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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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. Only 5 animals used per group in the GPMT.
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:
Guinea-pig maximization test according to the procedure described by Magnusson and Kligman (1969) with some modification (Nakamura, A. et al., 1994).
GLP compliance:
not specified
Type of study:
guinea pig maximisation test

Test material

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:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC Inc. (Shizuoka, Japan)
- Weight at study initiation: 350-400 g (guinea-pigs)

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Induction: intradermal FCA/saline and epicutaneous petrolatum; Challenge: 30% ethanol
Concentration / amount:
Induction: 1% nickel sulphate (intradermal and epicutaneous)
Challenge: 5, 2, 1, 0% nickel sulphate
Rechallenge: 0.5, 0.25% nickel sulphate
Challengeopen allclose all
Route:
other: epicutaneous, not further specified
Vehicle:
other: Induction: intradermal FCA/saline and epicutaneous petrolatum; Challenge: 30% ethanol
Concentration / amount:
Induction: 1% nickel sulphate (intradermal and epicutaneous)
Challenge: 5, 2, 1, 0% nickel sulphate
Rechallenge: 0.5, 0.25% nickel sulphate
No. of animals per dose:
5
Details on study design:
RANGE FINDING TESTS:
Preliminary irritation tests were performed to determine suitable concentrations for induction and challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 7 (6 x intradermal and 1 x epicutaneous)
- Exposure period: day 0 to day 9
- Test groups: intradermal: 1% NiSO4 in FCA/saline; epicutaneous: 1% in petrolatum
- Control group: intradermal: FCA/saline; epicutaneous: petrolatum
- Site: shoulder region
- Frequency of applications: 6 x intradermal injections; 1 x epicutaneous (occlusive) 7 days later for 48 hours
- Duration: totally 9 days (occlusive for 48 hours)
- Concentrations: 1% intradermal, 1% epicutaneous


B. CHALLENGE EXPOSURE
- No. of exposures: 1 ( 2 in case of rechallenge)
- Day of challenge: 14 days after induction (and 21 after induction: rechallenge of groups challenged first time with 1 and 0 %)
- Exposure period: 48 h
- Site: flank
- Concentrations: 1st challenge: 5, 2, 1, 0% in 30% ethanol; 2nd challenge 0.5 and 0.25%, respectively (only 1 and 0% 1st challenge groups)
- Evaluation (hr after challenge): 48
Challenge controls:
3 animals per group, groups challenged with 5, 2, 1 and 0%, respectively; rechallenge of 1 and 0% groups with 0.5 and 0.25%, respectively.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
8.04% (recalculated value, equivalent to 5% NiSO4)
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
3/5 intense; 1/5 moderate; 1/5 slight; 0/5 nothing visible
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 8.04% (recalculated value, equivalent to 5% NiSO4). No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: 3/5 intense; 1/5 moderate; 1/5 slight; 0/5 nothing visible.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
3.22% (recalculated value, equivalent to 2% NiSO4)
No. with + reactions:
4
Total no. in group:
5
Clinical observations:
1/5 intense; 2/5 moderate; 1/5 slight; 1/5 nothing visible
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 3.22% (recalculated value, equivalent to 2% NiSO4). No with. + reactions: 4.0. Total no. in groups: 5.0. Clinical observations: 1/5 intense; 2/5 moderate; 1/5 slight; 1/5 nothing visible.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1.61% (recalculated value, equivalent to 1% NiSO4)
No. with + reactions:
4
Total no. in group:
5
Clinical observations:
1/5 intense; 1/5 moderate; 2/5 slight; 1/5 nothing visible
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1.61% (recalculated value, equivalent to 1% NiSO4). No with. + reactions: 4.0. Total no. in groups: 5.0. Clinical observations: 1/5 intense; 1/5 moderate; 2/5 slight; 1/5 nothing visible.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
5/5 nothing visible
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: 5/5 nothing visible.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0.8% (1.61% in 1st challenge (1% NiSO4); recalculated value, equivalent to 0.5% NiSO4)
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
1/5 slight; 4/5 nothing visible
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 0.8% (1.61% in 1st challenge (1% NiSO4); recalculated value, equivalent to 0.5% NiSO4). No with. + reactions: 1.0. Total no. in groups: 5.0. Clinical observations: 1/5 slight; 4/5 nothing visible.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0.4% (0% in 1st challenge; recalculated value, equivalent to 0.25% NiSO4)
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
1/5 slight; 4/5 nothing visible
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 0.4% (0% in 1st challenge; recalculated value, equivalent to 0.25% NiSO4). No with. + reactions: 1.0. Total no. in groups: 5.0. Clinical observations: 1/5 slight; 4/5 nothing visible.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
8.04% (recalculated value, equivalent to 5% NiSO4)
No. with + reactions:
1
Total no. in group:
3
Clinical observations:
1/3 moderate; 2/3 nothing visible
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 8.04% (recalculated value, equivalent to 5% NiSO4). No with. + reactions: 1.0. Total no. in groups: 3.0. Clinical observations: 1/3 moderate; 2/3 nothing visible.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
3.22% (recalculated value, equivalent to 2% NiSO4)
No. with + reactions:
1
Total no. in group:
3
Clinical observations:
1/3 slight; 2/3 nothing visible
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 3.22% (recalculated value, equivalent to 2% NiSO4). No with. + reactions: 1.0. Total no. in groups: 3.0. Clinical observations: 1/3 slight; 2/3 nothing visible.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
1.61% (recalculated value, equivalent to 1% NiSO4)
No. with + reactions:
1
Total no. in group:
3
Clinical observations:
1/3 slight; 2/3 nothing visible
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1.61% (recalculated value, equivalent to 1% NiSO4). No with. + reactions: 1.0. Total no. in groups: 3.0. Clinical observations: 1/3 slight; 2/3 nothing visible.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
3
Clinical observations:
3/3 nothing visible
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 3.0. Clinical observations: 3/3 nothing visible.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0.8% (1.61% in 1st challenge (1% NiSO4); recalculated value, equivalent to 0.5% NiSO4)
No. with + reactions:
0
Total no. in group:
3
Clinical observations:
3/3 nothing visible
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.8% (1.61% in 1st challenge (1% NiSO4); recalculated value, equivalent to 0.5% NiSO4). No with. + reactions: 0.0. Total no. in groups: 3.0. Clinical observations: 3/3 nothing visible.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0.4% (0% in 1st challenge; recalculated value, equivalent to 0.25% NiSO4)
No. with + reactions:
0
Total no. in group:
3
Clinical observations:
3/3 nothing visible
Remarks on result:
other: see Remark
Remarks:
Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.4% (0% in 1st challenge; recalculated value, equivalent to 0.25% NiSO4). No with. + reactions: 0.0. Total no. in groups: 3.0. Clinical observations: 3/3 nothing visible.

Any other information on results incl. tables

NiSO4 caused positive reactions in the GMPT. All NiSO4 -treated animals showed skin reactions by challenge (mean response = 1.4 at 1% and mean response = 1.6 at 2%). However, as one of the control animals showed a weak reaction at these concentrations, diluted concentrations (0.5 and 0.25%) were rechallenged. With 0.5% NiSO4 (equivalent to 8.04% C6H6O7Ni (nickel citrate)) challenge, 1 of 5 animals (20%) showed positive reactions and mean response was 0.2.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information