4-chloro-o-cresol

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:

other: The study is GLP and in accordance with OECD guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

The standard test plate method and the pre-incubation test were both performed with and without the S-9 metabolic activator.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4-chloro-o-cresol

EC Number:

216-381-3

EC Name:

4-chloro-o-cresol

Cas Number:

1570-64-5

Molecular formula:

C7H7ClO

IUPAC Name:

4-chloro-2-methylphenol

Details on test material:

- Analytical purity: 97.5%

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

S-9 fraction extracted from rat livers

Test concentrations with justification for top dose:

1st experiment - std plate test with and without metabolic activator
0, 20, 100, 500, 2500 and 5000 micrograms /plate

2nd experiment - std plate test with and without metabolic activator
0, 4, 20, 100, 500 and 1500 micrograms/plate

3rd experiment - pre-incubation test with and without metabolic activator
0, 4, 20, 100, 500 and 1000 micrograms /plate

4th experiment - pre-incubation test with and without metabolic activator
0, 15, 30, 60, 125 and 250 micrograms/plate

Vehicle / solvent:

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

Controls

Untreated negative controls:

yes

Remarks:

solvent control and steriity control

Positive controls:

yes

Positive control substance:

other: see below for details.

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
NUMBER OF REPLICATIONS: 3 plates per dose or control

The following positive controls were used to check the mutability of the bacteria and the activity of the S-9 mix.

With S-9 mix - 2-aminoanthracene for all strains
Without S-9 mix - N-methyl-N-nitro-N-nitroso-guanidine (MNNG) for strains TA100 and TA 1535
4-nitro-o-phenylendiamine for the strain TA 98
9-aminoacridine chloride monohydrate for the strain TA 1537

Evaluation criteria:

In order for the substance to be characterised as having a postive Ames test it must fulfil the following requirements:
- doubling of the spontaneous mutation rate relative to the control
- 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:

Bacteriotoxicity was observed from 1500 micrograms/plate in the standard plate test and 125 micrograms /plate in the pre-incubation test.

Untreated negative controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results:
negative with metabolic activation Pre-incubation test
negative without metabolic activation Pre-incubation test
negative with metabolic activation Standard Plate Test
negative without metabolic activation Standard Plate Test

According to the results of this BASF study, 4-chloro-o-cresol is not mutagenic in the Ames test under the test conditions reported here.

Executive summary:

In a guideline study 4 -chloro-o-cresol was tested for mutagenicity in the Ames test.

Strains TA1535, TA 100, TA 1537 and TA98 of Salmonella Typhimurium were tested in the dose range 4 - 5000 micrograms /plate in the standard plate test and 4 - 1000micrograms/plate in the pre-incubation test.

Both were performed with and without metabolic activation (S-9 mix).

Clear bacteriotoxicity was observed from 1500 micrograms/plate in the standard plate test and 125 micrograms /plate in the pre-incubation test.

An increase in the number of histadine⁺ revertants was not observed in either the standard plate test or the pre-incubation test with or without metabolic activation. 4-chloro-o-cresol is not mutagenic in the Ames test under the test conditions reported here.