Magnesium chloride

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented publication and official European document.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

secondary source

Title:

Unnamed

Year:

2001

Materials and methods

Study type:

other: bibliographic study with clinical case studies and studies with volunteers

Endpoint addressed:

basic toxicokinetics

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

It is the opinion of the Scientific Committee on Food (SCF) on the upper levels of Magnesium on the basis of different human studies on therapeutic uses of magnesium or as food additive.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

This bibligrophic study is based on magnesium and magnesium salt as dichloride, sulphate....

Method

Type of population:

general

Subjects:

This bibliographic study included different studies with children, pregnant women, tetanic, hypertensive and cardiac patients and volunteers.

Ethical approval:

not specified

Route of exposure:

oral

Reason of exposure:

intentional

Exposure assessment:

measured

Details on exposure:

It is a bibligrophic study (see Direct observ. Humans-2-2001-SCF)

Examinations:

It is a bibligrophic study

Medical treatment:

No data

Results and discussion

Clinical signs:

See Direct observ. Humans-2-2001-SCF

Results of examinations:

Magnesium kinetics represent an open system consisting of several compartments: the intestinal tract (absorption compartment), blood (central compartment), cells, skeleton, central nervous system (deep compartments) and faeces, urine, sweat and milk during lactation (excretion). Mg balance is positive when the input is greater than the output in urine and faeces. This calculation seems simple at a first glance but becomes highly variable aiming to the following individual factors:

- At low dietary Mg intakes, enteral absorption considerably increases from the normal level of 30-40% up to 80% probably via an active transport system (although this has not yet been prooved); this system can, however, be completely defective (so-called “primary Mg deficiency”) or insufficient (“poor absorbers”).
- As in the latter cases Mg uptake depends mostly or exclusively on passive diffusion (10-30%), a Mg deficit will result at intake levels which are sufficient for normal individuals (Durlach, 1988; Schimatschek et al., 1997; Seelig, 1980; Wörwag et al., 1999).
- Mg turnover also differs individually, depending for example on age, growth, physical activity, pregnancy-lactation, fluid consumption, stress exposure, drugs and diseases (Classen, 1990). Estimates of requirement have therefore been performed on healthy individuals under strictly standardized essentially steady state conditions (FNB, 1997).
- Mg losses represent an important variable: diarrhea or bowel diseases adversely affect excretion? Under physiological conditions, the healthy kidney can reduce daily Mg excretion from 5 mmol to less than 0.5 mmol within a few days of low Mg intake. However, this Mg-sparing mechanism could be disturbed genetically, or affected by diseases associated with polyuria such as diabetes mellitus or by drugs (e.g. most diuretics) or alcohol.

Effectivity of medical treatment:

No data

Outcome of incidence:

No data

Applicant's summary and conclusion

Conclusions:

In the context of food additives, the SCF has showed that the principal information on magnesium toxicokinetic is
- Magnesium kinetics represent an open system consisting of several compartments: the intestinal tract (absorption compartment), blood (central compartment), cells, skeleton, central nervous system (deep compartments) and faeces, urine, sweat and milk during lactation (excretion).
- At low dietary Mg intakes enteral absorption considerably increases from the normal level of 30-40% up to 80% probably via an active transport system.
- As in the latter cases Mg uptake depends mostly or exclusively on passive diffusion (10-30%) a Mg deficit will result at intake levels which are sufficient for normal individuals.
- Mg losses represent an important variable and affect excretion.
- The dermal absorption can be considered minor compared to oral absorption (in the range of 0.1-1 %).

Executive summary:

In this context, the toxicokinetic information are mainly based on the opinion of the Scientific Committee on Food on the tolerable Upper Intake level of Magnesium (SCF, 2001).

The principal data are:

• Magnesium kinetics represent an open system consisting of several compartments: intestinal tract (absorption compartment), blood (central compartment), cells, skeleton, central nervous system (deep compartments) and faeces, urine, sweat and milk during lactation (excretion).
• At low dietary Mg intakes, enteral absorption considerably increases from the normal level of 30-40% up to 80% probably via an active transport system (although this has not yet been proved); this system can, however, be completely defective (so-called “primary Mg deficiency”) or insufficient (“poor absorbers”).
•  As in the latter cases, Mg uptake depends mostly or exclusively on passive diffusion (10-30%). A Mg deficit will result at intale levels which are sufficient for normal individuals.
• Mg losses represent an important variable: diarrhoea or bowel disease adversely affect excretion. Under physiological conditions, healthy kidney can reduce daily Mg excretion from 5 mmol to less than 0.5 mmol within a few days of low Mg intake.

These data are confirmed by some publications and only few are presented as disregarded studies. Indeed, these sources provide valuable information in humans on oral bioavailability of dietary magnesium or of soluble magnesium salts (as MgCl2), which confirm the SCF data (European document).