Registration Dossier

Administrative data

Endpoint:
additional toxicological information
Type of information:
other: K3/K4 Studies
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
other: K3/K4
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Though K3/K4 studies were evaluated and scored for reliability, robust summaries and unique IUCLID endpoint study records were not developed for such. Rather, a summary table of K3 and K4 studies evaluated and scored for this endpoint is provided in the field, "Any other information on results and tables" for informational purposes.
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Th2 immune response plays a critical role in the development of nickel-induced allergic contact dermatitis
Author:
Niiyama S, Tamauchi H, Amoh Y, Terashima M, Matsumura Y, Kanoh M, Habu S, Komotori J, Katsuoka K.
Year:
2010
Bibliographic source:
Int Arch Allergy Immunol. 153(3):303-14.
Reference Type:
publication
Title:
New views on the hypothesis of respiratory cancer risk from soluble nickel exposure; and reconsideration of this risk's historical sources in nickel refineries
Author:
Heller JG, Thornhill PG, and Conard BR.
Year:
2009
Bibliographic source:
J Occ Med Toxicol 4:23.

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Nickel nitrate (Niiyama et al. 2010), soluble nickel (Heller et al. 2009)
- Molecular formula (if other than submission substance): Ni(NO3)2 (Niiyama et al. 2010)

Results and discussion

Any other information on results incl. tables

 Data Source  Study Design and Findings  Reliability
 Niiyama S, Tamauchi H, Amoh Y, Terashima M, Matsumura Y, Kanoh M, Habu S, Komotori J, Katsuoka K. Th2 immune response plays a critical role in the development of nickel-induced allergic contact dermatitis. Int Arch Allergy Immunol. 2010 153(3):303-14.  The authors investigated the involvement of Th2 cytokines in Ni-induce contact hypersensitivity reaction using GATA-3 transgenic (Tg) mice. A nickel-titanium alloy was used as the sensitizing agent and a Ni(NO3)2 solution was used to challenge one month later. Serum IgE levels and skin tissue levels of IL-4 were elevated in Ni-Ti-sensitized GATA-3 Tg mice. The results suggested that Th2-type immune reactions might play an important role in Ni-induced contact hypersensitivity reactions.  K4: Mechanistic important for evaluation but not a direct measure of toxicity.
 Heller JG, Thornhill PG, and Conard BR. 2009. New views on the hypothesis of respiratory cancer risk from soluble nickel exposure; and reconsideration of this risk's historical sources in nickel refineries. J Occ Med Toxicol 4:23.  The authors reviewed the published, file and archival evidence covering the pertinent epidemiology, biostatistics, confounding factors, toxicology, industrial hygiene and exposure factors, and other exposures to evaluate the soluble nickel carcinogenicity hypothesis, and the likely contribution of a competing workplace carcinogen (arsenic) on sulphidic and oxidic nickel risk estimates. Based on a failure to accurately identify the source(s) of observed lung cancer risk in at least one nickel refinery, together with the negative long-term animal inhalation studies on soluble nickel and other toxicological evidence, the authors concluded that the designation of soluble nickel as carcinogenic should be reconsidered, and that the true causes of historical lung cancer risk at certain nickel refineries lie in other exposures, including insoluble nickel compounds, arsenic, sulphuric acid mists and smoking.  K4: Secondary literature source (review); mechanistic, risk assessment, or other endpoint important for evaluation but not a direct measure of toxicity.

Applicant's summary and conclusion

Executive summary:

Study rated by an independent reviewer.