Public Health Assessment Work Group
Meeting Minutes
December 15, 2003
Attendance
ORRHES Members:
Bob Craig (Chair), Susan Kaplan, Pete Malmquist, James Lewis, David
Johnson, LC Manley, George Gartseff, Kowetha Davidson, and Tony Malinauskas
Public Members and Others:
Norman Mulvenon, Danny Sanders, Tim Joseph (DOE), Roger Macklin, Al Brooks,
Gordon Blaylock, and Owen Hoffman
ATSDR Staff:
Bill Taylor, Paul Charp, Allan Susten, Melissa Fish, and Jack Hanley
(telephone)
Purpose
The purpose of the meeting was to present the basic purpose and components
of the public health assessment and to differentiate between ATSDR’s
Public Health Assessments and EPA’s site-specific Risk Assessments.
Meeting Minutes
Susan Kaplan moved that the November 6th Draft PHAWG minutes be approved.
LC Manley seconded the motion. The motion passed. The draft meeting minutes
for November 6th were approved.
Allan Susten’s Presentation Regarding ATSDR’s Public
Health Assessment and EPA’s Risk Assessment
All handouts used in this presentation are available in the Field Office
with the meeting minutes.
Paul Charp introduced Allan Susten to the group and provided some background
on the legal differences between a Risk Assessment and a Public Health
Assessment.
Paul Charp said that ATSDR’s public health assessment is mandated
under the Superfund act of 1986 under section 104(i) (6) and the EPA’s
risk assessment regulations are under the same act under section 121,
clean up standards.
Allan Susten is a board certified toxicologist and serves as the Assistant
Director for Science in the Division of Health Assessment Consultation
(DHAC) for ATSDR. One of Allan’s duties is to ensure that the best
available science and scientific principles are consistently applied to
the documents that DHAC produces. Allan Susten also serves on ATSDR’s
Minimal Risk Level Work Group that develops the MRL values used within
the agency. Before coming to ATSDR Allan worked for the Environmental
Protection Agency (EPA), the National Institute for Occupational Safety
and Health (NIOSH), and taught Pharmacology at the Kansas City College
of Osteopathy. In addition to being a toxicologist Allan Susten is also
a registered pharmacist and a Diplomat of the American Board of Toxicology.
PowerPoint Slide One- ATSDR Public Health Assessments
Allan Susten explained that his presentation would not be site specific.
Rather, it would be a general overview of how ATSDR approaches public
health assessments and what the differences are between public health
assessments and risk assessments.
Allan Susten said that ATSDR is a public health agency and looks at health
issues while EPA is a regulatory agency with regulatory mandates. EPA
uses the numbers and has different approaches from ATSDR.
PowerPoint Slide Two-Objectives
Allan Susten told the group that he would review the basic purpose and
components of the public health assessment and differentiate ATSDR’s
public health assessments (PHA) from site-specific risk assessments (RA).
PowerPoint Slide Three-Approach
Allan Susten told the group that he would be taking the opportunity to
perform a side-by-side comparison of the PHA to the RA by pointing out
the similarities and differences and by pointing out the advantages and
disadvantages of each from a public health perspective. In addition Allan
would provide case examples and provide some perspective regarding both
the PHA and RA. Allan added that the key message is that ATSDR’s
PHA focus is qualitative and looks at the public health issues while EPA’s
RA is more concerned with regulatory and clean up issues.
PowerPoint Slide Four-Definitions
Allan Susten explained that the PHA is a process used to evaluate exposure
to chemicals (as well as radionuclides) in the environment and the impact
on public health. The RA is an analysis that uses information—often
the same information used in the PHA—about toxic substances at a
site to estimate a theoretical level of risk for people. Allan said that
the RA tends to be more quantitative than the PHA. The PHA is more narrative
oriented that EPA’s RA.
PowerPoint Slide Five-PHA/RA Comparisons
Allan Susten compared the PHA to the RA. Allan said that the PHA tends
to be a qualitative evaluation of exposure and health effects. The PHA
defines likely exposure and populations by having the staff examine the
real population to see who could be exposed. Allan added that just because
someone lives in a community does not mean that they were exposed. Also,
the PHA’s focus is on the past, present, and the future of exposed
populations.
The RA is a quantitative evaluation that often does not require a specific
population be identified. Because the RA is regulatory oriented, the RA’s
focus is usually on the present and the future. It is typical for ATSDR’s
PHA to look at the past but looking at the past is not a typical practice
used in EPA’s RA.
Tim Joseph said that he disagreed with the statement that the PHA is
qualitative while the RA is quantitative. Almost everything that ATSDR
does for the PHA is based on a quantitative calculation. Tim does not
want to see value taken from a PHA by saying that it is qualitative.
Allan Susten responded that ATSDR does use risk assessment methodology
in the public health assessment. However, ATSDR’s PHAs are more
qualitative.
Tim Joseph responded that the PHA is every bit as quantitative as the
RA if not more so. The endpoint of both the PHA and the RA is based on
quantitative information. Tim Joseph believes that it is important to
not take anything from ATSDR by starting with a slide that lists the PHA
as qualitative and the RA as quantitative. Do not give the RA more credit
than the PHA-both products are quantitative.
Owen Hoffman said that ATSDR’s PHA has yet to embrace uncertainty
analysis in their evaluation. Tim Joseph responded that uncertainty analysis
is not a requirement to be considered quantitative.
Owen Hoffman said that he had been hired to perform a peer review of
the EPA Human Health Risk Assessment for General Electric PCB’s
released to the Housatonic River and a major criticism of the RA is that
EPA is not addressing the attributes of specific populations within the
context of its quantitative uncertainty analysis. Owen felt that because
of the peer review process itself, EPA might be asked to do something
similar to that of a PHA type of analysis, but that exposures and risks
to reference individuals representative of specific population subgroups
would be more fully characterized with respect to uncertainty.
Allan Susten responded that at the end of his presentation, he would
answer questions relating to sediment levels.
PowerPoint Slide Six-PHA/RA Comparisons continued
Allan Susten compared the data and information used in the PHA to the
data and information used in the RA. Allan said that the PHA and RA tend
to use the same data in terms of toxicology and exposure. For example
both the PHA and RA use environmental data such as sampling data. However,
there are differences in the way environmental data are used by both agencies.
When sampling data is not available ATSDR will use models. However, while
models are useful, ATSDR will not use models as a decision tool while
EPA may use a model as a decision tool.
Owen Hoffman said that the PHA at Hanford is entirely based on models.
Allan Susten replied that he does not know very much about site specific
PHAs and that he was speaking in general terms about the vast majority
of ATSDR’s PHAs.
Owen Hoffman said that in order to investigate the past and to see what
people were exposed to in the past, exposure is often based on models
that are used as a type of decision tool. Allan Susten responded that
he should reword his statement: at most places, ATSDR would not use models
as a decision tool. However, there are some locations where ATSDR does
use models as a decision tool. Allen Susten added that all models are
wrong, some are useful and it is important to be careful about how models
are discussed.
Allan Susten pointed out that another major difference between EPA and
ATSDR is how each agency looks at soil data. For example, ATSDR is interested
in the top two to three inches of soil and has asked EPA to sample the
top two to three inches of soil because the topsoil is what people will
be continually exposed to. EPA uses core samples that go from six to twelve
or eighteen to twenty-four inches as a basis for clean up.
Allan Susten pointed out that both ATSDR and EPA look at standards and
guidelines. But for ATSDR, the standards and guidelines are screening
values that answer the question of whether or not ATSDR needs to look
further at exposures, toxicity, and health effects data. EPA uses the
standards and guidelines to basically say that if an area is cleaned up,
a full-blown RA will not be necessary.
Regarding health outcome data, Allan Susten told the group that the PHA
uses health outcome data while the RA generally does not consider health
outcome data.
Allan Susten said that ATSDR actually walks around and talks with community
members to learn important community information such as community concerns.
The PHA is then often written in a way that will address the specific
community concerns. The PHA has a community focus that is not normally
found in the RA.
Concerning health effects data, Allan Susten said that ATSDR considers
health effects data in a different way than EPA when EPA is developing
standards and guidelines. ATSDR uses site-specific health effects data
to learn what is known about the health of the community. ATSDR is thus
considering the biological responses, dose responses, as well as how likely
the biological responses are, and not just a single number.
Allan Susten told the group that the endpoint for the PHA is that ATSDR
takes into consideration environmental data, standards and guidelines,
health outcome data, community information, health effects data, and evaluation
of exposures. The PHA will make a statement of hazard, which is based
on the dose. The endpoint for the RA (especially as it relates to cancer)
is that EPA will make a statement of the theoretical risk. Allan added
that theoretical risk is not an actuarial risk although the public often
gets confused. The theoretical risk is great for setting priorities and
comparing against guidelines, but it will not tell the public about adverse
health effects.
Al Brooks said that theoretical risk is not a good way to set priorities
unless the theoretical risk is accurate.
Some discussion was started regarding theoretical risk but Allan Susten
requested that further discussion be held off until the end of the presentation.
PowerPoint Slide Seven-PHA/RA Comparisons continued
Allan Susten described the outcomes that could result from a PHA and
from an RA. Allan said that the outcomes from a PHA are generally public
health actions while the outcomes from a RA are generally remedial alternatives.
The PHA outcomes might lead to health studies, health education, looking
for additional information to fill data gaps, exposure registries, recommendations
to cease or reduce exposure, address community concerns, and/or trying
to leverage public and private partnerships. The RA outcomes might lead
to meeting site-specific cleanup goals or site cleanup.
Owen Hoffman asked for how many federal facilities had ATSDR actually
performed an epidemiological study. Allan Susten responded that he knew
of several that had been done. Specific examples included Camp Lejeune,
Fallon Nevada, and Kelly Air Force Base. Allan added that the studies
are performed out of the Division of Health Studies at ATSDR, which is
made up mostly of epidemiologists. The Division of Health Studies determines
the feasibility of performing the study and then they carry out the study.
James Lewis asked if the sequence of events is important in helping the
public understand the PHA findings. Allan Susten responded that he had
not performed a PHA in a while and he deferred the question to Paul Charp
or Jack Hanley who are presently writing a PHA. Allan added that ATSDR
is always trying to get into the community, define exposure, and gather
all available data. Although many events are laid out in a sequence format
in the Guidance Manual, in reality, many events are performed in a parallel
or simultaneous fashion.
Jack Hanley agreed with Allan Susten’s comments about PHA activities
usually being performed in parallel with different teams working together.
Paul Charp added that several outcomes cannot be started until the PHA
is completed (such as filling data gaps and starting exposure registries)
and that certain activities do require a sequential order.
Susan Kaplan said that she had called the Centers for Disease Control
and Prevention (CDC) when the Camp Lejeune study was going on and there
being an automated phone system indicating which button to select if calling
about Camp Lejeune or CDC. Susan asked if there has been any other effort
like that attempted on a nation-wide basis at any DOE facility to track
down a population that might have been exposed.
Paul Charp said that ATSDR has not made such an attempt but CDC and the
National Center for Environmental Health (NCEH) has.
Allan Susten said that he could not answer the question for just federal
sites and that he would try to find out about any nation-wide attempt
to track down a population that might have been exposed at a DOE facility.
Allan added that at the non-federal site of Libby, Montana there is currently
an effort underway similar to what Susan Kaplan described.
Al Brooks asked if such an effort to track down a population would only
occur if there were sufficient exposure to warrant it. Allan Susten responded
that in the best of all worlds the answer would be yes. However, public
pressure can be powerful.
PowerPoint Slide Eight-Primary Difference
Allan Susten explained the primary difference between the PHA and RA.
PHAs make a determination about impact of sites on public health and identify
pubic health actions. The PHA tries to answer the questions: Has my health
been or will my health be affected? The RA makes a determination of acceptable
or unacceptable risks with respect to regulatory requirements. The RA
also identifies remedial options. The RA tries to answer the questions
pertaining to theoretical risk of disease. Allan Susten presented a quote
from EPA that stated that the actual risk might be less; the actual risk
may be zero.
Allan Susten said that EPA has put in a lot of effort trying to communicate
and explain what the risk numbers mean and do not mean. However, the message
explaining the risk numbers often gets lost.
Tim Joseph asked what is meant by the actual risk might be less—less
than what?
Allan Susten said that the risk numbers that EPA puts out are the upper
bound of the 95% confidence interval. So the actual risk may be lower
than that, in fact it might be zero. It is all in the assumptions that
drew that line/that slope value.
Owen Hoffman said that Allan Susten was absolutely correct in terms of
most chemicals-but for radiation that is not true. For radiation it is
a central estimate of the slope, it is not the upper 95% bound. In the
quantitative estimates of the uncertainty on radiation risk-there is no
credence given to zero.
Tony Malinauskas attempted to get involved in the conversation but there
was a lot of interruption by work group members and the conversation was
deferred to the end of the presentation. Allan Susten reminded the group
that the presentation was just a general overview and that he would get
into specifics at the end of the presentation during question and answer
time.
PowerPoint Slide Nine-Case Examples
Allan Susten provided two case examples of chemicals, one being DCE and
the other chloroform.
PowerPoint Slide Ten-What to think about during these examples?
Allan Susten suggested that as the group reviews the examples of DCE
and chloroform that they keep in mind the policy versus the science, what
is known and not known, as well as the public health conclusions and recommendations.
PowerPoint Slide Eleven-DCE Case Example
Allan Susten told the group that the DCE case example he was providing
was a real example. There was a groundwater plume affecting indoor air
and the levels of DCE were found to be exceeding the acceptable cancer
risk (as identified by EPA). Thus, the EPA made the public very aware
of the risk. In EPA’s discussions with the community EPA said that
they would create a sub-slab ventilation system for the homes that were
above the plume because those homes exceeded the criteria risk number.
Meanwhile EPA and other agencies throughout the world were re-looking
at DCE and reevaluating the existing data. After reevaluating the existing
data it was decided that there should not be a unit risk for DCE—that
it was not going to pose an inhalation cancer risk. Next, EPA told the
community that the DCE was no longer a risk for cancer and that the sub-slab
ventilation would not be performed after all. Allan Susten said that occurred
because the evaluation of more biology took away the cancer risk for this
chemical.
PowerPoint Slide Twelve-DCE Case Example continued
Regarding the DCE case example, Allan Susten provided an example for
oral drinking water and air inhalation.
Oral-drinking water: Allan Susten said that EPA at one time had a cancer
risk number for DCE in oral drinking water. Once the cancer risk was eliminated
from the drinking water, a new non-cancer value was developed for drinking
water. EPA’s new reference dose value for DCE would be equal to
a water concentration of 1700 parts per billion. (An RfD is an EPA estimated
dose at which no health effects are expected, and which EPA uses as a
criteria for cleanup.) The MCL is the enforceable water standard. For
DCE, the MCL is 7 parts per billion.
Allan Susten explained that the difference between EPA’s MCL and
reference dose is partly due to the fact that MCLs are not necessarily
all health-based and the best available technologies are associated with
the MCL.
Inhalation-air: Allan Susten said that the EPA at one time had a cancer
risk number for DCE in air. Once the cancer risk was eliminated for DCE
in the air, a new non-cancer value was developed. The new value is a reference
concentration of 50 parts per billion. Thus, levels below the reference
concentration are not going to cause adverse health effects. As a means
of comparison, the American Conference of Governmental Industrial Hygiene
has a worker value (8 hours per day, 40 hours per week, 40 years of lifetime
exposure) of 5000 parts per billion.
Allan Susten reviewed the DCE case example and said that 1) EPA went
in and told the community that there was a cancer risk and would be cleaning
it up and 2) EPA came back and said that they reevaluated the information
and it is not a cancer risk and it will not be cleaned up.
There was additional discussion regarding whether or not EPA had additional
data when it reevaluated the cancer risk. Allan Susten said that EPA did
not receive much new data. Instead, it reevaluated existing data using
biology and mechanisms of action.
PowerPoint Slide Thirteen-Figure 2.1
Allan Susten explained that this figure is from ATSDR’s Toxicological
Profile and shows the effects of DCE via inhalation in the male mouse
kidney. Effects from DCE were seen in the male mouse kidney only—not
in rats, female mice, or hamsters.
PowerPoint Slide Fourteen-Chloroform Case Example
Allan Susten provided the group with a chloroform case example. Allan
pointed out that chloroform is a common groundwater contaminant, that
there were cancer risk values for inhalation and oral (ingestion), and
that the cancer risk usually drove the remediation process. Allan said
that what he means is that EPA derives two types of numbers—they
derive a cancer risk number (unit risk) and a non-cancer value (reference
dose).
PowerPoint Slide Fifteen-Chloroform Case Example continued
Regarding the chloroform case example, Allan Susten provided an example
for oral drinking water and air inhalation.
Oral-drinking water: Allan Susten said that EPA at one time had a cancer
risk number for chloroform in drinking water because chloroform was considered
a likely human carcinogen but not at levels that humans would likely get
through environmental exposure. For the first time EPA was saying that
yes, this is a likely carcinogen at an extremely high dose, but not under
typical exposures. EPA dropped the cancer risk number because if humans
and animals were protected from liver damage, then they would also be
protected from cancer. Once the cancer risk was eliminated from the drinking
water, a new non-cancer value was developed. EPA’s new reference
dose (RfD) is a water concentration of 350 parts per billion. The MCL
is the enforceable water standard for chloroform; the MCL for chloroform
is 80 parts per billion as part of total trihalomethanes.
Owen Hoffman asked if EPA now uses the 350 parts per billion or the 80
parts per billion. Allan Susten responded that the MCL of 80 parts per
billion is the legally enforceable standard for public water supplies.
Inhalation-air: Allan Susten said that the EPA at one time had a cancer
risk number for inhalation of chloroform in air. The cancer risk was eliminated
for chloroform in the air, but a new non-cancer value has not been developed.
The American Conference of Governmental Industrial Hygiene has a threshold
limit value for worker exposure (not the general community where there
are children and pregnant women) of 10,000 parts per billion.
PowerPoint Slide Sixteen-Dose-Response Data—Gavage vs. Drinking
Water
Allan Susten presented some of the dose-response data for chloroform.
Allan pointed out the actual tumor response when chloroform was given
by gavage. (A gavage is when a tube is inserted through the mouth directly
into the stomach and all of a chemical or substance is administered at
one time.) When chloroform was given to animals by gavage at the dose
of 220 mg/kg/day and 350 mg/kg/day, tumors were observed. Chloroform is
so soluble that it could be put into the drinking water of rats. But when
chloroform was in the drinking water, the same percent of tumors were
not observed. On the basis of this information and biological changes,
EPA determined that chloroform does not pose a cancer risk under the conditions
of exposure that most people would be exposed. If people are protected
against liver damage they will also be protected against cancer.
Owen Hoffman said that the protective concentration for liver damage
is well within the EPA concentrations that lead to the EPA acceptable
cancer risk range of 10 to the minus 6, to 10 to the minus 4 (one in a
million to one in ten thousand risk of cancer incidence). Thus, the use
of a non-cancer health endpoint for decision-making in place of a health
endpoint based on the risk of cancer is a moot issue, because the concentration
that protects against a non-cancer health endpoint is also within the
range of concentrations that would be considered by EPA to be protective
of the risk of an excess cancer.
Allan Susten pointed out that the 350 parts per billion reference dose
is not an effect level and is likely to be 30 to 40 times below an effect
level.
PowerPoint Slide Seventeen-Dose-Response Assessment-Model Influence
Allan Susten said that the concept of risk is a theoretical estimate.
Allan pointed out a data point, which was the bottom point of an actual
experimental study, was the lowest value at which observable increases
in cancer were seen. Every line extending down is a risk calculation that
depends on the model that was chosen to extrapolate from that value. There
is a range of 5 orders of magnitude in risk estimates, all using exactly
the same data point. The model that is chosen, determines the theoretical
risk.
Owen Hoffman said if the above information was taken in the present time,
wouldn’t one use mechanisms of action to extrapolate below limits
of epidemiological and experimental detection?
Allan Susten responded yes, absolutely; more biology and mechanisms of
action are being used.
Al Brooks and Owen Hoffman stated that they have a difference of opinion
with one another regarding this topic and neither of their conversations
was audible.
PowerPoint Slide Eighteen-Dose-Response (Hormesis)
Allan Susten told the group that he left a few journal articles regarding
the topic of hormesis with Bill Taylor and those articles will be available
in the field office for those who are interested.
Allan Susten explained that for this slide he stylized the dose response
curve to show the dose on the X-axis, and “adverse” and “beneficial”
effects on the Y-axis. Marked on the dose-response curve are the lowest
observed adverse effect level (LOAEL), the no observed adverse effect
level (NOAEL), and screening values (RfD and MRL). There is also a “control”
dose-response line, showing no adverse or beneficial effects. The NOAEL
is plotted near the control. Allan added that it is never known exactly
where the NOAEL is because it is not an exact number; the NOAEL varies
depending on which experiment was performed, which animal studies were
performed, and the way the study was performed, etc.
Both EPA and ATSDR develop their non-cancer values through a process
using either the LOAEL or the NOAEL (often there is not a NOAEL or there
are numerous LOAELs). The process leads to the development of a reference
dose or the minimal risk level. These levels are then considered to be
“safe.”
Allan Susten said that as lower doses of certain chemicals are studied,
people are learning that for many chemicals there is an adaptive response/positive
effect (some work group members prefer one term over the other). This
is called hormesis. Allan added that the adaptive response phenomenon
is certainly the case for essential elements including iron, copper, zinc,
and selenium. Allan added that for essential elements, some is good but
more is not necessarily better. (Low doses show beneficial effects, higher
doses show adverse effects.)
Owen Hoffman asked what does this mean if the reference dose or the minimal
risk level is clearly below a range at which beneficial effects will occur?
Are we robbing the public of an opportunity for better health?
Allan Susten replied that EPA and other agencies could not figure out
how to incorporate this into [at this point the rest of Allan’s
statement was inaudible].
Owen Hoffman asked how ATSDR handles this type of (hormesis) situation
when performing its public health studies. Allan Susten responded that
except for essential elements, ATSDR tends to try to not talk about it
because ATSDR does not know how to deal with it.
Allen Susten told the group that male rats that received 0.001 micrograms
of dioxin did not respond. But female rats that received the 0.001 micrograms
of dioxin lived longer than the control rats and had fewer tumors. But
what do you do with those data? How can you tell people that a little
bit of dioxin is good for you?
Owen Hoffman said that there seems to be a fundamental issue when you
have such data, but rely instead on multiple safety factors to derive
a reference dose or minimal risk level from a lowest observed adverse
effects level or a no observed adverse effects level. Without properly
accounting for uncertainty, reference doses and minimum risk levels that
are presented as a single value or point estimate may lead to bad decisions
designed to be protective of public health and the environment.
Allan Susten said that there are more studies looking into the issue
of hormesis.
PowerPoint Slide Nineteen-Environmental and Clinical Perspectives
Allen Susten said this slide was prepared for clinicians who are familiar
with pharmaceutical doses but less familiar with environmental exposures.
This slide presents the relative magnitude of toxic doses, effective doses,
and no observed effect levels (NOELs) for pharmaceuticals, and lethal
doses, LOAELs, NOAELs, and regulatory or screening values for environmental
substances (such as EPA’s reference dose and ATSDR’s minimal
risk level).
In medicine, the ratio of a lethal dose to the dose intended to be given
to humans is called the therapeutic index (TI). The range of the TI is
typically 10 to 20, but it may be as small as 1, such as for the drug
digitalis. In that case, the therapy is literally the titration of a toxic
dose to strengthen the heart for a short period of time. For drugs, the
range of the ratio between the effective dose and the dose where you don’t
see anything at all (in studies of humans and animals) is about an order
of magnitude. For environmental exposures the range of the ratio of the
lethal dose to the lowest observed adverse effect level (LOAEL) and the
range of the ratio of the LOAEL to the dose where no adverse effect is
seen (NOAEL) are both about an order of magnitude.
Owen Hoffman asked how often ATSDR’s minimal risk level is different
from EPA’s reference dose.
Allan Susten said that sometimes ATSDR’s minimal risk level is
different than EPA’s reference dose because one agency has looked
at a more recent study or both agencies have used the same study but used
different uncertainty factors or considerations. However, most of the
time the agencies (MRL and RfD) are within a factor of two or three. Given
the uncertainties in a factor of two to three there is little to no difference.
Allan stressed that regulatory values and screening values are not threshold
values, they are regulatory screening levels—they are not threshold
values!
PowerPoint Slide Twenty-Esophageal Tumors from NDEA in Male Rats
Allan Susten told the group that he had left a copy of an article “A
Pharmacologist’s View of Risk Assessment” with Bill Taylor,
and that the article would be available in the Field Office for people
who were interested.
This slide (from Dr. William J. Waddell’s presentation) shows a
different way of looking at dose-response. The data (esophageal tumors
in male rats) were plotted (not calculated) as “Percent of animals
with tumors” on the y-axis, and numbers of “Molecules of N-nitrosodiethylamine
/kg/day” (in units of log-rhythmic, or powers of 10 molecules per
kilogram body weight per day) on the x-axis. There is an almost-horizontal
line at zero percent animals with tumors on the y-axis stretching from
1 molecule to about 10 to the 17 molecules/kg/day on the x-axis, at which
point the curve rises abruptly to 100 percent animals with tumors between
1017 and 1018 molecules/kg/day. These data are plotted; there is no extrapolation
or mathematical conversion. At 1017 molecules/kg/day you see essentially
a NOAEL. Dr. Waddell did not consider whether there is a hormetic response.
Al Brooks said that data can be taken as y = x and make the transformations
that Waddell made or the range of data that he made and with exactly the
same progression of scale at the upper end and make a straight line out
of anything.
Allan Susten said that these data are plotted.
Al Brooks said he didn’t care if they were plotted or calculated.
If they are plotted accurately they are the same as calculated, and you
can take any arbitrary function and squeeze it up and make it do that.
Al Brooks said he would send Allan Susten an example.
Kowetha Davidson said that for this data, you would not look at the straight
line; you would look at the R-value.
Power Point Slide Twenty One-Summary
Allan Susten said that ATSDR likes to use dose-based conclusions and
an integrated evaluation of exposure and health information, mechanism
of action, and site-specific approach because the question we are asking
is a different one from that of EPA. Allan pointed out that risk values
can change even when data do not change. Allan also said that the message
delivery does not have to change regardless of what risk values change
because if what is known and what is not known is discussed and put into
perspective—then the narrative and doses can be discussed without
having the theoretical risk being perceived as actual risk.
Owen Hoffman asked if this means that in the public health assessments
for chemicals, ATSDR does not show or mention what the risk is? Allan
Susten said that he did not say that ATSDR does not mention risk—he
did not say that at all.
Owen Hoffman said that he believes he has seen public health assessments
for chemicals where the ATSDR official has shown what the risk is.
Allan Susten replied that Owen was correct and that some states have
regulatory requirements to include risk—therefore they have to be
consistent with those requirements. Also, some health assessors include
risk because EPA is used to seeing “risk” as well as other
communities and members of the public are used to seeing “risk”.
But ATSDR does not make decisions based on risk—it is only one factor
that goes into the decision.
Owen Hoffman said that one of the reasons that he took the time to attend
the meeting was because of the perception that in the radiation area ATSDR
has problems with EPA risk; yet in the public health assessments ATSDR
will sometimes disclose what the risk is for chemicals. But in the radiation
area where we have not only quantifiable risk but also quantifiable uncertainty
in the risk—ATSDR refuses, and it is on record that Paul Charp has
said that he has been told to not show risk for radiation. Owen Hoffman
finds this position to be without merit and posed the question, why engage
in censorship of information?
Allan Susten responded that he does not believe that ATSDR is censoring
information. ATSDR does prefer to not talk about quantitative risk because
risk is theoretical, is misread, and that the way that it is presented
by most people gives a false sense of precision that it does not deserve.
I am sorry but the uncertainty bounds and uncertainty things that you
do are all quantitative, they go over my head very often, I understand
the big picture and the quantitative risk really does not add anything.
Allan believes that if ATSDR provides adequate narrative, ATSDR has a
better chance at helping the community understand their hazards. For example,
this way, each individual can see if they were a part of the actual exposure
pathway.
Al Brooks said that EPA takes animal studies (highly sensitive animals)
and develops a number, then applies an uncertainty factor/safety factor
of 10 to get from the specific animal to humans, and then another factor
of 10 to get from humans to sensitive humans. What this results in is
an estimate for animals (such as a rat) with a safety factor of 1000.
Owen Hoffman said that safety factors account for extrapolation from
animals to humans.
Al Brooks and Allen Susten said that the assumption is that humans are
more sensitive than animals.
Al Brooks said that there is a list of pharmaceuticals that would never
have made the market if they were tested on animals such as rats. Some
of today’s pharmaceuticals are absolutely lethal to some species
of animals. Allan Susten said that aspirin and penicillin are two examples.
Kowetha Davidson said that there are basic assumptions that have been
used for safety factors. One assumption is that humans are always more
sensitive than animals—and we know that is not always the case [at
this point Kowetha was interrupted by several work group members and the
rest of her statement could not be heard].
In her attempt to finish her statement, Kowetha Davidson said that it
is important to remember (and she was told this by a person in EPA) that
uncertainty factors and safety factors within EPA do not have a basis
in science. Uncertainty factors and safety factors within EPA are policy
and EPA is now trying to develop a scientific basis for applying uncertainty
factors. The policy came first, but now because of all of the questioning
about using a ten-fold uncertainty factor, EPA is trying to come up with
a scientific basis for applying the ten-fold uncertainty—but now
it is all default.
Owen Hoffman said that a community like Oak Ridge is not a lay audience;
there is a considerable amount of expertise that exists within the Oak
Ridge community. Thus, the strengths and weaknesses of the various safety
factors should be discussed openly. Owen added and that to the extent
that there is potential for risk below epidemiological limits of detection,
shouldn’t that potential also be discussed? Owen said that he would
be interested to see what would result if radiation was treated (through
the same process, as indicated on slide 18) as a non-carcinogen instead
of a carcinogen.
Kowetha Davidson said that Owen’s suggestion probably could be
performed because with radiation we are assuming that there is no radiation
dose that does not present a cancer risk. But also in that assumption,
it is not true that there is no repair. Because the only way that you
could make that assumption [At this point Kowetha was interrupted by a
work group member and the rest of her statement could not be heard].
Al Brooks said that he could make any assumption that he wanted as long
as I have the assumption as part of a policy.
Kowetha Davidson continued saying that with some chemical carcinogens
the assumption that is often made is that there is never a case of 100%
repair. But we know that our bodies have a really great ability to repair
damage.
Owen Hoffman said that at low doses, repair mechanisms are always taking
place. It is the infrequent occurrence of misrepair that is important.
The frequency of repair is never 100% and the frequency of misrepair is
never 0%, even at background levels of exposure.
Nevertheless, Owen Hoffman emphasized that he was not talking about extrapolating
down to zero dose nor was he talking about linear no-threshold dose-response
effects. Owen was talking about consistency in the methods used by ATSDR,
starting with the lowest observed effect level and extrapolating from
there to the no observed effect level and then from there to a level that
would be appropriate as a screening level for ATSDR public health assessments.
Owen Hoffman said he feels that limits of epidemiological detection are
being used directly by ATSDR as a surrogate for a threshold of concern
for the special case of radiation released from federal facilities. He
is very concerned that the ATSDR use of the limits of epidemiological
detection as a screening limit for evaluation of past radiation exposure
is very likely to lead to false negative conclusions. The margin of safety
inherent with this approach is inadequate and inconsistent with approaches
used elsewhere by ATSDR for screening of exposures to toxic substances.
Additional Conversation Regarding Presentation
Owen Hoffman went on to say that the reason that ATSDR is here, in Oak
Ridge is because of a strong objection to ATSDR’s Y-12 Uranium PHA
raised by the Office of Radiation and Indoor Air. Requests have been made
by some people in Oak Ridge for EPA to come to Oak Ridge to disclose whether
or not the ATSDR’s answers to their questions have been responsive.
Yet, there seems to be political pressure to keep EPA out.
Kowetha Davidson stressed that EPA—the Office of Radiation and
Indoor Air—has been invited and they are not here by their own decision.
Kowetha added that she had not received any response from EPA.
Paul Charp said that ATSDR called the Office and spoke to Bonnie Gitlin
and her response was that EPA did not want to talk to ATSDR about the
discrepancies if members of the public are present.
Owen Hoffman said that if what Paul is saying is true, then EPA is engaging
in an act of censorship.
Paul Charp explained that ATSDR has requested [the rest of Paul’s
comment could not be heard because he was interrupted].
Owen Hoffman asked if he personally calls EPA and asks them why they
have not come to Oak Ridge and if Owen receives a different answer than
what ATSDR provided, ATSDR will allow Owen to let everyone know.
Paul Charp said that would be fine with him. Paul added that ATSDR told
EPA that they wanted some members of ORRHES involved in the telephone
conversations and EPA said that they would not discuss these issues with
members of the public on the call.
James Lewis said that he felt Allan Susten provided an excellent presentation
and that he did not understand why it took so long to have a detailed
discussion regarding the issue of risk assessment and public health assessment.
James said that this presentation would have been very helpful two years
ago and would have helped people understand the direction that ATSDR and
ORRHES were headed. ATSDR needs to do a better job of getting adequate
information out to the general public at the beginning of the various
processes. If not, ATSDR will have ineffective message delivery. James
felt that the presentation that Allan provided should have been made at
the beginning of the public health assessment process and in a format
that both ORRHES and the general public can understand.
Referring to the slide that stated, “message delivery does not
have to change if clear narratives and perspective are presented”—assuming
that ATSDR does not have a “cracker jack” health education
program that is being applied in a timely manner and in such a way that
the public will understand what ORRHES and ATSDR are doing—the community
finds themselves in a dilemma associated with the aura of decision versus
the aura of confusion.
Tim Joseph said that it is important to talk about the ATSDR process
in a simple and educated way so that the public can understand the process.
It is absolutely critical that ATSDR present and explain the process and
not just provide the results of the public health assessment.
Paul Charp pointed out that there has been discussion about presenting
the information in Allan’s presentation as well as the conclusion
categories up front at the very beginning of the ATSDR PHA process.
Jack Hanley said that he understands what James Lewis is talking about.
Jack said that he thinks James is mainly referring to communication with
the broader public. Jack told the group that Allan Susten has been working
with Region IV EPA to develop a document comparing the public health assessment
and the risk assessment. This document was distributed at the December
ORRHES meeting and is available to the public.
Allan Susten said that he believes the document comparing the PHA to
the RA is supporting material, but he believes that James Lewis has made
a strong point and that a recommendation should be made about presenting
certain information up front to various audiences, at the beginning of
the ATSDR PHA process. James Lewis added that it is important that an
effective communicator is brought in to present the information.
Al Brooks said that he feels the statement made by EPA that “conservatism
in the face of uncertainty is wisdom” would be better stated as
“conservatism in the face of uncertainty is stupidity”. Al
Brooks disagrees that what EPA does is suitable for allocation of priorities.
Al added that unless you know from empirical data, the relative sensitivity,
you do not know enough to extrapolate.
Allan Susten said that EPA’s process is to measure the amount of
a substance in sediment and then model where it will go, etc. ATSDR does
not care how much of a substance is in the sediment, ATSDR will look at
the fish and perhaps measure levels of the substance in the bodies of
fishermen. EPA would clean up a groundwater contamination even if people
were not drinking it. ATSDR would not consider the groundwater a public
health hazard if people do not drink it. From the standpoint of sediment
standards, ATSDR is interested in a completed exposure pathway.
Owen Hoffman said that from the standpoint of a professional risk assessor,
reasonable assumptions are used in terms of exposure frequency and exposure
duration. And where the maximum exposure has been categorized, they clearly
state their assumptions. Owen said that he is concerned with ATSDR’s
practice of using limits of epidemiological detection as thresholds for
risk. Owen would like to see more rationale for taking information below
the limits of epidemiological detection in order to derive a screening
level of concern for use in a PHA.
Allan Susten asked what information Owen was referring to. Owen Hoffman
replied that he was referring to mechanisms of biological action and information
from other studies besides epidemiology. Owen added that his concerns
are more in the radiological area. Owen said that he has not found the
same type of consistency in approach with respect to how the health effects
of chemicals are evaluated and the radiation effects. Owen sees an attempt
to use the limits of epidemiological detection in radiation to determine
threshold levels of concern.
Kowetha Davidson said that once you are below the limit of detection,
then everything is just theoretical. If you are below the limit of detection
you need some sort of dose or else it is just theory and extrapolation.
Owen Hoffman said that all he is asking for is that ATSDR use all available
evidence and that there is careful consideration for what is done in the
area of radioactivity. Owen added that he feels there is political incentive
to keep the thresholds of concern at the highest level possible.
Paul Charp said that Dr. Falk had an expert panel meet to discuss some
radiological issues. The findings of that panel will be distributed to
ORRHES members in a report form.
Owen Hoffman asked if the panel was open or closed.
Regarding the expert panel, Paul Charp said that Dr. Falk selected the
panel and that the Division of Health Assessment and Consultation did
not have input as far as the actual panel selection.
In response to Owen’s question of who was on the panel, Paul Charp
said that the panel included Charles Miller, Tom Mason, Bob Spengler,
and David Kleinbaum.
Regarding mixtures and combined exposures, Allan Susten said that it
is known that there are interactions between substances. Where studies
have been performed at the no observed adverse effect level of each component,
it is difficult to find any effect from the mixture let alone super effects.
Most environmental exposures are hundreds to thousands times below the
no observed adverse effect level for individual compounds. Allan said
although everything is not known, the empirical data suggests that in
general when levels are well below (100 fold) the no observed adverse
effect level, all compounds combined will not show any effects.
Gordon Blaylock asked Allan Susten how many studies he had regarding
synergistic effects. Allan Susten replied that he has not seen any studies
for environmental chemical synergistic effects but has seen them for pharmacological
synergistic effects.
Kowetha Davidson said that mixtures encompass the range where hormesis
would have been observed, but undoubtedly they did not see hormesis. Perhaps
hormesis is an artifact of a single exposure. When there is multiple exposures
it all depends on the mechanisms [the audio was inaudible at this point].
Some chemicals are not toxic when taken alone, but may become toxic when
they are metabolized in the liver or vise versa. Toxification and detoxification
can be either increased or decreased.
James Lewis said that the community understands risk. If ATSDR elects
to not present risk data, how will ATSDR be effective when the world is
used to looking at risk data? When ATSDR leaves Oak Ridge, the Oak Ridge
community will still have the same questions if data is not presented
in a way that the general public can understand.
Allan Susten said that communication is the key and that the environmental
science agencies have created problems by using terminology that is not
clearly understood by the general public. It is important that ATSDR identify
what is known and put it in the proper perspective.
Owen Hoffman said that the “Making Choices: Screening for Thyroid
Disease” document includes estimates of risk and its uncertainty
and is not a regulatory document and was put together by the National
Cancer Institute and not by EPA. The “Making Choices” document
is a public health message, which contains risk as part of the message.
Owen Hoffman’s point is that full disclosure of information should
include risk and risk does not necessarily have to be a regulatory value.
James Lewis said that he is not asking ATSDR to make a call based on
risk. Instead, James is suggesting that ATSDR use risk as one way of communicating
with the public, especially for those who do not understand dose.
Kowetha Davidson said that risk is impossible to define and does not
tell an individual if they are safer. Risk provides an individual with
a calculated number but does not tell them if they will get a disease.
People need to understand that when it comes down to it, risk really does
not provide an answer or tell the individual anything.
At this point everyone was talking at once and the meeting was adjourned
at 7:45 PM.
Votes/Specific Actions Taken in the Meeting
The draft meeting minutes for the November 6th PHAWG meeting was approved.
Action Items
Allan Susten said that he would try to find out about any nationwide
attempt to track down a population that might have been exposed at a DOE
facility.
Allan Susten said that he would carry the message back to Atlanta about
the need for additional information regarding the risk assessment versus
public health assessment process to be provided to the communities at
the beginning of the ATSDR PHA process.
Al Brooks said that he would provide an example to Allen Susten of other
data that would reproduce Dr. Waddell’s dose-response plots.
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