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Toxicological information

Genetic toxicity: in vitro

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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

Constituent 1
Chemical structure
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.

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