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Toxicological information

Acute Toxicity: oral

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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:
Methodology well-documented Minor deviations from the guideline: - The stability of the test item was not stated. - According to the guideline, necropsy of all animals should be carried out. There was no information,if necropsy of the animals was carried out. - According to the guideline, the observation period should be at least 14 days. In this study only an observation period of 10 days was used. - According to the guideline, the number of animals that died or were killed during the test and the time of death after dosing should be stated. This information was missing in this publication. -According to the guideline, the LD50 values for the sex dosed determined at 14 days should be stated. The LD50 for combined sexes determined at 10 days was stated. - According to the guideline, the animals should be fasted before test item administration. There is no statement in the study, if this was done. - According to the guideline the individual weights of animals should be determined shortly before the test substance is administered, weekly thereafter and at death; changes in weight should be calculated and recorded when survival exceeds one day. At the end of the test surviving animals are weighed and then sacrificed. This information is missing in the report.

Data source

Reference
Reference Type:
publication
Title:
Acute oral toxicity of inorganic cobalt compounds in rats
Author:
Speijers, G.J.A. et al.
Year:
1982
Bibliographic source:
Fd Chem. Toxic, Vol. 20:311-314.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
, adopted 1987-02-24
Deviations:
yes
Remarks:
, see "rational for reliability"
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Cobalt (II) nitrate hexahydrate
- Molecular formula: Co(NO3)2 * 6H2O
- Molecular weight: 291.1 g/mol
- Analytical purity: 99 % pure
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: The colony of the Animal Breeding Unit, National institute of Public Health, Bilthoven
- Weight at study initiation: approx. 100 g
- Housing: Caged singly or in pairs of the same sex and dose group, in wire cages.
- Diet (ad libitum): Semi-purified diet (Murneon-SSP Tox (Trouw Ltd. Putten)
- Water (ad libitum): Drinking water

ENVIRONMENTAL CONDITIONS
- Temperature: 22- 25 °C
- Relative humidity: 35 - 55 %
No further information on the test animals was statd.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
The compound was dissolved in in distilled water.
No further information about the oral exposure was stated.
Doses:
450 mg/kg bw, 675 mg/kg bw, 1000 mg/kg bw, 1500 mg/kg bw, 2250 mg/kg bw
No. of animals per sex per dose:
5 males / 5 females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 10 days
- Frequency of observations and weighing: Signs of reaction and deaths were recorded for 10 days, and the rectal temperature was mesured in all survivng rats 1.5, 24 and 48 hr after administration of the cobalt compound.
- Necropsy of survivors performed: No data
No further information on the study design was stated.
Statistics:
The oral LD50 values for male and female combined, were calculated according to the method of mayximum likelihood of Finney (1971).

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
691 mg/kg bw
95% CL:
526 - 907
Remarks on result:
other: This is the LD50 for the cobalt compound tested.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
434 mg/kg bw
Remarks on result:
other: This is the LD50 for the anhydrous form of the test item. The LD50 of the anhydrous form of the cobalt compound was derived from the LD50 data of the cobalt compound tested.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
140 mg/kg bw
Remarks on result:
other: This is the LD50 for the cobalt (II) ion. The LD50 of the cobalt (II) ion was derived from the LD50 data of the cobalt compound tested.
Mortality:
No data
Clinical signs:
The highest dose caused sedation and diarrhoea. A decrease in body temperature was recorded. The temperature reductions were time- and dose-related.
Body weight:
No data
Gross pathology:
No data

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 value was determined for cobalt (II) nitrate hexahydrate:
LD50 (combined male and female rats): 691 mg/kg bw (95 % confidence interval: 526 - 907 mg/kg bw)
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 classified as Category 4.