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Diss Factsheets

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:
August 7 - September 10, 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008
Reference Type:
publication
Title:
Acute Oral Toxicity of Nickel Compounds
Author:
Henderson RG, Durando J, Oller A, Merkel DJ, Marone PA, and Bates HK.
Year:
2012
Bibliographic source:
Regul Toxicol and Pharmacol (doi.org/10.1016/j.yrtph.2012.02.002)

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Nickel di(acetate)
EC Number:
206-761-7
EC Name:
Nickel di(acetate)
Cas Number:
373-02-4
Molecular formula:
Ni(CH3CO2)2
IUPAC Name:
nickel di(acetate)
Details on test material:
- Name of test material (as cited in study report): Nickel acetate tetrahydrate
- Molecular formula (if other than submission substance): not different than submission substance
- Molecular weight (if other than submission substance): not different than submission substance
- Smiles notation (if other than submission substance): not different than submission substance
- InChl (if other than submission substance): not different than submission substance
- Structural formula attached as image file (if other than submission substance): not different than submission substance
- Substance type: Pure product
- Physical state: liquid (60% w/v in distilled water)
- Physical description: Green, solid (crystals)
- Analytical purity: 100%
- Stability: Test substance was expected to be stable for the duration of testing.
- Storage condition of test material: stored under nitrogen
- Other details on test material not reported or not applicable

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Received from Ace Animals, Inc., Boyertown, PA on July 22 and August 5, 2008.
- Age at study initiation: 9-12 weeks
- Weight at study initiation: 184-220 grams
- Fasting period before study: not reported
- Housing: singly housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): ad libitum (Purina Rodent Chow #5012)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 10-28 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 63-86%,
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

IN-LIFE DATES: Not reported

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE: 60% w/w mixture in distilled water
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg
Doses:
175, 550, 2000 mg/kg
No. of animals per sex per dose:
2-4 per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: Following administration, each animal was returned to its designated cage. Feed was replaced approximately 3-4 hours after dosing. Observed up to 14 days.
- Frequency of observations and weighing: days 0, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight measured
Statistics:
The Acute Oral Toxicity (Guideline 425) Statistical Program (Weststat, version 1.0, May 2001) was used for all data analyses including: dose progression selections, stopping criteria determinations and/or LD50 and confidence limit calculations.

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
550 mg/kg bw
95% CL:
191.7 - 1 680
Mortality:
175 mg/kg: 0/2
550 mg/kg: 2/4
2000 mg/kg: 2/2
Clinical signs:
other: 175 mg/kg: There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior. 550 mg/kg: Prior to death, these animals were hypoactive. One surviving female exhibited piloerection following test substance administration, but recov
Gross pathology:
175 mg/kg: no gross abnormalities were noted
550 mg/kg: Gross necropsy of the decedents revealed red intestines. No gross abnormalities were noted for the euthanized animals when necropsied at the conclusion of the 14-day observation period.
2000 mg/kg: Gross necropsy of the decedents revealed red intestines.
Other findings:
none reported

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
The acute oral LD50 of Nickel acetate tetrahydrate in female rats was estimated to be 550 mg/kg-bw (95% CI 191.7-1,680). A NOAEL of 175 mg/kg bw (or 42 mg Ni/kg bw/day) was observed.
Executive summary:

Eurofins Product Safety Laboratory (EPSL, 2008) reported the findings of the acute oral toxicity of nickel acetate tetrahydrate as determined by the acute toxicity up and down procedures in rats (carried out according to OECD Test # 425 guidelines and using GLP standards). The purpose of the study was to determine the potential for nickel acetate tetrahydrate to produce toxicity from a single oral gavage dose, and to estimate a LD50 for the test compound. The authors stated that females were chosen for the study, as they are typically more sensitive to the toxicity of test chemicals than males.

Eight healthy, female rats were used for the study. A default starting dose level of 175 mg/kg nickel acetate tetrahydrate (60% w/w mixture in distilled water) was administered to one animal by gavage. The decision to proceed with dosing the next animal was based on survival of the previous animal, following administration of the test compound. Using this procedure, seven additional rats were administered 175 (1 rat), 550 (4 rats) or 2,000 mg/kg (2 rats) of the test compound. For 14 days after dosing, or until death occurred, rats were observed at least once per day for signs of gross toxicity, behavioral changes and mortality. Body weights were documented at various times: prior to dosing, day 7and day 14 (termination), following dosing, or post-mortem. Necropsies were conducted on all animals. No effects were observed in the animal exposed to 175 mg/kg. Of the four rats exposed to 550 mg/kg, two animals died within 3 hours (prior to death these animals exhibited hypoactivity) and exhibited red intestines upon necropsy. Aside from piloerection in one of the two surviving animals, no other effects were noted. In the 2,000 mg/kg dose group, both animals died within 1 day, displayed hypoactivity, hunched posture, and red intestines upon necropsy. The authors estimated that the acute oral LD50 of nickel acetate tetrahydrate was 550 mg/kg, with an approximate 95% confidence interval of 191.7-1,680 mg/kg. STUDY RATED BY AN INDEPENDENT REVIEWER