Ref. HBGV type	HBGV		Critical endpoint	Based on	NOAEL	UF and rationale	Critical studies
	mg/day	mg/kg bw per day
(WHO,  1996 ) Upper limit to the safe range of intake	M: 12(a) F: 10(a) Including pregnant & lactating	0.18 (65 kg) 0.18 (55 kg)	NR	Human data	10 mg/day	1	No references cited
(IPCS,  1998 ) Upper limit to the Adequate Range of Oral Intake (AROI)	Uncertain > 2 or 3	–	–	Human data	Data inadequate to establish effect levels	NA	H: (Wyllie, 1957; Spitalny et al., 1984; O'Donohue et al., 1993; Knobeloch et al., 1994)
(IOM,  2001 ) Tolerable Upper Intake Level (UL)	10 Including pregnant & lactating	–	Liver damage	Human clinical studies	10 mg/day (Pratt et al., 1985)	1 NOAEL protective of the general population; ‘larger UF considered unnecessary as the large international database in humans indicated no adverse effects from daily consumption of 10–12 mg/day of Cu in foods [No refs cited] and due to the rarity of observed liver damage from Cu exposure in human population with normal Cu homeostasis’	H: (Pratt et al., 1985; O'Donohue et al., 1993)
(SCF,  2003 ) Tolerable Upper Intake Level (UL)	5 Excluding pregnant & lactating (lack of data)	–	Liver damage	Human clinical studies	10 mg/day (Pratt et al., 1985) 7 mg/day (O'Connor et al., 2003)	2 Decrease in copper absorption as copper intake increases; putative indices of status (plasma Cu, erythrocyte SOD, caeruloplasmin and urinary Cu excretion) resistant to change except under extreme dietary conditions (Turnlund et al., 1990, 1991) ‘UF of 2 adequate to allow for potential variability within the normal population’	H: (Pratt et al., 1985; O'Donohue et al., 1993; Baker et al., 1999; Rock et al., 2000; Turley et al., 2000; O'Connor et al., 2003)
(EVM,  2003 ) Safe upper level	10	0.16	R: Damage to the forestomach, kidney and liver H: Liver damage	90‐day study in rats; Supported by human clinical studies	R: 16 mg/kg bw per day (Hebert, 1993) H: 10 mg/day (Pratt et al., 1985) 7.5 mg/day (Turnlund, 1989)	R: 10 (interspecies) x 10 (intraindividual) H: 1	R: (Hebert, 1993) H: (Pratt et al., 1985; Turnlund, 1989; Olivares et al., 1998; Pizarro et al., 1999)
(ATSDR,  2004 ) Chronic oral Minimal Risk Level	–	–	–	Animal and human data	database inadequate for the derivation of a chronic oral minimal risk level	NA	Mice: (Massie and Aiello, 1984)
(France,  2007a ) Acceptable Daily Intake (ADI)	–	0.15	D: elevation of SGPT (= ALT) R: liver and kidney damage H: liver damage	1‐year study in dogs Supported by 90‐day study in rats and human clinical studies	D: 15 mg/kg per day (Shanaman et al., 1972) R: 16 mg/kg bw per day (Hebert, 1993) H: 10 mg/day (Pratt et al., 1985)	D: 100 R: 100 H: 1 ‘the population has a uniform genetic profile for copper metabolism, in that the proteins for copper transport are very uniform, not only in the human population, but also in most life‐forms, and in that genetic abnormalities which result in diseases of copper metabolism are both extremely rare and (if untreated) fatal. It is logical to conclude that as there is regular exposure and that as defects in sensitivity to copper result in dramatic (lethal) illness, the vast majority of the population are similar, and the traditional safety factor of 10 for individual variation could be considered as too high’	D: (Shanaman et al., 1972) R: (Harrisson et al., 1954; Hebert, 1993; Mylchreest, 2005) H: (Pratt et al., 1985)
(EFSA,  2008 ) Upper limit (b)	–	0.15	NS	WHO (1996) based on human data Supported by 1‐year dog study	H: 0.2 mg/kg per day in adults and 0.15 mg/kg per day in children D: 15 mg/kg bw per day in a 1‐year dog (Shanaman et al., 1972)	H: 1 D: 100	H: (WHO, 1996) D: (Shanaman et al., 1972)
(Nordic Council of Ministers,  2012 )	5	–	NA	(SCF, 2003)	NA	NA	NA
(VKM,  2017 ) Tolerable Upper Intake Level (UL)	5	–	NA	(SCF, 2003)	NA	2 ‘UF suitable because human data are limited, the uncertainty of the copper content of drinking water and the potential severe and irreversible adverse effects’	NA
(France,  2017 ) Acceptable Daily Intake (ADI)	–	0.15	Liver damage	WHO (1996) based on human data; Consistent with ULs from other bodies based on human clinical studies	H: 0.2 mg/kg per day in adults and 0.15 mg/kg per day in infants	H: 1	H: (WHO, 1996; IPCS, 1998; IOM, 2001; EVM, 2003)
(EFSA,  2018b ) Acceptable Daily Intake (ADI) (c)	–	0.15	Liver damage	WHO (1996) based on human data; Supported by 90‐day rat study	H: 0.2 mg/kg per day in adults and 0.15 mg/kg day in infants R: 16 mg/kg per day	H:1 ‘It was noted that an upper limit for copper as a nutrient had been established in an opinion of the EU Scientific Committee for Food (SCF, 2003), based on a NOAEL of 10 mg Cu/day value but adding an uncertainty factor of 2, resulting in a proposed tolerable upper intake level of 5 mg Cu/day for adults (corresponding to half of the ADI currently set in the PPPs area). This approach was considered by the Peer Review in 2008 as inadequate for setting an ADI in the area of pesticides (France, 2007b,c). It was considered at that moment that there is greater risk of health effects from deficiency of copper intake than from excess of copper intake (WHO, 1998), there is no evidence of significant variability within humans and the additional uncertainty factor does not take into consideration the natural homeostatic mechanisms that regulate copper. During the current Peer Review, the experts have confirmed the previous assessment, and no changes in the ADI are proposed.’ R: 100	H: (WHO, 1996) R: (Hebert, 1993)

ADI: acceptable daily intake; ALT: alanine aminotransferase; D: dog; F: females; GI: gastrointestinal effects; H: humans; HBGV: health‐based guidance value; M: males; NA: not applicable; NOAEL: no‐observed‐adverse‐effect level; NR: not reported; NS: not specified; R: rats; SGPT: serum glutamic‐pyruvic transaminase SOD: superoxide dismutase; UF: uncertainty factor; UL: tolerable upper intake level; WHO: World Health Organization.

^(a)‘This will take account of the quantity likely to be consumed from the usual diet (< 10 mg/day) and will limit both the amount of copper that can be introduced by dietary fortification and the quantity of contaminating copper that can be regarded as tolerable.’

^(b)‘It was felt by the meeting of experts that the term ‘ADI’ was not adequate to copper as an essential micronutrient essential for life; the term ‘upper limit’ was considered as more appropriate.’

^(c)‘It should be noted that it was felt by the experts that the term ‘ADI’ was not fully adequate to copper as a micronutrient essential for life; the term ‘upper limit’ used in the nutrient area would be more appropriate; therefore in the specific case of copper, the ADI is considered equivalent to an UL.’