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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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DOE OSTI2024

Modeling PAH Mixture Interactions in a Human In Vitro Organotypic Respiratory Model

One of the most significant challenges in human health risk assessment is to evaluate hazards from exposure to environmental chemical mixtures. Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous contaminants typically found as mixtures in gaseous and particulate phases in ambient air pollution associated with petrochemicals from Superfund sites and the burning of fossil fuels. However, little is understood about how PAHs in mixtures contribute to toxicity in lung cells. To investigate mixture interactions and component additivity from environmentally relevant PAHs, two synthetic mixtures were created from PAHs identified in passive air samplers at a legacy creosote site impacted by wildfires. The primary human bronchial epithelial cells differentiated at the air–liquid interface were treated with PAH mixtures at environmentally relevant proportions and evaluated for the differential expression of transcriptional biomarkers related to xenobiotic metabolism, oxidative stress response, barrier integrity, and DNA damage response. Component additivity was evaluated across all endpoints using two independent action (IA) models with and without the scaling of components by toxic equivalence factors. Both IA models exhibited trends that were unlike the observed mixture response and generally underestimated the toxicity across dose suggesting the potential for non-additive interactions of components. Overall, this study provides an example of the usefulness of mixture toxicity assessment with the currently available methods while demonstrating the need for more complex yet interpretable mixture response evaluation methods for environmental samples.

3D in vitro models↗

DOE OSTI2018

Effects of polychlorinated biphenyls (PCB) on California sea lion (Zalophus californianus) lymphocyte functions upon in vitro exposure

Highlights: • PCBs induce immunomodulation of California sea lion lymphocytes. • Non dioxin-like PCBs stimulate sea lion lymphocyte proliferation at low concentrations. • Sea lion NK activity can increase under high levels of some non-dioxin PCB congeners. • PCB-induced modulation of sea lion lymphocytes can influence tumor progression. • Frozen lymph node mononuclear cells are viable for ecotoxicological analyses. Polychorinated biphenyl (PCB) congeners are a cause for concern due to their persistence in the environment, their lipophilic properties that cause them to bio-accumulate in top predators, and their adverse effects on mammalian health. For example, the common urogenital carcinoma reported in California sea lions (Zalophus californianus) (CSL) is associated with high tissue levels of PCBs, but the mechanisms responsible for this association are unknown. This study investigated the effect of exposure to six PCB congeners and a congener mix at low and environmentally relevant concentrations on NK cell-like and T cell activity using in vitro assays on cryopreserved lymph node mononuclear cells isolated from dead CSL. Non dioxin-like congeners 153 and 180 increased lymphocyte proliferation at 5 and 10 ppm, while congener 138 decreased proliferation by up to 43% at 15 ppm. Dioxin-like PCBs 118 and 169 did not affect lymphocyte proliferation, while the effects of congener 105 depended on the mitogen concentration; these did not correlate with their predicted toxic equivalent factors. NK cell-like activity was affected only by the highest concentration of PCBs tested; it was increased by non-dioxin-like congeners 138 and 153, and decreased by dioxin-like congener 169. The PCB congener mix suggested that the effects of PCB congeners were not simply additive. Our results concur with effects of PCBs reported for other pinniped's lymphocytes and add further experimental support to the observation that dioxin-like PCBs are not the most toxic congeners for marine mammals, contrary to effects in other species. This is the first evidence of in vitro suppression of NK cell-like cytotoxicity by a dioxin-like congener in a pinniped. More importantly, the observed results suggest that PCBs can modulate the CSL immune system, increasing exposed individuals’ susceptibility to viral and oncogenic challenges.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2018

Are ingested plastics a vector of PCB contamination in northern fulmars from coastal Newfoundland and Labrador?

Highlights: • The ingestion of plastics can lead to increased contaminant exposure. • We examined PCB concentrations in seabirds and their ingested plastics. • No significant correlations were found between PCBs and ingest plastics. • There were differences in the PCB concentrations and congener profiles in plastics and livers. • Xenobiotics, such as PCBs, may undergo metabolism in upper trophic level species. While marine animals are exposed to environmental contaminants via their prey, because plastic pollution in the aquatic environment can concentrate some chemicals, ingested plastics are thought to increase the exposure of biota to contaminants. Currently, in the literature there are contradictory results relating to how higher levels of ingested plastics by birds may lead to higher levels of polychlorinated biphenyl (PCBs). To date none of these have incorporated known Toxic Equivalency Factors (TEFs) for non-ortho and mono-ortho congeners of PCB which is critical to assessing the potential effects from PCBs. We examined northern fulmars (Fulmarus glacialis) from the Labrador Sea region Canada, and the ingested plastics from these same birds for comparative PCB concentrations. We found no significant correlations between the PCB concentrations in the birds and the mass or number of retained ingested plastic pieces in the stomach, this held true when PCBs were considered by a number of different ways, including ∑{sub 4}PCB, ∑PCB, lower-chlorinated, high-chlorinated, non-ortho PCB, and mono-ortho congeners. PCB concentrations were lower in plastics as compared with livers. We found significant differences in congener profiles between the ingested plastics and seabird livers suggesting that while plastics do not contribute to the PCB concentrations, there may be some interactions between plastics and the chemicals that the birds are exposed to via ingested plastics.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2019

Indoor versus Outdoor Air Quality during Wildfires

The human behavioral modification recommendations during wildfire events are based on particulate matter and may be confounded by the potential risks of gas-phase pollutants such as polycyclic aromatic hydrocarbons (PAHs). Moreover, the majority of adults spend over 90 percent of their time indoors where there is an increased concern of indoor air quality during wildfire events. We address these timely concerns by evaluating paired indoor and outdoor PAH concentrations in residential locations and their relationship with satellite model-based categorization of wildfire smoke intensity. Low density polyethylene passive air samplers were deployed at six residential sites for one week in Eugene, Oregon with matched indoor and outdoor samples and twenty-four-hour time resolution. Samples were then quantitatively analyzed for 63 PAH concentrations using gas-chromatography. A probabilistic principal components analysis was used to reduce all 63 PAHs into an aggregate measure. Linear regression of the first principal component against indoor versus outdoor shows that indoor gas-phase PAH concentrations are consistently equal or greater than outdoor concentrations. Regression against a satellite-based model for wildfire smoke shows that outdoor, but not indoor gas-phase PAH concentrations are likely associated with wildfire events. Furthermore, these results point towards the need to include gas-phase pollutants such as PAHs in air pollution risk assessment.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2025

Investigating the FLASH Effect in a Rat Brain Organotypic Model With a Novel High-Energy Electron Beam

Ultrahigh dose rate (FLASH) radiation therapy is reported to reduce normal tissue toxicity while maintaining tumor control; however, mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a specialized high-energy electron linear accelerator, High Intensity Gamma Ray Source (HIGS), paired with an organotypic ex vivo brain metastasis model. We varied interpulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR). We characterized dosimetry and targeting accuracy of the FLASH beam with film dosimetry. We combined this FLASH beam with an organotypic rat brain slice/breast carcinoma coculture model of brain metastasis to assess effects on normal and neoplastic tissues. Live-cell and bioluminescence imaging demonstrated cancer cell growth effects, whereas normal tissue responses and immune activation were assessed using live-cell imaging, cytokine profiles, and confocal microscopy. Here, we performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) using conventional dose rates. The highest IDR of the FLASH beam to date was 20.7 ± 0.6 MGy/s, with maximum MDR of 20.7 MGy/s delivered in 1 pulse of 1 µs duration. Beam targeting was accurate to <1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cancer cell growth. HIGS-FLASH irradiation significantly increased tumor necrosis factor α and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology slices suggesting microglia activation. Our novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation in the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain.

Kay, Tyler V. [Duke University, Durham, NC (United↗