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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-07-20 to 2007-03-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Minor deviations with no effect on the results of the study: - 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. - 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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
2006-03-23
Deviations:
yes
Remarks:
, see "rational for reliability"
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no

Test material

Constituent 1
Reference substance name:
Neodecanoic acid, cobalt salt
EC Number:
248-373-0
EC Name:
Neodecanoic acid, cobalt salt
Cas Number:
27253-31-2
IUPAC Name:
Neodecanoic acid, cobalt salt
Details on test material:
- Name of test material (as cited in study report): Cobalt neodecanoate
- Physical state: Blue/purple thick liquid, maybe semi-solid
- Analytical purity: see "Composition of test material, percentage of components" below
- Composition of test material, percentage of components: 100 % Neodecanoic Acid, Cobalt salt (Percent Metal: 14.32 % Cobalt)
- Lot No.: 69431
- Stability under test conditions: 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.
- Density: 1.07 g/cm^3 at 25 °C
- Water solubility: estimated to be 309.5 mg/L at 20 m°C
- pKa: 6.52 at 20 °C
No further information on the test material was stated.

Test animals

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: 215.7 - 225.2 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.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: The test substance would not suspend in an aqueous vehicle. An acceptable solution was obtained using corn oil as vehicle.

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. The rats dosed at 2000 mg/kg were dosed at 20 mL per kg of body weight because the dose solutions at concentrations above 100 mg/ml were too thick to administer. The amount given to rats dosed at 2000 mg/kg was administered in two portions, 15 - 20 minutes apart. The dose solutions were stirred for at least 30 minutes prior to and throughout the dosing procedure.

DOSAGE PREPARATION: Cobalt neodecanoate was mixed with Mazola® corn oil and vortexed, stirred, and/or sonicated to form a solution. Dose solutions for the rats receiving 550 and 2000 mg/kg were stirred overnight to solubilize. It was not necessary to stir the dose solution overnight for the rat receiving 175 mg/kg. A new dose solution 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: three females
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. The rats were weighed on the 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 surviving rats were euthanized and necropsied to detect grossly observable evidence of organ or tissue damage or dysfunction. The rats were anesthetized by carbon dioxide and euthanized by exsanguination. The rats that died were also necropsied.
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.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
1 098 mg/kg bw
95% CL:
>= 550 - <= 2 000
Remarks on result:
other: The estimated LD50 is based on an assumed sigma of 0.5.
Mortality:
The rats dosed at 2000 mg/kg were found dead on test days 0 or 2.
Clinical signs:
other: All rats exhibited clinical signs of toxicity including diarrhea, high or low carriage, lethargy, ataxia, laboured or slow breathing, prostrate posture, various staining, wet fur, decreased muscle tone, clear oral discharge, paralysis, mydriasis, and/or d
Gross pathology:
There were no test substance related gross lesions found in the study. The only gross lesion observed, skin stains in two rats dosed at 2000 mg/kg, was non-specific and not indicative of target organ toxicity.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditins of this study, the oral LD50 for cobalt neodecanoate was 1098 mg/kg for female rats. the approximate 95 % confidence interval was 550 to 2000 mg/kg.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is classified as Category 4.