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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #120308


item Araya, Magdalena
item Mcgoldrick, Marie
item Klevay, Leslie
item Strain, John
item Robson, Paula
item Nielsen, Forrest - Frosty
item Olivares, Manuel
item Pizarro, Fernando
item Baker, Scott
item Poirier, Kenneth

Submitted to: Journal of Regulatory Toxicology and Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/22/2000
Publication Date: 4/1/2001
Citation: Araya, M., McGoldrick, M.C., Klevay, L.M., Strain, J.J., Robson, P., Nielsen, F.H., Olivares, M., Pizarro, F., Baker, S.R., Poirier, K.A. 2001. Determination of an acute no-observed-adverse-effect-level (NOAEL) for copper in water. Regulatory Toxicology and Pharmacology. 34:137-145.

Interpretive Summary: Standards of drinking water quality in the United States undergo periodic review and are based largely on taste and nausea thresholds. One hundred seventy nine people at three sites (USA, Northern Ireland and Chile) were given drinking solutions of copper sulfate to define the no-effect concentration. 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 two milligrams of copper per liter. Nausea as found between 4 and 6 mg/l, with greater effects at 8 mg/l and with women being somewhat more sensitive than men. Current US recommendations of 1.4 mg copper/l for public water supplies need not be revised. The data may be useful in planning dietary supplementation trials with copper salts.

Technical Abstract: A prospective, double blind controlled study was designed to determine the acute No-Observed-Adverse-Effect Level (NOAEL) of nausea in an apparently healthy population of individual who drank copper containing water as the sulfate salt. A target of sixty adults, 30 of each sex and 17-60 years of age, recruited at three different international sites (Coleraine of Northern Ireland, Santiago of Chile, and Grand Forks, ND USA). Individuals with occupational copper exposure, gastrointestinal (GI) illness, or who were pregnant were excluded. Pharmaceutical grade (USP) copper sulfate was used to prepare daily testing solutions containing 0,2,4,6, and 8 mg Cu/L. Each subject was given a blind, randomly selected dose of 200 ml of copper solution at room temperature once weekly over a consecutive 5 week period. Following dosing, all subjects were monitored by health care personnel for 1 hour. All subjects completed questionnaires at 0 time, 15 minutes, 1 hour and 24 hours that screened for positive GI effects (nausea, vomiting, abdominal pair, and diarrhea). Nausea was the effect most frequently reported usually within 15 minutes. All other GU effects were reported within 1 hour. For the combined tri- site position (n = 179), 8,9,14 25 and 44 subjects responded positively to one or more GI symptoms at 0,2,4, 6 and 8 mg Cu/L, respectively. Analysis of the data demonstrated a clear dose response to the combined positive GI effects and to nausea alone. Statistically significant greater reporting of effects occurred at 6 and 8 Cu/L than at 0, 2, and 4. Therefore, an acute NOAEL and Lowest-Observed-Adverse-effect Level (LOAEL) of 4 and 6 mg Cu/L, respectively were determined in a combined international human population.