Cyanocobalamin

Repeated dose toxicity: other routes

Administrative data

Endpoint:

sub-chronic toxicity: other route

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, accetable for assessment, GLP study, but intravenous route of administration, no guideline followed and only hematological observations.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2005

Materials and methods

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

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:

solid - liquid: suspension

Details on test material:

- Name of test material (as cited in study report): Vitamin B12
- Analytical purity: 97.74%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

intravenous

Vehicle:

not specified

Details on exposure:

Cyanocobalamin was administered intravenously as a slow bolus injection via the tail vein using either an ordinary needle or a butterfly needle (depending on the total volume to be administered) at a rate of approximately 3 mL/min.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

182 days (26 weeks)

Frequency of treatment:

Three times per week

Doses / concentrations

Remarks:

Doses / Concentrations:
1, 5, 25 or 100 mg/kg

No. of animals per sex per dose:

6 male and 6 female per dose

Control animals:

no

Details on study design:

- Rationale for animal assignment (if not random): Randomized.

Examinations

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes.
- Time schedule: Weekly.

BODY WEIGHT: Yes.
- Time schedule for examinations: No data.


HAEMATOLOGY: Yes. 0.5 mL from the jugular vein or the orbital sinus
- Time schedule for collection of blood: Days 1, 85 and 182 of treatment.
- Anaesthetic used for blood collection: Yes. CO2/O2 anaesthesia.
- Animals fasted: No data.
- How many animals: 6 rats (3 males and 3 females) after dosing. Another 6 rats (3 males and 3 females) before dosing.
- Parameters checked: Cyanocobalamin concentration by HPLC.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

not specified

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
No evidence of toxicity was detected by a detailed weekly examination and all animals survived throughout the study period.

BODY WEIGHT AND WEIGHT GAIN
All animals had similar growth rates.

Effect levels

Dose descriptor:

NOAEL

Effect level:

100

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No evidence of toxicity nor mortality were recorded after 26 weeks of intravenous administration of different doses of Cyanocobalamin to Sprague-Dawley rats so the NOAEL was stablished at least at 100 mg/kg.

Executive summary:

This study was conducted in compliance with GLP of OECD. A total of 48 Sprague-Dawley rats was randomly assigned to receive, intraenously, 1, 5, 25 or 100 mg/kg of cyanocobalamin (6 males and 6 females in each group) three times per week until completion of the study at 182 days (26 weeks).

The animals were weekly examined and blood samples were taken at days 1, 85 and 182 for Cyanocobalamin determination.

Finally, all animals survived throughout the study period and had similar growth rates. No evidence of toxicity was detected by a

detailed weekly examination of animals during the study period. Therefore the NOAEL can be stablished at least at 100 mg/kg under the test conditions.