Registration Dossier

Administrative data

Description of key information

Acute oral toxicity:
LD50= 708 mg/kg bw (confidence interval: 569-880 mg/kg bw)
Acute dermal toxicity:
Conduct of an acute dermal toxicity study is unjustified since dermal uptake is considered negligible.
Acute inhalation toxicity:
Conduct of an acute inhalation toxicity is unjustified since exposure is unlikely based on physical form.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
708 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

Oral acute toxicity is directly read-across from cobalt bis(2 -ethylhexanoate, resin and rosin acids cobalt salts and cobalt di(acetate). The lowest LD50 = 708 mg/kg bw is used and drives a classification for oral acute toxicity category 4.

The classification from the acute oral toxicity is read-across to the acute toxicity via inhalation. Further results from the ongoing testing programme will be included upon availability.

Dermal acute toxicity appears as unjustified since dermal uptake can be considered as negligible (cf. Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006). It can be noted that 3 studies on other cobalt compounds show that LD50 dermal acute toxicity is at least higher than 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint  

The four oral studies are considered reliable. The tested substances, cobalt bis(2-ethylhexanoate), resin and rosin acids cobalt salts and cobalt di(acetate) have respective LD50 of 3129 mg/Kg bw, > 2000 mg/Kg bw and 708 mg/Kg bw. Cobalt di(acetate) has the lowest value. In a precautionary approach, its LD50 can thus be considered as representative of Cobalt(2+) C2/C8/C20 carboxylates oral acute toxicity.  

Justification for selection of acute toxicity – dermal endpoint  

Weight of evidence information

Justification for classification or non-classification

Acute oral toxicity

Acute oral toxicity testing for cobalt bis(2 -ethylhexanoate), resin and rosin acids cobalt salts and cobalt di(acetate) being constituents of Salt reaction of cobalt(2 +) and C2/C8/C20 carboxylates are available. Read-across is considered justified for the following reasons:

- all substances are cobalt carboxylates with a divalent cobalt cation and an organic anion;

- cobalt di(acetate) has a higher cobalt content; under the assumption that cobalt is the relevant constituent for acute oral toxicity the acute oral LD50 of this substance can be considered as worst-case with respect to cobalt content.

- resin and rosin acids cobalt salts is a cobalt carboxylate with a longer carbon-chain anion; under the assumption that the carboxylate anion affects the toxicity, this substance is considered as worst-case with respect to carbon chainlength.

Based on the above argumentation read-across is considered justified without restriction.

The reference Speijers (1982) for cobalt di(acetate) is considered as weight of evidence study for acute oral toxicity and will be used as the key study for classification. The LD50 was calculated to be 708 mg/kg bw (confidence interval: 569-880 mg/kg bw).

The reference Pelcot (2007) for resin and rosin acids, cobalt salts is considered as weight of evidence for acute oral toxicity and will be used as supportive study for classification.

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic category 4 are met since the ATE is between 300 and 2000 mg/kg body-weight, hence Cobalt(2+) C2/C8/C20 carboxylates salts is classified as acute oral 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 and Specific target organ toxicant (STOT) – single exposure: dermal

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

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

Cobalt compounds are not generally associated with local effects following acute inhalation exposure; only after long-term exposure, some inflammatory responses are seen. Thus, any acute inhalation toxicity may reasonably be assumed to be predominantly determined by systemic availability.

Based on the outcome of dustiness testing (Heubach rotating drum method; for details, please refer to the IUCLID endpoint study record under IUCLID section 7.1.1 basic toxicokinetics) coupled with particle size analysis of the airborne fraction, all cobalt compounds have moderate to low values for total dustiness, indicating similar propensities to become airborne. Based on the concurrent particle size analysis, inhalation deposition modelling via MPPD clearly indicates that only minor substance amounts can be expected to be deposited in the pulmonary fraction of the respiratory tract of humans; in contrast, the majority of inhaled material will deposit in the extra thoracic and tracheo-bronchiolar regions, and therefore can safely be assumed to undergo translocation to the gastrointestinal tract via mucociliary escalation and subsequent swallowing.

Thus, any systemic effects may be read across from acute oral toxicity.

Based on the LD50 of 708 mg/kg observed in an acute oral toxicity test which is constituent of Salt reaction of  cobalt(2+) and C2/C8/C20 carboxylates, it is therefore proposed to adopt the same classification as for the oral route, inhalation acute toxicity category 4, and to waive the testing requirement for acute inhalation toxicity in accordance with section 1.1, annex XI of regulation (EC) 1907/2006.

Furthermore a testing program is currently being executed, investigation the acute toxicity of eleven cobalt compounds via inhalation. The aim is to cover a wide spectrum of substances to allow read-across to non-testes cobalt substances, to reduce the number of animals. Details can be found in the waiving part of section 5.2.1.1 of this CSR.