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. 2019 Dec;127(12):126001.
doi: 10.1289/EHP5133. Epub 2019 Dec 18.

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

Edo D Pellizzari  1 , Tracey J Woodruff  2 , Rebecca R Boyles  3 , Kurunthachalam Kannan  4 , Paloma I Beamer  5 , Jessie P Buckley  6 , Aolin Wang  2 , Yeyi Zhu  7   8 , Deborah H Bennett  9 ; (Environmental influences on Child Health Outcomes)
Affiliations

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

Edo D Pellizzari et al. Environ Health Perspect. 2019 Dec.

Erratum in

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. https://doi.org/10.1289/EHP5133.

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Figures

Figure 1 is a flow chart, where USDA, FDA, U.S. EPA, and NHANES databases and literature has an arrow leading toward drinking water, air, house dust, food, and biofluids and U.S. EPA, CPCat database: 372 product categories; approximately 170,000 chemicals has an arrow leading toward selected 45 consumer product categories. Drinking water, air, house dust, food, and biofluids has an arrow leading toward EM list. Selected 45 consumer product categories has an arrow leading toward CP list. EM list constitutes chemicals quantifiable in greater than 20 percent of samples. CP list constitutes chemicals selected with toxic moiety. An arrow each from EM list and CP list leads to C list (932 chemicals) once the duplicates are removed and inorganics are excluded. C list (932 chemicals) is sorted into chemical groups 1 to 5 in two parts. One part has G1, measured nation-wide (NHANES); G2, legacy chemicals. The second part has G3 (260), G4 (293), G5 (167), and total chemicals (720). This process leads to selected 155 chemicals—created eight panels: AFRs (23), APs (10), AAs (28), EPs (16), OPFRs (11), PFASs (8), PEs (43), and QACs (16). Following is the hierarchy in which chemicals are prioritized as: recommended for biomonitoring; deferred, insufficient data; or low priority for biomonitoring.
Figure 1.
Overview for identifying chemicals of interest in environmental media and consumer products. C list, combined list (EM plus CP lists); CP list, consumer product list; CPCat, Consumer Product Categories; EM list, environmental list; EPA, U.S. Environmental Protection Agency; FDA, Food and Drug Administration; GI, Group I chemicals with NHANES exposure data; GII, Group II Legacy chemicals with extensive environmental, exposure and health data; GIII, Group III, chemicals with extensive environmental and no NHANES exposure data; GIV, Group IV chemicals with U.S. EPA exposure predictions and limited environmental and exposure data; GV, Group V chemicals with no U.S. EPA exposure predictions and limited environmental and exposure data, AFRs, alternative flame retardants, APs, alternative plasticizers, AAs, aromatic amines, EPs, environmental phenols, OPFRs, organophosphorus flame retardants, PFASs, perfluoroalkyl substances, PEs, pesticides; NHANES, National Health and Nutrition Examination Survey; QACS, quaternary ammonium compounds; USDA, U.S. Department of Agriculture. *, number of chemicals.
Figure 2 is a flow chart, where chemical in a panel, with an arrow points toward Question 1: present in human biospecimens or environment media? If the answer is yes, then Question 2 is as follows: toxicity concern? (neurotoxic, endocrine disrupt, developmental, etc.). If the answer is yes, then Question 3 is as follows: available biomarker ? If the answer is yes, then statement 4 is as follows: candidate chemicals for biomonitoring. A bidirectional arrow, labeled insufficient information, connects Question 1 with deferred, pending further data, e.g., measure in biospecimen in U.S. population. A forward arrow, labeled monitored; not detected, leads from Question 1 to low priority for ECHO. A bidirectional arrow, labeled insufficient information, connects Question 2 with deferred, pending further data, e.g., recommend HTP in vitro assay tests. A forward arrow, labeled low or nontoxic leads from Question 2 to low priority for ECHO. A forward arrow, labeled No, leads from Question 3 to deferred pending its development or if not possible, use proxy-measure.
Figure 2.
Overview for identifying candidate chemicals for biomonitoring. ECHO, Environmental Influences on Child Health Outcomes; HTP, high throughput.
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