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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
There are no data for polyglycerine. Data are available for glycerol, the major component of target substance. Glycerol was negative in Ames tests, HGPRT assay and SCE assay in CHO cells, and an Unscheduled DNA Synthesis assay using rat hepatocytes. Given the lack of mutagenic responses in all the in vitro studies with the major component glycerol, conduct of an in vivo mutagenicity study is not required. In addition, data from rodent cancer bioassays with glycerol and polyglycerol (as part of polyglycerol polyricinoleate) indicated no evidence of carcinogenic potential.
Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
Not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to guideline and/or standard method but was non-GLP.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
yes
Remarks:
No cytotoxicity was observed at 1000 ug/ml, the highest concentration tested.
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay
Target gene:
HGPRT gene
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
rat S-9
Test concentrations with justification for top dose:
100, 200, 400, 600, 800 and 1000 ug/mL
Vehicle / solvent:
water
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
without S-9 ethyl methanesulphonate; with S-9 dimethylbenzanthracene
Details on test system and experimental conditions:
SYSTEM OF TESTING
- Cell type: CHO-K1-BH4
- Proficiences: HGPRT gene
- Metabolic activation system: rat S-9

ADMINISTRATION:
- Dosing: 100, 200, 400, 600, 800 and 1000 ug/mL
- Number of replicates: not indicated
- Negative control: water (solvent)
- Positive control groups: without S-9 ethyl methanesulphonate; with S-9 dimethylbenzanthracene
- Treatment: 5 hours
Evaluation criteria:
CRITERIA FOR EVALUATING RESULTS:
At least a three-fold increase in mutation frequency above controls in a dose dependent manner.
Statistics:
No additional information available.
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
no evidence of cytotoxicity at 1000 ug/ml, the highest concentration tested
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
- With metabolic activation: negative
- Without metabolic activation: negative

At 800 and 1000 ug/mL the mutation frequency was increased >= 3 fold (24E-06 and 6E-06, respectively) compared to controls (2E-06).

PRECIPITATION CONCENTRATION: not indiated

CYTOTOXIC CONCENTRATION: Not observed
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

The increased mutation frequency seen at the two highest concentrations (800 and 1000 ug/mL) in absence of a concentration response relationship are not considered biologically significant and do not fulfil the criteria for a positive response due to the absence of a dose-response relationship.

Table 1

 Treatment and Concentration (ug/ml) Cloning efficiency (%)  No. of mutants  Mutation Frequency (x10(-6))
  Activation assay     
Negative control   96  2  2
 Solvent control (H2O)  76  6  7
 Positive control  77  178  200*
 Glycerol      
100   65  6  7
 200  66  0  0
 400  77  2  3
 600  63  3  4
 800  72  7  9
 1000  80  12  15
   Non-activation assay    
 Negative control  75  4  5
 Solvent control (H2O)  84  2  2
 Positive control  79  122  153*
 Glycerol      
 100  87  0  0
 200  85  1  1
 400  85  1  1
 600  79  4  5
 800  83  20  24*
 1000  83  5  6*

* Values are at least three times that for the solvent control.

Conclusions:
Interpretation of results (migrated information):
negative

The test material did not meet the criteria set for a positive response set by the author of the report and was considered to be negative by the author.
Executive summary:

The test material was evaluated in the Chinese hamster ovary assay with and without metabolic activation. The test material did not meet the criteria set for a positive response set by the author of the report and was considered to be negative by the author.

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

Additional information

Additional information from genetic toxicity in vitro:

There are no data for polyglycerine. Data are available for glycerol, the major component of target substance. Glycerol was negative in two separate Ames tests, a Chinese hamster ovary HGPRT assay, a Chinese hamster ovary SCE assay and an Unscheduled DNA Synthesis assay using rat hepatocytes. Given the lack of a mutagenic response in all the in vitro studies with glycerol, and the lack of a carcinogenic response in a chronic tox/carcinogenicity study with glycerol and with polyglycerol (as part of polyglycerol polyricinoleate) (the relevant read-across analogues), conduct of an in vivo mutagenicity study is not required since according to Column 2 of Annex VIII and IX, further genotoxicity testing in vivo is only required if there are positive findings in the in vitro studies. For more read-across justification and support, please refer to the attached justification document.


Justification for selection of genetic toxicity endpoint
Data from glycerol, the major component of polyglycerine target substance.

Justification for classification or non-classification

Classification for genetic toxicity according to GHS and the Directive 67/584/EEC (DSD) is not warranted. Data on the major component, glycerol, indicated no genotoxic responses. In addition, data from rodent cancer bioassays with glycerol and polyglycerol (as part of polyglycerol polyricinoleate) indicated no evidence of carcinogenic potential.