Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 16,2008 to December 3,2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Fully GLP

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 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):nickel (II) fluoride tetrahydrate Code #N111-PTL
- Physical state: Yellow green powder
- Analytical purity:99%
- Solubility: 2.51 g/100g (water)
Test substance was expected to be stable for the duration of testing

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
- Age at study initiation: young adult
- Housing: The animals were housed in suspended stainless steel caging with meshfloors, which conform to the size recomnmendation in the recent "guide for care and Use of laboratory animals DHEW (NIH).Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (ad libitum): Pelleted Purina rabbit chow #5326
- Water (ad libitum): Filtered tap water
- Acclimation period :14 days
-Contaminants: There were no known contaminants reasonably expected to be found in the food or water at level which woul have interfered with the results of this study.Analyses of the food and water are inconducted regularly and the records are kept on file at Eurofins Product and Safety Laboratories.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 69-84

Test system

Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): one tenth of a milliliter (0.09g of test substance)
Duration of treatment / exposure:
Ocular irritation was evalueted using a high-intensity , white light (Maglite) in accordance with Draize method at 1, 24 , 48, 72 hours and at 4, 7 , 10 , 1417 and 21 days post instillation.
Observation period (in vivo):
21 days after the instillation.
Number of animals or in vitro replicates:
3 female rabbit New zeland albino.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1h
Score:
>= 36 - <= 41
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 24 hrs
Score:
>= 43 - <= 65
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 48 hrs
Score:
>= 43 - <= 65
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 72 hrs
Score:
>= 43 - <= 65
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 4 days
Score:
>= 28 - <= 65
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 7 days
Score:
>= 26 - <= 63
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 10 days
Score:
>= 26 - <= 63
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 14 days
Score:
>= 24 - <= 61
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 17 days
Score:
>= 24 - <= 61
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 21 days
Score:
>= 24 - <= 59
Irritant / corrosive response data:
After test substance instillation, all three treated eyes exhibited corneal opacity, iritis, and "positive" conjunctivis from 24 to 72 hours.The overall incidence and severity of irritation decreased gradually thereafter.Blanching around the eye tissue was noted for all animals from 24 hours to day 21, and a white discharge was noted for two animals from 24 hours to day 21.Ocular irritation persisted for all threee animals through day 21 (study termination).
Other effects:
no

Any other information on results incl. tables

All animals appeared active and healthy during the study. Apart from the eye irritation noted below, there were no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior.

After test substance instillation, all three treated eyes exhibited corneal opacity, iritis, and 'positive' conjunctivitis from 24 to 72 hours. The overall incidence and severity of irritation decreased gradually thereafter. Blanching around the eye tissue was noted for all animals from 24 hours to Day 21, and a white discharge was noted for two animals from 24 hours to Day 21.

Ocular irritation persisted for all three animals through Day 21 (study termination).

Time post  Incidence of positive Effect     
instillation Corneal Opacity Iritis Conjunctivitis
1 hour 3/3 3/3 3/3
24 hours 3/3 3/3 3/3
48 hours 3/3 3/3 3/3
72 hours 3/3 3/3 3/3
day 4 3/3 3/3 3/3
day 7 3/3 3/3 3/3
day 10 3/3 3/3 3/3
day 14 3/3 3/3 3/3
day 17 3/3 3/3 3/3
day 21 3/3 3/3 3/3

Time post instillation Severity of irritation - mean score
1 hour 39.3
24 hours 51.0
48 hours 51.0
72 hours 51.0
day 4 44.3
day 7 41.7
day 10 41.7
day 14 40.3
day 17 39.7
 day 21  39.0

Applicant's summary and conclusion

Interpretation of results:
other: Extremely irritating
Remarks:
Criteria used for interpretation of results: other: Draized method
Conclusions:
The Maximum Mean Total Score of Nickel (II) fluoride tetrahydrate is 51.0.Under the conditions of this study, Nickel fluoride tetrahydrate is classified as extremely irritatnting to the eye.
Executive summary:

A primary eye irritation test was conducted with rabbits to determine the potential for Nickel (II) fluoride tetrahydrate to produce irritation from a single instillation via the ocular route. Under the conditions of this study, the test substance is classified as extremely irritating to the eye.

One-tenth of a milliliter (0.09 grams) of the test substance was instilled into the right eye of three healthy rabbits.The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize et al.

After test substance instillation, all three treated eyes exhibited corneal opacity, iritis, and 'positive' conjunctivitis from 24 to 72 hours, The overall incidence and severity of irritation decreased gradually thereafter, Blanching around the eye tissue was noted for all animals from 24 hours to Day 21, and a white discharge was noted for two animals from 24 hours to Day 21.

Ocular irritation persisted for all three animals through Day 21 (study termination).