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ZINC OXIDE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) CHEMICAL/TOXIC CLASS - Zinc oxide is a metal oxide which causes metal fume fever when inhaled.

Specific Substances

    1) Chinese White
    2) C.I. 77947
    3) C.I. Pigment White 4
    4) Flowers of Zinc
    5) Philosopher's Wool
    6) Zinc Oxide
    7) Zinc White
    8) CAS 1314-13-2
    1.2.1) MOLECULAR FORMULA
    1) O-Zn
    2) ZnO

Available Forms Sources

    A) FORMS
    1) White or yellow, odorless powder or dust
    2) Hexagonal crystals (sublimed)
    3) Metal oxide fumes
    4) TECHNICAL GRADES - Zinc oxide content of 90% to 99%; may contain <1% lead
    5) (REFERENCES - Lewis, 1997; (Budavari, 1996; Hathaway et al, 1996; HSDB , 2001)
    B) SOURCES
    1) Zinc oxide fumes are produced as a result of welding, cutting on metal, or smelting of zinc alloys.
    2) An oxidation product prepared by vaporizing metallic zinc, franklinite, or zinc sulfide, and treating the vapors with preheated air (Budavari, 1996).
    C) USES
    1) PIGMENT USES
    a) In white paint instead of lead carbonate; also reduces mold growth in paints
    b) In quick-setting cements
    c) In floor tiles
    d) To color drugs
    2) MANUFACTURING PROCESSES -
    a) Opaque glass and certain types of transparent glass
    b) Enamel
    c) Automobile tires; as an accelerator activator and reinforcing agent in rubber
    d) White glue
    e) Matches
    f) White printing inks
    g) Porcelains
    h) Zinc green
    i) As a reagent in analytical chemistry
    j) In electrostatic copying paper; as a photoconductor in office copying machines and in color photography. In electrofax processes, zinc oxide powder is dye-sensitized by adsorption to extend its photosensitivity across the visible region
    k) As a flame retardant
    l) In electronics as a semiconductor, and as electrical insulation. Polycrystalline zinc oxide, with Bi203 and other additives, has nonohmic conduction and is used as a voltage-dependent resistor (varistor) to protect electronic equipment against voltage surges.
    m) In floor covering, fabrics, lubricants, plastics, and rayon manufacture (Stokinger, 1981).
    n) In carbon black mixtures (Kirk-Othmer, 1984)
    o) As an anticaking agent (Kirk-Othmer, 1984)
    p) In elastomer curing; in polybutadiene curing
    q) As a grease filler
    r) In hydrogen manufacture
    s) In hydrogen sulfide absorber cartridge
    t) Is the most commonly used phosphor powder in vacuum fluorescence displays
    u) To remove mercaptans, hydrogen sulfide and, to some extent, chlorine at temperatures of 350 to 400 deg C
    3) OTHER -
    a) Is an insecticidal adjuvant used in high concentration against screwworms and ear ticks (Rossoff, 1974).
    b) When used in many compounds, it makes them mildew resistant.
    4) (REFERENCES - Budavari, 1996; (Lewis, 1997; HSDB , 2001)

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) INHALATION (PRIMARY EXPOSURE/EFFECTS) -
    1) METAL FUME FEVER is a brief, self-limited illness characterized by fever, chills, myalgias, vomiting, and malaise which most commonly results from inhalation of freshly formed zinc oxide fume. Complete recovery generally occurs within 24 to 48 hours. Other metal oxides can cause metal fume fever and may be complicated by other serious health effects (e.g., cadmium).
    2) A few sources claim that finely divided zinc oxide dust can cause metal fume fever. Zinc oxide dust is generally considered a nuisance dust; adverse effects are unlikely when exposures are kept under reasonable control.
    B) ORAL EXPOSURE -
    1) Toxicity is low, based on animal studies. It has been speculated that severe oral exposure to airborne powders or dusts of zinc compounds, in general, may cause gastric upset and vomiting due to the swallowed dusts.
    C) CHRONIC EXPOSURE -
    1) It has been reported that working in environments with extremely high, uncontrolled concentrations of zinc oxide fumes or dust for more than 6 months may lead to development of dermatitis, boils, conjunctivitis and gastrointestinal disturbances. Exposures to other chemicals were likely in some reports.
    0.2.3) VITAL SIGNS
    A) Fever can develop after exposure to zinc oxide fume. Tachycardia and/or dyspnea may be present.
    B) Animals initially experience decreased body temperature, followed by elevated body temperature.
    0.2.4) HEENT
    A) NUISANCE DUST EFFECTS - Zinc oxide dust may be considered a nuisance dust. Exposure to massive quantities of the dust would be expected to cause mechanical irritation of the eyes and nose.
    0.2.5) CARDIOVASCULAR
    A) Sinus tachycardia may be present.
    0.2.6) RESPIRATORY
    A) Metal fume fever may occur after inhalation of freshly formed zinc oxide fume. Cough, dyspnea, rales, rhonchi, and occasionally reversible reduction in pulmonary volumes and carbon dioxide diffusing capacity have been reported in humans.
    B) Pneumonia has developed in animals following inhalation of high zinc oxide fume concentrations. Fume particle size and relative humidity may influence response.
    C) Dyspnea, decreased vital capacity and airway hyperresponsiveness have been reported in animals exposed to aerosols of zinc oxide and sulfur dioxide. Humidity and temperature appear to influence the irritancy and related pulmonary effects of this mixture.
    0.2.8) GASTROINTESTINAL
    A) Nausea and vomiting are associated with metal fume fever.
    B) Gastrointestinal complaints have been reported in workers chronically exposed to high concentrations of zinc oxide fumes, dusts and possibly other chemicals.
    0.2.9) HEPATIC
    A) Abnormal liver function tests were reported in one case series.
    0.2.13) HEMATOLOGIC
    A) Leukocytosis, with a shift to the left, is common. Zinc oxide has caused erythrocyte hemolysis in vitro.
    0.2.14) DERMATOLOGIC
    A) Diaphoresis may be present.
    B) Exposure to fumes or dust for over 6 months may produce dermatitis or boils, particularly if hygiene is poor.
    0.2.15) MUSCULOSKELETAL
    A) Muscle aches, malaise and shivering commonly occur following zinc oxide fume inhalation.
    0.2.19) IMMUNOLOGIC
    A) Leukocytosis or other inflammatory responses have been documented in humans and animals exposed to zinc oxide fume.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    B) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    0.2.22) OTHER
    A) Chronic zinc dust or fume poisoning is questionable. Information would indicate that relatively large amounts of zinc may pass through kidneys and the gastrointestinal tract for years without causing any detectable clinical damage.

Laboratory Monitoring

    A) Monitor arterial blood gases and chest x-ray in symptomatic patients.
    B) Urinary zinc levels and possibly blood or urine screens for other metal exposures may aid in differential diagnosis.
    C) Pulmonary function testing has been recommended as part of the initial medical examination and on a periodic basis for occupational groups. Persons with pre-existing pulmonary disease may have increased likelihood of adverse effects from zinc oxide fume.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Toxicity is low; treatment is symptomatic and supportive. There is no specific antidote.
    B) Ingestion is unlikely. Fume or dust inhalation is the primary route of exposure.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) The minimum lethal human dose to zinc oxide has not been delineated.
    B) Inhalation of air containing zinc oxide at 1 to 34 mg per cubic meter causes metal fume fever and pneumonitis.
    C) Volunteers exposed to 600 mg of zinc per cubic meter (as zinc oxide) developed moderate symptoms with typical febrile reaction and leukocytosis after an exposure duration of 10.5 and 12 minutes.

Clinical Effects

Summary Of Exposure

    A) INHALATION (PRIMARY EXPOSURE/EFFECTS) -
    1) METAL FUME FEVER is a brief, self-limited illness characterized by fever, chills, myalgias, vomiting, and malaise which most commonly results from inhalation of freshly formed zinc oxide fume. Complete recovery generally occurs within 24 to 48 hours. Other metal oxides can cause metal fume fever and may be complicated by other serious health effects (e.g., cadmium).
    2) A few sources claim that finely divided zinc oxide dust can cause metal fume fever. Zinc oxide dust is generally considered a nuisance dust; adverse effects are unlikely when exposures are kept under reasonable control.
    B) ORAL EXPOSURE -
    1) Toxicity is low, based on animal studies. It has been speculated that severe oral exposure to airborne powders or dusts of zinc compounds, in general, may cause gastric upset and vomiting due to the swallowed dusts.
    C) CHRONIC EXPOSURE -
    1) It has been reported that working in environments with extremely high, uncontrolled concentrations of zinc oxide fumes or dust for more than 6 months may lead to development of dermatitis, boils, conjunctivitis and gastrointestinal disturbances. Exposures to other chemicals were likely in some reports.

Vital Signs

    3.3.1) SUMMARY
    A) Fever can develop after exposure to zinc oxide fume. Tachycardia and/or dyspnea may be present.
    B) Animals initially experience decreased body temperature, followed by elevated body temperature.
    3.3.2) RESPIRATIONS
    A) Dyspnea has been reported in humans following fume inhalation (Rohrs, 1957; Dula, 1978; Ameille et al, 1992).
    3.3.3) TEMPERATURE
    A) FEVER/HUMANS - Fever, usually ranging from 102 degrees F to 105 degrees F (38.8 to 40.5 degrees C), can develop about 3 to 10 hours after exposure to zinc oxide fume and is often accompanied by flu-like symptoms. Fever and flu-like symptoms typically subside within 24 to 48 hours after ceasing exposure, but may only last 3 to 6 hours (Rohrs, 1957; Papp, 1968; Anon, 1969; Dula, 1978; Mueller & Seger, 1985; Gordon et al, 1992).
    B) DECREASED, INCREASED TEMPERATURE/ANIMALS - Guinea pigs exposed to an atmospheric concentration of 1000 to 2600 mg per cubic meter developed an initial drop in body temperature of 0.5 to 2 degrees C, followed 6 to 18 hours later by a 0.5 to 1 degree C increase in body temperature above normal (reviewed in ACGIH, 1986).
    1) Rabbits, rats, and cats exposed for 3.5 hours to zinc oxide fume concentrations of 110 to 600 mg per cubic meter had transient decreases in body temperature (HSDB , 2001).
    3.3.5) PULSE
    A) Rapid pulse (e.g, 100-125 beats per minute) has been reported (Anseline, 1972; Anthony et al, 1978; Dula, 1978).

Heent

    3.4.1) SUMMARY
    A) NUISANCE DUST EFFECTS - Zinc oxide dust may be considered a nuisance dust. Exposure to massive quantities of the dust would be expected to cause mechanical irritation of the eyes and nose.
    3.4.3) EYES
    A) CONJUNCTIVITIS - It has been reported that conjunctivitis may result from working in an uncontrolled environment of fumes or dust of zinc oxide for more than 6 months (Hamilton & Hardy, 1974).
    1) Mechanical irritation of the eyes may be expected from exposure to massive quantities of the dust.
    B) LOW IRRITANCY/DRAIZE TEST IN ANIMALS - Rabbit eye response in a standardized draize test was reported as mild (RTECS , 2001).
    C) BLURRED VISION occasionally occurs after fume inhalation by humans (US DHHS, 1981).

Cardiovascular

    3.5.1) SUMMARY
    A) Sinus tachycardia may be present.
    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) Sinus tachycardia has been reported with metal fume fever (Dula, 1978).

Respiratory

    3.6.1) SUMMARY
    A) Metal fume fever may occur after inhalation of freshly formed zinc oxide fume. Cough, dyspnea, rales, rhonchi, and occasionally reversible reduction in pulmonary volumes and carbon dioxide diffusing capacity have been reported in humans.
    B) Pneumonia has developed in animals following inhalation of high zinc oxide fume concentrations. Fume particle size and relative humidity may influence response.
    C) Dyspnea, decreased vital capacity and airway hyperresponsiveness have been reported in animals exposed to aerosols of zinc oxide and sulfur dioxide. Humidity and temperature appear to influence the irritancy and related pulmonary effects of this mixture.
    3.6.2) CLINICAL EFFECTS
    A) METAL FEVER
    1) Inhalation of zinc oxide fume can result in metal fume fever, which involves flu-like symptoms (e.g, fever, nausea, myalgia, headache, sore throat) not limited to the respiratory system (Rohrs, 1957; Papp, 1968; US DHHS, 1981; Mueller & Seger, 1985) ACGIH, 1986; (Barceloux, 1999).
    2) One source reported that symptoms may also result from breathing finely divided zinc oxide dust (Turner & Thompson, 1926 as reviewed in ACGIH, 1986). Zinc oxide fume, however, has been more frequently reported as the cause of metal fume fever (Rohrs, 1957; Anon, 1969; US DHHS, 1981; Mueller & Seger, 1985) ACGIH, 1986; (Gordon et al, 1992). Zinc oxide dust has been referred to as a nuisance dust (Hathaway et al, 1996; Beliles, 1994).
    3) INCIDENCE - The effects from freshly formed zinc oxide fume have been described in a survey of 102 brass foundry workers (Turner & Thompson, 1926 as reviewed in Stokinger, 1982):
    a) Twenty-six percent had "brass foundryman's ague" on an average of once per week, 13% once per month, 17% once per year, 11% twice per week, 14% twice per month, 6% twice per year, 2% three times per month, 1% three times per year, and about 10% four times per year.
    b) The majority of workers (88%) suffered symptoms only during the winter when ventilation was inadequate, while 12% of workers had symptoms regardless of the season. Zinc oxide exposure levels that were associated with symptoms were not established.
    B) COUGH
    1) Coughing commonly occurs during inhalational exposure and may precede flu-like symptoms (Rohr, 1957; (Dula, 1978; US DHHS, 1981).
    C) DYSPNEA
    1) Dyspnea, substernal tightness, and a sensation of chest constriction or soreness may be present following heavy exposure to zinc oxide fume (Rohr, 1954; (Papp, 1968; US DHHS, 1981) ACGIH, 1986).
    2) Chest tightness (n=2) and dyspnea (n=1) developed 6 to 10 hours in human volunteers after a 2 hour exposure to 5 mg/m(3) zinc oxide fume; one other subject did not report respiratory effects (Gordon et al, 1992). The symptoms resolved within 24 hours.
    D) DISORDER OF RESPIRATORY SYSTEM
    1) Rales or rhonchi may develop following zinc oxide fume inhalation (Fishburn & Zenz, 1969) Rohr, 1957; (Papp, 1968; Dula, 1978; Mueller & Seger, 1985). Chest x-rays are usually normal (Rohrs, 1957; Papp, 1968), but haziness and infiltrates resolving within 24 hours were reported in one case of exposure to unspecified welding fumes (Dula, 1978).
    2) REDUCED LUNG VOLUMES - Transient reductions in vital capacity, total lung capacity, and/or FEV(1) can occur in some but not all cases (US DHHS, 1981; Ameille et al, 1992; Kuschner et al, 1995). A slight decrease in vital capacity and forced expiratory volume in one second was noted by a forced expiration technique (Pasker et al, 1997).
    a) No effects on pulmonary function were reported in 4 human subjects exposed to 5 mg/m(3) zinc oxide fume for 2 hours and tested for up to 24 hours after exposure (Gordon et al, 1992).
    3) DECREASED GAS EXCHANGE - Significantly reduced diffusing capacity of carbon monoxide can result from fume inhalation (Ameille et al, 1992), but was not reported in two laboratory studies involving human exposure for 2 hours to 5 mg/m(3) zinc oxide (Gordon et al, 1992) or exposure to purified zinc oxide fume (3 to 37 mg/m(3) zinc) for 15 to 120 min (Kuschner et al, 1995).
    4) INFLAMMATION - A man exposed to zinc fumes during smelting or welding operations had bronchial inflammation with increased lymphocyte count (CD8 T-lymphocytes predominating) similar in pattern to hypersensitivity pneumonitis (Ameille et al, 1992).
    a) Kuschner et al (1995) measured increased inflammatory mediators in bronchoalveolar lavage fluid from humans exposed for 15 to 120 min to purified zinc oxide fume (3 to 37 mg/m(3) zinc).
    E) ACUTE LUNG INJURY
    1) PULMONARY EDEMA/COMBINED EXPOSURE TO ZNO + CADMIUM FUMES - Pulmonary edema can result from exposure to cadmium fume, in addition to zinc oxide fume (Anthony et al, 1978). Initial symptoms of metal fume fever due to zinc oxide fume are often present. The clinician must be alert to the possibility of delayed, serious pulmonary effects associated with the cadmium exposure.
    F) LACK OF EFFECT
    1) Twenty workers exposed to zinc oxide fumes while working in a zinc foundry in Baiyin, Peoples' Republic of China, did not develop any significant signs or symptoms of metal fume fever despite zinc oxide exposure levels of 36.3 mg/m(3) in less than 4 hours. Serum zinc levels were within the reference range of all workers, however urinary zinc levels were significantly elevated (Martin et al, 1999).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PNEUMONIA
    a) Heavily exposed animals showed signs of bronchopneumonia (HSDB , 2001).
    2) RESPIRATORY DISORDER
    a) IMPAIRED PULMONARY FUNCTION/GAS DIFFUSION -
    1) Guinea pigs exposed for one hour to submicrometer sized zinc oxide fume (1 mg/m(3)) developed progressive decreases in lung compliance during the 2 hour post-exposure monitoring period (Amdur et al, 1982). No significant changes in pulmonary resistance, tidal volume, respiratory rate or minute volume occurred.
    2) Significantly decreased functional residual capacity but only minor (not statistically significant) reduction of carbon monoxide diffusing capacity occurred in guinea pigs exposed 3 hours to 7.8 mg/m(3) zinc oxide (Lam et al, 1982). Other pulmonary function parameters (lung volumes) were unaffected.
    3) Another study by Lam et al (1985) reported decreased vital capacity, functional residual capacity, alveolar volume and carbon monoxide diffusing capacity in guinea pigs exposed to freshly generated, ultrafine zinc oxide particles.
    4) Relative humidity has been shown to influence pulmonary response to zinc oxide particles. Exposure to zinc oxide particles alone in 80% humidity produced no pulmonary function effects in guinea pigs; whereas, exposure to zinc oxide in 30% humidity caused decreased compliance (Amdur et al, 1983).
    b) HYPERRESPONSIVENESS, PFTS, DIFFUSION/ZNO + SO2 -
    1) Combinations of zinc oxide and sulfur dioxide in atmospheres of high temperature and high humidity (80%) can generate an irritant aerosol which adversely affects pulmonary function (Amdur et al, 1983). Decreased lung compliance, tidal volume, and increased resistance in guinea pigs occurred only at high humidity and high temperature conditions.
    2) Guinea pigs exposed under conditions which produced sulfuric acid-coated zinc oxide particles (sulfur dioxide + zinc oxide in a humidified furnace) developed increased pulmonary resistance following acetylcholine challenge. Neither zinc nor sulfur dioxide alone produced these effects (Chen et al, 1992).
    3) Decreased vital capacity, total lung capacity, functional residual volume, alveolar volume and diffusing capacity for carbon monoxide were associated with exposure of guinea pigs for 3 hours/day over 6 days to conditions which would generate sulfuric-acid coated zinc oxide particles (Conner et al, 1985). Inflammatory changes were apparent but otherwise the lung morphology appeared largely normal. Sulfur dioxide alone failed to produce any effects.
    4) No effects on respiratory rate, tidal volume, and pulmonary resistance or compliance were reported in another guinea pig study involving 3 hour exposure to mixtures of various concentrations of zinc oxide (0.8 to 7.0 mg/m(3)) and sulfur dioxide prepared in a water vapor saturated furnace (Lam et al, 1982).
    c) TOLERANCE
    1) In mice exposed to zinc oxide fumes (1.0 g/m(3)) for 1, 3 or 5 days, a tolerance to neutrophil infiltration into the lungs was noted. Induction of lung metallothionein was also observed. In contrast, there was no change in protein levels in bronchoalveolar lavage (Wesselkamper et al,2001).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea and vomiting are associated with metal fume fever.
    B) Gastrointestinal complaints have been reported in workers chronically exposed to high concentrations of zinc oxide fumes, dusts and possibly other chemicals.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) Self-limited nausea and vomiting are a common feature of metal fume fever, typically developing a few hours after exposure and lasting up to 48 hours (Papp, 1968) ACGIH, 1986).
    B) GASTRITIS
    1) ACUTE TOXICITY
    a) Zinc oxide is not readily absorbed (Henderson et al, 1995) and is unlikely to cause acute toxicity (Dreisbach & Robertson, 1987). Toxicity in animals fed zinc oxide for prolonged periods was very low (Stokinger, 1981).
    b) Ingestion of acidic liquids out of galvanized containers has been associated with gastric irritation (Beliles, 1994), most likely due to the formation of zinc chloride.
    c) Some zinc compounds may cause intense gastric irritation as a result of conversion to zinc chloride upon reacting with gastric acid (Arena & Drew, 1986).
    d) Refer to the management for Zinc Chloride.
    2) CHRONIC TOXICITY
    a) Working in an uncontrolled environment of fumes or dust of zinc oxide for more than 6 months reportedly may lead to development of gastrointestinal disturbances (Hamilton & Hardy, 1974), possibly due to the swallowing of large amounts of zinc compound dusts or vapors which theoretically may form corrosive zinc compounds upon reaction with gastric acid (Hegsted et al, 1945).
    b) Hegsted et al (1945) has reviewed reports which claim gastric disturbances from prolonged zinc oxide fume exposure. He concludes that exposures to other chemicals, such as lead, arsenic, cadmium, and zinc sulfate or chloride, cannot be ruled out in many case reports. Other inadequacies of the available studies limit the data interpretation. Several studies reported no adverse gastrointestinal effects (Hegsted et al, 1945).
    c) Studies reviewed by Stokinger (1981) reported that symptoms similar to those produced by ulcers (stomach pressure, nausea, weakness) were present in persons who engaged for years in galvanizing, torch cutting of galvanized metals, welding on galvanized iron, and brass foundry work. The symptoms were reduced by treatments (unspecified) typically used for ulcers. No results in unexposed comparison groups were reported.
    d) CASE SERIES - Radiological evidence of peptic ulcer and elevated uropepsin levels were found in 3 of 25 workers exposed to very high zinc oxide (50 mg/cu m) concentrations (Stokinger, 1981). The incidence of peptic ulcer and elevated uropepsin levels in unexposed workers was not reported.

Hepatic

    3.9.1) SUMMARY
    A) Abnormal liver function tests were reported in one case series.
    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) CASE SERIES - Abnormally elevated alanine transferase activities were reported in 15 of 25 workers exposed to very high (50 mg/m(3)) zinc oxide concentrations (Stokinger, 1981). No data were presented for unexposed comparison groups.
    2) Hepatic abnormalities are not reported as common adverse effects of zinc oxide exposure (Anon, 1969; US DHHS, 1981; Beliles, 1994; NIOSH , 1996; RTECS , 1996).

Hematologic

    3.13.1) SUMMARY
    A) Leukocytosis, with a shift to the left, is common. Zinc oxide has caused erythrocyte hemolysis in vitro.
    3.13.2) CLINICAL EFFECTS
    A) LEUKOCYTOSIS
    1) Leukocytosis, often with a predominance of immature polymorphonuclear leukocytes, is common in individuals with metal fume fever and typically persists until the patient has been afebrile for about 12 hours (Rhors, 1957; (Papp, 1968; Fishburn & Zenz, 1969; Mueller & Seger, 1985; Ameille et al, 1992).
    B) HEMOLYSIS
    1) Zinc oxide produced erythrocyte hemolysis in vitro (Delbeck & Delbeck, 1973).
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LEUKOCYTOSIS
    a) Rabbits, rats and cats exposed for 3.5 hours to zinc oxide fumes at concentrations of 110 to 600 mg per cubic meter reacted with transient fall in body temperature followed by marked leukocytosis (HSDB , 2001).

Dermatologic

    3.14.1) SUMMARY
    A) Diaphoresis may be present.
    B) Exposure to fumes or dust for over 6 months may produce dermatitis or boils, particularly if hygiene is poor.
    3.14.2) CLINICAL EFFECTS
    A) EXCESSIVE SWEATING
    1) Diaphoresis can occur with metal fume fever (Papp, 1968; Mueller & Seger, 1985).
    B) DERMATITIS
    1) It is reported that working in an uncontrolled environment of fumes or dust of zinc oxide for more than 6 months may lead to development of dermatitis and boils (Hamilton & Hardy, 1974).
    2) CASE SERIES - It was reported in 1921 that 14 of 17 men employed in making zinc oxide experienced "oxide pox", a dermatitis characterized by small, red and papules with a central plug involving the pubic region, scrotum, inner thighs, axilla, and inner arm surfaces. The skin disorder persisted 7 to 10 days (Turner, 1921).
    a) It was concluded that the skin conditions were due to clogging of the sebaceous glands with zinc oxide powder, body debris and bacteria from the skin, with secondary infection of the sebaceous glands (Turner, 1921). Daily bathing generally prevents oxide pox.
    C) LACK OF EFFECT
    1) Zinc oxide is used as a protectant in many topical dermatologic preparations (Budavari, 1996; Bestak et al, 1995) and has been used topically (40% concentration) in other experimental human studies (Derry et al, 1983) without significant adverse dermal effects. It has a low potential for skin irritation, based on animal studies (RTECS , 2001).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) Rabbit skin response in a standardized draize test was reported as mild (RTECS , 2001).

Musculoskeletal

    3.15.1) SUMMARY
    A) Muscle aches, malaise and shivering commonly occur following zinc oxide fume inhalation.
    3.15.2) CLINICAL EFFECTS
    A) MUSCLE PAIN
    1) Myalgia and malaise are common following inhalation of zinc oxide fume and metal fume fever (Rhors, 1957; (Papp, 1968; Mueller & Seger, 1985; Gordon et al, 1992).
    B) CHILL
    1) Intense shivering have been reported as a feature of zinc oxide-induced metal fume fever (Rhors, 1957; (Mueller & Seger, 1985).

Immunologic

    3.19.1) SUMMARY
    A) Leukocytosis or other inflammatory responses have been documented in humans and animals exposed to zinc oxide fume.
    3.19.2) CLINICAL EFFECTS
    A) LEUKOCYTOSIS
    1) Leukocytosis with increased immature polymorphonuclear leukocytes is common following fume inhalation (Rhors, 1957; (Papp, 1968; Fishburn & Zenz, 1969; Mueller & Seger, 1985; Ameille et al, 1992).
    B) LYMPHOCYTOSIS
    1) Increased lymphocytes (predominately CD 8) or increased inflammatory mediators have been measured in bronchoalveolar lavage fluid from humans exposed to zinc oxide fume (Ameille et al, 1992; Blanc et al, 1993; Kuschner et al, 1995).
    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IMMUNE SYSTEM DISORDER
    a) Increased LDH, increased Beta glucuronidase, depressed phagocytosis by macrophages, and increased protein content in bronchoalveolar lavage fluid have been measured from guinea pigs exposed to zinc oxide particles (Conner et al, 1988; Gordon et al, 1992).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    B) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) Specific information concerning the reproductive effects of zinc oxide were not located in the REPROTOX(R) System (1996). The Teratogen Information System reports no epidemiological studies of birth defects in children of mothers who used zinc oxide during pregnancy and no animal studies concerning the teratologic effects of zinc oxide have been published (TERIS , 1996).
    B) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) No teratogenic effects were reported in 2 studies involving dietary zinc oxide administered to adult female rats during pregnancy or administered to male and female rats prior to mating (Thompson et al, 1927; Ketcheson et al, 1969).
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) EMBRYOTOXICITY
    a) Dietary zinc oxide in concentrations of 4000 ppm, given to pregnant rats, caused resorption and fetal death (Venugopal & Luckey, 1978). These effects may have been due to copper deficiency (Hill, 1983).
    b) In another study involving male and female rats, dietary zinc oxide or organic zinc salts at 2 to 38 mg per day prior to mating, during pregnancy or during lactation had no effect on the health of the parents or the offspring (Thompson et al, 1927).
    c) In a study of developmental toxicity in rabbits, administration of zinc oxide on gestation days 8 and 10 actually decreased resorption rates in dams with hypozincemia (Pitt et al, 1997).
    2) STILLBIRTH
    a) Increased incidence of stillbirth was reported in one study involving 0.5% or 0.2% dietary zinc (as zinc oxide) administered to pregnant rats; however, the numbers of viable young per litter were not significantly different from that of a control group fed a basal level (9 ppm) of dietary zinc (Ketcheson et al, 1969). Maternal toxicity was not apparent.
    3) BIRTH WEIGHT SUBNORMAL
    a) Maternal dietary intake of 0.5% zinc (in the form of zinc oxide) was associated with significantly lower 0- and 14-day-old postnatal rat pup weight, and 0.2% dietary zinc to pregnant rat dams was associated with significantly greater birthweight as compared to pups from dams fed a basal level of zinc (9 ppm) during gestation (Ketcheson et al, 1969). Maternal toxicity was not apparent.
    4) WEIGHT INCREASE
    a) Dietary zinc (zinc oxide, 0.2% of diet) was associated with greater maternal weight gain during gestation in rats (Ketcheson et al, 1969).
    5) HEAVY METAL POISONING
    a) TISSUE ZINC, IRON AND COPPER LEVELS -
    1) Body levels of zinc were significantly greater in offspring of female rats fed 0.2% or 0.5% dietary zinc in the form of zinc oxide, as compared to offspring from rats fed a basal level (9 ppm) of zinc (Ketcheson et al, 1969). Maternal levels of zinc were also increased by 0.2% or 0.5% dietary zinc.
    2) Newborns and 14-day-old offspring of rats fed 0.5% dietary zinc (as zinc oxide) during gestation had significantly less total body iron than rats fed either 0.2% zinc or a basal level (9 ppm) of zinc (Ketcheson et al, 1969). Fourteen-day-old offspring from 0.2% or 0.5% zinc-fed dams also had significantly lower liver and total body copper levels than offspring of rats fed a basal level (9 ppm) of zinc.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) GROWTH AND DEVELOPMENT: Dietary zinc oxide or organic zinc salts at 2 to 38 mg per day during lactation in rats had no effect on the health of the dams or the growth and development of the offspring (Thompson et al, 1927).
    b) Metal fume fever may diminish milk production (HSDB).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) Dietary zinc in the form of zinc oxide or zinc salts did not significantly affect the health of male or female rats prior to mating and did not affect fertility (Thompson et al, 1927).
    a) Infertility in rats was reported in one study involving dietary zinc oxide to males and zinc citrate to females prior to mating; however, repeated studies using the same protocol by the same investigators did not report sterility or significant reductions in litter size (Thompson et al, 1927).
    2) When administered to chickens at 6 to 20 g/kg in the diet, it reduced egg production and diminished ovary weights (Jackson, 1986).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS1314-13-2 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.4) ANIMAL STUDIES
    A) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) Zinc compounds were not carcinogenic (except for zinc chromate and zinc chloride) when injected directly into the testes of chickens or rats, a route which is generally not relevant to human exposure. Zinc refinery workers had no increased mortality from any type of cancer, but the number of cases studied was small (Friberg et al, 1986).

Genotoxicity

    A) Zinc compounds generally have not been active in genetic assays. Zinc oxide was negative in salmonella reversion (AMES) assays, with and without activation, and did not alter epithelial DNA synthesis. No abnormalities were found in the micronucleus assay.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor arterial blood gases and chest x-ray in symptomatic patients.
    B) Urinary zinc levels and possibly blood or urine screens for other metal exposures may aid in differential diagnosis.
    C) Pulmonary function testing has been recommended as part of the initial medical examination and on a periodic basis for occupational groups. Persons with pre-existing pulmonary disease may have increased likelihood of adverse effects from zinc oxide fume.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Blood screens for some metals may aid in differential diagnosis if the history suggests exposure to metals other than or in addition to zinc oxide.
    B) ACID/BASE
    1) Monitor arterial blood gases in symptomatic patients with evidence of significant dyspnea or hypoxia.
    4.1.3) URINE
    A) URINARY LEVELS
    1) Monitoring of urinary zinc and other metals may aid in differential diagnosis. Urinary zinc levels may aid in evaluating the extent of zinc absorption from occupational exposure (Martin et al, 1999; US DHHS, 1981).
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) OCCUPATIONAL MEDICAL SURVEILLANCE - Medical surveillance shall be made available for all persons occupationally exposed to zinc oxide. Preplacement medical examinations shall include comprehensive or interim work history and comprehensive or interim medical history (HSDB , 1994). The examination shall give special emphasis to the respiratory tract. Chest x-rays and pulmonary function studies may be considered by the responsible physician (HSDB , 1994).
    b) OSHA RECOMMENDATIONS - The initial medical examination should involve a complete history and physical examination, with emphasis on the respiratory system. A chest x-ray and measurement of FVC and FEV (1 sec) is recommended, as individuals with pre-existing pulmonary disease may be more likely to have adverse pulmonary effects from zinc oxide fume exposure (US DHHS, 1981).
    1) Periodic medical examinations should include the examinations performed during the initial medical examination, except that a chest x-ray will be necessary only if pulmonary function testing indicates a possible problem. Urinary zinc levels may aid in monitoring the extent of zinc absorption (US DHHS, 1981).

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Monitor chest x-ray in symptomatic patients with significant dyspnea, evidence of hypoxia, or a history which suggests exposure to chemicals (e.g, cadmium oxide) in addition to zinc oxide.

Methods

    A) SPECTROSCOPY/SPECTROMETRY
    1) Atomic absorption spectrometry using flame or graphite furnace have been used to determine zinc in serum or urine (Baselt, 2000).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) When atypical signs are present such as an abnormal chest x-ray or pulmonary function tests, the patient should be observed for 24 to 48 hours. Further evaluation may be necessary to rule out pneumonitis caused from exposure to cadmium or other more toxic metals (Rosenstock & Cullen, 1986).

Monitoring

    A) Monitor arterial blood gases and chest x-ray in symptomatic patients.
    B) Urinary zinc levels and possibly blood or urine screens for other metal exposures may aid in differential diagnosis.
    C) Pulmonary function testing has been recommended as part of the initial medical examination and on a periodic basis for occupational groups. Persons with pre-existing pulmonary disease may have increased likelihood of adverse effects from zinc oxide fume.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Zinc oxide inhalation is the primary route of exposure. Ingestion is unlikely; zinc oxide has a low oral toxicity. Gastrointestinal decontamination and activated charcoal should NOT be necessary.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Zinc oxide inhalation is the primary route of exposure. Ingestion is unlikely; zinc oxide has a low oral toxicity. Gastrointestinal decontamination and activated charcoal should NOT be necessary.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Toxicity is low; treatment is symptomatic and supportive. There is no specific antidote.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) SUPPORT
    1) METAL FUME FEVER - In the majority of cases, little treatment is needed beyond supportive care. Bedrest, analgesics, and antipyretics are administered to ease the patient through the 1 to 2 days of symptoms.
    2) MILK AND ANTACIDS - are a frequent layman's treatment for exposure to metal fumes (Anseline, 1972). This has little effect on pulmonary involvement, but may decrease metal irritation in the gastrointestinal tract.
    3) CORTICOSTEROIDS - have OCCASIONALLY been recommended to reduce inflammatory response in patients with serious pulmonary involvement. Anseline (1972) administered 60 mg of prednisone per day which was then tapered over the next week. Armstrong et al (1983) administered one dose of methylprednisolone 250 to 500 mg IV to their patients. Controlled studies demonstrating the benefits of corticosteroids have not been performed.
    4) OXYGEN - Nasal oxygen appears to help the shortness of breath and dyspnea (Armstrong et al, 1983).
    5) CHELATION - Although several studies have documented elevated zinc or copper levels, chelation has not been considered necessary and is not recommended.
    6) OTHER MEASURES - Analgesics and antipyretics should be administered as necessary. Prophylactic antibiotics are not generally recommended.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) SKIN ABSORPTION
    1) OXIDE POX/FOLLICULITIS - Good personal hygiene and the use of clean work clothing with close weave cloth made to fit snugly at the wrists, ankles, and neck are recommended for workers who may be exposed to large amounts of zinc oxide dust. These measures generally prevent oxide pox/folliculitis (Turner, 1921).
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) The minimum lethal human dose to zinc oxide has not been delineated.
    B) Inhalation of air containing zinc oxide at 1 to 34 mg per cubic meter causes metal fume fever and pneumonitis.
    C) Volunteers exposed to 600 mg of zinc per cubic meter (as zinc oxide) developed moderate symptoms with typical febrile reaction and leukocytosis after an exposure duration of 10.5 and 12 minutes.

Minimum Lethal Exposure

    A) SUMMARY
    1) The lowest lethal inhalational dose for humans has not been established (Anon, 1969; RTECS , 2001).
    2) Workplace inhalational exposures to concentrations of 500 milligrams per cubic meter may be hazardous to life or health (NIOSH, 1994).

Maximum Tolerated Exposure

    A) ROUTE OF EXPOSURE
    1) INHALATION
    a) Metal fume fever or pneumonitis generally occurs with minimal inhalation exposures of air containing 1 to 34 mg of zinc oxide per cubic meter (HSDB , 2001) (ACGIH, 1986) (Anon, 1969).
    b) The phenomenon of tolerance can influence the degree of exposure which results in metal fume fever in previously exposed individuals. Exposure to 52 mg zinc oxide fume per cubic meter in one case and 23 mg per cubic meter in another case, resulted in metal fume fever. The next day, exposures to 330 or 610 mg per cubic meter were well-tolerated by case one and two, respectively (Anon, 1969).
    c) McCord (1960) reports concentrations of 14 mg per cubic meter of zinc oxide were well tolerated for exposures of 8 hours; 45 mg per cubic meter were tolerated for 20 minutes. Levels above this were poorly tolerated (McCord, 1960).
    d) The lowest published toxic concentration (TCLo) for humans is 600 mg per cubic meter. The effects were coughing and dyspnea (RTECS , 2001).
    e) THRESHOLD LIMIT VALUE: Time Weighted Average concentration for occupational exposure (average over 8-hour workday, 40-hour workweek) to zinc oxide fume is 5 mg per cubic meter, with a Short Term Exposure Limit of 10 mg per cubic meter (ACGIH, 1995).
    f) LACK OF EFFECT: No symptoms of metal fume fever were reported in 14 human study subjects following inhalational exposure to ultrafine zinc oxide fume concentrations of about 3 to 37 mg of zinc per cubic meter over 15, 30, 60 or 120 minutes (Kuschner et al, 1995). Pulmonary function changes (decreased FEV (1)), and increases of neutrophils and inflammatory mediators in the bronchoalveolar lavage fluid were present 18 to 20 hours after exposure.
    g) In many case reports of metal fume fever, the zinc oxide exposure was not quantitated or exposure to other chemicals also occurred (Papp, 1968; Fishburn & Zenz, 1969; Dula, 1978).
    h) OCCUPATIONAL EXPOSURE/GALVANIZERS: In a retrospective cohort study of 71 galvanizers exposed to zinc oxide and 117 workers not exposed (control group), workers exposed to zinc oxide vapors developed more respiratory symptoms including dyspnea, nose and throat irritation. Obstructive respiratory disease was significantly higher in the exposed group (Aminian et al, 2015).

Workplace Standards

    A) ACGIH TLV Values for CAS1314-13-2 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Zinc oxide
    a) TLV:
    1) TLV-TWA: 2 mg/m(3)
    2) TLV-STEL: 10 mg/m(3)
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: R
    3) Definitions:
    a) R: Respirable fraction; see Appendix C, paragraph C (of TLV booklet).
    c) TLV Basis - Critical Effect(s): Metal fume fever
    d) Molecular Weight: 81.37
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS1314-13-2 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Zinc oxide
    2) REL:
    a) TWA: Dust: 5 mg/m(3); Fume: 5 mg/m(3)
    b) STEL:
    c) Ceiling: Dust: 15 mg/m(3)
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 500 mg/m3
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS1314-13-2 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Zinc oxide
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Zinc oxide
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS1314-13-2 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Zinc oxide fume
    2) Table Z-1 for Zinc oxide fume:
    a) 8-hour TWA:
    1) ppm:
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 5
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed
    3) Listed as: Zinc oxide (Total dust)
    4) Table Z-1 for Zinc oxide (Total dust):
    a) 8-hour TWA:
    1) ppm:
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 15
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed
    5) Listed as: Zinc oxide (Respirable fraction)
    6) Table Z-1 for Zinc oxide (Respirable fraction):
    a) 8-hour TWA:
    1) ppm:
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 5
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: Lewis, 1992 RTECS, 2001
    1) LD50- (ORAL)MOUSE:
    a) 7950 mg/kg
    2) LD50- (INTRAPERITONEAL)RAT:
    a) 240 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

    A) METAL FUME FEVER -
    1) ALLERGY - Earlier investigations proposed that zinc enters the blood circulation and forms a sensitizing complex with plasma proteins which then results in an allergic response or foreign body response upon subsequent exposure (Papp, 1968; Friberg et al, 1986).
    2) INFLAMMATORY MEDIATORS - More recently, metal fume fever has been attributed to the activities of cytokines and other inflammatory mediators released in the lungs after exposure to zinc oxide fume (Blanc et al, 1993; Kuschner et al, 1995).
    3) FUME CHARACTERISTICS - The size of particles is an important factor in producing the illness. Metal fume fever is only associated with freshly formed fume of small diameter (Anon, 1969; Kuschner et al, 1995). As fumes age, the particles become less reactive because they tend to agglomerate or form aggregates and settle out of atmosphere. Particle aggregates are believed to be too large to penetrate the deeper lung tissues and are trapped in the upper respiratory tract (Anon, 1969).

Physicochemical

Physical Characteristics

    A) Zinc oxide is an odorless, white or yellowish (sometimes grayish) powder, with a bitter taste. It may be hexagonal crystals (Budavari, 1996; Lewis, 1997).
    1) When strongly heated, zinc oxide assumes a yellow color which disappears on cooling (HSDB , 2001).
    B) Zinc oxide is opaque to all wavelengths of light (American Medical Association, 1980).

Ph

    A) AMERICAN PROCESS ZINC OXIDE: 6.95 (Budavari, 1996)
    B) FRENCH PROCESS ZINC OXIDE: 7.37 (Budavari, 1996)

Molecular Weight

    A) 81.39 (Budavari, 1996)

References

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