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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

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:
From 28 July 1998 to 3 August 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride
EC Number:
928-729-8
Cas Number:
188416-20-8
Molecular formula:
C16H13ClF3N5O.HCl
IUPAC Name:
3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol hydrochloride
Details on test material:
- Analytical purity: 90%
- Lot/batch No.: 5ABJ002

Method

Species / strainopen allclose all
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:
S9 mix
Test concentrations with justification for top dose:
5, 15, 50, 150, 500, 1500, 5000 μg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The solubility of the substance was assessed at 50 mg active ingredient/ml in water and DMSO. At this concentration the test substance was insoluble in water but dissolved in DMSO.
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: N-ethyl-N'-nitro-N-nitrosoguanidine
Remarks:
In the absence of S9 mix for strain TA1535, TA100 and E. coli WP2.
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
In the absence of S9 mix for strain TA1537.
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
In the absence of S9 mix for TA98.
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene
Remarks:
In the presence of S9 mix for strain TA1535 and E. coli WP2.
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
In the presence of S9 mix for strain TA1537, TA98 and TA100.
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

NUMBER OF REPLICATIONS: 3

Two independent mutation tests were performed in the presence and absence of S9 mix. The first was a standard plate incorporation assay, the second involved a pre-incubation stage.
Dose levels of up to 5000 μg/plate were tested in the mutation tests. Other dose levels were used were series of ca half-log10 concentration. Six dose levels were used in the second test.
Evaluation criteria:
The mean number of revertant colonies for all treatment groups is compared with those obtained for the solvent control groups. The mutagenic activity of a test substance is applying following criteria:
a) If treatment with a test substance produces an increase in revertant colony numbers of at twice the concurrent solvent controls, with some evidence of a positive dose-relationship, in two separate experiments, with any bacterial strain either in the presence or absence of S9 mix, it is considered to show evidence of mutagenic activity in this test system. No statistical analysisi is performed.
b) If treatment with a test substance does not produce reproducible increases of at least 1.5 times the concurrent solvent controls, in either mutation test, it is considered to show no evidence of mutagenic activity in this test system. No statistical analysis is performed.
c) If the results obtained fail to satisfy the criteria for a clear "positive " or "negative" response given in paragraphs(a) and (b), additional testing may be performed in order to resolve the issue of the test substance's mutagenic activity in this test system. Modifications to the experimental method will usually be considered, such as the use of a narrower dose range and different levels of S9 in the mix. Should an increase in revertant colony numbers then be observed which satisfies paragraph(a) the substance is consider to show evidence of mutagenic activity in this test system.No statistical analysis is performed.

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:
cytotoxicity
Remarks:
5000 μg/plate in the first mutation test. 5000 μg/plate and 1500μg/plate in the second test .
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A pKM 101
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
5000 μg/plate in the first mutation test. 5000 μg/plate and 1500μg/plate in the second test .
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Toxicity:
In the first test, toxicity was observed towards all of the tester strains at 5000 μg/plate
In the second test, toxicity was observed towards all of the tester strains at 5000 and 1500μg/plate.
No substantial increases in revertant colony numbers of any of the tester strains were observed following treat with UK-103,446-01 at any dose level, in the presence or absence of S9 mix, in either mutation test.
The concurrent positive controls demonstrated the sensitivity of the assay and the metabolising activity of the liver preparations.
The mean revertant colony counts for the solvent controls were within the historical range. The mean revertant colony count for TA100 in the absence of S9 mix in the second test was just below the lower end of the current two year range. However, it was within the overall range for this laboratory.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

It is concluded that, when tested in DMSO, the substance shows no evidence of mutagenic activity in this bacterial system.