1,3-dichlorobenzene

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The study deviates from the TG by not using one of the following strains E. coli WP2 uvrA, or E. coli WP2 uvrA (pKM101), or S. typhimurium TA102.

Data source

Reference

Reference Type:

publication

Title:

Structural specificity of aromatic compounds with special reference to mutagenic activity in Samonella thyphimurium- a series of chloro- or fluoro-nitrobenzene derivatives

Author:

Shimizu M, Yasui Y, and Matsumoto N

Year:

1983

Bibliographic source:

Mutat. Res. 116, 217-238

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Rats were injected with PCB instead of Aroclor 1254. The S. thyphimurium strains, TA98, TA1538, TA1537, TA100 and TA 1535 were used instead of TA1535, TA1537 (or TA97a or TA97), TA98, and TA100 , and E.coli WP2 strains or S. typhimurium TA102.

Principles of method if other than guideline:

The mutagenicity of chlorobenzene compounds in Salmonella typhimurium (strains TA98, TA1538, TA1537, TA100 and TA1535) was examined.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1,3-dichlorobenzene

EC Number:

208-792-1

EC Name:

1,3-dichlorobenzene

Cas Number:

541-73-1

Molecular formula:

C6H4Cl2

IUPAC Name:

1,3-dichlorobenzene

Details on test material:

IUCLID4 Test substance: no data
- Name of test material (as cited in study report): m-dichlorobenzene
- Analytical purity: 98%

Method

Target gene:

his

Species / strain

Species / strain / cell type:

other: TA 98, TA 100, TA 1535, TA 1537, TA 1538

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

0.02, 0.04, 0.08, 0.16, 0.32, 0.64, 1.28, 2.56 µL

Vehicle / solvent:

- Vehicle used: DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-Ethyl-N´-nitro-N-nitrosoguanidine (ENNG), 2-nitrofluorene (2-NF), 9-aminoacridine (9-AA) and 2-aminoanthracene (2-AA)

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation
NUMBER OF REPLICATIONS: all test were performed in duplicate and repeated at least 3 times

Evaluation criteria:

Colonies of his+ revertants were counted after incubation, and chemicals inducing more than twice the number of revertant colonies on the control plate were considered as mutagenic.

Statistics:

Not performed

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

True negative controls validity:

valid

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

Vehicle controls validity:

valid

True negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

True negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Vehicle controls validity:

valid

True negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: TA 98, TA 100, TA 1535, TA 1537, TA 1538

Any other information on results incl. tables

Mutagenicity of 1,3-dichlorobenzene in S.typhimurium TA 98, TA 1538, TA 1537, TA100, and TA 1535

 

 

Dose per plate µL	His+ revertants/plate
	TA98		TA 1538		TA 1537		TA 100		TA 1535
	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
0.02	30 ± 3	29 ± 4	24 ± 4	24 ± 5	8 ± 2	6 ± 2	180 ± 22	228 ± 22	36 ± 5	32 ± 4
0.04	28 ± 3	33 ± 7	22 ± 3	18 ± 3	13 ± 3	9 ± 2	172 ± 16	196 ± 17	31 ± 4	38 ± 6
0.08	30 ± 5	24 ± 3	21 ± 3	22 ± 3	10 ± 2	9 ± 2	135 ± 25	190 ± 15	32 ± 5	30 ± 3
0.16	21 ± 3	29 ± 5	17 ± 2	30 ± 6	8 ± 2	8 ± 2	142 ±18	186 ±18	29 ± 4	24 ± 3
0.32	23 ± 4	22 ± 3	25 ± 5	20 ± 2	9 ± 2	11 ± 4	154 ± 13	177 ±16	22 ± 3	28 ±4
0.64	17 ± 2	25 ± 4	21 ± 4	31 ± 5	10 ± 3	9 ± 2	156 ±18	181 ± 17	28 ± 5	24 ± 3
1.28	15 ± 3 *	20 ± 3	0*	2± 8*	3 ± 3*	5 ± 3*	155 ± 9	164 ±14	6 ± 8*	17 ± 3
2.56	0*	0*	0*	0*	0*	0*	0*	42 ±22*	0*	0*

 

 

 

 

Applicant's summary and conclusion

Conclusions:

Under the conditions of the study, the test item was not mutagenic and not classified according to CLP Regulation (EC) 1272/2008.

Executive summary:

The mutagenicity of 1,3-dichlorobenzene was examined in Salmonella typhimurium (strains TA98, TA, 1538, TA 1537, TA 100, and TA 1535). The test was carried out with and without liver microsomal activation.

1,3-dichlorobenzene showed no mutagenic activity and toxicity at higher doses.