4-chlorobenzaldehyde

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

adopted 26 May 1983

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4-chlorobenzaldehyde

EC Number:

203-247-4

EC Name:

4-chlorobenzaldehyde

Cas Number:

104-88-1

Molecular formula:

C7H5ClO

IUPAC Name:

4-chlorobenzaldehyde

Details on test material:

- Name of test material (as cited in study report): p-Chlorobenzaldehyde
- Physical state: white to yellowish crystalline powder
- Molecular weight: 140.6
- Molecular formular: C7H5C10
- Analytical purity: 98.8 %
- Purity test date: 28.08.1990
- Product No.: 028924
- Sample No.: 050484/1990
- Expiration date of the lot/batch: until march 1991
- Storage condition of test material: refrigerator

Method

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

microsomal enzyme systems (S-9 fraction) from Aroclor 1254-induced male Sprague-Dawley rat liver

Test concentrations with justification for top dose:

1st test: 0, 8, 40, 200, 1000, 5000
2nd test: 0, 125, 250, 500, 1000, 2000, 4000

Due to the substance's toxicity, doses ranging from 125 to 4000 µg per plate were chosen for the repeat test.

Vehicle / solvent:

- solvent used: Ethylene glycol dimethylether (EDGE) for the test substance and DMSO for positive controls

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

solvent control

True negative controls:

no

Remarks:

with and without S-9 mix

Controls 2

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

without S9-mix, TA 1535

Controls 3

Positive controls:

yes

Positive control substance:

other: Nitrofurantoin

Remarks:

without S9-mix, TA 100

Controls 4

Positive controls:

yes

Positive control substance:

other: 4-nitro-phenylendiamine

Remarks:

without S9-mix, TA 1537, TA 98

Controls 5

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

with S9-mix, TA 1535, TA 1537, TA 98 and TA 100

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Incubation duration: 48 h at 37°C

NUMBER OF REPLICATIONS: 4

DETERMINATION OF TOXICITY
The toxicity of the test item was assessed in three ways:
a) background growth on the plates for mutant determination
b) marked and dose-dependent reduction in the mutant count per plate compared to the negative control
c) determination of the titer

Evaluation criteria:

Characterization of a substance as positive requires:
- doubling of the spontaneous mutation rate (TA 1535, TA 100, TA 98); threefold increase for TA 1537
- dose-response relationship
- reproducibility of the results

Results and discussion

Test results

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:

cytotoxicity

Remarks:

> 250 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

p-Chlorobenzaldehyde showed no mutagenic response in any strain with or without S-9 mix.

The test substance showed to produce bacteriotoxic effects at doses above 250 µg/plate. Neverthelesse doses

up to 4000 µg/plate could be used for assessment.

Applicant's summary and conclusion

Executive summary:

In a reverse gene mutation assay the bacteria strains TA 1535, TA 1537, TA 98 and TA 100 of S. typhimurium  were exposed to p-Chlorobenzaldehyde (98.8 %) at concentrations of 0, 8, 40, 125, 200, 250, 500, 1000, 2000, 4000 or 5000 µg/plate (4 plates/dose) in the presence and absence of mammalian metabolic activation.

The test substance showed to produce bacteriotoxic effects at doses above 250 µg/plate. Neverthelesse doses up to 4000 µg/plate could be used for assessment.

The positive controls induced the appropriate responses in the corresponding strains.

There was no evidence mutagenic activty of p-Chlorobenzyaldehyde. No biologically relevant increase in the mutant count, in comparison with the negative controls, waqs observed. Therefore, p-Chlorobenzaldehyde was considered to be non-mutagenic with or without S9 mix.