5-[4-Methoxy-2-(propan-2-yl)phenoxy]pyrimidine-2,4-diamine

Genetic toxicity: in vitro

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

Test material information

Constituent 1

Reference substance name:

5-[4-methoxy-2-(propan-2-yl)phenoxy]pyrimidine-2,4-diamine

EC Number:

839-944-0

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 / strain

Species / strain 1

Species / strain / cell type:

E. coli WP2 uvr A pKM 101

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 100

Species / strain 3

Species / strain / cell type:

S. typhimurium TA 98

Species / strain 4

Species / strain / cell type:

S. typhimurium TA 97

Species / strain 5

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).

Controls

Controls 1

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

with metabolic action

Controls 2

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 results

Test results 1

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

Test results 2

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

Test results 3

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

Test results 4

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

Test results 5

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.