[D-gluco-heptonato-κO1,κO2,κO3,κO6,κO7]calcium(II) nitrate

Genetic toxicity: in vitro

Administrative data

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:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well documented peer-reviewed report.

Data source

Reference

Reference Type:

publication

Title:

Gluconic Acid and its Derivatives. CAS N°: Gluconic Acid, 526-95-4 Glucono-Delta-Lactone, 90-80-2 Sodium Gluconate, 527-07-1 Calcium Gluconate, 299-28-5 /18016-24-5 Potassium Gluconate, 299-27-4

Author:

OECD SIDS

Year:

2004

Bibliographic source:

UNEP PUBLICATIONS: SIDS Initial Assessment Report For SIAM 18 Paris, France, 20-23 April 2004 (available via www.inchem.org/documents/sids/sids/gluconates.pdf, 2015-07-15)

Materials and methods

Test guideline

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

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report):
Glucono-delta-lactone: CAS 90-80-2
Sodium Gluconate, CAS 527-07-1
Calcium gluconate: CAS 299-28-5; CAS 18016-24-5

Purity (%) of :

Glucono-delta-lactone: 99-101%
Sodium gluconate: 98-102%
Calcium gluconate: 98-104%

Method

Target gene:

his-

Species / strain

Species / strain 1

Species / strain / cell type:

other: S.typhimurium TA 1535, TA 1537, TA 1538

Species / strain 2

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

Controls

Controls 1

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)

Controls 2

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.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 1535; TA 1537 and TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

valid for glucono-delta-lactone, sodium and calcium gluconate

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'.

Any other information on results incl. tables

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).

Applicant's summary and conclusion

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.