Magnesium ethanolate

Endpoint summary

Description of key information

Magnesium ethanolate rapidly hydrolyzes in aqueous environments (t_1/2< 1 minute) into ethanol and magnesium hydroxide (detailed description in section 5.1.2). Valid study data on skin sensitisation are available for the hydrolysis products magnesium hydroxide and ethanol.

Hydrolysis product magnesium hydroxide

Based on a weight of evidence approach using both animal testing and human information, the hydrolysis product magnesium hydroxide is not regarded and not classified as a skin sensitizer. 

Hydrolysis product ethanol

The hydrolysis product ethanol tested negative in a guinea pig maximization test, LLNA, and mouse ear swelling test.

Justification for classification or non-classification

Magnesium ethanolate rapidly hydrolyzes in aqueous environments (t1/2< 1 minute) into ethanol and magnesium hydroxide (detailed description in section 5.1.2). Valid study data on skin sensitisation are available for the hydrolysis products magnesium hydroxide and ethanol.

 

ETHANOL

An ear swelling study (Descotes 1988) was used to examine the skin sensitising potential of ethanol. Ethanol was applied twice on the right ear after an induction procedure involving two scapular subcutaneous injections of adjuvant and multiple topical ethanol applications to the abdomen over a period of 14 days. The degree of contact hypersensitivity is deduced from ear swelling measured 24 and 48 hours after application. Ethanol was found not to cause any statistical increase in ear swelling, in contrast to 3 positive controls which all caused a statistically significant increase.

 

Data is also available from studies (BP_1984, Lalko 2004) using ethanol as a vehicle. In a guinea pig maximisation study that used ethanol as a carrier solvent for the substance being tested (polyakylene glycol block copolymers) no positive reactions were obtained. It can be concluded that ethanol cannot have any significant skin sensitising properties since it was used as a solvent in this study at levels of up to 75%. A study was carried out to evaluate the effect of vehicles (e.g. ethanol) for use in the mouse local lymph node assay (LLNA), and their influence on the skin sensitization potential of fragrance materials. Groups of mice were treated with each test fragrance in ethanol (1:3 or 3:1 mixtures of the two), or with ethanol alone. Although there were no true control data for comparison with the ethanol-alone treated animals, the level of induced T-lymphocyte proliferation was low for ethanol when compared with that for fragrance materials known to be mild to moderate skin sensitizers, and comparable to other inert vehicles tested.

Ethanol did not show any signs of sensitising properties.

 

MAGNESIUM HYDROXIDE [Mg(OH)2] and MAGNESIUM CHLORIDE [MgCl2]

There are experimental findings from animal studies for Mg(OH)2 and MgCl2. Although a guideline-conform local lymph node assay (LLNA) showed a positive response, there are a number of reasons to suggest that Mg(OH)2 is highly unlikely to be a skin sensitiser. An expert opinion has been provided from the Informationsverbund Dermatologischer Kliniken (IVDK; Schnuch, A. 2010) in Germany. The IVDK is a network of more than 50 dermatological hospitals and was formed to monitor and survey the development of contact allergies in Germany. Despite 20 years of observations in 192,421 patients, they have not yet observed a case of a contact allergy with magnesium hydroxide being the causative agent. Furthermore, no case of contact allergy to magnesium hydroxide has been reported in the world literature, despite extensive exposure of the general population to the substance. Some reports on flame retardants address magnesium hydroxide toxicity, and no sensitising effects have been reported [DFE(EPA), 2008; NAP, 2000]. In addition, human health questionnaires were distributed among eight magnesium-hydroxide producing companies where, overall, 457 workers had been exposed to magnesium hydroxide, 182 of those had been exposed continuously and 227 intermittently. These workers were queried about any adverse effects or health problems they may have experienced due to exposure; these included allergy or occupational asthma. Among all the 457 workers surveyed, there were no reported cases of health problems or adverse effects experienced through exposure.

Furthermore, the results of a guinea pig maximisation test (GPMT) performed with magnesium chloride were obtained from the Magnesium Chloride Consortium. Magnesium chloride was negative in the GPMT. As any possible skin sensitising potential of magnesium hydroxide is likely to stem from the cation rather than the hydroxide anion, the outcome of this test provides additional evidence that magnesium ions should not be regarded as skin sensitisers.

Regarding the hydroxide portion of the compound, there is ample evidence in the literature that hydroxides of other metals are not skin sensitisers [NICNAS, 2003; Banerjee et. al., 2003; DFE (EPA), 2008].

False positives in the LLNA assay are not uncommon, and indeed the LLNA was judged to be no more than 90 % accurate during its validation (Basketter et. al., 2010). On this basis, certain substances have not been classified as contact sensitisers despite giving positive responses in the LLNA test. These include copper chloride (Basketter and Scholes, 1992), sodium lauryl sulphate (Loveless et. al., 1996; Montelius et. al., 1994), benzalkonium chloride (Basketter et. al., 2004) and ethanol (Basketter et. al., 2010).

Given the combination of the epidemiological data, the negative guinea pig maximisation test with magnesium chloride and the history of false positives using the LLNA test, the weight of evidence suggests that the positive results obtained in the LLNA test are inaccurate and, thus, a sensitising effect of magnesium hydroxide is unlikely. Therefore, magnesium hydroxide should not be classified as a skin sensitizer.

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References: see 7.4.1 entry "Hydrolysis Product Mg(OH)2: Skin sensitisation statement" with references.

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Migrated from Short description of key information: Based on a weight of evidence approach using animal testing and human information, magnesium ethanolate is not regarded and not classified as a skin sensitiser.