Cyanocobalamin

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Key study: Test method equivalent or similar to OECD Guideline 471 (Bacterial Reverse Mutation Assay). The test item was determined to be not mutagenic with or without metabolic activation in any of the tested strains.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test method equivalent or similar to OECD Guideline 471 (Bacterial Reverse Mutation Assay).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain / cell type:

S. typhimurium TA 1538

Species / strain / cell type:

E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

10% Aroclor 1254-induced liver S9 from male Sprague-Dawley.

Test concentrations with justification for top dose:

0.033, 0.10, 0.33, 1.0, 3.3 and 10 mg/plate.

Vehicle / solvent:

Solvent: Potassium or sodium phosphate buffer.

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Remarks:

Without metabolic activation, for S.typhimurium strains TA98 and TA1538.

Positive control substance:

2-nitrofluorene

Remarks:

(5.0 or 10 µg/plate)

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Remarks:

Without metabolic activation, for S.typhimurium strains TA100 and TA1535.

Positive control substance:

sodium azide

Remarks:

(0.50 or 1.0 µg)

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Remarks:

Without metabolic activation, for S.typhimurium strain TA1537.

Positive control substance:

9-aminoacridine

Remarks:

(50 or 100 µg)

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Remarks:

Without metabolic activation, for E.coli WP2.

Positive control substance:

furylfuramide

other: N-methyl-N'-nitro-N-nitrosoguanidine

Remarks:

(0.1 µg (furylfuramide) or 10 µg (N-methyl-N'-nitro-N-nitrosoguanidine))

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Remarks:

With metabolic activation, for all bacterial strains.

Positive control substance:

other: 2-Anthramine

Remarks:

(at 1.0 or 2.5 µg/plate for S.typhimurium strains TA98, TA100 and TA1538, at 2.5 µg/plate for strains TA1535 and TA1537, and at 10 µg/plate for E.coli stain WP2).

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation). The test substance was dissolved in 0.067 M potassium or sodium phosphate buffer, pH 7.0.

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Species / strain:

E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative (with and without metabolic activation)

The test substance was determined to be not mutagenic with or without metabolic activation in any of the tested strains.

Executive summary:

An in-vitro reverse mutation assay (Ames test) was performed with the test substance following a method equivalent or similar to OECD Guideline 471. Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538, and E.coli strain WP2 were exposed to concentrations of 0.033, 0.10, 0.33, 1.0, 3.3 and 10 mg/plate of the test substance, in the presence and in the absence of the S9 mix, using the plate incorporation method. Concurrent positive and negative controls were run with the test.

The test item did not significantly increase the number of revertant colonies both in the absence or presence of a metabolic activation. The test substance was determined to be non-mutagenic under test conditions.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Key study: An in-vitro reverse mutation assay (Ames test) was performed with the test substance following a method equivalent or similar to OECD Guideline 471. Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538, and E.coli strain WP2 were exposed to concentrations of 0.033, 0.10, 0.33, 1.0, 3.3 and 10 mg/plate of the test substance, in the presence and in the absence of the S9 mix, using the plate incorporation method. Concurrent positive and negative controls were run with the test. Cyanocobalamin did not significantly increase the number of revertant colonies both in the absence or presence of a metabolic activation. The substance was determined to be non-mutagenic under test conditions.

Justification for selection of genetic toxicity endpoint
Only study available.

Justification for classification or non-classification

Based on the available experimental data, the test substance was determined to be non-genotoxic, and therefore it is not classified in accordance with CLP Regulation (EC) no. 1727/2008.