α,4-dichlorotoluene

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:

September 1983

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:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

No follow-up experiments were done for confirmation of negative results

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

α,4-dichlorotoluene

EC Number:

203-242-7

EC Name:

α,4-dichlorotoluene

Cas Number:

104-83-6

Molecular formula:

C7H6Cl2

IUPAC Name:

1-chloro-4-(chloromethyl)benzene

Method

Target gene:

In the Salmonella typhimurium strains (TA 1535, TA 100, TA 1537, TA 1538, TA 98) the amino acid histidine locus is the target gene.
In the Escherichia coli strain (WP2 uvrA) the amino acid tryptophan locus is the target gene.

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538, Escherichia coli WP2 uvrA

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S-9 mix from Arochlor 1254 induced rats

Test concentrations with justification for top dose:

0.8, 4, 20, 100, 250, 500, 1000 µg/plate

Vehicle / solvent:

- Vehicle/solvent used: DMSO

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

yes

Remarks:

2-aminoanthracene (-S9: 0.5 µg/plate; TA98, TA100, TA1538)

Positive controls:

yes

Remarks:

TA98, TA100, TA1538

Positive control substance:

other: -S9: methylhydrazone derivative (5 µg/plate), +S9: 2-aminoanthracene (0.5 µg/plate)

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

yes

Remarks:

2-aminoanthracene (-S9: 1 µg/plate (TA1535, TA 1537), 10 µg/plate (WP2 uvr A))

Positive controls:

yes

Remarks:

TA 1557, TA 1535, WP2 uvr A

Positive control substance:

other: -S9: streptocotocine (5 µg/plate (TA 1535)), 9-aminoacridine (100 µg/plate (TA 1537)), N-ethyl-N-nitro-N-nitrosoguanidine (2 µg/plate, WP2 uvr A); +S9: 2-amioanthracene (1 µg/plate (TA 1535, TA1537), 2-amioanthracene 10 µg/plate (WP2 uvr A))

Details on test system and experimental conditions:

METHOD OF APPLICATION: Overlay (soft) agar (plate incorporation method)

Evaluation criteria:

The test substance is considered positive in this assay if the following criteria is met:
- Doubling of the revertant colonies compared to controls

Results and discussion

Test results

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: Without metabolic activation: >= 500 µg/plate, with metabolic activation: >= 1000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538, Escherichia coli WP2 uvrA

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Executive summary:

In a reverse gene mutation assay in bacteria Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 and Escherichia coli strain WP2 uvrA were exposed to p-chlorobenzylchloride at concentrations of 0, 0.8, 4, 20, 100, 250, 500, 1000 µg/plate in the presence and absence of mammalian metabolic activation. No preincubation was performed. There was no evidence of induced mutant colonies over background up to a concentration of 1 mg p-chlorobenzyl chloride / plate. The positive controls induced the appropriate responses in the corresponding strains. In conclusion, p-chlorobenzyl chloride did not show any mutagenic activity in any tester strains regardless of metabolic activation.