|Nielsen, Forrest - Frosty|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/24/2001
Publication Date: 2/1/2002
Citation: Poirier, K.A., Araya, M., Klevay, L.M., Nielsen, F.H., Johnson, L., Strain, J.J., Robson, P., Chen, B.H., Wei, S., Zhu, H.G., Baker, S.R. 2002. Determination of a human acute no-observed-effect level (NOAEL) for copper in bottled drinking water: volume, dose and concentration considerations [abstract]. The Toxicologist. 66:102. Interpretive Summary:
Technical Abstract: A human, acute NOAEL for nausea was determined in a prospective, double blind controlled study. We recruited 70 adult females (18-60 y) at each of 4 different international sites (final pooled n=269). The study design was a 3x3 factorial (volume x dose) for 100, 150, or 200 ml of bottled drinking water for 0.4, 0.8, 1.2 mg of copper (Cu) as sulfate. Two additional doses (0 and 1.6 mg Cu) were added at the 200 ml volume to determine a dose response. Each subject was given a blind, randomly selected Cu dose once a week. Then all subjects were carefully monitored for 1 h and completed a questionnaire at 0, 0.25, 1, and 24 h post-dosing for positive 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<0.032, Cu dose p<0.0001 and water x copper interaction is p<0.97). As volume increased, the effect of Cu-induced nausea decreased; as Cu dose increased; the incidence of nausea increased. At 200 ml, a significant increase in reported incidence of nausea at 0.25 hr occurred at 1.2 (6 mg Cu/L), indicating a NOAEL of 0.8 mg Cu (4 mg Cu/L) for adult females. An acute nausea threshold of 5.3 Cu/L can be determined from the factorial analysis (0.8 mg Cu in 150 ml). These data confirm a previously determined human acute NOAEL for Cu and provide additional, controlled human data for determining regulatory contaminant levels of Cu for drinking water.