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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, 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. - According to the guideline microscopic examination in animals surviving 24 or more hours should be considered. In this study, animals surviving 48 hours or more were microscopically examined.

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) oxide
- Molecular formula: CoO
- Molecular weight: 75.0 g/mol
- Analytical purity: 95 %
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 stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
The compound was suspended by means of an Ultra-Turrax (Janke u. Kunkel GmbH, Staufen, FRG) in a 1 % carboxymethylcellulose solution.
No further information about the oral exposure was stated.
Doses:
200 mg/kg bw, 300 mg/kg bw, 450 mg/kg, 675 mg/kg bw, 1010 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: Yes
Microscopic examinations of the heart, liver and kidneys was carried out on all rats survivng for 48 hr or more after treatment (i.e. on those dying between day 2 and day 10 or killed at the end of the 10- day observation period.
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 maximum likelihood of Finney (1971).

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
202 mg/kg bw
95% CL:
136 - 300
Remarks on result:
other: This is the LD50 for the cobalt compound tested.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
202 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:
159 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
Other findings:
- Histopathology:
Histopathological examination of animals that died during the experimental period was difficult because of autolytic changes. the follwoing summarises the histopathological findings made in the rats:
Heart: hyperaemia, haemorrhage, subendocardial haemorrhage, interstitial oedema and cell proliferation, myocardial changes
Liver: periportal cellular infiltrates, glycogen depletion moderate, glycogen depletion severe, vacuolization, hyperaemia, enlarged and eosinophilic cells, necrotic foci, periportal cells very pale
Kidneys: slight nephritis, hyperaemia, haemorrhage, tubular alterations, autolytic changes

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The following LD50 value was determined for cobalt (II) oxide:
LD50 (combined male and female rats): 202 mg/kg bw (95 % confidence interval: 136 - 300 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 3.