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 $300\hspace{0.17em}\mu \mathrm{g}/\mathrm{L}$ . Manganese concentrations in formula ranged from 69.8 to $741\hspace{0.17em}\mu \mathrm{g}/\mathrm{L}$ , with amino $\text{acid}>\text{soy}>\text{cow}’\mathrm{s} \text{milk}$ 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 $300\hspace{0.17em}\mu \mathrm{g}/\mathrm{L}$ 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