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Read across from well water soluble magnesium salts to magnesium:

The toxicity of magnesium salts can reasonably assume to be determined by the availability of magnesium ions in solution. The water solubility of magnesium (6.7 mg/L at 21°C/pH 10.8) is a minimium of 104 orders of magnitude lower than the water solubility of magnesium chloride (354 g/L at 20°C), magnesium sulfate (710 g/L at 20°C) or magensium chloride hexahydrate (1670 g/L at 20°C). Thus, read across from magnesium salts to magnesium, based on worst case consideration, is justified and will likely lead to rather conservative no-effect levels. In conclusion, it was decided to waive repeated dose toxicity testing of magnesium and to read across from magnesium salts for animal welfare reasons.

Discussion:

Taking into consideration the biochemical role of magnesium in the human body, an in vivo genotoxic effect in considered highly unlikely at test concentrations usually applied in genotoxicity testing, and in consideration of normal dietary requirements (i.e. 800 mg/d).

 

Although no data is available on the genotoxic potential of metallic magnesium, one may safely assume that metallic magnesium as such cannot cross cellular membranes, but instead only the magnesium cation. Therefore, read across with reference to information on the mutagenicity of other magnesium substances is clearly warranted. For soluble magnesium compounds, there is no data gap for in vitro genotoxicity, since at least one study for the three relevant endpoints (bacterial reverse mutation, in vitro chromosome aberration, in vitro gene mutation) of reliability grade 2 exist.

 

No data on the in vivo genotoxic potential for magnesium compounds could be identified. However, based on the negative results in the in vitro tests, further testing of genotoxicity is not required (cf. REACH regulation, Annex VIII, 8.4). However, regarding the in vivo genotoxicity of soluble magnesium compounds, the following comments are put forward:

 

-  the German federal institute for risk assessment (BfR) has conducted a comprehensive risk assessment on health effects associated with either magnesium deficiency (hypomagnesaemia) or increased systemic magnesium levels (hypermagnesaemia). It was concluded that the only adverse effect following overdosage (>250mg per day in a single dose) is an osmosis-related reversible diarrhoea

- magnesium is abundantly distributed throughout the human body, with the highest concentration in muscle (270mM) and bone (530mM)[1]. Further blood concentrations are reported as 27.1-43.9mg/L[2]. The majority of the systemic magnesium is present intracellularly, since over 300 enzymes are magnesium depended for the correct functioning of the catalytic reactions

-  in vitro genotoxicity tests are conducted with mammalians cells in standard cell culture media such as DMEM, Ham’s F12 and RPMI1640 which are supplemented with magnesium salts at concentrations ranging from 0.6 to 0.85mM.


[1]Swaminathan, R (2003)magnesium Metabolism and its Disorders, Clin Biochem Rev, 24(2): 47–66

[2]Iyengar, G.V.; et al.(Eds.) (1978) The elemental composition of human tissues and body fluids, Verlag Chemie,,



Justification for selection of genetic toxicity endpoint
Read-across information from studies conducted with magnesium salts

Short description of key information:
Some magnesium salts have been tested in bacterial reverse mutation assays, in vitro gene mutation and clastogenicity tests. The tests show a negative response. Since read across from magnesium salts to magnesium is justified, the test substance is considered not to be classified as genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

None of the in vitro genotoxicity studies rated as reliable showed any effect in bacterial reverse mutation assays, in mammalian cell gene mutation tests (TK assay) or in mammalian cell chromosome aberration tests, thus the classification criteria according to Regulation (EC) 1272/2008 and subsequent adaptations as germ cell mutagen are not met.

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