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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
Study period:
26 October to 03 December 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study undertaken to GLP to internationally accepted guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2009

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Notification of testing methods relating to the new chemical substances (Notification No. 1121002 of JMHLW, No.2 of JMETI, No. 031121002 of JMOE on November 21,2003).
Deviations:
not specified
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Constituent 1
Reference substance name:
Phenylphosphonic acid, zinc salt
IUPAC Name:
Phenylphosphonic acid, zinc salt
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Phenylphosphonic acid, zinc salt
- Substance type: inorganic
- Physical state: White powder
- Analytical purity: > 99%
- Purity test date:
- Lot/batch No.: 060725
- Stability under test conditions: stable in room temperature
- Storage condition of test material: in room temperature, shield from light

Method

Target gene:
No specific target gene as study is exploring general clastogenicity.
Species / strain
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
Negative controls - 0.015, 0.023, 0.035, 0.052 and 0.078 mg/ml
Positive control - 0.001 mg/l
Vehicle / solvent:
- Solvent used: CMC (carboxymethyl cellulose)
- Justification for choice of solvent/vehicle:
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
yes
Positive controls:
yes
Positive control substance:
other: 1%water solution of carboxymethy1cellulose sodium salt
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Positive controls:
yes
Positive control substance:
mitomycin C
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation);

DURATION
- Preincubation period:
- Exposure duration: 6 hours
- Expression time (cells in growth medium): 3 days
- Selection time (if incubation with a selection agent):
- Fixation time (start of exposure up to fixation or harvest of cells):

SELECTION AGENT (mutation assays):

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: 100 per rep

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

OTHER EXAMINATIONS:
- Determination of polyploidy: microscopic examination.
- Determination of endoreplication: microscopic examination.
- Other:

Evaluation criteria:
The test result was judged by comparing frequency of aberrant cells at each dose levels treated with the test substance in each structural and numerical chromosome aberration with the following evaluation criteria. The test substance was judged positive for c1astogenicity when either 10% or more increase in the frequency of the chromosome aberration cells with dose-relativity or 10% or more increase in the frequency of the chromosome aberration cells with reappearance was observed. The test substance was judged positive for clastogenicity also in case the test results with reappearance were observed when the positive result was inconclusive. The dose to induce aberrant cells in 20% of the analyzed cell (D20;mg/ml) was calculated when the test substance was judged positive for clastogenicity.

Evaluation criteria:

Negative (-) less than 5%
Inconclusive (±) from 5 to less than 10%
Positive (+) 10% or more
Statistics:
None

Results and discussion

Test resultsopen allclose all
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Untreated negative controls validity:
valid
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Positive controls validity:
valid
Remarks on result:
other: other: 1% carboxymethyl cellulose sodium salt
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive

It is concluded that PPA-Zn is clastogenic, under the conditions of this study.

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