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Zinc Toxicology Following Particulate Inhalation Free full text available from Review www.ijoem.com Article ZZincinc ttoxicologyoxicology ffollowingollowing pparticulatearticulate iinhalationnhalation mechanical ventilation for eight Ross G. Cooper Abstract days).[3] The patient left hospital 10 Division of Physiology, The current mini-review describes the toxic effects of zinc days after extubation. Spirometry at Birmingham City University, inhalation principally in the workplace and associated this time revealed a restrictive defect 704 Baker Building complications with breathing and respiration. The [3] (vital capacity 50% predicted). Franchise Street, Perry International ClassiÞ cation of Functioning, Disability and Barr, Birmingham B42 Health Criteria were used to speciÞ cally select articles. Acute metal fume fever is commonly 2SU, UK. Most of the commercial production of zinc involves the associated with zinc inhalation via E-mail: rgcooperuk@ galvanizing of iron and the manufacture of brass. The welding, galvanizing, brass plating, yahoo.com recommended daily allowance for adults is 15 mg zinc/ dyes and electroplating.[4] Zinc severely day. Metal fume fever associated with inhalation of fumes impedes mitochondrial functions of ZnO is characterized by fatigue, chills, fever, myalgias, attenuating ATP production.[5] Potential cough, dyspnea, leukocytosis, thirst, metallic taste and health risks to workers exposed to salivation. ZnCl inhalation results in edema in the 2 zinc oxide (ZnO) and zinc chloride alveolar surface and the protein therein the lavage ß uid (ZnCl ) are significant.[6] is elevated. Particular pathological changes associated 2 with zinc intoxication include: pale mucous membranes; The aim of this mini-review was to jaundice; numerous Heinz bodies; and marked anemia. describe the toxic effects of zinc Adequate ambient air monitors for permissible exposure limits, excellent ventilation and extraction systems, inhalation principally in the workplace and approved respirators are all important in providing and associated complications with adequate protection. breathing and respiration. METHODS Key words: Breathing, exposure, fumes, occupation, respiration, zinc. The criteria used in the current mini-review for selecting articles to be included were both theoretically INTRODUCTION and practically motivated and adopted from the proposed criteria Zinc is an essential mineral in cellular metabolism. It is a in The International Classification of cofactor for the activity and folding of proteins.[1] Because of Functioning, Disability and Health – the pleiotropic effects of zinc on every aspect of cell physiology, ICF.[7] These criteria were as follows: zinc deficiency or excessive rise in its cellular concentration, • Articles were chosen only with can have catastrophic consequences and are linked to major internationally recognized impact patho-physiologies including diabetes and stroke.[1] factors greater than 0.10 • Articles were chosen based upon The plasma concentration of zinc is about 15 µmol/L, the impact of lifestyle, stress principally bound to albumin and a third of which is bound and/or environmental factor/s to α2-macroglobulin.[2] Zinc occupies 10-20 % of plasma, is predisposing zinc exposure a constituent of the human genome, acts as a site-specific • Criteria for selection of literature antioxidant, acts as an active site in enzymes, and is essential used included yes-no responses for the action of insulin.[2] to: the appropriateness of methodology; adequacy of subject Initial symptoms following exposure to concentrated hexite numbers; specificity of sex and/or smoke, vomiting, cough and dyspnea, disappear after a few age of subjects; and statistically hours .[3] Thereafter, 48h later, acute respiratory distress significant response rates to syndrome appears requiring tracheal intubation and survey questionnaires Indian Journal of Occupational and Environmental Medicine - April 2008 - Volume 12 - Issue 1 10 CMYK 10 Cooper: Breathing zinc vapors • The time frame used was principally 1990-2007 inclusive, recommended threshold limit value of 5 mg/m3 ZnO.[18] although articles of extreme importance from earlier decades were used where appropriate ZnO is a common constituent of particulate air pollution and • A multi-factorial overview of the factors eschewed if inhaled in fine or ultra-fine fractions at a concentration concerning zinc exposure was elucidated. It was presumed exceeding 500 µg/m3 for 2h can induce acute systemic that collective articles detailing known factors of usage effects.[19] There may be rapid production and secretion of were not necessarily correlated with functionality and metalloproteinases in the lung following heavy metal particle health. deposition including zinc.[20] Concurrent exposure to zinc • Compilation of materials for the mini-review started and copper will result in significantly greater epithelial with published literature or easily accessible academic toxicity and stress.[21] Reduced glutathione levels have been research associated with zinc-induced cytotoxicity.[22] Inhalation of • The articles were accessible from on-line sources including ZnO at concentrations equal to and below a recommended PubMed and Medline. threshold value of 5 mg/m3 results in the induction of target haeme oxygenase gene expression.[18] Significant changes in RESULTS lavage fluid parameters have been described in guinea pigs and rats exposed to 2.5 mg/m3 ZnO.[23,24] Exposure of guinea Zinc inhalation and respiratory distress pigs at three hr/day for five consecutive days to ultrafine ZnO The respiratory tract can be a significant port for heavy at 7 mg/m3 resulted in a gradual decrease in total lung capacity metal toxicity, inhalants often associated with lung cancer.[8] and vital capacity.[25] Vital capacity, functional residual Most of the commercial production of zinc involves the capacity, alveolar volume and diffusing capacity for carbon galvanizing of iron and the manufacture of brass.[9] Others monoxide decrease following exposure to ZnO, although suggest exposure to zinc via fume inhalation during the active increases in flow resistance and decreases in compliance gas welding of steel coated with zinc protective layers.[10] and total lung capacity return to normal by 72h.[26] Total lung One study demonstrated that exposure to fumes of silver capacity, vital capacity, functional residual volume, alveolar solder containing cadmium was more likely to induce fever volume and diffusing capacity for carbon monoxide decrease [11] than fumes of zinc. The recommended daily allowance following exposure to ZnO-SO2 mixtures and did not return for adults is 15 mg zinc/day. Ingestion of 1-2 g zinc sulphate to normal by 72h after the last exposure.[27] Further exposure (ZnS04) produces emesis. Inhalation of high concentrations resulted in greater decrements in functional residual capacity of ZnCl2 from smoke bombs detonated in close spaces may and residual volume. result in chemical pneumonitis and adult respiratory distress [9] syndrome. Metal fume fever linked with inhalation of fumes ZnCl2 inhalation results in oedema in rats and measurements of ZnO is characterized by fatigue, chills, fever, myalgias, of alveolar surface protein in lavage fluid is variable, dose- cough, dyspnea, leukocytosis, thirst, metallic taste and dependent and maximal at three days, although at sub-lethal salivation. One study asked 12 healthy volunteers to inhale doses it regresses after seven days.[28] zinc oxide fumes through a mask for two hours at 0, 2.5 and 5 mg/m3 on separate days.[12] All but two developed a mild Zinc toxicity fever between 6 and 12 hours after exposure and all but one Zinc compounds can produce irritation and corrosion reported more symptoms (particularly fatigue, muscle ache of the gut, acute renal tubular necrosis and interstitial and cough) after zinc oxide exposure at 5 mg/m3 than after nephritis.[9] Inhalation would presumably contribute partially exposure to the control furnace gas.[12] Another case study of to pathological effects on the kidneys. Zinc toxicity can be a 25-year-old male welder with metal fume fever showed that treated with calcium disodium ethylenediaminetetraacetate, he was suffering from aseptic meningitis with pericarditis, a chelator.[9] Zinc administration is able to attenuate some pleuritis and pneumonitis.[13] The condition is associated with neurochemical, morphological and behavioral effects induced invasion of neutrophils into the airways through stimulation of by pesticides like malathion.[29] Particular pathological changes oxygen free radicals possibly associated with the associated associated with zinc intoxication include: pale mucous pathogenesis.[14-16] In another study, ZnO welding fumes membranes; jaundice; the presence of numerous Heinz were associated with a marked dose-dependent increase in bodies; and marked anemia.[30] the number of polymorphonuclear leukocytes recovered in bronchoalveolar lavage fluid 22h following exposure, although Influence on enzyme activity it was not associated with a clinically significant change Zinc-induced activation of epidermal growth factor in pulmonary function or airway reactivity.[17] The authors receptor in human airway epithelial cells involves a loss suggest a cytokine-mediated mechanism. Haeme oxygenase of tyrosine phosphatase activities, potentially disrupting gene expression occurs following inhalation of ZnO in welding dephosphorylation reactions in cellular protein metabolism.[31] fumes at concentrations equal to and below the current Cardiovascular
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