Effects of Toxic Metal Exposures and Their Mixtures on Adverse Health Outcomes in the Peruvian Amazon

Non-essential trace metals (lead, mercury, arsenic, and cadmium) are ubiquitous in our environment and have overlapping routes of exposure, yet mixed trace metal exposures are rarely considered in epidemiological studies. Instead, research often follows a single research question that focuses on a single trace metal of concern and does not incorporate potential co-exposures. The published literature of artisanal small-scale mining in the Amazon is a prime example as it has predominantly focused on mercury exposure, due to its use in the mining process. Once exposures of concern are identified, further studies evaluate health outcomes; however, the health effects cannot be accurately determined without accounting for co-exposures. This verification is becoming more important as there is a growing recognition that mixed trace metal exposures are more common than previously believed.To address the prevalence of mixed trace metal exposures and their health effects in the Peruvian Amazon region of Madre de Dios, I use epidemiological data from the COhorte de NAcimiento de MAdre de Dios (CONAMAD) birth cohort study (2018-Present), and two cross-sectional epidemiological studies (Amarakaeri Communal Reserve study (ACR, 2015), and Etiology and Toxic Metals study (EATM, 2018)). CONAMAD collected survey data along with maternal and cord blood samples at birth, which were processed for minerals and trace metals. The cross-sectional studies collected venous blood for trace metal analysis and hair samples for total hair mercury. Blood samples from the ACR were also processed for amino acids. In-depth demographic and health survey data were collected in all three studies. Structural equation models and random mixed effect models were used to evaluate research questions. The cross-sectional studies demonstrate a high correlation of lead and mercury exposure in communities that rely on wild fish and wild game as protein sources, which is prevalent throughout the Amazon. Consuming a meal of wild game resulted in an estimated lead dose of 500 µg, with those who eat wild game (Yes/No) associated with 1.41 µg/dL (95% CI: 1.20 – 1.70) higher blood lead levels compared to those who do not. This furthers the notion that mixed exposures are likely more common than previously believed. Mixed exposures target the same toxicological pathway, which may lead to synergistic or antagonistic effects. My research found that lead disrupts the arginine pathway and is associated with increased blood pressure. Mercury exposure was a modifier of the arginine pathway, with high blood mercury levels changing the effect of global arginine bioavailability from 17.16 (95% CI: 9.09 – 25.84) to -14.17 (95% CI: -31.88 - -0.33) on systolic blood pressure. Interestingly, mercury was not directly associated with the arginine pathway. Results from the birth cohort demonstrate the importance of nutrition and prenatal care for fetal development, which had a large positive effect on birthweight and gestational age. However, even low maternal lead exposure had detrimental effects on fetal health. A 1% increase in maternal blood lead was associated with a shorter gestational age of 0.05 days (β: -0.75, 95% CI: -1.51 - -0.13), even with the CONAMAD birth cohort having lower blood lead levels than other birth cohorts. There is a need for an integrated approach of nutritional and exposure assessments to better understand neonatal health outcomes.