Nickel dichloride

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No information on replication. Purity of test substance not reported.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity of various chemicals including nickel and cobalt compounds in cultured mouse FM3A cells.

Author:

Morita, H., M. Umeda, and H.I. Ogawa.

Year:

1991

Bibliographic source:

Mutation Research. 261:131-137.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosomal Aberration Test)

Version / remarks:

Nakamura et al.

Principles of method if other than guideline:

Year: 1983 (unclear if "Year of test guideline" or "Year of study completion".)

GLP compliance:

not specified

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Nickel dichloride

EC Number:

231-743-0

EC Name:

Nickel dichloride

Cas Number:

7718-54-9

Molecular formula:

Cl2Ni

IUPAC Name:

nickel(2+) dichloride

Details on test material:

- Reported as NiCl-6H20 (7791-20-0)
- Source: Wako Pure Chemical Industries.

Method

Species / strain

Species / strain / cell type:

other: Mouse mammary carcinoma cells (FM3A)

Metabolic activation:

with and without

Metabolic activation system:

2.5% S15

Test concentrations with justification for top dose:

0, 1.0 x 10e-4, 2.0 x 10e-4, 3.0 x 10e-4, and 4.0 x 10e-4 M

Controls

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Details on test system and experimental conditions:

FM3A cells were exposed to hypoxanthine, aminopterin, and thymidine for 1 week prior to use in the mutation assay, 
then cultured in Eagle's minimum essential medium supplemented with 3% fetal bovine serum, 1%  non-essential 
amino acids, hypoxanthine, and thymidine.  Cultured FM3A cells were then exposed to various concentrations of 
NiCl2 for 3-48  hours, washed in Hank's balanced salt solution, and then cultured for an additional 7 days.  
Then, 2 x 10e6 cells were inoculated into 40 ml of  selective agar medium containing 10 ug/ml 6-thioguanine (6-TG) and cultured for 14 days.  
The number of 6TG colonies were counted and  mutation frequency (per 10e6 surviving cells) was determined.    

Statistics:

Statistical analysis was performed using the Welch test. 

Results and discussion

Test results

Species / strain:

mammalian cell line, other: Mouse mammary carcinoma cells (FM3A)

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Additional information on results:

There was a concentration-dependent decrease in percent cell survival following treatment.  
At 0 M treatment, survival was 76%, with 100%  relative plating efficiencies.  
This decreased to 7% survival with relative plating efficiencies of 9% after treatment at 4.0 x 10e-4 M.   
The number of mutants per 10e6 surviving cells increased in a concentration-dependent manner, 
with a significant (P<0.05) increase seen at 4 x 10e-4 M.

Applicant's summary and conclusion

Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER.