Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-04-20 to 2010-06-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Remarks:
: none considered to have affected the integrity of the study
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Remarks:
: none considered to have affected the integrity of the study
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
nickel (II) oxalate dihydrate
IUPAC Name:
nickel (II) oxalate dihydrate
Constituent 2
Reference substance name:
6018-94-6
Cas Number:
6018-94-6
IUPAC Name:
6018-94-6
Details on test material:
- Name of test material (as cited in study report): nickel oxalate dihydrate
- Molecular formula (if other than submission substance): NiC2O4.2H2O
- Molecular weight (if other than submission substance): 182.7 g/mol
- Physical state: light green-blue powder with lumps
- Analytical purity: no data
- Lot/batch No.: MC_NiOx_NOTOX_100302
- Expiration date of the lot/batch: 2011-03-15
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland (Sulzfield, Germany)
- Age at study initiation: approximately 8-10 weeks
- Weight at study initiation: no data
- Fasting period before study: no
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm) containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF). Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance.
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 +/- 3.0
- Humidity (%): 40-70 (actual range: 37-60)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2010-02-01 To: 2010-02-06

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1% aqueous
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
- Purity: no data

DOSAGE PREPARATION:
- The formulations were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of mL/kg body weight.

CLASS METHOD:
- Rationale for the selection of the starting dose: no data
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
3 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality/viability were performed twice daily. Body weights were recorded on day 1 (pre-administration), 8 and 15. Clinical signs were observed at periodic intervals on day 1 and once daily thereafter until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: Yes. At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
- No statistical analysis was performed (the method does not allow for calculation of a precise LD50 value).

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
- No mortality occurred at either dose.
Clinical signs:
- Hunched posture and/or piloerection were noted for all animals at both dose levels on day 1.
Body weight:
- The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
- No abnormalities were found.

Any other information on results incl. tables

Temporary deviations from the minimum level of relative humidity occurred. The laboratory historical data did not indicate any effect of the deviation.

Applicant's summary and conclusion

Conclusions:
The oral LD50 value of nickel oxalate dihydrate in female Wistar rats exceeded 2000 mg/kg bw.