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Toxicological information

Genetic toxicity: in vitro

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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:
1980-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study report is classified as reliable with restrictions because while there is no statement regarding whether these studies were conducted according to GLPs or equivalent, the study appears to have been conducted in general accordance with OECD 471 guidelines.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1980-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study report is classified as reliable with restrictions because while there is no statement regarding whether these studies were conducted according to GLPs or equivalent, the study appears to have been conducted in general accordance with OECD 471 guidelines.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
Not applicable
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 1538
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
E. coli WP2
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
E. coli WP2 uvr A
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 fraction obtained from liver homogenate from Arochlor induced rats
Test concentrations with justification for top dose:
0, 0.2, 2.0, 20, 200, and 2000 micrograms/plate
Vehicle / solvent:
Vehicle(s)/solvent(s) used: Acetone
Justification for choice of solvent/vehicle: Not reported
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
Migrated to IUCLID6: 4-nitroquinoline-N-oxide and sodium azide also used.
Details on test system and experimental conditions:
METHOD OF APPLICATION: In medium; in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours at 37 degrees Celsius
- Expression time (cells in growth medium): Not reported
- Selection time (if incubation with a selection agent): Not applicable
- Fixation time (start of exposure up to fixation or harvest of cells): Not applicable

SELECTION AGENT (mutation assays): Not reported

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: Not reported

DETERMINATION OF CYTOTOXICITY
- Method: Not reported

OTHER EXAMINATIONS: Not applicable
Evaluation criteria:
Cultures were assessed for number of revertant colonies.
Statistics:
Not reported
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:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: Not applicable
- Effects of osmolality: Not applicable
- Evaporation from medium: Not applicable
- Water solubility:Not applicable
- Precipitation: Not applicable
- Other confounding effects: Not applicable

RANGE-FINDING/SCREENING STUDIES: Not reported
COMPARISON WITH HISTORICAL CONTROL DATA: Not reported
ADDITIONAL INFORMATION ON CYTOTOXICITY: Not reported
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

No tables are included because all results were negative.

Conclusions:

negative with metabolic activation
negative without metabolic activation

In an in vitro bacterial mutation assay, alpha C18 product was not mutagenic to five strains of Salmonella typhimurium or two strains of Escherichia coli in the presence or absence of metabolic activation.
Executive summary:

In a reverse gene mutation assay in bacteria, five strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537, and TA1538) and 2 strains of Escherichia coli (WP2 and WP2uvrA) were exposed to alpha C18 product in acetone at concentrations of 0, 0.2, 2, 20, 200, or 2000 µg/plate in the presence and absence of mammalian metabolic activation using the plate-incorporation method. No increase in reverse mutation rate was noted in either assay in the presence or absence of metabolic activation. A preliminary study to assess bacterial cytotoxicity to determine appropriate doses was not performed.

This study received a Klimisch score of 2 and is classified as reliable with restrictions because no GLP statement was included and although the study adhered to most of the principles outlined in OECD 471, a few study deficiencies were noted.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
Study performed before guideline introduced
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Alpha C18 Product
- Substance type: C18 alpha olefin
- Physical state: Liquid
- Analytical purity: Not reported
- Lot/batch No.: G.E.P. 78.4044
- Expiration date of the lot/batch: Not reported
- Stability under test conditions: Reported to be at least 4 hours
- Storage condition of test material: Not reported
- Other: Prepared in acetone

Method

Target gene:
Not applicable
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 1538
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
E. coli WP2
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
E. coli WP2 uvr A
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 fraction obtained from liver homogenate from Arochlor induced rats
Test concentrations with justification for top dose:
0, 0.2, 2.0, 20, 200, and 2000 micrograms/plate
Vehicle / solvent:
Vehicle(s)/solvent(s) used: Acetone
Justification for choice of solvent/vehicle: Not reported
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
Migrated to IUCLID6: 4-nitroquinoline-N-oxide and sodium azide also used.
Details on test system and experimental conditions:
METHOD OF APPLICATION: In medium; in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours at 37 degrees Celsius
- Expression time (cells in growth medium): Not reported
- Selection time (if incubation with a selection agent): Not applicable
- Fixation time (start of exposure up to fixation or harvest of cells): Not applicable

SELECTION AGENT (mutation assays): Not reported

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: Not reported

DETERMINATION OF CYTOTOXICITY
- Method: Not reported

OTHER EXAMINATIONS: Not applicable
Evaluation criteria:
Cultures were assessed for number of revertant colonies.
Statistics:
Not reported

Results and discussion

Test resultsopen allclose all
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:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: Not applicable
- Effects of osmolality: Not applicable
- Evaporation from medium: Not applicable
- Water solubility:Not applicable
- Precipitation: Not applicable
- Other confounding effects: Not applicable

RANGE-FINDING/SCREENING STUDIES: Not reported
COMPARISON WITH HISTORICAL CONTROL DATA: Not reported
ADDITIONAL INFORMATION ON CYTOTOXICITY: Not reported
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

No tables are included because all results were negative.

Applicant's summary and conclusion

Conclusions:

negative with metabolic activation
negative without metabolic activation

In an in vitro bacterial mutation assay, alpha C18 product was not mutagenic to five strains of Salmonella typhimurium or two strains of Escherichia coli in the presence or absence of metabolic activation.
Executive summary:

In a reverse gene mutation assay in bacteria, five strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537, and TA1538) and 2 strains of Escherichia coli (WP2 and WP2uvrA) were exposed to alpha C18 product in acetone at concentrations of 0, 0.2, 2, 20, 200, or 2000 µg/plate in the presence and absence of mammalian metabolic activation using the plate-incorporation method. No increase in reverse mutation rate was noted in either assay in the presence or absence of metabolic activation. A preliminary study to assess bacterial cytotoxicity to determine appropriate doses was not performed.

This study received a Klimisch score of 2 and is classified as reliable with restrictions because no GLP statement was included and although the study adhered to most of the principles outlined in OECD 471, a few study deficiencies were noted.