Manganese carbonate (EC: 209-942-9; Cas 598-62-9)- Testing Proposal
In 2018 - 2019: Review of available data on reproductive and developmetal toxicity and conerns highlighted from ECHA regarding the Japanese GHS classification for these endpoints.
Outcome of reveiw - in summary
Developmental toxicity data and the two generation reproductive toxicity data in the rat on the read-across substance manganese dichloride resulted in no classification. Although readacross is acceptable, there was no second species data for these endpoints on any inorganic Mn- based substance. A pilot study was therefore initated in the rabbit. Although the total number of rabbits used was very small, it identified that exposure up to the limit dose of 1000 mg/kg/day in non-pregnant rabbits was generally well tolerated for 14 days. However, this was not the case for pregnant rabbits. Embryo-foetal toxicity was observed at dose levels ≥ 150 mg/kg/day (decreased embryo-foetal survival) but only in the presence of overt, excessive maternal toxicity which manifested as premature mortality, with an associated decline in clinical condition, body weight loss and inappetence (150 mg/kg/day was associated with maternal mortality of 50 %). ECHA CLP guidance1 (Annex I:188.8.131.52.4) defines that “maternal mortality greater than 10 % is considered excessive and the data from that dose level shall not normally be considered further for evaluation”.
Hence, it is justified to consider that although identifying findings of concern in a limited data set, the preliminary study does not provide sufficient data for basis of classification owing to the excessive maternal toxicity apparent at all dose levels where embryo-foetal effects are apparent.
In order to clarify this concern it is recommended that a full OECD Guideline 414 study is conducted in the rabbit - based on this, an appriorpiate testing proporsal will be submitted in the next dossier update - Q4 2020
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