|Nielsen, Forrest - Frosty|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 6/19/2001
Publication Date: 9/1/2001
Citation: Poirier, C.A., Chen, B.H., Zhu, H.G., Shi, W., Araya, M., Johnson, L., Klevay, L.M., Nielsen, F.H., Robson, P., Strain, S. 2001. The determination of a human acute no observed adverse effect level [NOAEL] for copper: effects of volume and dose [abstract]. Society for Risk Analysis 2001 Final Program. Risk Analysis in an Interconnected World. p.81. Interpretive Summary:
Technical Abstract: A human, acute NOAEL (No Observed Adverse Effect Level) for nausea was determined in a prospective, double blind controlled study. We recruited 70 adult females (18-60 years of age) at each of four different international sites. The study design was a 3 x 3 factorial (volume x dose) for 100, 150, or 200 ml of drinking water for 0.4, 0.8, 1.2 mg of Cu as sulfate. Two additional doses (0 and 1.6 mg Cu) were added at the 200 ml volume to determine a dose response. Each subject was given a blind, randomly selected and freshly prepared concentration of copper once a week over a period of 11 weeks. Following dosing, all subjects were monitored for 1 hour and completed a questionnaire at 0, 0.25, 1, and 24 hours post dosing that screened for positive GI effects (nausea, vomiting, abdominal pain, and diarrhea). Nausea, the most prevalent symptom reported, generally occurred within 15 minutes. Results were analyzed by a Generalized Linear Model (Repeated Measures) model. The four site combined data reported incidences of nausea 15 minutes post dosing of 0, 2, 7, 14, and 25% for 0, 0.4, 0.8, 1.2, and 1.6 mg Cu (or 0, 2, 4, 6, and 8 mg Cu/L) respectively. Analysis of these data indicate that for nausea alone, an acute NOAEL and LOAEL of 0.4 and 0.8 mg Cu, respectively, in natural, bottled drinking water was determined in an adult female population. There was no interactive effect between volume and dose in the factorial design. All significant increases in probability of outcome for nausea at 15 minutes occurred at copper concentrations greater than 4 mg Cu/L. The results of Phase II are in agreement with previously reported data.