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Administrative data

Description of key information

Skin irritation: The test substance was found to be moderatly irritating in a primary skin irritation study in rabbits comparable to OECD guideline OECD 404 (K1; Eurofins, 2008). 


Eye irritation: The test substance was determined to be highly irritating in a primary eye irritation study in rabbits according to OECD guideline 405 (K1; Eurofins, 2008) leading to a classification as Eye Dam. Cat 1.


 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 16,2008 to October 8,2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Robinson services Inc, Clemmons, NC USA
- Age at study initiation: young adult
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of taborototy Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per weck.
- Diet (ad libitum): Pelleted Purina rabbit chow #5326
- Water (ad libitum): Filtered tap water ad-libitum by an automatic water dispending system.
- Acclimation period: 7 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 Labor atories.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 69-84
- Photoperiod (hrs dark / hrs light): 12 hours dark/light
There were no expected contaminants reasonably expected to be founf in the food or water at the levels which would have interfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Eurofins
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
The sample was applied as a dry paste (75% w/w mixture in distilled water). Five-tenth of a gram of the test substance (0.67g of the test mixture) was placed on a 1-inch x 1-inch, 4ply gauze pad and applied to one 6-cm2 intact dose site on each animal. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the pad.
Duration of treatment / exposure:
After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites were gently cleansed of any residual test substance
Observation period:
7 days
Number of animals:
3 female New Zealand abino rabbit
Details on study design:
A) Preparation and Selection of Animals
On the day before application, a group of animals was prepared by clipping the dorsal area and the trunk. On the day of dosing, but prior to application, the animals were examined for health and the skin checked for any abnormalities. Three healthy, naive animals (not previously tested) without pre-existing skin irritation were selected for test.
IDENTIFICATION:
Cage:
Each cage was identified with a cage card indicating at least the study number and identification and sex of the animal
Animal:
A number was allocated to each rabbit on receipt and a stainless steel ear tag bearing this number was attached to the animal. This number, together with a sequential animal number assigned to study 25622, consisted unique identification.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
7 d
Score:
ca. 2.4
Max. score:
5
Reversibility:
fully reversible within:
Irritant / corrosive response data:
The classification of irritancy was obtained by adding the average erythema and edema scores for the 30-60 minutes, 24, 48 , 72 hours scoring intervals and dividing by number of evaluation intervals.
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.

Evaluation of Test Sites

Individual dose sites were scored according to the Draize scoring system I at approximately 30 -60 minutes, 24, 48, and 72 hours and 7 days atter patch removal. The classification of irritancy was obtained by adding the average erythema and edema scores for the 30-60 minute, 24, 48, and 72-hour scoring intervals and dividing by the number of evaluation intervals (4).

Cage-Side Observations

The animals were observed for signs of gross toxicity and behavieral changes at least once daily during the test period. 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.

   Time after patch removal            
  30 -60 min   24 hrs  48 hrs  72 hrs  Day 7
Erythema 

 2.0

 1.7

 1.3

 1.3

 0

Edema   1.0  0.7  0.7  0.7  0
TOTAL (PDI) Erythema + Edema  3.0  2.4  2.0  2.0  0
Interpretation of results:
moderately irritating
Conclusions:
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 abnornial behavior.
Within one hour of patch removal, all three treated sites exhibited well-defined erythema and very slight edema. The overall incidence and severity of irritation decreased with time. All animals were free of dermal irritation by Day 7 (study termination).
The Primary Dermal Irritation Index for Nickel (II) fluoride tetrahydrate is 2.4.
Under the conditions of this study, Nickel (II) fluorIde tetrahydrate is classified as moderately irritating to the skin.
Executive summary:

A primary skin irritation test was conducted with rabbits to determine the potential for Nickel (II) fluoride tetrahydrate to produce írritation after a single topical application. Under the conditions of this study, the test substance is classified as moderately irritating to the skin. Five-tenths of gram of the test substance was moistened with distilled water and then applied tothe skin of three healthy rabbits for 4 hours. Following exposure, dermal irritation was evaluated by the method of Draize er et al.

Within one hour of patch removal, all three treated sites exhibited well-defined erythema and very slight edema. The overall incidence and severity of irritation decreased with time. All animals were free of dermal irritation by Day 7 (study termination).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
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:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
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
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.
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:
24 h
Score:
>= 43 - <= 65
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
48 h
Score:
>= 43 - <= 65
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
72 h
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

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
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 irritating 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).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation


In a primary skin irritation test comparable to OECD guideline 404 (key study, K1; Eurofins, 2008), 0.67g of the test substance was moistened with distilled water and then applied tot he skin of three healthy rabbits for 4 hours (semi-occlusive). Following exposure, dermal irritation was evaluated by the method of Draize. The observation period lasted 7 days. Within one hour of patch removal, all three treated sites exhibited well-defined erythema and very slight edema. The overall incidence and severity of irritation decreased with time. All animals were free of dermal irritation by Day 7 (study termination).The mean primary dermal irritation index was determined to be 2.4/5. Under the conditions of this study, the test substance is classified as moderately irritating to the skin.


No in vitro skin irritation study needs to be conducted because adequate data from an in vivo study are available .


Eye irritation


In a primary eye irritation study according to OECD guideline 405 (key study, K1; Eurofins, 2008), 0.09g of the test substance was instilled into the right eyes of three healthy rabbits. Ocular irritation was evaluated by the method of Draize. The observation period lasted 21 days. 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). The Maximum Mean Total Score was established to be 51.0. Under the conditions of this study, the test substance is classified as highly irritating to the eye.


No in vitro eye irritation needs to be conducted as adequate data from an in vivo eye irritation study are available.



Respiratory irritation


The available data do not allow any conclusion on respiratory irritation. The criteria for classification for respiratory irritation are mainly based on human experience, which is lacking. There is a concern for respiratory irritation.

Justification for classification or non-classification

Based on the available data and according to the criteria laid down in the CLP Regulation (EC) 1272/2008, the test substance should be classified as Skin irritant, Category 2 (H315) and Eye irritant Category 1 (H318).