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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study (OECD Test 404)
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Substance type: Nickel oxide sinter (Nickel oxide green)
- Physical state: dark grey, oderless granules
- Composition of test material, percentage of components: 98% NiO; 1.5% Colbaltous Oxide
- Lot/batch No.: Code #N112-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:insoluble in water

Test animals

Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Received from Robinson Services, Inc. Clemmons, NC on August 20,2008
- Age at study initiation: young adult
- Housing:The animals were singly housed in 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 was supplied ad-libitum by an automatic water dispensing system.
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-20°C
- Humidity (%): 69-84%; The 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-hour 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 (O.56g of the test mixture)
- Concentration (if solution):90% w/w mixture


VEHICLE
- Amount(s) applied (volume or weight with unit):test substance was moistened with in distilled water to achieve a dry paste by preparing a 90% w/w mixture
- Purity:distilled
Duration of treatment / exposure:
4 hours
Observation period:
up to 72 hours
Number of animals:
3
Details on study design:
On the day before application, a group of animals was prepared by clipping the dorsal area and the trunk. Prior to application, the animals were examined for health and the skin checked for any abnormalities. Three healthy animals were selected for test. Five-tenths of a gram of the test substance (0.56g of the test mixture) was placed on a 1-inch x 1-inch, 4-ply gauze pad and applied to one 6-cm^2 intact dose site on each animal. The pad and entire trunk of each animal were then wrapped with semiocclusive 3-inch Micropore tape. Elizabethan collars were placed on each rabbit. After 4 hours of exposure, the pads and the collars were removed and the test sites were gently cleansed. Individual dose sites were scored according to the Draize scoring system at approximately 30-60 minutes, 24, 48, and 72 hours after patch removal. The animals were observed for signs of gross toxicity and behavioral changes at least once daily. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, 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 hours
Remarks on result:
other: Within one hour of patch removal, all three treated sites exhibited very slight erythema
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: all three animals scored as 0
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 30-60 min
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
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 hours
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 hours
Score:
0
Max. score:
5
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 48 hours
Score:
0
Max. score:
5
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
5
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
erythema score
Basis:
animal: 3501
Time point:
other: 30-60 min
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 3502
Time point:
other: 30-60 min
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 3503
Time point:
other: 30-60 min
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 3501
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 3501
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 3501
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 3502
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 3502
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 3502
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 3503
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 3503
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 3503
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3501
Time point:
other: 30 - 60 min
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3501
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3501
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3501`
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3502
Time point:
other: 30 - 60 min
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3502
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3502
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3502
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3503
Time point:
other: 30 - 60 min
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3503
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3503
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3503
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Irritant / corrosive response data:
Not Applicable.
Other effects:
All animals appeared active and healthy during the study. Apart from the dermal irritation noted below, there were no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior.

Any other information on results incl. tables

There was no edema observed at any treated site during this 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 oxide sinter (Nickel oxide green) is 0.3.

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 - Acute Dermal Irritation/Corrosion 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 oxide sinter (Nickel oxide green) (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 oxide 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