# Metal Mixtures and the Role of Iron Status in Early Adolescent Cognition

> **NIH NIH F31** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $36,501

## Abstract

Project Summary/Abstract
Metals are known neurotoxicants in children, but less attention has been given to the impact of metal mixtures
on cognitive function. Further, few studies of metals have examined the role of iron status on cognitive
outcomes in adolescents. Our study aims to describe the neurotoxicity of an industrial-relevant metal mixture
(Mn, Pb, Cu, Cr) on the domains of attention and verbal learning and memory in adolescents, and to identify
subpopulations that may have greater susceptibility to metals by elucidating the role of iron status in metal-
induced toxicity. This proposed study will use previously collected data from the Public Health Impact of Mixed
element Exposure (PHIME) study, a cohort of 720 Italian children aged 10-14 years. Children in PHIME were
recruited from three distinct geographic regions of the Brescia Province with varying exposure to airborne
ferromanganese alloy industry. Under the mentorship of a multidisciplinary team of experts in environmental
epidemiology, biostatistics, exposure science, neurobehavioral toxicology, and mixtures, Samantha Schildroth
(PI) proposes the following aims: 1) describe associations of metal mixtures with attentional function and
verbal learning and memory in adolescents; 2) assess the role of iron status as a) a modifier of metals
neurotoxicity that alters associations between the metal mixture and cognition, and b) a mediator that is
impacted by the metal mixture and affects cognition. Metals in PHIME were measured in multiple biomarkers
(hair, nails, blood, saliva, urine) and iron status parameters were measured in whole blood (ferritin,
transferrin, and hemoglobin) and using hematocrit/serum iron levels. Objective measures of cognitive function
were used to assess attention (Conners-Wells Rating Scales) and verbal learning and memory (California
Verbal Learning Test). We will use state-of-the-art statistical approaches for mixtures, including Bayesian
Kernel Machine Regression and quantile-based g-computation, to address our proposed aims. The research
outlined in this proposal will contribute to our current understanding of the neurotoxicity of a metal mixture
relevant for communities living in proximity to ferroalloy emissions, an industry that is expanding globally, on
two domains necessary for the overall cognitive function of children and will examine iron status as a potential
susceptibility factor. The proposed training and research will expand upon the applicant's strong foundation in
environmental epidemiology and provide her with additional skills needed to study the joint effects of multiple
metals on cognition, while considering iron status. This research will 1) address the large data gap on health
effects of metal mixtures in adolescents, and 2) help characterize modifiable environmental factors, including
dietary factors like iron status, in adolescence that may be targets for future public health intervention.

## Key facts

- **NIH application ID:** 10461495
- **Project number:** 1F31ES033507-01A1
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Samantha Schildroth
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $36,501
- **Award type:** 1
- **Project period:** 2022-07-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10461495

## Citation

> US National Institutes of Health, RePORTER application 10461495, Metal Mixtures and the Role of Iron Status in Early Adolescent Cognition (1F31ES033507-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10461495. Licensed CC0.

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