SIAM 24, 17-20 April 2007

FI/ICCASIDS INITIAL ASSESSMENT PROFILE
Ferric chloride: 7705-08-0
Ferric sulfate: 10028-22-5
Ferrous sulfate: 7720-78-7
Ferric chloride hexahydrate: 10025-77-1
CAS No.

Ferric sulfate nonahydrate: 13520-56-4
Ferrous sulfate monohydrate: 17375-41-6
Ferrous sulfate heptahydrate: 7782-63-0
Ferric chloride hydrate, unspecified: 24290-40-2
Ferric sulfate hydrate, unspecified:15244-10-7
Ferrous sulfate hydrate, unspecified: 13463-43-9
Iron Salts Category

Chemical Name

Structural Formula

FeCl 3 , Fe 2 (SO 4 ) 3 , FeSO 4 , FeCl 3 .6H 2 O, Fe 2 (SO 4 ) 3 .9H 2 O,FeSO 4 .H 2 O, FeSO 4 .7H 2 O, FeCl 3 .xH 2 O, Fe 2 (SO 4 ) 3 .xH 2 O,FeSO 4 .xH 2 O

SUMMARY CONCLUSIONS OF THE SIAR
Iron is the fourth most common element in the natural environment, comprising about 5 % of the Earth’scrust. It is abundant in minerals, soils, sediments and natural waters. Iron is biologically an essential
element for micro-organisms, plants and higher animals. They have adapted to naturally occurring highenvironmental levels of iron, and have active intake mechanisms for it.
Rationale for iron salts category
Structural similarities of the inorganic iron ions, which will dissociate immediately in aqueous based
media to the respective anions and cations, and form common reaction products via environmental andphysiological processes. Iron dichloride (CAS No. 7758-94-3) was reviewed at SIAM 19 and the datafrom the SIAP and Dossier are published on the UNEP website.
Human Health
Toxicokinetics: Iron is an essential element in humans. Iron salts are absorbed from the GI-tract tovarying degree. Before absorption ferrous iron is oxidised to ferric form, which is then transferred into
the mucosal lining of the small intestine with the aid of various chelates such as ascorbate and citrate.
Tannins and plant phytates inhibit the absorption. Diet may have a significant effect on iron absorption.
Iron absorption in the rat is higher and the dietary intake is about 100 times greater than that of humans.
Percutaneous absorption of iron in non-chelated form has not been reported. No data is available on
respiratory iron absorption. Following absorption the majority of iron is bound to transferrin andtransported to the bone marrow where it is incorporated into haemoglobin. Any remaining iron iscontained within the storage forms, ferritin or haemosiderin, or as myoglobin, with smaller amounts
occurring in haem-containing enzymes or in plasma bound to transferrin. About 1-2 mg of iron is lostdaily.

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Acute toxicity: In rats, the oral LD 50 was 300-2000 mg/kg (132-881 mgFe/kg) for ferrous chloride. For
ferric sulfate, the oral LD 50 for iron is 500-2000 mg/kg (139 to 558 mg Fe/kg) in females. Ferrous sulfate
heptahydrate did not show acute toxicity in rats up to 2000 mg/kg (400 mgFe/kg). The following acutetoxic doses of ferrous sulfate have been considered to apply in humans: infants (<6 y) 20 mg/kg (7mgFe/kg) (for gastrointestinal irritation only), children 200-300 mg/kg (74-111 mgFe/kg), adults
1400 mg/kg (516 mgFe/kg). The dermal LD 50 for dry ferrous chloride in rats was >2000 mg/kg (881mgFe/kg). No relevant data were available for inhalation.
Irritation and sensitisation: Ferrous sulfate solids were irritating to skin. Ferrous chloride solid was
weakly irritating, ferric sulfate solid and ferrous sulfate solutions were non-irritating in OECD 404.
Ferric chloride was found irritating to respiratory tract in rats.
Ferrous chloride was corrosive, ferric chloride was irritating and ferrous sulfate heptahydrate solution
was not irritating to the eye. Ferric solutions are acidic, whereas ferrous ones are not until they oxidise toferric. The pattern of results is therefore somewhat inconsistent.
Although mixed results have been obtained from sensitisation tests, there is no convincing or reliable
evidence of iron sensitisation.
Repeated dose toxicity: In a 13-week study with 0.12, 0.25, 0.5, 1.0 and 2.0% w/v ferric chloride in
drinking water, a NOAEL of 0.5% approximately 277 mg/kg bw/day in males, and 314 mg/kg bw /day infemales was found. Ferrous sulfate heptahydrate was assessed in oral (gavage) toxicity in rats in anOECD combined repeated dose and reproductive/developmental toxicity screening test under GLP at
doses of 0, 30, 100, 300, and 1000 mg/kg/day. Based on extramedullary hematopoiesis of the spleen in
the males at 300 mg/kg and increased levels of inorganic phosphate in females at 300 mg/kg, the oral
NOAEL for repeated dose toxicity was considered to be 100 mg/kg/day, equivalent to 20 mgFe/kg
bw/day for both sexes. In an OECD TG422 study, 0, 125, 250 or 500 mg/kg/day ferrous chloride wasadministered to rats for up to 42 days in males or 42-54 days in females using oral gavage, deaths werenoted at 500 mg/kg. The NOAEL was concluded to be 125 mg/kg/day for males and females, equivalent
to 55 mg Fe/kg. These results are applicable across the category.
Mutagenicity and Carcinogenicity: Most Ames tests conducted with iron salts are negative. In an in vitro
mouse lymphoma test ferric chloride produced a positive and dose-related response in presence of S9with a marked increase of cytotoxicity. Ferrous sulfate heptahydrate produced chromosomal aberrationsin CHL/IU cells after short term treatment with and without S9. In vivo, iron has not produced positive
responses in the five studies available. Overall iron category substances are not mutagenic in vivo.
No increase in tumour incidence was reported for rats ingesting ferric chloride in drinking water atreceived doses of up to 320-340 mg/kg body weight/day (110-117 mg Fe/kg body weight/day) for twoyears. Epidemiological investigations have not provided evidence of an increased cancer risk in humanpopulations with increased iron intakes arising from food or clinical supplementation. The Scientific
Panel on Dietetic Products, Nutrition and Allergies of the European Commission has concluded thatsome results indicate the possibility of a role of luminal exposure to excessive iron in the development ofcolon carcinoma, but the evidence is limited and not convincing.
Reproductive toxicity: In an OECD 422 study rats received 0, 125, 250 and 500 mg/kg/day of ferrous
chloride by the oral route (gavage) for 42 days in males or 42 - 54 days in females with treatments
continuing through a 14 day pre-mating period. A NOAEL of 500 mg/kg body weight/day was obtained,based on no significant difference in mating data and pre-and post-implantation loss rate. In anotherOECD 422 study rats received ferrous sulfate heptahydrate orally at doses of 0, 30, 100, 300, and 1000
mg/kg/day. The NOEL for reproductive performance from this study was considered to be1000 mg/kg/day for both parental animals and pups. For developmental effects, the OECD 422 screening
study with ferrous chloride found a NOAEL of 500 mg/kg (220 mg/kg iron). The study with ferrous
sulfate heptahydrate using the same protocol found a development NOAEL of 1000 mg/kg, (200 mg/kgiron). These results are applicable across the category.

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Environment
Environmental fate: Fe (II/III) category salts are non-volatile solid substances which are very soluble inwater and have an acidic reaction with water (Fe(III) species being moderately strong acids). Fe(II)species are unstable in oxygenated water with a half-life under favourable conditions of minutes – hours,and oxidises easily to the Fe(III) state. Under conditions of high light intensity Fe (III) can be photoreduced to Fe (II). Fe (III) species are soluble and stable in aqueous solution only at very low pH
conditions. Normally they react with water to form colloidal and insoluble Fe(OH) 3 which in typicalaquatic environmental condition precipitates to sediments. Other metals and organic matter may bestrongly adsorbed to Fe precipitates. Fe may also typically form precipitates with phosphate. Iron ions,especially Fe(II) ions may be also adsorbed to dissolved organic material and some dissolved iron innatural waters may be present as soluble organic-complexes. Physical effects arising from the presence of
precipitated or colloidal Fe(OH) 3 may be responsible for the effects observed in the tests that aresummarised below.
Bioconcentration: Bioconcentration of iron to species is relatively low. Iron is an essential element formost living species and may be actively regulated in organisms.
Ecotoxicity: In general, Fe(II) seems to exhibit higher toxicity to aquatic species compared to Fe(III)ions. However, precipitating and colloidal Fe(OH) 3 may have lethal effects through clogging and causing
inflammation in respiratory organs of invertebrates and fish. It is difficult to separate these physicochemical effects from the true ecotoxic effects even in the standard laboratory tests, other than on thereasonable chemical basis of knowledge of the solubility properties.
Acutely toxic levels of the iron salts to aquatic organisms are observed in nominal exposure
concentrations in the range equivalent to 1 – 1000 mg/l salt, with the majority of the results being in the10 – 100 mg/l range. Chronic effects on aquatic organisms are also observed at nominal concentrations in
the range 1 – 1000 mg/l for each individual salt with the majority of the results being >10 mg/l. Summary
acute results expressed, for consistency of comparison, relative to concentrations of Fe are:
Green algae (Pseudokirchneriella subcapitata) E r C 50 (72 h) = 18 mg/l (growth rate)
Invertebrates (Daphnia magna, 4 results):
EC 50 (48 h) = 1 - 10 mg/l
Fish (various fish species):
LC 50 (96 h) = 0.41 - >28 mg/l
Micro-organisms (Vibrio fischeri)
EC 50 (15 min) = 40 mg/l
It is not possible to differentiate physical and direct toxic effect mechanisms as the cause of effects
observed in the tests.
Ferric(III): it is unlikely that ferric iron salts will have direct toxic effects in aquatic environments
because the rapid conversion to ferric hydroxide will result in very low concentrations of dissolved ironeven under conditions of low pH.
Ferrous(II): it is possible that ferrous iron could have true toxic effects in circumstances where pH is low(<5), oxygen content is low and iron concentration is high (of the order of the apparent E(L)C 50 values).
Physical effects are a genuine hazard expressed via the concentrations reported above, but these are not
an indication of a significant chronic hazard.
Exposure: Environmental exposure assessment takes into account exposure arising from intentional useof the specific iron salts in the Sponsor Country. It is important to note that Fe-ion discharges andenvironmental impact from other (potentially high) exposure sources like production of ferro metals andtitanium dioxide, mining and mineralogy are outside the scope of this exposure assessment.
It is noted also that these Fe-category substances typically contain impurities such as Cd and Zn;
however, their normal use does not give rise to concentrations exceeding international standards forsurface waters.
In 1999 the annual production of these iron salts was 3,44 million tonnes for the European member
companies of Inorganic Coagulants Producers Association (Incopa). The main application (ca. 45 % byvolume) of the substances in the iron salt category is water treatment: they are used as flocculating and3

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precipitating agents in mechanical and biological wastewater treatment plants and paper mills as well as
treatment of potable water. It has been estimated that about 30% of world iron coagulants are producedin Europe, about 40% in Asia Pacific and about 20% in North America.
Other applications include use as fertilizers, plant protection products, as raw material in synthesis,
etching of copper and stainless steel, corrosion inhibition, colouring agent in cosmetics, laboratory andtextiles, cement additive to prevent chromium(VI) dermatitis, and production of pharmaceuticals.

RECOMMENDATION AND RATIONALE FOR THE RECOMMENDATION AND NATURE
OF FURTHER WORK RECOMMENDED
Human Health: The chemicals in this category are low priority for further work. They do possess
properties indicating a hazard for human health, namely, acute toxicity (ferrous chloride, ferric sulfate),skin irritation (ferrous sulfate), eye irritation (ferric chloride) and eye corrosivity (ferrous chloride).
These hazards do not warrant further work as they are related to acute toxicity which may become
apparent only at high exposure levels. Based on data presented by the Sponsor country, adequate risk
management measures are being applied. Countries may desire to check their own risk management
measures to find out whether there is a need for additional measures.
Environment: The members of the category are currently of low priority for further work. The hazard
profile of iron salts is dependent on the environmental conditions and the necessary conditions forharmful effects to be expressed are very specific (low pH and low dissolved oxygen) and are, inthemselves, intrinsically unfavourable to many aquatic species.

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