DHA Public Health Toxicologists Collaborate with VHA to Advance Dried Blood Spot Testing for Military Exposure Assessments

DHA Public Health Toxicologists Collaborate with VHA to Advance Dried Blood Spot Testing for Military Exposure Assessments

One of the challenges for Department of Defense public health experts in determining the impact of exposures on service members is identifying specific exposures and quantifying the exposure level that can lead to adverse health outcomes.

Service members are exposed to a variety of chemical and biological substances, and the DOD and the Veterans Health Administration have responsibilities to care for service members who put themselves in harm's way.

Understanding Past Exposures

A significant barrier to improving health care for service members and veterans is the inability to determine whether a diagnosed medical condition is related to a previous exposure. Individuals are often unaware of the toxic substances they were exposed to, and it is difficult to reconstruct one's past exposure history.

"Understanding past exposure events and their potential influence on health is necessary to provide informed care and to reduce the probability of future adverse events," said Thomas Sussan, chief of the toxicity evaluation division for Defense Health Agency-Public Health in Aberdeen, Maryland, and co-chair of the interagency Toxic Exposures Research Working Group.

The Toxic Exposures Research Working Group is undertaking a study directed by the PACT Act to develop and guide a collaborative five-year strategic research plan on the health outcomes of toxic exposures during military service.

New Monitoring Approaches Needed

According to the Department of Veterans Affairs, the PACT Act, which was signed into law in 2022, provides significant resources to improve and expand health care to veterans who were exposed to toxic substances during their military service. This funding includes efforts to advance exposure assessment methods and to develop a greater understanding of the associations between exposure and health.

"Environmental sampling of air, soil, and water provides information on potentially toxic exposures, although detection of toxicants in environmental samples does not necessarily indicate the level of individual exposures," said Sussan. "Biological sampling can improve exposure assessment and more reliably quantify exposure levels."

Sussan says the DOD maintains large biorepositories that store serum, tissues, or other biological specimens; however, it's not practical to draw blood from every person on a base or deployment after each suspected exposure.

"New approaches are needed to improve exposure monitoring, especially for chemicals that may accumulate in service personnel," said Sussan.

Dried Blood Spot Sampling

A less-invasive alternative to the traditional blood draw is the use of dried blood spots, or DBS, in which a small amount of blood is collected from the fingertip, heel, or arm and deposited onto a paper card or strip where it is allowed to dry.

"DBS have many advantages over traditional blood draws," said Sussan. "DBS are easy to collect and store, require minimal processing, are stable, and are better suited for exposure monitoring due to their ability to be collected on location at the same time as an expected exposure. You can also self-administer a DBS collection."

Sussan says the stability and storage of DBS samples will enable future analysis of suspected exposures, and there are several benefits to maintaining a longitudinal DBS repository, including:

• It is easier to maintain than a serum repository because it requires less space and does not require cold storage.
• It is less expensive and may provide valuable information for emerging exposures.
• It could help the VA make decisions regarding veterans' claims for health care.
• It could be a resource to detect past exposures.

Sussan says DBS may serve as a valuable tool to better understand potentially toxic exposures to our military personnel, and the current study will help to demonstrate their utility.

DOD Firefighter Case Study

During firefighting activities, firefighters are exposed to a multitude of hazards, including industrial chemicals, combustion byproducts, and materials associated with firefighting (for example, per- and polyfluoroalkyl substances, or PFAS, associated with aqueous film-forming foam, or AFFF, use.

Sussan explains identifying exposure sources and levels is a challenge for DOD public health experts. Monitoring of multiple exposures that DOD firefighters may experience can assist the DOD in determining whether DBS can be used for complex exposures such as deployments.

"Health risk assessments will leverage ongoing PFAS blood tests offered to DOD firefighters to assess the effectiveness of DBS as a measure of exposure," said Sussan. "The Toxic Exposures Research Working Group study team will quantify PFAS concentrations in matched dried blood spots and blood samples to determine the degree of correlation between these two samples."

Results from these tests include total PFAS exposures that the firefighter's experienced from occupational and other PFAS exposure sources, such as drinking water and commercial products, said Sussan.

Sussan said exposure to PFAS is associated with a wide range of potential adverse health effects, although there is often a lack of consensus on the associated effects-particularly for low-level exposures. Numerous expert panels have reviewed the available evidence and identified the following potential health effects, including:

• Increases in cholesterol levels
• Small decreases in birth weight
• Lower antibody response to vaccines
• Kidney and testicular cancer
• Pregnancy-induced hypertension or preeclampsia
• Changes in liver enzymes

Sussan notes that identification of potential hazards associated with PFAS exposure has led to the gradual phase-out of many PFAS compounds from consumer products and AFFF, starting in the early 2000s. This phase-out has led to a decline in the measured levels of PFOS and PFOA, which are the two of the most common PFAS chemicals and the most studied, in the blood of the general U.S. population.

Monitoring PFAS Exposure in Firefighters

"Individuals who are occupationally exposed to PFAS during its production generally exhibit the highest levels of certain PFAS blood level concentrations," said Sussan. "Firefighters have exhibited higher blood PFAS levels than the general population for certain PFAS, and their body burden correlates with number of years of AFFF contact."

The planned study will quantify more than 30 PFAS in a targeted manner that specifically looks for those chemicals, said Sussan.

"Additionally, we will conduct a nontargeted analysis where we will screen the samples to see what other chemicals we find," said Sussan.

Sussan says the study may also find other compounds associated with firefighting, such as those related to combustion or to other fire suppressants.

"We chose the PFAS compounds to include PFAS associated with AFFF and turn out gear and other PFAS compounds to evaluate other potential PFAS exposures firefighters might experience during responses and to evaluate the analytical method," said Sussan. "We will also attempt to validate the use of DBS as biomarkers that correlate with potential exposures."

Traditionally, PFAS were included in AFFF used by firefighters because they create both a foam blanket to suffocate fires and a thin film to coat and cool the surface of the flammable fuel, said Sussan.

"PFAS are also used in the outermost layer of turnout gear to provide water resistance and protection to firefighters," said Sussan. "It is for these reasons that firefighters are expected to have higher exposures to PFAS than the general population."

The proposed study plans to build on the robust PFAS screening that is already in practice in the DOD and will quantify PFAS concentrations in matched DBS and blood samples from DOD firefighters to determine the degree of correlation between these two samples. It should be noted that DBS and blood testing will not identify the source of exposures, which could be due to the combination of occupational exposures, environmental sources (such as drinking water), and from consumer products.

The study will also evaluate other chemicals of importance to firefighters, including combustion products, like polycyclic aromatic hydrocarbons, or PAHs, said Sussan.

According to the Agency for Toxic Substances and Disease Registry, PAHs are a group of over 100 different chemicals that are formed during the incomplete burning of coal, oil and gas, garbage, or other organic substances like tobacco or charbroiled meat. These chemicals are associated with impaired lung health and with cancer and can be common indoor pollutants. During and following a fire, PAHs are usually found as a mixture containing two or more of these compounds, such as soot. Also, household objects-plastic toys, furniture, utensils, household pesticides, dyed textiles, and items containing rubber and plastic components-may burn and release PAHs into the air.

While the current proposal is focused on exposure to PFAS and other compounds associated with firefighting, Sussan said future studies may employ other expected exposure scenarios and military settings as well as a data sharing framework.

"The long-term goal of this study is to demonstrate the utility, feasibility, and logistics of a pipeline for DBS collection, storage, and analysis to explore the potential for a DBS repository," said Sussan.

Sussan said this data-sharing framework will allow for the flow of data collected from future efforts from the Defense Health Agency, military services, and VA that may eventually be incorporated into the individual longitudinal exposure record, or ILER. The ILER is a record of exposures designed in collaboration between DOD and the VA for each service member and future veteran. This record will begin with entry into military service and span across an entire military career.

"Finally, it will be important to understand what the blood concentrations of the measured PFAS compounds are for comparison as health study information becomes available from Centers for Disease Control and Prevention and ATSDR health studies, and we evaluate toxicological information with our U.S. government partners and others," said Sussan.

Sussan says it's equally important to understand exposures to other chemicals that DOD firefighters are experiencing.

"We are proud to partner with the VA to explore the potential of DBS as a tool for assessing exposure and to ensure that the PACT Act realizes its goal of expanding VA health care and benefits for veterans exposed to toxic substances," said Sussan.