Registration Dossier

Administrative data

Description of key information

Acute oral toxicity:
LD50(female rats)>2000mg/kg bw
Acute toxicity, dermal:
Conduct of an acute dermal toxicity study is unjustified since dermal uptake is considered negligible (cf. Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006).
Acute toxicity, inhalation:
Testing is technically not feasible.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-07-20 to 2006-2007-09-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study reliable without restrictions Minor deviations with no effect on the results of the study: - The stability of the test material was missing, but it was stated in the report that the test substance appeared to be stable under the conditions of the study. No evidence of instability, such as a change in colour or physical state, was observed. - According to the guideline, the volume for administration of the test substance should not exceed 1 ml /100g of body weight; however in the case of aqueous solution, 2 ml/100 g body weight can be considered. Also, the test substances should be administered in a constant volume. The test substance was not administered in a constant volume and the volume for nonaqueous solutions was exceeded. This was not considered to influence the results. - According to the guideline, the rats should be observed daily for a total of 14 days. One rat was not observed on day 9 for clinical signs. This test guideline deviation did not affect the validity of the study because no clinical signs were observed in this rat after the day of dosing.
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
, adopted 2006-03-23
Deviations:
yes
Remarks:
, see "rational for reliability"
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, North Carolina
- Age at study initiation: Approx. 10 or 11 weeks old on the day of dosing
- Weight at study initiation: 204.9 - 255.3 g (fasted body weight)
- Fasting period before study: The rats were fasted approx. 16 - 18 hours prior to dosing, with food being returned to the rats approx. 3 -4 hours after dosing.
- Housing: All animals were housed singly in stainless steel, wire-mesh cages suspened above cage boards.
- Diet (ad libitum): PMI® Nutrition International, LLC certified Rodent Lab Diet® 5002
- Water: ad libitum
- Quarantine period: At least 6 days


ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 26 °C
- Relative humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.
Route of administration:
oral: gavage
Vehicle:
other: 0.1 % Tween-80 (V/V) in 0.5 % aqueous methylcellulose
Details on oral exposure:
VEHICLE
The test item was suspended in 0.1 % Tween-80 (V/V) in 0.5 % aqueous methylcellulose.

MAXIMUM DOSE VOLUME APPLIED: Individual dose volumes were calculated using the fasted body weights obtained prior to dosing. The rats dosed at 175 or 550 mg/kg were dosed at a volume of 10 mL per kg of body weight. therats dosed at 2000 mg/kg were dosed at a volume of 20 mL per kg of body weight. Since the amount for one rat (2000mg/kg) exceeded 5 mL, the dose was administered in 2 portions, 16 minutes apart.The dose suspensions were stirred at least 30 minutes prior to and throughout the dosing procedure.

DOSAGE PREPARATION (if unusual): Cobalt distearate was in the form of pellets and was crushed into a fine poder with a mortar and pestle. The powder was suspended in the vehicles. The suspension was milled at high speed with glass beads for 15 - 19 hours on a shaker table. A new dose suspension was prepared for each day of dosing.
- Rationale for the selection of the starting dose: The starting dose level of 175 mg/kg was chosen based on the absence of toxicity data for this test substance.
No further information on the oral exposure was stated.
Doses:
175 mg/kg, 550 mg/kg, 2000 mg/kg
No. of animals per sex per dose:
175 mg/kg: one female
550 mg/kg: one female
2000 mg/kg: three females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality and signs of illness, injury, or abnormal behaviour were made daily throughout the study. The rats were observed for clinical signs at the beginning of fasting, just before dosing (test day 0), once during the first 30 minutes after dosing and 2 more times on the day of dosing, and once each day thereafter (day 9 excluded for one rat). The rats were weighed on test days -1 (day before dosing (weight before fasting)), 0 (day of dosing (weight after fasting)), 7, and 14.
- Necropsy of survivors performed: Yes
On test day 14 , the rats were euthanized and necropsied to detect grossly observable evidence of organ and tissue damage or dysfunction. The rats were anesthetized by carbon dioxide and euthanized by exsanguination.
No further information on the study design was stated
Statistics:
A software package (A0T425StatPgm) was used to determine the dose progression and to calculate the LD50.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred.
Clinical signs:
High carriage and ataxia were observed up to the day after dosing in the rat dosed at 550 mg/kg. Two rats dosed at 2000 mg/kg exhibited abnormal gait (hindlimb, bilateral, moderate) and/or high carriage on the day of dosing. No clinical signs of toxicity were observed in the remaining rats.
Body weight:
No body weight loss occurred after dosing.
Gross pathology:
There were no gross lesions found in the study.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the oral LD50 for cobalt distearate was greater than 2000 mg/kg for 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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for selection of acute toxicity – oral endpoint
Key study.

Justification for selection of acute toxicity – dermal endpoint
Weight of evidence data.

Justification for classification or non-classification

Acute oral toxicity

The reference Finlay (2007) and Schmidt et al. (1975) are considered as the key studies for acute oral toxicity and will be used for classification. According to Finlay (2007) female CD(SD) rats were dosed at 175, 550 and 2000 mg/kg orally via gavage. During the conduct of the study no mortalities occurred at the highest dose group

LD50 oral, rat >2000 mg/kg bw

According to Schmidt et al. (1975) female rats received a total dose of 150 mg cobalt stearate/ml. The LD50 for female rats was calculated to be 2390 mg/kg bw with a 95% confidence interval of 2130 to 2670.

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic are not met since the ATE is above 2000 mg/kg body-weight, hence no classification required.

 

Specific target organ toxicant (STOT) – single exposure: oral

The classification criteria acc. to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification of 300 mg/kg bw and at the guidance value, oral for a Category 2 classification of 2000 mg/kg bw. No classification required.

 

Acute dermal toxicity

Conduct of an acute dermal toxicity study is unjustified since dermal uptake is considered negligible.

 

Specific target organ toxicant (STOT) – single exposure: dermal

Conduct of an acute dermal toxicity study is unjustified since dermal uptake is considered negligible.

 

Acute inhalation toxicity and Specific target organ toxicant (STOT) – single exposure: inhalation

According to section 2, annex XI of regulation (EC) 1907/2006, the conduct of an acute toxicity study via inhalation for cobalt stearate is omitted. The substance is placed on the market and used as solid lumps with a particle size of >> 1 mm.

In order to assess the tendency of cobalt stearate lumps to generate fine particles via abrasion, a friability test was conducted (see Physical chemical properties/particle size distribution section for further details.The total amount of abraded material was 1.5% of the starting material. The total dustiness (airborne fraction) of the abraded fraction was 0.237% based on the total amount of starting material, with a mass median aerodynamic diameter of airborne fraction of MMAD=28.63 µm, GSD=4.72. The fractional deposition in human respiratory tract (MPPD model, based on calculated MMAD) is: Head (ET): 45.1 %, Tracheobronchial (TB): 0.1 %, Pulmonary (PU): 0.1 %.

Based on the above information it is concluded that cobalt stearate is not likely to generate elevated amounts of abraded particles under conditions of severe shear stress, hence is not capable creating an inhalable atmosphere, thus testing is technically not feasible.