Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Bacterial reverse gene mutation assay:
- OECD guideline 471, RL 1, GLP: S. typhimurium TA 1535, TA 1537, TA 98, TA 100, TA 102; tested up to limit/cytotoxic concentrations: negative

Mammalian cell gene mutation assay
- OECD guideline 490, MLA assay; RL 1, GLP: tested up to limit/cytotoxic concentrations: negative

In vitro chromosome aberration test:
- OECD guideline 473; RL 2, GLP: tested up to limit/cytotoxic concentrations: negative,
read-across D-Glucopyranose, oligomeric, C10-16-alkyl glycosides

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
adopted July 21, 1997
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Version / remarks:
dated May 30, 2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
Version / remarks:
August, 1998
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Target gene:
histidine operon
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Metabolic activation system:
S9-liver mix
Test concentrations with justification for top dose:
10.0, 31.6, 100, 316, 1000, 2500 and 5000 pg/plate, the max. concentration was chosen due to results from a pre-experiment.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The solvent was compatible with the survival of the bacteria and the S9 activity.
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
methylmethanesulfonate
other: 4-NOPD; 4-nitro-o-phenylene-diamine; 4-NOPD; without metabolic activation, 2-AA; 2-aminoanthracene; with metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation); preincubation
- Cell density at seeding (if applicable): approx. 1E09 cells/mL

DURATION
- Preincubation period: 60 min
- Exposure duration: 48 h in the dark

NUMBER OF REPLICATIONS: three


DETERMINATION OF CYTOTOXICITY
- Method: other: Cytotoxicity can be detected by a clearing or rather diminution of the background lawn or a reduction in the number of revertants down to a mutation factor of approximately < 0.5 in relation to the solvent control.

Rationale for test conditions:
The OECD Guideline for Testing of Chemicals, Section 4, No. 471 - Bacterial Reverse Mutation Test - recommends using a combination of S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 102.
Evaluation criteria:
A test item is considered as mutagenic if
- a clear and dose-related increase in the number of revertants occurs and/or
- a biologically relevant positive response for at least one of the dose groups occurs in at least one tester strain with or without metabolic activation.
A biologically relevant increase is described as follows:
- if in tester strains TA 98, TA 100 and TA 102 the number of reversions is at least twice as high
- if in tester strains TA 1535 and TA 1537 the number of reversions is at least three times higher than the reversion rate of the solvent control.
Key result
Species / strain:
S. typhimurium, other: TA 98, TA 100, TA 102, TA 1535, TA 1537
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: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Precipitation: not described
- Other confounding effects: no

RANGE-FINDING/SCREENING STUDIES: yes, a range finding study was performed in the strains TA 98 and TA 100.

HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: yes, the positive control plates were within the historical data range.
- Negative (solvent/vehicle) historical control data: yes, the negative control plates were within the historical data range.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
Cytotoxicity was observed in TA 100, TA 1535 and TA 1537 strains at a concentration of 5000 µg/plate, regardless whether the substance was tested with or without metabolic activation. However, there were no relevant increases in revertant colony numbers of any of the five tester strains following treatment with the test item at any concentration level, neither in the presence nor absence of metabolic activation.
Conclusions:
D-Glucose, reaction products with alcohols C16-18 was evaluated in the bacterial reverse mutation assay (Ames test) using Salmonella typhimurium tester strains TA98, TA100, TA102, TA1535 and TA 1537 in the presence and absence of rat liver S9 mix. Under the conditions of the study, the test substance was negative for mutagenic potential.
Executive summary:

In a reverse gene mutation assay in bacteria according to OECD guideline 471 (adopted 21 July 1997), Salmonella typhimurium strains TA98, TA100, TA102, TA1535 and TA 1537 were exposed either to D-Glucose, reaction products with alcohols C16-18 in DMSO in concentrations of 0 (control), 31.6, 100, 316, 1000, 2500 and 5000 µg/plate in all strains in the absence and presence of mammalian metabolic activation (rat liver S9 mix) and in concentrations of 0 (control), 10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/plate in all strains in the absence and presence of mammalian metabolic activation (rat liver S9 mix). The assay was performed using the plate incorporation method and the preincubation method.

The test substance was tested up to cytotoxic concentrations. Cytotoxicity was observed in TA 100, TA 1535 and TA 1537 strains at a concentration of 5000 µg/plate. Precipitation was not observed.The positive controls induced the appropriate responses in the corresponding strains. The mean numbers of revertant colonies in the negative controls were within the ranges of the historical control data.

There was no evidence of an increase in the number of revertant colonies that exceeded twice background in the tester strains TA98, TA 100, TA102 examined at dose levels up to 5000 µg/plate in the absence of a metabolic activation source (S9) or in the presence of S9. Therefore, test substance was considered to be non-genotoxic (non-mutagenic) in Salmonella tester strains TA98, TA100, TA102, TA 1535 and TA 1537 under the conditions employed.

There was no evidence of an increase of revertant colonies after treatment with the test item.

Under the conditions of the study, the test substance was negative for mutagenic potential.

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017-08-09 to 2017-12-
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 490 (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene)
Version / remarks:
(adopted July 29, 2016)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
Version / remarks:
(dated May 30, 2008)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
other: in vitro mammalian cell gene mutation tests using the thymidine kinase gene (migrated information)
Target gene:
Thymidine Kinase Gene
Species / strain / cell type:
mouse lymphoma L5178Y cells
Remarks:
TK locus (+/-) particular clone (3.7.2C)
Details on mammalian cell type (if applicable):
CELLS USED
- Source of cells: ATCC (American Type Culture Collection), 0801 University Blvd.,Manassas. VA 20110 2209, USA
- Suitability of cells: specific subline which has to be be used for the MLA

MEDIA USED
- Type and identity of media including CO2 concentration if applicable:
- Growth medium: RPMI 1640 with glutamaxTM medium supplemented with Pluronic® F68 , gentamycin , amphotericin B1 and horse serum1 (10% by volume)
- Treatment medium: growth medium with a reduced horse serum content (5% by volume).
- Plating medium: growth medium with increased horse serum content (approx. 20% by volume) but without Pluronic® F68.
- Selection medium is growth medium that contains 3 µg/mL of TFT3.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically 'cleansed' against high spontaneous background: yes
Additional strain / cell type characteristics:
other: heterozygous at the TK locus (+/-)
Metabolic activation:
with and without
Metabolic activation system:
S9-mix
Test concentrations with justification for top dose:
Without S9-mix:
1st experiment (3h exposure), 2nd experiment (24h exposure)
6.25, 12.5, 25, 50 and 100 µg/mL

With S9-mix:
1st and 2nd experiment (3h exposure)
12.5, 25, 50, 100 and 316 µg/mL

Top dose justified based on preliminary study:
10.0, 31.6, 100, 316, 1000 and 2000 µg/mL

Pronounced cytotoxicity (decreased survival and a relative plating efficiency (RPE) of 2% or 16%) was noted starting at a concentration of 100 µg/mL in the absence of metabolic activation (24-hour exposure) and starting at 316 µg/mL in the presence of metabolic activation (3-hour exposure).
Test item precipitation was noted macroscopically at a concentration of 316 µg/mL medium and higher in both experiments.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: solubility pretest
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
3-methylcholanthrene
methylmethanesulfonate
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in suspension
- Cell density:
Final cell density at start of treatment was 0.5E06 cells/mL.
Cell densities were adjusted to 2E05 cells/mL and incubated for 2 days for the expression period. Within the expression period cell densities were determined after incubation for 24 hours and, after adjustment to 2E05 cells/mL, the cells were incubated for another 24 hours.



DURATION
- Exposure duration: 3 hour, 24 hours( repeat experiment without metabolic activation)
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): 1 week

SELECTION AGENT (mutation assays): 5 trifluoro-thymidine (TFT)

NUMBER OF REPLICATIONS: 2 independent experiments, 1 replicate each

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Other:
No changes in pH or osmolality were noted in the test item formulations compared to the control.
Evaluation criteria:
- Adequate number of cells and concentrations should be analysable.
- The criteria for the selection of highest concentration are met:

Concentrations were selected using the following criteria: At least four analysable concentrations are used. Where there is cytotoxicity, these concentrations cover a range from the maximum to little or no toxicity and are separated by no more than a factor between 2 and 3.16 (half log dilution). If the maximum concentration is based on cytotoxicity then it should result in approximately 10 - 20% (but not less than 10%) relative survival or relative total growth (RTG). For relatively non-cytotoxic compounds, the maximum concentration is 2 mg/mL, 2 µL/mL, or 10 mM. In addition, among the criteria to be considered when determining the highest concentration are cytotoxicity and solubility in the test system and changes in pH or osmolality.

-a) data of the untreated/solvent control (Mutant Frequency, Cloning Efficiency and the Suspension Growth meet the IWGT MLA Workgroup acceptance criteria (M.M. Moore et al. 2006). Relevant data is given below:

Parameter MLA (Microwell Method)
Mutant Frequency (MF) 50 - 170 x E06
Cloning Efficiency (CE) 65 - 120 %
Suspension Growth (SG) 8 - 32 fold (3-4 hour treatment)
32-180 fold (24 hour treatment)
b) the positive control should demonstrate an absolute increase in total MF, that is, an increase above the spontaneous background MF [an induced MF (IMF)] of at least 300 x E06. At least 40% of the IMF should be reflected in the small colony MF, or the positive control has an increase in the small colony MF of at least 150 x E06 above that seen in the concurrent untreated/solvent control (a small colony IMF of 150 x E06).
c) Mutation Frequencies of both, negative and positive controls fall within the normal range (historical data).

Statistics:
Interpretation relies on the use of a predefined induced mutant frequency (i.e. increase in MF above concurrent control), designated as the Global Evaluation Factor (GEF).
The GEF (126 x E06) is based on the analysis of the distribution of the negative control MF data from participating laboratories (M.M. Moore et al., 2006).
Providing that all acceptability criteria are fulfilled, a test chemical is considered to be clearly positive if, in any of the experimental conditions examined, the increase in MF above the concurrent background exceeds the GEF and the increase is concentration related (e.g., using a trend test). The test chemical is then considered able to induce mutation in this test system.
Providing that all acceptability criteria are fulfilled, a test chemical is considered to be clearly negative if, in all experimental conditions examined there is no concentration related response or, if there is an increase in MF, it does not exceed the GEF. The test chemical is then considered unable to induce mutations in this test system.
In cases when the response is neither clearly negative nor clearly positive as described above and/or in order to assist in establishing the biological relevance of a result the data is evaluated by expert judgement and/or further investigations.
Key result
Species / strain:
mouse lymphoma L5178Y cells
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
- The pH and osmolality of the negative control and all test item formulations in the medium were determined for each experiment:
- Effects of pH: No changes in pH were noted in the test item formulations compared to the control
- Effects of osmolality: No changes in osmolality were noted in the test item formulations compared to the control
- Evaporation from medium: nt expected du to low VPof the test substance
- Precipitation: precipitation in the exposure medium at concentrations of 316 μg/mL and above. The test substance was tested beyond the limit of the solubility to obtain adequate cytotoxicity data, the concentration used as the highest test substance concentration for the dose range finding test was 2000 μg/mL.


RANGE-FINDING/SCREENING STUDIES:
10.0, 31.6, 100, 316, 1000 and 2000 µg/mL
Pronounced cytotoxicity (decreased survival and a relative plating efficiency (RPE) of 2% or 16%) was noted starting at a concentration of 100 µg/mL in the absence of metabolic activation (24-hour exposure) and starting at 316 µg/mL in the presence of metabolic activation (3-hour exposure).


ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: relative plating efficiency (RPE)

HISTORICAL CONTROL DATA
- Positive historical control data: refer to table
- Negative (solvent/vehicle) historical control data: refer to table

RATIO OF SMALL TO LARGE COLONIES
- no change was observed in the ratio of small to large mutant colonies, ranging from 0.40 to 1.08 for test substance-treated cells and ratios of 0.80 to 0.96 for
the negative controls

ACCEPTANCE CRITERIA
- As the increase in the small colony mutation frequency was at least 150 x 10-6 above the concurrent negative control, an absolute increase in total mutation frequency was at least 300 x 10-6 for the positive controls and the mean relative total growth (RTG) greater than or equal to 10%, the acceptance criteria for the positive controls were met.
Conclusions:
It is concluded that D-Glucose, reaction products with alcohols C16-18 tested up to cytotoxic concentrations, in two independent experiments was negative with respect to the mutant frequency in the L5178Y TK +/- mammalian cell mutagenicity test. In addition, no change was noted in the ratio of small to large mutant colonies. Therefore, PC-2016-711 also did not exhibit clastogenic potential at the concentration range investigated.
According to the evaluation criteria for this assay, these findings indicate that, D-Glucose, reaction products with alcohols C16-18 tested up to cytotoxic concentrations, neither induced mutations nor had any chromosomal aberration potential.

Executive summary:

In a mammalian cell gene mutation assay according to OECD guideline 490, adopted July 29, 2016 (thymidine kinase (TK+/-)), L5178Y mouse lymphoma cells cultured in vitro were exposed to D-Glucose, reaction products with alcohols C16-18 (100% purity) in DMSO in the following concentrations in the presence and absence of mammalian metabolic activation (S9 mix):

 

Without S9-mix:

1st experiment (3h exposure), 2nd experiment (24h exposure)

6.25, 12.5, 25, 50 and 100 µg/mL

 

With S9-mix:

1st and 2nd experiment (3h exposure)

12.5, 25, 50, 100 and 316 µg/mL

 

D-Glucose, reaction products with alcohols C16-18 was tested up to cyctotoxic concentrations. The highest concentrations of 100 and 316 µg/mL medium in the absence or presence of metabolic activation were not evaluated because of the complete or almost complete cytotoxicity of the test item.The positive controls induced the appropriate response. There was no evidence of induced mutant colonies over background. In addition, no change was observed in the ratio of small to large mutant colonies.

 

This study is classified as acceptable and satisfies the requirement for Test Guideline OECD 490 for in vitro mutagenicity (mammalian forward gene mutation) data.

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:
16 Nov - 02 Dec 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study with acceptable restrictions. Positive controls were only used in the 20-h treatment.
Qualifier:
according to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
yes
Remarks:
positive controls were only used in the 20-h treatment
Qualifier:
according to guideline
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
Deviations:
yes
Remarks:
positive controls were only used in the 20-h treatment
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test
Target gene:
Not applicable
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Details on mammalian cell type (if applicable):
- Type and identity of media: Eagle’s Minimal Essential Medium (EMEM) containing 10% (v/v) foetal calf serum, 1% L-glutamine, 1% non-essential amino acids and 2% Penicillin/Streptomycin
- Properly maintained: yes
- Periodically checked for karyotype stability: yes
Metabolic activation:
with and without
Metabolic activation system:
cofactor supplemented post-mitochondrial fraction (S9-mix) (CCR, Rossdorf, Germany), prepared from livers of male Wistar rats induced with Arochlor 1254 (500 mg/kg bw, single i.p. injection)
Test concentrations with justification for top dose:
Preliminary toxicity test: 0.5, 1, 2.5, 5, 10, 25, 50, 100, 250, 500, 1000, 2500 and 5000 µg/mL
7 h and 28 h culture period: 2, 4, 8 and 16 µg/mL (-S9); 20, 40, 80 and 160 µg/mL (+S9)
20 h culture period: 0.5, 1, 2, 4, 8 and 16 µg/mL (-S9); 5, 10, 20, 40, 80 and 160 µg/mL (+S9)

Vehicle / solvent:
- Vehicle(s)/solvent(s) used: medium and DMSO
Untreated negative controls:
no
Remarks:
medium
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 20 h experiment: ethylmethanesulfonate (EMS), 1.5 mg/mL in nutrient medium, -S9; cyclophosphamide (CP), 1 µg/mL in bidestilled water/nutrient medium
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Preincubation period (main expriment): approx. 1 day
- Exposure duration: 4 h
- Fixation time (start of exposure up to fixation or harvest of cells): 7, 20, 28 h

SPINDLE INHIBITOR (cytogenetic assays): colcemide 0.4 µg/mL medium (2-2.5 h before harvesting)
STAIN (for cytogenetic assays): Giemsa solution

NUMBER OF REPLICATIONS: duplicate cultures

NUMBER OF CELLS EVALUATED: 100 per culture

DETERMINATION OF CYTOTOXICITY
- Method: relative plating efficiency (preliminary toxicity test); mitotic index of 500 cells (main experiment)

OTHER EXAMINATIONS:
- Determination of polyploidy: yes
Evaluation criteria:
The test substance was classified as mutagenic if a significant, concentration-related increase in the proportion of structural aberrations was induced or a significant positive response for at least one test concentration was found.
The test substance was classified as non-mutagenic in this test system, if neither a significant concentration-related increase in the proportion of structural chromosomal aberrations nor a significant positive response at any of the analysed test substance concentrations was detected.
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Preliminary cytotoxicity test: ≥ 5 µg/mL (-S9) and ≥ 100 µg/mL (+S9); main experiment: at 160 µg/mL (+S9, all 3 fixation times)
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
RANGE-FINDING/SCREENING STUDIES:
In the experiment on plating efficiency, strong toxic effects were noticed at ≥ 5 µg/mL without metabolic activation and ≥ 100 µg/mL with S9 mix.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
In the cytogenetic experiment, the test substance was applied up to 16 µg/mL without and 160 µg/mL with metabolic activation. In the experiment without S9 mix, no substantial reduction of the Mitotic Index (MI) was observed at the highest concentration. With metabolic activation, there was no cellular growth to be detected at 160 µg/mL at all three fixation times, and nearly no mitoses to be detected at 80 µg/mL 7 h after treatment. No substantial reduction of the MI was determined at 80 µg/mL after incubation periods of 20 and 28 h. Treatment concentrations for chromosome analysis were selected by evaluating the effect of the test substance on the mitotic index. The highest concentrations for chromosome analysis from the 7, 20 and 28 h harvesting time points were those that resulted in 50-80% reduction of mitotic index or the highest test concentration if no cytotoxicity was observed.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Table 1. Test results of experiment without S9 mix

Test item

 

Concentration

Mitotic Index

Aberrant cells in %

in µg/mL

in %

with gaps

without gaps

Exposure period 4 h, fixation time 7 h

Medium

0

100

2.5

1.5

Test substance

16

93

2.5

2

Exposure period 4 h, fixation time 20 h

Medium

0

100

1

0.5

PC (EMS)

1.5

52

28.5

22

Test substance

2

n.d.

2

2

8

80

2.5

2

16

85

5

2

Exposure period 4 h, fixation time 28 h

Medium

0

100

2.5

1

 

16

98

1.5

1.5

PC (positive control): EMS (ethylmethanesulfonate)

Table 2. Test results of experiment with S9 mix

Test item

 

Concentration

Mitotic Index

Aberrant cells in %

in µg/mL

in %

with gaps

without gaps

Exposure period 4 h, fixation time 7 h

Medium

0

100

5

3

Test substance

40

113

3.5

2.5

Exposure period 4 h, fixation time 20 h

Medium

0

100

3.5

2.5

PC (CP)

1

25

34.5

33.5

Test substance

10

n.d.

1.5

0

40

n.d.

3.5

1.5

80

86

5

2

Exposure period 4 h, fixation time 28 h

Medium

0

100

4

2.5

 

80

93

3

3

PC (positive control): CP (cyclophosphamid)

Conclusions:
Interpretation of results (migrated information):
negative
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A reverse gene mutation assay in bacteria according to OECD guideline 471 shows negative results in the presence and absence of metabolic activation up to the maximum concentration of 5000 µg/plate.

 

The potential to induce mutagenicity in mammalian cells was investigated in an in-vitro mouse lymphoma assay according to OECD guideline 490. D-Glucose, reaction products with alcohols C16-18 tested up to cytotoxic concentrations, neither induced mutations nor had any chromosomal aberration potential.

 

Read across will be applied forchromosomal aberration.

There is a reliable chromosomal aberration test available for D-Glucopyranose, oligomeric, C10-16-alkyl glycosides, which does not show clastogenic activity in vitro. The read-across for genetic toxicity (chromosome aberration) is justified based on structural similarity, on common metabolic fate resulting in the formation of the physiologically occurring substances sugars and fatty acids. This is further supported by the fact that the target substance did not show any chromosomal aberration potential in the in-vitro mouse lymphoma assay according to OECD guideline 490.

Representative chemicals from the long chain alcohols category have been extensively tested to define their toxicological hazard properties. These chemicals do not show evidence of activity in genetic toxicity tests.

 

Since all available data on the in vitro and in vivo genetic toxicity of the members of the Alkyl Polyglycosides category were negative, it is concluded that none of the category members shows any genotoxic potential. This is further supported by their common metabolic fate, resulting in the formation of the physiologically occurring substances sugars and fatty acids, which are of no toxicological concern with regard to mutagenicity.

The data summarised above further support the general absence of a genotoxic potential of the source and target substance and support the reliability in the read-across for the chromosome aberration study.

Justification for classification or non-classification

Based on the available relevant and reliable data, D-Glucose, reaction products with alcohols C16-18 (even numbered) does not need to be classified and labelled according to the CLP Regulation (EC) No 1272/2008 with respect to genetic toxicity.