Umbra

Fresh air, rest.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

(General first aid procedures)

(General first aid procedures)

TIH (Toxic Inhalation Hazard) - Term used to describe gases and volatile liquids that are toxic when inhaled. Some are TIH materials themselves, e.g., chlorine, and some release TIH gases when spilled in water, e.g., chlorosilanes. [ERG 2016].

Persons not wearing protective equipment and clothing should be restricted from areas of releases until cleanup has been completed. If potentially hazardous amounts of iron oxide fume are inadvertantly released, ventilate the area of the release to disperse the fume.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity 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 and plant life; and conformance with environmental and public health regulations.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Residues of iron oxide are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to animals. Use: colorant in pesticide formulations for animal tags. Limit: none.

The concurrent administration of a cocarcinogenic carrier particle such as ferric oxide (Fe2O3) and the polycyclic aromatic hydrocarbon lung carcinogen benzo(a)pyrene (BaP) results in a decreased latency and an increased incidence in the production of lung tumors in hamsters compared to the administration of BaP alone. The pulmonary alveolar macrophage (AM), the primary lung defense cell, has been shown to endocytize BaP, metabolize BaP to a more biologically active form, and then release the metabolites. Therefore, a study was undertaken to determine in a dose-response manner the effect of AM phagocytosis of a carrier particle (Fe2O3) on the metabolism of a carcinogen (BaP) and on the production of reactive oxygen. The AM were lavaged from hamsters and cultured in suspension (2.5 x 10+6 cells/vial) with BaP (62.5 nmol, 14C labeled) alone or adsorbed onto 0.5, 1.0, or 2.0 mg Fe2O3 in the presence of cytochrome c. Following separate ethyl acetate extractions of the AM and medium, the metabolites were isolated by high-performance liquid chromatography (HPLC) and quantified by liquid scintillation spectrometry. The production of superoxide anions was monitored by the reduction of cytochrome c. Concurrent exposure of AM to BaP-coated Fe2O3 resulted in a significant increase in the amount of BaP metabolites and superoxide anions produced with dose of Fe2O3. The following metabolites were identified in both the medium and the AM: 9,10-dihydrodiol, 7,8-dihydrodiol, 4,5-dihydrodiol, 9-hydroxy, 3-hydroxy, and 3,6-quinone. In general, the 7,8-dihydrodiol, which is considered to be the precursor of the ultimate carcinogenic metabolite of BaP, and superoxide anions, which have been shown to produce localized lipid peroxidation and edema in vivo, were significantly enhanced (p = .05, Duncan's multiple comparison test) in AM exposed to all doses of Fe2O3 when compared to AM exposed to BaP alone. This Fe2O3 dose-related enhancement of superoxide anion production is indicative of increased endocytic capacity resulting in a greater amount of total metabolites being produced, in particular, the dihydrodiols of BaP, which are considered to be products of the active metabolic pathway of BaP.

The association of small quantities of ferric oxide with benzo(a)pyrene (BaP) appears to increase in vivo the toxic effect of BaP. The effect of Fe2O3 may be mediated by the recruitment of alveolar macrophages. These cells would contribute to the production of toxic and carcinogenic BaP metabolites and would stimulate development of tumors by producing cellular mediators of inflammation. In order to understand the mechanism of the synergic effect, ... male Sprague Dawley rats 3 weeks of age /were instilled/ with a single dose: Fe2O3 (3 mg) or BaP (3 mg)/combination Fe2O3-BaP (3 mg-3 mg) in 200 microliters of physiological saline solution. Control group of identical size (treated with physiological saline solutions and untreated) were used for this study. Animals were sacrificed 48 hours after instillation and a bronchoalveolar lavage (BAL) was performed. ... An increased malonaldehyde level /was observed/ for rats intoxicated with Fe2O3 (123%), BaP (31%) and Fe2O3 + BaP (56%). The levels of PMN elastase and cathepsin B and L were increased: Fe2O3 (51-58%), BaP (52-27%). This effect was not seen for rats intoxicated by Fe2O3 + BaP. The free alpha(1)-antitrypsin was decreased with the three toxics (Fe2O3: 44%--BaP: 42%--Fe2O3: 41%). The inhibitory capacity of alpha(1)-antitrypsin was lower in groups of rats instilled with toxics.

... The fibrogenic potential of quartz, quartz and ferric oxide administered together, fibrous glass, and hydrated alumina were studied by multiple intratracheal instillation in groups of male Lak:LVG Syrian golden hamsters. Dose-related decreases in survival were evident for the groups instilled with the two highest doses of quartz or quartz and ferric oxide. Instillation of quartz or quartz and ferric oxide induced the greatest pulmonary fibrosis in response to the materials tested. However, the dense fibrous tissue present in the lungs in classical human silicosis and in experimental silicosis of rats was not observed in this study... /Ferric oxide/

The repeated intratracheal instillation, in hamsters, of ferric oxide suspended in normal saline did not give rise to lung tumors. However, given together with benzo(a)pyrene or with systemically administered diethylnitrosamine, an increased yield of lung tumors was obtained. Ferric oxide was thought to be a carcinogenic cofactor, possibly acting by retarding clearance of an inhaled carcinogen or by inducing cytopathological changes that make the cells of the respiratory tract more susceptible to carcinogens.

... Sprague Dawley rats 10 d of age were exposed by inhalation to two different concentrations of ultrafine iron particles (30 or 100 ug/cu m) in combination with soot particles adjusted to maintain a total particle concentration of 250 ug/cu m. Exposure at 10 d and again at 23 d of age was for 6 hr/d for 3 d. Oxidative stress was observed at both Fe concentrations in the form of significant elevations in glutathione disulfide (GSSG) and GSSG/glutathione (GSH) ratio and a reduction in ferric/reducing antioxidant power in bronchoalveolar lavage. A significant decrease in cell viability associated with significant increases in lactate dehydrogenase (LDH) activity, interleukin-1-beta (IL-1beta), and ferritin expression was noted following exposure to particles containing the highest Fe concentration. Iron from these particles was shown to be bioavailable in an in vitro assay using the physiologically relevant chelator, citrate. Data indicate that combined Fe and soot particle exposure induces oxidative injury, cytotoxicity and pro-inflammatory responses in the lungs of neonatal rats. /Iron particles/

respiratory system

Eyes, skin, respiratory system

inhalation

inhalation, skin and/or eye contact

/OTHER TERRESTRIAL SPECIES/ Studies were conducted to determine the effects of a panel of seven nanomaterials (NMs), namely: alpha-alumina, gamma-alumina, precipitated silica; silica fume, calcined silica fume, colloidal antimony pentoxide (Sb(2)O(5)), and superfine amorphous ferric oxide (Fe(2)O(3)), on sediment dwelling invertebrates Chironomus tentans under controlled laboratory conditions. Percentage survival, enzyme activities, growth development, and DNA fragmentation parameters were studied as acute, biochemical, and physiological toxicities of NMs, respectively. Quantitation of catalase and peroxidase enzyme activity demonstrated that toxicant stress of the NMs increased enzyme activity in a concentration dependent fashion across all treatments. The percentage growth length of the test specimens exposed to different NMs was significantly reduced compared to the negative control while only five concentrations were not in the toxic range, namely; Fe(2)O(3) (5 ug/kg); silica fume (5 ug/kg, 50 ug/kg); Sb(2)O(5) (5 ug/kg) and calcined silica fume (5 ug/kg). Genotoxic stress assessed by use of DNA laddering showed complementary findings to the other ecotoxicological endpoints tested in this study-the percentage survival and growth length inhibition. /Amorphous ferric oxide nanoparticles/

Cough.

Redness.

Benign pneumoconiosis with X-ray shadows indistinguishable from fibrotic pneumoconiosis (siderosis)

irritation eyes, skin, respiratory system

/Protect/ from exposure those individuals with pulmonary diseases.

The following medical procedures should be made available to each employee who is exposed to iron oxide fume at potentially hazardous levels: ... A complete history and physical examination ... Examination of the respiratory system should be stressed; 14" X 17" chest roentgenogram; ... FVC and FEV (1 sec). ... The aforementioned medical examinations should be repeated on an annual basis, except that an x-ray is considered necessary only when indicated by the results of pulmonary function testing. /Iron oxide fume/

/HUMAN EXPOSURE STUDIES/ Bronchoalveolar lavage (BAL) was used to sample lung cells and biochemical components in the lung air spaces at various times from 1 to 91 d after intrapulmonary instillation of 2.6 um-diameter iron oxide particles in human subjects. The instillation of particles induced transient acute inflammation during the first day post instillation (PI), characterized by increased numbers of neutrophils and alveolar macrophages as well as increased amounts of protein, lactate dehydrogenase, and interleukin-8 in BAL fluids. This response was subclinical and was resolved within 4 d PI. A similar dose-dependent response was seen in rats 1 d after intratracheal instillation of the same particles. The particles contained small amounts of soluble iron (240 ng/mg) and possessed the capacity to catalyze oxidant generation in vitro. /These/ findings indicate that the acute inflammation after particle exposure may, at least partially, be the result of oxidant generation catalyzed by the presence of residual amounts of ferric ion, ferric hydroxides, or oxyhydroxides associated with the particles... /Iron oxide/

/HUMAN EXPOSURE STUDIES/ ... Some electric arc welders exposed mainly to iron oxide fume showed generalized discrete densities in their chest X-ray films. None of these welders, however, showed any demonstrable clinical disability. /Iron oxide fume/

/HUMAN EXPOSURE STUDIES/ /The authors/ found evidence of siderosis in welders with exposures below 10 mg/cu m, but with probable higher past exposures. /Other investigators/ found exposures to iron oxide fume well over 10 mg/cu m in electric arc and powder-burning operations. Chest X-rays revealed no significant changes in these workers, but relatively few of the workers had long exposure histories and none had worked with iron oxide fume for more than 12 years. /Iron oxide/

/HUMAN EXPOSURE STUDIES/ Ten human subjects were given 5 mg of iron oxide particles (2.6 um) by instillation with the use of a bronchoscope, followed by bronchoalveolar lavage at various time points, to assess the cellular and biochemical response to the instilled particles. Iron oxide particles were made via the hydrolysis and hot dialysis of ferric chloride, which resulted in spherical Fe2O3 particles that contained a soluble iron concentration of 0.036%. A transient acute inflammatory response was observed following instillation based on the appearance of an increased number of neutrophils and alveolar macrophages, and increased amounts of protein, lactate dehydrogenase and interleukin-8 in bronchoalveolar lavage fluid. The residual amount of soluble iron in these particles was shown to catalyze oxidant generation in vitro, which could at least partially explain the observed transient inflammatory response that resolved within 4 days.

For more Human Toxicity Excerpts (Complete) data for FERRIC OXIDE (28 total), please visit the HSDB record page.

Ferric oxide

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 1: (1972) Some Inorganic Substances, Chlorinated Hydrocarbons, Aromatic Amines, N-Nitroso Compounds, and Natural Products

1987

1987

/LABORATORY ANIMALS: Acute Exposure/ ... Fe(2)O(3) nanoparticles with mean diameters of 22 and 280 nm, respectively, were intratracheally instilled to male Sprague Dawley rats at low (0.8 mg/kgbw) and high (20 mg/kgbw) doses. The toxic effects were monitored in the post-instilled 1, 7 and 30 days. ... Fe(2)O(3) nanoparticle exposure could induce oxidative stress in lung. Alveolar macrophage (AM) over-loading of phagocytosed nanoparticle by high dose treatment had occurred, while the non-phagocytosed particles were found entering into alveolar epithelial in day 1 after exposure. Several inflammatory reactions including inflammatory and immune cells increase, clinical pathological changes: follicular hyperplasia, protein effusion, pulmonary capillary vessel hyperaemia and alveolar lipoproteinosis in lung were observed. The sustained burden of particles in AM and epithelium cells has caused lung emphysema and pro-sign of lung fibrosis. At the post-instilled day 30, the typical coagulation parameters, prothrombin time (PT) and activated partial thromboplastin time (APTT) in blood of low dose 22 nm-Fe(2)O(3) treated rats were significantly longer than the controls. We concluded that both of the two-sized Fe(2)O(3) particle intratracheal exposure could induce lung injury. Comparing with the submicron-sized Fe(2)O(3) particle, the nano-sized Fe(2)O(3) particle may increase microvascular permeability and cell lysis in lung epitheliums and disturb blood coagulation parameters significantly.

/LABORATORY ANIMALS: Acute Exposure/ ... When mice were treated with iron oxide nanoparticles (250 ug/kg, 500 ug/kg, and 1mg/kg) by a single intratracheal instillation, the level of intracellular reduced glutathione (GSH) was decreased in the cells of bronchoalveolar lavage (BAL) fluid. The arrest of cell cycles in G1 phase was observed, but S-phase was significantly decreased. The concentrations of pro-inflammatory cytokines (IL-1, TNF-alpha, and IL-6) were dose-dependently increased at day 1 after instillation in the BAL fluid and in the blood. During the experimental period of 28 days, pro-inflammatory cytokines (IL-1, TNF-alpha, and IL-6), Th0 cytokine (IL-2), Th1 type cytokine (IL-12), Th2 type cytokines (IL-4 and IL-5), TGF-beta, and IgE were also elevated. Expressions of many genes related with inflammation or tissue damage such as heat shock protein, matrix metalloproteinase, tissue inhibitors of metalloproteinases, and serum amyloid A were significantly induced. Formation of microgranuloma, which is one of the indicators for chronic inflammatory response, was observed in the alveolar space. In addition, distribution of B cell and CD8+ T cell in blood lymphocytes was increased at day 28. Based on the result, iron oxide nanoparticles may subchronically induce inflammatory responses via oxidative stress in mice by a single intratracheal instillation. /Iron oxide nanoparticles/

/LABORATORY ANIMALS: Acute Exposure/ ... The toxic effects of inhalation exposure to ferric oxide (Fe2O3) ... /were investigated/ in rats. Male Wistar rats were consecutively treated with Fe2O3 at 8.5 mg/kg body weight ... twice daily for 3 days. Content of Fe2O3 ... in tissues, biochemical parameters in serum, and hispathological examinations were analyzed at 12 hr and 36 hr after the 3 day treatment. In the Fe2O3-treated group, iron (Fe) content in liver and lung tissues was significantly increased at 36 hr. ... The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), creatine kinase (CK), and lactate dehydrogenase (LDH) ... were significantly decreased compared to the unexposed controls. Histopathological examination showed that /ferric oxide/ nanoparticles caused severe damage in liver and lung tissues. Although this damage progressed in both liver and lung throughout the postexposure period, no significant elevation of serum enzyme activities was observed...

Ferric oxide (iron (III) oxide, Fe2O3, CAS Reg. No. 1309-37-1) ... is used as an indirect human food ingredient with no limitation other than current good manufacturing practice. The affirmation of this ingredient as generally recognized as safe (GRAS) as an indirect human food ingredient is based upon the following current good manufacturing practice conditions of use: (1) The ingredient is used as a constituent of paper and paperboard used for food packaging. (2) The ingredient is used at levels not to exceed current good manufacturing practice.

Residues of iron oxide are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to animals. Use: colorant in pesticide formulations for animal tags. Limit: none.