I'm going to repeat a few things. The dose makes the poison a couple more times. So this is a different topic that I've dealt with, my group has dealt with, and it has to do with uniforms. And the question is, are the chemicals in clothing, and particularly uniforms, but it could be in clothing, frankly, because we can take a look at any type of material, are they causing dermatologic and respiratory problems? And so the idea here is, for example, you're wearing a shirt, and somehow a chemical from the shirt gets into the body, and then you have a dermatological risk. Whether it's allergic, or whether it's just contact dermatitis, that's what we're going to talk about. The other part of this is, I'm wearing my coat, I'm wearing my shirt, I'm wearing my pants, and what chemicals are emanating from me into the environment, such that when you're next to me, you're exposed. Does that make sense? That's an interesting question of how a chemical jumps off uniforms, and then causes people to have respiratory problems as well. And it could also occur to a person that's wearing a uniform. I've given you my disclosures, they haven't changed in an hour. Toxicology, some repetition here, risk equals hazard time exposure, so I'm showing you the way that toxicologists think about this. So the hazard would be the chemicals that are found in clothes, and there are a lot of them, by the way. We test over 500 different chemicals in clothes, for example. And then exposure. And exposure would be, what are you wearing, how long are you wearing it, things along that line. The hazard in this particular case is the, our friend Paracelsus again, dose makes the poison. I think I've said it a couple of times now, I'm just going to remind you that you need to proselytize this idea. I've got a little bit of a different version of this. It's ethyl alcohol, but it's mercatorium, sodium chloride, salt, nicotine, and botulinum. Now the other part that didn't necessarily play on the pumerides are the types of chemicals, let's say metals. What is the form that you can find them in? And the, for example, mercury, which you can find in clothing, not often, but you have inorganic mercury, you have elemental mercury, you have methylmercury. And as a toxicologist, from a hazard perspective, it's important to know what the particular compound is in order to determine what the effects are you're looking for. So inorganic mercury has kidney effects primarily, although with higher doses, GI effects. Elemental has central nervous system effects, and methylmercury has developmental effects. Okay. So there's a difference in this and the chemicals can, like with methylmercury, can actually climb, can bioaccumulate in the body over a period of time, where the other ones are excreted relatively quickly. And again, presence doesn't equal toxicity, just to re-support that point. So how do we conduct toxicological assessment? This is a part of the process that I used in the last presentation, but I'm going to go in just a little bit more detail as a toxicologist. First of all, we want to compare, we want to compare the outcome to a sensitive health effect, not just any effect, but a toxicologist wants to look at the most sensitive or the most subtle effect. And that could be senior patient rather than CNS folks. We look for the most sensitive endpoint from that perspective. We also over-predict the dose. Again, using the last example, I gave you an example of the space in Seattle. What I'm talking about is to say, he used that lowest dose, but it's still a very high dose. And that's important for the work that we do. So we over-predict the dose. We over-predict the exposure, for example. So when we do analysis on textiles, for example, if someone says, well, they wear it five days a week, well, we'll look at it for seven days a week. We're going to over-predict the exposure. So what we want to do as public health toxicologists is we want to protect public health and we want to do it making sure that we're not under-predicting, we're over-predicting, but we want to get to a point where we're comfortable that our over-predictions are still relevant. Because I mean, when he was just having a conversation, I mean, you could get chemical to zero and I guess that's protection, but that's not the real work that we live in. We use the lowest dose in the literature to cause that sensitive effect. We look for the most sensitive lab animal because we tend to use laboratory animals to help us. If there's good human data, we'll use human data. But in general, laboratory animals are the ones that we've used because we can do, we can control a lot of things except for the dose. And we can look for the end points in a much more systematic way. And then when we do our work, we assume the most sensitive individual. You know, someone again says I'm more sensitive to someone else. That's possible. They could have a genetic effect or whatever, but there's nothing that I've seen in the medical literature or during my practice where someone is 10,000 times more sensitive than anybody else. I'd say maybe 10 more times, 10 times more sensitive would be more relevant, but that's not a big effect when we're talking about sensitive populations. So we compare, we can do it two ways. We can do an analysis or we can compare it to a global standard of some sort. So for example, EPA has standards. APSDR has a standard. California has standards. Texas has standards. And we can compare chemical exposures to standards. We have to look at a relevant standard. Does it make sense? We'll even go to a more conservative, which is health protective standard if you need to. That's an easy way to do it. You just take the concentration and then you compare it to a standard. But for a lot of chemicals, we actually have to do what I did in the slide before that is we have to go through the data and actually churn out the right information to make it transparent. So the other part here is that chemicals are everywhere. And when we're talking about uniforms, it's probably not different than a person just sitting in a cabin in an aircraft. There's a lot of chemicals that are going around that aircraft, from people wearing the perfume to the food that's being produced to the carpeting to the plastic seats or the leather seats or whatever the seats are to the flight attendants moving carts up and down to whatever. There are a lot of chemicals on the planet. In fact, we're all made of chemicals. And so it's important to take that into consideration when you're doing an evaluation. And then the other things I've just mentioned before, everything is toxic, depends on the dose, presence of needle toxicity, and the same thing. So let's talk about uniforms and skin and respiratory issues. The skin issue seems most relevant, but it is possible, particularly historically. For example, formaldehyde was used as permanent breast component. And so they use lots of formaldehyde for a long time. And you can smell it on shirts, for example. It doesn't happen. It can happen. I mean, we see it. We can still measure formaldehyde in shirts, for example, but we don't see it at the levels that we used to see it at. So that's one thing. And formaldehyde volatilizes at room temperature and pressure. It'll volatilize. And so there is potential exposure. And what happens is that somehow, and remember, it goes out this way and this way and this way, somehow we've got to get it through the nose or through the mouth into the lungs in order to be affected by it. Well, those are pretty small orifices when something is getting 300 and complete X, Y, and Z axis of release. It's still possible and still could happen, but it has to be at a high enough concentration in order for that to occur. With skin, there are three routes that are important here. The appendageal route, the intercellular route, and the transcellular route. These are ways that chemicals can actually go through the epidermis and into the dermis and bloodstream and cause whatever effect they're going to do. The contact dermatitis can have a direct skin reaction. So you could see it in a local localized area. So if there's something on my sleeve, it could be on the arm at that point. If I have it around my belt waist, it could be around my belt waist. That would be where the pressure is actually pushing the fabric up against the skin, probably a better place. And the types of dry, burning, keratis pain that would occur. Allergic dermatitis exposed to areas of skin. I think it's slightly different vesicles and belay and keratis from that perspective. These are the typical types of reactions that we are seeing with wearing textiles. Respiratory effects, really in order, you can get irritation of mucous membranes throughout the pharynx and thrombi. But we're really looking for somehow the chemical to actually get into the body in order to have an effect. Okay. So irritation of mucous membranes and allergic reaction to that. So testing. What is a uniform? Now this becomes one of the more interesting questions because often we see uniform causes problem is causing a dermatitis. And I see this all over the place. Well, then I ask, well, what's a uniform? And we've been working a lot with various global airlines on their uniforms. And you can see there's differences in almost every one of these pictures here. But what's important is a uniform isn't just one thing. It's not like an orange jumpsuit and that's it. It's a jacket, it's a shirt. There's usually different shirts that are available. There's different pants that are available. There's a tie, there's scarves, there are vests, there are aprons. I mean, one airline has over 360 different pieces that flight attendants can use. That's a uniform. And so it starts to be interesting from a perspective, if you just use the word uniform, you're really missing the boat. You're missing all the other components that could be important. It could be that the belt might be the most important piece of the uniform that may cause a toxicological reaction, not the uniform. And that's an important piece. Another thing that's happening in textiles today is a lot of the work of producing fabric is done offshore. The United States cannot produce the type of textiles for 64,000 aircrews, for example. Just can't do it. Those facilities have closed down. So a lot of this material is produced in Asia, Vietnam, China, Bangladesh, and things like that, or in the Mediterranean, in Egypt, and Morocco. Those are two other places where it was. Right there, that also starts to raise questions. How good are their environmental, how good are their production manufacturing capabilities? That becomes a question for that. So anyway, there's a lot of work that goes into a uniform, but a uniform has to be defined as specific pieces. So when we test uniforms, what we do is we bring them in, we cut them apart. We cut them apart into their individual fabrics. And so like with this particular jacket, there's this part, this sleeve, there's all this stuff. We cut it all apart and then test each individual piece to it, and then put it back together so to speak, once we're done with that part. So we collect it, we deconstruct it, and then each component is tested. And we look for chemicals that are in the fabric, but we also look for chemicals that can possibly be released from the fabric as well. So let me talk about that a little bit more from this perspective. So here's some skin. Here's a piece of fabric, and the fabric in this case has dimensions. There's a thickness to my coat, the fabric, right? And in that fabric, there are chemicals. And I'm using these different colored dots, like pink dots, and gray dots, and black dots. And the black dots are ones that actually could be released in this diagram. Chemicals that can actually volatilize, yeah, be released from the fabric. So what's interesting is that the fabric has a dimension, and it has a thickness, and the question is, how will this chemical, for example, go to this tissue? Because there's a gap in general. Although, again, tighten your belt, and you're pushing stuff up against it, but there's still a bit of a gap there. And then you have to cross the dermis to get to the dermis in order to see that it's better. So that chemical, that paint chemical, has a ways to go. It has to travel from the fabric to the skin, through the skin to the body. Now, when you're thinking about that from a toxicological perspective, you need to have enough of that to have that. So again, dose makes a poison. Also, some of those chemicals can be released, and so we're trying to measure what these things are here. So the way we do it is we deconstruct these particular pieces of uniforms, scarves, ties, belts, shirts, whatever, skirts, and then put it in a material, and we shake it. We put it in something called artificial sweat. Why is that? Because we're going to try to enhance any chemical that's in here. We're going to try to pull it out. Remember I said over-predict and overdose? I mean, over-predict the dose. We want to, we want to go as hard as we can after this. Sometimes we'll even use a solvent to extract chemicals. That's not the real world, but it over-predicts the amount. So we'll shake it, and we'll shake it in these synthetics. Sweat, it's shaken. It's on there for could be eight hours, 10 hours. We pull it out. We analyze it. We have a laboratory that analyzes it. There is this data, and then we produce a report. What's important here is that when we measure a chemical in a fabric, it's not the dose. Okay, again, when I think about the media, and someone detects something in fabric. Now, flight attendants' issues with uniforms have made, for us, it's sometimes big stories in the New York Times, in the Washington Post, and whatever. What they'll say is, they detect a chemical in the fabric, and they'll say it's a toxic chemical, by the way. But the reality is, it's not the dose that a person receives. It's just the amount of chemical there. The other part of this is the analytical detection limit. I kind of feel asked to that in my last presentation is how low can we go to detect a chemical? And there's a analytical detection limit that we require the laboratory to set because we want to make sure we capture a level low enough that's above either some acceptable guideline level like EPA sets or APSCR sets or a threshold for a sensitive health effect. Does that make sense? We want to set it low enough that we can capture this and this and see. So if we have measures, detections, let's say here, it's above the analytical detection limit, but it's below a global guideline value, we're good. And if we don't have this and have to do the toxicology assessment below this, we're good. And that's what I mean in terms of the toxicological assessment. The alternative is we set a lot of analytical detection limit very high and we don't have any room to work to determine whether there's a health effect or not. And so that's a really important piece that we work on. So we consider the extraction method, the pull of the chemicals. We can use solvents. We can use artificial sweat. And for metals, we can actually burn the material. So you get a resident and you measure the metals in the residue. Now that's super conservative because that metal could be highly bonded internally inside that fabric that will never reach no matter what, but we're going to measure it anyway. And we can still compare it. And again, these are ways that we work to make sure we get the best data in order to make the best determination. We use the maximum detected chemical in any fabric. So if we have a scarf that has a high formaldehyde and we have a shirt that has formaldehyde and the scarf is higher than the shirt, we use the scarf as our toxicological assessment. That means anything below, if that's safe, everything else below it is fine, right? So that's an important... And then we compare fabric concentration to the dose needed to cause an effect. And we can get pretty sophisticated in the analysis here. Where do we find the list of chemicals? Here's a bunch of them. We look all over the world to find lists of chemicals. And today we're at this point, at this time it was 450. Today we're about 550 chemicals. We're not just picking any chemicals. We're picking chemicals that A, that have a history of being in fabrics. B, have had a history of being reported in the literature for dermatological arrestments. And then C, any of these organizations that have raised it. The Europeans have been generally much better at raising questions about chemicals in textiles. Yeah. What I'd like to ask is a point you just raised. When another agency, whether it be domestic or foreign, raises a standard, does that influence what we do in any way, or just one takes note of it and goes on and say, you've got a current standard, or how does that work? That's a good question. And I think what you mean, lowers the standard. Raising a standard, I hardly ever see it. Yeah, no worries, but I just want to be clear about that. We will look at that very carefully and we will likely adopt it if it's a global standard because we don't want to, we're not in the business of necessarily getting in a fight with another global standard. Unless we really feel it's not appropriate, then we will say, what's this data that you're using? This is the data we've seen. Let's talk about it. I'm sure it's right. I think France did something recently within the last year that many of you know who struggled to do, they lowered their standard. Yeah, no, it's going to always occur. Things are going to go lower and lower. Yeah. Here are some of the chemicals. Just memorize them for the test. There's a few more. We've got some metals. I think the other part that I want to say here is a detection limit that's set by these particular test methods that have been adopted by these organizations. So there's specific test method. You can't just throw something into a GCMS. You've got to have a test method that has been accepted. So all of these things have to be done in a way that is transparent, that's reproducible and reliable from the chain. Here's a few more, dichlorotoluene, trichlorobenzene. There's a lot of dyes that we look at as well. And those dyes tend to have a more interesting chemistry than we see with like the trichlorobenzene and things like that. The other thing can be done, we've been working with the dermatologists. That's a lot of work that I'm talking about. It's in order to do the tests the way that I'm talking about. Another way to do this is through patch test. And what we've been able to do is to take uniforms, cut them into pieces. We have a pharmacy that will actually then package it so that the dermatologist can then order the patch tests and it can be applied to new patients. Obviously a lot easier from that perspective. And that's a workable solution. The thing is, you just don't necessarily know what chemical you're talking about from that perspective. Of course, first you learn about. So what we do is we convert laboratory tests from milligrams per kilogram of textiles into grams per centimeter of tissue, select the chemicals of interest. We look at the rate of detection for chemicals, anything greater than 1% from detection, we will include into our risk assessment. We'll look for potential for germinal sensitization. And if there isn't any data on that, we'll do what we call read across studies. And we also use computer models that can help look at functional groups to see if there's a potential for it. If there's a potential, we then add it to our sensitization list. Whether the maximum concentration met or exceeded the standard. And for limits of detection, normally you can take that limit of detection and you just reduce it by half. That's better than taking zero. Again, there might be nothing in there, but we're gonna assume that there is since half the detection. So let me give you an example. We looked at nickel. I mean, of all the chemicals, the ones that popped up to the top here were nickel, copper, zinc, and formaldehyde. Did a dose response assessment. I'm gonna show you one of the examples here. Based on literature reporting allergic responses, because that's what sensitization is much more sensitive than contact dermatitis. So we use sensitization as a marker for our work. And then we assumed from this case, copper and zinc, which not great sensitizers. We just assumed that they were as strong sensitizer as nickel. I think that's pretty conservative from that perspective. So in this particular assessment, naphthalene was the highest detected chemical out of a group of uniform pieces for a particular enzyme, bear in mind out there, followed by FTOH, which is the kind of the acronym for the floral carbon compounds that are someone said PFOS earlier today. Well, it's not PFOS, but it's a lot like PFOS is smaller. They're using instead of PFOS, chemical companies are cutting the molecule down from eight carbons to about six or four carbons. Still chlorinated, but that's what we found here. Toluene, pentachlorophenol, dimethyl 10. Here's a metal. And then here's PFOA, by the way. And then here's another of these. So these, why are those compounds in there? They provide water resistance. We found some in aprons, for example, of flight attendants. And the reason is, is, you know, they could slash on sub. It protects their uniform and protects it. So the reason is not a bad reason for having it there. What we did with formaldehyde is you took this study, Flinholm 97, 20 healthy formaldehyde sensitive individuals in serial occluded applications. So what we did here is use this study to determine the sensitization to formaldehyde. So this would be an example of when we go to the literature and actually do the work ourselves. So these people are already sensitized to formaldehyde. Now we're going to expose it to them anyway. And you can see the percent response versus the dose that we gain, right? And so now what we have is from this level here, we don't get any response. That is pretty good data that tells us, even for the sensitive individual, we're not getting an effect at that level. So that's how we use that data. From a respiratory perspective, we look at chemicals that volatilize. That means they release over time. And this is a list of compounds. Formaldehyde is one of them. We had acetaldehyde, which was the most common detection in all the different pieces of uniform that we were looking at. And 78% of it is detected in uniforms. So we pulled together all of these particular compounds and we put these together and then took each piece where we found it and put an ensemble together. So in other words, there's a layer of pants, space pants, there's rain pants, there's bibs, gloves, hats, jackets, lanyards, sweatshirts, pants, shirt. These are all different pieces of a uniform that could be from above and below me. And then we took a look at it from male and female components and we built models. One in this case, a person would wear one of each thing. Model two was a partial ensemble where it was a shirt, pants, short, mid-layer, jacket. And then what we do is we take a look at different exposure scenarios. What if these people in this model, first model, was just sitting in their house? Just like you're sitting right here. Although this place has more ventilation, I think it's more like non-residential. But anyway, in a house, there's probably not much circulation going on. And this is the kind of variable that we started to see. And hazard quotient of one tells us, eh, maybe, let's look at it a little bit more carefully. Are we conservative enough in the work that we've done? If we are, the one is probably not a problem. If we're not conservative, we'll redo it again and see where we need to be more conservative. And if it's still one, then that raises a question to us as toxicologists. But this is them sitting or standing at their house. Put them in a building like here, you can see the concentrations drop primarily because of the ventilation system that's going on inside this building right now. And if you put them on an aircraft sitting or standing, because as you remember from the first lecture, the ventilation system in aircraft is amazing. So this is the respiratory component to it. How much would a person be breathing of those aldehydes that I just showed you that would cause, and you can see that when you have less of a uniform, this is a complete, everybody put everything on, and this is what normally we'd have. You can see that 0.2 is less than 0.1, we know. And so we're feeling very confident from that perspective. That's a way we do a toxicological risk assessment on that. So on clinical, again, good history is needed because you may have people that come in and say, my uniform is killing me or poisoning me. And the question is, okay, what are we gonna do? Good history is important. And remember what a uniform is. It's a lot of pieces, unless it's a jumpsuit. It's a lot of pieces. And so the detail of figuring out what it is is really important. Is it around the neck? Is it scar? A good understanding of the exposure. So I find this challenging to construct as a toxicologist, but if someone says, well, look, I sat in this seat, and I know someone else sat in the seat, and that person had a uniform that we think is causing her toxicity. And now I sit in that seat. And now I am then exposed to the chemicals that the person left on the seat. Does that make sense? Yeah. I find that challenging because that means that someone's left chemicals on the seat and that somehow when I sit down with my pants and I do wear underwear, I sit down on that, it's gotta go through a lot of layers pretty darn quickly in order for me to get there, right? So these are questions that make me interested in thinking about it, at least. Also is if I'm standing next to someone, I'm having a conversation with them, and then I say, why smelling? Now, let me separate the idea. I mean, I'm aware of people that wear perfume and some people find those perfumes offensive. So, I mean, I get that part, maybe from a physiological perspective, not from a toxicological perspective. But the question is when we have such low concentrations, how can a person then react? From a chemical perspective, it's harder for me to pull that together. I'm not saying so. But a good understanding of that exposure is important. Objective tests, well, call your friend the dermatologist or refer that person to a dermatologist would be the best thing to do. And make sure the dermatologist understands what you know now about that whole process. You can do a toxicological assessment. Don't have to go through everything that we've done per se. That test could work just fine as long as you've got the right materials for it. Remember too, is if someone is wearing a uniform or clothing and it says it's causing this and you go and test this, it's not the uniform that you may have received when it was brand new. Why? Laundering. Laundering, personal care products, for example. Sweating, all this kind of stuff. And so what we've seen when someone has brought the uniform in that says this is the uniform that's causing plasticity, we'll actually compare it to a brand new one, to the one that's being worn. And we'll find a lot more chemicals in the one that's worn. Yeah. And that's an important piece to understand. Who knows what a person did or has done during their life to understand what that is. And so the question, the flashlight goes on the uniform. Okay, that's possible. Let's be serious about that as a crew. But also outside that flashlight, there's a whole lot of stuff going on in a person's life. And that's important too. Also medications can have dermatological reactions, can't they? So even when I'd say a good history, understanding what kinds of therapeutic agents they're taking as well.

chemical exposure

textile safety

toxicology

dermatologic problems

respiratory issues

patch testing

uniforms