Benzene-1,2:4,5-tetracarboxylic dianhydride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In-vitro gene mutation (Ames) test

The study was performed in conformity to the guidelines for bacterial mutagenicity testing published by the major Japanese Regulatory Authorities, OECD no. 471 and EU-methods B.13/14. The test material was considered to be non-mutagenic under the conditions of this test.

In vitro chromosome aberration test

The study was performed in accordance with OECD no. 473, OPPTS no. 870.5375 and Japanese testing guidelines for chemicals. In both independent experiments, neither a statistically significant nor a biologically relevant increase in the number of cells carrying structural chromosomal aberrations was observed after treatment with the test item. In conclusion, the test item did not induce structural chromosomal aberrations in human lymphocytes in vitro and is considered to be non-clastogenic in this chromosome aberration test.

In vitro gene mutation test The test item was assessed using the HPRT locus using V79 cells of the Chinese hamster. The test was performed in accordance with OECD no. 476, EU-method B.17 abd the corresponding OPPTS-guidelines. No relevant toxic effects occurred up to the maximum concentration of 546.0 μg/mL. In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, the substance is considered to be non-mutagenic in this HPRT assay.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May-June 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OTS 798.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Sponsor's identification: LZ6119
- Description: white powder
- Batch number: CSA 0901038
- Purity: >= 99.5% w/w
- Date received: 01 May 2009
- Storage conditions: room temperature in the dark

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Details on mammalian cell type (if applicable):

CELLS USED
- Suitability of cells: characterisation checks were carried out
- Source of cells: University of California, Berkeley, USA on 4 August 1995 (Salm. typh.) and British Industrial Biological Research Association on 17 August 1987 (E. coli)

MEDIA USED
- Type and identity of media including CO2 concentration if applicable: dimethylsulfoxide (DMSO)
- Properly maintained: yes

Additional strain / cell type characteristics:

other: incapable of synthesising histidine

Metabolic activation:

with and without

Metabolic activation system:

S9 was prepared in-house from livers of male rats and induced with phenobarbitone/beta-naphthoflavone

Test concentrations with justification for top dose:

Preliminary Toxicity Test:
In order to select appropriate dose levels for use in the main test, a preliminary test was carried out to determine the toxicity of the test material. The concentrations tested were 0, 0.15, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 ug/plate. The test material was toxic to TA100 at and above 1500 ug/plate in both the presence and absence of S9. The test material was also toxic to WP2uvrA (absence of S9) at 5000 ug/plate but non-toxic to the same strain in the presence of S9.

Mutation Test- Experiment 1:
Seven concentrations of the test material (5, 15, 50, 150, 500, 1500 and 5000 ug/plate) were assayed in triplicate against each tester strain, using the direct plate incorporation method. Additional dose levels were included to allow for test material induced toxicity, ensuring that at least four non-toxic doses were achieved.

Mutation Test - Experiment 2:
The second experiment was performed using methodology as described for Experiment 1, using fresh bacterial cultures, test material and control solutions. The test material dose range was the same as Experiment 1 (5 to 5000 ug/plate).

Vehicle / solvent:

Dimethylsulfoxide (DMSO)

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

N-ethyl-N-nitro-N-nitrosoguanidine

Details on test system and experimental conditions:

METHOD OF APPLICATION:
- In agar (plate incorporation)

DURATION
- Exposure duration: 48 hours

Rationale for test conditions:

In order to select appropriate dose levels for use in the main test, a preliminary test was carried out to determine the toxicity of the test material. The concentrations tested were 0, 0.15, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 ug/plate.

Evaluation criteria:

The test material will generally be considered mutagenic to bacteria if the following criteria are achieved. If the following criteria are not achieved then the test material will be considered non-mutagenic to bacteria:
1) In strain TA98, TA100 or WP2uvrA-pKM101, a two-fold increase in the mean number of revertants per plate compared to the mean value of the concurrent vehicle control.
2) In strain TA1535 or TA1537, a three-fold increase in the mean number of revertants per plate compared to the mean value of the concurrent vehicle control.
3) Increases in revertant numbers for all strains must be related to increases in test material concentration.
4) A positive response in one tester strain either with or without exogenous metabolic activation is sufficient to designate the test material as a bacterial mutagen.

Statistics:

none

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

initially from 1500 ug/plate in both the presence and absence of S9 (500 ug/plate for TA98 in the absence of S9 in Experiment 2 only).

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The sensitivity of the tester strains to the toxicity of the test material varied slightly between strain type, exposures with or without S9-mix and experiment number. No test material precipitate was observed on the plates at any of the doses tested in either the presence or absence of S9-mix.

All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with or without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated.

Conclusions:

The test material was considered to be non-mutagenic under the conditions of this test.

Executive summary:

The study was performed in conformity to the guidelines for bacterial mutagenicity testing published by the major Japanese Regulatory Authorities, OECD no. 471 and EU-methods B.13/14. Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and Escherichia coli strain WP2uvrA pKM101 were tested with the test material using the Ames plate incorporation method at seven dose levels, in triplicate, both with and without the addition of a rat liver homogenate metabolising system (S9). The dose range was determined in a preliminary toxicity assay and was 5 to 5000 ug/plate in the first experiment. The experiment was repeated on a separate day using the same dose range as Experiment 1, fresh cultures of the bacterial strains and fresh test material formulations. Additional dose levels were included to allow for test material induced toxicity, ensuring that at least four non-toxic doses were achieved. The test material caused a visible reduction in the growth of the bacterial background lawns of all of the tester strains, initially from 1500 ug/plate in both the presence and absence of S9 (500 ug/plate for TA98 in the absence of S9 in Experiment 2 only). The test material was tested up to the maximum recommended dose level of 5000 ug/plate.

No test material precipitate was observed on the plates at any of the doses tested in either the presence or absence of 89-mix. No increases in the frequency of revertant colonies, in excess of two or three fold (depending on the tester strain type) greater than the concurrent solvent controls, were recorded for any of the bacterial strains, for any dose level of the test material, either with or without metabolic activation. The test material was considered to be non-mutagenic under the conditions of this test.

Reference 2

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August-September 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian cell transformation assay

Specific details on test material used for the study:

- Identification: LZ 6119
- Batch: NJC1506009
- Appearance: White, crystalline solid
- Purity: ≥ 99.5 %
- Expiry / Retest date: 10 December 2016
- Storage Conditions: At room temperature, moisture protected, under nitrogen
- Stability in solvent: Not indicated by the sponsor

Species / strain / cell type:

lymphocytes:

Details on mammalian cell type (if applicable):

Human lymphocytes:
Blood samples were drawn from one healthy non-smoking male donor (31 years old in Experiment I, 32 years old in Experiment II) not receiving medication. The lymphocytes of this
donor have been shown to respond well to stimulation of proliferation with PHA and to positive control substances. The donor had a previously established low incidence of chromosomal aberrations in his peripheral blood lymphocytes.

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not used

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital/β-naphthoflavone induced rat liver S9 was used

Test concentrations with justification for top dose:

Applied concentrations in μg/mL:
---------------------------------------
Without S9 mix
- Exp. 1 (prep interval 22 hours / exposure period 4 hours: 14.2; 24.8; 43.4; 75.9; 132.9; 232.5; 407.0; 712.2 (prec.); 1246.3 (prec.); 2181.0 (prec.)
- Exp. 2 (prep interval 22 hours / exposure period 22 hours: 14.2; 24.8; 43.4; 75.9; 132.9; 232.5; 406.9 (prec.); 712.0 (prec.); 1246.0 (prec.)
With S9 mix
- Exp. 1 (prep interval 22 hours / exposure period 4 hours: 14.2; 24.8; 43.4; 75.9; 132.9; 232.5; 407.0 (prec.); 712.2 (prec.); 1246.3 (prec.); 2181.0 (prec.)

Evaluated experimental points (in μg/mL):
-------------------------------------------------
Without S9 mix
- Exp. 1 (prep interval 22 hours / exposure period 4 hours: 232.5; 407.0; 712.2 (prec.)
- Exp. 2 (prep interval 22 hours / exposure period 22 hours: 132.9; 232.5; 406.9 (prec.)
With S9 mix
- Exp. 1 (prep interval 22 hours / exposure period 4 hours: 132.9; 232.5; 407.0 (prec.)

prec. = precipitation observed

Dose selection was performed according to the current OECD Guideline for chromosomal aberration studies. The highest test item concentration should be 10 mM, 2 mg/mL or, 2 μL/m, whichever is the lowest. At least three test item concentrations should be evaluated for cytogenetic damage.

Vehicle / solvent:

On the day of the experiment (immediately before treatment), the test item was suspended in culture medium. The test item is a dianhydride undergoing hydrolysis in aqueous media forming the free acid.

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

cyclophosphamide

ethylmethanesulphonate

Details on test system and experimental conditions:

CYTOGENETIC EXPERIMENT:
Pulse exposure and continuous exosure (without S9-mix)

DURATION:
Exposure time was 4 hrs (with and without S9 mix). The preparation interval was 22 hrs after start of the exposure.

STAIN (for cytogenetic assays):
Slides were stained with Giemsa

METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED:
Mounted after drying and covered with a cover slip

NUMBER OF METAPHASE SPREADS ANALYSED PER DOSE (if in vitro cytogenicity study in mammalian cells):
Per culture at least 150 metaphases were evaluated for structural chromosomal aberrations

DETERMINATION OF CYTOTOXICITY
Cytotoxicity is characterized by the percentages of mitotic suppression in comparison with the controls by counting 1000 cells per culture in duplicate. At least 150 well-spread metaphases were evaluated per culture for structural aberrations. Only metaphases containing a number of centromeres equal to a number of 46 ± 2 were included in the analysis. Breaks, fragments, deletions, exchanges and chromosomal disintegrations are recorded as structural chromosomal aberrations. Gaps were recorded as well, but they are not included in the calculation of the aberration rates since gaps are achromatic lesions of unknown biological relevance for which a clear relationship to treatment cannot be established.

Rationale for test conditions:

Evaluated in a toxicity pre-test

Evaluation criteria:

Providing that all of the acceptability criteria are fulfilled, a test item is considered to be clearly positive if, in any of the experimental conditions examined:
− At least one of the test item concentrations exhibits a statistically significant increase compared with the concurrent solvent control
− The increase is concentration-related in at least one experimental condition
− The results are outside the range of the laboratory historical solvent control data
When all of the criteria are met, the test item is then considered able to induce chromosomal aberrations in this test system.

Statistics:

Statistical significance will be confirmed by using the Fisher’s exact test (p < 0.05) using the validated R Script FisherMidP_V1.rnw for those values that indicate an increase in the number of cells with chromosomal aberrations compared to the concurrent solvent control.

Key result

Species / strain:

lymphocytes: human lymphocytes

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

In Experiment I precipitation of the test item in the culture medium was observed at 712.2 μg/mL and above in the absence of S9 mix and at 407.0 μg/mL and above in the presence of S9 mix at the end of treatment. In addition, precipitation occurred in Experiment II in the absence of S9 mix at 406.9 μg/mL and above at the end of treatment.

Conclusions:

In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce structural chromosomal aberrations in human lymphocytes in vitro. Therefore, the chemical is considered to be non-clastogenic in this chromosome aberration test, when tested up to precipitating concentrations.

Executive summary:

The study was performed in accordance with OECD no. 473, OPPTS no. 870.5375 and Japanese testing guidelines for chemicals.

The test item LZ 6119, suspended in culture medium, was assessed for its potential to induce chromosomal aberrations in human lymphocytes in vitro in the absence and presence of metabolic activation by S9 mix. Two independent experiments were performed. In Experiment I the exposure period was 4 hours with and without S9 mix. In Experiment II the exposure period was 22 hours without S9 mix. The chromosomes were prepared 22 hours after start of treatment with the test item. The highest treatment concentration in this study, 2181.0 μg/mL (approx. 10 mM) was chosen with regard to the molecular weight of the test item and with respect to the OECD Guideline for in vitro mammalian cytogenetic tests. In Experiment I precipitation of the test item in the culture medium was observed at 712.2 μg/mL and above in the absence of S9 mix and at 407.0 μg/mL and above in the presence of S9 mix at the end of treatment. In addition, precipitation occurred in Experiment II in the absence of S9 mix at 406.9 μg/mL and above at the end of treatment. In the absence and presence of S9 mix, no cytotoxicity was observed up to the highest applied concentration.

In both independent experiments, neither a statistically significant nor a biologically relevant increase in the number of cells carrying structural chromosomal aberrations was observed after treatment with the test item. In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce structural chromosomal aberrations in human lymphocytes in vitro. Therefore, the substance is considered to be non-clastogenic in this chromosome aberration test, when tested up to precipitating concentrations.

Reference 3

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August-October 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian cell transformation assay

Specific details on test material used for the study:

- Identification: LZ 6119
- Batch: NJC1506009
- Appearance: White, crystalline solid
- Purity: ≥ 99.5 %
- Expiry / Retest date: 10 December 2016
- Storage Conditions: At room temperature, moisture protected, under nitrogen
- Stability in solvent: Not indicated by the sponsor

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

Large stocks of the V79 cell line (supplied by Laboratory for Mutagenicity Testing; Technical University, Germany) are stored in liquid nitrogen in the cell bank of Envigo CCR allowing the repeated use of the same cell culture batch in experiments. Before freezing, the level of spontaneous mutants was depressed by treatment with HAT-medium. Each batch is screened for mycoplasm contamination and checked for karyotype stability and spontaneous mutant frequency. Consequently, the parameters of the experiments remain similar because of the reproducible characteristics of the cells.

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not used

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital/β-naphthoflavone induced rat liver S9 was used as metabolic activation system

Test concentrations with justification for top dose:

The maximum test item concentration of the pre-experiment (2181 μg/mL) was equal to a molar concentration of about 10 mM. The concentration range of the main experiments was limited by precipitation of the test item.

Applied concentrations in μg/mL:
---------------------------------------
Experiment I / Without and without S9 mix
- Exposure period 4 hours: 17.1; 34.1; 68.3; 136.5; 273.0 (prec.); 546.0 (prec.)
- Exposure period 4 hours: 17.1; 34.1; 68.3; 136.5; 273.0 (prec.); 546.0 (prec.)
Experiment II / Without S9 mix
- Exposure period 24 hours: 17.1; 34.1; 68.3; 136.5; 273.0 (prec.); 546.0 (prec.)
Experiment II / With S9 mix
- Exposure period 4 hours: 17.1; 34.1; 68.3; 136.5; 273.0 (prec.); 546.0 (prec.)

Evaluated experimental points (in μg/mL):
-------------------------------------------------
Experiment I / Without and without S9 mix
- Exposure period 4 hours: 34.1; 68.3; 136.5; 273.0 (prec.); 546.0 (prec.)
- Exposure period 4 hours: 34.1; 68.3; 136.5; 273.0 (prec.); 546.0 (prec.)
Experiment II / Without S9 mix
- Exposure period 24 hours: 17.1; 34.1; 68.3; 136.5; 273.0 (prec.)
Experiment II / With S9 mix
- Exposure period 4 hours: 17.1; 34.1; 68.3; 136.5; 273.0 (prec.)

prec. = precipitation observed

Vehicle / solvent:

On the day of the experiment (immediately before treatment), the test item was suspended in culture medium. The test item is a dianhydride undergoing hydrolysis in aqueous media forming the free acid.

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

7,12-dimethylbenzanthracene

ethylmethanesulphonate

Details on test system and experimental conditions:

STAIN (for cytogenetic assays):
The colonies used to determine the cloning efficiency (survival) were fixed and stained approx. 7 days after treatment.

METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED:
The cultures were incubated at 37 °C in a humidified atmosphere with 1.5% CO2 for about 8 days. The colonies were stained with 10% methylene blue in 0.01% KOH solution. The stained colonies with more than 50 cells were counted. In doubt the colony size was checked with a preparation microscope.

DETERMINATION OF CYTOTOXICITY
Toxicity of the test item is indicated by a reduction of the cloning efficiency (CE).

Evaluation criteria:

A positive response is described as follows:
1. A test item is classified as mutagenic if it reproducibly induces a mutation frequency that is three times above the spontaneous mutation frequency at least at one of the concentrations of the experiment.
2. The test item is classified as mutagenic if there is a reproducible concentration-related increase of the mutation frequency. Such evaluation may be considered also in the case that a threefold increase of the mutant frequency is not observed.
However, in a case by case evaluation this decision depends on the level of the corresponding solvent control data. If there is by chance a low spontaneous mutation rate within the laboratory´s historical control data range, a concentration-related increase of the mutations within this range has to be discussed. The variability of the mutation rates of solvent controls within all experiments of this study was also taken into consideration.

Statistics:

A linear regression ((least squares, calculated using Sum_neu_v2.xltm, version 2.0) was performed to assess a possible dose dependent increase of mutant frequencies. The numbers of mutant colonies generated with the test item were compared to the solvent control groups. A trend is judged as significant whenever the p-value (probability value) is below 0.05. However, both, biological and statistical significance was considered together.

Key result

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Precipitation of the test item was noted at 273.0 μg/mL and above in both main experiments with and without metabolic activation. Occasional grains of particles but no real precipitation was observed at almost all of the lower concentrations. Those grains are most likely based on test item that was still not hydrolyzed at the end of treatment. No relevant toxic effects occurred up to the maximum concentration of 546.0 μg/mL.

Conclusions:

It can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, the substance is considered to be non-mutagenic in this HPRT assay.

Executive summary:

The test item was assessed for its potential to induce gene mutations at the HPRT locus using V79 cells of the Chinese hamster. The test was performed in accordance with OECD no. 476, EU-method B.17 abd the corresponding OPPTS-guidelines. The assay was performed in two independent experiments. The cells were exposed to the test item for 4 hours in the first experiment with and without metabolic activation. The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation. Precipitation of the test item was noted at 273.0 μg/mL and above in both main experiments with and without metabolic activation. Occasional grains of particles but no real precipitation was observed at almost all of the lower concentrations. Those grains are most likely based on test item that was still not hydrolyzed at the end of treatment. No relevant toxic effects occurred up to the maximum concentration of 546.0 μg/mL. In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, the substance is considered to be non-mutagenic in this HPRT assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the data available the substance is not classified or labeled according to Regulation 1272/2008/EC (CLP).