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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:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1985/07/05-1985/07/15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles: GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
Not applicable
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 1538
Metabolic activation:
with and without
Metabolic activation system:
S9 liver fractions from Aroclor exposed rats
Test concentrations with justification for top dose:
Tests (done in triplicate) with and without Metabolic Activation: Acetone (vehicle control), 0, 50, 150, 500, 1500, 5000 ug/plate
Vehicle control: 0.1 ml/plate acetone
Positive controls: 0.5ug/plate 2AA, 5ug/plate MNNG, 80ug/plate 9AA, 2ug/plate 2NF
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
0.1 ml/plate Acetone
True negative controls:
yes
Remarks:
non treated
Positive controls:
yes
Positive control substance:
other: TA 1537 (+S9 2-aminoanthracene) TA 1537 (-S9 9-aminoacridine); TA 98 (-S9 2-nitrofluorene) (+S9 2-aminoanthracene); TA100 (-S9 MNNG) (+S9 2-aminoanthracene); TA1535 (-S9 MNNG) (+S9 2-aminoanthracene); TA138(-S9 2-Nitrofluorene) (+S9 2-aminoanthracene)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar
DURATION
- Exposure duration: 72 hours


NUMBER OF REPLICATIONS:
- triplicate

DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of revertants and/or clearing of the background lawn of bacterial growth
Evaluation criteria:
The mutagenicity study is considered valid if the mean colony counts of the control values of the strains are within acceptable ranges, if the positive controls meet the criteria for a positive response and if no more than 5% of the plates are lost through contamination or other unforeseen events.

A test substance is considered to be positive in the bacterial gene mutation test if the mean number of revertant colonies on the test plates increase in a concentration-related manner and/or if it is a reproducible two-fold or more increase is observed compared to that on the negative control plates.

A test substance is considered negative in the bacterial gene mutation test if it produces neither a dose-related increase in the mean number of revertant colonies nor a reproducible positive response at any of the test points.

Positive results from the bacterial reverse mutation test indicate that a substance induces point mutations by base substitution for frameshifts in the genome of Salmonella typhimurium. Negative results indicate that under the test conditions, the test substance is not mutagenic.
Statistics:
The mean plate count and standard deviation for each dose point were determined. Any test value that was equal to or greater than two times the mean value of the concurrent vehicle control was considered to be a positive dose.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Remarks:
not cytotoxic up to 5,000ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Based on these data, classification under EU requirements for dangerous substances and preparations and under EU GHS guidelines is not required.
Executive summary:

Petrepar 120 was examined for mutagenic activity in the bacterial reverse mutation test using histidine-requiring Salmonella typhimurium strains TA 1535, 1537, 1538, 98, and 100 in the absence and presence of a liver S9 fraction for metabolic activation. The test was performed in triplicate using doses of 0, 50, 150, 500, 1500, 5000 ug/plate.  In all cases, Petrepar 120 did not induce any significant changes in the number of revertant colonies.  It is concluded in this study that Petrepar 120 is not a mutagenic agent and classification under EU requirements for dangerous substances and preparations guidelines is not required, nor is it required under EU GHS guidelines.