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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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
The study is well-documented by the publication and thus acceptable for assessment.

Data source

Reference
Reference Type:
publication
Title:
Acute oral toxicity of inorganic cobalt compounds in rats
Author:
Speijers, G.J.A.; Krajnc, E.I.; Berkvens, J.M.; van Logten, M.J.
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)
Deviations:
yes
Remarks:
No information about: stability of the test item, individual weights, number of died or killed animals. Observation period was only 10 days. Necropsy information only of the animals which were treated orally with cobalt(II) fluoride and cobalt(II) oxide.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Details on test material:
Eight cobalt compounds were tested: Cobalt(II) nitrate hexahydrate (Co(NO3)2*6H2O), cobalt(II) sulphate heptahydrate (CoSO4*7H2O), cobalt(II) acetate tetrahydrate (Co(CH3COO)2*4H2O), cobalt(II) chloride hexahydrate (CoCl2*6H2O), cobalt(II) fluoride (CoF2), cobalt(II) bromide (CoBr2), cobalt(II) oxide (CoO) and cobalt(II) phosphate octahydrate (Co3(PO4)2*8H2O)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Doses:
Cobalt(II) fluoride (CoF2): 70, 112, 180, 290, 460 mg/kg body weight
Cobalt(II) oxide (CoO): 200, 300, 450, 675, 1010 mg/kg body weight
Cobalt(II) phosphate octahydrate (Co3(PO4)2*8H2O): 300, 450, 675, 1000, 1500 mg/kg body weight
Cobalt(II) bromide (CoBr2): 200, 300, 450, 675, 1010 mg/kg body weight
Cobalt(II) chloride hexahydrate (CoCl2*6H2O): 500, 600, 720, 864, 1137 mg/kg body weight
Cobalt(II) sulphate heptahydrate (CoSO4*7H2O): 450, 675, 1000, 1500, 2250 mg/kg body weight
Cobalt(II) nitrate hexahydrate (Co(NO3)2*6H2O): 450, 675, 1000, 1500, 2250 mg/kg body weight
Cobalt(II) acetate tetrahydrate (Co(CH3COO)2*4H2O): 250, 375, 560, 840, 1260 mg/kg body weight
No. of animals per sex per dose:
5 males / 5 females
Control animals:
not specified

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
150 mg/kg bw
Based on:
test mat.
Remarks:
CoF2
95% CL:
>= 115 - <= 195
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
202 mg/kg bw
Based on:
test mat.
Remarks:
CoO
95% CL:
>= 136 - <= 300
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
539 mg/kg bw
Based on:
test mat.
Remarks:
Co3(PO4)2*8H2O
95% CL:
>= 425 - <= 683
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
406 mg/kg bw
Based on:
test mat.
Remarks:
CoBr2
95% CL:
>= 330 - <= 500
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
766 mg/kg bw
Based on:
test mat.
Remarks:
CoCl2*6H2O
95% CL:
>= 677 - <= 867
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
768 mg/kg bw
Based on:
test mat.
Remarks:
CoSO4*7H2O
95% CL:
>= 594 - <= 995
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
691 mg/kg bw
Based on:
test mat.
Remarks:
Co(NO3)2*6H2O
95% CL:
>= 526 - <= 907
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
708 mg/kg bw
Based on:
test mat.
Remarks:
Co(CH3CO2)2*4H2O
95% CL:
>= 569 - <= 880
Clinical signs:
The highest dose caused sedation and diarrhoea. Rats given cobalt(II) sulphate or chloride also showed tremors and convulsions prior to death. Respiratory disturbances were apparent in rats given acetate. Animals in the cobalt(II) fluoride group did not show any of these effects. In all animals a decrease in body temperature was recorded. The temperature reductions were time- and dose-related.
Body weight:
No data
Gross pathology:
Rats given cobalt(II) fluoride revealed severely haemorrhagic mucosal tissue and in addition the stomach was filled with a colourless fluid.
Other findings:
Histopathological examination of animals that died in the groups treated with cobalt(ll) fluoride:
liver: glycogen depletion; frequently diffuse vacuolization; in some animals hyperaemia; cytoplasmic changes
kidneys: in some animals hyperaemia; glomeruli were very rich in cells and basal membranes were thickened; cells of the proximal tubules were swollen and exhibited slight vacuolization and degeneration.
other organs: Three of the animals given the 290-mg/kg dose showed myocardial changes consisting of proliferative and oedematous interstitial tissue and swollen muscle fibres with focal degeneration.

Histopathological examination of animals that died in the groups treated with cobalt(ll) oxide:
similar to the examination of animals that died in the groups treated with cobalt(II) fluoride
In addition to hyperaemia, some haemorrhage was observed, especially in the heart
heart: swollen and eosinophilic muscle fibres were observed.
In some animal's vacuolization, degeneration and necrosis of the myocardium was associated with disappearance of the cross-striations. In these areas mitotic activity was also apparent, probably in developing fibroblasts.

Any other information on results incl. tables

The oral LD50 values calculated for the anhydrous cobalt(lI) compounds were: cobalt(II) fluoride 150 mg/kg bw, cobalt(II) oxide 202 mg/kg bw, cobalt(II) phosphate 387 mg/kg bw, cobalt(II) bromide 406 mg/kg bw, cobalt(II) chloride 418 mg/kg bw, cobalt(II) sulphate 424 mg/kg bw, cobalt(II) nitrate 434 mg/kg bw and cobalt(II) acetate 503 mg/kg bw.

The oral LD50 values calculated for the cobalt percentage in the cobalt(II) compounds were: cobalt(II) fluoride 91 mg/kg bw, cobalt(II) oxide 159 mg/kg bw, cobalt(II) phosphate 187 mg/kg bw, cobalt(II) bromide 109 mg/kg bw, cobalt(II) chloride 190 mg/kg bw, cobalt(II) sulphate 161 mg/kg bw, cobalt(II) nitrate 140 mg/kg bw and cobalt(II) acetate 167 mg/kg bw.

Applicant's summary and conclusion

Conclusions:
Eight cobalt compounds were administered to rats by gastric intubation, and the following LD50 values were determined: cobalt(II) fluoride (CoF2) 150 mg/kg bw, cobalt(II) oxide (CoO) 202 mg/kg bw, cobalt(II) phosphate octahydrate (Co3(PO4)2*8H2O) 387 mg/kg bw, cobalt(II) bromide (CoBr2) 406 mg/kg bw, cobalt(II) chloride hexahydrate (CoCl2*6H2O) 418 mg/kg bw, cobalt(II) sulphate heptahydrate (CoSO4*7H2O) 424 mg/kg bw, Cobalt(II) nitrate hexahydrate (Co(NO3)2*6H2O) 434 mg/kg bw and cobalt(II) acetate tetrahydrate (Co(CH3COO)2*4H2O) 503 mg/kg bw.
Executive summary:

The oral LD50 values calculated for the cobalt percentage in the cobalt(II) compounds were: cobalt(II) fluoride 91 mg/kg bw, cobalt(II) oxide 159 mg/kg bw, cobalt(II) phosphate 187 mg/kg bw, cobalt(II) bromide 109 mg/kg bw, cobalt(II) chloride 190 mg/kg bw, cobalt(II) sulphate 161 mg/kg bw, cobalt(II) nitrate 140 mg/kg bw and cobalt(II) acetate 167 mg/kg bw.