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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 2009-January 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The LLNA is not applicable for use in evaluating skin sensitization since this methodology provides false negative results for nickel as a known human skin sensitizer (due to differences in the toll receptors in mice used in the LLNA and humans).

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Nickel sulfate hexahydrate
- Physical state: bule, crystalline
- Composition of test material, percentage of components: >99% nickel sulfate hexahydrate
- Stability under test conditions: stable
- Storage condition of test material: under nitrogen

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elm Hill Breeding Labs, Chelmsford MA
- Age at study initiation: young adult
- Weight at study initiation: 383-487 grams
- Housing: group housing in plastic perforated bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12-19 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22 degrees Celcius
- Humidity (%): 53-80%
- Photoperiod (hrs dark / hrs light): 12 hr light/dark cycle

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Induction: 3% w/w intradermal; 64% w/w topical
Challenge: 0.4% w/w or 0.5% w/w
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 3% w/w intradermal; 64% w/w topical
Challenge: 0.4% w/w or 0.5% w/w
No. of animals per dose:
Preliminary Irritation Group: 16
Test Group: 10
Naive Control Group: 5
Challenge controls:
In addition to the test animals, 10 guinea pigs from the same shipment were maintained under
identical environmental conditions and were treated with the HNIC of the test substance at
challenge only. These animals constituted the "sham control" group.
Positive control substance(s):
yes
Remarks:
alpha-Hexylcinnamaldehyde Technical (HCA)

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.4 w/w
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.4 w/w. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.4% w/w
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.4% w/w. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.4%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.4%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.4%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.4%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5%
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5%. No with. + reactions: 2.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5%. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
negative control
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
negative control
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
positive controcl
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: positive controcl. No with. + reactions: 8.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
positive control
No. with + reactions:
6
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: positive control. No with. + reactions: 6.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Based on the results of this study, the test substance is not considered to be a contact sensitizer. The positive response observed in the historical positive control validation study with alphaHexylcinnamaldehyde Technical (HCA) validates the test system used in this study .

Applicant's summary and conclusion

Interpretation of results:
other: see conclusions
Conclusions:
Nickel sulfate is a established dermal sensitizer in human studies. Therefore, results from this animal study should be interpreted with caution as animal models for testing of Ni compounds have been deems insufficient.