Papers of the Month
By Adeline Lopez
New method generates airborne free radicals for laboratory study
NIEHS-funded researchers developed a new approach to improve how environmentally persistent free radicals (EPFRs) are generated and studied in the lab. This strategy addresses a deficiency in methods to simulate realistic environmental exposures in animals.
Thermal remediation — a common approach for treating organic waste — can generate particulate matter containing EPFRs that vary in chemical composition based on their source. These compounds are highly reactive and can cause oxidative stress when inhaled. However, little is known about the human health effects of EPFR exposure, in part because relevant animal models and exposure techniques are lacking.
Scientists created and validated a novel combustion device to generate environmentally realistic EPFRs. They generated two batches of EPFRs that shared similar properties and a tendency to embed in the lungs when inhaled but contained either high or low radical concentrations. Team members also developed methods to aerosolize EPFR particles in the lab, more closely mimicking exposure conditions relevant to humans.
They compared mice exposed to filtered air with those exposed to air containing one of the groups of EPFRs. Mice exposed to EPFRs with higher free radicals had worse lung function and increased markers of vascular dysfunction. Those mice also showed greater activation of aryl hydrocarbon receptors — which play an important role in detecting and responding to pollutants — and increased expression of genes involved in antioxidant response.
The new method can produce more consistent particles and realistic conditions for EPFR studies, according to the team. It can also enable additional research investigating whether different combustion sources alter the mechanisms contributing to EPFR toxicity.
Citation: Aryal A, Noël A, Khachatryan L, Cormier SA, Chowdhury PH, Penn A, Dugas TR, Harmon AC. 2023. Environmentally persistent free radicals: Methods for combustion generation, whole-body inhalation and assessing cardiopulmonary consequences. Environ Pollut 334:122183.
Microbial process for PFAS breakdown uncovered
A study funded by NIEHS revealed important mechanistic information about how some microbes break down PFAS in the environment. The findings may inspire more cost-effective bioremediation approaches.
The team focused on chlorinated PFAS (Cl-PFAS), which are increasingly prevalent and not well studied. Cl-PFAS have the characteristic strong carbon-fluorine bonds that are challenging to break, as well as weaker carbon-chlorine bonds, which may be more vulnerable to microbial breakdown — a process called dechlorination.
The researchers evaluated the ability of an activated sludge microbial community to break down 12 different Cl-PFAS compounds with varying structures and numbers of chlorine-fluorine bonds. Then, they measured the amount of the original compound and fluoride left in the samples. They also used nontargeted analysis to identify breakdown products that would indicate the mechanistic pathways by which microbes destroyed PFAS. Finally, they identified which microbes were responsible for PFAS degradation, and the relationships between their activity and Cl-PFAS structure.
The scientists reported a novel pathway used by the microbes to ultimately break the carbon-fluorine bonds, called defluorination, and degrade PFAS by first attacking the weaker carbon-chlorine bonds. The microbes dechlorinated Cl-PFAS compounds using one of three different mechanisms. The most effective, called hydrolytic dechlorination, led to the highest spontaneous levels of subsequent defluorination. Hydrolytic dechlorination relies on water molecules to break the carbon-chlorine bond. Cl-PFAS compounds with more chlorine atoms underwent more hydrolytic dechlorination, and therefore, defluorination. Genetic analysis of the microbial community showed that two bacteria, Desulfovibrio aminophilus and Sporomusa sphaeroides, dominated PFAS breakdown.
According to the authors, the findings can help inform the design of readily biodegradable alternative PFAS compounds, as well as more cost-effective bioremediation strategies.
Citation: Jin B, Liu H, Che S, Gao J, Yu Y, Liu J, Men Y. 2023. Substantial defluorination of polychlorofluorocarboxylic acids triggered by anaerobic microbial hydrolytic dechlorination. Nature Water 1:451–461.
Higher summer humidity may increase hospitalizations for cardiovascular disease
NIEHS-funded researchers reported a link between exposure to higher humidity in the summer and more hospitalizations related to cardiovascular disease. Most climate-health studies focus on temperature, but increased humidity may be an important climate factor affecting health.
Because humid air limits sweat evaporation from the body, straining the cardiovascular system, the team set out to evaluate associations of long-term exposure to summer humidity and various cardiovascular system diseases.
The researchers used publicly available information for approximately 63 million Medicare beneficiaries living in the U.S. between 2000 and 2016. They assessed zip code-level summer average humidity and humidity variability based on daily estimates from the Gridded Surface Meteorological dataset. Using statistical models adjusted for individual and area socioeconomic status indicators, temperature, and winter humidity, they estimated associations between summer humidity and hospitalizations for cardiovascular disease, coronary heart disease, and cerebrovascular disease.
Higher summer average humidity and humidity variability were associated with an increased risk of hospitalization for all three diseases. These associations were more pronounced among those eligible for Medicaid, an indicator of low socioeconomic status, and with beneficiaries of unknown race or a race listed as “other.” Associations were not affected by adjusting for temperature or regions of the U.S.
According to the team, increasing humidity levels may be an important contributor to climate-related health effects.
Citation: Klompmaker JO, Laden F, James P, Benjamin Sabath M, Wu X, Dominici F, Zanobetti A, Hart JE. 2023. Long-term exposure to summer specific humidity and cardiovascular disease hospitalizations in the US Medicare population. Environ Int 179:108182.
Multiple screening assays provide complementary data on potential chemical hazards
Combining information from assays using zebrafish and cells can quickly provide a more complete picture of potential chemical toxicity, according to a study funded by NIEHS.
Alternative models, laboratory automation, and machine learning have increased the ability of modern toxicology studies to screen thousands to millions of samples. To propel these advances, more groundwork is needed to firmly establish approaches for comparative studies across species, assays to prioritize chemicals based on hazard potential, and understand how different model systems complement one another.
The team investigated whether assays using zebrafish and a human cell line would produce similar results following exposure to 87 known neurodevelopmental toxicants. Specifically, they examined chemical bioactivity — a measure of biological effect — related to abnormal embryonic development, mortality, and behavior in zebrafish. Then, they compared the results to chemicals classified as high risk by the Cell Health Screen (CHS), a tool that uses machine learning techniques to assess a chemical’s general toxicity in a human leukemia cell line.
The zebrafish assays were more robust, identifying 86 of 87 total bioactive chemicals, whereas the CHS identified only 20 chemicals. The zebrafish behavior assays were particularly sensitive in identifying bioactive chemicals.
The authors noted that, collectively, the results illustrate the advantages of using two different models in tandem for rapid chemical hazard assessment and prioritization.
Citation: St Mary L, Truong L, Bieberich AA, Fatig RO 3rd, Rajwa B, Tanguay RL. 2023. Comparative analysis between zebrafish and an automated live-cell assay to classify developmental neurotoxicant chemicals. Toxicol Appl Pharmacol 476:116659.