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Toxicological information

Genetic toxicity: in vitro

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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:
October 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, GLP-compliant
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:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: amber liquid
Details on test material:
- Name of test material: HTP-103
- Physical state: light yellow liquid
- Lot/batch No.: 87A006P251, received at IRI on 23 November 1988
- Stability under test conditions: stable
- Storage condition of test material: in the dark under ambient conditions

Method

Species / strain
Species / strain / cell type:
other: Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced rat liver S-9-mix
Test concentrations with justification for top dose:
Toxicity Test:
A toxicity test using strain TA 100 only was performed in the presence and absence of S9 mix to establish suitable dose levels for the mutation tests. One plate of each of the following concentrations of HPT-103 was used:
33, 100, 333, 1000, 3333 and 10000 ug per plate

Main Tests:
Two Independent mutation tests were conducted using 5 bacterial strains (TA 1535, TA 1537, TA 1538, TA 98 and TA 100).
The dose levels used in the first of these experiments, and selected on the basis of the results of the toxicity test, were 3, 10, 33, 100, 333 and 1000 ug per plate in the presence of S9 mix. Dose levels used in the absence of S9 mix were 1, 3, 10, 33, 100 and 333 ug per plate.
The dose levels used in the second of these experiments and selected on the basis of the results of the first experiment were:
3, 10, 33, 100, 333 and 1000 ug per plate (TA 1535 and TA 100 in the presence of S9 mix)
1, 3, 10, 33, 100 and 333 ug per plate (TA 1537, TA 1538 and TA 98 in the presence of S9 mix; TA 1535 and TA 100 in the absence of S9 mix)
0.3, 1, 3, 10, 33 and 100 ug per plate (TA 1537, TA 1538 and TA 98 in the absence of S9 mix)
A further test was carried out since TA 100 in the presence of S9 mix in Experiment 2 was unaccetable. This test was done exactly as in Experiment 2. Triplicate plates were prepared for each bacterial strain and dose level in both the presence and absence of S9 mix.
Vehicle / solvent:
Dimethylsulfoxide
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
other: 2-aminoanthracene
Remarks:
2-aminoanthracene used with S9-mix; sodium azide, 2-nitrofluorene and 9-aminoacridine used without S9-mix

Results and discussion

Test resultsopen allclose all
Species / strain:
other: Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(>= 100 ug/plate)
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
other: Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(>= 33 ug/plate)
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Remarks on result:
other: other: main test
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Precipitation was apparent only at the highest concentration (1000 ug per plate).

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

The substance can be considered as non-mutagenic in this Ames test.
Executive summary:

The reverse mutation assay was performed according to EU-test method B.13/14 with 5 Salm. typh. strains (TA98, TA100; TA1535, TA1537, TA1538) with and without metabolic activation. Tested concentrations ranged from 0.3 up to 1000 ug/plate. Metabolic activation system was Aroclor-induced rat liver S-9-mix. The test item was found to be non-mutagenic in this study.