Sulpiride

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Data source

Reference

Reference Type:

review article or handbook

Title:

Pharmacotoxicological aspects of levosulpiride.

Author:

Rossi F

Year:

1995

Bibliographic source:

Pharmacol Res. 1995 Feb;31(2):81-94.

Materials and methods

Test guideline

Guideline:

other: not specified

GLP compliance:

not specified

Type of assay:

other: see executive summary

Test material

Test material information

Constituent 1

Reference substance name:

N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-2-methoxy-5-sulfamoylbenzamide

Cas Number:

23672-07-3

Molecular formula:

C15H23N3O4S

IUPAC Name:

N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-2-methoxy-5-sulfamoylbenzamide

Test material form:

not specified

Results and discussion

Any other information on results incl. tables

The mutagenic potential of levosulpiride was studied by using different methods. The point mutation test in Saccharomyces cerevisiae, the bacterial test of B. Ames on Salmonella tiphymurium, the study on the DNA repairing activity, the chromosomal aberration test in human diploid cells, the DNA repair and damage test (evaluated by mitotic crossing-over and by gene conversion in Saccharomyces cerevisiae), and the gene mutation test in Schizosaccharomyces Pombe Pl, did not document any increase in mutation rate induced by levosulpiride. Furthermore, levosulpiride was tested in vitro for possible induction of structural and numerical chromosome aberration in PHA-stimulated human lymphocytes. The compound was added to the medium at various concentrations 48 h after the culture had been set up. The mean structural aberration rates for the levosulpiride cultures were between 0.5 and 3.0% (for aberrant metaphases including gaps) or 0 and 1.5% (for aberrant metaphases excluding gaps) and were thus found within the range of variation of long-term in-house negative controls. No aberration other than gaps, breaks and isolated isochromatid fragments was observed. There was no substance-related increase in comparison to the concurrent negative controls. Numerically aberrant metaphases were also included in the evaluation for structural aberrations. Under these experimental conditions the induction of structural chromosomal aberrations and numerical aberrations in the form of hypoploid and polyploid metaphases induced by levosulpiride is ruled out.

Applicant's summary and conclusion

Conclusions:

Levosulpiride was studied by different test methods and was not found to be genotoxic.

Executive summary:

The mutagenic potential of levosulpiride was studied by using different methods. The point mutation test in Saccharomyces cerevisiae, the bacterial test of B. Ames on Salmonella tiphymurium, the study on the DNA repairing activity, the chromosomal aberration test in human diploid cells, the DNA repair and damage test (evaluated by mitotic crossing-over and by gene conversion in Saccharomyces cerevisiae), and the gene mutation test in Schizosaccharomyces Pombe Pl, did not document any increase in mutation rate induced by levosulpiride. Furthermore, levosulpiride was tested in vitro for possible induction of structural and numerical chromosome aberration in PHA-stimulated human lymphocytes. The compound was added to the medium at various concentrations 48 h after the culture had been set up. The mean structural aberration rates for the levosulpiride cultures were between 0.5 and 3.0% (for aberrant metaphases including gaps) or 0 and 1.5% (for aberrant metaphases excluding gaps) and were thus found within the range of variation of long-term in-house negative controls. No aberration other than gaps, breaks and isolated isochromatid fragments was observed. There was no substance-related increase in comparison to the concurrent negative controls. Numerically aberrant metaphases were also included in the evaluation for structural aberrations. Under these experimental conditions the induction of structural chromosomal aberrations and numerical aberrations in the form of hypoploid and polyploid metaphases induced by levosulpiride is ruled out.