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7849201 
Journal Article 
Review 
How much manganese is safe for infants? A review of the scientific basis of intake guidelines and regulations relevant to the manganese content of infant formulas 
Mitchell, EJ; Frisbie, SH; Roudeau, S; Carmona, A; Ortega, R 
2021 
1 
Journal of Trace Elements in Medicine and Biology
ISSN: 0946-672X
EISSN: 1878-3252 
65 
126710 
English 
33450552 
WOS:000634880100008 
BACKGROUND: Recent research has uncovered the potential for excess manganese (Mn) intakes causing significant neurotoxic effects for early brain development.

METHODS: We identified the Mn tolerable intakes (TI) published by the U.S. Institute of Medicine (IOM), World Health Organization (WHO), Agence nationale de sécurité sanitaire (ANSES), and U.S. Environmental Protection Agency (US EPA) and examined the primary studies on which regulatory TIs are based. We converted the TIs to μg of Mn/kg/day using standard assumptions specific to each agency. We estimated μg of Mn/kg/day intakes due to formulas. Using our estimates for formula intakes, weights, and kcal content, we converted regulatory maxima and minima from μg of Mn/100 kcals to estimates of μg of Mn/kg/day.

RESULTS: Except for the proposed ANSES TI for drinking water, none of the primary studies on which Mn intake guidelines and regulations are based measured health outcomes. Some infant formulas may exceed the regulatory TIs, especially if prepared with water containing considerable concentrations of Mn (e.g. 250 μg/L), even while meeting national and international regulatory standards or guidelines.

CONCLUSIONS: Infant formula regulations must be revised to reduce the potential for excess manganese intakes and the practice of manganese supplementation of infant formulas should be ceased. 
Toddler formula; Neurotoxicity; Intellectual development; Tolerable daily intakes; Drinking water guidelines; Codex Alimentarius