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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: OECD guideline and GLP compliant study, completely adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: flakes
Details on test material:
- Physical state: white flake or powder
- Analytical purity: 99.9%
- Purity test date: 17 July 2012
- Lot/batch No.: 20522
- Expiration date of the lot/batch: 3 July 2013
- Storage condition of test material: ambient temperature
:

Method

Species / strain
Species / strain / cell type:
lymphocytes:
Metabolic activation:
with and without
Metabolic activation system:
Arochlor 1254 treated rat liver S9
Test concentrations with justification for top dose:
8.75, 17.5, 35, 70 and 90 ug/mL both in presence and absence of S9
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
cyclophosphamide (40 ug/mL +S9, mitomycin-C (0.3 ug/mL) -S9
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: 48 hours
- Exposure duration: Phases I and III, 3 hours 30 mins; Phase II, 24 hours
Evaluation criteria:
The test was considered to have shown clastogenic activity if the following criteria were met:
1. Increased frequency of metaphases with aberrant chromosomes observed at one or more test concentrations (concentration-related).
2. Increases were reproducible between replicate cultures and between tests (when treatment conditions are the same).
3. Increases in percent aberrant metaphases were statistically significant.
4. Increases in percent aberrant metaphases were not associated with large changes in pH and osmolality of the treatment medium.
Historical control data from the laboratory were also considered in the evaluation.
An increase in the number of polyploidy cells indicates that the test item has the potential to inhibit mitotic processes and to induce numerical chromosome aberration. Biological relevance was considered first. The test item was considered non-mutagenic if the results did not meet the above-mentioned criteria.
Statistics:
Gaps and polyploidy were not included in the calculation of total aberration frequency. Data on mitotic index, polyploidy and percent aberrant cells were subjected to Bartlett's test to meet the homogeneity of variance before conducting Analysis of Variance (ANOVA) and Dunnett's t-test (Gad and Weil, 1994). Where the data did not meet the homogeneity of variance, Student's t-test was performed to determine the level of significance between the negative control and three selected test concentrations (selected based on the mitotic index data) and positive controls.

Results and discussion

Test results
Species / strain:
lymphocytes:
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
p-PP did not show any potential to induce chromosomal aberrations, both in the absence and presence (2 and 4% v/v S9) of metbolic activation system under the present experimental conditions.
Executive summary:

p-PP did not show any potential to induce chromosomal aberrations, both in the absence and presence (2 and 4% v/v S9) of metbolic activation system under the present experimental conditions.