A tiered approach to investigate the inhalation toxicity of cobalt substances. Introduction: Cobalt's essential role in nature and technology
• Cobalt (Co) substances are required in many current technologies, e.g. batteries.
• Co substances can be toxic and carcinogenic following inhalation.
• Not all Co substances have the same toxicological profile.
• The present paper introduces a tiered testing strategy of key biological events.
• The tiers include several in vitro and in vivo (acute and repeated dose) tests.
Abstract - Cobalt occurs naturally in the earth's crust, is essential to some microorganisms and forms the core of vitamin B12. Cobalt substances are used in numerous technologies, such as catalysts or batteries. Some of these substances are classified as Carcinogens, while other cobalt compounds have a hazard profile that is less understood and are missing long term studies like cancer bioassays. There is a strong interest by society and industry to reduce and -where possible- eliminate animal testing, yet a necessity by industry and authorities to have sufficient data for hazard conclusions and risk assessments. The present paper introduces a strategy for a mode of action-informed tiered testing, aimed at full inclusion of existing hazard data and selection of relevant biological events towards a certain adverse outcome, i.e. inhalation carcinogenicity. The occurrence of these events following exposure to various cobalt substances is investigated with in vitro and with limited in vivo testing. The tiers of testing are described in the companion papers of this RTP special issue. This approach has given rise to the formulation of two distinct groups, containing substances with similar properties, that can be addressed with limited higher tier animal testing and read across of in vivo results.
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