1H-Perylo[3,4-cd]pyridine-1,3(2H)-dione

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

Study period:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline compliant

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

GLP compliance:

yes

Remarks:

Department of Toxicology of BASF Aktiengesellschaft, D-67056 Ludwigshafen/Rhein, GER

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1H-benzo[10,5]anthra[2,1,9-def]isoquinoline-1,3(2H)-dione

EC Number:

608-929-9

Cas Number:

33955-44-1

Molecular formula:

C22H11NO2

IUPAC Name:

1H-benzo[10,5]anthra[2,1,9-def]isoquinoline-1,3(2H)-dione

Details on test material:

- Physical state: Darkred powder
- Storage condition of test material: Room temperature

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

Aroclor-induced rat liver S-9 mix

Test concentrations with justification for top dose:

0; 21; 105; 525; 2,625 and 5,250 µg/plate (SPT)
0; 21; 105; 525; 2,625 and 5,250 µg/plate (PIT)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO;
- Justification for choice of solvent/vehicle: Limited solubility

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

see "details in test system" for positive controls

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

DURATION
- Preincubation period: 20 minutes (only PIT)
- Incubation duration: 48-72 h at 37°C in the dark

NUMBER OF REPLICATIONS: triplicates

DETERMINATION OF CYTOTOXICITY
- Method: decrease in revertants, background growth, reduction in the titer

POSITIVE CONTROLS With S-9 MIX
- TA 1535, TA 100, TA 1537, TA 98: 2-amninoanthracene (2-AA), 2.5 µg/plate, dissolved in DMSO
- E. coli WP2 uvrA: 2-amninoanthracene (2-AA), 60 µg/plate, dissolved in DM80

POSITIVE CONTROLS Without S-9 MIX
- TA 1535: TA 100: N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 5 µg/plate, dissolved in DMSO
- TA 98: 4-nitro-o-phenylendiamine (NOPD), 10 µg/plate, dissolved in DMSO
- TA 1537: 9-aminoacridine (AAC), 100 µg/plate, dissolved in DMSO
- E. coli WP2 uvrA: 4-nitroquinoline-N-oxide (4-NQO), 5 µg/plate, dissolved in DMSO

Evaluation criteria:

The test chemical is considered positive in this assay if the following criteria are met: A dose-related and reproducible increase in the number of revertant colonies, i.e. about doubling of the spontaneous mutation rate in at least one tester strain either without S-9 mix or after adding a metabolizing system.

A test substance is generally considered nonmutagenic in this test if: The number of revertants for all tester strains were within the historical negative
control range under all experimental conditions in two experiments carried out independently of each other.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

A weak bacteriotoxic effect was occasionally observed from 2625 µg/plate and higher

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Test substance precipitation was found from about 525 µg/plate onward.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
A weak bacteriotoxic effect (slight decrease in the number of revertants, slight reduction in the titer) was occasionally observed depending on the strain and test conditions from about 2,625 µg/plate onward.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

EXPERIMENTAL RESULT

- Standard Plate Test

	TA 1535		TA 100		TA 1537		TA 98		WP2uvrA
Dose (µg/plate)	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
solvent control	20	21	107	122	10	10	24	39	27	33
21	16	19	111	146	8	10	21	33	25	33
105	18	17	109	150	8	10	22	31	26	28
525	16	14	114	124	8	8	26	34	27	31
29625	13	15	98	130	6	8	23	30	25	26
5250	8	12	90	112	5	6	19	22	22	24
positive control*	679	182	787	1326	716	169	928	1097	657	180

- Preincubation Test

	TA 1535		TA 100		TA 1537		TA 98		WP2uvrA
Dose (µg/plate)	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
solvent control	17	13	101	112	9	10	20	27	36	34
21	12	17	97	102	8	8	22	25	39	27
105	13	14	106	102	8	9	22	26	40	24
525	12	9	98	114	8	7	19	20	36	25
29625	8	10	98	120	7	9	19	23	38	24
5250	10	11	79	98	7	9	19	23	32	22
positive control	1360	263	1628	910	759	104	547	748	1530	267

*see above for details

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Under the experimental conditions chosen here, it is concluded that the test article is not a mutagenic agent in a bacterial reverse mutation test.
in vitro.

Executive summary:

The test substance was tested for its mutagenic potential based on the ability to induce point mutations in selected loci of several bacterial strains in a reverse mutation assay. The tester strains (TA 1535, TA 100, TA 1537, TA 98 and E. coli WP2 uvrA) were tested in a standard plate test (SPT) and preincubation test (PIT) both with and without metabolic activation (Aroclor-induced rat liver S-9 mix). The dose range used was 21 - 5250 µg/plate in both assays. Precipitation of the test substance was found from about 525 µg/plate onward. A weak bacteriotoxic effect was occasionally observed depending on the strain and test conditions from about 2,625 µg/plate onward. An increase in the number of his+ or trp+ revertants was not observed in the standard plate test or in the preincubation test either without S-9 mix or after the addition of a metabolizing system. According to the results of the present study, the test substance is not mutagenic in the Salmonella typhimurium/Escherichia ccli reverse mutation assay under the experimental conditions chosen here.