Copper hydroxide nitrate (Cu2(OH)3(NO3))

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

other: scientific overview

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Overview includes Copper metal and other Copper compounds.

Data source

Reference

Reference Type:

publication

Title:

Copper hypersensitivity: dermatologic aspects

Author:

Hostynek,J.J. and Maibach, H. I

Year:

2004

Bibliographic source:

Dermatologic Therapy, Vol. 17, 328-333 (2004)

Materials and methods

Type of sensitisation studied:

skin

Study type:

other: overview of immune reactions

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The intent of this overview is to establish a synopsis of dermatologic immune reactions ascribed to copper exposure and to examine the criteria
applied in such diagnosis, as not always has such causation been demonstrated unequivocally. This review discusses the metallurgy of copper, predictive, and diagnostic tests; it describes the types of immune reactions, the potential for the copper ion to act as sensitizer, followed by critical examination of literature reports applying strict diagnostic criteria, with consideration given to a number of confounding factors, which may have led earlier investigators to the erroneous interpretation of signs, symptoms or test results.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Copper and Copper compounds

IUPAC Name:

Copper and Copper compounds

Method

Type of population:

occupational

Ethical approval:

not specified

Results and discussion

Results of examinations:

Reports of immune reactions of both the immediate and delayed types due to cutaneous or systemic exposure to copper have been reviewed, in the endeavor to draw a comprehensive profile of the immunogenic potential of that metal and its compounds. The metal’s immunotoxic potential is also briefly reviewed. In principle, as noted for other transition metals, the electropositive copper ion is potentially immunogenic due to its ability to diffuse through biological membranes to form complexes in contact with tissue protein. Based on predictive guinea pig test and the local lymph node assay (LLNA), copper has a low sensitization potential. Reports of immune reactions to copper include immunologic contact urticaria (ICU), allergic contact dermatitis (ACD), systemic allergic reactions (SAR) and contact stomatitis (STO), but considering the widespread use of copper IUDs and the importance of copper in coinage, items of personal adornment and industry, unambiguous reports of sensitization to the metal are extremely rare, and even fewer are the cases, which appear clinically relevant. Reports of immune reactions to copper mainly describe systemic exposure from intrauterine devices and prosthetic materials in dentistry, implicitly excluding induction of the hypersensitivity from contact with the skin as a risk factor.

Applicant's summary and conclusion

Executive summary:

Reports of immune reactions of both the immediate and delayed types due to cutaneous or systemic exposure to copper have been reviewed, in the endeavor to draw a comprehensive profile of the immunogenic potential of that metal and its compounds. The metal’s immunotoxic potential is also briefly reviewed. In principle, as noted for other transition metals, the electropositive copper ion is potentially immunogenic due to its ability to diffuse through biological membranes to form complexes in contact with tissue protein. Based on predictive guinea pig test and the local lymph node assay (LLNA), copper has a low sensitization potential. Reports of immune reactions to copper include immunologic contact urticaria (ICU), allergic contact dermatitis (ACD), systemic allergic reactions (SAR) and contact stomatitis (STO), but considering the widespread use of copper IUDs and the importance of copper in coinage, items of personal adornment and industry, unambiguous reports of sensitization to the metal are extremely rare, and even fewer are the cases, which appear clinically relevant. Reports of immune reactions to copper mainly describe systemic exposure from intrauterine devices and prosthetic materials in dentistry, implicitly excluding induction of the hypersensitivity from contact with the skin as a risk factor.