Confirmation of an acute no-observed-adverse-effect and low-observed-adverse-effect level for copper in bottled drinking water in a multi-site international study

In a double blind, 3 × 3 factorial (volume × dose) study, 70 adult females (18–60 years of age) at four different international sites (total pooled n=269) were given 100, 150, or 200 ml of bottled drinking water with 0.4, 0.8, or 1.2 mg of copper (Cu) as the sulfate salt once each week. Two additional doses (0 and 1.6 mg Cu) were added at the 200 ml volume to determine a dose–response relationship and corroborate previously reported results. All subjects completed a questionnaire at 0, 0.25, and 1 h post-dosing that screened for positive gastrointestinal (GI) effects (nausea, vomiting, abdominal pain, and diarrhea). Nausea was the most prevalent symptom reported and was generally reported within the first 15 min (water volume, p