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Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally acceptable scientific standards, well documented and acceptable for assessment.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
In Vitro Electron Microprobe of Carcinogenic Nickel Compound Interaction with Tumor Cells
Author:
Berry JP, Poupon MF, Judde JC, Galle P
Year:
1985
Bibliographic source:
ANNALS OF CLINICAL AND LABORATORY SCIENCE. 15: 109-120
Reference Type:
secondary source
Title:
Unnamed
Year:
1984

Materials and methods

Type of study / information:
Describes the uptake and effects of various nickel compounds in various cells in vitro via electron microscopy (EM).
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Rat rhabdomyosarcoma cells (9-4/0) were incubated with nickel compounds at 20 μg/mL for 24 hours. Cells were washed, fixed, and embedded for electron microscopy. Uptake of various nickel compounds was examined.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): NiO
- Substance type: high temperature green form; inorganic, black nickel oxide (NiO) (Prolabo R. P., Rhone-Poulenc, France)

Results and discussion

Any other information on results incl. tables

The results were mainly descriptive in nature. NiO was present as fine particles in large vacuoles, but other cell structures were unchanged. Llike nickel subsulfide, a dense substance (presumably Ni) accumulated in the membrane of the vacuole.

Applicant's summary and conclusion

Conclusions:
The authors state that the results show that nickel salts (Ni3S2 and NiO) are taken up by phagocytosis, whereas pure nickel and iron salts are not. Thus, there appears to be a certain specificity for the penetration of nickel salts in rhabdomyosarcoma cells. The authors further state that the capacity of nickel salts to be phagocytosed is not related to their carcinogenicity since black NiO is not carcinogenic whereas Ni3S2 can both penetrate cells and induce tumours. This suggests that there is no simple relationship between phagocytosis and carcinogenicity of nickel and its various compounds. In addition, there is no evidence of the dissolution of the intracellular crystalline structures, nor of nickel binding to nuclear structures.
Executive summary:

Berry et al. (1985) described the uptake and effects of NiO, Ni3S2 and colloidal nickel (Ni) in various cells in vitro via electron microscopy (EM). The model systems employed included rat rhabdomyosarcoma cells (9-4/0), murine lymphoma cells (YAC/1), normal human fibroblasts (I.C.I.G.7), and WAG rat peritoneal macrophages and spleen cells. All cells were incubated with nickel at 20 μg/mL for 24 hours. However, results for black NiO were only described in 9-4/0 cells. Following exposure, cells were washed, fixed, and embedded for EM. The results were mainly descriptive in nature. For example, NiO was present as fine particles in large vacuoles, but other cell structures were unchanged. Like nickel subsulfide, a dense substance (presumably nickel) accumulated in the membrane of the vacuole. The authors stated that the results showed that nickel salts (Ni3S2 and NiO) were taken up by phagocytosis, whereas colloidal nickel and iron salts were not. Thus, there appeared to be some specificity for the penetration of nickel salts in rhabdomyosarcoma cells. The authors further stated that the capacity of nickel salts to be phagocytosed was not related to their carcinogenicity (see K3/K4 entry by same author in this IUCLID section) since, according to the authors, black NiO was not reported to be carcinogenic, whereas Ni3S2 had been shown to induce tumors. This suggested to the authors that there is no simple relationship between phagocytosis and carcinogenicity of nickel and its various compounds. In addition, there was no evidence of the dissolution of the intracellular crystalline structures, nor of nickel binding to nuclear structures. Similar (or same) findings were published in Berry et al. (1984). STUDY RATED BY AN INDEPENDENT REVIEWER