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Description of key information

Acute oral toxicity:
LD50(rat)= 768 mg cobalt sulfate heptahydrate/kg bw
Acute dermal toxicity:
Conduct of an acute dermal toxicity study for cobalt sulfate is unjustified since dermal uptake is considered negligible.
Acute inhalation toxicity:
Conduct of an acute inhalation toxicity study is technically not feasible, since a stable inhalation atmosphere cannot be generated with cobalt sulfate.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
Qualifier:
equivalent or similar to guideline
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
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system 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.
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:
1000 mg/kh, 1110 mg/kg, 1232 mg/kg, 1368 mg/kg, 1520 mg/kg, 1685 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).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 330 mg/kg bw
95% CL:
1 220 - 1 450
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:
1000 mg/kg: 0 %
1110 mg/kg: 10 %
1232 mg/kg: 30 %
1368 mg/kg: 50 %
1520 mg/kg: 80 %
1685 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.
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Cobalt sulphate heptahydrate is moderately toxic if administered orally.
LD50: 1330 mg/kg (Confidence interval: 1220 - 1450)
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.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
768 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for selection of acute toxicity – oral endpoint
Key study

Justification for selection of acute toxicity – dermal endpoint
Weight of evidence information

Justification for classification or non-classification

Acute oral toxicity

The references Speijers (1982) and Llobet, Domingo (1983) are considered as the key studies for acute oral toxicity and will be used for classification. Female/male rats were dosed at 450, 675, 1000, 1500, 2250 mg/kg orally via gavage and at 1000, 1110, 1232, 1368, 1520, 1685 mg/kg orally via gavage respectively. During the conduct of the study mortalities occurred, thus the following LD50 values were derived:

·                   Speijers (1982): LD50 oral, rat = 1,330 mg cobalt sulfate heptahydrate /kg bw

·                   Llobet, Domingo (1983): LD50 oral, rat = 768 mg cobalt sulfate heptahydrate /kg bw

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic category 4 are met since the ATE is above 300 mg/kg body-weight and below 2,000 mg/kg body-weight.Cobalt sulfate will be classified as acutely toxic category 4 (H302).

 

Specific target organ toxicant (STOT) – single exposure: oral

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since the toxic effects observed in the acute oral toxicity test already leads to an acute oral toxicity classification. No additional effects in animals or humans are known that would justify a specific target organ toxicant (STOT) – single exposure: oral classification.

 

Acute dermal toxicity

Conduct of an acute dermal toxicity study for cobalt sulfate is unjustified since dermal uptake is considered negligible.

 

Specific target organ toxicant (STOT) – single exposure: dermal

Conduct of an acute dermal toxicity study for cobalt sulfate is unjustified since dermal uptake is considered negligible.

 

Acute inhalation toxicity and Specific target organ toxicant (STOT) – single exposure: inhalation

A study was originally designed to assess the acute inhalation toxicity of the test material in rats. The selected test method was in accordance with the following guidelines:

- OECD guideline 403 (May 1981),

- EC Guideline (Method B2 of Commission Directive 92/69/EEC, Annex V),

- US Environmental Protection Agency (EPA) Health Effects Test Guidelines, OPPTS 870.1300, Acute Inhalation Toxicity, August 1998, as well as

- Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147 (2-1-3), 24 November 2000 (partially revised on 26 June 2001).

However, during preliminary tests attempting to generate a stable test atmosphere prior to the conduct of the study (performed on September 23, 2010), it was verified that a stable test atmosphere could not be generated as described in the attached document in the endpoint study record in IUCLID section 7.2.2. As a result, the main study involving animal testing could not be initiated due to lack of technical feasibility.

Further experimental testing is therefore not foreseen in accordance with regulation (EC) 1907/2006, Annex XI, Section 2.