Lines of Evidence	Influence on conclusion
Line of Evidence 1 – Absence of direct hepatic copper measurements	?
Line of Evidence 2 – Lack of appropriate non‐invasive biomarkers of copper status	?
Line of Evidence 3 – Evidence of retention or positive copper balance from studies with controlled exposure at levels of 8 mg/day up to 5 months and at 6 mg/day up to 2 months	↓↓
Line of Evidence 4 – It is unclear whether the positive retention observed at 6 mg/day and 8 mg/day would reach zero balance over longer exposure and observation periods	?
Line of Evidence 5 – Interindividual variability of copper kinetics, absorption and excretion, in the population	?
Line of Evidence 6 – The population of ATP7B gene variant heterozygotes, may be susceptible to increased copper retention in the liver compared with the general population	↑
Line of Evidence 7 – In pregnant and lactating women, circulating levels of copper are regulated by the same homeostatic systems, with additional specific mechanisms operating at the level of the placenta and the mammary gland	●
Conclusion – based on a process of weighing the influence of the different lines of evidence, their consistency and semi‐formal expert judgement, the overall evidence does not support the premise that copper exposure up to 0.07 mg/kg bw per day leads to hepatic copper retention.	Very unlikely (5–10% probability)