Registration Dossier

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:
22 November 1996 - 16 December 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study performed in accordance with the corresponding OECD-/EU-testing guidelines
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Name used in the report: P0087
Batch No.: 265
Purity: 99.6%
Expiry date: 30 Dec 1996

Method

Target gene:
not applicable
Species / strain
Species / strain / cell type:
other: the following five strains were used: TA 1535, TA 1537, TA 98, TA 100 and TA 102
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9-liver fractions of Sprague-Dawley rats, induced with phenobarbital and betanaphthoflavone
Test concentrations with justification for top dose:
Test substance concentrations of 50, 158, 500, 1580 and 5000 microg/plate were used in the toxicity test.
Test substance concentrations of 313, 625, 1250, 2500 and 5000 microg/plate were used in the Experiment I (plate incorporation method) and Experiment II (pre-incubation method).
Vehicle / solvent:
- Vehicle: Distilled water
- Justification for choice of solvent/vehicle: high solubility, better than others
Controls
Untreated negative controls:
yes
Remarks:
each strain alone or in presence of the solvent
Negative solvent / vehicle controls:
yes
Remarks:
distilled water
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
further positive control substances were used: 9-Aminoacridine, 2-Nitrofluorene, 2-Aminoanthracene, Cumene hydroperoxide
Details on test system and experimental conditions:
The study was performed by the direct plate incorporation method w ith and without metabolic activation.
Evaluation criteria:
A mutagenic effect is significant when, at least in one strain, the number of revertants histidine+ is twice higher than that found in the control.
Statistics:
According to the OECD guideline 471, a statistical analysis of the data is not mandatory.

Results and discussion

Test results
Species / strain:
other: the following five strains were used: TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No precipitation

COMPARISON WITH HISTORICAL CONTROL DATA:
- not performed

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- no
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

It can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations in the five strains tested.
Executive summary:

The assay was performed 1996 in compliance with GLP. The test was performed with and without liver microsomal activation and used strains TA 1535, TA 1537, TA 102, TA 98 and TA 100. Each concentration and the controls, were tested in triplicate. The test item was tested at the following concentrations: 313, 625, 1250, 2500 and 5000 µg/plate (Experiment I and II). The test substance did not induce increases in the number of revertant colonies which were two-fold greater than the control values at any dose-level, in the absence or presence of S9 metabolism. On the basis of the stated criteria it must be concluded that P0087 is not mutagenic to S. typhimurium under the reported experimental conditions.