title: Determination of an acute no-observed-adverse-effect level (NOAEL) for copper in water.
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 179 individuals who drank copper-containing water as the sulfate salt. Subjects were recruited at three different international sites and given a blind, randomly selected dose (0, 2, 4, 6, or 8 mg Cu/L) in a bolus of 200 ml (final total copper dose was equivalent to 0, 0.4, 0.8, 1.2, and 1.6 mg) once weekly over a consecutive 5-week period. Gastrointestinal (GI) symptoms of nausea, abdominal pain, vomiting, or diarrhea were screened for a period of up to 24 h. Nausea was the most frequently reported effect and was reported within the first 15 min of ingestion. For the combined trisite population (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 mg Cu/L. Therefore, an acute NOAEL and lowest-observed-adverse-effect level of 4 and 6 mg Cu/L (0.8 and 1.2 mg Cu), respectively, were determined in drinking water for a combined international human population.
authors.affiliation: Institute of Nutrition and Food Technology (INTA), University of Chile, Macul 5540, Casilla 138 11, Santiago 11, Chile.
authors.forename: M
authors.initials: M
authors.lastname: Araya
authors.forename: M C
authors.initials: MC
authors.lastname: McGoldrick
authors.forename: L M
authors.initials: LM
authors.lastname: Klevay
authors.forename: J J
authors.initials: JJ
authors.lastname: Strain
authors.forename: P
authors.initials: P
authors.lastname: Robson
authors.forename: F
authors.initials: F
authors.lastname: Nielsen
authors.forename: M
authors.initials: M
authors.lastname: Olivares
authors.forename: F
authors.initials: F
authors.lastname: Pizarro
authors.forename: L A
authors.initials: LA
authors.lastname: Johnson
authors.forename: K A
authors.initials: KA
authors.lastname: Poirier
mesh_terms: D000328:Adult; D003300:Copper / Q000633:toxicity*; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D016015:Logistic Models; D008297:Male; D009325:Nausea / Q000139:chemically induced; D019055:No-Observed-Adverse-Effect Level; D011786:Quality Control; D014881:Water Supply / Q000032:analysis*
chemical_list: D003300:Copper