Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-07-21 to 2007-03-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study reliable without restrictionsMinor deviations with no effect on the study 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.- According to the guideline, the volume for administration of the test substance should not normally 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.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Cobalt borate neodecanoate- Physical state: Viscous liquid- Analytical purity: see composition of test material- Composition of test material, percentage of components: > 94 % Cobalt borate neodecanoate; < 6 % Cobalt borate propionate; 22.15 % Cobalt- Batch No.: A469 - 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: 1.32 g/cm^3 at 25 °C- Water solubility: 51.2 mg/L at 20 °C- pKa: 6.41 at 20 °CNo further information on the test material was stated.

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles River LAboratories, Inc., Raleigh, North Carolina, U.S.A.- Age at study initiation: approx. 10 or 11 weeks old- Weight at study initiation: 205.0 to 235.2 g- Fasting period before study: 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 suspended 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): 12/12No further information on the test animals was stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE & DOSAGE PREPARATIONThe test substance would not suspend in an aqueous vehicle. An acceptable solution was obtained using corn oil as vehicle. Cobalt borate neodecanoate was mixed with Mazola® corn oil, sonicated at approx. 45°C for several hours, and stirred overnight to solubilize. A new dose solution was prepared for each day of dosing.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 the rats dosed at 2000 mg/kg were administered in two portions, 15 or 19 minutes apart. the dosing solutions were stirred for at least 30 minutes prior to and throughout the dosing procedure.- 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 female550 mg/kg: three females2000 mg/kg: three females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days (or other?)- Frequency of observations and weighing: Observations for mortality and signs of illness, injury, or abnormal behaviour were made daily throughout the study. 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. Rats were weighed on the test days-1, 0, 7, and 14. Test day -1 is prior to fasting and test day 0 is after fasting. - Necropsy of survivors performed: YesOn 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 softeware 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: Approx. LD50 based on an assumed sigma of 0.5; The 95% CL is an approx. 95% confidence interval
Mortality:
The rats dosed at 2000 mg/kg were found dead 1, 3, or 4 days after dosing. All other animals surivied until sacrification.
Clinical signs:
No clinical signs of toxicity were observed in the rat dosed at 175 mg/kg. All rats dosed at 550 mg/kg or 2000 mg/kg exhibited clinical signs including various staining, wet fur, high carriage,diarrhea, lethargy, ataxia, clear ocular discharge, labored breathing, brown discharge from the vulva, prostrate posture, and/or decreased muscle tone.
Body weight:
No body weight loss occurred in surviving rats after dosing
Gross pathology:
There were no test substance-related gross lesions found in the study. The only gross lesion observed, skin stain in two rats, was non-specific and not indicative of target organ toxicity.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the oral LD50 for cobalt borate neodecanoate was 1098 mg/kg for female rats.According to 67/548/EC and subsequent regulations, cobalt borate neodecanoate has be classified as harmful.According to the EC Regulation No. 1272/2008 and subsequent regulations, cobalt borate neodecanoate is classified Category 4.