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United States Department of Agriculture

Agricultural Research Service


item Araya, Magdalena
item Chen, Bingheng
item Klevay, Leslie
item Strain, J
item Johnson, Luann
item Robson, Paula
item Shi, Wei
item Nielsen, Forrest - Frosty
item Zhu, Huigang
item Olivares, Manuel
item Pizarro, Fernando
item Haber, Lynne

Submitted to: Journal of Regulatory Toxicology and Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/12/2003
Publication Date: 12/1/2003
Citation: Araya, M., Chen, B., Klevay, L.M., Strain, J.J., Johnson, L., Robson, P., Shi, W., Nielsen, F., Zhu, H., Olivares, M., Pizarro, F., Haber, L.T. 2003. 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. Regulatory Toxicology and Pharmacology. 38:389-399.

Interpretive Summary: Standards of drinking water quality in the United States undergo periodic review and are based largely on taste and nausea thresholds. Two hundred sixty-nine women at four sites (USA, Northern Ireland, Chile, and China) were given copper sulfate dissolved in bottled spring water to define the no-effect concentration. Men were included as earlier work had shown them to be less sensitive to copper than were women. Solutions were given in random order and included copper-free water so that subjects and scientists were ignorant of the dose and sequence. No effect was found at 4 milligrams of copper per liter. Nausea was found between 6 and 8 mg/1, with greater effects at 8 mg/1. Current US recommendations of 1.3 mg copper/1 for public water supplies need not be revised. The data may be useful in planning dietary supplementation trials with copper salts.

Technical Abstract: In a double blind, 3 x 3 factorial (volume x dose) study, 70 adult females (18-60 yrs of age) at four different international sites (total pooled n=269) were given 100, 150, 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 hr 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 minutes (water volume p<0.032, copper dose p<0.0001 and water volume 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 mg Cu (6 mg Cu/L), indicated an NOAEL (No-Observed-Adverse-Effect Level) of 0.8 mg Cu (4 mg Cu/L) for adult females. These data confirm a previously determined human acute NOAEL for Cu added to distilled water and provide additional controlled human data for determining safe concentrations of Cu in drinking water.

Last Modified: 06/23/2017
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