Registration Dossier

Administrative data

Description of key information

Additional information

Read across MgO:

An acute inhalation study in human volunteers is available, in which the potential of MgO to cause symptoms similar to that of metal fume fever is investigated. Due to the fact that magnesium metal is passivated on its surface by the formation of an oxide layer, and since in the case of fine powders this oxide layer will form a substantial part of the particle mass, and also because magnesium oxide and magnesium metal are of similarly low solubility (interpreted as a measure of similar bioavailability), read across from data on magnesium oxide to magnesium metal is considered justified without restriction.

Discussion according to SCF, 2001:

Easily dissociable magnesium salts, especially the sulphate are used as “osmotic” and “saline” laxatives, respectively. Nevertheless mild diarrhoea can be taken as the most sensitive non-desirable effect if Mg supplements are taken for nutritional purposes. However it must be kept in mind that adaptation of the bowel to higher oral Mg intake is known, that a mild laxative effect may be desirable, that mild laxative effects have been frequently observed also in the placebo groups (perhaps caused by taste adjusters, vehicles a.o.), that a given daily dose of Mg is better tolerated when it is divided into several portions, and finally that the galenic form (aqueous solution, capsules, tablets, etc.) may play a role.

As discussed, mild diarrhoea is the most sensitive non-desirable effect of orally administered easily dissociable magnesium salts. Mild diarrhoea occurs in a small percentage of adult subjects at oral doses of about 360/365 mg Mg per day, hence presenting the LOAEL. No laxative effects have been observed in adult men and women -also during pregnancy and lactation- at doses up to 250 mg Mg per day. Therefore, this dose is considered as being the no-observed-adverse-effect level (NOAEL).

Characterisation of risk:

Diarrhoea induced by easily dissociable Mg-salts or compounds like Mg-oxide is completely reversible within 1 to 2 days and does not represent a significant health risk in subjects with 1 intact renal function. Poorly dissociable Mg salts (e.g. phytates) have a lower, if any, potential

to induce diarrhoea. While the UL is expressed as a daily intake it should be noted that most of the studies used in its derivation involved daily intake obtained from two or more doses. Therefore the UL should apply to daily intake of Mg consumed on two or more occasions. No UL could be established for 1-3 year old children. Although the incidence of diarrhoea is generally higher and its effects potentially more significant in this age group than in older children or adults, there is otherwise no basis for considering that they are more susceptible to the laxation effects of Mg. Toxic hypermagnesaemia, presenting e.g. with hypotension or muscular weakness, is only seen at oral Mg doses greater than 2,500 mg, i.e. doses exceeding the UL by a factor of more than 10.