Naphthalene-1,8-dicarboximide

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:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented study report, GLP conform

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Ames B.N. et al.: Proc. Nat. Acad. Sci. USA 70, 2281 - 2285, 1973
Ames B.N. et al.: Mutation Res. 31, 347-364, 1975
Green, M.H.L. and Muriel, W.J.: Mutation Research 38, 3-32, 1976

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Naphthalene-1,8-dicarboximide

EC Number:

201-379-7

EC Name:

Naphthalene-1,8-dicarboximide

Cas Number:

81-83-4

Molecular formula:

C12H7NO2

IUPAC Name:

3-azatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene-2,4-dione

Details on test material:

- Name of test material (as cited in study report): Naphthalimid
- Physical state: grey powder
- Analytical purity: 96.1%
- Impurities (identity and concentrations): Trimellitacid, Hemimellitacid as Ammonium salt (Amide, Imide)
- Storage condition of test material: dark at 22°C
- pH: 5.8

Method

Target gene:

S. typhimurium: his-
E. coli: trp-

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 100, TA 1535, TA 1537, TA 1538, TA 98; Escherichia coli WP2uvrA

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 mix from Aroclor 1254 induced rat livers

Test concentrations with justification for top dose:

0.8 to 10000 µg/plate, differing between strains; per strain and experiment 5 to 6 doses (in total 9 different doses)

Vehicle / solvent:

DMSO

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

benzo(a)pyrene

other: N-Methyl-N´-nitro-N-nitrosoguanidine (MNNG), 2-Aminoanthracene

Remarks:

see "details on test system"

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation), 2 independent experiments

DURATION
- Preincubation period: overnight
- Exposure duration: 48 - 72 h at 37°C

NUMBER OF REPLICATIONS: 2

POSITIVE CONTROL SUBSTANCES:
without metabolic activation:
Na-azide: TA 100, TA 1535
9-Aminoacridine: TA 1537
2-Nitrofluorene: TA 98, TA 1538
N-Methyl-N´-nitro-N-nitrosoguanidine (MNNG): WP2uvrA

with metabolic activation:
Benzo[a]pyrene: TA 98, TA 100, TA 1535, TA 1537, TA 1538, WP2uvrA
2-Aminoanthracene: TA 98, TA 100, TA 1535, TA 1537, TA 1538, WP2uvrA

Results and discussion

Test results

Test results 1

Species / strain:

other: S. typhimurium TA 100, TA 1535, TA 1537, TA 1538, TA 98; Escherichia coli WP2uvrA

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The test substance proved to be toxic >= 500 ug/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

other: S. typhimurium TA 100, TA 1535, TA 1537, TA 1538, TA 98; Escherichia coli WP2uvrA

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The test substance proved to be toxic >= 500 ug/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 3

Species / strain:

other: S. typhimurium TA 100, TA 1535, TA 1537, TA 1538, TA 98; Escherichia coli WP2uvrA

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The test substance proved to be toxic >= 500 ug/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: strain/cell type: S. typhimurium TA 100; E. coli WP2uvrA

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Mutagenicity tests

Experiment 1
Strain (dose range in µg/plate)	Metabolic activation system	mean revertants in Controls	maximum revertant factor*	dose dependency	Assessment
TA 98	no	38	0.8	no	negative
(4-10,000)	yes	41	1.3	no	negative
TA 100	no	198	0.8	no	negative
(4-10,000)	yes	174	2.0	ambiguous**	positive
TA 1535	no	18	1.1	no	negative
(4-10,000)	yes	13	1.5	no	negative
TA 1537	no	12	1.3	no	negative
(4-10,000)	yes	9	1.6	no	negative
TA 1538	no	25	1.5	yes	negative
(4-10,000)	yes	22	1.0	no	negative
WP2 uvr A	no	16	1.1	no	negative
(4-10,000)	yes	16	3.6	yes	positive
Experiment 2
Strain (dose range in µg/plate)	Metabolic activation system	mean revertants in Controls	maximum revertant factor*	dose dependency	Assessment
TA 98	no	25	1.0	no	negative
(4-2,500)	yes	27	1.3	no	negative
TA 100	no	149	1.0	no	negative
(4-2,500)	yes	151	2.1	ambiguous**	positive
TA 1535	no	22	0.7	no	negative
(4-2,500)	yes	13	1.1	no	negative
TA 1537	no	14	1.1	no	negative
(4-2,500)	yes	15	0.9	no	negative
TA 1538	no	11	1.4	no	negative
(4-2,500)	yes	18	1.1	no	negative
WP2 uvr A	no	18	1.1	no	negative
(4 -2,500)	yes	17	2.5	ambiguous**	positive
* only in non-precipitating, non-toxic doses

** in all cases, the dose-dependency showed the following scheme: dose-dependent increase of revertants up to second highest dose without precipitation accompanied by slight to very slight decrease of the maximum revertant number in the highest non-precipitating dose

Applicant's summary and conclusion

Conclusions:

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