Nickel difluoride

Acute Toxicity: oral

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Nickel(2+) fluoride Tetrahydrate

EC Number:

604-130-4

Cas Number:

13940-83-5

Molecular formula:

H8F2NiO4

IUPAC Name:

Nickel(2+) fluoride Tetrahydrate

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 or test system 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

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 310.2 mg/kg bw

Based on:

test mat.

95% CL:

> 175 - < 550

Remarks on result:

other: corresponding to 178 mg/kg bw nickel fluoride anhydrous

Clinical signs:

other: 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

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:

Category 3 based on GHS criteria

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 3 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.