Reaction mass of cobalt sulphide and nickel sulphide and trinickel disulphide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

At a first glance, there is a substantial data base on toxicity of soluble cobalt compounds to organs of male reproduction, which has been the reason to classify several cobalt substances for impairment of fertility. However, there is a complete absence of any data that would allow an assessment of any such effects on female reproductive parameters. Furthermore data on soluble cobalt substances cannot easily be extrapolated to less soluble compounds in the absence of data on absorption and distribution in the respective species in vivo that would allow to determine if sufficient amounts of the Co(2 +) cation have reached the target organ and would be able to produce a comparable effect.

 

Furthermore, none of the available studies represents state-of-the-art guideline-conform two-generation reproduction toxicity studies or other relevant study designs, based upon which robust no-effect levels for human risk assessment could be derived specifically under the REACH Regulation, so that DNELs for reproductive toxicity cannot be established with adequate reliability.

 

It is therefore proposed to perform a two-generation reproduction toxicity study according to OECD Guideline 416 in rats with cobalt dichloride and tricobalt tetraoxide; alternatively, in case the guidance on testing requirements is updated in the near future, instead the conduct of an extended one-generation study may be envisaged. Please refer to the attached document in the IUCLID endpoint summary for toxicity for reproduction for further information and a rationale for the selection of cobalt dichloride and tricobalt tetraoxide as test substance.

 

However, due to current lack of a 90-day repeated dose toxicity study via oral application, a waiving of the testing proposal in the registration dossier for the two-generation/one-generation reproductive study was considered appropriate prior to the results of the proposed 90-day study becoming available.

Short description of key information:
No reliable data are available which could be considered suitable for human health risk assessment. A testing proposal is issued for a 90-day oral toxicity study for cobalt dichloride and tricobalt tetraoxide, and testing for reproductive toxicity (effects on fertility) is thus postponed until these data become available. Please refer to the attached document in the IUCLID endpoint summary for toxicity for reproduction for further information and a rationale for the selection of cobalt dichloride and tricobalt tetraoxide as test substance.

Effects on developmental toxicity

Description of key information

The available studies show several deficiencies, thus rendering them of limited use in a regulatory context. Since the results are somewhat contradictory, they will not be used further for human health risk assessment.
A testing proposal for a developmental toxicity study is therefore issued for cobalt dichloride and tricobalt tetraoxide, to which read-across is considered feasible to other cobalt substances within the same read-across group. Please refer to the attached document in the IUCLID endpoint summary for toxicity for reproduction for further information and a rationale for the selection of cobalt dichloride and tricobalt tetraoxide as test substance.

Additional information

There is a very limited data base on developmental toxicity in several species (including rats and rabbits) for soluble bivalent cobalt compounds (largely cobalt (II) dichloride and cobalt (II) sulphate), which suffers from several defects:

- several studies (in particular those of Wide, 1984; Domingo et al., 1985) report effects on foetuses and neonates, but all studies suffer from several methodical and reporting deficiencies, thus rendering them of very limited use in a regulatory context.

- one study is apparently void of effects (Paternain et al., 1988) with regard to foetal effects, but maternal toxicity was observed at all dose levels, so that this study does not allow the derivation of a maternal no-effect level.

- another study (Szakmary et al., 2001) provides a multitude of information, but which is partly contradictory in nature and also has reporting and methodological shortcomings.

In conclusion, these and other available studies show several deficiencies, thus rendering them of limited use in a regulatory context. Since the results are somewhat contradictory, they are considered unsuitable for a human health risk assessment and DNEL-setting under REACH.

It is therefore proposed to conduct a guideline-conform prenatal developmental toxicity study (according to OECD Guideline 414) with cobalt dichloride and tricobalt tetraoxide. Please refer to the attached document in the IUCLID endpoint summary for toxicity for reproduction for further information and a rationale for the selection of cobalt dichloride and tricobalt tetraoxide as test substance.