Registration Dossier

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:
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 aquoues 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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Propionic Acid, Cobalt (2+) Salt
- Molecular formula: C6H10O4Co
- Molecular weight: 205.1 g
- Physical state: Light purple solid (powder)
- Analytical purity: see composition of test material below
- Composition of test material, percentage of components: 100 % Propionic Acid, Cobalt (2+) Salt ( no other known components); 30.30 % Cobalt
- Batch No.: LB1022-51
- 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.
No 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
- Age at study initiation: approx. 10 or 11 weeks old
- Weight at study initiation: 205.1 - 228.3 g (fasted body weight)
- 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 six 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:
other: 0.5 % aqueous methylcellulose
Details on oral exposure:
VEHICLE & DOSAGE PREPARATION
Cobalt propionate was suspended in 0.5 % aqueous methylcellulose. The suspension was milled at high speed with glass beads for 15 - 19 hours on a shaker table. A new dose suspension was prepare for each day of dosing. The dosing suspensions were stirred at least 30 minutes prior to and throughout the dosing procedure.

MAXIMUM DOSE VOLUME APPLIED: Individual dose volumes were calculated using the fasted body weights obtained prior to dosing. The rats dosed at 55, 175, or 550 mg/kg were dosed at a volume of 10 mL per keg of body weight. The rat dosed at 306 mg/kg was dosed at a volume of 17.5 ml/kg. the rat dosed at 2000 mg/kg was dosed at a volume of 20 mL per kg of body weight.

- 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 oral exposure was stated.





Doses:
55 mg/kg, 175 mg/kg, 306 mg/kg, 550 mg/kg, 2000 mg/kg
No. of animals per sex per dose:
55 mg/kg: one female
175 mg/kg: two females
306 mg/kg: one female
550 mg/kg: three females
2000 mg/kg: one female
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.Rats were observed for clinical signs at the beginning of fasting, just before dosing (test day =), 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 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: Yes
On the 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:
354.7 mg/kg bw
95% CL:
61.19 - 1 890
Remarks on result:
other: Approx. LD50 based on maximum likelihood; The 95% CL is a profile likelihood confidence interval
Mortality:
Two rats at 500 mg/kg and the rats dosed at 306 or 2000 mg/kg were found dead on the day of dosing.
Clinical signs:
No clinical signs of toxicity were observed in the rat dosed at 55 mg/kg and in one of the rats dosed at 175 mg/kg. Clinical signs observed in the remaining rats included lethargy, ataxia, low or high carriage, fast or labored breathing, prostrate posutre, decreased muscle tone (rigid spine or rigid whole body), hair loss, paralysis of forelimb/hindlimb, mydriasis, spasm, cold to touch, and/or dry mucous membrane.

Body weight:
No biologically important 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, red discolouration (glandular) of the stomach in one rat, was non-specific and not indicative of target organ toxicity.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the oral LD50 for cobalt propionate was 354.7 mg/kg for female rats.
According to 67/548/EC and subsequent regulations, cobalt propionate is classified as harmful.
According to the EC Regulation No. 1272/2008 and subsequent regulations, cobalt propionate is classified as Category 4.