Trimanganese tetraoxide (EC :215-266-5; Cas :1317-35-7)
The lead dossier was submitted in 2010 with no testing proposals. In July 2013 a compliance check was initiated, requesting more details with regard to the following information requirements/updates:
- Annex IX 8.7.2 (pre-natal developmental study, oral route, OECD 414)
- Annex X, 8.7.3 (two-generation reproductive toxicity study, oral route, OECD 416 or an extended one generation reproductive toxicity study, OECD 443)
By 27 September 2013 the consortium secretariat on behalf of the lead registrant had responded to the ECHA’s draft decision concerns, highlighting the lack of need for such animal-intensive studies and encouraging the use of already available data within the manganese data pool.
In July 2016 ECHA notified the competent authorities of the member states of its draft decision together with the registrant's comments. No member state commented on the draft decision. A final decision requesting the following study was published in September 2016:
- Pre-natal developmental toxicity study (Annex IX, 8.7.2.; test method: EU B.31/OECD 414) in rats or rabbits, oral route - while a decision was not yet reached on the two-generation reproductive toxicity study endpoint,
The Annex IX 8.7.2 (pre-natal developmental study, oral route, OECD 414) study, now completed (May 10, 2018) revealed several fetal effects. Litter size and mean fetal weights were slightly reduced. Embryo-fetal survival was considered unaffected by treatment, but fetal development was adversely affected with bent scapula(e); bent radius/ulna/fibula; short/bent/and thickened humerus with associated medially thickened/kinked/incompletely ossified ribs.
Therefore, the No-Observed- Effect-Level (NOEL) for maternal toxicity was 750 mg/kg/day and the No-Observed-Adverse-Effect-Level (NOAEL) for embryo-fetal toxicity was concluded to be 250 mg/kg/day. The dossier will be updated in Q3 2018 with a classification for developmental reprotoxicity. The CSR will be updated and suppliers will need to update their SDS's.