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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Adopted according to OECD SIDS (public available peer reviewed source). The original source is not available and has not been reviewed.

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
1,3-Dichlorobut-2-ene - CAS No: 926-57-8
Author:
OECD SIDS
Year:
2007
Bibliographic source:
SIDS Initial Assessment Report for 22th SIAM, UNEP Publications
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 10 rats were exposed to 0, 10, 100 ppm (0, 52, 530 mg/m³) 1,3-dichlorobut-2-ene
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,3-dichlorobut-2-ene
- Analytical purity: 99.5% (cis and trans mixture)

Test animals

Species:
rat
Strain:
other: Crl:CD(R)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8-10 weeks old
- Weight at study initiation: 220-260 grams

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Atmospheres were generated by passing nitrogen through midget impingers containing the test material. Dilution air carried the resulting vapours into 20-L glass exposure chambers.
TEST ATMOSPHERE
Atmospheric concentrations were analyzed via gas chromatography. Chambers were analyzed at 30- minute intervals. Chamber temperature and oxygen were monitored with a thermometer and an oxygen analyzer, respectively.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Atmospheric concentrations were analyzed via gas chromatography. For all exposures, chamber oxygen was >= 20% and temperature was maintained at <= 30ºC. The mean measured exposure concentrations were 10.0±1.20 (52±6.2 mg/m³) and 100±8.5 (520±44 mg/m³) for the 10 and 100 ppm exposure groups, respectively.
Duration of treatment / exposure:
two weeks
Frequency of treatment:
6 hours a day, 5 days a week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 10, 100 ppm (0, 52, 530 mg/m³)
Basis:
nominal conc.
No. of animals per sex per dose:
10 (only male rats were tested)
Control animals:
yes
Details on study design:
Post-exposure period: 14 days
Positive control:
no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily (excluding weekends) through the exposure period and for 14 days postexposure.

BODY WEIGHT: Yes
- Time schedule for examinations: daily (excluding weekends) through the exposure period and for 14 days postexposure.

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Blood samples were taken from the rats' tails after the 10th and 14th day of recovery.
- Parameters checked: 20 blood hamatology parameters were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Blood samples were taken from the rats' tails after the 10th and 14th day of recovery.
- Parameters checked: 20 chemistry parameters were examined.

URINALYSIS: Yes
- Time schedule for collection of urine: Clinical laboratory measurements were made on urine samples collected overnight following the 9th exposure and the 13th day of recovery.

- Parameters checked : Analysis included quantitative measures of the volume, osmolality, and pH, and semi-quantitative tests for occult blood, protein, sugar, bilirubin, acetone, and urobilinogen. Each specimen was noted for colour and appearance and the sediment from pooled specimens examined microscopically.

Sacrifice and pathology:
After the 10th exposure, 5 rats from each group were selected at random and sacrificed for gross and histopathological examination. Remaining rats were sacrificed on the 14th day of recovery for identical examinations. Twenty-three organs or tissues were examined. Heart, liver, lungs, kidneys, spleen, testes, and thymus were weighed.
Other examinations:
no data
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
During exposure, clinical observations of rats in both exposed groups included salivation, clear nasal discharge, hyperaemia, and ruffled fur.
Rats exposed to 10 ppm (52 mg/m³) had body weights indistinguishable from controls throughout the study. Rats exposed to 100 ppm (520 mg/m³) showed a significant weight depression throughout the exposure period and a rate of gain parallel to controls during the recovery period.
Clinical chemistry measurements after the last exposure showed that the average erythrocyte count, haemoglobin, and hematocrit were higher in rats exposed to 100 ppm (520 mg/m³) of 1,3-dichlorobut-2-ene when compared to controls.
Mean corpuscular haemoglobin was lower in these rats, and mean corpuscular haemoglobin concentration was lower in both exposure groups.
Blood glucose levels and urine pH were higher in exposed rats, but the increase was not dose-related. After a 14-day recovery period, no differences were noted between 1,3-Dichlorobut-1-ene exposed rats and controls.
A comparison of organ/body weight ratios between test and control rats showed no compound-related changes following the last exposure. After the 14-day recovery period, lung weights were significantly heavier in the rats exposed to 100 ppm (520 mg/m³) than in controls. The significance of this increase in lung weight was difficult to interpret since no specific microscopic lesions were observed at the end of the recovery period.
Pathological examination following the 10th exposure showed no compound-related macroscopic changes in any of the test rats and no microscopic changes in the rats exposed to 10 ppm (52 mg/m³). Rats exposed to 100 ppm (520 mg/m³) showed mild lung congestion (3/5 rats) and mild, but diffuse, degeneration of alveolar lining cells (1/5 rats). After the 14-day recovery period, no compound-related changes were noted.

CLINICAL SIGNS AND MORTALITY
During exposure, clinical observations of rats in both exposed groups included salivation, clear nasal discharge, hyperaemia, and ruffled fur.

BODY WEIGHT AND WEIGHT GAIN
Rats exposed to 10 ppm (52 mg/m³) had body weights indistinguishable from controls throughout the study. Rats exposed to 100 ppm (520 mg/m³) showed a significant weight depression throughout the exposure period and a rate of gain parallel to controls during the recovery period.

HAEMATOLOGY
Clinical chemistry measurements after the last exposure showed that the average erythrocyte count, haemoglobin, and hematocrit were higher in rats exposed to 100 ppm (520 mg/m³) of 1,3-dichlorobut-2-ene when compared to controls.

CLINICAL CHEMISTRY
Mean corpuscular haemoglobin was lower in these rats, and mean corpuscular haemoglobin concentration was lower in both exposure groups.
Blood glucose levels and urine pH were higher in exposed rats, but the increase was not dose-related. After a 14-day recovery period, no differences were noted between 1,3-Dichlorobut-1-ene exposed rats and controls.

ORGAN WEIGHTS
A comparison of organ/body weight ratios between test and control rats showed no compound-related changes following the last exposure. After the 14-day recovery period, lung weights were significantly heavier in the rats exposed to 100 ppm (520 mg/m³) than in controls. The significance of this increase in lung weight was difficult to interpret since no specific microscopic lesions were observed at the end of the recovery period.

GROSS PATHOLOGY AND HISTOPATHOLOGY: NON-NEOPLASTIC
Pathological examination following the 10th exposure showed no compound-related macroscopic changes in any of the test rats and no microscopic changes in the rats exposed to 10 ppm (52 mg/m³). Rats exposed to 100 ppm (520 mg/m³) showed mild lung congestion (3/5 rats) and mild, but diffuse, degeneration of alveolar lining cells (1/5 rats). After the 14-day recovery period, no compound-related changes were noted.

Effect levels

open allclose all
Dose descriptor:
NOAEC
Effect level:
10 ppm
Based on:
test mat.
Sex:
male
Dose descriptor:
LOAEC
Effect level:
100 ppm
Based on:
test mat.
Sex:
male
Basis for effect level:
other: based on histopathological changes in the lung and effects on red blood cell parameters in the 100 ppm (5201 mg/m³) group

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion