Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vivo

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation
Type of assay:
micronucleus assay
Species:
mouse
Sex:
male
Route of administration:
intraperitoneal
Vehicle:
Saline
Frequency of treatment:
1 dose
Post exposure period:
24h
Remarks:
Doses / Concentrations:
125 mg/kg
Basis:

Remarks:
Doses / Concentrations:
250 mg/kg
Basis:

Remarks:
Doses / Concentrations:
500 mg/kg
Basis:

No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle
Positive control(s):
Mitomycin C
Additional information on results:
No mortality
Conclusions:
Interpretation of results (migrated information): negative
Cystein Hydrochloride is negative in an in vivo micronucleus test in mice under the consditions described in the publication.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

The test item L-Cysteine was assessed for its potential to induce mutations at the HPRT locus using V79 cells of the Chinese Hamster according to OECD Guideline 476.

The selection of the concentrations was based on data from the pre-experiments. In experiment I and II 10 mM (with and without metabolic activation) was selected as the highest concentrations. Experiment I with and without metabolic activation and experiment II with metabolic activation were performed as a 4 h short-term exposure assay. Experiment II without metabolic activation was performed as 20 h long time exposure assay. The test item was investigated at the following concentrations:

Experiment I with and without metabolic activation: 0.010, 0.025, 0.05, 0.10, 0.25, 0.5, 1.0, 2.5, 5.0 and 10 mM

Experiment II without metabolic activation: 0.010, 0.025, 0.05, 0.10, 0.25, 0.5, 1.0, 2.5, 5.0 and 10 mM and with metabolic activation: 0.07, 0.1, 0.4, 0.7, 1.0, 2.0, 4.0, 6.0, 8.0 and 10 mM.

No precipitation of the test item was noted in the experiments. A biologically relevant growth inhibition (reduction of relative growth below 70%) was observed after the treatment with the test item in experiment I and II without metabolic activation. No biologically relevant growth inhibition (reduction of relative growth below 70%) was observed after the treatment with the test item in experiment I and II with metabolic activation. In experiment I without metabolic activation the relative growth was 36.8% for the highest concentration (10 mM) evaluated. The highest biologically relevant concentration evaluated with metabolic activation was 10 mM with a relative growth of 92.8%. In experiment II without metabolic activation the relative growth was 16.6% for the highest concentration (10 mM) evaluated. The highest concentration evaluated with metabolic activation was 10 mM with a relative growth of 137.8%. In both experiments no biologically relevant increase of mutants was found after treatment with the test item (with and without metabolic activation). No dose-response relationship was observed. DMBA and EMS were used as positive controls and showed distinct and biologically relevant effects in mutation frequency. In conclusion, in the described mutagenicity test under the experimental conditions reported, the test item L-Cysteine is considered to be non-mutagenic in the HPRT locus using V79 cells of the Chinese Hamster. To investigate the potential of L-Cysteine (99.6% pure) to induce structural chromosome aberrations in Chinese hamster V79 cells, an in vitro chromosome aberration assay according to OECD Guideline 473 was carried out.

The metaphases were prepared 20 h after start of treatment with the test item. The treatment interval was 4 h without and with metabolic activation in experiment I. In experiment II, the treatment interval was 20 h withoutand 4 h with metabolic activation. Parallel cultures were treated at each concentration. 100 metaphases per culture were scored for structural chromosomal aberrations.

The following concentrations were evaluated for the microscopic analysis of chromosomal aberrations:

Experiment I: without and with metabolic activation: 2.5, 5.0 and 10.0 mM

Experiment II: without metabolic activation: 1.25, 2.5 and 5.0 mM; with metabolic activation: 2.5, 5.0 and 10.0 mM

No precipitation of the test item was noted without and with metabolic activation in all dose groups evaluated in experiment I and II. No cytotoxic effects of the test item were noted without and with metabolic activation in all concentrations evaluated in experiment I and II. In experiment I without and with metabolic activation no biologically relevant increase of the aberration rates was noted after treatment with the test item. The aberration rates of all concentrations treated with the test item were within the historical control data of the negative control. In experiment II without metabolic activation a slight increase of aberrant cells (4.5%) was noted compared to the historical control data (0.0% - 4.0%). However, as there was no concentration relationship observed and only one of the four evaluated slides displayed an increase (2%, 1%, 3% and 12% aberrant cells observed) this effect was considered as not biologically relevant. In experiment II with metabolic activation no biologically relevant increase of the aberration rates was noted after treatment with the test item. In the experiments I and II without and with metabolic activation no biologically relevant increase in the frequencies of polyploid cells was found after treatment with the test item as compared to the negative controls. In the experiments I and II without and with metabolic activation no biologically relevant increase in the frequencies of polyploid cells was found after treatment with the test item as compared to the negative controls. EMS (400 and 900μg/mL) and CPA (0.83μg/mL) were used as positive controls and induced distinct and biologically relevant increases in cells with structural chromosomal aberrations, thus proving the efficiency of the test system to indicate potential clastogenic effects. In the first experiment without metabolic activation the positive control EMS (900μg/mL) displayed a percentage of 5% aberrant cells. However, on one of the two slides additional five aberrations were seen in metaphases with less than 21 chromosomes. This would lead to an aberration rate of 7.5%.

In conclusion, it can be stated that during the described in vitro chromosome aberration test and under the experimental conditions reported, the test item L-Cysteine did not induce structural chromosomal aberrations in the V79 Chinese hamster cell line. Therefore, the test item L-Cysteine is considered to be non-clastogenic in this chromosome aberration test.

Justification for classification or non-classification

L-Cysteine does not nedd to be classified.