Well, thank you very much for the opportunity to be here. I'm very honored to be here. Well, I'm feeling pretty welcome because I think it's going to rain here and I'm coming from Seattle, so it's kind of a welcome. Welcome to Texas. As Chris mentioned, aviation has been a big part of my family. Just a couple of things here. This is my grandfather flying a plane back in the 1940s. My dad, myself. There's me getting excited about aviation. My mom next to our beaver that we owned for a while. My dad ended up being a bush pilot in Alaska, so I got a chance to sit. There we go. And then my youngest brother, I soloed when I was 16. And then my young brother is a F-35, F-16 pilot in the Air Force. So I just love things that fly. In terms of just disclosures here, I am a professional toxicologist. I've been doing a lot of work on this. I think it's now 800 different projects. It could even be higher than that where I look at human exposure to chemical agents and biological agents. A couple of things that are important here is that I provided services to manufacturers of aircraft, airlines, global airlines and that to the military. I was part of the medical team on the F-18, what we call physiologic episodes. And then also I've been invited speaker to aviation type of things. So what do I want to cover today? I want to talk about fume events. That's one word. Another one is called air cabin quality events. Another one is odor events. And these are events that we'll talk a little bit about. But if you've flown on a commercial aircraft or even a military aircraft, every once in a while, you get this whiff of this odor. And that's what we're going to talk about. I also want to talk about the fundamentals of toxicology. If I get anything accomplished today, if you know a couple of key things about toxicology and you spread the word, I will feel like I have done a great job. And I'll tell you what those things are very shortly. We'll talk about these cabin air quality events. We'll talk about the chemicals of interest, the health impacts, conclusions. And if they've got some time, we'll do some questions as well. So fundamentals of toxicology. As an aerospace toxicologist, I follow the standard practice of my profession. That may not necessarily be known to everyone, but there's a very standard process that we are recognized globally for doing this work. And we follow those. We follow how that's done. And so you can count on it being scientific. You can count on it being reproducible. You can count on it being transparent. And then you can count on in terms of understanding what the outcome is from that. We access all scientific data and we use the best. So when it comes to cabin air quality, this stuff, this information has been around for maybe 30, 40, 50, 60 years, depending on what we're looking at. And we then take the best studies that make the most sense for the issues that we're going to be dealing with. And then we also consider the unique aspects of flying. You have different atmosphere, you have different oxygen tension, you have humidity and air pressures that are really different that some present kind of a physiologic challenge to the toxicology role. So one of the simple things that I want to have you remember on the toxicology is health risk is related to the hazard times exposure. I'm going to go through what hazard and exposure is here. But the risk, the health risk is related to those two concepts. So the hazard is about the chemical. And the exposure is about how much, how long. And just to give illustrate a point is if you could have the most toxic agent around, and if you have zero exposure, the health risk is zero. Does that make sense? But that's a really important piece because we can detect things at minute levels. Or if you put them in a container, you put plutonium in a lead container, while it is radioactive, it is also poison at certain doses. As long as it's in that container and it doesn't get out, there's no human health risk from that perspective. The aspect of an aircraft, though, is really important in terms of the exposure. When you're flying on a plane, when you came here, for example, as I did yesterday, what's happening in terminal aircraft, and this is occurring in other aircraft as well, it's modified a little bit, is that you have air coming into the engines at the front end of the engine. It's compressed. That compressed air then goes through ports and those ports then go through air conditioning units and then into the aircraft. So when you turn that little gasper on your head, if you need a little more air while you're sitting on a plane, it's coming from the outside air through this system in order to come. Then it's distributed throughout the aircraft. Depending on the model and the make of the aircraft, there's a little bit of change, whether the cockpit or the flight deck actually gets the same or a little bit less than the rest of the aircraft. But essentially, it gets distributed throughout this. There's no more air in the back of the cabin than there is in the front of the cabin for almost all aircraft. The last piece of this is that air is dumped off the back. So what happens, and this is important, cabin air is fully renewed every three to five minutes. That's a lot of ventilation going through that plane. And that's important from an exposure standpoint, right? Because if you have air exchanged over three to five minutes complete, the amount of exposure will go down depending on what's happening inside the aircraft. So that's a real key piece that we'll be looking at as well. All right, this is, yeah. Can you go back to that type of ventilation? Yeah. The way I look at this, so if there is some exposure in C2, because the air is circulating through the whole cabin, the person sitting in the very back is going to have the same exposure as the person sitting in the front. If it's coming off the engine, right, as opposed to someone that has COVID that's sitting in C2, that's a different story. So I'm talking about the air in the plane. I'm sorry. No, no. Yeah. No, that's a great question. Thank you. Yeah. All right. Keynote. This is really important. As a toxicologist, this is really important. If you take nothing more from this today, this is what I want you to know. And to make it real easy, the dose makes the poison. Paracelsus, which is one of our historic toxicologists back only 500 years ago, said all substances are poison. There is none which is not a poison. The right dose differentiates a poison from a remedy. So part of my background is in pharmacology. I know that was your favorite subject, right, in medical school. What did you have, three quarters of it or three terms of it or something? Couldn't have any more. Well, the idea on pharmacology is you want a therapeutic effect, right? But if you up the dose a little bit, you get a toxic effect. As an environmental toxicologist, we kind of take away this idea of therapeutic effects and we look more at what are the toxic effects. And from that standpoint, what chemical is poisonous? Well, Paracelsus said, well, all chemicals. So water, oxygen are all toxic. It depends on the dose. This is an important piece of information. Okay. So what we want to know is a little bit about the chemical, obviously, from that perspective. We want to ask how potent is that particular compound? And in the areas that I study and we're going to talk about a little bit more today is neuropharmacology or neurotoxicology. The potency is, well, how much is it binding to a particular receptor, for example, something like that. And I give a couple of examples. We have alcohol and we use what's called the LD50 lethal dose. We don't use the LD50 as toxicologists. It's not a desirable outcome. But it helps us understand the relative potency from one chemical to the next because lethality is a pretty good measure of something that we can count on. Okay. So the lethal dose, alcohol, takes 10,000 milligrams per kilogram body weight. Compare that to nicotine, which takes one milligram per kilogram body weight, compared to botulinum toxin, which is 0.0001 milligrams per kilogram. So here we have a different potency. And so exposure becomes a real important. The dose becomes real important. And what we have is on dose response, we have the typical S-shaped curve. You probably saw that with pharmacology as well. You can have a low dose and then at some point you get a response. So if you take a half an aspirin, you probably don't get much of a response. If you get two aspirins, you're probably in the average area where you're getting a responsive reduction in headache. And if you take a whole bottle of it, you can take two bottles, but it's not going to make a difference because it's going to hit the plateau of toxicity. So this is the common type of look things that we do here. The other part here that I think is really important is the presence doesn't equal toxicity. Another key piece for you to take home today. Why do I say that? Because my brothers and sisters in the chemistry departments of colleges around the planet, they love to find things. They really do. And they like to find them in the smallest amounts possible. And there's a continual and there will be a continual effort to finding less and less and less reliably. We want to make sure it's reliable. In other words, the results are reliable, but then it doesn't mean that it's toxic. And I make this point really clear because when you read the media, when they say something like toxic compound X. I find that not useful for the population as a public health official. It doesn't provide me any information. I think it actually ends up scaring people. On one hand, it could be appropriate. But on the other hand, I find more and more that the word toxic is not used in the way that I think toxicologists. I know toxicologists want to use. And I'm imploring you to be thinking about that as physicians as well. It's an important piece. So presence doesn't equal toxicity. You know, you do accident investigation. So when you find a med and the med is not a good one, then you have to draw up that med. That's something to do with the accident. I absolutely agree. And having done a number of forensic investigations. One of the things I look at is what medications with the person taking, for example. That's an important piece because there's some other things that could be involved in cognitive abilities, for example. All right. So then I want to talk now a little bit more about air cabin quality. But the way to talk about this is to give you a sense of what units am I talking about? What units? And you may be or you may not be familiar with this, but we're going to use milligrams per cubic meter. So what's a cubic meter? It's it's like that, a box. But it's like eight moving boxes on top of each other. I think that gives you a better sense of it, of the volume. OK. And then what's one milligram? It's a grain of sand or salt. It's the grain of a worker honeybee, if you're interested. Or it's that on the tip of a finger. It's not much, is it? When you look at it, it doesn't look like much. So one milligram per cubic meter is you break that into smaller particles inside this. Does that make sense? OK. And so from an air cabin quality component, we're talking about respiratory. We're talking about inhalation as the exposure as the source of exposure and inhalation would be the root of exposure. So let's talk about air quality events. As I said before, it's a detection of the odor. The odor smells like a dirty gym bag or dirty socks. Those are the two common things. I've been on a plane when I've smelled that. And the plane diverted and landed and made an emergency landing. That's what will happen in these cases. The exposure is generally of a short duration. What happens is there's a leak in the seals of the engine where jet engine oil enters the port that I mentioned earlier, goes through the environmental system and then is put into the cabin. All right. That's the way it is. And that's why you smell the odor, because you're smelling something about the jet engine oil. Odor events are generally uncommon. Has anybody smelled one? Yeah, it's uncommon. And in even more rare events, you can see a haze inside the cabin. And if you do YouTube, you're going to see some examples of haze on the inside of the cabin, because those become very important from a public perspective. What are the common symptoms? Headache, irritation of nose and throat, eye irritation, dizziness, weakness, nausea, lightheadedness. This is common in terms of the symptomatology of an odor event or a fume event. OK. Uncommon symptoms are tremors, problems, concentration, infusion, airway irritation. Those are less common, but they have been reported. And the way that they're recorded is a person on board, typically a flight crew, that is flight attendants mostly, although pilots have also claimed this, is that they will seek medical attention after an event. And they will be seeing people like you. And they're going to say to you, this is what I'm experiencing. These are the things that I'm experiencing. And they may include some of these as well. Does that make sense? So I've just mentioned the combustion. The one part here that's sometimes different is the engine operating temperature, because the temperature is high enough that there's a possibility of combustion byproducts. In other words, the oil actually burns. And that will release some chemicals. And we'll talk about that. And we'll put a pin in that and talk about that in a minute. These foul odors can also cause anxiety and physiological symptoms like a headache, nausea, and dizziness. So now we get into a little bit of differentiation between what's toxic and what's physiologic. And I think that becomes a really important piece as physicians to think about. Are we looking at a physiologic event? Are we looking at a toxicological event? And they do go away. I think of them in some ways similar to campfire. If you're sitting by a campfire and all of a sudden the wind turns around and then all of a sudden you get a big whiff of it in your face, you're going to get irritation, right? You might even cough. You might have tears in your eyes. You walk out of the flume and you resolve. You're not injured from that period on. Fair point. OK, so that's a similar idea between this. So what are the chemicals in cabin air quality events? Well, here's a big word, organophosphates. We did see a little bit of this on the previous slides with things like nerve gas agents. Have you ever heard of those? Those tend to be in the family of organophosphates. And what's interesting about an organophosphate is you have the phosphorus plus oxygen, and then you have these functional groups around here. In jet engine oil, you have tricrystal phosphate. I'm gonna use an acronym called TCP. There are 10 isomers of tricrystal phosphate. I don't wanna bore you to death with that, but the one that's most interesting is TOCP, which is a triortho-crystal phosphate, which means that basically it just changed some of these methyl groups in their orientation. That's it. Hydraulic fluid has tributylphosphate and triphenylphosphate and some other chemicals, and then there's some butadiene byproducts. And yeah, there might be some phosphorus oxides in there, but they're not organophosphates at that point. When we take a look at the LD50 of TCP, we're at 5,000 milligrams per kilogram. Just to put it into some kind of context, it's between toxicology has slightly toxic to practically non-toxic. It's close to table salt in terms of its LD50. Does that make sense? Whereas I mentioned botulinum toxin, that's down here, and then a little water, it's 90,000, and then 10,000 would be alcohol. So it's more potent than alcohol, less potent than nicotine, and roughly around table salt. And then the TBP, which is the tributylphosphate, which is an hydraulic fluid, and then TPP, which is triphenylphosphate, which is also in certain types of hydraulic fluids, they're a little more potent, but not by much. So let's talk about tricrystal phosphate. Here's a little can of jet engine oil. Tricrystal phosphate is between 1 and 3% of the weight of jet engine oil. So it's a pretty small amount. And of that amount of tricrystal phosphate, triorthylcrystalphosphate is less than 0.2% of this weight. So this particular isomer of tricrystal phosphate is in a very small amount. I've seen analysis of this, and it's consistent with what I see. And in fact, if you're gonna make jet engine oil, you have to follow aerospace standard of what it is. You have to do, I mean, that's what you have to do. So that's a common concern. So how much of TCP is in cabin air? Under normal operations, when we measure it, and you need sophisticated instruments for this, you need a sophisticated instrument. You can't just take a little handheld device and walk them through your cabin. You have to have big instruments that can take enough air in order to take enough of it because it's so dilute if it's in there. They're mostly non-detects, and the detection limit is 0.005 milligrams per meter. The highest levels, including cabin air quality events, so this is the fume event, 0.03 milligrams per cubic meter, or 0.05 in military aircraft. So if we take a look at this, this is one milligram. You can tell that these numbers are smaller than one. All right? So the idea here is to kind of get your head wrapped around this unit thing, because, I mean, I could make, if I change the units, I can make that number, that really small number, really big by just changing the eyebrows, for example. The other thing to look at here is 0.015 milligrams of TCP is approximately one part per billion. This is another way to talk about concentrations, and if we put that into perspective, this is half of this, right? So two parts per billion. The width of one human hair is, how much is one part per billion? It's the width of a human hair in 68 miles. So it would be two, the width of two human hairs in 68 miles. It's one second in two years. 1,001, 1,002. Now we wait for 32 years. It's a sheet of paper stretching from New York to London. Just another way to put it. So what we're talking about here are very small amounts, and when we're talking about it from a toxicological perspective, and again, we're going to put a pin in, how much does it take? And what are the characteristic signs and symptoms of TCP? How much does it take? We'll put a pin in that for a second, but the idea is this isn't a lot, right? But what we have seen, and I've seen in medical records, are physicians that people will come in and say, I've been exposed to tricrystal phosphate. Now, how many people here know what tricrystal phosphate is before I just started this lecture? Well, it's got a phosphate in it, and it sounds like an organophosphate, right? We're going to talk a little bit more about mechanisms of action. Tributyl phosphate, a lot more in hydraulic fluid, but hydraulic fluid isn't jet engine oil, and the odor events tend to focus only on jet engine oil, but to be complete, we look at hydraulic fluid as well, because there's a possibility, like at the APU, that somehow, particularly in some of the older aircraft where the engines were on the back of the fuselage, right under the tail, there was a lot of pipes going on in there, and there's an APU back there, and that's a jet engine by itself. It's possible that hydraulic fluid could be entered into the cabin. APU, auxiliary power unit. Auxiliary power unit, thank you. And then TPP is one to 2%, very small levels within that, and if we take a look at TPP and TPP, the normal operations, again, mostly non-detects, and I'm giving you 0.01 as what we call the detection limit, and what I mean by that is how low do we go in order to make sure we measure it adequately, because analytical equipment can only go to a certain level, and this is low enough for us to go. Highest concentration of PTP is 0.1 milligram per cubic meter, which is about one part per billion, and TPP has never been measured in cabin air. All right? Same thing, one part per billion, and then combustion byproducts, carbon monoxide, carbon dioxide, monoxides and phosphorous, aldehydes and other small molecules, and we'll talk about those. So what happens in this combustion process is you take large-chain carbon atoms that make up most of the jet engine oil, and you break them down into these small little particles. When we take a look at that in cabin air, carbon monoxide is non-detect to 4.6 milligrams per cubic meter, about 4%. Now, from a toxicological perspective, carbon monoxide is an important part, right, because you don't smell it, and it's insidious in terms of its impact. Fill in that word. Impact. Impact, thank you. Carbon dioxide, it'll make you uncomfortable. If it was a complete atmosphere of carbon dioxide, it'll kill you, but that's a different story. Formaldehyde becomes a more interesting compound, but it's at very low levels. Acetyl aldehyde, other aldehydes, and small particles, and the particles are important. Again, other than carbon dioxide and carbon monoxide, if we take a look at the milligrams per cubic meter, those are the ones that are four and up to nine milligrams per cubic meter, so it's nine. Anyway, it's important to think about it. None of these, from a toxicological perspective, for short periods of time are important, other than potential irritation, you know. So the health impacts. With tricrystal phosphate, what happens is this TOCP, it's broken down by cytochrome enzymes, blah, blah, blah, and it becomes this, and it hits a particular part of a neuron at a sufficient dose, and I'll show you what that is. Here's a neuron, our friend, the neuron. You have the dendrites, you have the axon, you have myelin, and then you have the gap between one neuron and another, the synapse, right? So where TCP works is on the myelin, where organophosphates, like nerve gas agents, is, they inhibit acetylcholinesterase at the synapse, right? That's a different mechanism of action, and that's one of the key things about the difference between TCP and all the organophosphates of nerve gas agents or pesticides or whatever. That's the difference between it, and that's a big difference, because here, when you get a sufficient dose of TCP, ataxia, distal numbness, muscle weakness, prosthesia, flaps and paralysis, gait abnormalities, and sensory defects, you're getting that effect. It's pretty clear and very classic because there's a history of TCP being used to expose humans, not inappropriately, because it was an accidental in soldiers. If you've ever heard of something called Ginger Jake, back at the time that ethanol was prohibited in the United States, for reasons I have never been able to figure out, someone started putting T-O-C-P in the alcohol, and so people, probably 10 to 20,000 people in the United States had this particular set of symptoms, very classic. It's called organophosphate-induced peripheral neuropathy, or OPIDM. Here, everybody knows, if you see someone that's been poisoned by nerve gas, you know it. Every emergency room physician, I'm sure, around the world knows, meiosis, sweating, involuntary urination, devastation, rhinorrhea, decrimination, cough, dyspnea, fatigue. These are really different signs and symptoms. So my point here is organophosphates is a big class of compounds. You can't put them all into one category. They're a big group, and here are examples of two different mechanisms of actions that have completely different outcomes. So again, the difference here is common symptoms of headache, irritation, eye irritation, weakness, nausea, lightheadedness, these are these tremors. They are completely different from the single-cholinesterase inhibition in organophosphate-induced delayed neuropathy, which are these. The other part of it is it takes one to four weeks post-exposure, if you get a sufficient dose. It doesn't occur like this. All right, how much? Well, how much jet engine oil to cause OPIDM, which is the classic outcome. If, for example, we have an odor and we had an odor panel do this, smell jet engine oil, they can smell it at 0.45 milligrams per cubic year. To give you a sense of what that is, this is this odor threshold. You put two M&Ms on top of each other, okay? That's where we're gonna start. If you get a haze in the cabin, it's the size of a Coke can or a Pepsi in terms of the relative difference between the level of jet engine oil with the visibleness and an odor. In order to get OPIDM, and so when I brought up this idea, we used the best science. We looked for studies all over the world. We looked at them very carefully. We found studies that we think are important. They're the endpoints that we're looking for. They're the most sensitive animal model in this particular case. There are dose response studies that did it. The lowest observable adverse effect level, I'm gonna salute Seattle here for a second. That's the space needle. It takes that amount compared to the odor. So I'm trying to give you relative difference in terms of dose that you can comprehend instead of just giving you numbers from that perspective. Does that make sense? Not only that, in that particular study, it was five days a week for 10 weeks. That was the lowest dose in the literature to show this OPIDM. Yeah, what would the null level? It would have been roughly this level. Good question. I wanna bring up a thing that you may be seeing relative to this whole issue. And I'm just gonna give you, this is a really recent paper published in I think 22, but I actually think it's more recent than this. Aerotoxic syndrome, a new occupational disease caused by a contaminated cabinet air. So I wanna bring this up because you may hear about this called aerotoxic syndrome. And what I'm saying is these common symptoms have been categorized as a syndrome. I'm gonna go back one this long. In other words, this, some people are calling aerotoxic syndrome. And I'm saying these are real syndromes. They're trying to make this a syndrome. And as you can tell, there's not much objective testing that can go on here. And if we've got enough time, I'll dive into that a little bit more. But I wanna alert you to the fact that this is not recognized by any medical association on any place on this planet. Okay, that's an important piece. Like the Aerospace Medical Association does not recognize this at all. And so I want you just to be aware of the fact that this is a controversial area that I'm talking about because people are claiming neurotoxicity from these fume events. So if you see a patient that comes in, for example, and they say, I've been exposed to triprosyl phosphate or I've been in a cabin air quality event, now you've got some understanding of what's going on. And they are thinking that they're getting this aerotoxic syndrome, which is not recognized. It's controversial. Where's that folks? Pardon? Where is that folks? This one is called Advances in Neurotoxicology. It sounds good. I needed to check because I had not heard this and I can't tell that it's peer reviewed. That said, this group plus some others have now published it in a peer reviewed literature. So if you Google aerotoxic syndrome, you're going to come up with some pages. This is what the flight attendants are complaining about something like this. Yeah. Yes. Controversy, yeah. Yeah. All right. Okay. I just want to make sure. So one of the things that we did for TDP and TPP is I use these protective action criteria. These are exposure guidelines used to protect from health effects of short-term exposure to pesticides, chemicals, air. And for TDP, the PAC-1, which is the shortest period of time is 50 milligrams per cubic meter or 1,400. Remember, the levels that were detected were one part per billion, not 1,400 parts per billion. So it's greater than 690 times the maximum detected in air, and TDP was never measured in air. If I use something similar for these other byproducts, carbon monoxide is 75. Nothing has hit that one. Carbon dioxide is 9,000 milligrams per cubic meters, 9,000 times higher than what the highest level measured in cabin air. Carbamaldehyde is 1.1 milligrams, so 25 higher than the highest detected in cabin air, and you can read the rest. One study I was a participant in, in terms of analyzing this, was for, whoops, why did that, was using a C-17, I think that's right, and we have a unit on the outside where they actually injected jet engine oil into the engine and then took samples from this unit right here, and this is the data that came out. It's a little complicated. These are all the compounds that it measured, but I think a couple of things are important here. If I just take ethanol, here is the level that was detected in black, the odor threshold is in blue, and then the TAP, which is the protective action criteria, is in maroon. What you can see here is that all the compounds that were measured, if you assume that this is identical, which is, I think, more conservative in terms of its approach, as opposed to going through an air conditioning system, but anyway, you can see that nothing rises above a TAP level. But what is interesting here is that, for example, with acetaldehyde, you see the blue below the level that was measured here, and then you can compare it to the TAP. So one of the things that we're seeing is, for some chemicals, you can actually smell them before you can detect them, or you can detect them and then you can smell them. And that becomes an interesting question in terms of the physiology of what's going on. So if we go back to some basic neuroanatomy and physiology, you've got the trigeminal nerve here, you've got the olfactory nerve here, the idea is that chemicals will bind to the receptors, right, and you have different types of receptors in the head, you've got temperature receptors, pressure receptors, irritation receptors, pain receptors, and if a chemical binds to those receptors, they're going to stimulate the receptor, and the person's going to say, oh, that's painful, or that's irritating, or that's whatever. But that's a physiological event, that's a toxicological event, is where the chemical is actually affecting the cell, or affecting an organ, or there's some pathology going, there's something going on. And what's interesting about it, particularly with odor, is that it's a direct line to the amygdala, and to the area of excitement and stimulation. And I get curious about the idea that if you smell something, and it's characteristic, I'm not saying you're not smelling it, I'm saying, how is it being interpreted? And if something is irritating, is that toxic, in the truest sense of toxicity? I get curious about that. And I can make a comparison. You cut an onion, these are the chemicals that are in an onion, this one, perpandethial S-oxide, is the one that makes you cry. And if you get out of the exposure of the onion, you stop. I think that becomes an interesting question. And with that, I can talk a little bit about biomarkers for a second. I think I have a few minutes for that. Is that a good? Yeah, so biomarkers of air cabin quality events, I think it becomes an interesting area. How can you measure if someone actually has been exposed? And there are a number of people trying to figure out, if I was exposed, what can my body tell me that I was exposed? And so, as they're going into our blood and urine biomarkers, and of those, you can look at metabolites of TCP, you can take a look at neuronal autoantibodies, you can take brain analysis, you can use tech, set, MRI, EEGs, you can look at hair testing, and you look at genetic testing. And a lot of this is the wave of the future, right? I mean, wouldn't it be great to have a PET scan that can actually not just do biochemistry and physiology, but actually have some ability to measure some subtle effect? But for a lot of us, none of these are going to demonstrate exposures to TCP, for example, or TBP, or any of these other compounds. That's the short stuff. But let's get into it. Some of the genetic testing, we've looked at a particular enzyme, the genetics of genes that express enzymes for detoxification. Are the genes upregulated or downregulated? And how would that affect toxicity to a compound? So, for example, if someone is, I'm sensitive to this compound, I'm more sensitive than someone else, one potential explanation is, well, maybe I'm genetically predisposed to these exposures. And so, so far, what I've seen in my experience is there's nothing that I've seen that demonstrates that. In this particular case, these are the PON1 and CYP genes. This was a case where I investigated it and found that these two genes, interesting, but the results proved nothing. Nothing that was substantial. Blood biomarkers. This is an example of some autoantibody work published in this particular paper. This is a figure out of it. Western immunoblots of autoantibodies tested against nervous system proteins in a seric control and case study pilot before and after exposure. It's one person, by the way. The control, the pilot serum before flying at time zero, the pilot after 12 days of flying, the subject after 16 months after the first sample, and the subject after 29 months. And here are the Western blots. Has anybody done a Western blot here? Aren't they fun? I, you know, it's almost looks like a Rorschach, Rorschach, Rorschach. Which one? Which one? Rorschach test. Thank you. And they've looked at a number of these particular ones. And so another way to look at this was this table is probably a little bit better. And you take a look at neurofilament protein or tau proteins, which are tubulin, blah, blah, blah. And what this person was pointing out is that there's a significance to those particular, that particular individual, nor these autoantibodies. Autoantibodies are good, particularly for things like a head injury, like someone's hit you in the head with a baseball hat, or you got shot, or something like that. That's where you really see these. But on a subtle effect of the TCP levels that we're talking about in Kevin Aircall, that's the case that's being tried, being made here. There's so much wrong with this paper, but one is, you can see really the differences in the visual components of it. So that's a question. I won't go into detail. This is significance. This is arbitrary. Because what's the control? What's against what? I won't go into the details, but the details showed up to be really important to understand this. So, specificity, the claim is that specifics are for smoke, odors, fumes, and links to the aeropositive movement. Yes. Yeah. Thank you, Chris, for bringing that together. Testing hair. I don't recommend testing hair from a toxicological perspective. It could tell you you've been exposed to something, and particularly maybe methylmercury might be helpful. But hair grows. And the question is, where do you cut the hair? And how do you then put it to some period of time that occurred at some other time? Really difficult. Also, tri-crystalline phosphate, it's not just unique to jet engine oil. It's a ubiquitous compound. It's part of making plastics. And if you sit in your car, you're going to be exposed to TCP just by being in the environment of plastics in your life. Anyway, you can see from this particular case, there was really nothing. They said a presence. But if you look at Mrs. Picogram's hologram here, you can see here the limit of quantification is two. It says it's less than two, and then they call it present. I have a question about the laboratory in this case. Now, authoritative organizations have conclusions regarding cabin air quality. The most recent is from France. I translated it. Recent research focuses on health effects of certain compounds in cabin air, particularly organophosphates. Current data do not show significant health effects of these compounds at low concentrations in the air. I've kind of put this in order from 2023 to 22 to 22 to 20 to 209. There's a consistent evaluation by medical authorities around the planet that are looking at this. Clinical considerations. This, I hope, is helpful because I've read a lot of history, medical histories, medical documents, and medical records. And what's really important from my experience is a good history is needed. For example, if you get someone that says, I've been exposed to tricrystal phosphate and you don't know what it is, which is reasonable, I would get as much information as you can, but also be wary that if you aren't familiar with it, I would say, say it. I think it's okay to be able to be transparent about the fact if you know something or not. That's why toxicologists do what we do. A good understanding of the exposure. This becomes another important part. Remember, risk is hazard times exposure. Well, what was the exposure? Under what situation? If it's just in a plane, write it down. How long? Write it down. Is this the first time? Write it down. Things like that. Good time on writing is really important. Are there any objective tests? No, not at this point. There might be in the future. Should you measure a silicone esterase? You can, but unless they were working on a pest, working with sheep in New Zealand, for example, and dipping sheep in pesticide, you're not going to get a phosphor. Carbon monoxide, carboxyhemoglobin? No, haven't seen it. If it was a fire on a plane, that's a different story. Fires are totally different. Now, all the stuff that I've been talking about with carbon monoxide and all the other agents become important because it's low. So, if you've done some crash analysis, they go up, and that is an important toxicological event from that perspective. So, I question. I mean, it's your decision, but I'm not confident unless the history is relevant to that. And then a toxicology assessment, which is, I'm rooting for toxicologists to help you all during those types of situations. I think that is it. So, my conclusion, I hope you found this interesting, and I hope you take home the dose makes the poison. Spread the word early and often. It's a waste of reason. Yeah, we'll take a break. As part of my work, when maybe I work with a few toxicologists on the environmental side, these points are very well made. Just because it's there doesn't mean it's toxic. Would you care to comment about our toxicologists who kind of have a fit with this? Is this no threshold dose limit? We're seeing the EPA and the ATSDR use now. We just think it's kind of a false premise. For many of these chemicals, and for example, PBAS, we'll use that, that there's just a straight line. The S-curve's not there. Would you care to comment about that? Yeah, in toxicology, the S-curve is the traditional curve, right? And that does apply to a lot of agents. Now, are there other curves? Some have talked about a U-shaped curve. So you start with a very low dose at a high response. The higher the dose, it drops, and then it goes back up. So you get the S on the other side of the immune system. That's good for things like vitamin C, for example, or a vitamin or something like that, because a lack of a nutrient will cause an adverse effect. For environmental agents, I don't think that applies. Unless those agents have a mimicking of one of these nutrients. There's another one kind of theory about the idea of a little bit would stimulate the system to detoxify better. That's another kind of thought behind that. When it comes to chemicals, and I've been talking about non-cancer effects, S-shape, I think, applies. If you have data that says something else, then use the other data as long as it's done well. But I think threshold still stands very, very strong. All the toxicology textbooks have that. If you're talking about cancer, cancer is evaluated slightly different because they're talking about the probability of developing a cancer, whereas I'm not talking about the probability of developing OPIDN. I can use data for that. Probability is pulse, not necessarily science. Does that make sense? In other words, EPA wants to be protective of public health. And so what do you do as toxicologists? We want to be protective of public health as well. But they've developed a policy that says this amount could cause a potential cancer risk. And so what you have is what we call a slope factor now. That's pretty standard now across the planet, and that's a different way. But we can play with this. There's ways of measuring it as well. Did I answer your question? Yeah, it's just this idea that there's no threshold. The example of PFAS, now EPA is trying to drive those levels down to parts per quadrillion. And it just sounds almost ridiculous. We're just driving these levels, as you say, to basically the laboratory means of detection with not a lot of science to back those numbers. Yeah, I'm familiar with the PFAS, and you're right about that. It's very, very low. And it clearly says it needs to protect people. There is a question of good science to make some very good decisions about exposures and things like that. There's a question over here. It's quick. Thanks a lot. I believe if I drive on the Blue Lands to downtown Houston, the concentrations are degrading. I drive from Houston to where the dust are. You mean the drop? So the question is, if you drive between here and Houston airport, your exposure is going to be higher to a number of different chemicals. Although some of them will be the same because you've got combustion engines, right? You've got car engines and you've got diesel engines. And that will be more than a flight from Houston to Japan. You're probably right.

air cabin quality

fume events

toxicology

tricresyl phosphate

aerotoxic syndrome

exposure symptoms

jet engine oil

public concern

scientific accuracy