Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In a key Ames test, the test item tested up to a concentration of 5000 µg/plate, caused no mutagenic
effect in the Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA1537 neither in the
plate incorporation test nor in the preincubation test each carried out without and with metabolic
activation up to 5000 µg/plate. In a key Mammalian gene mutation test the test item tested without
and with metabolic activation was negative in the HPRT-V79 mammalian cell mutagenicity test
conditions was negative for mutagenic effects up to cytotoxic concentration of 500 µg/mL. In a key
in vitro Micronucleus test, the test item was negative for chromosome damage in human peripheral
lymphocytes tested up to cytotoxic concentrations without and with metabolic activation up to 250 µg/mL. 

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See attached Read-across information
Reason / purpose:
read-across source
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Remarks:
The recommended maximum test concentration for soluble non-cytotoxic test items is 5 mg/plate or 5 µL/plate.
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
COMPARISON WITH HISTORICAL CONTROL DATA: Yes

ADDITIONAL INFORMATION ON CYTOTOXICITY: No signs of cytotoxicity were noted up to the top concentration of 5000 µg/plate. Hence, 5000 µg test item/plate were chosen as top concentration for the main study in the plate incorporation test and in the preincubation test.
Remarks on result:
other: all strains/cell types tested
Conclusions:
Interpretation of results: negative with and without metabolic activation

Under the present test conditions the read-across test item tested up to a concentration of 5000 µg/plate, caused no mutagenic effect in the Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA1537 neither in the plate incorporation test nor in the preincubation test each carried out without and with metabolic activation.
Executive summary:

The read-across test item was examined in the 5 Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA1537 in two independent experiments, each carried out without and with metabolic activation (a microsomal preparation derived from Aroclor 1254-induced rat liver). The first experiment was carried out as a plate incorporation test and the second as a preincubation test.

The read-across test item was completely dissolved in aqua ad iniectabilia. Aqua ad iniectabilia was used as vehicle control.

Preliminary test

The read-across test item was examined in a preliminary cytotoxicity test without metabolic activation in test strain TA100 employing a plate incorporation test. Ten concentrations of 0.316, 1.0, 3.16, 10.0, 31.6, 100, 316, 1000, 3160 and 5000 µg test item/plate were tested. No signs of cytotoxicity were noted up to the top concentration of 5000 µg/plate. Hence, 5000 µg test item/plate were chosen as top concentration for the main study in the plate incorporation test and in the preincubation test.

Main study

Six concentrations of 31.6, 100, 316, 1000, 3160 and 5000 µg test item/plate were employed in the plate incorporation test and in the preincubation test, each carried out without and with metabolic activation.

Cytotoxicity

No signs of cytotoxicity were noted in the plate incorporation test and in the preincubation test, each carried out without and with metabolic activation up to the top concentration of 5000 µg test item/plate in all test strains.

Mutagenicity

No increase in revertant colony numbers as compared with control counts was observed for the read-across test item, tested up to a concentration of 5000 µg/plate, in any of the 5 test strains in two independent experiments without and with metabolic activation, respectively (plate incorporation and preincubation test).

The results for the vehicle controls were within the range of historical control data of the laboratory. The positive control items showed a significant increase in the number of revertant colonies compared to the vehicle controls of the respective test strain and confirmed the validity of the test conditions and the sensitivity of the test system.

In conclusion, under the present test conditions the read-across test item tested up to a concentration of 5000 µg/plate, caused no mutagenic effect in the Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA1537 neither in the plate incorporation test nor in the preincubation test each carried out without and with metabolic activation.

 

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See attached Read-across information
Reason / purpose:
read-across source
Key result
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH and osmolality:
The pH and osmolality of the negative control and all test item formulations in the medium were determined for each experiment employing the methods given below:
pH values: using a digital pH meter type WTW pH 525 (series no. 51039051),
Osmolality: with a semi-micro osmometer .
No relevant changes in the pH or osmolality values of the formulations were noted.
- Precipitation: Test item precipitation was noted starting at a concentration of 100 µg/mL.

RANGE-FINDING/SCREENING STUDIES:
The best chance to observe a potential mutagenic effect is usually at the highest concentration of a test item which is tolerated by the cell. To determine the cytotoxicity, the same procedure was used as employed for the mutagenicity experiments, except that no mutant selection was carried out. Approximately 1500000 cells were placed in 30 mL DMEM-FCS per 150 mm diameter dish. On the following day, the cells were exposed to a wide range of concentrations of the test item. In the absence of S9 mix, the cells were exposed in DMEM-FCS to the test item for 24 hours.
In the experiments with S9 mix, the medium was replaced by 18 mL S9 mix and the exposure limited to 4 hours. After removal of the test item and washing of the plates with PBS the cells were trypsinised and a relative plating efficiency was determined for each dose to obtain an accurate measure of the toxic effect of the chemical.
Along with toxicity, the ability of the test item to cause precipitation in the test solution, changes in the pH and osmolality of the test solutions was assessed. Initial pH and osmolality determination were carried out in test solutions without target cells both in the presence and absence of metabolic activation. The pH was measured at the highest test item treatment level. The osmolality of the highest test item treatment condition, lowest precipitating test item level and the highest soluble test item level in test solution was measured.
Three replicate plates (60 mm diameter) were used with a known number of cells. After about 8 days, the cells were fixed and stained with methylene blue in ethanol. The colonies were then counted.
A concentration of the test item which produces a low level of survival (10 to 20%) would be used as highest concentration and the survival in the lowest concentration being approximately the same as that in the vehicle control. In the case of no cytotoxicity, the highest concentration would be determined by the solubility of the test item. Five adequately spaced concentrations are employed.
In this preliminary experiment without and with metabolic activation test item concentrations of 10, 25, 100, 250, 1000, 2500 and 5000 µg/mL medium were employed. Pronounced cytotoxicity in form of decreased plating efficiency was noted starting at concentrations of 250 or 1000 µg/mL medium in the experiments without and with metabolic activation (24-h or 4-h exposure), respectively. Test item precipitation was noted starting at a concentration of 100 µg/mL. Hence, 500 µg test item/mL was employed as the top concentration for the mutagenicity tests in the absence and in the presence of metabolic activation.


COMPARISON WITH HISTORICAL CONTROL DATA:
The historical background mutation frequency in this system has been reported to be 1 to 44 mutants per 106 survivors in non-activation solvent controls and 6 to 46 per 106 survivors in S9 activation solvent controls (Bradley et al.: Mutagenesis by chemical agents in V79 Chinese hamster cells: a report and analysis of the literature. A report of the Gene-Tox Program. Mutation Research 87, 81 - 142 (1981). The spontaneous mutation frequency may be variable from experiment to experiment, but should normally lie within the above-mentioned range. The positive controls EMS (600 and 700 µg/mL) and DMBA (20 and 30 µg/mL) should cause a 10-fold or greater increase in mutation frequency.
The background mutation frequency at LPT ranges from 1.30 to 38.36 x 10-6 clonable cells for the vehicle controls. The mutation frequency of the positive controls at LPT ranges from 112.1 to 1708.4 x 10 6 clonable cells for EMS and 130.0 to 2693.3 x 10-6 clonable cells for DMBA.
The mutation frequencies of the solvent controls and the positive controls without and with metabolic activation for the last 58 experiments (most recent background data, not audited by the QAU-department) are given as follows:
Mutation frequency per 106 clonable cells
Without metabolic activation (24-h exposure):
Solvent control (n = 58)
mean 14.11
SD 7.42
range 1.30 – 34.80
Positive control (µg/mL) (n = 58)
EMS (600)
mean 449.1
SD 444.2
range 112.1 – 1708.4
EMS (700)
mean 468.4
SD 268.6
range 152.0 – 976.9

With metabolic activation(4-h exposure):
Solvent control (n = 58)
mean 14.88
SD 8.20
range 2.18 – 38.36
Positive control (µg/mL) (n = 58)
DMBA (20)
mean 347.1
SD 241.8
range 130.0 – 844.8
DMBA(30)
Mean 563.8
SD 700.1
range 151.3 – 2693.3

SD = Standard deviation
EMS = ethyl methanesulfonate
DMBA = 9,10-dimethyl-1,2-benzanthracene


ADDITIONAL INFORMATION ON CYTOTOXICITY:
In the main study cytotoxicity in form of decreased plating efficiency (PE1) and (PE2) was noted in the first and second experiments at concentrations of 250 or 500 µg/mL in the absence and presence of metabolic activation, respectively. The concentration of 500 µg/mL caused complete cytotoxicity in the experiments without metabolic activation. In the main study cytotoxicity in form of decreased plating efficiency (PE1) and (PE2) was noted in the first and second experiments at concentrations of 250 or 500 µg/mL in the absence and presence of metabolic activation, respectively. The concentration of 500 µg/mL caused complete cytotoxicity in the experiments without metabolic activation. In addition, test item precipitation was noted starting at a concentration of 125 µg/mL medium.
Conclusions:
Interpretation of results:
negative with metabolic activation
negative without metabolic activation

Under the present test conditions, the read-across test item tested up to cytotoxic concentrations in the experiments without and with metabolic activation was negative in the HPRT-V79 mammalian cell mutagenicity test conditions where positive controls exerted potent mutagenic effects.
Executive summary:

The read-across test item was tested for mutagenic potential in a gene mutation assay in cultured mammalian cells (V79, genetic marker HPRT) both in the presence and absence of metabolic activation by a rat liver post-mitochondrial fraction (S9 mix) from Aroclor 1254-induced animals. The duration of the exposure with the test item was 4 hours or 24 hours in the experiments without S9 mix and 4 hours in the experiments with S9 mix.

The read-across test item was completely dissolved in aqua ad iniectabilia. Aqua ad iniectabilia served as the vehicle control.

The concentrations employed were chosen based on the results of a cytotoxicity study. In this preliminary experiment without and with metabolic activation test item concentrations of 10, 25, 100, 250, 1000, 2500 and 5000 µg/mL medium were employed. Pronounced cytotoxicity in form of decreased plating efficiency was noted starting at concentrations of 250 or 1000 µg/mL medium in the experiments without and with metabolic activation (24-h or 4 -h exposure), respectively. Test item precipitation was noted starting at a concentration of 100 µg/mL. Hence, 500 µg read-across test item/mL was employed as the top concentration for the mutagenicity tests in the absence and in the presence of metabolic activation.

Main study

Concentrations of 15.63, 31.3, 62.5, 125, 250 or 500 µg read-across test item/mL and 31.3, 62.5, 125, 250 or 500 µg test item/mL were selected for the experiments without and with metabolic activation, respectively.

Cytotoxicity
In the main study cytotoxicity in form of decreased plating efficiency (PE1) and (PE2) was noted in the first and second experiments at concentrations of 250 or 500 µg/mL in the absence and presence of metabolic activation, respectively. The concentration of 500 µg/mL caused complete cytotoxicity in the experiments without metabolic activation. In addition, test item precipitation was noted starting at a concentration of 125 µg/mL medium.

Experiments without metabolic activation

The mutation frequency of the vehicle control aqua ad iniectabilia was 8.65 and 8.37 x 10-6clonable cells. Hence, the vehicle controls were well within the expected range.

The mutation frequency of the cultures treated with concentrations of 15.63, 31.3, 62.5, 125 or 250 µg test item/mL culture medium ranged from 1.62 to 9.49 x 106clonable cells. These results are within the normal range of the vehicle controls.

Experiments with metabolic activation

The mutation frequency of the vehicle control aqua ad iniectabilia was 16.00 and 6.17 x 10-6clonable cells. Hence, the vehicle controls were well within the expected range.

The mutation frequency of the cultures treated with concentrations of 31.3, 62.5, 125, 250 or 500 µg test item/mL culture medium ranged from 1.30 to 18.97 x 106clonable cells. These results are within the normal range of the vehicle controls.

The positive controls EMS (ethyl methanesulfonate) in the direct test and DMBA (9,10-dimethyl-1,2-benzanthracene), a compound which requires metabolic activation, caused a pronounced increase in the mutation frequencies ranging from 522.73 to 690.53 x 10-6clonable cells in the case of EMS and ranging from 534.19 to 770.00 x 10-6clonable cells in the case of DMBA, indicating the validity of this test system.

The background mutation frequency at LPT ranges from 1.30 to 38.36 x 10-6clonable cells for the vehicle controls. The mutation frequency of the positive controls at LPT ranges from 112.1 to 1708.4 x 10-6clonable cells for EMS and 130.0 to 2693.3 x 10-6clonable cells for DMBA.

Under the present test conditions, the read-across test item tested up to cytotoxic concentrations in the experiments without and with metabolic activation was negative in the HPRT-V79 mammalian cell mutagenicity test conditions where positive controls exerted potent mutagenic effects.

Endpoint:
in vitro cytogenicity / micronucleus study
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See attached Read-across information
Reason / purpose:
read-across source
Key result
Species / strain:
lymphocytes: human peripheral blood lymphocytes
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH and osmolality:
The pH and osmolality of the negative control and all test item formulations in the medium were determined for each experiment employing the methods given below:
pH values: using a digital pH meter type WTW pH 525 (series no. 51039051),
Osmolality: with a semi-micro osmometer.
No relevant changes in pH or osmolality of the formulations were noted.
- Water solubility: The test item was completely dissolved in aqua ad iniectabilia.

RANGE-FINDING/SCREENING STUDIES:
In this preliminary experiment without and with metabolic activation test item concentrations of 10, 25, 100, 250, 1000, 2500 and 5000 µg test item/mL medium were employed. Cytotoxicity was noted starting at the concentration of 250 µg test item/mL. Hence, 250 µg/mL were employed as the top concentration for the mutagenicity tests without and with metabolic activation.

COMPARISON WITH HISTORICAL CONTROL DATA:
Data from vehicle and positive controls are used to establish historical control ranges. These values are used in deciding the adequacy of the concurrent vehicle controls or positive controls for an experiment.
The micronucleus frequencies of the vehicle controls without and with metabolic activation for the last 8 or 7 studies (most recent background data, not audited by the QAU-department) are given as follows:
Micronucleus frequency per 1000 cells
Without metabolic activation (4-h or 20-h exposure)
Untreated control (n = 8)
Mean: 4.9
SD: 2.0
range: 1 - 9
Vehicle control (n = 8)
Mean: 7.2
SD: 4.6
range: 1 - 18
Mitomycin C Positive control (n = 7)
Mean: 95.8
SD: 66.1
range: 24 - 286
Colchicine Positive control (n = 7)
Mean: 25.4
SD: 10.2
range: 7 - 43
With metabolic activation (4-h exposure)
Vehicle control (n = 8)
Mean: 10.8
SD: 6.2
range: 2 - 25
Cyclophosphamide Positive control (n = 7)
Mean: 60.3
SD: 37.8
range: 20 – 147
ADDITIONAL INFORMATION ON CYTOTOXICITY:
In the main study cytotoxicity was noted at the top concentration of 250 µg/mL in the experiments without and with metabolic activation.
Conclusions:
Interpretation of results:
negative with metabolic activation
negative without metabolic activation

Under the present test conditions, the read-across test item tested up to cytotoxic concentrations of 250 µg test item/mL medium, in the absence and in the presence of metabolic activation employing two exposure times (without S9) and one exposure time (with S9) revealed no indications of chromosomal damage in the in vitro micronucleus test.
In the same test, Mitomycin C and cyclophosphamide induced significant chromosomal damage and colchicine induced significant damage to the cell division apparatus, respectively
Executive summary:

Test sample of read-across substance Sodium bis(C11-14-isoalkyl, C13-rich) sulfosuccinate was assayed in an in vitro micronucleus test using human peripheral lymphocytes both in the presence and absence of metabolic activation by a rat liver post-mitochondrial fraction (S9 mix) from Aroclor 1254 induced animals.

The test was carried out employing 2 exposure times without S9 mix: 4 and 20 hours, and 1 exposure time with S9 mix: 4 hours. The experiment with S9 mix was carried out twice. The harvesting time was 20 hours after the end of exposure. The study was conducted in duplicate.

The read-across test item was completely dissolved in aqua ad iniectabilia. Aqua ad iniectabilia served as the vehicle control.

The concentrations employed were chosen based on the results of a cytotoxicity study. In this preliminary experiment without and with metabolic activation test item concentrations of 10, 25, 100, 250, 1000, 2500 and 5000 µg/mL medium were employed. Cytotoxicity was noted starting at the concentration of 250 µg test item/mL. Hence, 250 µg/mL were employed as the top concentration for the mutagenicity tests without and with metabolic activation.

In the main study cytotoxicity was noted at the top concentration of 250 µg/mL in the experiments without and with metabolic activation.

Mitomycin C and colchicine were employed as positive controls in the absence and cyclophosphamide in the presence of metabolic activation.

Tests without metabolic activation (4- and 20-hour exposure)

The micronucleus frequencies of cultures treated with the read-across test item at concentrations of 31.3, 62.5 or 125 µg test item/mL medium (4 h or 20-h exposure) in the absence of metabolic activation ranged from 5.0 to 8.5 micronuclei per 1000 binucleated cells. There was no dose related increase in micronuclei up to the cytotoxic concentrations. The dose level of 250 µg test item/mL medium led to cytotoxicity, no cells of sufficient quality were available for evaluation.

Vehicle controls should give reproducibly low and consistent micronuclei frequencies, typically 5 - 25 micronuclei per 1000 cells according to OECD 487. In this test the following frequencies were observed: vehicle control: 8.0 or 5.0 micronuclei per 1000 binucleated cells and untreated controls: 9.5 or 8.0 micronuclei per 1000 binucleated cells (4-hour and 20-hour exposure, respectively). Vehicle and untreated control values fell within acceptation ranges.

 Test with metabolic activation (4-hour exposure)

The micronucleus frequencies of cultures treated with the read-across test item at concentrations of 31.3, 62.5 or 125 µg test item/mL medium (4-h exposure) in the presence of metabolic activation ranged from 2.5 to 10.0 micronuclei per 1000 binucleated cells. There was no dose related increase in micronuclei up to the cytotoxic concentration. The dose level of 250 µg test item/mL medium led to cytotoxicity, not enough cells of sufficient quality were available for evaluation.

Vehicle controls should give reproducibly low and consistent micronuclei frequencies, typically 5 - 25 micronuclei per 1000 cells according to OECD 487. In this test the following frequencies were obsereved: vehicle control: 8.5 or 8.0 micronuclei per 1000 binucleated cells and untreated controls: 10.0 or 8.5 micronuclei per 1000 binucleated cells. Vehicle and untreated control values fell within acceptation ranges.

Under the present test conditions, the read-across test item tested up to cytotoxic concentrations of 250 µg test item/mL medium, in the absence and in the presence of metabolic activation employing two exposure times (without S9) and one exposure time (with S9) revealed no indications of chromosomal damage in the in vitro micronucleus test.

In the same test, Mitomycin C and cyclophosphamide induced significant chromosomal damage and colchicine induced significant damage to the cell division apparatus, respectively.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No data were availalable for registered substance, however key studies were available for a structurally similar test substance Sodium bis (C11-14-isoalkyl, C13-rich) sulfosuccinate (CAS number 848588-96-5). Justification for this read across is separately attached in Section 13.

 

Bacterial mutagenicity

In a key Ames test (Flügge, 2013a) the test item was examined in the 5 Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA1537 in two independent experiments, each carried out without and with metabolic activation. The first experiment was carried out as a plate incorporation test and the second as a preincubation test.The test item was completely dissolved in aqua ad iniectabilia. Aqua ad iniectabilia  was used as vehicle control. Based on a preliminary cytotoxicity test, six concentrations of 31.6, 100, 316, 1000, 3160 and 5000 µg test item/plate were employed in the plate incorporation test and in the preincubation test, each carried out without and with metabolic activation. No signs of cytotoxicity were noted in the plate incorporation test and in the preincubation test. No increase in revertant colony numbers as compared with control counts was observed for the test item, tested up to a concentration of 5000 µg/plate, in any of the 5 test strains in two independent experiments without and with metabolic activation, respectively (plate incorporation and preincubation test).

 

Mammalian mutagenicity

In a key mammalian gene mutation study (Flügge, 2013b) the test item was tested for mutagenic potential in a gene mutation assay in cultured mammalian cells (V79, genetic marker HPRT) both in the presence and absence of metabolic activation. The duration of the exposure with the test item was 4 hours or 24 hours in the experiments without S9 mix and 4 hours in the experiments with S9 mix.

The test item was completely dissolved in aqua ad iniectabilia. Aqua ad iniectabilia served as the vehicle control. Based on cytotoxicity at concentrations of 250 or 1000 µg/mL in the preliminary test, 500 µg test item/mL was employed as the top concentration for the main study.

Concentrations of 15.63, 31.3, 62.5, 125, 250 or 500 µg test item/mL and 31.3, 62.5, 125, 250 or 500 µg test item/mL were selected for the experiments without and with metabolic activation, respectively. The mutation frequency of the cultures treated were within the normal range of the vehicle controls. Under the present test conditions, the test item tested up to cytotoxic concentrations in the experiments without and with metabolic activation was negative in the HPRT-V79 mammalian cell mutagenicity test conditions where positive controls exerted potent mutagenic effects.

 

Chromosome aberration

A key in vitro micronucleus test was conducted using human peripheral lymphocytes both in the presence and absence of metabolic activation by a rat liver post-mitochondrial fraction (S9 mix) from Aroclor 1254 induced animals (Flügge, 2013c). The test was carried out employing 2 exposure times without S9 mix: (4 hours and 20 hours) and one exposure time with S9 mix (repeated). The harvesting time was 24 hours after the end of exposure. Each treatment was conducted in duplicate. The test item was completely dissolved in aqua ad iniectabilia, which also served as the vehicle control. Based on a preliminary experiment, cytotoxicity was noted starting at a concentration of 250 µg test item/mL in the experiment without and with metabolic activation. Hence, 250µg/mL were employed as the top concentration for the main test without and with metabolic activation in two independent experiments, each (4-hour and 20-hour exposure). There was no increase in micronuclei up to the cytotoxic concentration when compared to control both with and without metabolic activation. Under the present test conditions, the test item tested up to cytotoxic concentrations, in the absence and in the presence of metabolic activation employing two exposure times (without S9) and one exposure time (with S9) revealed no indications of any chromosomal damage in the in vitro micronucleus test. In the same test, Mitomycin C and cyclophosphamide induced significant damage.

 

Conclusion

Standard information requirements according to REACH Guidance Part 3 R7a were fulfilled for genotoxicity testing, including bacterial and mammalian mutagenicity and chromosomal aberration. Based on the available results, there were no indications of mutagenicity or genotoxicity, and no further testing is needed. The substance can be considered to have no mutagenic or genotoxic potential.

 

Justification for classification or non-classification

Based on these results and according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008), the test substance does not have to be classified and has no obligatory labelling requirement for genetic toxicity.