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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3rd October 2017 - 16th October 2017
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
no
Remarks:
Not performed according to GLP as done for in-house worker safety purposes and not for Reach.
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
5-[4-Methoxy-2-(propan-2-yl)phenoxy]pyrimidine-2,4-diamine
Cas Number:
865304-71-8
Molecular formula:
C14H18N4O2
IUPAC Name:
5-[4-Methoxy-2-(propan-2-yl)phenoxy]pyrimidine-2,4-diamine
Test material form:
solid: crystalline
Details on test material:

Off-white

Method

Species / strainopen allclose all
Species / strain / cell type:
E. coli WP2 uvr A pKM 101
Species / strain / cell type:
S. typhimurium TA 100
Species / strain / cell type:
S. typhimurium TA 98
Species / strain / cell type:
S. typhimurium TA 97
Species / strain / cell type:
S. typhimurium TA 1535
Metabolic activation:
with and without
Metabolic activation system:
Liver extract (S-9) from rats pre-treated with Xenobiotics
Test concentrations with justification for top dose:
5000, 3000, 1,000, 300, 100 and 30 μg/plate.
The top dose was limited due to toxicity beginning at 100 μg/plate in the Salmonella test strains and at 300 μg/plate in the E. coli test strain.
Vehicle / solvent:
L-001739764 was tested as a suspension in dimethyl sulfoxide (DMSO).
Controlsopen allclose all
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
with metabolic action
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
2-nitrofluorene
sodium azide
other:
Remarks:
without metabolic activation

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
E. coli WP2 uvr A pKM 101
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 100μg/plate.
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 97
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 100μg/plate.
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 200μg/plate with metabolic action
Vehicle 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:
cytotoxicity
Remarks:
at 100μg/plate.
Vehicle 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:
cytotoxicity
Remarks:
at 100μg/plate.
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
not determinable

Applicant's summary and conclusion

Conclusions:
L-001739764 is not mutagenic in bacteria and is negative in the Microbial Mutagenesis Assay.
Executive summary:

L-001739764, a Production Intermediate, was tested over a concentration range of 30 to 5000 μg/plate in a 5-strain Ames assay. In the first assay (TT #17-8113), the top dose was limited due to toxicity beginning at 100 μg/plate in the Salmonella test strains and at 300 μg/plate in the E. coli test strain. A repeat study (TT #17-8120) was performed at lower doses, 1 to 200 μg/plate, in all 5 strains. Toxicity was observed beginning at 100 μg/plate in the Salmonella test strains. Precipitate was seen on the plates beginning at 1000 μg/plate.
L-001739764 did not produce any 2-fold or greater increases in revertants relative to the solvent control in any of the strains tested, either with or without metabolic activation.
L-001739764 is negative in the Microbial Mutagenesis Assay.