The Rapidly Changing List of Harmful Substances Creates Analytical Challenges
“The constantly changing landscape of chemicals introduced into the environment makes it difficult to develop and validate methods in a timely enough fashion to evaluate early exposures,” says Dana Boyd Barr, professor at Emory University’s department of environmental health in Atlanta, Georgia, and past chief of the pesticide laboratory at the U.S. Centers for Disease Control and Prevention. “Of the more than 70,000 chemicals introduced into manufacturing, we have only developed methods for maybe 300, some of which are more relevant today than others.” This stacks up as a tricky challenge when government officials encourage enhanced biomonitoring of environmental chemicals.
Despite the challenges, the health ramifications drive governments to track the levels of environmental chemicals in people. For example, biomonitoring makes up part of the National Health and Nutrition Examination Survey (NHANES) in the United States, and the Consortium to Perform Human Biomonitoring on a European Scale (COPHES) provides data across the European Union. In general, biomonitoring surveys of environmental chemicals could help identify the need to reduce or prevent many public health problems. For instance, Barr’s SAWASDEE (Study of Asian Women and Offspring’s Development and Environmental Exposures) study—an investigation of the health impact on children in northern Thailand whose mothers were exposed to pesticides during pregnancy—revealed “extensive exposure during pregnancy in these women, and they have had essentially no education on safe-use practices in the field,” she says. In fact, Barr and her colleagues found that more than 95 percent of the women didn’t even think that pesticide exposure during pregnancy could harm the health of their babies. “We’ve found significant associations with prenatal pesticide exposure and motor skills, attention, and reflexes in their babies,” Barr says. “Biomonitoring was essential in identifying the magnitude of these exposures.”
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The health problems related to environmental chemicals, however, are not exclusive to developing regions. For instance, a 2015 report from the World Health Organization regarding Europe concluded: “The available data show that exposures to toxic metals remain a serious public health problem.” This exposes the global nature of this problem.
In 2006, the California Environmental Contaminant Biomonitoring Program (or Biomonitoring California) was established to measure and track potentially harmful chemicals in residents and help evaluate how well regulatory efforts were working to reduce peoples’ exposures to these chemicals. Sara Hoover, chief of the Safer Alternatives Assessment and Biomonitoring Section at California’s Office of Environmental Health Hazard Assessment, says, “Biomonitoring California’s laboratories are among only a few in the U.S. with the advanced analytical capability to measure trace levels of chemicals in very small volumes of blood and urine.” In fact, these labs can test for about 140 chemicals, with summary results tabulated in an online database. The program also returns individual results to any study participant who requests them, and provides national levels and levels of known health concern established by federal or state health agencies—such as for lead—for comparison.
Biomonitoring California has made a special effort to study exposures to flame retardants. For example, Hoover described a study of infants in San Francisco that showed “higher levels of certain chemicals compared to their mothers, including PBDE [or polybrominated diphenyl ether] flame retardants that have been banned in California due to health concerns.” Biomonitoring California also found higher levels of PBDE flame retardants in firefighters in southern California compared with the U.S. general population and with other California populations.
Those are just a couple of the findings that show potential danger from exposure of humans to environmental chemicals.
Moreover, Biomonitoring California continually adds new studies. Hoover says, “Biomonitoring California’s new initiatives include a study to measure environmental chemicals in serum from pregnant women across the state, and an effort to broadly screen samples for previously undetected chemical contaminants.”
In addition to the vast number of chemicals that could be in a sample, some fundamental challenges face chemists. As Barr says, “From a chemist’s perspective, it is often difficult to find pure enough versions of the chemical to allow us to appropriately quantify that chemical.” Other experts agree that more work remains to improve the technology and methodology behind biomonitoring. In a 2014 issue of Environment International, Judy LaKind, president of Maryland-based LaKind Associates and adjunct associate professor at the University of Maryland School of Medicine, and her colleagues reported: “To date, the scientific community has not developed a set of systematic guidelines for designing, implementing and interpreting studies of short-lived chemicals that use biomonitoring as the exposure metric or for evaluating the quality of this type of research for [weight-of-evidence] assessments.” To that end, LaKind and her colleagues developed the Biomonitoring, Environmental Epidemiology and Short-lived Chemicals (BEES-C) instrument; this is the first available instrument for evaluating the quality of research proposals and studies that incorporate biomonitoring data on short-lived chemicals.
Moreover, LaKind points out that interpreting the data can be complex. “For chemicals with short half-lives in the body, understanding what the data are telling us about exposure is challenging,” she says. “Exposures to these chemicals can be highly variable, and single measures of a chemical are not very informative for understanding longer-term exposures.”
Beyond the complexity in the data, the sample environment also raises challenges. “Many of the chemicals that are the focus of current biomonitoring studies are ubiquitous in the environment and can also be found in laboratory settings,” LaKind explains. “Making sure that collection, shipping, storing, and analysis of samples using approaches that prevent sample contamination is paramount.”
Even if the scientific community develops effective guidelines for all aspects of biomonitoring for environmental chemicals, the problem presents a moving target. As Barr explains: “The change of chemical space means that we need to continually develop methods for the newly emerging chemicals and begin researching their health outcomes.”
Connecting the Dots
In many cases, governments set exposure limits for chemicals, but those are not easily translated into the likely levels that end up in humans. To address this problem, Sean Hays, president and founder of Colorado-based Summit Toxicology, developed biomonitoring equivalents (BEs).
In brief, BEs translate exposure levels to levels that would be obtained via biomonitoring. To make that conversion, Hays and his colleagues use pharmacokinetic models of how a chemical is processed in the body.
The calculation comes from studies in the literature for a particular compound, and Hays makes his approach open and available to anyone. He says, “We purposefully didn’t trademark anything, because we want governments to use the BE method.” But here’s the tricky part: This approach is very chemical-specific, so assessing a new chemical usually requires a new method. As Hays says, “No one equation works for all chemicals.”
This technology can also connect exposure levels set by governmental agencies as not likely to cause health harm with in vitro toxicology testing. For example, the BE method will indicate the biological level created by a particular exposure level, and that biological level can be applied to cell lines in high-throughput screening systems. Then, scientists can study an exposure level’s impact on cell health.
The breadth of chemicals that might be troublesome makes biomonitoring difficult. In addition, the use of heterogeneous samples, such as human blood or urine, often requires significant sample preparation.
Moreover, analytical chemists in biomonitoring programs must make sure to analyze for the right things. According to Merle Plassmann, a postdoctoral fellow in the analytical environmental chemistry unit at Stockholm University in Sweden, “You have to differentiate between target analysis of chemicals and the search for emerging contaminants that might appear in human tissues.” She adds, “During a search for emerging contaminants the main problem is that one does not know what to look for.”
When biomonitoring must screen many possible chemicals, says Plassmann, “it is best to use broad extraction methods and new high-resolution mass spectrometry instruments. This way, even non-targeted emerging contaminants can be detected.”
In general, experts point to mass spectrometry as the stateof- the-art analytical approach for biomonitoring. Although this technology provides the most accurate output, some labs and even some countries might not be able to afford this approach. As Barr says, “Mass spectrometers are quite expensive, so that also drives up the cost of analysis.”
Keep it Cheap
To expand the application of biomonitoring, scientists must keep developing new methods. Some of them will use an extraction method called QuEChERS, which stands for: quick, easy, cheap, effective, rugged, and safe. “The QuEChERS technique is a really easy-to-handle and quick extraction method,” Plassmann says. “And the main benefit for biomonitoring is that it is a fairly broad method, meaning that it can extract many chemicals with different properties at once.”
Plassmann and her colleagues at the Helmholtz Centre for Environmental Research in Leipzig, Germany, tested QuEChERS for biomonitoring and reported their results in 2015 in Analytical and Bioanalytical Chemistry. They tested human blood samples for a variety of environmental chemicals. The scientists used QuEChERS to extract 64 analytes and then analyzed them with liquid or gas chromatography followed by mass spectroscopy. Just the first step of QuECh- ERS, which is a liquid-liquid extraction, captured more than 70 percent of 47 of the analytes; adding the second step of QuEChERS, which is a solid-phase extraction, didn’t significantly increase the amount of analyte captured.
This study showed that even broad approaches cannot always reveal all environmental chemicals. Even more troubling, the realm of what can be dangerous to health and the number and types of environmental contaminants found in biological samples increases every year. Still, experts strive to reduce environmental contamination to improve public health around the world.