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The Babylonians used zinc alloys more than 5000 years ago,2 and references to zinc oxide as a lotion to heal lesions around the eye can be found in the Ebers papyrus, written in 1500 b.c.18 Zinc oxide and zinc sulfate were used in Western Europe during the late 1700s and early 1800s for gleet (urethral discharge), vaginal exudates, and convulsions. In the late 1800s, brass workers who inhaled zinc oxide fumes were noted to develop “zinc fever,” “brass founders’ ague,” and “smelter shakes,” all of which are now identified as metal fume fever (Chap. 124).70

Throughout history, humans have contaminated the environment with zinc. For example, release of zinc from mines elevates concentrations in the local water supply and vegetation, which may lead to elevated tissue zinc concentrations and clinical effects in the nearby population.54,64

The antiinflammatory effects of zinc sulfate were studied in the late 1970s for acne vulgaris with mixed results. However, a double-blinded controlled study found no difference between zinc and placebo.75 The more recent use of zinc supplementation as an alternative preventive and treatment strategy for upper respiratory infections is exposing large numbers of patients to undefined risks for unclear benefits.

In more recent history, an epidemic of hematologic and, more importantly, neurologic impairment due to large unintentional exposures to zinc via denture cream was reported. This syndrome sometimes referred to as “Zinc swayback” is further described below.3,11,42,58


Zinc, a transition metal, has two common oxidation states, Zn0 (elemental or metallic) and Zn2+. The pure element exists as a blue to white shiny metal, but it also combines with other elements to form many compounds: zinc chloride (ZnCl2), zinc oxide (ZnO), zinc sulfate (ZnSO4), and zinc sulfide (ZnS). Once the metal is exposed to moisture, it becomes coated with zinc oxide or carbonate (ZnCO3).85

Like the other transition metals iron (Chap. 46) and copper (Chap. 95), zinc ions participate in reactions that result in the generation of reactive oxygen species such as superoxide radicals or hydroxyl radicals which can damage both local and remote tissues (Chap. 12).


Zinc is an essential nutrient and found in more than 200 metalloenzymes, including acid phosphatase, alkaline phosphatase, alcohol dehydrogenase, carbonic anhydrase, superoxide dismutase, and DNA and RNA polymerases.85 The average daily intake of zinc in the United States is 5.2 to 16.2 mg; foods that contain zinc include leafy vegetables (2 ppm), meats, fish, and poultry (29 ppm).85 The recommended daily allowance is 11 mg/d for men and 8 mg/d for women. Pregnant and nursing women require 12 ...

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