Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Hypothesis for read-across: Cobalt dihydroxide and nickel dihydroxide are the main components of the target UVCB-substance, and considered the major drivers for adverse effects based on its properties and relative quantity in the substance. For read-across purpose, data from the constituents (cobalt dihydroxide and nickel dihydroxide) of the target UVCB-substance is used in the REACH registration. GLP following guideline study (OECD Test #404), performed with nickel dihydroxide.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not Applicable
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Nickel dihydroxide
EC Number:
235-008-5
EC Name:
Nickel dihydroxide
Cas Number:
12054-48-7
Molecular formula:
H2NiO2
IUPAC Name:
nickel(2+) dihydroxide
Details on test material:
- Substance type: test substance
- Physical state: Green, solid (fine powder)
- Composition of test material, percentage of components: Nickel Dihydroxide >99%
- Lot/batch No.: Nickel hydroxide, Code #N106-PTL
- Expiration date of the lot/batch: Not Applicable
- Stability under test conditions: Test substance was expected to be stable for the duration of testing
- Storage condition of test material: Kept in a tightly closed container under nitrogen
- Other: Slightly soluble in water

Test animals

Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Received from Robinson Services, Inc. Clemmons, NC
- Age at study initiation: young adult
- Housing: Single, suspended stainless steel caging with mesh floors. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Pelleted Purina Rabbit Chow #5326
- Water (e.g. ad libitum): filtered tap water supplied ad-libitum by an automatic water dispensing system
- Acclimation period: 9 days
- Contaminants: Food and water analyses conducted regularly; no known contaminants reasonably expected to be found in the food or water at levels that would have interfered with the results of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 60-77% Humidity was above the targeted upper limit of 70% during the study due to exceptionally high, seasonal humidity. Portable dehumidifiers were used to lower the humidity levels during this time.
- Photoperiod (hrs dark / hrs light): 12 hr light/dark cycle


Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipping
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Five-tenths of a gram of the test substance (0.63 g of the text mixture)
- Concentration (if solution): 80% w/w mixture


VEHICLE
- Amount(s) applied (volume or weight with unit): test substance was moistened to achieve a dry paste by preparing a 80% w/w mixture
- Purity: distilled

Duration of treatment / exposure:
4 hours
Observation period:
72 hours after patch removal (and multiple intervals within this period)
Number of animals:
3
Details on study design:
Test substace placed on a 1 inch x 1 inch, 4-ply gauze pad and applied to one 6-cm2 intact dose site. Pad and trunk of animal then wrapped with semi-occclusive 3-inch Micropore tape. Elizabethan collars place on each rabbit during treatment. Dose sites were evaluated according to the Draize scoring system at ~30-60 minutes, 24, 48, and 72 hours after patch removal. Irritancy classification was obtained by adding the average erythema and edema scores for each interval and dividing by the number of evaluation intervals. Cage-Side observations of gross toxicity and behavioral changes were conducted at least once daily during the test period. Gross observational endpoints included: skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity, and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 30-60 min
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
other: all 3 animals scored as 1
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hrs
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
other: all 3 animals scored as 0
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hrs
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
other: all 3 animals scored as 0
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hrs
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
other: all 3 animals scored as 0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 30-60 min
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
other: all 3 animals scores as 0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hrs
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
other: all 3 animals scored as 0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hrs
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
other: all 3 animals scored as 0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hrs
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
other: all 3 animals scored as 0
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 30-60 min
Score:
1
Max. score:
5
Reversibility:
fully reversible within: 24 hrs
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 hrs
Score:
0
Max. score:
5
Reversibility:
fully reversible within: 24 hrs
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 48 hrs
Score:
0
Max. score:
5
Reversibility:
fully reversible within: 24 hrs
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 hrs
Score:
0
Max. score:
5
Reversibility:
fully reversible within: 24 hrs
Irritant / corrosive response data:
Not Applicable
Other effects:
All animals appeared active and healthy during the study. No signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior were observed.

Any other information on results incl. tables

There was no edema observed at any treated site during the study. Within one hour of patch removal, all three treated sites exhibited very slight erythema. The overall incidence and severity of irritation decreased with time. All animals were free of dermal irritation by 24 hours. The Primary Dermal Irritation Index for Nickel hydroxide is 0.3.

Justification for read-across: Cobalt dihydroxide and nickel dihydroxide are the main components of the target UVCB-substance, and considered the major drivers for adverse effects based on its properties and relative quantity in the substance. For read-across purpose, data from the constituents (cobalt dihydroxide and nickel dihydroxide) of the target UVCB-substance is used. According to section 1.5, annex XI of regulation (EC) 1907/2006, such studies do not need to be conducted, since adequate data from structurally analogous substances are available. Therefore read-across from these compounds is justified.

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: US EPA pesticides
Conclusions:
Not Applicable
Executive summary:

Eurofins Product Safety Laboratory (EPSL) conducted a primary skin irritation study in rabbits according to OECD Test #404 guidelines and using GLP standards. The study was completed on 2008-10-08 and the final report issued on 2008-12-04. Three healthy female rabbits were exposed via the skin to five-tenths of a gram of nickel hydroxide (moistened with distilled water) to determine if the test substance has the potential to produce irritation. The exposed area was semi-occluded for 4 hours following application, followed by evaluation at approximately 30-60 minutes, 24, 48, and 72 hours after exposure was ceased and the application site cleansed of residual substance. Application sites were evaluated using the Draize scoring system and included assessments of erythema (scores 0-4) and edema (scores 0-4). These endpoints were then used to derive the Primary Dermal Irritation Index (PDII). Individual animal data were provided as well as average data. Erythema was noted in all test animals at the 30-60 minute time point (each animal was scored as 1), but not at the remaining time intervals (scored as 0). No edema was observed during the study (each animal scored as 0 at all time points). The overall incidence and severity decreased with time, and the effects were fully reversible within 24 hours. The resulting PDII was 0.3, indicating that nickel hydroxide was slightly irritating to the skin. Aside from dermal irritation, no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior were noted. STUDY RATED BY AN INDEPENDENT REVIEWER