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Hello everyone, my name is Keeve Nachman.
I'm on the faculty of the Johns Hopkins Bloomberg School of Public Health in
the Departments of Environmental Health Sciences and Health Policy and Management.
I'm also the Director of the Food Production and
Public Health Program at the Johns Hopkins Center for Livable Future.
And I'm going to talk to you today about a particular tool that I use quite a bit in
my work and that, that hopefully will be very useful to you called risk assessment,
which is a real critical piece in environmental decision making.
Before I start, I'd like you to consider two different scenarios that will set up
how risk assessment can be used to make environmental decisions.
The first, I'd like you to imagine a drug called Roxarsone, which is
an arsenic based anti-parasitic drug that used to be used in the poultry industry.
When Roxarsone was used, there was concern that much of the drug ended up in poultry
waste as arsenic, and some of the drug stayed behind in chicken meat as arsenic.
And when the poultry waste was managed, it was typically applied to
agricultural land as fertilizer, where it could run off and contaminate groundwater.
Poultry waste was also incinerated in waste-to-energy generators,
at which time arsenic could be introduced into the air
through the stack emissions from the incinerator.
And lastly, poultry waste in many cases was turned into fertilizer pellets that
were sold at hardware stores for use on commercial and residential lands.
So risk assessment could be used in these various contexts to say,
based on the use of this drug in food animal production,
how might we expect people to be exposed to arsenic?
And as a result of that, what would be their increase in cancer risk or
the likelihood of developing some other non-cancer disease?
Now think of a completely different scenario.
I once worked on a project looking at a canine training facility for
a police department in the county of Baltimore that was
built atop a former unregulated landfill.
During a brief period of time that the officers and
dogs spent on site, there were reports of illnesses amongst the officers and
amongst the canines spending time on the facility.
Some sampling data were collected regarding environmental chemicals that may
be present on the site.
And so the main questions that were being asked by the police department were
are environmental exposures that our officers and
dogs are experiencing on site contributing to illness, and should we continue to
use the site as a training facility based on the chemicals that are present?
And risk assessment is really a key tool in answering these questions.
So there are many different applications of risk assessment.
The tool itself is a policy tool that allows us to look at environmental hazards
and environmental exposures to those hazards that may exist in order to
make decisions about whether or not to continue using a site, for example.
Or whether to set a stricter or looser standard for
exposures via foods or drinking water.
Risk assessment itself is really an integration of a wide array of
different scientific disciplines.
We're not going to cover many of them in detail today, but
I've listed a few on the slide.
They include toxicology, epidemiology, environmental exposure and
engineering, behavioral science and many others.
It's important to point out that risk assessment itself is not a science.
Instead, it's actually an integration of those disciplines that
I've previously mentioned.
And again, the key goal of risk assessment is to
really give a risk manager the information that he or she needs to
make decisions about environmental exposures and mitigating those exposures.
It is really a policy tool that in many cases will require that a risk analyst
make some subjective judgements about the scenario at hand, and usually is part of
the decision making process of the risk manager alongside other considerations
like economics, benefits to society and a whole host of other considerations.
So there are lots of different entities that routinely use risk assessment.
I've shown the logos of some these entities here.
It is widely used across the U.S. Federal government.
Risk assessment was actually first brought into practice by the Food and
Drug Administration sometime ago, but since,
it has been picked up by a number of federal regulatory agencies,
including the EPA, OSHA, the CDC, and, and many others that are listed here.
There are a number of international bodies that also rely on risk assessment for
decision making, including the World Health Organization and
the International Program on Chemical Safety.
Risk assessment is also used by state, environmental and health agencies.
Some key examples of agencies that are rather progressive with their use of
risk assessment are the California Environmental Protection Agency, and
the New York Department of Health and Mental Hygiene.
The regulated industry absolutely has an interest in stake and risk assessment, and
frequently produces its own assessments as well as non-governmental groups like
environmental advocacy organizations will have their own interest in risk assessment
and occasionally will produce their own assessments for use in influencing policy.
So risk assessment, as I mentioned before, can be used for
a variety of purposes with the aim of translating a human exposure into
a likelihood of some adverse health outcome.
So some examples that are notable are the use of
risk assessment in setting of environmental regulations.
The National Ambient Air Quality Standards, or the NAAQS are one very
well-known example of the application of risk assessment in standard setting.
Also, the Safe Drinking Water Act sets maximum contaminant limits, and related
goals to those limits for contaminants that may persist in drinking water.
The Food Quality Protection Act has routinely, set tolerances for
different pesticides that are used in food production that may reside in
foods as a result of the use of those compounds.
Risk assessment is also frequently used to make decisions about cleaning up
sites that were formerly contaminated, like Superfund sites or
for the redevelopment of Brownfields.
Their risk assessment is used outside of the context of chemicals in many cases,
though mostly I'll talk about chemicals today.
But there are also techniques for doing risk assessment for physical hazards like
radiation and noise, as well as microbial and even injury hazards as well.
So in 1983, the National Research Council convened a panel to formalize
the process of risk assessment, among other things, and they developed four
key steps of risk assessment that will guide the rest of my discussion today.
Those steps are hazard identification,
dose-response assessment, exposure assessment, and risk characterization.
And those four pieces were initially called the risk paradigm,
that up until recently guided all risk activities.
In 2008, the National Academies reconvened to reassess the process of
risk assessment, and really modernized the way the risk paradigm looks.
You'll see on this slide, at the core, the yellow highlighted portion is still
the same four steps that were initially put into place in 1983.
But the committee recognized that risk assessment is a little bit more of
a iterative process that must be led by a problem formulation step, in order
to figure out what are the questions that the risk assessment needs to answer and
what level of detail is required to answer those questions in
a way that would facilitate decision making.
There's also a formal recognition of the engagement of stakeholders who may
have some say or interest in the outcome of the risk assessment, or
of the management decision that would come from the results of the risk assessment.
So this is the more modern version of the risk paradigm and
it really does a nice job taking into account some of the many other
considerations that are inherent in assessing risk.
So let's talk about the various steps of risk assessment.
I, I showed you before,
the first step of risk assessment is the hazard identification step.
This is, in the case of a site redevelopment or a site clean up,
it would be where the chemicals of concern are identified and the potential of
adverse health outcomes associated with those chemicals would be assessed.
In the case of looking at a single chemical,
it would be to compile the evidence that exists in the scientific literature that
exposure to that chemical may be associated with some negative
health outcome or an adverse response.
And so the evidence that's usually used to support this determination would be
evidence from the toxicological literature, evidence from studies of
chemical exposures in humans or epidemiology, or studies of the impact of
chemicals in cellular models which we call in vitro studies.
There's also in the hazard identification step typically a weight of
evidence discussion which compiles the evidence about whether or
not the chemical is likely to illicit a carcinogenic response, and
it's a determination based on the totality of the evidence, whether or
not it's believed that the chemical acts as a carcinogen.
So in risk assessment,
we're often dealing with situations that are relatively data poor, or situations
where we lack a lot of the information that we'd like to have to make decisions.
So in the instances where we don't have the information we need, agencies that
conduct risk assessment have developed what we call default assumptions, or
they are policy decisions about how to act when information that we need is missing.
So in the hazard identification step I'm going to share with you a couple of
those default assumptions that we apply in the absence of better information.
The first piece of that is that the effects that are seen in
one human population are predictive for others.
That means that if we have an epidemiologic study of the impact of
a chemical on a particular population, perhaps in one metropolitan area,
we can assume that what we've observed in that study should generally be able to
be generalized to populations elsewhere that are not substantially different.
We also make the assumption that the average person is as sensitive as
the most sensitive animals.
So when we're relying on toxicological data or
studies of chemicals in animals, we assume that the animal that responds to
the lowest dose of a chemical is just as sensitive as the average human.
That's a conservative assumption and could be interpreted as protective of humans.
And lastly, we assume that site concordance of
effects do not necessarily hold across species.
So what that means is that if we do a cancer assay in an animal,
if the animal develops a tumor in an organ that humans may not have, the development
of the tumor is the key event, and not necessarily the location of the tumor.
So as an example, if we administer a chemical to an animal and that animal
develops a tumor in its fore stomach, well, humans don't have a fore stomach,
but we wouldn't disregard that just because humans don't have a fore stomach.
We'd still be concerned that there may be a risk of cancer in humans, so we would
cautiously proceed, assuming that there may be a risk of carcinogenesis in humans.
So the second step of risk assessment is the dose response assessment.
And this is where we hone on the health effects of greatest concern, and
we try and quantify the relationship between increases in dose of
the chemical and corresponding increases in the negative health response of humans.
So again, we rely on the same data that we spoke of before.
Epidemiologic studies in this case are the best data to have because we have to
do the least extrapolation when we're talking about human populations.
Whereas when we're dealing with toxicological studies we're dealing with
data in animals, and
animals are not people, so we have to make some assumptions and
in some cases, quantitative assumptions, about how similar the dose
response relationships are in animals to the dose response relationships in humans.
And in very limited cases, we will rely on data from cellular models to say something
about dose response relationships, but that's typically uncommon.
So we have to think about a couple of things when conducting a dose
response assessment.
We have to consider the type of endpoint we're dealing with.
In risk assessment we treat cancers differently from other health outcomes.
We typically assume that most chemicals in the absence of better information,
any exposure to a carcinogen corresponds to some increase, even if very small, in
cancer risk, whereas with most non-cancer health outcomes, we typically assume that
there is some level of exposure that can occur without a negative health outcome.
We also have to consider in the dose response assessment, the type of exposure.
So are we dealing with an exposure that occurs via inhalation of a chemical or
through ingestion of a chemical?
And we also have to think about how long that exposure occurs.
Some health outcomes result from a very high level exposure over a short period of
time to a chemical, whereas other like cancers typically require a long term or
perhaps even lifetime of exposure to a carcinogen.
I mentioned before that we often rely on tox studies of chemical exposures in
animals so we have to think about the relevance of the effect in
those animals to a, a similar situation in humans.
And then of course,
when we're conducting animal studies, we typically rely on higher dose studies,
because we can't afford enough animals to simulate the levels of risk to
environmental pollutants we'd see as a result of human exposure.
So we have to think about going from those high exposures to try and
say something about what the risks would look like at the levels that
people would actually be exposed in real life.
So the outcome of the dose response step would be the development of
reference values or quantitative toxicity metrics.
So again, I mentioned we typically divide things into non-cancer and
cancer based outcomes.
In the case of non-cancer, we try and
derive something called a reference dose for chemicals that are ingested or
reference concentration for chemicals that are inhaled.
And the idea here is that it is a dose below which we
wouldn't typically tend to worry about exposure, but
above which there is a likelihood of the development of an adverse health outcome.
In the case of cancer, I mentioned before,
we assume there is no threshold below, which there is no concern.
In most cases we assume that any increase in dose comes with
a corresponding increase in risk.
And so we developed something called a cancer potency factor,
which is just a quantitative estimate of the shape of the dose response curve.
So as you're more exposed, what's the corresponding increase in risk?
And we also will build, based on that cancer potency factor,
these tools called inhalation and drinking water unit risks that let us
say as the concentration in air or water increases by a certain amount,
what would we assume the corresponding increase in cancer risk to be?
So let's now move on to the third step, the exposure assessment.
So this is the piece of risk assessment where we're trying to say something about
the extent to which people come into contact with the chemical hazards.
So we need to know a couple of things to do an exposure assessment.
First, we need to know the concentration of the chemicals we're interested in,
in the environmental medium to which they're being exposed.
And the environmental media we tend to talk about in risk assessment are air,
water, soil, as examples, or foods.
We need to know something about human activity patterns.
So some key questions you might be concerned with here are how much air do
people breathe?
How much time do people tend to spend at work?
How much of a particular food item does the general population consume?
And we need to know population characteristics, like body weight, or
height, or lung capacity, or any number of other things.
So exposure assessment will draw from many different disciplines to
pull the data together that it needs to actually say how much of
the chemical are people actually exposed to.
And lastly, our aim in this is to predict the magnitude of human exposure, or
again, how much of the chemical in the form of an external dose, so
how much enters the body from outside of the body.
And the units we use for this, and
these aren't critically important for your purposes, are,
are milligrams of the chemical per kilogram of human body weight per day.
So here's a typical exposure scenario.
And what we tend to think about in exposure assessment is
different pathways of exposure.
And, and what a pathway of exposure is,
is how a chemical moves from a source into our bodies.
So one example of a pathway of exposure would be that a chemical would be
emitted out of the stack of a plant and that air would become available for
a human to inhale.
And the chemical contaminates that would exist in the air that would be
emitted from that chemical plant would then be inhaled by the human.
And so that would be one example of a pathway, and
an exposure incurred by that person.
So we need to think about many different things.
We need to think about the different types of people that may come into
contact with that air.
We think about adults,
we think about children, we think about infants, we may think about the elderly.
We'd think about the different types of exposure they'd have, so
we'd think about the exposures they'd incur as a person who lives in
a house that's downwind of the chemical plant.
We might think of a person who has an occupational scenario where they
come into contact with the chemical at work, or any number of other scenarios.
We also think about multimedia exposure.
So not only are we concerned about breathing these pollutants that
may exist in air, but we may think of these pollutants settling out of
the air onto crops that may be consumed by people, or
may be consumed by animals, and then the animals could be consumed by people.
So, you can imagine that things very quickly tend to snowball, and, and
consideration of all the relevant exposure pathways can actually be
quite challenging.
So exposure scenarios can be quite complex or can be very simple.
And I'm actually going to show you now a very simplistic exposure scenario to
illustrate how we would quantitatively estimate exposure to a chemical.
So if we're interested in a chemical, we need to know a couple of things.
We want to know the concentration of the chemical and the medium of interest.
So that would be the concentration of the chemical in drinking water, as an example.
We'd need to know the media intake rate, so
we'd need to know how much water does a person tend to drink in a typical day.
And then we'd need to know a couple of things.
How often does the person come into contact with the contaminant?
What's the schedule of exposure?
And that's what we tend to call frequency.
Then we think about duration.
So over what period of time, does the exposure occur?
Is it only during adulthood?
Is it during the entire life span or is it for
a 30 day period, where a person's spending time on a particular site?
And then depending on the type of health outcome we're interested in,
we select an averaging time, so when we're thinking about an exposure to a chemical
that causes cancer, we typically assume an entire lifetime as our averaging time.
But if we're looking at a chemical that causes an effect that's not cancer,
we tend to look at the averaging time as being the same as
the pre-specified duration I mentioned before.
And lastly, we need to know the body weight of the person being exposed.
And so, please don't balk at this simplistic exposure model.
This is no more than algebra, so
if your algebra is still adequate, you should be able to do just fine with this.
So these are the pieces I described before, and this is an example that
would be used to look at the exposure to a chemical through drinking water.
So D represents the dose, C is the chemical concentration and
the medium we're interested in, so that would be water.
IR is the ingestion rate, which would be how much water a person drinks in a day.
EF would be that schedule of exposure, or exposure frequency.
ED is the exposure duration.
BW is the body weight and AT is the averaging time.
And the corresponding units that you would use are presented on the slide.
So let's talk about a very simple exposure scenario.
We have a community with a water system that gets its water from an aquifer that's
contaminated with arsenic, which is a well-recognized human carcinogen.
So a number of epi studies have shown that drinking arsenic in
water over long periods of time has been linked to cancers of the lung and
bladder and the skin, as well as a number of other non-cancer health effects.
So we're hoping with our exposure assessment to figure out,
based on a person's typical intake of drinking water,
what would the dose of arsenic be to that person over a lifetime?
And in order to do that we have some sampling data for
arsenic in this community water system.
So here's plugging in the numbers into that model I showed you before.
So the data for concentration in water was what we had just talked about.
We have the water sampling data.
And I, I should point out here that we typically in risk assessment will look at
the scenario a number of different ways.
We'll try and come up with a middle of the road exposure assessment, or
estimate rather, and then we'll also aim to come up with a conservative estimate or
almost a worse case scenario estimate to look at the range of possibilities,
because in many cases we won't really know where the actual population exposures
would fall, so we try and capture that with looking at different scenarios.
So we have the concentration data that's plugged in here in the table.
We have the ingestion rate data, so the liters of water consumed per day.
In the case of a daily exposure, you'd set the exposure frequency at one.
The exposure duration we had talked that we were interested in a lifetime exposure,
and in risk assessment we typically treat lifetimes as about 70 years.
We use the average body weight in the U.S. for our average estimate, and
we used a slightly lower one for our conservative estimate,
which would ultimately increase the exposure dose at the end of the day.
And we used an averaging time that matches the exposure duration,
in this case, which would be 70 years as well.
And we came up with two different numbers, an average number for the average daily
dose, and then a conservative number for the average daily dose.
And you see they differ by about a factor of four.
That's the math for the most part that we're dealing with today, so
if you followed that you're in good shape.
So then the final step of the risk assessment is the risk characterization.
So this is an integration of information from the three previous steps of
risk assessment that we talked about, so just to review,
the hazard ID step is where we qualitatively look at the evidence for
exposure to a chemical and its relationship with adverse health outcomes.
The dose response evaluation is where we quantitatively determine the shape of
the dose response curve or
how much of it you need to elicit an adverse health outcome.
And then we looked the exposure assessment piece to figure out,
okay, we know how much of the chemical is a problem.
Now how much are people actually being exposed to?
And a risk characterization is where we pull it all together to say something
about risk and non-cancer hazard.
And so the outputs of this risk characterization are a prediction of
risks and the likelihood of a non-carcinogenic hazard.
In the case of cancer, we may say something about
the population burden of the exposure that we're describing, and
something that is key that I'll talk about at the end is the discussion of
uncertainties that are inherent in the risk assessment.
So a little bit into the math again.
This is a very straightforward formula.
We're aiming to estimate cancer risks.
So risk is equal to a lifetime average daily dose, so
the number we calculated before, times the cancer slope factor.
And the cancer slope factor, remember, is the increase in cancer that corresponds to
an increase in dose, or it's kind of the slope of the dose response curve.
Risk has no units, and
it's calculated from the estimate of the lifetime exposure.
So we're talking about cancer here, and
we're talking about people who are exposed for very long periods of time.
And so the interpretation of a risk number.
So if your risk was 1 times 10 to the negative 6th,
it would actually mean in English that one case of cancer would be
expected per million persons exposed over a lifetime.
So here's our drinking water example again.
So our risk again is equal to the lifetime average daily
dose times the cancer slope factor.
So the lifetime average daily dose that we calculated for the average scenario was 1
times 10 to the negative fourth milligrams per kilogram of body weight per day.
And then we multiply that by the cancer slope factor which comes from
the Environmental Protection Agency, and
that number is 1.5 per milligram of kilogram body weight day.
So the units there cancel, and you come up with a risk of 1.5 times 10 to
the negative 4, so the interpretation there rounding from 1.5 to 2,
is that 2 persons per every 10,000 people exposed to arsenic in
drinking water over a lifetime are expected to develop cancer.
So that is the risk.
So then we want to estimate the cancer burden in this population.
So we were interested in the number of cases of cancer that we would
expect given what information we have about the population.
So if we were going back to our drinking water example, we'd ask the question how
many cancers would we expect to see if the size of the affected community with
the contaminated water system is 27,000 people.
So, again, the formula, very simple.
The risk times the size of the population.
So the number of cases is equal to 1.5 times 10 to the negative
4 times 27,000 persons.
And the number of cases we would estimate from there would be 4.05 or about 4.
So the way we would interpret that is that we would expect to see in this population
drinking water contaminated with arsenic at the levels we described before,
four cases of cancer,
assuming a lifetime of exposure to arsenic in that drinking water.
So it's that simple.
So the final piece of a risk characterization, and
one of the most critical pieces, is a discussion of the uncertainty.
Now I mentioned before that in risk assessment we are often forced to rely on
situations where we do not have all of the information we'd like to have on hand, and
so the easiest way to think about uncertainty is scientific ignorance about
a particular situation or process.
So this is where we describe the areas where we lack information and
how we've approached dealing with that lack of information, and so
uncertainty discussions are very important to help risk managers make decisions with
a full understanding of the certainty of the estimates that have been derived.
So uncertainty discussions can take a number of different formats.
They can be written qualitatively as a narrative to describe the limitations.
And in some cases,
especially those surrounding some the environmental regulations that
are put forth by the Environmental Protection Agency, there are formal
quantitative uncertainty analyses that we won't really talk about here today.
But an example of an area where we talk about uncertainties would be in
the case of the drinking water data for
the community water system that we described before.
We took a finite number of samples at one point in time, and
we hope that they represent the conditions, or the exposures that
people would experience over a lifetime, but we're not certain about that, so
that would be one area where we would describe a limitation of that analysis.
We may also not feel so confident in our characterization of
the relationship between exposure to a chemical and the outcome.
In many cases, not arsenic, but many other cases, we may be relying on
a single poorly-conducted study as the basis for our understanding of how much of
the chemical one needs to elicit an adverse health outcome.
And in those cases that lack of certainty over the dose response relationship may
really reduce our certainty in the, in the resulting risk estimate that we
may provide to the risk manager as part of the risk analysis.
So it's critical, absolutely critical,
to ensure that the limitations of the analyses are presented clearly and
in a manner that's useful to the risk manager.
So that is a really key piece.
So in conclusion,
I hope I've convinced you that risk can be a very useful tool in decision making.
It is routinely used by a wide array of entities from federal agencies to NGOs.
It relies on data from many different public health disciplines, in order to
pull together the pieces that are needed to say something about the likelihood of,
of a particular risk or exposure.
There are four main steps and we went through each of those today.
Those are hazard identification, dose response assessment, exposure assessment,
and risk characterization, though it's key to recognize that the more
modernized risk paradigm encompasses the problem formulation step and
a formalized process of stakeholder involvement.
And lastly, the outputs of a risk assessment can include an estimate of
cancer risk, non-cancer hazard, a population cancer burden in some cases,
and a very thorough and detailed uncertainty discussion.
And that ends my discussion with you today.
Thank you for your attention and I hope you find it useful.
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