Magnesium chloride

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Acute DNEL

For dermal route, there is no acute toxicity hazard (leading to C&L), so no acute/short-term DNEL was derived. (Refer to ECHA Guidance on IR&CSA R.8 p.16).

For inhalation route, this route is not appropriate indeed magnesium chloride is deliquescent, which means that it tends to undergo gradual dissolution and liquefaction by the attraction and the absorption of the moisture from the air.

 

Long term DNEL

Inhalation DNEL:

This route is not appropriate indeed magnesium chloride is deliquescent, which means that it tends to undergo gradual dissolution and liquefaction by the attraction and the absorption of the moisture from the air.

 

Dermal DNEL

First of all, no information of dose response relationship were available and no adverse effects were observed, for local and systemic effects. Indeed, based on acute toxicological studies identified (limit test OECD 402 and in vitro skin irritation EU B46), there are no statistically or biologically adverse effects induced by MgCl2. In addition, the Health Risk Assessment Guidance for metal (HERAG, 2006) indicated that the penetration of the dermis by dissolved metal cations is generally low, i.e. in the range of 0.1 - 1%: this substance is quasi not available for the organisms (by dermal route), toxic effects are hence negligible.

 

In these conditions, a DNEL cannot be elaborated for the dermal route, except via a route to route extrapolation. 

 

A route to route extrapolation is proposed for the systemic effect on the basis of guidance on information requirements and chemical safety assessment R8. The NOAEL and the mean oral absorption (250 mg Mg per day and 35%) defined by the SCF (2001) and the estimate skin absorption defined by HERAG (2006) are used. For more details, see discussion for general population.

 

Assuming a human body weight of 70 kg and converted the value to magnesium chloride, the long-term oral NOAEL of workers is:

250 mg Mg per day = 981 mg MgCl2 per day

981 / 70 = 14 mg MgCl2/kg bw/day

The corrected dermal NOAEL is

Long term oral NOAEL * Oral absorption / skin absorption

14 * 35/1 = 490 mg/kg bw/day

 

For workers, no overall assessment factor was retained:

For intra-species variability, the studies used by SCF (2001) are based on a large number of subjects including sensitive sub-populations; consequently no assessment factor was retained.

For the duration study, the maximum duration is 76 weeks but the NOAEL is based on a mild, transient laxative effect, without pathological sequelae, which is readily reversible. It seems therefore appropriate not to assign an extra assessment factor for study duration, although none of the studies covers a chronic exposure time.

For the quality of data: the different clinical studies were reviewed by an European Commission expert group. There may be smaller deficiencies in individual studies but altogether they present an evident dose-response relationship. It does not seem therefore appropriate to introduce an additional assessment factor for data quality

In conclusion:

The long term dermal DNEL for workers is 490 mg/kg bw/day.

 

Otherwise because of the skin behaviour of MgCl2 (very low absorption) and the high level of the DNEL reached, this dermal DNEL was not considered relevant. Indeed for a worker (bodyweight of 70 kg), the level of exposition for a “theoretical” adverse effect is 34300 mg per day (of the anhydrite form) for a long term exposition. This exposition is not realistic.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7 mg/kg bw/day

DNEL related information

Overall assessment factor (AF):

2

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Acute DNEL

There is no acute toxicity hazard (leading to C&L), so no acute/short-term DNEL was derived. (Refer to ECHA Guidance on IR&CSA R.8 p.16).

For inhalation route, this route is not appropriate indeed magnesium chloride is deliquescent, which means that it tends to undergo gradual dissolution and liquefaction by the attraction and the absorption of the moisture from the air.

Long term DNEL

Inhalation DNEL

This route is not appropriate indeed magnesium chloride is deliquescent, which means that it tends to undergo gradual dissolution and liquefaction by the attraction and the absorption of the moisture from the air.

 

Oral DNEL

A long-term oral DNEL for general population was elaborated on the basis of animal and human studies. Both elaborations are presented below.

 

On the basis of animal studies

The DNEL is based on a NOAEL from a 96 weeks oral study. In this study, groups of 50 male and 50 female B6C3F1 mice were given MgCl2, 6H20 at dose levels of 0, 0 5 and 2 % in the diet. The NOAELs for female and male mice were, respectively 3930 mg/kg bw/day (2 % in the diet) and 2810 mg/kg bw/day (2 % in the diet). These results were corrected to magnesium chloride anhydrous: 1830 mg/kg bw/day for female mice and 1309 mg/kg bw/day for male mice.

The overall assessment factor was obtained as follows:

• For interspecies: 7 for allometric scaling factor for mice as compared to humans (for mice and 70 kg for man) and 2.5 for remaining interspecies differences
• For intraspecies: 10 for intraspecies differences in the general population.

No other factors were applied as the quality of the information was good and consistency.

The derived long term oral DNEL is

1309 / (7 x 2.5 x 10) = 7.5 mg/kg bw/day

 

On the basis of human studies

The Opinion of the Scientific Committee on Food of the European Commission (SCF 2001) summarized 20 different clinical studies on oral uptake of magnesium compounds. Considering these clinical studies, the SCF has set a human NOAEL of 250 mg/day for additional intakes (above diatery) based on mild diarrhoea (the most sensitive, non-desirable effect following oral administration of magnesium occurring at oral doses of 360/365 mg Mg per day, the LOAEL) and the absence of such at 250 mg Mg per day (NOAEL).

It seems applicable to use data from other easily bioavailable magnesium salts for read-across to magnesium chloride, 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 chloride ion.

An overall assessment factor of 2 was obtained as follows:

• For intra-species variability, a factor of 2 was appropriate. The studies used regard a large number of subjects including sensitive sub-populations (such as children, elderly, pregnant women, patients) but excluding in particular infants (<4 years). This factor seems therefore appropriate than 2.
• For the duration study, the maximum duration is 76 weeks but the NOAEL is based on a mild, transient laxative effect, without pathological sequelae, which is readily reversible. It seems therefore appropriate not to assign an extra assessment factor for study duration, although none of the studies covers a chronic exposure time.
• For the quality of data: the different clinical studies were reviewed by an European Commission expert group. There may be smaller deficiencies in individual studies but altogether they present an evident dose-response relationship. It does not seem therefore appropriate to introduce an additional assessment factor for data quality

Assuming a human body weight of 70 kg and converted the value to magnesium chloride, the long-term oral DNEL of the general population is:

250 mg Mg per day = 981 mg MgCl2 per day

981 / (70 * 2) = 7 mg MgCl2/kg bw/day

Conclusion

Both elaborations (for long-term oral DNEL) gave an equivalent result:

• 7.5 mg/kg bw/day on the basis of animal studies.
• 7 mg/kg bw/day on the basis of human studies.

These results confirm the read-across between magnesium and magnesium chloride.

The final long term oral DNEL for the general population is hence 7 mg/kg bw/day.

 

Dermal DNEL

First of all, no information of dose response relationship were available and no adverse effects were observed, for local and systemic effects. Indeed, based on acute toxicological studies identified (limit test OECD 402 and in vitro skin irritation EU B46), there are no statistically or biologically adverse effects induced by MgCl2. In addition, the Health Risk Assessment Guidance for metal (HERAG, 2006) indicated that the penetration of the dermis by dissolved metal cations is generally low, i.e. in the range of 0.1 - 1%: this substance is quasi not available for the organisms (by dermal route), toxic effects are hence negligible.

In these conditions, a DNEL cannot be elaborated for the dermal route, except via a route to route extrapolation. 

A route to route extrapolation is proposed for the systemic effect on the basis of guidance on information requirements and chemical safety assessment R8. The NOAEL and the mean oral absorption (250 mg Mg per day and 35%) defined by the SCF (2001) and the estimate skin absorption defined by HERAG (2006) are used.

Assuming a human body weight of 70 kg and converted the value to magnesium chloride, the long-term oral NOAEL:

250 mg Mg per day = 981 mg MgCl2 per day

981 / 70 = 14 mg MgCl2/kg bw/day;

The corrected dermal NOAEL is

= Long term oral NOAEL * Oral absorption / skin absorption

= 14 * 35/1 = 490 mg/kg bw/day

 

As the oral route, an overall assessment factor of 2 was appropriate for general population.

In conclusion:

The long term dermal DNEL for general population is 245 mg/kg bw/day.

Otherwise because of the skin behaviour of MgCl2 (very low absorption) and the high level of the DNEL reached, this dermal DNEL was not considered relevant. Indeed for an adult (bodyweight of 70 kg), the level of exposition for a “theoretical” adverse effect is 17150 mg per day (of the anhydrite form) for a long term exposition. This exposition is not realistic