p-cresol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Principles of method if other than guideline:

The objective of this in vitro assay was to evaluate the ability of p-cresol to induce chromosomal aberrations in chnese hamster ovary (CHO) cells with and without metabolic activation.

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

p-cresol

EC Number:

203-398-6

EC Name:

p-cresol

Cas Number:

106-44-5

Molecular formula:

C7H8O

IUPAC Name:

p-cresol

Details on test material:

Test substance: p-cresol, 99.8% pure

Method

Target gene:

no data

Species / strain

Species / strain / cell type:

other: Chinese Hamster ovary (CHO) cells

Details on mammalian cell type (if applicable):

- Type and identity of media: McCoy's medium
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

treatment time: 20 hrs:
-S9-mix, 100, 150, 200, 301 ug/ml performed twice; +S9-mix: 301, 601, 902 ug/ml;
treatment time: 10 hrs:
+S9-mix: 150, 225, 300 ug/ml performed twice.

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: MitomycinC (for nonactivation assay); Cyclophosphamide ( in the metabolic activated assay)

Details on test system and experimental conditions:

doses were chosen following a rangefinding assay.

Evaluation criteria:

positive if an significant increase in chromosoally aberrrant cells were observed.

Statistics:

Fisher's Exact Test with an adjustment for multiple  comparisons.

Results and discussion

Test results

Species / strain:

other: Chinese Hamster Ovary cells

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

other: Preliminary range-finding assays were performed (3.01-3010 µg/ml) to determine cytotoxicity: -S9-mix: >=301 µg/ml; +S9-mix: >=100µg/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

see section "Remarks on results"

Remarks on result:

other: Chinese hamster ovary cells

Any other information on results incl. tables

Non-activation assay and incubation for 20 hrs:
Increases in chromosomally aberrant cells ranging between 6.5 % and 11 % cell with aberrations (versus 1.0% of solvent control) or between 4% and 14 %.
Cells with aberrations (versus 2.0 % of solvent control), respectively.
Positive control was functional in each trial
Incubation for 20 hours with metabolic activation:
Increases in the chromosomally aberrant cells ranging between 18 % and 40.5 % cells with aberrations(902 μg/ml was toxic, versus 1.5% of solvent control) and between 17 % and 43 % cells with aberrations (902 μg/ml was toxic, versus 3.0% of solvent control, respectively.
Positive control was functional in each trial .
Incubation for 10 hours in the presence of S9-mix: no significant difference to the
solvent controls; positive controls were functional.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: positive

Executive summary:

p-Cresol induced chromosome aberrations in a test according to OECD TG 473 with Chinese Hamster Ovary cells in the presence and in the absence of a metabolic activation system and tested up to cytotoxicity.