Assessing children's exposure to manganese in drinking water using a PBPK model

Area of Science:

• Environmental Health
• Toxicology
• Pharmacokinetics

Background:

• Manganese (Mn) is an essential metal with potential toxicity at high exposures.
• Previous models did not fully account for Mn exposure from drinking water in children.
• Understanding Mn bioavailability across different exposure routes is crucial for risk assessment.

Purpose of the Study:

• To update a human physiologically based pharmacokinetic (PBPK) model for manganese (Mn) to incorporate drinking water as an exposure source in children (ages 0-18).
• To assess the impact of Mn from drinking water on overall Mn exposure and bioavailability in various pediatric age groups.
• To enhance the interpretation of Mn exposure-health effects relationships in children.

Main Methods:

• Updated a previously published human PBPK model for Mn.
• Incorporated Mn exposure from drinking water, considering age-specific consumption rates and bioavailability.
• Integrated age-specific dietary intake and inhalation exposure data.
• Simulated Mn pharmacokinetics across different age groups (0-18 years) and feeding types (breast-fed, formula-fed).

Main Results:

• The updated PBPK model describes Mn bioavailability from drinking water in children.
• Model simulations indicate that adding drinking water exposure does not disproportionately increase Mn exposure in children compared to adults.
• Even at concentrations double the USEPA's lifetime health advisory, Mn from drinking water posed no greater risk to children.
• Formula-fed infants, despite higher potential exposure, showed no increased risk.

Conclusions:

• The multi-route, multi-source Mn PBPK model for children provides valuable insights into Mn exposure risks.
• The model improves confidence in interpreting Mn exposure-health effects relationships in pediatric populations.
• Findings suggest current Mn exposure levels from drinking water are unlikely to pose significant additional risks to children.