Sodium ascorbate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Protective action of ascorbic acid against mutagenicityof aminopyrine plus nitrite

Author:

Pienkowska K. et al.

Year:

1985

Bibliographic source:

Pol. J. Pharmacol. Pharm., ) 1985, 37 , 601-607

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

shorter preparation time of the cells as recommended, highest dose not justified

GLP compliance:

not specified

Type of assay:

other: Mammalian Erythrocyte Micronucleus Test

Test material

Test material information

Constituent 1

Reference substance name:

Ascorbic acid

EC Number:

200-066-2

EC Name:

Ascorbic acid

Cas Number:

50-81-7

Molecular formula:

C6H8O6

IUPAC Name:

5-(1,2-dihydroxyethyl)-3,4-dihydroxyfuran-2(5H)-one (non-preferred name)

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: animal production section of this institute for drug research and control, Warzawa, Polland
- Weight at study initiation: 23 - 30 g
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Frequency of treatment:

First treatment at the start of the study and second treatment at 24 hrs after study start.

Post exposure period:

6 hrs

Doses / concentrations

Dose / conc.:

622 mg/kg bw/day

No. of animals per sex per dose:

3 male and female animals in the ascrobic acid dose group

Control animals:

yes, concurrent vehicle

Examinations

Tissues and cell types examined:

polychromatic erythrocytes

Details of tissue and slide preparation:

The bone-marrow smears were prepared and stained according to the method of Schmid except that Sorensen buffer (pH 6.8) was used instead of distilled water.

Reference
Schmid W.: The micronucleus test. Mutation Res., 1975, 31, 9 - 15.

Evaluation criteria:

Only polychromatic erythrocytes with clearly identifiable micronuclei were scored. The frequency, of micronuclei was calculated for each animal (2000 cells per mouse) and used to determine the mean value for the group. The results were evaluated according to Kastenbaum and Bowman. Smears from all groups of animals were also used to determine the ratio of erythrocytes to nucleated cells by counting about 500 cells for each mouse.

Reference
Kastenbaum M.A., Bowman K.O.: Tables for determining the statistical significance of mutation frequencies. Mutation Res., 1970, 9, 527-549.

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not examined

Vehicle controls validity:

valid

Any other information on results incl. tables

Compound	Dose mg/kg bw	Polychromatic erythrocytes
		scored	with MN
		n	n	‰
Control		16000	19	1.2
Ascorbic acid	2 x 622	12000	26	2.17

Applicant's summary and conclusion

Conclusions:

The test item did not induce a significant increase in the frequency of micronuclei in polychromatic erythrocytes. Therefore, the substance is considered non-mutagenic in this micronucleus test in vivo.

Executive summary:

The genetic toxicity of ascorbic acid was tested in vivo in a micronucelus test in mice. Ascorbic acid was tested as a satellite group in this study. Following oral treatment with the test substance (dose 2 x 622 mg/kg bw) ascorbic acid induced no significant increase in the frequency of micronuclei and was therefore non-mutagenic in the test system (Pienkowska, 1985).