Ferric nitrilotriacetate

Inhalation of ferric salts as dusts and mists is irritating to the respiratory tract. Ferric salts are regarded as skin irritants. /Iron salts/

If inhaled, iron is a local irritant to the lung and gastrointestinal tract. /Iron compounds/

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The following wastewater treatment technologies have been investigated for iron (Fe+2): Concentration process: Biological treatment. /Iron (Fe+2)/

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

All ... /iron/ preparations should be kept in child-proof bottles. /Iron preparations/

/LABORATORY ANIMALS: Acute Exposure/ ...A single intraperitoneal Fe-NTA treatment (15 or 30 mg Fe/kg bw) induced a rapid accumulation of thiobarbituric acid-reactive substances, a direct consequence of membrane lipid peroxidation, mostly within the cytosolic compartment of rat kidney. The accumulation of lipid peroxidation-derived aldehydes was associated with an apparent accumulation (from 67.9 nmol in untreated controls to 83.3 nmol/mg protein in Fe-NTA-treated rats at 3 hr after treatment) and subsequent elimination of aberrant proteins as assessed by a 2,4-dinitrophenylhydrazine postlabeling assay. Immunoblot analysis with two different polyclonal antibodies against 4-hydroxy-2-nonenal-modified and malondialdehyde-modified proteins detected a temporary accumulation of aldehyde-modified proteins in the cytosol. An immunohistochemical technique with serial sectioning revealed that immunoreactivities of these antibodies were observed in the identical portion of the renal proximal tubules.

/LABORATORY ANIMALS: Acute Exposure/ ...The levels of typical hydroxyl radical-induced DNA base modifications in renal chromatin of male Wistar rats treated with a single or repeated administrations of Fe-NTA /were investigated/. Five pyrimidine-derived and 5 purine-derived modified DNA bases were identified and quantified by gas chromatography/mass spectrometry with selected-ion monitoring. The modified bases were 5-hydroxy-5-methylhydantoin, 5-(hydroxymethyl)uracil, 5-hydroxycytosine, thymine glycol, 5,6-dihydroxyuracil, 4,6-diamino-5-formamidopyrimidine, 8-hydroxyadenine, xanthine, 2-hydroxyadenine and 8-hydroxyguanine. The amounts of most of these compounds were significantly increased over control levels in renal chromatin of Fe-NTA-treated rats as measured 3 and 24 hr after treatment. Elevated levels of modified bases were accompanied by proximal tubular necrosis. On the 19th day, however, accumulation of modified DNA bases was not observed. Morphologically, scattered karyomegalic cells were seen in the proximal tubules, but necrosis was rarely found. Some of the identified DNA base lesions are known to be promutagenic, although others have not been investigated. Presence of modified DNA bases concomitant with necrosis and regeneration of the renal proximal tubules may be a critical step in Fe-NTA-induced carcinogenesis.

/LABORATORY ANIMALS: Acute Exposure/ ...Acute and subchronic toxicity of a ferric iron chelate of NTA (Fe-NTA) was investigated in rats. When Fe-NTA was given ip, acute tubular necrosis and renal failure occurred following a single injection of 15 mg iron/kg.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... Repeated injections of sublethal doses produced degeneration and necrosis of the proximal tubular epithelium and was associated with polyuria, glucosuria, aminoaciduria, and azotemia. After 9 days of treatment, regeneration of the tubular epithelium with atypical cells was observed. Except for a parenchymal iron deposit, no marked changes were observed in other organs. None of these effects were observed in animals given noncomplexed NTA.

For more Non-Human Toxicity Excerpts (Complete) data for IRON (3+) NTA (22 total), please visit the HSDB record page.

...There is concern that the individual with metabolic defects that impair the ability to regulate iron absorption will be at risk from excessive exposure to iron, primarily as a result of acceleration of accumulation of iron in the body and an earlier onset of clinical symptoms of the disease. /Iron salts/

Evaluation: There is sufficient evidence for the carcinogenicity of nitrilotriacetic acid and its sodium salts in experimental animals. No data were available from studies in humans on the carcinogenicity of nitrilotriacetic acid and its salts. In formulating the overall evaluation, the Woring Group took note of the fact that nitrilotriacetic acid is liberated to some extent from nitrilotriacetate salts in solution. Overall evaluation: Nitrilotriacetic acid and its salts are possibly carcinogenic in humans (Group 2B)>

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. /Iron and related compounds/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start an IV with lactated Ringer's /SRP: "To keep open", minimal flow rate/. Watch for signs of fluid overload. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Iron and related compounds/

Maintain an open airway and assist ventilation if necessary. Treat shock caused by hemorrhagic gastrointestinitis aggressively with intravenous crystalloid fluids, and replace blood if needed. Patients are often markedly hypovolemic owing to gastrointestinal losses and third spacing of fluids into the intestinal wall and interstitial space. Treat coma, seizures, and metabolic acidosis if they occur. For seriously intoxicated victims (eg, shock, severe acidosis, and/or serum iron > 500-600 mcg/dL) administer deferoxamine. Monitor the urine for the urine for the characteristic orange or pink deferoxamine-iron complex. Therapy may be stopped when the urine returns to normal or when the serum iron level decreases to the normal range. Prolonged deferoxamine has been associated with adult respiratory distress syndrome and Yersinia sepsis.

Activated charcoal is not effective. Ipecac is not recommended, because it can aggravate iron-induced gastrointestinal irritation and interfere with whole bowel irrigation. Consider gastric lavage if product was a liquid formulation or tablets were chewed. Do-not use phosphate-containing solutions for lavage; these may result in life-threatening hypernatremia, hyperphosphatemia, and hypocalcemia. Bicarbonate and deferoxamine lavage are of doubtful efficacy. Deferoxamine lavage is not effective and may enhance iron absorption. Whole-bowel irrigation is very effective for ingested tablets and may be considered first-line treatment, especially if large numbers of tablets are visible on plain abdominal x-ray. Massive ingestions may lead to concretions or bezoars. Repeated or prolonged whole-bowel irrigation may remove tablets. Endoscopy or surgical gastrotomy is rarely required.

Hemodialysis and hemoperfusion are not effective for removing iron but may be necessary to remove iron-deferoxamine complex in patients with renal failure. Exchange transfusion is occasionally used for massive pediatric ingestions but is of questionable efficacy.

The mechanism of acute nephrotoxicity of an iron chelate in vivo has been investigated. Administration of a renal carcinogen ferric nitrilotriacetate (Fe-NTA) (15 mg Fe/kg bw, ip) led to selective loss of a renal protein with an apparent molecular mass of 17 kDa. Analysis of the 17 kDa protein by NH2-terminal sequence demonstrated its identity over 16 NH2-terminal residues as a kidney fatty acid-binding protein (k-FABP) that is a proteolytically modified form of alpha 2U-globulin, a major urinary protein of adult male rats. An immunochemical study using anti-alpha 2U-globulin polyclonal antibodies confirmed that a single injection of Fe-NTA led to a decrease in k-FABP levels. However, a 19-kDa protein identical to the alpha 2U-globulin progressively appeared in the kidney, suggesting that the proteolytic processing of alpha 2U-globulin in the renal proximal tubules was suppressed by the treatment with Fe-NTA. By monitoring k-FABP and its precursor alpha 2U-globulin, it was determined that repeated exposure to Fe-NTA caused suppression of both proteolytic and endocytotic activity of the kidney.

Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.

Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.

Although concentration /NTA/ decrease rapidly with cessation of intake, a small amount was retained in bone after each dose... /Nitrilotriacetic acid/

NTA-(14)C administered orally to rats. 95% was excreted in urine. Less than 1%...as CO2. Absorption of NTA from GI tract varied: dog greater than rat greater than rabbit and monkey. ... Deposited in skeleton. Concentration ... increases with number of doses administered. Most active areas for accumulation are at sites of very active bone formation. /NTA/

After injecting large amount of ferric nitrilotriacetate, complete saturation of transferrins followed. Most excess serum Fe3+-nta existed in association with serum protein rather than as free Fe3+-nta.

In cell, Fe2+ is converted to Fe3+ in ferritin, the latter not being absorbed until cell is physiologically "depleted." In the blood strain, iron could be quickly oxidized by dissolved oxygen to Fe3+, which complexes with specific Fe-transport beta1-globulin.