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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Based on the studies available on polyglyerol-2 -caprate and for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, a lack of mutagenic/ genotoxic potential for Polyglycerol-2 -caprate is concluded.

Link to relevant study records

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Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04.08.08-11.08.08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and batch No.of test material: Dr. Straetmans Chemische Produkte GmbH, batch: 512051
- Expiration date of the lot/batch: N/A
- Purity test date: June 16, 2008
- Physical state: liquid

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Not provided

FORM AS APPLIED IN THE TEST (if different from that of starting material)
liquid

Target gene:
Target mutation in 5 Salmonella Typhimurium strains:

TA98 His D 3052
TA100 His G 46
TA102 His G 428
TA 1535 His G 46
TA 1537 His C 3076
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 rat liver microsome fraction
Test concentrations with justification for top dose:
0.05 ul (1%), 0.167 ul (3%), 0.5 ul (10%), 1.67 (30%) and 5 ul (100%)
Vehicle / solvent:
Water
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
mitomycin C
Details on test system and experimental conditions:
METHOD OF APPLICATION:
Direct incorporation method

DURATION
- Exposure duration/incubation period: 72 hours

NUMBER OF REPLICATIONS: 3

CONFIRMATION TEST:
An independent confirmation test was performed with the test item according too the pre-incubation procedure. After the bacterial suspension, the test item and PBS (-S9) or metabolic activation system (+S9) were mixed and the mixture was incubated at about 37 C for 20 minutes. Thereafter the study was the same as for main study

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth;
Evaluation criteria:
R ratio was calculated:
R= Number of revertant colonies in the presence of test item / Number of revertant colonies in the absense of test item

Several criteria were used for determinung a positive result:
A dose-response in the range tested andor a reproducible increase (R≥2.5) at one or more concentrations in the number of colonies per plate in at lease one strain with or without metabolic activation
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle 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
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
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
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
Positive controls validity:
valid
Additional information on results:
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: yes
- Negative (solvent/vehicle) historical control data: yes

The controls of the test were in concordance with the expected results:

- sterility test showed no contamination during the study

- No cytotoxicity effect was observed

- All positive controls performed showed valid ratios (R) above 2.5

- Positive and negative controls showed absolute numbers of revertant colonies comparable to historical data

- No concentration of the test item showed a biological significant increase (R≥2.5) of the number of revertant colonies either with or without S9 metabolic activation

- No dose response was observed in any of the tested bacterial strains

Conclusions:
The following conclusions can be inferred from the obtained results:
- No experiment with the test item showed ratios (R) above 2.5 as compared to the negative control with or without S9
- No dose response was observed in any of the tested bacterial strains.

Based on these results the test substance, Dermosoft DGMC, was found to be non-mutagenic and non-promutagenic under the test conditions.
Executive summary:

The present bacterial reverse mutation test (Ames test) was performed in order to evaluate the mutagenic potential of the test iten, Dermosoft DGMC. The test was performed in accordance with OECD Guideline 471 and the ts Mthod B13/B14 of Commission Directive 2000/32/EC.

Doses ranging from 5 ul to 0.05 ul per plate were tested.

No cytotoxicity was observed at any dose.

Suspensions of amino-acid requiring strains of Salmonella typhimurium (TA98, TA100, TA102, TA1535 and TA1537) were exposed by direct plate incorporation method to five doses of the test item in the prsense and in absense of metabolic activation system S9. Both tests were repeated with the pre-incubation method.

The following conclusions can be inferred from the obtained results:

- No experiment with the test item showed ratios (R) above 2.5 as compared to the negative control with or without S9

- No dose response was observed in any of the tested bacterial strains.

Based on these results the test substance, Dermosoft DGMC, was found to be non-mutagenic and non-promutagenic under the test conditions.

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
other: weight of evidence analysis based on expert evaluated data on hydrolysis products and structural analogues
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: based on expert group reviews
Justification for type of information:
Data on this endpoint are not available for Polyglycerol-2-caprate. The possible cytogenicity of this substance is therefore assessed in the present weight of evidence analysis based on existing data on the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance.
Principles of method if other than guideline:
The conclusion is based on a collection of data performed according to OECD guidelines 473 and 476
Type of assay:
other: Collection of data on relevant assays. Please see the attached weight of evidence document
Key result
Species / strain:
other: Different mammalian cell lines
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Additional information on results:
EFSA (2017) found no structural alerts for genotoxicity of polyglycerol esters of fatty acids based on their own QSAR analysis for this end-point. Thus, the EFSA panel considered that the available information on polyglycerol esters of fatty acids and genotoxicity did not indicate a genotoxic potential of the substances
Conclusions:
Based on the studies available for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, a lack of mutagenic/ genotoxic potential is concluded for Polyglycerol-2 -caprate.
Executive summary:

Two OECD guideline studies performed on Polyglyceryl-2 Oleate, one mammalian cell gene mutation and one chromosome aberration assay, found no genotoxic effects of the compound. QSAR predictions performed using the Danish QSAR database indicted non-genotoxicity in all model predictions for: bacterial reverse mutation test,Ames test in S. typhimurium (in vitro); chromosome aberrations in Chinese hamster lung and ovary cells; and for in vivo genotoxicity test batteries for Micronucleus test in mouse erythrocytes and in the Sister chromatid exchange in mouse bone marrow.

Furthermore, studies performed on the hydrolysis product, decanoic acid, was shown to be negative in both cytogenetic test (OECD 473) with Chinese hamster Ovary K-1 cells and in gene mutation in mammalian cells (OECD 476) in mouse lymphoma L5178Y cells.

QSAR results on genotoxicity for the two constituents, diglycerol and triglycerol, also show a negative prediction.

Based on the studies available for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, a lack of mutagenic/ genotoxic potential is concluded for Polyglycerol-2 -caprate

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

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification