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Genetic toxicity in vitro

Description of key information

The genotoxicity of the test material was investigated in two in vitro studies (Ames test and Chromosome aberration test and mammalian cell gene mutation assay) which were conducted under GLP conditions.

Link to relevant study records

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Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
The study was performed according to a valid guideline without any deviations and was conducted under GLP conditions. Furthermore, the data were submitted by another legal entity, under Directive 67/548/EEC, at least 12 years previously. The registrant has been granted permission to use the information, which has been extracted from the ECHA databases, for REACH registration purposes. No full information related to the experimental result are available but these deficiencies do not affect the quality of the relevant results.
Qualifier:
according to guideline
Guideline:
other: Annex V (Ames test)
Deviations:
not specified
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
no data
Species / strain / cell type:
other: Salmonella typhimurium: TA1535, TA1537, TA98 and TA100. Escherichia coli WP2uvrA
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced, rat-liver S9.
Test concentrations with justification for top dose:
Concentration range in the main test (with metabolic activation): 50 ... 5000 microg/plate
Concentration range in the ma in test (without metabolic activation): 50 ... 5000 microg/plate
Vehicle / solvent:
Sterile distilled water
Details on test system and experimental conditions:
Concentration of the test substance resulting in precipitation: 5000 microg/plate
Rationale for test conditions:
no data
Evaluation criteria:
no data
Statistics:
no data
Species / strain:
bacteria, other: as specified above
Metabolic activation:
with
Genotoxicity:
not specified
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
>5000 micro g/plate
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
bacteria, other: as specified above
Metabolic activation:
without
Genotoxicity:
not specified
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
>5000 micro g/plate
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
bacteria, other: as specified above
Metabolic activation:
with
Genotoxicity:
not specified
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
>5000 micro g/plate
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
Observations:
Solvent control plates gave counts of revertant colonies within the normal range.
All positive control chemicals gave increases in revertants, either with or without the metabolising system as appropriate, within expected ranges.
No statistically significant increase in the numbers of revertant colonies was recorded for any of the bacterial strains with any dose of the substance, either with or without metabolic activation.
Remarks on result:
other: other: preliminary test
Remarks:
Migrated from field 'Test system'.

no data

Conclusions:
Interpretation of results (migrated information):
negative without metabolic activation
negative with metabolic activation
Executive summary:

The genotoxicity of the test material was investigated in a study which was conducted under GLP conditions and following the Ames test method.

Four strains of S. typhimuriumand one strain of E. coliwere treated with and without metabolic activation. Under the test conditions, no evidence of mutagenic activity in the bacterial system was observed.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
The study was performed according to a valid guideline without any deviations and was conducted under GLP conditions. Furthermore, the data were submitted by another legal entity, under Directive 67/548/EEC, at least 12 years previously. The registrant has been granted permission to use the information, which has been extracted from the ECHA databases, for REACH registration purposes. No full information related to the experimental result are available but these deficiencies do not affect the quality of the relevant results.
Qualifier:
according to guideline
Guideline:
other: Annex V (In vitro cytogenetics)
Deviations:
not specified
GLP compliance:
yes
Type of assay:
other: in vitro mammalian cytogenicity (B 10)
Specific details on test material used for the study:
no data
Target gene:
no data
Species / strain / cell type:
mammalian cell line, other: Human lymphocytes
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Phenobarbitone/11,-naphthollavone induced, rat-liver 89.
Test concentrations with justification for top dose:
Concentration range in the main test (with metabolic activation): 156.25 ... 625 microg/ml
Concentration range in the main test (without metabolic activation): 156.25 ... 6251 microg/ml
Vehicle / solvent:
Minimum Essential Media
Details on test system and experimental conditions:
Exposure period (with metabolic activation): 4 hours
Exposure period (without metabolic activation): 4 hours
Fixation time: 20 hours
Rationale for test conditions:
no data
Evaluation criteria:
no data
Statistics:
no data
Species / strain:
mammalian cell line, other: as specified above
Metabolic activation:
with
Genotoxicity:
other: yes (> 625 microg/ml)
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
other: All the negative control cultures gave values of chromosome aberrations with the expected range for normal human lymphocytes.
Positive controls validity:
other: All the positive control cultures gave highly-significant increases in the frequency of aberrations, indicating the satisfactory performance of the test and of the activity of the metabolising system.
Species / strain:
mammalian cell line, other: as specified above
Metabolic activation:
without
Genotoxicity:
other: yes (> 625 microg/ml)
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
other: All the negative control cultures gave values of chromosome aberrations with the expected range for normal human lymphocytes.
Positive controls validity:
other: All the positive control cultures gave highly-significant increases in the frequency of aberrations, indicating the satisfactory performance of the test and of the activity of the metabolising system.
Additional information on results:
Observations:

The substance was seen to induce no significant, dose-related increases in the frequency of aberrations in any of the treatment groups, either with or without S9.
The substance did not induce a significant increase in the numbers of hyperdiploid cells at any dose level in any of the treatment cases.
Remarks on result:
other: other: main test
Remarks:
Migrated from field 'Test system'.

no data

Conclusions:
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation
Executive summary:

The substance was tested in vitro in a chromosomal aberrations test, under GLP conditions.

No increase in chromosomal aberrations was noted for the direct method at exposure a concentration of 0.25, 0.5, or 1.0 mg/ml or the metabolic activation method at 0.75,1.5, or 3.0 mg/ml.

These results indicate that, under the conditions of this study, the substancedid not induce chromosomal aberrations in CHL cells.

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
not specified
Principles of method if other than guideline:
-
GLP compliance:
yes (incl. QA statement)
Type of assay:
other: in vitro mammalian cell gene mutation assay
Specific details on test material used for the study:
Analytical purity: 99.4% w/w.
- Lot/batch No.: Batch number RE13E005
- Storage condition of test material: Room temperature in the dark
Target gene:
Chinese hamster ovary
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
Chinese Hamster Ovary K1 cells
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
not specified
Test concentrations with justification for top dose:
no data
Vehicle / solvent:
no data
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Positive control substance:
not specified
Remarks:
no data available
Details on test system and experimental conditions:
no data
Rationale for test conditions:
no data
Evaluation criteria:
no data
Statistics:
no data
Key result
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
not specified
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
The absolute cloning efficiency in the negative control was above 60% during both the trials. The mutant frequency, in the negative control group was less than 20 per 10000000 clonable cells during both the trials, validating the acceptability of the test.
Remarks on result:
other: no mutagenic potential
Remarks:
no mutagenic potential
Conclusions:
The tested substabce does not have potential to induce gene mutations at the hgprt locus of CHO-K1 cells both in the absence and presence of metabolic activation, under the experimental conditions as described.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

no data

Mode of Action Analysis / Human Relevance Framework

no data

Additional information

Endpoint Conclusion: No adverse effect observed (negative) with and without metabolic activation.

Justification for classification or non-classification

In the Ames test, four strains of S. typhimurium and one strain of E. coli were treated with and without metabolic activation. Under the test conditions, no evidence of mutagenic activity in the bacterial system was observed.

In the chromosome aberration test, no increase in chromosomal aberrations was observed at the tested concentration

with and without metabolic activation.