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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames assay:

Ames assay was performed to determine the mutagenic nature of the test chemical. The study was performed using Salmonella typhimurium TA1537, TA1535, TA158, TA98 and TA100 both with and without rat liver S-9 microsomal activation system. In the study reported here, the test chemical was tested in the Ames bioassay at levels upto 13.9 mg/L (0.450 mg/plate) without S-9 activation 82.3 mg/L (2.7mg/plate) with S-9 activation. The maximum concentrations used in these studies resulted in reduced viability of the test organisms, indicating that the test chemical was being tested at biologically significant concentrations. The difference in maximum test concentrations as a function of the presence of S-9 indicates that the metabolite(s) of the test chemical formed by microsomal enzymes in the s-9 have less biological impact on the test organism than the test chemical itself. In the Ames bioassay , no test chemical- related increases in revertants were noted in any test strain either with or without S-9 liver enzymes. HQ was negative when tested in the standard Ames test in five strains of Salmonella typhimurium , both with and without rat liver S-9 microsomal activation.

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
1997
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2 uvr A pKM 101
Metabolic activation:
with and without
Metabolic activation system:
The concentration of S9 used in both phase A preliminary ceitotoxicity and phase B Micro Ames test , was 10%
Test concentrations with justification for top dose:
50 mcl/mL - highets allowed concentration. The solution resulted soluble.
Vehicle / solvent:
ddH2O
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
yes
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
9-aminoacridine
2-nitrofluorene
sodium azide
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 1535
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 1537
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
Key result
Species / strain:
E. coli WP2 uvr A pKM 101
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:
Positive results from the bacterial reverse mutation test indicate that a sbustance induces point mutations by base substitutions or frameshifts in the genome of either Salmonella typhimurium and / or Escherichia coli.
Negative results indictae that under the test conditions, the test substance is not mutagenic in the tested species.
On the basis of the results obtained, it can concluded that under the test conditions applied, thet test item is considered no to be mutagenic.

Additional information

Justification for classification or non-classification

On the basis of the results obtained, it can concluded that under the test conditions applied, thet test item is considered no to be mutagenic.