We Were There – PVC and Angiosarcoma

We Were There – PVC and Angiosarcoma


[ Beeping ] [ Music ]>>Good afternoon. Thank you so much for
joining us for We Were There. This session, the We Were
There series was started so that CDC disease detectives
could share the lessons that they learned in
their investigations so that others may be inspired
to carry on their work. Today’s session is about how
a rare cancer changed the workplace and environment. It was an investigation
of polyvinyl chloride and a very rare cancer
called angiosarcoma. And, now, a few words from the
Deputy Director Anne Schuchat.>>Good morning, and welcome to the latest installment
of We Were There. The first detection of an emerging health
concern often depends on an astute clinician,
someone who sees something and realizes it’s unusual. And then, follows
up to alert others. That’s the case here,
when the physician at a chemical plant
realized that three cases of an extremely rare
liver cancer was unusual. You’ll hear today about
linking these cancers to vinyl chloride gas exposure. In the 1960s and ’70s, vinyl
chloride was commonly used as a propellant in
hair and paint spray. The potential threat
was everywhere. Many times, the warning
that we have a new threat on our hands comes from just
a small number of cases. Toxic shock syndrome
was first recognized in seven children,
several of them boys. They presented with fever and a severe rash
leading to peeling skin. When just nine children
developed intestinal blockage or intussusception after getting
the first-generation rotavirus vaccine, Rotashield, the
signal prompted a national investigation and pause in
the immunization campaign. Small numbers pose
a predicament. How many do you need
to investigate? How many is enough to
take further action? How many, when you have
no idea wat the background or expected rate of an event is? Sadly, the Canaries in
the coal mines warning us about eminent threats
too often are humans. Even worse, for environmental
exposures, the workplace may amplify
a worrisome exposure and unmask the risk. But, at a high cost,
the health of people who are only doing their jobs. The story you are about to
hear launched a positive chain of events going from
detection to science to regulation to prevention. The young whippersnappers
who carried out this investigation are
now not so young gurus, but their story need
not remain in the past. Their work spared many the
risky exposures they were investigating, but also
spurred continuing research. Fast forward to 2015 for that
recent report on the discovery of the genetic mechanism
by which exposure to vinyl chloride
produces cancer mutations. Or to 2016, when a study of
vinyl chloride metabolites in workers linked the
metabolites directly to fatty liver. This finding goes
beyond vinyl chloride to validate the new science
of metabolomics for the study of many different kinds
of chemical exposures. The We Were There series reminds
us that we at CDC are part of a continuum of
scientific discovery. Learning from the past can help
us create a healthier future, and each of us is
challenged to up our game and incorporate the
best insights from these landmark
investigations that helped make CDC the
trusted agency we are today.>>It’s my pleasure to invite up the first young
whippersnapper speaker we have today, Dr. Henry Falk.>>Thank you very much. So, this talk is
about an investigation that I actually began a little over 44 years ago as
an EIS self-serve. It’s about a rare type of liver
cancer known as angiosarcoma which was very rare, very
obscure, but very fatal. And, a disease that had caused, in people who polymerized
vinyl plastics. So, this actually had a dramatic
impact for a number of reasons. One is that virtually
everybody had these PVC or vinyl or polyvinyl chloride plastic
products within their home. Dr. Schuchat just
mentioned hairspray, but in those hairspray
containers that people were using
back in the early ’70s, it would say “active
ingredient 1% inert ingredient” which was the vinyl
chloride, 99% of the product. Everybody considered this safe,
and so this came as a shock in that shattering
the illusion of safety for these types of chemicals. As Anne said, it’s not possible
to predict the evolution of a new disease, and
it raised many questions about was it more
than just this plant. What about people who
live near the plants? What about people
who use the products? What about other
kinds of chemicals that were fairly similar
to vinyl chloride? There were just many
questions that came out of this cluster
investigation. So, we were there. I was there, but
how did I get there? It was a very unintended career. I finished medical school at
the height of the Vietnam War, was drafted and sent off
for a pediatric internship for residency, and then
was assigned to the CDC because the Army
needed epidemiologists. I matched with a cancer branch. I wasn’t heading for a career
in infectious diseases. I thought it might
be interesting if they somehow discovered
a cause of cancer while I was there
during those two years. There was really, except
for Phil Landrigan, nobody was doing environmental
epidemiology at CDC at the time. NCH didn’t exist. NIOSH wasn’t even part of CDC, and EPA had only
recently been created. So, my assignment was at Texas
Children’s Hospital in Houston. I was asked to investigate
a number of cancer clusters, and those were all
negative investigations. Didn’t find any infectious
causes for them, but I was stationed in the
petrol chemical capital of the United States,
in Houston, Texas. And, all you had to
do was look around and there were chemicals
everywhere. So, on my own time, I started
taking courses at the School of Public Health at
University of Texas in chemical carcinogens,
environmental factors. I did a paper on asbestos and
mesothelioma, and, essentially, I was the only person in
the epidemiology program with an interest, I
think at that time, in chemical carcinogens. So, when this request came
of the NIOSH assistance and the Epi-Aid for
the cancer cluster in, at the BFGoodrich facility
in Louisville, Kentucky, I, who had never done an
occupational health investigation, never had seen
the inside of a chemical plant, there I was with the NIOSH team. So, this cluster was a
wildly improbable event. There are 27 cases per year of
this chemical, of this disease at that time in the
entire United States. So, four cases at one
plant had a relative risk which was somewhere above 6000. Nobody expected this. The alert chemical physician,
chemical plant physician that Anne Schuchat referred
to said it to me this way. When he saw the first
case, it was unusual. When he saw the second case,
he was getting anxious. When he saw the third case, it was like he had seen
three straight patients walk into his office with red white
and blue pimples on their nose. Had no idea what the problem was
but knew he had a big problem. So, I joined the NIOSH team. My original focus was
to verify the cases. When you’re doing cancer
cluster investigations, until you verify the diagnosis, you really have nothing
to work with. So, just so you understand
kind of the process here and what we’re dealing with, so in the upper lefthand
corner is vinyl chloride. It’s basically ethylene compound
with a chlorine attached to it. When you cook it up in those
kind of reactor vessels that you see in the middle of
this slide, they’re like 10, 15,000-gallon pressure cookers. You end up opening
the double bond, and you create the long chain which is a polyvinyl
chloride or PVC. And, depending on how
you actually do that and what chemicals you add to it and what plaster
sizes are there, you either get a very flexible
chemical, like saran wrap, or you get a very rigid
chemical like a PVC pipe. The toughest part of the
job here in the place where there was the greatest
exposure to vinyl chloride is that people had to be lowered
in through the hatch you see at the top of these tanks
to clean out the inside of the tanks between vessels. They basically scraped out
the inside of the tank. They were lowered in
in buckets, often, because these are big
tanks, as you can see. And, very often, people
were anesthetized and put to sleep while doing this work, they were exposed
to such high levels. They had to be carried
out with their bucket. So, again, just briefly,
the production of vinyl chloride monomer is a
closed system, limited exposure. At the bottom, producing
products from the plastic itself has
very little vinyl chloric monomer exposure. It was the polymerization
process itself with the cleaning out of the large vessel reactors that was the really
hazardous part of this job. Now, just to show
you the key dates. The plant opened in 1942. First reported cases of
hepatic angiosarcoma were in the ’73, ’74. But, there was yet
another rare disease seen in these workers called
acroosteolysis which is, as it says, holes at
the end of the bones. And, I think you can see
it if you look the end of the middle digit finger, you can actually see
a hole in that bone. It’s a black spot in
the middle of that bone. Unfortunately, this
was interpreted as a very localized
lesion, probably related to the constant scraping
and trauma to their hands. Wasn’t seen as possibly systemic
in nature, so it didn’t lead to a reduction of
vinyl chloride levels that these people
were exposed to. It led to better care for their
hands as they were working. So, this is the description
of the first four cases in the original MMW article,
and there are three things that I’d like to point out. One is the years of PVC work. These people had worked on
between 14 and 27 years. These original four cases,
but if you look at the date of diagnosis compared to date of
death, two were only diagnosed at autopsy, and there’s
a very short timeframe between diagnosis and death. And, if you look at the,
between the columns between date of onset and date
of diagnosis, again, except for one patient,
a very short period. These people had
a silent disease, and near the end progressed
rapidly to diagnosis and death. So, this is from our next
report which was in JAMA and covered 11 cases, seven
cases of hepatic angiosarcoma and four cases of what was a
nonmalignant hepatic disease, a precursor lesion that
went along with this. And, it’s interesting to point
out, if you look at the dates of diagnosis, there
were four cases that actually were diagnosed
in the ’64 to ’70 period, but it seemed to be rapidly
increasing the seven cases during that last three years. The initial symptoms were just
fatigue, weakness, weight loss. Nothing specific. One of the patients came
in for a hernia repair. They noticed the elevated liver. So, it was very little to
go by in terms of signals that disease might be
developing in these workers. And, this is result of our sort
of quick and rapid analysis of the work histories of
those original 11 cases, and Dick Lemen who’s following
me will give you the much more precise version of this from
the cohort mortality study. But, as you can see in the top
line, these people had worked, on average, 17 years in that
most heavily exposed job, cleaning the PVC
polymerization reactor vessels. They had a smattering of
time elsewhere in the plant, but there was nothing
common about the places where they worked outside of
the polymerization buildings. And, the largest majority of
people who worked elsewhere in the plant, none of the
cases had actually worked in those part. So, it was very clear, even
from the very beginning, that the vinyl chloride monomer
exposure was the critical factor here. So, we were very interested
in how this disease developed, and one of the things
I did is went back and get pathology specimens
from people who had ever worked at the plant and
had a liver biopsy or an autopsy for any reason. If somebody had been in
a motorcycle accident after nine years at the
plant and was autopsied, I had the liver specimen. So, we could array these
specimens over the lifetime of the workers and
actually, you know, see how the disease developed. I work closely with the
director of pathology at NCI, and with arguably the world’s
best liver pathologist, Hans Popper who is
visiting, just happened to be visiting Dr.
Thomas the day I walked in with my trove of specimens. He was one of the
heroes of my life, a great person to work with. We looked thousands of slides
together over the years. So, when I arrived, he
said, “Show me a slide.” Put on a slide of the tumor. He said, “Show me
another slide.” I put it on, he said,
“Angiosarcoma. No question. Show me the rest of the liver. What does it look like?” I showed him one slide. “Show me another.” Second, showed him another. And then, he was a
little shorter than me. I have never actually
seen the light bulb go on in somebody’s head
quite so clearly. He literally bounded out of
his chair, almost shouting that this was Banti’s syndrome. He had seen it in
Africa 50 years before, so it was an exciting
moment for him. But, he actually
understood the pathogenesis. So, this was the sort of
an original portrayal, this figure of what
we were seeing. There was activation
of the sinusoidal cells which are the vessel
lining cells in the liver, activation of the hepatocytes,
and sinusoidal dilatation. That was the precursor lesion. It could extend to angiosarcoma. The hepatocyte proliferation
might have extended carcinoma. It didn’t in people,
but it did in rats. And then, and the top, you
see that it could extend through hepatic fibrosis portal
hypertension and splenomegaly. And, if you look at this
from under the microscope, if you look at this on the left,
the straight hour is pointing to a somewhat dilated
hepatocyte with two nuclei. The curved arrow is
pointing to, so activated, these are normal looking
sinusoidal lining cells, but there are three of
them heaped one on top of the other inside
the sinusoid. And, in general, these
sinusoids are more dilated, larger than you would expect. If you look at the
photo on the right, the sinusoids are much larger, the lining cells are very
anaplastic and misshapen and clearly malignant. And, the arrows are pointing to actually very unusual
hepatocellular cells that have fat globules and other
things which are unexpected. So, you can see the contrast
in how the tumor developed from the precursor lesion. So, the liver disease in these
workers was very atypical. At this agency and, you know, really all through occupational
health, infectious diseases, classis hepatotoxicity comes
where the clinical signs and symptoms appear early. There are enzyme changes. Lots of laboratory
tests are abnormal. The functioning of
the cells is abnormal, and most hepatotoxins
function like that. What we were seeing was a
silent progression, the function of the liver cells didn’t
change until almost the end. There were no simple and effective screening
tests for the workers. In fact, we did a study at a PVC
plant in Pottstown, Pennsylvania and found almost nothing
except a small percent with a very modest
increase in liver size. So, this is actually, you know,
I think it’s a remarkable event in the annals of
occupational medicine, and Dick Lemen is going to go
through this in more detail. But, within a year or
two, through the work that we had done, through the
NIOSH cohort mortality studies, through the experimental work
that corroborated this disease in animal studies, the link
was demonstrated very clearly. And, as a result, the regulatory
fix came very clearly, and the permissible
limits were lowered from 500 parts per million
of vinyl chloride monomer to one part per million. And, the occupational
cases tapered off over the next decade,
and over 20 or 30 years, they pretty much dwindled
down to almost nothing. FDA and EPA did their
bit for food packaging and environmental regulations. So, at this point, I could
probably have gone home, felt that I had done my job
well, and just called it a day. But, we, being in
Atlanta, right, we thought that we could
add to what NIOSH was doing by conducting surveillance
for angiosarcoma of the liver. Maybe we would find
cases at other plants that weren’t being studied. So, we did a death certificate
survey, a national search, miscellaneous liver tumors. You have no idea what
an EIS cubicle looks like with 22,000 paper
certificates in them, but the shocking thing to me
was that we always expected that who would know about
hepatic angiosarcoma. We anticipated a lot
of false negatives. What I never suspected that
people would go to great lengths to call something hepatic
angiosarcoma when it wasn’t. But, less than 50% of the
cases that we retrieved from the death certificates
could actually be confirmed as hepatic angiosarcoma. We didn’t learn, we didn’t
find any more from PVC workers. It was a false cluster that
turned out to be nothing, and in the end, we
discovered that only 23% of cases could actually
be diagnosed on the death certificate. So, we concluded you couldn’t
study this rare disease by looking at death
certificates. So, we went on to
the pathologist. We sent a mailing to all
the U.S. pathologists. We collected specimens
from the files of the Armed Forces
Institute of Pathology. We looked, got pathology
specimens at all published cases. We’ve wrote to tumor registries,
and we identified a total of 168 cases, still with
many false positives. But, I suddenly just realized
that we had four cancer clusters that we were investigating because there were three
other likely causes that were identified,
Thorotrast, arsenic, and androgenic anabolic
steroids. And, together with
the vinyl chloride, 75% of the cases were
still idiopathic. So, just to go through
these one by one. Egas Moniz, whose picture
you see, got the Nobel Prize in Medicine in 1949 for doing
the first cerebral angiograms. And, a year later, a German
group improved on his technique by coming up with a
better contrast medium which was thorotrast colloidal
suspension of thorium dioxide. Thorium is very similar
to uranium, and what people did not
realize in the early days of radiation science was that
the thorium went to the liver, stayed there for the
life of the patient, and radioactively decayed for
the entire life of the patient. You see, the figure is
from a New England Journal of Medicine case study in
1981, and the arrows point to the actual alpha
particle tracks in the liver which are picked up by
special histologic technique, and of course, whatever cells
happen to be in the path of those alpha particles
could turn malignant. So, these thorotrast recipients
actually developed angiosarcoma, bile duct carcinoma,
hepatocellular carcinoma. This was primarily
in Europe and Japan. There were maybe five to ten
times as many malignant tumors that resulted from thorotrast
as from vinyl chloride. Had rarely been reported
in the United States. People, you know, kind of thought we were
doing pretty well. But, we identified 25 cases and
reported on them, and clearly, this was something that had been
going on probably unreported in the U.S. And, I was seeing
the end of this outbreak. So, the second cluster
related to arsenic. So, arsenic is a
known carcinogen, skin, lung, and bladder. The NCI and NIHS
have also concluded that it’s a hepatocarcinogen. And, historically, there have
been multiple case reports and small case series
of angiosarcoma related to arsenic going back to the
early part of the last century from pesticide exposure,
from drinking water, and from something
called Fowler’s solution, 1% potassium arsenite, which
was used in the first half of the 20th century
for treating asthma, psoriasis, and other diseases. We found seven cases,
four of whom were related to the last clinic in the U.S.
still treating asthma patients with Fowler’s solution. And then, finally, we
saw four cases related to androgenic anabolic steroids. These substances cause
classic hepatoxicity. They cause cholestatic jaundice. They also had been reported to
cause sinusoidal dilatation, an extreme form of blood filling
in the liver called peliosis. And, the four cases we
saw were actually filled in the blanks in this figure. So, in the center, you see the
core, the core precursor lesion for the angiosarcoma, and
some of the substances that can cause angiosarcoma
like thorotrast cause only some of the outcomes, like
cancer and angiosarcoma. But, after, with these cases, basically androgenic anabolic
steroids was seen to relate to all possible outcomes from this precursor lesion
including adenoma, peliosis, carcinoma, and angiosarcoma. So, we actually postulated that
it would have been interesting to have set up a rare tumor
registry before the vinyl chloride episode, and if
somebody had been able to do this efficiently
for multiple kinds of rare tumor markers,
we might have picked up the vinyl chloride
episode sooner. There are three reasons
why one would have thought about studying hepatic
angiosarcoma. There was a history
of thorotrast and arsenic in humans. There are multiple chemicals
that cause this disease in animal experimental studies,
and these tumors occurred in younger people with
predominantly males, suggesting occupational exposure
compared to other sarcomas of the liver like fibrosarcomas
and lymphosarcomas and so on. So, maybe if we had been
looking at the rare tumors, might have picked this
up a few years earlier. So, the final part to this
investigation brought me from PVC plants to
meat wrappers, asthma, and supermarkets. So, so, my wife was seven
months pregnant as I was going around the country from one
vinyl chloride plant to another, and at one point, we decided that we needed to,
I needed to be home. And, I was trying to figure
out how do I tell this to my supervisor in Atlanta. And so, what happened
is a woman walked into the Harris County
Health Department, said she was a meat wrapper. She had asthma. She was waving the paper of
that days’ Houston Chronicle which had reported the summary
of an article from the journal that actually described
the first few cases of meat wrapper’s asthma that
had been seen in the country. And so, when you go to the
supermarket, you can see this in these photos which are,
they’re current photos. I don’t have any
photos from 1974. The meat in the supermarket
sits in a Styrofoam dish, and it’s wrapped
from a huge roll of saran wrap kind
of a material. And, the challenge in 1974 was
how you actually cut the saran wrap because it clings
to a scissor. So, they use, like, a
600-degree centigrade hot wire. They would just pull the wrapped
portion across the hot wire. It would sear the plastic, but
there were shards of plastic that were left on the hot wire. And, the women doing this work
spent all day breathing the fumes of burning plastic. Which is toxins, allergens,
irritants, hydrochloric acid. It’s probably a very nasty mix. And so, with Ben Portnoy who was the EIS Officer at the
Health Department in Houston, we decided that people who actually have asthma
can’t do this work. They quit. So, we went off and did a
study of existing workers in 152 supermarkets which
took me exactly to the point of the birth of my first
son, and what we found was that meat wrappers,
compared to the controls, had increased numbers of
respiratory symptoms, illness, days off from work, and so on. And so, this was sort of the
final piece in the PVC study. The film wrap here is what
was considered a copolymer. It was PVC usually mixed with polyvinylidene chloride
or polyvinyl acetate. And, there was a class action
lawsuit for $284 million as supermarkets figured
out how to do this safely. And, by the end of this, realized that I’d probably
contributed in some way to helping 100 to 200,000
meat, lettuce, cabbage, and other wrappers,
tens of thousands of PVC polymerization workers. Kind of did a mental calculation of how many pediatric patients
I would have to see to get close to a quarter of a million,
how long that would take. And, I ended up, of
course, staying at CDC. I was the last of my class of
72 still here even 15 years ago. I love, you know, the
science, the prevention work, the variety of issues
we dealt with. People at CDC, the
policy issues. I succeeded Phil Landrigan as
Special Studies Branch Chief in 1980, President of
the creation of NCH, and still hanging in there. So, lot to be grateful
for my time here at CDC. So, with that, let me
introduce Dick Lemen. Dick was a Deputy
Director of NIOSH and also Acting Director
of NIOSH. He happened to be in
Cincinnati during those years when we were doing this work
and had a very birds’ eye view of what we were all about
and very familiar with all that NIOSH and OSHA achieve. So, thank you. [ Applause ]>>Thank you, Henry, and it’s
good to be back in the CDC. I haven’t been back for
a long number of years, but things have changed a lot. How did I get into this? Well, I begin my
career as a sanitarian for the Missouri State
Department of Health, and as you know, a
sanitarian is an inspector. We did hotels, motels, food
establishment, etc. And, then, as Henry happened to
get drafted, so did I, and I became a medic
in the U.S. Army. And, it was through that
experience that I got interested in epidemiology, and so,
after I got out of the Army, I joined the U.S.
Public Health Service and the Commission Corp. And, at
that time, NIOSH didn’t exist. It was called the Bureau of
Occupational Safety and Health, and six months later,
NIOSH came into being under a new law called
the Occupational Safety and Health Act of 1970
which created NIOSH and in the Department of Labor, the enforcement agency
called OSHA. At that time, there were
two trained epidemiologists in what was now NIOSH,
and I was one of them. And, we now have quite a few
more epidemiologists in NIOSH than when I first started. And, as Henry said, I worked
my way up to Deputy Director and Acting Director of the
institute before I retired. And, currently, I, after I
left, I went over to Emory and taught occupational
and environmental health for a few years,
and I currently am on the Presidential
Advisory Board, President Obama appointed me,
on radiation and worker health. Which I have been active
on for the last ten years. I’m going to repeat a little
bit of what Henry said, but vinyl chloride is
the main ingredient in the plastics industry. And, it was first discovered
in 1835, and Henry’s gone through the formulation, so
I won’t spend time on that. It’s normally in the gaseous
form but shipped in storage under a liquid under pressure. It was used to form
large, molecular chains, as Henry talked about, of PVC. And, polyvinyl chloride is
produced by the polymerization of vinyl chloride monomer. As Henry discussed, I won’t
spend much time on this. However, unreacted
vinyl chloride remains up to 8000 parts per million
after the polymerization process which is a large amount
of vinyl chloride. It’s synthesized from
hydrogen chloride and ethylene using mercuric
chloride as a catalyst. The production increased
dramatically during World War II, and the early
stages of toxicity of vinyl chloride were then
beginning to be recognized. In the 1940s during
World War II, it went up to seven
billion pounds per year due to the limited rubber
supply coming out of the rubber
plantations from Asia and other parts of the world. The first recommended
exposure was at 500 parts per million based
upon its anesthetic effects, and this was done by a conference called
the American Conference of Governmental Industrial
Hygienists which was a group of industrial hygienists who
worked for federal, state, or local governments
at that time. And, Henry has discussed
in the 1960, the acroosteolysis a rare bone
disease occurring among the PVC reactor cleaners, and also
some cutaneous lesions, collagen disease, and
Raynaud’s syndrome. Adverse human effects,
as I mentioned earlier, were basically at
that time known mainly because of its anesthetic,
anesthesia type properties. Exposure during this time were
poorly controlled in the plants. They were up in the 1000s
of parts per million. In the 1970s, PVC number two
plastic in the United States. It was a very widely
used and popular plastic, as Henry has eluded to, and
we, in the United States, did about 25% of the
world’s production. There were 14 plants
employing about 1500 workers. There were 37 plants in the
PVC production employing about 5000 workers, and there
were hundreds of thousands of workers involved in the
compounding and fabrication. It was Dr. Viola in Italy
who first produced tumors from high exposures in animals,
but they were not angiosarcomas. They were skin and ear
canal tumors found in rats. OSHA, as a result of what was
known to that point and time, as one of their original
standard in 1971 adopted what the ACGIH
had proposed the 500 parts per million as the exposure limit
to be allowed in U.S. plants. Cesare Maltoni, another Italian,
and you’ll hear more about him from Dr. Landrigan,
was the first person to produce tumors even including
angiosarcomas of the liver in animals at much
lower concentrations, at 50 parts per million. And, now, I’m going to take you
kind of on a chronology by month by month and year by year
over the next couple years of what really happened when
we started the investigations. Before the angiosarcoma was
even noted, NIOSH published in the federal register
a request for information on potential hazards associated with occupational
exposure to vinyl chloride. And then, in May of that
same year, the federal Food and Drug Administration banned
the use of packaging alcohols in polyvinyl chloride because
they found it was leaching into the alcohol that
was being consumed. So, this was a major
development, but in January, of 1974, that’s when we were
notified about the three deaths, at that time, that had
occurred in the BFGoodrich plant in Louisville, Kentucky from
angiosarcoma of the liver. NIOSH did an immediate
industrial hygiene survey of that facility, and NIOSH
and CDC, as Henry talked about, organized a surveillance network
to follow through on other cases and distribution of
cases of angiosarcoma of the liver among PVC
workers in the United States. In February of ’74, NIOSH
and CDC held a briefing of all federal agencies with an
interest in this to talk about, by that time, four deaths from
angiosarcoma of the liver. And, during this briefing, we
discussed how rare this was. Henry talked about this, but
20 to 30 cases were occurring in the United States
per year at that time. And, we had concluded,
at that time, that this was a new occupational
disease that was associated with exposure in the manufacture
of polyvinyl chloride. There were four working
groups that were convened in the U.S. government as
a result of this meeting. The first being on epidemiology. The second on toxicology, and
the third on industrial hygiene. And, finally, a fourth
on analytical methods. So, this was how the federal
government was setting up to address this new
occupational disease. On February 9th of 1974,
clinical descriptions on several cases of angiosarcoma
were now being published, as Henry talked about in the
MMWR, and also an article in the Journal of the
American Medical Association. So, we were getting the word out
that this was a new condition to alert physicians and other
clinicians to be on the lookout of potential persons and their
practices that may have exposure to vinyl chloride in the
polymerization process. OSHA, our sister agency, held
an informal factfinding hearing on possible hazards of vinyl
chloride manufacture and use, and then, at that time, Cesare
Maltoni, the man that I talked about earlier that
had experimented on the lower exposures at 50
parts per million, actually came to the United States
to address that hearing and to discuss the finding of
angiosarcoma in the rat studies that he had done at that time. Well, the first director
of NIOSH, Dr. Marcus Key, who I can say is still alive
today and remembers this, I think, fairly readily. Dr. Marcus Key was
the Director of NIOSH, and he addressed OSHA
saying that at this time, there was no safe exposure
concentration that we could find at NIOSH for vinyl chloride. And, there was no odor
threshold for vinyl chloride, so it wasn’t readily
detected by the workers. Workers were warned to wear air
supplied respirators any time they were exposed to any
concentration of vinyl chloride, and the current level of
sensitivity for monitoring through the analytical
methods that we had at that time were
one part per million. But, this, Dr. Key stressed, should not be considered
an acceptable level, and all workers at this
concentration should be wearing respirators. Well, on May 10th and
11th, the New York Academy of Sciences convened an
international working group on vinyl chloride, and
many of the luminaries on vinyl chloride
came to that meeting to discuss their findings. As a result, NIOSH proposed a
standard for vinyl chloride, and in June of 1974, Dr. Key
addressed this and reiterated that there is no safe exposure
limit that could be found. He reiterated that the current
analytical monitoring method sensitivity was down to
one part per million. He stressed that
all workers working with vinyl chloride be
afforded respiratory protection, and if NIOSH decides to set
a permissible exposure limit at one part per million, this
should not be considered safe. It only should be
considered acceptable. So, the exposure measurements
that NIOSH was finding when we went out throughout
the United States looking at exposures to vinyl
chloride were between .3 and 12 parts per million
in the United States. The time weighted average was
estimated in the working places that we surveyed to be at two
parts per million at that time. But, the problem was, we were
seeing peak concentrations getting up to 300
parts per million. And, who was, were the
people most at risk? It appeared to be the
maintenance and repair workers that were experiencing
the highest exposures. Angiosarcoma cases associated
mainly in those that worked in the reactors and the vessels where the reactions
were occurring. You saw those pictures
that Henry showed earlier. In June, Dr. Key testified
to Congress, and he talked about NIOSH and the Department
of Health Education and Welfare, now the Department of
Health and Human Services. Had set up a committee
to coordinate toxicology and related programs
to define procedures for designing animal studies to
determine the carcinogenic risk since at that time, did not
feel that the European studies or other U.S. animal studies to
date had been either too small or lacked statistical validity
to project no effect levels. So, the purpose was
to try and determine if there was a no effect level. We informed, he informed OSHA that NIOSH CDC surveillance
had identified by June of 1974 18 cases of angiosarcoma
of the liver in PVC workers, one case in a vinyl chloride
monomer production worker. Thirteen of those were
in the United States. Six were from other countries. The average age of those
workers was 48 1/2 years, and the average latency
was about 20 years. Two new cases in
workers using PVC and fabrication were
also identified. Dr. Joseph Wagner. Dr. Wagner was the first Head
of Epidemiology at NIOSH. He was a Harvard trained
epidemiologist and had come to NIOSH from the
National Cancer Institute. And, he followed Dr. Key’s
testimony to the Senate and identified where these
cases were occurring in Germany, Sweden, Norway, and
there were two cases that we were awaiting details at
that time from Czechoslovakia. The rest of the cases
identified around the world were from the U.S. It was interesting
in Dr. Wagner’s testimony that he also talked
about angiosarcoma of the liver found among non
vinyl chloride PVC workers. In the United States, we
saw a case of an accountant. As you can see, 47 years old, who worked in a vinyl
cloth plant. Those are plants
that use vinyl PVC to make vinyl cloth wall
coverings or table cloths or things of that nature. Another case in west
Germany in the 40 and age 40s also was a person
that filled pesticide cans with vinyl chloride propellent. As you heard Henry talk
about its use as propellent in hairspray, it was
also used in pesticides. And, a third case occurring
in another vinyl chloride, or a vinyl cloth plant. I don’t know, and we didn’t know at that time exactly what the
job of that individual was. And, the last case in Sweden was
among vinyl monomer production plant worker. Well, workers at potential risk. At NIOSH, we held, we
did a survey between 1972 and 1974 called the National
Occupational Hazard Survey. We sampled 900,000
workers at 4636 facilities, an unheard task at that time. But, we had industrial
hygienists spread across the United States living out of suitcases
taking these samples. What did we find? We estimated that there
were 27,000 workers with definite exposure
to vinyl chloride, and another two million
plus potentially exposed to vinyl chloride. Now, I’d like to switch
and talk a little bit about our cohort mortality
study that was done at NIOSH, and Dr. Rick Waxweiler
who is here in the audience should
be telling you about this because it was really he
that spearheaded this study. But, I’m so glad that he’s here
today and can address this, maybe, if we have
questions at the end. But, we did a study
of 1294 workers, amounting to about little
over 12,000 person years, almost 13,000 person years. Four plants with at least
five years of exposure as of the 31st of
December of 1973. Eighty-nine percent were alive. Ten percent were deceased, and less than 1% were
lost to follow up. What did we find? Well, we found that all cancers
were significantly in excess as compared to the other
causes of death you see here from heart, nonmalignant
respiratory disease, etc. If you look
closer at the cancers, the all malignant neoplasms
category, you can see that the, as the latency went up
from 10 years to 15 years, that also the significance or the standard mortality
ratio went up. And so, we were seeing a dose
response reaction occurring. We saw significant
excess of brain and central nervous
system cancers, also respiratory system
cancers, and if you look at the liver cancers
and the biliary cancers, you’ll see a very
significant excess of death. If we look at these seven
angiosarcomas of the liver that were found, you
can see the distribution of age, the total exposure. All of these were, with the
exception of one, were greater than ten years of exposure
with latencies all greater than 15 years of exposure. So, we’re seeing
this dosed response, but we are also seeing,
as we usually see in occupational cancers,
a latency period occurring from onset of exposure to
the development of disease. Also, in the study found
angiosarcoma of the gall bladder or the common bile duct,
gallbladder cancers, and adenocarcinoma of
the common bile duct. And, there were four people
that were not in the cohort, but they were found to
be alive in the plants that were diagnosed
with angiosarcoma of the liver at that time. If you look at the exposures, you’ll see that the highest
exposures were occurring in the reactor area and the
operators as well as the helpers that were working to help
the reactor operators because the reactor operators
actually, when they would go in after they were, the process
was done, would have to go into the reactors and actually
clean out the inside by chipping out and high pressure hoses to
wash out the reactor vessels to make them usable
for future use. You also see there was
high exposure occurring in the dryer area, but if you
look at just other operators or baggers or maintenance area,
the exposures did not peak to as high as we
saw in these areas where the actual cases
were coming from. If you look between 1975
and 1976, you’ll, again, see that we had exposures
in the reactor and operator charging areas,
but we found a new finding in bagger and reactor cleaners. Where, if you broke
it down, it was really when they were cleaning that this exposure was
exceptionally high. When they were working outside,
it was an enclosed process, so they were not getting
the exposure to the fumes. Again, this led us to looking
at what were the differences between the monomer plants,
the polymerization plants, and the fabrication plants? Well, we were seeing the
greatest amount of disease in the polymerization
plants, and as you can see from this table that the
concentrations were highest again in the reactor area and
in the dryer/operator area. So, this gave us a
little bit more clue to where the cases were
occurring and where we needed to concentrate our
efforts in trying to stop this disease
from occurring. So, now, we were concentrated
from the data on the reactors and the reactor cleaners
being those highest at risk. But, let us look what
happened after 1974. The picture was that
these concentrations were extremely high. Most of them, a majority greater
than five parts per million. But, as we started
instituting the OSHA standard and getting the word out that we
needed to reduce these exposures down to the one part
per million, the lowest analytical level,
you’ll see from ’75, ’76, ’77, these exposures went
down precipitously, so we were making progress on
getting the exposures down, and that was a result of
the OSHA standard that went into effect in the late 1971. Now, an update was done in
1989 of the Waxweiler study, and it’s interesting
that the findings in this update added
another 13 years of latency. And, what they did was to conduct a nested
case control study of the vinyl chloride monomer,
the PVC dust, and butadiene that was found in this plant. But, we were interested more in
the VC monomer and the PVC dust. And, what they found in updating
the study was a strong dose response between the vinyl
chloride monomer exposure and liver cancer. But, what we didn’t expect to
find was that while this held for the angiosarcoma of
the liver, it didn’t hold for the other liver cancers
that were in excess before, significantly in excess. After you added more
latency and took into consideration
the exposures, this kind of washed out, so we were seeing some
progress being made. The previous findings of lung and brain cancer were not
supported in the new analysis. And, why was this? Well, Wu suggested this could
be due, one, to the standard that was put in effect by OSHA
that became effective in 1974, or at least they could
have maybe been attributed to the 19 other chemicals that
we identified in the plant in the original study
that weren’t, as far as this study could tell, associated with the
vinyl chloride monomer. Or, could be due to
difference in smoking habits because these were
not controlled for. Interestingly, in May of
1976, the state of Ohio looked at a worker community
around vinyl chloride plants and started identifying
congenital malformations of the central nervous
system in residents that were near these plants. In September of ’78, as a
result of the NIOSH study and the findings to date, NIOSH and OSHA issued a joint
current intelligence bulletin. This is something to get
the message out quickly, but what NIOSH did and OSHA did
was to look at vinyl chloride and put it together with other
vinyl halides like vinyl bromide and vinylidene chloride and
recommend as a precaution that all of these be treated
as potential carcinogens because of their structural
similarities, the animal studies that had produced angiosarcoma
of the liver and other cancers in animals to all
of these compounds. So, finally, today,
we’re living still with the 1 part per
million standard. We haven’t improved our
analytical methods that readily, but the current OSHA standard is that vinyl chloride
be controlled to one part per million as an eight-hour time
weighted average. And, for a 15-minute sealing, it not exceed five parts
per million and be treated as a carcinogen and
that protective clothing and respirators be used and authorized personnel only
allowed into the work areas. So, this is a quick survey
of what NIOSH and CDC did in identifying where the hazard
was occurring, who the people that were being affected by this
hazard were, and where we needed to concentrate our preventative
method on in producing and preventing further exposures
from this particular carcinogen. Thank you very much. Now, I’d like to introduce Dr.
Phil Landrigan who’s a longtime colleague and researcher. And, Phil came to
NIOSH from CDC. I think he’ll probably tell you
a little bit more about that. But, headed up the NIOSH
epidemiology program. So, it’s with pleasure that
I introduce Dr. Landrigan.>>Thank you, Henry. [ Applause ]>>So, I want to start
by thanking Phoebe for having invited me to
come here to do this talk and say especially to my
former mentor sitting here in the second row, Lyle Conrad, how transformative
my time in EIS was. I came here pretty much straight
out of a pediatric residency. Very similar background
to Henry. He was from New York. I was from Boston. The Vietnam War was going on. All male physicians were
subject to the draft, two years national service. Most of my colleagues
ended up in the Army. Some in the Navy
and the Air Force. And, I got, I was
almost taken by the Army. I actually, I was interning
in Cleveland, and I got called down to the Cleveland
Federal Building to take a physical exam. And, then, I got a
call from Michael Grey who was then the Deputy
Director of the EIS program, and he asked me if
I was in a place where I could raise
my right hand. I was sort of like
one of those preachers that healed people
through the radio. And, I, in the intern ready room at Cleveland Metropolitan
General Hospital, I was sworn into the U.S.
Public Health Service, the EIS. And then, I asked Mike if I could have two more
years to do a residency. He said, “Sure. We’re overfull this
year anyway.” So, went to Boston and
finished my residency. I came here in April of 1970. I was thinking as I drove in
from the airport this morning that it was about 48 years ago
this week, give or take a week or two, that I made the first
passage from the Atlanta airport out to, up to Clifton Road. A long time. And, I got here knowing
nothing about epidemiology. I remember coming in
for the EIS conference, hearing people talking about
the denominator and trying to remember if that was the top
of the bottom of the fraction. I matched with the
immunization program. My supervisors were the late
John Whitte and Lyle Conrad, and for the first couple of
years, my job was basically to investigate measles
and rubella outbreaks. The vaccines existed,
but they were quite new. I think the measles
had come out in ’67, if memory serves me correctly, and the rubella a
year or two later. So, there was still
questions about how firm and how durable was
the immunity. I had a very interesting epi aid
up in Olmsted County, Minnesota, that’s Rochester, where the
County Health Officer had followed the British tradition
of vaccinating only the girls because they were afraid that
the immunity might not hold. And, the whole goal of rubella
vaccination, you’ll recall, was to prevent rubella,
congenital rubella syndrome. So, he vaccinated girls
who were hitting puberty. Didn’t bother to vaccinate the
boys, and so we had an epidemic of rubella where 90% of
the cases were in boys. I had a measles epidemic
in Texarkana which is a city bisected
by the state line between Texas and Arkansas. And, again, it was a
very bizarre situation. Ninety percent of the 600 cases
were in Texas, and the answer, it turned out, was
that Arkansas, even though it’s
a southern state, has always had a fairly
strong populist tradition. Think of Bill Clinton. They had a very aggressive
public vaccination program. Texas was Texas, and
you had to pay $10 or $20 to see the doctor. Which meant poor people
didn’t get vaccinated, and there was a large pool
of unvaccinated children. And then, probably the most
important epi aid at least in terms of my own life course
was going out to El Paso, Texas which is where
I first met Henry. We had gotten a call. I think it was Lyle that
took the call, actually, from Dr. Bernard Rosenbloom who was the City County
Health Officer in El Paso. They had just stumbled over
the fact that this big smelter which had been there
for decades, in just three years before our
epi aid had released all these tons of heavy metals in
the air in El Paso, Texas. The prevailing legend at
that time was that lead from smelters was not a hazard
for children because it came through the air, and it
didn’t really hurt them. But, we were worried,
and so we went out there, Steve Galback and I, and Henry joined us a bit later. And, we did first a pilot
study in a little local nursery where 90% of the
children had blood levels over 40 micrograms
per deciliter, which was, then, the limit. Today, of course, it’s 3.5. But, they were elevated. That prompted a big
investigation, and what we, this was a transitional
time for CDC. Just the year before, it
had, the name had changed from the Communicable
Disease Center to the Centers for Disease Control,
same initials. And, we were, the only
tools we had were the tools of infectious disease
epidemiology. So, we were applying infectious
tools to look at an outbreak of chronic disease much
as Henry did in chasing down the vinyl chloride
and peeling that onion layer after layer. This was a similar
story out here. And, we did big surveys
out there. We documented a major point
source of lead poisoning. We went on to do studies
showing that the children who had elevated levels of lead
had neurological deficits even in the absence of
clinical symptoms which is a very important
finding at that time. And, anyway, it was
also intriguing that I decided I wanted
to stay on at CDC. I didn’t want to go back
and become a pediatrician in New England which as plan
a. I ended up staying in CDC and NIOSH for the next 15 years. And, my first immediate
job was to switch over to the smallpox
program, mainly because that’s where billet was located. And, Bill Foege sent me off to Nigeria with Al Noonan for a year
to do some smallpox mop up. Then, I spent another year
in El Salvador the way, the reasoning got to El
Salvador, Lyle called me in one afternoon and
said, “Landrigan, do you speak Spanish?” I’d been in El Paso, and of
course I knew several phrases. Couple of them suitable
for polite company. And, I said, “Si, Senor.” And, he said, “Great.” And, he sent me off to El
Salvador for a year to ride around the country in a jeep
and run vaccine programs. I learned some Spanish. Not too well. [Spanish word] Then,
I came back to CDC. Those, my overseas
adventures had ended. My children were
forgetting who I was, and so I had to take a real job. And, I joined the, what
was called the Cancer and Birth Defects Division,
and we started a new program. We were going to call it the
Environmental Hazards Activity, but we ere afraid that that
would draw the wrath of EPA. So, we camouflaged the name, and we called it the
Special Studies Branch. And so, Henry and I
had adjacent offices. He was running the
Cancer Branch. I was running the
Special Studies Branch. I think each of our branches
was two people or three. No more than that, EIS officers. And, the place was changing. The NIOSH was coming in. You’ve just heard. I won’t go back over
that history. But, CDC was starting
to grow up. It was, by then, the Epidemic
Intelligence Service Program was about approaching its 25th
year, and the sole focus on infectious diseases which had
long been the modus operandi was beginning to shift. And so, I stayed at CDC. I worked with Henry, with
Ed Baker, with Roger Glass, with Kay Criss, Dale Morris
were some of the key players in that Special Studies Branch. I realized I needed more
education because I was, I was flying up to Wisconsin
one day to investigate a spill of phenol and having read about
the chemical in the airplane on the way to Wisconsin. And, thinking, “This is
no way to be an expert.” So, I got CDC to send me
out to the London School of Hygiene for a year. I had intended to take a course
in Environmental Medicine or Environmental Public
Health, but it didn’t exist. So, I took Occupational. Environmental was still a
few years in the future. And, following my return,
I was assigned to NIOSH. Worked on a number
of epi aids up there, health hazard evaluations. And then, in ’85,
I left active duty in the U.S. Public
Health Service. Fortunately, I checked
the box to remain in the inactive reserve
which I commend to any of you who might be contemplating
that decision and joined the faculty
at Mount Sinai. And, here, my initial
responsibility was to set up, to build on the work of the
great Irving Selikoff and to set up programs in occupational
medicine. So, one thing we did
was establish unique, to this date the only one in
the country, network of centers of excellence in occupational
health across New York State. These centers form the backbone
of the medical response to 9/11. For my sins, I became
a Department Chair. After 9/11, our department
became responsible for annual monitoring of
20,000 of the first responders, the police, the firefighters,
the paramedics, and so on. I built a program in
children’s environmental health, drawing on my pediatrics. I’ve just, the last
two years finished up producing this
massive lancet, the report of the Lancet
Commission on Pollution and Health, finding
that pollution in all its varied forms
kills nine million people around the world, making it
responsible for three times as many deaths as AIDS, malaria,
and tuberculosis put together. Spent a little time in the
Navy because I miss the fun of being an EIS Officer. And, because I don’t want to
retire, possibly not ever, on July one coming up this
year, I will be moving back home to Boston to launch a
new undergraduate program at Boston College in
Global Public Health. So, how did I get,
what was my involvement with the vinyl chloride episode? It was more peripheral than
either Henry or Richard, but I was, because of
the life course I took, I had the opportunity to
see some of the consequences of the vinyl chloride
investigation that played out in spheres beyond
the spheres that Henry and Richard have described. And, the fact that I worked with
Selikoff and became very close to Maltoni, whose name
you’ve already heard. So, this was Maltoni. A fascinating character. A real, a complete
piece of work. He was a cancer pathologist
in Italy. He pioneered what’s
called the lifetime carcinogenesis bioassay. But, so, typically,
when an organization, when a research group
does cancer testing, they expose adolescent animals. They keep them alive for
6 or 12 or 24 months, and they sacrifice them. They look for cancers. Maltoni said that’s silly. Most humans don’t
develop cancers until the last two
decades of their life. Let’s let the rats go
the whole lifespan. Let them die naturally,
and then autopsy them. And, it turned out to be a
much more sensitive means of diagnosing chemically
induced cancers in animals. And, it was through that
methodology that he was able to find that even relatively low
doses, low doses for the time at least, could cause vinyl
chloride, could cause cancer. Maltoni did his work in this
castle outside of Bologna, the Castello di Bentivoglio,
known to some of the locals as [Italian], the Castle of the
Rats, because there are hundreds of thousands of rats, and they’re in their various
toxicologic experiments going on. And, that’s, that castle is
today the home of the [Italian]. And then, this was my other
mentor during that phase of my life, Irving Selikoff,
a brilliant chest physician who had won the Lasker Award
which is like the Nobel Prize in Public Health, for his
pioneering work in the treatment of tuberculosis in the 1950s. Then, he had a clinic over
in Patterson, New Jersey, an industrial town about 15
miles from New York City, and in the ’60s and early
’70s, he’d began seeing workers with these very odd
transverse striations in their mid lung
fields on x-ray. End stage tuberculosis
mostly in the apices of the lungs up at the top. But, these people had
mid lung field lesions, not something he had
ever seen before. He was a smart physician. He took an occupational history. He found that all
these men had worked in a little factory
called United Asbestos and Rubber Company, UNARCO,
making asbestos gaskets for the Navy for use
during World War II. And, he set up cohort
studies and made a lot of the seminal discoveries
linking asbestos exposure to human cancer. And, very excellent scientist,
but also a powerful advocate. Well, these two giants
of science met at that fateful workshop that you’ve already heard
both Richard and Henry mention that was convened in May of
1974 at the New York Academy of Sciences to talk
about vinyl chloride. I was there also. I was way back in the
last seat in the back of the room just amazed at
what was going on around me. Not appreciating that this was
one of those points in history that could be described
as a fulcrum, when these two people
met for the first time and forged a powerful bond that
has, that resonates to this day. They decided through their
experiences in dealing with the scientists
and physicians of the plastic industry
that they needed to find, that they needed to form a
society in occupational health that was free of
industry influence. You have to understand,
back in that day, most big companies had
in-house physicians. Some were honest, decent, guys like Dr. Creech, the physician up at Louisville who
reported the first cases of vinyl chloride monomer
that Henry investigated. Many others, to put it bluntly,
were shills for the industry. They were people that argued that asbestos didn’t cause
cancer, that lead was a vitamin. Really, there were people in the
lead industry who tried to argue that lead was an essential
trace element in the face of studies showing that
it eroded children’s IQ. So, Selikoff and Maltoni
decided that they needed to form an organization,
small, tightly knit, independent thinkers, not
in the pocket of industry. And, they created this
Collegium Ramazzini which exists to this day. And, this collegium has become
a powerful independent voice, always based in science, but
doing evidence-based advocacy, pushing for change to protect
the health of the workers to protect the environment,
and I think we’ve made a lot of progress in some places. Although, there’s certainly
a great deal yet to go. And then, there were some
other long-term consequences of this episode that you heard
described in such detail today. There’s no question that the
vinyl chloride episode basically brought NIOSH and CDC together. When NIOSH and CDC
first came together, it was a shotgun wedding. David Sencer was the
Director of CDC at the time, a very aggressive guy. He saw a moment of opportunity,
and he gobbled up NIOSH. And, NIOSH people
were not happy at all. They had their institute. They were separate. But, the bonds that were
forged, the scientific and interpersonal
bonds that were forged in this investigation and in subsequent years
have proven very important and brought NIOSH
into the CDC family. These investigations that
you’ve heard described in such detail this
afternoon set a standard for the epidemiologic
investigation of these rare diseases. That just, that wasn’t
here before. Another consequence which both
of my colleagues have mentioned, but I want to just put in a
new, portray in a new light. When OSHA required that the
vinyl chloride standard be reduced from 500 ppm to 1 ppm,
you could have heard the screams of rage and pain from the
industry all the way to Seattle. They said it can’t be done. We’re going to have to move
our factories to China. We can’t meet that standard. Well, obviously, they did. Within a year, and I
think it was Goodrich who pioneered the new
closed loop technology where the reactor
vessels were cleaned by an internal rotating thing. No longer had to lower people
in on ropes to do the job. It actually made them
a very handsome profit because they weren’t wasting
substantial quantities of the very expensive
vinyl chloride monomer which previously had just
boiled off to the atmosphere. So, this was the
prototype, the archetype of a technology forcing standard that the industry
couldn’t meet the standard by simply tweaking that process. They had to fundamentally
rethink it, put smart engineers to work, [inaudible]
and get to work. And, finally, one more
consequence which I thought of only too late after I had
already made this slide is that the vinyl chloride episode
illustrates a recurrent pattern, unfortunately, in
American public health that we’ve seen time
and time and time again. That new chemicals
are brought to market, are presumed innocent,
are put into products, are widely disseminated
into the environment, result in the widespread
exposure of people. And then, oops, 10,
20, 30, 40 years later, we find out that
they’re causing, we saw this with [inaudible]. We saw it with
diethylstilbestrol, with vinyl chloride, with
polybrominated diphenyls, with phthalates, with Bisphenol
A, right up to present. Organophosphate pesticides which almost certainly
cause prenatal brain damage, despite what Scott Pruitt says. And, the way we regulate
chemicals in this country has
always favored industry over public health, even with
the modest legislative advances that were made in 2016. So, it’s, I think it’s
a wonderful story. It’s a prism through which to
see a lot of how environmental and occupational epidemiology
evolved in this country and how the CDC fostered it. And, with that, I thank you. [ Applause ]>>Hi, questions from
our online audience. One of our global listeners
wants to know outside of the U.S., how
widespread is PVC use, and are there efforts
underway to limit its use?>>Can you hear me now? I don’t know that I can
address that adequately, but PVC is still extremely
widely used throughout the world. But, hopefully, through
this early investigation and the knowledge that we’ve
gained from that investigation, and as Dr. Landrigan talked about how the systems
are now enclosed. This is a normal practice
to enclose systems and keep workers
away from the fumes that are causing the disease. So, I think that
is a consequence that has spread worldwide. And, through organizations
like the Collegium Ramazzini and others, this message
does get around the world. The World Health Organization
has an occupational health program that has adopted
these same principles that we have recommended as
a result of this evaluation, what 40 years ago, 50 years ago.>>So, if I let you
stay it a little bit, I did a quick literature
survey in anticipation of today’s session, and
as I mentioned before, the number of cases worldwide of hepatic angiosarcoma
tapered off rapidly. And, but, there still
are a smattering of cases that get reported in the
’90s and the early 2000s, particularly in Asia,
from developing countries. So, there are occasional cases of hepatic angiosarcoma
PVC still occur. Very small number, but
occasional ones still do occur.>>Thank you on behalf
of our online audiences.>>Yes, so, David Bell,
Division of Viral Diseases and EIS class of 1979. This is just wonderful
to listen to this story, and from three luminaries,
really, in the field is even
more of a blessing. I had three questions
if you’ll permit me. One was what was the reaction
of the company at the time in the early stages
of the investigation? It’s the occupational
health physician, I guess, that called you. So, the company must
have authorized that, but, or did they? But, then, when it came down
to the investigation were they delighted to hear
and all arms open, or how did this actually work? And, there were other
rubber companies and industries, and
just at the time. The second question is were
you surprised at all not to find more cases when you
did your nationwide search? I mean, I understand
there’s latency. I understand there has to be
intense exposure, but still, from what I heard,
or thought I heard, this was an almost ubiquitous
chemical in human life from hairsprays to making
plastic and saran wraps. And, I guess I’m, and here, there were three
cases at one plant. I guess I’m, were you surprised
that there weren’t more case? And, the last question is,
you know, it’s just intriguing that these, this, the list
of rare cancers that I forget who had a nice slide of
this, that were discovered to be caused by common
chemicals. And, is there a way that the? Somebody suggested making the
sentinel system or something. Is that real? Is there a way that can happen
so that humans don’t have to be the canaries, and
are there, are there, so many chemicals that, how, could you elaborate
a little more on what you were eluding to? Thank you.>>So, maybe I’ll begin
and then I’ll hand it over to Dick and Phil. But, in regard to your
first question, my, because I dealt a lot with the,
I did 13 trips to Louisville as part of that investigation. I spent a lot of time
with the plant physician. But, also spent time
with the Medical Director of the BFGoodrich company. And, I think they understood
that they had a very tough issue on their hand, and
my sense of them, in terms of my personal
dealings, they were very forthcoming. So, they provided me access to
all the files in the company when I wanted cases
of this or that. They arranged for me to
interview the families of people who used to work there. And, I even, I had one tense
moment at the end of seven weeks of collecting endless pathology
specimens in Louisville, as I was about to leave, sort
of the senior most pathologist in Louisville asked me
if I would please hand over all the pathology
specimens because he had a grant from BFGoodrich, and he really
needed to write a paper. And, I was, I called the
Medical Director, and I said, “It’s nice that you’ve
given him a grant, but this is work
that we’ve done. Our specimens are
going to Hans Popper.” And, they were very good
at following through. They supported rather than
interfered in any way. I can’t speak to
the legal issues and whether there were any
court suits, but in terms of my investigation, they were
as forthcoming as possible. And, the second question was.>>Why not more cases?>>Oh, why not more cases? So, you know, my,
the best I can say is that these people were
very heavily exposed, and I really think it takes a
fair amount of vinyl chloride to actually cause the
progression all the way to angiosarcoma of the liver. There was an industry led group
that took over from NIOSH, keeping track of all the
vinyl chloride related cases in the world, and
the last report I had from them was like 1991. At that time, there were
200 people, you know, vinyl chloride related cases. There are several more
in the literature. I just think that, you know,
these people were so heavily. You imagine these people were
effectively anesthetized doing their job. It really took a lot
of exposure, I think, to ultimately cause an
angiosarcoma of the liver. So, we were afraid there
might be many more cases, but they sort of topped
out at several hundred.>>I might address
your last question about human canaries, and. One of the things that
happened was that during, it really depends upon the
administration that’s running the country at the time
how things get done. But, during the Carter
administration, OSHA and EPA and other agencies, FDA, started
looking at what we could do. And so, an act was put together
called the Toxic Substance Control Act, which
essentially was that when a chemical was
introduced into the workplace, it had to be pretested before
it came into the workplace on at least animals to see
if there was any reaction. Well, it was nice on paper, but it never really
got much carried away. And, we’ve just seen in the Obama administration
the reintroduction of a toxic substance
control act to update this. Maybe Phil wants to talk
about this a little bit more, but we are trying
to get pretesting, and I think that is the answer. How far you go with
pretesting is another question, but one last comment
on the companies. I think BFGoodrich,
their physicians and their company were
unique among a lot of chemical companies,
and I worked with a lot of chemical companies. And, I’ve never seen many
chemical companies as open as what that company was
when these cases occurred. As Phil addressed in his,
you see a lot of companies that they want their doors
closed and they don’t want to share their information
with you. BFGoodrich, at that
time, was not like that, and I commend them for that. Phil?>>Yeah, I’ll just add a word
on the chemical testing issue. So, to give you some numbers, there are about 80,000 chemicals
registered with U.S. EPA for commercial use
in this country. There’s about 5000
that really matter. These are the ones that are
produced in sufficient volume to result in exposure. When CDC rolls around the
country under Anne Hanes and does their national
biomonitoring surveys, CDC routinely picks up
detectible levels between 200 and 300 chemicals in all of us. Most of them are chemicals
that were invented since 1960. The real issue is that
only a very small, relatively small percentage have
ever been tested for toxicity. As I said earlier, so
starkly illustrated by the vinyl chloride episode,
chemicals come on the market with little or no testing. In the 40 years that the
original Toxic Substances Control Act that Dick just
mentioned was on the books from 1976 to 2016, only five
chemicals were taken off the American market under that piece
of legislation in 40 years. It’s basically toothless. The new law was passed in
by partisan fashion in 2016 and was moving along
very nicely. But, there hasn’t been
much enforcement of late, and chemicals, it appears to me,
are, again, coming on the market with essentially no scrutiny. So, humans are the canaries.>>Mentioned the vinyl chloride
standard before this outbreak was 500 parts per million, or the monomer standard
was 500 parts per million. Where did that number come from?>>Well, as Dr. [inaudible]
who was with the Public Health
Service and was Chair of the vinyl chloride, or
of the ACGHTLV committee at the time often mentioned, these were seat of
the pants guesses. Most of them came
from the industry, and this is what he industry
said they could live with. I know I’m being a little bit
not very optimistic about it, but that’s how most of these
early standards were set. The industry said, “We
can live with this number, and we think it’ll work. But, we don’t know if it will.” And, that’s how they picked
500 parts per million. It didn’t put their workers
to sleep, and vinyl chloride at that concentration.>>Yeah, it was the
anesthesia threshold. Yeah. Yeah.>>Can I add one
additional comment. There’s no more questions. Just wanted to, just as an
update, again, just checked with the cancer program
here before. I just wanted, I was curious as to whether there are any new
causes of hepatic angiosarcoma that have cropped up since. But, the actual background
race of hepatic angiosarcoma, given the population size, have
not really changed since then, so there are undoubtedly
are other causes out there, but they haven’t
surfaced in any way yet. And, maybe the last
thing I would add is that Hans Popper was
really an exceptional person who later became President of Mount Sinai School
of Medicine, but.>>[inaudible] medical school.>>The medical school. And, he actually, Robin
might appreciate this. He actually was a resident at
the Lawson Army General Hospital which is now the [inaudible]
campus during World War II, and his family, they
were Jewish. They were in Austria in 1938. His family was told they had
eight hours to leave Austria. His father was a cardiologist. At age 75 came to this
country, did an internship at Cook County General Hospital. And, Hans Popper ended
up being a resident on the [inaudible] campus taking
care of evacuees that were flown into Peachtree-Dekalb Airport. So, he actually had a connection
with our work here at CDC. Okay. Thanks.>>I just want to
say in closing. I just want to just thank CDC,
the institution and all of you, because CDC changed my life. I would, there’s no way in the world I would have
done what I have done if it had not been for my
experiences in EIS Officer. So, thank you very much. Lyle.>>I would echo that that
CDC changed all of our lives. NIOSH didn’t want to become
part of CDC, but we did. We came kicking and dragging,
and they dragged us in, but it’s been a better
world since we came.>>And, I’d like to thank
all of you for joining us, and I’d like to ask you
to thank the speakers for their phenomenal
presentation and their work. Thank you. [ Applause ] And, also, if you want to
know a little bit more, the library has a
display downstairs on the polyvinyl chloride and
the angiosarcoma investigation. And thank you again for
coming and for tuning in, and we’ll see you for the
next We Were There in August.

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