. Upon removal from the chamber, all male and female rats were laterally recumbent, motionless and unresponsive to noise or touch. By day 2, all male rats were alert but weak with little movement. Female rats, however, were laterally recumbent and motionless on day 2 but did not respond to touch. All male and female rats appeared visibly normal by day 3.
Body weight:
6000 ppm: Body weights of both the sexes were decreased 11%, from pre-exposure values, on the day of exposure, but had exceeded pre-exposure weights within a week.
7000 ppm: Male body weights were decreased 10% from pre-exposure values, on the day after exposure, but had exceeded pre-exposure weights within a week. Female body weights on day 4 were decreased 11% from pre-exposure values and did not exceed pre-exposure values until day 11
Gross pathology:
6000 ppm: Gross examination of all animals after the two-week post-exposure period only found a unilateral corneal opacity in one female and there were no effects attributable to DOWANOL PM exposure.
7000 ppm: Gross examination of all animals after the two-week post-exposure period did not find any effects attributable to DOWANOL PM exposure
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In summary, female rats seemed to be affected to a greater degree as they required a longer period of time than males before returning to normal. There were no mortality or lesions in male or female Fischer 344 rats attributable to exposure to either 6000 ppm nominal (6038 ppm analytical) and 7000 ppm nominal (7559 ppm analytical) DOWANOL PM. The LC50 of DOWANOL PM to male and female Fischer 344 rats is in excess of 7000 ppm nominal (7559 ppm analytical)
Executive summary:

Groups of five male and five female Fischer 344 rats were exposed for six hours to nominal concentrations of 6000 ppm and 7000 ppm (analytical concentrations of 6038 ppm and 7559 ppm) of DOWANOL PM. Animals were observed daily, weighed two to three times per week and survivors were necropsied two weeks after exposure.

All rats survived the exposure to 6038 ppm and the two -week post-exposure period. All rats were laterally recumbent and generally unresponsive to noise during most of the exposure to 6038 ppm and did not appear normal until day 2 (males and two females) or day 3 (remaining females). For exposure to 7559 ppm, all rats appeared normal on day 3. Mean body weights of both sexes for either exposure were decreased to 10 -11%, from pre-exposure levels, on the day after exposure, but exceeded pre-exposure values generally within a week. There were no exposure-related, grossly visible lesions noted in any animal necropsied fourteen days after exposure to the test material.

Based on the results of the study, the six-hour LC50 for DOWANOL PM to male and female Fischer 344 rats is greater than 7000 ppm nominal (analytical 7559 ppm).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Good (Klimisch 1)

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to EU Method B.3 and was conducted in accordance with the Principles of GLP
Qualifier:
equivalent or similar to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 180-250 g (male) and 110-170 g (female)
- Fasting period before study: no
- Housing: 2-3 rats/cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not specified in the report

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): not specified in the report
- Air changes (per hr): not specified in the report
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area
- % coverage: 60% of the dorsal area
- Type of wrap if used: waterproof adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: at the end of the 24-hour exposure period

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Constant volume or concentration used: no data=
Duration of exposure:
24-hours followed by a 14-day observation period
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 male + 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights recorded on days 0, 7 and 14
- Necropsy of survivors performed: not specified in the report
- Other examinations performed: clinical signs
Statistics:
not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality was observed
Clinical signs:
No overt clinical signs were observed
Body weight:
All rats gained weight during the 14 day observation period
Gross pathology:
not specified in the report
Other findings:
no data
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, the LD50 of methyl proxitol to rats (combined) was greater than 2000 mg/kg (the maximum dose applied)
Executive summary:

The acute dermal toxicity study was evaluated in a group of rats (5 male + 5 female) at the maximum applicable dose of 2000 mg/kg, no mortality and clinical signs were recorded and all rats gained weight during the 14 day observation period. Based on the results of the study, the LD50 of methyl proxitol to rats (combined) was greater than 2000 mg/kg (the maximum dose applied)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Good (Klimisch 1)

Additional information

Oral - The oral LD50 value for propylene glycol methyl ether in experiments in rats ranges from 4016 to 7950 mg/kg. Oral LD50 values from other animal experiments were 10,800 mg/kg for mice; 1840 to 5300 mg/kg for rabbits, and 4600 to 9000 mg/kg for dogs. The key study identified for acute oral toxicity is the Shell (1985) study in rats and the LD50 value (male and female) is 4016 mg/kg body weight.

Dermal - When applied occluded to the skin of rabbits, the LD50 value was found to be in the range of 13 -14 g/kg. The acute (24 hr) percutaneous LD50 of the undiluted test material in rats was greater than 2000 mg/kg (the maximum dose that could be applied). The key study identified for acute dermal toxicity is the Shell (1985) study in rats and the LD50 value (male and female) is greater than 2000 mg/kg.

Inhalation - The LC0 values were >6000 to 15000 ppm (22478 to 56197 mg/m3) for rats; <6038 to 7559 ppm for mice (22620 to 28319 mg/m3), and >14600 ppm (54697 mg/m3) for guinea pigs. The key study is the Dow (1991) study in rats with an LC0 of greater than 7000 ppm (duration 6 hours), which would be equivalent to approximately 26.22 mg/l (based on conversion equation at 20 degree celsius and 1 atmosphere). Using Haber's law for converting this six hour exposure to a 4 -hour exposure, the equivalent value is 30.02 mg/l or 30020 mg/m3.


Justification for selection of acute toxicity – oral endpoint
Guideline equivalent study in accordance with the Principles of GLP

Justification for selection of acute toxicity – inhalation endpoint
Guideline equivalent study in accordance with the Principles of GLP

Justification for selection of acute toxicity – dermal endpoint
Guideline equivalent study in accordance with the Principles of GLP

Justification for classification or non-classification

LD50 values for oral and dermal route are greater than 2000 mg/kg/bw and LC0 values for the inhalation route are greater than 20 mg/l. As in the other acute oral studies and dermal and inhalation studies, there were no clinical signs and no mortalities observed, propylene glycol methyl ether will not be classified for acute oral toxicity as per UN-GHS (4th edition).

According to the EU criteria for classification and labeling, propylene glycol methyl ether is not classified for acute toxicity for any route of exposure.