v>EPA
               United States
               Environmental Protection
               Agency
               EPA-600/9-80-048
               October 1980
               Research and Devplopmeai
Proceedings of a
Workshop on
Exposure
Assessment
               January 2-3, 1979
               Belmont House,
               Maryland


               Sponsored by:
               Office of Health and
               Environmental Assessment
               Washington DC 20460
-.:
    EPA
    600
    9
    80
    048

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                                        EPA-600/9-80-048
                                        October 1980
           Proceedings of a Workshop
            on  Exposure Assessment
        January 2-3, 1979—Belmont House, Maryland
            John L. Buckley and David L. Jackson, Editors
..o
OJ
            OFFICE OF RESEARCH AND DEVELOPMENT
           U.S. ENVIRONMENTAL PROTECTION AGENCY
                  WASHINGTON. D.C. 20460
                      HEADQUARTERS LIBRARY
                      ENVIRONMENTAL PROTECTION AGENCY
                      WASHINGTON, D.C. 20460

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                        Preface

    The  general  conclusions reached  by  participants  in  the
Workshop on Exposure Assessment have been taken seriously by
EPA's Office of Research and Development.  We have initiated a
series of steps to increase recognition of the importance of exposure
assessments in the Agency's regulatory decisions and to improve the
coordination between specific media programs and the consistency
of their assessments.
    Specifically, The Administrator authorized the formation of an
Exposure Assessment Group as part of the Office of Health  and
Environmental  Assessment  in  the  Office  of Research   and
Development. The Group's responsibilities are: 1 ) to provide state-of-
the-art  methodology,   guidance  and  procedures for  exposure
determinations; 2) to ensure quality and consistency in the Agency's
scientific risk assessments; 3} to advise the Program Offices on
proposed testing requirements with emphasis on the information
needed for adequate exposure determinations;  and 4) to provide
independent assessments of exposure and recommendations to the
appropriate regulatory offices concerning the exposure potential of
specific agents.
    Also, an Agency-wide Exposure Assessment Work Group  has
been  formed to ensure  the full contributions  of the operating
programs within EPA during the dynamic period in the development
of policy  and guidelines  on  exposure  assessment. Under  the
leadership of Courtney Riordan, Chairman, and Tom McLaughlin,
Executive Secretary, this work group has reviewed the Workshop
report and supports its conclusions and recommendations: increased
priority  and  institutional  visibility are necessary  for  exposure
assessments; "standardization" of the detailed methodology for
making  assessments  is  not  possible  at  this  time;  integrated
assessments and  validation by measurement  should be attempted
whenever possible; peer review is desirable for both the assessment
plan and the completed program; consistency must be improved for
assessments made throughout the Agency; and uncertainties  and
limitations should be stated explicitly.
    The  Work  Group  has  applied these  recommendations in
constructing a draft of Exposure Assessment Guidelines to provide a
solid foundation for the formal operation of the Exposure Assessment
Group. The new Group will give valuable guidance to regulatory
decision-makers in assessing exposure to environmental pollutants.

                               Stephen J. Gage
                              Assistant  Administrator
                                for Research and Development
   ..
•/

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                Table of Contents
Preface	   ii
Acknowledgment 	   iv
  Introduction	,	    1
  Workshop Overview and Recommendations 	    3
  Introductory Presentation: Exposure Assessment
    Regulations and Enforcement
      Cara Jablon	    9
  Case Study #1: Participate Sulfates and the
    Catalytic Converter
      Roger Cortesi	   13
  Case Study #2: Chlorobenzilate
      David J. Severn 	   19
  Case Study #3: Benzene
      Michael Berry	   23
  Case Study #4: Bladder Cancer Epidemiology
    Study
      Kenneth Cantor 	   27
  Case Study #5: Lead
      Lester Grant 	   33
                            III

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                Acknowledgment
    The editors express their appreciation to Dr. Richard Mariandfor
his many hours of hard work in organizing the symposium and for his
substantive contribution to organizing this proceedings document.
We would also like to  thank Ms. Melinda Graves of ORD for her
continuing assistance in the organization of the symposium and the
preparation of this manuscript. Thanks are also extended to the
workshop participants:

    Elizabeth Anderson, Office of Research and Development/EPA
    Darryl Banks, Office of Research and Development/EPA
    Michael Berry, Office of Research and Develpment/EPA
    John Buckley, Workshop Co-chairman, Whitney Point, NY
    Kenneth Cantor, Office of Research and Development/EPA
      (on detail to National Cancer Institute)
    Stanley Coerr, Office of Air, Noise and Radiation/EPA
    Roger Cortesi, Office of Research and Development/EPA
    Phillip Enterline, University of Pittsburgh
    Stephen Gage, Office of Research and Development/EPA
    David Gaylor, Food and Drug Administration
    Lester Grant, Office of Research and Development/EPA
    George Hutchinson, Discussant, Harvard University
    Cara Jablon, Office of General Counsel/EPA
    David Jackson, Workshop Co-chairman, Case Western
      Reserve University
    William Marcus, Office of Water and Waste/EPA
    Richard Mar land, Office of Research and Development/EPA
    Thomas Murphy, Office of Research and Development/EPA
    William Murray, Office of Research and Development/EPA
    Charles Poole, Office of Toxic Substances/EPA
    Courtney Riordan, Office of Research and Development/EPA
    Judah Rosenblatt, Discussant, Case Western Reserve University
    Marvin Schneiderman, Discussant,  National Cancer Institute
    Edward Schuck, Office of Research and Development/EPA
    David Severn, Office of Toxic Substances/EPA
    Syed Shariq, Office of Research and Development/EPA
                             IV

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                    Introduction
    In January 1979, the Office of Research and Development (ORD)
of the Environmental Protection Agency sponsored a  two-day
workshop that permitted exchange of ideas and discussion among
regulatory  decision-makers  and  experts  in biostatistics,
epidemiology, and dosimetry/exposure modeling. Participants came
from  both  inside  and outside  the  Agency.  Their  discussions
emphasized: (a) risk assessment, (b) approaches to improve the
methodologic consistency in exposure assessment (c) improved use
of existing data bases, (d) areas where new methodology for data
acquisition  or data analysis are needed, (e)  methodologies for
identifying data requirements in a timely fashion forfuture regulatory
decisions, and (f) suggestions on priorities for ORD funding  and
research efforts in exposure assessment in the near* and long-term
future.
    This report summarizes the proceedings of the workshop  and
synthesizes the recommendations stemming from  the discussions.

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               Workshop Overview
             and  Recommendations
    Participants in the Exposure Assessment Workshop brought to it
 a keen awareness of the  difficulties inherent in the assessment
 process as well  as of the necessity for decision-makers to have
 reliable exposure information on which to base regulatory standards.
 One of the major topics of workshop discussions was the complexity
 involved in assessing exposures from multiple sources.
    None of the five case studies discussed represented a true multi-
 media assessment, though several did consider more than a single
 medium of exposure. The media orientation (air and water) of EPA
 program offices and the character of the authorizing legislation tends
 to  require,  or  at  least  encourage, single-medium  exposure
 assessments and single-medium regulations. Such assessments can
 be done reasonably well with existing methods and data that are
 already available or easily obtainable. Even in these relatively simple
 situations, it is important to state explicitly the assumptions made
 and the uncertainties in the assessment, making clear the range and
 most probable  kinds of exposure. Uncertainties will occur not only in
 the estimates  of geographic distribution, duration,  concentration,
 and transformation of the  pollutant of interest, but also in the
 behavior and movement of individuals in the area of concern. Such
 single-medium assessments can  be based on empirical data or
 models, with actual measurements used as bases for model verifi-
 cation whenever possible.
    Multi-media exposure assessment is inhibited by institutional
 arrangements,   traditional   scientific   disciplines  (for   example,
 hydrology, meteorology),  and the lack of agreed-upon assessment
 methodology. Also, legislatively and judicially imposed deadlines
 frequently prohibit adequate exposure assessments, so that there is
 time only to use existing  data or data that can be acquired quickly;
 there  may be  insufficient time for field measurements or model
 verification.
    The multi-media exposure monitoring and modeling conducted
 by the Environmental Monitoring Systems Laboratory (EMSL), Las
Vegas, is the on ly exa mp le we have wit hi n E PA that demonstrates an
 understanding  of complete and complex exposure assessment. The
relative freedom from regulatory pressures probably contributes to
this approach, since there is no stimulus to favor one aspect of control
over another. We suggest that a  larger investment in exposure
assessments drawing on Las Vegas  experience and personnel would
be worthwhile.

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    Participants   generally  believed  that the  bladder  cancer
epidemiological study {Case Study 4} was an excellent study model
that will be useful  in  the regulatory  decision process.  It was
emphasized that there was an extensive critique of the study before it
was undertaken.  A  similar  pre-study  critique  could well  be
incorporated  into all such extensive Federal  studies,  not only to
improve their scientific quality, but also to blunt post hoc attacks on
the results  once the study is completed.
    It was  also noted that an important  difference exists between
qualitative hazard identification and quantitative hazard assessment.
The possibility was raised of reviewing state implementation plan
(SIP)  guidelines  for  exposure  assessments  to  determine  the
consistency and  quality  of such guidelines. It  was also noted that
perhaps there was information to be gained from the SIP guidelines
in a broader EPA context.
    Additional emphasis was placed on the need for multi-media
exposure assessments  that include an estimate of the relative
contribution of each exposure route. Also emphasized was the
importance of conducting "real world" monitoring to verify modeling
estimates as early in the regulatory decision process as possible. It
was concluded that it is difficult to arrive at  a system that could
prioritize resource allocation, both for exposure assessment alone
and in combination with  other information needs. This is particularly
important since many of the methodologies required to improve our
abilities in exposure assessment are relatively costly.
RECOMMENDATIONS FOR PRIORITIES
AND FUNDING
    Workshop participants agreed that exposure assessments and
the methodologies necessary for generating adequate assessments
have  not been assigned a high enough priority in Federal resource
allocation. It was also clear that no obvious way currently exists to
"standardize" the details of an approach to exposure assessment.
The wide disparities in  data  base  uncertainties, the severity of
expected results, and the resources  available in the area under
review  necessitate a  case-by-case approach to many  exposure
assessments. Given this necessity for  individualization, it is critical
that the Agency's general approach to exposure assessment have an
inherent logical consistency. This is important not only for the legal
defense of a given regulatory decision, but also as a basis for ensuring
that all the important factors  in assembling  an  optimal exposure
assessment have at least been formally addressed in the process.

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RECOMMENDATIONS FOR ADMINISTRATIVE
AND ORGANIZATIONAL ARRANGEMENTS
    Because  of the  diversity  of  expertise within EPA,  total
centralization of the responsibility for exposure assessments is likely
to be less productive than an arrangement of clearly established lines
of responsibility across the Agency. For such an arrangement to work
effectively, it must avoid the dangers of a  too narrow, medium-
specific perspective. It is vital to have a central coordinating group or
office with major responsibility for issuance of general guidance for
exposure assessments. The group should also coordinate and review
the efforts in  exposure assessment across the Agency.
    The issue of coordination reaches beyond the  confines of any
single office within EPA, or even the boundaries of the Agency as a
whole. Exposure assessment methodology should be a major area for
interagency coordination and  cooperation, perhaps through a
working  group  of the  Interagency  Regulatory  Liaison Group.
Additionally, the Agency should continue efforts to establish stronger
ties with the  scientific and academic communities  concerned with
exposure  assessments. Multi-discipline, multi-agency workshops
like this one, as well as grant/contract strategies in this field, can all
help achieve this goal.
 RECOMMENDATIONS ABOUT TIME FACTORS IN
 REGULATORY ACTIONS
     No matter  what coordinative framework is  established, two
 generalities about the exposure assessment process should be
 emphasized. First, for maximum effectiveness, exposure assessment
 should be formally required to be considered at a very early stage in
 the regulatory decision and review process. This may be simply a brief
 qualitative review (for example, is there likely to be significant
 exposure or not?) in the early stages, becoming a complete, detailed
 exposure assessment when certain criteria are met. Secondly, the
 system should  include a formal attempt to conduct anticipatory
 research in exposure assessment, in an  effort to acquire data for
 future regulatory actions. This must be accomplished in addition to
 the more common "fire-fighting" mode of operation.
 RECOMMENDATIONS FOR SPECIFIC GUIDELINES
     A number of specific recommended guidelines for exposure
 assessment also emerged  from the discussions. .It was  almost
 universally agreed that any assessment should include consideration

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of multi-media exposure. Only if it can be specifically concluded that
other media do not contribute in any significant way to exposure of
any  population group can  a single-medium approach  be used.
Methodologies for  evaluating agent-specific as well  as  the more
common medium-specific exposure should be developed.
RECOMMENDATIONS FOR MODELING AND
DATA COLLECTION
    Modeling of exposures will  remain a key tool in  exposure
assessment, particularly for evaluating substances not yet produced
in commercial quantities. It was stressed that, whenever possible,
field measurement of the most critical parameters should be carried
out to evaluate the precision of model  estimations. Whenever
verification  measurements  cannot  be  made,   the   exposure
assessment  should  include  explicit statements  on the conditions
postulated in the model, the probabilities for each of the assumptions
in the model, and an estimate of the range of uncertainty introduced
by the inability to check on the model's accuracy. Whenever worst
case analyses are performed, it is particularly important that the
conditions of the worst case be clearly defined. A consistent approach
across the Agency  to the definition  of "worst case" should  be
encouraged. "Worst case" can be derived by generating a range of
estimates for exposure and taking the "worst" or highest level as the
one upon which to base the exposure assessment. Alternatively, one
could use the most susceptible population as the population to be
protected, thus generating a different worst case analysis.
    Whenever various control strategies are being considered in the
decision-making process, the long-range impact  of the various
strategies should be considered, as well as the short-term impacts. A
control strategy that achieves the greatest reduction in the  short-
term may not be the most effective strategy when all the long-term
implications are reviewed. In order  for the  long-term impact of
various control strategies on exposure assessments to be carried out
effectively, it is necessary that the transport and fate of the substance
under  consideration and the possibility of future exposure from
"sinks" be well understood.
SOME SPECIFIC RESEARCH AND DEVELOPMENT
NEEDS
    Some of the case study discussion groups noted research and
development needs specific to their areas. The sulfate discussion
group took note of exposure assessment needs in the areas of diesel
emissions, toxic substances and control, and resource conservation

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and recovery. They also urged work in measurement methods, model
verification, and diesel emissions transport and fate studies.  The
need for personal dosimeters was noted by both the chlorobenzilate
and the bladder cancer discussion groups. The chlorobenzilate group
called attention to the urgent  need for an evaluation of exposure
information pertaining to home and  garden pesticides. They also
suggested that industries need guidelines on generation of data for
pesticide exposure  assessment  for  the  Rebuttable  Presumption
Against Registration (RPAR)  process. The  bladder  cancer group
suggested a search for indicator variables or "flags" that might be
used as evidence of exposure; they also suggested a study to consider
the implication and utility of the concept of a "risk budget."

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           Introductory Presentation:
              Exposure  Assessment
        Regulations and  Enforcement
                      Cara Jablon
          Office of General  Counsel, EPA
    Exposure assessment is a key factor in any statutory scheme
requiring either that exposure considerations be taken into account
or that a risk/benefit analysis be performed to determine whether a
substance poses an unacceptable health risk. Without adequate
exposure data, it  is extremely difficult  to arrive  at  reasonable
regulatory decisions or to defend such decisions at Agency hearings
or in judicial review.
    The  Rebuttable Presumption Against  Registration  (RPAR)
process under the  Federal Insecticide, Fungicide, and Rodenticide
Act (FIFRA) is an example of a regulatory scheme in which exposure
assessment is an important factor. Many of the considerations faced
in this process are applicable to any statutory scheme that requires a
risk/benefit analysis. The RPAR process is a review of pesticides to
determine if these substances pose an unreasonable adverse risk to
human beings or to the environment. The statutory provisions of
FIFRA give a broad mandate to EPA to conduct these reviews. The
regulations provide  risk criteria to measure the potential for adverse
effects and require that the Agency issue an RPAR notice when the
risk criteria are met or exceeded.  The risk criteria require that the
Agency take  exposure into account  in  determining  whether a
rebuttable presumption should be issued for chronic effects other
than oncogenicity or mutagenicity. These latter two effects  give
cause for issuing an RPAR notice, even in the absence of a specific
exposure assessment.1  After an RPAR notice has been issued, the
registrant has 105  days to  respond with  rebuttal information.  EPA
then reviews the rebuttal submissions and any additional available
information to determine whether any of the presumptions have
been successfully rebutted. Any remaining presumptions  are then
    'The conference report to the 1978 FIFRA amendments directs the Agency to
"establish suitable scientific protocols for the development of human exposure data; to
work cooperatively with the registrants in the assembly and collection of such data;
and then to evaluate and weigh such data prior to initiating an RPAR process." Thus, it
is likely that all available exposure information for oncogenicity and mutagenicity will
be considered prior to the issuance of  an RPAR.

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subjected to a  risk/benefit  analysis, using exposure data that
incorporate the information generated during the rebuttal period, to
determine the potential risk attributable to the various uses of the
pesticide. If a determination is made that the risk is greater than the
benefits, a notice of intent to cancel or restrict the use of the pesticide
is issued. At this point,  registrants usually request  an Agency
hearing.
    At the Agency hearing level, the exposure data base is often a
major  area  of concern. In previous cancellation hearings, solid
evidence was often presented  of exposure such as measurable levels
of the pesticide substances in human tissues and fluids. However, for
many of the pesticides currently under review, sufficient data are not
available to  determine levels  of  exposure.  The lack  of  data
necessitates that a multitude of assumptions must be made in order
to generate  an exposure assessment. These assumptions may be
difficult to defend against a rigorous attack in any formal hearing or
court review. Thus, it is essential not only to generate more exposure
data, but also to assure that the data developed  will be  useful in
arriving at a supportable regulatory decision. There is a specific need
with regard to pesticides for studies on levels of human exposure by
dermal, inhalation, and ingestion routes, as well as for information on
the size and exposure profile of the population at risk. Studies must be
generated to allow a determination  of the actual  human  intake by
inhalation from ambient levels, the actual  amount of absorption of
the material  through the skin,  and the actual level of  pesticide
residues present in raw and processed foods.
    Unless studies are designed to provide information concerning
real world exposure,  they provide little aid  in arriving at reasonable
regulatory decisions.  Both physical monitoring (human and residue)
and animal studies are important in assessment  of exposure to a
hazardous substance. As a starting point, it is useful to have studies
on methods  and rates  of application for families of chemicals. The
most valuable information is, of course, derived from studies on the
specific pesticide of concern.  Particular emphasis  should be placed
on performing monitoring studies on the specific population at risk in
order to determine the exposure per unit time.
    Each exposure study  must consider critical  exposure factors
such as the specific chemical formulation, the population at risk, the
geographic and meteorologic conditions, the frequency and duration
of use, the method of application, the particle size, and any customary
use not in accordance with  label directions. Information is most
useful when  the  exposure  data are generated by the highest
application rate permissible by label instructions. The design of these
studies  requires  specific input from  toxicologists,  engineers,
environmental  and  analytical  chemists, biomedical scientists,
agricultural experts,  and attorneys. Attorneys should be consulted
early in the planning process as to the usefulness of the study design
in generating data that can form a basis for a supportable regulatory
decision.
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    In the design of animal studies, similar considerations must be
applied. These include attention to realistic routes of exposure, the
proper selection of animal species, an adequate number of animals in
the exposure groups and appropriate  levels of exposure.
    Clearly, if properly designed studies are not available to form the
basis for  an exposure  assessment,  the Agency will have great
difficulty in promulgating a regulatory decision, and in defending this
decision. Although  the burden  of proof  is on  the registrant to
establish the safety of his product, it is incumbent upon the Agency to
establish the validity of the data base on which regulatory action is
taken. When exposure assessment  is  based on  a  multitude of
unsubstantiated assumptions, the Agency's regulatory action may
be  effectively challenged in  court. The more  uncertainties and
assumptions  that are  present,  the greater the chance that the
registrant will be able to successfully challenge the impact of the
exposure assessment and render it potentially "unreasonable." A
risk assessment can be seriously damaged by the demonstration of
potential error in each sequential step of the exposure estimate. The
decision process may become so clouded by the magnification of the
potential error from such an analysis that the regulatory decision will
not be upheld under review. These problems can be greatly reduced
by using data from well-designed studies that provide information
about real-world exposure. In the absence of definitive studies, it is
essential that the potential error in each assumption be limited by
reference to a solid data base on related compounds and application
methodology. The presence of confirmatory data from a number of
sufficiently different sources is important in establishing the validity
of any assumptions underlying the assessment.
    Several other considerations about the use of exposure data in a
hearing or court situation are important. First, in order to effectively
convince a judge to support an Agency decision that a given pesticide
poses a significant health or environmental problem,  the Agency
must be forthright about the shortcomings of the data base. It is often
helpful  to  state  a  range of estimated values  for an  exposure
assessment if the assessment is based on assumptions that cannot
be  directly substantiated. Also,  the  process by which exposure
assessments are generated should  be consistent with Agency
treatment of  other pesticides and other substances amenable to
similar treatment, as well as internally consistent for the given
pesticide under review. If there are inconsistencies in the process,
the professional quality of the Agency's supporting documentation
may be called into question  and the Agency's  case seriously
damaged.
    In the judicial review  process,  the  standard of review is
substantial evidence on the record as a whole. Thus, a regulatory
decision will be upheld in judicial review if it is within the regulatory
authority of the Agency, if the Agency took  into account all relevant
issues and considered  all the evidence,  and if the  decision is
reasonable based on this evidence. Thus, from the perspective of the
Office of General Counsel, the importance of designing studies with a
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view toward whether the data will hold up in court and will convince
the judge cannot be overemphasized. It is essential that the Agency's
exposure assessments be based on relevant data derived from well-
designed studies and that the Agency take a consistent approach to
the generation of such exposure assessments.
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                  Case Study #1
            Particulate Sulfates and
            the Catalytic  Converter
                    Roger Cortesi
  Office of  Research and  Development, EPA

THE PRESENTATION
    In the spring of 1973, the Administrator granted a two-year delay
to auto manufacturers for meeting the statutory emission standards
under the Clean  Air Act. At about the same time. Ford Motor
Company notified EPA that it had measured increased sulfuric acid
(H2S04) emissions from autos fitted with the oxidative catalytic
converter,  one technology that had  been projected to provide
eventual  compliance with  the  statutory  automotive  emission
standards.
    EPA was sharply divided in opinion as to the significance of the
health  threat from  H,S(X  emissions. The Air Program Office
considered the problem to be relatively insignificant. The Human
Health Effects group within the Office of Research and Development
(ORD)took a strong stand that a significant health hazard could occur
in two  to six  years after widespread introduction of the catalytic
converter. This ORD position was based  on the assumption  that
significant adverse  health effects  occurred after exposure to 10
ug/m3  of acid sulfate—an exposure effects level derived from the
Community Health Environmental Surveillance Study (CHESS) data,
and from estimates  derived  from  both direct and surrogate (for
example, carbon monoxide carboxyhemoglobin) models. Various EPA
modeling efforts produced a wide range of exposure estimates, some
considerably  exceeding  10 ug/m3. In fact, major uncertainties
pervaded all  key  data elements:  emission factors, ambient level
model predictions (which are highly dependent upon assumptions of
worst case meteorology), and levels of exposure that produce adverse
health effects.
    In late 1973 and early  1974, a review of the issues involved in
this dispute was undertaken by representatives of the Office of the
Administrator, the Office of Research and Development, and the Air
Program Office. Some of the modeling assumption differences were
resolved and the areas of uncertainty were made explicit. So  that
"real world" emission levels could be approximated, a roadside
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monitoring   program  in  California   was   recommended  and
implemented for H2S04 particles. Later, a joint General Motors and
EPA study of H2S04 roadside emission levels was also completed at
the GM test track.
    In  January 1975, the  Administrator was petitioned for an
additional year's delay in imposing the statutory emission standards.
Faced  with  strong arguments by some EPA scientists that the
technology  for meeting  these standards could present a health
hazard greater than the  hazard of not meeting the standards, he
granted the one-year detoy.
    Internal arguments  within EPA  were  intense.  The  major
technical disputes related to exposure estimates, including modeling
techniques, modeling assumptions, and data interpretation. By late
1975,  the  California  roadside study and GM/EPA  test track
monitoring  had added substantial data to the  questioning. In both
studies,

    •  Emissions proved to be about a third as high as previous
       estimates

    •  Model estimates  of exposure levels fell into the lower end of
       the range of previous EPA estimates

    •  The advent of oxidation/reduction catalysts promised further
       emissions reductions.

    By early 1976,  EPA declared the HjSOj  issue no  longer of
immediate concern and announced that the Agency would not set an
H2SO4 emission standard for automobiles, as  previously planned.
THE WORK GROUP DISCUSSION

    The group made the following general observations on exposure
assessment:

A.  Exposure assessments cannot be  performed  by any single,
uniform method; each case may differ significantly in:

    1)  Purpose: One can be dealing with such disparate cases as
    single-medium  exposure  to sulfates from catalyst-equipped
    automobiles, to TSCA-type analyses where a large number of
    new chemicals potentially present in several media are involved,
    to analyses of the relative significance of multi-media exposure
    pathways (for example, cadmium, benzene, or lead).

    2)  Timing: This can range from relatively crude assessments
    early in the regulatory analysis in order to evaluate the problem,
    to detai led assessments that q uantify exposure assessment for a
    major regulatory decision.
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    3}  Relative application of necessary disciplines: That is, what
    role  is  required  of  meteorology,  environmental chemistry,
    population dynamics, pharmacokinetics, etc. in a given exposure
    assessment?
B.  One must recognize that:

    1)   Exposure assessments will always be "custom-made," and
    often the approach  used successfully in one case will not be
    suitable  for  other  problems.  However,  major  efforts  at
    consistency in some basic issues are still important.

    2}   Exposure assessments must  be  an integral part  of a
    regulatory analysis. These considerations should be included
    early in the process and  integrated with  other elements  of
    regulatory analysis, especially the consideration of potential for
    adverse health effects.

    3)   All media and pathways for exposure should be considered
    from the outset. The process must identify, and when possible
    quantify,  both  significant and  insignificant sources  and
    pathways. The potential impact of cumulative exposure from all
    media/sources also must be specifically addressed.

    4)   Exposure  assessment  within  EPA  should  not be
    organizationally centralized, although the new ORD Exposure
    Assessment Group will play a major role in generating many of
    these assessments. There is a  need to institutionalize the more
    formal,  detailed assessments,  at least  by  the  mandatory
    involvement of all interested offices in the exposure assessment
    process.
    In discussing  the  state-of-the-art for  exposure assessment
methodology, the  group pointed out  the  following  needs and
priorities:

A.  Exposure assessments can be done reasonably well on specific,
single-medium problems, when this is the appropriate assessment
approach.

    1) The studies  must have  been carefully designed,  clearly
    testing well defined hypotheses.

    2) All assumptions, methods, and uncertainties must be dealt
    with explicitly.

    3) Data from both predictive models and empirical studies must
    be integrated.
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    4)  Recognition  must  be given  to  the different levels  of
    complexity  required  for  exposure assessment analyses  at
    different stages of regulatory decision-making.

    5)  The possibility of significant multi-media exposure must be
    explicitly analyzed before a single-medium approach is adopted.

B.  Data acquisition to test the applicability of exposure models to a
given case is a high priority need. However, some participants felt this
need might not be met simply  by the expenditure of additional
resources.

C.  In  the formalized exposure  assessment process,   some
systematization of methodology would be useful (recognizing that the
entire process often must be individualized).

D.  Exposure can be assessed in two ways:

    1)  Predictive or modeled. The greater short-term need for the
    Agency is the development of more accurate predictive methods
    and for the methodology/resources necessary to validate the
    modeling estimates.

    2)  Evaluated/estimated from actual data for chemicals already
    in the environment.

    The group  agreed upon  several specific EPA  Research and
Development needs in exposure assessment:

A.  There are specific areas in which very real short-term Agency
needs exist for optimal exposure assessments to be produced. These
include:

     1)   Air: diesel emissions;

    2)   Toxic Substances Control Act: new and existing chemicals;

    3)   Resource Conservation and Recovery Act: the total dimen-
    sion of the need was still unknown; and

    4)   Water:  toxics  control strategies  will  require  technically
    sound, legally defensible exposure assessments.

B.  Methodologic development to enable better exposure assess-
ments in the future.

     1)   Correlation of actual human  exposures with ambient levels
    through:

          a)  Human behavior and mobility analyses
          b)  Personal monitors/individual dosimetry
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2)  Verification of modeling predictions. Early in any analysis
involving a substance or substances already in the environment
(in contrast  to a new chemical under TSCA),  it should be
determined whether or not the models to be  used can feasibly
and economically be verified. If they can, this validation effort
should be incorporated into early resource allocation decisions. If
model  validation  is not feasible, other models that might be
verifiable should be explored. Alternatively, the model should be
used with the explicit caveat that no validation efforts will be
undertaken and an estimate given of the range of uncertainty
introduced by the use of such a model.

3)  General environmental transport and fate studies to develop
better  approaches (for example, pathways analysis  or mass
balance determinations) are required to improve  multi-media
assessment capability.
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                   Case Study  #2
                  Chlorobenzilate
                    David J. Severn
        Office of Pesticides Program, OTS

THE PRESENTATION
    Pesticides differ from most chemicals of environmental concern
 in that they are deliberately distributed into the environment. An
 Agency assessment of Chlorobenzilate exposure made in   1978
 stands as an example of how the Office of Pesticide Programs (OPP)
 used  an existing  base of exposure  data for  other pesticides to
 estimate  the  exposures  received by  workers  who  apply
 Chlorobenzilate.
    A considerable bank of data is available concerning pesticide
 applicator exposure. However, much of this information is focused on
 application techniques rather than on  specific pesticides. Like many
 other pesticides, Chlorobenzilate is applied  by air blast or speed
 sprayer equipment;  these  techniques produce a fine  spray that
 penetrates  the foliar canopy and that  also creates  potential for
 exposure of the applicators.
    The  Wenatchee  Research Station  of  ORD has  developed
 techniques to measure both inhalation and dermal exposure during
 pesticide operations. To make the measurements, a series of pads
 made of alpha-cellulose is attached to the arms, chest, and back of
 the applicator. At the conclusion of the exposure period, the center
 100 cm2 are cut out of the pads and analyzed. Cartridge respirators
 are worn during exposure to measure inhalation; these cartridges are
 also analyzed. Alternatively, air concentrations of pesticides may be
 measured by air sampling devices, and the concentrations converted
 to inhalation exposure values by assuming a standard breathing rate.
 The exposure data are tabulated in terms of milligrams per hour of
 dermal and inhalation exposure.
    In various airblast operations, average values for dermal expo-
sure have ranged from about 15 to 50 mg/hr. Inhalation exposure
 has been observed to be much lower, averaging about 0.1 mg/hr.
OPP used these values as reasonable  estimates of applicator expo-
sure to Chlorobenzilate. In order to convert the dermal values into ac-
tual doses absorbed by the applicators,  it was necessary to correct for
the efficiency of penetration and absorption through human skin. No
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data were available for chlorobenzilate, but, based on data for a num-
ber of other chemicals, it was concluded that 10 percent may be a
reasonable estimate.  The dermal  exposure value estimated for
chlorobenzilate was accordingly reduced to 1.5 to 5.0 mg/hr, or 1.6 to
5.1 mg/hr for the combined routes of exposure.
    Since the toxic effect of chlorobenzilate for which a risk
assessment was required was carcinogenesis, the exposure had to
be presented as long-term or chronic exposure. OPP relied on data
from USDA and user groups to estimate that there are about 700
people who apply chlorobenzilate to orange groves. Each person
probably works about 20 to 40 days per year applying the pesticide.
The lifetime daily average exposure was then computed by assuming
that the applicators work 8 hours per day, 40 days per year, for 40
years of a 70-year life. With the higher exposure rate, the resulting
lifetime  value was  2.57  mg per  day. Finally,  the Carcinogen
Assessment Group of ORD used this higher exposure estimate with
data on  tumor incidence from a chronic mouse feeding study to
predict a tumor incidence of 400 to 1,400per million exposed people.
 THE WORK GROUP DISCUSSION
     The discussion  revealed that a great deal  of information is
 needed for pesticide exposure assessment. Exposure is dependent on
 actual use practices as well as on the nature of the pesticide. The
 group recommended that:

 A.  A synthesis of known exposure information be undertaken for
 home and garden pesticide use (including interior use pesticides), to
 be followed by an analysis of exposure assessment data needs. Home
 and  garden use of  pesticides  has recently  been  shown to be
 unexpectedly high. In addition, recent surveys have revealed that the
 overall national incidence of acute human poisoning is highest in the
 home, particularly  with young children. The  undertaking of this
 synthesis should receive the highest priority.

 B.  There is an urgent need to collect and analyze available data and
 to identify data gaps relative to exposure of farm workers who enter
 pesticide-treated fields to cultivate or harvest crops.  Attempts to
 develop simple, effective field indicators of personnel exposures
 (dosimeters} should be augmented. A large number of farm workers
 are unknowingly exposed to pesticide residues. Recorded incidents,
 as well as  additional  (extrapolated) situations  not  documented,
 represent considerable impetus for corrective action.  The highest
 priority is represented by this recommendation.

 C.  Protocols should be developed for industry (applicant) guidance
 in their provision of human exposure data. These data are required in
 the RPAR process in order to assure reasonable safety in the uses of
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pesticides for which application for registration  is  made. HEW
guidelines for human testing, as applied by EPA,  restrict overt
exposure of human subjects to pesticides. Yet, the burden of proof of
the safety of pesticides is on the registrants. The industry, as a group,
is unclear as to what exposure data are expected. Work to be carried
out under this recommendation is of second level priority.

D.  Total exposure of all populations should be assessed. Exposure
may occur to workers during manufacture, formulation, application,
and field operations such as cultivation and harvest. Other exposed
populations include those in areas adjacent to treated areas and
those who utilize products that may still contain residues.
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                   Case  Study #3

                       Benzene

                     Michael Berry
  Office of Research  and Development, EPA


THE PRESENTATION

    Three years ago the Environmental Protection Agency was faced
with legal action to require the listing of benzene under Section 112
of the Clean Air Act (hazardous pollutant emission limit). At that time,
the Air Programs Office, with the National Air Quality Data Bank in its
domain, took  the lead role in generating a population exposure
assessment. The Office of Research and  Development took major
responsibility for the assessment of health effects data and, through
the Carcinogen Assessment Group, for the formal risk assessment.
The outcome  of these efforts was an EPA decision that benzene
should be regulated as a potential human carcinogen, though it was
not yet proven that benzene actually acts as a human carcinogen.
    The exposure assessment for benzene was based on a worst
case analysis that took into account the maximun possible number of
exposed individuals exposed at the maximum projected levels. It is
very difficult to translate the experience from industrial exposures
that range in hundreds of parts per million exposure over 40 hours a
week to the final range of 0.1  to 10 parts per billion as the limit for
annual average exposure for the general population. The study gives
no number as a discrete value,  nor does it provide estimates of
variance. However, as several workshop participants noted, it is
extremely difficult to state the variance for any number that is in
reality based  on a  model that already includes inherently large
uncertainties.  The  "body count" used in the  risk assessment was
based on the non-threshold linear dose/response assumption. The
validity of this  assumption is still open to scientific debate. However,
the basis for regulatory action should be and was a detailed risk
analysis. One of the major shortcomings of the exposure assessment
in the case of benzene was the lack of a truly broad multi-media base
for  the  assessment.  The  possible contribution  of non-airborne
sources of benzene was not included in this analysis. For example, it
was noted in the workshop that upto650mrcrogramsof benzenecan
be inhaled by a smoker who consumes one pack of cigarettes per day;
also,  some commercially produced  eggs  contain  up to  100
micrograms of  benzene.  The  need for  multi-media exposure
assessments was again emphasized.
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    Another area of concern was that, where there were monitoring
data available to  compare with the estimates generated by the
models used in the  exposure assessment,  the data did not agree
closely.  The  importance  of  verifying  modeled  concentration
estimates with real world monitoring data was also emphasized. It is
important to target those areas where monitoring data will be of
immediate help in  improving the modeled estimations. When a worst
case analysis is generated by a model, it is important that the basis for
such a worst case be stated  quantitatively and explicitly.  It is also
useful to state the  probability estimates that surround the worst case
circumstances.
THE WORK GROUP DISCUSSION


    The  group used  the experience of the benzene exposure
assessment as a basis on which to assess the state-of-the-art and to
recommend improvements in the existing methodology. Their review
of the benzene  document  and their collective knowledge about
exposure assessments led them to the following recommendations:

A.  Integrated Assessments. The consensus of the group was that
assessments should include all sources and all media.  Partial
assessments were deemed inadequate because they might not result
in the adoption of cost-effective and rational control strategies.

B.  Fate and Future Exposures. Assessments should account for the
fate of the substance. If "sinks"  exist,  the assessment should
estimate  the  future  exposures that  might result  from those
accumulations. If a  substance has  toxic degradation products,
exposures to  the latter  should be  estimated.  Conversely,  if a
substance is rapidly degraded to non-toxic by-products, this should
be recognized.

C.  Define Uncertainty. In  any assessment, gaps will exist with
respect to some part of the analysis—for instance, inadequate data
on releases, transport, or transformation. Any credible assessment
should make  explicit the assumptions that have been made to
overcome such gaps. Such openness identifies priority areas for
research and data gathering and also invites attempts at improving
the methodology and the  substantive basis for making decisions.

D.  Actual  Field Measurement.  Every  assessment  should be
supported by field measurement whenever possible. When field
measurements are not possible, laboratory  data from various test
procedures designed to provide insights into environmental behavior
and fate should be used.

E.  Single Effects and Exposure Document. There was a strong
feeling among the  group  members  that  exposure and effects
                             24

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documents produced thus far display a  lack of coherence.  For
example, effects documents often ignore  the exposure data. The
exposure documents often may conflict with or duplicate material in
the effects document. At a minimum, it was urged that preparation of
the documents be more closely coordinated. At least one member of
the group urged that the effects and exposure estimates be combined
into one document, thereby forcing coherence.

F.  Consistent Methods. One member of the group felt strongly that
the exposure assessment process could be improved by development
of guidance or, in some cases,  even the standardization of methods
for carrying out exposure estimates. However, because of our present
lack of information on environmental quality and spatial activities and
behavior of populations, it would seem  prudent to evaluate the
desirability of developing guidelines for standardizing assessment
methods.
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                  Case  Study #4
   Bladder Cancer  Epidemiology  Study
                   Kenneth  Cantor
  Office of Research and Development, EPA
      (on detail  to National Cancer Institute)

THE  PRESENTATION
    The impetus for establishing the Bladder Cancer Epidemiology
Study was a recent surge of interest in the relationship between
saccharin  ingestion  and bladder cancer.  However,  the general
problem of potential organic carcinogens  in the Nation's water
supplies has been debated for a much longer time.
    It is known that chlorinated organic substances in water supplies
come not only from the water source itself, but also from substances
produced by  the water treatment process. Ten  years  ago, the
introduction of gas chromatography to examine drinking water
supplies revealed  multiple peaks  representing the  presence of
numerous  organic compounds in many water supplies. A supply
survey in 1973 showed that there were 81 identifiable compounds in
the water supply for New Orleans. The Environmental Defense Fund
helped support a  study that showed  higher  rates of  cancer in
Louisiana  parishes  where the  water supply  came  from the
Mississippi River than in parishes using  other water sources. In the
Miami, Florida, water supply (obtained from an area of the Everglades
which has relatively  high natural  organic  content,  and then
chlorinated) chloroform levels are 350 times higher than in deep well
water sources in the same areas. There have been a number of
studies correlating increased rates of cancer mortality in counties
whose water  supply is from a  surface or shallow source. High
trihalomethane levels in particular have been linked to elevated
cancer  mortality,  especially bladder  cancer. These suggestive
correlations have not clearly been established as causal. There is
debate within  EPA about whether regulation of such substances can
be  based on  suggestive correlations or whether more definitive
evidence is necessary.
    The review of saccharin as a potential carcinogen by the FDA in
1972 did not trigger application of the Delaney clause at that time.
However, in 1977, a Canadian animal study in  which one group of
rodents was exposed to pure saccharin, a  first control group was
                           27

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exposed to the most common contaminant of commercial saccharin,
and a second control was unexposed showed an increased bladder
cancer  rate in  male rats who ingested saccharin. This  increased
cancer rate was not seen in the contaminant control group. On the
basis of this evidence, the FDA started proceedings to decide whether
saccharin should be removed from the market in the United States.
While this was  occurring, results became available from a Canadian
epidemiology case control  study which  showed  a statistically
significant positive  correlation  between bladder  cancer  and
saccharin ingestion in males, but no such correlation in females.
There were also negative studies reported at this time,  but these
studies  used hospitalized individuals with hospitalized  controls,
rather than a random sample of the general population.
    Because of the debate about saccharin in the U.S., the Congress
mandated that  the National Cancer Institute and other concerned
agencies organize a broad nationwide epidemiological study on the
relationship of saccharin and bladder cancer.  It was desirable and
necessary to study as many of the interactive variables as possible,
obtaining  a history not  only of saccharin ingestion, but also  of
industrial  exposure to bladder carcinogens,  smoking (both non-
filtered  and filtered cigarettes), water supply, and coffee drinking.
Nine regional surveillance areas plus the state of New Jersey were
chosen. (In each of these areas, there was a population-based tumor
registry to maximize total  case reporting. With a rapid ascertainment
procedure, the  lag time between  diagnosis of bladder cancer and
notification of the tumor  registry is less than six months. Less than
four percent of the patients died between their original diagnosis and
the time the epidemiology survey  team attempted to contact them.)
The ten epidemiology survey areas represent 12 to 15 percent of the
U.S. population.  These groups are  not totally random,  because
minority population  groups  are  slightly  over-represented. It  is
estimated that 4,000 of the 30,000 expected cases per year of bladder
cancer in this country will be included in the study.  Controls for age,
race, and sex-specific  case  groups are randomly  selected from a
stratified population sample. Control selection takes account of the
demographic  characteristics of bladder cancer patients; patients
have a median age of 67 years, and the disease occursthreetimes as
often in males as in females. The control series subjects have similar
characteristics.
    A personalized questionnaire is used that includes a complete
residential history of water supply. To support this, a separate survey
of historical municipal water supply characteristics in the area under
study has been  undertaken. Items included in this survey include
source of water (surface versus ground), the history of chlorination
levels, and the  possibility of any  upstream industrial or municipal
contamination for those areas with surface supplies. Water samples
from the ten areas in the  study are also being analyzed. If there has
been no change in the  treatment methodology or water supply
source,  present  samples  will be used as a measure of long-term
water quality/organic pollutant content.
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    The  interviewers, who  have  not  been  informed that the
questionnaire is related  to a  bladder  cancer study,  also ask
patients/controls to quantitate their use of saccharin, including
artificial  sweeteners,  diet  drinks, and other uses. It is known that
approximately 10 to 20 percent of the population used saccharin to
some extent 20 years ago. A worst case estimate is that there may be
as many as 15,000 people who have developed bladder cancer each
year and who report some past saccharin use.
    To date, there has been an 80 percent response rate for both
cases and controls. In the case series, there is approximately a 4 per-
cent fatality rate prior to interview. Some patients move out of the
study area and a few patients have refused to participate. In some
study areas, physicians have not permitted study personnel to
contact their patients. Morethan 90 percent of the controls contacted
have been willing to participate. The cost of the study has been $1.4
million over  18 months for the more than 10,000 respondents. The
study will include all those cases diagnosed in the ten areas in the
calendar year 1978. This figure does not include the cost of the water
testing. Mid-1979 was the target date for a preliminary report of
study findings with regard to saccharin. Such epidemiology studies
require the best possible  assessment of individual exposure. The
retrospective construction of exposure profiles is the  best one can do
in this type of epidemiology study. Additional  useful information
could be gathered by studying epidemiology data from workers in the
saccharin production  industry in its early years, when it was a
particularly dusty process. These individuals constitute a relatively
easily defined group of high level exposure individuals.
    Animal studies show saccharin by itself to be a  relatively weak
carcinogen. However, if an animal is given a short exposure to a low
concentration of a known bladder carcinogen and then is given a high
dose of saccharin, there is a much higher incidence of bladder cancer.
This co-carcinogenicity potential makes a multi-factor epidemiology
approach mandatory if any useful data are to be generated.
THE WORK GROUP DISCUSSION
    The discussions of the workshop centered on two broad areas: (1)
the generation of a systematic list of generic issues to be confronted
in organizing  an adequate  exposure assessment, and  (2) some
general recommendations for further research efforts within EPA in
the area of exposure assessment. First, the group strongly felt that in
the past there  has been a lack of consistent organization in the
generation of exposure assessments within the Office of Research
and Development in particular and throughout the Agency in general.
It was suggested that there might  be some benefit from applying a
systematic list of questions that must be asked in conducting any
exposure assessment. The workshop group decided that some efforts
should be expended in developing a general outline or approach that
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all exposure assessments could utilize. They proposed a partial list of
such generic issues, including:

A.  Where is the pollutant? What is known about the dispersion of
the pollutant from its known sources? Are there any available models
that can be used to predict pollutant dispersal? Can such models and
predictions be feasibly validated by ambient monitoring in the real-
world setting?

B.  Where are the people (that is, the population at risk)?

    1.  Additional information is necessary concerning the distribu-
    tion of the population in space {in terms of population distribution
    around known sources of pollution) and in time.

    2.  Sampling studies or survey interview studies should be used
    to  gather data on personal behavior  patterns as they relate to
    exposure assessment.

C. What are the routes of exposure?

    1.   It is  necessary to  define  all of the potential  sources of
    exposure for the population at risk.

    2.  Methodologic problems  associated  with  measuring  the
    "insult" (exposure) must be addressed. This includes the area of
    personal dosimetry technology.

    3.   Data are also necessary concerning thedistribution frequen-
    cy in both time and space of the exposure to the population at
    risk.
D.  In  defining the interactive role between health effects assess-
ment and exposure assessment, two aspects should be considered:
    1.   What are the sources of information available? That is, are
    there human data  from either occupational or  accidental
    exposure? Are there primate, other mammalian, or other in vivo
    animal exposure data available? Are there in vitro laboratory
    screening data available? The relative importance assigned to
    these various sources of information is controversial, and some
    overall coordinating guidelines would be useful.

    2.   Which health effects should be looked for specifically? That
    is, should all potential adverse health effects be screened for, or
    can we predict for a given category of pollutants which poten-
    tially adverse health effects should be specifically  evaluated?
E.  Non-human ecological impact  of the pollutant  must also be
formally considered in the decision  process.
                              30

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    In the area of high priority  items for further ORD  resource
allocation, the work group recommended that the following efforts
should receive high priority:

A.  Research in the area of validation  of both exposure and effect
models. This was felt to be one area where there was the possibility
of relatively  high  potential  information gain for  limited  resource
expenditure.

B.  Are there any indicator variables ("flags") for a given exposure of
a population to a specific pollutant or class of pollutants that can
supply generic information with regard to the population at risk?

C.  Measurement methodology research:

    Anticipatory research,  which  might assist in developing ex-
    posure measurement methodology for substances that might
    have  the potential to result in health effects on the exposed
    population many years in the future.  This might help avoid a
    situation similar to asbestos  exposure, where even  after the
    adverse effect was clearly documented, uncertainty on measure-
    ment  methodology and on the  characteristics of dangerous
    fiber  types (size,  composition, etc.) hampered the regulatory
    decision  process.

D.  Long-range development and  validation of the "risk budget"
concept for exposure assessment. ORD should develop and evaluate
a system for assigning a risk budget (upper limit of risk) for exposure
to any environmental  hazard (for example,  individual  pollutant,
aggregate health risk). This concept  would dictate management/
monitoring   of  population  exposure  to the environmen-
tal  hazard  under  consideration  until  the  limit  specified  by
the risk budget  is  reached. At that  point, before any additional
exposure/risk could be permitted, it would have to  be balanced by a
concomitant  reduction  in exposure/risk within this defined area.
Such  an  approach would require significant  resources for  its
development. Evaluation of the efficacy of such an approach, and a
full discussion of the social/political implications are, of course,
necessary before it could be implemented even on a trial basis.
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                  Case  Study #5
                          Lead
                     Lester Grant
  Office of Research and  Development,  EPA

THE PRESENTATION
    In September 1978, a National Ambient Air Quality Standard for
lead was promulgated by EPA. The standard selected, 1.5 ug per
cubic meter (1.5  ug Pb/m-*) averaged over a calendar quarter, was
based mainly on health effects /exposure information evaluated in
Air Quality Criteria for Lead, published by ORD in December 1977.
The standard  is designed to protect 99.5% of the most sensitive pop-
ulation, which is children.
    Setting of the final standard involved difficult policy decisions
that centered on resolving uncertainties about some aspects of the
basic information and the provision of an appropriate margin of safety
within the standard.
    Partly,  the difficulty in decision-making was related to several
unique properties of lead as  an air pollutant. First, a significant
fraction of  population exposure to lead occurs  from sources other
than  respiration  of  airborne lead  particles. Second,  there is
substantial variability in the blood lead levels of individuals who have
had similar lead exposures. Third, there is considerable scientific
debate over the public health significance of lead-induced biological
changes that occur before marked symptoms of disease are detected.
    The sequence used in developing the standards was  first to
derive estimates of internal dose (blood lead levels) associated with
the induction of various health effects, and to  define or select the
pivotal adverse effect(s) encountered as a function of increasing
internal exposure. The most susceptible population at risk was then
defined, and  efforts  were made to estimate the  proportion  of the
population that would be at risk for particular health effects, given a
mean level of integrated external exposure to all sources of lead.
Contributions of non-air lead sources to an "acceptable" mean level
of internal exposure were then subtracted out, leaving an allowable
amount of  exposure due to air alone. This was then translated in
terms of equivalent allowable external exposure, or, in other words,
the ambient air level(s) chosen as the standard, including a margin of
safety.
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    In the development of the standard, 30 micrograms of lead per
deciliter was defined as the maximum safe level for any individual
child. Statistically, for protection of 99.5% of the target population,
this translates into a geometric mean population blood level of 15
micrograms Pb/dl. Of this latter level, only 3 ug Pb/dl are attributable
to air exposure. Given that in children a 1  ug Pb/m3 change in air
results in a change of blood lead of 2 ug Pb/dl, and given the policy
decision to establish the population blood level at 12 ug Pb/dl in order
to provide an adequate safety margin, the calculated standard is 1.5
ug Pb/m3.
THE WORK GROUP DISCUSSION
    The work group  on the lead case study initially reviewed the
overall meaning of  exposure  assessment  in the context of the
requirements of   regulatory  decision-making  within   the
Environmental Protection Agency. It was generally agreed that the
five individual case studies presented at the symposium highlighted
individual aspects of the exposure assessment problems, but that no
one case study by itself represented a "total" exposure assessment.
The group further felt that the Agency, at this time, possesses neither
the methodology nor the institutional mechanisms to implement
successfully a truly  "total" exposure assessment. At the present
time,  there  are  available   methodologies  and  institutional
mechanisms for separately defining the various aspects of a  total
exposure  assessment.  For  example, water-borne exposure is
evaluated separately  from air-borne exposure, etc. While each of
these analyses is an  essential part of the total, individually they do
not,perse, represent  an adequate "total exposure"assessment.The
major recommendation of the work  group was that the Agency
should use whatever  administrative/legislative/resource-allocation
means necessary to ensure  the necessary coordination for the
production   of  effective total  exposure  assessments.  It  was
additionally  felt that  coordination of exposure assessment efforts
within EPA are at the present time not as effective as they could be.
The establishment of an Exposure Assessment  Group within the
Office of Health and Environmental Assessment(EPA-ORD) provides
an opportunity for such coordinative efforts in the future.
    It was further concluded that EPA was the proper and logical
focal  point within  the government for the performance  of  total
exposure assessments. The necessary coordinative effort does not
require  any  additional legislative  authority,  but does  require
continued effort in developing close working relationships with other
federal agencies interested in exposure assessments (for example,
the Intergovernmental Regulatory Liaison Group). A major advantage
in the regulatory decision-making process ot adequate total exposure
assessments is that  such assessments can. help  to define more
clearly where the most environmental gain (that is, reduction in an
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exposure) can be obtained for a given resource allocation. Thus, a
combination  of  strategies  could  be evaluated,  and  the  control
approach most likely to be optimally cost-effective can be selected.
These options could range from strict control of a pollutant in one
medium to partial control in several different media, each option of
which could lead to a total exposure at an acceptable level.
    It was also emphasized that the long-term effects, as well as the
short-term effects, of  any control strategy must be evaluated. For
example, in the case of lead exposure, if one found that elimination of
metal and plastic food containers could reduce the general exposure
to acceptable levels, would one then choose as a major emphasis the
modification of containers or the control of air-borne lead? Obviously,
in many cases, the most attractive option in the short-term might not
necessarily be the best long-term solution.
    Within the concept of total exposure assessment, it was felt that
EPA should develop and evaluate an agent-specific approach in
addition to the traditional media approach. An additional area of
concern was the approach to control of pollution  in uninhabited or
sparsely  inhabited  areas.  For  example,  should  the  emission
requirements  for  a lead  smelter be  different  in  a  relatively
uninhabited area from one in a more urban area? Restating the issue,
should the emphasis on  pollution control be on environmental
contamination or on human health  effects? The group felt that both
should be considered, though health should receive more weight in
the final  decision  process.  However,  it  was emphasized   that
environmental contamination must be  considered because of its
potential wide-spread impact on the ecosystem and for what it could
possibly contribute in future human exposure.
    There was also some discussion that questioned whether the
time pressure generated by various legislative and court decisions
was counter-productive to optimal  operation of the EPA decision-
making system. It was felt that in some cases, attempts to alleviate
the time pressures, especially in the face of an inadequate data base,
could be  useful. However,  in  some instances a  deadline  has
generated a more timely Agency response, and thus EPA should not
completely disregard time pressures.
    There were  three further general recommendations from the
lead case study work group:
A.  It was felt that a major effort was required  in anticipatory
planning,  in an  attempt to avoid the recurrent "fire-fighting"
approach to environmental  problems.  It was  recognized that no
matter how effective the Agency becomes in the prediction of future
informational needs, it is very likely that it will still need an effective
mechanism to deal with unanticipated crises.

B.  A number of the participants felt that, as a corollary to the need
for a stronger anticipatory effort, the Agency should strengthen its
ties with the general scientific community by use of grants and/or
                             35

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other mechanisms to support appropriate research. It was felt that
the  workshop  format,  with input  both  from the  regulatory
governmental community and the academic and general scientific
community, could   also  be  a   useful  tool  in improving  the
communications between the scientific community and EPA.

C.  In the final recommendation of the work group, it was noted that
the air-borne lead standard was based explicitly on  a decision to
protect 99.5% of the population. The group felt strongly that this was
a welcome, though  unusual, departure from previous regulatory
decision processes. It was recommended that for all future exposure
assessments, data should be provided to permit proposed standards
or revisions of existing standards to provide an explicit statement of
the fraction of the  population to be  protected by the proposed
standard. The fraction to be protected, a non-technical decision, will
vary as a function of several factors, including the severity of the
effect, the size of the population at risk, extent of exposure, and the
type of control  available. It was also noted that one could make
additional statements about the percent of the population protected
by the lead standard. Setting the lead standard at level X results in
protecting 99.5% of the  population from  adverse effect A, while
protecting 99.9% against adverse effect B, and perhaps 100% against
adverse effect C.
                                             : 1980 — 757-073/0506
                             36

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