Borate cobalt(2+) C3/C8/C10 carboxylates salts

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

310 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 borate neodecanoate, cobalt borate 2-ethylhexanoate and cobalt borate propionate which are main constituents of Borate Cobalt(2+) C3/C8/C10 carboxylate salts. The lowest LD50 = 310 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 three oral studies are conducted according to OECD Guideline 425 and are fully reliable. The tested substances, cobalt borate neodecanoate complexes, cobalt borate 2-ethylhexanoate complexes and cobalt borate propionate complexes LD50 are respectively 1098 (but lower 95%CL is 550), 2210 and 310 mg/kg bw. Cobalt borate propionate complexes has the lowest value. Cobalt borate propionate complexes can be considered as a part of Cobalt(2+) Borate C3/C8/C10 carboxylates salts. In a precautionary approach, its LD50 can thus be considered as representative of Cobalt(2+) Borate C3/C8/C10 carboxylate salts 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 borate carboxylates being constituents of Salt reaction of borate, cobalt(2+) and C3/C8/C10 carboxylates are available. Read-across is considered justified for the following reasons:

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

- the three constituents of Salt reaction of borate, cobalt(2+) and C3/C8/C10 carboxylates, cobalt borate neodecanoate, cobalt borate 2-ethylhexanoate, and cobalt borate propanoate, are three-constituent substance (cobalt cation, borate anion and carboxylate anion) and have similar water solubility and dissociation constant, and so a similar bioaccessibility.

- cobalt borate propionate 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 borate 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 Mac Kenzie (2013b) for cobalt borate propionate complexes is considered as weight of evidence study for acute oral toxicity and will be used as the key study for classification. The test was conducted according to OECD 425. The LD50 was calculated to be 310 mg/kg bw.

The reference Finlay (2007) for cobalt borate neodecanoate is considered as weight of evidence for acute oral toxicity and will be used as supportive study for classification. Female 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 Cobalt(2+) Borate C3/C8/C10 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

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

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 310 and 1098 mg/kg observed in two acute oral toxicity test which are major constituents of Salt reaction of borate, cobalt(2+) and C3/C8/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.