Magnesium carbonate hydroxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE CATEGORY APPROACH
Eye irritation/corrosion are important concerns in human health. They are important in both product and workplace safety considerations. Eye irritation refers to the establishment of changes in the eye after exposure to the test chemical that are (fully) reversible, in a time period defined by the particular test. In the GHS system2, such chemicals are labelled as “UN GHS Category 2". In some cases, a Category 2A or 2B can be assigned, to differentiate between chemicals that cause irritation that is reversed in 7 days (2B) or not (2A). Eye corrosion or serious eye damage refers to the production of actual tissue damage in the eye or a decay of vision after exposure to the test chemical which is not (fully) reversible in the time period defined by the test method. Such chemicals are labelled as “UN GHS Category 1" in the aforementioned GHS framework. A chemical not classified under UN GHS Category 1 or 2 are referred to as “UN GHS No category". The most widespread in vivo test for eye irritation/corrosion has been the OECD Test No 4053, where one eye of an albino rabbit is treated with the test article by placing the chemical (solid, liquid or aerosol) in the conjunctival sac, while the other eye serves as a control. The results should be observed during a 21 day period. The ocular response is graded upon each examination, however, the results are necessarily subjective and reliable scores require highly trained personnel. Eye irritation is known to have positive correlation with the hydrophilicity/water solubility of a compound. The key issues for an irritant are the transport from eye surface into the biophase, binding to the phospholipid membrane and possible binding.


1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
The present expert opinion is based on the hypothesis that the source and target substances have similar toxicological properties – eye irritation in particular. The analysis prediction is supported by the known properties of a pair of inorganic magnesium compounds that consist of the same ions as the target compound; and upon dissolution release the same cations (Mg2+) and anions ((CO3)2-, OH-) as the target compound. Therefore, the source and target compounds can be considered structurally very similar. Moreover, the target compound can be considered structurally in between the source compounds, as it combines the anions present in the source compounds in its structure.


2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL )
A) Structural similarity: In principle, the composition of the target compound is the combination of the source compounds, every structural feature of the target compounds is represented by the sources. The ions released into an aqueous solution upon dissolution by the target compound matches those of a mixture of the source compounds.

B) Physicochemical similarity
Most of the physicochemical properties of the source and target compounds are very close to each other. All of the substances are solids, their aqueous solutions have a basic pH. However, since there are variable formulations of the target compound from anhydrous to those with 4 or 5 crystallization water molecules, the water solubility can be rather different from the source compounds that are both relatively poorly soluble in water.

C) Classification and labelling
Neither of the source compounds have been classified as an eye irritant. Therefore, based on the above, it can be concluded that the results of the eye irritation studies of the source substances are likely to predict the properties of the target substance and are considered as adequate to fulfill the datagap. Assuming similar mode of action due to the similar composition and similar physico-chemical properties (with the uncertainty introduced by the water solubility), the target compound can be read-across from the source compounds to be not irritating for the eyes.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Magnesium carbonate hydroxide

EC Number:

235-192-7

EC Name:

Magnesium carbonate hydroxide

Cas Number:

12125-28-9

Molecular formula:

Mg5(CO3)4(OH)2(H2O)4

IUPAC Name:

Magnesium carbonate hydroxide

Test material form:

solid: particulate/powder

Test system

Vehicle:

physiological saline

Results and discussion

In vitro

Results

Results 1

Irritation parameter:

in vitro irritation score

Value:

5.1

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

mean percent tissue viability 

Value:

111

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

no indication of irritation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The structural similarities between the source and the target substances and the similarities in their ionic constituents support the read-across hypothesis and the analysis. Adequate, reliable and available scientific information indicates that the source and target substances and their dissociation products (cations and anions) have similar toxicity profiles. In in vitro studies, the source compounds have been identified as not irritating to the eye. Based on the considerations, the experimental assessment of the target compound is expected to yield the same results as that of the source compounds, resulting in a "not irritating" interpretation. The main source of uncertainty to the assessment lies in the variability in the aqueous solubility of the target compound formulations.

Executive summary:

The structural similarities between the source (Magnesium hydroxide) and the target (Magnesium Carbonate) substances and the similarities in their ionic constituents support the read-across hypothesis and the analysis. Adequate, reliable and available scientific information indicates that the source and target substances and their dissociation products (cations and anions) have similar toxicity profiles. In in vitro studies, the source compounds have been identified as not irritating to the eye. Based on the considerations, the experimental assessment of the target compound is expected to yield the same results as that of the source compounds, resulting in a "not irritating" interpretation. The main source of uncertainty to the assessment lies in the variability in the aqueous solubility of the target compound formulations.

	Source 1	Source 2
Substance	Magnesium hydroxide	Magnesiium Carbonate
Enpoint	Eye irritation: in vitro / ex vivo	Eye irritation:in vitro / ex vivo
Type and adequacy of information	Experimental study, key study	Experimental study, key study
Reliability	1 (reliable without restriction)	1 (reliable without restriction)
Year	2010	2010
Test guideline or principle	OECD Guidelines for testing of Chemicals - Guidelines no. 437: "Bovine corneal opacity and permeability (BCOP) tet method for identifying ocular corrosive and severe irritatnts.	SkinEthic Reconstituted Human Corneal model (HCE, SkinEthic Laboratories, Nice, France) after a treatment period of 10 minutes. The test is based on the hypothesis that irritant chemicals are able to penetrate the corneal epithelial tissue and are sufficientyl cytotocix to cause cell death.
GLP compliance	yes	yes
Test material and vehicle	Unknown, physiological saline	30 mg, as supplied
Exposure	240 ± 10 minutes	10 minutes
Irritation parameter and timepoint	In vitro irritancy score (IVIS) = mean opacity + (15x mean OD490 value), 240 min.	Relative mean tissue viability (%), 10 minutes
Score	5.1	111%
Interpretation	Not irritating	Nor irritating