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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
Study period:
December 18, 1998 to December 16, 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline Study. Body weight data at start and end of the test period were not reported.
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:
1999
Report date:
1999

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Equivalent to OECD Guideline 404
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
nickel metal
IUPAC Name:
nickel metal
Constituent 2
Chemical structure
Reference substance name:
Nickel
EC Number:
231-111-4
EC Name:
Nickel
Cas Number:
7440-02-0
Molecular formula:
Ni
IUPAC Name:
nickel
Constituent 3
Reference substance name:
"INCO® Type 123", gray metal powder
IUPAC Name:
"INCO® Type 123", gray metal powder
Constituent 4
Reference substance name:
NiPERA.
IUPAC Name:
NiPERA.
Details on test material:
- Name of test material (as cited in study report): INCO(R) Type 123 Nickel Powder
- Molecular formula (if other than submission substance): Not different than submission substance
- Molecular weight (if other than submission substance): Not different than submission substance
- Smiles notation (if other than submission substance): Not different than submission substance
- InChl (if other than submission substance): Not different than submission substance
- Structural formula attached as image file (if other than submission substance): Not different than submission substance
- Substance type: Solid
- Physical state: Gray powder
- Lot/batch No.: 347-2165
- Storage condition of test material: Stored at room temperature
- All other details on test material not reported or not applicable

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Myrtle's Rabbitry, Thompson Station, TN, USA.
- Age at study initiation: Adult, age not reported
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: housed individually in suspended stainless steel cages
- Diet (e.g. ad libitum): ad libitum (PMI Certified Rabbit Chow #5322, Purina Mills, Inc.)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21 deg.C
- Humidity (%): 20-50%
- Air changes (per hr): 10-15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12-hr light/12-hr dark cycle


IN-LIFE DATES: From: December 18, 1998 To: December 24, 1998

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: close-clipping
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g Nickel Powder
- Concentration (if solution): 100% Nickel Powder

VEHICLE
- Amount(s) applied (volume or weight with unit): Nickel powder was moistened with 4 drops of deionized water to form a paste
prior to administration.
- Concentration (if solution): Not reported
- Lot/batch no. (if required): Not reported
- Purity: Not reported
Duration of treatment / exposure:
4 hour(s)
Observation period:
up to 72 hours
Number of animals:
1 Female (3-minute period)
1 Female (1-hour period)
1 Female, 2 Males (4-hour period)
Details on study design:
TEST SITE
- Area of exposure: Approximately 24 hours pre-exposure, a patch of fur on the dorsal trunk area of three test animals was removed by close-clipping.  One test animal had 3 separate skin sites prepared.  
- % coverage: Not reported
- Type of wrap if used: The test substance (0.5 g moistened with deionized water) was applied to the 
patches of exposed skin via a semi-occlusive gauze patch (1 inch by 1 inch square of 4-ply gauze patch) .  The patches were kept in contact with 
the skin for periods of 3 minutes, 1 hour, and 4 hours, respectively for the animal with 3 exposure sites), and 4 hours (for the remaining animals 
with a single exposure site).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test article was removed using gauze moistened with deionized water, followed by dry gauze.
- Time after start of exposure: 4 hours

SCORING SYSTEM: The exposed skin sites were observed and evaluated for up to 72 hours following application.  Animals were observed twice daily, and unusual observations and/or mortality were recorded.  Animals were examined for signs of erythema and edema, and reactions were scored 
according to the Macroscopic Dermal Grading System based on the work of Draize (1959).  The 4-hour exposure data were classified according to 
EEC guidelines (1983) and mean scores were calculated to obtain Primary Irritation Indexes (PIIs) for erythema and edema.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 3 minutes or 1 or 4 hours
Score:
0.5
Reversibility:
fully reversible
Remarks on result:
other: nonirritant
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52671
Remarks:
female
Time point:
other: 1 hr
Score:
0
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52671
Remarks:
female
Time point:
24 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52671
Remarks:
female
Time point:
48 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52671
Remarks:
female
Time point:
72 h
Score:
0
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52725
Remarks:
male
Time point:
other: 1 hr
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52725
Remarks:
male
Time point:
24 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52725
Remarks:
male
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52725
Remarks:
male
Time point:
72 h
Score:
0
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52727
Remarks:
male
Time point:
other: 1 hr
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52727
Remarks:
male
Time point:
24 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52727
Remarks:
male
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Remarks:
after 4 hr exposure
Basis:
animal: 52727
Remarks:
male
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 3 minutes or 1 or 4 hours
Score:
0
Reversibility:
fully reversible
Remarks on result:
other: nonirritant
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52671
Remarks:
female
Time point:
other: 1 hr
Score:
0
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52671
Remarks:
female
Time point:
24 h
Score:
0
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52671
Remarks:
female
Time point:
48 h
Score:
0
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52671
Remarks:
female
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52725
Remarks:
male
Time point:
other: 1 hr
Score:
0
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52725
Remarks:
male
Time point:
24 h
Score:
0
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52725
Remarks:
male
Time point:
48 h
Score:
0
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52725
Remarks:
male
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52727
Remarks:
male
Time point:
other: 1 hr
Score:
0
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52727
Remarks:
male
Time point:
24 h
Score:
0
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52727
Remarks:
male
Time point:
48 h
Score:
0
Irritation parameter:
edema score
Remarks:
after 4 hr exposure
Basis:
animal: 52727
Remarks:
male
Time point:
72 h
Score:
0
Irritant / corrosive response data:
3-Minute Exposure Period (1 animal): no dermal irritation observed.  
All erythema and edema scores = 0 (observations made at 0, 24, 48, and 72 hours post-exposure).

1-Hour Exposure Period (1 animal): no dermal irritation observed.   
Erythema scores = 1 (for observations at 0, 24, and 48 hours) and 0 (for  observation at 72 hours).  
All edema scores = 0 (all observations).   Skin at the test site was discolored (green), possibly due to the test
substance (observed at 0, 24, and 48 hours).

4-Hour Exposure Period (3 animals): very slight dermal irritation observed.  
Erythema scores = 1 (for animal #1 at 24 and 48 hours, and   animals #2 and #3 at 1 and 24 hours) and 0 (for all animals at 72 hours).   
All edema scores = 0 (for all animals at all observations). For all 3 animals (at 1, 24, and 48 hours), and 2 of the 3 animals  (at 72  hours), 
skin at the test site was discolored (green),  possibly due to the  test substance.  Additionally, irritation outside of  the test site was 
noticed occasionally, probably due to the binding tape  material rather  than the test substance.

Mean erythema score = 0.50 (nonirritant)
Mean edema score = 0.00 (nonirritant)

Under the conditions of the test, there was no evidence that INCO® Type  123 nickel powder was corrosive to the exposed skin of 
male and female adult New Zealand White rabbits during exposure periods of 3 minutes, or 1 or 4 hours.
Other effects:
None reported

Applicant's summary and conclusion

Conclusions:
Under the conditions of the test, there was no evidence that INCO® Type 123 nickel powder was corrosive to the exposed skin of male and female  
adult New Zealand White rabbits during exposure periods of 3 minutes, or 1 or 4 hours.
Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER.

ROBUST SUMMARY DEVELOPED BY AN INDEPENDENT REVIEWER.

Robust Summary for SLI (1999):


The potential irritant/corrosive effects of nickel powder were evaluated using male and female adult New Zealand White rabbits, obtained from  

Myrtle's Rabbitry, Thompson Station, TN, USA.  Test animals were individually housed under constant conditions of temperature (19-21 deg.C), 

relative humidity (20-50%), and photoperiod (12-hr light/dark cycle). Food and water were provided ad libitum.

Approximately 24 hours pre-exposure, a patch of fur on the dorsal trunk area of three test animals was removed by close-clipping.  One test  

animal had 3 separate skin sites prepared.  The test substance (0.5 g moistened with deionized water) was applied to the patches of exposed  

skin via a semi-occlusive gauze patch.  The patches were kept in contact with the skin for periods of 3 minutes, 1 hour, and 4 hours, respectively  

for the animal with 3 exposure sites), and 4 hours (for the remaining animals with a single exposure site).

After the respective exposure periods, the patches were removed and residual test material was removed with water.  The exposed skin sites  

were observed and evaluated for up to 72 hours following application. Animals were observed twice daily, and unusual observations and/or  

mortality were recorded.  Animals were examined for signs of erythema and edema, and reactions were scored according to the Macroscopic Dermal  

Grading System based on the work of Draize (1959).  The 4-hour exposure data were classified according to EEC guidelines (1983) and mean scores  

were calculated to obtain Primary Irritation Indexes (PIIs) for erythema and edema.


3-Minute Exposure Period (1 animal): no dermal irritation observed.  All erythema and edema scores = 0 (observations made at 0, 24, 48, and 72  

hours post-exposure).

1-Hour Exposure Period (1 animal): no dermal irritation observed.  Erythema scores = 1 (for observations at 0, 24, and 48 hours) and 0 

(for  observation at 72 hours).  All edema scores = 0 (all observations). Skin  at the test site was discolored (green), possibly due to the test  

substance (observed at 0, 24, and 48 hours).

4-Hour Exposure Period (3 animals): very slight dermal irritation observed.  Erythema scores = 1 (for animal #1 at 24 and 48 hours, and  

animals #2 and #3 at 1 and 24 hours) and 0 (for all animals at 72 hours).  All edema scores = 0 (for all animals at all observations).

For all 3 animals (at 1, 24, and 48 hours), and 2 of the 3 animals (at 72  hours), skin at the test site was discolored (green), 

possibly due to the  test substance.  Additionally, irritation outside of the test site was  noticed occasionally, probably due to the binding tape 

material rather  than the test substance.

Mean erythema score = 0.50 (nonirritant)
Mean edema score = 0.00 (nonirritant)

Under the conditions of the test, there was no evidence that INCO® Type 123 nickel powder was corrosive to the exposed skin of male and female  

adult New Zealand White rabbits during exposure periods of 3 minutes, or 1 or 4 hours.