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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:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only secondary literature. However, according to OECD SIDS a reliability of 2 was given.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Toxicity of chloroprene, 1,3-dichlorobutene-2, and 1,4-dichlorobutene-2
Author:
Clary JJ
Year:
1977
Bibliographic source:
Environm. Health Perspect 21, 269-274.
Reference Type:
secondary source
Title:
1,4-Dichlorobut-2-ene - CAS No: 764-41-0
Author:
OECD SIDS
Year:
2006
Bibliographic source:
SIDS Initial Assessment Report for 22th SIAM, UNEP Publications.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
6 animals/group/strain were tested; 3/6 were sacrificed 1 day after the last exposure, while 3/6 were sacrificed after a 14 d-recovery period.
GLP compliance:
no
Remarks:
GLP was not mandatory at the time of the study

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance: low boilers 0.07% (weight%)
3,4-DCB-1 0.15%
cis 1,4-DCB-2 11.14%
trans 1,4-DCB-2 86.86%
cis 1,3,4-TCB-2 0.96%
trans 1,3,4-TCB-2 0.49%
other high boilers 0.30%
DCB= dichlorobutene, TCB= trichlorobutene.

Test animals

Species:
rat
Strain:
other: CHR-CD and Long Evans (LE)
Sex:
male

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Details on inhalation exposure:
Vapour generation: liquid 1,4-dichlorobut-2-ene was delivered at a constant rate by a syringe pump into a heated (ca. 110°C) round-bottom flask. Air metered into the flask carried the resulting vapours into a glass 30-liter chamber containing the test animals.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Chamber atmosphere was examined in 1h-intervals by gas chromatography (electron capture detector):
0.11 +/- 0.05 ppm
10.9 +/- 2.5 ppm
Duration of treatment / exposure:
2 weeks
Frequency of treatment:
6 h/day, 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0.1, 10 ppm = 0.00052, 0.052 mg/L
Basis:
nominal conc.
No. of animals per sex per dose:
6 (only male rat tested)
Control animals:
yes
Details on study design:
Post-exposure period: 2 weeks.
Positive control:
No

Examinations

Observations and examinations performed and frequency:
No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes. At autopsy the following organs were weighed: Heart, liver, kidney, spleen, thymus and testes.
HISTOPATHOLOGY: Yes. The following organs and tissues were examined microscopically: Trachea, lung, heart, liver, esophagus, stomach, intestine, pancreas, thyroid, parathyroid, adrenal glands, bone marrow, lymph node, spleen, thymus, brain, eye and skin.

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:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
at 0.052 mg/L, reversible
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
at 0.052 mg/L, reversible
Histopathological findings: neoplastic:
not examined
Details on results:
0.00052 mg/L: No effect
0.052 mg/L: reduced weight gain; 1 day after last exposure 2/3 (CHR) and 1/3 (LE) showed growth retardation with concomitant atrophy of the liver, kidneys, spleen, thymus, testes and adrenal glands but without any histopathological alteration. These effects were reversible within the 14 days post-observation period. In most rats an inflammation of the tracheobronchial area was observed, including, in most rats, epithelial changes such as flattening, squamous metaplasia, hyperplasia, hypertrophy, denudation, and vesiculation. The severity decreased gradually from the upper respiratory tract to the lower portion. There was also a slight acute inflammatory response characterized by dilation of the lumen which contained some exudate consisting of mucus, cells with abundant vesiculated cytoplasm (perhaps due to glycogen accumulation), and a few neutrophils.
These microscopic changes were reversible within the 14-day recovery period except for some luminal exudate still present in a few rats.

Effect levels

open allclose all
Dose descriptor:
NOAEC
Effect level:
0.001 other: mg/L
Based on:
test mat.
Sex:
male
Dose descriptor:
LOAEC
Effect level:
0.052 other: mg/L
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Reduced body weight gain and inflammation of the respiratory tract

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion