 Welcome everyone. Welcome to this afternoon's program. We're going to begin with session three. In this session we're addressing indoor chemistry and exposure. And it's going to kick off with Dr. Crystal Paul it speaking to us about indoor chemistry and exposure. Her title is we are living in a material world indoor chemistry and exposure. Let me tell you a little bit about Dr. Crystal Paul it. She's presently at Yale and associate professor in the Department of Environmental Health Sciences. She also has an appointment in the Yale School of Engineering and Applied Science. Her background she got her BS and master's degree at University of Toronto chemical engineering, and then she went to London, and there she got a PhD in toxicology chemical toxicology from King's College. Her research has focused on different approaches to evaluating our exposure to chemicals. An example is using high resolution mass spectrometry and non targeted analysis to examine some of the chemicals that we are exposed to. She's developed and deployed wristbands that sort of chemicals from the air, and she can then analyze those wristbands for, I think, literally almost 1000 compounds. She has received from the International Society of Exposure Science, the John M. Daisy outstanding young scientist award from Yale School of Public Health. She's received the early career research award. And with that, I bring you, Dr. Paula. Thank you for that introduction. And I thought after lunch we needed a little bit of a provocative title just to get you thinking. And we really are living in a material world from everything that we have talked about. We have a number of different sources around us, and as we move into the next session, I want you to look around and think about what is in your indoor space around you. If you're joining us here in person so looking around this room thinking and then also back at home for those that are online. What does the space look like that you are now other spaces that you are frequent ink. What are the other chemicals around you what are other features of that indoor space, what aspects of this material world around us are then impacting your exposures. How might that differ from others living in your house how is that changed over time as well what are other factors that are then going to further modify what these exposures look like. Here's a picture of a wonderful PhD student that I'm fortunate to work with Elizabeth Lynn, and she is studiously working in our office space at the Yale School of Public Health in New Haven. And speaking about what her exposures are like there. So she's busy working on her thesis and she is ingesting water in a water bottle she has a good source of snacks there as well that she has exposures through ingestion around her. You can also think about her dermal contacts that she has around her personal care products, different cosmetics around be it lotions or sanitizer that we so frequently use that's also presence. But then we can also think about inhalation exposures, and I've opened the entire picture up because there are chemicals that are coming into the air from what we have talked about earlier in this workshop from so many different places. We have many many sources of particles as well as gas phase chemicals that are coming from all around. So we can look at what I talked about before related to the water she's consuming contaminants that are volatilizing into the air different food products that we also see within the air, be it additives preservatives that are no longer just within that that food product there. We also have remnants residues from the cleaning products that are being released other fragrances be it from cosmetic products from personal care products that's that are being applied in different ways. Textiles and garments also mentioned previously being a source and a sink for for these different chemicals. We can look at pharmaceuticals that do not stay put within that same medicine ingredient but we see them also volatilizing we've been able to detect those within the air. We can look at features of the built environments as well so building materials be it from the building material itself to other applications of coatings we put on there with paints. Resuspension of dust, the carpets are radiating chemicals, as many of us in this room have also measures, and then we can think about other locations as well, be it from different other combustion products, smoking cooking and other environments, and then also pollutants that have originated from outdoors that are infiltrating inside. So this is an incredibly complex mixture that we are exposed to. This extensive list of sources that we're exposed to you are all environmental influences that are going to impact our health, and understanding how this complex mixture of exposures, and from these various sources, that's the motivation for my work. So what I'm showing here this environmental health paradigm that's going all the way from sources to exposure to health. And it's an incredibly complex pathway that we have here. We've already discussed in this workshop, the range of different sources that are present within our indoor spaces. What this means in terms of transportation, their fates their dispersion. Within that these environments and their transports. But today I'm going to focus solely on the exposure. And this is my area that I really love to study and be able to develop measurement techniques that operationalize our ability to study exposure at the personal level, and in different environmental indoor spaces. And I'll share some of these findings that we've learned from studies today is. So three different aspects that I'm going to talk about today. So I'm going to share some examples of studies where you've looked at indoor exposures and the chemical diversity that we see in different indoor spaces. I'll talk about spatial variability that we've been able to detect within individual households, but then also between households as well. And then finally, I'll talk about the dynamic nature of these exposures. So how do they change over time. And then how are they also influenced by occupants practices, their consumer product use, as well as their behaviors. Okay, so before I get into all of that, I'm going to start with just some of the measurement science the techniques that we are using to be able to facilitate all of these studies. And the way that we go about capturing the human experience of this lived experience from all these different places that we go to on a daily. And our daily routine, we use silicone films, very simple material, we talked a lot previously about surfaces and now we're just taking an aspect of the surface. And silicone is a fantastic material for being able to collect a range of different chemicals. Within my studies we use a specific type of silicone silicone called polydymethylsiloxane or PDMS the sorption properties of PDMS are proportional to the optional air partitioning coefficient or the log KOA. And to give you a sense for the range of different compounds, more prevalent chemicals that we're able to detect, you can have a range of different VOCs, PAHs, PCBs range of pesticides, PBDEs, ballets, and most recently we've also been able to show that we can effectively sample a range of different PFAS as well given the emergence of this chemical contaminants. We understand the sampling behavior using these silicone films with passive sampling for gas phase constituents. When we start sampling with these these compounds, we can look at this x axis here with the sampling time in which we would have them be collecting an exposure estimate for. We'll start with a linear phase of uptake of chemicals into the silicone film where chemicals are taken up by the sorbents at over time by at a constant rates. This uptake rates is going to depend on the thickness of a stationary boundary layer, so stagnant layer of air over top of that polymer film above the sorbents. As we increase the amounts of chemical that's taken up by that polymer film, we then approach through a curvilinear phase into an equilibrium phrase where the uptake rate equals the loss rates. That rate is uncontrolled by the partitioning between the sorbent and the air for that chemical. By understanding these uptake kinetics, it's key for them being able to then quantify our exposures to the different chemicals. So we have deployed these passive samplers in various forms, and then we're able to use high resolution mass spectrometry to then measure the mass of chemicals that have been captured that have been absorbed by these these films. And when we measure that we can then express that in a picogram amount for the amount of sorbent or silicone that we've analyzed. But then understanding how long we've sampled for, we can then apply a conversion mass loading factor. If we deployed for a shorter amount of time and we're still within this linear range of uptake we can apply an uptake rates, or for sampling within the equilibrium range we can then apply an equilibrium absorption coefficients. And the key to being using that is then we can then convert that mass loading into a volumetric concentration to then estimates exposure concentration. So we can now have that comparable to many other different forms of measurements for evaluating chemical exposures in the air. So we have the silicone film, we understand how it's uptake behaves, and now we've started embedding it into wearable forms. So we can put it in a noninvasive type of wearable form like a wristbands, and you can go around and do all of your daily activities. So we can then use the elements of physical activity and not have it be a burden, or create any type of immobilization or change to to what you normally do. So the silicone film that we have, we, we have it contained within a bar form that we call a PDMS sorbent bar. We put it into a sampling case. So that means that we are only sampling chemicals that are from the air. So we have four replicates that we typically put into a sampler that we deploy with an individual. So we have replicates we can analyze one have backups, be able to then analyze those at a later later dates. The sampling case also provides a stagnant boundary layer as I mentioned that's key for having normalizing the rate of uptake of compounds, and we've done a amount of computational flow modeling so we understand the variation of that boundary for types of movement from say sedentary activity to high paced more of physical intense activities. We still see a consistency which in that boundary layer. So now we've normalized and have a constant rate of uptake. And then that means we can quantify what our exposure concentrations are using this wearable form in a pica gram per cubic meter amounts. That's incredibly powerful when we start relating that and thinking about what that means in terms of health to have a quantified measure of exposure with standardized units. So we've also thought about other vulnerable populations. Right. We don't want to just characterize an adult going around. So we know that childhood especially early life are going to introduce increased susceptibilities to different chemical exposures. So we've come up with alternative wearable forms that we can put on to babies. And I've been fortunate enough to be able to test this out even at home with my little one and compliance is good. Not a choking hazard. And we've also deployed it within studies as well to be a usable wearable form that we can detect early life exposures. We can also put on other vulnerable populations throughout childhoods. We can look during pregnancy to think about prenatal exposures older adults as well that might have more limited mobility, especially also different types of disease populations. We can use the exact same type of wearable and then put that into a clip form and use it now as a stationary area monitor. So we can use the same approach, the same means for analytical as well as computational analysis for the chemical exposures in different fixed locations be those indoors or outdoors so we now have a harmonized technique that we can evaluate exposures in different environments. We have a high throughput form for chemical analysis. And this is key if we want to be able to deploy this type of measurement technology to look out of range of different environments, very large populations that we need to be able to study health, then we have to be able to do this on a large scale. So we have these wristband devices that we have kits that we send out to different populations internationally. They're worn typically for anywhere from one to 14 days, depending on the study design. Once they return back to the lab, we're then able to use an internal standard that allows us to have quality controls and standardization, and then we thermally disorb the compounds off of that silicone film. So that speeds up the entire process we're no longer doing a solvent extraction and creates a bottleneck. That thermal distortion goes directly onto the endless of a high resolution mass spectrometer we're using a gas chromatography technique for separation, and then that allows us to then have a data sets to you exposure assessment with a use of a high resolution mass spec we're then fortunate to use different techniques to be able to mine the data and we spent a lot of time developing our computational workflows, standardizing those making them as rigorous as possible, so that we can have three different means for analyzing what our exposures are. We can use a targeted approach we have authenticated analytical standards that we include with every batch. We include about 100 of those for cost related reasons balancing for prevalent compounds with the known health outcomes of concern. And with this we're able to provide then quantified exposures and this program per cubic meter amounts. And we can also use and we can mine our high resume aspect data to do a suspect screening analysis. This starts letting us get to about 500 compounds that were able to detect from a single wristbands. So this really excites me just being able to wear wristbands, you can now gets at this, this breath of chemical structures that were able to confidently annotates. This is semi quantitative technique because we are using a library based screening approach. But then we can get really interesting and then also do non targeted analysis. And this is now letting us get to 10,000 plus chemical features that we can get by wearing a single wristbands. These are more qualitative based approaches, but still it's giving us an indication for what is present within our exposures from a range of different sources. Okay, so let's start here. Indoor exposures are chemically diverse. I'm going to share a study that we worked on and we're really lucky to work with a fantastic group of environmental epidemiologists at Boston University. We worked on a study called presto for one component of it. So this is an internet based preconception cohort study. And we had 139 women from across the US from 39 states where the wristbands. We worked for five days. So we had a kit we developed we sent that out to them. They wore the wristband for five days they sent it back. They were all within the range of 21 to 45 years, interested in trying to conceive. So really interested in different types of exposures influencing reproductive health. We did it over a fairly narrow band from a June to November stretch. And then we also had a range of different questionnaires that Presto was asking that we were able to leverage to be able to look at time activity patterns. I'm presenting the study here because we did this during COVID. A lot of these women were spending time at home indoors, greater than 90% of their time. So a lot of their exposures then going to be represented of their indoor environments. So I'm showing results here to start from exposures from our targeted analysis where we're just looking at more prevalent compounds that are better understood with recognized health outcomes. So I'll start here and orient you with this figure so here is showing a range of different pHs. And you can see the distribution of the pHs that are being detected each one of those dots is one individual from this cohort, and then shown on the right hand side there is the detection frequency across those 139 participants. And you can see just that these are prevalent compounds, we're detecting them for most for most of these compounds across our entire population. You can also look at other compounds that we're seeing very frequently across this population. We can see a range of different flame retardants, different pesticides, smoking related compounds from nicotine to THC9. There were women that reported that they were active smokers that they were smoking marijuana as well. We're able to cross validate that with their wristband measures and we did see those as being outliers in terms of the magnitude of their exposures. Cosmetic products coming from a range of different sources and phthalates and just highlighting a couple here. And you can see for a range of these compounds, they are all have high detection frequencies that we find. So we can dive into this a little further, and we can then apply our suspect screening techniques and we use these library searches we can identify about 500 different compounds 491 unique chemicals that we confidently annotates. We paired this data with a fantastic resource from the EPA called the Comtax dashboard that includes 1.2 over 1.2 million compounds, and we use that to be able to screen for potential product usage associated with each one of these compounds. These compounds are coming from a range of different sources. Some of our fruit related flavorants, pharmaceuticals as I mentioned before we can detect they migrate they off gas from the different medications that these individuals were reporting that we were able to cross validate combustion products pesticides antimicrobials and a range of different smoking compounds as well. So just one step further with Comtax and be able to then also look at predicted toxicity. So this is really powerful because when we have a list of over 500 compounds, we want to be able to scream for what are the predicted unknown toxicities. And we look at this list here for the suspect screening we're able to find that there are a number of chemicals of concern. Most of these are endocrine disruptors. Which again string games of concern when we're looking at a preconception cohorts. We look at concerns related to developments. Again, this is a concern for this cohorts, and a number of them 68 were also identified to have reproductive hazards. This is powerful information. Take it a step further and I can show you some of the results from a non targeted analysis. So this is really the most comprehensive analysis that we're able to do that provides insight into the indoor chemistry to which these these individuals are exposed. I'm showing here a molecular network of the chemical features that we've identified and each one of the clusters that you're seeing here indicates chemicals that are structurally similar. So we can look at and can highlight what some of these these chemical clusters are we see aromatic hydrocarbons we see oxygen and hydrocarbons within this mix here. Oxygen alkanes, and then we can also look at some other compounds that are of known issues when we think about reproductive health, including sysilic acid and benzoates. So I'll dive a little bit further into this benzoate cluster. So all of the compounds that I've highlighted there in red have potential sources. And then I've pulled just a couple of them out to see what these potential sources are for the compounds we've detected. So remember, these are still detected within these wristbands that are within indoor air. These compounds are found within cosmetic products and then other ones we've seen as potential preservatives within food products as well that we're able to detect with this high res mass spec technique at trace levels. There was another really interesting aspect to the study that I loved is that we were able in a subset of the population of that 139 females also give response to their male partners. Most of their time in the same indoor environments. So now we're able to look at differential exposure of occupants in the same household and see if they were differences. It's really cool. And we were able to find that when we looked over that prevalent list of about 100 compounds that we measured for their target analysis, they were similar. So when we started to dig further into that data and pull out that suspect screening data that 491 compounds. That's when we saw some differences. And what I showed here on this for the volcano plots looking at differences between females versus males so what's higher in the females is shown in green, what's higher in the males is shown in in blue. So we see some food related compounds higher in females, we have some compounds that we weren't able to identify what a potential source was because it wasn't found within com talks, but then there's also a range of other compounds that the males were higher exposed to different flavorants different preservatives different food related compounds. So this all tracks back to differences within activity patterns differences within consumer use. So being within the same household and assuming that you have the same exposure as a consequence is not the case. So much of it depends on our personalized use of consumer products and our activity patterns we have to understand that if we want to be able to then further understand what that consequence on health is going to be when we have these exposures. So let's move on to the second one, the spatial variability within households in between households. So following up on that we found that there were differences between males and females we thought well, can we further pry to see what the spatial variability is within households. We worked on another really cool study we partnered with a group at EPL in Switzerland. And we were able to deploy these passive samplers in 37 homes in Switzerland and three cities with participants that were all adults 21 to 58 years, and we were able to collect six samples from each one of their homes. So what the question was is that they had to work in their homes were doing this during COVID in 2021. They had to have a single level home so it was a contained smaller type of apartments. And then we put the samplers one on their terrace so they all had a balcony so we put it right outside we could look at outdoor exposures, and at the same time over the same five day periods. We also had a sampler in their living room in their bathroom in their bedroom, and in their kitchen, and then the top of F to get it, you know, more data, they also were spent. So we could see how there were differential exposures if there were in the different spaces and smaller spaces compared to larger dwellings that we might have within the United States, and then how they interacted with those spaces to see the key factors in the different locations that were driving exposure. It was a beautiful study design. It made me very happy. So pairing with the meticulous collection of samples, the PhD students that worked on this also had a tremendous questionnaire that logs their time activity. Most of their time was spent at home as per our condition for enrollment within the study 94% of their time. And then we looked at what the breakdown was for these people. We looked at how they spent their time within their spaces. Most of their time was spent in their bedroom, you know, sleeping. They did a lot of their work in their home office or their living room, sometime within their kitchen. And then a little bit of time in their washroom so 2%. I'm going to show you some of these results here so this is from our targeted analysis we're just focusing on the limited panel. So we can see here a plot of chemicals that we detected in the different indoor locations, bathroom, kitchen, living room and bedroom. And it's showing a Z score. So the Z score is representing if there is an increase, an increase over the mean of the other indoor locations. And the ranked here based on highest to lowest for the different environments. What comes to your eyes that the most number of elevated exposures across the panel that are measured here are found in the bathroom. Not overly surprising right it's a closed environments, huge number of products that are used their personal care cosmetic products, the highest levels. We also saw some that were elevated within the kitchen. So this particular one was from a food compounds. And then we looked at, there was a fewer number that were also coming from the bedroom as well. So then we probed a little bit more and then we did a correlation analysis to see how did those compounds vary between the different locations. So the was there a higher correlation between some that might suggest perhaps different amounts of dispersion or then also exposure with interaction with personal exposures. So what I'm showing here on this, this inset here these these little series of dots is the different exposures in the different locations and then if there is a line a black line connecting them that means that we detected a significant correlation between those compounds. In this case here there's a red dots for this particular personal care product that was the highest detected within the bathroom. We see that that's then correlated with personal exposures, as well as in the living room. So we see that having those elevated exposures within the bathroom then deadly to a signature that we detected on the wristband, despite only having a 2% of their time activity log within that space. We can then look at other types of personal care products as well that were detected within the bathroom. So home sat assassinate and then a mass ketone, also highest detected within the bathroom and then we see that a signature of that in the different environments as well. Some of those compounds didn't follow the same trends. So this was a particular compound of food related compounds that we found within the kitchen, highest levels within the kitchen, but we did not see that then associated with the wristband based exposures. So we see differences in how these compounds migrates and how we're interacting with these, these, these compounds for the bedroom as well we see differential patterns in terms of how these correlations are happening. So for the particular pesticide that had the highest concentrations, we see a correlation with the outdoor environment and as we do these, these correlation analysis we can then start to have cues in terms of what potential sources of exposure might be in the sources that they originate from. So I'll end here with one last study where we looked at the dynamic nature of these exposures. Again, a really nicely designed study where we're fortunate to pair and work with the China CDC. Unfortunately, we did this right before COVID. And we measured indoor air longitudinally. So I measure we measure indoor air but we measured in a personal form where people spent most of their time indoors. We're able to have people that 80 people wear the wristbands every month for five consecutive months, three days every single month, starting in September going all the way until January. It's really nice that we could track the same people over time. This was also done in another beautifully designed study where the China CDC partners that we had tracked everything. They tracked all aspects of their activities from their window openings to their cooking the time spent indoors. Their product use and they even had pre prepared meals for them as well that everyone got standardized. In parallel with that they took biological samples of everything from urine to blood they took it at all time points and then did a lot of other physiological measurements and that well. We paired that also with outdoor data so we could see differential exposures between indoors versus outs and personal, and then I'll just highlight some cases here from personal care products, control diets, cleaning activities. We can look at these exposures now over time from September to January. And what shown here within this box plot is the concentrations that we detected for this particular compound dichlorose which is a product used for mosquito control, a band substance. But given the population they historically had come to use it and it was a cultural practice where they placed it under their beds. It was an account of originally within our activity logs, but because we detected it we went back to and they all did then confirm use. We can see higher concentrations in the warmer months cooler in the less than the cooler months as you would expect, but it follows our assumption or trends. Similarly, we can look at other products like limonene. So this will come from a range of different food sources as well as cleaning sources. We see increased exposure as there is decreased window opening time so less ventilation, higher concentrations that we detect indoors. Other compounds that didn't have any change across the five month time periods. We see no variation, no significant variance from the start warm to cold periods. Things like triglycine and antibacterial microbial that we find within personal care products, we find that migrating out into the air that we're detecting with the wristbands. And this one I found really interesting food preservatives as well. We also found and because they had a consistency of diet a standardized diet over the five months for those three days. They also had consistent exposures. We tried them to look for predictors of exposures, and we did a principal component analysis we found that two clusters were identified that explained about 50% of the variance. We then looked at the breakdown to see what compounds were associated with those two clusters. So the first one was primarily loaded with pHs and in the second one here we have a range of other volatile compounds some some ethers and nature benzene and some polyethylene naphthalene as well. We then did a random forest analysis to look at predictors of behavioral environmental features. We were then able to find three factors that then were primarily associated with just the second factor so more of those volatile compounds, heavily driven by outdoor temperature, the month that they was assessed, ranging from September to January, and then also the window opening time. The building practices were really driving what the exposures were. And sure enough when we then looked at how people's activity pattern change with the amount of time that they spend outdoors, we can then differentiate what some of the sources of exposure were their originate or origination of some of these pollutants. So here I'm showing a plot for the amount of time spent outside while wearing the wristband over the three days for one particular compound to hexachlorobutadiene and we see increased exposure with more time spent outdoors, suggesting then an outdoor source or origination, and then we can do the exact same type of analysis for indoor sources to start looking at where we might be having the sources of these compounds. So overall, I hope that I've been able to show you some advances in measurement technologies and see this as a real way that we can start operationalizing how we do exposure assessments to better understand indoor chemistry as well. And by coupling these passive samplers with high resolution techniques, we now have this omics scale measurements of chemicals and indoor air and that's really powerful. So non invasive design let's us get at a range of different geographies a range of difference environments as well by having a harmonized approach. The indoor air as a consequence but which we can measure is chemically diverse. And then we also have a highly dynamic environment that is influenced by our behaviors as well as our consumer use. So moving forwards, a couple of thoughts. So addressing data inconsistencies, we need harmonized approaches that are robust, reliable and rigorous. We need a framework that's going to have a standardized method of measurements with standardized protocols data collection and analytical methods. These need to include analytical methods as well as computational methods, right, as we use these high res mass spec methods it's generating tremendous amounts of data to define best practices. As we do these measurements, we have to think about health. We have an extremely complex chemical mixture to which we are exposed, all the way from emissions from known sources to transformation products. And we have to be able to then evaluate and understand what that means in terms of human health and disease. And this then can potentially guide policy decisions. We're talking at this workshop here about indoor chemistry. But I want to push this forward and say we need to think about the ensemble of exposures. So all of the exposures that we are exposed to chemistry is just one. And when we think about all these exposures it's also the physical exposures. It is also the biological exposures it's the psychosocial exposures that will drive biology so taking an exosomic approach using systems to look at what that means in terms of our health. And finally, we're doing all this measurement we're thinking about health we also have to have actionable solutions. We need to be able to capture product use activity use to understand chemistry, right, but that also then has benefits for being able to enable precision interventions to mitigate exposures. So with that I'll wrap up there and thank my fantastic team that I'm fortunate to work with and then all of our wonderful collaborators and funding sources. Thank you. I'm afraid we're a bit short on time, but let's take one question before we move to the panel. Thank you so much for this presentation it really gave us a great sense of the diversity and in the dynamic nature of this indoor species. I was wondering about the time variability again and particularly I was wondering if you observe change over time I remember a conversation a few years ago with Kenichi Azuma who did a survey of indoor VOC's in Japanese homes and one thing that stuck with me is that he said that at the end of this by the end of the study they were seeing already different compounds that at the beginning. And that's part of the conversation we had today what do we bring in our homes and these products change did you see any evidence for changes in your measurement. So there was a study that I showed that was based in China where we we sampled over a five month time course. Ideally, if we had sampled longer we would expect to see even greater changes but we did get that the peaks of order to cooler. And as we showed with the the PCA random forest analysis that much of the exposures that we see in doors are going to be impacted by seasonal changes and in the outdoor environment. So yes, I showed a couple but we can look further and we can see especially within those VOCs that they would be dramatic changes recently. Thank you. Now, would you please take a seat at the panel, and I'll ask the other panelists to step up. And in a moment I'll introduce them. The focus of this panel discussion is going to be the connection, the handshake between indoor chemistry and indoor exposure. And Antonio Caliphot is the chief of the organic analytical toxicology branch at CDC, and she is a world expert on biomarkers and has been very involved in the NHANES biomarker program that many of you are familiar with. Dr. Jason Ham is a research scientist at the health effects laboratory division in at NIOSH in Morgantown. And Jason has done lots of measurements of various reactions, their rates, their mechanisms that occur indoors. Dr. Elaine Cohen Hubble is a senior science advisor to the US EPA. She's also editor-in-chief of JESCE, that's the Journal of Exposure Science and Environmental Epidemiology. And I forgot to mention that Dr. Antonio Caliphot is editor-in-chief of the International Journal of Hygiene and Environmental Health. So we have two journal editors sitting on the panel today. You know Crystal, you just heard her deliver a fascinating presentation. And then Trey Thomas is the lead toxicologist and program manager. You've heard him ask some probing questions today in the chemicals, technology and emerging materials program at the Consumer Products Safety Commission. And with that, I'll begin with the question that I'll direct to Elaine, but invite all the panelists to comment on what important exposures influenced by indoor chemistry might we be missing? Where do you see the research gaps? Okay, thank you, Charlie. So, oh, I didn't talk to Crystal before I wrote up my, since I haven't really been intimately involved with this group, even though I've certainly followed the work of the years, I actually spent a couple days thinking about the question. And Crystal just set things up perfectly. But what we've heard today, and I think we'll hear a little bit more after this one is that buildings and people are complex and dynamic. Sources of chemicals and buildings change, right? So the materials, the products, the behaviors, these things are not constant. And they, and they're changing more rapidly than ever before. And then I think I saw some things in the report, but climate change and climate adaptation practices are going to have consequences for indoor chemistry and certainly for exposures. So, I just want to kind of, in terms of gaps and what exposures, you know, we should be looking for, I want to sort of throw out this idea that we hear a lot of today in terms of use inspired research. I've got a perfect example that in the last panel, but I'm just going to throw out sort of three broader ones and we've already heard a lot of people sort of elude or even outright express these kinds of ideas. So nothing I'm saying is new, I'm just going to reiterate. But focusing on solutions use inspired research focuses on solutions and design designing research that's going to provide actionable information. And it gets a little overwhelming when we think about the complexity that we've heard about today. So to do use inspired research what tools do we need to develop and deploy to in particular measure. I'm really liking the emphasis on measuring, but we've heard really good information about ideas about how to use models. So what tools do we need to develop and deploy to measure, predict, mitigate and monitor indoor chemistry so that we can really minimize exposure to toxic chemical mixtures. And you know I know everybody's goal is really to foster a healthy indoor environment, not just today, but in the future right so we've a lot of work to do. And I'm just going to reiterate that it's, I would posit that we really need to move beyond regulatory exposure assessment methodologies. We're going to get really stuck. If those are the kinds of exposure. The regulators have to do those assessments, but they've been struggling for we they, I don't do regulatory exposure assessment but struggling to how you get around address complexity mixtures and everything else. And we heard a really good thought today in terms of where you know this group could engage, but I'm going to just say that actually I'm, I'm a real advocate of more of the kind of approach that crystal is proposing. So, I really think there has to be a lot more taking advantage of advances in data driven approaches and doing more of a fusion of the complex chemistry that we're hearing about today the dynamic characteristics of the indoor environment and human behavior, without necessarily getting at the mechanistic details of all those things. And I would also sort of argue that human behavior is not necessarily something that we can get at in a first principles way in the way that engineers and I'm actually trained in chemical engineer in the way that engineers think about first principles. So just to throw out my three sort of use driven things. One, I would say is sort of where more of the fundamental kinds of things come in but this is where as a as like a society we're going to want to engage is screening to identify new and emerging concerns so I think we've heard a lot about that in terms of how we would measure. But what is the minimal set of measures that can be collected in surveys and health studies. If you want to connect to exposure and health. We have a lot of surveys that this government does implement. And there are opportunities but but we're not always prepared to get those measurements in because they do need to be minimal. And they need to be efficient. And then we need to have to do that the data driven models, including machine learning methods. Crystal had to like fly through her last example but there's some amazing stuff in there. And where we are using machine learning to get at the potential predictors and surrogates as determinants of exposure. And I'll keep I'll go faster but mechanistic models would have to be a part of this and that's predict to predict potential for wider sets of compounds from those minimal measurements over time and space. So that's one use use inspired example the other one would be screening for safety and again I do mean measuring. So the way we do now for rate on what minimal set of measures can be collected so the first set are people are collected in surveys by researchers right this set is what are this one of the minimal sets that can be collected by building managers, or residents, and that they can send to a certified lab but one day the goal would be to have the sensors measuring in situ we're moving toward the Internet of Things and our smart homes and all this stuff and we can like think from a market driven perspective. What's the uses that this community, you know beyond grants, you know from federal money there's, there is there is a compelling market for what you all do. And so with that would be guidance to do something with those results right what are, how do you eliminate the sources remove the contaminants or transform the chemicals and those need to be specific and targeted to the set of measurements. And then the final one I'll just throw out is planning for climate change and climate climate adaptation and this is going to have to be a lot where your science feeds in to these models that can be used to look at different scenarios so models here that designers, building operators and policymakers can use to evaluate new materials and technologies for constructing buildings and modifying existing ones. And with that would be the technologies then for monitoring indoor chemistry that can be deployed in a range of indoor environments and there again huge market. And then I'll just end by saying that I did look EPA's indoor environments division did charge their clean air act advisory committee with prioritizing your, your report. recommendations and the number one priority that they came out with was prioritizing acquisition of actionable data and research to link sources with exposures and understand impacts and mixtures on health so you know I think that's all kind of aligned. Thank you Elaine would other panelists like to comment. Are there chemicals that we are being exposed to today that we are missing and I heard you Antonio say oh yes. So would you would you please elaborate. I mean, I'm pretty sure I mean the tens of thousands of chemicals that I used in commerce and we are only able to measure and tackle just a few of them so I'm pretty sure we're exposed to tons of chemicals, not in isolation even though it tends to be at least for targeted analysis that's how we measure them one by one because this is how our framework for regulation is set up, but we oftentimes you hear people say we're just looking at the tip of the iceberg. Yes, we are only looking at the tip of the iceberg but being optimistic is better looking at some that look at that not so I'm hopeful that little by little and making some progress but yeah we're missing something for sure. Thank you and Tony. Elaine yes. I just want to add just one more point on that which I guess I missed but related to Antonio's comment is that we are you know looking under the lamppost and that the point of these untart and these non targeted approaches is is to be able to use kind of this more exposomic thinking where we are looking for what are the biggest differences right so using that data driven kind of approach to say what where are we seeing big differences in these clusters of different patterns of chemicals and then you can do the deeper and then you can try you know to go figure out sources and and and chemistry and things, but I just think we're just, we have no choice but to move in this direction. Thank you. Other comments. First of all you're doing non targeted analysis, and that has the advantage of alerting us to chemicals that we might not be thinking of, but the chemical has to reach the detector in the first place right. That's an excellent point. And so as we move to to measuring all exposures as this exposomic approach. I don't think that we can be limited ourselves by by the perfect. We have to go with what is feasible. And we know that we are able to be more comprehensive with these approaches with these non target methods. And that still provides a very rich repository of the sources that we didn't previously appreciate it's that we now are able to study. True. Elaine, I see you want to say one more thing. Yeah, I'm sorry, you're, it's been so exciting today. Barbara made some amazing points about the iterative nature of needing to do, you know, sort of the experimental lab, you know, lab scale kinds of studies that's like that, you know, having that mechanistic I'm in no way suggesting that we abandon the mechanistic side of things that's really critical but if you sort of know which things mechanistically you would expect to see together. You're only measuring the ones that are getting to whatever sampling medium or media, I hope, then you ought to be able to go back to what you've learned experimentally and connect those dots. Thank you, Elaine. I speaking personally I do worry that there's classes of chemicals that we're doing a poor job on today, and includes thermally labial compounds I see Vicki wants to comment here. And, and compounds that do have different are going to condense before they reach the detector. Vicki. Yeah, I just wanted to ask one question and we crystal didn't get a lot of questions and she did give a really nice talk and so it's directed to you but anybody on the panel who makes these measurements can answer about exposures. And my question is, you know, you have this very specific way of collecting and then analyzing what percentage of the organic compounds that are present. Are you measuring what percentage is unknown. And the reason why I asked that is a lot of times if you do the mass balance and bar mentioned this zero to 100%. A lot of times, the majority is unknown and I'm just wondering in your measurements if you have an idea about that. Excellent question, challenging one. So, I suppose the root of that is that we haven't measured that total to know what percentage that we are detecting. And we are just measuring organics, but we can then use the same sampling strategies a to do ICP MS, and we can measure metals with particles deficit deposit on there. With COVID, we're able to spin the same device and repurpose it to measure respiratory viruses so now we can then do a biological type of analysis. So, I think we can we can start thinking about other other technologies and different analytical methods that we can compare with it. Thank you. Okay, Jason. So yeah, yeah, I absolutely agree that, you know, as you already mentioned is carbon mass balance we lose about or missing about 50% of this stuff and, you know, so new technologies and in actually using new chemistry such as derivatization chemistry to look at these oxygenated products that are formed due to these reactions is something that's hopefully getting to discovering at least a few more percent of that mass balance. But as already pointed out, we still need more technology to understand these this transient chemicals these radicals that are being formed that which we really don't have a good handle on just yet. Also, because those are going to be formed that lower concentrations presumably that the parent compounds, you're going to need methodologies that have squished sensitivity, and that sometimes you know when we look at a lot of things then we lose some sensitivity so we're going to have to look complimentary tools and complimentary approaches that I think in my mind they're not exclusive from each other but they just help each other. Thank you everyone. I have a question I'd like to start with Trey first on. In the case of consumer products. How do you treat how do you address chemicals, not originally present, but formed later by a chemical transformations. That's an interesting question. I think, you know, for those not familiar with CPSC we have a wide jurisdiction, and also the comments that I make our mind and not necessarily those of the commission. But you know it's been said earlier that we tend to have we look at that we approach it by product by product basis and I think when we talk about this more broadly in terms of the exposure science. We have a good idea, or really a robust understanding of what happens when you use these products in an in an exposure scenario. What is released what's what's in the product matrix. What is released. What are the other compounds that are released and then what happens to them so I think it goes to your question about the byproducts we certainly have seen that there's questions for example with ozone and we talked about ozone generating air cleaners. And in the indoor environment, I think part of the challenges we've all talked about that's been just well stated is how complex it is I mean when you think of just products under our jurisdiction everything from large products, but maybe sources of BLCs, like mattresses furniture would all the way down to household cleaners and everything in between. There's even exposures when we talk about that we use like toys and so forth that where you know there's direct contact and you know what happened so I think that is since we're talking about research we need to clearly understand what are those releases. We talked about do we have how long do they last, and you know what are those interactions that do occur. And again, and it may change seasonally temporally I mean what you know if you're mopping the floor and there's the air exchange rates that occur if it's in the summer versus winter and are we talking about a studio apartment or a McMansion and what type of, you know, you know, exchange is occur so I think that given all that variability we do and I think this is where the methodology. Do we have robust methods to characterize and quantify these reaction byproducts. So then we can talk about ways that we can for example with mixtures, we've added hazard indices that's one approach, but there may be other approaches and my colleagues we've talked about ways that we can do that models tools to do that. And I think this is an important resource that with that we've heard, and just in this conversation, how can we really measure and quantify and characterize those those mixtures that occur. Thank you trade. Other comments from the panelists. I'm going. Oh, excuse me, Barb. Dr. Barbara Turpin. Well, I was thinking I enjoyed your talk. Great deal crystal and and I enjoyed having a conversation with Antonia lunch today so it got me thinking about the focus of the expose own largely work has largely been on biomarkers of exposure. And I don't know that much about what happens once chemicals are in the body. But it got me thinking about, you know, to what extent do we need to worry about transformations in between when people are exposed to something and when they end up in your blood, let's say, and, you know, if we might be fooling ourselves in terms of what we think the exposures are. So I know probably both of you and maybe all of you up there have been thinking about these questions. I can try to start by saying like, we are all interested in measuring exposure but we cannot measure exposure. We only assess exposure so we have different tools to measure concentrations of mainly exposure biomarkers. We have other biomarkers of effect. And, but here we've been talking mainly exposure biomarkers so we find concentrations and we tend to think high concentrations mean high exposures. And it's true at a certain time, but like the exposure may have been very high a long time ago but by the time we captured that sample, the exposure was gone. Or the body had got rid of the chemical. So it's really a complex scenario. And then I think that like the measurements that I'm most familiar with that are like biomarkers, biomonitoring is a snapshot. It gives you a snapshot idea of the concentrations of the chemical. When you look on a population basis, which is what we do at CDC, then on average, you know, in some cases you're going to look at high concentrations and low concentrations that kind of average out. And on exposure on a population level, which is what we're interested for population health for public health, we get a pretty good idea of exposure to different chemicals that we're looking for again like Elaine was saying we're looking under the lamppost. If we want to, and all depends on the question that you're trying to address the information that you're trying to get. So if you want to have like an agnostic, you know, going and saying, what are we supposed in indoors, what are the chemicals that we're finding a targeted approach may not be the best one unless you want to remediate those exposures initially you want to know everything that is in there so a non targeted approach, the use of the, the, the, the silicone markers that that's perfect much better that collecting blood or urine because you're not going to have standards for all of that. So I don't know if I answered your question but again this is what I'm trying to say that all these different approaches to assess exposure are in my mind complimentary and this is only measurement you need to get information about the sources you need to get information about how often people use the chemicals and so on or the. Thank you, Antonia. Dr turpin anticipated a question I was going to ask related to that. Jason, I know that you also have have concerns about. Yeah, I agree. I think oxidation pathways are, you know, not well understood. They're not well appreciated either. And because of that, the IH keep community is just doesn't recognize them. And so, you know, the question is what should we be measuring, you know, we have some type of health effect that may occur but you know what what chemical compounds causing that health effect. You know, I think trying to understand that is, you know, what you're trying to say so. So I just wanted to sort of point out that the power of the expezomic approach is, and why I think there's a useful analogy that could be done that, you know, already crystals looking at in terms of environmental exposures is that you're, you know, they really look they do look at biomarkers typically of effect, and then work out from there and they're looking in case control. They're looking at two different groups and they're saying what's the same and what's different. And when they find something that's different then then it leads you to to go learn more right so that would be. So rather than trying to figure out every little, every little exposure and every little effect and every little transformation, whether that be in the environment or in our bodies. We're first doing the data driven discovery, the screening measures the data driven discovery and then you go into, you know, sort of, you'll have clues as to which things are the real big important things that we need to study more carefully. Thank you Elaine now there's potential. Well, it's tricky. Right. As Dr. Williamson pointed out, think of think of ozone, and we know that there's good epi showing correlations between ozone increasing and morbidity and more about mortality increasing. But we also recognize that we actually inhale roughly as much ozone indoors as we inhale outdoors, but indoors were also exposed to the products of ozone initiated chemistry, typically at two or three levels higher than an indoor ozone. So how do we know that the health effects that we're ascribing to ozone aren't due to the oxidation products. So you see the point I'm trying to make in terms of making those kind of associations. Absolutely which is why you, which is why once you see those differences so you're you're now taking where you've seen a difference. Right. And now you're saying here's the research question that we have to investigate so absolutely 100%. Thank you. Jason I'm going to come back to you please. Our work environments are changing. They've certainly changed since the pandemic. We have more remote workers. We have more DIY workers. We have more Amazon workers. How do these changing work environments affect the link between indoor chemistry and indoor exposures. That's a very tricky question, but an important question. So, you know, thinking about the pandemic. In 2018, 2019, there was only 5% of us that were doing some type of telework or hybrid work in 2020 that spiked to 4050% doing some type of hybrid work. After COVID, did it drop back down? No, it only dropped back down to maybe 25 to 30%. So it'd be interesting to figure out and because we're doing that we're spending more time at home, we're doing more activities at home. You know, we're working, but we have these extra activities where we cook and clean, introduce more chemicals and at home, which we're already spending a lot of our time at. So it would be also interesting if during that trend when we saw this up spike of people being in home to see an uptrend in illness related to non well non COVID related illness during that time. There's probably a lag in there somewhere right because it didn't occur immediately. Right. So it'd be an interesting thing for remote work. As far as do yourself work or doing new gig economy, where we have now approximately 5 million workers involved in the gig economy and that's people bringing extra income, doing other in other in jobs. So, you know, examples be Uber and Lyft, but this also includes making products at home. For instance, 3D printing, you know, so we're bringing in new chemicals and new processes into our home, introducing new chemicals and as Delphine pointed out earlier, thinking about we're bringing in if we add new chemicals to our homes. How does that affect the chemistry and we need to think about that cautious. As far as Amazon workers as well. I mean, you're talking about, you know, Amazon, I think employees 1.6 million and workers. There's I think 110 fulfillment centers in the United States each one holding has about 1500 employees in these large warehouses that are about 600,000 square feet. And so you can think about all those products there and all the emissions that occur in those places. What kinds of chemistry are they exposed to. Thank you, Jason, trade. Jason beat me to it. I was going to earlier to your earlier question, you know, I've been involved in nanotechnology for several years and I think it's important to talk about these new materials. And now the term is your is advanced materials so as we still deal with traditional chemicals there are these new types of chemicals that are that are coming into commerce. And I think the technology changes is something that I deal with in my program, and it's very interesting one. Jason talked about 3D printing. And so we have now consumers we have manufacturing in our homes. So we talk about raw materials, some of these use powders others use thermoplastics. And so it came a question, you know, should they even have, you know, child resistant packaging, you know, in the home, you know, children and others may have to use just the raw materials. And certainly when we talk about the printing the emissions that occur, you know, our, do you have the kinds of, you know, person protective equipment or engineering controls, and really this, we now have the sub population of manufacturers. We have the health and safety training that they need and I know Nios just recently put out some guidance on 3D printing. So, you know, this whole idea of this trend of manufacturing, also with our electronic eat platforms. You can get just about any material from anywhere in the globe and this whole idea of supply chain. So, you know, what types of materials are going into these products, and that's going to impact the emissions that occur during the product production, and what happens across the lifecycle of that product. You know, for example, if we have a toy that's less durable, does it degrade more rapidly doesn't release particles into the indoor environment. So I think this is a very interesting time as we see these new technologies, new types of materials that are being used. And do we understand it so it goes to your other question to do we have the techniques, the, the analytical techniques to be able to measure them. One area that's really very interesting or there's a lot of interest are the micro and now nano plastics, you may have heard about that it's it's it's in 3D printers actually may produce these and so their questions about how can we can measure these nano scale plastics or micro what's contained in them. So, this is a new area of research where we do need a lot of questions to be answered. Thank you. Yeah, and then I think the other element too is that there's also a push about recycling plastics, like cleaning bottles, tide balls, gang bottles and such, and making those into filaments that you could do 3D, 3D printing at home. And so understanding those new types of missions that could occur there could be, I mean, I think it's deserved a study on that. That's another layer of complexity to it. Thank you, Jason crystal. You're doing multidisciplinary research. And my question to you has to do with funding for this type of research. Have you encountered barriers, trying to trying to find funding for the multidisciplinary research. I've learned about the funding different agencies that are funding, perhaps being a bit too siloed to support multidisciplinary research. Your comments please. That's a wonderful question and a challenge that I deal with regularly, how do we go from understanding the sources, the chemistry of the sources to the exposure to the health. The nature of our funding bodies really is, as you say, it is siloed. It is predominantly focused on health or focused on characterization of the chemistry of the sources. And I'm really hopeful as we move more into this ex mesomics approach, there's a recognition that we need to think holistically and we need to be more comprehensive with our measurements. And that would then allow for the means for recognizing that we need to have these robust, reliable, rigorous measurement technologies that will operationalize our ability to to look at health. And by having that team science approach that is transdisciplinary that will then allow and pave the way for for increased funding that will go all the way from source through to health. Thank you crystal. Yeah, I've been really enjoying this panel and I would really love to hear your thoughts on different mechanisms of exposure and namely how much does it matter if a compound is in the gas phase versus a particle phase versus an ultra fine particle something really small. So I'd love to hear your thoughts on that and and where you think the research gaps are in terms of how those different types of mechanisms or places where chemicals reside how much that matters. I think it's, you know, I think it's a quite, you know, it's an important question. You know the fate and transport within the indoor environment what happens. For example, if you have this is when we looked at, for example, what products and you're, you're sitting on the deck and you come in and you sit on the couch and, you know, what happens to those particles or if there is an indoor air release, you know, does it deposit onto surfaces, you know, and particularly with children, you know, who may crawl on the floor and so forth. So I think one of the questions is the receptor, you know, if we're talking about young children that may mouth more and so forth. The suspension and the deposition of these in the indoor environment is important. I think, looking at things like furniture, we certainly and I think earlier talked about like the walls and other things absorbing and re releasing, but I think also to with the particulates what happens to those, if it's on the couch, the mattress and so forth. I think that adds, you know, another layer of the complexity and do we understand that sort of again fate and transport life cycle of these particles in in the end also airborne. But again, what happens do they deposit out, you know, that whole dynamic. I think an understanding that if you want to call it the life cycle. I don't know what term we would use for it, but that certainly is a question. Antonio, did you want to also speak. I just wanted to say, I mean, it depends. Many of the chemicals that we're exposed indoors are chemicals that somehow we bring indoors, but we do not know that we did. You know, like we use products all the time and then sometimes people assume by because of the food that we eat we may, if you don't buy organic products then then you may be exposed to pesticides but you know by the use of personal care products then we are we bring who knows how many chemicals home but yet we are only aware of the chemicals that are on the label of the of the product not some of the other chemicals that are in there. And this goes into like the citizen science that Robin was talking earlier today, in terms of prevention, you know, we, we keep on looking at the spoils are very reactively after the spoils are has already happened. And wouldn't it be beautiful that we, if we know that something is going to be harmful, we prevent the spoils are from happening, and then so we stop bringing the products are using the chemicals in the products, forget about regrettable situations but that's a different story but but I'm trying to say is it really all depends on what you're trying to do with the information that you get. If the chemical from like when we look at a chemical we look at that blood sample or a urine sample, we do not know what came from the from ingestion from from inhalation or from dermal exposure we only know that that person was in contact somehow to that chemical. You know, again, from a exposure standpoint, it would be good to know if you want to stop that exposure from happening so you can prevent it from day one if you want so again be more proactive rather than reactive. This is not all in indoor in all type of chemistry I just don't know whether we're in there but I think we're making a step toward that. You know, with this positive concept if you want people want to know what they're supposed to want to get a better idea of what they can do in order to stop those exposures from happening. Thank you, Antonia. We're technically out of time, but there's a gentleman who's been standing for a couple of minutes, please identify yourself and ask your question, and then we will break. This is Charles Bevington from CPSC. You can either respond to the question or just think about it and take it home with you. But as I've been thinking about everything that's happened today I've been thinking a lot about timing of exposures and one of the questions that we asked at the beginning is, does this chemical or agent contribute to an effect either at a lifetime level or a chronic term level or an intermediate level or an acute level. So the question was, what kinds of tools, measurements, techniques would we need, you know, probably different complimentary tools to answer that question at different time scales. I think that's a very good question. And let me suggest that we think about that. And I thank you for the question and I thank the panelists for being here. I thank you who are here in person for your attention. I thank the people who are remote for logging in. Enjoy the break.