Nickel monoxide

Genetic toxicity: in vivo

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for publication.

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:

Distinct Mechanisms of Oxidative DNA Damage Induced by Carcinogenic Nickel Subsulfide and Nickel Oxides

Author:

Kawanishi S, Oikawa S, Inoue S, Nishino K

Year:

2002

Bibliographic source:

Environmental Health Perspectives. 110 (S5): 789-791

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

DNA damage was evaluated in cultured cells and in lungs of rats; no standardized guidelines were followed.

GLP compliance:

not specified

Type of assay:

other: 8-hydroxydeoxyguanosine

Test material

Test material information

Constituent 1

Reference substance name:

Nickel monoxide

EC Number:

215-215-7

EC Name:

Nickel monoxide

Cas Number:

1313-99-1

Molecular formula:

NiO

IUPAC Name:

oxonickel

Details on test material:

- Name of test material (as cited in study report): NiO
- Substance type: green and black

Test animals

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

Not reported.

Administration / exposure

Route of administration:

intratracheal

Vehicle:

- Vehicle(s)/solvent(s) used: no data

Details on exposure:

Noty applicable.

Duration of treatment / exposure:

acute

Frequency of treatment:

single

Post exposure period:

48 hr

Doses / concentrations

Remarks:

Doses / Concentrations:
1 mg
Basis:
nominal conc.

No. of animals per sex per dose:

4 to 9

Control animals:

yes

Positive control(s):

Not applicable.

Examinations

Tissues and cell types examined:

Lung tissue

Details of tissue and slide preparation:

Not applicable.


METHOD OF ANALYSIS:
Defrosted lungs were gently homogenized in 3 mL of PBS. The nuclei were obtained by centrifugation at 1,750×g for 5 min. For isolation of DNA, nucleic acid extraction system (model 341; Gene Pure, Applied Biosystems, Foster City, CA, USA) was used. DNA isolation was performed under helium. The content of 8-OH-dG was determined after enzyme digestion of DNA using an HPLC–ECD.

Evaluation criteria:

Not reported.

Statistics:

Not reported.

Results and discussion

Test results

Sex:

not specified

Genotoxicity:

positive

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

not examined

Additional information on results:

see Table.

Any other information on results incl. tables

	8 -OH-dG/dG x 10^5 in Rat Lung
	Mean	SD	N
Control	0.78	0.51	9
NiO black	2.33*	0.55	4
NiO green	2.33*	0.61	5

*, p < 0.01

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): positive
The authors posited that the in vivo damage could be explained by evidence that NiO causes inflammation and that inflammation subsequently causes the DNA damage.

Executive summary:

Kawanishi et al. (2002) measured 8-hydroxydeoxyguanosine (8-OH-dG) adducts in lung tissues of Wistar rats sacrificed 48 hours after exposure to 1 mg of various nickel compounds, including both black and green nickel oxides, via intratracheal instillation. Lungs were harvested, homogenized, and nuclei isolated by centrifugation. DNA was isolated and analyzed for 8-OH-dG by enzyme digestion and HPLC-ECD (high performance liquid chromatography-electrochemical detection). Relative to control cells, both black and green NiO increased DNA damage from approximately 0.78 to 2.33 8-OH-dG/dG×105. In contrast, neither NiO induced 8-OH-dG damage in vitro (see the Genetic Toxicity In Vitro section). The authors posited that the in vivo damage could be explained by previous studies that indicate NiO causes inflammation and that inflammation subsequently causes the DNA damage. However, the findings of this study are difficult to interpret given that only a single dose was administered via a non-environmentally relevant route and only a single species was evaluated. STUDY RATED BY AN INDEPENDENT REVIEWER