Lines of Evidence	Influence on conclusion
Line of Evidence 1 – Evidence of non‐Indian childhood cirrhosis, or of idiopathic childhood cirrhosis, from high copper exposure, far exceeding the UL (up to 6.8 mg Cu/L, equivalent to 6.8 mg/day), combined with unidentified genetic component	↑
Line of Evidence 2 – It is very unlikely that copper exposure in children leads to hepatic copper retention (see question 3)	↓↓
Line of Evidence 3 – High copper levels in drinking water in Germany, far exceeding the UL (9–26.4 mg Cu/L, equivalent to 9–26.4 mg/day), leading to childhood cirrhosis	↑
Line of Evidence 4 – Susceptible subpopulation of children carrying unidentified genetic component	↑
Line of Evidence 5 – The HBGV is established based on conservative criteria, as described above, related strictly to retention in adults without accounting for higher needs in children	↓↓↓
Line of Evidence 6 – There are recognised higher nutritional requirements during life stages of physical growth compared to adults	↓↓↓
Line of Evidence 7 – The rather limited data in infants do not suggest higher sensitivity to Cu toxicity as compared to the adult population	↓↓
Line of Evidence 8 – The exceedance of the HBGV in children is primarily associated with the maximum estimated exposure of the 95th percentile which is unlikely to result in sustained hepatic retention (see question 3)	↓
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 the estimated copper exposure in children at the highest end of the P95 range relative to the HBGV of 0.07 mg/kg bw per day leads to copper toxicity.	Very unlikely (5–10% probability)