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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: other: bacterial mutagen
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 3 December 1985 to 14 July 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 84-2
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): XRD-498
- Molecular formula: C12H9F2N5O2S
- Molecular weight: 325.3

- Analytical purity: 99.7%

- Lot/batch No.: AGR 224099

- Stability under test conditions: stable in DMSO
- Storage condition of test material:
- Other:

Method

Target gene:
histidine
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
The S-9 rat liver homogenate (from Aroclor 1254 induced 8-10 week old male Sprague-Dawley rats)
Test concentrations with justification for top dose:
0.01, 0.0316, 0.1, 0.316, 1.0 mg per plate
= 10, 3.16, 1.0, 0.316, 0.1 mg/ml
Vehicle / solvent:
-DMSO
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: direct-acting mutagens for nonactivation assays and mutagens that require biotransformation in activation assays
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation); preincubation

DURATION
- Preincubation period: 30 minutes
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 3
Evaluation criteria:
A test chemical is considered a bacterial mutagen if the mean number of revertant colonies observed is at least three times higher than the mean of the negative (solvent) control and it produces a dose response relationship over several concentrations. If a chemical produces reproducible reversion rates in excess of 3X over background but no definitive dose response relationship, it is considered to be a presumptive bacterial mutagen. If a chemical produces reproducible reversion rates greater than 2X but less than 3X over controls the results are considered to be equivocal or inconclusive.
Statistics:
No information

Results and discussion

Test results
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
Vehicle controls validity:
not specified
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Toxicity (reduced growth on plates) was evident at 1.0 mg test chemical per plate in all strains of bacteria, both with and without metabolic activation, and also at 0.316 mg/plate without activation in all strains of bacteria except TA1538. Comparison of XRD-498 treated plates to negative controls (spontaneous reversion) indicates that a positive response (3-fold increase over controls and a dose response) was not elicited in any bacterial tester strain, with or without the addition of the mammalian metabolic activation preparation. The responsiveness of bacteria to known mutagens is demonstrated by the activity of the positive controls.
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 without metabolic activation
negative with metabolic activation

XRD-498 was not mutagenic to any of the bacterial tester strains, with or without metabolic activation, indicating a lack of genotoxic activity under the conditions of the present study.
Executive summary:

XRD-498 was evaluated for genetic activity in the Ames' test with and without the addition of a mammalian metabolic activation preparation using a pre-incubation assay. The studies were conducted using Salmonella typhimurium bacterial tester strains TA98, TA100, TA1535, TA1537, and TA1538. XRD-498 was tested at amounts of 0.01, 0.0316, 0.1, 0.316, and 1.0 mg per plate and was observed to be toxic (reduced growth on plates) to all strains at 1.0 mg per plate with or without the mammalian metabolic activation preparation and at 0.316 mg per plate without activation in all strains except TA1538. XRD-498 was not mutagenic to any of the bacterial tester strains, with or without metabolic activation, indicating a lack of genotoxic activity under the conditions of the present study.