Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
circa 1968
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Publication has limited information on methods and the study was conducted prior to the introduction of GLP guidelines or standardised test methods.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Toxic action of dichlorobutadiene in single experiments. Mater Of itogovoi Of nauch Of konf Of vop Of gig Tr Of profpatol Of khim Of gornorud Of prom
Author:
Grigoryan, A. O.
Year:
1968
Bibliographic source:
Chem. Abstr. 72: 119600x (1970) and in the review of DuPont, updated by R.C. Graham, January 21, 1982.

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The study design was similar to the subsequently defined OED method 401. The standard requirements for determination of a median lethal oral dose level were included - groups of male and female rats or mice, acutely dosed at various dose levels and mortality patterns evaluated.
GLP compliance:
no
Test type:
other: design similar to OECD method 401 - median lethal dose determination
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual):
Doses:

100, 500 and 600 mg/kg bw
Details on study design:
- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing:
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Preliminary study:
Not applicable
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 222 mg/kg bw
Remarks on result:
other: rats
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 110 mg/kg bw
Remarks on result:
other: mice
Mortality:
Deaths occurred at dose levels of 100 mg/kg bw and above. Deaths occurred within 2 days of dosing (80% of unscheduled deaths) or within 4 days of dosing.
Gross pathology:
Examination of animals which died during the first 2 days after application revealed polyhemia of all internal organs. The liver was nutmeg-like enlarged with a dark coloured central part and pale edges. In most cases the spleen was a dark brown colour and enlarged with dull edges. The stomach was full, dilated, and had the characteristic odour of 2,3-dichlorobuta-1,3-diene.
Other findings:
In the animals sacrificed at the end of the observation period some enlargement of the spleen was observed macroscopically while the other internal organs appeared normal. Microscopic examination of the internal organs revealed deep or superficial necrotic changes of the mucous envelope of the stomach with polyhemia as well as protein and fatty dystrophy of the epithelial tissues of the kidneys of the animals of the 500 and 600 mg/kg bw groups.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 values for rats and mice were determined as 222 mg/kg bw and 110 mg/kg bw respectively. This indicates DCBD should be considered to be harmful. Toxic effects were observed as clinical signs of reaction to treatment, including mortality, pathological changes in the liver, spleen and stomach with associated histopathological changes.
Executive summary:

In rats and mice the LD50 was determined as 222 and 110 mg/kg bw, respectively. Immediately after application of 2,3-dichlorobuta-1,3-diene of unknown purity the animals became slightly more active followed quickly by depression, low mobility and indifference to food and environmental stimuli. At 100 mg/kg bw and above deaths occurred (80 % of the deaths during the first 2 days and 20 % during the next 3-4 days); 600 mg/kg bw were absolutely lethal. Examination of animals which died during the first 2 days after application revealed polyhemia of all internal organs. The liver was nutmeg-like enlarged with a dark coloured central part and pale edges. In most cases the spleen was dark brown coloured and enlarged with dull edges. The stomach was full, dilated, and had the characteristic odour of 2,3-dichlorobuta-1,3-diene. No significant pathological changes were observed in the other organs. In the animals sacrificed at the end of the observation period some enlargement of the spleen was observed macroscopically while the other internal organs appeared normal. Microscopic examination of the internal organs revealed deep or superficial necrotic changes of the mucous envelope of the stomach with polyhemia as well as protein and fatty dystrophy of the epithelial tissues of the kidneys of the animals of the 500 and 600 mg/kg bw groups.