Since its inception in 1987, Superfund Research Program (SRP) grantees have conducted research that environmental managers and risk assessors can use to make decisions related to hazardous substances. As specified in the Superfund Amendments and Reauthorization Act (SARA), the legislation that established the SRP within the National Institutes of Health, SRP research responds to four mandates:
- Advanced techniques for the detection, assessment, and evaluation of the effects on human health of hazardous substances
- Methods to assess the risks to human health presented by hazardous substances
- Methods and technologies to detect hazardous substances in the environment
- Basic biological, chemical, and physical methods to reduce the amount and toxicity of hazardous substances
As we look back on 30 years of the SRP, this feature highlights an example of fundamental research in each of the program’s mandates, which has led to important discoveries that can improve public health.
Mandate 1: Evaluating the human health effects of benzene
University of California, Berkeley SRP Center grantee Martyn Smith, Ph.D., and colleagues have identified biomarkers of benzene exposure to systematically explore relationships between benzene and health effects, including variability in human metabolism of benzene. Smith has been a grantee since the first SRP grants were awarded in 1987.
Using biomarkers to assess exposure, they showed that exposure to benzene levels in air below the U.S. occupational standard of one part per million may lead to a decrease in circulating blood cells. They also found that benzene is toxic to progenitor cells, the unspecialized cells from which all other blood cells develop.
Building on this work, they studied a group of non-smoking women and identified an unknown pathway responsible for benzene metabolism at low levels. Because benzene must be metabolized to be toxic, these results provided evidence that the metabolism of benzene and its associated leukemia risk could be greater in the population than previously thought. According to Smith, benzene affects the blood-forming system at low levels with no evidence of a threshold, and there is probably no safe level of exposure to benzene.
In a large-scale evaluation of genes, Smith and colleagues identified associations between benzene toxicity and five genes related to DNA repair and genomic maintenance. Studies of cell function provided evidence that these genes play an important role in benzene-induced damage to blood cells.
Smith’s current work also focuses on systematically organizing mechanistic data to evaluate whether chemicals are human carcinogens. This method is intended to create a more manageable, ordered way to evaluate data based on key characteristics of human carcinogens. Smith is also working with collaborators to explore the exposome, or the accumulation of exposure to environmental stressors that people receive throughout their lives.
Mandate 2: Assessing risks to human health presented by tetrachloroethylene
In 1997, Ann Aschengrau, Sc.D., from the Boston University SRP Center, initiated a study in the Cape Cod region of Massachusetts to determine whether exposure to tetrachloroethylene (PCE) is linked to negative health effects.
Beginning in 1968, a vinyl liner containing PCE was applied to pipes in the Cape Cod drinking water distribution system. The vinyl liner was improperly cured, leaching PCE into the water supply. Due to the irregular pattern of the affected pipes, the region had drinking water with a range of PCE concentrations and little differences in other contaminants when the PCE contamination was discovered in 1980.
Aschengrau and her team conducted a study to evaluate the relationship between PCE exposure and the risk of breast cancer. They found small increases in breast cancer risk among women exposed to PCE from public drinking water. A larger study confirmed this finding, suggesting that women with the highest PCE exposure levels have a small to moderate increased risk of breast cancer.
Building on their work with the Cape Cod community, Aschengrau and colleagues investigated other relationships between PCE exposure and health effects. They revealed that prenatal and early-life exposure to PCE may be associated with increased risk of epilepsy and cancer, visual dysfunction, and mental illness later in life.
Other results suggest that risky behaviors, particularly drug use, are more frequent among adults with high PCE exposure levels during gestation and early childhood. In another study, the researchers found that prenatal exposure to both alcohol and PCE may increase the risk of using multiple illicit drugs as a teenager in an additive fashion. Moving forward, Aschengrau and her team will continue to examine the link between substance abuse and early-life exposure to PCE and social stressors, alone and in combination.
Mandate 3: Immunoassays to detect hazardous substances in the environment
Bruce Hammock, Ph.D., part of the University of California, Davis SRP Center since 1987, has pioneered the use of immunoassay technologies to detect hazardous chemicals. Immunoassays use antibodies to bind to a chemical of interest. Labels on the antibodies are used to detect this binding, which measures the presence and concentration of the chemical.
Hammock began this work by developing a biochemical tool to test for the presence of pyrethroids, a class of pesticides. Since then, his laboratory has developed more than 40 immunoassaysfor pesticides, pesticide metabolites, and other environmental contaminants. The immunoassays can be used to monitor contaminants in the environment as well as the levels that humans are exposed to contaminants using their urine.
For example, Hammock and his team have developed immunoassays for polybrominated diphenyl ether BDE-47, the insecticide fipronil, and the antimicrobials triclocarban and triclosan. These tools may be applied to further explore potential links between exposure and negative health outcomes. Recently his laboratory has been pioneering recombinant nanobodies from animals in the camel family to make cheaper more sensitive assays.
Because immunoassays don’t require expensive equipment or extensive training, Hammock and his colleagues work with partners to facilitate their use in the field. For example, they recently initiated a project with the Yurok Tribe in northern California, training them to use immunoassays to identify and monitor exposure to pesticides and other contaminants. They are also used to test pesticide exposures in agricultural workers to identify whether they need to limit their exposure or use more protective equipment.
Hammock is also known for his discovery of soluble epoxide hydrolase (sEH), an enzyme in cells that degrades chemically stable fatty acid epoxides. Some of his SRP-funded sEH work is featured in the February 2017 Science Digest.
Mandate 4: Biological methods to detoxify chlorinated compounds
James Tiedje, Ph.D., and colleagues use a variety of molecular methods to explore how bacteria detoxify chlorinated compounds. Tiedje has been a part of the Michigan State SRP Center since 1989.
Tiedje and his team have been exploring the genes involved in degrading polychlorinated biphenyls (PCBs), a family of hazardous chemicals once widely used in industrial applications that still persist in the environment. Tiedje pioneered the use of gene-targeted metagenomics, which is the study of genetic material recovered directly from environmental samples.
Tiedje and colleagues studied PCB-degrading bacteria that act in aerobic environments, which is characterized by the presence of oxygen, and bacteria in anaerobic environments, which do not contain oxygen. They found that combining an anaerobic step with an aerobic step achieved extensive degradation of PCB mixtures, including toxic PCB forms.
The researchers found a large diversity of genes in microbial populations in soils, sediments, and water. They also used tools to identify potential PCB-degrading microbial populations in PCB-contaminated river sediment and recovered genes potentially involved in the first step of PCB degradation.
Tiedje’s work reveals broad genetic potential for PCB and dioxin degradation by soil and sediment microbial communities. Knowledge gained about the anaerobic-aerobic process can be applied to the biological remediation of soils and sediments contaminated with PCBs.