L-methionine

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented non GLP study, although the isomer tested was not specified.

Data source

Reference

Reference Type:

publication

Title:

Activity of coded compounds in the micronucleus test.

Author:

Tsuchimoto,T. and Matter,B.E.

Year:

1981

Bibliographic source:

In de Serres,F.J and Ashby,J. (eds), Progress in Mutation Research, Vol. 1, Evaluation of Short-term Tests for Carcinogens. Elsevier, Amsterdam, The Netherlands, pp. 705–711.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

DL-methionine

EC Number:

200-432-1

EC Name:

DL-methionine

Cas Number:

59-51-8

Molecular formula:

C5H11NO2S

IUPAC Name:

methionine

Details on test material:

- Name of test material (as cited in study report): Methionine

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles-River, Paris

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: water

Frequency of treatment:

each substance was administered i.p. twice, 24 hr apart

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
250 mg/kg
Basis:
other: injected

Doses / concentrations 2

Remarks:

Doses / Concentrations:
500 mg/kg
Basis:
other: injected

Doses / concentrations 3

Remarks:

Doses / Concentrations:
1000 mg/kg
Basis:
other: injected

No. of animals per sex per dose:

each group consisted of two males and two females

Control animals:

yes

Examinations

Tissues and cell types examined:

femoral bone marrow cells

Details of tissue and slide preparation:

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
Animals were killed 6h after the 2nd application
Femoral bone marrow cells were obtained and smears were prepared according to the method described by Schmid (1973, 1974).

DETAILS OF SLIDE PREPARATION:
For staining the slides phosphate buffer pH 6.88 was used instead of distilled water.

METHOD OF ANALYSIS:
Screening of the slides was performed using 10x16 magnification, for regions where cells were well spread and optimally stained.
1500 polychromatic erythrocytes per animal were analyzed under oil-immeresion high power magnification (10x100). The number of micronucleated polychromatic erythrocytes (MPEs) were counted.

OTHER:

Evaluation criteria:

A substance was judged positive when the following criteria were met:
1. two or more mice per group with MPE frequencies above 0.4%
2. one or more treated groups with mean MPE frequencies above 0.3%
3. statistical significance (Kastenbaum and Bowman, 1970) in one or more treated groups

The substance was judged negative if none of the criteria was met and it was judged questionable if only one or two criteria were met.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Additional information on results:

Micornucleated polychromatic erytrocytes (%):

negative control => 0.03 (0.00-0.07)
low-dose group => 0.13 (0.07-0.2
mid-dose group => 0.08 (0.07-0.13)
high-dose group => 0.03 (0.00-0.07)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative