Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: No guideline was followed. Only few data on test method reported.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1950

Materials and methods

Principles of method if other than guideline:
10 albino mice per group were given single peritoneal and subcutaneous injections of the test substance.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Cyanocobalamin
EC Number:
200-680-0
EC Name:
Cyanocobalamin
Cas Number:
68-19-9
Molecular formula:
C63H88CoN14O14P
IUPAC Name:
cyanocobalamin
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): Vitamin B12.

Test animals

Species:
mouse
Strain:
other: albino mice.
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 11 g

Administration / exposure

Route of administration:
other: intraperitoneal and subcutaneous.
Vehicle:
unchanged (no vehicle)
Doses:
Intraperitoneal injections: 0.75 mg/kg (Group 1), 1.5 mg/kg (Group 2) and 3 mg/kg (Group 3).
Subcutaneous injections: 3 mg/kg (Group 4).
No. of animals per sex per dose:
10 animals/dose.
Control animals:
no

Results and discussion

Effect levelsopen allclose all
Sex:
not specified
Dose descriptor:
LD100
Effect level:
3 mg/kg bw
Based on:
test mat.
Remarks on result:
other: (intraperitoneal route)
Sex:
not specified
Dose descriptor:
LD100
Effect level:
3 mg/kg bw
Based on:
test mat.
Remarks on result:
other: (subcutaneous route)
Mortality:
No mortality was found in the 0.75 mg/kg dose group. Two out of 10 animals died after an intraperitoneal administration of 1.5 mg/kg of the test substance and the highest dose tested (3 mg/kg) was lethal for 100 per cent of the animals treated, both subcutaneously and intraperitoneally.
Clinical signs:
Excitation and convulsions were observed after administration of 1.5 mg/kg of Vitamin B12 intraperitoneally and 3 mg/kg, both subcutaneously and intraperitoneally. In the 3 mg/kg dose groups, the excitatory state ended in cardiac and respiratory failure.
Body weight:
No data.
Gross pathology:
At necropsy, only congestion and edema of the lungs and slight congestion of the visceral organs was observed.
Other findings:
- Histopathology: The lungs presented intense hyperemia. Histologic study of liver, kidney, adrenal gland, intestine, thymus, testicle and spleen did not show any pathologic change.

Any other information on results incl. tables

Table 1. Data Concerning Experimental Administration of Vitamin B12.

Group

Animals treated

Route of Injection

Amount of Vitamin B12 (mg/kg)

Signs of Toxicity

Mortality Rate

1

10

Intraperitoneal

0.68

None

None

2

10

Intraperitoneal

1.36

Excitatory state with convulsions

2/10

3

10

Intraperitoneal

2.73

Excitatory state with convulsions ending in cardiac and respiratory failure

10/10

4

10

Subcutaneous

 2.73

Excitatory state with convulsions ending in cardiac and respiratory failure

10/10

 

Applicant's summary and conclusion

Conclusions:
The intraperitoneal and subcutaneous LD100 of the test substance is determined to be 3 mg/kg.
Executive summary:

Forty albino mice were given intraperitoneal injections of the test substance in doses of 0.75, 1.5 and 3 mg/kg and 3 mg/kg of the test substance subcutaneously.On the basis of the study findings, it can be stated that an intraperitoneal dose of 0.75 mg/kg is devoid of toxicity, while an intraperitoneal dose of 1.5 mg/kg is toxic, causing excitation and convulsions to the exposed animals. The highest dose tested (3 mg/kg) is lethal for 100 per cent of the animals treated, administered either intraperitoneally or subcutaneously. Mice that died after injection of Vitamin B12 showed no pathologic changes other than congestion of the lung. From these findings, the intraperitoneal and subcutaneous LD100 of the test substance is determined to be 3 mg/kg.

Categories Display