Well, thank you for staying and I think it's a, it says a lot about ACOM members that during a fire alarm there wasn't a stampede out to escape the building. So the level headedness of ACOM members has been proven once again. So and it creates an easy act to follow. Hopefully the dulcet sounds of our voices will be a little more soothing than what you just had to be subjected to. So thank you all again for coming. I'm Dr. Ken Spaeth. I am Chief of Occupational and Environmental Medicine at Northwell Health in New York. I am joined up here by Dr. Erin Bell and Dr. Brian Lind. Dr. Bell is Professor of Biostatistics and Epidemiology at the School of Public Health at the University of Albany, where she does research on environmental issues, including PFAS. Dr. Lind is Chief of Occupational Health Services for the, which now used to be at Yale, but now it's at the VA Palo Alto. Things have changed since we got started on this. And we will be talking today, as you know, about the clinical guidelines that came out last year from the National Academy of Sciences. Dr. Lind and Dr. Bell were panelists, committee members on the panel, and they will be talking about the process and the methodology and the findings. As we'll talk about, this has been a long time in the making. PFAS has been increasingly realized as an important environmental and occupational health hazard. And as many of you may know, until these guidelines came out, there was very little clinically to base any kind of decisions, evaluations, et cetera on. So our hope is that by the end of today, you'll have a better sense of that and understand the process by which some of these recommendations were established. And hopefully recognize, too, that there's still a lot of work to be done here. This is by no means intended to represent, you know, the final determination. This is a work in progress, which is one of the themes, I think, that you'll hear throughout today's talk. So I'll put this away before it falls off. All right. So we'll start out by just talking basically about what PFAS chemicals are. So as you all likely know, this is a fairly large group of chemicals. They have been around for about, well, over 100 years. They are purely synthetic, human-made. They do not exist in nature, which is related to why toxicologically they're so problematic. They're essentially a carbon chain, usually a minimum of three, as many as 10 in the chain with fluorine attached in what, as I'm sure you can imagine, is a very large array of various compounds, somewhere around 15,000 compounds exist within the PFAS category. So by the way of disclosure, I should have started with this. So you can see the disclosures here. Dr. Bell is getting funding related to her research on PFAS. Dr. Lin had nothing to disclose. I have done PFAS-related litigation, including proposed medical monitoring for class action litigants. So as I said, there's a huge number of these compounds, and typically we don't speak of them on an individual basis. The body of literature, as you may know, focuses on a relatively small number of these 12,000 or 14,000, depending on how you count them, and those become proxies for understanding the toxicological profile of the rest of the class. And as is fairly common in the history of public health and the history of environmental health, certainly we once again come upon a substance for which there's tremendous utility. There are an incredibly large number of applications for these chemicals. There are way too many to spend a lot of time on that now. You can see some of the examples here, and as has been the case with many similar kinds of substances, be it asbestos, be it lead, where the introduction held great promise and possibility for the kinds of benefits and applications that were possible, rushing into it led to tremendous public health dangers. And we are seeing this play out once again with PFAS. So the exposure and the products really started full bore probably in the 30s and 40s. Most in the lay population, most people became introduced to what they didn't realize was a PFAS chemical, but in the form of Teflon, which actually was invented in the 40s and had widespread commercial use. But that's really just kind of the tip of the iceberg. As you can see on the slide, there's any number of sources that we are exposed, that become exposure sources on a daily basis. And the list is literally in the thousands of the kinds of products, to the point where much like other kinds of exposures, for example with phthalates, where we are essentially being exposed on an ongoing basis, and that has been the case for decades. And as we'll talk about in a couple minutes, in general the background levels to which we are exposed do seem to be going down and the body burdens tracking downward as well, but are still markedly high. Okay. So when you read about PFAS in the mainstream press, it's almost inevitably going to be with the headline or the phrase, the forever chemicals. And that in large part has to do with the fact that given the molecular structure that we talked about, these really don't degrade readily, either in aqueous media or in soil. There are members of the PFAS class that can exist in the ambient environment for a thousand years. In the human body, once there's an entry, a route of entry into the body, how long they stay really depends on the particular compounds that we're talking about. The newer ones tend to have a shorter half-life in the body, the older ones tend to persist a little more, but the range is going to be somewhere between days to years, depending on which ones we're talking about. And again, most of what we know about them come from just three or four compounds, really two in particular, PFOS and PFOA. Those have still become the proxies by which our epi and our toxicological understanding have really been formed. So as I mentioned, it appears that our levels, our body burdens, have been dropping over the years. And the basis for saying that comes from the NHANES data, right, and hopefully this audience is familiar with NHANES, but it's a cohort of about 5,000 people in the U.S. that the CDC follows for a variety of health issues, but they take a subset of that, about 2,500 people, and they assess them for a variety of industrial pollutants, something like 350 or so. And they do this on a periodic basis, and PFAS has been included amongst those. So there are a number of PFAS chemicals, I think they do a dozen or so, and they have been following the trend in the population for a while, and it does seem to be going down. There's been an upswell of attention on PFAS probably in the last five, six years, and growing pressure on industry to do better to protect the public, but as is often the case, protecting the public and the voluntary measures has tended to take the form of modification of existing PFAS molecules to bypass the particular molecules of concern. Okay, so how are we being exposed? We talked about some of the products, but really it's kind of a multi-tiered approach as to how we end up with this, both in the environment and also directly through contact with products. So obviously the manufacturing itself becomes a source of exposure for the workers and has historically been the case, the communities living around where these kinds of chemicals are processed. But once it's out there, like I said, the half-lives in the ambient soil is extraordinarily long and through runoff, one of the big issues has been widespread contamination of drinking water sources throughout the country. And I can tell you that in New York State, that's been a particularly big issue. There are a number of communities in New York State where the levels in the drinking water were found to be exceedingly high, some of the highest levels that have been demonstrated. And PFAS will adhere to household dust and atmospheric dust, so it can be breathed in, it can be brought back down through precipitation. Waste, both in terms of products but also in terms of larger industrial sources, end up in landfills and then it leaches out into the local area. And so there's this constant stream of potential exposure and abatement remediation is a major focus now, but there are still no easy answers for how best to do that, how to do that most safely. So there's still a lot of work to be done in those areas as well. Just to put it in some kind of historical context, as I mentioned, they were discovered last century and have really been in use in the modern world since the 50s at really high levels. In 1999, there was this very important lawsuit that was brought and it's been made into a major motion picture. If you have Netflix, you can watch the Dark Waters movie. As a result of that, one of the things that happened was in the settlement, money was put aside for research. And so a panel of epidemiologists was brought together, people who were really renowned researchers came and began doing good studies on both the workers and also the communities around the sites where this occurred and published some really important data that still are, that serve as the backbone of our basic understanding of the toxicological profile. So by 2012, EPA started to be paying attention to this. In 2016, they set some health advisories. And interestingly, at that time, they put it at 70 parts per trillion of PFAS in total. So they didn't really distinguish, it was really more about the total amount of PFAS in the water. Last year, they then lowered it for PFOA, I think it was 0.004 parts per trillion. And for PFOA, it was 0.002, I think those are the right attributions. So you can see from 70 to 0.004, we're talking, you know, orders of magnitude lower. It also raises a little bit of a problem in that it's very hard to find water levels that aren't in exceedance of that. And so there are some feasibility issues and some clinical issues because there are suddenly going to be a lot of people who are living in communities that are in exceedance of this new EPA standard. And that raises important clinical questions, which we'll get to in a little bit. Okay, and just to give you a sense, so this is a map from the Environmental Working Group, which is kind of an environmental group that does research and publishes on issues. Now this is not peer-reviewed data, but they do make their methodology available on the website. And it's an interesting map because it shows you where there has been identified levels of elevated sources of PFAS. And it's from mostly the blue is the drinking water. The purple are military sites, typically air bases. And bear in mind that here it's about 3,000 sites in all 50 states, but this is based on the prior EPA advisory of 70 parts per trillion. So if you now adjust this for the current EPA health advisory, the map would essentially be full. So these are really important issues and obviously have important clinical ramifications. So I can tell you in my clinical practice, we've seen several hundred PFAS-exposed individuals from some of the most heavily contaminated drinking water sites in the country. And previously, up until last year when this document came out, there was no guidebook. We were really doing our best to use the available science to try to come up with some way to do an evaluation. Issues of how to check someone's serum levels was and continues to be a problem. But as you'll hear now, the development and the findings of this publication bring a tremendous clinical benefit and become an important foundation for how to think about this going forward given that there's literally hundreds of millions of people who are now exposed. And with that, I'll turn it over to Dr. Bell. Dr. Debra Bell. Thank you. Okay. So as Dr. Spaeth mentioned, the C8 studies, which is really the first large-scale study resulting from the lawsuits coming out of West Virginia examining PFOA, was remarkable in its size. It had 69,000 participants. And as per the settlement, the team of scientists were charged with identifying health endpoints that more likely than not, so legal term, not necessarily medical or even epidemiological, but given the evidence from their survey data and from their epidemiology study, what did they declare? So with regard to PFOA, high cholesterol, ulcerative colitis, thyroid disease, testicular cancer, kidney cancer, and pregnancy-induced hypertension were identified as being more likely than not associated with the PFOA exposure. Those studies started to roll out in the early 2000s. Subsequent to that, a great deal of work was done nationally and globally by additional epidemiologists and clinical groups examining data from NHANES as well as other studies and communities throughout the country. And those studies started to show additional health endpoints of interest, in part because animal studies were very strong in telling us that these chemicals are endocrine disruptors. There's a very strong association with the impact on the immune system, lower antibody production resulting from, as a result of, with vaccination. So this was particularly in children, but also started to see this result in adults, asthma, diabetes, changes in liver enzymes, and high blood pressure in adults. In addition, because these chemicals, again, through the animal studies, were showing an impact on what is the PPAR mechanism activity, there is concern around infant birth weight, child growth, learning and behavior, changes in hormone levels, and childhood cancer has not been studied given the challenges there. But all of this together, along with the fact that newer PFOS that were brought into production after PFOA and PFOS were phased out, were less persistent. But there are communities in the United States, North Carolina in particular, that experienced contamination with these newer PFOS, and those communities and those studies are starting to show some of the same health endpoints. So being less persistent does not necessarily indicate safe. And with all of that in mind, where did we? Ah, there we go. The National Academy of Sciences, Engineering, and Medicine was tasked with developing a community, thank you, a committee to examine the literature to provide additional guidance for clinical guidance and processes in place for testing as well as reviewing that guidance over time. The committee had 15 members comprised of clinicians, epidemiologists, toxicologists, environmental scientists, and a philosopher who is very important and I'll speak to his critical role in a minute. We were given a very large task. For those of you familiar with the National Academy, our reports are consensus reports, meaning everyone on the committee must agree to the contents of that final report. And in this instance, we were tasked with examining the human health literature that was available in peer-reviewed literature, characterize exposure pathways, develop principles for exposure reduction, develop principles for biological testing and clinical evaluation given that we have substantial scientific uncertainty still given in part because there are up to 12,000 of these chemicals and we only really have a lot of information on about four of them at this point. Provide recommendations on blood testing, provide recommendations on patient follow-up, and then advise ATSDR with regards to a process for how to update that clinical guidance moving forward. NIEHS was also interested in help to provide support for this committee because they wanted to use the findings from this committee's report to help establish research priorities for moving forward. So the committee in our first few meetings had a lot on our plate to try and tease apart. Many of us had completed epidemiology studies or were in the process of working on epidemiology studies. And one of the first things to keep in mind with regards to PFAS, as often happens with environmental exposures, attention from the scientific community started because of the advocacy of the committee member or the community members of the residents. It was the residents that brought attention to the local health departments and to local scientists and clinicians saying there's a problem. Something's wrong with our water. That's what happened with the C8 community. It's what's happened in New York in both Hoosick Falls and Newburgh. And we knew as a committee that we needed to hear from the community members to understand what their concerns are and what their questions were with regard to PFAS. So with that in mind, the National Academy also established a companion committee of community members from across the country as well as clinicians who work within these communities to help provide key testimony and advise the committee with information as we work through the process. We held town halls across the country and we also accepted written testimony as well as the oral testimony from this committee. We had to then work on developing principles for decision making under substantial uncertainty. This is where having people and committee members with backgrounds in philosophy was particularly helpful as we had to consider environmental justice. Many of the communities that have these high exposures are environmental justice committees. Communities that are struggling with lead, they're struggling with air quality issues as well as health disparities, many of which are suspected as being associated with PFAS. We also have a number of communities that are in rural areas that have less access to financial support and infrastructure with regards to their water systems and other exposures. So we developed these principles in mind as we worked through our process. We then examined the evidence from the epidemiology study to provide some recommendations on the human health effects of PFAS and suggested a strategy for reducing exposure to PFAS and provided recommendations on testing. Again, many of the community members and residents want access to testing. We considered the benefits and risks related to that question and provided guidance on that. And then again, recommendations moving forward for how to provide this clinical guidance and keep it updated for clinicians. And with that... All right. So for the next few minutes, I just want to carefully go through some key clinical recommendations from the report. And part of the reason to do that, one, is so you walk away from here knowing what the report says. Yeah. Sorry. So you know what the report says. But then also just to reiterate what Dr. Bell said, these aren't my ideas. They're not her ideas. They really flow from a process that begins with the statement of task through the input of a variety of stakeholders and then through the consensus process and peer review. So the words are important. So again, just to, in terms of the task and how we did our work, we focused, as requested, on the PFAS chemicals that are currently measured in the NHANES study. And again, one of the aspects that the committee decided on was to assess our recommendations based on the sum of PFAS as a group because it was very difficult to try and look at each one of these separately. There often isn't enough literature in any one on its own. We used our health literature review. We examined the authoritative reviews from ATSDR and EPA that had already been published as well as systematic reviews that are coming out regularly in the peer review literature and then the newer studies that had not yet been included in any review. And with that, I think there were about 600 papers total that we reviewed in depth as a committee. While we did not look at animal evidence separately, we did consider the animal evidence that was included in the authoritative reviews and in particular the ATS toxicological profile to help support some of our evidence. So in terms of Classic National Academy of Medicine, using this similar terminology to what they've used with the Agent Orange reports that have also been published through that organization, the committee established and identified health endpoints that we felt after reviewing the literature that there's sufficient evidence of an association with PFAS chemicals and these articles suggest strong evidence. They have limited bias and, again, just telling us in terms of the preponderance of evidence that there's sufficient evidence of that association. So this included decreased antibody response from vaccination in both adults and children. This was particularly critical in the time as we come out of a pandemic. Dyslipidemia in adults and children, decreased infant and fetal growth, and increased risk of kidney cancer in adults. A second category for the committee was limited suggestive evidence of an association. So here, the epidemiology studies are slightly more mixed, but still the majority are pointing to the direction of an association, but we couldn't rule out bias in all of them. And so this category, it's leaning in the direction of sufficient evidence but not quite there yet. So in this group, we have increased risk of breast cancer in adults, increased risk of testicular cancer, liver enzyme alterations, increased risk of pregnancy-induced hypertension, thyroid disease and dysfunction, increased risk of ulcerative colitis. In the report itself, there's a third category of all of the endpoints that, again, much more mixed results, more studies that had issues with bias. We've listed those out, but many more related to particularly child neurodevelopment and reproductive outcomes like infertility, again, warranting a need for more research. We haven't listed them here for time, but they are spelled out in the report. Most notably, we did not identify any health endpoints where we could positively say there's absolutely no association. So there's no endpoint or health outcome or diagnosis in that group. And with that, I think now it's your turn. There you go. Okay. Thank you. So can you hear me? So given those health outcomes and concern about those health outcomes, obviously the clinical guidance is very important. What can we do? And so like I said, I just want to sort of carefully go over that now so you know what the report says. And so as we do, these things all start with the exposure assessment and the exposure. So recommendation 4.1 states that clinicians advising patients on PFOS exposure reduction should begin with a conversation aimed at first determining how they might be exposed to PFOS and what exposures they are interested in reducing. This exposure assessment should include questions about current occupational exposures to PFOS, such as working with fluorochemicals or firefighting, and exposures to PFOS through the environment. Common environmental exposures to PFOS include living in a community with PFOS contaminated drinking water, living near industries that use fluorochemicals, serving in the military, and consuming fish and game from areas with known or potential contamination. And that's important because as we get to the testing guidance, you know, that's going to be based on one's level of exposure. And so the report delineates what some of those things might be. Recommendation 4.2, excuse me, is about occupational exposure and says if patients may be exposed occupationally, such as by working with fluorochemicals or as a firefighter, clinicians should consult with occupational health and safety professionals knowledgeable about the workplace practices to determine the most feasible ways to reduce that exposure. And that's because the workplace is a very specific environment and hopefully, not always, but there'll be health and safety professionals there that can be helpful in assisting a community clinician in understanding the exposure and what could be done about it. So on to recommendation 4.3. This has to do with drinking water. So clinicians should advise patients with elevated PFOS in their drinking water that they can filter their water to reduce the exposure. Drinking water filters are rated by NSF International, an independent organization. The NSF database can be searched online for PFOA to find filters that reduce the PFOS in drinking water, including the committee's charge. Individuals who cannot filter their water can use another source of water for drinking. And of course, the key thing with water filters is they need to be maintained, they need to be used properly, and they need to filter what you're looking to filter. So that needs to be done. And again, many of you in the room know this, but obviously, the report goes to the whole nation and so we need to make sure, you know, people know what the right sources of information are and that's what a lot of this is aimed towards. Recommendation 4.4 extends to now fish and wildlife. And so in areas with known PFOS contamination, clinicians should advise patients that PFOS can be present in fish, wildlife, meat, and dairy products and direct them to any local consumption advisories. Again, Department of Public Health maintains these things in many states, but not everybody knows they exist. And so just making sure people really know the resources that are out there to understand their sources of exposure. And then the report continues with recommendation 4.5, and this is it. There are fewer evidence-based exposure reduction recommendations for patients without known sources of exposure. And I'll just say there, too, that there was a white paper commissioned for the report on, you know, individual strategies to reduce exposure, and there's not a lot of great evidence for that, partly because it's very hard to measure the effect of the intervention given the long half-life of the agents, but it's hard to make individual recommendations and it was out of the scope of the report to, you know, make recommendations about regulations. So we have a narrow set of things an individual can do, but they're addressed in the report. So for recommendation 4.5, it states clinicians should direct patients interested in learning more about PFOS to authoritative sources of information on how exposure occurs and what mitigating actions they can take. Those include the PSHUs, ATSDR, EPA, and again, you know, you Google PFOS and you'll get, I don't know what will come up at the top of the list, but, you know, trying to help people know what are the peer-reviewed, what are the, you know, the reliable sources of information. 4.6 is very important, it has to do with breastfeeding, and this is a very, you know, emerging area within PFOS and PFOS health effects, and essentially there, we have a lot more certainty about the benefits of breastfeeding in general and a lot more uncertainty about what the health effects of PFOS and breast milk are. And the recommendation, which I'll read in a second, just encourages really to be transparent about both of those things and have an individualized, you know, talk with the patient, share decision-making. So when clinicians are counseling parents of infants on PFOS exposure, they should discuss infant feeding and steps that can be taken to lower sources of PFOS. The benefits of breastfeeding are well-known and recommended by the societies listed there. And also, clinicians should explain that PFOS can pass through breast milk from a mother to her baby. It may also be present in other foods, such as the water used to reconstitute formula in infant food and potentially in packaged formula in baby food. It is not yet clear what types and levels of exposure to PFOS are of concern for child health and development. So just a very accurate statement of what we know at the time of the report. Section 4.7, just in line with that uncertainty, the report makes a recommendation that this is, you know, an area where more research is needed and recommends federal environmental health agencies to pursue that. So that was the information about exposure and exposure reduction. And then the testing recommendations follow next. And so essentially, once again, who should get tested, right? This is a huge question and a huge issue. And it does start with, you know, trying to figure out who's exposed. So before that, however, there's just a general recommendation that as communities with PFOS exposure identified, the main government entities should support clinicians with educational materials about PFOS testing so they can discuss testing with their patients. So again, this is one of the things we did here, you know, in the town hall process that the community members were not, were dissatisfied with the level of knowledge amongst their providers and others. And so really get the information, get the best information in the hands of the clinicians. And this includes how people are exposed. And you can see a long list of sources there. The potential health effects, the limitations of blood testing, which is a very important discussion, as well as its benefits and harms. And so this is what I was starting to mention, Recommendation 5.2. Clinicians should offer PFOS testing to patients likely to have a history of elevated exposure. We've gone through now how one might determine what that is. The report gives certain sites and criteria. And in all discussions of PFOS testing, clinicians should describe the potential benefits and harms of that testing and the potential clinical consequences, related social implications, and limitations of the testing so that patient and clinician can make a shared informed decision. Patients who are likely to have a history of elevated exposure include those who haven't. We've discussed that. That's really important. Part of the report there is that there's an offer of testing to those who have elevated exposure. And then there needs to be a frank discussion about what the testing can and cannot do. And in the report, there are some nice tables that go into the benefits and harms of the testing. So then, you know, one of the tasks really was to give, so the ATSDR has clinical guidance available. Many of you may have seen it. And there's a lot of good information in that guidance. But one of the, I guess, criticisms was there wasn't a lot of specific information. And that's why one of the tasks was to furnish that information. And so we were tasked to look at specific levels that could inform action, clinical action. And what we weren't tasked with was to conduct a risk assessment ourselves. So what was done was there was a search done for what were the existing risk assessments available to use. And there's a lot of good information in the report about, you know, reference range levels versus risk-based levels. And these are the risk-based levels. So there were two that were found. One from the German Human Biomonitoring Commission, which I'll tell a little about. And then from the European Food and Safety Agency. And so the German Human Biomonitoring Commission, their risk assessment has an HBM1 level and an HBM2. For their risk assessment, they used a variety of clinical outcomes and then took sort of a more protective one as their sort of point of departure and what informed the levels. So the HBM1 level, as you can see on the slide, is the level below which there is not considered to be risk, or their effects are not expected. And then for HBM2 is a level above which adverse health effects are possible. And with respect to the space in between those two, between HBM1 and HBM2, it's not indicative of risk per se, but there should be an emphasis on exposure reduction. And their methodology is, you know, published and it's summarized in the report, but that's about as far as we'll go here. But that was, those values were used in helping to determine our recommendations as far as value to use. The other one is European Food Safety, and they used immune response to vaccination as their clinical outcome, which they determined their point of departure. And that had been shifted previously with cholesterol. And you can see in the table, those were the values there. So those are the two best risk-based levels available at the time of the report. And this is a graph for PFOA, and it shows you where those levels fall and where NHANES 95th percentile falls in those levels, because obviously there will be implications in terms of the number of people the recommendations apply to based on where that line is. And you can see that the HBM2 was published both for a general population and also for pregnant women, which is a more protective value. And this is the table for PFOS. And so based on those values, the recommendation, you know, is to split, you know, once the testing's, you know, obtained and the values are back, there's three sort of action levels, which would be less than two. And this is the sum of PFAS, which is, you know, one of the procedures or ways of dealing with it. There's others, but the sum is a sort of established way. So you would take the sum of the measured values, and if it's less than two, adverse health effects are not expected, and you would proceed with the standards of care. If it's between two and 20, which is sort of that intermediate level, there's going to be additional actions that are recommended, small but meaningful additions to the standard of care or points of emphasis within the standards of care. And we'll look at those. And then above 20, a little bit more. And this was really, so the basis of the clinical recommendations here is both sort of standards of care and then the C8 panels, what they had recommended also was a major primary source for these recommendations. And I think probably just in the interest of time, we'll kind of move through this one pretty quickly, but you can go to the report to see this, but that would be an example in that middle range within the usual standard of care, prioritize screening for dyslipidemia with a lipid panel, screen for hypertensive disorders, screen for breast cancer. So maybe as they're having that conversation, those things, you would, it would shade up the risk level or the importance of looking at those factors. And this is for the high levels. So I think in the interest of time, I'll hand it back to you and hopefully we'll be able to discuss this more in the question. All right. Thank you. So on, thank you. The, on the app for today, we've provided a two-page flyer that includes links to a number of resources for PFAS, including the link to the report. And that is downloadable for free. And for those who might still like paper, we did bring a few hard copies as well. We just wanted to briefly touch on the response to the report. It's been, it was very, it's been an excellent response. We've been very pleased. The communities were so appreciative, as well as the clinicians working with these community members for the help that's provided. We received an email, I think it's the highest or second highest report that's been read at NSM. So National Academy's thrilled. But, so we did, and just again, just to highlight the importance of this report to the communities that have been most impacted by that. And again, just another link to the publication, which is available in the app. We intentionally designed this with, not planning on a fire drill, so that we could open it up for questions. Because we're assuming you have questions. And especially since it's the last session of a conference. So we're going to do that now. And we'll just, so if you raise your hand or come to the mics, and then we can have some discussion. Thank you. Thank you for an interesting presentation. I'm not sure how to feel emotionally about the whole issue. It's been a long time since I've done organic chemistry. So I'm going to ask what may be a stupid question. It's been a long time since I've done organic chemistry. And so this may be a stupid question. But is it conceivable that as PFAS chemicals degrade, either in the environment or through biometabolism, that you will go from one long chain molecule to multiple small chain molecules, which has the effect of magnifying the impact? Absolutely. And you nailed it on the head. That is one of the great concerns. And the newer, and it started to highlight with the newer PFAS that were shorter chain, and then people started to look at the longer chain as they break down. And so this is exactly the challenge that we have. Okay. So it's like analogous to microplastics. So micro PFAS. Yes. And in fact, a study came out not too long ago that also detected PFAS in some of the microplastics. So it's, the story gets more complicated as we go down. But yes, it's a very similar story to the microplastics. Thank you. Hi. Thank you so much for bringing up this topic. I was just wondering with this article, I kind of still feel like at a loss, even despite all the work that was put into it. I get to tell somebody, like, go ahead and not drink the PFAS water. Don't eat the PFAS contaminated foods. But nothing is labeled. I don't know if what I had for breakfast was contaminated by PFAS. I don't know if this water contains it. So how do I, as a clinician, give that advice to somebody and then test their level, have them do an intervention, retest? Do you have any experience with doing interventions and having this help? Yeah. Well, that's, you raise some very important points. I mean, given the ubiquity of these chemicals and the, you know, ever-changing benchmarks, it's highly problematic. And as you said, as with many exposures, be it phthalates or BPA, you know, packaging, labels, et cetera, are really of little to no use to the average consumer and certainly, therefore, to the patients. And I think, as I said, you know, we know that all of us are walking around with PFAS levels in us. And, you know, as with many of the industrial pollutants that are in our bodies, as evidenced by the other 350 NHANES chemicals, there's only so much a reasonable person can do. You know, putting aside the, you know, the spaghetti strainer hat crowd, there are limitations. And, you know, so like with a lot of things, you kind of have to, I think, and in my clinical experience, you know, it's about, you know, sort of picking useful and relevant sources and also targets. So clearly, for those communities where drinking water levels, for example, have been found to be elevated, you know, that's one sphere and that creates a lot of public health concern and appropriately so. For the average consumer, I think it's about finding an appropriate, you know, exposure history to see if there's a basis for a clinical reason to say this person is likely to have elevations above background. And so, like a lot of what we do as occupational environmental medicine doctors is taking that thorough history and then ultimately arriving at a determination as to whether there's a clinical basis for proceeding with any kind of testing. To further complicate the story, PFAS levels are not available in every lab. So it's not even accessible for probably the majority of people who might be interested in having it. And then to further complicate it, well, who's going to pay for that? Will insurance cover it? That's not clear. And it's certainly not been mandated that that be the case. So, and because these are specialized tests, doing so is not cheap. And it also tends to be that many of the communities affected are under-resourced and so environmental justice issues come up. So these things get very complicated. And I don't think there's any, in my experience there's no easy answers on this. You know, so before these guidelines came out and before, now we have some commercial labs that are starting to do PFAS levels in their testing. But before that, you know, we were, we had, we developed clinical protocols that were looking at all the proxies, evidence of injury. So, you know, cholesterol and thyroid, et cetera. Those are obviously much more available and typically covered by insurance. So that gets us out of a lot of these more complicated issues. But it's not as useful and not as meaningful. And then, well, what do you do with the levels? How do you interpret them appropriately in a clinical context to give them meaning? And I'm sure we could do a talk or many just on that alone. But that was not the burden of the National Academies Committee. Theirs was to simply come up with recommendations. But I think it's a long-winded way to get to, we don't have a good answer for any of that. And I think it's really going to be based on the community you live in, the patient who's in front of you, and what resources are available to you. Brent, I don't know if you have more. I'm just going to add one thing. Well, two things. But I think to the last point, it is incremental work. It's a very complicated issue to try to summarize into something that we can work with as human beings with our cognitive limitations. So I think the thing is, this is a start. It goes to the ATSDR. They're working with it now to update their clinical guidance in a document. And one of the recommendations of the committee is for that process to repeat every two years, you know, as more information becomes available. And I think as far as a clinical encounter, there is a lot of uncertainty, and it's frustrating. But you can try to ensure that the risk assessment is as good as you can make it at the current time, you know, so everyone's on the same page about what the potential harms are and what they aren't. I appreciate your presentation on an interesting subject, and I hope my question is not too narrow. Can you briefly comment on firefighter turnout gear that's PFAS-free, and where that may be headed, and when? So firefighters are a huge concern and are garnering a lot of attention in New York. We're talking about this. The turnout gear does have the PFASs in them for obvious reasons. So there's a concern when they come back. It's the dust that comes off of that gear, in addition to obviously exposures with the firefighting foam. And then in communities like in upstate New York, what we're grappling with in Hoosick Falls where there was a contamination is many of the residents are also volunteer firefighters. So they have both the environmental exposure as well as the occupational exposure. So if you are working with a population where you know someone's a worker, where they've used the firefighting foam, it's both the turnout gear as well as using the foam. Do you, I know you're working on, working with firefighters. Do you have anything to add? Yeah, sure. Yeah, so look, we know from the literature that firefighters have elevations compared to the general population. So it's a critical issue occupationally. The extent to which firefighting foam versus turnout gear is the explanation for this, it hasn't really fully been or adequately determined or proportioned. But we know it's in the gear. We know there are issues with, as Dr. Bell was just mentioning, with proper decontamination protocols either lacking or not being followed. And so I think, you know, there's a piece of this that is going to require education and risk communication with the firefighting community on this. It's already, of course, a big issue and a big topic there. But it's really not, we're not anywhere near with it where we need to be. So, you know, between cooperation with the manufacturers and, you know, education piece, there's certainly a lot of work to be done, you know, in the fire service. This is more maybe a comment than a question. As you said, it's very complicated how to interpret these blood measurements. Should you really go from the societal level and group level to individual level when you don't have the basic principles of screening? You don't know where's the effect level. You don't have any treatment. So how should the doctor really interpret this? And the risk communication, for example, the kidney cancer, as the absolute risk increases very small, maybe going from lifetime risk from 1.5 to 1.9%. How should the citizen react to these small changes? So in Denmark, the National Board of Health have decided not to ask for blood measurements, doing research measurements. And then, of course, use the resources to, as you said, get rid of the exposure, stop the pathways into the people. But it's not used to the resources for blood testing in general. Yeah, no, that's an excellent comment. And it's something that the committee grappled with extensively. Two comments based on that, and then I'll have you hop into Brian, but first of all, one of the key recommendations that we didn't dwell on is that the committee strongly recommended that the scientific literature be evaluated and updated every two years using a National Academy of Medicine model with updating that clinical guidance in part because this is a moving process. It's moving very quickly. With regards to concerns over, you know, it's uncertain, how can we set guidance now? With the exception of kidney cancer, the other guidance markers that have been put in place by the committee for the most part are very similar to standard of care with perhaps a little bit of an uptick in it or maybe a lower age. And we discussed that heavily, understanding that we had a challenge here with the uncertain science. The kidney cancer is more of a challenge, as you all know, much better than I do. But with that, do you have anything to add? No, I just thank you for the comment because those are very important points. I mean, one is that exposure reduction is probably the one area where we would have certainty that you can recommend that pretty much with a minimum of, I mean, there are some tradeoffs involved, but it's a pretty easy recommendation to make that is a good recommendation. And, you know, as far as biomonitoring, it has limitations. It doesn't tell you the source of exposure. It doesn't tell you when the exposure occurred. It doesn't tell you the trajectory. And, you know, also it might not even be, you might not even be testing for the PFAS that the person was exposed to. So all these things have to be discussed in the clinical encounter. And, you know, we're trying to present it in an hour. The report tries to do some sort of summarization on it. And so we didn't mention that, but I really appreciate you bringing that up because that is, biomonitoring has a place. And also given the uncertainty, it might come to pass that we'll be happy people have their baseline value, even with all those asterisks that we don't know a lot about it, you know, 10 years down the road. So it's just important that we're very transparent and honest about where we are with everything. And uncertainty rules the day on this one, unfortunately. Hi. I was just wondering about excretion and post-intervention biomonitoring. Like after removal from exposure, if we have a known exposure like say a Camp Lejeune military base or something, then that person's removed. Do the levels go down? And. The levels should go down in, for those that we know and are measuring in the half, even though the half-life for the oldest PFAS are in years. Certainly in Hoosick Falls and Newburgh where we've had multiple years of biomonitoring, you do see that half-life, that reduction due to the half-life once the exposure is removed. And that's why the committee really did emphasize exposure reduction. One of the gaps in the scientific literature is that we know half-life varies by key characteristics, most notably by men and women. And it's because of pregnancy history and breastfeeding history. And so a number of us have, are working in that realm right now, trying to better understand so that hopefully clinicians then would be able to use that information to better advise their patients. I read with interest the Environmental Working Group's report on just how much PFAS was contained in fish in our, you know, just our streams and rivers and And how easy it was to actually exceed the recommended levels with just really moderate, you know modest fish intake and so that leads me to think about the food supply in general in in the country and If the fish although they swim in the water and probably have the largest exposure to water all the other animals in the country drink the water too and so it seems to me that there is a very large role here for our Government agencies regarding evaluating food safety In in looking at these various PFAS and I'm wondering if you could shed any light into What you know what they're doing and and what they should be doing yeah, I so one of the the key areas in the report we talked about is is the importance of Following and being up-to-date on what the local and state level agencies are looking at So I'm not again just to even get even darker here. It's not just the fish in the water Sludge from wastewater treatment plants have been applied to fields And so and then the cows from eating the grass have been contaminated So we heard testimony on the committee from a dairy farmer out west and that the cattle had been Have tremendous high levels there also are problems in Maine and Michigan with with contaminated fields so and I think Initially certainly with state health departments focused on drinking water on those contaminated and now they are starting to with DEC's Looking out to game wildlife and in agricultural exposures It is being it is measurable and will need to adjust They will need to adjust their advisories the fish advisories are being updated again It depends on where you live and in what state so the Northeast is going to have more guidance than areas in the Midwest for example And again, I think EPA's is looking in that direction. So yes, absolutely One of the key recommendations was to keep updated. We've provided links here on Trusted sources that you could also be providing and again a TSDR is taking this information And hopefully we'll be updating their own clinical guidance to have that information where you can leave, but that's an excellent point. Thanks Hi, thank you for the presentation and I've Working in the DoD. I've had the dubious honor of being involved in Several on base and off base drinking water exposure assessments and the risk communication efforts that are done to kind of help Help alleviate and alleviate concerns and manage expectations the public when they find out. Hey, we're coming to test for this And so just a couple Things that I have learned that I've kind of helped with the the patient Interaction general population one thing when you're talking about like mitigating exposure That it tends to be helpful in the fact that most people don't realize that they've already been doing it although there that can be high levels of PFAS in the groundwater and even at the tap things as simple as your commonly held refrigerator type Filters the activated charcoal filters the pure filters the britter filters as long as they're properly maintained Essentially eliminate all of the PFAS that go through the filter that is in the drinking water And that's something that tends to help that's a study out of the University of Arizona That was looking at just a wide variety of commercially available available and then I also think it's important to notice that When people are asking you because eventually people can come to you and say hey, by the way, I lived in this exposed area You know, I did have kidney cancer. What should I do? I think it's important to highlight that at this point there's nothing to do differently other than to mitigate your exposure, so the The Emphasizing that there is no treatment The standard of care is the standard of care whether you're exposed to a high level medium level or a low level of PFAS I think it's important making people feel a little bit better that you know You feel like you have a loss of control when it's in your drinking water and it elevates everybody's emotional state But there are some pretty simple things that you can do to minimize your level at this point And then there also there's no change that would happen in the standard of care For how you should how your primary care physician should be treating your standard, you know Health concerns, even if you do have high levels. Thank you Thank you for that comment and I think it just made me want to underscore again We probably all have some preconceived notion of how big of an issue this is or how small of an issue it is But the important thing in the clinical encounter is to do an exposure assessment and figure out who you're talking to And and they could be in a heavily exposed community or occupation or they could be a worried Well, and you have to get that information and you have to start from that information And Then just to follow up and this ties into the organic chemistry Question earlier that filters do work You can filter the water both at the supply as well as in the house But the type of filter may matter especially the newer shorter chain PFAS Requires in some cases a different filter so again, this is another burden that is put on both clinicians and in residents to try and figure out which filter is best and Again there are some some key websites that are that we've provided in the links for you so that you can be up-to-date on that But that again is another changing target that will be as we learn more Hi, it's Steve Castellar from the Air Force just a couple of comments and questions too for you guys to comment on first would be the Can you comment on the strength of? Association for a lot of these because as far as I'm aware, they're not really causal links They're so if you can speak a little bit to the strength of association for each of those different factors, then the second piece is just we I do I test a lot of DOD firefighters and many of them have had decades of history working with a Triple F the firefighting foam They all wear PFAS containing gear and there's a lot of concern and our message to them and as especially as we have done Testing regularly for them and found actually that their levels are Normal, I mean I got my own PFAS levels tested by my physician to compare to what I'm seeing in my firefighters And of course, I've I've never been a firefighter and my levels are about the same as theirs And so that was reassuring to a lot of them to know like hey this probably this might be occupationally related But our message to them is that it's most likely actually Environmentally related because as we know the three ways that they get exposed are mainly through ingestion Minorly through inhalation and minimally if at all really through dormal absorb dermal absorption So you start to talk about like the turnout gear. I'm not sure that there's a lot of Absorption that's occurring from that and at least moving forward I tell them, you know, you're you're wearing your SCBA when you go to fight a fire So anytime you're going to be using your foam, you shouldn't be eating the foam You should be wearing your SCBA so you shouldn't inhale it and it's not really dermally absorbed I've got I've had people who come to me and they say we used to bathe in this stuff because they didn't know what It was they'd wash the trucks with it and their levels are actually very normal Yeah, you know so I'll start and yes to I fully the the turnout gear is not because of dermal Exposure fully agree on that that it is from again But you need to have the proper techniques to to to clean it and to store it so that the dust it's it's the Flow of the dust that comes out that where they can then ingest it and inhale it. So a few things the I'm reminded of I've been doing this long enough. This is similar to lead So when I started training as a graduate student 30 years ago The the regulatory level for lead was much higher than it is now because as we did more science We understood that the lower levels were needed and we see something similar in PFAS So I'll push back a little bit on there is really no normal level What we do have is what it is ubiquitous. I did a study in New York of 3,000 infants from their newborn blood spots and we were able to detect measurable amounts of PFAS in 99% Of the three that so it and that's solely from prenatal exposure. It was that so it's it's definitely there What we are grappling with is is there such a thing as a threshold is there a safe level we don't know What we know is there is a mixture Firefighting foam by definition is a mixture of PFAS We are exposed more to more than just one and we have the breakdown Problem where it's coming into to a combination of shorter chains in terms of the epidemiology that the report has all of the tableaus and in our results and I the Strength of association varies dependent on the outcome that we're looking at You know any but certainly in those that we declared sufficient. It would have been Above two and and then some and very consistent over time No epidemiology study will ever be causal and now that so that's this again is part of the challenge and in the the experience with National Academy Committees in general for all of these reports is to look at the preponderance of evidence and that is why The committee really said every two years this needs to be revisited To account and and consider bias consider strength of association consider study design and the animal literature Which is very important and really thoroughly evaluate to better understand. So there's still a lot of uncertainty I think again the messaging to to patients is In certainly, there's occupational exposure, but we are all exposed environmentally It's the amount of exposure and again It's that shared decision making and making sure their standard of care if they're getting standard of care They're going to be followed up on many of the things that we recommended The only really different one might be the kidney cancer one could and that's difficult to screen for but the everything else a pregnant woman Should have her blood pressure measured every time she goes in So this is you know again just being very alert and really it's a an awareness for clinicians that if you know Someone's in it in an occupation where they might have higher exposure or in a contaminated community That this is something to be aware of and just to ensure and work with them and communicate with them that the standard of care Is going to be very important I'm just gonna just say just again emphasizing dealing with the specifics in front of you and it sounds like you described a case where you had an exposed group and The biomonitoring was helpful to provide some information where you could counsel them. So Things were working well there that process worked well and as far as the evidence-based The strength of association is based on the quality of evidence and as was pointed out the magnitude of effect tends to be smaller And that so that on one hand represents the best we know now But as you mentioned to the the quality of the studies, they're limited They're hard to do and so there's an element where of you know precautionary principle involved to the the true effect size Could be larger or smaller than what we're able to do in these observational studies. So some element of precaution If I or when I download that publication will I find that it has within it what I need to Counsel patients and Do appropriate exposure evaluations, for example, is there a questionnaire that you've recommended or created? yeah, so I think that the the The document is the report is not really for the point of care It's really that stuff will now be taken up by a TSDR who will make a more, you know user-friendly document for clinicians So the report itself has a lot of good information I encourage you to read it and at the very least just the the executive summary which you could read in a half an hour In the preface, I think and then from there selected, but it so it you can work with it But the idea is that ultimately that information will then be looked at, you know by the a TSDR group making specific documents for clinicians Presumably research has been conducted with specific questionnaires to do exposure evaluations. And are they readily available? Yeah, well we certainly have questionnaires in the field I can't I do know that a TSDR is working on developing new clinical guidance based on the report on they've they've shared that level of information with us in terms of Certainly lots of studies have been done that we could share information to the level of detail. We use what actually works best for clinicians That's very close to one of the recommend. We part of the recommendations. We didn't go over today was we reviewed the the old clinical guidance and as a committee provided suggestions And one of the things we I believe one that we asked was to evaluate How do we what the intake should be and what should the questions be and to evaluate that process? So I don't know where a TSDR is with that But that's a good point and we can always share that type of information. That's where we should be keeping our eyes peeled Yeah, look look to a TSDR. Yeah, exactly This was really a great presentation and we really appreciate your hanging in coming here to tell us about the publication, you know and Clinicians out there. How how will they know if their community has high level? You know Or if the fish are bad Is there a source thing go to can they rely on the public health departments or not? So now quickly punted back to Ken this so a couple things It's still a little bit of the Wild West every state's different and so part of it is is Again an awareness of with your local health departments and local DEC's and local water utilities, New York State mandated a Year and a half ago that all water utilities measure some PFAS and in Michigan is a little ahead in that regard as well and As well as a few other states most states aren't testing routinely EPA right now is under a 60-day rule discussion That would mandate measurement of PFAS six of them In the water systems and so those would be the typical annual reports that would come out through the water utility Similarly do local DOH's and DEC's would have the water or the wild game advisories for the area To do that New York State has an environmental public health tracking So if your state is part of that that's funded through CDC They are uploading that information as they get it. So it will depend on very much unfortunately, and this is why we have a problem on many levels by the state There's a report from the Environmental Council of the states 2020 processes and considerations for setting state PFAS standards that has very good background on What each state does and there is a huge heterogeneity with some states that have nothing and others that are very particular but it Maybe indirectly provides a lot of information about what the resources are Yeah, if you could send that to Ken and then we could maybe attach it to the presentation Thank you very informative, sorry, I stepped out for a few minutes, so sorry if you already answered this question So I know of only one one lab that does the testing How readily is the testing available and as for like a non-occupational Exposure testing, you know like a primary care physician Again how readily is the testing available and then the cost and the your general health insurance. Is there any coverage? Thank you Yeah, so this is a really important practical consideration I can just tell you from the experience I've had with our Group of patients We don't we have found that you know, if it's not available Locally, you know finding a distant lab somewhere a highly specialized lab is pretty problematic in most circumstances So but it has come that some of the major national commercial labs like lab core now offers PFAS testing NMS they were here and featuring their their new PFAS testing offering so so it is growing and I think you'll continue to see others will join in As the protocols get established and of course just like with PCB testing and dioxin testing the assay and and the Approach are going to be important because you want to be able to compare apples to apples when you have different labs involved in terms of The insurance issue, you know, that's ultimately going to have to be a policy determination that comes for now and thus far we've had consistent success using generalized billing codes ICD 10 codes to capture environmental exposures without specifying So we've had some good success in keeping those covered with with insurance. But of course it tends to be insurance That's a little better quality I haven't had to try with with you know Medicare for example, so I don't know how that would go But I think that's going to be one of those intersections of policy and and public health and and kind of the politics But like I said in the small sample at least in New York, I've had some success in getting it through Sure, thank you All right, thank you, thank you all so much for sticking out and I hope you had a great conference and safe

clinical guidelines

PFAS chemicals

National Academy of Sciences

PFAS exposures

health effects

exposure assessment

occupational exposure

drinking water filtration

PFAS in fish and wildlife

testing for elevated exposure

current guidelines