DETERMINATION AND CONFIRMATION OF AN ACUTE NO-OBSERVED-ADVERSE EFFECT LEVEL (NOAEL)FOR COPPER IN DRINKING WATER

Authors: ARAYA, MAGDALENA - UNIV OF CHILE; Klevay, Leslie; STRAIN, J - UNIV OF ULSTER; ROBSON, PAULA - UNIV OF ULSTER; Nielsen, Forrest - Frosty; OLIVARES, MANUAL - UNIV OF CHILE; PIZARRO, FERNANDO - UNIV OF CHILE; JOHNSON, LUANN - UNIV OF NORTH DAKOTA; POIRIER, K - UNIV OF CHILE; CHEN, BINHENG - FUDAN UNIVERSITY; SHI, WEI - FUDAN UNIVERSITY; ZHU, HUIGANG - FUDAN UNIVERSITY; HABER, LYNNE - TOXIC EXCELL RISK ASSESS

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/30/2003
Publication Date: 10/13/2003
Citation: Araya, M., Klevay, L.M., Strain, J.J., Robson, P., Nielsen, F.H., Olivares, M., Pizarro, F., Johnson, L., Poirier, K.A., Chen, B., Shi, W., Zhu, H., Haber, L.T. 2003. Determination and confirmation of an acute no-observed-adverse-effect level (NOAEL)for copper in drinking water. [Abstract]. Web-based European Knowledge Network on Water (WEKNOW) Drinking Water Conference, October 13-14, 2003, Kuopio, Finland.

Interpretive Summary:

Technical Abstract: Since the mid 1950s, there has been concern that the amounts of copper found in drinking water could result in adverse gastrointestinal (GI) effects in free-living humans. Indeed, anecdotal reports have demonstrated that consuming beverages or water contaminated with variable copper concentrations can result in epigastric pain, nausea, vomiting and diarrhea. However, the data from several of the anecdotal reports are not repeatable, and interpretation of the data is complicated by unknown factors such as variations in inter and intra-individual responses to copper, the type of copper salts in the waters/beverages consumed, and potential adaptation to prolonged higher exposures of copper. Despite these limitations, such data have been used to inform the development of guidelines and legislation concerning levels of copper in drinking water, such as the maximum contaminant level goal of 1.3mg Cu/L set by the US Environmental Protection Agency (6), and the drinking water guideline of 2mg Cu/L suggested by the World Health Organization. Owing to the paucity of well controlled, randomized trials designed specifically to define the tolerable levels of copper in drinking water, the primary goal of the research described in this summary document was to determine the threshold for acute GI effects associated with drinking water containing varying copper concentrations. The work was undertaken in two phases. In phase I, the aim was to determine the acute NOAEL (No-Observed-Adverse-Effect-Level) for copper (as CuSO**4.5H**2O dissolved in distilled deionized water) in an international, culturally diverse population recruited from three sites (Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile; Grand Forks Human Nutrition Research Center, ND, US; and the Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, Northern Ireland). In phase II, the aims were (i) to attempt to confirm the NOAEL for copper (as CuSO**4.5H**2O dissolved in a commercially available bottled mineral water) found in phase I, (ii) to increase cultural and geographic diversity by adding a new study site (Fudan University, Shanghai, China), and (iii) to determine the effects of copper dose and water volume as interacting variables. In order to minimize between-centre variation, all protocols, questionnaires, data sheets, and operational definitions of the outcome variables were standardized over all sites. In both phases, study progress was monitored by Toxicology Excellence for Risk Assessment (TERA), a non-profit risk assessment research organization. Ethical approval was provided by each site's Institutional Review Board or Ethics Committee, and subjects recruited for each phase at each site provided informed written consent prior to participation. At each of the three sites, 60 adults were recruited, with approximately equal numbers of men and women. 179 subjects completed the study. A single lot of CuSO**4.5H**2) (USP) pro analysis grade (Fisher Scientific, NJ, USA) was distributed to the three study sites. At each site, four test solutions (2, 4, 6 and 8mg/L of copper) were prepared daily by dissolving CuSO**4.5H**2O in distilled deionised water. The bolus of water administered to each subject on each study occasion was 200 ml, providing a dose of 0.4, 0.8, 1.2 and 1.6mg of elemental copper per dose, respectively. A 200 ml volume containing distilled deionised water only was used as the control. Subjects fasted overnight and came to each test facility on one morning a week for five successive weeks. On arrival, individuals were asked to complete a questionnaire containing a list of symptoms, indicating whether these were present or absent. The list of symptoms included the primary GI outcome variables (nausea, abdominal pain, vomiting, and diarrhea), as well as several distractor symptoms (backache