Nickel bis(sulphamidate)

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

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).

Data source

Reference

Reference Type:

review article or handbook

Title:

Experimental nickel elicitation thresholds - a review focusing on occluded nickel exposure

Author:

Fischer, L.A., Menne, T., Johansen, J.D.

Year:

2005

Bibliographic source:

Contact Dermatitis 2005: 52: 57-64

Materials and methods

Type of sensitisation studied:

skin

Study type:

other: review article for risk assessment (DNEL for elicitation threshold))

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Experimental open exposure to Ni can be done as a single or repeated application, and to mimic the effect of Ni on irritated skin, the experimental
exposure can be done with or without an irritant. Studies have tried to visualize the dose-response characteristics of open and occluded exposure to Ni under these different conditions.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Nickel sulphate hexahydrate

IUPAC Name:

Nickel sulphate hexahydrate

Constituent 2

Reference substance name:

Nickel sulphate

EC Number:

232-104-9

EC Name:

Nickel sulphate

Cas Number:

7786-81-4

Molecular formula:

NiSO4

IUPAC Name:

nickel(2+) sulfate

Method

Type of population:

general

Ethical approval:

not specified

Subjects:

Sensitized individuals from the general population

Clinical history:

Not available

Controls:

Use of controls was dependent on the studies reviewed

Route of administration:

dermal

Details on study design:

OCCLUDED EXPOSURE STUDIES
Occluded exposure to Ni is the most common method in experimental studies used to define the thresholds for elicitation. 13 studies were identified and of these, 8 studies were selected for further analysis based on the following criteria:
(1) at least 5 dilutions (including vehicle) had been used for the patch test;
(2) at least 10 patch-tested Ni-sensitized persons;
(3) the patch-test method was similar to the Finn Chamber method and 2 days of occlusion were used;
(4) a fair description of the study details was available in the articles chosen.

OPEN EXPOSURE STUDIES
The 2 single open application studies evaluated gave remarkable similar results.

Results of both types of tests were analyszied within each group and between groups.

Results and discussion

Results of examinations:

The thresholds for elicitation of Ni allergy are dependent on the conditions under which the Ni exposure occurs, e.g. open/closed/penetrating exposure, single or repeated applications, the presence of an irritant or irritated skin, the selection of the study group, the definition of a positive reaction and the vehicle used for testing. The patch-test data presented in this analysis show that the elicitation thresholds determined differ by a factor of 10 between studies. Results of 8 occluded single exposure studies demonstrated that:
• 5% of a sensitized population will react to a dose of 0.44/µg Ni/cm2
• 10% of a sensitized population will react to a dose of 1.04/µg Ni/cm2

Comparison of all the study results showed that:
• elicitation threshold for single open exposure is around x 6 higher than the elicitation threshold for single occluded exposure
• sensitization and elicitation thresholds for penetrating exposure are lower than the elicitation threshold for single occluded exposure

Any other information on results incl. tables

Table2. Results of logistic regression analyses performed on the data from each of the chosen occluded nickel dose-response studies
Reference	Dose (µg/cm^2)		Agreement		Estimated doses (µg/cm^2)
	Minimum	Maximum	X^2	P value	ED1%	ED5%	ED10%	ED25%	ED50%	ED75 %	ED90%	ED95%	ED99%
(12)	0.067	335	0.2	0.91	0.15	0.43	0.7	1.4	2.8	5.7	11.5	18.5	53
(17)	0.0063	558	0.31	0.96	0.Q28	0.124	0.24	0.64	1.72	4.6	12.2	24	104
(19)	0.17	335	24.3	0.0068	0.054	0.36	0.85	3	10.8	38	135	320	2148
(20)	3.9	495	8.57	0.2	0.38	1.37	2.5	5.8	13.5	32	74	132	476
(21)	0.087	335	13.3	0.1	0.29	1.6	3.5	10.8	34	106	330	715	3956
(22)	0.23	254	3.18	0.67	0.05	0.3	0.67	2.2	7.2	24	77	173	1030
(15)	0.087	838	6.74	0.24	0.0175	0.172	0.48	2.2	10.1	46	210	590	5783
(16)	0.087	838	4.76	0.31	0.165	0.9	1.94	6	18.5	57	177	382	2083

Table 3. Studies investigating the elicitation of nickel allergy on different exposures to nickel: open, occluded, single, repeated, with and without an irritant
Open		Occluded
Single	Repeated	Single	Repeated
without an irritant   (10) Menne and Calvin 4/51 = 7.8 % positive to 6.8 µg Ni/cm^218/51 = 35.3% positive to 27.37 µg Ni/cm^2   (11) Christensen and Wall 6/15 = 40% positive to 37.1 µg Ni/cm^2 10/15=67% positive to 74.1 µg Ni/cm^213/15 = 87% positive to 148.2-222.4 µg Ni/cm^2 14/15 = 93% positive to 296.5 µg Ni/cm^2   with an irritant*   (10) Menne and Calvin 1/51 = 2% positive to 6.84 µg Ni/cm^2 1/51 = 2% positive to 27.37 µg Ni/cm^2	without an irritant   (12) Nielsen et al. - increased blood-flow in finger exposed to: 1^stweek: 10ppm NiCl2x 10 minutes 2^ndweek: 100 ppm NiCl2x 10 minutes 4/17 = 23.5% follicular reaction on forearm exposed to 1^stweek: 10 ppm 2^nd week 100 ppm   with an irritant*   (12) Nielsen et al. 8/17 = 47% follicular reaction on arm exposed to: 1^stweek: 10 ppm NiCl2 2^nd week: 100 ppm NiCl2 (compared to 1/17 = 6% follicular reaction when exposed to vehicle combined with SLS)	with an irritant*   (13) Allenhy and Basketter - An arm immersed daily into SLS until erythema. Following patch test: 2/20 = 10% positive to 0.5 ppm = 0.0049 µg Ni/cm^2(compared to no positives when patch testing at this concentration on normal skin)   (14) Agner et al. - 4 fold increase of inflammatory response when patch testing with SLS and NiCl2(compared to NiCl2alone)   (15) Hindsen and Braze - lowered test-score when pretreating the patcht test site with SLS one month prior to exposure to nickel, (compared to the site with no SLS pre-treatment)	without an irritant   (15) Hindsen and Braze - patch test on an area treated with nickel 1 month earlier: 12/20 = 63% positive to 3.43 µg Ni/cm^2(compared to 15% at this concentration when no pre-exposure to nickel (p = 0.08))   (16) Hindsen et al. patch test on area treated with nickel 1 month earlier: 2/23 = 8.7% positive to 0.0871 µg Ni/cm^2(compared to 0% at this concentration when no pre-exposure to nickel (p = 0.03))   with an irritant* No studies
*the irritant was SLS

10.  Menne T, Calvin G. Concentration threshold of nonoccluded nickel exposure in nickel-sensitive individuals and controls with and without surfactant. Contact Dermatitis 1993: 29: 180-184.

11.  Christensen 0 B, Wall L M. Open, closed and intradermal testing in nickel allergy. Contact Dermatitis 1987: 16: 21-26.

12.  Nielsen N H, Menne T, Kristiansen J, Christensen J M, Borg L, Poulsen L K. Effects of repeated skin exposure to low nickel concentrations: A model for allergic contact dermatitis to nickel on the hands. Br J Dermatol 1999: 141: 676-682.

13.  Allenby C F, Basketter D A. An arm immersion model of compromised skin (II). Influence in minimal eliciting patch test concentrations of nickel. Contact Dermatitis 1993: 28: 129-133.

14.  Agner T, Johansen J D, Overgaard L, Volund A, Basketter D, Menne T. Combined effects of irritants and allergens. Synergistic effects of nickel and sodium lauryl sulfate in nickel-sensitised individuals. Contact Dermatitis 2002: 47: 21-26.

15.  Hindsen M, Bruze B. The significance of previous contact dermatitis for elicitation of contact allergy to nickel. Acta Derm Venereal 1998: 78: 367-370.

16.  Hindsen M, Bruze M, Christensen 0 B. The significance of previous allergic contact dermatitis for elicitation of delayed hypersensitivity to nickel. Contact Dermatitis 1997: 37: 101-106.

Table 4. Studies investigating the sensitization and elicitation of nickel allergy during penetrating exposure (ear piercing)
Penetrating
Sensitization	Elicitation
Rasanen et al. investigated 9 persons with symptoms related to ear piercing, 6/9=67% had a positive patch test to nickel, the studs the 67% were pierced with had the following nickel-release: (a: in plasma, b: in water) A1: 22.44 ug Ni/cm^2/week B1: 0.46 ug Ni/cm^2/week A2: 0.15 ug Ni/cm^2/week B2: 0.02 ug Ni/cm^2/week A3: 104.59 ug Ni/cm^2/week B3: O.79 ug Ni/cm^2/week A4: 10.06 ug Ni/cm^2/week B4: 0.04 ug Ni/cm^2/week A5: 0.17 ug Ni/cm^2/week B5: 0.01 ug Ni/cm^2/week A6: 2.03 ug Ni/cm^2/week B6: 0.03 ug Ni/cm^2/week	Fischer et al. investigated 10 nickel sensitive persons with pierced ears who were wearing nickel containing ear-rings with different release of nickel for a maximum of 1 week. (Release in synthetic sweat). Positive symptoms: itching, redness and dermatitis 4/10=40% positive to 0.05 ug Ni/week 3/11=27% positive to 2.3 ug Ni/week 4/6=67% positive to 7.7 ug Ni/week 6/6=100% positive to 15 ug Ni/week   Ingber et al. investigated 25 nickel sensitive persons whose ears were pierced with piercing-studs with a nickel content of 11.5-12.9% 2/25=8% had a transient itch and erythema 48 h after piercing with studs releasing 0.11-0.2 ug Ni/cm^2/week

35.  Rasanen L, Lehto M, Mustikka-Miiki U P. Sensitization to nickel from stainless steel ear-piercing kits. Contact Dermatitis 1993: 28: 292-294.

36.  Fischer T, Fregert S, Gruvberger B,Nickel release from ear piercing kits and earrings. Contact Dermatitis 1984: 10: 39--41.

37.  Ingber A, Hershko K, Horev L AISI 316L Stainless steel ear piercing post assembly does not cause dermatitis in nickel-sensitive subjects. Exog Dermatol 2003: 2: 195-200.