4-chlorobutyryl chloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab.

Test material

Test material information

Constituent 1

Reference substance name:

4-chlorobutyryl chloride

EC Number:

225-059-1

EC Name:

4-chlorobutyryl chloride

Cas Number:

4635-59-0

Molecular formula:

C4H6Cl2O

IUPAC Name:

4-chlorobutanoyl chloride

Details on test material:

Name of the test substance used in the study report: 4-chlorobutyryl chloride
Purity : 99.5% (GC analyses)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Mean body weights: approx. 317 g (males), 197 g (females) on the day of treatment.
Feed: standard diet and tap water ad libitum.
Housing: During exposure the animals were housed individually in the holders. Immediately after the exposure, the rats were housed 5 per sex and cage in a hood room because of intense smelling. The next day the animals returned to their stainless steel living cages and were housed 5 per cage under conventional conditions.
Environment: temperature: 18.5-23.5°C, relative humidity 70-77 %, 10 air changes per hour, 12-hour dark-light cycle.

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Details on inhalation exposure:

Analytical measurement of atmosphere concentration: 1 sample per hour was examined. 10 l test atmosphere were passed through an impinger filled with n-pentane at a rate of 2 l/min. Analytical method: GC/FID.
Determination of actual concentration: calculation using the calibration graph obtained by plotting the peak heights measured by GC analysis.
Exposure system: Nose-only inhalation polypropylene/PVC chamber, volume 35 l, with 20 ports which allowed exposing 5 male 5 female rats, and test atmosphere sampling and monitoring.
Atmosphere generation: Dynamic vapor generation. TS was evaporated into compressed fresh air (humidity less than 1% in order to prevent hydrolysis), using an infusion pump that delivered TS to a U-shaped glass tube (filled with glass beads and heated to room temperature) before the atmosphere entered the inhalation chamber.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.51, 0.65, and 0.87 mg/L

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

Observation period: 14 days.
Observations: Signs of toxicity during exposure and the observation period. Bodyweights were taken pre-exposure, and on days 7 and 14.
Autopsy: Gross pathology was performed on all animals.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.65 - 0.87 mg/L air

Exp. duration:

4 h

Mortality:

8 of 10 rats exposed to 0.87 mg/l died or had to be killed in extremis during the observation period. None of the rats exposed to 0.51 or 0.65 mg/l died. Thus, the LC50 was 0.65 mg/l < LC50 > 0.87 mg/l.

Clinical signs:

other: A moderate to severe, visually decreased breathing frequency was noted during exposure and shortly thereafter at all dose levels. Dyspnea, sniffing, and laboured breathing were noted in most animals at all dose levels throughout the 14-d observation perio

Body weight:

Body weights of most rats were severely decreased (up to 120 g weight loss in some animals) by day 7. There was only a small recovery of body weight between days 7 and 14 post treatment.

Gross pathology:

In deceased rats, pale or dark, spotted and /or swollen lungs were observed which occasionally showed irregular surface or a spongy appearance. Several rats showed an air-filled stomach and/or intestines, resulting from mouth-breathing. Grayish, pale or spotted lungs were noted in several of the rats at the terminal necropsy.

Applicant's summary and conclusion

Conclusions:

The LC50 was 0.65 mg/l < LC50 > 0.87 mg/l in male and female rats. The dose response curve was very steep, as mortality was 0 % at 0.65 mg/l and 80 % at 0.87 mg/l.