Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)

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 with initial body weights of 248-289 grams were exposed to an 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.
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
No further details.

Test animals

Species:
rat
Strain:
other: ChR-CD
Sex:
male
Details on test animals and environmental conditions:
Six male albino ChR-CD rats 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 heated to 40 °C for H-8798 and 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:
8798 was tested at concentrations of 1.02, 1.13, 1.15, 1.71, 1.84, 1.98 and 3.05 mg/litre.
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 (8798 and 8849).
Control animals:
no
Details on study design:
Groups of six male albino rats with initial body weights of 248-289 grams 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:
Probit analysis (1964) was undertaken.

Results and discussion

Preliminary study:
Not performed.
Effect levels
Sex:
male
Dose descriptor:
LC50
Effect level:
2.08 mg/L air
Based on:
test mat.
Mortality:
8798 (LRT-218)
1.02 mg/L = 0/6 mortality
1.13 mg/L = (this group was used for serial sacrifice)
1.15 mg/L = 1/6 mortality
1.71 mg/L = 1/6 mortality
1.84 mg/L = 1/6 mortality
1.98 mg/L = 3/6 mortality
3.05 mg/L = 6/6 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:
8798 (LRT-218)
None reported during exposure. Post exposure - severe initial weight losses and rapid respiration. Deaths occurred from one to nine days. Delayed deaths were preceded by weight gains at three to four days and then continued losses.

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 continous losses.
Body weight:
No bodyweight data post exposure was included in the study report.
Gross pathology:
H-8798 (Pathology report No. 79-74)
Both rats that died on one day post exposure at 3.05 mg/litre demonstrated necrosis of: bronchiolar epithelium, centrilobular to midzonal hepatocytes, renal tubular epithelium and germinal cells of the testes; pulmonary oedema and haemorrhage were also observed. Rats exposed to 1.13 mg/litre showed basically similar lesions as those described above at one day post-exposure. A reparative process was observed in rats sacrificed at two, seven and fourteen days.

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

Interpretation of results:
harmful
Remarks:
Migrated information 2,3 -Dichlorobutadiene had an LC50 of 2.08 mg/L requiring classification as harmful by inhalation and R20 labelling in respectof the risk phrase Criteria used for interpretation of results: EU
Conclusions:
H-8798 (LRT-218)
The median lethal concentration (LC50) for young adult male rats exposed to 2,3 -Dichlorobutadiene for four hours was 2.08 mg/litre with 95% confidence limits of 1.79 and 2.68. This compound caused no obvious clinical signs during exposure, but severe weight losses and rapid respiration were observed during the early recovery period. Deaths, both early and delayed were preceded only by severe weight losses. Histopathologically this compound produced necrosis in the bronchiolar epithelium, liver, kidney and testes. The survivors demonstrated partial recovery from these injuries at the end of the 14 -day recovery period. 2,3 -Dichlorobutadiene should be considered moderately toxic by inhalation exposure.

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:

Six male albino ChR-CD rats were exposed to atmospheres containing the test material for a single 4 -hour period. All surviving animals were weighed and observed daily for 14 days post-exposure. Selected animals were sacrificed at 1, 2, 7 and 14 days post-exposure for histopathological examination. The LC50 was 2.08 mg/L. The test substance caused no obvious clinical signs during exposure, but severe weight losses and rapid respiration were observed during the early recovery period. Deaths, both early and delayed, were preceded only by severe weight losses. Histopathologically, the test substance produced necrosis in the bronchiolar epithelium, liver, kidney, and testes. The survivors demonstrated partial recovery from these injuries at the end of the 14 -day recovery period.

2,3 -Dichlorobutadiene (LRT-218) should be considered moderately toxic by inhalation exposure and 2 -chloro-1, 3 -butadiene is classified as a slightly toxic compound by inhalation exposure (LRT-220). Under REACH Classification the material is harmful by inhalation, R20.