The following information has been extracted from our CHEMINFO database, which also contains hazard control and regulatory information. [More about...] [Sample Record]

Access the complete CHEMINFO database by contacting CCOHS Client Services.

 
SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 327
CCOHS Chemical Name: Zinc oxide

Synonyms:
Calamine
Chinese white
CI 77947
CI Pigment White 4
Flowers of zinc
Zinc monoxide
Zinc white
Zincite
Zincoid
Zinc oxide fume

Chemical Name French: Oxyde de zinc
Chemical Name Spanish: Oxido de cinc

Trade Name(s):
Azo
Protox

CAS Registry Number: 1314-13-2
RTECS Number(s): ZH4810000
EU EINECS/ELINCS Number: 215-222-5
Chemical Family: Zinc and compounds / inorganic zinc compound / metal oxide
Molecular Formula: O-Zn
Structural Formula: ZnO

SECTION 2. DESCRIPTION

Appearance and Odour:
White or yellowish-white, granular, odourless powder or crystals.(4,5,6)

Odour Threshold:
Odourless

Warning Properties:
None - material is odourless.

Composition/Purity:
The purity of zinc oxide depends upon the purity of the source of the zinc vapour, from which zinc oxide is made. Very pure zinc oxide (98-99.99%) is made by the indirect French process. Less pure zinc oxide (98%) is manufactured by the direct American process. Possible impurities, which may be present, can include lead (0.001-0.25 wt %), cadmium (0.001-0.03 wt%), copper (less than 0.005 wt %) and manganese (less than 0.001 wt %) in very small amounts. Oxides containing more than 5 wt % basic lead sulfate are called leaded and are made in the American process from high lead materials, and can contain from 12-35 wt % basic lead sulfate.(13,14) Consult your manufacturer or supplier or Material Safety Data Sheet for information regarding the exact composition of the zinc oxide you are using. The presence of impurities can contribute significantly to the overall hazards of the product.

Uses and Occurrences:
The most important use of zinc oxide is in the rubber industry, where it is used as an activator for vulcanization accelerators and as a reinforcing agent in natural and synthetic rubber. It is also used as a pigment in white paints, coatings and inks; as a mildewstat and acid buffer in paints; in antifouling and anticorrosion paints; as a source of zinc in animal feeds; as a zinc dietary supplement for humans; as a fertilizer supplement; in powders, ointments and pastes in the pharmaceutical and cosmetic industries; in dental cements; in electrostatic copying paper; in photo reproduction processes; in driers and quick-setting cements; in the manufacture of glass, enamels, white glue, matches, and porcelains; in electronics as a semiconductor; as a starting material for many zinc compounds; as a catalyst in organic synthesis; in ceramic glazes; as a colourant for plastics and cosmetics; as a filler; for the removal of hydrogen sulfide, mercaptans, and to some extent chlorine from natural gas; in sulfur cure systems for polyether elastomers; used with additives as a voltage-dependent resistor; and as a reagent in analytical chemistry.(4,5,13,14)
Occupational exposure to zinc oxide may occur during its manufacture (dust), or through its formation as a fume when subjecting zinc or zinc-containing alloys to elevated temperatures.(12)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
White or yellowish-white, granular, odourless powder or crystals. Does not burn or support combustion. Zinc oxide fumes may cause flu-like symptoms (e.g. fever, shivering, fatigue, muscle aches, headache, cough, shortness of breath, abdominal pain and chest discomfort). The dust is essentially non-toxic following short-term exposure.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Zinc oxide dust is practically non-toxic if inhaled, except for a few reported cases of metal fume fever, which occurred following exposure to fine, respirable-size dust. In general, high concentrations of dust can cause coughing and mild, temporary irritation.

Zinc oxide fume particles are small (0.2-1 micrometres) (23) and can remain airborne for long periods of time. Inhalation of zinc oxide fumes (e.g. from welding on galvanized steel) can cause a delayed flu-like illness commonly called metal fume fever.(1,3,22,23) Metal fume fever symptoms are typically experienced 4-8 hours after exposure to the fumes. Symptoms include thirst, a metallic taste in the mouth, fever and shivering, often with muscle aches, headache, cough, shortness of breath, abdominal pain and chest discomfort. These symptoms typically clear up 24-48 hours after the end of the exposure and recovery is complete. At the time of exposure, there may be no symptoms experienced or there may be throat irritation and a dry cough.(1,3,12,23) Therefore, the warning properties are not sufficient to alert the worker that they are being exposed. There have been reports of metal fume fever cases following exposures to concentrations as low as 2.5 mg/m3.(3,12,24,50)
Freshly formed fumes have smaller particle size and are more able to penetrate into the lower lung. They are believed to be better capable of causing metal fume fever than "aged" (aggregated) fumes or dusts, which have larger particle size. Although metal fume fever reactions following exposure to the dust are very rare, they have been reported.(25,26) Therefore, both types of particulate, if in a small enough in size, are considered capable of causing metal fume fever.(23,27)
Some workers may develop a tolerance after repeated daily exposure to zinc oxide fume, with the result that no metal fume fever symptoms are experienced. This tolerance is accompanied by reduced lung inflammation.(55) However, the tolerance is quickly lost after short periods away from work (e.g. weekends).(3,23)
Zinc oxide fumes can irritate the throat and lungs. Individuals with pre-existing asthma are more sensitive to these irritating effects.(23)

Skin Contact:
Zinc oxide is not expected to be irritating to the skin, based on human and animal evidence. Zinc oxide is used in cosmetic and skin treatment preparations, such as calamine lotion.(1)
In a study with 15 male and female volunteers aged 22-54 years, application of a 25% zinc oxide patch for 48 hours caused no signs of irritation.(56) Daily application of 100 micrograms of zinc oxide powder, under a sealed chamber, to damaged (lightly scarified) skin for 3 days caused mild irritation in 5 volunteers (score less than 0.4/4).(57)
Zinc oxide can be absorbed into the body through intact skin, but this route of exposure is not expected to produce harmful effects. The amount absorbed depends on a number of factors including the concentration of zinc already in the bloodstream, the pH of the skin, and the amount of zinc oxide applied.(1,12)

Eye Contact:
Zinc oxide may cause mild irritation, based on unconfirmed animal information. In general, dusts may cause tearing, blinking and mild, temporary pain as the solid material is rinsed from the eye by tears.
There is no human or animal information suggesting that zinc oxide fume is irritating to the eyes.

Ingestion:
Zinc oxide is not expected to be harmful if ingested, based on an unconfirmed animal toxicity value and on studies with other zinc compounds. The most common symptoms of zinc toxicity include nausea, vomiting, abdominal pain, diarrhea and, in severe cases, vomiting of blood.(1,22,29) Zinc is an essential nutrient to humans and animals. Both zinc deficiency and overexposure to zinc by ingestion have been associated with toxic effects.(1) Ingestion is not a typical route of occupational exposure.

Effects of Long-Term (Chronic) Exposure

Historically, harmful effects have been observed in people occupationally exposed to zinc dust and/or zinc oxide dust or fumes. However, these effects have been attributed to contaminants that were present in the zinc (mainly arsenic and lead) and not to zinc itself.(12,29,31) For more information on the health effects of these contaminants, refer to the CHEMINFO reviews on these metals.

Harmful effects on the lungs are reported in studies of welders exposed to welding fumes over a prolonged period. However, no specific conclusions can be drawn for zinc oxide, as exposures were to a mixture of chemicals.

In general, zinc is considered a low toxicity metal. Zinc is a very important trace element for humans. It is an important constituent of many enzymes and other proteins and has an essential role in many processes of normal growth and development. A number of reversible harmful effects (red and white blood cell deficiencies (anemia and leukopenia), headache and stomach symptoms, and copper deficiency) can result from long-term ingestion of zinc compounds (to doses as low as 2 mg/kg/day as zinc), based on non-occupational human reports and animal information.(1,22,29,30)

Lungs/Respiratory System:
Respiratory disease and/or harmful effects on the lungs (e.g. bronchitis, altered lung function) have been observed in some, but not all, studies of welders exposed to various types of welding fumes over a number of years.(32,33) In a study of 607 shipyard workers, there was a significant association between breathlessness in welders or caulker/burners who smoked. After correcting the data for age and smoking, the occurrence of wheeze was related to welding fume exposure, and was more common in workers with previous metal fume fever.(58) In another relatively small study, sore throat and frequent coughing were reported significantly more often and some significant lung function changes were observed in steel manufacturing workers exposed to zinc oxide fumes and other airborne particulate ranging from 1-23 mg/m3, with an average of 39% particles in the respirable size range.(28) However, because of the mixed exposures in these studies, no specific conclusions can be drawn about the potential long-term respiratory effects of zinc oxide fume exposure.

Zinc oxide dust is expected to cause only minor, reversible effects on the lungs.(12) In general, long-term exposures to high concentrations of dust may cause increased mucous flow in the nose and respiratory system airways.(3) This condition usually disappears when exposure stops.

Respiratory Sensitization:
It is not possible to conclude that zinc or zinc oxide is a respiratory sensitizer.
A small number of cases (five) of asthma, increased bronchial responsiveness or a generalized allergic reaction have been associated with zinc oxide following occupational exposure to fumes generated by soldering or welding galvanized metal.(36,37,38,39) In many cases, symptoms of metal fume fever were also noted.(36,37,38,39) In two cases, there did not appear to be a history of allergies.(37,38) In another case, allergic history was not discussed.(36) In two cases, there was a personal or family history of allergies.(37,39) Galvanized metal is coated with zinc. However, the fumes generated from soldering or welding galvanized zinc do not just include zinc oxide, but generally consists of a number of different metals, depending on the composition of the underlying metal. In addition, there may be fluxes, paints or other coatings present, which could thermally decompose, adding to the chemical mixture to which the worker is exposed. It is, therefore, not possible to solely attribute these respiratory effects to zinc or zinc oxide exposure.
A more recent study evaluated the respiratory health of 6 welders who were experiencing increased bronchial reactivity. In a welding challenge test, 3/6 developed bronchial reactions. One reacted to fumes from mild and stainless steel; two reacted to fumes from galvanized metal and one of these welders also reacted to mild steel fumes. It was concluded that the reaction was due to irritation rather than a sensitization reaction. Immunological tests (patch tests and inhalation challenge tests with zinc salts) on the two welders who developed bronchoconstriction to galvanized metal welding were negative.(34)

Skin:
Long-term exposure does not cause harmful effects on the skin, based on limited human information.
In a historical study, a skin reaction (itchy eruptions) was observed among workers exposed to zinc oxide dust during bagging or packing. However, the reaction was related to general dust exposure and lack of adequate personal hygiene, not specifically to zinc oxide.(35)

Carcinogenicity:

The available information does not suggest that zinc oxide is carcinogenic.
In a study of 978 men, who worked in a zinc refinery for at least 1 year between 1946 and 1975, the causes of death were examined for the 73 men who had died. There were no increases in mortality from cancer.(59) However, firm conclusions cannot be drawn because numbers were small. There is also minimal exposure to arsenic and antimony reported.
No conclusions can be drawn from a limited study where an association was found between living near an old lead-zinc mining and smelting area and deaths from lung cancer.(1,22) Confounding variables were not adequately controlled in this study.
The International Agency for Research on Cancer (IARC) has concluded there is limited evidence that occupational exposure to welding fumes and gases is carcinogenic to humans (Group 2B).(40) Welding fumes contain many different metallic and chemical compounds, including zinc oxide. This conclusion does not specifically apply to zinc oxide exposures. The potential carcinogenicity of zinc oxide to experimental animals has not been studied.

The International Agency for Research on Cancer (IARC) has not evaluated the carcinogenicity of this chemical.

The American Conference of Governmental Industrial Hygienists (ACGIH) has not assigned a carcinogenicity designation to this chemical.

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Teratogenicity and Embryotoxicity:
In general, zinc compounds are not known to cause developmental effects in the absence of maternal toxicity. There is no specific human information available for zinc oxide. In animal studies, harmful effects were observed in the offspring of rats in one study, which used high doses and did not evaluate maternal toxicity, and in another very limited study.

Reproductive Toxicity:
There is no human information available for zinc oxide. The only animal study located for zinc oxide did not show reproductive effects. In general, zinc compounds are not known to cause reproductive toxicity.

Mutagenicity:
It is not possible to conclude that zinc oxide is mutagenic, based on the limited information available. Mutagenic effects were observed in tests of blood cells of workers employed in zinc industries. However, because these workers are also exposed to compounds such as lead and cadmium, no specific conclusions can be drawn about zinc oxide.(41) Urine from workers in the rubber industry, who were occupationally exposed to several chemicals including zinc oxide, did not cause gene mutations in bacteria.(54) A positive result was obtained in a limited study using rats. An unconfirmed positive result was obtained in cultured mammalian cells and a negative result was obtained in bacteria.

Toxicologically Synergistic Materials:
When zinc is absorbed into the body, it interacts with other trace elements, especially copper. It also competes with other metals, such as lead or mercury, which may sometimes reduce the harmful effects of these metals.

Potential for Accumulation:
Zinc can accumulate in the body. Intestinal absorption of zinc can vary widely following oral administration (in animals ranges of less than 10 to over 90% are reported) and is influenced by age and a number of dietary factors. Zinc is stored mainly in the muscle and bone, and also in the prostate, liver, gastrointestinal tract, kidney, skin, lung, brain, heart and pancreas.(60,61) In humans ingesting normal amounts of zinc, the reported half-lives have been from 100-500 days.(60) The body regulates the amount of zinc stored by decreasing absorption and increasing excretion when intake is increased.(30) It is excreted mainly in the feces.(60)


SECTION 4. FIRST AID MEASURES

Inhalation:
If symptoms are experienced, immediately remove source of contamination or move victim to fresh air. Obtain medical advice. NOTE: Metal fume fever may develop 4-8 hours after exposure. If symptoms of metal fume fever (flu-like symptoms) develop, immediately obtain medical attention.

Skin Contact:
Remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Quickly and gently blot or brush away excess chemical. Wash gently and thoroughly with lukewarm, gently flowing water and non-abrasive soap for 5 minutes. If irritation persists, obtain medical advice.

Eye Contact:
Do not allow victim to rub eye(s). Let the eye(s) water naturally for a few minutes. Have victim look right and left, and then up and down. If particle/dust does not dislodge, flush with lukewarm, gently flowing water for 5 minutes or until particle/dust is removed, while holding the eyelid(s) open. If irritation persists, obtain medical attention. DO NOT attempt to manually remove anything stuck to eye(s).

Ingestion:
If irritation or discomfort occur, obtain medical advice.

First Aid Comments:
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
Not combustible (does not burn).(17)

Lower Flammable (Explosive) Limit (LFL/LEL):
Not applicable

Upper Flammable (Explosive) Limit (UFL/UEL):
Not applicable

Autoignition (Ignition) Temperature:
Not applicable

Sensitivity to Mechanical Impact:
Probably not sensitive. Stable material.

Sensitivity to Static Charge:
Zinc oxide is unlikely to accumulate static charge. Since it does not burn, it will not be ignited by a static discharge.

Electrical Conductivity:
Not available

Minimum Ignition Energy:
Not applicable

Combustion and Thermal Decomposition Products:
No harmful chemicals are expected to be formed.

Flammable Properties:

Extinguishing Media:
Zinc oxide is not combustible (does not burn). Use extinguishing media suitable for the surrounding fire.

Fire Fighting Instructions:
Zinc oxide does not burn or support combustion and is not a fire hazard. No special firefighting procedures are required.

Protection of Fire Fighters:
Protect firefighters appropriately for the chemical(s) and the combustion and decompostion products of the chemical(s) burning. If there is zinc oxide dust in the air then firefighters may enter the area if positive pressure self-contained breathing apparatus (NIOSH approved or equivalent) and Bunker Gear is worn.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Comments:
NFPA has no listing for this chemical in Codes 49 or 325.


SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 81.39

Conversion Factor:
Not applicable

Physical State: Solid
Melting Point: 1975 deg C (3587 deg F) (3,13,42)
Boiling Point: Sublimes at normal pressure.(5)
Relative Density (Specific Gravity): 5.607 at 20 deg C (water = 1) (5)
Solubility in Water: Practically insoluble (0.16 mg/100 mL at 29 deg C) (3,4,5,12)
Solubility in Other Liquids: Soluble in dilute acetic or mineral acids, ammonia, ammonium carbonate and fixed alkali hydroxide solutions.(5) Insoluble in ethanol.(3,12,17)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 1.53 (estimated) (43)
pH Value: 6.95 (American Process); 7.37 (French Process) (5)
Viscosity-Dynamic: Not applicable
Surface Tension: Not applicable
Vapour Density: Not applicable
Vapour Pressure: Not applicable.
Saturation Vapour Concentration: Not applicable
Evaporation Rate: Not applicable

SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable.

Hazardous Polymerization:
Does not occur.

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


CHLORINATED RUBBER - reacts violently or explosively with zinc oxide powder at about 216 deg C.(44,45)
MAGNESIUM - can react explosively with zinc oxide when heated.(44,45)
ALUMINUM, HEXACHLOROETHANE - may react violently.(44)
STRONG ACIDS (e.g. hydrochloric acid or sulfuric acid) - may react vigorously.(4)

Hazardous Decomposition Products:
None expected.

Conditions to Avoid:
Generation of dust.

Corrosivity to Metals:
Zinc oxide is not corrosive to aluminum and silver.(46) It is probably not corrosive to other common metals.

Corrosivity to Non-Metals:
Zinc oxide does not attack nylon, polyethylene plus fibreglass, polypropylene and styrene-acrylonitrile.(47)


SECTION 11. TOXICOLOGICAL INFORMATION

LC50 (mouse): 2500 mg/m3 (duration unspecified; particle size unspecified) (7,8-unconfirmed)

LD50 (oral, mouse): 7950 mg/kg (8, unconfirmed)

Eye Irritation:

Unconfirmed information indicates that zinc oxide is a mild irritant.

Mild irritation was observed in rabbits following administration of 500 mg for 24 hours.(8, unconfirmed)

Skin Irritation:

Zinc oxide caused no irritation following prolonged contact (5 days). An unconfirmed study reports mild irritation.

No signs of irritation were observed in mice, rabbits and guinea pigs following application of zinc oxide (20% suspension in a non-irritating liquid (Tween 80)) for 5 days (minimum purity of zinc oxide was 98%).(9) Mild irritation was observed in rabbits following application of 500 mg for 24 hours.(8, unconfirmed)

Effects of Short-Term (Acute) Exposure:

Inflammatory effects and changes in lung function were observed in animals exposed to freshly formed, ultrafine zinc oxide particles at concentrations as low as 1.0 mg/m3.

Inhalation:
Guinea pigs are uniquely susceptible to functional impairment of the peripheral airways due to physiological differences (thicker airway smooth muscle and reduced alveolar surface area).(54) The only significant effect in 23 male guinea pigs exposed to 0.91 mg/m3 zinc oxide aerosol (ultrafine; 0.05 micrometres) for 1 hour was a decrease in lung compliance, a minor physiological response, which persisted and progressed for 2 hours after exposure. Repeating this experiment with 7 male guinea pigs did not show a significant initial reduction in compliance, but the effect still progressed following exposure, becoming statistically significant. The authors suggest that this progression may relate to the persistence of the deposited zinc oxide particles.(15) Male guinea pigs were given nose-only exposures to 0, 2.3, 5.9 or 12.1 mg/m3 freshly generated zinc oxide particles (ultrafine; projected diameter 0.05 micrometres) for 1-3 days (3 hrs/d). Dose-dependent harmful effects on the lungs (functional changes and inflammation, including edema) were observed at 5.9 and 12.1 mg/m3.(10) In two other studies, male guinea pigs exposed nose-only to zinc oxide particles (ultrafine; median diameter 0.05 micrometres) at concentrations of 7 mg/m3 for 5 days (3 hrs/d), or 5 mg/m3 for 6 days (3 hrs/d) experienced significant harmful effects on lung function. Reversibility of these effects was not assessed. At 2.7 mg/m3 for 5 days, there were no effects noted.(11,49) A single 3-hour exposure of male guinea pigs to 7.8 mg/m3 (ultrafine; projected diameter 0.05 micrometres) had no effect on lung function.(48) Rats and guinea pigs were exposed nose-only for 3 hours and rabbits for 2 hours to 0, 2.5 or 5.0 mg/m3 of freshly generated zinc oxide particles (ultrafine; median diameter 0.06 micrometres). In guinea pigs and rats, there were dose-dependent, significant effects in the lungs indicating acute inflammatory changes at both 2.5 and 5 mg/m3. No effects were seen in rabbits.(50) Male mice were exposed to 1.0 mg/m3 zinc oxide particles (0.3 micrometres) for 1, 3 or 5 days (3 hrs/day). Mice exposed once had a significant increase in an indicator of lung inflammation (polymorphonuclear leukocyte levels in lung fluid), which decreased after 3 and 5 exposures indicating a developed tolerance. An indicator of lung permeability (protein in lung fluid) was significantly increased in all exposed mice, with the response increasing with the number of days exposed. Detailed examination of the tissues showed an increase in lung injury with the number of days exposed.(51)

Ingestion:
In a study, which is limited by the small number of animals used, ferrets (3-4/group) were fed 1500 or 3000 ppm zinc as zinc oxide (AR grade) in their diet for 7-21 days. (Approximate doses were 420 or 840 mg/kg/day, as zinc; 525 or 1050 mg/kg/day, as zinc oxide). Ingestion of 3000 ppm for 12 days, or 1500 ppm for up to 21 days, resulted in large decreases in body weight and food consumption, intestinal bleeding, anemia, harmful effects on the liver and kidneys, and pancreatitis. The authors suggest that ferrets are more susceptible to an excess of dietary zinc than other species studied.(16) Minor nerve degeneration and enzyme changes were observed in rats intubated with 100 mg of zinc oxide (approximate dose 481 mg/kg/day as zinc; 600 mg/kg/day as zinc oxide) for 10 days.(52) No statistical evaluation of the data was reported.

Effects of Long-Term (Chronic) Exposure:

Ingestion:
In a study, which is reported by abstract, male rats were fed 18.6 (control), 340, 982, 3228, or 6448 ppm zinc oxide in the diet for 90 days. (Approximate doses were 0.8, 16, 47, 155 or 311 mg/kg/day as zinc; 1, 20, 59, 193, or 387 mg/kg/day as zinc oxide). Significant changes in one behavioural test (impaired passive-avoidance behaviour) were observed at 193, but not at 387 mg/kg/day.(18) There are no further details available. In a study, which is limited by the small number of animals used, no significant effects were observed in 3 ferrets fed 500 ppm zinc, as zinc oxide, in their diet for up to 191 days. (Approximate dose 140 mg/kg/day as zinc; or 175 1050 mg/kg/day as zinc oxide).(16)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
It is not possible to draw firm conclusions regarding the potential developmental toxicity of zinc oxide, based on the limited information available. Harmful effects were observed in the offspring of rats in one study, which used high doses and did not evaluate maternal toxicity, and in another very limited study.
Female rats (10-20/group) were fed 0.2 or 0.4% zinc, as zinc oxide, in the diet starting 21 days before mating, or at day 0 of pregnancy and continuing throughout the pregnancy. (Approximate doses were 100 or 200 mg/kg/day, as zinc; 125 or 250 mg/kg/day, as zinc oxide). At 250 mg/kg/day zinc oxide, with exposure starting 21 days before pregnancy, all embryos were resorbed. When exposure to 250 mg/kg/day started at the beginning of pregnancy, a significant reduction in fetal weights and a non-significant increase in resorptions were observed. There were no effects reported at 125 mg/kg/day. No malformations were noted in the offspring at any dose.(19) Maternal toxicity was not evaluated. In a limited study, female rats (10/group) were fed 0.2 or 0.5% zinc, as zinc oxide, in the diet from day 1 of pregnancy to day 14 of lactation. (Approximate doses were 100 or 250 mg/kg/day as zinc; or 125 or 313 mg/kg/day as zinc oxide). There were no effects on maternal body weight, or of the viable young/litter. No external malformations were noted. At the high dose, 2/10 mothers had stillborn litters. At 125 mg/kg/day, there were 4 stillborn pups. No stillborn animals were reported for the controls.(20) This study is limited by factors such as the incomplete assessment of maternal toxicity, statistical evaluation of the data was not reported and the relatively small number of animals/group.

Reproductive Toxicity:
The only study available did not show reproductive effects.
Female rats (10-20/group) fed 0.2 or 0.4% zinc oxide starting 21 days before mating had normal fertility cycles and normal mating. (Approximate doses were 100 or 200 mg/kg/day as zinc; 125 or 250 mg/kg/day as zinc oxide).(19)

Mutagenicity:
It is not possible to conclude that zinc oxide is mutagenic, based on the information available. A positive result was obtained in a limited study using rats. An unconfirmed positive result was obtained in cultured mammalian cells and a negative result was obtained in bacteria.
Rats exposed continuously by inhalation to 0.1 or 0.5 mg/m3 zinc oxide aerosol (particle size and purity not reported) for 5 months showed a significant increase in numerical, but not structural, chromosome aberrations in bone marrow cells.(21) This study is limited by inadequate reporting of details, such as the number of animals used, and the numerical aberrations observed (described only as hyperdiploid cells).
In a study, which is not available in English, positive results (unscheduled DNA synthesis, sister chromatid exchange) were obtained in mammalian cells.(53, unconfirmed) A negative result (gene mutation) was obtained in bacteria, with and without metabolic activation.(54) Negative results are also reported for bacteria in standard Ames tests, with and without metabolic activation.(12, unconfirmed)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Agency for Toxic Substances and Disease Registry. Toxicological profile for zinc (Update). TP-93/15. Public Health Service, US Department of Human Services, May 1994
(2) Zinc oxide. In: NIOSH pocket guide to chemical hazards. National Institute for Occupational Safety and Health, June, 1997
(3) Jakubowski, M. Zinc and cadmium: zinc oxide. In: Patty's Industrial Hygiene and Toxicology. Edited by G.D. Clayton, et al. 5th ed. Vol. 2. Toxicological issues related to metals; neurotoxicology and radiation; metal and metal compounds. John Wiley & Sons, 2001. p. 269-276
(4) US National Library of Medicine. Zinc oxide. Last revision date: 2002-02-13. In: Hazardous Substances Data Bank (HSDB). CHEMpendium. [CD-ROM]. Canadian Centre for Occupational Health and Safety (CCOHS). Also available at: <ccinfoweb.ccohs.ca/chempendium/search.html>
(5) Zinc oxide. The Merck index: an encyclopedia of chemicals, drugs and biologicals. Edited by M.J. O'Neil, et al. 13th ed. Merck and Company, 2001. p. 1811
(6) Zinc oxide, 99.999%. Sigma-Aldrich Website. Sigma-Aldrich Corporation. MSDS. Date updated: 2002-07. Available at: <www.sigmaaldrich.com/suite7/homepage/New_Site_Redirect.html> (Password required)
(7) Takahashi, A. Problems of hygiene maintenance for food coming into contact with rubber and plastics products. International Polymer Science and Technology. Vol. 3, no. 1 (1976). p. 93-105
(8) National Institute for Occupational Safety and Health (NIOSH). Zinc oxide. Last updated: 2002-10. In: Registry of Toxic Effects of Chemical Substances (RTECS(R)). [CD-ROM]. Canadian Centre for Occupational Health and Safety (CCOHS). Also available at: <ccinfoweb.ccohs.ca/rtecs/search.html>
(9) Lansdown, A.B.G. Interspecies variations in response to topical application of selected zinc compounds. Food and Chemical Toxicology. Vol. 29, no. 1 (1991). p. 57-64
(10) Conner, M.W., et al. Lung injury in guinea pigs caused by multiple exposures to ultrafine zinc oxide: changes in pulmonary lavage fluid. Journal of Toxicology and Environmental Health. Vol. 25, no. 1 (1988). p. 57-69
(11) Lam, H.F., et al. Functional and morphologic changes in the lungs of guinea pigs exposed to freshly generated ultrafine zinc oxide. Toxicology and Applied Pharmacology. Vol. 78 (1985). p. 29-38
(12) American Conference of Governmental Industrial Hygienists (ACGIH). Zinc oxide. In: Documentation of the Threshold Limit Values and Biological Exposure Indices. ACGIH, 2003. p. 1-5
(13) Goodwin, F.E.. Zinc compounds: zinc oxide. In: Kirk-Othmer encyclopedia of chemical technology. 4th ed. Vol. 25. John Wiley and Sons, 1998. p. 840-850
(14) Heine, H, et al. Pigments, inorganic: zinc oxide (zinc white). In: Ullmann's encyclopedia of industrial chemistry. 5th completely revised ed. Vol. A 20. VCH Publishers, 1992. p. 294-297
(15) Amdur, M.O., et al. Respiratory response of guinea pigs to zinc oxide fume. American Industrial Hygiene Association Journal. Vol. 43, no. 12 (1982). p. 887-889
(16) Straube, E.F., et al. Zinc toxicity in the ferret. Journal of Comparative Pathology. Vol. 90 (1980). p. 355-361
(17) Lewis, Sr., R.J., ed. Zinc oxide. Hawley's condensed chemical dictionary. [CD-ROM]. 14th ed. John Wiley and Sons, Inc., 2002
(18) Komiskey, H.L., et al. Influence of subchronic zinc oxide on a passive-avoidance response in male rats. [Abstract]. Toxicologist. Vol. 36, no. 1, pt. 2 (1997). p. 183
(19) Schlicker, S.A., et al. Maternal dietary zinc, and development and zinc, iron, and copper content of the rat fetus. Journal of Nutrition. Vol. 95 (1968). p. 287-294
(20) Ketcheson, M.R., et al. Relationship of maternal dietary zinc during gestation and lactation to development and zinc, iron and copper content of the postnatal rat. Journal of Nutrition. Vol. 98 (1969). p. 303-311
(21) Voroshilin, S.I., et al. Cytogenetic effects of inorganic compounds of tungsten, zinc, cadmium and cobalt on animal and human cells. [Translation]. Tsitologiya i Genetika. Vol. 21, no. 3 (1978). p. 241-143 (NIOSHTIC Control Number: 00226594)
(22) Barceloux, D.G. Zinc. Clinical Toxicology. Vol. 37, no. 2 (1999). p. 279-292
(23) Rask-Andersen, A. Inhalation fever. In: Occupational and environmental respiratory disease. Edited by P. Harber, et al. Mosby-Year Book Inc., 1996. p. 243-258
(24) Fine, J.M., et al. Metal fume fever: characteristics of clinical and plasma IL-6 responses in controlled human exposures to zinc oxide fume at and below the threshold limit value. Journal of Occupational and Environmental Medicine. Vol. 39, no. 8 (Aug. 1997). p. 722-726
(25) Drinker, P., et al. Metal fume fever: III. The effects of inhaling magnesium oxide fume. Journal of Industrial Hygiene. Vol. 9, no. 5 (May 1927). p. 187-192
(26) Rohrs, L.C. Metal-fume fever from inhaling zinc oxide. AMA Archives of Industrial Health. Vol. 16 (1957). p. 42-47
(27) Blanc, P., et al. The lung in metal fume fever. Seminars in Respiratory Medicine. Vol. 14, no. 3 (May 1993). p. 212-225
(28) Pasker, H.G., et al. Short-term ventilatory effects in workers exposed to fumes containing zinc oxide: comparison of forced oscillation technique with spirometry. European Respiratory Journal. Vol. 10, no. 7 (July 1997). p. 1523-1529
(29) Fisher, D. Zinc. In: Hazardous Materials Toxicology, Clinical Principles of Environmental Health. Edited by J.B. Sullivan, Jr., et al. Williams and Wilkins, 1992. p. 865-868
(30) Walsh, C.T., et al. Zinc: health effects and research priorities for the 1990s. Environmental Health Perspectives. Vol. 102, suppl. 2 (1994). p. 5-46
(31) Batchelor, R. P., et al. A clinical and laboratory investigation of the effect of metallic zinc, of zinc oxide and of zinc sulphide upon the health of workmen. Journal of Industrial Hygiene. Vol. 8, no. 8 (1926). p. 322-363
(32) Liss, G.M. Health effects of welding and cutting fume: an update. Occupational Disease Panel, Ontario Ministry of Labour, 1996
(33) Sferlazza, S.J., et al. The respiratory health of welders. American Review of Respiratory Disease. Vol. 143, no. 5 (1991). p. 1134-1148
(34) Contreras, G.R., et al. Bronchial reactions to exposure to welding fumes. Occupational and Environmental Medicine. Vol. 54, no. 11 (1997). p. 836-839
(35) Turner, J.A. An occupational dermatoconiosis among zinc oxide workers. Public Health Reports. Vol. 36 (Nov. 1921). p. 2727-2732
(36) Ameille, J., et al. Occupational hypersensitivity pneumonitis in a smelter exposed to zinc fumes. Chest. Vol. 101, no. 3 (Mar. 1992). p. 862-863
(37) Malo, J-L., et al. Occupational asthma due to fumes of galvanized metal. Chest. Vol. 92, no. 2 (Aug. 1987). p. 6375-377
(38) Kawane, H. et al. Metal fume fever and asthma [letter]. Chest. Vol. 93, no. 5 (May 1988). p. 1116-1117
(39) Farrell, F.J. Angioedema and urticaria as acute and late phase reactions to zinc fume exposure, with associated metal fume fever-like symptoms. American Journal of Industrial Medicine. Vol. 12, no. 3 (1987). p. 331-337
(40) International Agency for Research on Cancer (IARC). Welding: welding fumes and gases. In: IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 49. Chromium, nickel and welding. World Health Organization, 1990. p. 455-507
(41) Leonard, A., et al. Mutagenicity, carcinogenicity and teratogenicity of zinc. Mutation Research. Vol. 168, no. 3 (1986). p. 343-353
(42) Lide, D.R., ed. Handbook of chemistry and physics. [CD-ROM]. Chapman and Hall/CRCnetBASE 1999
(43) Syracuse Research Corporation. Interactive LogKow (KowWin) Database Demo. Date unknown. Available at: <syrres.com/esc/kowdemo.htm>
(44) Urben, P.G., ed. Bretherick's reactive chemical hazards database. [CD-ROM]. 6th ed. Version 3.0. Butterworth-Heinemann Ltd., 1999
(45) Fire protection guide to hazardous materials. 13th ed. Edited by A.B. Spencer, et al. National Fire Protection Association, 2002. NFPA 491
(46) Corrosion data survey: metals section. 6th ed. National Association of Corrosion Engineers, 1985. p. 154-3
(47) Corrosion data survey: nonmetals section. 5th ed. National Association of Corrosion Engineers, 1983. p. 397 (9-13)
(48) Lam, H.F., et al. Changes in lung volumes and diffusing capacity in guinea pigs exposed to a combination of sulfur dioxide and submicron zinc oxide mixed in a humidified furnace. Toxicology and Applied Pharmacology. Vol. 66, no. 3 (1982). p. 427-433
(49) Lam, H.F., et al. Pulmonary function of guinea pigs exposed to freshly generated ultrafine zinc oxide with and without spike concentrations. American Industrial Hygiene Association Journal. Vol. 49, no. 7 (1988). p. 333-341
(50) Gordon, T., et al. Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats and rabbits. American Industrial Hygiene Association Journal. Vol. 53, no. 8 (1992). p. 503-509
(51) Wesselkamper, S.C., et al. Development of pulmonary tolerance in mice exposed to zinc oxide fumes. Toxicological Sciences. Vol. 60, no. 1 (Mar. 2001). p. 144-151
(52) Kozik, M.B., et al. Morphological and histochemical changes occurring in the brain of rats fed large doses of zinc oxide. Folia Histochemica et Cytochemica (Krakow). Vol. 18, no. 3 (1980). p. 201-206
(53) Suzuki, H. Assessment of the carcinogenic hazard of 6 substances used in dental practices. II. Morphological transformation, DNA damage and sister chromatid exchanges in cultured Syrian hamster embryo cells induced by formocresol, iodoform, zinc oxide, choroform, chloramphenicol and tetracycline hydrochloride. (Japanese). Shigaku. Vol. 74, no. 6 (Feb. 1987). p. 1385-1403
(54) Crebelli, R., et al. Mutagenicity studies in a tyre plant: in vitro activity of worker's concentrates and raw materials. British Journal of Industrial Medicine. Vol. 42, no. 7 (1985). p. 481-487
(55) Fine, J.M., et al. Characterization of clinical tolerance to inhaled zinc oxide in naïve subjects and sheet metal workers. Journal of Occupational and Environmental Medicine. Vol. 42, no. 11 (Nov. 2000). p. 1085-1091
(56) Agren, M.S., Percutaneous absorption of zinc from zinc oxide applied topically to intact skin in man. Dermatologica. Vol. 180, no. 1 (1990). p. 36-39
(57) Frosch, P.J., et al. The chamber-scarification test for assessing irritancy of topically applied substances. In: Cutaneous Toxicity, Proceedings of the 3rd Conference, 1976. Edited by V.A. Drill et al. Academic Press Inc., 1977. p. 127-154
(58) Cotes, J.E., et al. Respiratory symptoms and impairment in shipyard welders and caulker/burners. British Journal of Industrial Medicine. Vol. 46 (1989). p. 292-301
(59) Logue, J.N., et al. A historical prospective mortality study of workers in copper and zinc refineries. Journal of Occupational Medicine. Vol. 24, no. 5 (May 1982). p. 398-408
(60) Elindar, C.-G. Zinc. In: Handbook on the toxicology of metals. 2nd ed. Vol. II: Specific metals. Edited by L. Friberg, et al. Elsevier Science Publishers, 1986. p. 664-679
(61) Cleven, R.F.M.J., et al. Integrated criteria document zinc. National Institute of Public Health and Environmental Protection Bilthoven. Aug. 1993
(62) Occupational Safety and Health Administration (OSHA). Zinc oxide. In: OSHA Analytical Methods Manual. Revision Date: Mar. 1989. Available at: <www.osha-slc.gov/dts/sltc/methods/toc>
(63) Occupational Safety and Health Administration (OSHA). Metal and Metalloid Particulates (including zinc). In: OSHA Analytical Methods Manual. Revision Date: Feb. 2002. Available at: <www.osha-slc.gov/dts/sltc/methods/toc>
(64) Occupational Safety and Health Administration (OSHA). Metal and Metalloid Particulates (including zinc). In: OSHA Analytical Methods Manual. Revision Date: Sept. 2002. Available at: <www.osha-slc.gov/dts/sltc/methods/toc>
(65) Occupational Safety and Health Administration (OSHA). Metal and Metalloid Particulates from Solder Operations. In: OSHA Analytical Methods Manual. Revision Date: May 1991. Available at: <www.osha-slc.gov/dts/sltc/methods/toc>
(66) Occupational Safety and Health Administration (OSHA). Gravimetric Analysis. In: OSHA Analytical Methods Manual. Revision Date: Mar. 2003. Available at: <www.osha-slc.gov/dts/sltc/methods/toc>
(67) National Institute for Occupational Safety and Health (NIOSH). Zinc Oxide. In: NIOSH Manual of Analytical Methods (NMAM(R)). 4th ed. Edited by M.E. Cassinelli, et al. DHHS (NIOSH) Publication 94-113 (Aug. 1994). Available at: <www.cdc.gov/niosh/nmam/nmammenu.html>
(68) National Institute for Occupational Safety and Health (NIOSH). Zinc and Compounds, as Zn. In: NIOSH Manual of Analytical Methods (NMAM(R)). 4th ed. Edited by M.E. Cassinelli, et al. DHHS (NIOSH) Publication 94-113 (Aug. 1994). Available at: <www.cdc.gov/niosh/nmam/nmammenu.html>
(69) National Institute for Occupational Safety and Health (NIOSH). Elements by ICP. In: NIOSH Manual of Analytical Methods (NMAM(R)). 4th ed. Edited by M.E. Cassinelli, et al. DHHS (NIOSH) Publication 94-113 (Aug. 1994). Available at: <www.cdc.gov/niosh/nmam/nmammenu.html>
(70) National Institute for Occupational Safety and Health (NIOSH). Particulates Not Otherwise Regulated, Total. In: NIOSH Manual of Analytical Methods (NMAM(R)). 4th ed. Edited by M.E. Cassinelli, et al. DHHS (NIOSH) Publication 94-113 (Aug. 1994). Available at: <www.cdc.gov/niosh/nmam/nmammenu.html>
(71) National Institute for Occupational Safety and Health (NIOSH). Particulates Not Otherwise Regulated, Respirable. In: NIOSH Manual of Analytical Methods (NMAM(R)). 4th ed. Edited by M.E. Cassinelli, et al. DHHS (NIOSH) Publication 94-113 (Jan. 1998). Available at: <www.cdc.gov/niosh/nmam/nmammenu.html>
(72) European Communities (EC). Commission Directive 2004/73/EC. Apr. 29, 2004
(73) Zhumdal, S. S. Chemistry. 2nd ed. Heath and Company, 1989. p. 657-658 (zinc oxide)

Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 2005-09-28

Revision Indicators:
Bibliography 2006-03-22
Flammable Properties 2007-02-13



©2007 Canadian  Centre  for  Occupational  Health  &  Safety  
www.ccohs.ca  E-mail: clientservices@ccohs.ca  Fax: (905) 572-2206  Phone: (905) 572-2981  
Mail:  250  Main  Street  East,  Hamilton  Ontario  L8N  1H6