Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 813-399-9 | CAS number: 1821694-26-1
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Overall conclusion on mutagenicity of
Magnesium glucoheptonate in bacterial cells is based on several studies
available for gluconates, its derivatives, and inorganic magnesium
compounds.
No mutagenicity in bacterial cells
can be expected for Magnesium glucoheptonate since all in vitro tests
(reliable and less reliable) in bacterial cells conducted with the
structural analogues gluconates, and inorganic magnesium compounds were
overwhelmingly negative. Moreover, in vivo chromosome aberrations
studies conducted with glucono-delta-lactone and sodium gluconate were
negative clear showing that no genetic toxicity can be attributed to
gluconate and glucoheptonate ions.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: other: summry of available in vitro and in vivo genetic toxicity data
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable well documented peer-reviewed report.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- The study was made on one yeast strain : Saccharomyces cerevisiae, strain D4 and 3 bacteria strains: S. typhimuriumTA1535, TA1537 and TA 1538. Positive controls are different from those in the OECD 471; only 3 concentration tested.
- Principles of method if other than guideline:
- Summary of genetic toxicity data on glucono-delta-lactone, sodium or calcium gluconate
- GLP compliance:
- not specified
- Type of assay:
- other: summary of a variety of data
- Target gene:
- his-
- Species / strain / cell type:
- other: S.typhimurium TA 1535, TA 1537, TA 1538
- Species / strain / cell type:
- Saccharomyces cerevisiae
- Details on mammalian cell type (if applicable):
- strain D4
- Metabolic activation:
- with and without
- Metabolic activation system:
- The tissue homogenates and supernatants (9000 g) were prepared from tissues of mouse (ICR random bred adult males); rat (Sprague-Dawnley adult males) and monkey (Macaca mulatta adult males).
- Test concentrations with justification for top dose:
- Sodium gluconate: 0.06, 0.012, 0.024 µg/mL (Salmonella typhimurium); 12.5, 25 and 50 µg/mL (yeast);
Glucono-delta-lactone: 2.5, 5 (5 µg/mL plate test; Salmonella typhimurium); 12.5 and 25 µg/mL (yeast);
Calcium gluconate: 12.5, 25 and 50 µg/mL (Salmonella typhimurium); 7.5, 15 and 30 µg/mL (yeast). - Vehicle / solvent:
- - Solvent used: 0.067 M phosphate buffer, pH 7.4
- Untreated negative controls:
- yes
- Remarks:
- solvent control
- Negative solvent / vehicle controls:
- yes
- Remarks:
- vehicle control
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- without S9
- Positive control substance:
- 2-nitrofluorene
- ethylmethanesulphonate
- other: Quinacrine or quinacrinemustard (QM)
- Untreated negative controls:
- yes
- Remarks:
- solvent control
- Negative solvent / vehicle controls:
- yes
- Remarks:
- vehicle control
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- with S9
- Positive control substance:
- 2-acetylaminofluorene
- N-dimethylnitrosamine
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation) and in suspension
DURATION
- Exposure duration:
- Glucono-delta-lactone: 4 days: bacteria and yeasts (plate test); 4 hours (yeasts) and 1 hour (bacteria) in suspension test.
- Sodium gluconate: 48 to 72 hours bacteria and yeasts (plate test); 4 hours (yeasts) and 1 hour (bacteria) in suspension test.
- Calcium gluconate: 4 days: bacteria and yeasts (plate test); 4 hours (yeasts) and 1 hour (bacteria) in suspension test.
DETERMINATION OF CYTOTOXICITY
- Glucono-delta-lactone: 50% survival in bacteria calculated was at 1% (10 μg/mL) test substance and 5% (50 μg/mL) for yeast;
- Sodium gluconate: 50% survival in bacteria calculated was at 0.0024 % test substance and 5% for yeast;
- Calcium gluconate: 50% survival in bacteria calculated was at 5.00 % test substance and 3.00% for yeast.
Tests in suspension without S9 mix: Bacterial plates were scored after incubation for 48 hours at 37°C. The yeast plates were incubated at 30°C for 3-5days before scoring. - Species / strain:
- S. typhimurium, other: TA 1535; TA 1537 and TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
The available in vitro mutagenicity data with glucono-delta-lactone, sodium or calcium gluconate were negative. - Executive summary:
Sodium gluconate, glucono-delta-lactone and calcium gluconate were tested on Saccharomyces cerevisiae and Salmonella typhimurium with and without metabolic activation. OECD Guideline 471 was deviated for the number of strains tested and the choice of positive controls. The substances were tested on Saccharomyces cerevisiae (strain D4) and Salmonella typhimurium (3 strains) with and without metabolic activation. Only 3 concentrations were tested where OECD guideline recommends at least 5 concentrations. None of the test substances showed mutagenicity on the strains tested.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable well documented publication which meets basic scientific principles.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Mutagenicity of Magnesium Carbonate, basic heavy and Magnesium Oxide, Heavy, dietary supplements, were examined in Ames' tester strains, Salmonella typhimurium TA97 and TA102. The mutation test was carried out by the preincubation procedure described by Ames et al. The test chemical was tested with and without S9 mix.
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- his-
- Species / strain / cell type:
- S. typhimurium TA 97
- Species / strain / cell type:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- no data
- Test concentrations with justification for top dose:
- - Magnesium Oxide, Heavy: 0. 0.1, 0.5, 1.0, 5.0 and 10.0 mg/plate;
- Magnesium Carbonate, Basic, Heavy: 0, 0.01, 0.05, 0.1, 0.5 and 1.0 mg/ plate. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: phosphate buffer (pH 7.4).
- Untreated negative controls:
- yes
- Remarks:
- Phosphate buffer (pH 7.4)
- Negative solvent / vehicle controls:
- yes
- Remarks:
- negative control
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- in TA97
- Positive control substance:
- 9-aminoacridine
- other: 2-AA
- Remarks:
- -S9 mix: 9-AA (30 µg); +S9 mix: 2-AA (5 µg)
- Untreated negative controls:
- yes
- Remarks:
- Phosphate buffer (pH 7.4)
- Negative solvent / vehicle controls:
- yes
- Remarks:
- negative control
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- in TA102
- Positive control substance:
- mitomycin C
- other: 2-AA
- Remarks:
- -S9 mix: MMC (0.5 µg); +S9 mix: 2-AA (5 µg)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min - Statistics:
- Statisticaly significant defference by Kruskal-Wallis test ( p <0.05) and dose-related incleasing by regression analysis (p < 0.01).
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
Magnesium Carbonate, basic heavy and Magnesium Oxide, Heavy were negative in two tester strains Salmonella typhimurium TA97 and TA102. - Executive summary:
Mutagenicity of 28 food additives including 7 dietary supplements, 7 free flowing agents, 5 antioxidants, 3 thickening agents, 3 food colors, 2 color fixatives, and an anticaking agent were examined in Ames' tester strains, Salmonella typhimurium TA97 and TA102. The mutation test was carried out by the preincubation procedure described by Ames et al. The test chemicals were preincubated with S9 mix or phosphate buffer (pH7.4) for 20 min. Magnesium dietary supplements: Magnesium Carbonate, basic heavy and Magnesium Oxide, Heavy were negative in two tester strains.
- Endpoint:
- genetic toxicity in vitro
- Remarks:
- Type of genotoxicity: other: summary of mutagenicity data
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable well-documented peer-reviewed report.
- Qualifier:
- according to guideline
- Principles of method if other than guideline:
- Summary of genetic toxicity study results conducted with monosaccharides, disaccharides, and related ingredients as used in cosmetics.
- GLP compliance:
- not specified
- Type of assay:
- other: summary
- Species / strain:
- other: The genotoxicity of a number of the mono- and disaccharides has been evaluated in in vitro and in vivo studies. The results of these studies are overwhelmingly negative.
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- other: not applicable (summary result)
- Untreated negative controls validity:
- other: not applicable (summary result)
- Positive controls validity:
- other: not applicable (summary result)
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
The genotoxicity of a number of the mono- and disaccharides has been evaluated in in vitro and in vivo studies. The results of these studies are overwhelmingly negative - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable well-documented peer-reviewed report.
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Magnesium sulfate was evaluated in the following bacterial strains at doses up to 5,000 μg/plate, with and without metabolic activation: Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and Escherichia coli strain WP2 uvrA (Oguma et al., 1998). The genotoxicity of magnesium sulfate was evaluated in the SOS Chromotest using Escherichia coli strain PQ37, with and without metabolic activation (Olivier and Marzin, 1987).
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- his-
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Species / strain / cell type:
- E. coli, other: PQ37
- Metabolic activation:
- with and without
- Test concentrations with justification for top dose:
- - Five dose levels (313-5000 micrograms/plate) were selected for all strains except for TA98 without metabolic activation and for TA1537 with metabolic activation, for which 6 dose levels (156-5000 micrograms/plate) were selected (Oguma et al., 1998);
- 30,000 nM/mL: MgSO4·7H2O (Olivier and Marzin, 1987). - Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- not specified
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- E. coli, other: PQ37
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
Magnesium sulfate induced no increase in the number of colonies with reverse mutation in any of the strains irrespective of the absence of presence of metabolic activation in the dose-range-finding study or in the main study (Oguma et al., 1998). Magnesium sulfate heptahydrate was not genotoxic, with or without metabolic activation (Olivier and Marzin, 1987). - Executive summary:
Magnesium sulfate was evaluated in the following bacterial strains at doses up to 5,000 μg/plate, with and without metabolic activation: Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and Escherichia coli strain WP2 uvrA (Oguma et al., 1998). Magnesium sulfate did not induce an increase in the incidence of reverse mutations in any of the bacterial strains tested in this assay.
The genotoxicity of magnesium sulfate was also evaluated in the SOS Chromotest using Escherichia coli strain PQ37, with and without metabolic activation (Olivier and Marzin, 1987). The SOS Chromotest is a colorimetric assay that measures the expression of genes induced by genotoxic agents in E. coli by means of fusion with the structural gene for β-galactosidase. Magnesium sulfate (MgSO4·7H2O) was tested at concentrations up to 30,000 nM/ml and was not genotoxic, with or without metabolic activation.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable well documented publication which meets basic scientific principles.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Salmonella/microsome tests (Ames tests) and chromosomal aberration tests in vitro using a Chinese hamster fibroblast cell line were carried out on 190 synthetic food additives and 52 food additives derived from natural sources.
- GLP compliance:
- no
- Remarks:
- the study was performed prior to adoption GLP regulation.
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- his-
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- S. typhimurium, other: TA 94
- Metabolic activation:
- with and without
- Metabolic activation system:
- The liver microsome fraction (S-9) from the liver of of Fischer rats pretreated 5 days before with polychlorinated biphenyls (500 mg/kg bw of Kanechlor KC-400 in olive oil, ip).
- Test concentrations with justification for top dose:
- - Six different concentrations were used:
- 100 mg/plate (max. non-cytotoxic dose): Magnesium chloride and Magnesium sulphate;
- 40 mg/plate (max. non-cytotoxic dose): Magnesium sulphate exsiccated. - Vehicle / solvent:
- - Distilled water: Magnesium chloride;
- Phosphate buffer: Magnesium sulphate, magnesium sulphate exsiccated. - Untreated negative controls:
- yes
- Remarks:
- solvent control
- Negative solvent / vehicle controls:
- yes
- Remarks:
- negative control
- True negative controls:
- no
- Positive controls:
- no
- Remarks:
- The result was considered positive if the number of colonies found was twice the number in the control.
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min
- Exposure duration: 2 days. - Evaluation criteria:
- The result was considered positive if the number of colonies found was twice the number in the control.
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- not examined
- Species / strain:
- S. typhimurium, other: TA 94
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- not examined
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
No significant increases in the numbers of revertant colonies were detected in any S. typhimurium strains at the maximum non-cytotoxic doses applied. - Executive summary:
Magnesium chloride, Magnesium sulphate and Magnesium sulphate exsiccated were tested in a Salmonella/microsome test (Ames test) during the course of primary mutagenicity screening of 190 synthetic food additives used in Japan (Ishidate et al., 1984). Reverse mutation assays using S. typhimurium strains TA92, TA1535, TA100, TA1537, TA94 and TA98 were carried out. The liver microsome fraction (S-9) was prepared from the liver of Fischer rats (Charles River Japan Co.) pretreated 5 days before with polychlorinated biphenyls (500 mg/kg body weight of Kanechlor KC-400 in olive oil, ip). Cells cultured overnight were pre-incubated with both the test sample and the S-9 mix for 20 min at 37°C before plating. Duplicate plates were used for each of six different concentrations of the sample. 100 mg/plate and 40 mg/plate were the maximum non-cytotoxic doses used for Magnesium chloride, Magnesium sulphate and Magnesium sulphate exsiccated, respectively. The number of revertant (his +) colonies was scored after incubation at 37°C for 2 days. The result was considered positive if the number of colonies found was twice the number in the control (exposed to the appropriate solvent or untreated). No positive control substances were included in the experiment.
The substances did not induce significant increases in the numbers of revertant colonies in any S. typhimurium strains at the maximum non-cytotoxic doses applied. Magnesium chloride, Magnesium sulphate and Magnesium sulphate exsiccated can be considered negative under the condition of this test.
Referenceopen allclose all
Cytotoxic concentration (50% survival) (μg/ml):
Sodium gluconate: 0.024 (bacteria), 50 (yeast);
Glucono-delta-lactone: 10 (bacteria), 50 (yeast);
Caclium gluconate: 50 (bacteria), 30 (yeast).
Table 1. Results of Mutation Test with magnesium dietary supplements
Dose (mg/plate) |
No of Revertants /plate |
|||
Magnesium Oxide, Heavy |
||||
|
TA97 |
TA102 |
||
|
-S9 |
+S9 |
-S9 |
+S9 |
10 |
111 |
148 |
216 |
469 |
5 |
108 |
185 |
193 |
461 |
1 |
103 |
187 |
183 |
460 |
0.5 |
101 |
182 |
179 |
425 |
0.1 |
119 |
178 |
192 |
445 |
0 |
118 |
179 |
205 |
461 |
Positive control |
178 |
3,987 |
3,576 |
1,820 |
Magnesium Carbonate, Basic, Heavy |
||||
|
-S9 |
+S9 |
-S9 |
+S9 |
1 |
123 |
160 |
227 |
419 |
0.5 |
114 |
167 |
219 |
454 |
0.1 |
103 |
166 |
210 |
391 |
0.05 |
98 |
182 |
192 |
440 |
0.01 |
100 |
169 |
234 |
403 |
0 |
115 |
175 |
245 |
416 |
Positive control |
175 |
1,997 |
3,187 |
2,112 |
Solvent: DW (not specified) |
||||
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Glucono-delta-lactone and sodium gluconate did not induce chromosomal aberrations in mice (CIR, 2014). The frequency of cells with chromosomal aberrations in the test groups was comparable to the control group in both experiments: single administartion and 4-d repeat administration (CIR, 2014).
Link to relevant study records
- Endpoint:
- in vivo mammalian germ cell study: cytogenicity / chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable well-documented peer-reviewed report.
- Qualifier:
- no guideline available
- GLP compliance:
- no
- Remarks:
- the study was conducted prior to adoption of guidelines (in 1974).
- Type of assay:
- chromosome aberration assay
- Species:
- mouse
- Strain:
- C57BL
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 12 or 13 weeks - Route of administration:
- oral: feed
- Vehicle:
- - Vehicle(s)/solvent(s) used: physiol. saline;
- Concentration of test material in vehicle:
- Amount of vehicle (if gavage or dermal): 1 mL/mouse - Duration of treatment / exposure:
- single dose and 4 days
- Frequency of treatment:
- not specified
- Post exposure period:
- The animals were sacrified at 24 hours (single dose) and 27 hours after last administration (4-days repeated dose).
- Dose / conc.:
- 2 000 mg/kg bw/day (nominal)
- Remarks:
- single dose administration
- Dose / conc.:
- 4 000 mg/kg bw/day (nominal)
- Remarks:
- single dose administration
- Dose / conc.:
- 8 000 mg/kg bw/day (nominal)
- Remarks:
- single dose administration
- Dose / conc.:
- 2 000 mg/kg bw/day (nominal)
- Remarks:
- 4 day repeated dose
- Dose / conc.:
- 4 000 mg/kg bw/day (nominal)
- Remarks:
- 4-day repeated dose
- No. of animals per sex per dose:
- Single dose administration: 3 (vehicle control and test groups); 2 (positive control);
4-day repeated dose administration: 2 (vehicle control); 3 (test group 1: 4 g/kg); 2 (test group 2: 2 g/kg); 2 (positive control). - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- MMC (mitomycin C) dissolved with 0.9% physiological saline solution and administered intraperitoneally at a dose of 0.5 mL/mouse (= 5mg/kg bw).
- Tissues and cell types examined:
- At least 200 metaphase cells per mouse were examined for the presence or absence of chromosomal aberrations (gaps, breaks, translocation, fragments, ring chromosomes and minutes chromosomes).
- Details of tissue and slide preparation:
- TREATMENT AND SAMPLING TIMES: After receiving the single dose and the repeated dose test substance, the animals were sacrified at 24 hours (single dose) and 27 hours after last administration (4-days repeated dose). 0.3 mL of 500 μg/mL colchicine was intraperitoneally injected to each mouse at one hour before sacrifice so that the metaphase cells could be observed.
DETAILS OF SLIDE PREPARATION: After the bone marrow cells were washed, treated and fixed with a fixing solution (1:3 acetic acid:ethanol solution), the cells were suspended and dripped on a slide glass and stained with Giemsa solution and examined. - Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- in both experiments: single administration and 4-d repeated dose administration.
- Toxicity:
- yes
- Remarks:
- At 8 g/kg, all mice died (single dose administration experiment)
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results (migrated information): negative
The frequency of cells with chromosomal aberrations in the test groups was comparable to the control group in both experiments: single administartion and 4-d repeat administration. - Endpoint:
- in vivo mammalian germ cell study: cytogenicity / chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable well-documented peer-reviewed reports.
- Qualifier:
- no guideline available
- GLP compliance:
- no
- Remarks:
- the study was conducted prior to adoption of guidelines (in 1974).
- Type of assay:
- chromosome aberration assay
- Species:
- mouse
- Strain:
- C57BL
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 12 or 13 weeks - Route of administration:
- oral: feed
- Vehicle:
- - Vehicle(s)/solvent(s) used: physiol. saline;
- Concentration of test material in vehicle:
- Amount of vehicle (if gavage or dermal): 1 mL/mouse - Duration of treatment / exposure:
- single dose and 4 days
- Frequency of treatment:
- not specified
- Post exposure period:
- The animals were sacrified at 24 hours (single dose) and 27 hours after last administration (4-days repeated dose).
- Dose / conc.:
- 2 500 mg/kg bw/day (nominal)
- Remarks:
- single dose administration
- Dose / conc.:
- 5 000 mg/kg bw/day (nominal)
- Remarks:
- single dose administration
- Dose / conc.:
- 10 000 mg/kg bw/day (nominal)
- Remarks:
- single dose administration
- Dose / conc.:
- 1 250 mg/kg bw/day (nominal)
- Remarks:
- 4 day repeated dose
- Dose / conc.:
- 2 500 mg/kg bw/day (nominal)
- Remarks:
- 4-day repeated dose
- No. of animals per sex per dose:
- Single dose administration: 3 (vehicle control and test groups); 2 (positive control);
4-day repeated dose administration: 2 (vehicle control); 3 (test group 1: 2.5 g/kg); 2 (test group 2: 1.25 g/kg); 2 (positive control). - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- MMC (mitomycin C) dissolved with 0.9% physiological saline solution and administered intraperitoneally at a dose of 0.5 mL/mouse (= 5mg/kg bw).
- Tissues and cell types examined:
- At least 200 metaphase cells per mouse were examined for the presence or absence of chromosomal aberrations (gaps, breaks, translocation, fragments, ring chromosomes and minutes chromosomes).
- Details of tissue and slide preparation:
- TREATMENT AND SAMPLING TIMES: After receiving the single dose and the repeated dose test substance, the animals were sacrified at 24 hours (single dose) and 27 hours after last administration (4-days repeated dose). 0.3 mL of 500 μg/mL colchicine was intraperitoneally injected to each mouse at one hour before sacrifice so that the metaphase cells could be observed.
DETAILS OF SLIDE PREPARATION: After the bone marrow cells were washed, treated and fixed with a fixing solution (1:3 acetic acid:ethanol solution), the cells were suspended and dripped on a slide glass and stained with Giemsa solution and examined. - Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- in both experiments: single dose administration and 4-d repeated dose administration.
- Toxicity:
- yes
- Remarks:
- At 10 and 5 g/kg, all mice died (single dose administration); at 1.25 and 2.5 g/kg, one mouse died in each group (4-day repeated dose administration).
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results (migrated information): negative
Induction of chromosomal aberration by sodium gluconate was not detected after in vivo single and repeated dose treatment.
Referenceopen allclose all
Single dose administration:
At 8 g/kg, all mice died.
MMC induced chromosomal aberrations in at least 20% of bone marrow cells.
GDL induced chromosomal aberrations in the cells at a frequency of about 0.5% comparable to the control.
4-day repeated dose administration:
MMC induced chromosomal aberrations at about 30% cells.
The frequency of cells with chromosomal aberrations was 1 % or less in the test groups which is comparable to the control group. Induction of chromosomal aberration by GDL was not detected after in vivo single and repeated dose treatment.
Single dose administration:
At 10 and 5 g/kg, all mice died.
At 2.5 g/kg, observation could be made only on 2 animals (preparation of the chromosome specimen failed).
MMC induced chromosomal aberrations in at least 20% of bone marrow cells. Sodium gluconate induced chromosomal aberrations in the cells at a frequency of about 0.5% is comparable to the control. (1 gap and 1 minute chromosome for 283 cells).
4-day repeated dose administration:
At 1.25 and 2.5 g/kg, one mouse died in each group.
MMC induced chromosomal aberrations at about 30% cells. The frequency of cells with chromosomal aberrations was 0.5% in the test groups which is comparable to the control group.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
There are no genetic toxicity in vitro studies available for Magnesium glucoheptonate. Since Magnesium glucoheptonate is expected to be dissociated into magnesium and glucoheptonate ions, data on structurally similar substances: gluconic acid, its derivatives and some inorganic magnesium compounds have been taken into account to assess mutagenicity potential of magnesium and glucoheptonate ions in bacterial cells.
In vitro genetic toxicity studies with Calcium gluconate, Sodium gluconate and glucono-delta-lactone
Sodium gluconate, glucono-delta-lactone and calcium gluconate were tested by plate incorporation method and in suspension on Saccharomyces cerevisiae and Salmonella typhimurium with and without metabolic activation (SIDS, 2004). OECD Guideline 471 was deviated for the number of strains tested and the choice of positive controls. The substances were tested on Saccharomyces cerevisiae (strain D4) and Salmonella typhimurium (3 strains: TA 1535, TA 1537, TA 1538) with and without metabolic activation. Only 3 concentrations were tested where OECD guideline recommends at least 5 concentrations. None of the test substances showed mutagenicity on the strains tested.
The genotoxicity of a number of sugar-like substances the mono- and disaccharides has been evaluated in in vitro and in vivo studies. The results of these studies are overwhelmingly negative (CIR, 2014).
In vivo genetic toxicity studies with glucono-delta-lactone and sodium gluconate.
Since glucono-delta-lactone, sodium and calcium gluconates were tested only in three strains of Salmonella typhimurium with three concentrations, the results of in vivo studies conducted with glucono-delta-lactone and sodium gluconate (SIDS, 2004) can be taken into account to assess genetic toxicity potential of glucoheptonate ion.
Glucono-delta-lactone and sodium gluconate did not induce chromosomal aberrations in mice (CIR, 2014). The frequency of cells with chromosomal aberrations in the test groups was comparable to the control group in both experiments: single administartion and 4-d repeat administration (CIR, 2014).
Based on these data, no genetic toxicity can be attributed to gluconate ions, its derivatives and other sugar-like compounds including glucoheptonate ion.
In vitro genetic toxicity studies with organic and inorganic calcium compounds
Mutagenicity of 28 food additives including 7 dietary supplements, 7 free flowing agents, 5 antioxidants, 3 thickening agents, 3 food colors, 2 color fixatives, and an anticaking agent were examined in Ames' tester strains, Salmonella typhimurium TA97 and TA102. The mutation test was carried out by the preincubation procedure described by Ames et al. The test chemicals were preincubated with S9 mix or phosphate buffer (pH7.4) for 20 min. Magnesium dietary supplements: Magnesium Carbonate, basic heavy and Magnesium Oxide, Heavy were negative in two tester strains.
Magnesium chloride, Magnesium sulfate and Magnesium sulfate exsiccated were evaluated for genotoxicity in the Ames test using the following Salmonella typhimurium strains: TA92, TA94, TA98, TA100, TA1535, and TA1537 (CIR, 2014a; Ishidate et al., 1984). The test substances were evaluated at doses up to 100 mg/plate (Magnesium chloride, Magnesium sulfate) and up to 40 mg/plate (Magnesium sulfate exsiccated) with and without metabolic activation, and results were negative in all bacterial strains tested. In another Ames test, magnesium sulfate was evaluated in the following bacterial strains at doses up to 5,000 μg/plate, with and without metabolic activation: Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and Escherichia coli strain WP2 uvrA (CIR, 2014a; Oguma et al., 1998) Magnesium sulfate did not induce an increase in the incidence of reverse mutations in any of the bacterial strains tested in this assay.
The genotoxicity of magnesium sulfate was also evaluated in the SOS Chromotest using Escherichia coli strain PQ37, with and without metabolic activation (Olivier and Marzin, 1987) The SOS Chromotest is a colorimetric assay that measures the expression of genes induced by genotoxic agents in E. coli by means of fusion with the structural gene for β-galactosidase. Magnesium sulfate (MgSO4·7H2O) was tested at concentrations up to 30,000 nM/ml and was not genotoxic, with or without metabolic activation.
Based on these data, no genetic toxicity potential in bacterial cells can be attributed to magnesium ion.
Justification for classification or non-classification
All available genetic toxicity studies in vitro in bacterial cells and yeasts conducted with calcium gluconate, sodium gluconate, glucono-delta-lactone, sugar-like compounds and their derivatives as well as with inorganic magnesium compounds were negative. Additionally, in vivo studies conducted with glucono-delta-lactone and sodium gluconate did not induce chromosomal aberrations in mice, clear showing that no genetic toxicity can be attributed to glucoheptonate ion. Based on these data, Magnesium glucoheptonate can be considered as not mutagenic as well.
According to European Regulation (EC) No. 1272/2008, Magnesium glucoheptonate does not need to be classified and labelled as mutagenic substance.Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
