Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study with acceptable restrictions - The purity and stability of the test material were not stated. Minor deviations with no effect on the study results: -According to the guideline, the volume administered to the animals should not exceed 1ml/100 g bw. The information on the volume administered was missing in the study report. -According to the guideline, the diet and environmental conditions shoud be stated in the test report. This information was missing in this report.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984
Reference Type:
publication
Title:
Acute oral LD50 study in rats w Co(II) carbonate hydrate
Author:
Reagan
Year:
1992
Bibliographic source:
In: Richard Parent, (Ed.) Acute Toxicity Data. American College of Toxicology. Mary Ann Liebert Inc., (Pub.) Vol. 11, No. 6, p. 687.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
, see "rational for reliability"
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Cobalt carbonate
EC Number:
208-169-4
EC Name:
Cobalt carbonate
Cas Number:
513-79-1
Molecular formula:
CH2O3.Co
IUPAC Name:
lambda2-cobalt(2+) carbonate
Details on test material:
- Name of test material (as cited in study report): Cobalt (II) carbonate hydrate
- Molecular formula: 16CoCO3 * Co(OH)2* 8H2O
- Lot No.: 030383
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, MA
- Weight at study initiation: Males 215- 253 g; females 182 - 219 g
- Fasting period before study: Food was withheld the night prior to dosing.
- Housing: Rats were individually housed in wire mesh bottom cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Rats were held in environmentally controlled rooms.
No further information on the test animals was stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration prepared: 50 % suspension
PREPARATION PROCEDURE: Weighed 25 gm test article , Q.S. to 50 ml with diluent. The test article was administered at a constant concentration.
No further information on the oral exposure was stated.

Doses:
300 mg/kg, 480 mg/kg, 770 mg/kg, 1240 mg/kg, 2000 mg/kg
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:Animals were observed frequently on the day of dosing and twice daily thereafter. Body weights were recorded initially (prior to dosing), on days 8 and 15 or at death.
- Necropsy of survivors performed: Yes
All animals that died during the study and those sacrificed at termination were subjected to a gross necropsy and abnormalities were noted.
No further information on the study design was stated.
Statistics:
The LD50 value was determined according to Finney, D.J., 1971. Probit Analysis.Third Edition. Cambridge University Press. pp. 383.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
664 mg/kg bw
95% CL:
463 - 983
Sex:
female
Dose descriptor:
LD50
Effect level:
732 mg/kg bw
95% CL:
585 - 923
Sex:
male/female
Dose descriptor:
LD50
Effect level:
697 mg/kg bw
95% CL:
575 - 854
Mortality:
The following number of rats died at the different dose levels:
300 mg/kg: no rats died
480 mg/kg: 1 of 5 males (dead on day 7)
770 mg/kg: 3 of 5 males (dead on days 4,5,6); 3 of 5 females (dead on days 4,5,6)
1240 mg/kg: 5 of 5 males (dead on days 2,4,5,6); 5 of 5 females (dead on days 2,3, 4,5)
2000 mg/kg: 5 of 5 males (dead on days 3,4,6); 5 of 5 females (dead on day 3)
Clinical signs:
The follwoing clinical sigsn were seen at the different dose levels:
300 mg/kg: Diarrhea ( 1 of 5 males)
480 mg/kg: Decreased activity ( 1 of 5 males); Diarrhea ( 2 of 5 males)
770 mg/kg: Decreased activity (4 of 5 males; 5 of 5 females); Ataxia (3 of 5 males; 5 of 5 females); Diarrhea ( 5 of 5 males; 5 of 5 females)
1240 mg/kg: Decreased activity ( 5 of 5 males; 5 of 5 females); Ataxia (3 of 5 males; 2 of 5 females); Diarrhea ( 4 of 5 males; 4 of 5 females)
2000 mg/kg: Decreased activity ( 5 of 5 males; 5 of 5 females); Ataxia ( 3 of 5 males; 5 of 5 females); Diarrhea ( 4 of 5 males; 4 of 5 females)
Body weight:
Surviving animals gained weight from study initiation to termination.
Gross pathology:
At the dose level 300 mg/kg, 480 mg/kg, 770 mg/kg and 2000 mg/kg no noteworthy necropsy findings were made.
At the dose level 1240 mg/kg the instestines were found to be red in 1 male rat. No noteworthy necropsy findings were made in the remaining rats at this dose level.

Any other information on results incl. tables

In the original paper the LD50 value was determined according to Miller and Tainter (Proc. Soc. Biol.Med. 57, 261 (1994)). The results were later new calculated according to Finney, D.J., 1971. Probit Analysis. Third Edition, Cambridge University Press. pp. 383. The LD50 values stated under "Effect levels" are the values obtained according to Finney (1971).

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The following LD50 values were found:
LD50 (male rats): 664 mg/kg (Confidence interval: 463 - 983 mg/kg)
LD50 (female rats): 732 mg/kg (Confidence interval: 585 - 923 mg/kg)
LD50 (male and female rats): 697 mg/kg (Confidence interval: 575 - 854 mg/kg)
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is classified as harmful.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is Category 4.