Inhalation of zinc oxide

Toxicology. Inhalation of zinc oxide fume causes an influenza-like illness termed metal fume fever. 

Toxicity and health effects Exposure to zinc oxide causes adverse health effects to the lungs and the reproductive system in experimental animals. Inhalation of zinc oxide fumes by workers causes metal fume fever. ° ... 

Exposure to zinc oxide can occur through inhalation, ingestion, and eye or skin contact. Ingestion of zinc oxide ointments is most common in household settings and is generally considered nontoxic due to relatively low product concentrations. Inhalation of zinc oxide in industrial areas, as particulate matter or fumes, may lead to potentially toxic exposures. 

I. Mechanism of toxicity. Metal fume fever results from Inhalation of zinc oxide (neither ingestion nor parenteral administration induces the illness). The mechanism is uncertain, but may be cytokine-mediated. It does not Involve sensitization and can occur with the first exposure. 

Humans have reported nonspecific neurological effects such as headaches and malaise in association with other symptoms following inhalation of zinc oxide and in metal fume fever (Rohrs... 

In humans, inhalation of zinc chloride causes greater damage to respiratory tissue than inhalation of zinc oxide. Reported lesions included acute pneumonitis, ulceration of mucous membranes, subpleural hemorrhage, and pulmonary fibrosis. Exposed individuals have died from respiratory distress syndrome (Evans 1945 Hjortso et al. 1988 Johnson and Stonehill 1961 Matarese and Matthews 1966 Milliken et al. 1963 Schenker et al. 1981). 

Drinker P, Thomson RM, Finn JL. 1927a. Metal fume fever II. Resistance acquired by inhalation of zinc oxide on two successive days. J Ind Hyg 9 98-105. 

Zinc is non-toxic in general, however, a surplus of it can be stored in the bones and spleen, and the most significant toxic effect of zinc is fume fever, that can result from acute inhalation of zinc oxide fumes. Zinc oxide is used in the rubber industry (it is a catalyst during manufacture and also used as a heat dispenser in the final product), as well as in pigments for plastics and in wallpaper. It also functions as a UV stabiliser for plastics and rubbers. In addition to these, it is possible to find mercury vapour indoors, emitted mainly from the biocides used in paints. 

A number of studies of the toxicity of zinc oxide/hexachloroethane smoke have been conducted (Brown et al. 1990 Karlsson et al. 1986 Marrs et al. 1983). These studies demonstrate that smoke exposure results in pulmonary inflammation and irritation. When male Porton Wistar rats were exposed to hexachloroethane/zinc oxide smoke for 60 minutes, the lungs showed pulmonary edema, alveolitis, and areas of macrophage infiltration 3 days later. At 14 days, there was interstitial fibrosis and macrophage infiltration. At 28 days, increased fibrosis and macrophage infiltration were noted. However, these same symptoms occurred when the animals inhaled zinc chloride there was no apparent synergism between the zinc chloride and residual hexachloroethane (Brown et al. 1990 Richard et al. 1989). This is consistent with the fact that smoke contains little hexachloroethane and the observation that acute exposure to 260 ppm hexachloroethane had no effects on the lungs of rats (Weeks et al. 1979). 

Magnesium deficiency, usually the result of decreased absorption or excessive excretion, results in neuromuscular weakness and ultimately convulsions. Dietary deficiency in catde is known as the grass staggers. Magnesium toxicity from impaired excretion or excessive consumption of antacids results in vomiting, hypertension, and central nervous systems effects. Inhalation of magnesium oxide from welding can cause metal fume fever similar to that from zinc. 

A number of zinc compounds with organic constituents (e.g., zinc salts of organic acids) have therapeutic uses. These include antidandruff zinc pyridinethione, antifungal zinc undecylenate used to treat athlete s foot, zinc stearate and palmitate (zinc soap), and antibacterial zinc bacitracin. Zinc naphthenate is used as a low-toxicity wood preservative, and zinc phenolsulfonate has insecticidal properties and was once used as an intestinal antiseptic. The inhalation of zinc soaps by infants has been known to cause acute fatal pneumonitis characterized by lung lesions similar to, but more serious than, those caused by talc. Zinc pyridine thione (zinc 2-pyridinethiol-l-oxide) has been shown to cause retinal detachment and blindness in dogs this is an apparently species-specific effect because laboratory tests at the same and even much higher dosages in monkeys and rodents do not show the same effect. 

Prolonged, recurring zinc oxide exposures to the skin may cause papular-pustular eruptions. This skin condition may be referred to as oxide pox. Studies of zinc refinery workers found no correlation between exposures and lung or other types of cancer. Chronic inhalation of zinc compounds has been implicated in cases of fatal liver damage. 

Metal fume fever as an immunological reaction to the inhalation of metallic oxide aerosols (e.g., zinc oxide smoke) (Geldmacher von Mallinckrodt 1991a). 

Metal fume fever, a critical end point, was observed in workers who inhaled high levels of zinc oxide fumes or dust. The mechanism of metal fume fever has been reported to be an immune response to zinc oxide in the respiratory tract. The anemia observed in humans and animals after oral exposure to high levels of zinc could result from a zinc-induced copper deficiency. Excess levels of dietary zinc inhibit the transport of copper to the blood from either the intestinal lumen or the intestinal mucosal cell. 

The absorption of zinc oxide fumes lead to increased levels of zinc measured in the liver, kidney, and pancreas of cats exposed to zinc oxide fumes for durations ranging from 15 minutes to 3.25 hours (Drinker and Drinker 1928). The usefulness of the study is limited because reporting was inadequate and particle size of the zinc oxide aerosol was not determined. Some inhaled particles of zinc oxide are subject to ciliary clearance and swallowing. Thus, a portion of the inhaled zinc may ultimately be absorbed from the gastrointestinal tract. 

Metal fume fever has been observed in humans who inhaled high concentrations of zinc oxide fumes. Metal fume fever is believed to be an immune response characterized by increased body temperature, impaired lung function, increased number of leukocytes in the blood, and bronchoalveolar lavage fluid. Similar effects were observed in animals. Metal fume fever has been observed after acute, intermediate, and chronic inhalation exposures to zinc oxide. 

Up to 30% of ingested zinc is absorbed from the small intestine, although absorption is controlled by a homeostatic mechanism. Despite its essentiality, too much zinc interferes with iron and copper metabolism which may result in copper deficiency. Excessive absorption can result in symptoms such as nausea, cramps and vomiting. Inhalation of zinc, zinc oxide and zinc chloride fumes by occupationally exposed workers causes pulmonary oedema and metal fume fever, with symptoms such as fever, chills, sweating and weakness occurring within 4-6 hours of exposure. Chronic inhalation of zinc compounds can result in liver damage. 

Health and Safety Factors. Zinc oxide is considered nontoxic, but inhalation of freshly formed fume can cause zinc chills also known as brass-founder s ague. The symptoms are fever and cough followed by chills after ca 4—8 h (43). No aftereffects have been noted and workers who are... 

Structural chromosome aberrations, particularly chromatid gaps and increased frequency of fragment exchange, were observed in rat bone marrow cells after 14 days of exposure to 240 mg Zn/L drinking water (Kowalska-Wochna et al. 1988). Chromosomal aberrations were observed in bone marrow cells of mice fed diets equivalent to 650 mg Zn/kg BW daily, in mice exposed to zinc oxide by inhalation, and in mice maintained on a low-calcium diet (USPHS 1989). Aberrations in bone marrow of mice given 5000 mg Zn/kg diet may be associated with calcium deficiency (Leonard and Gerber 1989). Calcium is displaced by zinc in calcium-depleted conditions, leading to chromosomal breaks and interference in the repair process (USPHS 1989). 

Inhalation of 5 mg Zn/m3, as ultrafine zinc oxide, 3 h daily for 6 days... 

The critical factor in the development of the syndrome is the size of the ultrafine zinc oxide particles produced when zinc is heated to temperatures approaching its boiling point in an oxidizing atmosphere." The particles must be small enough (zinc oxide powder is either inhaled or taken orally. Only freshly formed fume causes the illness, presumably because flocculation occurs in the air with formation of larger particles that are deposited in the upper respiratory tract and do not penetrate deeply into the lungs. ... 

Gordon T, Chen Lc, Fine JM, et al Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and Tidohixs. Am Ind Hyg Assoc J 53 503-509, 1992... 

Zinc is an essential nutrient and is not regarded as toxic. However, the metal fumes, its oxide fumes, and chloride fumes can produce adverse inhalation effects. (See Zinc Oxide and Zinc Chloride, Toxicity) Ingestion of soluble salts can cause nausea. 

Pine, 1. M. et al. 2000. Characterization of clinical tolerance to inhaled zinc oxide in naive subjects and sheet metal workers. Journal of Occupational and Environmental Medicine 42(11) 1085-1091. 

Exposure to zinc oxide will mainly take place in the workplace by means of the inhalation and dermal exposure route. Exposure due to handling of solid zinc oxide... 

SAFETY PROFILE Human systemic effects by ingestion cough, dyspnea, and sweating. A human skin irritant. Pure zinc powder, dust, and fume are relatively nontoxic to humans by inhalation. The difficulty arises from oxidation of zinc fumes immediately prior to inhalation or presence of impurities such as Cd, Sb, As, Pb. Inhalation may cause sweet taste, throat dryness, cough, weakness, generalized aches, chills, fever, nausea, vomiting. 

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