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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Documentation insufficient for assessment. Sex and strain of test animals not specified. No information on methods and materials is provided. Small test group sizes. System of classification not reported. No statistical analysis of the data. Unclear what the dose level actually was; reported as 2.5-5.0 mg/rat. The chromosomal aberrations test appears to be positive, as there was a 14-fold increase in the percentage of aberrations/cell in the pure nickel group (8.5%) vs. the control group (0.6%). However, no statistical analysis of the data was performed. This test should be considered ambiguous, based on no statistical analysis of the data, single exposure, inappropriate sampling time (1-1.5 months), and no information on methods or materials. The micronucleus test appears to be positive (2-fold increase over negative control), but should be considered ambiguous. No statistical analysis of the data, single exposure, small group size, no information slides were blind coded or read, inappropriate sampling time, and no information on methods or materials. The SCE test appears to be negative (results for pure nickel are similar to the control group), but should be considered ambiguous. No statistical analysis of the data, single exposure, small group size, inappropriate sampling time, and no information on methods or materials.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Study mutagenesis and carcinogenesis of productive nickel dust. Mutation and the Environment. Part E. Environmental Genotoxicity, Risk, and Modulation.
Author:
Zhong, B.-Z., Z.-Q. Li, G.-Y. Ma, and B.-S. Wang.
Year:
1990
Bibliographic source:
Proceedings of the Fifth International Conference on Environmental Mutagens. Pages 41-46.

Materials and methods

Test guideline
Guideline:
other: not reported
GLP compliance:
not specified
Type of assay:
other: Chromosomal aberrations, Micronucleus assay, Sister Chromatid Exchange

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
other: intratracheal instillation
Details on exposure:
Rats were given a single dose of 2.5-5.0 mg Ni/rat by intratracheal instillation and observed for 1-1.5 months.  

Chromosomal aberrations test: Treatment groups: control (n=9), mineral dressing (3.45% Ni, 6.01% SiO2;  
n=7), smelting (22.72% Ni, 25.61% SiO2; n=7), and pure (99.9% nickel;  n=7).  95% of the particles in the powder were <5 um.

Micronucleus test: Treatment groups: control (n=3), mineral dressing (n=4), smelting (n=3), 
pure (n=2), and positive control (cyclophosphamide; n=2).
Duration of treatment / exposure:
1-1.5 months
Doses / concentrations
Remarks:
Doses / Concentrations:
2.5-5.0 mg Ni/rat
Basis:

Results and discussion

Test results
Sex:
not specified
Additional information on results:
Chromosomal aberrations test:  The number of cells examined varied by treatment group, but was approximately 400.  
Chromatid gaps and breaks, fragments, and reciprocal translocations recorded.
Control group = 0.6% aberrations/cell Mineral dressing = 5.3% aberrations/cell
Smelting = 7.4% aberrations/cell Pure nickel = 8.5% aberrations/cell

Micronucleus test: The number of cells examined varied by treatment group, but was  
approximately 3000. Micronucleated cells reported. Control group = 3.6% Mineral dressing = 2.0% Smelting = 10.0%  Pure nickel = 8.0% 
Positive control = 20.0% Sister Chromatid Exchange (in bone marrow): The number of cells examined varied by treatment group, but was 13-20.   

Frequencies of SCEs/cell and SCEs/chromosome reported. Control: 5.46% cells with SCEs, 1.28% chromosomes 
with SCEs Mineral dressing: 5.85% cells with SCEs, 1.10% chromosomes with SCEs Smelting: 6.10% cells with SCEs, 1.08% chromosomes 
with SCEs Pure nickel: 6.20% cells with SCEs, 1.10% chromosomes with SCEs

Applicant's summary and conclusion

Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER.