Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Pre-GLP study following a method similar a recognised guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
The principles of the method were in accordance with the US 16 CFR 1500.3 definitions.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Physical state: liquid

Test animals

Species:
rat
Strain:
other: CD Strain, Crl: COBS CD (SD) BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: recognised animal supplier
- Weight at study initiation: male 154 - 266g; female 150 - 172g
- Fasting period before study: 24h before dosing
- Housing: housed in suspended wire-mesh stock cages
- Diet: standard laboratory diet ad libitum (except during the 24h period immediately prior to dosing)
- Water: ad libitum
- Acclimation period: at least 5 days

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All doses were administered directly into the stomach of the rats using a hypodermic syringe equipped with a ball-tipped intubating needle.
Doses:
600, 2025, 3038, 4556, 6834 mg/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Initial and final body weights, mortalities and reactions were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 362 mg/kg bw
Based on:
test mat.
Remarks on result:
other: calculated LD50
Mortality:
One animal from the 3038 mg/kg dose group died on day 2. All four animals from the 4556 mg/kg dose group died on day 1. All four animals from the 6834 mg/kg dose group died on day 1 and 2.
Clinical signs:
Clinical signs observed during the observation period include: hypoactivity, salivation, convulsions, muscular weakness, labored breathing, prostration, lacrimation, vasoconstriction (females), tremors, nasal discharge, exophthlmos (males), head motions (males), sitting on haunches with arm motions (males), hyperirritability.
Body weight:
No significant findings.
Gross pathology:
Necropsy examination of the animals that died revealed hemorrhaged lungs in animals 17-M, 18-M and 19-F. In addition, pale mottled livers were noted in animals 9-M, 11-F and 12-F; pale kidneys in animals 20-F, 9-M, 10-M, 11-F and 12-F; a distended gastrointestinal tract in animals 10-M and 11-F; gastric hemorrhages in animal 10-M; intestinal hemorrhages in animal 11-F and advanced postmortem autolysis (due to overnight mortality) in animal 16-F. Examination of the survivors revealed necrotic tissue in the stomach lining in animal 15-F.

Any other information on results incl. tables

Table 1. Mortality data

Dose level (mg/kg) Animal number Sex Number dead/Number tested % Dead
600 1 Male 0/4 0
2 Male
3 Female
4 Female
2025 5 Male 0/4 0
6 Male
7 Female
8 Female
3038 13 Male 1/4 25
14 Male
15 Female
16 Female
4556 17 Male 4/4 100
18 Male
19 Female
20 Female
6834 9 Male 4/4 100
10 Male
11 Female
12 Female

Applicant's summary and conclusion

Interpretation of results:
sligthly toxic
Remarks:
Migrated information Criteria used for interpretation of results: US CPSC / US OSHA
Conclusions:
Under the conditions of this study, the LD50 of the test substance was determined to be 3362 mg/kg in the male/female rat.
Executive summary:

The pre-GLP study was performed following a method similar to OECD 401 to assess the acute oral toxicity potential of the test substance to male/female CD Strain, Crl: COBS CD (SD) BR rats. The test material was administered as a single oral dose, by gavage, to a group of 10 male and 10 female rats following an overnight fast. The animals were observed for 14 days and survivors were then euthanized. All animals were subject to necropsy. One animal from the 3038 mg/kg dose group died on day 2; all remaining animals below this dose survived to the end of the study. Clinical signs of toxicity were noted in most animals on the day of dosing. There was no adverse effect on bodyweight gain in animals of either sex. Necropsy examination of the animals that died revealed haemorrhaged lungs in animals. In addition, pale mottled livers, pale kidneys, a distended gastrointestinal tract, gastric haemorrhages, intestinal haemorrhages and advanced postmortem autolysis (due to overnight mortality) were observed. Examination of the survivors revealed necrotic tissue in the stomach lining in one animal. Under the conditions of this study, the LD50 of the test substance was calculated to be 3362 mg/kg.