N,N,N',N'-tetrakis(2,3-epoxypropyl)-m-xylene-α,α'-diamine

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Industrial Safety and Health Department, Labor Standard Bureau, Ministry of Labor, Japan

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

1

Reference substance name:

N,N,N',N'-tetrakis(2,3-epoxypropyl)-m-xylene-α,α'-diamine

EC Number:

264-438-6

EC Name:

N,N,N',N'-tetrakis(2,3-epoxypropyl)-m-xylene-α,α'-diamine

Cas Number:

63738-22-7

Molecular formula:

C20H28N2O4

IUPAC Name:

N,N,N',N'-tetrakis(2,3-epoxypropyl)-m-xylene-α,α'-diamine

Specific details on test material used for the study:

Purity: 75 wt%
Name cited in study report: NNN’N’-tetraglycidyl metaxylenediamine or PGA-X
Description at room temperatur: liquid

Method

Target gene:

- S. typhimurium: Histidine gene
- Escherichia coli: Tryptophan gene

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Additional strain / cell type characteristics:

not applicable

Species / strain 3

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Polychlorinated biphenyl (PCB, KC-500) induced S.D. rat S9

Test concentrations with justification for top dose:

10, 50, 100, 500, 1000 and 5000 µg/ plate. 5000 µg is the recommended maximum test concentration according to the OECD guideline.

Vehicle / solvent:

DMSO
Justification for choice of solvent: The substance is readily soluble in DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

N-ethyl-N-nitro-N-nitrosoguanidine

other: 2-Aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION:
preincubation

DURATION
- Preincubation period: 20 minutes at 37°C
- Exposure duration: 48 hours at 37 °C

NUMBER OF REPLICATIONS:
duplicates

DETERMINATION OF CYTOTOXICITY
Not specified

Evaluation criteria:

Test results were judged to be positive (+) if mutant colony counts were at least twice as high as natural mutant colony counts. Test results were judged to be negative (-) if mutant colony counts were lower.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Top dose, only in absence of S9

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Top dose, only in absence of S9

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Top dose, only in absence of S9

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

5000 µg/ plate

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

at 1000 and 5000 µg/plate

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 6

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

1000 to 5000 µg/plate

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 7

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 8

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 9

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

ADDITIONAL INFORMATION ON CYTOTOXICITY:
In absence of S9 inhibition of bacterial growth is observed at the top dose for all tester strains

Remarks on result:

other: mutagenic potential was fairly weak compared to that of existing mutagens.

Applicant's summary and conclusion

Conclusions:

The substance shows weak mutagenic potential in the Salmonella Typhimurium TA 100, TA 1535 and Escherichia Coli WP2 uvra in presence of metabolic activation.

Executive summary:

The mutagenic activity of the test substance was evaluated in a study similar to OECD TG 471. A pre-incubation assay was performed in the tester strains S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100 and E. coli WP2 uvr A both in absence and presence of Polychlorinated biphenyl (PCB), induced rat S9 as metabolic system. The substance was tested at concentrations ranging from 10 to 5000 µg/ plate (the maximum recommended dose level). Cytotoxicity was only observed at the top-dose in absence of S9, details on the method for cytotoxicity determination are not reported. Concurrent solvent and negative controls were included and gave appropriate responses. An increase in mutant frequencies was only observed at concentrations between 1000 to 5000 µg/plate in the strains TA 100 and TA 1535 and E. coli WP2 uvr A in presence of metabolic activation. The mutagenic potential was however fairly weak compared to that of existing mutagens. Although a weak positive response in the Salmonella typhimurium and Escherichia coli reverse mutation assays was obtained, insufficient data is available to concluded if the test substance is an actual mutagen.