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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study (OECD #405)
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 405 (Acute Eye 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:
Ni(OH)2
IUPAC Name:
nickel(2+) dihydroxide
Details on test material:
- Name of test material (as cited in study report): nickel hydroxide
- Substance type: test substance
- Physical state: green, solid (fine powder)
- Composition of test material, percentage of components: nickel dihydroxide >99%
- Stability under test conditions: expected to be stable for the duration of testing
- Storage condition of test material: kept in a tightly closed container under nitrogen
- Expiration date was not applicable
- Other: Code #N106-PTL, slightly soluble in water

Test animals / tissue source

Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Robinson Services Inc, Clemmons NC
- Age at study initiation: young adult
- Housing: singly housed in suspended stainless stell caging with mesh floors; litter paper was placed beneath the cage and changed at least three times per week
- Diet (e.g. ad libitum): not specified; Pelleted Purina Rabbit Chow #5326.
- Water (e.g. ad libitum): ad-libitum
- Acclimation period: 6 days
- 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 (%): 61-84% - humdity was above targeted upper limit of 70% during the study due to exceptionally high, seasonable humidity; portable dehumidifiers were used to lower the humidity levels during the study
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: left eye (untreated) served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): one-tenth of a ml (0.10 g)


Duration of treatment / exposure:
Test substance instilled into the conjunctival sac; upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance
Observation period (in vivo):
7 days (scoring conducted at 1, 24, 48, 72 hours, 4 and 7 days) post instillation
Number of animals or in vitro replicates:
3
Details on study design:

SCORING SYSTEM: Scale for Scoring Ocular Lesions (scores 0-4, according to Draize et al 1944)

TOOL USED TO ASSESS SCORE: high-intensity, white light (Maglite), fluorescein dye procedure (one drop of 2% opthalmic fluorescein sodium was instilled into the treated eye, then rinsed with physiological saline [0.9%] NaCl approximately after instillation of the dye)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1 h
Score:
15
Max. score:
110
Reversibility:
fully reversible within: 7 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 h
Score:
15
Max. score:
110
Reversibility:
fully reversible within: 7 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 h
Score:
4
Max. score:
110
Reversibility:
fully reversible within: 7 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 h
Score:
3.3
Max. score:
110
Reversibility:
fully reversible within: 7 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 h
Score:
0.7
Max. score:
110
Reversibility:
fully reversible within: 7 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 4 d
Score:
0.7
Max. score:
110
Reversibility:
fully reversible within: 7 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 7 d
Score:
0
Max. score:
110
Reversibility:
other: no effect
Irritation parameter:
cornea opacity score
Basis:
animal: 3401
Time point:
other: 1 hr
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal: 3401
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal: 3401
Time point:
other: 4 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal: 3401
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3401
Time point:
other: 1 hr
Score:
1
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3401
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3401
Time point:
other: 4 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3401
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3401
Time point:
other: 1 hr
Score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3401
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3401
Time point:
other: 4 d
Score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3401
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3401
Time point:
other: 1 hr
Score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3401
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3401
Time point:
other: 4 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3401
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal: 3402
Time point:
other: 1 hr
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal: 3402
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal: 3402
Time point:
other: 4 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal: 3402
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3402
Time point:
other: 1 hr
Score:
1
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3402
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3402
Time point:
other: 4 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3402
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3402
Time point:
other: 1 hr
Score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3402
Time point:
24/48 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3402
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3402
Time point:
other: 4 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3402
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3402
Time point:
other: 1 hr
Score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3402
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3402
Time point:
other: 4 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3402
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal: 3403
Time point:
other: 1 hr
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal: 3403
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal: 3403
Time point:
other: 4 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal: 3403
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3403
Time point:
other: 1 hr
Score:
1
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3403
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3403
Time point:
other: 4 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: 3403
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3403
Time point:
other: 1 hr
Score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3403
Time point:
24/48 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3403
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3403
Time point:
other: 4 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 3403
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3403
Time point:
other: 1 hr
Score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3403
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3403
Time point:
other: 4 d
Score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: 3403
Time point:
7 d
Score:
0
Reversibility:
fully reversible
Irritant / corrosive response data:
Incidence of Positive Effects (1 h, 24 h, 48 h, 72 h, 4 d, 7 d):
Corneal Opacity: 0/3, 0/3, 0/3, 0/3, 0/3, 0/3
Iritis: 3/3, 0/3, 0/3, 0/3, 0/3, 0/3
Conjunctivitis: 3/3, 0/3, 0/3, 0/3, 0/3, 0/3
Other effects:
All animals appeared active and healthy during the study. Apart from the eye irritation, no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior were observed.

Any other information on results incl. tables

Individual scores for ocular irritation:

Animal 1 (Rabbit No 3401)

 Time Point  1 h  24 h  48 h  72 h  4 d  7 d
I. Cornea            
A. Opacity  0  0  0  0  0  0
B. Area  4  4  4  4  4  4
(AxB) x 5  0  0 0  0  0  0
 II. Iris            
 A. Values  0  0
 A x 5  5  0  0  0  0  0
 III. Conjunctivae            
 A. Redness  2  1  1  1  1  0
 B. Chemosis  1  0  0  0  0  0
C. Discharge   2  1  1  0  0  0
 (A+B+C) x 2  10  4  4  2  2  0
 Total  15  4  4  2  2  0

Animal #2 (Rabbit No 3402)

 Time point  1 h  24 h  48 h  72 h  4 d  7 d
 I. Cornea            
 A. Opacity  0  0  0  0  0  0
 B. Area  4  4  4  4  4
 (AxB) x 5  0  0  0  0  0  0
 II. Iris            
 A. Values  1  0 0  0  0
 A x 5  5  0  0 0  0  0
 III. Conjunctivae            
 A. Redness  2  1  1  0  0  0
 B. Chemosis  1  0  0  0  0  0
 C. Discharge  2  1  1  0  0  0
 (A+B+C) x 2  10  4  4  0  0  0
 Total  15  4  4  0  0  0

Animal 3 (Rabbit No 3403)

 Time Point 1 h   24 h  48 h  72 h  4 d  7 d
 I. Cornea            
 A. Opacity  0  0  0  0  0  0
 B. Area  4  4  4  4  4  4
 (AxB) x 5  0  0  0  0  0  0
 II. Iris            
 A. Values  1  0  0  0  0
 A x 5  5  0  0  0  0
 III. Conjunctivae            
 A. Redness  2  1  1  0  0
 B. Chemosis  1  0  0  0  0 0
 C. Discharge  2  1  0  0  0
 (A+B+C) x 2  10  4  2  0  0 0
 Total  15  4  2  0  0 0

Applicant's summary and conclusion

Interpretation of results:
other: mildly irritating
Remarks:
Criteria used for interpretation of results: other: Kay and Calandra 1962 (Interpretation of eye irritation tests, J Soc Cos Chem; 13:281-289)
Conclusions:
Under the conditions of this study, nickel hydroxide is classified as mildly irritating to the eye.
Executive summary:

Eurofins Product Safety Laboratory (EPSL) conducted a primary eye irritation study in rabbits according to OECD Test #405 and using GLP standards. The study was completed on 2008-10-06 and the final report issued on 2008-12-04. Nickel hydroxide (one-tenth of a milliliter, or 0.10 grams) was instilled into the right eye of three healthy female rabbits to determine the potential to produce irritation. The left eye served as a control in each animal. Ocular irritation was then evaluated according to Draize et. al. (1944) at multiple time points (1, 24 48 and 72 hours, 4 and 7 days) following instillation. Individual animals were assessed for effects in the cornea, iris, and conjunctivae, as well as other lesions, gross toxicity, and behavioral changes. In the treated eyes, no corneal opacity was observed in any of the animals, though all three treated eyes exhibited iritis and positive conjunctivitis one hour after instillation. All observed effects were reversible; incidence and severity of irritation decreased with time and all animals were free of ocular irritation by Day 7. Aside from eye irritation, no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior were observed in the animals. Using the classification system of Kay and Calandra (1962), the time interval with the highest mean score (Maximum Mean Total Score, MMTS) of 15 was used to classify nickel hydroxide as mildly irritating to the eye under the conditions of this study. STUDY RATED BY AN INDEPENDENT REVIEWER