1-propoxypropan-2-ol

Endpoint summary

Description of key information

Several non-GLP studies equivalent to OECD guidelines 401, 402 and 403 are available for propylene glycol n-propyl ether.

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:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP study equivalent to OECD guideline 401

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 - 300 g
- Fasting period before study: overnight
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 8.0 ml/kg

Doses:

males: 2.0, 4.0, 8.0 ml/kg
females: 1.0, 2.0, 4.0 ml/kg
The relative density of Propasol Solvent P is 0.88 g/ml.

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weights were recorded at days 0 (before dose), 7, 14 (just prior to sacrifice)
- Necropsy of survivors performed: at death or sacrifice each animal is subjected to gross pathologic evaluation

Statistics:

LD50's and the estimated LD50 slopes are calculated by the moving average method and are based on a 14-day observation period.

Sex:

male

Dose descriptor:

LD50

Effect level:

4.92 mL/kg bw

95% CL:

3.58 - 6.78

Sex:

female

Dose descriptor:

LD50

Effect level:

2.83 mL/kg bw

95% CL:

1.61 - 4.98

Sex:

male

Dose descriptor:

LD50

Effect level:

4 330 mg/kg bw

95% CL:

3 150 - 5 976

Sex:

female

Dose descriptor:

LD50

Effect level:

2 490 mg/kg bw

95% CL:

1 417 - 4 382

Mortality:

males (8.0 ml/kg): 5/5
males (4.0 ml/kg): 1/5
males (2.0 ml/kg): 0/5

females (4.0 ml/kg): 4/5
females (2.0 ml/kg): 1/5
females (1.0 ml/kg): 0/5

Clinical signs:

other: males (8.0 ml/kg): sluggishness, unsteady gait at 3 min; marked sluggishness at 5 min; prostration at 10 min; death of 1 at 1.5 h males (4.0 ml/kg): sluggishness, unsteady gait at 3 min; marked sluggishness at 10 min; lacrimation in 1 at 1 day; survirvors

Gross pathology:

males (8.0 ml/kg): lungs of 2 red; stomachs liquid-filled; glandular portion of 1 stomach red
males (4.0 ml/kg): in victim: lungs red; stomach liquid-filled; in survivors: nothing remarkable
males (2.0 ml/kg): nothing remarkable

females (4.0 ml/kg): in victims: lungs darks red; stomachs of 2 liquid-filled; in survivor: nothing remarkable
females (2.0 ml/kg): in victim: lungs red; stomach liquid-filled; in survivors: nothing remarkable
females (1.0 ml/kg): kidney of 1 small

Other findings:

none

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the the LD50 value for male and female reported to be > 2000 mg/kg this material is not classified as acutely toxic according to EU criteria via oral ingestion.

Executive summary:

Three groups of 5 male and 5 female Sprague-Dawley albino rats received by stomach intubation with a ball-end stainless steel needle dose levels of 8, 4, 2 ml/kg bw and 4, 2, 1 ml/kg bw, respectively. The LD50 for male rats receiving peroral doses of PROPASOL Solvent P was 4.92 ml/kg bw; that for females was 2.83 ml/kg bw. Signs of toxicity included sluggishness, unsteady gait, lacrimation, tremors (in one) and prostration. Most death occured at 1.5 hours to 3 days. One female succumbed at 6 days. Survivors recovered at 1 to 4 days. At necropsy, there were red lungs, liquid-filled stomachs, one red stomach (glandular section) and one small kidney.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 490 mg/kg bw

Quality of whole database:

good

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:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP study equivalent to OECD guideline 403

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratory, Kinsgton, NY
- Age at study initiation: 8 weeks
- Fasting period before study: n.a.
- Housing: individual housing in stainless steel wire mesh cages
- Diet (e.g. ad libitum): standard Purina diet ad libitum (except during exposure)
- Water (e.g. ad libitum): ad libitum (except during exposure)
- Acclimation period: minimum 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 50%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours


IN-LIFE DATES: From: To:

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: glass and stainless steel Rochester-type chambers under dynamic airflow conditions
- Exposure chamber volume: 112 liter
- Source and rate of air: 30 liters/min
- Method of conditioning air: test material was pumped into a counter-current, multi-plated distillation colum where it was vaporized and mixed with compressed air
- Temperature, humidity in air chamber: 24-26°C, 31-32% humidity,


TEST ATMOSPHERE
- Samples taken from breathing zone: no (nominal chamber concentration was calculated based on the amount of test material used and the total amount of air that passed through the chamber during the xposure period)

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

0, 1725 ppm (highest concentration attainable at room temperature 25°C)

No. of animals per sex per dose:

6 male rats

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation-during exposure and at least once per day during observation period; weighing-on the first day and twice per week during observation period

Statistics:

Means and standard deviations of animal body weights were calculated for descriptive purposes.

Sex:

male

Dose descriptor:

LC0

Effect level:

> 1 725 ppm

Exp. duration:

4 h

Remarks on result:

other: highest attainable concentration at room temperature

Mortality:

no mortality

Clinical signs:

other: none

Body weight:

Body weights of animals exposed to the test material were comparable to control values throughout the two week observation period and all animals appeared to be within normal health limits during the post-exposure period.

Other findings:

- Other observations: During exposure, the rats being exposed to the test material appeared to be slightly lethargic; rats in the control chamber appeared to be normal.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this study, PnP should not pose any significant acute inhalation hazards in humans; although a slight sedative effect may occur with prolonged exposure to near-staurated atmospheres.

Executive summary:

Six male rats were exposed for four hours to vapors of propylene glycol propyl ether (PnP) at a nominal concentration of 1725 ppm. This was the highest concentration attainable at room temperature (25°C). Simultaneously, 6 male rats (serving as controls) were housed in a chamber supplied with clean, filtered air. Animals exposed to the test material appeared to be slightly lethargic during exposure. Mean body weights of exposed animals were comparable to to control values throughout the two week observation period and each animal appeared to be within normal health limits. No mortality was encountered in association with exposure to this test material. Based on the results of this study, PnP should not pose any significant acute inhalation hazards in humans. A slight sedative effect may occur however, with prolonged exposure to saturadted atmospheres.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

good

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:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP study equivalent to OECD guideline 402

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.0 - 3.0 kg
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped intact skin of the trunk
- Type of wrap if used: Test material was retained under impervious sheeting. Vetrap Bandaging Tape was wrapped over the impervious sheeting.

REMOVAL OF TEST SUBSTANCE
After the contact period (24 hours) excess fluid was removed to diminish ingestion.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0, 4.0, 8.0 ml/kg
- Concentration (if solution): pure (liquid) substance
- Constant volume or concentration used: doses are varied by adjusting the volume of the test material

Duration of exposure:

24 hours

Doses:

2.0, 4.0, 8.0 ml/kg
The relative density of Propasol Solvent P is 0.88 g/ml.

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals weights were recorded at 0 days (before dose), 7 days and 14 days (just prior to sacrifice)
- Necropsy of survivors performed: at death or sacrifice each animal was subjected to gross pathologic evaluation

Statistics:

LD50's and the estimated LD50 slopes are calculated by the moving average method and are based on a 14-day observation period.

Sex:

male

Dose descriptor:

LD50

Effect level:

4.29 mL/kg bw

95% CL:

2.9 - 6.34

Sex:

female

Dose descriptor:

LD50

Effect level:

4.92 mL/kg bw

95% CL:

3.58 - 6.78

Sex:

male

Dose descriptor:

LD50

Effect level:

3 775 mg/kg bw

95% CL:

2 552 - 5 579

Sex:

female

Dose descriptor:

LD50

Effect level:

4 330 mg/kg bw

95% CL:

3 150 - 5 966

Mortality:

8.0 ml/kg (males): 5/5
4.0 ml/kg (males): 2/5
2.0 ml/kg (males): 0/5

8.0 ml/kg (females): 5/5
4.0 ml/kg (females): 1/5
2.0 ml/kg (females): 0/5

Clinical signs:

other: 8.0 ml/kg (males): erythema, edema, necrosis at death; ecchymosis on 2 at death; comatose appearance within 15 min; dilated pupils in 2 at death; death of 4 at 2.5-3.5 hours 4.0 ml/kg (males): erythema, edema at 1 day; ecchymosis on 2 at 1 to 7 days; necr

Gross pathology:

8.0 ml/kg (males): tracheas red
4.0 ml/kg (males): in victims: lungs mottled, dark red; tracheas red; in survivors: nothing remarkable
2.0 ml/kg (males): nothing remarkable

8.0 ml/kg (females): lungs dark red; trachea of 1 red
4.0 ml/kg (females): in victim: lungs and trachea red; in survivors: nothing remarkable
2.0 ml/kg (females): lungs of 2 mottled light and dark pink

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

PROPASOL Solvent P was moderately toxic following single dermal application. According to EU criteria no classification for acute dermal toxicity is required based on the LD50 > 2000 mg/l.

Executive summary:

Three groups of 5 male and 5 female New Zealand White rabbits, weighing between 2.0 and 3.0 kg, were subjected to 24 hours of contact with 8.0, 4.0 or 2.0 ml/kg of PROPASOL Solvent P which was retained under impervious sheeting on the clipped, intact skin of the trunk. As necessary for larger doses, gauze was wrapped around the trunk over the sample to prevent leakage. Vetrap Bandaging Tape was wrapped over the impervious sheeting and the animal was returend to its cage for the contact period. Doses were varied by adjusting the volume of the test material. After the contact period, excess fluid is removed to diminish ingestion. Observations for skin reaction were made at one hour, 7 days and 14 days after the contact period.

The LD50 for male rabbits was 4.29 ml/kg. The LD50 for females was 4.92 ml/kg. Local dermal effects included erythema, edema, ecchymosis, necrosis, desquamation, fissuring, ulceration, scabs and alopecia. A rapid comatose appearance, followed by dilated pupils, unsteady gait, sluggishness and prostration were among the signs of toxicity observed. Time to death ranged from one hour to 2 days. Survivors recovered at one to 2 days. Gross pathologic findings included red lungs and red tracheas.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 775 mg/kg bw

Quality of whole database:

good

Additional information

The oral LD50 values for propylene glycol n-propyl ether were consistenly greater than 2000 mg/kg bw in several experiments in rats. in the key study, the LD50 for males was 4330 and for females was 2490 mg/kg bw. This LD50 for the females is therefore taken as the acute oral LD50 for the chemical safety assessment. When applied to the skin of rabbits, the dermal LD50 values ranged from 3170 to 4330 mg/kg bw. The most reliable acute dermal toxicity study had a LD50 value for male rabbits of 3775 mg/kg bw. No mortality was observed in any of the acute inhalation studies in rats at saturated vapor concentrations up to the maximum attainable concentration at room temperature (1725 ppm = 8430 mg/m3).

Justification for selection of acute toxicity – oral endpoint
reliable study

Justification for selection of acute toxicity – inhalation endpoint
reliable study

Justification for selection of acute toxicity – dermal endpoint
most reliable study

Justification for classification or non-classification

According to EU criteria Propylene Glycol n-Propyl Ether is not classified for acute toxicity based on the oral and dermal LD50s >2000 mg/kg bw in rats and rabbits and the inhalation LC0 > 8340 mg/m3 in rats.