[carbonato(2-)]tetrahydroxytrinickel

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Meets generally accepted scientific methods with sufficient documentation. Relevant exposure to submission substance, adequate detail on study methods. (A detailed description of the scoring criteria can be found in the .pdf document attached to the 'Sensitisation Scoring Rationale Document' record at the beginning of Section 7.10.4). (reported T scores and M values may be incorrect (e.g., the T score [i.e., sum of all scored reactions] for the Group I nitrate patients should be 49, but is reported as 94).

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:

The influence exerted by cutaneous ligands in subjects reacting to nickel sulfate alone and in those reacting to more transition metals.

Author:

Santucci, B., C. Cannistraci, A. Cristaudo, E. Camera, and M. Picardo.

Year:

1998

Bibliographic source:

Exp. Dermatol. 7:162-167.

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

No standard guideline followed. Test methods provided in the following sections.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Nickel dichloride

EC Number:

231-743-0

EC Name:

Nickel dichloride

Cas Number:

7718-54-9

Molecular formula:

Cl2Ni

IUPAC Name:

Nickel (II) chloride

Details on test material:

- Name of test material (as cited in study report): Nickel chloride hexahydrate
- Molecular formula (if other than submission substance): not different than submission substance
- Molecular weight (if other than submission substance): not different than submission substance
- Smiles notation (if other than submission substance): not different than submission substance
- InChl (if other than submission substance): not different than submission substance
- Structural formula attached as image file (if other than submission substance): not different than submission substance
- Substance type: Pure product
- Physical state: Liquid
- Analytical purity: 98% (BDH) NiCl2, 99% (Erba) NiSO4 hexahydrate, >99 (Aldrich) Nickel nitrate hexahydrate,
>99% (Flutka) nickel acetate tetrahydrate
- Other details on test material not reported or not applicable

Method

Type of population:

general

Ethical approval:

not specified

Subjects:

- Number of subjects exposed: 151
- Other details not reported

Clinical history:

- History of allergy or casuistics for study subject or populations: no history of atopy
- Other: Test subjects in this study included individuals who previously gave a positive
patch test reaction to nickel sulphate 5% petrolatum (pet) alone, and individuals who gave a positive patch test reaction to nickel sulphate
5% pet + at least one other transition metal (i.e., cobalt chloride 1% pet, palladium chloride 1% pet, or potassium dichloride 0.5% pet).
- Other details not reported

Controls:

not reported

Route of administration:

dermal

Details on study design:

TYPE OF TEST(S) USED: patch test (epicutaneous test)

ADMINISTRATION
- Type of application: occlusive
Group I = 71
Group II = 30
Group III = 25
Group IV = 25
- Description of patch: Finn chambers with scanpor tape
- Vehicle / solvent: petrolatum
- Concentrations: Group I and II: nickel chloride (0.1 M, pH 5.3)
Group III and IV: nickel chloride (0.025 M, pH 5.3)
- Volume applied: not reported
- Testing/scoring schedule: read at 48 and 96 hrs
- Removal of test substance: not reported
- Other:
Group I (71 individuals who previously reacted to nickel sulphate alone) and Group II (30 individuals who previously reacted to nickel sulphate
plus other metals) test subjects were contemporaneously re-patch tested to 200 ug Ni2+ contained in 20 mg of nickel sulphate 5% pet,
and to 47 ug Ni2+ contained in 8 ul of 4 aqueous solutions of nickel salts, i.e., nickel sulphate (0.1 M, pH 4.6), nickel chloride (0.1 M, pH 5.3),
nickel nitrate (0.1 M, pH 6.7), and nickel acetate (0.1 M, pH 7.3), respectively.

Group III (25 individuals who had reacted to nickel sulphate alone) and Group IV (25 individuals who had reacted to nickel sulphate plus
other metals) test subjects were re-patch tested respectively to 200 ug Ni2+ contained in 20 mg of nickel sulphate 5% pet, and to 12 ug
Ni2+ contained in 8 ul of 4 aqueous solutions of nickel sulphate (0.025 M, pH 4.6), nickel chloride (0.025 M, pH 5.3), nickel nitrate
(0.025 M (pH 6.7), and nickel acetate (0.025 M, pH 7.3).

The allergens were applied to the backs of the subject individuals via Finn Chambers on Scanpore (for nickel sulphate 5% pet) and A1 tests on
Leucotest (for aqueous nickel solutions) and read at 48 and 96 hours post-application. The aqueous Ni solutions were applied to a circular
area (8 mm diameter) to all subject individuals, arranged in a single horizontal row. The order of the 4 salts were rotated so as not to be in
the same order.

EXAMINATIONS
- Grading/Scoring system: At 48 hours, the contact sites were visually examined and graded in accordance with international standards
- i.e., a ranking/score of 0, +, ++, or +++ was assigned, corresponding to the degree of the reaction.
The total (T) score and the mean (M) value of the reactions to each compound were calculated and reported.
- Statistical analysis: Differences between the mean values of the reactions of each tested compound were evaluated by analysis of variance with
Fisher's F-test.
- Other: none

Results and discussion

Results of examinations:

SYMPTOMS/NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
Patch test summary results, by group tested:
Group 1 (n = 71 patients)
200 ug Ni, from sulfate: 71/71 positive reactions (24 patients = 3+; 47 patients = 2+); T score = 166; M value = 2.38
47 ug Ni, from acetate: 45/71 positive reactions (17 patients = 3+; 17 = 2+; 11 = 1+); T score = 50; M value = 0.70
47 ug Ni, from chloride: 32/71 positive reactions (10 patients = 3+; 17 = 2+; 5 = 1+); T score = 69; M value = 0.97
47 ug Ni, from nitrate: 31/71 positive reactions (3 patients = 3+; 12 = 2+; 16 = 1+); T score = 94; M value = 1.32
47 ug Ni, from sulfate: 35/70 positive reactions (7 patients = 3+; 17 = 2+; 11 = 1+); T score = 67; M value = 0.94

Group 2 (n = 30 patients)
200 ug Ni, from sulfate: 30/30 positive reactions (25 patients = 3+; 5 patients = 2+); T score = 85; M value = 2.83
47 ug Ni, from acetate: 25/30 positive reactions (13 patients = 3+; 8 = 2+; 4 = 1+); T score = 59; M value = 1.96
47 ug Ni, from chloride: 30/30 positive reactions (16 patients = 3+; 12 = 2+; 2 = 1+); T score = 74; M value = 2.46
47 ug Ni, from nitrate: 29/30 positive reactions (14 patients = 3+; 14 = 2+; 1 = 1+); T score = 71; M value = 2.36
47 ug Ni, from sulfate: 26/30 positive reactions (10 patients = 3+; 11 = 2+; 5 = 1+); T score = 58; M value = 1.93

Group 3 (n = 25 patients)
200 ug Ni, from sulfate: 25/25 positive reactions (5 patients = 3+; 20 patients = 2+); T score = 55; M value = 2.21
12 ug Ni, from acetate: 3/25 positive reactions (2 patients = 2+; 1 = 1+); T score = 5; M value = 0.20
12 ug Ni, from chloride: 5/25 positive reactions (3 patients = 2+; 2 = 1+); T score = 8; M value = 0.32
12 ug Ni, from nitrate: 5/25 positive reactions (3 patients = 2+, 2 = 1+); T score = 8; M value = 0.32
12 ug Ni, from sulfate: 3/25 positive reactions (3 patients = 2+); T score = 6; M value = 0.24

Group 4 (n = 25 patients)
200 ug Ni, from sulfate: 25/25 positive reactions (19 patients = 3+; 6 patients = 2+); T score = 69; M value = 2.76
12 ug Ni, from acetate: 14/25 positive reactions (5 patients = 3+; 5 = 2+; 4 = 1+); T score = 29; M value = 1.16
12 ug Ni, from chloride: 18/25 positive reactions (6 patients = 3+; 9 = 2+; 3 = 1+); T score = 39; M value = 1.56
12 ug Ni, from nitrate: 18/25 positive reactions (4 patients = 3+; 9 = 2+; 5 = 1+); T score = 35; M value = 1.4
12 ug Ni, from sulfate: 14/25 positive reactions (2 patients = 3+; 5 = 2+; 7 = 1+); T score = 23; M value = 0.92

Applicant's summary and conclusion

Conclusions:

Test results demonstrated that subjects allergic to nickel plus other transition metals were more sensitive than those allergic to nickel only.
The authors theorized that, based on a QSAR model, subjects reacting to more metals had a "more uniform availability of cutaneous ligands"
leading to the formation of more immunogenic complexes and a stronger, less specific allergic reaction.

Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER.

(A detailed description of the scoring criteria can be found in the .pdf document attached to the 'Sensitisation Scoring Rationale Document' record at the beginning of Section 7.10.4).