2,3-epoxypropyl isopropyl ether

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

other: publication

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Sufficiently documented publication, scientifically reasonable method, testing performed on the registered substance itself.

Data source

Reference

Reference Type:

publication

Title:

The Toxicology of Glycidol and Some Glycidyl Ethers

Author:

Hine HC, Kodama JK, Wellington JS, Dunlap MK, Anderson HH

Year:

1956

Bibliographic source:

AMA Archives of Industrial Health. (Chicago, IL) 14,250,1956

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not applicable

GLP compliance:

no

Remarks:

conducted prior to GLP implementation

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isopropyl glycidyl ether

IUPAC Name:

Isopropyl glycidyl ether

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Isopropyl glycidyl ether

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, Calif.
- Weight at study initiation: 110 - 140 g
- Housing: 6 rats per cage
- Diet (e.g. ad libitum): standard laboratory pellets

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: The motor-driven syringe assembly previously described by Hine and associates (Hine et al., Toxicology and Safe Handling of CBP-55, A. M.A. Arch. Indust. Hyg. 7:118, 1953) 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 (Jacobs MB, Analytical Chemistry of Industrial Poisons, Hazards, and Solvents, New York, Interscience Publishers, Inc., 1949: vol. 1.) and were checked by determining the total quantity of material vaporized.
- Exposure chamber volume: 19.5 L
- Temperature, humidity, pressure in air chamber: 30±1°C

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

8 h

Concentrations:

graded concentrations

No. of animals per sex per dose:

six

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 10 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

LD50 values were calculated by the method of Litchfield and Wilcoxon (Litchfield JT, Wilcoxon F, Simplified Method of Evaluating Dose-Effect Experiments, J Pharmacol & Exper Therap, 96:99, 1949

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

1 100 ppm

Based on:

test mat.

95% CL:

790 - 1 530

Exp. duration:

8 h

Mortality:

no details given

Clinical signs:

other: Dyspnea, lacrimation, salivation, nasal discharge, and aerophagia were much severer following vapor exposure than intragastric administration (see respective study in oral section), while depression of the central nervous system appeared usually as a ter

Body weight:

no details given

Gross pathology:

The commonest pathologic finding was irritation of the lungs, and pneumonitis was confirmed by microscopic examination.
Discoloration of liver and kidneys was also noted frequently on gross examination, but tissue changes were not consistently confirmed microscopically. In occasional livers focal inflammatory cells were observed, and moderate congestion of the central zones.

Other findings:

IPGE would not be classified as more than "moderately toxic" on single exposure, rather "slightly toxic" or "practically nontoxic" according to the classification of Hodge and Sterner.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The studied was conducted scientifically reasonable with sufficient documentation similar to OECD 403, it was assessed with Klimisch 2. Hence, the results are sufficiently reliable to assess the acute toxicity of isopropyl glycidyl ether in rats. An inhalatory LC50 was determined as 1100 ppm, which needs to be converted into the unit mg/L as the tested substance was a vapour and classification of vapours according to Regulation 1272/2008 is foreseen in the unit mg/L. Therefore, the formula (ppm * molecular weight) / 24450 L/mol = mg/L is used, resulting in (1100 ppm * 116.1583 g/mol) / 24450 L/mol= 5.226 mg/L. This value is between the boundary values of 2.0 and 10.0 mg/L for classification as acute toxic Cat. III according to Regulation 1272/2008. Hence, the substance should be classified as acute toxic Cat. III and can be regarded as moderately toxic to rats.

Executive summary:

In an acute inhalation toxicity study (similar to OECD 403), groups of 6 male Long-Evans rats were exposed by inhalation route to vapour of 2,3-epoxypropyl isopropyl ether for 8 hours to whole body at graded concentrations. Animals then were observed for 10 days.

 

LC₅₀Males = 1100 (95% C.I. 790 - 1530)

 

2,3-epoxypropyl isopropyl ether is classified as acute toxic Cat.III. The commonest pathologic finding was irritation of the lungs, and pneumonitis was confirmed by microscopic examination.