United States
Environmental Protection
Agency
Office of the Administrator
Science Advisory Board
Washington, DC 20460
SAB-CASAC-S&021
May 1986
Report of the
Clean Air Scientific
Advisory Committee
Review
U.S.
Health Effects
Assessment
on Nitrogen
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             UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

                            WASHINGTON, D.C.  20460


                                May 9, 1986
                                                                    OFFICE
                                                                 THE AD
Honorable Carol Dawson
Acting Chairman
U.S. Consumer Product Safety Conrnission
Washington, DC 20207

Dear Ms. Dawscm

     The Clean Mr Scientific Advisory Cormittfie (C^SAC) of the U.S.
Environmental Protection Agency has completed its review of the health
effects and exposure assessment documents on nitrogen dioxide provided by
the U.S. Consumer Product Safety Commission*  This review was conducted
at the Commission's request in order to obtain independent outside scienti-
fic advios on the potential health hazards associated with exposure to
0.1 to 1,0 ppm nitrogen dioxide generated by undented indoor combustion
sources,  IXte are pleased to transmit to you the enclosed report which
represents the Committee's analysis and reccsmendations concerning the
documents and the specific' questions that you raised.

     The Committee has concluded that: 1) repeated peak exposures at concen-
trations of 0.3 ppm of nitrogen dioxide may cause health effects in some
individuals and there is a possibility that such effects may occur at
concentrations as low as 0.1 ppm.  We note, howaver, that both the epide-
roiolcgical and chamber studies at or near this range of concentrations
have produced inconsistent evidence regarding the health effects of such
exposures? 2) the population groups that appear most sensitive to nitrogen
dioxide exposure include children, chronic bronchitics, asthmatics, and
individuals with emphysema; and 3) the most direct evidence regarding lung
damage associated with nitrogen dioxide is obtained frcm animal studies -
such studies conclude that a number of effects occur in a variety of
animal species, many of which can be considered serious and irreversible.
Bae relevance of these studies to human exposure at concentrations found
indoors is uncertain.

     The Committee also addressed the adequacy of the CPSC documents as
a basis for assessing the risks of exposure to nitrogen dioxide emissions,
and provided guidance regarding further efforts to assess the risks
associated with indoor use of appliances producing nitrogen dioxide
emissions.  We found that the CPSC documents addressed the appropriate
issues, but that they were repetitive and not well integrated.  Perhaps
this was reflective of their being prepared by various authors at different
times for different purposes.  We recommend that the CPSC utilize more
fully the EPA Criteria Document and Staff Paper on Nitrogen Dioxide as
primary resources  in developing an assessment of the health risks of
indoor  combustion  sources.

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                                  -2-
     The Committee appreciates  this unictue opportunity to interact with  the
Commission and to provide scientific advice on an issue of current interest
and great importance to us all*
                               Sincerely,
                                        \Ware, Chairman
                                        Inel on Nitrogen Dioxide
                                       'Advisory
                                Morton Lippann/Chairman
                                Clean Air Scientific Advisory Conmittee
                                Science Advisory;Board .
cc:  Lee Thomas
     A. James Barnes
     Don Ehreth
     Craig Potter
     Peter Preuss
     Terry Yosie

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A 1EVIEW OP THE CONSUMER PRODUCT SAFETY
COMMISSION'S HEALTH EFFECTS AND EXPOSURE
ASSESSMENT DOCUMENTS ON NITFDGM DIOXIDE
  A. Report by the Clean Air Scientific
     Advisory Committee of the U.S.
    Environmental Protection Agency
         Science Advisory Board
   U.S.  Environmental Protection Agency
             Washingtonr I3C
                  May 1986

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                                  NOTICE
     This report has been written as part of the activities of the
Environmental Protection Agency's Gongressionally established Science
Advisory Board, a public group providing advice on scientific issues.
The Board is structured to provide a balanced, independent, expert
assessment of the scientific issues it reviews.  "Che contents of this
report do not necessarily represent the views and policies of the U.S.
Environmental Protection Agency, the U.S. Consumer product Safety
Conmission nor of other agencies in the Executive Branch of the Federal
government.

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                   U.S.  finvirontnental Protection Agency
                          Science Advisory Board
                 Clean Air Scientific Advisory Conmittee
             Panel for the Review of Nitrogen Dioxide Health
            EffectsandExposure Assessment Documents for the
                    Consumer Product Safety Ccmniss ion.
Chairman

Dr. James Ware, Department of Bios tat is tics, Harvard School of Public
     Health, Boston, Massachusetts
Panel Members
Dr. Ekjjward Crandall, Division of Pulmonary Medicine, Cornell Medical
     College, New York, New York

Dr. Robert Prank., Department of Environmental and Health Sciences,
     School of Hygiene and Public Health, Johns Hopkins University,
     Baltimore, Maryland

Dr. Jack Hackney, Environmental Health Laboratories, Saneho Los Ainigos
     Hospital, University of Southern California, Downey, California

Dr. Ian T»T, Higgins, American Health Foundation, Mew York, New York

Dr. Timothy Larson, Department of Civil Engineering, University of
     Washington, Seattle, Washington

Dr., Brian Leaderer, Pierce Laboratory, Yale University, New Haven,
     Connecticut

Dr. Mark Utell, Pulmonary and Critical Care Unit, University of Rochester
     Medical Center, Rochester, New York

Dr. James whittenberger. Southern Occupational Health Center, University
     of California, Irvine, California
Executive Secretary
Mr. A, Robert Flaak, Science Advisory Board, U,S. Environmental Protection
     Agency, Washington, DC

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                   U.S. Environmental Protection Agency
                          Science Advisory Board

                 CleanAir Scientific
Chaipnan

Dr. Morton Lippmann, Professor, Department of Environmental Medicine,
     New York University Medical Center,  Tuxedo,  New York
Members

Dr. Robert Frank, Professor of Environmental Health Sciences,  Johns
     Hopkins School of Hygiene and Public Health,  Baltimore, Maryland

Dr. Warren B, Johnson, Director, Atmospheric Science Center, SRI
     International, Menlo Park, California

Dr. Paul Kotin, Adjunct Professor of Pathology, University of  Colorado
     Medical School, Denver, Colorado

Dr. James H. Ware, Associate Professor, Department of Biostatistics,
     Harvard School of Public Health, Boston, Massachusetts

Dr. Jerry Wesolowski, Chief, Air and Industrial Hygiene Lab, California
     Department of Health, Berkeley, California
Executive Secretary

Mr. A, Robert Flaak, Environmental Scientist, Science Advisory Board,
     U.S. Environmental Protection Agency, Washington, DC

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                           TABLE OF CONTENTS
1.    EXECUTIVE SUMMARY   .   ,	   1


2.    INTRODUCTION	   2

      A.  Background   *	...'....   2

      B.  Report Format   »»,»......»....   2


3.    COMMENTS ON THE GOALS OP THE REVIEW   ........   3
4.    MAJOR CONCLUSIONS MID RECOMffiNDMTONS ON ISSUES
        POSED BY CPSC  ................   4
5.    ADDITIONAL ISSUES	   7


6.    APPENDICES

      A.  Document Review - More Detailed Comments   .....   A-l

      B.  Nitrogen Dioxide Closure Letter of the Clean Air
          Scientific Advisory Committee - October 18,  1984 .   .   .   B-l

      C.  Letter from CPSC Commissioner Scanlon
          March 29, 1985  ..............   C-l

      D.  Letter from EPA Administrator Lee Thomas
          May 1, 1985	   D-l

      E.  Literature Cited	   E-l

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1.     EXECUTIVE JgUMMftRY

     This Is the report of the U.S. Environmental Protection Agency's  (EPA)
Congressionally established Clean Air Scientific Advisory Committee  (C&SAC)
concerning its review of the Nitrogen Dioxide {N02)  Health Effects and
Exposure Assessment Documents of the U.S* Consumer Product Safety Commission
(CPSC),  Under the provisions of an interageney agreement between the  two
agencies, the CASAC reviewed the CPSC documents at a public meeting  on
September 26-27, 1985, in Bethesda, Maryland.

     Following its ire view of the documents prepared  by the CPSC,  the CAS&C
reached the following major conclusions:

     * Preliminary evidence from epidemiologic and related indoor air
       pollution monitoring studies suggest that repeated peak exposures
       at concentrations of 0*3 ppni of NOj may cause health effects  in
       some individuals and raises the possibility that such effects
       may occur at concentrations as low as 0*1 pptu  However, the
       epideraiologic and controlled human exposure studies provide
       somewhat  inconsistent evidence which makes it difficult to be
       more definitive.

     • Population groups that appear to be most sensitive to N02 exposures
       include children, chronic bronchitics, asthmatics, and individuals
       with emphysema.

     • Human epidemiologic studies suggest that exposure to N02 may lead
       to increased respiratory illness rates among children.  However,
       the most direct evidence regarding lung damage associated with
       t«2  is obtained from animal studies.  Such studies conclude  that
       a number of effects occur  in a variety of animal species, many
       of which can be considered serious and  irreversible*

     * The work undertaken by the CPSC to quantify the indoor NO2 concentra-
       tions produced by kerosene space heaters  is innovative and important
       and provides  information 'that  is essential to assess human health
       risks from these and other appliances producing N02 emissions.

     * The EPA Air Quality Criteria Document and Staff Paper for N02
       provide peer reviewed  information and assessments directly relevant
       to questions facing the CPSC.  The CASAC recommends  that CPSC use
       these documents more fully as a primary resource  in developing an
       assessment of  the health risks of  indoor combustion sources*

     * The  documents  submitted by CPSC for CASAC's review were prepared
       at different  times by various authors,  for different CPSC purposesj
       therefore,  they were sometimes repetitive and not well  integrated.
       Although the documents generally identified the appropriate  issues,
       they were not sufficiently developed  to provide a primary resource
       for  risk assessment without further revision.  However, in light
       of the availability of the EPA Nitrogen Dioxide Criteria Document
       and  Staff Paper, such revision may not  be needed.

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2.   INT5QDOCTION

   •  ^*  Background

     The Consumer Product Safety Commission (CPSC) has been concerned
about exposure to nitrogen dioxide associated with the use of gas cooking
stoves and a variety of home combustion heaters.  Various studies, including
several conducted for the CPSC, have shown that the levels of nitrogen
dioxide exposure associated with the use of these appliances significantly
exceed the national ambient air quality standard (NAAQS) as well as the
short-term standard for nitrogen dioxide recommended by staff of the o.S*
Environmental Protection Agency (EPA).

     On March 29, 1985, Coronission Chairman Terrence Scanlon requested the
assistance of the EPA's Congressionally established Clean Air Scientific
Advisory Comnittee (CASAC) in conducting the CPSC's review of the potential
health hazards associated-with exposure to 0.1 to 1,0 plus parts per million
(ppm) nitrogen dioxide generated by the unvented combustion sources used
in the home (see Appendix C).  In this request, the CPSC requested guidance
on issues such ass

          *  the levels of nitrogen dioxide for which there are data
             indicating adverse health effects*

          •  the identity of subsets of the population more sensitive
             to nitrogen dioxide than others? and

          »  whether exposure to nitrogen dioxide leads to irreversible
             lung damage.

     On May 1, 1985, SPA Administrator Lee M. Thomas agreed to this
request, noting that the CASAC, which has reviewed the scientific basis
of EPA's NAAQS for nitrogen dioxide, is well qualified to address the  issues
raised by the CPSC (see Appendix D), 'Staff of both agencies then developed
an interagency agreement which was signed in August 1985.

     Under the provisions of this interagency agreement, the C&SAC reviewed
the CPSC documents at a public meeting on-September 26** 27, 1985,  in Bethesda,
Maryland.  At this meet ing, the Committee'heard presentations from CPSC
staff on exposure assessment, controlled human exposure, animal toxicology
and epidemiology relating to nitrogen dioxide, as well as conroents from
the  interested public.  The focus of this review was  the September 1985
report of the Commission entitled Review oj_J^LbrQ^nJ3ioxide;_ Health
Effects..and_ jSxBpsure. f_r^m^Consumer jfiroducts,  a six-part document discussing
health effects of nitrogen dioxide and presenting  information on kerosene
heaters and unvented gas space heaters.

     B.  Report Format

     This report has been divided into an Executive Sutonary, Introduction,
three major Sections and an Appendix.  Of the three major sections, Section
3 discusses the similarities between the assessment needs of the EPA and

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the CPSC as well as the CASAC's view of its role in the CPSC review,
in particular, the Comnittee's views regarding use of information generated
by the EPA to simplify CPSC's assessment process.  Section 4 contains the
conclusions and recommendations of the Committee concerning Chairman
Scanlon's three questions.  Section 5 addresses additional issues that
go beyond the information requested by Chairman Scanlon.  Appendix A
addresses in wore detailed fashion some of the CASAC's comments on the
documents supplied by the CPSC.  Appendix B is a copy of the October 18,
1985 CASAC report to EPA detailing its findings and recommendations
concerning EPA's National Ambient Air Quality Standard for nitrogen
dioxide.  Appendix C contains Chairman Scanlon's March 29 , 1985 letter
requesting the review.  Appendix D presents Administrator Thomas1 May 1,
1985 response to the request.  Appendix E contains full citations to the
literature referenced in this report.

3.     CCmEOTS.pN THE GOALS OF THE REVIEW

     During the course of its meetings on September 26-27 , the CASAC
sought to clarify the goals of the review.  The Committee concluded that
it had three  tasks;

       • To conroent on the three questions posed by Chairman Scanlon
         regarding the healtih effects of
       • To assess the adequacy of the documents prepared by CPSC
         staff as a basis for assessing the risks of exposure to
         emissions.

       » To provide guidance to CPSC regarding further efforts to assess
         the risks associated with indoor use of space heaters and other
         appliances producing NO2 emissions.

     The questions posed by Chairman Scanlon in his letter to the SPA are
both difficult and highly relevant to CPSC concerns about the potential
health effects of kerosene space heaters.  Fortunately, the EPA Criteria
Document and Staff Paper on NC>2 provide peer-reviewed information directly
relevant to these questions.  We encourage CPSC staff to use these documents
as a primary resource  in future efforts to assess  the health risks of  indoor
combustion sources.

     The second and third tasks are similar to those that the CASAC ordi-
narily performs  in advising EPA on the adequacy of air quality criteria
documents and staff papers.  Given the availability of these EPA documents,
we believe that further CPSC efforts should focus  on quantification of
the peak and average NC-2 concentrations produced in residences by unvented
combustJjDn sources and on systematic revaluation  of the evidence summarized
in the EPA Criteria Document and Staff Paper with  a focus on the higher
indoor NC>2 concentrations produced by unvented combustion sources relative
to the tjpical ambient concentrations of N02 implicitly addressed in the
EPA documents.

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4.    MAJOR CONCLUSIONS MD RfiOCMMENDATlONS ON ISSUES POSED BY CPSC

     In its evaluation of the materials provided by the CPSC,  the CASAC
drew a distinction between the material on exposure assessment and the
documents reviewing the health effects literature.  The Committee noted
that CPSC staff and contractors have undertaken important and innovative
work to quantify the indoor KfC>2 concentrations produced by different,
but typical uses o£ kerosene space heaters.  The documents summarizing
this work provide new and important information directly relevant to
CPSC concerns.  This information is central to assessing the health risk
of indoor use of these and other applicances producing N02 emissions.
Moreover, this material is unlikely to be assembled by other government
or private groups.  Thus, the CASAC urges the CPSC to continue this work
and to further investigate the implications of these data for the impact
of space heaters and other indoor sources on the population distribution
of exposures to WC>2«  Specifically, further efforts by CPSC staff to
assess, .t^_,h^jj±_ri^s_asspciatedrwith, indoor use of kerosene space
heaters and other sources of nitrogen dioxide emissions should focus on
efforts to quantify the nitrogen dioxide concentrations produced by
.these,.sources.  We urge the CPSC to avoid duplication of EPA's effort to
develop a comprehensive review of  the literature on health effects of NC>2.

     The following paragraphs respond to the questions posed by CPSC
Chairman Scanlon.

     * For what levels of nitrogen dioxide are there data indicating
       adverse health effects?

     The CASAC has concurred with  EPA's reconmendation to retain the
current Annual Primary National Ambient Air Quality Standard of 0.053
ppm (Appendix B).  Evidence suggests  that  this average annual concentra-
tion should provide adequate protection against the adverse health effects
associated with long-term exposure and protect to a lesser degree against
short-term effects related to peaking of outdoor concentrations.  Among
the adverse effects related to chronic exposure  in animals are a reduction
in resistance to respiratory  infection, accelerated aging of the lung
manifested as a loss of elastic recoil^ f ibrotic and eKphyseiroatous-like
structural changes  in the lung, and  impairment of function.

     The lowest concentrations) associated with acute adverse health
effects  can be expressed  in a range of estimates.  Preliminary epideraiologic
findings and related  indoor air pollution  monitoring studies assessing  the
variation of NQ2  levels  in gas stove  homes suggest  that  repeated peaks  in
the range of  0.15  to  0.30 ppm may  be  of concern for children  (USEPA, 1982).
The limited number of controlled laboratory studies on human subjects,
both healthy and with underlying lung disease, have produced conflicting
results.  For example,  increased bronchial reactivity to a provocative
aerosol  has been  reported after exposure  to 0.1 ppm NC>2  in asthmatics
 {Orehek  et al,f 1976).  This  finding  was not confirmed  in a second  study
at  the same concentration  involving asthmatics and  healthy subjects
 (Bazucha et al.,  1983), while a third study found a "...variable
effect..." on bronchial  reactivity (Ahmed  et al.,  1982). The  effect

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of 0.2 ppm NC>2 on bronchial reactivity in asthmatics has been equivocal
{Kleinman et al*, 1983).  Although both bronchoconstriction (Bauer et al.,
1984; Rogers et al., 1985) and increased airway reactivity (Bauer et al,f
1984) were found in response to 0,3 ppti NQ2, another study could find
little or no effects at 4.0 ppm (Linn et al., in press).  Therefore,  the
data base remains too sparse and the between-studies variance too great to
project definitive dose-response relationships and complicates the task of
identifying "safe levels" for the general population.  Moreover, the
mechanisms underlying these effects, and consequently their potential for
contributing to chronic lung damage, are unknown.  Such information may
be vital in judging which effects are adverse, but much of this latest
generation of studies has not yet appeared in the peer reviewed literature.
Nonetheless, this preliminary evidence suggests that repeated peak exposures
at concentrations of 0.3 ppm of N02 may cause health effects in sews indi-
viduals and raises the possibility that such effects may occur at concentra-
tions as low as 0,1 ppm, encouraging a cautionary approach in matters of
pol icy.

     As discussed in Appendix A, both the epidemic-logic studies of children
exposed to gas stove emissions and the controlled exposure studies of
adults exposed to NOj have reported inconsistent findings regarding the
health effects of these exposures.  Such large uncertainties in clinical
and epidemiological data are troubling to policy makers but are a reality
in interpreting the currently available evidence on the health effects
of NQ2-

     * Which subsets of ,_j^e_j»gul_atipnTi_are TOS^^^nsitiye^to^Aitycgen
       dioxide?

     The EPA Staff Paper on NC»2 states that:

               ».,the groups that appear to be most sensitive to exposures
               to NC>2 include children, chronic bronchitics, asthmatics,
               and individuals with emphysema....Health effects data from
               epideraiological studies in gas stove homes suggest that young
               children are at  increased risk of respiratory symptoms and
               infection from exposures to elevated concentrations of
               NOj	Other groups at risk to NOj exposures are asthmatics
               and bronchitics.  Human clinical study data have provided
               evidence that sane of these  individuals suffer mild sympto-
               matic effects {nasal discharge, headaches, dizziness, and
               labored breathing) after light to moderate exercise during
               an exposure to 0.5 ppm NO2 for two hours.1

     CASAC concurs with this statement.
  Review of  the National Ambient Air Quality Standards for Nitrogen Oxides:
  Assessment of the Scientific and Technical Information.  U.S. EPA, Office
  of Air Quality Planning and Standards, Research Triangle Park, NC,
  EPA 450/5-82-002, Page 41, August 1982.

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     • Does exposure to nitrogen dioxide lead to irreversible lung damage?

     As noted in Appendix A, controlled exposure studies  provide little
information about this question.  Human epidemiologic studies suggest
that exposure to_nitrogen dioxide may lead to^j^reas^ respiratory
illness rates among children.  Although a history of respiratory illness
in childhood may be predictive of respiratory disorders in adult life,
relatively little is knewn about this relationship at the present time.
Thus, the irost direct evidence regarding lung damage resulting from
exposure to nitrogen dioxide is obtained from animal studies.  These
studies are reviewed in EPA's Criteria Document and Staff Paper. The
Staff Paper provides the following summary of this complex and extensive
data base:

               In critically assessing animal studies involving short-term
               exposure to N02, it is obvious that numerous effects  have
               been observed for a variety of animal species (dogs,  rabbits,
               guinea pigs, monkeys, rats, and mice.).  There is presently
               no reliable way to relate human and animal dose-response
               data.  Many of the effects associated with short-term ex-
               posures appear to result not from a single exposure,  but
               from multiple exposures in the range of 0.2 ppm to 0.5 ppm
               for several hours.  Of particular interest is that exposure
               of animals to concentrations slightly above those currently
               being experienced in the ambient air appears to cause a
               decrease in resistance to bacterial infection,... this
               same type of effect has also been reported to occur  in
               huraans,              ,

               ,.. effects which have been associated with animals exposed
               to NC>2 over relatively long periods (1 day to several years)
               ...  includet  (1) significantly increased susceptibility
               to infection resulting in  increased mortality for continuous
               and  intermittent exposure  to > 0.5 ppm NQ2; (2) decreased
               immunologieal response resulting in increased respiratory
               infection for exposures of 0.5^1.0 ppm NOj, continuous and
               intermittent? (3)  increased lung protein content suggesting
               edema and cell death for 3-6 week exposures to 0.5 or 1*0
               ppm NOj  in Vitamin C deficient animals; (4) hematological
               disturbances  (e.g. increased cholinesterase lysozyme levels)
               suggestive of liver and heart damage at 0,5 ppm N02 f°r 1
               week;  (5)  increased EBC 2,3-diphosphoglycerate,  indicating
               tissue deoxygenation after 1 week exposure to 0.36 ppm
               N02;  (6) eraphysematous alterations resulting from a six
               month exposure  to  0,1 ppm  M32 with daily spikes of 1.0 ppm
               N02  or 68 months exposure  to 0.64 ppm NQ2 an<3 °*25 PP* NO
               followed by a 2 year period in clean air.

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                    A critical assessment of the available animal toxioo-
               logical data for long-term exposure to NC>2  reveals that
               many of the above effects occur in a variety of animal
               species, and that many of the effects can be considered
               serious and irreversible.  For exanple,  the eraphysematous
               alterations in dogs associated with long-term  exposure  to
               Nt>2 are of major concern since the occurrence  of  this
               type of effect in humans would clearly be adverse.

                    While most of the chronic studies were conducted at
               exposures considerably higher than those encountered in
               the atnbient air, it should be noted that one study did
               observe epphysematous alterations in mice when exposed  to
               N02 levels about twice the current annual standard. However,
               in this study, the chronic exposure was  supplemented with
               daily spikes of 1.0 ppn and it is not possible to determine
               if the cause of the effect was chronic exposurer  short-term
               spikes or a combination of these two.

                    Currently there is no means available  to  extrapolate
               the results of the animal studies (either short-term or
               chronic) directly to humans.  Nevertheless, the animal
               toxicology studies do indicate that N02  exposure  causes
               serious biological damage to a number of animals.  These
               studies clearly raise a "warning flag" for  potential
               effects in humans.^

     Thus, whilethe animal studies do provide evidence that  both short-
term and long~term exposureto nitrogen dioxide can lead to irreversible
health effects in a variety of animal speciesf it is difficult at the
present tame to determine whether these effects are of  concern at con-
centrations associated with use of kerosene heaters/ gas stoves, or other
indoor sources of N02-

5.  ADDITIONAL ISSUES

     The documents summarizing the evidence regarding the health effects
of NC>2 exposure correctly  identify many of the inportant  issues and
studies, but the Comnittee believes that the materials have some  important
deficiencies.  In particular, we note that the various documents have not
been integrated, and we also have numerous questions about the studies
chosen for emphasis and about  the interpretation of some of the evidence.
An informal compilation of CftSAC's comments regarding the CPSC's review
of the health effects literature  is included as Appendix A*
2 Keview of  the National Ambient Air Quality Standards for Nitrogen Oxides:
  Assessment of the Scientific and Technical Information.  U.S. EPA, 'Office
  of Air Quality Planning and Standards, Research Triangle Park, Nt,
  EPA 450/5-82-002, Pages 10-11, August 1982.

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     The EPA's experience in. preparing Criteria Documents and Staff Papers
for the periodic assessment of criteria pollutants has shown that prepara-
tion of such reviews is enormously difficult and time consuming.  Moreover,.
SPA staff routinely submit several revisions of each of these documents
to CASAC in their efforts to develop a consensus on the relevant literature
and its triplications.  In our view, the CP9C materials are conparable to
the first draft of such integrated documents.  From that perspective, the
documents could provide a basis for developing an integrated review of the
relevant literature.  Given the effort involved in developing an integrated
risk assessment, however, the Conmlttee uzxjes CPSC not to duplicate the
resource-consuming effort required of the EPA in its periodic assessment
o€ the health effects of NQ2«  ttether>	CPSC should make extensive use
of the EPA Criteria Document and^ Staff Paper on Nitrogen Dioxide in its
assessment of the health risks associated with indoor sources of nitrogen
dioxide*  In particular, the CPSC sj^ld^tjljgeJpPV.s_Staff_ Paper  to the
extent practicable.  Every effort should be made to avoid duplication of
reviews of the health effects literature carried out by EPA and reviewed
by CASAC under the requirements of the Clean Air Act.

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                                           WPENDIX A
                            Document Review - More Detailed Coraraents
*

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*
DQCtWENT JREVIljW

     The CPSC provided the following six documents to the Committee as
background for the review:

          * Update on Health Effects Associated with N02
          * Health Effects of Nitrogen Dioxide
          * Status Report on Kerosene Heaters (includes updates   Health
            Effects of N02? Nitrogen Dioxide Health Assessment 1984}
          * Status Report:  Pollutants Generated by Unvested Gas
            Space Heaters
          * Kerosene Heater Emissions:  Estimation of Exposure
          * Indoor Air Quality Kerosene Heater Testing Documentation

     A.  Overall Comments

     Because these documents were prepared at different tiroes by various
authors for different CPSC purposes, they were sometimes repetitive and
not well integrated,  An introduction for the documents presented by CPSC
delineating the purpose of the review would have been helpful.  In addition,
the CASAC's decision not to recouraend a short term standard for  ambient
NOj concentrations  in its review for EPA should not be interpreted as
implying that no adverse effects are associated with the higher  concen-
trations produced by indoor sources.  Thus, an introduction discussing
the potentially high M02 concentrations caused;by space heaters  and other
sources and the need to re-evaluate the health effects literature with
these concentrations in mind would have provided a sharper focus for the
assessment.

     The CPSC should consider organizing the material according  to major
topics and issues.  This has already - and conroendably -* been done  in part,
i.e., Biochemistry, Pulmonary Functional Effects, and Extra Pulmonary
Effects.  In dealing with any category of effects, emphasis should be
given to what is known about the mechanisms of the effect - this being a
particularly valuable contribution of animal and in vitro toxicology - and
whether similar mechanisms have been demonstrated or are plausible  in humans*
An  faportant way of organizing and classifying effects is by duration, i.e.,
acute and chronic.  Virtually the only e;xplieit information available on
the chronic effects of NC>2 (short of  industrial accidents affecting indi-
vidual workers) results from animal studies.

     The CPSC should atteirpt to define the actual exposure levels of the
indoor environment  and to focus the discussion of health effects on those
levels,  insofar as possible.  This effort should include any  information
on  the frequency of occurance of such levels as well as the relationship
between pollutant level and averaging time.  Such an approach would help
distinguish this document from the EPA documents which were concerned
with outdoor effects.

     There  is a tendancy  in the CPSC documents to overstate findings
which may actually  be more attributable  to chance and which are not really
statistically significant.  Normal variation  is a reasonable expectation,


                                   A-l

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but 'wore caution is needed in interpreting statistical significance*   The
Committee was advised by the CPSC that their normal practice Is to state
when a finding is not statistically significant and may have been attrib-
utable bo change and that caveats have been added when necessary.

     For animal toxicology studies, the GASAC recognizes that one of the
major problems, beyond the issue of whether or not the animal's health is
adversely affected, is how to extrapolate animal data to humans.  Relative
dosing is one of the major issues in these extrapolations*  This document .
need not exhaustively review dosimetry, but giving some perspective
relative to the problems with animal studies would be helpful.

   B,  Exposure

     Nitrogen dioxide is produced by a variety of combustion sources
within the home, including space heaters and gas stoves.  Although the
CPSC document carefully describes a limited number of studies concerning
emissions from certain space heater devices, additional discussion is
needed of the relative N02 contribution of these devices compared to gas
stoves.

     The current protocols used by the CP9C to characterize emissions from
space heaters are carefully conceived and well executed.  Their approach
focuses on the contributions to steady state levels represented by a 4 to
6-hour average concentration*  The extrapolation of this information on
steady state levels in confined spaces to actual homes  is obviously wore
difficult.  To the extent that additional information on the potential
for shorter term (one-hour) peaks and their spatial distribution within
the home can be generated from current data, this  information would be
very useful.

     The chamber studies ;and modeling work carried out by CP3C and its
contractors have been informative.  In particular, these studies have
identified a range of steady state concentrations associated with contin-
uous operation of space heaters  in chambers, and have characterized the
•relative emission rates of white and blue flame heaters, as well as the
reductions  in emissions achieved by catalytic converters and dual chamber
designs.  Such modeling activities are  insufficient, however, to charac-
terize distribution and temporal pattern of concentrations experienced
by persons using.space heaters  in  their homes.  Factors  that could affect
the distribution of exposure  include model preferences, age of heating
units, mode of operation, and hero characteristics.  Given the potential
health and regulatory significance of  issues concerning kerosene space
heaters, additional direct resasurements of  indoor'concentrations are
urgently needed.  Such data should ideally be gathered  in the context of
a well designed sampling'frame, with attention  to  temporal and home-to-home
variability and  to such covariates as wind speed and  indoor and outdoor
temperature.  Given the paucity of direct measurement data available, a
well-defined set of measurements  in 50  to 100 homes, for example, would
be of great value.  If  the CPSC is unable to undertake  such a study,
                                    A-2

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interested scientific and industry groups should be encouraged to collect
NOj measurements in homes, using kerosene heaters.  To the extent that
long-tern exposures of NC>2 are relevant to health, the present passive
collector technology can be directly applied to this large home to home
survey.  If short-term (less than 6-hour) peak concentrations are more
relevant, then the passive sanpler technology must be supplemented with
continuous M>2 analyzers.
   C.  Animal Studies

     The section on .in vitro and animal toxicology is concise, and, for
the most part, clearly stated.  However, at times it is too selective
and superficial in its atbenpt to reduce some complex problems to siaple
judgments.

     If the CPSC chooses to rewrite the document, it should consider
organizing the material more effectively.  Effects might be organized
under Pulmonary (biochemical, functional, innwnological, resistance to
infection, morphological), and Extra-pulmonary.  Wherever possible, the
document should distinguish between acute, subacute and chronic effects.
Virtually the only eitpirical information available on the subacute and
chronic effects of N02 (short of occupational accidents) comes from
animal studies and, thus, this information is particularly important,

     A topic not treated anywhere in the document is the uptake of NC>2
within the respiratory system, an issue which has implications for regional
dose and for  identifying target tissues.  N02 uptake has been measured in
some animal species;  it has also been modeled in a preliminary way for
the human lung.  A critical issue in any atbenpt to extrapolate from
animals to humans  is  the extent to which, for a specified ambient concen-
tration, both total dose (corrected for differences  in size) and regional
dose are comparable across species.

     An important  issue that warrants separate,  integrated treatment  is
a discussion of factors influencing susceptibility.  These might  include
age, sex, nutritional status, and any anitnal models of underlying  lung
disease or extrapulmonary disease that nay have been tested.  This is
another area of research  in which animal toxicology can contribute signif-
icantly to  insight  into human risk.  Whatever information  is available
on mechanisms of effect should also be added.

     Summary  tables for all three sections  (animal, clinical, epidentiol-
ogical) providing details on selected critical studies are useful and
could  tae organized  to show effects as functions of  increasing concentrations
 (separate  tables for  acute and 'chronic exposures).   Such tables could also
 include whatever  information  is available on  the reversibility of  effects.

     The  animal toxicology discussion  includes a variety of biochemical
changes that  occur  in response  to single or repeated exposures to NC>2»  In
general,  these changes are reversible; even dead epithelial cells may be
replaced  through regenerative processes.  However, some of  the changes may


                                   A-3

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become part of a process that culminates in irreversible tissue damage
and deformity.  This process may be sustained if the exposure to NC>2 is
sufficiently protracted or severe, if other forms of environmental stress
are also present, or if the defensive and reparative responses of  the body
are conproroised.  The studies of Gillespie and co-workers suggest  that
the evolution of changes that are "emphysema tous-1 Ike'1 in character may
continue even after cessation of exposure to NOj; howeverf this work has
defects in esqaeriroental design and should be redesigned.  Hew reversible
the effect of N02 may be following protracted exposure must be determined
empirically by allowing the animals to survive after ending the exposure,
data of this sort are presently scarce.

   D»  Controlled Human Exposure

     This section of the CPSC Report gives a useful review of the  key
scientific literature.  The Committee identified no substantial errors  or
omissions in this material.  Nevertheless, a reader wishing to conpare
and contrast the various studies needs a tabular summary similar  to Tables
2 and 6 in the EPA Staff Paper on Nitrogen Dioxide (USEPA, 1982).

     Committee members offered many suggestions for changes in content,
enphasis, or language.  The specific comments below highlight some issues
about responsiveness of population sub-groups, .'interpretation of pulmonary
function meas«rem0ntst and interpretation of conflicting results  from
different controlled human exposure studies.   '.

Specific Suggestions?

     Coiments  in the CPSC document that inply definitive knowledge about
the relative N02 responsiveness of population sub-groups who have lung
disease should be revised  (see pages 19 and 20)3.  Because, available
results are conflicting, they should be cautiously interpreted and
statements about them referenced whenever possible.

     The discussion of confounding issues that arise in the interpretation
of pulmonary function measurements (see page 20)3 should be changed to
indicate!  1)  that  intra-subject variability in clinical studies  is mitigated
by using repeated measures with subjects serving as their own control,
2) that with due care, subjects with decreased lung function reserve from
respiratory disease can and are being studied to collect evidence about
how  their responsiveness to N02 exposure varies with disease severity,  and
3) that the use of  the term "significance" has statistical support?  if not,
another word should be used.

     As pointed out  in the CPSC document  (see page 21) ,3 results of  the
presently available studies on N02 effects are  inconsistent.  The CPSC
should expand  its discussion of the reasons for Such  inconsistency to include
 3 Page references  are to the  CPSC  Report Update on Health Effects Associated
   with Nitrogen Dioxide,  1985 by Lori Saltzman

                                   A-4

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other factors that are also likely (if not wore likely)  for this
development - such as differences in exposure methods as well as  differ-
ences in subject populations*  For example, the "positive"  studies
have probably involved more sensitive asthmatics than the "negative"
studies, but judging this will be very difficult until detailed results
have been released and critically reviewed-

     Prom short-term (1-hour) controlled studies of adults, one could es-
timate the lowest-observable-effect level to be below 0.2 ppm at  one
extreme, or above 4.0 ppm at the other extreme depending on the response
being tested.  This large discrepancy between different  findings  is trou-
bling to scientists as well as to policymakers*  With ozone ancl sulfur
dioxide, the discrepancies between different studies and different
laboratories are much smaller.  However, two recent reports (Bauer et al.,
1984; Rogers et al., 1985) have observed changes in lung function in
exercising asthmatics exposed to 0.3 ppm N02*  Despite the  failure of
other studies to demonstrate such changes, these levels  may provoke
responses in some asthmatic individuals.  There is no good  explanation
for the widely divergent results on NQ2-       •:

     The controlled human studies which have suggested unfavorable effects
at lew concentrations  (0,2 - 0,3 ppm or even Icwer) all have employed
adult asthmatics.  Asthmatics thus are the best candidates  for the "more
sensitive" designation.  However, other studies have concluded that many
mild asthmatics experience a detectable effect at concentrations  an order
of magnitude higher.  This has led to the suggestion (not explicitly
tested as yet) that N02 sensitivity is correlated with an  index of severity
of asthma, perhaps the degree of airway obstruction or baseline airway
hjperreactivity.

     The demonstration of unfavorable short-term reversible effects is
sometimes thought to imply a possible risk of long-term irreversible
effects, but any direct relationship between short-and long-term effects
remains unclear*  As indicated above, even short-term effects have not
been demonstrabed unequivocally for WQ2*

   E.  Epidemiology

     The most relevant studies for the CPSC's needs are the British and
U.S. studies of the health status of  children and adults living  in
homes where gas is used for  cooking or heating.  The CPSC  review document
 is an accurate evaluation of  these studies.  The Staff Paper  (USEPA, 1982)
represents a more extensive evaluation of  all N02-related epidemic logic
studies, with conclusions that are consistent with the CPSC evaluation.
In brief,  the extensive  information available  is suggestive but not
conclusive that unvented :gas  combustion devices  in heroes are  associated
with slight  excesses of respiratory illnesses, especially  in  children.
The  inconsistent  findings among  investigators and among different studies
by the  same  investigators, seme  of which  are  eonparisons of cross-sectional
                                    A-5

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and longitudinal observations, suggest that the many confounding  factors
which inevitably occur have not been adequately accounted for  (andr  in
some instances possibly "over-corrected").

     It is evident that use of gas for cooking or heating is not  a risk
factor of great magnitude In conparison with a factor such as  cigarette
smoking.  It is also not certain that N02 is the  causal factor for whatever
risk may be associated with gas stoves or heaters.  Unfortunately the
majority of epidemiologic studies include no information on NO2»  and
among those that do have actual measurements, the number of homes and
characterization of concentrations are very limited*  This suggests  that
better 
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         APPENDIX B
--^- Closure
               .. .

-------

         NEW YORK UNIVERSITY MEDICAL CENTER
         A private university in the public service

         Institute of Environmental Medicine
         550 FIRST AVINUl, NEW YORK, N.Y,  1001$
         AREA 212 J«-?300» EM, 8*5-
         ANTHONY j. LANZA RESEARCH LABORATORIES AT UNIVERSITY VALLEY
         iONC MEADOW ftOAD, STERUNC FOREST, TUX£00, N.Y, 10§87
         MAIL AND TiLfiPHONi ADDRESS: 550 F1S5T AVINUE, NEW YORK, N.Y. 10015

                                   October IS,  1984

        Honorable William RacJcelshaus
        Administrator
        U.S.  Environmental Protection Agency
        401 M Street,  S*W*
        Washington,  DC 2Q46Q

        Dear Mr*  Ruckelshaus:

             On July 19-20, 19S4, the Clean Mr scientific advisory Committee
        (caSAC) met to consider the Agency's proposal regarding  revisions  to
        the National Mdbient Mr Quality Standards (NAAQS) for Nitrogen  Dioxide.
        Included in this proposal-is the reaffirmation'of the existing annual
        average standards for nitrogen dioxide at 0*053 ppm  (100 ttg/m ), and
        solicitation of public comments on both the need to  set  a  separate
        short«term standard and -the need to use an alternative form of the
        standard (statistical  instead of deterministic)*  The Committee  has
        prepared this closure  letter to advise you of its major  conclusions
        and recommendations concerning the scientific and technical aspects  of
        these and other issues associated with 'the Agency's  proposal for the
        revision of the NM.QS  for'nitrogen dioxide.    :
                     previous' -closure letters dated June  19, 1981  and July 6;
        1982, respectively, the CASAC advised, that the 'revised Air Quality
        Criteria Document for Nitrogen Oxides was scientifically adequate for
        standard setting and that the office  of Air Quality Planning and
        Standards (QAQPS) Staff Paper represented a balanced and thorough
        interpretation of the scientific  evidence contained in the criteria
        document*   The Committee has reviewed relevant research which has been.
        published since those docuicents were  prepared , and concludes that the
        scientific conclusions reached in those doeKaents are still satisfactory.
             The CASAC has concluded that the  existing1 annual average primary
        standard for nitrogen dioxide adequately protects  against adverse health
        effects associated with long-term exposure  and. provides some neasure of
        protection against short-term health effects*   Therefore, the Committee:
        concurs with the Agency's- recommendation to retain the cijrrent annual
        average primary standard  of 0*053 ppm.  The Committee farther concludes
        that, while short-tern effects  frcpt nitrogen dioxide are documented in
        the scientific literature, the  available information was insufficient
.SESQUl'*                          :            &~1
•CENTEN:
'MfliSi;;
OLE:

-------
                                  -2-
to provide an adequate scientific basis for establishing any specific
short-term standard, or for determining an acceptable number of
exceedances, a concentration limit, and an averaging time for such a
standard.  Indeed, the scientific basis for set-ting a separate short-term
standard appears to be less firm than it was ait the time of the Committee's
previous review.  We recommend that the Agency vigorously pursue a research
program designed to address and resolve the issues related to short-tera
effects of nitrogen, dioxide.

     The Committee reaffirms its conclusion from two years ago that a
secondary standard set at a level equivalent to the annual primary standard
would -offer sufficient protraction against the identified welfare effects of
nitrogen dioxide.      '  '.

     Members of the Cemmittee who held 4 view on the issue of the form  of
the standard favored retaining the present deterministic form, rather than
adopting a statistical form for the annual standard.

     R. more extended analysis of the factors leading to the Cosmittee's
recommendations is contained in the enclosed report.  Thank you for the
opportunity to present the Committee1s views on this important public
health issue*
                                    Sincerely,
                                    Morton Lippiaaxm, Ph.D.
                                    Chairmant Clean Air  scientific
                                      Advisory Conmitfcee   >  •
Enclosure
cc:  Mr. Alvin Aim
     Mr. Joseph Cannon
     Dr» Bernard  Goldstein
     Dr. Terry
                                     B-2

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            Findings and Recommendations oa the Scientific Basis for
                   a Revised NM.QS  for Nitrogen Dioxide
                  by the
     Agency 'staff presented for  CASAC review and  comment  three options
     the Agency could pursue in  concluding its  current review of the
      for nitrogen dioxide.  These  are  as  follows:

     1*  Reaffirm the an.iiu.al standard at the current level  and propose
         a ghort-term standard ,  or

     2»  leaf firm the annual standard at the current level  and conclude
         that a short-term standard is  not needed r  or

     3*  Reaffirm the annual standard at the current level, defer  a
         decision on a  short-term standard , and perform high priority
         research on short-term  effects 'of nitrogen dioxide*

     Based OH the Committee's  review of the scientific issues associated
 with the reaffirmation  of  the  annual standard  and the possible short-term
 standard as  discussed below, the Committee believes t 1)  that there is  an
 Insufficient scientific basis  for action on option  1; and,  2} that options
 £ and 3 are  functionally equivalent, i.e.  a vigorous program of  research
 j,nto the short-term effects, of nitrogen dioxide is  needed and can  be
 accflaplished " under either option.

 5cientifi.c_Is_sues^_in .Revising  the Standards

     In C&SAC's closure letter of July  6,  1982, the Coaxnittee discussed-
    review of the nitrogen oxides staff paper,  noting that  no single
      provided the  scientific  basis for a  decision  on revising the -primary
 ptjanciard for nitrogen dioxide*  Kather, it could  be based on a  "-weight;
 of .evidence™ approach,  using animal studies, controlled human exposure
        and  epidemiology studies to provide both  quantitative (i.e.
              t:) and qualitative (mechanistic )  support  for  such  a  decision.
 gince that time new studies have been  completed and, along  with previously
 'discussed studies,  form the basis for  the  Committee's conclusions  and
 recommendations concerning the critical issues associated with reaffirming
 the annual  standard and evaluating a short-term standard for nitrogen
 dioxide.

      1.  Animal Toxicology Studies.

     The results from recent  animal studies provide further substantiation
' of the  effects  of nitrogen dioxide  exposure on immune functions and increased
 susceptibility  to infection.    Seme of these  studies also examine patterns
 of exposure  to  nitrogen dioxide  that are closer simulations of what may be
•actually occurring  in,  for example, gas stove  homes*  An example of this

                                        B-3

-------
                                  -2*
is superimposing repeated short-term higher levels of exposure to nitrogen
dioxide (e-f* 0.4 to 5.0 ppn, or more) on relatively low background levels
of nitrogen dioxi<3e, such as found in gas stove homes •

     2*  Controlled Human Exposure Studies-

     The more recent controlled human exposure studies (mostly unpublished)
present rather mixed and often contradictory results concerning respiratory
effects in asthmatic and normal subjects exposed -to concentrations in the
range of 0.1 to 4.0 ppta nitrogen dioxide.  Kagawa and $suru {1979} reported
results possibly suggestive of short-term nitrogen dioxide effects on
pulmonary function in normal subjects without combined provocative challenge
by other agents {Such as carbmchol) *  Although they reported no significant
differences for mean pulmonary function changes for a group of six subjects
exposed to 0*15 ppm nitrogen dioxidet there were small significant decreases
in airway conductance in three of the six subjects*  However, the smallness
of these decrements and questions regarding the statistical analyses used
suggest caution in accepting the reported findings as demonstrating
nitrogen dioxide effects on pulmonary function1at Q.1S ppm.  More recently,
Bauer et al, (1384 - abstract) exposed asthmatics to 0,3 ppm nitrogen
dioxide and observed effects on both pulmonary function after exercise
and airway reactivity following cold air challenge.

     3*  Epidsiiologieal Studies*

     The most recent epidemiclogical studies indicate less conclusive
findi-gs of an association between,nitrogen dioxide and respiratory
effects than previously•reported.  The first report of the Harvard six
cities Study* published several years ago/ noted one positive result —
an association between both lung function changes and respiratory ill-
nesses in children under age two and  exposure  to gas stoves — among a
number of associated variables*  More recent analyses, published in
Ferris et al,  (1983) and Ware et al,  (1984) made adjustment  for the
socio-economic status of the children under age two and reported that
the association between their living in homes  with gas stoves and their
incidence of respiratory illness is  no longer  statistically significant*
Prom these results, as well as those reported  by other investigators
studying people living in hopes with gas stoves, CAS&C concludes that
the scientific evidence supporting an association between  living in
homes with gas stoves and increases  in respiratory illnesses  and symptoms
is insufficient to support specific  limits for: either short-term or
long-term standards for nitrogen dioxide.

Annual Standards

      1«  Primary Standard.

     •She C&SAC reviewed the results  of animal, controlled  human  exposure,
and epideaiological studies  to  determine if  such  evidence  provided a scien-
tific basis  for retention of the annual  standard  and  scientific  support

                                     B-4

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                                       -3-
for establishment of a short-term standard.  The most serious effects
associated with nitrogen dioxide exposures that are reported in the
scientific literature result from animal studies conducted at concentra-
tions well above those permitted by the current annual standard.  Although
there are large uncertainties in extrapolating these results directly to ,
humans, the seriousness of these effects coupled with the biological
similarities between animals and humans suggests that there is risk to
human health from long-term exposure to nitrogen dioxide.  This set of
factors, widely accepted within the scientific community, leads the
Committee to conclude that there is a continuing need for a long-term
nitrogen dioxide standard.

     The results from recent studies showing some evidence of detectable
health effects due to short-term nitrogen dioxide exposures do not provide
sufficient evidence  to develop a concentration level, an averaging time, or
a number of exceedences for a'short-term standard*  For example, the gas
stove studies were originally used in support of the rationale for a short-
term standard; however, recent reassessments by the authors of these studies
led them to reduce the level of statistical significance of their reported
results.  Moreover,  the results of the recent clinical studies have been
inconsistent.  As a  result, the overall scientific support for a short-term
standard Is more equivocal than previously thought.'  If the CASAC were to
make a recommendation favoring a short-term standard, the Committee would
also have to take Into account the need to determine the number of allowable
exceedances, the establishment of a concentration level, and the identifi-
cation of an averaging time.  At the present time, the Committee is unable
to nake such recommendations due to the absence of a sufficient body of
Information on such  factors.

     2.  Secondary Standard.
                                       i
     The CASAC has not identified any further information to change its
conclusion  from  two  years ago that a.secondary standard  set equivalent to
the annual  primary standard would offer sufficient protection against  the
identified  welfare effects of- exposures to nitrogen,  dioxide.  Although the
Issue of visibility  impairment was raised, several members noted that,
given the present state of knowledge, It is difficult to identify the
degree  to which  nitrogen  dioxide concentrations may  contribute  to this
phenomenon.  The Agency Indicated that further work  on this complex, multi-
pollutant issue  has  been  assigned a high priority in relation to the task
force on visibility  and that the issue will be addressed further at subsequent
CASAC meetings.  The Committee  Is looking  forward to reviewing  the results of
the Agency's progress on  this important issue*

Form_of the Standard

     The Committee did  not  reach a consensus  on" the  desirability of
changing the  form of the  standard  from the present deterministic  form
to a  statistical form which  uses  the  available arithmetic averages  from


                                         B-5

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                                    .4-
the last three—years to determine ccaplianee*   Although jnostt members of
the Cofflftittee took no position, one member suggested that there Is a
stronger argument for a statistical approach to1short-term standards than
for annual standards.  Two others favored the retention of the current
deterministic form for the' annual standard•

ResearchT Efforts

     The C&.S&C ws encouraged to learn that the Agency is currently
pursuing research which addresses some of the issues raised in our December
30, 1983 report to you on Besearch Needed to Support the Development of
NAAQS.  We look forward to, continued reports from the Agency on the pro-
gress of this important research.  The Committee feels compelled  to
reiterate that witheat an adequately funded research jsrograia aimed at
assessing the significance" of the health effects associated with  short-term
nitrogsn dioxide exposures, the Agency cannot make  scientifically informed
decisions concerning the need for a short-term standard, its coneen.trat.ioa
level, averaging tine or an acceptable nuafcer of exceedances*

S-omnary of C&.S&C Recoimendatioias

     For the reasons stated* the Committee recommends that you. reaffirm
the annual standard at the current level, and that  you defer a decision
on the short-term standard' while p«rS"«i»g an aggressive research  program
on short-term effects of nitrogen dioxide*
                                       B-6

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              APPENDIX C

Letter £rcm CPSC Coiroiss loner Scanlon
       :     March 2.9, 1985

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                                       UNITED STATES
                             CONSUMER PRODUCT SAFETY COMMISSION
                                   WASHINGTON, D.C, 20207
*
                                                                       The Chairman

                                             March 29, 1985
         Honorable Les M. Thomis
         Administrator
         U.S. Environmental Protection Agency
         401 H Street S.W.
         Washington, DC  E046Q

         Dear Mr. Thomas:

              I am requesting the assistance of the Environmental Protection
         Agency's Clean Air Science Advisory Committee (CASAC) in our review of
         the potential health hazards associated with exposure to 0.1 to 1.0 plus
         ppm nitrogen dioxide generated by the unvtnted combustion sources used
         in the home.

              The Commission has been conctrned about consumer exposure to
         nitrogen dioxide associated with the use of gas cooking stoves and a
         variety of combustion  home heaters.  Various studies, including several
         conducted for the CPSC, have shown that the levels of nitrogen dioxide
         exposure associattd, with the use of these appliances significantly
         exceed the ambient air standard as will as the short term standard
         previously recommended by the  EPA staff.

              Various gas stove and combustion heater industry representatives
         have indicated  a willingness to modify their product in order to reduce
         consumer exposure to nitrogen  dioxide but there remains some
         disagreement as  to what the target level should be.  In an effort to
         expedite this process,  1 believe that the. CASAC, since it has recently
         reviewed the dati on NQ_f could- give the Conmisslon guidance on
         questions such  as:

              -the levels of  nitrogen dioxide for which there are data indicating
               adverse health effects;
              -the identity of  subsets  of the population more sensitive to
               nitrogen  dioxide than others; and
              -whether exposure to nitrogen dioxide leads to irreversible lung
               "damage.
                                             c-i

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                                   -2-
     Please advise me es to the feasibility of obtaining  such
assistance, and, if it is feasible,  the  process for obtaining  CASAC
review.  Thank you for your assistance in  this matter.

                                  Sincerely yours,
•f
                                  Terrenes Scan Ion
                                  Chairman
                                              C    I
                                               D^^^
                                 C-2

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               APPENDIX D
LgtterJErqm EPA Administrator Lee Thomas
              May 1,  1985

-------
           UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
\^~^f                     WASHINGTON. D-C. 20460



                                MftY  11385

                                                        TH£ ADMINISTRATOR

  Honorable Terrence Scanlon
  Chairman
  U. S. Consumer Product Safety
    Commission
  Washington, D. C.  20207

  Dear Mr. Scanlon:

       Thank you for your March 29 letter in which you request the
  assistance of EPA's Cleafc. Air Scientific Advisory Committee (CASAC) in
  evaluating consumer exposures to nitrogen dioxide associated with the
  use of gas cooking stoves and a variety of combustion hone heaters.
  The Committee, which has reviewed the scientific basis of EPA*s National
  Ambient Air Quality Standard for Iltrogen Dioxide, Is well qualified to
  address the Issues identified in your letter, and I support your request
  to solicit its scientific advice.  I know that the CASAC Chairman,
  Dr. Morton Llppmann of New York University, would also be willing to
  assemble his "panel to undertake this review,

        I suggest that your staff coordinate the preparation for the CASAC
  sseetlng with Dr.  Terry F. Yosie, Director of EPA*s Science Advisory Board,
  (382-4126) and Mr, Bruce Jordan of IPA's Office of Air Quality Planning
  and  Standards (919) 541-5655.  Two specific requests that I have of the
  Commission staff  Is to work closely with Dr« Yosie and Mr« Jordan in
  preparing the scientific tuaterlals to  submit to CASAC, and to provide
  budgetary support to defray the cost of the meeting*  I  estimate that
  the  costs of the  review will approximate $15,000 - $20,000.

        Thank you for your Interest  in working with the Agency on this
  important public  health Issue.

                                        ^Sincerely,
                                         Lee M. Thomas
                                         Administrator
                                  D-l

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   APPENDIX E
Literature Cited

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                             LITERATURE CITED
Ahmed, T., B. Marehette, I. Danta, S. Birch, R.L. Dougherty, R. Schreck
     and M.A. Sackner.  1982.  Effect of 0.1 ppm NQ2 °n bronchial reactivity
     in norrnals and subjects with bronchial asthma.  Am. Rev. Respir.  Dis.r
     125:A152 (abstract).

Bauer, M.A., M.J. Utell, P.E. Morrow, D.M, Speers and F.R. Gibb.  1984.
     0.30 ppm nitrogen dioxide inhalation potentiates exercise-induced
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