Tetraammonium hexamolybdate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

This dossier is one of several dossiers prepared under the auspices of the REACH Molybdenum Consortium (“MoCon”). To avoid unnecessary (animal) testing, a comprehensive grouping and read-across concept has been developed amongst several molybdenum containing substances. This grouping/category approach is described in detail in a separate report, in accordance with the ECHA's "Read-Across Assessment Framework" (RAAF). This document is attached to section 13 in the technical dossier and to the CSR. This endpoints summary is therefore applicable to all substances in the category.

 

The following guideline-conform, highly reliable genotoxicity tests with a soluble molybdenum substance (sodium molybdate) are available:

- an AMES bacterial reverse mutation assay (Beevers, 2009),

- an in vitro micronucleus assay in human lymphocytes (Taylor, 2009),

- an in vitro gene mutation assay (tk) in mouse lymphoma cells (Lloyd, 2009), and

- an in vivo micronucleus study in rat bone marrow (Cockburn, 2021). This study was commissioned by the International Molybdenum Association, and conducted by Charles River Laboratories USA in December 2020, because it is a required datapoint under Korea-REACH for substances > 100 tonnes.

All four tests produced unequivocally negative results, and thus provide strong evidence for an absence of concern for genotoxic effects of molybdenum substances. This includes the OECD TG 474 in vivo micronucleus study in rat bone marrow, tested to the limit dose, which was conducted to comply with Korea-REACH for substances >100 tonnes per year. Since the substance tested represents a highly soluble molybdate, and all molybdenum substances in the MoCon read-across group, regardless of their solubility, speciation and valence have been shown to transform rapidly to molybdate anions upon dissolution in aqueous media, these results can be read across to all other molybdenum substances in the group without restriction. Because of their ubiquitous physiological presence in biota and/or their essential role in human physiology, the sodium/ammonium/calcium/iron moieties in some of the molybdenum substances are not considered to be of concern for genotoxicity (see read-across justification document in section 13 of the technical dossier, chapter on "formation of non-common compounds").

In conclusion, hazard classification for genotoxicity is not required.

 

Apart from these high quality, reliable GLP test results, a large number of published studies exist of varying quality and extent of documentation, which is why these were subjected to a detailed quality and reliability screening, the outcome of which can be summarized as follows:

(i) unequivocally negative results were obtained in guideline-conform, valid bacterial reverse mutation assays for high purity (moderately soluble) molybdenum trioxide (studies by Jones, 2004 and Zeiger et al., 1992). Negative results were also obtained in the same test system with (highly soluble) sodium and ammonium molybdates, which however from a perspective of formal regulatory compliance are considered incomplete because of the selected tester strains (studies by Armitage, 1997 and Kubo et al. 2002).

(ii) all in vitro clastogenicity test considered as assignable and reliable with or without restrictions are negative.

(iii) in view of the unequivocally negative results in all three in-vitro key studies, the conduct of any further in vivo testing would not be required under EU REACH. However an in vivo micronucleus study (OECD TG 474) was conducted in 2020 to comply with data requirements for Korea-REACH substances >100 tonnes per year and is therefore also reported here. This study was negative. Already available in vivo studies were subjected to a thorough evaluation and were found to be seriously flawed and of poor quality, and were thus assigned reliability grades of either 3 or 4. In this context it is explicitly noted that the studies published by Titenko-Holland (1998) have already previously been critiqued as deficient and disregarded by the Classification and Labelling Committee of the ECB during discussions on molybdenum trioxide in 2004.

Short description of key information:
Four (three in vitro, one in vivo) guideline-conform, highly reliable genotoxicity tests produced unequivocally negative results, and thus provide strong evidence for an absence of concern for genotoxic effects of molybdenum substances, which is supported by reliable supplementary data.

Justification for classification or non-classification

Based on the review of key experimental studies as well as supportive information on genetic toxicity, no hazard classification is required for genotoxicity/mutagenicity.