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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
04 Sept - 12 Nov 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Secretariat général du GIPC, DGE Simap, 12 rue Villiot, 75572 Paris cedex 12, France
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Nickel(2+) hydrogen citrate
EC Number:
242-533-3
EC Name:
Nickel(2+) hydrogen citrate
Cas Number:
18721-51-2
Molecular formula:
C6H8O7.Ni
IUPAC Name:
hydrogen nickel(2+) citrate
Details on test material:
- Name of test material (as cited in study report): Nickel Hydrogencitrat
- Physical state: green powder
- Analytical purity: > 99%
- Lot/batch No.: WRG 09012701037
- Expiration date of the lot/batch: 26 Jan 2011
- Storage condition of test material: room temperature, in dryness

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER, 53940 Le Genest St Isle, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 191-205 g
- Fasting period before study: 24 h before dosing
- Housing: in groups of three in solid-bottomed clear polycarbonate cages
- Diet (e.g. ad libitum): M20 rat/mouse maintenance
- Water (e.g. ad libitum): tap water from public distribution
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 15 Sept To: 07 Oct 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 g or 300 mg in 10 mL each
- Amount of vehicle (if gavage): 10 mL/kg bw
- Purity: distilled water


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: assumed limit dose
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
6 (3 animals in step 1 and step 2, respectively)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed daily; animals were weighed just before substance administration and then on days 2, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Remarks on result:
other: According to the OECD guideline 423, the LD50 cut-off has to be considered 500 mg/kg bw.
Mortality:
All six rats treated with 2000 mg/kg bw died; one animal died 24 h post-dosing, two animals died 48 h after dosing and three animals 72 h after dosing.
No death occured in the animals administered 300 mg/kg bw.
Clinical signs:
Prior to death in animals treated with 2000 mg/kg bw, a decrease in spontaneous activity (6/6) associated with partial ptosis (3/6), piloerection (6/6) and bradypnea (4/6) occured. A decrease in muscle tone (1/6) and righting reflex (1/6) and increased lacrimation (1/6) were also observed.
In animals treated with 300 mg/kg bw, no clinical signs were observed.
Body weight:
A significant decrease in body weight was noted on day two in the three animals which died 72 h after recieving 2000 mg/kg bw.
The treatment with 300 mg/kg bw did not affect body weight.
Gross pathology:
The macroscopical examination of the dead animals in the 2000 mg/kg bw treatment group showed a thinning of the forestomach (5/6) associated with a red (3/6) or green coloration (1/6) and red (2/6) or white spots (3/6), a thinning of the corpus (2/6) associated with a red (1/6) or green coloration (2/6) and red (1/6) or black spots (1/6), and occurrence of red spots on the intestine (2/6) and of a green intestinal content (1/6).
The macroscopical examination of animals recieving 300 mg/kg bw at the end of the study did not reveal treatment-related changes.

Applicant's summary and conclusion