M. Olivares et al., Nausea threshold in apparently healthy individuals who drink fluids containing graded concentrations of copper, REGUL TOX P, 33(3), 2001, pp. 271-275
Ingestion of drinking water with a high copper content may induce acute gas
trointestinal effects, mainly nausea and vomiting, rarely diarrhea and abdo
minal pain. The objectives of this study were to define nausea threshold in
apparently healthy adult volunteers who received graded concentrations of
copper and to explore how individual thresholds were modified by delivering
copper in an orange-flavored drink Sixty-one healthy subjects received 200
mL of a copper-containing solution in purified water, at concentrations 0,
2, 4, 6, 8, 10, and 12 mg/L, as copper sulfate, in random order. Nausea th
reshold concentration for first response was established and then this thre
shold was confirmed. Subsequently, following the same design, subjects rece
ived the same copper concentrations (up to 12 mg/L), delivered in an orange
-flavored drink, starting at the confirmed threshold concentration found in
water. Mild nausea shortly after ingestion of copper-containing water was
the most frequent finding (33/61 subjects), starting at 4 mg/L; vomiting wa
s observed in 7 individuals, starting at 6 mg/L. The NOEL for copper in pur
ified water was 2 and 4 mg/L for nausea and vomiting, respectively. When co
pper was provided as an orange-flavored drink, 11 subjects (18%) reported n
ausea, starting at 8 mg Cu/L, and no subjects vomited up to 12 mg Cu/L. It
is concluded that after consumption of copper in purified water, the NOEL i
s 2 mg Cu/L and the LOAEL 4 mg Cu/L for nausea, while tolerable intake is b
etween 2 and 4 mg Cu/L in water depending on whether apparent or confirmed
nausea is used as the criterion to define critical effects. (C) 2001 Academ
ic Press.