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EC number: 940-441-4 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Link to relevant study records
- 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:
- Experimental Starting Date 11 June 2014, Experimental Completion Date 03 July 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Valid and conclusive guideline study under GLP; Relevant and adequate for this endpoint
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- Commission Regulation (EC) number 440/2008 of 30 May 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Version / remarks:
- (including METI, MHLW and MAFF guidances)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Statement of compliance in accordance with Directive 2004/9/EC, Department of Health of the Government of the U.K., 12 September 2014, inspection date 12 to 14 March 2014
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Histidine for Salmonella typhimurium, Tryptophan for Escherichia coli
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 Microsomal fraction prepared in-house from male rats induced with Phenobarbitone/β-Naphthoflavone at 80/100 mg/kg/day, orally, for 3 days prior to preparation on day 4, protein content adjusted to 20 mg/mL
- Test concentrations with justification for top dose:
- Formulated concentrations were adjusted to allow for the stated water/impurity content (3 %) of the test item.
Experiment 1: 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate
The dose range used for Experiment 2 was determined by the results of Experiment 1 and was 50 to 5000 μg/plate.
Experiment 2: 50, 150, 500, 1500 and 5000 µg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO (dimethyl sulphoxide)
- Justification for choice of solvent/vehicle: The test item was insoluble in sterile distilled water, dimethyl sulphoxide, dimethyl formamide and acetonitrile at 50 mg/mL, acetone at 100 mg/mL and tetrahydrofuran at 200 mg/mL in solubility checks performed in–house. The test item formed the best doseable suspension in dimethyl sulphoxide, therefore, this solvent was selected as the vehicle. - Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO (dimethyl sulphoxide)
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG): 2 µg/plate for WP2uvrA, 3 µg/plate for TA100 and 5 µg/plate for TA1535; 9-Aminoacridine (9AA): 80 µg/plate for TA1537; 4-Nitroquinoline-1-oxide (4NQO): 0.2 µg/plate for TA98
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- N-ethyl-N-nitro-N-nitrosoguanidine
- Remarks:
- Without metabolic activation (-S9)
- Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO (dimethyl sulphoxide)
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- 2-Aminoanthracene (2AA): 1 µg/plate for TA100, 2 µg/plate for TA1535 and TA1537 and 10 µg/plate for WP2uvrA Benzo(a)pyrene (BP): 5 µg/plate for TA98
- Positive control substance:
- benzo(a)pyrene
- other: 2-Aminoanthracene
- Remarks:
- With metabolic activation (+S9)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: In suspension
Experiment I: In agar (plate incorporation; 0.1 mL of the appropriate concentration of test item, vehicle or appropriate positive control was added to 2 mL of molten trace amino-acid supplemented media containing 0.1 mL of one of the bacterial strain cultures and 0.5 mL of phosphate buffer or S9 mix. These were then mixed and overlayed onto a Vogel-Bonner agar plate.
Experiment II: Preincubation: 0.1 mL of the appropriate bacterial strain culture, 0.5 mL of phosphate buffer or S9 and 0.1 mL of the test item formulation, vehicle or 0.1 mL of appropriate positive control were incubated at 37±3 °C for 20 minutes (with shaking) prior to addition of 2 mL of molten amino-acid supplemented media and subsequent plating onto Vogel-Bonner plates.
DURATION
- Preincubation period (Experiment 2): 20 minutes
- Exposure duration: Approximately 48 hours
NUMBER OF REPLICATIONS
Eight concentrations of the test item were assayed in triplicate against each tester strain, using the direct plate incorporation method.
DETERMINATION OF CYTOTOXICITY
- Method: The plates were viewed microscopically for evidence of thinning (toxicity).
OTHER EXAMINATIONS:
- Other: All of the plates were scored for the presence of revertant colonies using an automated colony counting system.
OTHER:
Incubation temperature 37±3 °C - Evaluation criteria:
- There are several criteria for determining a positive result. Any, one, or all of the following can
be used to determine the overall result of the study:
1. A dose-related increase in mutant frequency over the dose range tested
2. A reproducible increase at one or more concentrations.
3. Biological relevance against in-house historical control ranges.
4. Statistical analysis of data as determined by UKEMS
5. Fold increase greater than two times the concurrent solvent control for any tester strain (especially if accompanied by an out-of-historical range response).
A test item will be considered non-mutagenic (negative) in the test system if the above criteria are not met.
Although most experiments will give clear positive or negative results, in some instances the data generated will prohibit making a definite judgment about test item activity. Results of this type will be reported as equivocal. - Statistics:
- Standard deviations
- 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, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- not valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: The test item was considered not initially soluble and thus tested in suspension.
- Precipitation: A test item precipitate (greasy/particulate in appearance) was noted at 5000 µg/plate, this observation did not prevent the scoring of revertant colonies.
RANGE-FINDING/SCREENING STUDIES
Experiment 1 – Plate Incorporation Method
COMPARISON WITH HISTORICAL CONTROL DATA
The controls were found in line with the historical control data. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
Hydronium Jarosite was considered to be non-mutagenic under the conditions of this test. - Executive summary:
- The capability of the test item Hydronium Jarosite to induce bacterial
reverse mutation as a sign of gene mutation indicating genetic toxicity
was measured in a GLP-compliant study using the “Bacterial
Reverse Mutation Assay” compliant with EU Method B.13/14 (Commission
Regulation (EC) No. 440/2008), OECD TG 471 (1997), US EPA OCSPP (former
OPPTS) 870.5100 (1998) and the Japanese Guidelines for Screening
Mutagenicity Testing of Chemicals protocols. The validity criteria were
met and the experiment can be considered relevant and adequate for the
endpoint. Therefore it is deemed conclusive and was rated „reliable
without restrictions“, i.e. “Klimisch 1” according
to the scale of Klimisch et al. (1997).
Five endobacterial strains from the species Salmonella (Salmonella
typhimurium), TA 1535, TA 1537, TA 98 and TA 100, and coliform
bacteria (Escherichia coli), WP2 uvr A, were treated with
suspensions of the test item using both the Ames plate incorporation and
pre-incubation methods at up to eight dose levels, in triplicate, both
with and without the addition of a rat liver homogenate metabolizing
system (10 % liver S9 in standard co-factors). The dose range for
Experiment 1 was predetermined and was 1.5 to 5000 µg/plate. The
experiment was repeated on a separate day (pre-incubation method) using
fresh cultures of the bacterial strains and fresh test item formulations.
The dose range was amended following the results of Experiment 1 and was
50 to 5000 μg/plate. The control system comprised untreated negative,
solvent and positive controls using substances known to give a positive
response in also absence (N-ethyl-N'-nitro-N-nitrosoguanidine,
9-Aminoacridine and 4-Nitroquinoline-1-oxide) or only in presence
(2-Aminoanthracene, Benzo(a)pyrene) of metabolic activation (S9).
The vehicle (dimethyl sulphoxide) control plates gave counts of revertant
colonies within the normal range. All of the positive control chemicals
used in the test induced marked increases in the frequency of revertant
colonies, both with or without metabolic activation. Thus, the sensitivity
of the assay and the efficacy of the S9-mix were validated.
There was no visible reduction in the growth of the bacterial background lawn
at any dose level, either in the presence or absence of metabolic
activation, in the first mutation test (plate incorporation method) and
consequently the same maximum dose level was used in the second mutation
test. Similarly, there was no visible reduction in the growth of the
bacterial background lawn at any dose level, either in the presence or
absence of metabolic activation, in the second mutation test
(pre-incubation method). A test item precipitate (greasy/particulate in
appearance) was noted at 5000 µg/plate, this observation did not prevent
the scoring of revertant colonies. There were no significant increases in
the frequency of revertant colonies recorded for any of the bacterial
strains, with any dose of the test item, either with or without metabolic
activation in Experiment 1 (plate incorporation method). Similarly, no
significant increases in the frequency of revertant colonies were recorded
for any of the bacterial strains, with any dose of the test item, either
with or without metabolic activation in Experiment 2 (pre-incubation
method).
In conclusion the test item was considered to be non-mutagenic under the
conditions of this test.
- Klimisch HJ, Andreae M, Tillmann U (1997). A Systematic Approach for Evaluating the Quality of Experimental Toxiclogical and Ecotoxicological Data. DOI 10.1006/rtph.1996.1076 PMID 9056496 Regul Toxicol Pharmacol 25:1-5.
Reference
The vehicle (dimethyl sulphoxide) control plates gave counts of revertant colonies within the normal range. All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with or without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
This endpoint is covered by the category approach for dissociating, inorganic and non-toxic iron compounds (please see the section on toxicokinetics, metabolism and distribution for the category justification/report format).
-in vitro
bacterial gene mutation:
• FeCl3 is deemed negative for bacterial gene mutation. One reliable study (Dunkel 1999a) is available, conducted according to OECD 471 using the strains Salmonella typhimurium strains TA97a, TA98, TA100, TA102, TA1535, TA1537 and TA1538 with and without activation in a plate incorporation assay. The test was performed with FeCl3 x 6H2O with concentrations up to 10’000 µg/plate which is equivalent to 6001 µg/plate anhydrous FeCl3.
• Fe2(SO4)3 is deemed negative for bacterial gene mutation. No studies are available for this substance accordingly a read across from FeCl3 is employed.
• FeCl2 is deemed negative for bacterial gene mutation. One reliable study (Kim 2004) is available, conducted according to OECD 471 and GLP using the strains S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A and concentrations up to 5000 µg/plate in a plate incorporation assay.
• FeSO4 is deemed negative for bacterial gene mutation. No studies are available for this substance accordingly a read across from FeCl2 and FeCl3 is employed.
• FeClSO4: no classification, no studies available, accordingly read across is used from FeCl3.
mammalian gene mutation:
• FeCl3 is negative for in vitro mammalian gene mutation. Two reliable studies (Dunkel 1999b; McGregor 1988) are available, conducted according to OECD 476 (Dunkel 1999b only) in mouse lymphoma L5178Y cells with cytotoxic concentrations or precipitation as the upper boundaries. In Dunkel,1999b the test was positive with metabolic activation only at cytotoxic concentration and otherwise negative, whereas in the McGregor study the test was negative. This was supported by the study Ohno,1982.
• FeCl2 is deemed negative for in vitro mammalian gene mutation. No studies are available for this substance accordingly a read across from FeCl3 is employed.
• FeSO4 is deemed negative for in vitro mammalian gene mutation. One reliable study with mouse lymphoma L5178Y cells
is available (Dunkel 1999c) presenting a negative result in non-cytotoxic concentrations.• FeClSO4 is deemed negative for in vitro mammalian gene mutation. No studies are available for this substance accordingly a read across from FeCl3 is employed.
mammalian chromosome aberration:
• FeCl3 is deemed negative for in vitro mammalian chromosome aberration. One reliable OECD 487, GLP study (Schulz 2009) is available, with Chinese hamster lung fibroblasts (V79) up to 1650 µg/mL reporting a negative result.
• FeCl2 is deemed negative for in vitro mammalian chromosomal aberration. No studies are available for this substance accordingly a read across from FeCl3 is employed.
• FeSO4 is deemed negative for in vitro mammalian chromosomal aberration. No studies are available for this substance accordingly a read across from FeCl3 is employed.
• FeClSO4 is deemed negative for in vitro mammalian chromosomal aberration. No studies are available for this substance accordingly a read across from FeCl3 is employed.
-in vivo
mammalian gene mutation:
No studies available for any of the members of this iron salt category.
mammalian chromosome aberration:
• FeCl3 is deemed negative for in vivo mammalian chromosome aberration. One reliable study (Bianchini 1988a) is available, conducted according to Wargovich et al, J Natl Cancer Inst 71 125-131 1983 analysing micronuclei induction in the GI tract and reporting a negative result. This result is supported by a negative Drosophila wing spot test (Ogawa 1994). All other studies of low reliability except two (Liao, 1988; BASF, 1992) also show negative results. Overall weight of evidence suggests that the substance is negative in chromosomal aberration test.
• FeCl2 is deemed negative for in vivo mammalian chromosome aberration. One reliable study (Ji Yoon 2004) according to OECD 474/GLP with ICR mice and doses of 2, 5, 10, 20, 50, 100 and 200 mg/ml in the dose range-finder and 1.25, 2.5 and 5 mg/ml in the micronucleus experiment was negative. No further data are available for FeCl2.
• FeSO4 is deemed negative for in vivo mammalian chromosome aberration. Two reliable studies are available (Bianchini 1988b and Hayashi 1988). Bianchini 1988b analysed micronuclei induction in the GI tract and reported a negative result. Hayashi 1988 a Mammalian Erythrocyte Micronucleus Test according to OECD Guideline 474 using ddy mice treated intraperitoneal with 25, 50, 100, 180 mg/kg bw. The test result was negative. This result is supported by the Drosophila sex linked lethal test (Lee, 1983)
• FeClSO4 is deemed negative in vivo mammalian chromosome aberration. No studies are available for this substance accordingly a read across from FeCl3 is employed.
General:
Human data is not available for genetic toxicity. Both, gene mutation and cytogenicity are cover by a plethora of studies. All relevant studies express that the iron compounds are non-genotoxic. Two short abstracts (Liao 1988 and BASF AG 1992) indicate that FeCl3 might have shown positive results in mammalian chromosomal aberration studies. Nevertheless, these data are considered to be unreliable since insufficiently reported.
In summary, the overwhelming majority of data support the conclusion that iron salts of this category are non-genotoxic. Accordingly, classification for this category is not appropriate or for any of the individual category members.
Justification for selection of genetic toxicity endpoint
Reliable study conducted according to OECD TG 487 and GLP in Chinese hamster lung fibroblasts (V79) using FeCl3
Justification for classification or non-classification
Based on the above stated assessment of the genotoxic potential all members of this iron salt category are deemed non-genotoxic and accordingly do not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (5th ATP of Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.
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