Nickel(2+) hydrogen citrate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

in vivo

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: Acceptable, well documented publication which meets basic scientific principles.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Evaluation of skin sensitization potential of nickel, chromium, titanium and zirconium salts using guinea-pigs and mice.

Author:

Ikarashi, Y. et al

Year:

1996

Bibliographic source:

Biomaterials 17: 2103-2108

Materials and methods

Principles of method if other than guideline:

Sensitive mouse lymph node assay according to Ikarashi, Y. et al. (1993): in contrast to the LLNA, the mice were treated intradermally and epicutaneously at the ears, the lymph node cells from the excised lymph nodes were cultured with 3H-methyl thymidine ex vivo.

GLP compliance:

not specified

Type of study:

other: Sensitive mouse lymph node assay

Test material

Test material information

Constituent 1

Reference substance name:

Nickel sulphate

EC Number:

232-104-9

EC Name:

Nickel sulphate

Cas Number:

7786-81-4

IUPAC Name:

nickel(2+) sulfate

Details on test material:

- Name of test material (as cited in study report): nickel sulphate
- Molecular formula (if other than submission substance): NiSO4
- Molecular weight (if other than submission substance): 154.755
- Analytical purity: no data
- Other: Source: Wako Pure Chemical Industries, Ltd. (Osaka, Japan)

In vivo test system

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Japan SLC Inc. (Shizuoka, Japan)
- Age at study initiation: 6-8 weeks (mice)

Study design: in vivo (LLNA)

Vehicle:

other: intradermal: saline/FCA; epicutaneous: 70% DMSO

Concentration:

intradermal: 2% and 0% NiSO4, respectively; epicutaneous: 5% and 0% NiSO4, respectively

No. of animals per dose:

3

Details on study design:

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: sensitive mouse lymph node assay (SLNA)
- Criteria used to consider a positive response: Total Stimulation Index comparing test groups and control greater than 3


TREATMENT PREPARATION AND ADMINISTRATION:
Groups of mice (n=3) were initially injected intradermally, totalling 50 µL of the NiSO4 -FCA/saline into two sites of the abdominal skin. Five days after injection, the mice received 25 µL of NiSO4 in saline on both sides of each ear for three consecutive days. Control mice were treated by intradermal injection of FCA/saline into the abdomen and, after 5 days, the mice were exposed to vehicle alone on the ears for three consecutive days. The day after the final application, auricular lymph nodes were excised, pooled for each experimental group and weighed. A single cell suspension of lymph node cell (LNC) was prepared. The increase in LNC number relative to saline-treated controls was derived for each experimental group and recorded as a stimulation index of LNC number (SI(n)). The LNC supensions (1 x 10E5 cells) were seeded into 96 -well plates and cultured with 0.5 µCi [3H] methyl thymidine (3HTdR) for 24 h at 37 °C in a humidified atmosphere of 5% CO2 in air. The increase in 3HTdR incorporation relative to saline-treated controls was recorded as stimulation index of LNC proliferations SI(p). SI(total) was obtained from SI(n) x SI(p) and indicates the total lymph node activation induced by NiSO4.

Positive control substance(s):

not specified

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: SI(n) = 3.33 SI(p) = 7.23 SI(total) = 24.08

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Test group: 12570 mean cpm from 5 culture vessels Control: 1739 mean cpm from 5 culture vessels

Any other information on results incl. tables

Results of SLNA assay for NiSO4 [equivalent concentration of C6H6O7Ni (nickel citrate) in brackets]:

Conc. [%] intradermal	Conc. [%] topical	Lymph node weight [mg]	Lymph node cell number [x 10E5]	SI(n)	³HTdR incorporation (mean cpm)	SI(p)	SI(total) [SI(n) x SI(p)]
0 (saline)	0 (70% DMSO)	23.3	16.51	--	1739	--	--
2 [3.22]	5 [8.04]	47.2	54.99	3.33	12570	7.23	24.08

NiSO4 induced strong lymph node responses with a 2% (equivalent to 3.22% C6H6O7Ni) intradermal injection concentration in the SLNA.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information