Toxicity Profiles

Condensed Toxicity Summary for ZINC AND ZINC COMPOUNDS

NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.

April 1992

Prepared by Dennis M. Opresko, Ph.D., Chemical Hazard Evaluation and Communication Group, Biomedical and Environmental Information Analysis Section, Health and Safety Research Division, Oak Ridge National Laboratory*, Oak Ridge, Tennessee

Prepared for OAK RIDGE RESERVATION ENVIRONMENTAL RESTORATION PROGRAM

*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400

Zinc is used primarily in galvanized metals and metal alloys, but zinc compounds also have wide commercial applications as chemical intermediates, catalysts, pigments, vulcanization activators and accelerators in the rubber industry, UV stabilizers, and supplements in animal feeds and fertilizers. They are also used in rayon manufacture, smoke bombs, soldering fluxes, mordants for printing and dyeing, wood preservatives, mildew inhibitors, deodorants, antiseptics, and astringents (Lloyd, 1984; ATSDR, 1989). In addition, zinc phosphide is used as a rodenticide.

Zinc is an essential element with recommended daily allowances ranging from 5 mg for infants to 15 mg for adult males (NRC, 1989).

Gastrointestinal absorption of zinc is variable (20-80%) and depends on the chemical compound as well as on zinc levels in the body and dietary concentrations of other nutrients (U.S. EPA, 1984). In individuals with normal zinc levels in the body, gastrointestinal absorption is 20-30% (ATSDR, 1989). Information on pulmonary absorption is limited and complicated by the potential for gastrointestinal absorption due to mucociliary clearance from the respiratory tract and subsequent swallowing. Zinc is present in all tissues with the highest concentrations in the prostate, kidney, liver, heart, and pancreas. Zinc is a vital component of many metalloenzymes such as carbonic anhydrase, which regulates CO2 exchange (Stokinger, 1981). Homeostatic mechanisms involving metallothionein in the mucosal cells of the gastrointestinal tract regulate zinc absorption and excretion (ATSDR, 1989).

In humans, acutely toxic oral doses of zinc cause nausea, vomiting, diarrhea, and abdominal cramps and in some cases gastric bleeding (Elinder, 1986; Moore, 1978; ATSDR, 1989). Ingestion of zinc chloride can cause burning in the mouth and throat, vomiting, pharyngitis, esophagitis, hypocalcemia, and elevated amylase activity indicative of pancreatitis (Chobanian, 1981). Zinc phosphide, which releases phosphine gas under acidic conditions in the stomach, can cause vomiting, anorexia, abdominal pain, lethargy, hypotension, cardiac arrhythmias, circulatory collapse, pulmonary edema, seizures, renal damage, leukopenia, and coma and death in days to weeks (Mack, 1989). The estimated fatal dose is 40 mg/kg. Animals dosed orally with zinc compounds develop pancreatitis, gastrointestinal and hepatic lesions, and diffuse nephrosis.

Gastrointestinal upset has also been reported in individuals taking daily dietary zinc supplements for up to 6 weeks (Samman and Roberts, 1987). There is also limited evidence that the human immune system may be impaired by subchronic exposures (Chandra, 1984). In animals, gastrointestinal and hepatic lesions, (Allen et al., 1983; Brink et al., 1959); pancreatic lesions (Maita et al., 1981; Drinker et al., 1927a); anemia (ATSDR, 1989; Fox and Jacobs, 1986; Maita et al., 1981); and diffuse nephrosis (Maita et al., 1981; Allen et al., 1983) have been observed following subchronic oral exposures.

Chronic oral exposures to zinc have resulted in hypochromic microcytic anemia associated with hypoceruloplasminemia, hypocupremia, and neutropenia in some individuals (Prasad et al., 1978; Porter et al., 1977). Anemia and pancreatitis were the major adverse effects observed in chronic animal studies (Aughey et al., 1977; Drinker et al., 1927a; Walters and Roe, 1965; Sutton and Nelson, 1937). Teratogenic effects have not been seen in animals exposed to zinc; however, high oral doses can affect reproduction and fetal growth (Ketcheson et al., 1969; Schlicker and Cox 1967, 1968; Sutton and Nelson, 1937).

The reference dose for chronic oral exposure to zinc is under review by EPA; the currently accepted RfD for both subchronic and chronic exposures is 0.2 mg/kg/day based on clinical data demonstrating zinc-induced copper deficiency and anemia in patients taking zinc sulfate for the treatment of sickle cell anemia (U.S. EPA, 1992). The chronic oral RfD for zinc phosphide is 0.0003 mg/kg/day (U.S. EPA, 1991a), and the subchronic RfD is 0.003 mg/kg/day (U.S. EPA, 1992).

Under occupational exposure conditions, inhalation of zinc compounds (mainly zinc oxide fumes) can result in a condition identified as "metal fume fever", which is characterized by nasal passage irritation, cough, rales, headache, altered taste, fever, weakness, hyperpnea, sweating, pains in the legs and chest, leukocytosis, reduced lung volume, and decreased diffusing capacity of carbon monoxide (ATSDR, 1989; Bertholf, 1988). Inhalation of zinc chloride can result in nose and throat irritation, dyspnea, cough, chest pain, headache, fever, nausea and vomiting, and respiratory disorders such as pneumonitis and pulmonary fibrosis (ITII, 1988; ATSDR, 1989; Nemery, 1990). Pulmonary inflammation and changes in lung function have also been observed in inhalation studies on animals (Amur et al., 1982; Lam et al., 1985; Drinker and Drinker, 1928).

Although "metal fume fever" occurs in occupationally exposed workers, it is primarily an acute and reversible effect that is unlikely to occur under chronic exposure conditions when zinc air concentrations are less than 8-12 mg/m3 (ATSDR, 1989). Gastrointestinal distress, as well as enzyme changes indicative of liver dysfunction, have also been reported in workers occupationally exposed to zinc (NRC, 1979; Stokinger, 1981; U.S. EPA, 1991a; Guja, 1973; Badawy et al., 1987a); however, it is unclear as to what extent these effects might have been caused by pulmonary clearance, and subsequent gastrointestinal absorption. Consequently, there are no clearly defined toxic effects that can be identified as resulting specifically from pulmonary absorption following chronic low level inhalation exposures. Animal data for chronic inhalation exposures are not available.

An inhalation reference concentration has not been derived for zinc or zinc compounds (U.S. EPA, 1992).

No case studies or epidemiologic evidence has been presented to suggest that zinc is carcinogenic in humans by the oral or inhalation route (U.S. EPA, 1991a). In animal studies, zinc sulfate in drinking water or zinc oleate in the diet of mice for a period of one year did not result in a statistically significant increase in hepatomas, malignant lymphomas, or lung adenomas (Walters and Roe, 1965); however, in a 3-year, 5-generation study on tumor-resistant and tumor-susceptible strains of mice, exposure to zinc in drinking water resulted in increased frequencies of tumors from the F0 to the F4 generation in the tumor-resistant strain (from 0.8 to 25.7%, vs. 0.0004% in the controls), and higher tumor frequencies in two tumor-susceptible strains (43.4% and 32.4% vs. 15% in the controls) (Halme, 1961).

Zinc is placed in weight-of-evidence Group D, not classifiable as to human carcinogenicity due to inadequate evidence in humans and animals (U.S. EPA, 1991a). Retrieve Toxicity Profiles Formal Version

Last Updated 8/29/97