Trinickel dicitrate

Acute Toxicity: oral

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

Test material information

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:

other: 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 la

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.