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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

additional toxicological information
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Method not standard for determination of effect.
Reason / purpose for cross-reference:
reference to same study

Data source

Reference Type:
The effect of exposure to carcinogenic metals on histone tail modifications and gene expression in human subjects
Arita A, Shamy MY, Chervona Y, Clancy HA, Sun H, Hall MN, Qu Q, Gamble MV, Costa M
Bibliographic source:
J Trace Elem Med Biol. 2012 Jun;26(2-3):174-8. Epub 2012 May 24.

Materials and methods

Type of study / information:
Gene expression
Test guideline
no guideline followed
Principles of method if other than guideline:
Gene expression measured in subjects with occupational exposure to nickel.
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
Nickel sulphide
EC Number:
EC Name:
Nickel sulphide
Cas Number:
Molecular formula:
nickel(2+) sulfanediide
Details on test material:
As cited in paper: subjects with occupational exposure to nickel worked for at least 1 year in the flash smelting workshop of the nickel refinery where sulphidic ores are processed.

Results and discussion

Any other information on results incl. tables

H3K4me3 was found elevated (p= 0.0004) and H3K9me2 was found decreased (p= 0.003) in PBMCs of subjects with occupational exposure to high levels of nickel at a nickel refinery in China when compared to referent subjects (Table 1) [28]. H3K9ac did not vary between the two exposure groups (p= 0.098). In this same study, the intra-individual variance (variance within subjects) in comparison with inter-individual (variance between subjects) of global histone modifications was measured in order to determine if measurements of global histone modifications in PBMCs are fairly constant within subjects over time. The variations of H3K4me3, H3K9ac, and H3K9me2 were substantially larger between subjects relative to the variations within subjects in both groups, resulting in reliability coefficients (an estimate of the consistency of a set of measurements) of 0.60, 0.67, and 0.79 for H3K4me3, H3K9ac, and H3K9me2, respectively, for nickel-exposed subjects and 0.75, 0.74, and 0.97, respectively, for referent subjects (Table 2). These results suggest that global H3K4me3, H3K9ac, and H3K9me2 histone modifications are relatively stable over time in PBMCs from both nickel-exposed and referent subjects.

The gene expression profiles of PBMCs from both exposure groups were analyzed using the Affymetrix Human Gene 1.0 ST Array containing 28,869 well-annotated genes. The gene expression profiles of subjects with occupational exposure to nickel showed a clear separation from referent subjects (unpublished results). A total of 1646 genes in PBMCs from subjects with occupational exposure to high nickel levels displayed a greater than 1.25-fold change difference in all subjects when compared with the expression in PBMCs of referent subjects with low levels of nickel. The numbers of gene entities decreased to 312 and 35 when the cut-off threshold was increased to 1.50 and 2.0-fold difference, respectively (Figure 4A). The gene expression profiles in subjects with occupational exposure to high nickel levels clustered more closely with other subjects having a similar exposure compared to referent subjects. This separation was reported with Principal Component Analysis (PCA) of the microarray data (Figure 4B, red vs blue). A similar separation was observed with hierarchical clustering analysis of genes changed more than 1.5-fold in all subjects with occupational exposure, in which samples were sorted based on the similarity of gene expression (Figure 4C). Among nickel-induced genes, the largest group with respect to both degree of significance and number of genes was regulation of DNA binding and response to wounding in Biological Process. KEGG pathways overrepresented with nickel-induced genes were cytokine-cytokine receptor interaction and Graft-versus-host-disease. Among nickel-repressed genes, the largest group with respect to both degree of significance and number of genes was immune response and defense response in Biological Process and KEGG pathways overrepresented with this list of genes were cytokine-cytokine receptor interaction and chemokine signaling pathway (unpublished results).

Applicant's summary and conclusion

Executive summary: