Reaction mass of 1,4-dichlorobut-2-ene; 3,4-dichlorobut-1-ene

Repeated dose toxicity: inhalation

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

Reference

Reference 1

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 2

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

Test material information

Constituent 1

Reference substance name:

1,4-dichlorobut-2-ene

EC Number:

212-121-8

EC Name:

1,4-dichlorobut-2-ene

Cas Number:

764-41-0

Molecular formula:

C4H6Cl2

IUPAC Name:

1,4-dichlorobut-2-ene

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

1

Dose descriptor:

NOAEC

Effect level:

0.001 other: mg/L

Based on:

test mat.

Sex:

male

2

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