Biphenyl-4,4'-diol

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:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted in accordance with OECD TG 473 and GLP

Data source

Reference

Reference Type:

secondary source

Title:

Unnamed

Year:

2004

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:

Test method was in accordance with the OECD 473 Test Guideline and the Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan)

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Biphenyl-4,4'-diol

EC Number:

202-200-5

EC Name:

Biphenyl-4,4'-diol

Cas Number:

92-88-6

Molecular formula:

C12H10O2

IUPAC Name:

[1,1'-biphenyl]-4,4'-diol

Details on test material:

No further details.

Specific details on test material used for the study:

- Analytical purity:99.96

Method

Target gene:

Chromosomal aberrations in Chinese hamster lung cells (CHL/u)

Species / strain

Species / strain / cell type:

other: Chinese hamster lung cells (CHL/u)

Metabolic activation:

with and without

Metabolic activation system:

Rat liver induced with phenobarbital and 5,6-benzoflavone S-9

Test concentrations with justification for top dose:

0.03; 0.06 and 0.12 mg/mL with and without S-9

Vehicle / solvent:

dimethyl sulphoxide (DMSO)

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

mitomycin C

Remarks:

without S-9

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

with S-9

Details on test system and experimental conditions:

No further information

Evaluation criteria:

According to criteria set out in OECD Test Guidelines No 473 and Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan)

Statistics:

Chromosome analysis conducted using one-sided Fisher's exact probability test. Significant results tabulated for p<0.01

Results and discussion

Test results

Key result

Species / strain:

other: chinese hamster lungs cells (CHL/U)

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

clastogenicity and polyploidy with or without metabolic activation at 0.03 or 0.06 mg/mL and above

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

A significant increase in frequency of cells with chromosomal aberrations was noted at all three treatments, 0.03, 0.06, 0.12 mg/mL, without metabolic activation and in the two higher dose levels with metabolic activation (Chromosome analysis conducted using one-sided Fisher's exact probability test. Significant results tabulated for p<0.01). A significant increase in polyploidy was also observed at 0.06 or 0.12 mg/mL, with and without metabolic activation.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: positive

A statistically significant (p<0.01: Fisher's Exact Test) increase in frequency of cells with chromosomal aberrations was noted at all three treatments, 0.03, 0.06, 0.12 mg/mL, without metabolic activation and in the two higher dose levels with metabolic activation.
A statistically significant increase in polyploidy (p<0.01: Fisher's Exact Test) was also observed at 0.06 or 0.12 mg/mL, with and without metabolic activation.

A positive response for induction of chromosomal aberrations was observed in chinese hamster lung cells treatd with 4,4'-biphenyldiol, typically at dose levels of 0.06 mg/mL and above, the response was typified by clastogenic and polyploidy effects.

Executive summary:

The cytogenicity of biphenyl-4,4'-diol (biphenol) was investigated in Chinese Hamster cells (CHL/IU) cells in vitro. A significant (p<0.01) increase in frequency of cells with chromosomal aberrations was noted at all three treatments, 0.03, 0.06, 0.12 mg/mL, without metabolic activation and in the two higher dose levels with metabolic activation. A significant increase in polyploidy was also observed at 0.06 or 0.12 mg/mL, with and without metabolic activation.