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Genetic toxicity: in vitro

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in vitro gene mutation study in bacteria
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Comparable to guideline study with acceptable restrictions. As this study is being used for read-across, the reliability has been chosen to reflect this. Read-across from magnesium chloride to magnesium carbonate is justified on the following basis. Due to the presence of acid, mainly in the form of hydrochloric acid, in the stomach, magnesium carbonate will be converted into magnesium chloride when orally ingested. Furthermore, magnesium chloride is significantly more soluble than the carbonate salt and therefore represents the worst case in terms of its bioavailability for systemic absorption. In addition, both salts have been shown to have no acute toxicity and do not exhibit evidence of systemic toxicity when tested at a concentration of 2000 mg/kg bw in acute oral studies. Magnesium carbonate and magnesium chloride also occur in the natural environment and humans are widely exposed to naturally occurring magnesium carbonate and chloride, e.g. via drinking water and food on a day to day basis. Ingested magnesium, carbonate and chloride ions are actively regulated by the body. Systemic toxicity is likely to be caused by absorption of the magnesium ion rather than either the carbonate or chloride counterions and hence studies on magnesium salts can be read across from one to the other. This study is therefore deemed reliable for read across to magnesium carbonate as it represents the worst case for potential genotoxicity.

Data source

Reference Type:
Primary Mutagenicity Screening of Food Additives Currently used in Japan
Ishidate M, Sofuni T, Yoshikawa K, Hayashi M, Nohmi T, Sawada M & Matsuoka A
Bibliographic source:
Fd. Chem. Toxic., 22(8): 623-636

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
The bacterial strains tested are slightly different to those recommended in the guideline. Some details regarding the method and results are not described in the report.
Principles of method if other than guideline:
Salmonella/ microsome tests (Ames tests) were carried out on 190 synthetic food additives and 52 food additives derived from natural sources, all of which are currently used in Japan. One of the test materials used in the study was magnesium chloride.
GLP compliance:
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
Magnesium chloride (see endpoint summary for justification of read-across)
Magnesium chloride (see endpoint summary for justification of read-across)
Constituent 2
Reference substance name:
Magnesium chloride
EC Number:
EC Name:
Magnesium chloride
Cas Number:
magnesium dichloride
Details on test material:
Purity: 96.3%


Species / strain
Species / strain / cell type:
S. typhimurium, other: TA92, TA1535, TA100, TA1537, TA94 and TA98
Metabolic activation:
with and without
Metabolic activation system:
Liver microsome fraction (S9) - prepared from the liver of Fischer rats
Test concentrations with justification for top dose:
Maximum dose: 100 mg/plate (represents the highest non-cytotoxic dose used in the experiment)
Vehicle / solvent:
- Solvent used: distilled water
Negative solvent / vehicle controls:
Details on test system and experimental conditions:
Cells cultured overnight were pre-incubated with both the test sample and the S9 mix for 20 min at 37 °C before plating. Duplicate plates were used for each of six different concentrations of the sample. The number of revertant (his+) colonies was scored after incubation at 37 °C for 2 days.
Evaluation criteria:
The result was considered positive if the number of colonies found was twice the number in the control.

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA92, TA1535, TA100, TA1537, TA94 and TA98
Metabolic activation:
with and without
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
not specified
Additional information on results:
No significant increases in the number of revertant colonies were detected in any S. typhimurium strains at the maximum dose.
Remarks on result:
other: all strains/cell types tested
Migrated from field 'Test system'.

Applicant's summary and conclusion

Interpretation of results (migrated information):

Magnesium chloride was considered to be non-mutagenic under the conditions of this test.