2,3-epoxypropan-1-ol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not documented

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

The toxicology of glycidol and some glycidyl ethers

Author:

Hine, C.H. et al.

Year:

1956

Bibliographic source:

Arch. Ind. Health 14, 250-264 (1956)

Report date:

1956

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Vapor exposure - In these experiments graded concentrations of the compounds were used when death was produced with exposures to concentrated vapour. The term "saturated vapor" is not used, since in the author's experience the theoretical concentration at saturation is frequently not obtained.
The concentrated vapors approached theoretical saturation, however, except with DGE, where, owing to a small volume of sample, only about 200 ppm, was obtained.
Four-hour period. Groups of five or six mice (20 to 28 gm.) Were exposed to graded concentrations of the vapors of glycidol, AGE, and IGE at 30±1 C and to DGE at room temperature (25±1 C) for four hours in a glass chamber of 19.5 liters capacity. The motor-driven syringe assembly previously describcd by Hine and associates delivered measured amounts of the test compound from a 10 mL Luer-Lok syringe into an evaporator through which metered air moved at a uniform rate. The air flow was set at approximately 3 to 11 liters per minute, depending on the concentration desired. Nominal concentrations were calculated by the standard gas-concentration formula of Jacobs; and were checkcd by determining the total quantity of material vaporized.

Eight-hour period. Groups of six rats ( 110-140 gm.) were exposed to graded concentrations of glycidol, AGE, llGE, and IGE, with temperatures and apparatus as , described above. Groups of six rats were also exposed for eight hours to concentrated vapours of MCH, DGE, and PGE, using temperatures and apparatus as described above.

GLP compliance:

no

Remarks:

study prior to adoption of GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,3-epoxypropan-1-ol

EC Number:

209-128-3

EC Name:

2,3-epoxypropan-1-ol

Cas Number:

556-52-5

Molecular formula:

C3H6O2

IUPAC Name:

(oxiran-2-yl)methanol

Details on test material:

- Name of test material (as cited in study report): Glycidol
- Molecular weight (if other than submission substance): 74.05
- Physical state: Liquid

Test animals

Species:

rat

Strain:

Long-Evans

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: commercial laboratory in Gilroy, California
- Age at study initiation: Not documented
- Weight at study initiation: 110 - 140g
- Fasting period before study: Not documented
- Housing: 5 or 6 to a cage.
- Diet (e.g. ad libitum): standard laboratory pellets.
- Water (e.g. ad libitum): Not documented
- Acclimation period: Not documented

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not documented
- Humidity (%): Not documented
- Air changes (per hr): Not documented
- Photoperiod (hrs dark / hrs light): Not documented

IN-LIFE DATES: From: To: Not documented

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

not specified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass chamber
- Exposure chamber volume: 19.5L
- Method of holding animals in test chamber: Not documented
- Source and rate of air: The air flow was set at a rate of approximately 3 to 11 L/minute, depending on the desired concentration. A motor-driven syringe assembly delivered measured amounts of the test compound from a 10ml Luer-Lok syringe into an evaporator through which metered air moved at a uniform rate.
- Method of conditioning air: No information provided
- System of generating particulates/aerosols: No information provided
- Method of particle size determination: No information provided
- Treatment of exhaust air: Not documented
- Temperature, humidity, pressure in air chamber: Temperature: 30 ± 1°

TEST ATMOSPHERE
- Brief description of analytical method used: Nominal concentrations were calculated by the standard gas-concentration formula of Jacobs and were checked by determining the total quantity of material vaporized.
- Samples taken from breathing zone: not documented

VEHICLE
- Composition of vehicle (if applicable): not documented
- Concentration of test material in vehicle (if applicable): not documented
- Justification of choice of vehicle: not documented
- Lot/batch no. (if required): not documented
- Purity: not documented

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not documented
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not documented

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

8 h

Concentrations:

not documented

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

Test animals were observed for 10 days post-treatment for signs of test-substance related effects.

Statistics:

Litchfield and Wilcoxon

Results and discussion

Preliminary study:

Not documented

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

580 ppm

Exp. duration:

8 h

Mortality:

not documented

Clinical signs:

other: Signs of intoxication: dyspnea, lacrimation, salivation, nasal discharge, aerophagia, terminal CNS depression but also signs of stimulation, death due to pulmonary edema. Corneal opacity was also observed following the 8 hour exposure.

Body weight:

not documented

Gross pathology:

In the case of glycidol an inexplicable pulmonary emphysema was also detected.

Other findings:

The commonest pathological finding was irritation of the lungs, and pneumonitis was confirmed by microscopic examination.

Any other information on results incl. tables

The concentration level of 580 ppm is equivalent to 1.75 mg/L.

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Remarks:

Migrated information

Conclusions:

In this acute inhalation toxicity study in rats the LD50 of 580 ppm (1.75 mg/L /8h) was determined. Under the conditions of this study, the test substance should be classified as a Category II toxicant according to Regulation EC No. 1272/2008 and should have the signal word Danger and the hazard statement H330: Fatal if inhaled associated with it. According to Directive 67/548/EEC, the test substance should be classified as R23, toxic by inhalation since the LC50 was between 0.5 and 2.0 mg/L - the limits for a vapour to warrant R23.

Executive summary:

In a study conducted by Hine et al in 1956, the test substance, Glycidol, was tested for its ability to acute cause toxicity when administered to male Long Evan rats via whole-body inhalation. The test animals were exposed to the test substance for a period of 8 hours and the animals were observed for effects for 10 days post-treatment. Following this observation period, signs of intoxication included dyspnea, lacrimation, salivation, nasal discharge, aerophagia, terminal CNS depression but also signs of stimulation, with death usually caused by pulmonary oedema. The commonest pathological finding was irritation of the lungs, and pneumonitis was confirmed by microscopic examination and an inexplicable case of pulmonary emphysema was also recorded. Based on the results of this study, the LD₅₀ was determined to be 580ppm. Under the conditions of this study, the test substance should be classified as a Category II toxicant according to Regulation EC No. 1272/2008 and should have the signal word Danger and the hazard statement H330: Fatal if inhaled associated with it. According to Directive 67/548/EEC, the test substance should be classified as R23, Toxic by inhalation