Potential for Manganese-Induced Neurologic Harm to Formula-Fed Infants: A Risk Assessment of Total Oral Exposure

Abstract

Background: High oral exposure and biological vulnerabilities may put formula-fed infants at risk for manganese-induced neurotoxicity. Objectives: We sought to characterize manganese concentrations in public drinking water and prepared infant formulas commonly purchased in the United States, integrate information from these sources into a health risk assessment specific to formula-fed infants, and examine whether households that receive water with elevated manganese concentrations avoid or treat the water, which has implications for formula preparation. Methods: Manganese was measured in 27 infant formulas and nearly all Minnesota community public water systems (CPWS). The risk assessment produced central tendency and upper-end exposure estimates that were compared to a neonatal animal-based health reference dose (RfD) and considered possible differences in bioavailability. A survey study assessed esthetic concerns, treatment, and use of water in a Twin Cities community with various levels of manganese in drinking water. Results: Ten percent of CPWSs were estimated to exceed the EPA health advisory level of . Manganese concentrations in formula ranged from 69.8 to , with amino formula concentrations. Central tendency estimates of soy and amino acid formula reconstituted with water at the CPWS 95th percentile manganese concentration exceeded the neonatal-based RfD. Upper-end estimates of manganese intake from formula alone, independent of any water contribution, equaled or exceeded the neonatal-based RfD. In the survey study, we observed increased awareness of esthetic issues and water avoidance at higher manganese concentrations, but these concentrations were not a reliable consumption deterrent, as the majority of households with inside tap drinking water results above reported drinking the water. Discussion: Excessive exposure to manganese early in life can have long-lasting neurological impacts. This assessment underscores the potential for manganese overexposure in formula-fed infants. U.S. agencies that regulate formula and drinking water must work collaboratively to assess and mitigate potential risks. https://doi.org/10.1289/EHP7901

Manganese Intake in Babies: Drinking Water plus Formula Can Cause High Exposures

“…which can lead to product recall." 1 Thus, an unintended consequence of no maximum level may be harmful exposure levels during a vulnerable time of life, they suggested.…”

“…Now, in Environmental Health Perspectives , the Minnesota researchers report findings from a wider investigation of manganese levels in the state’s public water supplies and powdered infant formula, as well as the total exposure and potential risk to formula-fed infants. 1 …”

“…The authors noted that, given that the FDA standard is a minimum rather than a maximum, “it may be in the manufacturers’ interest to ensure that levels are well above the legal minimum concentration, as well as labeled levels, to avoid products being found [by the FDA to be] misbranded … which can lead to product recall.” 1 Thus, an unintended consequence of no maximum level may be harmful exposure levels during a vulnerable time of life, they suggested.…”

“…Now, in Environmental Health Perspectives, the Minnesota researchers report findings from a wider investigation of manganese levels in the state's public water supplies and powdered infant formula, as well as the total exposure and potential risk to formula-fed infants. 1 An essential nutrient, manganese is neurotoxic at high levels of exposure, 2 and evidence suggests that infants could be uniquely vulnerable to its effects. 3,4 Manganese exposures in children have been associated with neurodevelopmental outcomes that include reduced IQ, inattention, hyperactivity, and impulsivity.…”

Effects of Manganese on Genomic Integrity in the Multicellular Model Organism Caenorhabditis elegans

“…High concentrations of inhaled Mn, mostly in an occupational setting, cause acute toxicity in the respiratory system. Even higher nutritional Mn exposure arises from long-term parenteral nutrition therapy [10,11] or in formula-fed infants [12,13].…”