Toxic Dose of Zinc
Acute zinc toxicity symptoms appear when ingestion exceeds 1-2 grams (1,000-2,000 mg) in a single dose, causing immediate gastrointestinal distress including nausea, vomiting, and epigastric pain 1, 2.
Acute Toxicity Threshold
- Single-dose toxicity occurs at 1-2 grams of zinc, far above therapeutic ranges, with symptoms of emesis, gastrointestinal irritation and corrosion, and potentially acute renal tubular necrosis 1, 3.
- Ingestion of 1-2 grams of zinc sulfate reliably produces vomiting as the body's protective mechanism 3.
- Extremely high acute intakes cause overt toxicity symptoms including lethargy, fatigue, and epigastric pain in addition to gastrointestinal effects 4.
Chronic Toxicity at Lower Doses
Chronic intake of 100-300 mg daily (well below acute toxic levels but far above the RDA of 15 mg) causes copper deficiency, anemia, neutropenia, and impaired immune function 4.
Upper Intake Limits from Regulatory Bodies
- The European Food Safety Authority (EFSA) sets the tolerable upper intake level at 25 mg per day 5.
- The FDA allows 40 mg per day as the upper limit 5.
- These limits are designed to prevent chronic toxicity effects, not acute poisoning 5.
Chronic Toxicity Effects by Dose Range
- At 100-300 mg daily: Induced copper deficiency with anemia, neutropenia, impaired immune function, and adverse LDL/HDL cholesterol ratios 4.
- At doses closer to the RDA (15-40 mg daily): Potential interference with copper and iron utilization, and adverse effects on HDL cholesterol 4.
- Above 15 mg daily: Copper status monitoring is recommended, maintaining an 8:1 to 15:1 zinc-to-copper ratio 2.
Clinical Context for Toxicity Assessment
- The population reference intake is 12.7 mg/day for women and 16.3 mg/day for men (total from food plus supplements) 2.
- Therapeutic doses for specific conditions (Wilson's disease) use 150 mg daily in divided doses, which requires medical supervision and monitoring 1, 6.
- The narrow margin between the RDA (15 mg) and the upper safe limit (25-40 mg) makes unsupervised supplementation risky 7.
Route-Specific Toxicity Considerations
- Inhalation of zinc oxide fumes causes metal fume fever with fatigue, chills, fever, myalgias, cough, dyspnea, and leukocytosis in occupational settings 3.
- Inhalation of zinc chloride smoke in closed spaces can cause chemical pneumonitis and acute respiratory distress syndrome 3.
- Topical application and other non-oral routes may also pose intoxication risks 5.
Treatment of Zinc Toxicity
- Treatment is primarily supportive for acute toxicity 3.
- Calcium disodium EDTA (CaNa2EDTA) is the chelator of choice based on case reports showing normalization of zinc concentrations, though clinical efficacy data are limited 3, 8.
- Severe cases may require protective lung ventilation and extracorporeal membrane oxygenation (ECMO) for inhalational exposures 8.