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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
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.
Year:
1988
Bibliographic source:
Fd Chem Toxic 26(7): 631-635

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
The highest concentration was 1000 ug/plate without evidence of cytotoxicity or precipitate.
GLP compliance:
not specified
Type of assay:
bacterial reverse 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:
propane-1,2,3-triol
Details on test material:
purity >99.5%

Method

Target gene:
gene for histidine production
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537, TA 1538
Metabolic activation:
with and without
Metabolic activation system:
Metabolic activation system: rat S-9
Test concentrations with justification for top dose:
200, 400, 600, 800 and 1000 ug/plate
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: without S-9: 2-nitrofluorene (TA98, TA1538), sodium azide (TA100, TA1535) and 9-aminoanthracene (TA1537) with S-9: 2-aminoanthracene
Details on test system and experimental conditions:
SYSTEM OF TESTING
- Species/cell type: Salmonella typhimurium TA98, TA100, TA1535, TA 1537 and TA1538
- Deficiences: histidine
- Metabolic activation system: rat S-9

ADMINISTRATION:
- Dosing: 200, 400, 600, 800 and 1000 ug/plate
- Number of replicates: 3
- Application: preincubation assay
- Positive and negative control groups and treatment:
without S-9: 2-nitrofluorene (TA98, TA1538), sodium azide (TA100, TA1535) and 9-aminoanthracene (TA1537) with S-9: 2-aminoanthracene
- Pre-incubation time: not indicated

DESCRIPTION OF FOLLOW UP REPEAT STUDY: indepent repeat with TA100 (not reported)


Evaluation criteria:
CRITERIA FOR EVALUATING RESULTS:
reproducible, dose-related increase in the number of revertants
Statistics:
No data.

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
Not cytotoxic at 1000 µg/plate, highest concentration tested
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
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
Remarks:
Not cytotoxic at 1000 µg/plate, highest concentration tested
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
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
Remarks:
Not cytotoxic at 1000 µg/plate, highest concentration tested
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
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
Remarks:
Not cytotoxic at 1000 µg/plate, highest concentration tested
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
Not cytotoxic at 1000 µg/plate, highest concentration tested
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
- With metabolic activation: negative - Without metabolic activation: negative

In TA100 the number of revertants was increased compared to solvent controls, without relationship with the applied concentration. Therefore the test was repeated with TA100 at slightly higher glycerol concentrations with a negative result (no data available)

PRECIPITATION CONCENTRATION: not indicated

CYTOTOXIC CONCENTRATION: no cytotoxicity up to 1000 ug/plate
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1 Salmonella typhimurium mutagenicity assay

               No. of revertants per plate in strain:
Treatment and conc. (ug/plate  TA98   TA100  TA1535  TA1537  TA1538
               Non-activation assay
Solvent control   21.3 + 6.7  103.0 + 5.2  13.0 + 5.3 11.3 + 3.1   15.7 + 8.6
Glycerol           
200   23.3 + 1.5  137.0 + 7.0  13.3 + 2.5  13.0 + 1.7  12.7 + 2.1
 400  23.0 + 2.6  142.7 + 32.7  16.3 + 2.1  9.3 + 1.5  14.3 + 1.5
 600  25.7 + 5.5  149.3 + 17.2  17.7 + 2.1  10.7 + 1.5  11.0 + 1.7
 800 29.7 + 9.5 149.3 + 6.4  19.3 + 7.2    12.7 + 2.1  13.7 + 1.5 
 1000  23.0 + 5.3  149.0 + 6.1  12.7 + 1.5 17.0 + 2.6  9.3 + 5.1 
 Positive control  1190.3 + 154.9  1409.7 + 144.9 1109.0 + 49.4  2721.0 + 145.0   1278.0 + 102.6
               Activation assay
 Solvent control  30.3 + 12.3  141.0 + 5.3  10.0 + 2.6  10.3 + 2.1  25.3 + 3.2
 Glycerol          
 200 32.0 + 3.5   140.0 + 21.0 13.3 + 2.5   12.3 + 2.1 24.0 + 4.6 
 400 29.0 + 6.2   163.7 + 7.2 12.7 + 4.0  10.0 + 2.6  20.7 + 5.7 
 600 38.0 + 3.0  157.0 + 11.5  13.3 + 2.1  13.7 + 2.5  22.7 + 5.5 
 800 33.7 + 5.5    147.3 + 5.1 12.3 + 5.5  14.3 + 2.5  19.3 + 5.1 
 1000  31.7 + 6.1 155.7 + 1.5  13.0 + 3.5  15.0 + 1.7  17.3 + 5.1 
 Positive control  818.3 + 72.8 638.3 + 81.7   85.3 + 5.1 32.3 + 3.1  563.7 + 31.3 

Values are means + SD for triplicate plates.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

The test material did not induce point mutations in five strains of S. typhimurium with or without metabolic activation.
Executive summary:

The test material was evaluated in the Ames test. The test material did not induce point mutations in five strains of S. typhimurium with or without metabolic activation.