4,4'-[isopropylidenebis(4,1-phenyleneoxy)]dianiline

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:

10 - 29 Sep 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

no information on historical data, acceptance and evaluation criteria; only 1 assay performed, tested up to 8000 µg/plate

Data source

Reference

Reference Type:

other: Summary of translation of japanese report

Title:

Unnamed

Year:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

adopted in 1997

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-[isopropylidenebis(4,1-phenyleneoxy)]dianiline

EC Number:

235-985-8

EC Name:

4,4'-[isopropylidenebis(4,1-phenyleneoxy)]dianiline

Cas Number:

13080-86-9

Molecular formula:

C27H26N2O2

IUPAC Name:

4,4'-[isopropylidenebis(4,1-phenyleneoxy)]dianiline

Method

Target gene:

his operon, trp operon

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Species / strain 3

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

cofactor-supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of male rats, induced with PCB (KC-500)

Test concentrations with justification for top dose:

Following concentrations were used in main experiment (preincubation):

all strains: 1, 5, 10, 50, 100, 500, 1000, 5000, 8000 μg/plate (with and without metabolic activation)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

benzo(a)pyrene

other: AF-2; ethyl-N-nitro-N'- nitrosoguanidine (ENNG), 2-aminoanthracene (2AA)

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: duplicate

DETERMINATION OF CYTOTOXICITY
- Method: inspection of bacterial background lawn

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 1538, E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Precipitation of the test substance was observed at a concentration of 1000 µg/plate.

Any other information on results incl. tables

Table 1: Test results (experiment 1, preincubation)

With or without S9 Mix	Test substance concentration (μg/plate)	Number of revertant colonies per plate (single and average of 2 plates)
		Frameshift type						Base-pair substitution type
		TA 98		TA 1537		TA 1538		TA 100		TA 1535		WP2 uvr A (pKM 101)
-	Solvent control (DMSO)	25	26	12	16	30	32	139	142	34	37	34	35
		27		20		34		145		40		35
	1	24	27	19	21	30	30	107	127	33	34	25	25
		29		22		30		147		34		24
	5	39	31	12	12	23	31	144	147	37	37	26	29
		23		12		39		150		37		32
	10	27	27	15	15	30	26	137	145	39	38	24	31
		27		15		22		153		36		38
	50	24	27	13	14	24	24	115	136	38	31	28	27
		30		14		24		157		23		26
	100	21	24	12	14	30	30	113	129	18	22	25	27
		27		15		29		145		26		28
	500	24	26	10	12	30	31	131	137	35	33	22	27
		28		14		31		142		31		31
	1000 P	25	29	13	16	22	29	126	141	31	35	28	33
		32		19		36		155		39		38
	5000 P	33	29	18	21	29	27	153	155	33	40	35	34
		24		24		25		157		47		33
	8000 P	29	29	-		-		148	149	-		-
		29						150
	Positive controls (µg/plate)	AF-2 (0.05)		9AA (80)		4NQO (0.25)		AF-2 (0.01)		ENNG (5)		AF-2 (0.05)
	No. of colonies/plate	263	255	957	843	186	187	471	435	1916	2048	987	1027
		246		729		188		399		2180		1066
+	Solvent control (DMSO)	34	32	19	19	31	32	180	169	18	14	28	26
		30		19		32		157		9		24
	1	40	44	12	12	35	36	163	158	12	14	26	29
		48		12		36		152		15		31
	5	42	43	9	8	36	37	136	137	19	18	24	23
		43		7		38		138		16		21
	10	33	35	23	17	27	27	137	142	11	14	20	24
		36		11		27		147		16		27
	50	41	43	13	21	24	33	150	149	14	17	23	28
		45		28		41		148		20		32
	100	34	34	19	21	33	35	140	151	19	19	35	34
		34		23		36		162		19		32
	500	35	38	10	12	43	46	135	136	16	13	33	29
		41		14		48		137		9		25
	1000 P	44	45	16	17	39	41	156	160	15	17	41	40
		45		17		42		163		18		39
	5000 P	24	41	15	17	38	43	149	152	11	13	33	33
		40		18		47		155		15		33
	8000 P	45	46	-		-		150	151	-		-
		47						151
	Positive controls (µg/plate)	B(a)P (5)								2AA(5)		2AA(5)
	No. of colonies/plate	853	801	289	320	270	276	1051	1021	764	780	256	245
		749		350		281		990		796		234

2AA = 2-aminoanthracene

4NQO = 4-nitroquinoline-N-oxide

9AA = 9-aminoacridine

B(a)P = benzo(a)pyrene

ENNG = ethyl-N-nitro-N'- nitrosoguanidine

P = precipitate

Applicant's summary and conclusion

Conclusions:

Based on the results of the conducted study the test substance did not exhibit mutagenic properties in bacterial cells.