Next, we have John Meeker, our Associate Chair.
An exposure scientist who has also morphed into a biomarker epidemiologist
doing his cutting-edge work.
This title, I will say, he was too shy to invent it himself.
But we invented it for him.
uh... "Endocrine Disruptors: Sexy Stuff"
Yes, thank you to the Communications Office for that.
And I did receive some good advice just now, just go out and dazzle 'em.
So, no pressure. 0:00:40.210,0:00:42.430 So with that I guess I'll get started.
So there are anywhere from eighty to a hundred thousand chemicals in use
in the United States today, depending on where you look.
Among those there's
a number somewhere around three thousand, according to the EPA,
that are considered to be high production volume chemicals.
These are chemicals that are
produced or imported into the U.S., at volumes of greater than or equal to
one million pounds per year.
Among these, there's one that I'm sure you've all heard of
that Dr. Dolinoy just spoke about, which is BPA.
BPA obviously has been controversial.
A lot of countries have been phasing it out for certain uses,
as well several states in the U.S.
Last year it came up for a vote in the state of Maine
where the governor was quoted as saying,
And this was his way of justifying his stance against it.
So no matter where you fall on your opinion
for the spectrum of toxicity of BPA, I think we can all agree here that
we would hope our decision makers
have a little more respect for the science,and try to make more
evidence based decisions in the process.
So, if you mentioned estrogen-- so he did get that part right,BPA is estrogenic.
But, the more we study endocrine disruptors, the more complex we're realizing
this endocrine hypothesis to be.
Impacts can happen at various levels of the endocrine axis. It could be
the hypothalamus, the pituitary, the thyroid, the adrenal gland,
the gonads. It can also impact other organs in the body.
And we're also learning that it's not just the receptors
that might be the point of action. It could be
something impacting the census, the secretion,
the the transport binding or metabolism of
the hormones that might throw off that balance.
And because of it's a system, it's like other systems.
If you take away one or more pieces of that system
it can have some some pretty drastic and maybe unpredictable consequences down the line.
I'm going to go into a little bit of history
Endocrine disruptors, as it turns out, have been around all along.
We have naturally occurring endocrine disruptors in things like genistein
and other isoflavones,a lot of metals.
Some current research is showing that several metals
also act as endocrine disruptors.
Let's take you through a little bit of history.
The book "Silent Spring,"
in the early 1960s by Rachel Carson,
was a New York Times bestseller.
It really put on the radar the environmental movement
and because the focus of the book
much was DDT and other organic cholrines
as it related to persistence and wildlife affects.
It is credited with sort of moving the discussion and generating more
careful consideration for pesticide regulation in this country.
During that same time,
from about the 1940s to 1970,
another estrogenic, synthetic estrogen,
sort of like BPA, was being prescribed for women with recurrent miscarriage
in order to prevent those or other adverse pregnancy outcomes.
However, in the early 1970s it was found that these are leading to
reproductive tract disorders in the offspring.
These offspring then
became known as DES daughters and DES sons.
This has become a mode, a human model, unfortunately,
for what endocrine disruption for a certain type of endocrine disruptor
what it might do in the human body.
And there's research coming out now, actually, on the third generation
also showing reproductive tract issues,
which is thought to be due to epigenic changes as Dr. Dolinoy talked about.
Moving ahead to the 1990s,
the book on the left was called "Our Stolen Future,"
also widely-read by the the general public.
By Theo Colborn and colleagues with forward by Al Gore.
This one took all the existing science to date, there were, you know,
some studies on endocrine disruption, but not really.
It hadn't really gained much steam yet.
And they put those together and then really broadend the scope
And they hypothesized,
it's not only a range of reproductive problems that we're looking at,
this could have far-reaching effects.
Things like obesity, metabolic syndrome, diabetes, neuro development effects,
neuro degeneration, a range of cancers.
So it really put it out there, and really got the discussion going.
A few years later, in 1999, the National Academies put together a committee
that came out this book on hormonally active agents.
They concluded
put together all the studies and said there's some evidence there that's insonsistent,
but this could be real. More research is needed.
And since then, there's been quite a bit of research, a lot of studies going on.
And now I'm just gonna touch on a couple of the more controversial ones that
I think are good examples of how some of these results can lead to
just a firestorm of media action, some public outcry and heavy debate with
the people who manufacture these chemicals.
The first example is one of frogs
This is the work of Tyrone Hayes out at Berkeley
who in the early part of this century put out a series of papers showing
that the pesticide atrazine was leading to the demasculinization and hermaporditism
among frogs.
They dosed these frogs with the atrazine at low doses.
And they were finding that they were growing both male and female reproductive organs.
Now, atrizine is a heavily used herbicide, primarily on corn.
And as a proud Iowa native, of course I have to show a picture of "Field of Dreams."
"Is this Heaven?" "No, it's Iowa!"
Though Shoeless Joe and his buddies might wanna find another place to hang out. I don't know.
Although, if I remember correctly, they're ghosts. And I don't know if ghosts have
endocrine systems. I don't know what to think there.
The next example is another chemical many of you are probably aware of, phthalates.
In the late '90s,several different groups were reporting male reproductive tract
anomalies in rodents doesed with very high levels of of certain phthalates.
You know, that's hard to interpret because they were such high doses.
However, several years later, an epidemiology study by Shanna Swan and her colleagues
did see that levels of phthalate exposure during pregnancy,
at levels found among the general population, were associated with
some markers of anti-antigenic activity,
and smaller genetalia, and things like that.
So, obviously that led to a lot of media,
a lot of public, and a lot of corporate reaction that is actually still going on.
And a lot more studies are needed to really replicate this work.
That brings us to present day.
With the current regulatory system, I mentioned that there's tens, if not
hundreds of thousands of chemicals out there. And only a
very small fraction of theses have been thoroughly tested for toxicity based on
our risk assessment framework. And then we further go along that line,
some of these tests are considered outdated, and may not be
sensitive to changes in function that might be important to this system.
And beyond that,
studies in humans are extremely limited still.
When you think about all the chemicals out there,
how things are done,
there's a lot of agreementgrowing now
that things should change.
So, this is just a letter in science last year
showing that several societies, the American Medical Association,
the Endocrine Society, several others,
signed this letter. It represents forty thousand scientists and clinicians
saying, "Hey, government and other decision makers,please call upon our expertise
to help you figure out how to deal with these things."
The future.
This is a very basic figure that
hopefully my students remember from class, something like this.
But we have the basic risk assessment process. You have Hazard Identification,
Dose-Response, Exposure Assessment,
Risk Characterization, and then, ultimately, Risk Management.
So, moving forward,
I'm gonna talk about some things that we really need to improve upon
if we want to get a grasp of this situation.
And a lot of these revolve around exposure, one of my interests.
So, one is life stage.
We know that developmental exposures are likely the most
susceptible to this type of exposure.
But how do we measure it?
What time frames?
Is it early pregnancy? Late pregnancy? Childhood?
Previous generations? What about a adulthood? We can't ignore that.
If we look at diseases in adulthood, like cancers,
how are we gonna estimate exposures early on?
And this comes around to the whole exposome idea, which Dr. Zellers will talk about later.
And things like,
how are we gonna measure exposure
most effectively for risk assessment and for epidemiology?
How do we do that?
We're gonna need new markers. We have a lot of good biomarkers, but
they're cost prohibitive when you think about how many chemicals are out there.
You can't measure everything.
When I say exposure assessment, this is what a lot of people probably think of.
These point sources that are easily visible,
that's kind of somebody else's fault, kind of situation.
You have a smokestack, you have this green goo coming out of a pipe,
you have an airplane spraying pesticides everywhere.
That's what people think of. However, when we talk about endocrine disruptors,
through some of my work, this is what I start to think of.
You know, going into the store,
you have just rows and rows and warehouses full of products,
that we go in, we willingly buy,that we take into our home, that contain
all kinds of chemicals that were used in the manufacturing.
Some are left there on site,
which may be a worker exposure issue.
But, then some are either found in the product or are added to the product,
and can leach out. Things like flame retardants and phthalates can leach out.
So, you can see just in this picture alone, you can identify a lot of plastic.
So, plastics actually make up a good portion of the chemicals that are produced.
The most recent estimate that I've seen, it accounts for 8% of global oil production.
You can see it's exponentially increasing in the last few decades.
So, what this means is, we have more and more plastics. They're very useful for many things.
They are beneficial in a lot of ways,
but, we need to think a little bit more about, "What are the consequences?"
How are we exposed? We're likely exposed in a lot of different ways.
And moving forward, when things start to become banned, or the usage changes
and we start disposing of these things.
According to the EPA, last year, about 12% of the two hundred fifty million tons
of waste put into landfills was by plastics.
Thinking of this, in the future
maybe the sources of exposure are gonna change. Maybe it's gonna be
more of these point sources, these waste things.
Maybe it's gonna be in the diet, kind of like the situation with PCBs
and other organic pesticides that we're seeing now.
So, history may be repeating itself.
Dose-Response. A paper just last week came out talking about what it means,
what Dose-Response means, in an industrial endocrine disruption setting.
And they reviewed more than eight hundred papers, this is a new paper by Vandenberg et. al,
that point to or support their stance that
non-linear and non-monotonic dose responses are occurring
with the use of some endocrine disrupting chemicals.
So, here's something representing the classic view of dose-response.
Maybe, you know, linear. Or at least monotonic,
where that slope might change, but it's always gonna go in the same direction.
However, if we were to take a step back,
we might see something like this. This is where this idea is going.
Where if you are testing something in animals at a high dose,
say where comes back down again, that might not be able to be adequate
for predicting something that might be happening at a low dose.
That's the thinking there.
I love Chex Mix.
I love Trail Mix
They're both in the same aisle at the grocery store, of salty snacks.
But they do different things.
The Chex Mix, it's got all these little different bits,
but they're all doused in the same salty mix of either traditional, teriyaki,
maybe barbecue, they're coming up with new ones all the time.
But, you know, they look different, they have a different crunch, crisp.
But you get that additive response of flavor of the saltiness.
Whereas, Trail Mix I like because
you eat some of the salty,
but then you go to the sweet. You bite into an M&M, and it really enhances that flavor.
And vice versa.
So, this is sort of analogous, I think, and other mechanisms to what can be going on
with chemical mixtures.
I talk about the number of chemicals out there, this recent study showed among
pregnant women and NHANES, that dozens of potential or known endocrine disruptors
are measureable in pregnant women.
and that's only with what they tried to measure.
Who knows what's out there that they didn't even try to test. So, how do we
account for this? How we test for this? It's gonna take
new approaches. The way we're doing it now is not going to be able to get at this.
And then, finally, to Risk Management.
So, say we do find these to be harmful.
What do we do then?
Another study that came out just last week in Environmental Health Perspectives
shows that they measured
about fifty different endocrine disruptors and a few other chemicals, in a range of
consumer and personal care products. And they show a lot of these hits
of these chemicals in these products they just grabbed off the shelves.
And these dark red circles,
those indicate that for certain phthalates and other chemicals,
more than 10% by weight of the product was was that chemical.
There are some
wide-ranging, multiple chemicals in these products, many at high concentrations.
They also tested some alternative products advertised as natural,
and still got some hits. So where does that leave us for Risk Management?
We can't, as consumers, really...
How do we go about our day? I can't wake up in the morning and say,
"I'm gonna avoid endocrine disruptors today."
That's not gonna be possible. So something else is gonna have to happen.
So, what we do? Do we just ignore it? Do we despair? Do we go off the grid?
Do we go overboard and overprotect ourselves? We don't know what to do.
So, the best I can say is, we need more information. We really want to know
which chemicals are harmful? How harmful? What are they doing?
And how best can we reduce exposure?
And to do that i think it's gonna require
some of the things that we've been talking about, and will be themes
throughout the day. This is multidisciplinary, interdisciplinary
research. And that's
why the University of Michigan is a great place for this to happen. We have
leading toxicologists, epidemiologists exposure scientists. We have other
disciplines around campus in medicine and engineering, and other places.
We really need to work together to try to address some of these things.
And we already have started. We have several examples. One is a formative children's center,
led by Karen Peterson, who will be up next.
We also have the NIEHS Core Center
that also studies endocrine disruptors.
The example I'm gonna touch on briefly is the study in Puerto Rico we're doing.
Puerto Rico has the highest rate of preterm births in the U.S. of all jurisdictions.
They also have a very large number of
hazardous waste sites with endocrine disrupting compounds.
So, we have a multidisciplinary team of all the disciplines I talked about--
physicians, engineers-- looking at exposure,
looking at predictors of preterm birth, whether these are connected.
And there's a lot of collaboration going on, and we're seeing a lot of
things coming out of this that transcend any single discipline, and gives us that
trans-disciplinary approach that I think is gonna be needed to solve some of these
very large public health and environmental health issues in the future.
Thank you.