Registration Dossier

Administrative data

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:
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 404 (Acute Dermal 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
- Substance type:salt
- Physical state: yellow green powder
- Analytical purity: 99%
- Solubility: 2.51g/100g water
- Lot/batch No.:25622
Test substance was expected to be stable for the duration of testing

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals 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

Test system

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) wthout 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 anumal number assigned to study 25622, consisted unique identification.

Results and discussion

In vivo

Results
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Score:
ca. 2.4
Max. score:
5
Reversibility:
fully reversible within: 7 days
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 abnornial
behavior.

Any other information on results incl. tables

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

Applicant's summary and conclusion

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: US EPA pesticides
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).