Propyl chloroformate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is comparable to OECD 403 (inhalation risk test) with acceptable restrictions mostly due to reduced reporting in times before GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1970

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

other: inhalation risk test

Test material

Test material information

Constituent 1

Reference substance name:

Propyl chloroformate

EC Number:

203-687-7

EC Name:

Propyl chloroformate

Cas Number:

109-61-5

Molecular formula:

C4H7ClO2

IUPAC Name:

propyl carbonochloridate

Details on test material:

- Name of test material (as cited in study report): n-Propyl-chlorkohlensaeureester
- Physical state: liquid
- Purity: approx. 95%
- Expiration date of the lot/batch: not reported
- Stability under test conditions: not reported
- Storage condition of test material: not reported

Test animals

Species:

rat

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Mean weight at study initiation: males 165 g; females 133 g
no further details given

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Rats exposed for 3 min, 1 h, respectively, to a vapour saturated atmosphere.
Vapour was generated by bubbling 200 l/h dry air (no CO2) through the liquid substance column (volume ca. 50 ml) of about 5 cm above a fritted glass disc in a glass cylinder. The glass cylinder was heated in a water bath. The air pressure was 754 mm Hg. Temperature in the exposure chamber was 20°C. Concentration was stated in the raw data to be 1.385 mg/L (= 272.5 ppm) in the case of the 3 min exposure and 200 ppm (= ca. 1.091 mg/L) in case of the 1 h exposure.
The vapour saturation treshold is calculated to be approx. 135 mg/L (at 23.3°C).

Analytical verification of test atmosphere concentrations:

no

Remarks on duration:

3 min or 1 h

Concentrations:

1.385 mg/L in the case of the 3 min exposure; 1.019 mg/L in case of the 1 h exposure.

No. of animals per sex per dose:

6 animals each were treated for 3 min in two trials; 10 animals were treated for 1 h in one trial

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No weighing was done. Observation was several times at the day of exposure and afterwards presumably daily except on weekends and holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

none

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

other: IHT

Remarks on result:

other: Mortality appeared within 3 min

Mortality:

3 min at 1.385 mg/L: 12/12 animals died within 2 h
1 h at 1.019 mg/L: 3/10 animals died within 6 d

Clinical signs:

other: 3 min at 1.385 mg/L: Vigorous attempts to escape; extremely severe irritation to the mucosa; gasping breathing 1 h at 1.019 mg/L: Restlessness; irritation to the mucosa; dyspnea

Body weight:

Mean body weight after 14 d
1 h at 1.019 mg/L: males 190 g (+25g); females 157 g (+24 g)

Gross pathology:

3 min at 1.385 mg/L: Congestion and edema of the Iungs
1 h at 1.019 mg/L: Acute pulmonary emphysema

Other findings:

3 min at 1.385 mg/L: A concentration of 40 ppm phosgen was measured above the TS by Draeger tube method pointing to the fact that the TS has partly hydrolised to phosgen.

Applicant's summary and conclusion

Executive summary:

Study is comparable with the inhalation hazard test described in the Annex of OECD Guideline 403 (adopted 1981) with acceptable restrictions mostly due to reduced reporting in times before GLP. Rats were exposed for 3 min and 1 h, respectively, to a vapour saturated atmosphere. Concentration was stated in the raw data to be 1.385 mg/L in the case of the 3 min exposure and 1.019 mg/L in case of the 1 h exposure. A measured concentration of 40 ppm of phosgen above the test substance in the 3 min trial indicates a partial hydrolisation of the test substance.

12/12 animals died within 2 h after 3 min exposure to 1.385 mg/L; 3/10 animals died within 6 d after 1 h exposure to 1.019 mg/L.

Animals of the 3 min exposure showed vigorous attempts to escape, extremely severe irritation to the mucosa and gasping; animals of the 1 h exposure showed restlessness, irritation to the mucosa and dyspnea.

Necropsy findings were congestion and edema of the lungs in the 3 min treatment and acute pulmonary emphysema in the 1 h treatment, respectively.

Inhalation of 1.385 mg/L propyl chloroformate for 3 min or 1.019 mg/L for 1 h may cause death. According to CLP No. 1272/2008 Part 3.1.2, for the conversion from 1 h to 4 h exposure, the data are divided by factor 2.