Ferric ammonium citrate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

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: see 'Remark'

Remarks:

Research publication. Reasonably documented meets generally accepted scientific principles, acceptable for assessment. Read-across to the registered substance is considered scientifically justified. The original study and the read-across to the registered substance are considered to be reliability 2.

Data source

Reference

Reference Type:

publication

Title:

Genotoxicity of iron compounds in Salmonella typhimurium and L5178Y mouse lymphoma cells.

Author:

Dunkel V C, San R H C, Seifried H E, Whittaker P

Year:

1999

Bibliographic source:

Environ Mol Mutagenesis 33: 28-41

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Principles of method if other than guideline:

Method: other: Ames (1975)

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Ferric chloride hexahydrate

IUPAC Name:

Ferric chloride hexahydrate

Constituent 2

Reference substance name:

10025-77-1

Cas Number:

10025-77-1

IUPAC Name:

10025-77-1

Details on test material:

The substance tested was ferric chloride hexahydrate (CAS number 10025-77-1, FeCl3.6H2O - 100% pure ex Mallinckrodt)

Method

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA97a, TA98, TA100, TA102, TA1535, TA1537, TA1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat and hamster liver S9

Test concentrations with justification for top dose:

Plate incorporation assay up to 10,000 µg Fe/plate + and - S9. Pre-incubation assay

Vehicle / solvent:

Vehicle used: distilled water

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

distilled water

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA97 without activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

no

Remarks:

distilled water

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 98 without activation

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 100 without activation

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

distilled water

True negative controls:

no

Positive controls:

yes

Positive control substance:

cumene hydroperoxide

Remarks:

TA 102 without activation

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

TA 98 and 100 with activation

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

distilled water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: sterigmatocystin

Remarks:

TA 102 with activation

Controls 7

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

distilled water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

TA97 with activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation - in medium

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 hours
- Expression time (cells in growth medium): 48 hours concurrent with exposure

SELECTION AGENT (mutation assays): minimal agar

NUMBER OF REPLICATIONS: doses were tested in triplicate in the plate incorporation assay . 10 dose levels were tested in the pre-incubation assay, and at least 5 doses in the plate incorporation assay

DETERMINATION OF CYTOTOXICITY
- Method: cytotoxicity was determined by plating 10 doses with and without activation. Criteria to evaluate toxicity are not presented.

Evaluation criteria:

A substance is considered positive if it shows induction of doubling of mean number of revertants in at least one tester strain, accompanied by a clear dose response. In strains TA 1537 and 1538, an increase in revertants of less than threefold will be confirmed in a repeat experiment.

Statistics:

Plates were counted in a MiniCount automated colony counter. The mean number of revertants of three plates was calculated.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA98, TA100, TA102, TA1535, TA1537, TA1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

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

GENOTOXIC EFFECTS: 
Plate incorporation assay 
- With and without metabolic activation: No increase in reverse mutation rate in any strain at dose levels up to 10,000 ug/plate (revertant counts not 

reproduced in the publication)
- Preincubation assay: 

Results not presented for ferric chloride but lack of activity in this assay was demonstrated with ferrous sulphate and ferrous fumarate.

PRECIPITATION CONCENTRATION: None reported

Applicant's summary and conclusion

Conclusions:

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

No evidence of mutagenicity to bacteria was obtained when ferric chloride (CAS 10025-77-1 FeCl3.6H2O) was tested using the bacterial reverse mutation assay in Salmonella typhimurium strains TA97a, TA98, TA100, TA102, TA1535, TA1537, TA1538 at dose levels up to 10000 µg Fe/plate. It is concluded that ferric chloride is negative for mutagenicity to bacteria under the conditions of this test.