An Industry-Relevant Metal Mixture, Iron Status, and Reported Attention-Related Behaviors in Italian Adolescents

Background: Exposure to environmental metals has been consistently associated with attention and behavioral deficits in children, and these associ­ations may be modified by coexposure to other metals or iron (Fe) status. However, few studies have investigated Fe status as a modifier of a metal mixture, particularly with respect to attention-related behaviors. Methods: We used cross-sectional data from the Public Health Impact of Metals Exposure study, which included 707 adolescents (10-14 years of age) from Brescia, Italy. Manganese, chromium, and copper were quantified in hair samples, and lead was quantified in whole blood, using induc­tively coupled plasma mass spectrometry. Concentrations of Fe status markers (ferritin, hemoglobin, transferrin) were measured using immunoassays or luminescence assays. Attention-related behaviors were assessed using the Conners Rating Scales Self-Report Scale-Long Form, Parent Rating Scales Revised-Short Form, and Teacher Rating Scales Revised-Short Form. We employed Bayesian kernel machine regression to examine associa­tions of the metal mixture with these outcomes and evaluate Fe status as a modifier. Results: Higher concentrations of the metals and ferritin were jointly associated with worse self-reported attention-related behaviors: Metals and fer­ritin set to their 90th percentiles were associated with 3.0% [b = 0:03; 95% credible interval (CrI): -0:01, 0.06], 4.1% (β = 0:04; 95% CrI: 0.00, 0.08), and 4.1% (β = 0:04; 95% CrI: 0.00, 0.08) higher T-scores for self-reported attention deficit/hyperactivity disorder (ADHD) index, inattention, and hyperactivity, respectively, compared with when metals and ferritin were set to their 50th percentiles. These associations were driven by hair manga­nese, which exhibited nonlinear associations with all self-reported scales. There was no evidence that Fe status modified the neurotoxicity of the metal mixture. The metal mixture was not materially associated with any parent-reported or teacher-reported scale. Conclusions: The overall metal mixture, driven by manganese, was adversely associated with self-reported attention-related behavior. These find­ings suggest that exposure to multiple environmental metals impacts adolescent neurodevelopment, which has significant public health implications.