Nickel sulphide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD #405)

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

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

Test material information

Constituent 1

Reference substance name:

Trinickel disulphide

EC Number:

234-829-6

EC Name:

Trinickel disulphide

Cas Number:

12035-72-2

Molecular formula:

Ni3S2

IUPAC Name:

Trinickel disulphide

Details on test material:

- Name of test material (as cited in study report): nickel subsulfide
- Substance type: test substance
- Physical state: grey, powder
- Composition of test material, percentage of components: nickel subsulfide, other ingredients
- Stability under test conditions: expected to be stable for the duration of testing
- Storage condition of test material: kept in a tightly closed container
- Expiration date was not applicable
- Other: Code #N18A-PTL, sparingly soluble in water

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

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 steel 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: 34 d
- 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 (%): 24-51% - low humidity was noted during the study. Portable humidifiers were used to increase the humidity levels during this time.
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): one-tenth of a gram (0.1 g Ni3S2)

Duration of treatment / exposure:

Test substance was ground with a mortar and pestle then 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):

72 h (scoring conducted at 1, 24, 48, and 72 h) 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 both eyes, then rinsed with physiological saline [0.9% NaCl] approximately 30 seconds after instillation of the dye)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 1 h

Score:

19.3

Max. score:

110

Reversibility:

fully reversible within: 72 h

Results 2

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 h

Score:

19.3

Max. score:

110

Reversibility:

fully reversible within: 72 h

Results 3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 h

Score:

13.7

Max. score:

110

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 48 h

Score:

4.3

Max. score:

110

Reversibility:

fully reversible within: 72 h

Results 5

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 h

Score:

0

Max. score:

110

Reversibility:

other: no effect

Irritant / corrosive response data:

Incidence of Positive Effects (1 h, 24 h, 48 h, 72 h):
Corneal Opacity: 3/3, 2/3, 1/3, 0/3
Iritis: 3/3, 3/3, 0/3, 0/3
Conjunctivitis: 3/3, 2/3, 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

Not Applicable

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 subsulfide 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. Testing was completed on 2009-01-16 and the final report issued on 2009-03-10. Nickel subsulfide (0.10 gram) 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) following instillation. Individual animals were assessed for effects in the cornea, iris, and conjunctivae, as well as other lesions, gross toxicity, and behavioral changes. All three treated eyes exhibited corneal opacity, 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 72 hours. 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 19.3 was used to categorize nickel subsulfide as mildly irritating to the eye under the conditions of this study. STUDY RATED BY AN INDEPENDENT REVIEWER