Magnesium carbonate hydroxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

11/02/2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE CATEGORY APPROACH
Acute inhalation toxicity data are used to assess human health and environmental hazards of consumer products, industrial chemicals, biocides, insect repellents, etc, as required by hazard classification and labelling requirements. They are important in both product and workplace safety considerations. The acute inhalation toxicity describes the total of adverse effects brought along by a single uninterrupted inhalation exposure of less than 24 hours of airborne test chemicals. Usually, acute inhalation toxicity studies consider exposures of 4 hours in duration. The above-mentioned adverse effects include changes in biochemistry, morphology, physiology, growth, development, or lifespan of an organism which results in impairment of functional capacity or of capacity to compensate for additional stress.
Acute inhalation toxicity studies should be based on mass concentrations, thus, gas, vapor, and aerosol concentrations are expressed using a mass per volume metric, such as mg/L or mg/m3, where the mass concentration is related to the test chemical. The test animals should be observed frequently during the exposure period with an emphasis on observing the time of onset of toxic signs. Following exposure, careful clinical observations should be made during the post-exposure period. The duration of the latter is not fixed. The "median lethal concentration" (LC50) is often used as a measure of acute inhalation toxicity. The median lethal concentration is defined as the concentration that kills half of a suitably large number of animals exposed for a specified duration. In the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), substances can be allocated to one of the five toxicity categories based on acute toxicity by the inhalation route according to the numeric cut-off criteria as shown below. Acute toxicity values are expressed as (approximate) LC50 values or as Acute Toxicity Estimates (ATE).
With a large number of possible modes of action, acute inhalation toxicity is difficult to correlate with particular structural features of compounds. Overall, the acute inhalation toxicity has often a positive correlation with the chemical reactivity of a compound and an inverse correlation with the chemical stability.

Structural similarity
Each of the structural features as ions/fragments existing in the target compound is represented by ions/fragments of the source compounds. The magnesium and hydroxide parts in magnesium hydroxide and the carbonate part in calcium carbonate.

Physicochemical similarity
Most of the physicochemical properties of the source and target compounds are close to each other. All of the substances are ionic solids, their aqueous solutions have a basic pH (pH>7). However, since variable formulations of the target compound exist anywhere from anhydrous up to those with 4 or 5 crystallization water molecules, the interaction with humidity in air (water vapor) and that on surfaces can be somewhat different among the formulations as well as from the source compounds, some hydrate forms of target compound are significantly more soluble in water than the source compounds.

Toxicology data
The acute inhalation toxicity of Source 1 and Source 2 have been studied in vivo, with a reliability score 1 study (reliable without restrictions), as described on the ECHA listing of the respective chemicals2,3. Some key experimental conditions and results are listed below.

ANALYSIS HYPOTHESIS AND JUSTIFICATION
The present expert opinion is based on the well-accepted hypothesis that the source and target substances have similar toxicological properties – acute inhalation toxicity in the present case – due to structural similarity. The analysis prediction is supported by the known properties of a pair of inorganic compounds representing the same ions/groups making up the target compound. Therefore, the source and target compounds can be considered structurally similar. While magnesium carbonate would be a preferred source compound due to closer similarity, inhalation toxicity studies for this compound are not available, therefore, calcium carbonate has been chosen instead.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

other: Expert opinion

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

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 animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

other: whole body, nose

Vehicle:

air

Duration of exposure:

ca. 4 h

Control animals:

not specified

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.1 mg/L air

Exp. duration:

4 h

Remarks on result:

other: whole body

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 3 mg/L air

Exp. duration:

4 h

Remarks on result:

other: nose

Mortality:

No mortality

Body weight:

normal

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 rigorous in vivo studies, the source compounds have not been classified as acutely toxic via the inhalation route, while applying the highest concentrations technically achievable in the experiment. 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 “practically nontoxic” interpretation. The main source of uncertainty to the assessment lies in the variability in the aqueous solubility and hence also the interaction with humidity in air of the target compound formulations.

Executive summary:

Neither of the source compounds have been classified acutely toxic via inhalation route Therefore, based on the above, it can be concluded that the results of the acute inhalation 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 classified as acutely toxic via the inhalation route.