Nickel dihydroxide

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:

disregarded due to major methodological deficiencies

Study period:

Not Reported

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment

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:

Effects of nickel administration on the synthesis of nucleic acids by nuclei isolated from rat liver

Author:

Ono H, Matsui H, Ono T, Wada O

Year:

1979

Bibliographic source:

J of Toxicol Sci. 4(3):287

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Incorporation of3H-dTTP and 3H-UTP by nuclei isolated from normal and regenerating liver of nickel administered rat was compared with those of corresponding controls. The contents of nickel in the nuclei and nucleioli were also determined in an effort to approach the mechanism of carcinogenic action by metals.

GLP compliance:

not specified

Type of assay:

other: synthesis of nucleic acids

Test material

Test material information

Constituent 1

Reference substance name:

Nickel dihydroxide

EC Number:

235-008-5

EC Name:

Nickel dihydroxide

Cas Number:

12054-48-7

Molecular formula:

Ni(OH)2

IUPAC Name:

nickel(2+) dihydroxide

Details on test material:

- Name of test material (as cited in study report): Ni(OH)2

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 100 g

Administration / exposure

Route of administration:

subcutaneous

Vehicle:

sesame oil

Details on exposure:

40 mg of Ni(OH)2 suspended in sesame oil was injected subcutaneously

Duration of treatment / exposure:

single administration

Frequency of treatment:

Not Applicable

Post exposure period:

up to 13 weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
40 mg
Basis:
other: injection

No. of animals per sex per dose:

Not Reported

Control animals:

other: corresponding controls referenced but no information provided

Positive control(s):

Not Applicable

Examinations

Tissues and cell types examined:

Incorporation of 3H-dTTP and 3H-DUTP by nuclei isolated from normal and regenerating liver of nickel administered rat was compared with those of corresponding controls. The contents of nickel in the nuclei and nucleioli were also determined, including a digestion assay to determine binding properties.

Details of tissue and slide preparation:

Not Reported

Evaluation criteria:

Comparison to concurrent controls

Statistics:

Not Reported

Results and discussion

Test results

Sex:

male

Genotoxicity:

other: suggestive

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

The synthesis of nucleic acids of normal and regenerating liver was affected after single administration of nickel and the adverse effects continued for 10-13 weeks, when the contents of nickel in the liver returned to a control level.

The contents of nickel in the nuclei and nucleoli per g of tissue was not increased by the administration of nickel throughout the experiment. However, the content of nickel n the nucleioli expressed as per mg protein, DNA or RNA, respectively, was about two times more than the control for 3 days to 11 weeks after administration.

Digestion of nucleioli by RNase and DNase indicated that almost nickel in the nucleoli bound to sites indigestible to RNase or DNase.

Any other information on results incl. tables

Not Applicable

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: suggestive of genotoxicity (as stated by authors)
The authors conclude that results might suggest that nickel affects directly the structure or function of the nucleoli, or indirectly through the change of binding site of nickel in the nucleoli to alter the ability of nucleic acids synthesis in the nuclei. It may not also be ruled out the possibility that nickel in the cytoplasm affects the biological activity of the nuclei.

Executive summary:

Study rated by an independent reviewer.