Ethyl chloroformate

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Results of the study are not described in detail. The numbers of rats in each group is only 8. Concentrations of test material were not confirmed analytically.

Data source

Reference

Reference Type:

publication

Title:

The subacute inhalation toxicity of 109 industrial chemicals.

Author:

Gage JC.

Year:

1970

Bibliographic source:

Brit J Indust Med 27:1-18

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

no

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl chloroformate

EC Number:

208-778-5

EC Name:

Ethyl chloroformate

Cas Number:

541-41-3

Molecular formula:

C3H5ClO2

IUPAC Name:

ethyl chlorocarbonate

Details on test material:

- Name of test material (as cited): ethyl chloroformate
- Physical state: liquid
- Other: boiling point 95°C

Test animals

Species:

rat

Strain:

other: Alderley park

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Alderley Park
- Weight at study initiation: 200 g
- Diet (e.g. ad libitum): withheld during exposure
- Water (e.g. ad libitum): withheld during exposure

ENVIRONMENTAL CONDITIONS
No data

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Remarks on MMAD:

MMAD / GSD: vapor, therefore not applicable

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Generation of the test atmosphere: The exposure chamber was not described in detail. Air used for the atmospheres was filtered, dried to a relative humidity of less than 10%, and supplied at a line pressure of 1 atm. Test material was dissolved in petroleum ether and injected into a metered stream of air with a controlled fluid-feed atomizer. The concentrations tested were calculated from the rate of introduction of test material into the air stream. They were not verified analytically.

Duration of treatment / exposure:

6 h / day

Frequency of treatment:

5 days/week for 2-4 weeks

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1, 5, 20 ppm
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
4.5; 22.6; 90.2 mg/m³
Basis:
nominal conc.

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

no data

Positive control:

not necessary

Examinations

Observations and examinations performed and frequency:

Rats were weighed each morning and their conditions and behavior were recorded throughout the exposure period. They were allowed free access to food and water at all times except for during exposure. Urine was collected overnight after the last exposure day. On the following day, the rats were euthanized and blood was collected via cardiac puncture. Urine was analyzed for specific gravity, pH, reducing sugars, bilirubin and protein. Blood was analyzed for hemoglobin concentration, packed cell volume, mean corpuscular hemoglobin content, white cell count (total and differential), platelet count, clotting function, and the concentrations of urea, sodium and potassium. The results of these analyses were compared to those from blood collected before exposure.

Sacrifice and pathology:

After a gross examination of the organs, the lungs were inflated with fixative and examined histologically. The liver, kidneys, spleen and adrenals (and occasionally the heart, jejunum, ileum and thymus) were also fixed and examined histologically.

Statistics:

none

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

There were no signs of toxicity in rats exposed to 1 ppm. Rats exposed to 5 ppm had reduced weight gains and normal appearing organs at necropsy. Rats exposed to 20 ppm exhibited nasal irritation, difficulty with respiration, poor condition and weight loss. Autopsies revealed distension and
hemorrhage of lungs.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

1 ppm

Sex:

male/female

Basis for effect level:

other: body weight

2

Dose descriptor:

LOAEC

Effect level:

5 ppm

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified