Envtronnwttftf      Board iA-101)
ft UlACUQfl t
AN SAB REPORT:
POTENTIAL
CARCINOGENICITY OF
ELECTRIC AND MAGNETIC
FIELDS

REVIEW OF THE ORD'S
BY THE RADIATION
ADVISORY COMMITTEE'S
NONIONIZING ELECTRIC
AND MAGNETIC FIELDS
SUBCOMMITTEE


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               UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                          WASHINGTON, D.C. 204fQ

January 29, 1992

fiPA-SAB-RAC-92-013                '        '    " '     ' '' -

                                                        QFRCEQP
Mr, William K. Reilly, Administrator                  ncMMMnwoi
U.S. Environmental  Protection Agency
401 M Street SW
Washington, DC 20460

Res  Pote_nfc|g.A C?arej.nogenicity of filectromajmejtic  Fields

Dear Mr.  Reilly:

     The  enclosed is the  report of the Nonionizing Electric and
Magnetic  Fields Subcommittee of the Science Advisory Board's
Radiation Advisory  Committee*  The report has been endorsed by
the science Advisory Board on the recommendation of its Radiation
Advisory  Committee.

     The  Subcommittee was set up  in response  to  the October 12,
1.990, memorandum from the Directors of the Environmental
Protection Agency's offices of Health and Environmental
Assessment (William Farland), Health Research (Ren Sexton),  and
Radiation Programs  (Richard Guimond).  The letter  requested a
peer review of the  draft  report, Eyalujajblgn.- o_f—the  Potential
Carcinogenicitv of  Electromagnetic Fields  (IPA/600/6-90/005B).

     The  Subcommittee met three times.   Its first  meeting,  on
January 14-16, 1991, in Washington, D,C., elicited an uncommonly
strong public participation:  over 200 people, 19  formal  and
several informal presentations, and a lively  debate between
Subcommittee members (sitting as  a panel) and members of  the
audience.  Among the formal presentations were those made by
Congressman Frank Pallone (Dem.-New Jersey),  Mayor J.  Connors
(Scranton, Pennsylvania), Dr. D.  N. Erwin of  the United States
Air Force Arpntrong Laboratory for Human Systems,  and Dr.  Robert
Adair, sterling Professor of Physics at  Yale  University.   At its
second meeti&g on April 12-13, 1991, in  San Antonio,  Texas,  the
Subcommittee, received preliminary drafts prepared  by its  three
subgroups (on physics, biology, and epidemiology)  and heard
invited presentations by  biophysicist Dr. Arthur Pilla of Mt.
Sinai Hospital in Mew ¥ork City,  biologist Dr. Russel Reiter of
the University of Texas Health Science Center in San Antonio,  and
physiologist Dr. Asher Sheppard of the Pettis Memorial Veterans
Hospital  in Loma Linda, California.  At  its third  meeting,  July
23-25, 1991, in Washington, the Subcommittee  reviewed a draft of
the present report  which was subsequently approved  by mail
with some amendments.
                                                   Printed sn flecycW Paper

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     The charge to the Subcommittee was to review the document as
to the accuracy and completeness of the information provided, as
well as th* interpretation of the scientific data.   The EPA
document has serious deficiencies and needs to be rewritten.  As
the result of many internal inconsistencies, it is often
difficult to tell what the EPA's position is when reading th*
Evaluation of the Potential Careinogfen^eitv of Electromagnetic
Fields.  Portions of the draft lead to conclusions which are not
the conclusions stated elsewhere in the document*  Such
inconsistencies appear not only between the body and the
executive summary, but also between different pages of the
document itself.                 '  ;      "-   —•••••

     Consequently, the document requires a logical reorganization
and complete rewriting with particular attention to careful and
precise use of language.  A simple editing of the present text
would not be sufficient.  The Subcommittee consciously refrained
from providing a list of particular inconsistencies because it
does not want to mislead the EPA into believing that editing
alone will address the Subcommittee's concerns.
                                                                 *

     Six specific questions were posed in the charge to the      :
Subcommittee.  Before responding to these questions explicitly,
the Subcommittee feels it important to express its viewpoint on
three underlying scientific issues, concerning (a) epidemiology,
(b) biological effects, and (c) carcinogenicity.  These issues
are critical for the understanding of scientific issues in
research regarding electric and magnetic fields and must be
addressed in any future EPA discussion, of the potential
carcinogenicity of electric and magnetic fields.

     a.   The Subcommittee  concluded that some epidemiological
evidence is suggestive of an association between surrogate
measurements of magnetic-field exposure and certain cancer
outcomes,  in such studies, the existence of confounders is
always a possibility, but since no common confounder has yet been
identified, the existing evidence cannot be dismissed.  In the
absence of much better exposure information and an understanding
of which exposures are significant, no precise exposure-response
relationship has yet been adduced.  This lack, together with
limited understanding of possible biological mechanisms, prevents
the inference of cancer causality'from these associations at this
time.

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     b.   The Subcommittee accepts that'Effects on some
biological systems have been shown to occur at moderate field
intensities. (An example of such effects is the well-documented
work on phosphenes.)  However, the evidence for effects at very
low field strengths is not so widely accepted*  Even if effects
on living systems at lower fields do occur, t'he assumptions
leading to estimations of physical constraints thought to
preclude effects on isolated small spherical cells without
ferromagnetic structures may not be applicable to larger cells, or
cell systems such as neurons or neuronal networks.  Many
intervening steps must be clarified before the biological
phenomena so far shown can be taken as direct evidence of health
impairment or carcinogenesis in the human.

    "e.   The EPA document does not present a holistic model of
carcinogenesis within which the strength of .existing evidence
concerning the carcinogenic properties of electric and magnetic
fields can be assessed.  The revised document should do so.  Lew-
frequency electric and magnetic fields do not carry enough energy
to cause mutations directly.  The Subcommittee recognizes that
the incidence of cancer might well be affected by an agent that  *
does not produce mutations.  The known influence of factors sucb :
as hormonal imbalance and nutrition on cancer promotion is an
example of epigenetic effects*

     With respect to the Subcommittee's charge and the six
questions that were posed, the Subcommittee responds as follows.

     1*   Is the interpretation of the human and animal evidence
     of carcinogenicity supported by the available information?

     Currently available information is insufficient to conclude
that the electric and magnetic fields are carcinogenic.  Some
human epidemiologic data report an association between surrogates
for electric and magnetic field exposure and an increased
incidence of some types of cancer, but the conclusion of
causality is currently inappropriate because of limited evidence
of an exposure-response relationship and the lack of a clear
understanding of biologic plausibility.

     2,   De*s the animal or biological effects information
     provid* a basis for postulating that there is a human
     hazard from exposure to extremely low-frequency fields
     or either modulated or unmodulated radiofrequency
     -radiation?

     Some of the in vitro and in vivo data on unmodulated RF have
suggested the existence of mechanisms by which human health

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     5.  . la the Agency's carcinogen classification system
     applicable to electromagnetic fields?

     Nonionizing electric and magnetic fields should not be
classified under EPA's chemical carcinogenesis system because of
present "major uncertainties. • These involve an "incomplete
understanding of which aspects of field-tissue interactions give
rise to biological effects. "properties of the various electric
and magnetic fields such as phase angle, polarization,
transients, and frequency range nay contribute to .different
biological effects.  For these reasons, the use of the EPA'a
classification scheme at this time would fee inappropriate and
confusing.

     6*   Does the information cited in the document support
     the conclusion that there is not enough information to
     designate specific values of magnetic field strength as
     being hazardous to human health?


     Yes, there is insufficient information to designate specific
values of magnetic-field strength that may be hazardous to human :
health, for two reasons,

     a.   There is insufficient evidence from the human
     epidemiology data and from animal/cell experiments to
     establish eause-and-effect relationships between low-
     frequency electric and magnetic field exposure and
     human health effects and cancer.

     b.   The precise nature of the environmental low
     frequency electric and magnetic field potentially
     related to human disease remains to be elucidated,  in
     addition to field strength,  parameters such as the
     time-varying nature of the magnetic fields and the
     relevant time/exposure parameters need to be
     determined.

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     The  Subcommittee also wishes to express two specific policy
 recommendations that in its view follow inescapably from the
 scientific  recommendations.

     POLICY SSCOMMENDAMON #lj    The Subcommittee is unanimous
 in its belief that the question of electric and magnetic field
 effects on  biological systems is important mnd exceptionally
 challenging/ and that the Subcommittee's advice to the EPA should
 be that the report should be rewritten,by EPA, and then re-
 reviewed  by the Science Advisory Board*

     POLICY RECOMMENDATION |2i     EPA should complete its
 efforts with regard to RF electromagnetic fields (including
 microwaves) and issue exposure guidelines independent of present
 issues pertaining to lower frequencies.  The current EPA report
 inadvertently leads even the careful reader to conclude that the
 potential careinogenicity of electric and,magnetic fields of ELF
 (i.e., powerline) frequencies is the only—or at least the
 principal—subject of concern with regard to nonioni^ing fields.
 Such a conclusion would reinforce the skewed and somewhat
 sensationalized picture presented to the public in recent years
 by the news media and government agencies responding to this     :
 publicity.  The report should therefore declare explicitly that  "
 the attention given to nonionizing electric and magnetic fields
 derives in  the first place from long-standing concern over the
hazards of  RF (including microwave) radiation.  EPA has expended
 substantial resources on the study of such radiation over a
period dating back to the EPA's inception, and EPA should
 complete its efforts directed toward the issuance of RF exposure
guidelines,   RF fields present long-known and well-understood
hazards such as temperature elevation in tissue and heat stress
 resulting from acute exposures against which users and the
general public must be warned and protected.  Any published
exposure guideline should specifically identify the hazards from
RF exposure.

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     The Science Advisory.-Board appreciates the opportunity to
review issues of this importance and looks forward to a written
responsetefroa the Agency concerning its schedule for revising the
Evaluation 
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                              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; hence,
the comments of this report do not necessarily represent the
views and policies of the Environmental Protection Agency or of
other Federal agencies.  Any mention of trade names or commercial
products does not constitute endorsement or recommendation for
use.

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                             ABSTRACT

     This review constitutes comments by an Environmental
Protection Agency (EPA)  appointed subcommittee of seventeen
experts in twelve disciplines to review a draft, version of EFA's
report Evaluation of the .Potential carcinogenicitv of
Electromagnetic. JTields (EFA/600/6-90/0051) .  The reviewers
suggest numerous changes in emphasis,  coverage, and wording;
comment on some policy considerations; and conclude that the
draft report in effect will have to be rewritten if all of these
suggestions and comments are to be taken into account.  The
Subcommittee also presents its conclusions on the substantive
scientific questions discussed in the EPA report,

Keywords: electric, magnetic, electromagnetic, cancer
                                11

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                                       • August a V "1991
              0. S. ENVIRONMENTAL PROTECTION AGENCY
                      SCIENCE ADVISORY BOARD
                   RADIATION ADVISORY COMMITTEE
      NONIONIZING ELECTRIC  AND MAGNETIC FIELDS SUBCOMMITTEE
                              ROSTER
Chairman
Dr. Genevievc M. Matanoski, The Johns Hopkins University
     School of Hygiene and Public Health, Baltimore, Maryland
Vice Chajrjgajj
Dr. David V. Bates, Vancouver, CANADA   •
MEMBERS
Dr. A. Karim Ahmed, Princeton, New Jersey
Dr. Patricia A. Huffier, University of Texas Health
      Center in Houston, Houston, Texas
Dr. Craig V. Byus, University of California, Riverside,
     California
Dr. Kelly H. Clifton, University of Wisconsin Clinical
     Cancer Center, Madison, Wisconsin
Dr. John DiGiovanni, University of Texas,  M. D. Anderson
     Cancer Center, Smithville, Texas
Mr. William E. Feero, Electric Research and Management,
     State College, PA 16804
Dr. Robert £'. Harris, School of Public Health,
     University of North Carolina, Chapel Hill, North Carolina
Dr. Clark w. Heath, American Cancer Society, Atlanta, Georgia
Dr. Nan M, Laird, Harvard School of Public Health
     Boston, Massachusetts
Dr. M. Granger Morgan, Carnegie-Mellon University,
     Pittsburgh, Pennsylvania
                               111

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Dr. Mary Ellen O'Connor, University of Tulsa,Tulsa, Oklahoma

Dr. Donald A. Pierce, Oregon State University, Corvallis, Oregon

Dr. Charles Susskind, College of Engineering,
     University of California, Berkeley, California

Dr. Bary M, Wilson, Battelle Pacific Northwest laboratory
     Richland, Washington

Dr. Richard Wilson, Department of Physics
     Harvard University, Cambridge, Massachusetts


DESIGNATED FEDERAL OFFICIAL

Mrs. Kathleen w» Conway
     Science Advisory Board
     U.S. Environmental Protection Agency
     401 M Street, S.W., A-101F
     Washington, D.C.  20460

STAFF ..SECRETARY

Mrs. Dorothy M. Clark
     secretary, Science Advisory Board
     U.S. Environmental Protection Agency
     401 M Street, S.W., A-101F
     Washington, D.C.  20460
                                IV


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                      1.0 EXECUTIVE SUMMARY

     The charge to the Subcommittee was to review the document as
to the accuracy and completeness of the information provided, as
well as the interpretation of the scientific data.  The EPA
document has serious deficiencies and needs to be rewritten. As
the result of many internal inconsistencies, it is often
difficult to tell what the EPA's position is when reading the
Evaluat_jgn_ef^the Potential^earcinoaenicitv of Electric and
Magnetic Fields.  Portions of the draft lead to conclusions which
are not the conclusions stated elsewhere in the document.  Such
inconsistencies appear not only between the body and the
executive summary, but also between different pages of the
document itself.

     Consequently, the document requires a logical reorganization
and complete rewriting with particular attention to careful and
precise use of language.  A simple editing of the present text
would not be sufficient.  The Subcommittee consciously refrained
from providing a list of particular inconsistencies because it
does not want to mislead the EPA into believing that editing
alone will address the Subcommittee's concerns.                  T

     Six specific questions were posed in the charge to the
Subcommittee.   Before responding to these questions explicitly,
the Subcommittee feels it important to express its viewpoint on
three underlying scientific issues, concerning (a) epidemiology,
(b) biological effects, and (c) carcinogenicity.  These issues
are critical for the understanding of scientific issues in
research regarding electric and magnetic fields and must be
addressed in any future EPA discussion of the potential
carcinogenicity of electric and magnetic fields.

     a)   The Subcommittee has concluded that some of the
          epidemiological evidence is suggestive of an
          association between surrogate measurements of magnetic-
          field exposure and certain cancer outcomes.  In such
          studies, the existence of confounders is always a
          possibility, but since no common confounder has yet
          been identified, the existing evidence cannot be
          dismissed.  In the absence of much better exposure
         "information and an understanding of which exposures are
          significant, no precise exposure-response relationship
          has yet been adduced.  This lack,  together with limited
          understanding of possible biological mechanisms,
          prevents the inference of cancer causality from these
          associations at this time.

     b.   The Subcommittee accepts that effects on some
          biological systems have been shown to occur at moderate
          field intensities. (An example of such effects is the
          well-documented work on phosphenes.)   However/ the
          evidence for effects at very low field strengths is not
          so widely accepted.   Even if effects on living systems

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          at  lower  fields do occur,-the assumptions-leading to
          estimations  of physical constraints for effects on
          'Isolated  small spherical  calls without ferromagnetic
          .structures may not be applicable to larger cells or
          c»ll systems such as neurons or newronal networks.
          Many intervening steps must be clarified before-the
          biological phenomena•so far. shown can be taken as
          direct evidence of health-'impairment or earcinogenesis
          in  the human,

     c.   the EPA- document' does not present a holistic model of
          carcinogenesis within which the strength of existing
          evidence  concerning the carcinogenic properties of
          electric  and magnetic fields can be assessed.  The
          revised'document should do so.  .Low-frequency electric
          and magnetic fields do not carry* enough energy to cause
          mutations directly.  The  Subcommittee recognizes that
          the incidence of cancer might well be affected by an •
          agent that does not produce mutations.  The known
         . influence of such factors as hormonal imbalance and
          nutrition on cancer promotion is an example of such •an -t
          epigenetic effect.                                     .

Response to the Charge

     with respect to the Subcommittee's charge and the six
questions which it  posed, the Subcommittee responds as follows.

     1*   Is  the interpretation of  the human and animal evidence
          of  carcinogenicity. supported by the available
          information?

     Currently available information is insufficient to conclude
that the electric and  magnetic fields are carcinogenic.  Hunan
epideraiologic data  report an association between surrogates for
electric and  magnetic'field exposure and an increased incidence
of some types of cancer, but the conclusion' of causality is'
currently inappropriate because of  limited evidence of an
exposure-response relationship and  the lack of a clear
understanding of biologic plausibility.

     2.   Does the  animal or biological effects information
          provide a basis for postulating that there is a human
          hazard from  exposure to extremely low-frequency fields
          or  either modulated, or unmodulated radiofreguency
          radiation?

     Some of  the in...,vitro and in vivo data on unmodulated RF have
suggested the existence of mechanisms by which human health
effects, but  not carcinogenicity, may be inferred.*  Both
unmodulated and extremely low frequency,(ELF)-modulated
radiofrequency (RF)  fields of sufficient intensity can give rise

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to thermal effects.  Noivthermal biological effects also have been
reported in some animals exposed to RF fields*  It is well
established that some in vitro and in__YJtYQ experiments on 1LF
have shown nonthemal biologic effects at fields of moderate
intensity, and there are some suggestive effects at lower levels.
Furthermore, ELF-modulated RF fields assumed to be nonthemal can
produce many of the biological effects of ELF fields alone.
Hypothetical constructs relating observed biological effects to
possible health effects (specifically, increased cancer risk)
have been delineated.  However, there are at present insufficient
data on raany of the critical steps in the linkage to infer
causality on the basis of animal or cellular data.

     3.   Has the Agency properly evaluated the way in which the
          findings on biological effects and field-tissue
          interaction mechanisms affect the interpretation of the
          human studies?                   ..  _

     No, the EPA has not evaluated how the findings on biological
effects and nonionizing field and tissue interaction mechanisms
relate to the interpretation of human studies.  The strength of
epidemiologic data depends on identification of supporting       *
evidence from in vitro and jji	vivo data.   This relationship has :
not been developed in the report.    The critiques of studies of
biological effects are contained in the discussions of the
several chapters.

     4.   Is the choice of topics in Chapter 5 appropriate and is
          the interpretation of the biological effects literature
          as it relates to carcinogenesis supported by the
          available information?

     The heading of chapter 5, "Supporting Evidence of
Carcinogenicity," is inappropriate.  The interpretation of the
biological effects in the in...,.yitro systems as presented by the
report does not make a case for Carcinogenicity.  The
Subcommittee found a lack of balance in the analysis and
presentation of evidence in this chapter.  Specific individual
experiments ,need critical review.

     5*   Is the Agency's carcinogen classification system
          applicable to electromagnetic fields?

     Nonionizing electromagnetic fields should not be classified
under EPA's chemical carcinogenesis system because of present
major uncertainties.  These involve an incomplete understanding
of which aspects of field-tissue interactions give rise to
biological effects.  Properties of the various electric and
magnetic fields such as phase angle, polarization, transients,
and frequency range may contribute to different biological
effects.  For these reasons, the use of EPA's classification
scheme at this time would be inappropriate and confusing.

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     6.   Does the information cited in the document support the
          conclusion that there is not enough information to
         • designate specific values of magnetic field strength as
          being hazardous 'to human health?


     Yes, there is insufficient information to designate specific
values of magnetic-field strength that may be hazardous to human
health, for two reasons.

     a.   There is insufficient evidence from the human
          epidemiology data and from animal/cell experiments to
          establish eause-and-effeet relationships between low
          frequency electric--and magnetic field exposure and
          human health effects and cancer.

     b.   The precise nature of the environmental lov frequency
          electric and'magnetic field potentially related to
          human disease remains to be elucidated*  In addition to
          field strength, parameters such as the time-varying
          nature of the magnetic fields and the relevant
          time/exposure parameters need to be determined.        *
     The Subcommittee also wishes to express two specific policy
recommendations that in its view follow inescapably from the
scientific recommendations.
     POLICY RECOMMENDATION #1:  The Subcommittee is unanimous in
its belief that the question of electric and magnetic field
effects on biological systems is important and .exceptionally
challenging, and that the Subcommittee's advice to the EPA should
be that the report should be rewritten by EPA, and then re-
reviewed by the Science Advisory Board.

     POLICY RECOMMENDATION 12;     EPA should complete its
efforts with, regard to RF electromagnetic fields (including
microwaves) and issue exposure guidelines independent of present
issues pertaining to lower frequencies.  The current EPA report
inadvertently leads even the careful reader to conclude that the
potential 
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substantial resources on the study of such radiation over m
period dating back to the EPA's inception, and EPA should
complete its efforts directed toward the issuance of RF exposure
guidelines,  RF fields present long-known and well-understood
hazards such as temperature elevation in tissue and heat stress
resulting from acute exposures against which users and the
general public must be warned and protected.   Any published
exposure guideline should specifically'identify the hazards from
RF exposure.

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 *•- ---x     ••>*.. *.:u-*" ort^2-Q  INTRQB0CTION - •  -•***•
 ;•.•••..          ...    ,,,-.   ,  ,..,,,    .  .. -.,.--.      ,,.. > •  ,.  ,,,.
 2.1  Background

      At th» request of the Environmental Protection Agency's
 Office of Radiation Programs, the Office of Health and
 Environmental Assessment prepared Evaluation of ti^e Potential
 Carclnoaenicitv of Electromagnetic Fields,  m January 1990, EPA
 staff  requested orally that the Science Advisory Board (SAB)
 review this document.  At its next meeting, in May 1990, the
 SAB's Radiation Advisory Committee (RAC) responded by
 establishing a Nonionizing Electric and Magnetic Fields
 Subcommittee under the chairmanship of RAC member Dr. Genevieve
 Matanoski,  An earlier draft of the Evaluation was reviewed on
 June 23, 1990, by a panel chaired by Dr. Richard Griesemer of the
 National Institute of Environmental Health Sciences;  this review
 was not a Science Advisory Board review. .....

      After wide consultation and consideration of more than 250
 scientists,  the Director of the Science Advisory Board selected
 seventeen members for the Nonioniiing Electric and Magnetic
 Fields Subcommittee:                                             *

 Dr.  A.  Karira Ahmed, Princeton, New Jersey
,Dr.  David Bates,* University of British Columbia
 Dr.   Patricia A.  Buffler, University of Texas Health Center
        in Houston,  School of Public Health
 Dr.  Craig V.  Byus, Biomedical Sciences and Biochemistry,
      University of California-Riverside
 or.  Kelly H*  Clifton,  Department of Human oncology and
 Radiology, University of Wisconsin clinical Cancer Center
 Dr.  John DiGiovanni,  Department of carcinogenesis,
      M.D. Anderson Cancer Center
 Mr.  William E. Peero,  Electric Research and Management,
      State College, PA
 Dr.  Robert Harris,  Department of Environmental Science and
      Engineering,   School of Public Health,
      University of North Carolina
 Dr.  Clark He,ath,   American cancer Society
 Dr.  Nan Laird, Department of Biostatistics, Harvard School of
      Public Health
 Dr.  Genevieve Matanoski,**  School of Hygiene and Public Health
      The Johns Hopkins University
 Dr.  M.  Granger Morgan,  Department of Engineering and Public
 Policy,  Carnegie-Mellon University
 Dr.  Mary Ellen O'Connor, Psychology 'Department,  University
      of Tulsa
 Dr.  Donald Pierce,  Department of Statistics,  Oregon State
      University
 Dr.  Charles  Susskind, College of Engineering,
      University of California-Berkeley
 Dr.  Bary Wilson,  Battelle Pacific Northwest Laboratory

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 Dr. Richard Wilson, Department of Physics, Harvard University
      *Vice Chairman of the Nonionizing Electric and Magnetic
 Fields Subcommittee.
      **Chairman of the Nonionizing Electric and Magnetic Fields
 Subcommittee.

      On October 12, 1990, the Directors of the Office of Health
 and Environmental Assessment, Health Research, and Radiation
 Programs formally requested SAB review of EPA's Evaluation of
 Potential Carcinogenicity of Electromagnetic Fields and a related
 research agenda.   (This memorandum is Appendix A.)  The
 memorandum contained the charge to the Subcommittee* (The charge
 also  appears in Section 2.2)

      At its October 23-24, 1990 meeting, the Executive Committee
 accepted a workplan for the SAB which included four Fiscal Year
 1991  meetings of the Subcommittee to undertake, and complete its
 reviews of the carcinogenicity and research agenda documents.

      The Federal Register published a notice December 18, 1990,
 announcing both the availability of the Evaluation of i^he
 Potential Carcinoaenicity of Electromagnetic Fields and the first;
 meeting of the Subcommittee.  At the first meeting, January 14-  :
 16, 1991, in Washington, D.C., IPA staff and contractors briefed
 the Subcommittee on the document, the public provided more than a
 day of oral comment, and time was allotted for Subcommittee
 discussion.  Before adjourning, the Subcommittee formed into
 three groups which would prepare papers for consideration by the
 Subcommittee at its next meeting.  These groups were:
 Physics;  Mr. Feero, Dr. Susskind,* Dr. Richard Wilson
 Biology:  Dr. Ahmed, Dr. Byus, Dr. Clifton, Dr. DiGiovanni,
          Dr. O'Connor, Dr. Bary Wilson*
 Epidemiology;  Dr. Bates, Dr. Buffler, Dr. Harris, Dr, Heath,*
               Or, Laird, Dr. Pierce
      * Authored paper after discussion with group.

     The Subcommittee met for the second time April 12-13, 1931,
 in San Antonio, Texas.  The Subcommittee considered three group
papers, heard three invited speakers (Dr. Russel Reiter of the
University of Texas Health Science center at San Antonio, Or,
Asher Sheppard of the Pettis Memorial Veterans Hospital in.Loma
 Linda, California, and Dr, Arthur Pilla of Mt. Sinai School of
Medicine In Mew York City), listened to oral comment from three
members of the public, and appointed a writing group to prepare a
draft Subcommittee report for consideration at the Subcommittee's
July 23-25, 1991,  meeting in Washington, DC. (This July meeting
also began the Subcommittee's review of the research agenda.)

     During the course of its review, the Subcommittee received
almost a thousand pages of written public comment from about
three dozen individuals and organizations.  The Subcommittee
listened to oral comment from about 40 individuals.  There was

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some_;overlap, 'between those ..providing "oral' and""written public
comments.  •••  ;•'"•'•        •          ":- >• -'"

     The Subcommittee edited this report at the July 23-25, 1991,
meeting, subsequently approved it by mail, and forwarded it to
the Radiation Advisory Committee.  The Radiation Advisory.
Committee addressed the Subcommittee report at its September 18-
20, 1991, public meeting and forwarded it to the SUB'S Executive
Committee to be considered at its October' '29-30, "1991, public
meeting.  After approval by the Executive Committee and minor
editorial corrections as suggested by the 'Executive committee,
the report was transmitted to the Administrator of the
Environmental Protection Agency.

2.2  Charge to the Subcommittee

          The Agency seeks the advice of the. Board on the
     accuracy and completeness of the entire document and on
     the question of whether the interpretation of the
     available information reflects current scientific
     opinion,  in addition, we would "like the Board to
     address the following specific issues!

          1.   Is the interpretation of the human and
          animal evidence of carcinogenicity supported
          by the available information?

          2.   Does the animal or biological'effects
          information provide a basis for postulating
          that there is a human hazard from exposure to
          extremely low frequency fields or either
          modulated or unmodulated radiofreguency
          radiation?

          3.   Has the Agency properly evaluated the
          way in which the findings on biological
          effects and field-tissue interaction
          mechanisms affect the interpretation of the
          human studies?

          4.   Is the choice of topics in Chapter 5
          appropriate and is the interpretation of the
          biological effects literature as it relates
          to carcinogenesis supported by the available
          information?

          5.   Is the Agency's carcinogen
          classification system applicable to
          electromagnetic fields?

          6.   Does the information cited in the
          document support the conclusion that there is

                                8

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not enough information to designate specific
values of magnetic field strength as being
hazardous to human health?

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                    3.0 REVTEW OF THE DOCDMEHT

 3.1 Response to the Charge

      The charge to the Subcommittee was to review the document as
 to  the accuracy and completeness of the information provided, as
 well as the interpretation of the scientific data.  The EPA
 document has serious  deficiencies and needs to be rewritten. It
 is  often difficult to tell what  the EPA's position is when
 reading the Evaluation due to many Internal inconsistencies.
 Portions of the draft lead to conclusions which differ from the
 conclusions stated elsewhere  in  the-documents-Such
 inconsistencies appear not only between the" body and the
 executive summary,  but also between different pages of the
 document itself.

      Consequently,  the document  requires a logical reorganization
 and complete rewriting with particular attention to careful and
 precise use of  language.   A simple editing of the present text
 would not be sufficient.   The Subcommittee consciously refrained
 from providing  a  list of particular inconsistencies because it
 does not want to  mislead the  EPA into believing that editing     4
 alone will  address  the Subcommittee's concerns.                  •

      six specific questions were  posed in the charge to the
 Subcommittee,   with respect to the Subcommittee's charge and the
 six  questions that  were posed, the Subcommittee responds as
 follows,

      1.    Is  the  interpretation of the human and animal evidence
           of  carcinogcnicity  supported by the available
           information?

      currently  available information is insufficient to conclude
 that  the electric and magnetic fields are carcinogenic.   Some
 human epidemiologic data report an association between surrogates
 for  electric' and  magnetic  field exposure and an increased
 incidence of  some types of  cancer, but the conclusion of
 causality  is  currently inappropriate because of limited evidence
 of an  exposure-response relationship and the lack of a clear
 understanding of  biologic plausibility.

      ?.   Do«s the  animal or biological  effects information
          provide a basis  for postulating that there is a human
          hazard  from exposure to extremely low-frequency fields
          or  either modulated or unmodulated radiofrequency
          radiation?

     Some of the in...vitro and ijD_giy.o data on unmodulated RP have
 suggested the existence of mechanisms by which human health
effects, but not carcinogenicity, may be' inferred.   Both
unmodulated and extremely low frequency  (ELF)-modulated

                               10

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radiofrequency  (RF) fields of sufficient intensity can give rise
to thermal effects.  Nonthermal biological effects also have been
reported in some animals exposed to RF fields.  It is well
established that some in vitr^ and in viyg experiments on ELF
have shown nonthermal biologic effects at fields of moderate
intensity, and there are some suggestive effects at lower levels
Furthermore, ELF-modulated RF fields assumed to be nonthermal can
produce many of the biological effects of ELF fields alone.
Hypothetical constructs relating observed biological effects to
possible health effects (specifically, increased cancer risk)
have been delineated.  However, there are at present insufficient
data on many of the critical steps in the linkage to infer
causality on the basis of animal or cellular data.

     3.   Has the Agency properly evaluated the way in which the
          findings on biological effects and field-tissue
          interaction mechanisms affect the interpretation of the
          human studies?

     No, the EPA has not evaluated how the findings on biological
effects and nonionizing field and tissue interaction mechanisms
relate to the interpretation of human studies.  The strength of  '
epidemiologic data depends on identification of supporting       •
evidence from in vitro and in vivo data.   This relationship has
not been developed in the report.    The critiques of studies of
biological effects are contained in the discussions of the
several chapters.

     4.   Is the choice of topics in Chapter 5 appropriate and is
          the interpretation of the biological effects literature
          as it relates to carcinogenesis supported by the
          available information?

     The heading of chapter 5, "Supporting Evidence of
Carcinogenicity," is inappropriate.  The interpretation of the
biological effects in the in vitro systems as presented by the
report does not make a case for carcinogenicity.  The
Subcommittee found a lack of balance in the analysis and
presentation of evidence in this chapter.  Specific individual
experiments heed critical review.

     5    Is the Agency's carcinogen classification system-
          applicable to electromagnetic fields?

     Nonionizing electromagnetic fields should not be classified
under EPA's chemical carcinogenesis system because of present
major uncertainties.  These involve an incomplete understanding
of which aspects of field-tissue interactions give rise to
biological effects.  Properties of the various electric and
magnetic fields such as phase angle,  polarization, transients,
and frequency range nay contribute to different biological
                                11

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effects.  For,these reasons, the use of EPA's classification
scheme at this time would be inappropriate and confusing,

  -. ,  6.   Does the information cited in the document support the
          conclusion that there is not enough information to
          designate specific values of magnetic field strength as
        ,-••• being hazardous to human health?


     Yes, there is insufficient information to designate specific
values of magnetic-field strength that may be hazardous to human
health, for two reasons.

     a.   There is insufficient evidence from the human.
          epidemiology data and from animal/cell experiments
          to  establish unequivocal cause-and-effeet
          relationships between low frequency electric and
          magnetic field exposure and human health effects
          •and cancer.

     b.   The precise nature of the environmental low
          frequency electric and magnetic field potentially      *
          related to human disease remains to be elucidated.     :
          In addition to field strength, parameters such as
          the time-varying nature of the magnetic fields and
          the relevant time/exposure parameters need to be
          determined.

3.2 Comments on the Executive Summary

     The executive summary of Potentiaj^.jgaffcjiioqenicitv of
ElectroinaLgflgJt-i-C._F.i.eldg is not adequate.  Special care should be
taken to ensure that it reflects the contents of the revised
freport exactly, without drawing any conclusions not substantiated
by the body of the report.  Not a few readers (and post news
sredia) are sure to give only cursory attention to the full 366-
page text and to depend'for the gist of it on the executive
summary, so special care must be taken to make it.readable and
accurate*

3.3  Comment* on Chapter 2

   3*3.1  Eloctric and Magnetic Fields and Mechanisms for
Biological Interactions

     Chapter 2 attempts to do four things: describe the physical
characteristics of electromagnetic fields? explain how fields
couple with the body; quantify ambient exposuresi and discuss
mechanisms of biological interactions,  A comprehensive treatment
of these four areas would constitute a book-length text.  The
authors have compounded their difficulties by attempting to make
the presentation relevant to the entire range of frequencies,

                                12

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from ELF to microwaves.  Trying to present all the above in less
than forty pages was destined to result in a superficial and
spotty treatment.  The authors should reduce their scope to a
more manageable level by emphasizing the lower-'frequencies, for
which guasi»tatic analysis is appropriate.  The report should not
attempt to teach field theory.  Instead, it should present
material toward the physical, understanding needed in later
chapters.  Simplified but logical and correct relationships mist
be drawn from the large body of Knowledge that encompasses the
theory of electricity and magnetism, together with the second law
of thermodynamics.  In particular, relationships of charges,
forces, motion, and time rates of change should be presented for •
simple situations.  It is an assumption, not yet disproved, that
they also apply to more complex (biological) situations.  The
difficulties lie in calculating such complex situations and
knowing the boundary conditions.

     The draft report separates electric and magnetic fields
according to frequency, but the way in which these fields are
likely to differ is poorly described.  The following' should be
highlighted,
                                                                 >

     a)   Ionizing frequencies (e.g., gamma and x radiation): the
          product hf (PlancJc's constant times frequency) is above
          the ionization threshold, so that ionization and
          destruction of a simple cell are possible (even at low
          intensity, although with correspondingly lower
          probability).

     b)   High nonionizing frequencies (e.g., microwave and other
          radiofrequency radiation): hf is below threshold and no
          ionization takes place, but both electric and magnetic
          fields penetrate insulating and partially conducting
          bodies and can produce heating, as do microwave ovens,

     c)   Extremely low frequencies (e.g., powerline
          frequencies): electric fields are strongly attenuated
          in partially conducting bodies.  The electric field E
          in such bodies derives primarily from changes in the
          magnetic field B, according to the equation
          curl E = -*9B/Bt, or in words, the spatial rate of
          change of the vector 1 equals the negative of the time
          rate of change of the vector B, so that it is not alone
          the magnitude of the magnetic field that is important,
          but also the rate at which it changes with time.

     The draft report lacks a discussion of the actual parameters
of the total electromagnetic fields that are likely to be
important for subsequent chapters.   There is no recognition that
the effects on a system of charges (including the human body)  are
in forces,  as summarized by the Lorenz force law


                               13

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  F -  q(E + v x B),  where v is  the velocity vector and q is the
  charge?  or in words,  that the force consists  of two components-
  (1)  the product  of charge and electric field,  and  (2)  the product
  of charge and velocity times  the magnetic field and sine of the
  angle between them.   This point  is  not made in the draft report.
  There are many implications.

      Under some  circumstances charges  in some bodies act
  coherentlyi   this  provides one potentially promising route for
  investigating mechanisms of biological interactions with electric
  and  magnetic, fields.   Another route for investigation is the
  existence in biological tissues  of  permanent  magnets,  such as
  those found in some soil microorganism and in honey bees.  In
  some circumstances these magnetic structures  appear important  to
  living organisms;   however,, there has  not been systematic
  investigation of the  prevalence  of  such structures or their
  importance.

      3.3.2   Exposure....:  .   ,..„„.   ..  ^	 ...... ,    ._.   ....

      in  the  discussion of epidemiology,  all mention of exposure
  is couched  in the  vague terms of "electromagnetic  fields" or ev«i
  "magnetic  fields."  The EPA's Human Health Assessment Group      :
 normally relates cancer incidence to a long-term average of some
 exposure parameteri   Although that  may be appropriate for most
 cancer-indue ing  agents,  the averaging  time may well be shorter
 for an agent  that  increases cancer  in  a new way.   However, if
 there are risks, it is not clear which parameters  of electric  or
 magnetic fields  will  be the important  ones.   It is appropriate
 for the  report to  focus on the time-integrated exposure (or dose)
 metric,  but  it is  important as well that other parameters be
 adequately treated.

      which critical parameter of the magnetic-field intensity  H
 should be discussed?   It  could be dH/dt (the time  rate of change
 of H),  or dH/dt  above some threshold applied randomly  or in some
 particular sequence over  some period of  time.  It  could be
JH(t)  dt  (the  integral  or  sum  of  H over a time  t),   as  implied by
 the draft report? or  the  amount  above  a  threshold Hc,_
 \[H(t) - H } dt,*  or the  amount with  a saturation H_, JH(t)  dt
^(for H < Hm) andjH(t)  dt  +J5 dt (for H > H_).  ft may not t
 f ^ ^ ft ^ t* *l rfH, ^m db_ _ %*_«» « 1 *l  	i bk ^^.^ __ ._ — _^^_  ^^i__._ ^ __	,	_» *	^? __*_	   __»  *_•_
feasible t&'be ali-inelusive,sbut some disculsion~of""the
plausible possibilities is recommended.

     The report also fails to discuss background fields other
than fluctuations,  if we accept there is no new force, the
exposure parameter is E + v x B; and inside the body,
curl E = -^B/dt.  One of the principal contributions to
background exposure comes as we move with a velocity v through
the earth's magnetic field B.  For many of us, this component is
vastly increased when v is the velocity of an aircraft.  Yet the
draft report is written as if the only background of importance

                                14

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were the ambient SO-Hz  field.  That  is clearly wrong and should
be corrected.  And of course this varying background is a source
of confusion in any epidemiological  study in ways that the draft
report  fail* to discuss.               ,   .»,.,,.- .

     3.3.3  Models

     The rather extensive discussion of models in the report
should  be reduced to a  tabulation of the prevalent hypothesized
models, with reference  to when each  was introduced and to what
extent  attempts to explain experimental findings by each have
been successful.  The strengths and  weaJcnesses identified in the
literature should be tabulated.  For example, the cyclotron-
resonance model has been criticized  on two counts in a simple
paper by John Sandweiss (Bioelectromaemeti,gg llj 203-205, 19§o) :
(l) the cyclotron radius at the assumed field exceeds the size of
the object, yet several revolutions  inside are needed to get a
resonance,* and (2) the  mean free path of an 'electron in the
medium  is so short that no resonance seems possible—a problem to
which reference is made, but whose fundamental nature is not
brought out.

     3.3.4  Fluctuations                                         -

     A  graph on p. 2-15 of the draft report shows the current
densities at which biological effects are expected, as well as
the noise fluctuations.  There are other papers on fluctuations,
A recent publication by Robert Adair in the Physical Review (A43:
1039-1048, 1991), which also served  as the basis of his
presentation at the Subcommittee's 15 January 1991 meeting, is a
good summary of the apparent points  of conflict between the
biological effects attributed to weak electric and magnetic
fields  and the constraints of known  physical principles.

     If a finding is repeatable but  not explainable by existing
physical theory,  it must be clearly  labeled as such.
Hypothesized mechanisms in such cases are desirable and should be
presented.  However, they must be discussed in terms of strengths
and weakness.es in predicting the observed phenomena, and the
points  at which they do not fit present understanding.  For
example, the calculation of thermal  noise in a single cell would
prove to b* inapplicable if it could be demonstrated that the
bodies under consideration are not isolated cells but
agglomerations of cells of substantially larger dimensions than
individual cells, so that calculations based on single cells
would have to be revised? or if ferromagnetic materials are
involved,  An additional point is that biological systems are
inherently nonlinear in hierarchies  that extend from molecules to
cells,  to tissues, and  finally to organs and organ systems,  so
that appropriate physical models must account for nonlinear
behavior, as well as noneooiilibrium  physical characteristics,
commonly seen at the atomic level rather than the molecular.

                               15

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3.4  Comments on Chapter 3

     3.4-1  Comments

     The Subcommittee feels that the report's discussion of
epidemiologie findings is •• seriously deficient, given the central
importance of -'such data in evaluating possible human health risles
in.this perplexing field.  Extensive revisions are therefor®
necessary both' in. chapter 3 and in 'the report * s summary and
Conclusions'.  Although the EPA report achieves nearly couplet®
coverage 'of pertinent epidemiologic work- published through 1989
and properly approaches workplace exposures separately from
residential exposures, the manner in which these data are
described and-''evaluated is inadequate-In major respects.

     a)   In general, the report's review 'and analysis of
          epidemiologic findings is unfocused-and diffuse.  Its
          writing is often repetitive and imprecise, and
          descriptions of data are frequently mingled with
         'interpretative comments. '-As a 'result, -the report lacks
          cohesiveness, is difficult to read, and loses          -
          effectiveness in communicating its findings and        *.
          conclusions.                                           :

     b)   The manner in which studies are reviewed is uneven.
          Some studies are clearly less substantial than others,
          yet they often receive equal or greater attention.
          Discussion of findings includes too much unwarranted
          speculation about causal interpretation,  often such
          speculation appears unbalanced, giving emphasis to
          positive findings while de-emphasizing negative ones.

     c)   The critical inportance of exposure assessment does not
          receive sufficient attention, particularly in relation
          to surrogate measures and to potential
          misclassification.

     <3)   In evaluating individual studies, and then reaching
          conclusions for the field as a whole, the report fails
          to focus coherently on the major epidemiologic issues
          that ultimately shape any assessment of risk.  In
          addition to exposure assessment, these issues
          particularly involve ability to discern exposure-
          response relationships, to make precise measurements of
          risk levels, and to evaluate the potential influence of
          confounding variables.  The report greatly needs to
          address these particular issues in an organized and
          critical manner.
                                16

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3.4.2  Reconmendat i ons

a)   Chapter 3 should be extensively re-worked.

          Major consideration should be given to full
     published studies or studies in which manuscripts have
     received peer review and are in press.  Data presented
     in abstract form, as letters to journals, or as case
     series anecdotes should be clearly labeled as such.
     Where other data deserve review (such as the recent
     work by Peters et al.), their pre-publication nature
     should be recognized.

          The Subcommittee suggests focusing detailed
     discussion of findings on the several studies of
     greatest importance and, in those instances, perhaps
     not exceeding three or four pages..each.  Other studies
     (abstracts, letters, etc.) could be summarized more
     briefly.  An appendix might be used if it seems
     necessary to include extensive detail,

b)   Coverage of the literature should be extended through  '
     1990, and beyond as available, especially with respect :
     to the study by Peters et al.  The 1989 Coleman et al.
     study (Brift jTf Cancer) deserves fuller consideration,
     as does information suggesting a role for traffic
     density as a confounding factor.

c)   A succinct summary table displaying only key findings
     (Note;  There is a "summary table" on pp. 3-127 to 3-
     131 of the EPA's October 1990 document.) and
     limitations in major studies may help to focus the
     assessment and might become a nucleus for formal meta-
     analysis of data.  It nay also be useful to construct
     graphs that display odds ratios and confidence
     intervals for various population/exposure comparisons
     in major studies.

d)   It. may be useful to compare data across studies in
     relation to cancer site, e.g.,  risks observed for
     childhood cancers as a whole as opposed to leukemia or
     central nervous system tumors in particular.

e)   Throughout the report,  special care should be taken to
     avoid gratuitous speculation or surmise which may favor
     either negative or positive interpretations of data
     beyond the actual limits of those data.   The
     conservative intent of the report can only benefit by
     evenhanded caution and careful precision in its
     wording.
                          17

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     3.4.3  Exposure Assessment-.;->>*   •-•'- w  •-  .

     A separate, expanded section should be developed addressing
issues of exposure assessment.  Such a section should
particularly discuss the value and limitations of exposure
surrogates, gradients, and models in relation to epidemiologic
investigations.          ^iTi

     a)   gxposure Surrogates.  The "use of surrogates for
          exposures, particu^arly^for  pasfrmnmeasured exposures,
         _ is not uncommon.in'occupational epidemiologic studies.
          The use of wire codes in community studies, as done in
          the tfertheimer, Savitz, and  Peters studies,, ;ls
 ......     appropriate and defensible.  g?hV use of surrogates may
          very well result in less misclassification than occurs
          when inherently variable spot present-day measurements
          are used to represent unmeasured average exposures that
          occurred in past years.

     b)   Exposure Gradients«  A gradient in exposures of study
          subjects is necessary in environmental or occupational.
          epidemiologic studies.  The  choice of cut-points in
          dichotomous or multistage exposure classifications may :
          influence the results of statistical analyses.  This
          matter may deserve some summary comment relative to
          reported studies.

     c)   Exposure Models.  Use of exposure models may be
          superior to the direct use of exposure measurements for
          current exposures.  Exposure models based on available
          historic information that can be validated by use of
          current measurement data are particularly useful for
          studies dealing with past unmeasured exposures.  Wire
          code surrogate data have been indexed to magnetic field
          levels in a relatively unsophisticated approach to
          modeling.  Progress is being made in this area (H. R.
          Plynn et al., "Validation of expert judgment in
          assessing occupational exposure to magnetic fields in
          the utility industry," Appl. Occup. Envj,ro^,_^Hvq. 6:
          141-145, 1990).  Exposure modeling has been addressed
          in the course of the Peters  study and one hopes this
          tt£il be discussed in the forthcoming publication of the
          work.

     3.4.4  Criteria for Assessing Significance of Data

     The revised report should summarise the epidemiologic and
statistical principles that govern the report's assessment of
epidemiologic data.  Such a section should include both
methodologic aspects and interpretive  considerations and should
apply those principles to the overall  evaluation of epidemiologic
evidence in this field.

                                18

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      Important methodologic topics  useful  for assessing
 individual  studies  include  how a  study measures  exposure  (extent
 of  exposure miselassification), how subjects  are selected to
 insure  comparability, how potential confounding  variables are
 addressed,  choice of statistical  measures,  and considerations of
 study size  and power.   Criteria for interpretation of results in
 the field as a whole include consistency among different studies,
 strength of association,  degree of  evidence for  exposure-response
 relationships, and  potential clinical specificity.

      Also important for assessment  of epidemiologic data is
 consideration of the biological plausibility  of  epidemiologic
 findings in relation to findings  from other research disciplines.
 Although the Subcommittee did not directly  address this larger
 issue in detail, the Subcommittee does recognize the critical
 importance  of such  issues in reaching a valid assessment of
 possible cause-effect relationships between.nonionizing-radiation
 exposures and human cancer.   Such considerations will ultimately
 need  to balance the strengths and weaknesses  of  epidemiologic
 findings in relation to the strengths and weaknesses of evidence
 in  allied disciplines (experiments  in animal  toxicology, in
 cellular and molecular  systems, and in the  physics of nonionizing
 radiation).

 3.5   Comments on Chapters 4  and 5

      3.5.1  Overview

      Both chapters  mix  review and evaluation  in  an inappropriate
manner.  Studies should first be  suTOnarized objectively.  They
 should then be evaluated  in  a discussion that covers both strong
 points and  weaK points.

      Biological and potential  health effects  from 1LF exposure
now constitute an active  area of  research.  The  report should  be
updated to  include  data that  have become available since the
release of  the present  draft.

      ELF and. RF data should be presented and discussed in
completely  separate sections  of the report, with comment and
conclusion* provided separately for each frequency range.  •
However, wb,*re both ELF and RF are present  (e.g., ELF-modulated
RF;  ELF transmission lines carrying or picking up RF),  such data
should be presented and discussed under both headings.

      The summary tables included  in the chapters were helpful,
Such  tables should be expanded and updated to reflect recent
research findings.

     From the information presented in chapters 4 and 5,  it is
clear that hypothetical constructs relating observed biological
effects to possible health  effects  (specifically, increased

                                19

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cancer risk) can toe delineated. ^.However, there are insufficient
data on many of the critical steps'in the linkage to infer
causality on, the basis of animal oy eelluJ«.ar data*

     3.5.2  Comments on Chapter 4

     This chapter deals with biological effects observed in
animals exposed to electric and magnetic fields in the ELF range
and to RF fields assumed to be nontharmal.   "  '  '

 7"  Taken as a whole, 'animal 3ata reviewed and discussed in this
chapter, together with data from moire .recent animal experiments,
strongly suggest (and in some instances can, be said to
demonstrate) that ELF  magnetic and electric fields are capable
of eliciting biological effects*

     The distinction between biological effects and health
effects is an important one.  It is especially relevant in the
context of, .the question of possible health .effects from, electric
and magnetic field exposure.  ' The report must be precise in
distinguishing between these two concepts and carefully guard    ,
against the tacit assumption that the observation of one         !
(biological effects) automatically implies that the other (health
effects). exists.

     in response to the specific charge to the Subcommittee to
comment on the value of animal data in Interpreting human
epidemiologic studies, the Subcommittee believes that the animal
data provided are not easily applied to the interpretation of
results from human epidemiologic studies for the following
reasons:

     a)   There are few data from different laboratories that
          demonstrate consistent biological effects using the
          same experimental protocols.  However, newly published
          information is emerging that will address this
          shortcoming.

     b)   There have been no lifetime animal studies in which
          carcinogenesis was specifically investigated as a
          consequence of magnetic-field or electric-field
          exposure.

     c)   With few exceptions, animal studies were not directed
          at testing of a specific model or hypothesis relevant
          to possible mechanisms of electric and magnetic field
          effects in biological systems.

     d)   There is insufficient evidence of linear or
          monotonically increasing exposure response from the
          animal studies reviewed, and  where response is linked


                                  20

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           to exposure (or dose),  the effects appear to  be  "all or
           none11  above some threshold,

      e)    Fi*ld  intensities used  in the experiments reviewed vary
           widely and  are often above those commonly encountered
           by humans.

      3.5.3  Comments on Chapter 5:

      The title of Chapter 5 should  be changed.   The studies
 reviewed and cited should not  be  presented  as "supporting
 evidence for carcinogenicity." The report,  in fact,  reviews data
 that  are relevant to and consistent with the hypothesis that
 electric and magnetic fields may  increase cancer risk,  A
 positive lifetime carcinogenicity study would constitute
 supporting evidence.   Such a study  has not  yet been done.  In
 fact,  this chapter deals with  potential mechanisms  of interaction
 of electromagnetic fields with biological systems.   The revised
 report should make it clear that  these cellular effects can only
 establish relationships and mechanisms of interaction.

      In  view of  the testimony  to  the Subcommittee regarding the  *
 theoretical  (mainly therpodynamic)  constraints on biological     "'
 effects  of low-frequency low-intensity fields,  Chapter  5 should
 include  a discussion of the underlying assumptions  regarding
 size,  structure,  and conductive and dielectric properties  of the
 biological  systems (cells,  organs,  or  whole  animals)  under
 consideration.   The lumped transmission line model  for  signal
 detection in collections of cells as presented to the
 Subcommittee in  testimony by Dr.  Arthur Pilla,  for  example, may
 serve  as  such a  set of  assumptions.  These should be  contrasted
 with the  assumptions  used by Dr.  Robert Adair in  his  recent
 Physical .Review  paper (A43;  1039-1048,  1991),

     EPA  should  consider deleting discussion of data  on electric
 and magnetic field exposure of plant cells,  but adding  the
 voluminous results available in connection with electric and
 magnetic  field stimulated bone repair.

     Not  mentioned in this  document  is  the lack of effects
 reproducible among laboratories,   and lack of agreement or
 understanding of what constitutes'exposure or dose.  Until there
 is progres*  in these  two areas it will  remain impossible to
 summarize the results of this field  in  a manner that will
 approach  "a  consensus viewpoint."

     A carefully worded  statement regarding the difficulty of
 some of the  assay  techniques should be  included in this chapter.
 Training  in  one aspect of biological assays may not qualify one
to conduct an assay on another system.'Many laboratories have
 reported  failure to replicate a result when  in  fact the
 laboratory lacked the necessary expertise to conduct the assay

                               21

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appropriately.  Conversely,.,a laboratory may report positive
results because it lacks the necessary expertise to carry out
reliable experiments.

     A number of studies are presented dealing with DMA/field
interaction.  No effects were found on breakage of strands or
repair of damaged strands.  There is no evidence that genetic
mutations are induced by ELF electromagnetic fields.  However,
effects cf ELF magnetic fields on gene transcription and
translation have been reported.

     EPA should  carefully review epigenetic factors in cancer
risk.  Such factors include possible effects on:
transcription/translation, hormonal effects, and  effects on the
immune system.

     Fairly small fields have been reported .to..alter the flux of
calcium ions across cell membranes.  Although some of the jjj
Xi£.£o calcium efflux data are open to concern about experimental
design and physiological interpretations, these effects appears
to be characterized by "windows" in frequency and intensity.
Although lower in amplitude, this alteration in calcium ion flux*
appeared in  the same direction as changes caused by known cancer
promoters.    An important consequence of altered calcium flux
would be a change in production of parathyroid hormone and
ornithine-decarboxylase.

     Melatonin is a hormone with important regulatory functions.
A number of experiments have shown correlation between breast
cancer and decreased melatonin production.  Exposure of rats to a
variety of low-strength electric and magnetic fields has been
shown to decrease melatonin levels in  blood and pineal gland.
                                                     -**

     The melatonin data are an important reason for recognizing
the existence of biological effects due to electric and magnetic
fields.  It is not clear, however, that melatonin changes lead to
health effects.  Although the phenomena are well described in the
report, they should not be presented as "supporting evidence of
carcinogeniQity."  More recent data on breast cancer and prostate
cancer  in males should be included in the melatonin discussion,
because increased risk for these specific cancers was
hypothesized on the basis of the melatonin findings.

     References that are missing include the Gabriel et al. paper
and the Heltz references that were supplied to the subcommittee
by Dr. Martin L. Meltz.  This chapter (or the mechanism chapter)
should include mention of the work of Dr. James C. Weaver and
Dr. R. Dean Astumian.  The work of C. A. L. Bassett and others on
pulsed electromagnetic field (PEMF) treatment of bone is also
pertinent (see, for example, C. T. Brighton and S. R. Pollack,
Eds., Electromagnetisjn_jja_Mediej.ne and Biology. 1991).
                                22

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In summary, the Subcommittee believes the following;

a)   The EPA's interpretation of the human and animal
     evidence of earcinogenicity is not supported by data
     available in the literature.

b)   Biological effects and health effects must be'clearly
     distinguishedi and although there may now be
     hypothetical constructs for linking observed biological
     effects to cancer risk, there is insufficient basis
     from animal and cellular data for postulating human
     cancer risk from exposure to ELF electric and magnetic,
     fields.

c)   In part because of insufficient data, EPA has not
     properly evaluated the ways in which proposed
     biological mechanisms of electric-.and magnetic fields
     may affect interpretation of human data.  However, the
     melatonin findings as they relate to male breast and
     prostate cancer, and other work on DMA transcription
     leading to enhanced growth, may constitute findings
     from which biological mechanisms to assist in          *
     interpretation of human data may eventually be         :
     developed.

d)   The title for Chapter 5 is misleading and should be
     changed; although the topics discussed in Chapter 5 are
     relevant to the issue,  the underlying assumption of
     the existence of increased risk is disturbing*

e)   The data presented in Chapter 5 do not constitute
     supportive evidence for carcinogenic effects of
     electric and magnetic fields in humans and animals.
                          23

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              4.0  ADDITIONAL COMMENTS OH THE SCIENCE

      The Subcommittee's mandate was  to  review the EPA report
 answer specific «|uestions in relation to it. In view of "the
 opportunity that the Subcommittee.had during its Amiiberations to
 hear testimony and discussions .regarding.the 4ssue of any risk
 associated with ELF.,  in the brief sections that follow, the
 Subcommittee gives a summary of its  collective  response to what
 it has identified as substantive  questions.  Until these questions
 have been answered,  no opinion can be advanced  on the possibility
1 of a relationship between ELF and human disease.

      The Subcommittee 'of 17 individuals represented expertise in
 twelve disciplinary areas:   biostatistics, engineering,-
 epidemiology,  experimental biology,  exposure assessment,
 medicine,  neuro-endocrinoiogy, physics,  physiological psychology,
 radiation oncology and earcinogenesis,  risk  analysis and
 toxicology.   The breadth of opinion  and diversity of view within
 the  Subcommittee would likely be  replicated  by  any other group
 with a correspondingly wide spectrum of expertise.

      The Subcommittee feels it important to  express its viewpoint?
 on three underlying scientific issues,  concerning (a)            !
 epidemiology,  (b)  biological effects, and (c) carcinogenicity.
 These issues are critical for the understanding of scientific
 issues in research regarding electric and magnetic fields'and
 must be addressed in  any future EPA  discussion  of the potential
 carcinogenicity of electric and magnetic fields.

      a)    The  Subcommittee has concluded that the epidemiological
           evidence is suggestive  of  an  association between
           surrogate measurements  of  magnetic-field exposure and
           certain cancer outcomes.   In  such  studies, the
           existence of  confounders is always a  possibility, but
           since no common confounder has yet been identified, the
           existing evidence cannot be dismissed,  in the absence
           of much better exposure information and an
           understanding of  which  escposures ;-are  significant, no
           precise exposure-response  relationship has yet been
           adduced.  This lack, together with limited
           understanding of  possible  biological  mechanisms,
           prevents the  inference  of  cancer causality from these
           associations  at this time.

      b)    The  Subcommittee  accepts that  effects on biological
           systems have  been shown to occur at moderate field
           intensities.  (An  example of such effects is the well-
           documented  work on phosphenes.)  However,  the evidence
           for  effects at very low field  strengths is not so
           widely accepted.   Even  if  effects  on  living systems at
           lower fields  do occur,  the assumptions leading to
           estimations of physical constraints for effects on

                                24

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     isolated small spherical cells without ferromagnetic
     structures may not be applicable to larger cells or
     cell systems such as neurons or neuronal networks.
     Many intervening steps must be clarified before the
     biological phenomena so far shown can be taken as
     direct evidence of health impairment or carcinogenesis
     in the human.

c)   The EPA document does not present a holistic model of
     carcinogenesis within which the strength of existing
     evidence concerning the carcinogenic properties of
     electric and magnetic fields can be assessed.  The
     revised document should do so.  Low-frequency electric
     and magnetic fields do not carry enough energy to cause
     mutations directly.  The Subcommittee recognizes that
     the incidence of cancer might well be affected by an
     agent that does not produce mutations.  The known
     influence of factors such as hormonal imbalance and
     nutrition on cancer promotion is an example of
     epigenetic effect.
                          25

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                   5.0  Policy Recommendations

     The Subcommittee also wishes to express two specific policy
recommendations that in its view follow inescapably from the
scientific recommendations.

     POLICY RECOMMENDATION fl:  The Subcommittee is unanimous in
its belief that the question of electric and magnetic field
effects on biological systems is important and exceptionally
challenging, and that the Subcommittee's advice to the EPA should
be that the report should be rewritten by EPA, and then re-
reviewed by the Science Advisory Board.

     POLICY RECOMMENDATION #2:     EPA Should complete its
efforts with regard to RF electromagnetic fields (including
microwaves) and issue exposure guidelines independent of present
issues pertaining to lower frequencies.  The current EPA report
inadvertently leads even the careful reader to conclude that the>
potential carcinogenicity of electric and magnetic fields of ELF
(i.e., power line) frequencies is the only—or at least the
principal—subject of concern with regard to nonionizing fielda.*
Such a conclusion would reinforce the skewed and somewhat        ;
sensationalized picture presented to the public in recent years
by the news media and government agencies responding to this
publicity.  The report should therefore declare explicitly that
the attention given to nonionizing electric and magnetic fields
derives in the first place from long-standing concern over'the
hazards of RF (including microwave) radiation.  EPA has expended
substantial resources .on the study of such radiation over a
period dating back to the EPA's inception, and EPA should
complete its efforts directed toward the issuance of RF exposure
guidelines.  MP fields present long-known and well-understood
hazards such as temperature elevation,in tissue and heat stress
resulting from acute exposuresagainst which users and the general
public must be warned and protected.  Any published exposure
guideline should specifically identify the hazards from RF
exposure *

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                                           APPENDIX A
M» tnff.
           UNITED STATES ENVIRONMENTAL PROTECTION'

                         WASHINGTON. Q.C 20460
                                                   AGENCY
                           , ocr 12 m
                                                      OfftCC Of
 SUBJECT:  Science Advisory Board Review of the EPA
           th* Carcinofenieity of Slectro«af^?i
 FROM:
           William a. Fmrlana,
           Director
                 °5
                 of
TO:
of
           Ken Sexton, Sc*0.
           Director
           Qffica of Health ,.
           Office of Research
          Director
          Office of Radiation
          office of Air mud Radiation  (AHE-45i)

          Kathleen Cortvmy,  0FO, Radiation Advisory
          Science Mvisory  Board  (A-liUF)

                                                         review
                        doe«a«nt» ver* prepared *M reviewed
                         ?a omc* off »«««axfeft 2
                      will b* availtisie to the  SA1 in e*rl
                        * •?**»}•* *or »!•«•• to tfte public in
                 an external review draft.  TUe Atfenev im
                      *1}0 °°— nt "«*•* »S » »!^««=
                      »viw.-An-Mrii.r drift IM* *lr«dy- l»«rv

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   .            ,               ir
relating to tha  oia2li! w? ?S*


                                                       -

     *'    5 ™^lltMpW;tl011 of   *  ujwn-and aniaal evidence
          of oarcinogwueity rapport* by tha
          inrozmation?



     2 *                                 '
                         f°r P°««*«in«r that  thare is     ian
         hazard froB exposure to «xtr«B«ly  low tz*m*ncy  fiiiSs

                       lltad °
    «£ *    fi&Sif i.^itz «£x**nrrw T^T-r.|^%^^w1 tjt j^,,^ ^ 4m_..^ ^_ j ^%_ ^      .   .  .
                                           th* way  in which the
                                        and
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                          to?ic\in chapter S appropriate and is
                   <                      *upp
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or which organization might do the research.  We are-.'requesting
the SAB to address the  following  issues in theiir-feview' of the •*••
documents                         •             "-'W^r?^',^*-..*:'

     1}  Does the document identify  the major research needs for
         EMF?  specifically are any  identified needs
         inappropriate  and are all the needs identified?

     2)  Is the level of detail sufficient to set priorities
         among the research needs?

     3)  Do any research needs stand out  as higher priority
         issues for assessing human  health risks?
                           "A~r"

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             APPENDIX B:  Detailed Technical Comments

Comments o£ the individual group members on Chapter 4 follow*

     The described animal studies focus exclusively on RF
exposures and thus bear little relevance to ELF fields produced
by transmission lines and household electricity.  The mechanisms
of tissue effects from  1000 Khz exposure may not relate to
mechanisms at 60 Hz.  Therefore, as pointed out previously, RF
and ELF field effects should be handled separately in this
section of the report.

     The specific presentation of experiments in this chapter
introduces problems.  For example, reanalysis of the Guy et al.
data from 1985 to reach conclusions other than those presented by
the authors is inappropriate in this type of report.  Sealing to
normalise absorption rate is questionable.  Some RF studies may
be excessively thermal. The relevance of all studies should! be
discussed in regard to  the spectrum of exposure frequencies.

     The cited studies  appear to have little relevance to ELF    t
fields as produced by transmission lines and household           *
electricity.   For example, there is no evidence that the
interaction mechanisms  involved at 1000 MHz are in any way
similar to those at 60  Hz.   Since the interaction is most likely
to depend critically on frequency, scaling to normalize
absorption rate is certainly inappropriate. Moreover, the
grouping of glandular organs implied in the presentation is
highly unorthodox.  No  conclusions for ELF can be derived from
these experiments.

     The microwave chapter should give the conclusion as
originally stated in the  1985 report by Guy et al., which
combined all malignant  tumors and reported a significant
difference between exposed and controls, but this difference
disappeared when benign tumors were included.  The Guy report
concludes that the observed differences are not of biological
significance,.

     Kuch attention is  given to the fact that the exposure
condition*via .the Guy study were "...calibrated to simulate human
exposure at; the. upper limit allowed by the ANSI standards" scaled
from the weight of a small child exposed to 450 MHz (a standard
radar).  These calculations  apparently do not take into account
that resonance for animals in the circularly polarized waveguide
used by Guy differs from estimates on resonance taken in an
anechoic chamber or a multimode cavity.
                               S-l

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      The  use  of  the  post  hoc analysis  of  the  Guy data  in this
 document  must be seriously questioned.  Such  an analysis should
 at  the very least be submitted for publication before  it can add'
 any benefit to the document.   Such re-analysis of data is quite
 common in literature.   If Kuni believes  in this re-analysis, he
 should submit it for publication with  all the appropriate
 co-authors. If the study  had been  intended as a cancer study or
 if  it were ELF one might  think that  it was important enough to
 the overall theme of the  report to waive  the  peer review
 requirement.  Since  the original Guy study meets neither of those
 two criteria, there  is no reason to  include such a re-analysis in,
 the present document*

      The  report  states that the Sprague Dawley rat was chosen to
 mimic heterafenaus variety of human  population.  But the Guy
 study used all males and  sprague Dawleys  are  an albino strain.
 Creel has suggested  many  unusual attributes .of albinos.   The
 paper by  Creel on albino  rats as experimental 'animals  should
 therefore be  cited and  discussed.

      If the Guy  post hoc  analysis  is included in Chapter 4, it
 should be given  much less attention  and the statistical        .  *
 guestionability  of the results should  be  focused.  Four       .  :
 significant differences can be found in the post hoc analysis of
 the Guy data.  The fact that the exposed  group lived longer than
 the control was  not  significant; nor was  the  analysis  of the
 cause of  death,   with regard to the  tumor incidence, the post hoc
 analysis  showed  significant differences using a one-tailed
 Fisher's  exact test  for benign pheoehromocytoma of the adrenal
 medulla (p <  0.023), malignant tumors  at  all  sites (p  < 0.0012),
 carcinomas at all cites (p <  0.018), and  glandular carcinoma for
 combined  glands  (p <  0.018)*  The EPA report makes no mention of
 how many  statistical tests were done on these data.  It would
 seem  that multiple independent tests on all the possible effects
 would have yielded a suspected significance that might even
 exceed the four  reported.

      The  Prausnitz and Susskind study was excessively  thermal.
 It  is unclear how an exposure  of o.l mW/c»2 over 4.5 minutes
 could indue* a 3.3 degree  C temperature increase, for  example.
 this  study has been criticized and these other criticisms Should
 be  included in this  report.  The most  important to include are
 probably  Roberts and Michaelson (Health Phvsics 44: 430-433.
 1982)  and Kirk (Life span  and  careinogenesis,  in J. Elder and

 EPA-60Q/8-83-Q26F, 1984).   The  criticisms focus on the fact that
 the colony of mice had an  infection  of pneumonitis during the
 study and that the leucosis reported may not have been leucosis.
 The authors note that the  exposed animals lived longer than the
 controls  (an observation also made by others)  and suggest that
 the mild  heating enabled exposed animals to thwart the virus with
which the colony was infected.  There is also a question of how

                                B-2

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many multiple  comparisons were made to arriv** **• +-K
statistical  significant effects reported          h* Very fev





a robust study or  conclusion.
                              B-3

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