Preparatory work for the update of the tolerable upper intake levels for manganese

This technical report describes collection and appraisal of scientific evidence that could be used to derive an upper intake level (UL) for manganese. Two systematic reviews were conducted to assess the relationship between ‘high’ manganese oral exposure and neurological effects in i) humans (all life‐stages) and ii) animals (mammals). Other sources of evidence were described though narrative reviews. For the two systematic reviews 14,471 records were screened at title and abstract level resulting in 49 human and 63 animal studies being included after full text screening. Two studies in adults and 19 studies in children reporting on outcomes that were judged suitable for establishing an UL were assessed for risk of bias, while all animal studies were assessed for risk of bias. Due to the lack of human studies addressing the same outcomes in comparable manner the evidence was considered too scarce to perform meta‐analyses. Evidence from the animal studies was also not considered suitable for meta‐analyses given the large heterogeneity in study design. The human evidence provided some evidence for an adverse association between manganese exposure from drinking water and intelligence quotient (IQ) in children. The reported effect size in studies reporting significant associations was in the range of 2 to 4 lower IQ points per 10‐fold increase in manganese concentrations in drinking water. Animal studies provided more consistent evidence for adverse effects on neurodevelopment at relatively high doses compared to human exposures. Animals exposed during early life were found to be more sensitive to Mn neurodevelopmental effects.