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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:
Comparable to guideline study with acceptable restrictions Spanish article translated into english. - The stability of the test item was missing. - According to the guideline, at least 5 rodents of the same sex should be used at each dose level and later at least one group of the other sex should be tested to establish that animals of this sex are not markedly more sensitive to the test substance. In the publication it was not clear how many animals were used at each dose level and it was also not clear how many males and females were used at the different dose levels. - Observation period was only 7 days instead of the recommended 14 days by the guideline. In the publication it was stated that animals rarely died after 48 hours, but it was not clear at which time point for certain animals did not die anymore. According to the guideline, the time of death should be recorded as precisely as possible. In addition, it was not mentioned how many animals showed signs of toxicity. - According to the guideline, the animals should be weighed, but nothing was stated about weighing the animals. - According to the guideline, clinical examination should be made at certain time intervals. In the publication was nothing stated about the time points at which observations were made. - According to the guideline, animals which die during the test are necropsied, and at the conclusion of the test the surviving animals are sacrificed and necropsied. In the publication it was only stated that surviving animals were sacrificed after 7 days. - According to the guideline, the volume administered to rodents should not exceed 1 ml/100g body weight, except in the cases of aqueous solutions where 2 ml/ 100 g may be used. Variability in the test volume should be minimised by adjusting the concentration to ensure a constant volume at all dose levels. There was no indication on what volume was administered to the rats and if it was at a constant volume.

Data source

Reference
Reference Type:
publication
Title:
Toxicidad aguda y alteraciones hematológicas y séricas por algunas sales de cobalto en ratas
Author:
Llobet, J.M. & Domingo, J.L.
Year:
1983
Bibliographic source:
Revista Española de Fisiologia, 39: 291 - 298.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
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 dichloride hexahydrate
- Molecular formula: CoCl2 * 6H20
- Analytical purity: The salt was analytically pure
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: Mean weight 192.5 +/- 22.3 g
- Diet: ad libitum
- Water:ad libitum
- Fasting period before study: Fasted for 24 hours before administration
No further information on the test animals was stated.




Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Rationale for the selection of the dose levels: They chose the dose levels based on pre-tests with a small number of rats. It was tested at which dose no deaths occurred and at which dose all test animals died.
No further information on the oral exposure was stated.
Doses:
350 mg/kg, 392 mg/mg/kg, 450 mg/kg, 518 mg/kg, 595 mg/kg, 684 mg/kg, 787 mg/kg
No. of animals per sex per dose:
8 or 10 animals (It was not clearly stated in the publication how many males and females were used per dose and if the genders were equally distributed.)
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: Yes
No further information on the study design was stated.
Statistics:
Method for determination of LD50, and confidence limit according to Litchfield and Wilcoxon (1949).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
537 mg/kg bw
95% CL:
479 - 601
Mortality:
Death occurred in 95 % of animals within the first 24 hours after administration. Most animals even died within the first 6 hours. Rats rarely died after 48 hours.
The following percentage of animals died at the different dose levels:
350 mg/kg: 0 %
392 mg/kg: 10 %
450 mg/kg: 37.5 %
518 mg/kg: 50 %
595 mg/kg: 75 %
684 mg/kg: 75 %
787 mg/kg: 100 %
Clinical signs:
Intoxication symptoms: (occurred shortly after intoxication) decrease of general activity and especially exploiting behaviour, frequency of "getting up"; increase of water consumption; deficit in motivity of hind legs, less pain sensitivity
Clinical signs: general redness, bleeding around the eye, increase of the rhythm of the heart, and irregularly increase of the respiratory, intensive diarrhoea, all animals showed pilo erection.
Most effects disappeared after 72 hours.
Body weight:
No data
Gross pathology:
No marcoscopic alterations were observed at the most significant organs.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Cobalt dichloride hexahydrate is moderately toxic if administered orally.
LD50: 537 mg/kg (Confidence interval: 479 - 601 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.