Undid »*f«      0«lc,« 
-------
              UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D,C,  204SO


                            September 30, 1987

                                                                    OFFICE OF
                                                                TME AOMIN(§
The Honorable Lee M. Thomas
Administrator
U.S. Environmental Protection Agency
401 M Street, S.W.
Washington, DC  20460

Dear Mr. Thomas:

     The Clean Air  Scientific Advisory  Committee  (CASAC)  has completed
its assessment of research  needed to  support the development  of National
Ambient Air  Quality  Standards  (NAAQS)   for  Ozone  and  for  Lead.   This
report, along with the  December  30, 1983 report which outlined research
needs for  carbon  monoxide,  nitrogen  oxides,  particulate  matter,  and
sulfur oxides,  is in response  to  the mandate  under the  Clean  A1r Act
Amendments of 1977 to provide you  with advice concerning research needs
for ambient pollutants.

     Within each  of  the major  research  areas identified  for ozone and
for lead, we summarize  the  need  for the research and assign  priorities.
These priorities  represent  a  continuum since  we  believe  that all  of the
research needs that we  have identified  are  of importance to  the Agency.
For ozone, we have  identified research  needs  in atmospheric chemistry,
health effects,   and  agriculture,  forests  and  related  ecosystems;  for
lead, we  have  identified  research  needs in  atmospheric processes, ex-
posure, metabolism,  and biological   and  health  effects.   We have also
provided recommendations on the design of the National Health and  Nutri-
tion Evaluation  Survey (NHANES III).  Clearly,  each  research  program must
be structured so  that  those studies  which  can determine the importance
of critical  variables  and  mechanisms   are  started  early  and pursued
vigorously.  This places  additional  responsibility  on  the Agency's re-
search staff  to  ensuri  that timely  and appropriate  research  resource
allocations are  made.    It  is  worth emphasizing  that  the  planning   of
future studies  should  be  Integrated  with  the  findings  from ongoing
research.

     The research program which the Committee recommends  for ozone  can  be
pursued and completed within the next  five  years at a cost  which,  while
relatively large  in  relation  to the  current  EPA  budget  for  criteria
pollutant research is   relatively  modest in  relation to  the  costs   of
current monitoring and  control efforts.  The  research  results are  almost
certain to provide  a much  better  scientific basis  for  the  ozone  NAAQS
promulgation in  the mid  1990s than  that available today.

-------
                                    -2-
     Tharik you for the opportunity to present our views on these important
human health and welfare issues.  We request that the Agency officially respond
to the scientific advice contained in the attached report.
                                         Sincerely,
                                         Morton Lippmarin
                                         Chairman
                                         Clean Air Scientific
                                           Advisory Committee
cc:  A. James Barnes
     Vaun Newill
     Craig Potter
     Terry Yosie

-------
                   U.S. ENVIRONMENTAL PROTECTION AGENCY


                                  NOTICE
     This report has  been written  as  a part  of the  activities  of  the
Science Advisory  Board,   a  public  advisory  group  providing  extramural
scientific information and advice  to the Administrator and other officials
of the  Environmental   Protection  Agency,   The  Board  is  structured  to
provide a  balanced  expert assessment  of  scientific  matters  related  to
problems facing the Agency.  This report has not been reviewed for approval
by the Agency,  and  hence  the  contents of this  report do  not necessarily
represent the views and policies  of the  Environmental  Protection  Agency,
nor of other agencies  in the Executive Branch  of the  Federal  government,
nor does mention of trade  names or commercial products constitute endorse-
ment of recommendation for use.

-------
                              TABLE OF CONTENTS

                                                                         Page

  I.  EXECUTIVE  SUMMARY                                                     1

 II.  INTRODUCTION                                                         3

HI.  RESEARCH NEEDED  FOR  FUTURE  DECISIONS ON NATIONAL AMBIENT              4
        AIR QUALITY  STANDARDS  FOR OZONE

        A.   Introduction                                                    4

        B.   Atmospheric Chemistry                                          4
            1.   Modeling Program                                            5
            2.   Trend  Analyses Program                                      7
            3,   Predictive A1r Quality Models for Long-Term Ozone           8
                  Concentration Averaging Tiroes

        C,   Health Effects                                                  8
            1.   Chronic Health Effects                                      §
            2.   Acute  Effects                                              10
            3.   Mechanistic  Studies                                        11

        D.   Agriculture, Forests, and Related Ecosystems                   13
            1*   Agriculture                                                13
            2.   Forests                                                    16

 IV,   RESEARCH NEEDED  FOR  FUTURE  DECISIONS ON NATIONAL AMBIENT             19
        AIR QUALITY  STANDARDS  FOR LEAD

        A,   Introduction                                                   19

        B.   Atmospheric Processes                                         20

        C.   Exposure Considerations                                        21

        D.   Lead Metabolism                                                23

        E.   Biological and Health Effects                                  24
            1.   Developmental  Effects                                      24
            2.   Cardiovascular Effects                                     25
            3.   Other  Effects                                              26

-------
                                                                  May  1987
                   U.S. Environmental  Protection Agency
                          Science  Advisory Board
                 Clean Air Scientific  Advisory Committee

                       Research  Needs  Subcommittee
Dr. Morton Lippmann, Professor,  Institute of Environmental Medicine,
     NYU Medical Center, Tuxedo, New  York  10987


Members

Dr, James 0, Crapo, Associate Professor  of Medicine, Chief, Division  of
     Allergy, Critical  Care and  Respiratory Medicine, Box 3177, Duke
     University Medical  Center,  Durham,  North Carolina  27710

Or. Robert Frank, Professor of Environmental Health Sciences, Johns Hopkins
     School of Hygiene  and Public Health, 615 N. Wolfe Street, Baltimore,
     Maryland  21205

Dr. Paul B. Hammond, Professor of Environmental Health* University of
     Cincinnati College  of Medicine,  Ketten'ng Laboratory, 3223 Eden
     Avenue, Cincinnati, Ohio 45267-0056

Dr. Jay S. Jacobson, Plant Physiologist, Boyce Thompson Institute, .
     Tower Road, Ithaca, New York  14853

Dr. Jane Q. Koenig, Research Associate Professor, Department of Environmental
     Health, SC-34, University of Washington, Seattle, Washington  98195

Dr. Timothy Larson, Environmental Engineering and Science Program,
     Department of Civil Engineering, FX-10, University of Washington,
     Seattle, Washington  98195

Dr. D, Warner North, Principal,  Decision Focus Inc., Los Altos Office
     Center, Suite 200,  4984 El  Camlno Real, Los Altos, California  94022

Dr. Gilbert S. Owtnn, Professor  and Dean, School of Public Health and
     Community Mtd1c1ne, SC-30,  University of Washington, Seattle,
     Washington  98195

Dr. Michael 8. Rabinowitz, Harvard Medical School, c/o Marine Biological
     Laboratory, Woods  Hole* Massachusetts  02543

Dr. Robert D. Rowe, Vice President, Environmental and Resource Economics,
     Energy and Resource Consultants, Inc., 207 Canyon Boulevard,
     Boulder, Colorado   80302

-------
DP. Ellen K. Sllbergeld, Senior Scientist, Environmental Defense Fund,
     1616 P. Street, N.W., Washington,  D.C.  20036

Dr, Mark J. Utell, Co-Director, Pulmonary Disease Unit, Associate Professor
     of Medicine and Toxicology in Radiation Biology  and Biophysics,
     University of Rochester Medical  Center, Box 692, Rochester, New
     York  14642

Dr. James HU Ware, Associate Professor, Harvard  School of  Public Health,
     Department of Biostatisties, 677 Huntington Avenue, Boston,
     Massachusetts  0211S

Dr. George T. Wolff, Senior Staff Research Scientist, Seneral Motors
     Research Labs, Environmental Science Department, Warren, Michigan  48090


Executive Secretary

Hr. A, Robert Flaak, U.S. Environmental Protection  Agency, Science
     Advisory Board (A-101F), Washington, D.C.  20460

-------
                                                                  September 1987
                       U.S. Environmental  Protection Agency
                              Science Advisory  Board

                     .P..1 e. Jfl. Ai r Sc 1 ent 1 f i c  Adv 1 sory  Commi ttee
Chalrman

Dr. Morton Lippmann, Professor, Institute of Environmental Medicine,
     NYU Medical Center, Tuxedo, New York  10987
Members

Dr. Robert Frank, Professor of Environmental  Health Sciences,  Johns
     Hopkins School  of Hygiene and Public Health,  615 N.  Wolfe Street,
     Baltimore, Maryland  21205
Dr. Warren B, Johnson, Manager, Research Aviation Facility,  National
     Center for Atmospheric Research, P.O.  Box 3000,  Boulder,
     Colorado  80307
Dr. Timothy Larson, Research Associate, Environmental  Engineering and
     Science Program, Department of Civil Engineering  FX-10,  University
     of Washington, Seattle, Washington  98195


Dr. Gilbert S. Oraenn, Professor and Dean, School  of Public Health and
     Community Medicine, SC-30, University of Washington, Seattle,
     Washington  98195
Dr. James H. Mare, Associate Professor, Harvard School of Public Health,
     Department of 81ostatisties, 677 Huntington Avenue, Boston,
     Massachusetts  021 IS
Or. Jerry Wesolowskl, Chief, Air and Industrial Hygiene Laboratory,
     California Department of Health, 2151 Berkeley Way, Berkeley,
     California 94704
Executive Secretary

Mr. A. Robert Flaak, U.S. Environmental Protection Agency, Science
     Advisory Board (A-101F), Washington, D.C.  20460

-------
1.  EXECUTIVE SUMMARY


     This 1s  the  second in  a  series of  reports  prepared by the  Clean Air
Scientific Advisory Committee  (CASAC) providing  recommendations  to the U.S.
Environmental Protection Agency  on  research  needed to develop  and support
National Ambient Air Quality Standards  (NAAQS).  The first report,  issued in
December 1983, provided research recommendations  on four of the six criteria
pollutants: carbon monoxide, nitrogen oxides, particulate matter, and  sulfur
oxides.  This present  report provides  research  recommendations  for the two
remaining criteria pollutants:  ozone and lead.

     The research  recommendations  for  ozone  are  presented  in  three  parts;
1) atmospheric chemistry; 2) health  effects; and 3) agriculture, forests and
related ecosystems.  Each part  is  critical  to setting  an ozone NAAQS,  The
litter two areas are critical in establishing  exposure-response  relationships
for the  effects  that  ambient   ozone produces.   However,  without  a   better
understanding of exposure profiles, scientists ind regulators  cannot  accurate-
ly establish the extent  of  the effects  of  ambient ozone  exposure  on  public
health and welfare.   Furthermore,  without  a  better understanding  of  atmos-
pheric chemistry,  we  cannot  predict  either the  frequency   of   excessive
exposures or the influence of the various sources  of the  ozone  precursors on
the ambient concentrations.

     The Committee has the  following high priority research  recommendations
for ozone:

     Atmospheric Chemistry

     *  The Committee proposes two  research programs which will  help  develop
        urban-scale and regional-scale models  that  can  be  used for  regulatory
        purposes, and which will  determine existing and future ozone trends to
        assess the impact of precursor emissions.

     Health Effects

     t  Research which emphasizes  the identification of ozone health  effects
        related to chronic low-level exposures,

     •  Population studies linking  long-term ozone exposure  with development
        of chronic respiratory  system damage.

     t  Quantitative animal-to-human extrapolation.

     •  Interactions of ozone with  other air pollutants.

     i  Influence of ozone on host defenses  against infections and
        neoplastic diseases,

     t  Role of inflammation in response to ozone.

-------
     Agrl culture,^Forests, and Rel ated_EcosjfSteins

     •  Additional  exposure statistics  research.

     •  General  physiological/biological  process  models  for  crops  and
        trees.

     •  Comparisons of ozone flux 1n chambers  to crop canopies.

     *  Ozone  dosi-response   of  major  tree  species  and  overall  forest
        productivity analyses.

     The research  recommendations  for  lead  are presented 1n four parts:
1) atmospheric processes;  2)  exposure considerations; 3}  lead metabolism;
and 4} biological and  health effects.  In addition,  the Committee has pro-
vided recommendations on  the  design of  the forthcoming National Health
and Nutrition Evaluation Survey (NHANES III).

     Atmospheric Processes

     t  Reassessment of the relative Impact  of point sources  and gasoline
        on ambient  air lead.

     *  Assessment  of the  impact  of air lead  on  lead  in other media to
        which man 1s exposed  (i.e., food and water)i

     *  Assessment  of factors which determine the transfer of lead from
        dump sites  to air  and water.

     Exposure Considerations

     *  Importance  of soil and dust ingestion in  children as  sources of
        lead.

     »  Bioavailability of lead as a function of particle size and  chemical
        form.

     •  Contribution of foods  to total  lead  intake.  Including  processing
        and packaging.

     »  Contribution of drinking water  to  total  lead intake,  including
      •  water used  1n food and beverage preparation.

     Lead Metabolism

     »  Development of better indices of lead exposure,

     •  Blokinetic  modeling with special  emphasis on the fetus and placen-
        ta, as well as  bone  1n  both pregnant women and in  the  elderly.

     »  Dietary factors influencing lead absorption.


                                   -2-

-------
     Biological Bind Health Effects

     •  Continued, uninterrupted support for  current prospective studies
        of neurobehivioral effects of lead In  children to  school age and
        beyond.

     In connection with  the  forthcoming NHANES III study, the  Committee
urges EPA  to  consider questionnaire items  to aid  in  establishing if a
subject's blood lead concentration is representative of  long-term duration
of exposure or if it reflects a recent significant incident, and secondly,
to use  the  best  possible   methodology  for  blood lead  determinations.

II.  INTRODUCTION

     A major responsibility of the Clean Air Scientific Advisory Committee
(CASAC), as established 1n the Clean A1r Amendments of 1977, 1s  to provide
scientific advice on additional  knowledge that is required for  evaluating
existing, or setting new or revised National Ambient A1r Quality Standards
(NAAQS).  On December 30, 1983,  the CASAC issued the first of an eventual
series of  reviews  intended  to evaluate the  state of research  knowledge
and needs for criteria air  pollutants.   This first  report assessed  five
generic research needs for such  pollutants that Included:   1) development
of a program in  air pollution epidemiology;  2) development  of  a program
in extrapolation modeling; 3) research  relating  concentrations at moni-
toring sites to human  exposures; 4).  research  relating  exposures to dose;
and 5) responses to multiple pollutant  exposures.  In addition, the CASAC
identified research  directions  and  needs  for  four specific  pollutants
for which  it had reviewed air  quality  criteria  documents:  carbon  mon-
oxide, nitrogen oxides, particulate matter, and sulfur oxides.

     The Committee met on May 21-22, 1987 and July 15, 1987 to discuss and
identify research directions  and  needs  for ozone and for  lead.  In  this
present report,  the  CASAC has reviewed the  research  recommendations  for
ambient ozone and lead prepared by EPA  staff, members  of tht public, and
its own members  and  consultants, and  has  prepared  a  set  of  research
recommendations  for  each  pollutant  with  a statement  of  priorities  for
the next five years.   The priorities are based upon the  need  to  address
scientific issues hiving the greatest potential impact on setting  a NAAQS
to protect the public health and welfare*

     Research recommendations are Identified  as  first,  second, and third
priorities.  It should  be noted that the Committee believes that  all the
recommendations  presented are of  great  concern to the Agency.   The three
priorities should be viewed as a continuum.  While the recommendations and
priorities are those  of  CASAC, we  gratefully acknowledge the excellent
preliminary work  by EPA  staff, and  contributions  from  members   of  the
public*
                                   -3-

-------
 III.  RE$EARGtij,MEEDED FOR FUTURE DECISIONS ON  NATIONAL AMBIENT AIR
       ~PAlTfy STANDAROS FOR OZONE  ~           ~~       ~™

     A,
     While research performed since the last ozone NAAQS promulgation in
 1979 has  greatly  increased  our  knowledge  of ozone formation and persis-
 tence in the troposphere, its effects on public welfare, and its effects
 on human health,  major knowledge gaps and  areas  of uncertainty remain,
 These gaps and  uncertainties limit the ability  of the Administrator to
 identify the effects  which  result from various  combinations  of concen-
 tration, exposure time,  and ventilation rate,  and the degree  to  which
 some pollutant  associated  effects are  attributable  to ozone  alone, or
 to ozone  1n  combination  with  other  airborne pollutants.   Thus,  while
 much is  known   about   ozone  exposures  and  their  effects,  our current
 knowledge of effects  remains incomplete,  possibly  leading to a promul-
 gation of a standard which fails to protect  against some adverse effects.
 On the other hand* the use of an  overly conservative margin of  safety to
 compensate for our incomplete understanding of the effects could lead to
 the promulgation of a  standard which imposes  very large burdens in society,
 in terms of  unnecessary  costs  of  control and/or  restrictions on normal
 activities.

     CASAC has  approached the  identification  of  research  needs  in  a
 comprehensive manner,  and it does  not  expect  all  of the needed research
 to be performed or funded by EPA.  The Committee  recognizes that some of
 the ozone research needs  are  being addressed by other sponsors of research
 in the public and private sectors, e.g. National  Oceanic and  Atmospheric
 Administration (NOAA)   in  atmospheric  chemistry,  U.S.  Department  of the
 Interior (USDOI)  and  U.S. Department of Agriculture (USDQA)  in welfare
 effects, and the  Health  Effects  Institute  (HEI)  in health  related  re-
 search.  While CASAC  understands  the  importance of these  other research
 programs, it clearly  sees EPA playing  a lead role, and having  the major
 responsibility for ensuring that  all  of the important scientific issues
 relevant to standard setting are addressed.

     i.  Atmospheric Chemistry

     Because most of  the major metropolitan  areas in the United States
 still fail  to  meet the  current  National  Ambient  Air Quality Standard
 (NAAQS) for ozone, additional  controls on emissions of volatile  organic
 compounds (VOC) and,  perhaps,  nitrogen  oxides  (NOX) may be  required,
All of  the  sources that were  relatively   easy  to  control  are  already
subject to some degree of control.  Thus,  any additional  controls  will
certainly be more expensive than previous  ones,  and they  will  have  a
significant economic  impact  on  society.   For these reasons,  it 1s  vital
to know  with  reasonable  certainty the impact  that additional controls
will have on  ozone air  quality.   At  present, scientists  and  regulators
do not have that  information because existing models have  not  been  vali-
                                   -4-

-------
dated.  It 1& also  Important to analyze emissions and air quality trends
so to document the  Improvements 1n  air  quality  resulting from emissions
controls.  At present,  the documentation is inadequate.

     In order to validate the models and document the trends,  there is a
need to develop an  integrated, targeted research  agenda  for  ozone.  Two
ultimate goals   of  these programs  should  include:    1)  developing  an
urban-scale and a regional-scale model which  can  be  used for regulatory
and planning purposes,  and  2} determining  existing  and  future  ozone
trends to  assess  the  impact  of  perturbations  in precursor  emissions.
The CASAC  proposes  two  research  programs to  achieve these  goals,  the
elements of which  are described  below.  In  addition, a third program
relating to a longer-term NAAQS for  ozone  is presented.

     1.  Modeling Program

         a) Conduct  sensitivity analyses usin^existing models to Identi-
            fy  and Improve critical  model  elements^-Existing models have
            not  been validated, and they  can  be  improved.   They can and
            should,  however,  be  used to  identify the types  of ambient
            measurements  needed for validation purposes and to determine
            which assumptions   lead  to the  largest  uncertainties.  The
            models should be exercised  to determine  the  sensitivity of
            the  results to chemical  mechanisms,  boundary conditions, VOC
            speciatlon, VOC  reactivity,  aromatic  chemistry,  number of
            monitoring  sites  and  locations,  VOC/NOX  ratio,  upwind  and
            aloft concentrations  of  03,  VOC,  NOX and  carfconyls,  grid
            size,  meteorological  parameters  and   other  variables.  ..Once
            the  critical   elements   have   been  Identified,  programs  to
            reduce the  uncertainty of the  model results due to uncertain-
            ties in  the  critical  elements  should  be  initiated.   Such
            programs will undoubtedly include case (field studies),  labor-
            atory, and  smog-chamber studies.   In addition,  there  are
            several  aspects  of  the models  that are deficient and require
            further  investigation.   These  include night time and hetero-
            geneous  chemistry,  reactions  involving and/or  resulting in
            the  production  of   aerosols,  H2Q2»  HCOOH,  PAN,  and  HN03,
            reactions Involving natural  hydrocarbons, cloud venting,  de-
            position velocities as  a function  of time  of day and surface,
            nocturnal jets,  Inability for  the combined use of primitive-
            equation model  and  observations.   Methods  development   for
            \\$2 should be a high priority because #2®2 data, would  help
            test various   chemical   mechanisms  used   in  modeling.   The
            models should be used  to identify  additional  high priority
            species.
                                   -5-

-------
b) Bevel op ambient data bases for model  testIng  and model vali-
   dation -  The first Issue that needs "to" be addressed is the
   suitability of existing data  bases  generated from previous
   case studies.   If there  are  any adequate data  bases that
   exist, then testing should  begin.  Perhaps data bases gen'
   erated from PEPE/NERQS  or other  studies are adequate.  The
   regional-scale model,  which  Incorporates  long-range trans-
   port, should be  applied 1n the  Northeast  while the urban-
   scale model  should  be  applied in Los  Angeles and another
   city 1n the Northeast,  The Southern California A1r Quality
   Study (SCAQS), conducted  this summer  (1987),  was designed
   to generate a data base  that can be used to test and validate
   models for ozone  and  particulate  matter (PM-10).  This data
   base is expected  to be  ready  for use by 1990.  Since there
   is such a  long lead time  required to plan  and then validate
   the data  from  such studies,  planning  for additional  field
   studies should begin as  soon as possible.

c) Improve emission Inventories  -  Present  evidence  suggests
   that the  error  levelIF the  best   available  estimates   of
   existing VOC and  NOX  source  strengths is  nearly  an order
   of magnitude  larger  than  the magnitude  of  emissions   re-
   ductions contemplated   in  current  control   strategies   for
   03,  Consequently, this  is a critical  element  that needs
   improvement.  Improved  regional and  urban-scale  inventories
   for NOX  and  speciated   VOC  are  needed  for  the modeling
   and trend  analyses,  and  an  improved nation-wide inventory
   1s need  for  the  trend   analysis.   The  overall  emissions
   inventory should be examined first and uncertainties assigned
   to each  category.  Subsequent  decisions  can  be  made  and
   priorities established  based  on  which  sources can achieve
   the greatest reduction  in the  overall  VOC  and  NO* emissions
   uncertainty.  Some sources deserving priority  attention  in-
   clude present  in-use,  on-road and  off-road  vehicles   and
   equipment; diurnal, hot-soak  and  refueling  emissions; small
   stationary sources; restaurants;  end marine-related  opera-
   tions.  Also, an accurate inventory  of natural  VOC emissions
   1s needed because  current  estimates  of the  flux  of  natural
   VOC in the northeastern United States  are at the  same level
   as those from anthropogenic sources,

d) Run the validated models to determine optimum control  strat-
   egies - The models should  be exercised for a variety of urban
   areas to determine not  only the degree of  control  required
   for attainment, but also  the  effect  of  nitrogen  dioxide  re-
   ductions on  ozone concentrations.   Depending  on the  local
   VOC/NOX ratio, reducing  NQX could either increase or decrease
   ozone.

-------
     2-  Trend Analyses Program

     Even 1f Models adequately represented real world phenomena, trend anal-
yses are needed because they are the truer measure of  progress.  In addition,
1t Is vital  to know how much of the ozone problem is due to man's activities
and how much Is due  to nature.

          a) Establish and  maintain ambient data bases- EPA needs to Insure
             that the stations established for trend analysis ire sited pro-
             perly,  and not relocated or terminated.

               *  Metropolitan   ozone  sites  - The  existing  networks  are
                  probably  sufficient.

               *  Rural  ozone  sites  - A  network  of  rural  monitors needs
                  to  be established  in  both agricultural and remote areas.
                  The remote sites  should  be  1n  areas  away  from local
                  sources so trends  1n the  "background" ozone  can  be  es-
                  tablished.

               •  VOC and  N0?  sites -  Networks of  VOC and  NOX monitors
                  1n  metropolitan  areas  are  needed.   Many of the  VOC  and
                  NOX monitors  need  to be co-located so  that the VQC/NOX
                  ratio, which  1s a critical  input  for any model,  can be
                  determined accurately.   It  is also Important  that  the
                  ratio be   representative  of the  area  as  a  whole.   In
                  addition, periodic measurements of individual  VOC species
                  at  these  sites are needed to determine the trends in VOC
                  composition,

          b) Trend analyses  -*The  following trends  should  be examined:

               t  Trends  in the ambient concentrations  of ozone, nitrogen
                  dioxide,  and   volatile  organic  compounds  by  geographic
                  area,

               •   Trends  in the emissions  of  volatile  organic  compounds and
                  nitrogen  dioxide,

               •   Trends  In  ozone  adjusted  to  eliminate  the  influence
                  of  meteorological  variations.

          c) Background Ozone -   Because EPA  1s considering a  long-term
             ozone standard  that  is  approaching the  natural   background
             range of  of   30  -  50  ppbt  it  Is extremely  important  that
             this range be   documented  spatially and  temporally, and  that
             the  sources of the background be quantified.   For this  effort,
             the  following  action  should  be taken:
                                    -7-

-------
               *  A  network  should  be  established to  monitor the  long-term
                  trend in background  ozone.  The siting of these monitors
                  is critical.  It  is  important that  they be upwind of the
                  synoptic-scale region of  interest  to assess whether the
                  regional ozone levels  are elevated  with  respect  to the
                  upwind values,

               •  The  relative  magnitude of  ozone  from stratospheric in-
                  trusions and 1n-situ photochemical  processes in the free
                  troposphere needs to be determined.  This  will  involve
                  the monitoring of ozone and several stratospheric tracers,
                  such as  'beryllium  and  ^strontium  simultaneously,   at
                  different altitudes  in the  stratosphere  and 1n the free
                  troposphere, as  well as  on the  surface.   By  examining
                  the ratios  of  the tracers  to  each  other  and  to ozone,
                  and accounting  for  their  natural  decay  and  deposition
                  processes, better  estimates  of these contributions can
                  be made.

               •  The  importance  of natural  hydrocarbons  needs  to be de-
                  termined.  This will Involve improved emission  estimates
                  for not only the natural  hydrocarbons but fop the  anthro-
                  pogenic ones as well.  In addition,  laboratory experiments
                  to obtain  kinetic  and  mechanistic  data for  the  major
                  natural hydrocarbons are  needed.   These data  would  be
                  used to develop improved reaction mechanisms which  would
                  be incorporated  into photochemical  models.   The models
                  would then  be  tested  using  appropriate  smog  chamber
                  data.  In addition*  accurate ambient air measurements  of
                  all the hydrocarbons,  natural  as  well as  anthropogenic,
                  will be required,

     3.  Predictive Air Quality Models forlong-Term Ozone  Concentration
         'Ave~rag1ng_ Times/                              —-—

     All the  modeling efforts described  above are  designed  to  predict a
one day, daytime  hourly  ozone profile, which could be used to generate  an
8-hr or  7-*hr  mean 1f  such  a standard is implemented.  However, there  is
also some thought being  given to longer standards  such as a  3-month mean
of the daily  7-hr maximum values.   At present, no  models  exist  to  address
such a standard.   When and if  such a standard is implemented, models will  be
needed.  Therefore, work should begin  on the development of such  a model  if
it appears that such a standard is likely.

     C.  Health Effects

     The effects of ozone on human health have received intensive scientific
scrutiny.  Recent evidence has shown that inhalation of ozone at concentra-
tions near ambient levels  produces  acute reversible  changes  in  lung  func-
                                    -8-

-------
tion.  Yet stprtfleant gaps remain in the health effects data  base for ozone:
effects of lowMevel chronic exposure, relationships between acute and chronic
effects, exposure-response  relationships,  and  mechanisms  of  ozone-induced
injury identify  broad  areas that are incompletely understood.  The research
program developed  by the  EPA  his identified many  of these  major  gaps and
proposed realistic  strategies  for  narrowing  the  remaining   uncertainties.
Given the wide array of  research needs,  and  the limited  resources available,
the program has  appropriately  integrated  controlled human clinical studies,
animal toxicology, and/or epidemiology into its  research  planning.

     The CASAC  endorses  the  EPA  efforts  to advance  ozone health research
using a  broad-based program including  both  human and animal  studies.  Al-
though the  CASAC Is  cognizant  of the  multiple  approaches  for subdividing
the broad  research  categories,  it  chose  to organize the long-range  goals
of the ozone  research  program  into  three  general  areas;   a)  chronic  health
effects, b) acute health effects, and c) mechanistic studies.

     1.  Chronic HealtJLjffects

         a)  Objective

     The objective  of  this research is  to achieve an Improved understanding
of effects  of chronic,  low-level  ozone exposure  on the  respiratory  tract.
At present, knowledge  of  acute  effects  following short-term  ozone exposure
is considerably  greater  than that following  long-term, low-level  Inhalation.
Several Investigative approaches are identified:

     *  Chronic low-level  animal  exposures with endpoints including biochem-
        ical alterations,  structural changes, alterations in  pulmonary  func-
        tion, or  other  early  Indicators  of  ozone-induced  lung  disease.

     •  Population  studies designed to  determine whether long-term exposure
        is linked to development of chronic respiratory disease,

     •  Measurements of  ozone  dose and  toxic  effect in target tissues  of
        several species  to enhance the  possibility  of animal-to-man  extra-
        polatlon.

         b)  Research Needs

     The EPA  should give   very  high priority  to  those  components  of  Its
research program targeted   at  identifying ozone health  effects related  to
chronic low-level exposures,   ienerally thest  efforts should take advantage
of the findings  from  recently  completely  chronic  exposure  studies  before
developing new protocols.
                                     -9-

-------
         F1 rst Priority jesearch Needs

      t  Effects  of  chronic ozone exposure*   A major limitation of the
         ozone data-base relates to the 11 suited understanding of chronic
         effects resulting  from  low-level  exposure.   The CASA6  strongly
         supports studies Involving long-term  exposure  of animals which
         are designed to elucidate the structural/functional  Implications
         of chronic diseases as  determined by  lung function, morphology,
         and biochemistry.  Although efforts to develop  early indicators
         of ozone-Induced chronic lung disease  are appropriate,  it  is not
         clear whether  useful  blomarkers  would be developed  for use In
         clinical epidemic!ogic  studies  of low-dose oxidant Inhalation.

      t  The carefully designed  epidem1olog1c  study  remains the  ultimate
         mechanism for  linking long-term  ozone  exposure  with development
         of chronic  respiratory  system damage In  humans.   Despite the
         enthusiasm for such  studies, the CASAC  acknowledges their com-
         plexities.  For example, the  difficulties  related  to poor docu-
         mentation of exposures,  the   variety  of confounding variables,
         and uncertain  endpolnts have severely curtailed  Interpretation
         of such studies to  date. Although the CASAC finds the possibili-
         ty of using results from autopsies of  accident victims  interest-
         Ing and Imaginative, the problems of obtaining good tissue rapid-
         ly from autopsies,  and  difficulties 1n  obtaining accurate expo-
         sure histories, somewhat dampened enthusiasm for this  approach.
         Despite these  reservations,   the Committee encourages  EPA to
         support and encourage studies of  human populations 1n relation to
         chronic lung diseases associated with  ozone exposure.

      *  Quantitative Animal-to-Man Extrapolation,  This  is  an  important
         research area that  presents the opportunity to develop dosimetric
         models which allow adequate estimates  of dose to specific target
         lung tissues across a variety of  animal species.   Emphasis should
         be placed on  distinct  species-specific  as  compared to across-
         sped es phenomena.   Such an  approach  should enhance application
         of the toxicologictl data-base to risk assessment.

     2.  Acut_e_ Effects

         a)  Objective

     The objective of  this  research   area is  to better  understand  the
acute effects  of  ozone  related to Intermittent or  prolonged daily expo-
sures; in addition, it  focuses  on the potential  connection between acyte
cellular damap  to  the respiratory tract and subsequent development  of
chronic disease.
                                   -10-

-------
      b)  Research Needs

      EPA should  continue to assign  priority  to the controlled  clinical
 studies using  the  environmental  chamber  facility at  Chapel  Hill.  The
 controlled clinical  studies have  been  remarkably productive  over the
 past  five  years in  enhancing   scientific  understanding  of  acute  ozone
 effects on healthy populations

         First Priority Research Needs

      •  Health effects of prolonged daily exposures.   The CASAC strongly
         endorses the  concept  of prolonged daily  studies, with  emphasis
         on the  influence  of   concentration  and  duration  of  exposure.
         Such studies  should prove  instrumental   in  helping  EPA  decide
         whether a separate  standard using a longer averaging  time (for
         example, eight hours)  is warranted for ozone,

      •  Determination of  factors  influencing the  magnitude of  the ozone
         response.  One  of the  most  interesting  findings  of the clinical
         ozone exposure  study  is the existence of wide variation  in the
         magnitude of  response  in  a  healthy population.  The CASAC sup-
         ports further efforts  to characterize the  variability of response
         and to  identify  factors ranging  from  genes  to  cells  that may
         influence this variability.

      •  Relationship between effects of acute and  chronic ozone exposure.
         The Committee supports  efforts to  obtain  a  better understanding
         of the  potential  interaction between  cellular and  molecular
         events surrounding  damge  to the  respiratory  tissue from acute
         oxidant exposure  and  development  of chronic  pulmonary disease.
         The Committee  recognizes the difficulty of undertaking  such
         studies in  the  absence  of  valid  markers  of early  Injury  or
         disease.  However, it  encourages  in vivo studies  at the biochemi-
         cal  and molecular level aimed atlJiterminlng whether acute ozone
         exposed humans respond  by producing  factors  capable  of inducing
         inflammation, fibrosis, etc.

     3.  Mfchjnist1c^Studj_es

         a) Objective

     The objective of such  studies is to  further elucidate  mechanisms
reponsible for tither acute or  chronic  ozone injury.  This goal  Is broadly
stated and applies to research  recommendations that overlap between  acute
and chronic categories.   EPA should continue to give  very  high priority
to mechanistic research  with  ozone  ranging from  clinical  physiological
studies to the rapidly advancing arena of molecular biology.
                                   -11-

-------
b)  Research Needs

    First Priority  Research Needs

 •  Interactions  of  ozone with other  air  pollutants.   There  1s  a
    need to investigate the  potential  for  ozone to interact  with
    other co-existing pollutants  either in the  air  or  in  their
    effects after  being  taken up  in  the  lungs.  The  real  world
    ratios of  pollutants  are likely  to  be  an  influencing  factor
    in provoking  a  potentiation of airway response.  The few studies
    conducted  fh  this area have  not  been highly rewarding, and this
    emphasizes the  need for studying exposure-response curves rather
    than effects  of single pollutant concentrations.

 t  Influence  of  ozone  on  host  defenses   against  Infectious  and
    neoplastic diseases.   Effects  of ozone  on  viral  infections are
    not well understood and  studies of  host-defense  mechansims in
    both animals  and humans  are  needed.  There  is  also  a  need to
    better understand alterations in  the  immune system  following
    both acute and  chronic ozone  exposure.   In contrast,  the CASAC
    has expressed less enthusiasm for studies designed  to  examine
    host defenses against  "neoplastic disease".   If the relationship
    between ozone exposure and neoplasia should  be strengthened, then
    such studies  would warrant a much higher priority.

 •  Role of inflammation in response  to  ozone.   Inflammatory process-
    es have been  linked both to development of chronic lung disease
    as well as the  acute development of airway  hyperreactivity.  The
    use of  new clinical   tools  such as  broncho-alveolar  lavage in
    efforts to evaluate  acute responses  to ozone  is  a  promising
    research opportunity,-   Inflammatory events  may serve as a poten-
    tial link  bttwten acute and chronic health effects resulting from
    ozone exposure.  However* the  Committee emphasizes the need for
    animal  models  to  validate lavage  flndlnp  and  predictions of
    long-term  effects.

    Second Priority Research  Needs

 t  Ozone  molecular  mechanisms  of  action.  The Committee encour-
    ages studies  aimed at elucidating the  molecular  mechanisms of
    ozone tffects.    However,  it  notes  that while  specific probes
    for studying  molecular  mechanisms are  rapidly  evolving,  their
    current applications  have yet  to be demonstrated.

 *  Methodology  development.  There  is  a  need  for  further method
    development,  including physiological  techniques to asstss  small
    airway function,  monitoring  of individual exposures, and statis-
    tical  design  and  analysis.  However,  in some  circumstances, such
    development would best be  undertaken by other agencies with  even-
    tual application  in EPA laboratories.

-------
      *  Influence  of  ozone  exposure on  inhaled  particle  dosi«etry.
         Alttl'ltlons of  dosiraetry  Induced  by  ozone  Inhalation  should
         prove-useful in the extrapolation modeling process.

      *  Studies on the attenuation of ozone effects.   Further evaluation
         of the biochemical. Inflammatory,  and morphologic changes  asso-
         ciated with  the well  recognized  phenomena  of  adaptation has
         merit.  The  influence  of pharmocologic  agents on the  phenomena
         of ozone adaption warrants investigation.

      •  Responses  of  human bronchial  and alveolar epithelium to ozone*
         Permeability of the pulmonary epithelial   barrier  is  increased
         after ozone exposure.   Further studies of changes  In permeability
         from the  nose  to  the  alveolar  level  are encouraged  in   both
         laboratory animals and humans.

         ThirdPriority Research Needs

      •  Identification of groups  potentially at risk from ozone  exposure.
         This 1$  of obvious Importance  in  protecting populations  from
         ozone exposure but can best  be  investigated by  studying  factors
         influencing the magnitude of response.

      •  Genotoxic, carcinogenic,  and  co-carcinogenic  effects  of ozone.
         Although the influence of  pollutant exposure  on  the  development
         of cancer is of concern, it is not currently an area that warrants
         a higher priority because of the  present lack of data on associa-
         tions between ozone and cancer.

      •  Extrapulmonary  effects.   The Committee   is  not  convinced that
         ozone studies targeted to  effects beyond the  respiratory  tract
         should represent a major focus of the  research program,

     0.  Agriculture, Forests,  and Related Ecosystems

     1.  Agriculture

         a)  Objectives

     The objective of research on the effects of ozone on agriculture is to
improve the tff1c1ent evaluation  of alternative secondary ozone  ambient
air quality standards.  Broadly speaking, this  requires:

      •  Accurate Information  as  to the  form  of  the standard  that will
         best characterize  the  relationship between  ozone and relevant
         measures of  damage to  crops  and  other  important  vegetation.
                                   -13-

-------
      *  Accurate  and  comprehensive  information  as  to  the   physical,
         ecotMjMftc and social  Importance  of ozone impacts on vegetation.
         What crops are affected; how  much physical  damage occurs; what
         1s the  economic  and  soda!  Importance  of  this  damage  and to
         whom, where, and when;  and what is to be considered  "adverse"?

      •  Provide  generalizable  understanding and  modeling  of the  ozone-
         crop-welfare impacts' relationships that will provide  the  basis
         for updating the  evaluation  of  the  standard  and stimulating
         methods to prevent and mitigate damage.

      *  Providing information in the most cost effective manner.

     b)  Research Needs

     The National  Crop  Loss Assessment   Network  (NCLAN)   has  been an
intensive, coordinated  research  effort   sponsored   by   EPA  and  is  now
nearing completion.  This  program has  developed a wealth  of data.   EPA
should give first  priority  to  a  complete evaluation of the results of
this research  and  related  efforts  supported  by   U.S.  Department  of
Agriculture (USDA).  The new  information  obtained and the  remaining gaps
in knowledge  should  be  Identified.   Given the  knowledge  provided by
NCLAN, EPA should  identify the  additional  information needed to evaluate
the current  standard  and  support   recommendations   for  modifications,
where appropriate.

         First Priority  Research Needs

      •  Additional Exposure  Statistics Work.  In order  to  set efficient
         but not overly complicated  standards, two lines of research ire
         needed;

         (1) Examine alternative characterizations of exposure  to ambient
         ozone and their effects upon crop yield.  NCLAN focused  upon 7-
         hour ind 12-hour average exposures, but  peak concentrations may
         be of more  concern.  Additional  investigations should consider
         exposure characteristics in terms of duration, frequency, peak
         concentration,  and maturity of plants.

         (2) Explore the relationship between patterns of  ozone exposure
         and climate In different geographic regions and the response of
         vegetation.  Different dose characteristics may  best  represent
         the  scientific  relationship  between  ambient  ozone  and  crop
         yield for different  regions, but  they may be overly complex for
         standard setting.   Therefore,  generalized  ozone  dose-response
         relationships satisfactory for  a range of  environmental  condi-
         tions should be developed  for the most  susceptible crop plants.
                                   -14-

-------
   As r natural   consequence  of  addressing  alternative  exposure
   measures 1n the dose-response relationship, the functional form
   of th«  relationship  must be simultaneously addressed* although
   emphasis on this 1s In the second priority of  research pursuits.
   This 1s because once  general functional  forms for the dose-res-
   ponse relationship are determined, refinements tend  to have only
   a small impact on the physical  and economic assessments.

t  General physiological/biological process models.  Seneral process
   models are required concerning susceptibility  and resistance  to
   ozone.  This provides  explanations  for dose-response relation-
   ships found and a  basis for development of  genetic  lines  of
   plants that  can  maintain  satisfactory  yield  and  quality  at
   ambient levels of ozone, as  it  may be well Into the  next century
   before ambient  levels  decrease.   This will  reduce  the need  to
   repeat exposure studies for  each  new variety of crop.

§  Accurate  exposure  data.   Accurate  monitoring  Information  1s
   needed on the  concentrations  of  ozone and their variation  with
   time 1n agricultural regions.   Very limited ozone data is  avail-
   able for major agricultural regions.   Often  this  data  is the
   estimated growing  season average  based  upon  distant monitors.
   Improved data   bases  of  multiple characteristics  of exposure
   conditions throughout the growing season are  needed to improve
   the application  of dose  response  functions  to better estimate
   yield losses  and  their  resultant economic  Impacts on  a  more
   site specific  basis.

t  Flux comparisons.  Compare flux of ozone to crop canopies  in the
   field and 1n  chambers  used  in  the NCLAN  program.   The specific
   objective would  be to  determine  whether fluxes  in  chambers,
   given the patterns and rates of air movements there* are similar
   or different than fluxes  of ozone In the field, given the patterns
   and rates of air movements  found  in the  regions where  crops are
   grown.  This effort would have to  be undertaken for three seasons
   to encompass different climatic conditions and should be  perform-
   ed for those crops previously studied by NCLAN.

   Second Priority Research Needs

•  Additional  dose-response studies  on  selected key  high-valued
   crops 1n selected  regions.  The  NCLAN  program analyses  are most
   applicable to  major crops and growing conditions in the mid west
   and selected other locations.  Additional dose-response analyses
   for the same crops  in other regions and  for  key  regional  crops
   are needed  to  broaden  the  basis  for  evaluating  the  current
   secondary standard.
                             -15-

-------
      *  Analysis of mitigation  effectiveness,  costs  and  Implementation.
         chemical protectants and mitigation behavior, In terms of develo-
         ping and  producing   resistant  crop  varieties,  may  potentially
         reduce ozone induced crop yield losses  at  low  cost.   Additional
         studies on  the  costs  and  effectiveness  of these  actions are
         merited to reduce the burden of ozone impacts and ozone control,

      •  Improved economic assessment.  The NCLAN program, and other work
         at EPA's Office  of  Air  Quality  Planning and  Standards  (QAQPS)
         and the  California  Air  Resources  Board  (CARI),  have   signif-
         icantly Increased  the  reliability  of  national  and regional
         economic assessments.  However, the  models  are  still sensitive
         to many key Inputs and assumptions which can be readily address-
         ed.  Model refinements important to pursue Include:

              -  Adding more crops, especially regional  crops,.
              -  Sensitivity  of   results  to  omitted  crops  assumptions.
              -  Rerunning dose-response and economic model with improved
                 rural  ozone data.
              -  Additional  model  development  to deal   with  government
                 subsidy issues,  international  trade, sensitivity  analy-
                 sis on economic  inputs and assumptions  on demand  elasti-
                 cities, substitution activities* etc.
              -  Expansion of the issue of what  is an  "adverse"  impact.

      t  Urban ornamentals.  Urban ornamentals are exposed to significant
         ozone levels  and may  be associated with  significant  welfare
         loss.  Initial  assessments  of  damage magnitudes are  warranted
         for grasses,  bushes, and trees.   If  damages  are  potentially
         large, then  longer-term research should be planned.
                             *

         Thjrd Priority Research  Needs

      •  Genetic  control  of  pollutant  susceptibility.   NCLAN and  other
         research efforts have generally addressed ozone Impacts with the
         most intensively-used cultivars of  key crops.   Breeding  for Im-
         proved yield and harvesting characteristics continually produces
         new cultlvars with unknown pollutant susceptibility.  Better un-
         derstanding of how susceptibility to  injury  and  yield reduction
         by exposure to ozone is  inherited would enable the inclusion of
         pollutant susceptibility in  the list  of  desirable characteristics
         used In breeding new crop cultlvars,

     2.  Forests
         a)  Objectives

     Currently, there is a substantial research program supported by EPA,
the U.S.  Forest Service  (USFS), the  Electric Power  Research Institute
(EPRI), and the  National  Council on  Air and  Stream Improvement (NCASI)
                                   -16-

-------
concerning tree  response  to acid rain  ind  related pollutants Including
ozone.  This program 1s coordinated  under the National Add Precipitation
Assessment Program  (NAPAP), which  is  required  to  provide   an  overall
assessment by the year 1990.

     Current short-term research efforts  of NAPAP will provide  a basis
for a first-order evaluation of  tree  response  to pollutants.  Given the
perennial nature  and  longevity  of  trees,  their  close  association  with
climatic factors, and  the  likelihood  that emissions  of  precursors  of
ozone and add  rain will continue  into the next  century,  we recommend
that EPA focus upon developing a long-term program  of research on forest
response to pollutants, including ozone.

     The aim of the EPA long-term program  should  be to extend  the  initial
efforts of  NAPAP and  provide  a more thorough and extensive evaluation
than can be  obtained from a short-term research  program.  The EPA research
plan should provide for interim changes in  emphasis  because the assessment
to be completed  in 1990  will  undoubtedly  provide important guidelines
for future research.  The plan should  provide  for a coordinated  program
of research  on  effects  of ozone and other long-range transported pollu-
tants on forests to Insure continuity  of effort over  a period  of at  least
ten years.

     b)   Research Needs

     The needs  specifically Identified  in this  section  are long-term
research directives.

         First Priority Research Needs

      •   Exposure statistics*   61ven the  perennial  habit of trees  and
         their close  dependence on  edaphie   and  climatic   conditions,
         quite different exposure statistics may be  required to  protect
         forests against injurious  effects of ozone and  other pollutants.
         This work  will  take  a  long  time period  to resolve because  it
         must take  Into  account  cumulative effects  and the   capacity  of
         trees to recover from  stress.

      •   Ozone dose-response of major tree species and overall forest pro-
         ductivity analyses.   Dose-response  relationships  between  ozone
         and other  long-range  transported  pollutants and  trees   need  to
         be developed   using field  chambers  on  whole  trees  and/or  on
         branches of mature trees.   These, too, will  have  to  be long-term
         studies because the effects of competition, and different edtphic
         and climatic   conditions on  growth,  development,  competition,
         and reproductive success  need  to  be  established.   These  long-
         term studies  also  need  to  address  the effects of air pollution
         impacts on trees upon the  entire forest  ecosystem in a  unified
         approach.
                                   -17-

-------
      t  ienerilizible tree  physiological  models.   Physiological  models
         have greatest potential  for  prediction  of  effects  over  long
         time periods.  To be  of greatest value, they  should be linked
         to models of climate change and  geochemical cycling  of elements.
         Model development  is   a  difficult  undertaking  and  requires  a
         substantial  multldlsciplinary effort.  Therefore, this research
         requires secure  funding  over  a  substantial  period of  time.

         Second Priority Research Needs

      t  Economic model  development.  This  includes   considerations  of
         forest productivity  and  succession, aesthetics  and non-timber
         service flows from  forest  ecosystems.  In the long-term, this
         analysis requires a  comprehensive and integrated forest ecosystem
         valuation framework.   Work  should  also  extend  and integrate
         available regional  timber  models,  account  for  different timber
         quality and  design sensitivity analyses of the  economic models.
         This research must  be closely  linked to  the  other research
         efforts because   it  Is dependent  on them  for accurate Inputs.

     c)   Short-Term Research  Initiatives

     While the most important focus  should be upon long-term initiatives,
several  short-term initiatives  already  underway  or  planned that CASAC
supports.  These include, but are not limited to:

      •  Characterization  of the resource  at  risk.   Mapping of  forest
         resources against ozone  levels  and  current  information/hypo-
         theses about tree species sensitivity to assess the  resource at
         risk are used as  a  tool that  can be updated  and Improved  as the
         science developes.  These   efforts   are  underway  it  1PA,  the
         California Air Resources 8oard»  the National  Park Service and
         elsewhere.

      •   Retrospective study.  A resurvey of the San  Bernardino National
         Forest to  validate   projected  impacts,  trace  long-term  tree
         impacts and  succession, validate or reject  hypotheses and  review
         other forest ecosystem Impacts would provide  substantial  insight
         in developing long term direction.

      •   Preliminary  economic studies.  These studies  are  underway under
         the NAPAP program  and will  provide  useful  information  upon
         which to develop long-term  analyses.
                                   -18-

-------
 IV.  RESEARCH HEEDED FOR FUTURE DECISIONS ON NATIONAL AMBIENT  AIR
       QUALITY STANDARDS FOR LEAD

     A.   Introduction

     Since  1977 there has occurred a steady downward trend  in atmospheric
 lead concentrations  along  with a  similar downward  trend  in  the  lead
 burden of adults and children.  Although both of these trends are  impres-
 sive,  concerns about the  impact of lead  on  human  health remain a  valid
 scientific  and public  policy Issue,   This  is mainly  because of  recent
 epidemiological evidence that adverse effects occur at levels of exposure
 previously  thought  to  be  safe.   In  short,  lead  exposure  1s declining
 while  perceptions and evidence  of what  constitutes  a safe  level   of  ex-
 posure are  also shifting  downward. The implications  of this development
 for  future  directions of  research  are  substantial.  For exposure  issues,
 the  current major contributions to total  lead  Intake  are quite different
 than previous data indicated, at  least  as applies  to  the general  popula-
 tion.  Since  scientists  and  regulators have  indentifled  blomedically
 adverse effects  within  the  usual  range  of  human  exposure, EPA  needs
 better information  on   which media  and  sources  to  target   for  further
 reduction in human exposure.

     Further lead exposure  reduction may not prove  to be  equally  fea-
 sible  or  sufficient to  prevent  harm  to  certain   populations  at  risk,
 notably the  fetus.   Information,  therefore,  1s   needed  concerning  the
 circumstances {apart from high lead  exposure) which result  in  adverse
 effects 1n  certain  individuals  but not  in others,  e.g.  unusual patterns
 of lead absorption and  deposition.

     The Committee discusses these and  other  issues  1n approximate order
 of their urgency and importance,  bearing in mind  the  regulatory  role of
 EPA.   It  strives to  make research  recommendations to better Inform the
Apncy's decisions  on   whether  to take  further   regulatory actions  to
minimize the risk  of adverse health effects due to  lead.

     Finally, EPA staff requested the  Committee   to  present recommenda-
tions concerning the design of the forthcoming National Health and Nutri-
tion Evaluation Survey  (HHANES  III).   The  earlier   NHANES II  survey,
completed 1n 1980,  proved  to  be  a  valuable  resource for identifying
health effects  of  lead  in  the  general  population that were  not  widely
understood at that time.  In developing its recommendations,  CASAC recog-
nizes that  any broad-based  survey e.g.  NHANES, has  competing scientific
needs  and priorities to reconcile.  The Committee has relied  heavily upon
the OAQPS staff paper and the  EPA  Air  Quality Criteria Document  for Lead
as source documents for this activity.
                                   -19-

-------
      B.   AtnKtspheH c Proces ses

      The  phasedown 1n  the sale of leaded gasoline has probably been the
 major contributor to the  accompanying reduction in ambient air levels of
 lead. The  specific  extent  to which  this is  true   has  some remaining
 uncertainties since  other regulatory actions  hive been in effect during
 the  same  general  time  period,   Basically, this  has  been a  matter of
 enforcing regulations which limit the emission of  lead from point sources
 to achieve  and  maintain  ambient  air quality  levels   at or below 1.5 ug
 lead/it^,  fhe  Committee  urges  EPA to  reassess  the   relative  impact of
 various point sources and of  leaded  gasoline  on general ambient air  lead
 concentrations.  As  one  means  of Implementing this   recommendation, EPA
 should consider the  use  of existing, or the  development  of new, tracer
 techniques.

      IPA's  regulation of ambient lead has exclusively focused on inorganic
 lead,  although it is  known that alkyl species of lead exist  1n the environ-
 ment.  Alky! lead Is released from sources such as the use of  tetra-ethyl
 lead  (TEL)  1n  mobile sources.   Inorganic lead can be alkylated 1n the
 environment.  Little  is  known  of the  distribution  of alky!  lead,  its
 concentrations 1n ambient air, or  the processes of bioalkylation.  Because
 of the substantial toxldty of  alkyl  lead compounds,  additional  research
 on these  topics 1s useful.

      Sampling sites  should Include  areas in  the  Immediate  vicinity of
 major  stationary  sources such  as primary and  secondary  lead smelters,
 battery plants, and  other sources such  as municipal  waste incinerators.
 Such  sites  should be distributed  around the country to capture different
 climatic  and geographic conditions.

     The  above recommendations have high priority, but the impact of  lead
 emissions on total  lead  concentrations  in various media is   an equally
 important issue.  Current estimates  relating  air lead  concentrations to
 surface soil and dust  lead  levels are derived mostly  from older studies
with  no  site-specific   indication  of whether  the trends   are  upward or
downward,  A  series  of  measurements are needed,  over time,   in various
locations to assess the impact of changes in lead air  quality and  particle
size on soil and dust lead pools and other sources (e.g.,  snow)  of  depo-
sited  lead  accessible  to children,  and  the   turnover rate  of  lead in
these media.  Sites  selected  for study  should Include areas where the
total  lead  concentration is  both high  and  low.   This 1s necessary in
order to  identify the  role of  atmospheric contributions  and  compare it
with other pathways.

     Because of their  relevance to deposition processes,  more attention
should be given to the  measurement  and  characterization of lead  particle
size distributions.    It  is   also important  to  determine  the  chemical
compostion of both the lead-bearing particulates and  the chemical  form of
the lead  in the matrices.  Such investigations would  provide a basis for
                                   -20-

-------
 tracing the  source(s)  of  lead  in  the  air using  fingerprinting techniques
 and  would  assist biologists researching  the  bioavailability  of lead as
 it relates to chemical composition*

      EPA already is confronted with the need to  make decisions concerning
 the  disposal  of lead-contaminated soil  and refuse.  There is a  pressing
 need  for  more  information  about  the  transfer  of  lead to  the general
 environment  from dump  sites via ground water and air.  Such information
 would greatly  aid  in  establishing  criteria  for  identifying  those  dump
 sites having minimal Input on human exposure to  lead.

         First Priority Research Needs

      The following  recommendations  are  assigned  approximately  equal,
 first priority.  To  the  extent  that  is  necessary to implement  these
 recommendations, EPA should consider developing  new tracer methodologies.

          * Reassessment  of the  relative  impact  of  point  sources and
            gasoline on ambient air lead.

          • Assessment of the impact of air lead on lead in various media
            to which man  1s exposed,  with  special  emphasis  on  food and
            water.

          • Assessment of factors which  determine  the transfer of lead
            from dump sites to air and water,

         Second Pripnty_Research  Need

          • Studies concerning the concentration, speciation and sources
            of alky!  lead in ambient air.

      C.  Exposure Considerations

      It is especially  important to  quantify the amount of dust  and soil
that  young  children  ingest through  hand-to-mouth activities in various
settings and to examine 1n detail  the factors  that Influence lead exposure
through this route  (e.g.* household  dust lead  levels, parental  occupa-
tions, housekeeping  practices,  thumb-sucking,  finger  licking  and  nail
biting tendencies,  and child-rearing practices.)

     Bioavailability of ingested  lead (and  of  inhaled lead) is another
issue urgently  1n  need  of  intensive  investigation.   Estimates  of the
impact of soil  lead  concentrations on  the blood  lead  of  young  children
have  varied  widely  from  one  study to  another.  Essentially nothing  is
known, however, about the reasons  for these discrepancies.  In the absence
                                   -21-

-------
 of more  specific  Information  it is difficult,  if  not  impossible, to make
 rational  site-specific  decisions  as to maximum  safe  limits  of lead 1n
 soil  or  dust.  The  influence  of chemical and physical characteristics of
 lead  1n  soil and dust on bioavallability, therefore, needs to be thoroughly
 investigated.

      Given  the  growing data base  identifying lead-contaminated  soil,  and
 both  interior and  outdoor dust, as major remaining exposure  sources  for
 children (especially in older urban areas),  it is increasingly  important
 to determine  the most  effective  soil-lead  abatement protocols.  These
 abatement protocols  should Include evaluation of removal  of leid-bised
 paint and  lead-contaminated   street  and house dusts, as  well  as lead-
 contaminated soil.

     Although a  great  deal  of  Information Is  available  concerning human
 exposure to  lead  from  multiple sources, much of  it may  no longer be
 valid, particularly if gathered a decade ago or more.  Changing technology
 (e.g. food  packaging),  eating  habits,  and  reduction of  lead  emissions
 may have  substantially altered the relative  Importance  of the  various
 sources, as well as  the level  of total intake.  A reassessment of exposure
 needs to  be undertaken in order to properly Identify the  most  promising
 strategies  aimed at further reduction In human exposure.

     Because harmful  effects  from  lead exposure have  been  observed at
 relatively  low  levels,  particularly to  the fetus, the relative  contribu-
 tions of  various sources,  under normal  conditions of intake  must  not be
 overlooked, EPA  should work  with  the  Food  and  Drug Administration  to
 evaluate the  means  by  which  lead  significantly  enters the classes  of
 foods which  contribute most  to total  dietary  intake, beginning with  the
 raw products and ending with  the fully processed and packaged  products.

     Studies are also  needed  to determine how  much  lead  derived from tap
 water is  consumed  by various segments  of the population  (e.g.  children
 and pregnant women).   This effort  should  take into  account the  use of
water for food  and  beverage  preparation,  in addition to water  which  has
 remained overnight  1n  plumbing.   Such  water contains considerably  more
 lead than water drawn after the plumbing has  been flushed.

     In connection with the forthcoming NHANES III  study the CASAC urges
 EPA to  consider  questionnaire  items  to  aid in  establishing  whether
 the subject's blood lead  concentration  is  representative  of  a  fairly
 constant long-tern  exposure  history  or whether  some recent significant
 change in exposure  is  to be considered in interpretation of the data,  e.g.
 recent interior  renovation  of  an  old  residence  which  had  been  grossly
 contaminated with lead-base paint*  Second, NHANES planners should consid-
er the importance of  using the best possible  methodology  for blood  lead
 determinations,  given the low concentrations and  relatively narrow range
which will  likely be encountered.
                                   -22-

-------
         First Priori tyjtesearch Needs

     All of these are  assigned  first  priority,  although  EPA's  responsi-
bility is uncertain In some cases.

          * Determination of  the  importance  of soil  and dust  ingestion
            as sources of  lead  exposure in young  children,  taking Into
            account social  and  other  factors  that  Influence  such inges-
            tion.

          • Bloavaliability  of  lead,  particularly  in  soils and  dusts
            as a function of particle  sizes and  chemical  form.

          • Reassessment   of  the  contribution  of  foods  to total  lead
            intake, including the   contributions  attributable  to  food
            processing and packaging.

          t More detailed determination of the  contribution  of drinking
            water to total  lead  intake, including water used in food and
            beverage preparation.

     D)  Lead Metabolism

     Past studies of  the  relationships between  dose  and  effects of lead
in roan have relied almost exclusively  on whole blood  lead as  the index of
dose.  Scientists  now  recognize that  this  index has  shortcomings.  It
reflects only recent exposure, and  it  does not bear a  linear  relationship
to concentrations in tissues  or at  receptors, e»g. ALAD.  Thus, develop-
ment of  better  biomarkers  of  human   lead  exposure  and  techniques for
measuring lead  concentrations  In  biological  media  are  needed.  X-ray
fluorescence instrumentation for jjn vjvo measurement  of  lead in mineral-
ized tissue appears  promising and   ought  to  be  further  explored.  This
should include investigations  of novel biomarkers of dose.  As an example,
kidney and brain tissue  contain a  unique  lead-binding protein which may
be of diagnostic interest  to assess  toxic manifestations of lead exposure.
Development of a radiolmmunoassay for  detection  of  this protein in bio-
logical fluid specimens such  as  urine  is  underway.   This 1s  particularly
important since  current   blomarkers are  either  inadequately  sensitive
(e.g. erythrocytlc protoporphyrin)   or  are  not readily amenable to  field
investigations (e.g. ALAD).

     There is  also  a  need  to   develop better  methods  for monitoring
fetal lead  exposure  across  the full  period  of  gestation.   This  Is  a
challenging problem requiring some  innovative Ideas  and  the use of more
appropriate animal  models  of human  pregnancy than  rodent   species e.g.
perhaps sheep and subhuman primates.

     Better understanding also is needed of  the  impact of bone  resorption
in old age on  the  concentration of lead in  blood and, more  importantly,
at lead-sensitive  sites.   Thus, blakinetic modeling  of  lead metabolism
                                   -23-

-------
 must  Include  detailed attention to  the  significance  of  bone stores of
 lead,  particularly  In situations  where  calcium mobilization  occurs,  i.e.
 pregnancy,  lactation  and old age.

     The question of  how various dietary constituents affect  lead  absorp-
 tion and tissue  distribution  In man Is very poorly  understood, not  only
 in  the general  population,  but in  special  risk-associated groups (e.g.,
 children; pregnant,  lactating»  or  postmenopausal women).  Specif1cally»
 the effects  of  varying  levels  of  calcium, iron and,  perhaps,   of  high
 sulfur in the diet may be of particular relevance.

         First Priority Research Needs

          t  Development  of  better indices  of  lead  exposure,   notably
             lead in  hard tissues  and  circulating lead-binding proteins.

          •  Biokinetic  modeling  with  special   emphasis  on  the  fetus
             and placenta,  as well  as  bone  in  both  pregnant  women and in
             the elderly,

          •  Dietary  factors influencing lead absorption.

     E.  Biological and Health Effects

     1,  Developmental Effects

     Recent epidemiological  evidence reinforces and extends the conclusion
 that the early stage of human  development is an especially critical period
 for deleterious  effects  of  low-level  lead  exposure*   Findings  from
 prospective studies  in  Boston,  Cincinnati,  Port Pirie (Australia), and
 Cleveland indicate  that  disturbances  in  fetal  development,  as   well  as
 postnatal  neurobehavioral development, may  occur at lead  exposure levels
 well below those previously considered "safe" or even "normal11.  The most
 clearly identified  effect thus  far has  been  lower   scores on  the Hental
 Development Index  of the Bayley  Scales of  Infant   Development,   a well-
 standardized test of  infant intelligence.   Other developmental endpoints
 such as shorter gestational  age and lower birth weight have also been asso-
 ciated with prenatal  lead exposure in many of these studies.

     Results of  these  studies   to  date  suggest that  adverse  effects
 resulting from prenatal  exposure may  be  largely irreversible,  at least
within the first Z years  of  life.  Ongoing prospective studies, therefore,
 should be continued  without interruption,  at  least to the  age  at which
 school  performance  can  be  properly evaluated,  and  even  on  to   puberty.
                                   -24-

-------
     Additional prospective  studies  of the effects of lead on  pregnancy
 outcomes also  are  needed,  focusing on such unresolved issues as  whether
 fetal exposures  at maternal  blood  lead  concentrations   higher than  in
 current studies  result  in  correspondingly  greater  adverse   cognitive
 outcomes, or  whether different  (or  additional)  adverse   effects  emerge.
 Although of  -considerable  interest,   such  studies would be  of  lesser
 importance than  additional  studies   at   current   general  lead  exposure
 levels, examining  the  impact of lead  exposure when  combined with  other
 factors known to carry a risk  for  adverse., f etaj -/ojitcomes »
     Because so little is known regarding the Mechanism whereby lead acts
to compromise  fetal  development,  the Committee_is  uncertain a$ to  what
specific measurements  should  be recommended for inclusion InlfHANES III
that would  add to  current  knowledge  regarding  the effects  of lead  on
pregnancy outcome*   It urges that those designing the  study  consult with
qualified reproductive  endocrinologists  and  reproductive  lexicologists
to develop recommendations concerning possible neuroendocrine measurements
that would be useful  in assessing adverse  influences on fetal  development.
Also, developmental psychologists currently studying the  effects  of lead
on postnatal  neurobehavioral  development  should be  asked to  review any
currently proposed battery  of  psychological  and  neurophysiologlcal  tests
for the  purpose  of  recommending  additions or  raodifi cations that  would
enhance their  utility  in  furthering knowledge regarding  adverse  effects
of lead exposure.

     Numerous animal studies  currently in progress are aimed  at  gaining
a better  understanding of  meehanismsrfcf * wh4cft " T.ea'*'"*'"« M *jto'.'"a * "™ ""
     There are large information  gaps  regarding the dose- response  rela-
tionships of  chronic  alky!  lead  exposure  in  the  general  population
(particularly pregnant  women  and  infants),  US|R§_  measures- ..af ^.subtle
neurobehavioral or other  effects.   Although it  slews unlikely thai alkyl
lead is harmful at the concentrations  likely  to  occur  in  general  ambient
air, this judgment  is  based   on  occupational  exposure  rather than  on
exposure of  fetuses  and   infants  or animal models  thereof .   Appropriate
animal  studies should  be  undertaken to  establish  the relative  potency
of chronic alkyl  lead vis a vis Inorganic lead using sensitive indices of
effects.

     2.  Cardiovascular Effects

     As discussed in the  recent  addendum  to the  EPA Air Quality Criteria
Document for Lead (1986), a growing  body  of literature suggests that low
level lead exposure has both direct  and indirect  effects on end-arteriolar
                                   -25-

-------
 smooth muscle  contract!!1ty  and  cardiac  function,  and  thus  essential
 hypertension may  be  causally related to  chronic  low-level  lead  exposure*
 though this is far from certain given the small effect reported  (approxi-
 mately 2-7 iron Hg  per 15 ug Pb/dl in blood).  Nonetheless,  a better under-
 standing  of the health implications of lead effects on the cardiovascular
 system is needed  since a large  number of people  are potentially at risk.
 Prospective human studies would  be desirable  in  principle,  but  the power
 of  such  studies would  need  to be  carefully evaluated.  Although  a study
 of  the morbidity  and mortality Implications  of  the hypertensive  effects
 of  lead  also  would  be  desirable,  the feasibility  of obtaining  useful
 studies is questionable.

     Studies in  experimental animals  and studies  conducted 1n  occupa-
 tional exposed workers strongly suggest  that the  blood  pressure  effect
 occurs only within  a  rather narrow  range and  that,  in  fact,  lead  may
 have a hypotensive effect at exposure levels  somewhat above the range in
 the general population.  It  1s»  therefore,  important that future epiderolo-
 logical studies  should  be   designed  to  include a  wide   range of  lead
 exposures.  Future animal  studies  should be  directed toward  gaining  a
 better understanding  of  the  mechanism(s) underlying the  hypertensive
 effect of  lead,  particularly in  regard  to the  effects  of lead   on  the
 second messenger  functions of calcium.

     The Committee is  pleased to  note that  the forthcoming NHANES  III
 study will include a  determination of cadmium concentrations along with
 lead since the vasopressor  effects of lead ind  cadmium may be  additive.
 It  is  the Committee's  impression, however, that blood cadmium  has never
 been shown to correlate well  with  toxic effects.  Perhaps cadmium metallo-
 thionein  (CdMt) in seruro would be better than elemental Cd concentrations
 as  a biomarker.  It  is  our understanding that  a sensitive radioimmunoassay
 for CdMt  has   been   developed;    Cadmium   experts   should  be  consulted.

     3.  Other Effects

     The two most currently significant  health  effect issues  are those
 relating to growth  and development  in  children, and  to  hypertension in
 adults.  These appear  to be  critical effects, using the  term  "critical"
 to denote  "most   lead-sensitive".   If this  belief  is correct,  further
 reductions in lead exposure  should  serve  to  decrease the  risk of other
 adverse effects to  which man  way  be less or equally sensitive.  Here
 information is needed regarding the significance of other effects* parti-
 cularly in subpopulations  other than those  already  identified as being
most sensitive to neurobehavloral   and  cardiovascular  effects.    As an
 example, old  people  are a  separate  subgroup  peculiarly  sensitive to
 factors which  contribute to  the  development of osteoporosis.  The impact
 of  lead on the incidence and  severity of osteoporosis needs more attention.
Again, some  valuable  information  in  this regard  may emerge  from  the
NHANES III study, particularly if cadmium  exposure  can also be  effective-
 ly assessed.   Cadmium  has   been   shown  to  induce  bone   resorption  and
                                   -26-

-------
osteoporosis In postmenopausal  women,  particularly in  conjunction  with
Vitamin D deficiency.  A major  contributing  factor may  be the fact that
cadmium accumulates in the  body  with  age  to  an even greater degree than
lead.  Further, there  is  evidence that  lead also has  toxic  effects on
bone development.    Admittedly,   the  evidence  is   very  limited  and  has
focussed mainly on  young  children and young experimental animals.  Pos-
sible additive effects involving lead  and  cadmium  should be investigated*
This should  include  studies  of  the  toxicokinetics  of  skeletal  lead,
including the  influence of  age  (See  discussion  under Lead Metabolism).
In this context, NHANES III  should consider including a  sufficient number
of old people to establish whether a  significant  lead problem exists.  A
meaningful measure  of  vitamin D status  Is  also  important,  serum 1,25
dihydroxycholecalciferol  in  particular.

     Numerous studies  have  reported effects of  lead on the immune system,
and a small  number of  studies  report  an association between lead  and can-
cer.  No convincing evidence has surfaced, however, suggesting that lead
is a human  carcinogen  or  that it  has  any role 1n the etiology  of other
diseases involving the Immune  system.  EPA  should consider  convening a
small group  of immunotoxicologists and experts  in oncogenic toxicology
to jointly examine whether  current information identifies any particular
sub-population in  which a  special risk may  exist Involving the effects
of lead  on  the  immunologlcal  system  and the sometimes-related cancer
endpoint.

     Although the  scientific literature identifies  other potential toxic
effects of  lead,  there is  no  current basis for  believing that current
standards do not adequately protect  against  known or potential  effects.

         First Priority Research Need

     The Committee  recommends  the following issue as  a first  priority
research need:

           •  Continued,  uninterrupted support for current  prospective
              studies  of  neurobehavioral  effects  of lead in  children  to
              school age  and beyond.

         Second Priority Research Needs

     Other recommendations   are  made  as   only  somewhat  lesser  second
priority research  needs:

           •  Additional  prospective  studies  examining fetal and  early
              postnatal development examining a wider  range of fetal  lead
              exposures,  and with  additional risk factors, e.g.  diabetes
              and  toxic substances other than lead.
                                   -27-

-------
           •  Continued support for investigations concerning the mechan-
              isms whereby  lead  adversely  affects   neurobehavior  with
              greater emphasis  on  neuroendocrinological  Influences  on
              brain development,

           t  Initiation of prospective studies of the relationship of the
              lead exposure to blood pressure, as well as consideration of
              the consequences with respect to the incidence of  hyperten-
              sion.  Although this  is  an  important  objective,  the sub-
              committee recognizes that  it may not be feasible.

           •  Initiation of  studies regarding  the  role of lead exposure
              In osteoporosis.  This should include epidemiologies!
              approaches and  investigation  of  meehansims  using  animal
              models.

           •  Studies  of  toxic  effects  of alkyl  lead  compounds  most
              prevalent 1n  the  environment,, with   emphasis  on  subtle
              chronic effects  in  developing animal  systems and potency
              relatle to inorganic lead.

     Finally, the  Committee  recommends  (with  moderate enthusiasm) that
the EPA convene a  meeting  of immunotoxicologists and oncogenic  toxicolo-
gists to assess further  research  needs  relating to  the possible role of
lead in cancer and other diseases involving the  immune system.
                                   -28-

-------