Benzoyl chloride

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:

other: Study very similar to OECD 471 with no deviations. Study well documented. Klimisch 2.c study, comparable to a guideline study with acceptable restrictions.

Data source

Reference

Reference Type:

publication

Title:

Assay of 855 test chemicals in ten tester strains using a new modification of the ames test for bacterial mutagens

Author:

McMahon R.E., Cline J.C. and Thompson C.Z.

Year:

1979

Bibliographic source:

Cancer research, 39, 682-693.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Benzoyl chloride

EC Number:

202-710-8

EC Name:

Benzoyl chloride

Cas Number:

98-88-4

Molecular formula:

C7H5ClO

IUPAC Name:

benzoyl chloride

Details on test material:

No data

Method

Target gene:

Histidine, gal-bio-uvrB, LPS were the target genes for the Salmonella typhimurium strains used and the tryptophan gene was the target gene in the Escherischia coli strains used.

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

Species / strain 4

Species / strain / cell type:

E. coli WP2 uvr A

Species / strain 5

Species / strain / cell type:

bacteria, other: S. typhimurium G46, C3076, D3052

Metabolic activation:

with and without

Metabolic activation system:

S9 mix freshly prepared

Test concentrations with justification for top dose:

The test concentrations range from 0.1 to 1000 µg/mL. No further data are available

Vehicle / solvent:

- Vehicle(s)/solvent(s) no data
No further data

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: streptozotocin

Remarks:

without S-9 mix

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

2-acetylaminofluorene

Remarks:

with S-9 mix

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar, plate incorporation with a gradient plate technique

DURATION
- Exposure duration: 48 hours


NUMBER OF REPLICATIONS: six to eight


DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

No further data

Evaluation criteria:

In the gradient technique, the concentration range over which chemically induced mutant colonies are present is recorded. The minimal inhibitory concentration is observed as a clear zone in the agar gel. This level is a basis for the expert to judge on the mutagenicity potential of the test substance compared with positive controls.
It is assumed then than all substances showing no revertants over 1000 µg/mL or to the concentration showing first sign of toxicity are considered as negative in this test.

Statistics:

No data

Results and discussion

Test results

Test results 1

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

bacteria, other: S. typhimurium G46, C3076, D3052

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

No data

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

The authors tested the mutagenicity potential of benzoyl chloride with a methodology similar to the OECD guideline 471. In the test conditions, benzoyl chloride was found negative. Therefore, benzoyl chloride should not be considered as a potent mutagen in in vitro bacterial systems.

Executive summary:

The authors tested the mutagenicity potential of benzoyl chloride (CAS n° 98 -88 -4) with a methodology similar to the OECD guideline 471, with the recommended strains of salmonella typhimurium and E. coli. They conducted this test with a slightly modified protocol proposed by Ames for the plate incorporation. They did a gradient technique for the plate incorporation allowing to test a full range of concentration ranging from 0.1 µg/mL to 1000 µg/mL or to cytotoxic concentrations. They included also in this test four other strains of S. typhimurium to cover all major kind of mutations. All strains were tested with and without metabolic activation and positive and negative controls were included in the experiment.

With this gradient technique, the concentration range over which chemically induced mutant colonies are present is recorded. The minimal inhibitory concentration is observed as a clear zone in the agar gel. This level is a basis for the expert to judge on the mutagenicity potential of the test substance compared with positive controls. It is assumed then that all substances showing no revertants over 1000 µg/mL or to the concentration showing first sign of toxicity are considered as negative in this test. Besides a complementary analysis on the number of revertants may be undergone to confirm the expertise.

According to the authors, this test was negative for benzoyl chloride for all strains. Even if this test system requires an expert judgement, we could assume that this test is enough robust and sensitive to detect mutagen. And since all strains returned negative, benzoyl chloride should not be considered as a potent mutagen in in vitro bacterial systems.

The GLP status of this study is unknown but the methodology used was very similar to the OECD guideline 471. Since no deviations were observed regarding the guideline requirements and as it is well documented. This study should be considered as reliable with restrictions, a Klimisch 2.c study, comparable to a guideline study with accpetable restrictions.