Yoon M, Ring C, Van Landingham CV, Gentry PR, Taylor MD, Keene AM, Clewell HJ. Assessing early life drinking water exposures to manganese (Mn). Poster at Society of Toxicology Annual Meeting, Baltimore, MD, March 2019.
A previously published human PBPK model for Mn in infants and children, which was able to successfully capture age-dependent Mn homeostasis at dietary steady-state and various environmentally relevant inhalation exposure conditions, has been updated with drinking water Mn as an additional exposure source. Built upon the ability to capture Mn source-specific regulation of intestinal uptake in nursing infants between breast milk and formula milk, the updated model also describes the bioavailability of Mn from drinking water during this life period as being the same as that for a non-breast-milk-based diet. Formula-fed infants of 1 to 3 months have the highest potential exposure to Mn from drinking water compared to all other age groups, as shown by the analysis from Brown and Foos (2009). To examine the impact of drinking water exposure on Mn internal exposure in this age group, Mn concentrations in the blood and brain of 3 month old infants fed with human breast milk or formula milk prepared with drinking water with and without Mn were simulated using the updated neonatal model. The estimated neonatal drinking water Mn intake was 1 mg Mn/day, based on age-specific drinking water consumption rates and Mn levels in drinking water from US EPA’s National Inorganics and Radionuclides Survey conducted in 2003. The total daily Mn intakes for these three scenarios were at 0.0023, 1.145, and 2.145 mg Mn/ day, respectively. Model-predicted whole-blood Mn concentrations in breast milk-fed infants were about 80% of that in formula-fed infants, which agreed with the observation described in Stastny et al. (1984). Adding drinking water Mn exposure to the formula milk exposure increased infants’ blood and brain concentrations by approximately 9.3 and 7.6 %, respectively, the extent of which falls within the observed variation of Mn concentrations in infants’ blood in Stastny et al. study. This multi-route, multi-source Mn PBPK model for infants and children will contribute to evaluating the realistic impact of drinking water exposure to Mn in early age populations and will thereby improve the level of confidence in understanding exposure-health effects relationships reported to be associated with early age Mn exposure in human epidemiological studies.