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00:00:00 – 00:47:28
The video features Karsten Prossa, an expert in environmental chemistry, discussing the complexities and challenges of analyzing and treating chemical contaminants in water. Prossa highlights the significant number of chemicals regularly used and their environmental impact, particularly through everyday products that end up in water systems. He underscores the limitations of current analytical tools like liquid chromatography-mass spectrometry in detecting a full range of chemical compounds and byproducts, particularly those that are toxic but less abundant.
Advanced water treatment methods, including oxidative treatments and membrane technologies, are explored, with Prossa advocating for a more personalized approach tailored to specific contaminants in source water. He introduces the "MIAMI" approach for managing complex chemical mixtures and emphasizes the importance of focusing on toxicological relevance, specifically organic electrophiles known for their toxicity in drinking water.
Prossa details his reactivity-directed analysis method which combines traditional assays with advanced mass spectrometry to better understand and identify toxic compounds formed during water treatment processes. His research reveals the formation of harmful byproducts like dicarbonyl compounds from phenolic reactions with oxidants. Collaborative efforts with institutions, such as chemoproteomics studies, highlight the reactivity of these compounds with proteins and the consequential toxicological effects.
The video calls for improved drinking water regulations and the adoption of bioassays to better detect and mitigate the impact of harmful contaminants. Prossa emphasizes the need for a proactive regulatory approach and tailored water treatment strategies, critiquing the inefficiencies of current broad applications like chlorination, and advocates for comprehensive evaluation methods to protect public health more effectively.
00:00:00
In this part of the video, Karsten Prossa is introduced as a speaker, detailing his academic background and career, including his roles and collaborations at various institutions like the University of Beirut, UC Berkeley, and Johns Hopkins University. The introduction highlights that this seminar is Prossa’s last one before his wife’s due date. Prossa begins his talk focusing on the significance of chemical exposures, especially in complex mixtures, and discusses how many chemicals, around 168 for women and half for men, we apply daily through products. He raises points on the environmental impact of these chemicals, particularly when they are washed down drains, and questions if the right compounds are being monitored. Prossa mentions advancements in analytical tools like high-resolution mass spectrometry that have increased the detection of numerous chemicals and transformation products in the environment, amplifying the complexity of assessing and mitigating chemical impacts.
00:05:00
In this segment, the speaker discusses the challenges related to analyzing compounds in environmental samples, specifically water. The main points include how researchers typically focus on the most abundant transformation products of a compound, though less abundant ones may be more toxicologically relevant. The limitations of current analytical tools, such as liquid chromatography-mass spectrometry, are highlighted, emphasizing that no single method can detect all compounds present. The discussion includes the complexity of understanding disinfection byproducts in drinking water, stating that known compounds only explain a fraction of the observed toxicity. The importance of pre-concentration steps, like solid phase extraction, is noted, but the inefficacy of these methods to capture all organic compounds accurately is a concern. The segment concludes with the importance of analyzing low molecular weight and highly polar compounds, which pose significant challenges for current methods.
00:10:00
In this part of the video, the speaker discusses advanced water treatment methods and the challenges they present. These methods include oxidative treatments using UV hydrogen peroxide and ozone, membrane treatments like reverse osmosis, electrochemical water treatment, and resource recovery. The speaker highlights the inadequacy of current evaluation methods for these technologies and proposes a more personalized approach to water treatment. This approach, akin to personalized medicine, involves assessing the specific compounds in source water and tailoring the treatment accordingly to reduce toxicity. The speaker mentions the need for better assessment techniques for complex chemical mixtures and suggests a prioritization system focusing on health-threatening toxic compounds. They also introduce the “MIAMI” (Mixture Assay Measure Innovate) approach and acknowledge the challenges of integrating analytical chemistry with toxicology.
00:15:00
In this part of the video, the speaker discusses traditional toxicology approaches and the evolution of the adverse outcome pathway (AOP) concept. The classical method involved exposing fish to chemicals and observing outcomes, like death, without understanding intermediate processes. The AOP concept provides insights into molecular initiating events, where chemicals interact with biomolecules, leading to adverse outcomes through a series of key events.
The speaker emphasizes the importance of electrophiles, especially organic electrophiles, in toxicology, noting their presence in drinking water and their significant role in chemical toxicity. To assess these compounds holistically, the speaker developed the reactivity-directed analysis approach, combining toxicity assessment with contaminant identification.
The approach uses “in chemical” assays, focusing on biomolecules like proteins and DNA, rather than organisms or cells, to understand reactions with electrophiles. The speaker is particularly interested in amino acids like cysteine and lysine, which are primary reactive sites for electrophiles. This method has been used for assessing skin sensitization in cosmetics but is proposed for broader applications in environmental systems to identify transformation products.
00:20:00
In this part of the video, the speaker discusses the interaction of lysine, an amino acid, with electrophilic transformation products formed during certain reactions. By analyzing these reaction products with high-resolution mass spectrometry, they gain precise molecular insights. The speaker highlights their research on phenolic compounds, common in both anthropogenic chemicals and natural organic matter, and their role as precursors to disinfection byproducts like trihalomethanes and haloacetic acids in drinking water. Notably, they discovered a specific dicarbonyl compound for the first time in water, formed through reactions with oxidants like hydroxyl radicals, chlorine, and ozone. This compound, though challenging to detect with conventional methods, appears in significant yields and is potentially highly toxic. The research extends to various phenolic compounds, revealing the ubiquitous formation of these dicarbonyl species.
00:25:00
In this part of the video, the speaker discusses the reactivity and toxicity of a dicarbonyl compound with amino acids and various proteins. Collaborating with Dan Nomura, they used chemoproteomics to show that the compound is highly reactive with the mouse liver proteome, particularly cysteine. They found that the compound inhibits the enzyme GAPDH, impacting glucose breakdown. Additionally, this compound, formed by cytochrome P450 enzymes from furan (found in wood and cigarette smoke), reacts with DNA bases, highlighting its toxicity.
The speaker then shifts to environmental chemistry, focusing on the formation mechanisms of these compounds using chlorine. Despite expecting a C4 compound with chlorine, they found that chlorinating phenols leads to the formation of BDA and chlorobda. Experiments ruled out some pathways, suggesting a new mechanism involving catechol. They propose that catechol’s oxidation leads to the formation of the toxic compounds BDA and chlorobda, supported by their experimental observations.
00:30:00
In this part of the video, the speaker discusses chlorination experiments with phenols to determine which carbons from a C6 compound end up in a C4 compound. Collaborating with experts from Towson University and the University of Southern California, they use stable isotope-labeled compounds synthesized by Keith Reber. Through these experiments, they identify which carbons from the C6 compound are present in the C4 compound.
The speaker acknowledges that they haven’t yet figured out why chlorine follows the observed reaction pathway but are close to solving this. They emphasize the promise of a new approach called reactivity directed analysis, which combines chemical identification with toxicity assessment for low molecular weight compounds that are challenging to track.
The speaker mentions receiving an NSF career award to continue this research and describes a new method, solid phase reactivity directed extraction, involving microbeads functionalized with nucleophilic groups to measure electrophiles through fluorescence assays and mass spectrometry based on click chemistry. This project aims to apply the new approach to real treatment samples and enhance the development of advanced drinking water treatment methods.
00:35:00
In this segment of the video, the speaker discusses the limitations of current analytical tools in detecting byproducts and the importance of focusing on the most toxic ones. They emphasize that while this new approach won’t replace existing toxicological methods, it will help prioritize chemicals for deeper evaluation. The speaker also mentions a submitted proposal to use this approach to study e-cigarettes, highlighting concerns about harmful radicals and electrophiles formed during vaping.
The discussion shifts to water treatment practices, suggesting a more selective approach to chlorination rather than broad application, given its link to toxicity and bladder cancer. They critique the energy-intensive treatment methods in the US and propose tailored treatment strategies to minimize unnecessary environmental impacts. The speaker also touches on the challenge of addressing long-known issues like PFAS contamination in groundwater, stressing the need for timely regulation to protect public health.
00:40:00
In this part, the speaker expresses frustration with current drinking water regulations, criticizing their reactive rather than proactive approach. The speaker highlights that existing regulations focus on individual contaminants and do not adequately protect against more harmful by-products, such as nitrogenous disinfection by-products (DBPs).
To address these issues, the speaker suggests adopting bioassays and a battery of tests to assess different endpoints. This approach is being explored in Europe, including Germany, where there’s an emphasis on the precautionary principle requiring utilities to test and report unknown compounds promptly.
The speaker also discusses the intersection of toxicity and reactivity in water contaminants, noting current research involving computational chemistry and electrophile experiments to predict reactivity. The speaker concludes that although the process is complex and ongoing, tackling these challenges is crucial for better public health protection.
00:45:00
In this segment, the presenter discusses the potential of a certain approach to provide a good indication of the overall toxicity of water, particularly focusing on chemical binding. They reflect on the challenge of identifying chemicals with limited current approaches. A question is raised about the overall toxicity of disinfection by-products and whether analyzing them collectively would yield higher toxicity results than assessing individual compounds. The presenter mentions considering this and refers to a study by Susan Richardson. This study found significant loss (80-90%) of disinfection by-products when using current extraction methods, which could affect toxicity assays. They plan to compare their current method, involving a microbead approach, to see how it holds up under different conditions, emphasizing ongoing research and development.