2-chlorobuta-1,3-diene

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: study report with acceptable limitations (one sex, predated testing guideline), but overall acceptable for risk assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Six male albino rats per group, in an initial body weight range of 248-289 grams, were exposed to atmospheres containing the test material for a single four-hour period. All surviving animals were weighed and observed daily for 14 days post-exposure. Selected animals were sacrificed at one, two, seven and fourteen days post exposure for histopathological examination.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,3 Butadiene, 2-chloro

IUPAC Name:

1,3 Butadiene, 2-chloro

Constituent 2

Reference substance name:

8849

IUPAC Name:

8849

Constituent 3

Reference substance name:

LRT-220

IUPAC Name:

LRT-220

Details on test material:

2-chloro-1,3-butadiene (H-8849)

Test animals

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

Six male albino ChR-CD rats per group with initial body weights of 248-289 grams were used in the study.

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

whole body

Vehicle:

other: The test material was metered along with nitrogen in a delivery tube in order to carry the test material into the 20-litre glass exposure chamber

Details on inhalation exposure:

The test material was metered using a syringe infusion pump, into a 1/4-inch stainless steel delivery tube. The tube was maintained at room temperature for H-8849. Nitrogen was also metered into the delivery tube to carry the test material to the 20-litre glass exposure chamber. At the port of entry into the chamber, oxygen was added in order to produce a 20% oxygen atmosphere.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Known volumes of the atmosphere were drawn through two midget impingers in series, each containing 15 milliliters of methanol and analysed directly by gas chromatography. Time-weighted concentrations were calculated.

Duration of exposure:

4 h

Concentrations:

chamber concentrations were quantitatively analysed

8849 was tested at concentrations of 1.95, 6.24, 8.42, 13.04, 13.30 and 19.58 mg/litre.

No. of animals per sex per dose:

6 rats in total were used for each substance at each dose level

Control animals:

no

Details on study design:

Six male albino rats per group were exposed to atmosphere containing the test material for a single four-hour period. All surviving animals were weighed and observed daily for 14 days post-exposure. Selected animals were sacrificed at one, two, seven and fourteen days post exposure for histopathological examination.

Statistics:

Group mortality was analysed using Probit analysis.

Results and discussion

Preliminary study:

Not performed.

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

>= 8.42 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 2-chloro-1,3-butadiene

Mortality:

8849 (LRT-220)
1.95 mg/L = 0/6 mortality
6.24 mg/L = 0/6 mortality
8.42 mg/L = 1/6 mortality
13.04 mg/L = 2/6 mortality
13.30 mg/L = 2/6 mortality
19.58 mg/L = (this group was used for serial sacrifice)

Clinical signs:

other: 8849 (LRT-220) Laboured respiration and pallor at all concentrations above 1.95 mg/L. Severe initial weight losses. Deaths from two to nine days post-exposure. Delayed deaths were preceded by weight gains at two to four days and then continuous losses.

Body weight:

No bodyweight data post exposure was included in the study report.

Gross pathology:

H-8849 (Pathology report No. 80-74)
One rat that died two days post exposure demonstrated haemorrhagic infarctions in the lungs. Rats that were sacrificed at one and two days showed, in addition to the above, desquamation and degeneration of the bronchial and bronchiolar epithelium and pulmonary oedema. The tissue changes in the lungs and liver seen at seven and fourteen days were due to regeneration and healing processes of acutely damaged tissue.

Other findings:

No additional information provided.

Any other information on results incl. tables

No additional information provided.

Applicant's summary and conclusion

Conclusions:

H-8849 (LRT-220)
The approximate lethal concentration (ALC) for young adult male rats exposed to 2 -chloro-1, 3 -butadiene for four hours was 8.42 mg/litre. On the basis of the available data, a median lethal concentration could not be determined for this compound. Laboured respiration and pallor were observed during exposures and severe weight losses and deaths, often delayed, were observed in concentrations of 8.42 mg/L and above. Histopathologically this compound caused severe damage in the lungs and liver which was partially healed by 14 days post-exposure. 2 -chloro-1, 3 -butadiene is classified as a slightly toxic compound by inhalation exposure.

Executive summary:

2 -chloro-1, 3 -butadiene is classified as a slightly toxic compound by inhalation exposure (LRT-220).