2-ethylhexyl 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:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl chloroformate

EC Number:

246-278-9

EC Name:

2-ethylhexyl chloroformate

Cas Number:

24468-13-1

Molecular formula:

C9H17ClO2

IUPAC Name:

2-ethylhexyl carbonochloridate

Details on test material:

- Name of test material (as cited in study report): 2-Ethylhexylchlorformiat (2-ethylhexylchloroformate)
- Physical state: liquid
- Analytical purity: 99%
- Impurities (identity and concentrations): phosgene and Di-2ethylhexylcarbonate
- Storage condition of test material: dry, cool, in glas containers
- Sability under storage conditions > 2 years

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K Thomae GmbH
- Age at study initiation: ca 8 weeks
- Weight at study initiation: 251 ± 44 (male); 178 ± 25 (female)
- Housing: in groups of five in cages type D III of Becker.
- Diet (e.g. ad libitum): ad libitum: laboratory diet 10 mm (Klingenthalmühle, Kaiseraugst, Switzerland)
- Water (e.g. ad libitum): ad libitum: drinking water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70 %
- 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:

Generation of inhalation atmospheres: a vapor/air mixture was generated by a continuous infusion pump and a glass vaporizer with thermostat. The vapor was mixed with supply air and passed into the ventilation system. The temperatures in the exposure systems ranged from 19-25 °C. The pressure ratios in the inhalation system were adjusted so that the amount of discharge air was about 3% less than air supply negative pressure) in order to avoid contamination of laboratory air.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gas chromatography

Duration of exposure:

4 h

Concentrations:

0.37; 0.27; 0.21; 0.18 mg/L

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighing was performed at day of applicaion, 7 days after application and14 days after application (termination of the study). Observation of clinical signs was several times on the day of administration and once daily afterwards with the except on weekends and on holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, mean body weight

Statistics:

The LC50 value was analyzed according to the Probit analysis of Finney (1971) using a computer program.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 0.27 mg/L air (analytical)

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

0.24 mg/L air (analytical)

95% CL:

> 0.21 - < 0.27

Exp. duration:

4 h

Effect levels 3

Sex:

female

Dose descriptor:

LC50

Effect level:

> 0.27 - < 0.37 mg/L air (analytical)

Mortality:

None of the animals exposed to 0.13 mg/l died. With one exception deaths occurred at the higher concentrations on the day of exposure or the day after (For details see table below).

Clinical signs:

other: During exposure: closed lids; bloody nasal and eye discharge; forced breathing ; apathy; restlessness; hunched posture (0.27 mg/L); ruffled fur. After exposure: forced breathing, breathing sound, gasping (0.37 mg/L); reddish nasal discharge, encrustation

Body weight:

Compared with historical controls, body weight gain was affected in male and female animals of the two low dose groups. Overallbody weight development of the surviving animals was positive.

Gross pathology:

Gross pathology revealed general congestion in several animals that died, pulmonary emphysema in all died animals, and additionally pneumonia in 2 females that died late.
There were no pathological findings in animals that were sacrificed.

Any other information on results incl. tables

Dose (mg/L)	Males (dead/exposed)	Females (dead/exposed)
0.37	10/10	10/10
0.27	7/10	2/10
0.21	4/10	1/10
0.18	0/10	0/10

Applicant's summary and conclusion

Conclusions:

2 -ethylhexylchloroformate is very toxic by inhalation

Executive summary:

The study is according to OECD 403 with acceptable restrictions mostly due to limited documentation (e.g. only mean body weights are reported) and no GLP. Groups of rats (10 per sex and does) were exposed to 0.37; 0.27; 0.21; 0.18 mg/L 2 -ethylhexylchhloroformate for 4 h. The test atmosphere concentration has been determined by gas chromatograhy. None of the animals exposed to 0.13 mg/l died. The LD50 is 0.27 mg/L/4h. With one exception deaths occurred at the higher concentrations on the day of exposure or the day after. Gross pathology revealed pulmonary emphysema in all died animals, and additionally pneumonia in 2 females that died late. There were no pathological findings in animals that were sacrificed.

Conclusion. 2 -ethylhexylchloroformate is very toxic by inhalation