|Nielsen, Forrest - Frosty|
Submitted to: Society of Toxicology
Publication Type: Abstract only
Publication Acceptance Date: 3/3/2000
Publication Date: 7/1/2000
Citation: Poirier, K.A., Araya, M., Klevay, L.M., Strain, J.J., Nielsen, F.H., Robson, P., McGoldrick, M.C., Baker, S.B. 2000. Determination of a human acute no observed adverse effect level (NOAEL) for copper [abstract]. The Toxicologist (Suppl). 54:73. Interpretive Summary:
Technical Abstract: This prospective, double blind controlled study was designed to determine the acute NOAEL of nauea in an apparently healthy population of individuals who drink copper containing water as the sulfate salt. Sixty adults, 30 of each sex and 18-50 years of age, were recruited at three different internal sites (Coleraine, Santiago, and Grand Forks). Pharmaceutical grade copper was used to prepare testing solutions containing 0, 2, 4, 6, and 8 mg Cu/L (as copper sulfate) daily 30 minutes before administration by dissolving copper sulfate into freshly made room temperature, deionized water and maintained at the same temperature until dosing. Each subject was given a blind, randomly selected dose in a bolus of 200 ml (final total copper was equivalent to 0, 0.4, 0.8, 1.2, and 1.6 mg) over a consecutive 5 week period. Following dosing all subjects were monitored by health care personnel for 1 hour. All subjects complected questionnaires at 0 time, 15 minutes, 1 hour and 24 hours that screened for positive GI effects, (nausea, vomiting, abdominal pain, and diarrhea). Nausea was the most frequently reported effect and was reported within the first 15 min. All other GI effects were reported within 1 hour. For the combined tri-site population (n=180) 8, 9, 14, 25 and 44 subjects responded to one or more GI symptoms at 0, 2, 4, 6 and 8 mg Cu/L, respectively. Chi-square analysis of the data demonstrated a clear dose response to the combined positive GI effects and to nausea alone. Statistically significant greater reporting of the effects occurred at 6 and 8 mg Cu/L. There are, an acute NOAEL and LOAEL of 4 and 6 mg Cu/L, respectively is determined in a combined international human population.