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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:
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:
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

Reference
Name:
Unnamed
Type:
Constituent
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)
Controlsopen allclose all
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
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.