Iron digluconate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ferrous gluconate is devoid of mutagenic properties and is thus classified as non-hazardous for this end point There are no studies for this endpoint on ferrous gluconate. Results of studies conducted with a structurally similar compound, Glucono-delta-lactone, are reported and used for read across. From this read across ferrous gluconate is classsified as non-hazardous for this endpoint. Read across justification summary is attached to the end point summary

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Missing S. typhimurium strains TA98, TA100, and TA102 or E. coli strain WP2 uvrA; use of only 1 (in plate) and 2 (in suspension) concentrations instead of recommended 5.

GLP compliance:

no

Remarks:

Study predates GLP

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535

Additional strain / cell type characteristics:

not applicable

Species / strain / cell type:

S. typhimurium TA 1537

Additional strain / cell type characteristics:

not applicable

Species / strain / cell type:

S. typhimurium TA 1538

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Lung, liver, and testes homogenates from adult male mice, rats, and monkeys

Test concentrations with justification for top dose:

0.50% (plate method) and 0.25% or 0.50% (suspension method)

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Saline or <10% DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-acetylaminofluorene

2-nitrofluorene

N-dimethylnitrosamine

ethylmethanesulphonate

other: Quinacrine Mustard

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

other: For plate tests, it is not clear if the vehicle controls were valid since no numerical results were reported. For suspension tests, vehicle controls appear to be valid.

Untreated negative controls validity:

not applicable

Positive controls validity:

other: For plate tests, it is not clear if the positive controls were valid since no numerical results were reported. For suspension tests, some of the positive control results do not appear to be valid.

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

other: For plate tests, it is not clear if the vehicle controls were valid since no numerical results were reported. For suspension tests, vehicle controls appear to be valid.

Untreated negative controls validity:

not applicable

Positive controls validity:

other: For plate tests, it is not clear if the positive controls were valid since no numerical results were reported. For suspension tests, some of the positive control results do not appear to be valid.

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

other: For plate tests, it is not clear if the vehicle controls were valid since no numerical results were reported. For suspension tests, vehicle controls appear to be valid.

Untreated negative controls validity:

not applicable

Positive controls validity:

other: For plate tests, it is not clear if the positive controls were valid since no numerical results were reported. For suspension tests, some of the positive control results do not appear to be valid.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

Glucono-delta-lactone, was negative both with or without metabolic activaton. However, some of the positive controls did not appear to be valid.

Executive summary:

Compound FDA 71 -72, glucono-delta-lactone, was negative both with or without metabolic activaton. However, some of the positive controls did not appear to be valid.

Reference 2

Endpoint:

genetic toxicity in vitro

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 480 (Genetic Toxicology: Saccharomyces cerevisiae, Gene Mutation Assay)

Deviations:

yes

Remarks:

only 2 concentrations used; post-treatment incubation was 3-5 days; study done only once; positive control in the presence of S9 did not produce anticipated results so results deemed unreliable

GLP compliance:

no

Remarks:

Study predates GLP

Type of assay:

gene mutation assay in fungi

Species / strain / cell type:

Saccharomyces cerevisiae

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Lung, liver, and testes homogenates from adult male mice, rats, and monkeys (it was not reported whether or not an enzyme inducer was used)

Test concentrations with justification for top dose:

Concentrations reported as "high-dose" and "low-dose"

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

saline

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-dimethylnitrosamine

ethylmethanesulphonate

Species / strain:

Saccharomyces cerevisiae

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

not valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

Glucono-delta-lacton, was not genetically active, either directly or in the presence of organ homogenates, in any of the in vitro assays employed in this evaluation

Executive summary:

Compound FDA 71 -72, glucono-delta-lacton, was not genetically active, either directly or in the presence of organ homogenates, in any of the in vitro assays employed in this evaluation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Ferrous gluconate is devoid of mutagenic properties and is thus classified as non-hazardous for this end point Results of a study conducted with a structurally similar compoud, Glucono delta-lactone, are reported and used for read across in section 7.6.1. Glucono-delta-lactone, was not genetically active, either directly or in the presence of organ homogenates, in any of the in vitro assays employed in this evaluation. Read across justification summary is attached to the end point summary

Link to relevant study records

Reference

Endpoint:

in vivo mammalian germ cell study: gene mutation

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

GLP compliance:

not specified

Type of assay:

Drosophila SLRL assay

Species:

Drosophila melanogaster

Strain:

not specified

Sex:

male

Route of administration:

oral: unspecified

Duration of treatment / exposure:

10 days

Key result

Sex:

male

Genotoxicity:

negative

Ferrous Gluconate was not mutagenic at any exposure level used. Ferrous Gluconate was devoid of mutagenic properties.

Conclusions:

Interpretation of results (migrated information): negative
ferrous gluconate is devoid of mutagenic properties.

Executive summary:

This substantial paper is principally an introduction to the method. The Drosophila test is considered to check for mutations at 600 to 800 loci. It can detect both point mutagens and promutagens which require activation. Ferrous gluconate was one of 421 substances tested. The objective being to correlate known carcinogenic properties with this mutagenic end-point. The authors of the study, reviewed in this US-EPA report, found ferrous gluconate to be devoid of mutagenic properties.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Justification for classification or non-classification

Results from in vivo studies confirmed that Iron Gluconate is classified as non-hazardous for this end point.

Results of an in vitro study conducted with a structurally similar compoud, Glucono delta-lactone, are reported and used for read across. Iron Gluconate did not contain any structural alerts for mutagenicity. The lack of alert and the physical-chemical properties indicate that iron gluconate should not be reactive to DNA.

 

Iron Gluconate consists of two gluconanic acids coordinated in an ionic bond with the ferrous ion. The molecule readily dissociates to form free gluconic acid which then cyclizes to form the corresponding lactone. D-glucono-1,5-lactone is the stable intermediate of the dissociation of ferrous gluconate and is therefore a reasonable surrogate for predicting the effect of the of the parent material . Neither the ferrous ion or D-glucono-1,5-lactoneare are genetically active (Lima et al, 2011). As such Iron Gluconate is considered to be not genetically active based on read-across. Full read across justification is attatched to this endpoint summary