Ferrous iron toxicity

The different oxidation states of a metal can have dramatically different chemical properties, which in turn affect their biogeochemical forms and significance. For example, almost 4 g/L ferrous iron, Fe(II), can dissolve in distilled water maintained at pFi 7.0. However, if the water is exposed to air and the iron is oxidized to Fe(III) essentially all the iron will precipitate, reducing the soluble Fe concentration by more than eight orders of magnitude. Oxidation state can also affect a metal ion s toxicity. For instance, the toxicity of As(III) results from its ability to inactivate enzymes, while As(V) interferes with ATP synthesis. The former is considerably more toxic to both aquatic organisms and humans. 

Ferrous iron, by its reaction with hydrogen peroxide in the Fenton reaction, can yield the toxic hydroxyl radical, OH, which will further potentiate oxygen toxicity. 

Although O2 leakage compromises the root s internal aeration, some leakage is desirable for a number of purposes. These include oxidation of toxic products of anaerobic metabolism in submerged soil such as ferrous iron (van Raalte, 1944 Bouldin, 1966 van Mensvoort et al., 1985) nitrification of ammonium to nitrate, there being benefits in mixed nitrate-ammonium nutrition (Kronzucker et al., 1999, 2000) and mobilization of sparingly soluble nutrients such as P (Saleque and Kirk, 1995) and Zn (Kirk and Bajita, 1995) as a result of acidification due to iron oxidation and cation-anion intake imbalance. 

Yildiz G, Demiryurek AT. Ferrous iron-induced luminol chemiluminescence a method for hydroxyl radical study. J Pharm Toxic Methods 1998 39 179-84. 

In conclusion, any attempt to reconcile toxicological and chemical data on superoxide should take into account two important prerequisites first, it is essential to distinguish the toxicity of intra- versus extracellular superoxide second, the one-electron oxidizing properties of HO2 should not be overlooked and one should exercise a certain amount of caution before adopting the common viewpoint that the key toxicity of superoxide comes from its ability to recycle ferrous iron complexes from their ferric homologs. 

Biological Implications of Chemical Forms. The biological availability of many trace elements is influenced by their valence state. Ferrous iron is believed to be more readily available than the ferric form, and selenium is better absorbed in its high oxidation state than in its lower ones. The organism is able to oxidize or reduce some, but not all, trace elements to their biologically active form. It is important, therefore, to determine the valence state in biological material, particularly in those cases where great differences of availability or toxicity exist, as in the case of chromium or of mercury. 

Tuovinen, O.H. and Kelly, D.P., (1974 (a) (b) (c). Studies on the growth of Thiobacillus ferrooxidans. II. Toxicity of uranium to growing cultures and tolerance conferred by mutation, other metal cations and EDTA. Arch. Mikrobiol., 95 153—164. III. Influence of uranium, other metal ions and 2,4-dinitrophenol on ferrous iron oxidation and carbon dioxide fixation by cell suspensions, ibid, 95 165—180. IV. Influence of monovalent metal cations on ferrous iron oxidation and uranium toxicity in growing cultures, ibid, 98 167—174. 

Antidotes can change the chemical nature of a poison by rendering it less toxic or preventing its absorption. Formaldehyde poisoning can be treated with ammonia to promote formation of hexamethylenetetramine sodium formaldehyde sulfoxylate can convert mercuric ion to the less soluble metallic mercury and sodium bicarbonate converts ferrous iron to ferrous carbonate, which is poorly absorbed. Chemical inactivation techniques seldom are used today, however, because valuable time may be lost, whereas emetics, activated charcoal, and gastric lavage are rapid and effective. The treatment of choice for ingestion of either acids or alkalis is dilution with water or milk. Similarly, bums produced by acid or alkali on the skin should be treated with copious amounts of water. 

Iron transport systems must maintain a balance between the amount of iron needed within the cell and the amoimt which is toxic. Iron transport is complicated by the fact that iron in the extracellular environment is generally present as bio-imavailable insoluble ferric chelates [3]. Cells have devised several mechanisms to overcome this insolubility. Soluble carrier molecules, such as siderophores and transferrin, may be used to chelate the ferric iron and make it soluble [4]. Alternatively, cells may reduce the insoluble ferric iron to the more soluble ferrous form. Cells may use an enzymatic cell surface ferrireductase or may secrete organic molecules that accelerate the ferric to ferrous conversion [5]. The ferrous iron is then transported into the cell by elemental iron transport systems. 

The ferrous iron produced by the ferrireductases can be transported through either a high affinity or a low afiinity iron transport system. The low affinity iron transport system has a Kta for iron of 30 pM and transports other metals in addition to iron including the potentially toxic metals cadmium and cobalt [25]. The FET4... 

Pregnant women require an increased an amount of iron, but they need to avoid a megadose in the first trimester because it might cause birth defects. Larger doses of iron are necessary in the second and third trimester. Iron is absorbed in the intestine where it enters plasma as heme or is stored as ferritin in the liver, spleen, and bone marrow. Food, the antibiotic tetracychne, and antacids decrease absorption up to 50% of iron. However, the patient should take iron with food to avoid GI discomfort. Vitamin C may slightly increase iron absorption. Iron toxicity is a serious cause of poisoning in children. Toxicity can develop with as few as 10 tablets of ferrous sulfate (3g) taken at one time—and can be fatal within 12 to 48 hours. 

---