Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-08-23 to 2010-09-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

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
Test type:
up-and-down procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Cobalt hydroxide oxide
EC Number:
234-614-7
EC Name:
Cobalt hydroxide oxide
Cas Number:
12016-80-7
Molecular formula:
CoHO2
IUPAC Name:
cobalt hydroxide oxide
Details on test material:
- Name of test material (as cited in study report): Cobalt Oxide Hdyroxide
- Physical state: Black hydrated solid
- Stability under test conditions: Test substance was expected to be stable for the duration of testing.
- Storage condition of test material: At room temperature
- Solubility: Very low water solubility

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
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 176-205 g
- Fasting period before study: Naive rats were fasted overnight.
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 1996). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet: Purina Rodent Chow # 5012; feed was replaced approx. 3-4 hours after dosing.
- Water (ad libitum): Filtered tap water
- Acclimation period: 8-21 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 47-77; humidity was above the targeted upper limit for one day during the study. A portable dehumidifier was used to lower the humidity levels during this time.
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: The test substance was administered as a 60% w/w mixture in distilled water.
- Justification for choice of vehicle: Preliminary solubility test conducted by EPSL indicated that mixtures in excess of 60% (i.e., 70% or 80%) were too viscous to be administered properly.

MAXIMUM DOSE VOLUME APPLIED:
5,000 mg/kg

DOSAGE:
Individual doses were calculated based on the initial body weights, taking into account the specific gravity (determined by EPSL) and concentration of the test mixture.

Based on a limit dose of 5,000 mg/kg, at the request of the sponsor, a Main test was conducted using a default starting dose level of 175 mg/kg administered to one healthy female rat and following the Up and Down procedure, five additional females were dosed.
Doses:
175, 550, 1,750 or 5,000 mg/kg bw
No. of animals per sex per dose:
1 animal per 175 mg/kg dose level
1 animal per 550 mg/kg dose level
1 animals per 1,750 mg/kg dose level
3 animals per 5,000 mg/kg dose level
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All 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. Individual body weights were recorded prior to administration (initial) and again on Days 7 and 14 (termination) following dosing.
- Necropsy of survivors performed: yes; all rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Other examinations performed: Observations included gross evaluation 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 observations of tremors, convulsions, salivation, diarrhea and coma.
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 determinations and/or LD50 and confidence limit calculations.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals of the 175, 550, 1750 and 5000 mg/kg dose levels survived the test substance administration.
Clinical signs:
All animals of the 175, 550, 1750 and 5000 mg/kg dose levels appeared active and healthy during the study; no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour were noted.
Body weight:
All animals of the 175, 550, 1750 and 5000 mg/kg dose levels gained body weight during the study.
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-days observation period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the acute oral LD50 of Cobalt Oxide Hdyroxide is estimated to be greater than 5,000 mg/kg in female rats.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified.