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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
other: expert opinon based on the similar subtances
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
The present expert opinion is based on the well-accepted hypothesis that the source and target substances have similar toxicological properties – reproductive toxicity in the present case – due to structural similarity. The analysis prediction is supported by the known properties of a trio of inorganic compounds representing the same ions/groups making up the target compound. Therefore, the source and target compounds can be considered structurally very similar. Moreover, in the acidic (hydrochloric acid in particular) environment of the stomach, the target compound entering via the oral route would be quickly converted into magnesium chloride -compound Source 3. While magnesium carbonate would be a preferred second source compound due to closer similarity, reproductive toxicity studies for this compound are not available, therefore, calcium carbonate has been chosen instead.

Purity and impurities
The source and target compounds can be considered to be of similar purity, as these inorganic compounds can be obtained with similar purity at similar cost/effort. Neither the source nor the target compounds contain impurities relevant to the classification.

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. The actual form of the target compound after oral administration can be taken as that of source 2 compound.

Physicochemical similarity
Most of the physicochemical properties of the source and target compounds are close to each other. All of the considered substances are ionic solids, soluble in the acidic medium of the stomach.

Toxicology data
The reproductive toxicity of Source 1 and Source 2 have a reliability score of 2, being read-across from Source 3 and a nano-form of the chemically identical compound, respectively. The Source 3 compounds has been assessed in vivo, with a reliability score 1 study (reliable without restrictions), as described on the ECHA listing of the respective chemicals.
Cross-reference
Reason / purpose for cross-reference:
reference to other study
Reference
Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
other: expert opinion
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH AND JUSTIFICATION
The present expert opinion is based on the well-accepted hypothesis that the source and target substances have similar toxicological properties – genetic 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 very similar. Moreover, in the acidic (hydrochloric acid in particular) environment of the stomach, the target compound entering via the oral route would be quickly converted into magnesium chloride - the Source 2 compound.
While magnesium carbonate would be the direct source compound due to closer similarity, genetic toxicity studies for this compound are not available, or rather the analysis for regulatory purposes has also been read-across from Source 2, according to similar justifications as presented above.
The source and target compounds can be considered to be of similar purity, as these inorganic compounds can be obtained with similar purity at similar cost/effort. Neither the source nor the target compounds contain impurities relevant to the classification

Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
GLP compliance:
no
Type of assay:
in vitro mammalian cell gene mutation test using the Hprt and xprt genes
Target gene:
hypoxanthine-guanine phosphoribosyl transferase gene – the HPRT test (Hprt and HPRT in rodent and human cells, respectively), and the xanthine-guanine phosphoribosyl transferase transgene (gpt) (the XPRT test).
Metabolic activation:
not applicable
Metabolic activation:
not applicable
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
not applicable
Untreated negative controls validity:
not applicable
True negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
not measured/tested
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 experimental studies, the source compounds have not been classified as genotoxic or mutagenic. Based on these considerations, the experimental assessment of the target compound is expected to yield the same results as that of the source compounds, resulting in “non mutagenic” interpretation. The conclusion is further justified by the fact that magnesium is an essential element to life, the levels of which in a body are actively regulated, while magnesium deficiency causes serious disorders.
Executive summary:

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 experimental studies, the source compounds have not been classified as genotoxic or mutagenic. Based on these considerations, the experimental assessment of the target compound is expected to yield the same results as that of the source compounds, resulting in “non mutagenic” interpretation. The conclusion is further justified by the fact that magnesium is an essential element to life, the levels of which in a body are actively regulated, while magnesium deficiency causes serious disorders.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2021
Report date:
2021

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
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

Administration / exposure

Route of administration:
other: oral (feed and gavage)
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Endocrine findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day
Based on:
not specified
Sex:
male/female
Remarks on result:
not measured/tested

Target system / organ toxicity (P0)

Critical effects observed:
no
System:
other: not specified

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Endocrine findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Immunological findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Effect levels (P1)

Remarks on result:
not measured/tested

Target system / organ toxicity (P1)

Critical effects observed:
no

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Sexual maturation:
no effects observed
Anogenital distance (AGD):
no effects observed
Nipple retention in male pups:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Other effects:
no effects observed

Developmental neurotoxicity (F1)

Behaviour (functional findings):
no effects observed

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
no effects observed

Effect levels (F1)

Remarks on result:
not measured/tested

Target system / organ toxicity (F1)

Critical effects observed:
no
System:
other: not specified

Overall reproductive toxicity

Reproductive effects observed:
no
Lowest effective dose / conc.:
1 000 mg/kg bw/day (nominal)
Treatment related:
not specified

Applicant's summary and conclusion