Nickel oxalate

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:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Meets generally accepted scientific standards with acceptable restrictions. The study lacks information on replication. No positive control group included. No information on a vehicle (acetone) control. Only a single dose level used for chromosome aberration tests; no dose-response can be determined. No statistical evaluation of the data. Non-standard cell line used (embryo cells).

Data source

Reference

Reference Type:

publication

Title:

Induction by inorganic metal salts of sister chromatid exchange and aberrations in human and Syrian hamster cell strains.

Author:

Larramendy ML, Popescu NC, and DiPaolo JA

Year:

1981

Bibliographic source:

Environmental Mutagenesis, 2: 597-606.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

No standard guideline followed. Sister chromatid exchange assay and Chromosomal aberration test.

GLP compliance:

not specified

Type of assay:

other: Sister chromatid exchange assay and Chromosomal aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Nickel sulphate hexahydrate

IUPAC Name:

Nickel sulphate hexahydrate

Constituent 2

Reference substance name:

10101-97-0

EC Number:

600-152-3

Cas Number:

10101-97-0

IUPAC Name:

10101-97-0

Details on test material:

- Name of test material (as cited in study report): Nickel sulphate hexahydrate (10101-97-0)
- Molecular formula (if other than submission substance): NiO4S.6H2O
- Molecular weight (if other than submission substance): 333.083
- Smiles notation (if other than submission substance): S(=O)(=O)([O-])[O-].[Ni+2]
- InChl (if other than submission substance): InChI=1/Ni.H2O4S/c;1-5(2,3)4/h;(H2,1,2,3,4)/q+2;/p-2
- Purity: 97%
- Other details not reported or not applicable

Method

Target gene:

Not applicable

Species / strain

Species / strain / cell type:

other: Syrian hamster embryo cells and human lymphocyte cultures

Details on mammalian cell type (if applicable):

- Type and identity of media: Hamster embryo cells were collected after trypsinization of the embryos minus the liver and plated (density of 10e7 cells/100 mm dish) in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum.

Additional strain / cell type characteristics:

not specified

Metabolic activation:

without

Test concentrations with justification for top dose:

0, 1.0, 2.5, 5.0 ug/mL

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Acetone

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

Sister chromatid exchange (SCE) and chromosomal aberration tests were conducted with Syrian hamster embryo cells and human lymphocyte 
cultures. Hamster embryo cells were collected after trypsinization of the embryos minus the liver and plated (density of 10E+07 cells/100 mm dish) 
in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum.  

DURATION
Hamster embryo cells were incubated at 37 deg. C in an 11% CO2 air incubator. 24 hours later, monolayer cultures (10E+06 cells/100 mm dish) were treated with nickel sulfate (prepared in acetone) and 10 ug BrdUrd/mL medium and incubated for 24 hours.  Four hours prior to  harvest, cells were treated with Colcemid (0.13 ug/mL), then collected, centrifuged, suspended in KCl, and fixed in methanol:glacial acetic acid.   

For SCE tests, slides were prepared and stained with 4% Giemsa in Gurr's buffer solution. A minimum of 30 metaphases were scored.  For 
chromosome aberration tests, preparations were air dried and stained with Gurr's buffer solution and 5% Giemsa.  At least 125 metaphases were 
examined.  Aberrations were scored per the International system for human cytogenetic nomenclature (1978).

For chromosome aberration tests, preparations were air dried and stained with Gurr's buffer solution and 5% Giemsa.  At least 125 metaphases 
were examined. 

Evaluation criteria:

Aberrations were scored per the International system for human cytogeneic nomenclature (1978).

Statistics:

no data

Results and discussion

Test results

Species / strain:

other: Syrian hamster embryo cells and human lymphocyte cultures

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not examined

Untreated negative controls validity:

valid

Positive controls validity:

not examined

Additional information on results:

NiSO4 increased the frequency of SCEs in hamster embryo cells in a dose dependent manner:

Hamster embryo cells [frequency of SCEs/metaphase (standard error)]:
BrdUrd control: 11.55 (0.84)
1.0 ug/ml: 15.95 (0.92)
2.5 ug/ml: 17.25 (1.44)
5.0 ug/ml: 21.25 (1.13)

NiSO4 also increased the number of chromosomal aberrations relative to the control:

Hamster embryo cells [percent cells with aberrations and mean aberrations/metaphase (standard error)]:
Control: 1.50%, 0.01 (0.01)
5.0 ug/ml: 16.50%, 0.16 (0.03) (Chromosomal aberrations noted in embryo cells included gaps, breaks, exchanges, and minutes)

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

NiSO4 increased the frequency of SCEs in human lymphocytes and hamster embryo cells in a dose dependent manner:

Human lymphocytes [frequency of SCEs/metaphase (standard error)]:
BrdUrd control: 11.30 (0.60)
2.5 ug/ml: 17.20 (0.90)
5.0 ug/ml: 18.95 (1.52)

Hamster embryo cells [frequency of SCEs/metaphase (standard error)]:
BrdUrd control: 11.55 (0.84)
1.0 ug/ml: 15.95 (0.92)
2.5 ug/ml: 17.25 (1.44)
5.0 ug/ml: 21.25 (1.13)

NiSO4 also increased the number of chromosomal aberrations relative to the control:

Human lymphocytes [percent cells with aberrations and mean aberrations/metaphase (standard error)]:
Control: 1.50%, 0.01 (0.01)
5.0 ug/ml: 11.20%, 0.07 (0.02)
(Chromosomal aberrations noted in human lymphocytes included gaps, breaks, rings, and minutes)

Hamster embryo cells [percent cells with aberrations and mean aberrations/metaphase (standard error)]:
Control: 1.50%, 0.01 (0.01)
5.0 ug/ml: 16.50%, 0.16 (0.03)
(Chromosomal aberrations noted in embryo cells included gaps, breaks, exchanges, and minutes)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive

Nickel sulphate induced genotoxicity in rat lung tissue after 90 day inhalation exposures of >=1.0 mg NiSO4/m3.