Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research

Abstract

BACKGROUND: The National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns. OBJECTIVES: Our aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research. METHODS: We searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring. RESULTS: For the 155 chemicals, 97 were measured in food or water, 67 in air or house dust, and 52 in biospecimens. We found in vivo endocrine, developmental, reproductive, and neurotoxic effects for 61, 74, 47, and 32 chemicals, respectively. Eighty-six had data from high-throughput in vitro assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring. DISCUSSION: The 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals.

Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program

“…To characterize chemicals in environmental media to understand sources of exposures, we extracted results from cohort or probability-based population studies that included children, were conducted primarily in the US, and reported levels in ambient air [ 27 – 49 ], personal air [ 27 , 28 , 30 – 34 , 37 , 42 , 43 , 46 , 50 – 55 ], indoor air [ 27 , 29 – 31 , 33 , 34 , 37 , 39 , 41 , 42 , 45 , 46 , 49 , 56 – 66 ], house dust [ 29 , 41 , 61 , 62 , 64 , 67 – 97 ], drinking water [ 97 – 108 ], or food [ 97 , 104 , 108 – 115 ]. For each chemical, we recorded the highest median, mean, or geometric mean values across multiple studies that were detectable in ≥20% of samples (for food, the highest detection frequency for a commodity was selected) [ 26 ]. For chemicals that were detected in ≥20% of samples of one medium and monitored but not detected in another medium, we also display the non-detects.…”

“…We indicate the parent compound as well as the relevant metabolite(s) where applicable. To describe concentrations, we recorded the highest 75 th percentile value that was found at any of the NHANES reporting cycles [ 26 ]. To describe linear trends over time, we calculated cycle-to- cycle percentage changes in geometric mean concentrations of biomarkers detected in adolescents during at least three consecutive cycles.…”

“…The cross-sectional sampling strategy used by NHANES may not be optimal for detecting extensive seasonal exposures, which may occur in rural communities with agricultural exposures. In addition, other fungicides or herbicides not previously included in NHANES may be relevant for study in ECHO [ 26 ].…”

“…Finally, we discuss opportunities and challenges for chemical research in ECHO with the aim of spurring high-impact studies to inform interventions and policies to improve children’s health. This review focuses on chemicals currently included in NHANES biomonitoring, which also have been measured by several ECHO cohorts; we previously published recommendations for novel chemicals with limited available biomonitoring data [ 26 ].…”

Direct sample introduction GC-MS/MS for quantification of organic chemicals in mammalian tissues and blood extracted with polymers without clean-up

“…Since human tissues are generally not easily accessible for the analysis of POP concentrations, blood is often used as sample matrix for the investigation of human exposure [8]. As exposure of humans to POPs has decreased due to restrictions in the last decades, biomonitoring studies are now focusing on other bioaccumulative compounds like flame retardants, plasticizers, environmental phenols, or fungicides [9]. These compounds are not as persistent as POPs and hence have lower bioaccumulation factors, but the elimination from specimens can still require weeks up to months [9].…”