Abstract
Decades of study indicate that copper oral exposures are typically not a human health concern. Ingesting high levels of soluble copper salts can cause acute gastrointestinal symptoms and, in uncommon cases, liver toxicity in susceptible individuals with repeated exposure. This focused toxicological review evaluated the current literature since the last comprehensive reviews (2007–2010). Our review identified limitations in the existing United States and international guidance for determining an oral reference dose (RfD) for essential metals like copper. Instead, an alternative method using categorical regression analysis to develop an optimal dose that considers deficiency, toxicity, and integrates information from human and animal studies was reviewed for interpreting an oral RfD for copper. We also considered subchronic or chronic toxicity from genetic susceptibility to copper dysregulation leading to rare occurrences of liver and other organ toxicity with elevated copper exposure. Based on this approach, an oral RfD of 0.04 mg Cu/kg/day would be protective of acute or chronic toxicity in adults and children. This RfD is also protective for possible genetic susceptibility to elevated copper exposure and allows for background dietary exposures. This dose is not intended to be protective of patients with rare genetic disorders for copper sensitivity within typical nutritional intake ranges, nor is it protective for those with excessive supplement intake. Less soluble mineral forms of copper in soil have reduced bioavailability as compared with more soluble copper in water and diet, which should be considered in using this RfD for risk assessments of copper.
Highlights
While copper is an essential nutrient for humans, animals, and plants, it can pose risks to human health with elevated exposure
A broader review of the scientific basis for this drinking water level was conducted for Environmental Protection Agency (EPA) in 2000 (NRC 2000), which concurred with this level at the time, EPA has not since reevaluated the maximum contaminant level goal (MCLG) or formally developed an oral reference dose (RfD) to support risk assessments of environmental copper exposure
Reduced excretory capability is in part balanced by nutritional requirements in this rapidly developing life stage; formula-fed infants may be more susceptible to liver toxicity at elevated copper exposures in drinking water
Summary
While copper is an essential nutrient for humans, animals, and plants, it can pose risks to human health with elevated exposure. Copper exposure through drinking water has been regulated in the United States since 1991 (56 FR 26460-26564), when the US Environmental Protection Agency (EPA) set a maximum contaminant level goal (MCLG) and drinking water action level for copper at 1.3 mg Cu/L. EPA based the MCLG on acute gastrointestinal effects observed in nurses who consumed cocktails contaminated with copper (Wyllie 1957) (estimated minimal dose of 2.65 mg Cu/L, divided by an uncertainty factor of 2) (Donohue 1997). A broader review of the scientific basis for this drinking water level was conducted for EPA in 2000 (NRC 2000), which concurred with this level at the time, EPA has not since reevaluated the MCLG or formally developed an oral reference dose (RfD) to support risk assessments of environmental copper exposure. An update of the literature and an assessment of an RfD would be timely
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