Bob started his clinical career as a family practice physician assistant with the Johns Hopkins Hospital Network, and we've had the tremendous fortune of bringing him on board to work with us 10 years ago. And in those 10 years, he has truly cultivated an expertise in developing clinical practice guidance for the Department of Defense for novel military hazards and how we manage personnel working with those hazards. And so what Scott is going to do today is showcase a methodology that is adopted and how we in the DoD develop medical surveillance practice guidance for hazardous agents, in this case chemical compounds for which workers are exposed to where there's no precedence established in the literature. And so it's remarkable that you lead this for us at the Defense Centers for Public Health. He is a fellow of the American Academy of Physician Assistants. He's also an Army veteran, having served nine years, including one combat tour in support of Operation Iraqi Freedom. Without further ado, it really gives me tremendous pride to introduce this young professional, Mr. Scott Monks. Thank you. Thank you, Dr. Mirza. Well, thank you for joining me this morning. Not too early in the morning, I guess. I think a couple of the ones that are going on the rest of the week are a little earlier, but 930 is not too bad. So again, welcome to AOHC. Thank you for having me. So today, again, we're going to kind of talk about something that occurred, I guess it's been probably close to 10 years ago was when it started. We've had different cases since then, but this one kind of stood out just because of kind of how things occurred at the time. So basically what we'll do is we'll go ahead and kind of first start talking about the methodology about how to go about developing a medical surveillance exam for a hazard that there's not an OSHA standard for or that is new to the military civilian, whatever it tends to be. The outline basically is these three points. We'll go ahead and kind of talk about the occupational health clinics role. Again, there's multiple professionals that get involved in something like this, and we'll kind of touch on all of what has to happen in that regard. We'll talk about the five steps that are required to develop a medical surveillance exam, and then we'll talk about the case study with IMX 101. So anytime you're trying to do surveillance in a workplace or for a workplace hazard where there isn't any, there's no guidelines, there's no OSHA standard, the general duty clause is going to be what applies. You've got to find a way to protect your workers using the hierarchy controls, right? You have to eliminate the hazard if that's possible or substitute if it's a chemical hazard, you have to substitute or at least look for a substitution if that's possible. You go through your engineering, your administrative, and your PPE. Medical surveillance really is kind of the second tier of defense per se that would allow below all these other interventions, you want to try to stop it at the source first before you get all the way down to medical surveillance. The goal obviously is trying to never have that hazard reach the worker, again, if that's at all possible. Again, a little bit more of the verbiage from the actual clause, provisions are used in inspections and only where there's no specific standard applicable to the particular hazard involved. Moving on here. In the case of IMX, and again, we'll talk about what IMX is shortly, again, there was no OSHA standard regarding controls or surveillance or anything in the beginning when they were doing the development. They had defense contractors that were developing it. There was limited toxicology info on the constituents of IMX. There had been some tox clearance studies in order for them to get going to do the research in order to come up with the formula, but they hadn't really done a really thorough job of doing the tox, the health risk assessments and tox clearance studies that were needed. Again, in order to get going through the acquisitions process, you have to have a certain level of toxicologic information, but it's typically not very in depth. In the DOD, we have certain documents, we have instructions, we have guidance manuals, and then we have service level bulletins and guidance documents, again, that kind of help steer us in a direction where we should go when we're conducting certain types of medical surveillance. Again, you have the instructions, which typically say you have to have a program. Then you have things like manuals that will actually give you the specifics about how to go about conducting medical qualification exams, medical surveillance exams, and so forth. Then the services, the Air Force, Navy, Army, a lot of times will have things like technical bulletins that will give a little bit more granularity into specific types of exams. For this particular case, one of the technical bulletins that the Army had was one on surveillance, both with IH surveillance safety and OH regarding TNT, which again, we'll talk about a little bit here in a minute, TNT obviously being one of the older explosives available to the military. Now, again, it's easy when you have manuals that tell you what to do, but what do you do when there are no instructions? As we'll see with the case study here later on, you've got to have sort of a regimented way to kind of systematically go through and make sure you're not missing any of these five steps. These are the steps that are required to develop a medical surveillance exam protocol for something that's new or that's never been sort of seen or in any great detail. The first one, again, is conduct a thorough literature search. Again, that's kind of the easiest, most immediate thing that somebody can do. Basically, there tend to be a lot of resources where you can get this information. It's not as easy sometimes if it's a brand new hazard to actually find anything on the topic that you're looking for. The ABT, TeraORS, sometimes you can find an SDS on a topic on something that's relatively new, but not always. Looking through your clinical outcome studies that are in JAMA, in the ACOM, in JOEM sometimes appear, New England Journal of Medicine and so forth, Lancet, things like that. Sometimes you can obtain actual research and development studies and the data. A lot of the times the developers, the defense contractors that are the ones making these new chemicals may have some data that is available that may give some indications about health effects. Then again, peer-reviewed studies. Every now and then you'll see something maybe in popular science or something like that. Again, not particularly scientific reliable necessarily, but it might be something that alerts you that there's something out there that may assist in your kind of trying to obtain some of that health hazard information. The second step, again, this is kind of the point where you can't really do it on your own. You can't do this, especially if you're a physician, PA, nurse practitioner in a clinic. Again, not going to have a ton of time to do a lot of this. You're going to need some help. Again, it's going to be easier for those of us in the DOD, but it's also going to be easier for those of us that have academic colleges and universities nearby that can maybe help with research. There's typically funding involved and things of that nature. Again, getting toxicology researchers, IH and safety professionals, those are all those resources. That's kind of where you wind up pulling all those resources in. We're lucky in the DOD. We have DOD, DHA. We have the service level assets that can help us with a lot of this stuff. That, again, makes it a little bit easier for us on our end. Again, the civilian world does have those university assets and research assets. Step three, again, consulting with your installation or your medical facility, your IH folks, your safety folks. Again, is the hazard actually being contained at that first tier? Are there proper controls in place? Is the PPE that has been selected appropriate? We did have a question about some of that with our case study, whether or not they were overdoing it. The tendency tends to be to overdo it, which is a good thing, but sometimes it's not always necessary to do it that way. Again, it's developing the controls that will, again, protect the worker in that first tier in the hierarchy. Then, also being aware of any countermeasures. If the PPE has issues with heat or cold or some sort of other physical hazard, you don't want to have something that's protective, but also creating another hazard. That's step three. Step four, this is the one that's probably the most difficult and probably takes the longest, is actually developing an OEL or a biological exposure index, if it can even happen. Again, the PEL is an ocean mandate exposure limit. Again, that's probably the best case scenario, but, again, we're talking long periods of time to even accomplish something like that. Again, with the DOD, a lot of what our toxicology folks will do is develop an occupational exposure level. Again, there's protocols that they use to do that. Some of the other exposure limits are listed here. Again, you have ACGIH that has theirs. You have the workplace environmental exposure levels. There are other avenues to develop exposure limits to, again, give you an idea about whether or not there is an actual exposure in the workplace or not. Again, with biological exposure indices, again, their guidance values for something that can be tested biologically, and, again, it's looked at, again, as a biomarker. There are not many of those, but there are some. And you could also say that, again, lab testing that is directed towards that specific hazard that's known can also be biomarkers, but if it's direct testing of the actual chemical in the body itself, and then developing a limit of high, low, or positive, negative, depending on how it comes about, is what we're looking to do ultimately, but, again, not as easy as it sounds. And then the final step, once you have all of this information, you're looking to develop sort of a comprehensive protection program, as it were. You're looking at the industrial hygiene protective protocol. You're looking at the medical surveillance protocol, and, again, today we're kind of focusing mainly on the medical surveillance part, but those other parts, again, are very, very important. You want to know, obviously, what organ systems are affected, what kind of screening tests, and sometimes we cross over into diagnostics versus screening, and that's always sort of a difficult thing to kind of separate. We have a lot of tests that we do to diagnose people with things, but screening sometimes is a little bit different. How frequently. Frequency is kind of another one. How often should we be evaluating these folks? Monthly? Yearly? You know, how often is it required? And, again, it kind of depends on what is determined by the research. There's an education piece, again, that health risk education, being able to explain why you're doing things with the person that's being examined. And, again, an impact to continued work. If you do have somebody that has been overexposed, what do you do with them? Do you have to sit them out? Do you have to monitor them with an alternate pathway? Again, there's a lot of considerations with that as well. Lastly, of course, again, as medical professionals, we tend to focus on the medicine and maybe not as focused on how much things cost, although that is a consideration usually for us. It's not the primary consideration. But that is something that people will ask, especially in military treatment facilities and in the civilian world as well. So now we're going to kind of transition into the actual case study. So we'll kind of go over a little bit of how things kind of went about. Part of the story happens before our organization. We were formerly Army Public Health Command. We're now DCPHA, Defense Centers of Public Health. So I'll probably talk about us interchangeably here. So, again, this story happens when we were associated with the Army. So we'll probably talk more about it from the Army perspective than anything. The case study is sort of an example of how important it is to have a very structured, regimented approach with dealing with these type of cases because it's sort of a tale of kind of how things get a little bit disjointed, and we start getting over our skis a little bit with what we need to do, and you have to kind of maybe take a look at what's going on and then, again, go through the appropriate steps before you can actually arrive at an appropriate decision. So a little bit about what insensitive munitions explosive is. There is more than one type of insensitive munitions explosive. We're talking specifically about the 101 formula. There's 104. There's one. There's illuminated IMX. There's different kinds. And then there are new, even today, there are new insensitive munitions that have different acronyms that are being developed. So, again, the defense contractors are always kind of looking, and the Army and the military in general's demand for these type of munitions, again, continues. So this is just a tale about one particular type. IMX 101's formula had three components. We'll kind of refer to them as DNAN, NTO, and NQ. So DNAN, again, was the primary constituent of the mixture that was looked to be the replacement for TNT. TNT has been around for decades. And that was where they were trying to substitute to create this new type of explosive, and we'll talk a little bit about why they wanted to do that here shortly. DNAN, just physically, it was kind of a yellowish crystalline solid. It kind of looked like peanut brittle, actually, when it was in a solid form, and then they would melt it down to do the mixture. It did actually have other applications. It was used in dyes, and it also had been in the past used as an insecticide before it kind of ventured into this explosive world. DNAN actually has a metabolite called DNP that back in the 30s was used as a weight loss drug. That's kind of its interesting background story. It was, again, it was shown to cause health effects and was subsequently taken off the market. But every now and then, throughout the last couple of decades, you would see similar compounds to DNP in sort of off-label, marketed outside of the medical world for weight loss. But that is kind of one of the aspects of this particular constituent of IMX that is interesting. Again, NTO was the other one that was being investigated to replace another explosive called RDX. RDX was primarily used in hand grenades, and TNT was used in mostly projectiles. It was also, again, a yellow crystalline solid. It didn't have any other uses other than an explosive. NQ has been around for a long time. It's actually a propellant, so that was, it was sort of a minor part of the mixture for IMX 101. Colorless had been used in biochemical studies over the years. It had some pesticide use, relatively benign compared to the other two chemicals that were being looked at. So this is kind of the brief history of why we even got into this situation in the first place with IMX. Again, TNT was being used in 155 artillery rounds, and amongst other things, but in particular 155 rounds. The Army, however, began to investigate probably, it was in like the early 2000s. They started looking for a new explosive material, again, that was a little bit more stable, less reactive, and the term they use is insensitive. So the example that the BAE systems and the contractors that were making this particular type of explosive would give is if you have a truckload of 155 rounds made with TNT in a war zone, going down the road, and decide that the truck gets shot with a small arms round, the whole truck blows up. It takes that little bit of energy to ignite the entire truck. There's also another instance with a Navy ship, I think it was the Forrestal, I can't remember, there was another incident where, again, there was somebody hit a pile of rounds in a Navy ship and the whole magazine exploded. So again, they were looking to reduce those hazards to service members. So BAE systems developed these explosives with DNAN, with NTO, to create IMX 101. There was a 104 version that has another substitute for the RDX-like component in it. So the same scenario, you have the same truck, now you have these IMX rounds for the 155 driving down the road, it gets shot in the side of the truck, and it hits those rounds, they don't explode. The only thing that creates the conditions for it to explode is when it is actually fired out of the weapon system. So again, it has a higher threshold for that to occur. So again, it's based on the desire for something safer and for it to explode when you want it to, basically. So the production of IMX 101 and the compounds that make the rounds once they're mixed started at Holston Army Ammunition Plant in 2011, so again, kind of early 2010s is when things started to get going. And again, through the acquisitions process, they had to have some knowledge of the toxicologic effects and things to kind of move it through the process. But again, the way acquisitions works is you don't have to have a full-blown evaluation of it. You just have to have enough to kind of have a general idea, possibly enough to make an SDS or to make other documents that kind of give you some information. So what was going on is a lot of these, there were other ammunition plants throughout the Army that were beginning to make these rounds as well. Some of them were owned by the government, some of them were all contractor. The one, again, Holston, I believe, was one of the contracted areas that as part of the contract, it was required that they collect medical surveillance data on the workers that were there while they were making the rounds. That created a dilemma with the folks on the ground. The Army has what's called the Joint Munitions Command, and the command has a surgeon that is responsible for all of the medical assets inside of those Army ammunition plants. So they were faced with a dilemma. Again, they had these new explosives, these new chemicals that they were dealing with. They didn't have a ton of information about what was going on with the toxicology and the health hazard effects that might be exposing workers to something that we had concerns about. So again, and the other part of it was we weren't 100% sure that they were actually exposed. Again, it kind of goes back to that hierarchy of controls. Were the IH controls good enough to even have it get to the level of the worker? Were they wearing appropriate PPE? Did they have certain engineering controls that kept them away from it? So again, a lot of this was kind of going on simultaneously as we were concerned about this medical surveillance piece. So if you're the medical, if you're the joint command surgeon, what do you do? Do you just go through and ask for expert opinion? Do you say, hey, we don't know enough about the health effects of this stuff. Should we maybe hold off production until we figure out what's going on here? Which again is likely not going to make a contractor very happy. Do we just swag it? Do we give it a best guess? None of those are really great ways to handle it. So, and again, we did have some toxicologic studies which ultimately began the process of informing us what the medical surveillance exam should look like. So what I'm going to do is I'm going to kind of go through the five steps that you use to develop a medical surveillance exam protocol. But the way the story goes, things didn't always happen kind of in the same order with the case that we're talking about. And a lot of it happened simultaneously. That is kind of the underlying truth about all this is a lot of these things happen in parallel. They happen at the same time. So you'll discover something ahead of maybe another step along the way. So we'll kind of talk about it and kind of try to keep the timeline as linear as possible. So again, using that first step of conducting a thorough literature search, again, it started with the JMC surgeon. Then APHC folks kind of came in a little bit later to kind of look and see what had already occurred and then make adjustments as needed. So the folks at the clinics and at the command levels started to kind of look through the literature to see what was there. They were looking to see if anything in the private sector had occurred. They did look to BAE and some of these defense contractors that were the ones making these chemicals. There had been some studies at Letterman, which I don't believe is around anymore, and where they had looked at things like NQ and some of the older chemicals that was in this mixture. And again, you start looking through, they look through medical textbooks. We did have the TB med that talks about TNT. So, and again, that was kind of at, that was actually published at the beginning of the manufacturing of all this. So TNT and explosive medical surveillance was kind of the hot topic back in that era anyway. So we had some of these documents that we could kind of refer and draw parallels to what they were developing that was new. And this is sort of a graph that kind of shows what the landscape looked like at the beginning of when they were trying to figure out that first iteration of medical surveillance and what it needed to entail. It wasn't a lot. Again, the first, there's first three green blocks there for DNA and NTO and NQ and the acute oral studies. Those were the ones that were from the initial toxicology studies that were done to kind of get through that initial acquisitions process. Part of that was also the dermal. There were dermal studies that were done as well. NQ had a little bit more, again, from the work they had done at Letterman and they had done previously, just simply because it was an older chemical and it was something that we had more information on. All the areas in yellows were basically the holes. That's where the gaps existed in our knowledge. So once we kind of figured out what we knew and what we didn't know, we obviously need to fill those knowledge gaps. So we needed subchronic health effects studies. We needed chronic ones. And again, these studies take months to do and there's time involved. They wanted inhalation effects, ocular immunogenicity, carcinogenicity, and then again, some more dermal information. So again, we needed a lot more information to really make an improved version of what was being originally put out as the medical surveillance that they were looking to do. So again, that's kind of one line that was occurring kind of separate from the other lanes that were going on as well. So using step two, solicit help with the scientific community. Again, this was kind of happening in parallel. We knew what we had study-wise, we knew what we didn't have and we need to obtain. So the Army Public Health Command has its own toxicology directorate that can actually do some of these subchronic studies, dermal studies, studies for mutagens and cancers and things of that nature. So that is a luxury, obviously, that we have in the DoD that we can refer back to a research arm that we have inherently. Again, in the civilian world, again, you're going to have to tap into the academia and universities to kind of get this type of support. So they used in silico models, they used live animal models and they basically developed the test protocol and then they were able to actually find a couple of other research studies from outside of the country with the DRDC from Canada had done some initial work on some of these chemicals as well. So they were in the process of filling the gaps, but again, those things take time. However, by the time they got to the end of all the studies this is kind of where we wound up. So kind of down in the bottom right here is the initial graph. And we wound up with most, if not all of the studies that we needed. They were able to complete subchronic, chronic inhalation studies, ocular and all the mutagen and carcinogen studies. So we, and it took them, again, the subchronics and take about two, I think they're about two weeks and the chronics take about 90 days if I remember right. So again, it was the good part of a half a year to maybe a full year to get a lot of these studies completed but once we had it, we now were armed with all of this information. They only did one acute study with IMX 101 as a mixture. They did most of their studies as separate components. The one study that they did do with IMX 101 didn't really change what they found in those separate studies. It didn't make it worse for health effects or better for, it didn't really kind of change a whole lot. And we'll kind of talk about the specifics about that here shortly as well. So now we're armed with all this information to kind of help us make better decisions about how to develop the medical surveillance exam. Again, a third pillar of what was going on too was we had engaged our group at APHC at the time, our industrial hygiene and safety folks were also looking at the industrial hygiene practices at the contracted sites, at the government sites and kind of making sure that all the engineering controls, PPE and so forth were correct and working properly. So they looked at, again, they looked at engineering controls. They did wipe and air sampling. They did a very, very thorough job. We focused a lot on PPE. The nature of the work for the workers making these rounds did require them to come in contact, unfortunately, and they did have some engineering controls, but PPE was a pretty big topic. A lot of times what was happening was they would wear cotton coveralls was the PPE of choice in the TNT sites, which was adequate enough that they would have other protections, obviously. But when we were in that kind of unknown phase with IMX, they were having them wear Tyvek suits, which created problems with concerns about heat exposure. The MO plants, in order for them to mix some of these chemicals properly, the MO plants have to be in the mid 80s temperature wise. So they were wearing Tyvek suits and sweating, and there was concerns about having heat injury. So again, they were working through all those, whether or not Tyvek was appropriate, was cotton coveralls appropriate, respiratory protection, the whole eye protection, the whole thing. So the APHC's IH directorate did do their evaluations and did their own reports. And then they kind of made their recommendations on what was appropriate, again, as along the same lines as we were doing with our medical surveillance evaluations. So step four, again, kind of getting to that occupational exposure limit. There really wasn't any ability to develop a biological exposure index. However, they were able to develop OELs for all three of the constituents. And they published a report where they listed all of those OELs. And those were the OELs that the IH folks would use to determine exposure, no exposure, and then kind of make the appropriate changes there. It was asked the contracted sites, it was asked that the work that APHC had done at the time be sort of reevaluated. I guess double-checked maybe is probably a more appropriate way to describe it. So the Occupational Alliance for Risk Sciences did their own evaluation of APHC's work. They did their own kind of look into it. And they developed, again, their version of the OEL called the Workplace Environmental Exposure Levels, the WIELs. They developed WIELs for all three, for DNA and NTO and NQ, and basically confirmed the work that APHC had done. So that was kind of a pat on the back for them. We knew they'd do good work, and they just needed to prove it to somebody else. So that was good for us. And now we get to kind of the final step here. So the final step in the process is developing that medical surveillance exam protocol. So again, we kind of go back to the dilemma that the JMC surgeon at the time had. They had limited information. We were working on getting new information, but we were still not quite there yet. The APHC studies weren't available. The frequency of exam question was still kind of hanging out there. So the surgeon at the time tended to want to be extra cautious, just because there's so much uncertainty. And again, in that situation, being overcautious isn't exactly the worst thing in the world, really. You want to make sure that you can do anything you can to protect the workers in the area that's of your universe, right? So they created a very thorough protocol that included a lot of things that was basically born out of the uncertainty. So what happened was is there was concern that there was too much being done. They were having them come in very frequently at first, because, again, just mainly because of the uncertainty. And so APHC, again, at the time, we were consulted to come in, take a look, kind of get an overview of what was going on. And then if there were any adjustments that needed to be made at the time, we would come in and make the adjustments. We were given the data that was collected by the contractors to look at all of the lab work that was being done on these workers. We looked at the, they had a health hazard, they had a questionnaire that they would do. And they were doing, again, they were doing spirometry and they were doing a lot of testing. So this next slide, hopefully you can see it fairly well. This was the list. This was the original IMX 101 medical surveillance lab and diagnostic testing guidelines that was put out initially by the JMC surgeon. And it contained a lot of stuff. It had a lot of things. They were concerned, again, they had concerns about evaluating the liver and the thyroid. There was concerns initially, and again, from the studies about reproductive health. And again, they pretty much had a lot of these tests that were being done. Some of them were being done monthly. Some of them were being done a little less frequently. So, and again, one of them, they were offering to do sperm counts on some of the male workers. It was mostly male workers. Looking through the data, I don't remember actually seeing any female workers at the one plant that we had data for, but there were some tests in that panel. And again, it was just a lot of testing, mainly due to a lot of uncertainty. So, things like EKGs, X-rays, questionnaires, PFTs. So, I mean, some of this stuff obviously is appropriate. And then some of it, again, as we'll see, we'll kind of talk about what we found out as we got more information. So that's the list. Again, kind of going back to what we found out about DNAN, ANTIO, NQ as we developed all of these tests was DNAN, and one of the big questions was how close to TNT were any of these chemicals? Through the research, we found out that DNAN was very similar to TNT in its health effects, the heme system. There was a concern with hemolytic anemia with TNT. It also kind of showed up in the test with DNAN. Again, they looked at that DNP metabolite component with DNP, and one of the reasons why it was pulled off the market was there was concern with liver and renal toxicity. There was some reproductive concerns as well. One of the big things that also got it pulled off the market when it was used as a weight loss drug in the 30s was it would increase heart rate. People would become diaphoretic, and they would have sort of this hypermetabolic condition that would occur. So again, they found that in the studies, mainly the lab animal studies that were conducted. NTO, they did find that it did directly affect the tissues of spermatogenesis. So there were some decreased testes sizes in the rats, and then again, there was a little bit of hepatic damage that they did find as well. We're talking in for both of these in typically high doses, higher doses than a worker would expect to be exposed to in a workplace. So it's the high level of exposure is kind of the key that they were finding. So at the lower exposure levels, there wasn't really much change. Same thing with NQ. NQ again, primarily a dermal irritant. There was one study that showed a possible diuretic effect, but otherwise relatively benign. So it didn't really, there wasn't a ton of concern for this as a health hazard, at least for humans. They did do that one study for IMX. And again, it showed the same things that the separate tests showed, but not in any greater effect. So there was splenomegaly and the hematologic changes, but again, they were equal to what they were finding with just DNAN alone. Same thing with the lab rats and the decreased testes sizes. Again, same thing with NTO, not really a big change. There was one aspect of that test where there was slightly enhanced dermal absorption. They did the study on cadaver skin, so they didn't put a lot of weight on that particular result. So they didn't think the mixture of IMX increased the rate of dermal exposure. So once we became armed with all of this toxin formation and admittedly it's in silico testing, it's rat testing, trying to extrapolate that to humans, that's part of it, but we were able to fairly quickly eliminate a couple of the initial lab tests that we were doing in that first iteration of the medical surveillance exam. So again, there was no evidence that lipid levels were at all affected by any of the three chemicals. So that's one we kind of took out right away. Also the same thing with the thyroid. There were no evidence, there was not evidence that DNAN and NTO had any thyroid function or endocrine disruptors, anything of that nature. When it came to the endocrine and sex hormone evaluation, so NTO and DNAN, they did it for both. There's no estrogenic or anti-androgenic endocrine changes that were seen. It didn't seem to affect the endocrine pathways in that regard as well. Again, it was more of a direct effect on the tissues for those organ systems, and again, it was primarily at high doses, not expected doses in an occupational setting. So and again, so all of the sex hormone testing that was recommended, we didn't feel was going to get us anywhere, you know, useful, you know, when it's the old adage with, you know, don't do a test that you don't have anything, you know, you don't have anything to kind of deal with that abnormal result. Again, as far as EKGs and x-rays and other diagnostic tests, there was no evidence that it affected anything, you know, cardiovascularly, except, again, there were the hematologic components that we did have to be aware of, but doing EKGs and chest x-rays, again, weren't exactly, there wasn't a high specificity or sensitivity for doing those tests on these workers at this time, and again, looking at the TNT protocol for medical surveillance, there wasn't, you know, there were a lot of parallels that we could glean from what was recommended for that, for this new chemical as well. So what it wound up looking is, is we wound up taking a lot of the stuff out, simply because there was no evidence that there was any effects, nothing in the workers' lab data, nothing in the tox studies, nothing in the literature that suggested anything with the areas shaded in red there. So the stuff that's not shaded, we did feel needed to stay. So we did still have concerns about the liver, the hematopoietic system, things of that nature. So what we wound up keeping, and again, and why we kept them were listed here. So for DNAN to evaluate that DNAN and DMP metabolite piece, we wanted to make sure, and again, there wasn't any situation with anemia occurring. So we included this, we kept the CBC, we added a haptoglobin and LDH. We also wanted to know of the G6PD status of folks as well. And then if needed, or if there was, you know, an abnormality starting to develop, you know, there was, part of it was checking out retic counts and blood smears as sort of a confirmatory. We, again, we wanted to keep an eye on that hypermetabolic effect due to the DMP component. So we left the complete metabolic panel, which has all of your electrolytes, and it has your liver function studies in it. Your analysis, again, for the renal effects, and then again, hepatic toxicity. We also added the GGT. GGT is a little bit more of a direct indicator whether or not there is some sort of liver abnormality or bile duct abnormality. NTO, again, similar crossover. We were doing, we were already watching for hepatic toxicity. So we were, again, we kept the CMP. Positive effects, we kind of felt that using a questionnaire for fertility was a little bit more appropriate than doing some of these other tests that were being suggested. So we did develop a questionnaire and a protocol for any abnormalities that came about from positive on that. With NQ, again, you know, just, it mainly was based on questionnaire, and then we were still kind of watching for any kind of diuretic effect using the urinalysis and the CMP. So the final kind of version of what we came up with for the second iteration, I guess, of the medical surveillance exam was we had a baseline exam, which included the elements here. We did a 90-day, it was really more of a 90 to 120-day recheck after that baseline exam, and again, that was for that red blood cell component, the, you know, life cycle of red blood cells, about 90 to 120 days. So we wanted to make sure after they started working with any of the components that they would get that kind of 90 to 120-day check just to kind of see if there was any initial change based on that first red blood cell cycle. And then, if everything kind of clears through there and there's no indication that there's any kind of health effects through questionnaires, laboratory, things of that nature, we were going to a semiannual exam, and again, this was kind of still sort of in the beginning, so we were being pretty cautious still. So every six months, you know, you get through two red blood cell cycles roughly, you're still kind of watching, you know, haptoglobin and LDH to make sure there's no hemolytic anemia situation. They're not symptomatic. If they became symptomatic, we'd have them, you know, go for an acute visit, things of that nature. The optional test, again, if we were starting to see abnormalities, then we could go into looking a little further with retic counts and peripheral smears and things of that nature. And then we were doing, they were in a respiratory protection program, so we were doing spirometry on them and the IH folks, like I say, were handling those with fit testing and things like that. And then the termination exam, we were recommending a termination exam. Once they stopped working with IMX, they would get a termination exam as well. So that's pretty much kind of the conclusion, again, it's sort of a case of where, you know, a lot of things are happening kind of in parallel and, you know, making decisions that sort of are overly protective isn't always the worst thing in the world initially, but you've got to kind of really have a full picture of what you're doing in order to make good decisions about what a final medical surveillance exam protocol should look like. So the take-home message, I guess, with this case is, you know, before work begins with any new hazard, you really want to, you know, collaborate, you know, with your IH partners, OAH, safety personnel, you've all got to be kind of pulling on the rope in the same direction, right? Having that formal procedure for developing a new surveillance exam is 100% necessary just because if you're doing things in disparate directions, it's, you know, you're going to have sort of results that are not going to kind of be what you want. You need every new hazard should be thoroughly checked. When there's evidence lacking, reaching out into the community, if it's DOD, you know, the research assets with the DOD, if it's civilian, your academic universities should be able to assist. Again, using an evidence-based approach to developing medical surveillance exams, using that good medical science, and keeping it sort of focused on the occupationally related health issues. It gets tough when you're trying to separate out non-occupational things with some of this stuff sometimes. So trying to, as best you can, focus on the occupational portion of the exam is very important. And then, obviously, periodic review. If something changes, new studies come out, that sort of alter or adjust what you need to do with the exam, periodic review is always a good idea. These are the resources. They should be in the slides that you have afterwards, and again, a lot of these reports were produced by the APHC. Dr. Merza and myself wrote the, I guess, the white paper for what we recommended to the joint munitions surgeon. So what our role was, basically, was to write a recommendation to joint munitions on what they should do for their medical surveillance exam, and then it was up to them to implement the actual exam. And they are, we had another situation where there's a new explosive that they're looking at at one of the arsenals, and they reached back to us, again, within the last year, to ask, like, hey, can we use the IMX 101 protocol for this new explosive, and again, you kind of have to go through all these steps and kind of see where the evidence lies. So they are still using the protocol as it's written, and to my knowledge, there haven't been any health issues. I think the IH, the controls protocols are pretty good, and we're not, we're luckily and thankfully not having any health issues come up with folks. So that's what it's all about. That's it for me. Thank you for attending. Does anybody have any questions? All right. Thank you. That was very interesting. I'm glad we had the presentation. I don't see the thing about surveillance for 10 or 20, 30 years from now for our considerations. So some plan to follow on it for decades to see if there's a spike, to get that cancer. Right. So, and I can actually... Can you repeat your question please? I'm up here and the mic is holding this to be recorded. Oh, is there? Oh. So the question had to do with, is there any plan to look at the long-term health effects specifically in relation to the carcinogenic effects, mutagenic effects? Our toxicology folks at now the defense centers of public health are the ones that kind of go into that. They are the ones that sort of set the protocols of when to continue. I do believe at the time, the gentleman that was in charge of doing all those who's just retired, I guess, Mark Johnson just retired a couple months ago. There is a plan for that. We are... So we did this work. It's been about 10-ish years. This was like one of the first projects that I got started starting to work for the army. So it's been about 10, 11 years. So they will, and again, they will start kind of doing that. So yes, there is a plan for that, but they get overwhelmed with a lot of lab study requests. So I think that it is in their long-term plan, but I'm not privy to the plan. It's not part of the directorate that I belong to. Yes. Yeah. Appreciate the presentation. Very, very informative. My question is, you're describing a lot of work. So, as I understand what they, again, this is, I guess, sort of opinion, is they were very interested in getting this project moving as quickly as possible, right? So they, you know, I think the tendency is to go with the, you know, they can get started with a certain level of information, and if they get the go-ahead and it clears all of the hurdles, then they'll go forward. This was something, again, at that time, it was a very high interest, you know, in the military. They wanted to get started as quickly as possible, but again, it was really the people in the OHIH safety community that said, hey, wait, you know, we understand, you know, you've cleared the acquisitions hurdles, however, you know, we really need to slow things down. We were the ones that actually put the brakes on a little bit to try to slow things up. What actually wound up happening is we wound up, you know, kind of, again, we kind of were doing it, they were starting to mix and produce as we were trying to catch up, you know, and again, it was, that's kind of, again, that's why we overdid, you know, some of it just because there was so much uncertainty. It's really, it's not the best way to do things from a medical standpoint, quite frankly, but that is kind of the way it happened and it likely had to do with forces outside of the medical community that caused that. So however, you know, I think we did a fairly admirable job of catching up as quickly as, you know, studies like that take and, you know, if you're going to do it right over, do it at first and then back off, that creates other problems, worker, you know, from the worker standpoint, you know, hey, I was getting all these labs every month and now I'm not getting these labs. What's going on? You know, that's, you heard those questions and again, you've got to have a really, really good, you know, education campaign and, you know, health risk communication campaign to kind of do it that way, but you'd rather not have to do it that way, clearly. Right. The caveat is the acquisition folks. are available to us after all. Yeah. Right. So just, I guess for the recording portion of the session, as far as the health hazard assessment, the HHA evaluation portion, that is, it's more focused on the effect to the end user, the warfighter in this case, the service member. So we were dealing more with the folks that were manufacturing the actual explosive material. So before it got to the end point. So that's, yeah, there was a difference in what those evaluations do versus what was kind of happening in this case. Yes, sorry. Quick question, when you're drawing, you're doing all these labs, are you doing any? The kind of follow on is, are there any IRB issues with this kind of data collection? So no, that was all, all of those things were handled. It was, so the, all the data that we received. So the question basically was, you know, was there, I guess the second part of this question was, were there any IRB issues with data collection from the workers? Again, these were contracted workers. This is part of the contract. The workers are aware, you know, that this is going on. So, and again, we're, they're not, we were not doing the evaluation of their lab data for research. It wasn't a research situation. So no, there wasn't any IRB considerations with that. And the first part of your question? Like, are you doing, so you're drawing on these labs. Yeah. If it changed, are you doing blood levels of the actual substance? Of the actual, yeah. I was gonna say, if there's a CBC change, but they have zero, zero, commonly there's zero of the substance in their blood, then that CBC change would probably grow something. Right. So are you trying to correlate these labs, or are you just getting labs, and it's a change, but. So, yeah, so the question again was, you know, if we're drawing labs, and were we doing anything to kind of correlate it with the exposure to the specific chemicals? So they were not drawing to find the chemical. I don't think that they had the ability. They couldn't, you know, again, they were so new, we weren't able to kind of actually find it in an assay that way. So they weren't doing that directly. It was really, if there were abnormalities found, and again, in the data we had, there weren't any, which again, is a good thing. But if they were finding anything, they would actually go, they'd go more into a, they would, into a questionnaire type situation. You know, what kind of, how often were you working with the chemicals? How, you know, what was the IH situation? Were you wearing your PPE? Were you taking, you know, were you dining and doffing things improperly? They were kind of going into those and trying to, again, bring it back. Is this sort of an occupational? Yeah, it was, yeah, correct. Yeah, yep. I think we have one more question. So this is kind of a two-part one, but they're related to each other. So the first part of this is you've done a lot of work here. Can you kind of summarize that for a minute into kind of an after-action part, lessons learned about when would be the proper timing? The second part goes in, when you look at that, have you thought about maybe the acquisitions pipeline at the wrong time? They're gonna be addressing this, and then it should have been done as a key performance parameter that helped risk assessment, the ICD, the initial capabilities document, or a material solution before acquisition? So the first question is, has there been like an after-action report or a report based on what we all did? So yes, we did, we, again, we produced a white paper, again, that described all of the findings and then gave recommendations for the future. We do remain in contact with those, again, you're talking about government. What I mean by that is, it's not your findings of your study, but basically saying that this should be done before the acquisition process begins, and that's not a white paper on what the metabolic effects are, but that this should be done before acquisition. The second part is, instead of having... Right. So I am not, again, I personally am not aware of that level of after action. That, again, we, our job was mainly focusing just on that. Now we did feed information up the chain of command, so I don't know if we have anything that we gave to acquisitions. It's likely not. We have done, we have addressed that this was an issue in the beginning with our higher headquarters that, hey, this is, you know, this is not the way we should be doing things. I don't know of any formal, there were brief, we did do briefings about this. I don't think there is any formal, like, paper that summarizes all of it. It was more in a briefing format. I'm aware of that, yeah, I don't know. I'd have to get back to you on that one. Any more questions? All right. Oh, go ahead. One more question, sorry. So I'm wondering, are there any plans to utilize medical surveillance to know where these... So if they're being used by the warfighter in a war zone, again, this focused mainly on folks manufacturing the ammunition. But it's now unfolding, and I'm wondering if it makes sense to go ahead and begin planning for surveillance in these areas. Thank you very much.

medical surveillance

guidance

workers

military hazards

chemical compounds

occupational exposure limits

industrial hygiene experts

health effects

collaboration

evidence-based approaches