Magnesium neodecanoate

Endpoint summary

Description of key information

No acute toxicity studies with magnesium neodecanoate are available, thus the acute toxicity will be addressed with existing data on the individual moieties magnesium and neodecanoic acid.

Signs of acute oral or acute dermal toxicity are not expected for magnesium neodecanoate, since the two moieties magnesium and neodecanoic acid have not shown signs of acute oral or acute dermal toxicity in experimental testing (both LD50 > 2000mg/kg).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

No acute toxicity studies with magnesium neodecanoate are available, thus the acute toxicity will be addressed with existing data on the individual moieties magnesium and neodecanoic acid.

Magnesium

Acute Oral Toxicity

Humans must consume magnesium at regular intervals via diet or supplementation, mainly via oral application. “The daily recommendation for magnesium is controversial, as the literature is conflicting and varies between countries, although values of >300 mg/day are usually reported for healthy adults with adjustment for age, sex and nutritional status” (Kass et al., 2017). However, an excessive use can lead to mild side effects. When unabsorbed magnesium reaches the intestine or colon it can attract water from nearby tissue through osmosis. Therefore excessive use of magnesium and high amounts of unabsorbed magnesium in the intestine lead to diarrhoea. Side effects like diarrhoea or hypoventilation are known but mostly owing to the abuse of magnesium. For instance, Fung et al.(1995) reported the case of a 69 years old multimorbid woman who took about ca. 24 000 mg magnesium daily as an antacid. The observed serum levels increased up to 6.7 mmol/L and caused hypoventilation, but the patient recovered. “Magnesium in foods derived from plant or animal sources has not been demonstrated to induce diarrhoea nor other adverse effects in healthy persons, probably as magnesium is bound to matrices and hence is mostly not easily bioavailable. On the other hand, easily dissociable magnesium salts (e.g. chloride or sulphate; included are compounds like magnesium oxide becoming readily dissociable after the reaction with gastric hydrochloric acid) which are present in water, many supplements and drugs, exert dose-dependent laxative effects” (EFSA scientific opinion on dietary reference values for magnesium). Diarrhoea induced by easily dissociable magnesium salts or compounds like magnesium oxide is completely reversible within 1 to 2 days and does not represent a significant health risk in subjects with intact renal function. Poorly dissociable magnesium salts (e.g. phytates) have a lower, if any, potential to induce diarrhoea.

Acute dermal toxicity

In the absence of measured data on dermal absorption, current guidance suggests the assignment of either 10 % or 100 % default dermal absorption rates. In contrast, the currently available scientific evidence on dermal absorption of metals yields substantially lower figures, which can be summarised briefly as follows: Measured dermal absorption values for metals or metal compounds in studies corresponding to the most recent OECD test guidelines are typically 1 % or even less. Therefore, the use of a 10 % default absorption factor is not scientifically supported for metals. This is corroborated by conclusions from previous EU risk assessments (Ni, Cd, Zn) and current metal risk assessments under REACH, which have derived dermal absorption rates of 2 % or far less (but with considerable methodical deviations from existing OECD methods) from liquid media. However, considering that under industrial circumstances many applications involve handling of dry powders, substances and materials, and since dissolution is a key prerequisite for any percutaneous absorption, a factor 10 lower default absorption factor may be assigned to such “dry” scenarios where handling of the product does not entail use of aqueous or other liquid media. This approach was taken in the in the EU RA on zinc. A reasoning for this is described in detail elsewhere (Cherrie and Robertson, 1995), based on the argument that dermal uptake is dependent on the concentration of the material on the skin surface rather than its mass. The following default dermal absorption factors for metal cations are therefore proposed (reflective of full-shift exposure, i.e. 8 hours): From exposure to liquid/wet media: 1.0 %; From dry (dust) exposure: 0.1 %. This approach is consistent with the methodology proposed in HERAG guidance for metals (HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption for metals and inorganic metal compounds; EBRC Consulting GmbH / Hannover /Germany; August 2007).

For reference list please refer to endpoint summary of the moieties.

Neodecanoic acid

Neodecanoic acid has a low potential for toxicity via the oral, inhalation, and dermal routes. 

 

Acute oral toxicity

Male and female rats were gavaged with neodecanoic acid at concentrations of 1, 1.5, 2, 3, or 4 ml/kg to assess acute oral toxicity.  All animals that died during the study did so within 3 days of exposure. Signs of toxicity included lethargy, hypothermia, piloerection, dyspnea, and ataxia. Based on these results, it is concluded that the LD50 is approximately 2.27 ml/kg (2066 mg/kg). 

 

Acute dermal toxicity

In a study that assessed acute dermal toxicity, male and female rats were exposed to 4 ml/kg (3640 mg/kg) neodecanoic acid via an occluded dermal patch for 24 hours. After 24 hours, the patch was removed and clinical observations were made once daily for 9 days. There were no deaths observed in this study and there were no signs of a toxicity response.  It is concluded that the LD50 is greater than 3640 mg/kg. 

 

Magnesium neodecanoate

Signs of acute oral or acute dermal toxicity are not expected for magnesium neodecanoate, since the two moieties magnesium and neodecanoate respectively nodecanoic acid have not shown signs of acute oral or acute dermal toxicity in experimental testing (both LD50 > 2000mg/kg). Under the assumption that the moieties of magnesium neodecanoate show their toxicological profile individually upon dissolution, an acute toxicity estimates (ATE) for the acute oral and dermal (systemic) toxicity of magnesium decanoate can be calculated using the equation given in regulation (EC) 1272/2008, Annex I, Section 3.1.3.6.1.

A study for acute toxicity via inhalation was not conducted with magnesium neodecanoate, since it is produced and placed on the market in a form in which no inhalation hazard is anticipated, thus acute toxic effects are not likely to occur during manufacture and handling of that substance. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

The calculated oral and dermal LD50 for magnesium neodecanoate is > 2000mg/kg bw, hence the substance is not to be classified according to regulation (EC) 1272/2008 for acute oral and dermal toxicity as well as for specific target organ toxicity, single exposure (STOT SE).

Justification for classification or non-classification

Based on in vivo oral and dermal LD50 data on the moieties, acute toxicity estimates for magnesium neodecanoate have been calculated resulting in LD50 values > 2000 mg/kg bw.

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptions, magnesium neodecanoate does neither have to be classified and has no obligatory labelling requirement for acute oral or dermal toxicity.

Magnesium neodecanoate is not classified for acute inhalative toxicity because of lacking data.