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Description of key information

Acute oral toxicity:
LD50= 355 mg/kg bw
Acute dermal toxicity:
Conduct of an acute dermal toxicity study for the salt reaction of cobalt (2+) and C3/C10 carboxylates is unjustified since dermal uptake is considered negligible.
Acute inhalation toxicity:
Inhalation acute toxicity is not an expected route for cobalt compounds on a short-term because of the medium to low values for total dustiness, and all the more for Salt reaction of cobalt(2 +) and C3/C10 carboxylates as this compound is manufactured and used as pellets.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
355 mg/kg bw

Additional information

Oral acute toxicity is direcly read-across from neodecanoic acid cobalt salt and cobalt dipropionate which are main consitituents of the salt reaction of Cobalt(2 +) and C3/C10 carboxylates. The lowest LD50 = 355 mg/kg bw is used and drives a classification for oral acute toxicity category 4.

Inhalation acute toxicity is not an expected route for cobalt compounds on a short-term because of the medium to low values for total dustiness, and all the more for Salt reaction of cobalt(2 +) and C3/C10 carboxylates as this compound is manufactured and used as pellets.

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 two oral studies are conducted according to OECD Guideline 425 and are fully reliable, even it can be noted that they are conducted only on female rats. The tested substances, neodecanoic acid cobalt salt and cobalt dipropanoate LD50 are respectively 1098 (but lower 95%CL is 550), and 355 mg/kg bw. Cobalt dipropanoate has the lowest value and can be considered as a part of the salt reaction of Cobalt(2+) and C3/C10 carboxylates. In a precautionary approach, its LD50 can thus be considered as representative of the salt reaction of Cobalt(2+) and C3/C10 carboxylates oral acute toxicity.

Justification for classification or non-classification

Acute oral toxicity

Oral acute toxicity is direcly read-across from neodecanoic acid cobalt salt and cobalt dipropionate which are main consitituents of the salt reaction of Cobalt(2 +) and C3/C10 carboxylates. The lowest LD50 = 355 mg/kg bw is used and drives a classification for oral acute toxicity category 4.

Read-across is considered also justified for the following reasons:

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

- the two constituents of Salt reaction of cobalt(2+) and C3/C10 carboxylates, cobalt neodecanoate and cobalt propionate, are two-constituent substances (cobalt cation and carboxylate anion) and have similar water solubility and dissociation constant, and so a similar bioaccessibility.

- cobalt dipropanoate 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.

- cobalt neodecanoate 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 Finlay (2007a) for cobalt propionate is considered as weight of evidence study for acute oral toxicity and will be used as the key study for classification. Female CD rats were dosed up to 2000 mg/kg orally via gavage. The LD50 was calculated 355 mg/kg bw with a 95 % confidence interval of 61.2 - 1890 mg/kg.

The reference Finlay (2007b) for cobalt neodecanoate is considered as weight of evidence and will be used as supportive study for classification. Female CD(SD) rats were dosed at 175, 550 and 2000 mg/kg orally via gavage. During the conduct of the study mortalities occurred at the highest dose group: LD50 oral, rat = 1,098 mg/kg bw.

The classification criteria according to regulation (EC) 1272/2008 as acutely toxic category 4 are met since the ATE, in both studies, is between 300 and 2000 mg/kg body-weight, hence Salt reaction of cobalt (2+) and C3/C10 carboxylates is classified asacute 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 undergovtranslocation to the gastrointestinal tractvia mucociliary escalation and subsequent swallowing.

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

Based on the LD50of 355 and 1098 mg/kg observed in two acute oral toxicity test which are major constituents of Salt reaction of cobalt(2+) and C3/C10 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.