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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication which meets basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
The genotoxic activity of glycerol in an in vitro test battery
Author:
Doolittle, D.J. et al.
Year:
1988
Bibliographic source:
Food Chem Toxicol. 1988 Jul;26(7):631-5

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
yes
Remarks:
limited documentation; the highest concentration was 1000 µg/mL without evidence of precipitate and/or cytotoxicity.
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Glycerol
EC Number:
200-289-5
EC Name:
Glycerol
Cas Number:
56-81-5
Molecular formula:
C3H8O3
IUPAC Name:
glycerol
Details on test material:
- Name of test material (as cited in study report): glycerol
- Analytical purity: > 99.5%

Method

Target gene:
HPRT locus
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 µg/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: -S9: ethyl methanesulphonate; +S9: dimethylbenzanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 5h
- Expression time (cells in growth medium): not reported
- Selection time: not reported
- Fixation time (start of exposure up to fixation or harvest of cells): not reported

SELECTION AGENT: not reported
STAIN: not reported

NUMBER OF REPLICATIONS: 1

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency
Evaluation criteria:
A test result was considered positive if the test material induced at least a three-fold increase in mutation frequency above the solvent control in a dose-dependent manner.

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
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
The increase in mutation frequency observed at 800 and 1000 µg/mL in the absence of metabolic activation were not considered biologically significant and did not fulfil the criteria set for a positive response due to the lack of a dose-response relationship.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1. Results of the HGPRT assay

Cloning efficiency (%)

No. of mutants

Mutation Frequency (x10(-6))

Without metabolic activation

Negative control

75

4

5

Solvent control

84

2

2

Glycerol (µg/mL)

100

87

0

0

200

85

1

1

400

85

1

1

600

79

4

5

800

83

20

24*

1000

83

5

6*

Ethyl methanesulphonate (100 µg/mL)

79

122

153*

With metabolic activation

Negative control

96

2

2

Solvent control

76

6

7

Glycerol (µg/mL)

100

65

6

7

200

66

0

0

400

77

2

3

600

63

3

4

800

72

7

9

1000

80

12

15

Dimethylbenzanthracene (5 µg/mL)

77

178

200*

 

* At least three-fold increase compared with the solvent control

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative