Pizarro et al. (1999) have shown a significant increase
in the incidence of gastrointestinal symptoms
(nausea, vomiting, and cramps) in adult subjects consuming
drinking water with a copper concentration
¸3 mg/L. Nausea was the most frequent gastrointestinal
symptom. Studies performed by Zacarias et al.
(2001) have demonstrated that the taste threshold for
copper (as copper sulfate or copper chloride) in drinking
water is 2.6 mg/L. Administration of a mixture containing
varying proportions of soluble (CuSO4) and insoluble
(CuO) copper salts, maintaining the Cu concentration
at 5 mg/L, has recently suggested that the stomach
pH may play an important role in determining gastrointestinal
effects (F. Pizarro, unpublished). These preliminary
data, plus others available in the literature, have
led researchers to postulate that nausea may be an adequate
early indicator of gastrointestinal adverse effects.
The rationale for this is that if copper reaches
an empty stomach (without other compounds present
to bind the copper), gastrointestinal symptoms may be
elicited by smaller amounts of copper than if there was
food present in the stomach. It has also been postulated
that excess copper can cause generation of reactive oxygen
species. In animal models, excess copper has been
shown to generate oxygen radicals that in liver form
etheno–DNA adducts and lipid peroxidation (Landolph,
1999). Such redox reactions generating oxygen radicals
may also play a role in the gastrointestinal cascade of
acute copper toxicity.