So many chemicals—how do we decide which ones to study?

The question is no longer whether environmental chemical exposures produce adverse health effects in children, but rather which chemicals have the most harmful impact. Fetuses and children are especially susceptible to environmental influences. Scientists and physicians are concerned that over the last 10-30 years, the prevalence of certain childhood diseases has increased, including adverse birth outcomes, neurodevelopmental delays and deficits, respiratory effects, obesity, and diabetes. This trend drove the National Institutes of Health (NIH) to launch the Environmental influences on Child Health Outcomes initiative (ECHO) in 2016. The ECHO initiative has approximately 70 cohorts and more than 50,000 children which means the science will have far-reaching implications. We set out to identify which chemical exposures should be included in the ECHO initiative and ended up creating a novel, evidence-based method for screening and prioritizing chemicals for biomonitoring.

Because industry produces so many chemicals—selecting which ones to study is a major challenge. More than 170,000 chemicals have been created for commercial use, and more than 8,000 are produced in quantities greater than 12 tons per year. Scientists have detected a thousand plus chemicals in human blood, but these represent an unknown fraction of the total chemicals manufactured. During the past 30 years, researchers have expanded the number of chemicals that can be measured in the U.S. population, but they have only measured a few hundred chemicals and examined even fewer for human health effects. Because of the plethora of chemicals and the effort required to study each, it is not surprising that we have only a paucity of knowledge about chemical exposure and health effects.

We wanted to look for novel chemicals that had not been previously biomonitored nation-wide or in ECHO, so we set out to develop a method of identifying them. After we identified the chemicals, we prioritized them as recommended for biomonitoring, deferred pending additional data, or low priority for biomonitoring.

We identified chemicals that had a high likelihood of exposure among children and that are likely to increase risk to one of the four ECHO priority adverse childhood outcomes—adverse pregnancy, neurodevelopment, respiratory, obesity outcomes. To do this we used a two-prong approach.

First, we examined USDA, FDA, and EPA databases and the literature. We selected only chemicals that were prevalent in air, house dust, drinking water or food samples; chemicals that are likely to result in human exposures.

Second, we reviewed chemicals found in consumer products that the EPA has identified as likely to be used by children and women. For this case, we visually examined more than 20,000 chemicals for chemical structures that have been empirically shown to exhibit toxic effects in humans and animals.

From the combined lists of 932 chemicals, we selected chemicals that had not been studied in the Centers for Disease Control and Prevention’s National Health and Nutritional Examination Survey. Though this approach helped us to narrow our focus, we were still only able to survey a small segment of the universe of synthetic chemicals.

Armed with our list of 720 potentially toxic chemicals, we set out to prioritize them. We reduced the list to 155 chemicals by categorizing them into 8 chemical groups with similar chemical properties—alternative flame retardants, alternative plasticizers, aromatic amines, environmental phenols, organophosphorus-based flame retardants, perfluoroalkyl substances, pesticides, and quaternary ammonium compounds (Figure 1).

Figure 1. A novel, evidence-based method for screening and prioritizing chemicals for biomonitoring.

Next, we used published data to answer the following three questions:

  1. Is the chemical found in quantifiable levels in human biospecimens (e.g., blood, urine, hair, breast milk)?
  2. Is there evidence that the chemical may cause health effects of interest (e.g., predictive modeling, high-throughput in vitro assay, animal, and human data)?
  3. Is there a method for a biomarker to assess body burden to the chemical?

Of the 155 chemicals, we found enough evidence to recommend 36 for biomonitoring in the ECHO program. The other 108 chemicals were deferred pending more information, and currently 11 are categorized as low priority for biomonitoring.

The top 12 chemicals prioritized for biomonitoring are shown in Figure 2. We found these chemicals to be detected at a frequency greater than 40% in human biospecimens and many of them may elicit a combination of multiple health effects—endocrine, developmental, reproductive, neurotoxicity, or obesity.

Top 12 Chems
Figure 2. Top 12 of the 36 chemicals with the highest detection frequency in human biospecimens and potential toxic effects recommended for biomonitoring in the ECHO study.

We are thrilled that the 36 chemicals we recommended for biomonitoring will be included in the ECHO study. Also, our novel, evidence-based method for screening and prioritizing chemicals has made it easier to identify research opportunities, especially regarding the 108 deferred chemicals. The next challenge is to categorize the 560 plus chemicals that we had to leave on the table. With so little knowledge about so many chemicals—we cannot emphasize enough the need for more research to improve our understanding of the potential health consequences for pregnant women, infants, and young children from exposures to chemical pollution.

About the authors

EdoDr. Edo Pellizzari is internationally recognized for his contributions to environmental health science. He has served as principal or co-principal for more than 100 projects studying human exposure to toxic chemicals. He was the first environmental health scientist to conceptualize and implement population-based total exposure to toxins studies, and he pioneered the design and implementation of probability-based population exposure studies. He has served on National Academy of Sciences committees, the Environmental Protection Agency’s Science Advisory Board, and is currently a fellow at RTI International.

DeborahDr. Deborah Bennett is a Professor of Environmental Health in the Division of Environmental and Occupational Health of the Department of Public Services-Epidemiology at University of California, Davis. Her research focuses on the measurement and modeling of organic compounds in homes, offices, and indoor spaces. Ultimately, the goal of her work is to develop tools to help policy makers reduce human exposure, and subsequent health effects to pollutants in the environment. Her current work focuses on childhood asthma, autism, and how to rapidly evaluate exposure in indoor environments.