Exam #2

Okay. Okay, it's that time. Um, so far today, we've had a fire alarm

in this building. And I just got an email

that some lab equipment was possibly on fire and smoking in one of my

labs in St. Paul, so I'm starting to feel a little plagued like I'm causing fires, but, um, we'll hope

this building is okay. It didn't take that long for

us to be allowed back in, so I'm assuming there's nothing

actually wrong in here. But it's been kind

of a weird morning. Okay, I didn't actually update this to reflect exactly what we're

talking about today. I'm now realizing, so we're just gonna blow past

that and ignore it. Um I don't have a whole

lot to say about the exam. Excuse me, today, there's

still a couple of people who have to take

makeup exams this week. You know who you are,

if that applies to you. They're not going to get

the exact same test, but there's enough overlap

that I'm not going to go over the whole

test here in class and I haven't really figured out what the best way is to give you all feedback on what you

got wrong if you want it. Can you see in Canvas which ones you got wrong or can you just see your score

and nothing else? The ladder. Okay. So

I'll think about that. I don't know if we're going

to go over the whole test or if you can just check in with me if you want to know

what you got wrong, while we're waiting for

people to take makeup exams, I'll ponder that and

come up with a plan. The average was a

pretty average average is the textbook what

you would expect for a mean on a test was 75%. A couple of people

emailed me nervous about their scores on the

test because they didn't notice that your score in Canvas is your points out of

75, it's not your percent. So if you looked

at that and had a little mini heart attack, hopefully you realized that that was your points out of 75, not your percentage

that's showing in Canvas. I did give everybody 1.5 points, so the points for one

question worth of a bump and that's

already incorporated into your score on Canvas. There was this question. Which more people got

wrong than right by a significant enough

margin that I feel like either there's something

wrong with the question, which I think the

question is okay. I think maybe I

just didn't cover that topic very well in class. Usually, if a whole lot of people get the

same question wrong, it's something about

the question or my coverage of the topic and

not something about you all. I just gave everybody 1.5 points added to their

score across the board, so that bumps you up about 2% if you're thinking

in percentages. So that's all about the

exam for now until we get the maker uppers through their version of the

exam and then we can talk more about it

maybe. On another day. Okay. So before the

day before the exam, so a week prior to today, we did some review

for the exam and then we spent a little bit of class time going over some

general toxicology content. We talked about

what the field of environmental toxicology is. We talked about some

overarching ideas that we'll come back to a few times or that you can think about as we're

going over the different, these different

categories of toxicants and different case studies, et cetera, within toxicology. Remember we talked about the

precautionary principle, how you make

decisions about when to ban or regulate something. Do we wait until we have

a huge amount of data, and then we know for sure

we should ban something. But then there's harm

happening that whole time that we're waiting for

the huge amount of data, or do we ban something a little bit preemptively

when there's a little bit of evidence and then wait for the science to catch

up and revisit. We talked about that. We

talked about biomagnification, laying the groundwork for

talking about toxicology. Now, today we're

going to get into the different categories of toxicants and we'll

start looking at some toxicants of

particular interest or concern, case

studies and such. I didn't talk last week about the toxicology topic

assignments because I figured you super did not care

because you were focused on there was about to be a test, and that's what you

were thinking about. There are two topic assignments

in the toxicology unit, and just like with the

intro biodiversity unit, they're up at the top

above the schedule table. They're linked there

with their due dates. So one of them is

due later this week, hopefully you saw

that on your Canvas schedule and that's

not a surprise. I don't think this one

takes super long to do. So if you didn't know about

it until this moment, you've still got about 48 hours to do it where you're going to look at an EPA

Superfund site. Those are sites that

have been designated for tox cleanup by the EPA. You're going to look at what

an EPA superfund site is. There's a map of sites,

you're going to pick a site. You could just pick one

randomly off the map. You could pick one that's

near where you're from, whatever metric you want to

use to decide what site to pick and then answer some questions about what's going on at that superfund site. When I set up this

assignment before the semester started or around the beginning

of the semester, the EPA superfund site had

moved to a different URL. Hopefully the one I have

is still there, but again, sometimes some of the

government agency sites are getting moved around and reshuffled at

this point in time. If you find that that

site has moved again, let me know and I'll find

the right one for you or you could probably Google up the correct one if it's moved. Um, so we have that one due this week and then

due on March 6. We have an assignment

about atrazine, which is a pesticide

that we're going to talk about later. You're not actually

going to have a debate, but you're going to

pick a stakeholder, so there are a few

different groups that have different interests in whether we use atrazine in

agriculture or not, so you're going to pick one

of those and do some readings from that point of view of that group and

answer some questions. And then of course, that

popular press topic assignment is ongoing for the

whole semester. I think that one's number two in the topic assignment

numbering system. A few people have

done it so far, so that one's also linked in with the toxicology

assignment. So that'll be

linked in each unit so you don't forget

that it exists. But remember, if

you see something in the news or in a newspaper or wherever that's relevant to something that we have or are going to talk

about in class, you can use that for

that topic assignment. So Okay. I think I showed you this slide. Last time. Today

we're going to talk about the different

types of toxicants. We're not actually

going to talk about endocrine disruptors yet. We're going to wait until

we're going to actually talk about some case studies of particular

endocrine disruptors. So when we get to the

pesticide section, we'll talk about

endocrine disruption, over the course of the

next few lectures, we're going to lean

a little heavier on I didn't mean to make a pun

there on the heavy metals, we're going to talk about a

few different pesticides. We're going to talk about

endocrine disruptors. We will also talk a bit

about air pollution. And throughout that we'll

have some conversations about how we measure

how toxic something is. The goal is to understand where information about toxins

and toxicants comes from, what the research looks like. If you read about something or see something click Baty

about something being toxic, you have some framework upon which to make

your own decisions, maybe know how to get

to the peer reviewed literature to answer

your own questions. Okay, so we're going to talk about the first four

on this list today. We're going to

wait a little bit. On endocrine disruptors. So we're going to talk about

carcinogens, mutagens, teratogens and neurotoxins,

what those are, and some examples of those, but we'll spend more time on neurotoxins because we're going to talk about some heavy metals. We have a little more

to say about those. First up in our list Otxicans or categories of toxicants

are carcinogens. Carcinogens are simply any

substance that causes cancer. There's lots of different

types of cancer, but if it's a cancer causing

toxicant, it's a carcinogen. Cancerous cells are also

called malignant cells. If you've heard that

term malignant versus benign being non cancerous,

that's what that means. So I'm guessing at some point in your history

of taking biology classes, even if you haven't

taken college level biology classes in high school, you probably learned about I would hope you learned

about the cell cycle. So think back to your

cell cycle learning here. Normal cell division, and this doesn't illustrate every

part of the cell cycle, cells are on a clock. There's a control to the cell cycle that tells the cell when

it's time to divide. Duplicate the genetic material, divide into two cells. Basically make little

daughter cells that are clones of

the original cell. So built into the cell cycle is sort of a timing

mechanism for that. What happens when you have

cancer cells is again, there's lots of different

kinds of cancer, so this is not exactly the

same in every kind of cancer, but there's something out of

control about this process. The G signal that tells cells when to divide,

something's wonky with it, so division just kes

happening and keep happening, and it keeps happening

rather than happening on a normal clock or

normal timing system. So the cells aren't

responding appropriately to the control signals that

would tell it when to divide. Cancer is basically just

unchecked cell division that kes happening and keep happening and

keeps happening. Also cancerous cells usually don't die when

they're supposed to. In that cell cycle clock, there are control

mechanisms that tell the cell when it's time to divide and there

are also mechanisms that tell the cell when

it's time to just die. We have healthy normal

turnover of all of our cells. They turnover at different rates depending on what cells we're talking about

within an organism. But cancer cells

are dividing like crazy and they're also not dying when

they're supposed to. You just have this

unchecked cell division. That's in a very small

nutshell, what cancer is. Carcinogens are things

that basically screw up that cell's response to

the controls about when to divide and when to die and you get something

like what you see in the lower

image here where it's just dividing like crazy. So some examples of carcinogens, obviously there are lots

and lots of carcinogens. I just put a few

common examples here. Whoops, foot cught in. There's this weird

little box down here that's stuck to the floor. Asbestos is a carcinogen that

you have probably heard of. Asbestos it's actually

a group of minerals. It's not just one

thing, but they occur naturally as these sort

of fibrous bundles, they're found in soil and rock. The asbestos fibers are

really strong and they are resistant to heat and a lot of chemicals and they don't

conduct electricity. So they were used

for a long time. Asbestos was used as

insulating material, since the Industrial Revolution, we figured asbestos

out a long time ago. You know, and it's

not until during my lifetime that we figured out asbestos was a carcinogen

and we stopped using it. It's still used in some things, but it's not really

used as much in insulation and buildings and things that we would

come into contact with. So this lab bench is pretty new because this

buildings not that old. So this probably doesn't

have asbestos in it, but in some of the lab buildings

that are old on campus, these black lab benches

are infused with asbestos so that if you have a fire in your benchtop,

your bench doesn't burn. Um, so we know now

that breathing in asbestos fibers or particles causes scarring in the lungs

and it's carcinogenic. So generally, if we're using it in something

like lab benches, we're using it on something

where it won't be, you wouldn't sand an

asbestos lab bench because then you would be

getting particles into the air. We don't use it in things

like insulation where particulates could

get into the air. So when it comes to asbestos, if it's intact and

not scuffed up and you're not getting

it up into the air, it's still relatively safe. So we don't use asbestos in most things anymore that we would be coming

into contact with. Um, dioxins are another

really common category of carcinogen or

type of carcinogen. They are environmental

pollutants that are pretty

persistent in organisms, so they stay in the body

for a really long time. If you get dioxin exposure, they accumulate in

organisms over time. Remember last time

we talked about biomagnification

up the food chain versus accumulating in an

individual's body over time. They also biomagnify actually, they do both dioxins

there byproduct of industrial processes

a little bit comes out of volcanoes

and some natural sources. Things like chlorine bleaching, paper pulp to make paper white, things like that produce

some level of dioxins. Manufacture of some

herbicides and pesticides, dioxins come from sources like that most of our

exposure to dioxins is actually through food because it is stored in animal

fat for eating animals, meat, fish, things like that. We can get some level

of dioxin exposure. Um, and then we have PAHs. Those are organic compounds that usually occur in mixtures. They're found

together in groups. They are created from

burning organic matter, burning fossil

fuels, burning wood, refining petroleum,

things like that. If we're burning organic matter, there's some amount of PAHs that are being

released into the air, any combustion that

isn't complete, which is most combustion. And they're persistent

in the environment. If you've heard of pHs, you've probably heard people talking about the fact

that they stay in the environment for really

long periods of time. I wouldn't ask you detailed info about these

particular toxicants. It's more of just an FYI, about some common carcinogens. I wouldn't ask you

detailed questions. Know that asbestos

is a carcinogen. I'm not going to

ask you what we put asbestos in since we just had a test and maybe you're

more thinking about test stuff now that you've

seen one of my tests. So the thing about

cancer causing agents, carcinogens is they don't

cause cancer immediately. They're not an acute toxin. Acute meaning you're

exposed to it and it affects you right away

in a significant way. It can be complicated to figure out what is causing cancer. There's a lot of

different carcinogens. There's a lot of different

things people get exposed to over the course of a lifetime

at different levels. Um there are also non

toxicant types of cancer. It can be complicated

to figure out what's carcinogenic and what's not and which things we

need to worry about. EPA here in the US, our Environmental

Protection Agency has a system for categorizing

carcinogens and carcinogen risk based on the type of evidence

we have that something causes cancer and

how much evidence we have about that thing. There are three categories of

data that are listed here. That they use to decide how

carcinogenic something is. They combine data from these

categories to figure out an overall carcinogenicity classification or rating system. And so we often have

animal studies that are used to assess how carcinogenic

something is or is not. Animals will be used

as a model organism, studies done with a group

of animals treated with a potential carcinogen and then their outcomes would be

compared to a control group. Treating a group of

rats, for example, with a compound of interest and then having a

control group of rats and seeing what cancer outcomes look like

in those two groups, um, you can obviously do a

study like that with humans. You can't have a group of humans where you treat them with a potential carcinogen and a

controlled group of humans, obviously wouldn't be ethical

to do that with humans. It's debatable

whether it's ethical to do that with animals, but that's outside the scope of what we're

talking about here. Human evidence is harder to

come by because we can't do lab experiments or controlled

on purpose experiments. But there are instances of

people being exposed to potential carcinogens because of something like an

occupational exposure, for example, or an

accident or a spill. If you have a population of

people who you know were exposed to a particular

carcinogen, for whatever reason, you can use them as a case

study group and then look at a control group of people

that you didn't have that kind of

environmental exposure. We do have human data. It's just not experimental data. Um, then this is from the EPA's 80s version

of these guidelines. There is a newer version of these guidelines that

was published in 2005, that's the newest

one, so this hasn't been updated in a

couple of decades. But the 2005 version

doesn't have this tidy little table

that's easy to look at, um and the information that's in this table hasn't really changed that

much in the 2001. I still use this one from the 80s just because

it's a little easier to see it all

in one table here. This was 1986 was the first time the EPA

published these guidelines. And so here we're looking across the top at animal evidence

and down the left, we're looking at human evidence, and so they categorize

it into sufficient, meaning we have a pretty

good body of data limited. We have some data, but

not as much as we'd like. Inadequate meaning

there's not enough data, no data at all that indicating that we just don't have information about

that particular carcinogen, or we can have data that tells us there's no evidence

of carcinogenicity. So if we have enough studies and the studies are showing

no carcinogenic effects, that would be a no evidence. Category. And so

you can see how we combine the human

and animal evidence to figure out what the risk is, and the risk is

categorized as A, B one, B two, CD, E. So if

we have no evidence in human data and no evidence in animal data that indicates

that it's carcinogenic, it's E, that's the

lowest risk level. The class A carcinogens

up in the top row here, those are the ones that we're pretty sure

are carcinogenic. I'm not sure why the no evidence one has an A here on this table. A would be, we've got

plenty of human evidence, we've got plenty of

animal evidence. You can see by looking

across here that the humid evidence trumps

the animal evidence. Even if we have

inadequate animal data, if we've got enough human data, we're solid on it

being carcinogenic. The human evidence is more weighted than the

animal evidence. So as an example of, human occupational exposure

to a potential carcinogen, and human epidemiological

data that we have, meaning you're looking

at a population of people who've been

exposed with asbestos, people were

occupationally exposed to it over a long

period of time, and you could follow long term health outcomes

of those people. That's given us a high level of human evidence for asbestos

being carcinogenic. We also have animal

data about asbestos. So, the populations of people that would have

been exposed to a lot of asbestos would be people who installed

insulation for a living back when asbestos was in all the insulation in

people's houses, for example. So if there's something where we don't have much human evidence, but we have really

solid animal evidence, it gets classified a little

bit lower on the scale. This is a table used to figure out how

certain we are that something is carcinogenic

or not. Oops. Back to our three

categories here, um, just to reiterate, if it's

easier for you to look at it in bullet point

form, here it is again. I didn't mean to really

duplicate that slide in there. For a particular carcinogen, the EPA takes the data from Humans, data from animals. Sometimes there's also

sorry, I'm flipping back. There's also a supporting

data category, which wasn't represented

on that table. That would be things

like cells in culture, not in actual living organisms. So it's an animal cell, but it's not in a

living organism, it's in vitro as

opposed to in vivo. If you're wondering what that

supporting category was. The EPA takes the data from those three categories,

human animal, cell or other studies as

the supporting category, and they combine those to

determine the classification. So those are the ABC,

et cetera levels. If it's a category A, it's classified as

carcinogenic to humans. We have enough data to say

it is for sure carcinogenic. If it's a B one, it's likely carcinogenic to

humans, et cetera. In the lower categories, they'll say it's

suggestive evidence of carcinogenic potentials, so they're hedging their

bets because we don't have enough data to really be sure. And then the lowest

category is not likely to be

carcinogenic to humans, meaning we have no evidence for it being carcinogenic

in at least a couple of different animal tests in different species or maybe on a human study in

an animal study. If we've done multiple studies and there's no evidence

for it being carcinogenic, then it'll get this

lowest ranking. That's how we define how

carcinogenic something is. Carcinogens, things

that cause cancer. Then another category of

toxicants is mutagens. We've talked about mutations a little bit when we

were talking about different ways that we get genetic variability when we were talking about what you need

for evolution to happen, variability in the population is the key ingredient

that you need for evolution to be able to happen through

various mechanisms. We talked a little bit briefly

about mutations back then. Mutation again is just a

change in the genetic code. It can be a deletion,

it can be an addition, it can be a change of a base from one letter

to another letter, one nucleotide to another. There are different types of mutations and we don't need

to get super into that. But we're talking

about some error or change in the DNA code. This can lead to cancer, so we can have mutagens that cause cancers. You

can ask a question. So UVlite is my little example over on the right here

incoming UVPhotons. We know that I think

we all know that being exposed to UVLite from the

sun can cause skin cancers. That would be an

example of a mutagen that can lead to a cancer. UVlite I don't think we would

call that a carcinogen, but it's a mutagen that

can lead to a cancer. These categories of toxicants

aren't mutually exclusive. We often have toxicants that fall into a couple of

different categories, sometimes a few

different categories. They don't necessarily all

have to be one or the other. So with mutations, you can

have loss of function of certain genes that can have

non cancerous effects. I can have no effect,

but in some cases, they have cancerous effects. With UV, it actually causes, um bonding between bases, which is what we're seeing

in the little diagram here, you've got UV light coming

in and the bases that are next to each other on the same side of the helix

start bonding with each other. That's an oddball

type of mutation, but that affects DNA replication pretty significantly

when you have bonds in here where they're not

supposed to be Um, and then we have things like

if you've heard of PAHs, sometimes those pop

up in the news, polycyclic aromatic

hydrocarbons. You don't need to

know that. I think I also had PAHs in my carcinogen

list a few slides ago. Those are the ones that are created from incomplete

combustion of organic materials. Again, when we're burning

things, we're putting pHs out into the air out

into the atmosphere. They are also mutagens. Radiation is a mutagen. So that's why when you go to the dentist and you need Xrays, they put that heavy

lead apron over you to try to protect your

reproductive organs from the radiation we don't want your DNA being

mutated from your Xrays. I think the risk is pretty low when it comes to radiation. I think they're more

worried about someone potentially being pregnant, but um, so we try to stay away from

radiation sources to the extent possible

in modern society. Yeah, mutagens, things

that mutate DNAs. I want to one example of a mutagen and I forgot I did the click through animation

thing, so bear with me here. I always forget

what's on the next. Click I always think it's

a good idea when I'm sitting alone and then when I'm in classes, I find it awkward. The example here is BAP, which is benzoapyne again, you don't need to know that. This is an example of a PAH. It falls in that category

I was just talking about. Um, so it's a known carcinogen. It's found in coal tar,

so we're talking about, you know, something coming

from burning coal here. So like chimney sweeps

in the 18th century were exposed to a lot of benzopyrene, people who worked in

the fuel industry where a lot of stuff was being burned. Were exposed to BAP. If you burn wood

at home, you know, you're probably being exposed

to a little bit of BAP, um, So BAP, when our body tries to metabolize it or

does metabolize it, it breaks down into, you know, we don't

need to worry too much about the specific

structures here. But when I talk about

metabolizing something, so we've got enzymatic reactions or reactions catalyzed

by enzymes happening, where the molecule on the

left is through interactions with enzymes being converted into the molecule

on the right here. Then if we're

metabolizing it out, it goes through a few

different changes and then it becomes something that can

be excreted from the body. However, with BAP, what we're metabolizing

it into this in between product before we're

able to excrete the product on the

right is something that actually binds to our DNA

resulting in mutations. This is an example of

a mutagen that people could be exposed to and it is something we're

able to metabolize, but there's this product in the middle that will

bind covalently to our DNA and cause mutations which can down the

road lead to cancer. So as an example of immutagen. Immutagens or anything that

alters our DNA can lead to cancer can lead to

other health effects. Down the road. Then we have teratogens. Teratogens are toxicants that interfere with the development

of an embryo or a fetus, they lead to birth defects or developmental differences

or malformations, whichever term you

like to use there. And so how teratogenic

something is depends on the ability if we're

thinking about mammals, the ability of something

to cross the placenta. If it's a really high

molecular weight, it wouldn't be able to cross. Here as an example, I've given

you a fish example here, um, so these are

Japanese ice fish. That's the scientific

name down there at the bottom if you're curious, you don't need to know that. But fish embryos are often

used as developmental models. It's easy to have a

lot of fish in a lab, they're an easy

organism to study. Also when they're

small like this, they're partially see through. This is a dark image, so it doesn't show up

grade on the top here, when they're in their chorion, their little egg sac,

it's totally see through, and so we can watch the

early stages of development, which makes them a

good model organism. A lot of the fish we

study in labs have a pretty high level of genetic

conservation with humans, meaning we have a lot of

the same genes in common. It's really quite common to see studies and tratagens and things where we're

looking at fish. So um, here we have fertilized

eggs that are fertilized, I guess, we call

these larval fish because they're already

out of the coron here. They're five days

past fertilization. These are five day

old larval fish, and they were exposed to

valpuric acid for 48 hours. Then they looked at the

fish later after hatching here out when

they're a little bit older we consider

them larval fish. You can see some of the

teratogenic effects here. So we see a yolk edema. So fish would normally have

a little yolk sac here. That's where they get

their nutrients from the first for the

first several days, depending on what kind of fish it is and how fast it grows up. So they have a little yolk sac that's attached to their belly. An edema just means a swelling

or it's filled with fluid. So here we see a really

big swollen yolk sac. And here we see a bent tail, which is also a

really common effect of teratogens or something that's affecting the

development of a fish. Instead of having

a straight tail at this age, they're

kind of bent. So kind of standard ways we measure

teratogenicity in fish. Sometimes you also see

pericardial edema, which we can't

really see in this, but that swelling of the

sac around the heart. That would be another

common thing to look for. Here's an example

of a cyanobacteria. This is more of an

environmental example. A lot of what you

read about with teratogens is related

to human drugs, pharmaceuticals,

things like that. That tends to be where a lot of the teratogen information is if you're reading around

online or looking for example. I thought I'd bring

you at least one Out in the environment,

non human example. This is shown on the right here, a particular species

of cyanobacteria. It's also called

blue green algae, if you've heard of that. It's a bacteria that

does photosynthesis, its name is a little confusing

because it's bacteria, but people often refer to

it as blue green algae. But it's a bacteria

that has chlorophyll and can do photosynthesis. It's naturally occurring

in aquatic systems, but human activities

can increase the population size of these bacteria pretty

significantly. If you've heard of algal blooms, um, if you've heard

that term before. Algal blooms can happen when

there's a situation where there's a lot of extra nutrients being added to a water system. That can come from things like there's a golf

course and they're using tons of fertilizer, when it rains and

water washes down into whatever the body of

water is near the golf course, there's all those

extra nutrients from the fertilizer getting into

the water system or output from a wastewater

treatment facility that's going to have

a higher level of nutrients for microorganisms and other organisms runoff from

urban areas in general. That situation where there's extra nutrients being

put into the water, extra nitrogen, extra

phosphorus end up in the water from fertilizers

or other sources. Which gives these populations of cyanobacteria a chance to

have what's called a bloom, meaning their population all

of a sudden gets really big, really fast because you've added all this extra stuff that helps

them grow into the water. This species produces

a few toxins as a byproduct of its

cellular respiration, just a natural byproduct of living its life

and doing its thing, which is not at a risk to anyone when their populations

are relatively low, normal level populations, but

when you get a bloom, um, you get a lot more of those waste products,

byproducts being produced, and then it's a risk

to humans and animals, um, when those retire

levels in the water. And one of those byproducts that this cyanobacteria

produces is a teratogen. So that's kind of an oddball, slightly rarer example of a teratogen being found

in the environment. It's still associated

with human activities, but it's produced naturally

by a living organism. We don't hear about

too many of those. They also produce some

neurotoxins and other types of toxins in addition to

the teratogenic toxin. This is an example of

a toxin because it's produced by a living organism, not a toxicant that is

human made or synthetic. If you've ever been somewhere at a beach or something

and there's a sign about not going in the water

because there's high levels of blue green algae or

there's been some bloom, it might be due to this species. I guess we're not a

very beachy society here in Lake Beaches. Here in Minnesota. One of the most famous teratogens

is thalidomide, a lot of people have

heard of this one. Thalidomide was developed

originally in Germany, so this is a

pharmaceutical product. It was prescribed in

Europe and the US, starting back in

the 50s to it was prescribed to pregnant women who were experiencing

morning sickness. It was prescribed as

a sedative to help them sleep and just

be more comfortable during the uncomfortable

early stage of pregnancy where

you're feeling queasy. And it was generally

used in people for insomnia for headaches. I was prescribed for a

lot of different things. Turns out thalidomide is a

pretty intense teratogen, but people didn't know

that at the time. So in people who are pregnant, it impacted the development of the fetus if the mother

was taking the medication. At the time, people didn't know medical research wasn't at

a place yet where people knew that drugs taken by

pregnant people could pass across the placenta

and affect the fetus. That just wasn't something we knew yet at that point in time. It sounds irresponsible

and egregious when we talk about it with a modern

sensibility, but at the time, they were working with the science and the medical research they had and didn't know that this was going

to cause problems. Because it was being prescribed pretty heavily back in the 50s, there was this large

wave or cohort of babies that were born with physical or developmental

differences. Largely the thing that they saw the most

was missing limbs, babies with no arms or very

shortened small limbs. And in the 60s, they withdrew the

drug from the market once they figured out

what was going on. Today, thalidomide still exists. It's used for people with certain kinds of cancers

in their plasma cells, and some really rare

diseases of fat cells. There are some use cases where

thalidomide is still used in rare forms of

disease and cancer. But obviously, they're

very careful about not letting people who are

may become pregnant use that. So it's very

strictly controlled. Nowadays. And so one of the

because this has been such a well studied

pharmaceutical over the years and people are still looking at it and

learning things about it, is this is a good case

study for how we figure out when something

is teratogenic. If we're thinking

about this from a human medicine perspective, we're thinking about a

pregnant person taking this medication or an

environmental exposure that a pregnant person could

have if we're not talking about a drug or a medicine, is that there's

this concept called a critical window when

it comes to teratogens, that would be the

period of time in which exposure to that

thing, whatever it is, thalidomide in this case, would have a

significant effect on the developing embryo or fetus and what

effect it would be. Here we see a graph

for thalidomide. So we're looking at

embryonic and fetal period. So we're looking at the first

part of a pregnancy we're looking in weeks and

then we're looking at the remaining months

of that pregnancy. That's why it goes

out to nine here. You can see if there's

exposure to thalidomide during the first couple of months of pregnancy because this

is the eight week mark. We're a couple of months

in where the line is here. These are the critical windows

for different effects. These are when these

different things are developing in that

embryo in this case. The central nervous is

developing in the early weeks. The lower limbs and upper

limbs here are developing. That's why if exposure happens during that first

trimester of a pregnancy, we saw so many limb

differences in people who were whose parents were taking thalidomide during

their development, heart, eyes, ears, et cetera, lips and face and palette

are developing here. So thalidomide was mostly

being prescribed for people in that first part of

their pregnancy because that's when people were feeling queasy and not feeling well, so that's when the critical

window for a lot of the developmental milestones is. Whereas later in the pregnancy, we have external genitalia developing and not as many people were

taking thalidomide, but also the critical window for that would be later in the

pregnancy, for example. We think about these what's called highly

sensitive periods on the graph here when we're

talking about any teratogen. And we will often use

model systems like the fish like mice,

in some cases, other animals to study how these different ratogens

affect development. We're going to get into

neurotoxins in a minute, but we have a little

more to say because we're going to go into

mercury and then lead in a little more detail than the examples

I've been giving you. Let's pause for a few minutes, see if you're comfortable

with what carcinogens, mutagens, and teratogens are. As usual, talk to people sitting near you if you

want to try to explain what those are or just think

it or write it to yourself. We'll just pause for

a couple minutes. Okay. All right. So let's I've got a few chime in questions

just to check in about this. So it's hop over there. Not

a lot of chiming in today. Just a few factual questions. Did you do noes. Didn't

need to do that. I'm really bad at using my computer when

it's on the screen. There we go. Okay. These are just factual

questions about those categories

before we move on. So hopefully, these feel easy. All right. Let's

see where we are. So mutagen is a substance that causes changes in

the genetic code. Almost all of you

got that one, great. And we classify carcinogens based on human and animal data. We don't use plant data, and

we don't use microbe data. Sometimes we use

cells in culture, but they would be animal cells. People are changing

their answers now. So most of you got that one. Great. Then one more. Tratogens that person left the room right before we did the chime in and

they're not back, so I have to remember

to catch them at the end of class

and get their name. Because I feel bad that the

timing worked out that way. Tteratigens teratogens

have similar effects on a developing embryo

fetus regardless of when during development that

happened, that's false. That comes back to

that critical window. If you took thalenovide during the last month of a

pregnancy, for example, it would have a

very different and probably lesser effect

than if you took it during the beginning

when a lot of important developmental

things are happening. Those three categories

that we just covered. Those are the ones obviously we're spending the

least time on. We're done with those. They'll come up again

because as I said, some of the toxicants

we're going to talk about fall under more

than one category. So things are

endocrine disruptors, but they also have other impacts and might fall into one of

these other categories. But most of our time

when we're talking about these different

categories of toxicants, is going to be spent

in the neurotoxins and the endocrine disruptors, which we'll get to later. So neurotoxins are toxicants

that act directly, they can be toxins or toxicants

natural or synthetic. Act directly on nerve

cells or neurons, they're impacting the

nervous system directly. Some living organisms produce neurotoxins like snake venom, like spiders who have poison of some sort or a toxin of some sort

when they bite you, some puffer fish

produce neurotoxins. There are some animals that

are producing neurotoxins. A really common example of a neurotoxin would

be carbon monoxide, if you get exposed to it in

high enough concentrations, that can act as a neurotoxin. That forms when

something is burned in a situation where

there might not be enough oxygen or an

oxygen poor situations. Picture like a stove or an engine or something

in an enclosed space without good airflow. That would be running a car engine in a garage

with the door closed. Eventually, you're going

to get a buildup of carbon monoxide and it's

going to act as a neurotoxin. We're talking about

things that have effects on the brain's neurons

or our nerve cells depending on dosage

and how you're getting exposed to what it is and which particular toxin

we're talking about. Um, with neurotoxins, the common things that you see are loss of muscle control, loss of mental

abilities, numbness, think about things that

would impact parts of your nervous system and

what that would look like. Some of them damage nerve cells, others block the signaling

capability of the neurons. So the cells aren't

actually getting damaged, but the signaling

doesn't work anymore. The way signals

move from nerve to nerve in your nervous

system doesn't work. Carbon monoxide heavy metals

like mercury and lead, which we're going to

talk more about today. I don't know how long

mercury will take. I don't know if we'll

make it to lead today, but we're going to talk about

both of those upcoming. That's what we're talking

about with neurotoxins. It's something that affects

your nerve cells or your neurons or some aspect

of your nervous system. Mercury is really, I don't

know if importance is the right word, a

big neurotoxin. I think Mercury was

one of the ones when we made that

word cloud last week, lead was huge on the word cloud, but mercury was also in

there pretty significantly. A lot of you know about

mercury being a toxicant, um if you know Alice

and Wonderland, this is the mad hatter. Mercury used to be used

in making felt hats, fancy hats and the type of wool felt that they

used to be made out of. This mad hatter or mad as a hatter trope that you see

in Alice and Wonderland and other pieces of fiction was about the fact that

people who made hats used to be basically suffering from high levels

of mercury poisoning. They used a mercury

solution to turn um, animal skins with fur

into felt for hats before they started using wool more to make felt for hats. So, the haters who were making

the hats were breathing in all the fumes from this mercury solution that

they were using. So you would see,

they would have shaky hands and

be uncoordinated, maybe their speech

would be slurred, memory loss, irritability. That's where this

mad hatter trope that we see in Alison

Wonderland comes from. Mercury used to be in, um, you know, red ink. There used to be skin cream

that had mercury in it. It used to be a treatment for

syphilis a long time ago. There's been a lot

of different things that we've used mercury for. It's used for extracting gold. It used to be used

in hat making, dental fillings, the

silvery dental fillings. It's been phased out over

the last few decades. It's not completely phased out. There's still a little

bit of mercury in metal dental fillings, to

the best of my knowledge. Um, it's inorganic mercury, though not organic mercury, so the health risk is

supposed to be very minimal. It's not in a form

that supposedly can be neurotoxic to us. There used to be teething

powder for babies that had mercury in it like

that you would rub on the baby's gums when

they were hurting. I used to be used

for a lot of things. We used to have mercury

thermometers where the stuff inside the analog

type thermometer, the stuff that rose up,

used to be mercury. Now it's alcohol based. We've used mercury

in a lot of things. It crosses the blood

brain barrier. That's how it acts

as a neurotoxin. There are a couple

of different forms of mercury which we'll get into, but methylmercury is the

one that's especially toxic and crosses our

blood brain barrier. It's hard to say the iteration

of that concentrates in our brain and has

neurotoxic effects. So Um, this might

look a little bit, this might look like a lot, but we're going to talk through it and I've got a couple of

different versions of this. One has the words on it instead of the CH three

HD plus. It has words. We'll go through a couple of different versions

of this and you can study off of whichever one jives with

your brain the best. Our primary way that

mercury is getting out into the ecosystem and into organisms in a way that's causing

significant effects. At this point in history is

us burning coal for power. Coal fired power plants. They're emitting, I haven't

looked up a recent estimate, but last time I looked

about 40% of the human caused mercury in

the environment is because of coal

fired power plants. As a society, at least

in this country, it's not exactly true in

every region of this country, but we've been

working on reducing using coal in our power plants and Minnesota has had a really significant

reduction in how much coal we're using

as part of our energy mix. Places that have less coal in this country have almost

completely phased it out. Places in Appalachia

where there's a lot of coal and that's

what they have are still a little more coal using. It varies a little

region by region. But we're trying

societally over time to use less coal and at least if we're going

to use fossil fuels, use other fossil fuels

that aren't emitting mercury and causing as

much air pollution. At the top of our diagram here, we've got a coal fired

power plant, um, HG zero here, that's

elemental mercury. That's periodic table. It's just mercury,

it's inorganic, it's just the element itself. That's what's

getting emitted from these coal fired power plants. That's generally not

a health concern. It's not something we

can absorb very well. Our digestive tract doesn't

really absorb it very well, and we can pretty much excrete it if we get exposed to it. We're not really worried about elemental

inorganic mercury. In the atmosphere, some of

that becomes HG two plus, which is ionic mercury. Remember if you've

taken chemistry before, the little plus indicates that we've got an ion happening here. Some of that mercury is

turning into ionic mercury. Again, I have another version

of this that has the words instead of the chemical

abbreviations. When you're studying, you can look at that and not

this if it helps you. The ionic mercury

is less volatile. Um, and so what we see

happening here is we go from elemental mercury to

ionic mercury and some of that is settling

out of the air. It's essentially falling onto it can fall onto

land, obviously, but here we're focused on an aquatic situation

because that's where more of that mercury is going to be converted

into other forms. So here we have some of that ionic mercury being

deposited on water and on land, or focusing on the water. This ionic mercury forms in the atmosphere from the

elemental mercury vapor and then deposits down. Um, and so most of the mercury that we find

in aquatic systems, if you've heard about

mercury in fish, fish as a food source and how

worried should we be about eating different kinds of fish because it has some

amount of mercury in it, um, that's why we're focusing

on the aquatic system here. And most of that mercury that's in fish

ultimately came from the ionic mercury that

was depositing out of the air from us burning coal. Once mercury is in the water, obviously, it starts out in the surface water

and then sinks down, but it enters a cycle

where it converts between different forms in

the aquatic system. Some of it's going to get

released back up into the atmosphere by

volatilization, just going from

the ionic mercury back to the elemental mercury. We have a little bit

of that happening. Some of it ends up in sediments. As we can see down way

at the bottom here, a little bit of it ends up in the sediments in the bottom of the water and the mercury

that's causing us problems, the mercury that we're

concerned about, gets taken up by

bacteria in the water. These little flag

the little flagella, that tail like structure, blue guys are meant

to be bacteria. Obviously, this is

not to scale because the bacteria are the

size of small fissure. But these are meant

to be the bacteria. And there are

bacteria in the water that can take elemental

or ionic mercury. They take it into

their cells and they convert it

into methylmercury. This CH three HG plus

is methylmercury. That's the one that's

particularly neurotoxic. That's the one we worry about. Um, because it's now an

organic form of mercury, meaning living organisms can

take this up really readily. There are bacteria that are converting it into an

organic form in the water. Um, essentially, they're

putting a methyl group. If you're into chemistry,

and this is helpful, they're adding this methyl

group to the mercury. That's why we're calling

it methyl mercury. Methyl group being bonded

to the mercury ion, this methyl mercury has a

high affinity for proteins, meaning it can be

very reactive or interactive with

things once it gets inside a living organism. The bacteria that have

produced the methylmercury, some of that's staying

in the bacteria, some of that's going

to get excreted. But we've got organisms that

are eating the bacteria. Other microorganisms, remember, our food

webs where we have phytoplankton and zoplankton and it's going to work its

way up the food chain. That's how mercury gets in an organic form and it

gets into the food chain. Then we've got all

these other uh, fish and little

planktonic organisms that end up with that

methylmercury in them, I biomagnifies up

the food chain, like the DDT that we talked

about with bald eagles. There's a little bit

of methylmercury in these small organisms and as we get up to the big fish or the fish eating bird up here, they're going to have more

methylmercury in them. So I don't know that we need to necessarily talk through

the whole cycle again, but this is that same graph,

but I put it in word form. If you don't care

about the chemistry, what the molecules look like and this works better for you, you can use this version

when you're studying. We've got inorganic

mercury, ionic mercury, that gets in the water, bacteria convert it into methylmercury, and then that methylmercury

is going to be everywhere else in

the food chain, it's going to biomagnify This is the same thing just

in a different diagram. I like to sometimes include a couple of different

diagrams just in case one jibes with your

brain better than the others. On this diagram, we've got

different color coding for the inorganic form

is the pink dots, organic, that's

the methylmercury, that's the stuff that acts as a neurotoxin, is orange dots. It looks a little

chaotic because of the dots everywhere,

but it's the same idea. We've got the coal

burning power plant, putting the inorganic into the air that settles

into the water, and we've got bacteria converting that into the orange dots into

the methylmercury. We've got some numbers here,

10% of methylmercury enters the food web and then it's biomagnifying up the food chain. It's the same idea here. I feel like that was a lot. Let's take a few beats and I'm going to let

you just process this. See if you can answer these

questions on the right. You can talk it through with somebody sitting near

you if you want. Um, and I'm just going

to hang out here for a few minutes and

let you look at this diagram and think

that through because I feel like I just said

it at you kind of fast. See if you can process

this for a few minutes. And check in with somebody near you if you're not sure

about some of this. Okay. The people that we're

talking stop talking and it seems like nobody's looking

at the screen anymore. Does that mean you're done

and ready to move on. Mostly. Okay. And this will probably

be one of those things we circle back to when we review before the exam,

which is totally fine. So as I said, mercury

biomagnifies up the food chain, up through the trophic levels. So methylmercury is a

neurotoxin of concern. And if we as fairly

high level predators, if we're eating predatory

fish or anything like that, I don't think there's any fish eating birds that we eat as humans off the top of my head. It would be mostly

about us eating fish. It can be of concern if you eat a lot of

fish in your diet, you might want to look into the fish consumption guidelines because different kinds of fish have more or less

mercury in them. If you're somebody

who likes to go fishing and you eat

what you catch or you're just somebody who

buys a fish at the store, there are lots of different

resources that you can look to for um, guidelines about

fish consumption. So the Minnesota

Department of Health puts out a fish

consumption guide. They do have a more updated one. This one's from 2012. I'm using a really old one here. The more updated one doesn't have a nice

handy table again, it's easy to view in a slide, and it looked upon quick glance when I was side

by side comparing them, it doesn't look like it's

really changed that much. But if this is

something that applies to your daily life that

you're concerned about, go grab the 2025 guidelines. But in general, what you see in fish consumption guidelines

is they have sort of a green, yellow, red, traffic light

kind of system here. Um, and so we're looking at Minnesota

cod fish in this case, and they have

separate guidelines for people who are not and are not planning

to be pregnant. They have a separate set of

guidelines for people who are or may soon become pregnant

because it's higher risk, if you're pregnant to be taking in a significant

amount of methyl mercury. The green ones are unrestricted or X

number of meals a week, whereas the yellow

species would be things you would only want

to eat one meal a month. That's how these

guidelines work. If you're going to eat

this kind of fish, how often can you eat it and not be super worried

about the mercury. Some of these are Minnesota cut. Obviously, some of these are

not shark and swordfish. Those aren't things that we're

going to be catching here. You can think of this in

terms of trophic levels, something like a shark

an apex predator is going to be higher up

on the trophic levels, so that's going to

have a higher level of methylmercury because of

the biomagnification. This is the same set of

guidelines, but here, it's for pregnant people

or people who may become pregnant and also for

kids under age 15. I don't know what magically

happens when you turn 15. That makes you less concerned

about mercury intake. Um, anyway, you don't have

to know these guidelines, but if you're somebody who eats a significant amount of fish, you might want to look into that and then they have a don't eat list of just

don't eat these. So there's some

Minnesota caught. I feel like the shark was on the yellow one and the red one. Oh, because this is the guideline for the

pregnant people. That's why. Pregnant people aren't supposed

to eat these things at all because they'll have

more mercury in them. This is from a somewhat

old Star Tribune article where they were

looking at levels of mercury in babies up on the

North Shore in Minnesota. And they found that one in ten babies along the North Shore in Minnesota are born

with unhealthy levels of mercury in their bodies. The assumption there

is that people out there maybe catching

and eating more fish, and that's why they were

studying this population. Minnesota infants

were more likely to have unhealthy

mercury levels in their blood than

their counterparts in Wisconsin and Michigan. Also Great Lake states. I don't know what's

going on there, but this says it's probably because

their mothers ate more fish. I don't know why on the

North Shore you'd be eating more fish than

Wisconsin or Michigan, but that's what they were

finding in that study. So there is definitely

a correlation between fish consumption and

mercury in the bloodstream. This says babies born in the summer months when local

fish consumption is highest, had more mercury than those

born in winter, for example. Um, and this is, again, this is an old article from MPR News where they were

talking about how Excel energy, which is where a lot, not all of our I guess, not every single

place in Minnesota, but where the

majority of people in the state are getting

their power from, including the university, um, that Excel Energy has

been working over the last couple of decades

to really reduce and ultimately eliminate

our reliance on coal as a power source for

reducing mercury emissions. We're leaning a

little more towards natural gas in the

fossil fuel landscape. Here in Minnesota, we don't

use a whole lot of coal. Um this wasn't meant to be a crossing out,

something shifted here. I must have moved something

a little bit on the slide. I didn't mean to be striking

through the text here. But again, this is just stating

that here in Minnesota, we're trying to reduce

mercury emissions and also other sources of mercury in dental fillings, et cetera. This is something

that we definitely at the regulation level have

been paying a lot of attention to for the

last few decades. Other than eating fish,

we just talked about, which is a way that we get

exposed to methyl mercury, there are some jobs

where people get higher mercury

exposure than others. So industrial jobs, some construction jobs could involve some level

of mercury exposure, but people generally will take safety precautions these

days if that's the case. There is, as I

said, a little bit of mercury or dental fillings, I say because I have

some dental fillings, the metal kind as far as I know, the white dental fillings

don't have any mercury. It's just the

silvery metal ones, but that's in organic mercury. That's not the one

that really poses a significant health risk to us. It's the methyl mercury, the organic mercury that we most worry about it's

neurotoxic effects. There is another mercury

that I haven't mentioned yet another organic form of

mercury called ethyl mercury. Um, that's a little different from

methylmercury chemically. That is found in these days, not very many, but a couple

of kind of vaccines. I don't know in your

current age group and status in life if this is something that's on

your radar or not, but there's been

this I don't know if debate is the right

word because that puts both sides of it at

an equal footing, but there's been this

conversation happening in the public for I don't know, at least a couple of

decades now about vaccines. Are they safe for babies

and small children? Are vaccines causing autism, if you've heard

people talking about that childhood and

infant vaccines. Some of that comes down to this additive in vaccine

is called thymisol. Timisol is a preservative. It prevents mold

or fungal growth. In a vaccine and you've probably gotten vaccines

like this if you get a flu shot or a COVID vaccine where there's more than

one dose in the bottle, I guess they don't really

take the dose in front of you that often anymore now

that I'm thinking about it. But in the situation

where they're taking a dose with a syringe

out of the bottle, but there's multiple

doses in the syringe, it'll have thymisol in it because even though

the syringe is sterile, you've got something going

in and out of there. It helps preserve the rest of the doses in that little bottle. So that fimsol does

have ethylmrcury in it. That's part of how it

works as a preservative, so it's mercury containing, but it's ethylmrcury,

not methylmercury. Methylmercury is the one that we were talking about

the fish having. Methylmercury stays in the body and it doesn't really

metabolize out. We metabolize a tiny

little bit of it, but the reason it

biomagnifies is because animal bodies and human bodies aren't metabolizing it

out, it stays in there. Ethylrcury is something we can actually metabolize

fairly quickly. It doesn't hang around, it

doesn't stay in our bodies, it doesn't build up and

accumulate over time. If we're thinking about a

natural system out in the wild, it doesn't biomagnify

up the food chain. It can be a neurotoxin if you have it in your body and

high enough quantities, but it doesn't build

up in your body, the tiny little bit you get from a vaccine dose isn't going to build up in

your body enough. We don't have enough

data to directly compare methyl and ethylmrcurys

toxicity very well, but it's thought to be

significantly less toxic then. Ethylmrcury. But

there's this persistent belief kind of in a fear

mongering way if you go too far down the rabbit hole

online and start reading about it about childhood vaccines and ethylmrcury and people blaming vaccines for causing autism in their children and

things like that. So I realize at

your stage of life, you may not be seeing much of that conversation because I'm guessing most of you aren't having kids at this

stage in life, so getting your kid vaccinated isn't something you

need to think about. But we have a lot of data over a pretty

long period of time. I mean, this is from 2003,

this is 20-years-old. It's not like we haven't

been looking at this. People have been talking about this possible thymosol autism

connection for a long time. Um, and here we're looking

at person years at risk, and we're looking at thymosol free vaccines if

we're just looking at the top, couple of rows here, and then vaccines

containing thymrsl. Thymosols not in every vaccine and it's actually been removed. Again, kind of a precautionary

principle at work here, it's been removed

from most vaccines. It's only in a couple now. Um, so that person years

at risk is an estimate of the actual time

at risk in years, months or days, um, and here we're looking at years. Um And in certain studies, people are followed for

different lengths of time, so this is a way for making sure it's apples to apples

and we're looking at the same if somebody

was only followed for a few months versus somebody who was followed

for a few years, you put it all in this one

metric so you can compare. Here we're looking at, people who are

diagnosed with autism, people diagnosed with other

autism spectrum disorders. I'm not liking that they use

the word disorders here, and that's certainly not what we would put

on something in more modern in a

more modern study, but this is from 2003, where that was still

standard terminology, unfortunately, it

says disorders. So here we have um, we're comparing

thimerosol free vaccines to thymosol vaccines and we

see that the numbers are actually lower in the

thymosol vaccines that they are in the

thymosol free vaccines. If we look at the ratios, again, we're not seeing a

significant difference here. The rate ratios are

not significantly different for the two groups. When you look at a

table like this, if something's

significantly different, they'll usually put

a little asterisk or some symbol next to it, so you know that it's

significantly different. Even though the numbers are

a little bit different, if you run the

statistics, these are not significantly different

from each other. The conclusion from a dataset like this is that the risk of autism didn't differ

between these two groups. So kids who are only given thymosol free vaccines

or maybe were unvaccinated versus kids who were getting vaccines

with thymosol. No causal relationship there. Some people have accepted

because that's what the data tells us that thymosol with the FO mercury isn't

linked to autism. But also, if you get into this, if you go too far down the rabbit hole with this

autism and vaccines debate, there's also concern

that there's something in the MMR vaccine

that we get as kids. That's the measles

mumps rubella vaccine specifically that is causing

autism in some children. Sometimes those two

debates get conflated. People hear about

thymosol and mercury um and then even in a

thimerosol free situation, you see people online freaking out about

not giving their kids the MMR vaccine because they're worried that

it causes autism. I just wanted to look into

that a little bit more. Um, as a public

service announcement, we are told that we get

this as kids and it's a multi shot series and we are told that it gives us

lifetime immunity, but I definitely got the

mumps several years ago when we had a mumps outbreak

on campus, it wasn't fun. All the nurses I spoke to who are around my age

said, Oh, yeah, our immunity totally wears off, and we have to get

booster shots as nurses. Anyway, when you're older, when you're in your 30s,

maybe get a booster for this. This is also why

you occasionally see in the news every

couple of years, there's a measles outbreak

going around because a lot of people are afraid of

giving their kids this vaccine so they

don't vaccinate. My brother hasn't vaccinated his kids with the MMR because

he was worried about it. For example, he's a bit

of a conspiracy theorist. We did this whole

MMR thing come from? I'm realizing we're out of time, so we'll get into

the bad science of where that idea about

MMR came from next time. Cliffhanger.

Today. Open. Okay. So we talked about mercury last time, so we'll just see how we're feeling

about mercury content, and then we'll keep

going with neurotoxins. I mean, it can be online, but we talked about it in

the water, yeah. Our connected people number is real low today. I don't I don't feel like

there's fewer people here, but maybe everyone's too

factoring and getting logged in. All right. Well, just

leave that open for a minute while we see

where we're at here. So what form of mercury is

released when we burn coal? So we looked at a couple of

different versions of that. Who sorry, of that.

Diagram last time. When we're burning coal, we're releasing

inorganic elemental just straight up inorganic

mercury into the atmosphere. And then that deposits in aquatic systems

and goes through a couple of different potential

reactions and changes. So the inorganic

elemental is what's being released into

the atmosphere. And then, remember, we

looked specifically at a couple of those

different diagrams and how it gets into the

food chain last time. All right. So how does

mercury enter the food chain? Let's see where we're at. It looks like most

people got this one, the majority of

you, and of course, now it's all going to change

because left it open. Last time we look at that

diagram and we saw that bacteria were the

ones converting it in aquatic systems

to methylmercury. The first choice here on the

left A is the correct one. We looked at a diagram specifically of that happening

in an aquatic system. The same thing happens,

although maybe at a slightly lower rate in

terrestrial systems also, there are bacteria in the soil that can do the same conversion. C wasn't correct here

because plants aren't the ones converting

it to methylmercury, but it can biomagnify up the

terrestrial food chain too. It's just more of an

issue in aquatic systems. That's why we were

focusing on that. Then I think I've got

one more here. Yeah. All right. So how can

we limit our exposure, assuming we don't have

any occupational war? Uh, whoa, that looks crazy. The text at the

bottom got all funky. I don't know what's

going on. I don't know what in the HTML is

happening there. But the correct answer was, A, researching mercury levels in fish and limiting consumption. So if you're somebody

who eats fish, that's probably the best. If you're worried about mercury, that's kind of your best

day to day lifestyle way to avoid mercury exposure. Suppose if you have

fluorescent bulbs instead of LED bulbs

in your house, there's a potential

little bit of mercury exposure if you

break one of those open. But disposing of your

fluorescent light bulbs and not eating tons of fish with mercury in it would

be your best bets for day to day day to

day life changes. Um, and it looks like body or if somebody

picked this one, they changed it as

I was talking here, and I didn't notice,

but vaccines, as we were talking

about last time, contain ethylmrcury, which is different

from methylmercury. Not really of that much concern. Is it toxin cause our bodies can get rid of ethylmrcury

pretty quickly. We haven't talked about

air pollution yet, but we'll talk about

it later today. Okay. I don't know why the formatting on that

one came out so weird. Okay, so we talked about thymosol last time.

That's a preservative in. These days, there's only flu

shots that have thymosol in, and not all flu shots do, but that's the only

place thymosol is left. We used to use it in lots of different vaccines.

It's a preservative. It has ethylmrcury that I

was just talking about, which isn't really

something that we're that concerned

about as a toxicant. And so we talked about

some of this last time. This is just sort of

a little nutshell of what to know about

thymerisol all in one slide. So we don't have it left in

very many vaccines anymore. There are multiple studies. There's lots of studies you

could go dig up if you want, where people have

looked at rates of autism diagnosis in groups

of children who did or didn't receive childhood

vaccines containing thymosol we don't see any difference in autism

rates between those groups. Even though it's something

people were talking about for decades and worried about with mercury and

vaccines and autism, there doesn't seem to be a

connection there at all. And then since we were on

the topic of vaccines, I was about to last time launch into launch into

makes it sound big, but tell you a little bit about the other

reason that there seems to be this

virality online, this conversation

that just won't die about vaccines and autism. Some of it is about thysol

and mercury and some of it is about specific concerns with the measles mumps

rubella vaccine. I'm not sure why

specifically this vaccine has been the target of a

lot of those conversations, but this has been going on. This has been something

that's pervasive in the public and has been for a long time. So

what's the deal with this? Um, I don't know if some people are worried about the particular strains of viruses that are in this

vaccine or the fact that it's three different

things given as a combo shot. Sometimes that

freaks out parents of babies and young children. I just wanted to talk a

little bit more about where that originated or

where that came from or why that's something

that's in the public space. This is the front page of a published research

article that came out in the late 90s by someone

named Andrew Wakefield. If you go down the

rabbit hole online of researching this

vaccine autism debate, this is a name that

you'll see come up. I guess this is a bit of

a spoiler because I'm showing you that this paper

was eventually retracted. Um, it's very well known. It gets talked about

a lot in this sphere, so it's worth just spending

a minute looking at, and you can also

consider this a case study for any topic

you hear about online in a sensationalized

or clickbaity way or people on social media are

debating about this thing, how you might go about

figuring out what's actually going on or what the science

is behind that conversation. This paper from the late 90s showed a link between

the MMR vaccine, that measles mumps rubella

vaccine and autism. One thing that's

a giant red flag is that it was a

very small study. It was only 12

children and there was no control group.

That's a problem. No control group should

be a giant red flag. Sometimes initial

exploratory studies do have really small

groups of participants, but you wouldn't want to

make a giant sweeping claim about something

that only had um, 12 people in the study. Um most of the claims made in this paper rely

on parental recalls or just things the parents told the researchers or beliefs of the parents or

parents opinions. There were lots of

other studies that followed this because

this made a huge splash when it was published

and it was all over the media and people were

freaking out about it, um, there were lots and lots of follow up

studies and no one ever in a follow up study

found a link between this vaccine and

autism diagnosis. Eventually, the paper did get retracted and this researcher

was totally discredited. It was found to be

not real science, and shouldn't have been

published in the first place. Um, this is a little more

info about the retraction. A medical panel

found that Wakefield actually mistreated some

of the kids in the study, maybe all of the kids in the

study was subjecting them to unnecessarily invasive

or painful procedures. Things like colonoscopies

and spinal punctures with needles and to collect

fluids and things that just didn't need to

be part of this research. There were also some pretty

extreme conflicts of interest who the funding came from for the work was called

into question. It was partially

from the funding was partially from

lawyers who were representing parents hoping to sue the manufacturers

of the vaccine. That's who was

funding the research. Whenever you're researching,

even if you're digging into the science literature,

a controversial topic, and we'll probably talk

about this again when we talk about genetically

modified organisms, we'll probably talk

about this again when we talk about

climate change. It's good to look at who's paying for the

research because yes, science peer review journal

article is the gold standard for what we know about things in the world from a

science perspective or a science way of knowing. But You can get corporations

that are funding research, so it pushes things towards outcomes that the

corporation wants to see. Sometimes people who work for corporations are the

authors of journal papers. So it's always good to pay

attention to who wrote the thing and who paid

for the research. If you're looking at

a research paper, you look in the acknowledgments

and that's where they say where their

funding came from. This paper, which had lots of problems, small sample size, mistreatment of subject studies, and it was just the

subject children, and it was just bad science. It was published in 1998. It was retracted in 2010. I wasn't retracted

for over a decade. This paper was out there being considered to

be somewhat real science. The scientists were

suspicious right away, but it took a while

for the retraction actually happen and

for that to get to a level where it was actually

officially retracted. How does the scientific

paper retracted? Basically the journal

it's like when a newspaper makes a mistake in an article and then the next day they publish a little oops, we made a mistake

yesterday as a retraction, it basically works the

same in a science journal, the journal will publish

that it's been retracted. I don't actually know if

you tried to go dig up the PDF of that article in the original issue that

it was published in. I've never tried to do that.

I don't know if it would come up with a note that

it had been retracted. My guess would be

that it would be. Yeah, one of the issues is when a paper like that

gets retracted. I made this huge media splash when it first got published. And then it didn't

get retracted for about a decade and there

was a little fizzle of a few mentions in the

media and a paper getting retracted isn't

fun media coverage, so it didn't get the

kind of coverage that the initial publishing did. So also in that ten year span

before it got retracted, there was a celebrity that I'm guessing people your age

would have no reason to know, but her name is Jenny McCarthy. She was married to Jim Carrey. I feel like that's the most

famous thing about her. She wrote a whole book about

her child who has autism and she really leaned into this

vaccines cause autism thing. So it became in the

public awareness at a little higher level than

just a research paper might have otherwise. So that happened. Um, and so we saw some articles like this coming out after

the retraction. So this is from 2011. So this definitely got

a lot of coverage in Science magazines

and science spheres. I don't think it got

a lot of coverage in the actual public facing

non science media. This is from a British

medical journal, like the British

medical journal. It's kind of the equivalent of Jama on the British

side of things. The Journal of American Medical Association would

be our equivalent. Um, but is the general public reading the British medical

journal on a regular basis? Not really. There

wasn't a lot of coverage in the

public facing news. And just a little

quote from that. It's intensely science is intensely skeptical about

the possibility of error, but totally trusting about

the possibility of fraud. So it was kind of an

interesting case study in how topics become controversial

and what gets pushed out to the public versus what

the scientists are seeing, you know, in reading different periodicals and

different sources. So where we land on the vaccines

and autism conclusions, there's a big body of

research because again, this conversation has been

happening for decades. We've got lots and

lots of studies. None of them show a

compelling evidence for a link between

vaccines and autism. There's been a huge investment

of money and resources over decades of people trying to see if

there's a link there. We haven't found one. There are several twin studies

that suggest that there's a large genetic

component to autism. There are some studies that

indicate maybe there's some interaction

between environmental and the genetics playing

a role in autism. That's maybe a little bit outside of my scope

of expertise, but you could go look up

those research articles if that's a topic that's

of interest to you. Um, and so this is an example of this

could be an example of what you might do if you're not an expert in a field

and you're seeing things online or in the news or wherever you're wondering

what the deal is. I always recommend to people to go to the peer

reviewed literature, go to the science literature

and see what you can find. If it's a topic that's

not something you're already deep into or reading

about or know a lot about, I think it's always good to

start with review articles. There'll be journal

articles that say they are review papers

right in the title. It'll be something something colon a review of

whatever topic. Review papers are

really nice because it's the authors haven't

published original research. They're pulling

everything we know from all the other published

research on that topic. Review articles are really

good starting point. Um, so if you hadn't

been in this class and heard these lectures

and just heard that there might be some connection

between vaccines and autism, you could go find some

review papers where they're pulling together all the

data from different studies about whether or not there's

a link between vaccines and autism and they'll give you all the data in nice

easy to read tables, and then you can go

back and look at those individual

articles as you want. Um we always try to go back

to the peer reviewed data, and I do that pretty

regularly when I'm seeing things in the news

or on social media. Even if the science is a

little bit beyond you, you can usually read the

abstract to the paper, read some of the conclusions, look at some of the data

tables and figures and get the gist of what the important takeaways

from that paper are. That's mercury and

a little tangent about the MMR vaccine. The other neurotoxin

heavy metal that we want to talk about is lead. This is an important neurotoxin, and it's something that

environmental exposure happens on a somewhat

regular basis in this country and in

other parts of the world. So we're going to get

into some of that. I talked previously. I guess it would have been

in the intro unit when we were talking about

environmental justice briefly. I gave you the example of the water crisis that

happened in Flint Michigan about a decade ago where they switched part of the

city's water source, and that new water source

that they were using had different

chemical composition and slightly different pH, and it led to reactions between the water and the

lead in the pipe, lots of lead was leeching

into the water system. Um, and actually, they just stopped in all areas of Flint

that were affected by that, they just stopped the city

is the day that I mean just stopped distributing

free bottled water to residents a

couple of years ago, this has been dragging

on a long time. I think for the last two,

three years, at least, the water in Flint has been

passing safety checks. So whatever level of lead

there is in the water is below the threshold that's considered

acceptable or unsafe. But there's a big public

trust situation now. So a lot of people

are still relying on bottled water because they

don't trust the city. They don't believe

that the city's giving them accurate

information. The lead levels in the water. So they probably have a

permanent or very long term public trust

situation happening now. Another case study like

that or another situation where lead contamination has been an issue for

residents in an area. This is in Indiana. I put the URL to more info at the bottom there in case later when you're

looking at the slides, you want to go read a

little bit more about this. But there were people

in a town in Indiana a few years ago where

they were informed that the lead levels in their yards. That's what the sign in

the picture here is about, in the soil in their

yards were many, many times higher than the EPA considers

safe or acceptable. And so one of the short

term ways to deal with that is basically

they told people don't touch the dirt,

don't go in the grass, don't play in the

grass, which isn't really that practical, um, so this was an apartment

in an apartment complex. That's where this picture comes from and what the linked

article here is about. And this big apartment

complex was actually built in an EPA superfund site that was associated with lead

smelters and lead refining. There was lots of lead activity

happening on this site. It was an EPA superfund

cleanup site and then they built an

apartment complex there, you know about EPA superfund sites from

your assignment, right? This article is about

how everyone was pointing fingers and

they were trying to figure out who dropped

the ball on this. How was an apartment complex

allowed to be built on this superfund site

that clearly wasn't cleaned up well enough for

people to be living there. Um, so another example of lead exposure in a day to day people's living space in addition to the Flint

Michigan situation. We do we get exposed to lead? Where is lead? What's

the deal with lead? Lead, we've had lots of different human exposure

routes over the years and we've changed what we

put lead in or what we use lead for in some cases

to minimize some of these. Lead used to be added to

gasoline because it helped prevent wear in engines and

helped engine performance. A long time ago there

used to be lead gas. Um, we phased that out in

this country starting in the early 70s and in the 90s, the Clean Air Act band led

for any on road vehicles. Partially because of air

and soil lead levels and partially because

leaded fuel isn't great for the type of

car engines we have now. As the car technology changed, that lead additive became

less useful over time. As of a few years ago, there were still a handful of countries using lead

in gas and I haven't followed up to see if in the last couple of years

anything's changed there, there were a small number of countries that still

have leaded gas. I think in this country, again, I haven't checked up on this in the

last two years. I think there are still

some very small airplanes that don't use jet fuel

but use a leaded fuel. But again, I'm not sure

that info might be a little bit out of

date in my brain. We used to have lead in some of the paint that we

used in households and toys and products you

would be in contact with in your day to day life. You put lead in paint,

it dries faster. It lasts longer, it's more

durable on the walls, looks nicer for a

longer period of time, and is a little more

moisture resistant. Houses before the 70s when

lead and paint was banned, well sometimes still

have lead paint on the walls or if you're in an older house and it's like

people have painted and then painted another layer and then painted another layer

over the years. If you chip down to

the older layers, sometimes there's leaded paint. A house I used to

live in Minneapolis had a layer of lead paint on the exterior of the garage

under another layer of paint. So we're not that many decades past lead and paint

that it's not an issue. It just depends on when

when a structure was built. Then old TVs used to have

lead behind the glass, screens cell phones used to sometimes have a coating of lead in some of the components. There've been herbal

remedies with lead in them. Of course, there

are leaded pipes through the 20th century and still in use in a

lot of structures. That's what happened

in Flint Michigan. Um, and lead is malleable, so it's really

good for plumbing. There was usually lead

in the solder that connects copper pipes

and pipe joints. So it was definitely used a

lot in plumbing applications, and there used to be, toys that had lead

paint on them. So if you go to thrift

stores and antique stores, sometimes you see weird old toys and they have those

stickers on them that say, don't give this to a kid.

It's for display only. That's what that's about. We've had lead in lots in

lots of stuff over the years, but we've tried to

eliminate those over time. But because buildings we live

in aren't all brand new, sometimes we still have lead

exposure routes through places we live and pipes and

paint and things like that. Um, and then of course,

we have lead smelters. That apartment complex in

Indiana that I showed you a picture of was built on a site where there had

been lead smelters. That's why it was an

EPA superfund site, pre apartment complex. Smeelting is where

you take a metal from the ore that's

actually mined out of the ground and produce the actual usable metal from

that ore. You mine the lead, you're separating that from

the ore and refining it into whatever lead

products it's going to be. Um, Today, again, we're not putting

lead in as many things. We've eliminated it from as

many things as possible. I think there's still lead in

certain types of batteries. Car batteries have lead in

them, if I'm not mistaken, and some roofing products and radiation shielding

and things like that. Like that little apron they

put over you at the dentist, the little heavy apron that protect you from the X

rays at the dentist, which I think also

came up last time. I don't know why that keeps

coming up in my mind, that's heavy because

it has lead in it. It's a radiation shield, but that's sealed in whatever the plastic outside

of the apron is made up so you're

not actually getting exposed to the lead. The map here is showing lead smelting sites and

population at risk. So it's a heat map kind of map, the bigger the dot is,

the more population, the higher the population

at risk there. So we don't have a

lot of lead smelting, as you can see

happening in the US. Canada doesn't really

have anything going on. You can see where

populations at risk living near lead smelters

are on this map. This is showing elevated

blood lead levels. That's what the EBLL there

is, this is in Michigan, this is just one dataset I

found going into the 20 teens. We're looking at kids less

than 6-years-old here. Um and so the two

different lines, the two different colors are related to how high that

elevated blood lead levels. So all the kids in

this dataset have higher than you would consider acceptable blood lead levels, and the red group, the lower line that's kind of

a red maroon color here has a higher blood lead level

than the orange group, so you can see this

one's 5 micrograms per deciliter and

this one's over ten. So we're looking at the

late 90s into the 2010. So you can see that

both of these are downward trending over time. So as we got the lead out of

more of our household items, newer builds are going to have pipes without lead in them. We're going to paint

without lead in it. We're only a couple decades past lead being banned in paint

when this dataset starts. But over time, we have seen really nice decreases in

children's blood lead levels. So this is something

we've been slowly working on for decades in this country and it

seems to be helping. So what does lead do to us? We know it's a neurotoxin. It interferes with a lot of

different organ processes. It can be toxic to organs, it interferes with our

nervous system and it is a developmental

neurotoxin. So it's especially

dangerous for children. It impacts the development of

the central nervous system. If you get exposures in early childhood

or during childhood, it can cause learning

and behavior disorders. Here we're looking at data from a study that began in 1979. This is an old paper, but it had really nice figures that were easy to easy to

digest and look at. I'm keeping it even

though it's old paper. This was a study where

they started in 1979, and they followed the

same kids until 1999. This is a longitudinal

long term study. We're looking at the

same people over a couple of decades here. Here, as you see in

the key at the top, we're looking at PBB, which is lead levels, PB is the chemical symbol for lead lead and

then B for blood. Excuse me. So here we've got

prenatal blood lead levels, that's the black bars. And then you've got

average childhood levels, the symbols are hard to tell

apart here on the screen, and then at 78 months. Those are the different

categories here. 78 months is 6.5-years-old ish. And so those are the different groups that we're looking at, and the SRD B on the vertical. On the Y axis here, that's self report of

delinquent behavior. Not loving the

delinquent terminology, but this is a study from a

long time ago and that would not have been frowned upon

as a way to phrase it. And so we're looking

at self reported or parent reported levels

of problematic behavior, I guess, would be the

way to say it based on categories of how much

lead is in the blood. We see a difference here, in the high lead level kids. They seem to have higher, self reported

delinquent behavior as compared to the group

with the lowest levels. They did find that there was a statistically significant

correlation with problematic childhood

behavior in the higher led groups than

the lower lead groups. Again, this is another

oldie but a goodie, so it looks low resin strange. But this was a study where they were again looking

at school children, they're looking at behaviors. Now they're drilling

down a little bit into specific behaviors,

distractable, disorganized. They had a list of

specific behaviors that you can see

along the X here, not persistent seems

like that's hard to give up on stuff easily. That seems a little

hard to judge in a kid. Are they dependent as opposed

to being independent? Are they hyper? Are

they impulsive? Do they get frustrated? Do they daydream? It seems like a mean thing to

judge about kids. Can they follow simple

directions and sequences? As someone with ADHD, I'm feeling there's a lot of similar traits in ADHD folks in these things that

they're assessing here and low overall functioning. Here they were

taking tooth samples where it just basically take a really not that greedy

file and slough off a little bit of the

exterior tooth material and you can measure

lead levels that way. This isn't blood lead levels. These data were reported by the teachers observing

the kids in the classroom. So they were asking

the teachers, do you see these

behaviors in this kid? Does this kid show

these behaviors? We should acknowledge

that there may be and probably is some bias here. If there's bias on the part of the teachers about

different kids' behaviors, whatever the bias the

teachers holding would be present in this dataset, but we're going to take

this with a grain of salt. But if we look at so they're

classing one through six, six is the highest

tooth lead level. One is the lowest, and so that's how each clump of bars goes 1-6. We can see there's a

pretty clear trend in the distractable in the

not persistent and actually everything on the

left here shows a trend or the lower lead kids

have lower ratings and, you know, it's not perfect, but that's the general trend

we're seeing here. Actually, in all of these, that's how the general

trend seems to go. We're seeing higher metrics for the daydreaming one is a little less obvious what's

going on there. We're seeing higher on

each of these metrics for the high lead level kids. This is from a study in the 90s where they looked at

infant IQ scores. I'm not I don't know the details of how you measure

the IQ of an infant, but they're looking at umbilical

cord blood lead levels. When the baby was born, taking a little sample of

the umbilical cord blood and then later when the

baby's a little older, they're measuring the

intelligence of the babies. I haven't thought of an

unintelligent baby seems sadder than the thought of

an unintelligent adult. At this moment. I

don't know why. Here we have high, medium

and low lead groups. That's what the

different lines are. The black circle is

the low led group and the open circle or white circle is the

high lead group. You see we have a difference in infant intelligence scores or IQ scores here that also

correlates with level. There are lots of

studies like this. What they're measuring

is a little different, how problematic or solid

the way they measure it. Like, are we just asking the

teachers what they think? Are we actually testing kids in various skills and abilities? What they're measuring varies. But in most of these studies, if not all of I

mean, I've looked at every single study, but

all the ones I've seen, there is a correlation

between lead level in a child and some kind of developmental or

intelligence milestones. We know that lead is

a real problem if kids are getting

exposed to it in terms of their development,

their mental abilities. Um, so what do we do with that? We know as a society, again, there's lots of examples

and case studies and data that shows us that lower income families are disproportionately

more exposed to lead, at least in this country. We populations of people who are living in older buildings. Oftentimes older

rental buildings that maybe aren't kept

up the same way a person would keep up their own

house if they owned it in terms of doing lead remediation on old

layers of paint. If the paints peeling up and old layers of paint are

exposed that are from, you know, the 70s and prior,

there could be lead in that. And so when you're

living in older housing that's maintained by a landlord, you're kind of at the mercy

of what the landlord feels like keeping up with in terms of the pipes and

the paint and such. Um, we know that red

lining in cities where certain neighborhoods have

been set aside to have different standards for home

loans and home ownership, so in Minneapolis and lots of other cities

around the country, there's been this

historical relationship between lower income

neighborhoods, people being prevented

from getting home loans, so they're stuck in

a cycle and then they're getting more exposed

to things like lead. It's an uncomfortable reality, but the data are

pretty clear on this. There's no real easy answer. Building codes have been

shifting over time and landlords are being forced to

improve their structures. In some cases, that's going

to help a bit if we have more regulation

around inspections and upkeep and things like that. I we do have a lead contamination

Control Act from the 80s in this country which

authorized the CDC to help develop childhood lead

poisoning prevention programs, educating the public

about testing for lead around where they live, testing kids routinely for

their lead blood lead levels. That's a standard. If

you take little kids to the doctor at a couple of different ages when

they're small, they do a little

finger prick and see what the kids'

lead levels are. We've made some progress on

the public health front. The EPA proposed a new rule a couple of years ago for nationwide replacement

of all lead pipes. Um, so that's been phased out their use over time, but

in older structures, there are still lead pipes

and there's been nothing, forcing people to change that. We have water quality standards, so you test the water that's

coming through the pipes. Um So this new rule says

that cities would have to replace all their

lead pipes within a decade if this

goes into effect. Um People are worried

about funding, where's the money going

to come from to make everybody do that or how are

we going to enforce that? I'm assuming nothing

with this is going to move forward under

the current administration, but this proposal

is sitting there. So maybe whoever

whoever comes in next, um, will move this forward. I'm guessing this

is just going to be sat on in the meantime. We do have some proposals, hopefully forcing some of these changes around

lead exposure, especially with pipes

and paint and such. Hopefully, things will continue to go in the direction

they're going, um, with respect to childhood lead blood

levels going down. Um, so we're going to

shift gears a bit, although not entirely

because with lead smelting and burning coal, we're putting mercury

into the environment, so those do relate

to air pollution. We haven't been

specifically talking about them as air pollutants. We're going to switch

over and we're going to talk about

air pollution. We're talking about gases or particulates

that are added to the atmosphere that can have various effects depending on which pollutants

we're talking about. I have a couple of chime ins about air pollution and

then we'll get into it. Okay, as has become

our standard, we'll do a little word cloud for what air pollutants

you're familiar with. Are you from the readings or just things

you've heard about? This one's going up slow. Are people, Googling

or a balloons or oh All right. There's about

ten people out there who haven't Last couple people. Okay. All right. Okay. We got a lot

of carbon dioxide and carbon and carbon monoxide. A lot of carbon monoxide. Oh, I guess it's

case sensitive, huh? Okay. It's kind of a bummer. Smoke, smog, ozone, lead. The number five. I'm not sure what that was connected

to. Fossil fuels. I don't know what PM two is. Factor. Asbestos. Okay. Cool. And then we've got one more. This one's kind of we're

gonna talk about this one. This is just kind of

a pre quiz question before we've talked about

the topic, just to see. What you know about ozone. So if you don't know this one, it's obviously totally fine, we're gonna talk about

it in a few minutes. All right, see where

we're at here. So which of the following

is true about ozone? Is it gonna do the weird I

no. Okay. The text is fine. It's just that one

question that had the funky HTML down here. Um so there's more than

one correct answer here. So the first one is correct. So A was correct, high up in the atmosphere in the

stratosphere, it's good. It protects us from UV rays. Yep. And at ground level, it's considered a pollutant. That is also true. So the two

in the middle are not true. So with ozone, high up

in the stratosphere, it's good down

here where we are. It's a pollutant. And so we're

going to talk about that. In a bit here. Okay. There are quite a few different types

of air pollutants, of course. This is a big category, we're just going to talk

about a few of them as examples or key air

pollutants to think about. One key distinction that's important when

you're talking about air pollutants is whether something's a primary or

a secondary pollutant. A primary pollutant is something that's emitted in a

form that causes harm, that is a pollutant. It's something being emitted, being put out into

the air that is a toxicant or harmful in some way. In some cases though, the thing being emitted. Picture whatever's coming out of the smokestack from a factory is a generic example

of air pollution being put into the environment. Sometimes the thing that's being emitted isn't

considered a pollutant. It's not harmful,

it's not toxic, it's not really a problem. But obviously, there's other

stuff in the atmosphere. There's all kinds of molecules of all kinds of things

in the atmosphere. If it's going through

a chemical reaction in the air that

forms a pollutant, then we refer to that as

a secondary pollutant. A secondary pollutant

is something that in and of itself being emitted

into the atmosphere, it's not a problem, but it

reacts with other things in the atmosphere and

creates a pollutant. So that's the secondary. So in the US, we have

the Clean Air Act. We've had the Clean Air

Act for a long time. We've had it since the 60s. There have been major

amendments to it in the 70s in the 90s and one just

a few years ago, they made a batch of

amendments to it in 2022. So we've had a few times

when it's been updated and more things have

been added or more um, more rain given to

the EPA to control or regulate air pollutants depending on which amendments

we're talking about. The Clean Air Act funds

research on air pollution, it sets standards for what are acceptable and

unacceptable levels of different pollutants, standards for what to do about

air pollution, basically. The EPA is in charge of that. It also establishes

limits for how much of specific pollutants can be

put into the atmosphere, what amount of emissions are acceptable for various

categories of pollutants. What's an acceptable level of something to have in

the air and what can be added on an annual basis

pollutant by pollutant. It also allows people to sue parties that violate the

Clean Air Act regulations. The way it's set up is

that states are supposed to do the monitoring and

set the regulations. Minnesota has a group that does the monitoring and sets

our Minnesota regulations. Then the states need to get

approval from the EPA at the federal level for their plan and the way they're going

to regulate things. An individual state sets up

their plan and how they're going to implement the

plan and then they send out to the

EPA for approval. They can't just say,

we're not going to allow more than X amount

of this pollutant. They actually have to have

an implementation plan or they'll get in

trouble with the EPA. If the EPA doesn't think the

state's plan is adequate, they can change it

themselves or they can take over basically

regulation of it themselves. The EPA can go so far as to withhold federal

funding for things like big transportation projects if the states aren't in compliance

with the Clean Air Act, that's how that works. Um, and here we have the key elements of

the Clean Air Act. These are the cornerstones

of the Clean Air Act. It's meant to reduce

outdoor concentrations of pollutants that cause smog, haze, acid rain, et cetera, reduce emissions of toxic

air pollutants and phase out the use of chemicals that destroy the

stratospheric ozone. So we're going to

look at some of these in a bit more detail, including talking about ozone, which relates to that chime

in question that we just did. With respect to the

second key element, reducing emissions of

various air pollutants, this is the list of the six

critical air pollutants that the Clean Air Act is

meant to control emissions of. There are these six

categories or types of pollutants that this act is meant to be keeping

under control. The first one is

carbon monoxide, which I think I mentioned

briefly before. It's a gas that's produced

primarily by burning fuel. I think I gave that

to you as an example. CO is an example

of a neurotoxin. Vehicles and engines account for about 80% of the carbon

monoxide emissions that are happening

in this country. This is mostly a vehicle issue. There's also some that comes

from industrial processes and things burning waste, things that involve large

fires and things like that, burning stuff produces

carbon monoxide. In addition to acting

as a neurotoxin, which is why I

mentioned it before, it actually binds to hemoglobin

in our red blood cells. The hemoglobin is what carries

oxygen around our body, from our lungs to various

parts of our body. So if you get carbon

monoxide poisoning, part of the issue is that

it can deprive our cells, deprive us of oxygen. Um, so carbon monoxide, sulfur dioxide is a

gas that results from burning coal in

industrial processes and for coal fired power plants. A lot of air pollutants come from coal fired power plants. Um, so the sulfur in the coal reacts with

oxygen to form SO two. You don't need to know the chemical

abbreviations for these. On a test, I would always put the actual words with something like this with

SO two in parentheses. I just I put the chemical

formulas up there because that's how my brain tends to be used to seeing them. But if you're not a

chemistry person, don't worry about that. You don't have to know that

sulfur dioxide is SO two. Um, so once the AO two is

out in the atmosphere, it can react to form SO three, another oxygen can

hang on there. Then we have sulfur trioxide, and that reacts with water

and you get sulfuric acid. Sulfuric acid is one of the big things that we worry about with respect to acid rain. Sulfur dioxide

leads to acid rain. We'll talk more about

that in a few minutes. Nitrogen dioxide also

contributes to acid rain. It's also a component of smog. You get it from

combustion engines. Most of the nitrogen dioxide is coming from vehicle engines. Then we have tropospheric ozone, that's ground level ozone. That's what our chime

in question. One of the items was about that. Ozone is 03, if it's easier

to remember that way, we'll talk about that as a

pollutant. In a bit here. Then the Clean Air Act also regulates particulate

matter as a category. We're talking about solid

particles or liquid droplets in some cases that can be

in the atmosphere and damage respiratory tissues

when we inhale them. Smog is usually a mix of different chemical pollutants

and particulate matter. Soot and dust, things like that would be particulate matter. Then we've talked about lead already just a few minutes

ago as a heavy metal. It is also considered an air pollutant under

the Clean Air Act. So sulfur dioxide, one of the six pollutants on that

list that we just looked at it reacts to form other chemicals that come down in precipitation as

acid rain or acid snow. It's not always

rain. Generally, we just call it acid deposition, but I feel like acid

rain is the term people tend to hear in the

non science sphere. In the 90s, there

was an amendment to the Clean Air Act that established

the acid rain program. That's what it was

called at the time. And so when setting regulations for sulfur dioxide

emissions for polluting, um, they set up a CAP

and trade system. Cap and trade is one

option for how you regulate how much of a pollutant people are

allowed to emit. We'll circle back to

this when we talk about climate change

and carbon dioxide. We'll talk about cap

and trade again. But the way cap and

trade works is it forces polluting groups to

either reduce how much output, how much emission of something

they're putting out there, which could mean changing

their machinery, changing their

technology, changing something about their operation. Um, which can be

expensive upfront. If they can't do that because they can't afford to do that

or don't want to do that, then they have to buy

emissions permits from other groups within

the same sector who are polluting less. The CAP part is you set

limits for everybody in this industry is allowed

to emit a maximum of this amount of sulfur dioxide in this case, as an example. And if you emit more than

that, you have to pay for it. Basically, you have to

buy permits from someone else who emitted less than

they were allowed to. Um, so that's how

cap and trade works. So we set that up for

SO two emissions. How much could be

emitted by power plants, electric plants or power

plants would then get permits for how much SO two

they're allowed to put out. So there's a financial

incentive for releasing less SO two

because then you'll have leftover permits

that you didn't use you can sell to someone

else for a profit. So it creates a financial

incentive for emitting less and a financial disincentive for emitting more

because you have to find someone else that you

can buy extra permits from. There have also been nitrogen

dioxide emissions standards set under this

acid rain program, but the compliance part isn't quite as strict as the

SO two cap and trade, so I don't actually

know how much people are following that in

various industries. With respect to the

third key element on that slide that listed

the key elements of the Clean Air Act

was phasing out the use of chemicals that

destroy stratospheric ozone. Ozone down here in the

troposphere where we are. This is showing us

the different layers. The troposphere is the part

of the atmosphere we're in. It's the lower part

that's closest to Earth. We don't want ozone

down here with us, it acts as a pollutant. I upsets people's asthma and can have other

potential toxic effects. It's part of smog, basically. The next layer out is the stratosphere where

this red line is. That's ozone layer

is that you've probably heard of that's out in the stratosphere.

We want that there. That's where ozone

is supposed to be. That helps protect us from

some of the sun's UVrays. These are just showing

you the different layers of our atmosphere. Down here in the troposphere, that's where our weather is

happening. It's where we are. Um, so the deal with

tropospheric ozone, pollutant ozone, as I said, it can irritate people's asthma, but also ozone is 03, it's three oxygen molecules or atoms together in

a molecule, and That's not a very stable form depending on the

environmental conditions to have three oxygens together, very readily one of them

will split off and then you'll have a molecule of

oh two, which is oxygen. Great. No problem

with that. But then that other lonely oxygen who's floating around

by himself will react with lots of other things in

the air and that can cause other chemicals

because you're having new molecules form with

those free floating oxygens, other chemicals that can cause all kinds of respiratory

problems for people. But the stratosphere is where

we want the ozone layer. So the deal with stratospheric ozone when we're thinking about air pollutants, is that we used pretty heavily use these chemicals called

chlorofluorocarbons or CFCs, if you've heard of

that in short form. They're still used to

some extent in coolants. It's a component of freon, so the stuff that makes

your refrigerator cold, coolants like that still

have some CFCs in them. But it used to be also

used pretty heavily in basically any

aerosol type spray can. I had CFCs as a propellant. That's what makes

the good spray. We figured out other chemical

ways to do that now, modern aerosol cans

don't have CFCs. But for a long time,

all aerosol cans, various propellants, things

like that also had CFCs. CFCs used to be in

a lot of things. CFCs are very stable. They don't go through a lot

of stable meaning they don't easily react with other

things in the atmosphere. But up in the stratosphere, the solar radiation is

really intense and that will break the bonds

in CFC molecules and you get chlorine atoms

being released and those can split ozone, 03 molecules. You don't really need to have a deep understanding of the

chemistry happening there. But when we get CFCs up

in the stratosphere, they mess up the 03

molecules in the ozone, CFCs had a negative impact on the good ozone layer out in the stratosphere that we want. In the 80s, researchers found

that the ozone levels over Antarctica were nearly half of what they'd been

the previous decade. In the late 70s, they

started monitoring, measuring ozone layers and they were finding in the 80s

that over Antarctica, particularly, there was this

hole in the ozone layer. You've heard about the

hole in the ozone layer, that's when we figured it

out in the early to mid 80s. So we started eliminating

CFCs slowly over in the 80s. I don't think we were really

cutting down on CFCs yet. Over the course of

the 90s, early 2000s, CFCs were getting phased out

and eliminated from things. Again, they're still

used in a few things, but that's pretty

regulated, and we're using much fewer CFCs than we used to. Over time, over the

last couple of decades, we've seen that the

hole in the ozone over the Antarctic has shrunk

pretty considerably. This is a really nice example of we figured out

something was a problem. We fixed the regulations. Look, we can see

that it's working. We don't get a lot of clear Ws in environmental science,

but this has been one. Um, so I just pulled this from there's a NASA webpage where they're taking

NASA and NOAA. That's the Oceanic and

Atmospheric Association. They have a website set up

where you can go and look at their annual what's going on with the ozone layer updates. And there's some videos and sort of little animated models of a

hole in the ozone. So if this is something you're interested in you can go to that website and

see the updates. Um, I'm assuming

this Paul Newman, Chief Scientist for Earth

Science is that NASA is not the salad dressing

and Cookies Paul Newman. I think that Paul Newman

is actually dead, so they're definitely

not the same person. That would be crazy lower, though, if they were

the same person, right? So we've done well

by the ozone layer. We've eliminated

CFCs not entirely, but pretty close to entirely, and we've actually seen

really great progress in the hole in the

stratospheric ozone layer. This shows a dataset

that we have about what's going on with that

ozone layer on the vertical, on the Y, we have

total ozone um, don't worry about the DU units. That's a weird unit used

when measuring the amount of gas in a vertical column of the atmosphere. Let's

not get into that. But the different color

dots on this graph represent data from

different instruments. The Hale and the

Toms and the OMI, those are just

different instruments that we're measuring the data. They're compiling data

from multiple instruments. We see a clear downward

trend over time here. So this starts at 1960, and so from 1960 to about 1990, we're seeing a clear

downward trend. So this is where

we're using CFCs intensely and we're seeing

that whole neozone forming, and we didn't really

figure out it was a problem until

somewhere around here. And then we're working

on eliminating CFCs. The data is getting a little

scattered in recent years, but we see that I think

we're going to see when we have about another

decade worth of data on here that it's going

to be going back up. The hole isn't gone, but it's a lot smaller than it used to be. The expectation, last

time I looked at people's projections

was that by about 2070, we'll be back to where we were before we started screwing

up the ozone layer. So we're headed in

the right direction. Um, obviously, this is the issue that needs to be addressed at the

international level. We can't just look at

what the US is doing. Air pollution issues

span large areas. There are some air

pollution issues that are somewhat localized

or regionalized, but stratospheric ozone is

certainly one that needs international buy in for

us to have made progress. The Montreal protocol

is a treaty that 196 countries

signed onto back in the 80s agreeing to

cut CFC production in half by the end of the 90s, basically, there have been several follow up

agreements since then, making the reductions

greater and greater and advancing the

timetables for reductions. Obviously, we're

going to get into greenhouse gases a lot more when we get to our

climate change unit. We're going to do a

deeper dive on what the deal is with

greenhouse gases with respect to climate change. But since we're talking

about the Clean Air Act, greenhouse gases are

relevant here because they are regulated under

the Clean Air Act, they are considered

air pollutants. Greenhouse gases are gases that absorb infrared

radiation released from the surface of the Earth. Basically heat coming off

of the Earth gets absorbed. Some of it just goes

off into space, some of it gets absorbed by

greenhouse gases and then gets re emitted back toward

the surface of the Earth. If you've learned about

greenhouse gases, sometimes people

like to say it's like a little blanket around the Earth that helps

keep it warmer. Which is a natural normal system that this planet has always had. Greenhouse gases are an important component

of the atmosphere because they help our

planet from being too cold to sustain life. They basically prevent some of that heat from

being lost to space, they bounce it back

towards Earth. Without that, it would be

too cold for all of us to be here on this planet. They

have a warming effect. The issue with respect to climate change is that

we're putting out a lot more greenhouse gases than would naturally

be out there, so we're increasing that

blanket insulating effect. We'll get into that more when we talk about climate change. Um, so we're talking

about carbon dioxide, water vapor, um, and methane. We'll get into the

specific greenhouse gases when we get to that unit. In 2007, we had a court

case in Massachusetts, Massachusetts versus the EPA, and that's where

the Supreme Court found that greenhouse gases are a threat to human health and therefore could be regulated

under the Clean Air Act. In the early 2000s, we started regulating greenhouse gases

under the Clean Air Act. And since then,

we've seen things like different standards

for fuel economy in cars, different standards about the emissions that can come out of our vehicles with respect

to greenhouse gases. Um, there is a permit

system for anything that's going to create large new

sources of greenhouse gases. We have new regulations around fossil fuel power plants

and pollution standards, just a couple of years ago, um, there were another set of amendments made to the Clean

Air Act where they added more tax incentives and grants to help companies and people

meet emissions standards, so to help make it a little

less expensive for people to update technology and emit

fewer greenhouse gases. Again, we'll talk more about greenhouse gases later

on in the semester, but they are regulated

under the Clean Air Act. So in the little bit

of time we have left, let's talk acid rain or acid deposition as it's slightly more technically called because it's not always rain. It can be fog or snow. So it's pretty self

explanatory with the name. We're talking about the

deposition of something acidic or acid

forming pollutants coming from the atmosphere

down to the Earth's surface. This is another border

crossing issue. It's an international

multi regional at least pollution issue. I certainly crosses borders. So The deal with acid rain, this is kind of it in a

nutshell in this diagram. So we have from pollution

emitting sources, we've got a little cartoon

factory over here on the left. We've got truck over here as examples of where our

pollution's coming from. So as was in that list of air pollutants

several slides ago, sulfur dioxide and

nitrogen oxide, also nitrogen dioxide, um,

would fall under this. Sometimes when you

hear people talk about acid rain and acid deposition

and air pollution, you hear people

talk about NOx and sock because it's

not just SO two, it can be SO and

then other numbers. So people will put an X here like they did with

the nitrogen oxide. And OX, meaning it could

be various numbers, so it could be oxide,

it could be dioxide. So if you hear people

talking about NOx and sock, they're just talking

about nitrogen and sulfur oxides sort

of generically. You can think of them as nox and ox, it's easier for

you to remember. I don't care if you know the actual chemical

symbols here. These things are

being emitted into the atmosphere and

they're mixing with water in the atmosphere. That's what these chemical

equations are showing us plus h2o, that's water. And then we get the

formation of acids. We get nitric acid from the nox, and we get sulfuric acid from the sox that's

what's coming down in some cases in particulates

and in precipitation. Nitrogen and sulfur

oxides being put into the atmosphere

combining with water to make actual liquid acids

that are then raining down. That's why it's

called acid rain. With respect to acid deposition, we can get Acids changing what's going on in the top soil at the soil level. Those acids can go through

chemical reactions that are leeching or changing

nutrients in the soil. In some cases, there

are acids causing toxic metals to convert

into forms that are more soluble and can get

into the water system then. That's something that we

see happen with acid rain. We see acid deposition

directly affecting plants, altering the pH of lakes and rivers and streams

and water systems. Then you may have

heard of acid rain. Uh, eroding stones, and so

there have been lots of, you know, photographic

studies of, you know, famous statues or buildings in Europe over time and

what they looked like a long time ago and

what they look like now because acid rain is physically physically affecting

some of our structures. Yeah. So in the US, we're doing quite a bit better. If we track data over time

with respect to acid rain. The Clean Air Act

has helped a lot. I feel like acid rain was

a huge problem in, like, 80s 90s and creeping a little

bit into this century, but we've got a better

handle on it now. We've had that cap

and trade system for the sulfur oxides, nitrogen oxides

or dioxide levels of emissions have been

lowered via EPA regulations. We saw in a pretty

obvious clear way what was going on

with acid rain. I took us a while to

get a handle on how to actually implement

the regulations, but we've seen a really big

reduction in acid rain. This is another win in terms of US regulations that we've done a pretty good

job regulating. Acid rain related emissions. In countries that are on a slightly different

timeline than us in terms of when

they industrialized at a really heavy level, some other countries are in their phase of acid

rain getting worse now. If they industrialize a

little later than us, they're at a different

place on the timeline in terms of lots of industrial, um, lots of industrial

processes coming up to a really high level

and getting a lot of industry and then

creating a lot of acid rain and then

figuring out it's a problem and then working

on your regulation. We're on the we've got a better handle on it

side of our timeline. Other countries aren't

quite where we are yet in terms of they're having their acid rain crises now. Also countries that

would be more dependent on coal because they

have more coal where they are would also be having more acid rain

problems than we are. But we're in a pretty good place and a lot of other

countries that are in the same place on their timeline are also in a pretty good place. Now hopefully not

just us, the US, but hopefully there's

some groundwork laid for the countries who are

dealing with acid rain now. They can see how other countries have regulated it

and got it under control so they can

possibly do the same. Um, I'm blowing off indoor air pollution here in lecture just for time's sake. This slide is just in

here as a note to read. One of the readings in the less intense stuff is about indoor air pollution

specifically, so it's not a terribly

long section. But be familiar with the common or big indoor

air pollutants that are on the list here. Just know what these are, know which air pollutants

are the ones to be most concerned about with respect to indoor air pollution. So this is just a little, I'm not going to have

time to talk about this, but go learn about this on your own note for when

you're studying later. Next up, we're going to start

talking about pesticides, but given that we

have 5 minutes left, it doesn't really make much

sense to launch into that. Next week, we're going to talk about several

different pesticides. We'll talk about

endocrine disruptors, and that's what we're mostly

going to do next week.

Category, realizing

I didn't hit record. Okay, recording now. So we'll talk about a couple of pesticides that are neurotoxins. Then we're going to get

into endocrine disruption, what that is, what that

means categorically. And then we also have

a couple of pesticides we're going to talk

about as examples of endocrine disruptors and

that'll slush into Thursday. So we'll still be

talking about endocrine disrupting pesticides

on Thursday. Um, and then after Thursday, of course, we have spring break. And then when we come

back from spring break, we'll have that

Tuesday's class to review whatever topics you want me to review from our Tx unit. So on Thursday, like I did, towards the end

of the last unit, I'll give you one of

those surveys that lists all the topics

and you can check off which ones you want

me to review and we'll review the most

popular from that list. So we'll do that when we

come back after break, probably start a little

bit of our food unit, and then we'll have the exam

the Thursday after break. So that's where we're headed, just to keep everybody on track here since we're all

thinking about spring break. Um, Okay. Pesticides. Um, most

pesticides of concern, this is painting

with a broad brush, do act as neurotoxins, some more seriously than others. There are also lots of pesticides that act as

endocrine disruptors. So act as both. These aren't I said before with the different

categories of toxicants. Every toxicant doesn't fit

neatly into just one category. So act across

multiple categories. Um, so I'm going to start by talking about a few

pesticides that are both neurotoxins and

endogrin disruptors. When we talk about

pesticides in general here, but we'll get into what

endocrine disruptors are A. Before we launch

into pesticides, I'm going to hop

over to chime in. I've only got a few chime

in questions for you today. I think I've just got

three, we'll go through those if I can get

my cursor free here. And if you're just walking in, this is the first

chime in question, so you didn't miss anything yet. We talked about the

precautionary principle maybe maybe two lectures ago. What's up? This

unit's short, yeah. And the next one is short, too. You know, it feels like we just took a test 5 minutes ago, and we're talking about

the next one already. Alright, I'm gonna

leave it open, but let's see where we're at. So which of these

is an example of the precautionary

principle? Do deal. Um, yeah, most of

you got this one. So the precautionary principle, cautions in the name

there is when if we have some evidence indicating that something is toxic or

problematic or harmful, this doesn't only

apply to toxins. You can apply a precautionary

principle to other things. But we're thinking about

it with respect to toxins. If we have some evidence

that it's harmful, we ban it, regulate it,

reduce our use of it. What that looks like can vary, just to be on the safe side, and then we keep reassessing

as we get more evidence. Sometimes we do that in this

country with some toxicants, sometimes we go the other route and wait for large

bodies of evidence. Oh, we talked about

ozone last time. I don't know. I

never thought about it. That's a good

question, though. Go look at the etymology

of troposphere. That would make sense.

Okay. So which type of ozone is the bad one? And, looks like the

majority of you got that. Tropospheric ozone troposphere

is down here where we are. This is where we don't want

ozone, ozone is oh three. It's a pollutant down here. Stratospheric ozone,

that's the good kind of ozone out in the

stratosphere where we want it. We talked about that hole in the stratospheric ozone layer last time. That feels

like forever ago. That was just last time,

right? Now, this next one is a pre question because we haven't

talked about this yet, but you have done readings

that cover this topic, so see how you feel about this, but we're gonna talk

about this today. So if you're not sure, don't feel bad or anything. Not that you should

ever feel bad about not being sure

about the answer to a question. Okay. I'm not going to

hit the bar graph thing because then I think we'll have trouble seeing that in the table all in

one screen here. When it comes to LD 50s and we're going to

talk about this today, the LD 50 is the dose that kills 50% of subjects in

whatever the study is. And so here we're looking

for the lowest number, so the correct answer

here is caffeine. Caffeine is the most toxic by weight of the things

listed in this study. When it comes to

LC 50s or LD 50s, lower equals more toxic always. But Okay, so let's hop over and start

talking about pesticides. So pesticide

categorically, means anything that's designed to

kill some kind of a pest. Usually, I think in sort

of lay person speak, when we hear the term pesticide, we're often thinking

insecticide, but these other types of isds also would fall

under pesticides. So herbicide, a weed killer would also qualify

as a pesticide. The pests in this

case are just weeds, plants instead of

some kind of animal. So fungicides that kill

mold are also pesticides. So we're not exclusively

talking insecticides, even if that's what

comes to mind. So starting out with a

little study example of how we've looked at pesticide

toxicity in humans. Obviously, this is one

of those things like we've talked about when we

talked about carcinogens, where you can't just

intentionally expose people to a potential

toxicant to see what happens, but we do have studies

like this one, excuse me, where populations

that we know have had exposures at a higher level than people living

in other places, you can find match

populations in two places and look at

different outcomes. So that's the kind

study that we have for a lot of these pesticides when

it comes to human data. So, um, we're talking about a

study done on a population. This black and white map was kind of the

best I could find out here in the western

coast of Mexico in Sonora. That's the state within Mexico

that we're talking about. Um, and going back to 50s, 60s in that area, there were people living in

the Aki Valley who kind of divided philosophically on what should go on with

their agriculture. So there was a group of

people that wanted to adopt more modern

farming techniques. We'll talk about, you know, the Green Revolution

and farming techniques and stuff when we get

to our food unit. But that would include the

use of chemical pesticides, the use of tractors,

things like that. Other people wanting to continue more traditional farming

and ranching practices. So there was a little bit of a physical separation

of people who wanted to do the different

kinds of agriculture, and this Yaqui Valley is one of the largest agricultural

areas in Mexico. So we kind of had this

population that sorted itself out into two

different types of agricultural practices, and they were a little

bit physically divided. So in the 80s and 90s, people started doing

research studies, looking at physical symptoms, developmental

symptoms in people in these two sub populations

in this valley. So they were looking at people where they were being

exposed to more pesticides, people living not that far away that were being potentially exposed to less

fewer pesticides. So those are the two groups, um, and so they were matched pretty well because they were

living not that far away from one another

and the people in the foothills population

were doing the more, um, traditional

to their culture, farming methods, lower tech, low or no pesticide exposure. Then we had people in the valley population

that were using pesticides in a pretty

widespread manner. That's the setup for this study. There have been several studies done over the years

on these populations. But one we're looking at Performing tests and by tests, I mean, written tests, verbal tests, not experimenting on four and 5-year-old children. So things like

what's listed here. Physical stamina tests, coordination tests,

testing their memory, having them draw certain things, which is not an uncommon way to measure developmental

milestones in little kids. You ask them to draw a

picture of a person. And how much like a

person does it look? They're developmental

markers for where kids should be

with tasks like that. These are the things that they were measuring

with this group of four and 5-year-old kiddos

from these two populations. They also surveyed parents in the two populations about

their kids development, about the pregnancies,

about what their kids were like when they were babies,

things along those lines. And they found that parents

in the valley population, the pesticide exposed

population reported higher, um, they called them

problem pregnancies, and that includes things like miscarriages,

premature births, um, babies that didn't survive long after birth,

things along those lines. We found that the

pesticide population has higher instances

of that situation. They also found

that the children in the foothill population, that's the low or

no pesticide group, perform better at the

tasks listed here. Memory, some of the physical

tasks, and the drawing task. And so this is from that study. So these are different

sets of drawings. The text is kind of small

under the figures here. And so in the upper figure, we're looking at

drawings of a person. That's what the kids are

asked to do, draw a person. The top picture is from the four year olds

and the bottom picture is from the 5-year-old. That's the difference between

the two pictures here. And then you can see up at

the top, they're labeled. So the two pictures on

the left are from kids in the foothill, no

pesticide population. And the drawings from

the kids on the right are from the pesticide

exposed population. There's a pretty

staggering difference in the four year olds of what their drawings

of people look like. Um, it's also pretty different

than the five year olds. Although the five

year olds will look a little more like

objects in some cases. And again, this is

a really common developmental test

given to little kids. Kind of like a common test for elderly people that

they're testing for dementia is to have

them draw a clock. There are kind of standards

that we can measure. Developmentally. Whoops. That one has a video on it.

This is a case study of developmental

differences that we see in kids in populations

that are exposed to relatively high levels of pesticides and it was multiple

different pesticides. It wasn't one

particular pesticide that these people were

using or exposed to. Exposed to pesticide versus

not exposed to pesticide. Remember, we talked last time about developmental

neurotoxins. Neurotoxins or anything that

affects the nervous system. Some of them are

worse in terms of affecting babies and little children through

their development. We talked about that

a bit last time. So one really famous Ooh, the audio is not coming

through. Well, that's okay. So this is an old video from the 40s of basically a

DDT truck going around, fogging everything and

everyone in sight. DDT, we've talked about before. It's a really, really effective pesticide against lots

of different insects. It's particularly effective

against mosquitoes. But it can work for lots

of different insects. So we used to use this

really heavily because it's so effective at killing insects. So here's some nun

fogging a little kid. I would kill lice, things like that that would

be in your hair. Just an idea of how ubiquitous the use was back in the day. That was from the 40s. You don't need to know

the chemical structure of DDT, but as usual, I put it there in case you're a chemistry person

and that helps you. Here's the long name of DDT. You absolutely don't

need to know that. But if you're wondering why

we call it DDT, there you go. Um, the deal with DDT, it's toxic to insects. That's obviously why we

use it as a pesticide. It opens up the sodium

channels in their neurons, it causes their neurons to fire in a crazy, unregulated way. That's how it kills the insects, the acute toxicity to humans

is actually quite low. If that wasn't the

case, we wouldn't have been fogging people

with it back in the day because they would have seen

acute immediate effects and realized it was poisonous. If you get exposed

to DDT one time, it's not going to have

any acute effects on you. But that's how it works

as an insecticide. It's a very effective

insecticide. Circling back before

we talk more about DDT to that topic that was on

your chime in question, one of the important tenets of toxicology is foundational

things to understand in toxicology is how we

measure how toxic something is and

you may have heard people say that dose makes the poison line before when people are talking

about how poisonous or how toxic something is. We often will measure the LD 50, LD stands for a lethal dose, the 50 stands for 50%. The LD 50 is the dose of

whatever the thing is you're studying that kills half

the treated organisms in a controlled study. We're talking about

doing studies with lab animals or lab

organisms depending on what you're studying and what it's pesticide

for in this case, if we're thinking

about pesticides. You also can have I don't

have a slide of it, but you also sometimes

will see LC 50s. It'll be a C here instead of a D. That means lethal

concentration. If you're talking about

something like studying fish and something in

the water with them, that would be an LC 50 because you're not literally

dosing the fish, you're just putting it in the

environment with the fish. LD 50s would be something that you're treating orally or you're physically applying to

the body of the organism. So sometimes they'll

say oral LD 50, meaning they were actually

given an oral dose, sometimes it'll be

a dermal LD 50, meaning exposed on the

surface of the body. So depending on what

data you're looking at, you might have a slightly

different kind of LD 50. But here's some

examples of Rat LD 50s. Sucrose, which is

just table sugar. Oh, like regular sugar

you'd put in your coffee. Here's the LD 50. It's 29,000, almost 30,000

milligrams/kilogram. That's milligrams of

sugar per kilogram of the rat's body weight is usually how you see

those represented. If we're talking

about oral doses. For nicotine, it's

obviously much lower. We would expect

nicotine to be more toxic to a rat than sugar. Cyanide, more toxic

than nicotine. Um, and so cyanide

has a really low relatively low to these

other things, LD 50. So it only takes 6.4

milligrams/kilogram of rat weight to kill half the

rats in a study population. And so that's how you

read these LD 50s. The lower the number is, the smaller amount of that toxicant it takes to

kill half the population. Lower means more toxic, more lethal when you're talking

about LD 50s or LC 50s. Um, I didn't look at the

bar graph on that question, so I don't know how many

of you got that one right, but I know you read

a little bit about LD 50s or lethal doses. Here's just clarifying

what that's about. We always look at

LD 50s when we're comparing or thinking about

how toxic something is. I don't know why

this is scooch so far down to the bottom

of the slide here. Here's a table from an

old from an old book actually about what we're

looking about the relationship between toxicity and

safety of pesticides. We've got different pesticides

listed at the left here, DDT is among them, and then we've got some

other pesticides here. Then we've got oral and

dermal LD 50 values. So we've got both of those. Um, and what kind of exposures, ingestion, ingestion

and occupational. These are human LD 50s based on, you know, accidental or

occupational exposures. Um And then you've got severity of

occupational poisoning over here on the right. This is just one

example of comparing LD 50s of different

toxicans again, the lower the number,

the more toxic it is. You can see that for humans, DDT has a relatively high value. If we're comparing

them to each other, some of these other

pesticides are much more toxic to

humans than DDT is, um, I know that lindane is one that's used for head lice and scabs

and things like that. I'm not sure specifically off the top of my head what some of these other

pesticides are. But DDT not super toxic to humans in the grand

scheme of things. So the deal with DDT

and we've talked about this a little bit before because I

was talking about, we've talked about it

once when we talked about a DDT mosquito study

when we were talking about evolution in populations and DDT resistant mosquitoes. We talked about the eggshell

thinning issue when I was talking about the Endangered

Species Act and bald eagles. We've talked before

about the fact that DDT can thin the eggshells

of predatory birds. It also acts as an

endocrine disruptor, so we'll circle back to what those mean in a little bit here. Later today, we'll talk about what endocrine disruptors are, it's neurotoxic and

endocrine disrupting. Um, and so it's not acutely

very toxic to humans, but we do have some

indication that it can have these other non acute

human toxicity effects. Um, we have some evidence of it being carcinogenic

in non human animals. So it's not a very

high ranking on that EPA scheme of carcinogens, but it does it

does have ranking. I don't remember what letter

off the top of my head. We know that it acts as an estrogenic

endocrine disruptor. Again, we'll come back to endocrine disruption

in a minute. Um, and some of these

other effects have to do with it being an

endgrin disruptor. In humans, there's some

evidence that DDT exposure, for example, can

make breastfeeding, people have a shorter

duration of lactation, meaning they can't maintain

breastfeeding for as long, for example, increased chance of problematic pregnancies

or preterm delivery. Um, change in semen quality, that would be things

like how well the semen is the

sperm or swimming, things like that, and

change in menstrual cycles. All these things at

the bottom of the list relate to it being an

endocrine disruptor. While it's not that

acutely toxic to humans, it's not exactly

completely safe either. We know it has some of these

longer term effects if people are getting exposed to it at significant levels

for periods of time. This we've talked a little bit about before the effect

of DDT on birds. We used to use DDT pretty heavily to control

Dutch elm disease. Maybe if we still had DDT around the Dutch elm disease

wouldn't have gotten as out of

control as it has. We've lost most

of our elm trees. But in addition

to it doing great at keeping Dutch elm disease

in trees under control, people started noticing

really big die offs of Robins and some of their

songbird populations. There were studies showing

really high DDT levels really high DDT levels in earthworms and some other

non insect organisms. Way back in the 40s and 50s, people were seeing the predatory bird populations declining, although they hadn't figured out what was causing that yet. There have been lots of

studies over the years of eggs in museum collections. So it's pretty common for

natural history museums to have collections of bird eggs are shown

in the picture here. You can see one of these

eggs has writing on it. So that's in a

museum collection. So they blow out the insides

and just keep the egg shell. You can do studies of how

thick the egg shells are in a collection of

some species eggs across different decades. So people started figuring out the egg shell

thickness situation. Um there have been

studies where birds were fed DDT or

metabolites of DDT. Sometimes it's not exactly DDT. It's one of the

breakdown products that DDT turns into a body. There have been

controlled studies that actually show the eggshells thinning when birds are

given DDT on purpose. It took across a span of decades people started figuring

out what was going on with DDT with respect to birds and the eggshell

thinning situation. Here's a different example

that's not bald eagle, so this is an

American kestrel um, our littlest raptor in

this part of the world. Here we're looking

at shell thickness, um, across the X axis, we're looking at DDE

residues in the eggs. DDE is an isomer of DDT, isomers are just different

different shapes of the same molecule, basically. So it's a molecule that's made

up of all the same atoms, but you can have a couple of

different varieties of what that actual molecule will

look like or be shaped like. For our purposes, we can

just pretend that it's DDT. It's just an isomer of DDT, you can see that at

lower DDE or DDT levels, the egg shells are thicker. The higher the DDE

residues in the eggs are, the thinner the shells are is essentially

the takeum there, a pretty clear

linear relationship. Um, so we have a very solid handle on

what DDT does to birds. We know it has

endocrine disrupting effects in humans

and other mammals, um, and so what have we

been doing with that? So because we figured

out DDT was problematic a pretty long time

ago relative to some of the other pesticides that we're going to talk about. We started restricting

it back in the 70s in this country, and then it was banned

like mid 70s in the US, early to mid 70s. So it's been banned in the

US for quite some time. Here we've seen the

positive bounce back in bird populations

after banning DDT and we're pretty far past the time where it's been

banned in this country. So some of those human

effects were less worried about because we're

not using it anymore. So there's a DDT metabolite, that's the red line that

we're mainly looking at here. Um, PCBs. The manufacturer them

was banned back in the 70s and PBDE that's the

other line on this graph, was more of a slow phase out. Here we're looking at data

from Sweden where they also banned DDT back in the 70s. The trajectory for the US wouldn't look that

different here. We're looking at levels of these three

different chemicals, although DDT, the red line

is the one of interest. We're looking at the

concentration of that in human breast milk here from

the 70s into about 2000. And so we can see that

since banning it, restricting it and banning it, the amount of DT metabolites found in human breast

milk has gone way down, along with PCBs are kind of

showing that same trend. And then with the PBDEs, which I know a

little less about, I'm guessing they didn't

go into use until later, so we saw a spike

and then there was some regulation and those levels were starting to go down. It's kind of hard to say

what's going on here until we had some more data to add

to the end of that graph. With respect to DDT, we're seeing a lot less of it in human breast milk post banning,

which makes sense, right? We've seen recovery

of bird populations. So here's another graph

about the bald eagle. We've talked about the

bald eagle before. So we're looking at pairs in the lower 48 states of the US. Back in the 60s, we were way way way down here in

probably the double digits, and now we're up into the

thousands these days. I just saw a pair of bald

eagles by my house yesterday, and I'm really hoping they stick around and make a nest

because that would be cool. Here we have the

Eastern Brown pelican. Fish eating bird, pelicans. I think everybody knows

what pelican is right? Again, similar trajectory from the 70s through the late 90s, breeding pairs or this is nests, which is essentially

measuring the same thing as breeding pairs, um, peregrine falcon,

another raptor, again, increase in

breeding pairs. This is the trajectory

that we see for predatory birds

after we banned DDT. They were all in trouble and had relatively low populations, but they managed to come back. After we ban DDT. It seems pretty straightforward

in some ways DDT, harmful to wildlife,

harmful to humans, although again,

not acutely toxic. We've banned DDT use

in this country. The other side of that coin

to think about is that DDT is probably the

most effective thing to use against mosquitoes

and there are places in the world where malaria is

still a very real concern. There are still lots of cases

of malaria in some places. There are still places where DDT is used as vector control

as mosquito control. Um, where malaria

is more of concern. So we don't have really a malaria issue here in

the United States. We do have that genus of

mosquitoes that carry malaria, but we don't tend to have

malaria issues here in the US, but there are places

where there are a lot of anophalese mosquitoes and a

lot of malaria going around. In the 90s in South Africa, they discontinued DDT use for the reasons we've

been talking about, and then they had a

big malaria outbreak, just as one example. We've had DDT banned

since the early 70s, for the most part in the US. We kept manufacturing it to export it to other

countries until the mid 80s, which feels a

little shady to me, we said it was too

dangerous for us to use, but we were okay selling it to other countries for a while. I guess that tracks with

what the US is about, right? Um, as of the early 2000s, the Stockholm convention, which is an international treaty, says that DDT can be used as vector control for

mosquitoes if there aren't good alternatives

available wherever we're talking about

controlling malaria. In some cases, people

have shifted to other things that don't

work quite as well as DDT for the mosquitoes but do a decent enough job that we don't have to worry about

DDTs toxic effects. There are still cases where it's being found to be used in small places illegally in

agricultural settings. So Um, so that's where

we're at with DDT. We don't use it in this country. There are still places

where we're using it to help keep malaria down, and there's still little

pockets of, you know, people using DDT for agriculture if they can

get their hands on it. One example of a neurotoxic and endocrine

disrupting pesticide. Another example is lopiifos. Um, and chloropropos is

also an insecticide. We've had it since the

60s in this country. It's a very effective

insecticide, works differently than DDT. Copifos actually blocks

an enzyme that's involved in the

messaging system, the signaling

between nerve cells, it works a little differently. This one used to be used

in household foggers, those cans where you

press a button and it fogs your whole room or your whole apartment

with insecticide, roach traps, things like that. Old plant collars used to

have chloropiifos in them, then it's also used, of course, for agriculture as

an insecticide. We know and we've known

for quite a long time that lots of people have

chloropiifos in us, we found in surveys

of people's urine, urine collection

and checking for metabolites of chloropifo

not Clopifos itself, but something that your

body brings it down into, you know that people would

have had lopifos in. Um, um, in 82% of

subjects in one case, um, in studies that have

looked at blood samples from parents and newborns

at the time of birth, at the time of delivery,

looking at blood samples, 64-70% of people had chloropipos

metabolites in them. There have been studies

that look specifically at umbilical cord. Blood CPF is an abbreviation

for chloropiifos. Um, so we're finding

it in cord blood, we're finding it in the babies, we're finding it in the parents, and there is a negative

correlation with lopipos in umbilical cord

blood and birth weight, meaning babies that have

more lopifo in them have lower birth weights and other things have been

tested semen kids urine. Meconium is, um, is a newborn

baby's first poop or two? It's like the poop the baby's

making inside its body when it's still

inside the uterus. So the baby's not eating yet. It was living off

the umbilical cord. Meconium is just weird

newborn baby poop, if you're not familiar

with that term. There have been lots of

studies where we're looking at uh, human bodies, various things that we

excrete from our bodies, and there is lopipos metabolites found in them in lots of people. I guess it's the take

home message from this bullet list of stuff. What is lopipos

doing to mammals? It's an insecticide, that's what we're intending

to use it on. What effect does it

have on mammals? We often have rat

study data, um, if we don't have human

data about pesticides. This is a set of

data from a study done on newborn

rats, neonatal rats. It says up in the title

there above the figure. Baby rats, and they gave

them nicotine or chlopiphas. Those are the two

treatment groups here. Obviously, they also

had control groups. They looked at the change in DNA synthesis

compared to control. How much lower DNA synthesis, making new DNA was

than the controls. This tells us about

DNA production in cells of a newborn

because there's a lot of physical development

cell growth, cell division happening

in the brain of a newborn human or rat. That tells us it's basically a proxy for measuring

neural development. The three categories we have here are brainstem

in the black bars. That's the part of

your brain that does basic vital life functions like breathing and your heart beating and things like that. Then we have the forebrain in the I don't know if we call them that the speckled

black and white bars. That's the biggest

part of your brain that does most of your braining. Then we have the cerebellum

and the white bars. That's regulation of your

coordination and movement and posture and balance and

physicality, things like that. Here we're looking again

at nicotine versus lopiipos and this tells us that chloropiipos is decreasing

neural development in newborn rat brains. We're seeing nicotine obviously

also is having an effect. Maybe a bigger effect here. But in all cases, we're seeing a significant difference

from the control. The way this particular

figure works is we're looking at

change from control. So rather than having a

set of bars for nicotine, a set of bars for chloropiipos, and a set of bars

for the control, and then you have to

compare them to each other. Um, here we're looking at essentially how far lower

than the control is. So if it was the

same as the control, it would be at zero. These are all lower

than the control. We're going negative

as we go down here. The nicotine is way lower and

the lopiipos is lower also. We've seen figures before like this from research

studies where they put little asterisks

above or in this case, it would be below the bars that are significantly

different. These folks didn't

do it that way, but they told us

their P values here. So when we're looking at a

research study, obviously, we can just eyeball what the differences are that these are all lower than the control. But you want to think about how different from the control it is till we consider

it a real difference. By chance, maybe

some numbers were a little bit different

from the control, but how much different from the control does it need

to be before we say, well, this biologically

actually means something. That's what we call

statistical significance in the sciences. Without this obviously

isn't a stats course, so we're not going

to go way into um but whatever statistical

tests we did here, um, it doesn't say what

stats tests they used, we get a P value, which is a measure of

statistical significance. Usually in the life sciences, we use P of 0.05 as our cutoff. So anything below 0.05, we would consider a

significant difference. These are all way below 0.05, the're 0.0 oh one. These are all significantly

different from the control. You'll often see the little asterisk used to indicate that, but sometimes you've

got to actually look at the P values here. We know that

chloropropos decreases neural development in

newborn rat brains. Also, we know that nicotine

is really bad for baby rats, so don't give your

baby rats nicotine. Um, here we're looking

at a behavior study. So it's not the most intuitive

title for a figure here. Prenatal means rats

exposed when they're still in utero in the

uterus of the mom at. We're looking at lopifos

and we're looking at its effects on spontaneous

alternation latency. Um, so spontaneous alternation is a behavioral test of

memory and spatial learning. It's a maze task, basically. You don't need to learn the

term spontaneous alternation. This figure just has

an obnoxious title, so I'm trying to make

it less obnoxious. So we're looking at

how well they do on sort of a memory behavior

task in a maze situations. So you get a maze shaped

like a Y or a T or like a plus with different arms of the maze that

the rats can go in. And you put them in there

and you see if they can remember which arm

or part of the maze they've already been to and explore other places

for some reward. It's essentially

what we're doing. Latency is just a measure of time spent in

part of the maze. How long does it take

them to realize, hey, there's nothing

good in this part? Maybe I should go check

out some other part. That's essentially

what we're doing here. On the X axis, we have trials. They did five trials, five rounds of this maze task. And the ideas, we're looking at how well

the rats can learn, which part of the maze

has good stuff in it. I don't remember in

this study if it was a food reward

or something else. And over time, you would expect that the rats would

get better at figuring out and remembering

which part of the maze had good stuff and go

there more efficiently, how much time they

spent exploring, how much time they

spend wandering through the dead end parts of

the maze that are no good and figuring out they

should go somewhere else. So that's the task that

we're talking about. Then on the why there's

seconds per trial. How long were they spending

doing these things? Um, then the zero,

one, and five, the different lines

on the graph are telling us the lopiipos doses. The boxes that are filled in,

that's the control group, and you can see that they got better um at exploring

that maze over time. Then we've got the two

different lopiifos groups here. What they found was that

the lopiifos exposed rats. Here we're looking at um, rats whose pregnant

mother was exposed and then these babies

were born and then they were tested when they

got old enough to be tested. They showed decreased latency. Decreased time spent exploring thoroughly the different

parts of the maze. Basically, they

showed hyperactivity. So it was more impulsive

kind of running around quickly into the

different parts of the maze rather than

taking their time, checking this part, checking this part,

checking this part. Um, in the end, they learned the task as well as

the control group. They all ended up

in the same place, but they were very impulsive

and hyperactive relative to the control group in the

beginning of the studies. So, just one example of a study. There are lots of

different studies like this about lopifos about lorepiifos affecting focus on a task when they're trying

to learn something. You can draw correlation between some of the

behaviors they described in these Clopifo rats to ADHD

behaviors in human kids, hard time focusing,

hyperactivity, things like that. Here is a little bit of info about a Cloppos study

done with zebrafish, so it's not just mammals

that we're looking at the effects of

chloropropos on. We know it has some effect on DNA synthesis in rat brains, which is affecting

neural development. We know there's a correlation

with hyperactivity in baby rats that were

exposed in utero. Um, here they exposed

zebrafish embryos, fish eggs, essentially, fertilized

fish eggs to lopifos and then

grew those fish up. Zebrafish only take a

few months to grow up. Then when they were adults, they tested them in a choice

chamber like this. Here we're looking

at a fish tank. We're looking at the overhead

view of the fish tank, and they've got a chamber on the left and a

chamber on the right, and they start them

in the middle and they have little sliding doors. So the fish starts out in the middle and

then they can open these doors to let

the fish go back and forth to the different sides. This was a study of

how well the fish can escape or avoid danger. Can they learn which side

of the tank is safe and which side of the

tank is less safe? The researchers

decide which one's going to be the safe side. And if the fish goes that way, they're left alone and

nothing happens to them, they're just hanging

out in the tank. If they go to the danger

side or the wrong side, they this feels

like a mean study, but they have these sliding

partitions in the tank. The danger side in this

case is they start sliding the partitions from either end to give the fish less and

less space in the tank. So it's the trash compactor in Star Wars or something like

that, closing in on them. You can do studies like

this where you show them a picture of a predator

or something else. That's what they used as

the danger signal was like, Oh, no, your tanks

getting smaller. That stresses the fish out. They do that to the fish, then they test it again

to see if the fish can remember which sides the safe side and which

sides the danger side. Can the fish learn that task? Um, so that's what they did.

Here are their findings. So here again, we've

got our friends the asterisks for

statistical significance, and you'll often

see one asterisk, meaning it's less than

0.05 the P value, and then sometimes you get a

double or triple asterisk. If it's way less than 0.05, it gets really

statistically significant. Here we're looking at

different copiipas doses, control, and then

two different doses, a lower dose and a higher dose, and we're looking at the percent of times the fish was correct, meaning it went

to the safe side. It was able to learn

which side was the safe side and go

to the safe side. The control fish, you know, 60 I don't know, three, 4% of them learned this

task successfully. So they're still fish.

They're not going to be the most awesome

learners ever, right? So our control group is 60

something percent of the fish, and then it's significantly lower for the two

Carpiopos groups. So they were not as able

to learn that task. So it's a little

simpler dataset to look at the rat latency figure. We know there's negative

effects of Cloppos on rats, zebrafish. What do we

have about people? These data show us

the proportion of 36 month olds because

for some reason we always got to talk about babies in months instead of years, 36 months, that's three

year olds who scored in what's considered the clinical

problem range on the CBCL, which is a standard study. We've got groups of three

year olds who were exposed to either high levels or

low levels of ropifos. This obviously is not an

experiment where we on purpose expose three

year olds to ropifos. Again, this is based on environmental exposure

wherever these folks lived. Um, the CBCL is just a child behavior checklist so the parents fill it out like, yes, I see my kid do this,

yes, my kid does this. That's the checklist. It's a long 100 item list of behaviors reported

by the parents. They even conveniently put

their N up at the top. That's their sample size, there were 228 kids

in this study. These were parent

reported behaviors, high exposure group,

low exposure group. And so we see a difference. I'm just eyeballing

the numbers right now, but we see a difference

in attention problems. ADHD problems seems like a

big brush to paint with. Um, PDD is it's a

developmental disorder. I can't remember what

the P stands for, but that has to do with behavioral

developmental disorders. Externalizing and

internalizing behavior is about harming self or others, is the kid doing things to

physically hurt itself? Are they hurting itself? That was a weird way

to say kid themselves. Sorry. Are they hurting others? Are they hurting themselves?

Externalizing would be hurting other

people or other kids. Um, I'm looking for, I was just looking for where

the Ps were on this graph. The right most column

then is our P values. Again, anything less than 0.05 would be

considered significant, the PDD problems, that's not a significant difference

between these groups. The attention problems are

significantly different. The ADHD stuff is

significantly different. The other ones aren't. Here's a set of data from kids here are more data

from the same study. Now we're looking at one, two, and three year olds again with high or low chloroprop exposure. And so you don't really

need to know these terms, but just so you know what

we're talking about here, this BCID two is a scale used to measure

infant development. And we've got things related

to mental development index. We've got things related to psychomotor

development index. We've got delays, mental

delays, psychomotor delays. Then we've got the three

different age groups here. Again, you can just

skim down some of these and look at

how the high and low exposures compare

to each other. We can look at the P values. It looks like some of the

psychomotor developments stuff here is significant

in 12 month old, but it's not significant

in the 2-year-old, so we're a little bit

all over the place. But we can see that some of

these categories do show significant differences between the different

lopipoEposure groups. We know that lopifos has developmental effects on kids if you're

getting exposed to lopiipos or potentially if your parent was exposed to lopifos while you

were in the womb, it looks like if we

skim through some of these that by 3-years-old significantly more

highly exposed children show developmental delays, I think we're trying to make

a general pattern here. It doesn't always show up as a difference in

the younger kids, but by the time we

get to 3-years-old, everything, well,

no, not the top one. Most things here

are significant. We have lots of studies

like this that correlate developmental effects and

kids and lopiifos exposure. So what do we do with that?

We have lab studies on rats, brain development

behavior, we have the fish lab studies

related to learning. We have some correlative

studies for humans, or there seems to be

a correlation between lopiphos exposure and

ADHD type of challenges, and we see that decreased mental development index

in lopipho exposed kids. Do we know for sure that lopipos

is causing those things? Not in all cases in the

lab studies with animals, we know because they

were lopipos exposed. In the human populations where they were

exposed to lopipos, we can't know 100%, whether it's only the lopipos

causing those things, could be other pesticides, could be other

environmental factors, it could be other

things going on there. You always want to

think about whether it's causaly or

just a correlation. Then remember we have our friend the precautionary principle. Um, that we talked about

a couple of lectures ago, if there's something

that might be harming us or the environment, precautionary principle tells us that we should take action, even if we don't

have a full picture in terms of scientific data. I would say DDT or banning of DDT leans to the side of the

precautionary principle. We had a lot of different

kinds of data and information about DDT at the

time that it was banned. But certainly,

we've learned a lot more about it since banning it, but we had enough

evidence to say, Hey, this seems to be causing a

problem in the environment and wildlife and in

humans, we banned it. Chloropiifos, we haven't

exactly gone in that direction. You know, we have

evidence to suggest that chloropropos is a problem. We have it across

multiple organisms. We've been a little bit

back and forth with lorepiifos over the decades

here, as you can see. Household use was phased

out more than 20 years ago, so it's not in flea

and tick collars and insecticides that you can buy to use around your

home and yard. That seemed like a pretty

easy thing to phase out. And often with these

agricultural pesticides that are also used

residentially, that's sort of the

first step is just phasing out regular people who aren't farming from

being able to use it. Um, and then in 2021, the EPA said they were

going to ban lopifos. They decided we have enough

evidence of it being harmful, of it being a toxicant, that it was dangerous

enough that they were going to ban it in agricultural practice

that was supposed to go into effect in

February of 2022. But then it was thrown

to the Court of Appeals, the eighth circuit,

specifically, the eighth circuits

where we are. That's this part of

the country that ended up getting

overturned in 2023. We never actually got to the

point where it got banned. I almost got baned and

then a court overturned. So we're still using Clopifos as an agricultural

insecticide in this country. It's back in limbo. The

EPA says they're going to take another run at it. So we'll see what

happens with that. We haven't banned Clopifos yet, but the EPA has

been working on it, and we'll just have

to see what happens. I'm assuming nothing will happen under the current

administration, but, you know, I don't know. So DDT, we leaned a little more toward the precautionary

principle, clopipos. We don't seem to be

taking that tack and we're still using it even though we have

a pretty good body of evidence that it's harmful. I mentioned that a

lot of pesticides, some are neurotoxins, some are

also endocrine disruptors, some are just

endocrine disruptors, but we have a lot of

pesticides that have some connection to

endocrine disruption. Endocrine disruptors

are chemicals that interfere with the

body's endocrine system, as the name implies, in some way and depending on how they act

and what they're doing, that can have

developmental effects, I can have reproductive effects, it can have

neurological effects. It can affect our immune system. There's a wide range of

substances that act as endocrine disruptors

and a pretty wide range of things they can do. Just a very little brief lesson in what the endocrine

system is and how it works. You have an idea of what

we're talking about. Your endocrine system is all your hormone secreting glands. And then the hormones

themselves would be considered part of this system, they regulate lots of different aspects of the

functions of our body. The hormones are the molecules

that are secreted by the glands and specific

to the endocrine system, hormones are molecules

that are secreted in one place and then have activity or action

in another place. The glands that are labeled here are the things

secreting the hormones, and then the hormones

move somewhere else via your bloodstream and actually

have action elsewhere. That's one of the hallmarks of a hormone. Hormones

are very potent. It takes a very

small concentration of a hormone to affect whatever tissue or

cells it's targeting. These are the components

of your endocrine system. We've got some glands in

our brain and then glands elsewhere in our body that

are producing hormones. So an endocrine disruptor

is something that affects endocrine system

signaling and that can happen in a few different

ways that are listed here. In the diagram, um, we've got the secreting cell, so that would be

the cell in one of those glands like

we're looking at here, maybe it's coming from

your thyroid, for example, is there secreting cells in your thyroid that are

making a hormone. The little blue dots here are the hormone

in this diagram. So a cell makes the hormone, secretes it, it goes

into your bloodstream, it moves to wherever it's going to interact

with target cells. The target cells are the

cells that are actually doing something in

response to that hormone. So the hormones are little

messenger molecules that control a lot of

our bodily functions. Again, it only takes a

very small amount of a hormone to have an effect. They're very potent

and they have specificity with

their receptor cells. Here we see these target cells that have little receptors on their exterior surface and the hormones fit in there like

a lock and key situation. So any old hormone wouldn't necessarily interact

with this target cell, only this particular hormone, whatever you want to imagine

this generic hormone as being would interact with

the receptors on this cell. There's specificity here. So I don't know, adrenaline could be an

example of a hormone, you're in a dangerous

or a scary situation. You're endocrine cells, you're secreting cells

secrete adrenaline, that moves through your blood to hormone receptors

on target cells. Target cells in your

heart that would increase your heart rate because you're in some dangerous situation. Target cells throughout

your body to increase blood flow to your vital organs and decrease

blood flow to your limbs. If you've ever been really scared and in a

dangerous situation, you might have that

thing where your limbs start to feel heavy

or numb or weird. It's because your

body is saying, send all the blood to our guts, protect our guts in case you're being mauled by a

bear or something. You have target cells in your

skin that make you sweat. There's all kinds of different target cells in

different parts of your body that would respond

to adrenaline as an example. So a disruptor then, an endocrine disruptor is something that

affects this system. That can happen by a substance

mimicking a hormone. We have this lock and key specificity on the target cells. If there's some other chemical that has a very similar

shape to the hormone, it might also fit with these receptors and interact

with the target cells. Even if your body's

not making and secreting much of

whatever this hormone is, there's some other

chemical that can get in there and interact

with these receptors and make the target cells react as though that hormone is present,

that would be a mimic. Um, there are chemicals

that can mess up these receptors on

the target cells so they don't have the right

shape or don't work anymore, so they can't interact, they can't receive the hormone. Sometimes that aspect of the

signaling gets messed up. Then there are endocrine

disruptors that actually affect what's going on at the

secreting cell site. In the gland itself, if there's a chemical

that messes up the production or

secretion of the hormone, maybe everything's fine about the target cells

and the receptors, but if there's not

hormone being produced, then that system is

going to be affected. There are a few

different ways that endocrine disruption can happen. So what evidence do we have just broadly for

endocrine disruption? Evidence that there are things

in the environment that we can be exposed

to that can have effects on our endocrine system. Then we'll get into actually specific

endocrine disruptors in a bit here or next time,

we'll see how it goes. We have there been a

bazillion studies over the years to use a

technical numerical term about sperm counts? Um, there's some evidence for localized reduction

in sperm counts in sperm producing individuals. There have been

some studies that show no decline or

no differences, a lot of different studies, and they're all over the place. It seems like there are geographic differences

sometimes in sperm counts, so it's a little

complicated to study. Some studies indicate that rural populations and

urban populations are showing differences

in sperm counts and it's not quite clear if that's related to

environmental exposures. If you're somewhere

rural, are you getting exposed to

different things? If you're somewhere rural

that's very agricultural, maybe you're getting

exposed to pesticides and other endocrine disruptors. You're getting exposed to

other things in urban places. It's a little

challenging to make any sweeping generalizations

about what's going on with with sperm counts, but we do have evidence from some studies that

some pesticides seem to have an impact

on sperm counts, other things that we look at in human populations with

various exposures to potential

endocrine disruptors. You can look at genital effects, increases in things

like testicular cancer, non descended testicles, meaning the testicles

are still up in the body and

haven't come down, um a urethra that

doesn't extend to the end of the penis that exits somewhere on the

side of the penis. There are lots of

studies where people have looked at genital

effects like that in populations that have

and haven't been exposed to different

endocine disceptors. Again, we're not talking

about experiments because we don't

experiment on humans, but if you find

populations of people that have exposures that

you know about occupationally or because

of where they live, you can look at some

of those features, things like instances

of breast cancer, infertility, early

onset of menstruation, meaning when a young woman gets her first period, things

along those lines. If you really zoom out and

look across all the studies, it can be a little

challenging to know what's causing some of these trends in different human

populations because again, it's not like there's a

population of humans that's getting exposed to one

thing and nothing else. There's lifestyle, there's diet, there's all these

different things that we're exposed

to depending on where we live and what

we do for a living and just our life. We know that

endocrine disruption is suspect in a lot of

these correlative studies, but we can't always say for sure what endocrine disruptor might

be causing these things. Often with endocrine disruption, we're looking at studies of lab animals because it

can be a little hard to get anything even remotely close to a controlled study

in human populations, of course, working

at lab animals where we can expose to specific

endocrine disruptors. We also have quite a bit of wildlife evidence for

endocrine disruption. In terms of specific case

studies and datasets, we're mostly going to look

at wildlife studies here. So our old friend DDT, again, DDT, neurotoxin, and

endocrine disruptor. I put the tiny URL here

that goes to a video if you want to look

at that later when you're studying or

just for funzies. I made that tiny URL

a long time ago. I hope it still works, but

the full link is down here. If you want to go

watch a YouTube video about how people

study this thing, Um, you can go watch

that video if you want. But here, we're thinking about

a lake called Lake Apopka, which is where this

red dot is in Florida, so not too far from, you know, Orlando and Disney

World and such. There was a pesticide spill of DDT at this location in 1980, there was a chemical

company that manufactured DDT that disposed improperly of large amounts

of it in this lake. Actually, I think it was

DDE with a isomer of DDT, but essentially similar thing. Um, so they dumped a bunch of DDT in a lake Lake

Apopka in Florida, and it's still a place

that's being studied, wildlife in this lake are still being studied

decades later. The DDT metabolite that's in

the lake now is fat soluble, so it gets into organisms. It hangs around for a long time. Remember, we've talked before

about DDT is something that biomagnifies up up

the food chain. Um, and so this

variant of DDT, DDE, which was on one of the other

graphs that we looked at, it actually binds to

estrogen receptors. So on target cells that would be undergoing some kind

of estrogenic activity, it can bind to those receptors, so it can act as

an estrogen mimic. It can also bind to

androgen receptors, um, and so it acts as an endocrine

disruptor in multiple ways. But in both Androgen and

estrogen receptor cells, it's affecting that

receptor situation and acting like a mimic. So here's some data from a study done quite a long time ago at

this lake comparing, here we're looking

at penis size of juvenile alligators in

this lake Lake Apopka and also another control lake

called Lake Woodruff that did not have a

DDT spill and is not connected to Lake Apopka in terms of the way

the water flows. So that's our control lake. So we've got two different lakes here, Apopka is the black one, Woodruff is the control lake, that's the stripy one here. I can't get my pointer

free. There we go. So we're looking at penis

length here in millimeters. Um, and we're looking at a diameter measurement and

a length measurement here. That's what the PL and the CDR. You see that in the description

down here at the bottom. We're seeing that in the control lake longer

juvenile penises, alligators and bigger around. Then this is another

example of the way. I don't know why we do

this so many ways that we show whether something's statistically

significant or not. Sometimes you get the asterisk. If you see the asterisk,

it's significant. Sometimes you get just a P value somewhere here down

in the description, we have P less than 0.05. Um, and when we're

looking at a graph like this where we're

comparing two categories, sometimes you'll see letters. So if they're given

different letters like this one's group A

and this one's group B, they're significantly

different from each other. If they were the same,

they would both have As. So I apologize on behalf

of science that we have so many different ways that

we represent significance, but just as a heads up when

you're looking at a graph. So these are significantly

different from each other. So significantly larger on both metrics in

the control lake, significantly smaller in the

lake that had the DDT spill. DDT mostly is acting like

an estrogen here and preventing binding

of testosterone to receptors where it would be. You see an increase in female hormone estrogen

effects and a decrease in the more male traits

androgen effects in populations of

alligators in this lake. This is just one example

people been studying alligators in this

lake for decades, but we see decrease in male hormone effects

and increase in female hormone effects

in this population. Males and females both

have estrogens and androgens in alligators

just at different levels. Another pesticide tributytin. This one is used to keep organisms off the

exterior of boats. That's its primary application. Um, so you take your

boat in a lake, you take it out and

you spray it down with tribultin to kill whatever's on the exterior of your boat, which is good for not

having to scrape things off your boat and good

for not moving organisms from one

lake to another. But it does act as an

endocrine disruptor. Here in studies of

tribultin and snails, there have been instances of female snails growing penises, which is called Imposex

in this type of organism. And so here's a

dataset about that. Here's one where you

have the asterisks denoting whether something is significantly different or not. SN is the abbreviation for TI. I guess we could find it up on the periodic

table there if you want. SN is TI. I don't know why

it's SN. As the abbreviation. Excuse me. So Tributal

tin actually breaks down. It's got tin in

part of the name. It actually breaks down

into tin over time. I feel like I've got

to catch of my throat, and I'm gonna stop

being able to talk. I'll either get it

together or we'll end. No, I think we're done. I can't I don't know

what happened there. I got a catch on

my throat, and I'm just done. We're close

enough to the end. Let's just be done. We'll

pick up here next time.

Okay, here we go. Still

teaching sitting down, still feels weird.

Rolling with it anyway. Um Okay, so last time we were talking

about endocrine disruptors, we talked about that broadly. What didn't really go over how the whole

endocrine system works, but the gist of what

your endocrine system is about and different ways that endocrine disruptors

can impact that system. We talked about DDT. I was starting to talk about

tributyltin and snails, and then I had that

weird thing where I started coughing and

couldn't talk anymore, so we bailed at that point. That's where we'll pick up today and then

we're going to talk about another pesticide that acts as an endocrine disruptor, atrazine, which you

already know about from your readings and doing that

atrazine debate assignment. We'll talk a bit about that. And then today this is our last chunk of toxicology

content before the exam, which is two weeks from today because we have

spring break next week. Today, we have another one of those surveys in place

of chiming in where all the topics are

listed and you can check the ones

that you want me to review when we get back

from spring break. I think I set that

to open at 10:30. If you're the person who can listen and do that at

the same time, go for it. Otherwise, I think I'm probably going to end a little early so you'll have time to sit here and finish it before you leave. I'm planning on making

it'll probably be close in length in terms

of number of questions. I might not be able to

squeak 50 questions out, but it'll probably be

40 something questions. It's worth the same

amount as the first exam. The first exam by amount

of content should have been worth a little more than

this exam in the food exam, but because people usually

do a little worse on the first exam than the others, we make that one equal to the smaller exams so

it's not as high stakes. Usually the score in the first

one is just a little lower because you're getting used to the kind exam

questions I ask, it'll be maybe a little bit

shorter but not way shorter. I don't want to make it too

much shorter because then every questions worth

more points and every question is higher stakes. Um, Okay, so last time

we talked about DDT, just as a little

wrap up refresher, this is what you

should know about DDT. We talked about the fact

that it bioaccumulates. We talked about the birds in

the eggshell thinning thing a couple of times this semester. We talked about

the fact that it's not acutely toxic to humans, but it does act as an

endocrine disruptor and it's something

that bioaccumulates. It's still definitely

of concern. We also talked about

how we measure toxicity in part of

that DDT conversation, although that applies

to any toxicants. Then we looked at

just a little bit of wildlife evidence for it acting as an

endocrine disruptor. That was the data that

I showed you about male alligator penis

size in a lake where there had been

a spill of DDE, which is a variant of DDT. For the purposes of study, you can think of it

as being basically the same thing as DDT, male alligators had shorter, smaller penises when they

were exposed to DDT, we know it acts as an

estrogenizing endocrine disruptor. That's what we talked

about last time with DDT. We didn't really get a chance

to wrap that up very well. I wanted to briefly mention that again just so now

you have the slide later as the nutshell

of what to know about DDT when you're

studying later. Then this is what I was

about to talk about last time when I lost my voice

toward the end of class. Tribuletin another pesticide. This one is an anti

fouling agent. That's how it's referred

to. It's something you can spray on the

exterior of boats. More commonly, it was put in paints that were used to

paint the exterior boats. The idea being prevent things from latching

on and living on the exterior of boats

or kill things that would be living on the

exterior of boats. Keeping your boat clean is

what this pesticide is about. This was a very, very widely used pesticide. It was banned quite a long

time ago and we'll talk about that in a couple

of minutes here. What we've seen as a

result of tributyl tin in water systems because

some of it would leech out of the paint and

off the exteriors of boats, is that if you look

at marine snails. We're talking mostly about

marine environments, salt water environments here. Uh, we were seeing this

condition known as Imposex. This is a term specific

to gastropods. This is a term that's

only used in gastropods. Gastropods being snails, slugs, and whelks, which are another

subcategory of snails. This is when an

organism develops sex organs in contrast to

what their genetic sex is. In this case, from tributltin you see female snails growing

penises and in some case, vast deepfrins and

other male sex tissues. So this is the opposite of DDT in terms of sex trait effects. With DDT, we saw male alligators

having smaller penises. Here we're seeing with

tributltin we're seeing female organisms developing male physical sex

characteristics. This is from a study where female snails were

experimentally exposed. This is in a lab situation. They did use environmentally

relevant concentrations, which I don't think

I've mentioned as a term or a phrase

before in this course. Maybe I have in passing. One thing when you're looking at tox studies to pay

attention to is what concentrations are being

tested in compared to what concentrations of something

would actually be found out in the real world. It's not uncommon for

lab studies to start out from a place of let's

use really high doses of whatever this toxican is that we're

testing just to see if it has the effect that

we think it might have. But then at some point, you want to get to a point where

you're saying, Okay, we know that this toxicant has this effect on this

organism in a lab setting, we use really high

concentrations just to see if it worked. Then you want to see follow

up studies where they're using environmentally

relevant concentrations, you would actually find

out in the world to see if that effect that

you measured with the high concentrations

is still happening. An example of that would

be if you've heard about reef safe sunscreens. There are certain chemicals in US sunscreens and sunscreens used in some

other parts of the world, too, um, where people

have been concerned about them killing corals and other organisms, but

primarily corals. And so now lots of sunscreens are marketed

as being reef safe, meaning they're not

using those particular UV filters or chemicals. But if you go look at the

studies that all that was based on, they

used really, really, really high concentrations in a lab setting of

those chemicals, and they did find that

it killed corals. But at environmentally

relevant concentrations, which are much lower, there really isn't any

impact on coral reefs. So the reef safe sunscreen

thing is kind of based on it's not

based on bad science. The science was fine, but it's kind of an extrapolation

of the science. It's sort of unrealistic. Climate change and other things are definitely more

of an impact for coral reefs than us being in

the water with sunscreens. But anyway, as an aside, if you're ever researching

a particular toxicant that you're interested

in or for future course, if you're going down this

route in your life, um, environmentally relevant

concentrations is always a thing to know whether you're

looking at a lab study where they're using really

high concentrations or whether you're

looking at a study where they're using

concentrations that would actually be found

out there in the world. In this case, they treated

female snails with tributytin at environmentally relevant

concentrations that had actually been measured

in aquatic systems. So the TBT abbreviation here. It's always so hard to

get my pointer going. That stands for tributytin and then of course, we

have a control group, which is in the light blue,

which is hard to see because it's just this tiny

little bar down here. On this particular

graph in this dataset, they have this VDSI which is their abbreviation for a

measure of the vas deferens. They had an index

that they were using. The vas deferens is a

tube that carries sperm. This is a male sex

trait that they were looking at after one month, pretty minimal there's

deference in the female snails. Then after two months, you

can see that it's quite high, and this is in a

meaningless unit. But you can see that there's

a really big difference between the treatment

and the control. And it took a couple of

months to take effect. Here we have our friends the asterisks telling us that this is a

significant difference. I think it would

be a pretty safe bet just from eyeballing how different these bars are to say this is statistically

significant. But we've got the asterisk

there telling us that it is. This is from the same study. Here we're looking at

that impo sex condition, females presenting with a penis, and we're looking at percent of the snails in the study

that showed that condition. Again, it doesn't look

that different from the previous graph,

the control group. There is an interestingly low

percent of the population that have imposex happening

regardless of tributyltin. There is just some amount

of that that happens with these marine snails without

pollutants being involved. But then we see a really high I'm looking at a weird angle 90 something percent imposex in the tributytin treated snails. So TributlTm was actually

banned globally. Not many things get flat

out banned globally, but this one did

a long time ago. It's been banned

for a long time. This is a study, the title of a study from just

a few months ago. This was published

in December of 2024. This group did a long term

study for over a decade. They were looking at Imposex in marine snails off

the coast of Colombia, in the Caribbean at

various sites, um, and they were

finding that they're still seeing high levels of Imposex even though tributyltin has been banned

for quite a long time. Even though we haven't

been using tributtin, it's still out there

as a pollutant, it's persisting in

the environment. We think it's mostly

in the sediments and activities like

dredging and turning up soil down low in shallow waters is keeping it moving around in

the aquatic system. It's in the sediments and

it's being churned up. This is an image from that study that I just showed

you the title of. These names down here

are different sites along the Colombian coast. Again, we're looking

at percent incidents. The bars on the left in

each little graph are from a decade ish ago 2012, 2016, depending on the site. Then we've got data from 2023. The incidences of impo sex, the percentage of Imposex

that they're finding in snails they're

sampling is lower. You could see that the bar on the right in each

of these is lower. Well, no, that's

not true over here. I don't know what's going

on at this particular site. But for these three, it's lower, but it's still happening

at levels above what you would expect in a

non polluted population. I actually didn't notice this

till right at this moment. What's going on with this site. So I would have to look back

in the paper and see what they think is. Is

going on there? Why it went up so much? It was suspiciously

low at 20:16, so I'm guessing it

has something to do with the sampling

that happened in the 2016 batch

there. I don't know. Um, then our main pesticide that we wanted to talk

about today that you've read a few different

articles from a few different points

of view about and you chose whoever you chose for that atrazine debate

assignment that was due today. Our friend atrazine here. Atrazine has been

around a long time. We've had atrazine

since the 50s. It's the second most widely used herbicide in

the United States. It's pretty cheap to produce. It's an herbicide, so it's a weed killer. It

controls weeds. It controls a really

broad range of weeds, it's our second most

popular weed killer used in agriculture

in this country, the most popular being

glyphosate or round up um, we'll probably talk about round up more when we talk about genetically modified organisms

because it's really um, it's really common to make GMO crop plants in this country that are

resistant to round up, so you can spray your field with roundup and it

kills the weeds, but it doesn't kill your corn or whatever

you're trying to grow. We'll probably talk about

roundup more later. Atrazine is number two

in the game in terms of herviicides that are used in

agriculture here in the US. Um, it interferes with if you're familiar with the details of

how photosynthesis works, it interferes with the electron transport chain part

of photosynthesis. You don't need to know

that for this course. But if you know about

photosynthesis, that might mean

something to you. We as humans, of course,

do not photosynthesize, direct application

of atrazine to you wouldn't kill you the

way it would kill a weed, but that's how it works

as a weed killer. Um, it's a pre

emergent herbicide, meaning you can spray it before the weeds have actually

come up and it will still impact them and you can apply

it to corn post emergent and it won't affect

your corn if you've got resistant corn that's been genetically modified, but

it'll kill the weeds. It's a weed killer. Um,

the graph that we're looking at here and the text is tiny because I

smooshed it down. This is from the USGS, that's the US

Geological surveys. They have a couple web

pages with data on different pesticides and herbicides and

things that we use. So this is estimated

use by year end crops. The different colors are the

different crops, although, as you can see, the yellow

is corn aptly color coded, then all the other crops

are tiny little slices that are hard to

see because they don't compare really to how

much we use atrazine on corn. The furthest dataset I could

get here was 2018, 2019. They haven't updated this

on the USGS set in a while. But you can see that

we use a ton of this. I guess you'd need

other pesticides to compare by use in pounds. We use a lot of it and we use a lot of it

specifically on corn, and we grow a lot of

corn in this country. A little bit of

corn for us to eat, a lot of corn for corn syrup, a lot of corn for

feeding livestock. We're a big corn growing

country here. This is the USGS. Again, they didn't

have anything past 2019 on their website, so this is as updated

as I can get. So we're looking at, again, pounds per square mile usage, but here in a map setting. South of us, this whole

swath of the country is where a lot of

atrazine is being used. Obviously we're using

it other places too. Again, where the corn

is being grown is also where we're using

the most atrazine. Um, agricultural runoff is the main source of

atrazine pollution, so we're applying

it to farm fields, essentially, and then

some amount of that is running off into

water sources. So the EPA does regulate how much atrazine is considered safe in

our drinking water. I looked yesterday and I don't think this

number has changed, although what I was reading

was a little convoluted. They've changed what

amount they think officially affects

aquatic plants and some other organisms. But as far as I can tell

for our drinking water, this is still where we're

at with uh, the standard. So we get runoff from agricultural fields that

ends up in nearby streams, lake ponds, whatever bodies of water or near those

agricultural fields. So it's in our water system. Therefore, it can impact

our drinking water. And so the EPA regulates

that three parts per billion is what is the

acceptable upper limit to have in our drinking water, um or micrograms per liter, if that unit makes more sense to you, whichever one of these? Um, what's the deal with atrazine as far as it being

an endocrine disruptor, as far as it being a pollutant that's in our water system? What do we know about

what atrazine does? You know some of this

from your reading, so um we'll just go

through some of this. This is from a

relatively old paper, some of this research was

done quite a long time ago. This is about atrazine inhibiting testosterone

production in rats, perpubital exposure, perpubital means

just before puberty, just before they start to

mature into adult rats. That's what the

perpubital means. That's when rats were exposed. This is a lab study. And so here we've got

a little data table where we're looking

at a control group and an atrazine group, and we're looking at

serum testosterones, basically blood levels

essentially of testosterone, and then they also

looked specifically in the testicles at

testosterone levels. We're looking at

testosterone levels. We've got our asters

here to indicate that these two groups are significantly different

from each other. In both testosterone measures, a tidy little simple

data table here. The plus and minus

just indicates that that's the error

around this number, or you can think of that

as how certain they are about this number two

is plus or -0.79. The levels are higher in the control groups

for both of these, and they are statistically

significantly higher. We see from this study that exposing just before going

through puberty rats to atrazine will lower their testosterone levels or inhibit testosterone production. Um, This is one example

of a study that we have about atrazine

affecting mammals. Then you did a couple

of readings in your O readings on atrazine. A couple of the

things that you read were by Tyrone Hayes. He's a famous

player in the world of what's up with atrazine

affecting wildlife. Um, he teaches out at

Berkeley in California, so this is the title

of one of his papers. Here he's looking at, um, the impact of atrazine

on leopard frogs. This is what an American

leopard frog looks like. He did lab studies

and field studies. This particular paper had a combination of data from both. He found that leopard frogs

exposed to atrazine had, um, unexpected gonad

development, essentially, and some frogs in his study ended up being what you would

consider a hermaphrodite, meaning having both male and female gonad

characteristics. Remember that three

parts per billion is what the EPA allows in

our drinking water. He's looking at 0.1 PPB, quite a bit lower than our

EPA drinking water standards. So here is one bit of data

pulled from his work. Here we're looking at

the size of the larynx, the laryngeal size from

a Tyro and haze study. The larynx is a male

characteristic in frogs, male frogs call to attract female mates and that larynx is part

of the vocal system. When you hear frogs

doing their thing during the mating

season at night, you can hear making whatever sounds they make depending on what

kind of frog it is. The larynx is part of that. Here we're looking at

larynx size as a measure of what you would consider a male physical characteristic

in these frogs. And you can see that he went up to 25 parts per billion starting at very low concentrations,

working up to 25. We have different

atrazine exposure levels. This is a lab study, and then we're looking

at larynx size. You can see down here at the

very low atrazine levels, the larynx is quite a bit

higher and then we see a drop off as the atrazine

exposure gets quite. Atrazine doesn't actually

shrink the frog's larynx, it reduces testosterone

levels in the frogs and larynx development and growth of the larynx is

partially controlled by testosterone in the frog. If you expose frogs as they're

developing to atrazine, they won't develop

as large a larynx. It's not like you're taking

a fully adult developed frog and it's shrinking the larynx. Here he used larynx

size as a measure of a male trait determined

by male hormone levels, in this case, testosterone. So in this dataset, we

see that atrazine levels below, I don't know, maybe two. I'm just eyeballing

it on the graph. Two parts per billion

correlate with a fairly sharp drop

in larynx size. So again, that's below our

EPA drinking water standard. Here's some more data

from the same researcher. Here they were treating

male frogs with atrazine again in a

lab study situation. They found that some of the male frogs were also

developing ovaries, they had both testes

and ovary tissue. Um I think this image might have been in your reading

also that you did for today. Um males had lower

testosterone levels and males were developing ovary

tissues in the graph here. We're looking at testosterone

levels in control males, not treated with

atrazine atrazine treated males and

control females. We can see that the

atrazine treated males have testosterone levels more similar to the female frogs here. So when you see data like this, part of the question is always, well, what's the

mechanism causing that? What's the mechanism here for atrazine

affecting amphibians? Why is it affecting

testosterone levels? How does that work? This

is the mechanism that Tyrone Hayes has proposed for how Atrazine affects amphibians. Testosterone is a male hormone, it's an androgen

more specifically, arguably the most

important androgen in terms of how it impacts

physical characteristics. Strodle is an estrogen. Which I think is

evident by the name. Both males and females have

both of these hormones. It's just a matter of

different levels of each. So it's not like males

only have testosterone and females only have estrodiol. So speaking to this

mechanism then, this enzyme, aromatase,

whenever you see something that ends in ace you can assume that's an enzyme. Enzymes catalyze

chemical reactions and aromatase is involved in

the synthesis of estrodiol. In males, we're thinking about male frogs here,

some small percent, less than 1%, a small percent of testosterone gets

converted into estrodiol, that just happens naturally. Um estradiol is interestingly about 100 times more

potent to cells hormone receptors

than testosterone is. Even a small amount

of estrodiol has a pretty significant effect. Males need to have 100 times

as much testosterone as estrodiol just to have equal

affinity with the receptors. The proposed mechanism here

is that atrazine is somehow inducing more production

of this aromatase enzyme. There's a gene, I don't know if it's one

gene or a couple of genes that code for aromatase. I think

it's just one gene. Um and so your

genes aren't turned on and being transcribed and

translated all the time. This enzyme wouldn't naturally

be produced all the time. There are responses to environmental signals

that say, okay, let's turn that

aromatase gene on, let's get some aromatase

production happening. Sometimes the genes not

functioning and sometimes it is. The proposed mechanism is that atrazine keeps the

gene that codes for aromatase turned on being transcribed and translated

into a protein. More frequently or

at a higher rate than would normally

be happening. You've got more aromatase in the frog's body than you would normally have without

atrazine being present. This reaction is happening more, you get more of the

testosterone being converted into estradiol

and as I said, estradiol is really potent. This same system

exists in humans, this aromatase conversion of

testosterone to estradiol. Tyrone haze has proposed

this for frogs, but it stands to reason that if this is how it's

working in frogs, this could be how it works as an endocrine disruptor

in humans also. That's the proposed mechanism. Aside from the frog

data or amphibian data, there are some data this

is from fathead minnows. This is from a fish study

done by someone else. He exposed minnows. I

think this was a he. Actually, I have to go look

up who this author is. I'm pretty sure it

was a he, exposed minnows to atrazine and looked at how many

eggs they laid. That's what we're

looking at here. The different lines are for

different doses of atrazine, you can see in the key

in the upper left. Circle, the black circle line, this one is the control group

and the rest are different. Concentrations of

atrazine, so it's usually just easiest to look at

the most extreme ones. The highest dose is

this diamond line here. So this is exposure period, so we're looking over time along the X axis up to a month. And then we're looking at

mean eggs per breeding tank. They would put fish

in a breeding tank. They're either

exposed to atrzine or they're not and they're

seeing how many eggs are produced in that breeding tank that has males and

females together. You can see if we're

just looking at the control group and

the high dose group, there's a pretty

widespread here. The control group is producing more eggs when we're a month out than any of the atrusine groups and the

high atrozine group is lower. Again, we have our asterisk

here indicating that each of these three

atrusine groups, they're all

significantly different from the control group. We see significantly

lower egg production. In the atrazine treated

groups of fish. These research group also saw gonad abnormalities

with both sexes of fish when they were

exposed to atrazine, and they attribute the lower egg counts to fewer spawning events. So fish data to add in

with our frog data there. So you also in your batch

of Atrazine readings, you had a review paper by

Solomon and some other authors. That was the really

long one where there was a note about which

parts of that to pay attention to and which

parts of that you could just skim or pay

less attention to. And so the goal with

this review paper was to piece together all the information that we had at the time that it was written about what atrozine was

doing to amphibians, aquatic vertebrates,

more specifically. They had this set of guidelines for how

they were going to assess whether atrazine is actually causing these effects. There seemed to

be a correlation, but was it caused by atrozine. This slide, this list here is just breaking down what

they were using to assess. They were looking

at temporality. They saw effects in

sexual development in some frog species. Prior to atrazine coming

on the market in 1957, when were we starting

to see these effects in amphibians compared

to when atrazine came on the market and

started being used at really high levels because we do know there are other things out there that are

endocrine disrupting. There is some level of sex characteristic

changes that we see in amphibians just because

it happens naturally, how are we sorting out whether atrazine is the cause

of some of this? Um, so in this paper, they say that there's

no temporal evidence of an association between atrazine and reproductive

issues in frogs. Maybe it's other

endocrine receptors. We can't say for sure that

it's atrazine was one of their positions with respect to the timing of when

we started seeing these changes or having

data about these changes. They also looked at

strength of association. They said, if the aromatase

theory is correct, if that's the correct mechanism, They were looking at whether we see a clear dose response curve, and their take was that

studies don't seem to show a clear

concentration response. Normally, you would

expect a dose response where the higher the

dose of atrazine, the more extreme the effect was. If we flip back here, this is from one of

Tyrone Haze' studies, they're saying

that datasets like this aren't totally

clear that the response and dose correlate

in a way that you would necessarily expect flipping

around through the slides. So some studies do seem

to show that some studies don't Crew didn't think that that was necessarily a

strong enough association. They also looked at consistency. Beyond just Tyrone haze studies and these

couple of other ones that I showed you and

the other studies that were existing at that time, um, are we seeing a

consistent trend? Do most of the studies on atrazine show

that it has the kind of effects that these

researchers that I was showing you um are finding. Their position was with

respect to amphibians, that Tyrone Hayes' work seems to show these

effects quite clearly, but other people who tried to

do similar studies weren't finding the same thing that

Tyrone Hayes was finding. They were saying it's

not consistent enough. That's obviously one of

the hallmark things that we look at with published

science research. We want to be able

to have a bunch of different people

do the same study and find the same thing. If that doesn't happen, then we're questioning

what's going on. It is true that

Tyrone Hayes found the most significant atrazine

effects on amphibians and other people who tried to

duplicative studies were not finding the same results

that he was finding. Um, I think they agreed in this review

paper that the aromatase, theory that aromatase converting testosterone to

estradiol was plausible, but that we don't have enough

experimental evidence to support it or to know for sure

that that's the mechanism, um, then their last

criterion was recovery. If we take Atrazine away, do we see the effect go away? I feel like they

phoned this one in a little bit because they

were just like, well, if we haven't seen any

effects of Atrazine and Wildlife and we don't necessarily believe

that they're happening, we can't really test the

recovery guidelines. This was the framework that they used in that Solomon

paper that you read. This is the header of that

critical review paper. They said based on a weight of evidence analysis

of all the data, the central theory that environmentally relevant

concentrations of atrazine affect reproduction and or reproductive

development in fish, amphibians and reptiles is not supported by the vast

majority of observations. However, it's worth noting that if you look in the acknowledgments

of the Solomon paper, which I don't know if

anybody looked at that. This review was developed

with a grant from Syngenta Crop Protection Inc. Those are the folks who make atrozine. We take this with a bit

of a grain of salt. I think I've mentioned

before. I don't remember what the context was

that you always want to look at who wrote the

paper and where they work and who paid

for the research. This is one of those times. That doesn't mean that

nothing they said is valid, but you take it with

a grain of salt that the people who

make the herbicide are commenting on atroze not having an

effect on wildlife. Do you have a question? Yes. And that is what my next slide

is about exactly. This table is actually adapted from one of

Tyrone Hayes' papers. You can take this

with another grain of salt on the other side of this science beef between Hayes and Syngenta

about atrazine. This is a list of papers

that were published around the time period that all this was going down and being

talked about a lot. Author and year of

the paper here, the sponsor is who paid for

the research essentially. S is Syngenta E is ego

risk in the author column. Ego Risk is a Syngenta

funded panel of researchers, the E's and the Ss are

both syngenti stuff. We're looking at what species. These are frog species. You don't need to know the

genus and species are frogs, because they're all

different kinds of frogs. Whether it was a

field or a lab study, whether the design was

considered appropriate. Again, this is appropriate

according to Tyrone Hayes, um, so appropriate meaning there wasn't a really high

mortality rate with the frogs. The controls weren't

contaminated with atrazine. Some of the critiques

of these papers were that they were

using tap water, which would have had some

amount of atrazine in it anyway and so the controls

weren't real controls. That's the thing we're

looking at with the design. Um, the frogs mostly

survived the study and do we know that the controls were

not actusin contaminated? Then the effect is whether

they found some endocrine disrupting effect in the

frogs in that study or not. And so the ones that

are in red here, are all the nos, basically, this one's

a yes and a no, different parts of the study. They found yes or no, depending on which piece

of their study it was. All the nos are in red here. All the nos are also

the syngenta ones. Syngenta and their syngenta

funded research panel here. All the ones that were yeses

were the non syngenta ones. I have to look back

at the key to see which which research group

specifically did these? But you could see

that Tyrone Hayes is on quite a few of these. There's a few other

players in the game, but he's the main

researcher finding these endocrine disrupting

effects of atrazine, and Syngenta is funding all this research

that's saying that atrazine doesn't have Endocrine disrupting effects on frog. This turned into a major feud between Tyrone

Hayes and Syngenta. It got personal. There

were ugly emails. You could probably go

find the ugly emails online if you wanted to um, whenever Tim around

Hayes would go give a talk at a

research conference, Syngenta would send someone

or multiple people to sit in the audience and ask leading questions and

not exactly heckle him, but ask questions that would give him a hard time

and they wanted to keep tabs on what he was talking about to other scientists

at research conferences. So he felt like he was getting paranoid and Syngenta was

following him around. It got weird. If you're

into science beefs, you can go look more

about that online. Um, this is in here if you

want to look it up later. This is a YouTube video of Tyrone Hayes doing a

rap about Atrazine. It's not actually a video. It's just a picture

of him in the audio. So if you want to hear his

rap about Atrazine, go ahead. Where are we at with Atrazine

in more up to date time. Because all that,

as you can see from the paper dates happened

quite a while ago. Um, in 2020, the EPA

reapproved atrazine. We're still using it. This is not an example of

when we have used the precautionary

principle because we have some evidence that it is

an endocrine disruptor. It's compelling evidence. I didn't show you every

single research study, but there are other

ones out there that you could go

look up if you want. We have evidence that it's

an endocrine disruptor. We're not exactly positive

about the mechanism, but we have wildlife evidence, but we're still

continuing to use it. We're not employing the precautionary

principle and by we, I mean, our country and our government

regulation of atrazine. Um, every pesticide

that's registered for use in this country gets

reviewed every 15 years, so we're a ways out

from the next time it gets re upped for approval. The EPA on their site about

atrazine now and it hasn't changed in the last few years says oversight of

atrazine is dynamic. Um, which isn't very helpful. But the EPA has been re

evaluating regularly, even though we're

not at that 15 year mandatory approval point yet. This decision to reapprove

Atrazine happened in 2020, um, previous Trump

administration would be when that happened. And then in 2022, now we're in the Biden

administration in 2022, the EPA proposed

additional mitigation to protect aquatic communities. So they set some guidelines

about not applying it when soils are saturated with water to help

prevent extra runoff. They said you can't apply

it when it's raining, you can't apply it

from the air and set some other restrictions about how you can apply it and

when you can apply it. That was what the EPA had

suggested as guidelines. There was a public

comment period that fall, um, and then not much

has happened since then. A lot of the stuff

on the EPA website about atrazine is

still from 2022. Then at the very end of

the Bide administration, we had the EPA proposing updated mitigation

and reduced use, they went a little further

than what they'd said in 2022. Um, and what they said and what they suggested in just

this past December was more monitoring, more assessment, more money

for research studies. The EPA has been

saying for years, we need to be looking at

atrazine a little harder, we need to be regulating

it a little more. We need to be doing

more research and possibly restricting its use in more ways

than we have been doing. So that's where we left it

at the end of Biden's EPA. There was a bill

proposed last fall by a couple of Democrats

New York and Massachusetts. They introduced a bill

to fully ban atrazine, but that died in committee and we didn't make it to a vote. It's an ongoing what's going

to happen with atrazine? We've been using it

for a long time. It's a really good weed killer. It seems to be an

endocrine disruptor. I think we have enough

evidence to say that, and so it's just a matter of whether whether regulations

are going to change or not. That's where we're at

with atrazine. Okay. Thus endeth our

toxicology content. Atrazine was our last topic

that I wanted to hit, a couple of things

about the exam. It's not a week from

today, a week from today is spring break. That's crazy. It's two weeks from today.

Pretend that says two weeks. I often get asked, particularly with

the toxicology unit, what do I need to know about

the specific toxicants that have been

mentioned in lecture? This is a shorthand study guide. You can come back

to these slides. I noticed this morning

that I forgot to post the lecture recording

from Tuesday. This afternoon, I'll post all of this week's recording.

Sorry about that. For the toxicants that we spent some time talking about, um, know what they do what they

do in the environment, to wildlife, to humans, to the extent that we've

talked about it in class. For the categories of toxicants, know generally

broadly what they do. Know that mutagens

cause DNA mutations, know that teratogens cause developmental effects

on embryos and fetuses. Know the basics of what

each category does. If we talked about

specific mechanisms here in class about how

different toxicans work, like last time on Tuesday, I talked about the

three different ways that endocrine disruptors can mess with your endocrine

system, understand those. In terms of categories

of toxicants, know what they do broadly. If we talked about specifics

of how they do that, if it's in the

lecture slides and I talked about it here

in class, know that. For example, um, digging

down a little more in that. I won't ask you. There are lots of toxicants

that I mentioned just in passing as examples of I gave you

a category and said, here's a few examples of toxicants that fall

in that category. I wouldn't ask you an exam

question about something that I just briefly mentioned. But the toxicants we

spent some time on. They had multiple slides. We looked at datasets like DDT, tributltin the things

we talked about today. Um, atrazine, know

about those toxicants. The things like asbestos that I just briefly mentioned

as an example, you don't need to know about. Use how much time I spent on them in class

as an indicator. If it was a brief mention of an example, don't

worry about it. If we actually looked at

data and talked about it, then know what the deal

is with that toxicant. The list here is

what you should know about those, um, toxicants. The last item in the list is about what you should

know about those. Know what category

of toxicant they are and sometimes they fall in

more than one category. DDT is a neurotoxin and

an endocrine disruptor, so you should know

that about DDT. What they generally

do, understand the gist of the datasets

we looked at in class. If I give you a

little data table, be able to interpret what that data table or a little graph or something is telling you.

What do we know they do? How do they function

as a toxicant, and what evidence

we have about that. So hopefully that helps you

not feel overwhelmed by all the random little

toxicants that I've mentioned as examples. Know the ones we spent time on. I didn't cover

indoor air pollution here in class just

for time's sake, but there is a slide on the day we talked about air

pollution that tells you to go look at the

lesson ten readings about indoor air pollutants, so you should know about those. This is the one oddball example where I'm asking you

to just go learn from the reading and we're not

talking about it in class. So hopefully that helps

a little bit that you feel less worried

about which toxicants you need to know what

about for the exam. We're obviously

ending early today, so you've got time

if you want to sit here and pull up

that survey about the different topics

that you maybe want me to review when we

get back from Spring break. So you can do that if you need some time to flip

through the slides from previous days and remind

yourself what we talked about or look at your

notes or whatever. Then when we get back

from spring break, we'll do some review. We'll start talking a

little bit about food for our food unit and then

we'll have our exam. So go ahead and fill

out that survey, and then you can go or if

you have questions for me, you're welcome to hang out.