Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1965
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1965
Report Date:
1965

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: Acute Oral Gavage (pre-guideline pre-GLP study)
- Short description of test conditions: The test material was administered by intragastric intubation to five group of ten young adult rat at dose of 5000, 3400, 3020, 2630, 2250 mk/kg. Surivors were sacrificed 14 days later. The oral LD50 was calculated.
- Parameters analysed / observed: Cliinical signs, gross pathologic changes
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
CD-1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Species: Charles River CD
- Sex: males

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Vehicle detalies not specified
Doses:
5000, 3400, 3020, 2630, 2250 mg/kg
No. of animals per sex per dose:
5 groups - 10 animals each group
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Examinations performed: clinical signs, Gross pathologic changes
Statistics:
Oral LD50 calculated from mortality data using the method of Litchfield and Wilcoxon (1949).

Results and discussion

Effect levels
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 2 875 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 614 - <= 3 162
Mortality:
2250 mg/Kg - 1/10
2630 mg/Kg - 2/10
3020 mg/Kg - 7/10
3400 mg/Kg - 8/10
5000 mg/Kg - 10/10
Clinical signs:
Pallor, apparent discomfort, belly-crawling after dosing, weight loss for 1-2 days, diarrhoea, stained ventral area and hematuria at two higher doses.
Body weight:
Weight loss for 1-2 days (no additional infomation provided)
Gross pathology:
Animals that died (5): dark bone marrow, hyperemic thymus, stomach and intestine distended with fluid, intestine and glandular mucosa of stomach hemorrhagic
Animal that survived (8): thickened stomach mucosa and, at higher levels, adhesions of liver to stomach

Any other information on results incl. tables

Mortality observed in the study

Dose mg/kg

Solution %

Mortality Ratio

5000

50

10/10

3400

20

8/10

3020

30

7/10

2630

30

2/10

2250

40

1/10

Applicant's summary and conclusion

Interpretation of results:
other: Not classified according to the CLP Regulation
Conclusions:
Under the conditions of this study, the acute oral LD50 of the test material in male rats was determined to be 2875 mg/Kg (95% C.I: 2614 - 3162 mg/Kg).
Executive summary:

In a key pre-guideline acute oral toxicity study, the test material was administered via intragastric intubation to Charles River CD rats (10 males/dose) at doses of 2250, 2630, 3020, 3400, or 5000 mg/Kg. Animals were observed for clinical signs and gross pathologic changes with surviving animals sacrificed 14 days post exposure.

 

Mortality was observed at each dose level as follows: 2250 mg/Kg (1/10); 2630 mg/Kg (2/10); 3020 mg/Kg (7/10); 3400 mg/Kg (8/10); 5000 mg/Kg (10/10). Clinical signs observed through the study period included pallor, discomfort, belly-crawling after dosing, weight loss for 1-2 days, diarrhoea, stained ventral area as well as hematuria observed at the two higher doses.

 

Dark bone marrow, hyperemic thymus, stomach and intestine distended with fluid, and hemorrhagic intestine and glandular mucosa of the stomach were observed in animals that died (5). In animals that survived (8), thickened stomach mucosa and, at higher dose levels, adhesion of the liver to the stomach were observed. 

 

Based on mortality and clinical signs of toxicity as well as gross pathology observed in the study, the acute oral LD50 (calculated using the Litchfield and Wilcoxon method (1949)) was determined to be 2875 mg/Kg (95% C.I: 2614 – 3162 mg/Kg).