Table 1.
Summary of human ingestion studies
| Group | Cu form | Treatment | Water concentration or dose (mg/L or mg/day) | Results summary | Cu NOAEL or LOAEL | Reference |
|---|---|---|---|---|---|---|
| Women (n = 60) | CuSO4 | 0, 1, 3, and 5 mg/L in tap water for 2 weeks followed by 1 week of tap water without copper | 0, 1, 3, and 5 | Acute (GI) symptoms increased at >3 mg/L, no significant differences in effects between different copper ratios | NOAEL: 2 mg/L | Pizarro et al. (1999) |
| Adult women (n = 45) | Copper sulfate: copper (II) oxide ratios | 5 mg/L in tap water for 1 week followed by 1 week without copper in tap water, alternating for a total of 9 weeks, double-blind study | Ratios of soluble (copper sulfate) to insoluble (copper (II) oxide): 0:5, 1:4, 2:3, 3:2, and 5:0 | Liver enzymatic function not affected, increase in GI symptoms, 6/12 diarrhea during first week, both copper compounds caused 54 or 18% nausea incidence in water or orange juice, respectively | ND | Pizarro et al. (2001) |
| Women (n = 269) | CuSO4 | Single dose in bottled water | 0, 0.4, 0.8, 1.2, and 1.6 mg Cu in 200 mL bottled spring water (0, 2, 4, 6 and 8) | Nausea first/most common symptom, within 15 min of ingestion | LOAEL (nausea): 6 mg/L; NOAEL 4 mg/L | Araya et al. (2003a) |
| Men and women (n = 179) | CuSO4 | Weekly dose for 5 weeks | 0, 2, 4, 6, and 8 | Nausea first/most common symptom, within 15 min of ingestion | LOAEL: 6 mg/L; NOAEL 4 mg/L, both for GI effects and nausea | Araya et al. (2001) |
| Men and women (n = 1365) | CuSO4 | Daily dose for 2 months, water prepared for drinking and used in food preparation | <0.01, 2, 4, and 6 | Gastrointestinal effects increased at 6 mg/L, no effects for other endpoints | LOAEL (nausea) 6 mg/L | Araya et al. (2003b) |
| Men and women (n = 61) | CuSO4 | Weekly dose administered in water or orange-flavored juice for up to 12 exposures | 0, 2, 4, 6, 8, 10, and 12 | Nausea and vomiting reported | In water NOAEL (nausea): 2 mg/L; NOAEL (vomiting): 4 mg/L; in orange-flavored drink NOAEL (nausea): 8 mg/L, LOAEL (nausea): 4 mg/L | Olivares et al. (2001) |
| Men and women (n = 7) | Copper gluconate | 1 pill/day for 12 weeks, double-blind study | 10 mg/day | Normal liver function, no gastrointestinal effects quantified | NOAEL: 10 mg/day | Pratt et al. (1985) |
| Men (n = 24) | (1) CuSO4; (2) Cu glycine chelates | Daily supplements for 2 weeks each; 3 mg Cu/day as (1) 3 mg Cu/day form (1); 3 mg Cu/day as form (2); and 6 mg Cu/day as form | 3.6 mg | No effects on liver or genetic damage | 6 mg/day | O’Connor et al. (2003) |
| Men (n = 9) | Cu supplement | Daily intake for 147 days | 7 mg/day | Plasma Cu not affected, increased Cu retention and Cu-related enzyme activity, possible immune effects | LOAEL: 7 mg/day in addition to 1.6 mg/day diet | Turnlund et al. (2004, 2005) |
| Men (n = 1) | Copper tablet, form not provided | Daily intake for 2 years of tablet, followed by higher dose for additional but unspecified time period | 30 mg/day for 2 years, 60 mg/day for additional time | Acute liver failure | LOAEL: 30 mg/day | ECI (2008) |
| Infants (n = 148) | CuSO4 | Formula-fed or breast-fed between 3 and 12 months | <0.1 or 2 (water) | No acute or chronic effects at 2 mg/L | No effect level: 2 mg/L | Olivares et al. (1998) |
Please see Supplementary Table S2 for additional detail on these studies