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Toxicological information

Genetic toxicity: in vitro

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Administrative data

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.

Data source

Reference
Reference Type:
publication
Title:
The genotoxic activity of glycerol in an in vitro test battery
Author:
Doolittle, D., Lee, D.A. and Lee, C.K.
Year:
1988
Bibliographic source:
Fd Chem Toxic 26(7): 631-635

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
purity >99.5%

Method

Target gene:
HGPRT gene
Species / strain
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
Controls
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.

Results and discussion

Test results
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'.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.