Methyl 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)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

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:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methyl chloroformate

EC Number:

201-187-3

EC Name:

Methyl chloroformate

Cas Number:

79-22-1

Molecular formula:

C2H3ClO2

IUPAC Name:

methyl chloroformate

Details on test material:

- Name of test material (as cited in study report): Methylchlorformiat (methylchloroformate)
- Purity: about 99%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mura : SPRA (SPF 68 Han), MUS RATTUS, Brunnthal, Germany,
- Weight at study initiation: 185 +/- 15 g
- Fasting period before study:
- Housing: fully air-conditioned rooms
- Diet (ad libitum): ad libitum (except exposure); Herilan MRH of H . EGGERSMANN KG, RintelnNVeser
- Water (ad libitum): ad libitum (except exposure)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 5 %
- Photoperiod (hrs dark / hrs light): 12 / 12
:

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Exposure system: Whole-body inhalation system (Groups of 5 animals are placed in wire cages which are located in a glass-steel inhalation chamber, V= 200 I.) Generator system: Continuous infusion pump UNITA I(B . Braun); Glass evaporator with thermostat (BASF ). By means of a continuous infusion pump, constant amounts of the test substance (see Table) were supplied to an evaporator heated to 45°C . The vapors that were formed were mixed with a flow of fresh air and passed into the inhalation chamber.
By means of an exhaust air system, the pressure ratios in the inhalation system were adjusted in such a way that there was a pressure slightly below
the atmospheric pressure (negative pressure) . The inhalation mixture was offered to the animals for inhalation for 4 hours .

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Analytical concentration: 0.006 (group 4); 0.053 (group 3); 0.120 (group 2); 0.130 mg/l (group 1)
Nominal concentration: 0.06; 0.25; 0.49; 0.37 mg/l

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighing was before treatment, after 7 days, after 14 days. Observations were several times at the day of exposure and atleast once daily afterwards.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: daily

Statistics:

The statistical evaluation of the study was carried out based on a probit analysis of D .J . Finney (Finney, D .J. : Probit Analysis 1971, pp 1-150 .
Published by the Syndics of the Cambridge University Press, Bentley House, 200 Euston Road, London N.W. 1) . The calculations were carried out in
the BASF Computer Center.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.06 mg/L air

95% CL:

0.04 - 0.074

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 0.053 mg/L air

Effect levels 3

Sex:

female

Dose descriptor:

LC50

Effect level:

0.07 mg/L air

95% CL:

0.032 - 0.095

Mortality:

0.006 mg/l: males 0/10, females 0/10; 0.053 mg/l: males5/10, females 3/10; 0.120 mg/l: males 10/10, females 10/10;
0.130 mg/l: males 10/10, females 7/10
The fatally intoxicated animals died during the test up to 11 days afterward.

Clinical signs:

other: (Group 1-3): Dyspnea ; gasping breathing with whooping sounds in some cases; blistering in front of the noses ; reddish discharge from the eyes and noses ; incrustations around the eyes and noses occurring later ; ruffled and sticky fur with yellow discol

Body weight:

As regards the relative body weight gain, the males of Group 3 and the females of Groups 1 and 3 were considerably impaired after 7 days, but there
was an adjustment to the control groups after 14 days . The males and females of Group 4 did not reveal any substantial differences from the controlanimals .

Gross pathology:

Animals that died:
Heart: acute dilatation ; acute passive hyperemia
Lungs: infarctoid congestion, wet and sarcoid in some cases; edematized; marginal emphysema ; hydrothorax in several cases
Liver: slight and sometimes only focal peripheral hepatocellular fatty degeneration sporadically
Sacrificed animals :
Organs: no abnormalities detected