Magnesium carbonate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - workers

The available information indicates that magnesium carbonate is non-hazardous and no hazard classifications are proposed. Magnesium carbonate is always prepared and used as a suspension and is never isolated in its solid or powder form; therefore, exposure to aerosols, particles or droplets of magnesium carbonate of an inhalable size will not occur. As magnesium carbonate is an inorganic ionic solid, the potential for absorption through the skin is also expected to be negligible.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.23 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

2

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.23 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

2

Modified dose descriptor starting point:

NOAEL

Additional information - General Population

Justification for derivation of a DNEL for long-term oral exposure of the general population

The Opinion of the Scientific Committee on Food of the European Commission (SCF, 2001), which reviews and summarises a number of clinical studies on oral uptake of magnesium compounds, serves as the key study for repeated-dose oral toxicity. As stated in the endpoint summary of IUCLID Section 7.10, use of data from other easily bioavailable magnesium salts for read-across to magnesium carbonate is considered appropriate, based on the assumption that the first adverse effect to occur (mild diarrhoea) is triggered by magnesium concentration rather than by an effect of the carbonate ion.

 

Based on the clinical studies data, SCF (2001) identified a NOAEL for oral supplementation with easily dissociable magnesium salts (i.e. on top of the normal presence of magnesium in food and beverages) of 250 mg magnesium per day. In deriving the Tolerable Upper Intake Level (UL), SCF concluded that no assessment factor (i.e. “an uncertainty factor of 1.0”) was necessary, since “data are available from many human studies involving a large number of subjects from a spectrum of lifestage groups, including adults, pregnant and lactating women, and children…[and] the NOAEL is based on a mild, transient laxative effect, without pathological sequelae, which is readily reversible and for which considerable adaptation can develop within days”. The UL for readily dissociable magnesium salts was therefore set at 250 mg Mg/day, and applies to adults, including pregnant and lactating women, and children from 4 years on. The SCF concluded it could not establish an UL for 1–3 year old children as no data were available for this age group. SCF did note, however, that “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”.

 

The assessment of the SCF is supported here for use in establishing a long-term oral DNEL for the general population for magnesium carbonate. Thus:

– the starting point is the NOAEL of 250 mg Mg/day, which based on the ECHA default adult human bodyweight of 60 kg is equivalent to 4.17 mg Mg/kg bw/day;

– no interspecies assessment factor is required as the data are from human studies;

– although none of the studies covers a chronic duration, the data that are available and nature of the adverse effect is such that the present assessment supports the SCF opinion in that an assessment factor for study duration is unnecessary.

– while there may be smaller deficiencies in individual studies, taken together the available data present an evident dose-response relationship and, consequently, the present assessment supports the SCF Opinion that an assessment factor to account for data quality deficiencies is unnecessary.

 

However, the SCF UL does not apply to 1–3 year old children as the clinical studies did not include children within this age range. In deriving a DNEL applicable to the general population as a whole, therefore, consideration must be given to the potential additional intraspecies variability presented by this age group. In accordance with the SCF Opinion that, aside from the incidence of diarrhoea generally being higher and the effects potentially more significant in this age group, there is no basis for considering they are more susceptible to the laxation effects of magnesium, the addition of an intraspecies assessment factor of 2 is considered sufficiently protective.

 

Application of this intraspecies assessment factor to the NOAEL of 4.17 mg Mg/kg bw/day results in a magnesium intake of 2.08 mg Mg/kg bw/day. This corresponds (based on molecular weight conversion of magnesium to magnesium carbonate) to a DNEL for magnesium carbonate of 7.23 mg/kg bw/day.