Cyanocobalamin

Endpoint summary

Description of key information

Acute toxicity (oral):
Supporting study: Only few data on test method reported. No toxic effects were observed for the test substance up to a dose level of 5000 mg/kg bw/day.  
Acute toxicity (other routes):
Supporting study: No guideline was followed. Only few data on test method reported. The intraperitoneal and subcutaneous LD100 of Vitamin B12 is determined to be 3 mg/kg. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Only few data on test method reported.

GLP compliance:

not specified

Test type:

other: Writhing test

Limit test:

no

Species:

mouse

Strain:

NMRI

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Lippische Vesuchstierzucht, Hagemann GmbH & Co, Extertal, FRG.
- Weight at study initiation: 21-28g.
- Diet (e.g. ad libitum): standard mouse diet, ad libitum.
- Water (e.g. ad libitum): ad libitum.

Route of administration:

oral: gavage

Vehicle:

other: hydroxypropyl methylcellulose gel.

Details on oral exposure:

DOSAGE PREPARATION
The test compound was suspended in 0.8% aqueous hydroxypropyl methylcellulose gel.
The test substance was given alone or in combination at a ratio of 1:1:0.0025 for thiamine, pyridoxine, and cyanocobalamin.

Doses:

Not determined

No. of animals per sex per dose:

Groups of 5 animals

Control animals:

yes

Statistics:

A Kruskal-Wallis one-way analysis of variance in conjunction with a Wilcoxon two-sample test was used for the statistical analysis.

Sex:

female

Dose descriptor:

discriminating dose

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: (maximum tolerated dose)

Mortality:

No mortality was observed for cyanocobalamine given alone or in combination up to a dose level of 5000 mg/kg bw.

Clinical signs:

other: No toxic effects were observed for cyanocobalamine given alone or in combination up to a dose level of 5000 mg/kg bw.

Following repeated oral administration for 7 days cyanocobalamin alone exerted a slight antinociceptive effect at 5620 mg/kg bw p.o.

The number of writhing reactions was reduced by 18% compared to the control.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No toxic effects were observed for the test substance up to a dose level of 5000 mg/kg bw/day.

Executive summary:

In the present acute oral toxicity study, the maximum tolerated dose was determined for cyanocobalamin. The test substance was given alone or in combination at a ratio of 1:1:0.0025 for thiamine, pyridoxine, and cyanocobalamin, to female mice. No toxic effects were observed for the test substance given alone or in combination up to a dose level of 5000 mg/kg bw/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

Only few data on test method reported.

Additional information

Acute toxicity (oral):

Supporting study: In the present acute oral toxicity study, the maximum tolerated dose was determined for cyanocobalamin. The test substance was given alone or in combination at a ratio of 1:1:0.0025 for thiamine, pyridoxine, and cyanocobalamin, to female mice. No toxic effects were observed for the test substance given alone or in combination up to a dose level of 5000 mg/kg bw/day.

Acute toxicity (other routes):

Supporting study: Forty albino mice were given intraperitoneal injections of Cyanocobalamin 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 the test substance showed no pathologic changes other than congestion of the lung. From these findings, the intraperitoneal and subcutaneous LD100 of the test item is determined to be 3 mg/kg.

Justification for selection of acute toxicity – oral endpoint
Only one study available.