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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 16,2008 to October 13,2008
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 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
yes
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):nickel difluoride tetrahydrate, Code #N111-PTL
- Purity: 99%
- Physical description:yellow-green powder
-solubility (water): 2.51g/100g
Test substance was expected to be stable for the duration of the testing
- Lot/batch No.:080707-36H

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals Inc, Boyertown PA USA
- Age at study initiation: young-adult
- Weight at study initiation:182-230
- Fasting period before study: overnight prior to each dosing
- Housing:singly housed in suspended stainless caging with mesh floors
- Diet (ad libitum): Purina Rodent Chow #5012
- Water (ad libitum): filtered tap water
- Acclimation period: 10-23 days
-other: the female rats are nulliparous and non pregnant.
Contaminants: THere were no known contaminants reasonably to be expected to be found in th efood or water at level 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 Eurofin

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19-21°C
- Humidity (%):63-86%. The humidity was above targeted upper limit of 70% during the study due to exceptionally high seasonal humidity. Portable dehumidifiers were used to lower the humidity levels during this time
- Photoperiod (hrs dark / hrs light):12 h light/dark cycle

IN-LIFE DATES: From: To:8/8/2008 to 10/10/2008

-CHOISE:
-choise of sex: Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle:55% w/w
Doses:
The test substance was administered as a 55% w/w mixture in distilled water using a stainless steel ball-tipped gavage attached to an appropriate sysinge.Following administration, each animal was returned to its designed cage.Feed was replaced approximately 3-4 hours after dosing.
No. of animals per sex per dose:
6 in total, 1 per step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Prior to administration and again after 7 and 14 days
- Necropsy of survivors performed: yes. Tissue and organs of the thoracic and abdominal cavities were examined on both decedents and euthanised animals
Statistics:
The Acute Oral Toxicity (Guideline 425) Statistical program (Westat, version 1.0, May 2001) was used for all data analyses including: dose progression selections, stopping criteria determination and/or LD50 and confidence limit calculations

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 310.2 mg/kg bw
Based on:
test mat.
95% CL:
> 175 - < 550
Clinical signs:
The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours post-dosing and at least once daily thereafter for 14 days dosing or until death occured.Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behavior pattern. Particular attention was directed to observation was directed to observatory of treemors, convulsions, salivation diarrhea, and coma.
Body weight:
Individual body weights of the animals were recorded prior to test substance administration (initial) and again on days 7 and 14 (termination) following dosing after death.
Gross pathology:
The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing or until death occured. Observations included gross evaluatuion 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, coma.

Any other information on results incl. tables

Animal N. Sex Dose Level (mg/kg)  Body weight (g)   DOSE Mortality  
    Initial Day 7 Day 14 mL Day Weight (g)
3101 F  175 193 212 252 0.044 E  
3103 F 175 215 259 271 0.049 E  
3105 F  175 207 224 256 0.048 E  
3102 F  550 222     0.16 3 201
3104 F 550 182     0.13 0 176
3106 F  550 230     0.17 2  

E= eutanized via CO2 inhalation after weighing on day 14

Animal Number Finding Day of Occurrence
175 mg/kg Dose level    
3101 active and healthy  0 -14
3103 active and healthy 0 - 14
3105  active and healthy  0 - 14
550 mg/kg Dose level    
 3102 active and healthy 0(1-5 Hrs)
  Ano-genital stainig  1-2
Hypoactivity and reduced fecal volume 2
  dead 3
 3104 Hypoactivity 0(1 hr)
dead 0(3 hrs)
 3106 active and healthy 0 (1-4.5 hrs)
Piloerection and reduced fecal volume 1
  dead 2

Animal Number Tissue Findings
175 mg/kg Dose level    
3101   All tissues and organ   No gross abnormalities
3103 All tissues and organs No gross abnormalities
3105   All tissues and organ  No gross abnormalities 
550 mg/kg Dose level  
3102   Intestines  Red
3104 Intestines Red
3106  Intestines  Red

DEVIATION FROM PROTOCOL:

The protocol requires that all decedents will be wheight immediately, or as soon as possible after death. Due to a technician error, the terminal bodywheights for animal n° 3106 was not recorded at the time of death. This deviation had no material impact on the results of study.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the acute oral LD50 of nickel fluoride tetrahydrate is estimated to be 310.2 milligrams per kilogram of body weight in female rats an approximate 95% confidence interval of 175 mg/kg bw (lower) to 550 mg/kg bw (upper). This value is derived from the study of Nickel fluoride tetrahydrate. The correspondent value of Nickel fluoride anhydrous is 178mg/Kg bw, justifying the classification in Category III of the CLP regulation
Executive summary:

An acute oral toxicity test (up and down Procedure) was conduced with rats to determine the potential for nickel(II) fluoride tetrahydrate to procedure toxicity from a single dose via the oral route. Under the conditions of this study, the acute oral LD50 of the test substance is estimated to be 310.2 mg/kg of body weight in female rats with an approximate 95% confidence interval of 175 mg/kg (lower) to 550 mg/kg (upper).

A main test was conducted using a default starting dose level of 175 mg/kg, which was administered to one healty female rat oral gavage. Following the up and down procedure, five additional animals were dosed at levels of 175 or 550 mg/kg. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing or until death occured. Body weights were recorded prior to administration and again on days 7 and 14 (termination) following dosing or after death. Necropsies were performed on all animals.