Nausea threshold in apparently healthy individuals who drink fluids containing graded concentrations of copper

Ingestion of drinking water with a high copper content may induce acute gastrointestinal effects, mainly nausea and vomiting, rarely diarrhea and abdominal pain. The objectives of this study were to define nausea threshold in apparently healthy adult volunteers who received graded concentrations of copper and to explore how individual thresholds were modified by delivering copper in an orange-flavored drink. Sixty-one healthy subjects received 200 mL of a copper-containing solution in purified water, at concentrations 0, 2, 4, 6, 8, 10, and 12 mg/L, as copper sulfate, in random order. Nausea threshold concentration for first response was established and then this threshold was confirmed. Subsequently, following the same design, subjects received the same copper concentrations (up to 12 mg/L), delivered in an orange-flavored drink, starting at the confirmed threshold concentration found in water. Mild nausea shortly after ingestion of copper-containing water was the most frequent finding (33/61 subjects), starting at 4 mg/L; vomiting was observed in 7 individuals, starting at 6 mg/L. The NOEL for copper in purified water was 2 and 4 mg/L for nausea and vomiting, respectively. When copper was provided as an orange-flavored drink, 11 subjects (18%) reported nausea, starting at 8 mg Cu/L, and no subjects vomited up to 12 mg Cu/L. It is concluded that after consumption of copper in purified water, the NOEL is 2 mg Cu/L and the LOAEL 4 mg Cu/L for nausea, while tolerable intake is between 2 and 4 mg Cu/L in water depending on whether apparent or confirmed nausea is used as the criterion to define critical effects.