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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from J check

Data source

Reference
Reference Type:
other: J check
Title:
Reverse Mutation Test of Phthalimide on Bacteria
Author:
National Institute of Technology and Evaluation
Year:
2016
Bibliographic source:
Japan Chemicals Collaborative Knowledge Database, 2016

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
Bacterial reverse mutation assay was performed for the test chemical phthalimide using Salmonella typhimurium strain TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA
GLP compliance:
not specified
Type of assay:
bacterial gene mutation assay

Test material

Constituent 1
Reference substance name:
Pthalimide
IUPAC Name:
Pthalimide
Constituent 2
Chemical structure
Reference substance name:
Phthalimide
EC Number:
201-603-3
EC Name:
Phthalimide
Cas Number:
85-41-6
Molecular formula:
C8H5NO2
IUPAC Name:
1H-isoindole-1,3(2H)-dione
Details on test material:
- Name of test material: Pthalimide
- Molecular formula: C8H5NO2
- Molecular weight: 147.133 g/mol
- Substance type: Organic
- Physical state: White powder
- Purity: 99.9%
- Impurities (identity and concentrations): 0.01%
Specific details on test material used for the study:
- Name of test material: Pthalimide
- IUPAC name: 1H-isoindole-1,3(2H)-dione
- Molecular formula: C8H5NO2
- Molecular weight: 147.133 g/mol
- Substance type: Organic
- Physical state: White powder
- Purity: 99.9%
- Impurities (identity and concentrations): 0.01%

Method

Target gene:
Histidine for Salmonella typhimurium and Tryptophan for E. coli
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
E. coli WP2 uvr A
Details on mammalian cell type (if applicable):
Not applcable
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
No data
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
0, 313, 625, 1250, 2500 or 5000 μg / plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: No data available
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
N-ethyl-N-nitro-N-nitrosoguanidine
other: 2- (2-furyl) -3- (5-nitro-2-furyl) acrylamide, 2-amino-anthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 hrs
- Expression time (cells in growth medium): 48 hrs
- Selection time (if incubation with a selection agent): No data
- Fixation time (start of exposure up to fixation or harvest of cells): No data

SELECTION AGENT (mutation assays): No data
SPINDLE INHIBITOR (cytogenetic assays): No data
STAIN (for cytogenetic assays): No data

NUMBER OF REPLICATIONS: Duplicate test was performed with 3 plates/dose level

NUMBER OF CELLS EVALUATED: No data

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data

OTHER EXAMINATIONS:
- Determination of polyploidy: No data
- Determination of endoreplication: No data
- Other: No data

OTHER: No data
Rationale for test conditions:
No data
Evaluation criteria:
Twice the number of revertant colonies as compared to the control was judged to be a positive result.
Statistics:
No data

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:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No data
- Effects of osmolality: No data
- Evaporation from medium: No data
- Water solubility: No data
- Precipitation: the test plates were observed for precipitation
- Other confounding effects: No data

RANGE-FINDING/SCREENING STUDIES: Dose range finding study was performed at dose levels of 5000, 1250, 313, 78.1, 19.5, 4.88, 1.22 μg / plate. No mutagenic activity was noted in the dosed levels.

COMPARISON WITH HISTORICAL CONTROL DATA: No data

Applicant's summary and conclusion

Conclusions:
Pthalimide failed to induce mutation in the Salmonella typhimurium strain TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA with and without S9 mix and hence is negative for gene mutation in vitro.
Executive summary:

Bacterial reverse mutation assay was performed for phthalimide (IUPAC name: 1H-isoindole-1,3(2H)-dione ) using Salmonella typhimurium strain TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA. The study was performed using the preincubation protocol at dose levels of 0, 313, 625, 1250, 2500 or 5000 μg / plate with in incubation period of 48 hrs in the presence and absence of S9 mix. Dose range finding study was performed at dose levels of 5000, 1250, 313, 78.1, 19.5, 4.88, 1.22 μg / plate to decide the doses for the main study. No mutagenic response was noted for the test compound in the preliminary dose range finding study and the main study performed.   Pthalimide failed to induce mutation in the Salmonella typhimurium strain TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA with and without S9 mix and hence is not likely to classify for gene mutation in vitro.

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