N-hydroxyphthalimide

Genetic toxicity: in vitro

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: Authoritative database

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

Test material information

Constituent 1

Reference substance name:

Pthalimide

IUPAC Name:

Pthalimide

Constituent 2

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
- 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 / strain

Species / strain 1

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 2

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

Remarks:

DMSO

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 results

Test results 1

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

Test results 2

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:

The test compound 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 the test chemical phthalimide 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. The doses for the main study were determined by performing dose range finding study at dose levels of 5000, 1250, 313, 78.1, 19.5, 4.88, 1.22 μg / plate. No mutagenic response was noted for the test compound in the preliminary dose range finding study and the main study performed.

 

The test compound pthalimide failed to induce mutation in theSalmonella 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.