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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:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.
Justification for data waiving:
other:
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2007

Materials and methods

Test guideline
Qualifier:
no guideline followed
Deviations:
not applicable
Principles of method if other than guideline:
The clastogenic activity of zinc chloride was determined by studying chromosome aberrations in human dental pulp cells in vitro, both in the presence and absence of exogenous metabolic activation.
GLP compliance:
no
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Constituent 1
Reference substance name:
Zinc chloride
EC Number:
231-592-0
EC Name:
Zinc chloride
Cas Number:
7646-85-7
IUPAC Name:
zinc dichloride
Details on test material:
- Name of test material (as cited in study report): Zinc chloride
- Analytical purity: 99.9%

Method

Target gene:
Not applicable
Species / strain
Species / strain / cell type:
other: Human dental pulp cells (D824 cells)
Details on mammalian cell type (if applicable):
- Dental pulp tissue obtained from a lower third molar extracted from a 22 years old woman
- Type and identity of media: α-minimum essential medium supplemented with 20 % fetal bovine serum (FBS), 100 µM L-ascorbic acid phosphate magnesium salt n-hydrate, 2 mM L-glutamine, 0.22% NaHCO3 and 100 µg/mL streptomycin
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
5% rat liver postmitochondrial supernatant (PMS) mixture
Test concentrations with justification for top dose:
30, 100 and 300 µM
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO (60mM)
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
None

Migrated to IUCLID6: 50 µM
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium


DURATION
- Preincubation period: Overnight
- Exposure duration: 3 h


NUMBER OF REPLICATIONS: Triplicate


NUMBER OF CELLS EVALUATED: 1.6×10 (5) cells/dish


DETERMINATION OF CYTOTOXICITY: Yes
- Method: The cytotoxicity of the test material was determined as the number of cells treated with the test material relative to the number of cells in the control cultures×100


OTHER EXAMINATIONS:
- Determination of polyploidy: Yes


OTHER: The pH range of the culture media containing the highest concentrations of test agents was approximately 7.2–7.5.
Evaluation criteria:
No data
Statistics:
χ2-test was used to assess the significance of the difference in the incidences of chromosome aberrations between control cultures and cultures treated with test agents. The level of significance in the statistical analysis was determined at p<0.05.

Results and discussion

Test results
Species / strain:
other: Human dental pulp cells (D824 cells)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
No data
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Chromosome aberrations in D824 cells induced by treatment with ZnCl2 for 3 h and 30 h:

Test material

Time

Concentration

Relative cell number (%)

Number of metaphases scored

Type of structural aberrations(a) (%)

Aberrant metaphases (%)

Polyploidy and endoreduplication (%)

ctg

csg

ctb

csb

cte

D

O

F

Control

3 h

0

100

500

0.8

0

0

0

0

0

0

0

0.8

2

Zinc chloride (µM)

30

91

100

0

0

0

0

0

0

0

0

0

0

 

100

74

100

1

0

0

0

0

0

0

0

1

1

 

300

77

100

0

0

0

0

0

0

0

0

0

1

Control

30 h

0

100

500

1

0

0

0

0

0

0

0

1

2

Zinc chloride (µM)

30

85

100

0

0

0

0

0

0

0

0

0

2

 

100

77

100

1

0

0

0

0

0

0

0

1

2

 

300

74

200

3.5

0

0.5

0

0

0

0

0

4

0

a = ctg, chromatid gaps; csg, chromosome gaps; ctb, chromatid breaks; csb, chromosome breaks; cte, chromatid exchanges; D, dicentric chromosomes; O, ring chromosomes; F, fragmentations.

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Under the test conditions, the test material was considered to be non-clastogenic to human dental pulp cells in vitro.
Executive summary:

A study was conducted to investigate the ability of Zinc chloride to induce chromosome aberrations in human dental pulp cells.

Human dental pulp cells (D824 cells) treated with the test material, were evaluated for chromosome aberrations at up to 3 dose levels, together with vehicle and positive controls. Rat liver (5%) post mitochondrial supernatant mixture was used as the exogenous metabolic activator. Ability to induce chromosome aberrations was examined in cells treated with test material for 3 and 30 h.

The test material failed to induce chromosome aberrations in the presence or absence of exogenous metabolic activation. The percentages of cells with polyploid or endoreduplication were not enhanced by test material.

 

Under the test conditions, the test material was considered to be non-clastogenic to human dental pulp cells in vitro.

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