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Toxicological information

Genetic toxicity: in vitro

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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:
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 / strainopen allclose all
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
Controlsopen allclose all
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.

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.