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Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
6th December 2018 to 31 December 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Please refer to the Read Across Justification document enclosed in Chapter 13 for further details.
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
LME 11311
Batch Ua05 (258)
Purity 99%
Yellow Orange Solid
Target gene:
histidine synthesis
Species / strain / cell type:
S. typhimurium TA 98
Species / strain / cell type:
S. typhimurium TA 100
Metabolic activation:
with and without
Metabolic activation system:
Rat liver S9 liver homogenage purchased from MolTox Boone, NC
Test concentrations with justification for top dose:
1000, 300, 100, 30, 10, 3, 1 and 1.3 ug/well
Vehicle / solvent:
DMSO
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
sodium azide
other: 2-aminoanthracene
Details on test system and experimental conditions:
The test article was prepared in dimethyl sulfoxide (DMSO) and tested via the plate incorporation method at eight dose levels.
The tester strains will include the S. typhimurium histidine auxotrophs TA98 and TA I 00 as described by Ames er al. (l975). The S. typhimurium tester strains were from Dr. Bruce Ames, University of California, Berkeley.

Each tester strain culture will be inoculated from the appropriate frozen stock,
lyophilized pellet(s), or master plate. To ensure that cultures are harvested in late log
phase. the length of incubation will be controlled and monitored. Each inoculated
flask will be placed in a shaker/incubator programmed to begin shaking at 125 to
175 rpm and incubating at 37±2°C.
All cultures will be harvested by spectrophotometric monitoring of culture turbidity
rather than by duration of incubation since overgrowth of cultures can cause loss of
sensitivity to some mutagens. Cultures will be removed from incubation at a density
of approx imatcly l 09 cclls/m L.
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
True negative controls validity:
valid
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
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
True negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
Under the condictions of the study, the results of the Bacterial Mutagenicity Screening Assay were concluded to be negative.
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
27th November 2018 to 12th December 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Please refer to the read across justification document enclosed in Chapter 13 for further details.
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
LME 11194
Batch Xbm06
Purity 99%
Whitish yellow orange solid
Target gene:
histidine synthesis
Species / strain / cell type:
S. typhimurium TA 98
Species / strain / cell type:
S. typhimurium TA 100
Metabolic activation:
with and without
Metabolic activation system:
Rat liver S9 liver homogenage purchased from MolTox Boone, NC
Test concentrations with justification for top dose:
1000, 300, 100, 30, 10, 3, 1 and 0.3 ug/well
Vehicle / solvent:
DMSO
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
sodium azide
other: 2-aminoanthracene
Details on test system and experimental conditions:
The test article was prepared in dimethyl sulfoxide (DMSO) and tested via the plate incorporation method at eight dose levels.
The tester strains will include the S. typhimurium histidine auxotrophs TA98 and TA I 00 as described by Ames er al. (l975). The S. typhimurium tester strains were from Dr. Bruce Ames, University of California, Berkeley.

Each tester strain culture will be inoculated from the appropriate frozen stock,
lyophilized pellet(s), or master plate. To ensure that cultures are harvested in late log
phase. the length of incubation will be controlled and monitored. Each inoculated
flask will be placed in a shaker/incubator programmed to begin shaking at 125 to
175 rpm and incubating at 37±2°C.
All cultures will be harvested by spectrophotometric monitoring of culture turbidity
rather than by duration of incubation since overgrowth of cultures can cause loss of
sensitivity to some mutagens. Cultures will be removed from incubation at a density
of approx imatcly l 09 cclls/m L.
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
True negative controls validity:
valid
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
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
True negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
Under the condictions of the study, the results of the Bacterial Mutagenicity Screening Assay were concluded to be negative.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for classification or non-classification

Based on testing conducted on similar substances, no classification or labelling is neccessary. Further information on the Read Across is available in the Read Across justification document enclosed in Chapter 13.