VOLUME 2
             COMMENTS  ON  THE
  ADVANCE NOTICE  OF  PROPOSED RULEMAKING
 "OZONE - DEPLETING  CHLOROFLUOROCARBONS
     PROPOSED PRODUCTION RESTRICTION"
                   BY  THE
     ENVIRONMENTAL  PROTECTION AGENCY
               SUBMITTED  BY
E. I. DU PONT DE NEMOURS  &  COMPANY (INC.)
           WILMINGTON,  DELAWARE
             JANUARY  5,  1981

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                             VOLUME 2

                        Table of Contents
                                                           Page
X..  APPENDICES

    A.   Description of Major Pertinent Reports and
         Submissions on the Chlorofluorocarbon/Ozone
         Issue                                             A-l-13

    B.   The Du Pont Development Program on the
         Alternatives to Commercial Chlorofluoro-
         carbons                                           B-l-15

    C.   The Energy Consequences of Chlorofluoro-
         carbon Regulation (Battelle Report)                C-1-2S

    D.   A Comparison of Some of the Principal
         Findings of the November 1979 National
         Academy of Sciences' Report and the
         October 1979 United Kingdom Department
         of the Environment's Report                       D-l-5

    E.   Chlorofluorocarbons and Ozone - The
         Science                                           E-l-69

    F.   Effects of Ozone Depletion

         1.  Human Skin Cancer;  Review by Professor
             Frederick Urbach, M.D.                        F-l(1-199)

         2.  Measurement and Instrumentation;  Review
             by Dr. William H. Klein.                      F-2(l-19)

         3.  Agricultural Crops; Review by
             Professor R. Hilton Biggs.                    F-3(l-13)

         4.  Aquatic Ecosystems; Review by
             Dr. David M. Damkaer.                         F-4(l-36)

NOTE:  Appendices G-L  and  Section  XI-Bibliography-appear  in
       Volume 3.

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APPENDIX A
                  DESCRIPTION OF MAJOR PERTINENT
                  REPORTS AND SUBMISSIONS ON THE
                  CHLOROFLUOROCARBON/OZONE ISSUE
                                A-1

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                                          Reports & Submissions
          In  this  appendix  we  provide  a  listing  and  brief
abstract  of   important  publications,   reports,    updates   and
submissions on  the Chlorofluorocarbon/Ozone  Issue.   While  this
list  by no  means  exhausts the  available  literature,   it  does
incorporate major  documents  which  we believe should  be  reviewed
as part of any evaluation of this  complex  issue.   Full copies of
the cited documents which are not  already  listed by  EPA  as being
in the  public  record  are submitted  as  part of  the  Du Pont  ANPR
comments.
                               A-2

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                                          Reports & Submissions
1.    Flurocarbon/Ozone Update, Du Pont, September, 1977.

          This was the first  in  a  continuing  series  of bulletins
published by  Du Pont  to  provide  customers  with an  overview  of
the most current developments in the CFC/0., controversy.

          This  edition  includes  an  assessment  of  the  signi-
ficance  of   the ozone  depletion  theory,   a  discussion  of  the
September, 1976  NAS  report,  a  review of  technical  developments
and  future   technical  needs,  and   a  brief  look  at   the  inter-
national situation.

2.    Non-Aerosol   Propellant   Uses    of    Fully   Halogenated
      Halocarbons, Du Pont, March,  1978.

          A   comprehensive   response   to   EPA's  request   for
information on  non-aerosol propellant uses of  fully  halogenated
halocarbons,   this  Du Pont  submission  supplements  information
provided  to   EPA  in  ten   previous  verbal  presentations at  EPA
public meetings.

          The report  describes  the  essentiality or  benefits  of
the  major  nonpropellant  uses of  chlorofluorocarbons.   It  also
provides  a   status   report  on   the   alternative  fluorocarbon
development   program   and   the   possibility   for   control   of
inadvertent CFC emissions.

3.    The   Ozone   Controversy    and   Its    Relationship    to
      Refrigeration and Air Conditioning, ARI, June, 1978.

          This  bulletin  was  published   by  the  Air  Conditioning
and  Refrigeration  Institute.  It  addresses principle  issues  in
the  CFC/0-  controversy,   including:   status  of  theory,  essen-
tiality  of   refrigeration  and  air-conditioning,  CFC  emission
                                A-3

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                                          Reports & Submissions
control,  risks  of  regulating,  economic  scope,  action  of  other
countries and regulatory options.

4.    Fluorocarbon/Ozone Update, Du Pont, October, 1978.

          The  second  in  a  series,  this  bulletin  reviews  the
CFC/0,  issue  and  briefly  explains  EPA's  Phase  I  regulations
banning  aerosol  propellant  use   of  CFCs.   It  also  offers  a
simplified  discussion  of  recent  technical  developments  in  the
science and comments on the program for future research.

5.    Non-Propellant Uses of Fully Halogenated Halocarbon -
      No 2, Du Pont, June, 1979.

          This   Du  Pont    report   updates    and    supplements
information provided to EPA in  the March  15, 1978  report  of  the
same title.

          The  specific  areas of  mention  are  the  status  of  the
CFC/0.,  Depletion Theory,  development  programs on  alternatives
to  commercial  CFCs,  potential  for  CFC  emission  control  and
refrigerant  emission  control   through  the  use of  Dytel®  leak
detective.

6.    The Fluorocarbon Industry Research Program and Current
      Uncertainties in the Ozone Depletion Theory, CMA, November,
      1979.

          This  report  summarizes  the   research  programs  being
sponsored by  the Chemical  Manufacturers Association Fluorocarbon
Project Panel  (CMA/FPP)  to  reduce uncertainties in  the science
of  the  theory  of  depletion  of  ozone  by  CFCs.   The  summary
identifies  major  uncertainties  and their  significance,  reviews
the  pertinent  research  program   and  comments   on  the  expected
results and timing.

                                A-4

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                                          Reports & Submissions
7.    Chlorofluorocarbons and Their Effect on Stratospheric
      Ozone (Second Report), UK DOE, October, 1979.

          This report is  a  comprehensive review of  UK  policy in
light  of  the  state  of  knowledge  of  the  science  of  ozone
depletion.  Part  2  of the  report  is  a detailed analysis  of  the
CFC/03   science   prepared    by    "The   Stratospheric   Research
Advisory Committee"  (STRAC).  The  committee  consisted of experts
from  the  UK  Meteorological office,  universities,  industry  and
government laboratories.

8.    Stratospheric  Ozone  Depletion  by Halocarbons:   Chemistry
      and Transport, NAS, November, 1979.

          This report was prepared  by  the  Panel on  Stratospheric
Chemistry  and  Transport   (PSCT)  of  the  National  Academy  of
Sciences  (NAS).   It is  an  update  on  the effects  of halocarbons
on the  stratospheric  ozone  layer based on available data  at the
time of preparation.  It  also assessed  the  uncertainty limits of
predictions based on those  available data.

9.    The  National   Academy  of   Sciences   (NAS)   and   U.   K.
      Department  of  the   Environment   (DOE)  Reports,  Du Pont,
      November, 1979.

          Du Pont  prepared   this  comparison of  the  first  eight
principle findings of the NAS report  with  quotations from the UK
DOE report addressing the same subject matter.

10.   The  Stratosphere;    Present  and  Future,  NASA  Reference
      Publication 1049, December, 1979.

          The Clean  Air  Act Amendment of 1977  requires that the
National   Aeronautics  and   Space  Administration   report   its
                                A-5

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                                          Reports & Submissions
assessment of the current state of knowledge  of  the stratosphere
to both the EPA and Congress biannually.

          This  report  is  the  first  in  that  series.   Summary
documents of  seven working  groups  organized by  NASA  to  assess
the state of  knowledge  in  different areas  of  the  science  were
assembled into this report.

11.   Protection  Against Depletion  of  Stratospheric  Ozone  by
      Chlorofluorocarbons,  NAS, December, 1979.

          This report  is a  two part report  of  the work  of  two
committees of the National  Academy of Sciences.

          Part I - Causes and Effects of Stratospheric Ozone
                   Depletion.

              Prepared   by   NAS   Committee   on   Impacts   of
              Stratospheric   Change  (CISC),  it is  often referred
              to as  the CISC Report.   It  examines  the effects,
              including  both  biological  and  climatic  effects,
              which may occur as  a result of  the  predicted ozone
              depletion  described in  an earlier  NAS  report  by
              the Panel on  Stratospheric Chemistry and Transport.

          Part II - Alternatives for  the Control  of Chlorofluoro-
                    carbon  Emissions   and  Options   for
                    Implementation.
              The   NAS   Committee   on   Alternatives   for   the
              Reduction of  Chlorof luorocarbon  Emissions (CARCE)
              examines the  alternatives,  costs,  feasibility and
              timing of possible methods for reducing chloro-
              fluorocarbon emissions.
                               A-6

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                                          Reports & Submissions
12.   Comments  on  the  National  Academy  of  Sciences  Report;
      "Stratospheric Ozone  Depletion by  Halocarbons;   Chemistry
      and Transport", Du Pont , January,  1980.

          A Du  Pont submission  to  EPA,  this report  comments  on
the  uncertainty  estimates  and  various  technical  points  in  the
science,  and  provides  a comparison  of   the  NAS  report  by  the
Panel on  Stratospheric Chemistry and  Transport (PSCT)  with  the
UK DOE 1979 report.

13.   Fluorocarbon/Ozone Update, Du Pont, January,  1980.

          Du  Font's third  update  in  this  series focuses  pri-
marily  on  the   NAS PSCT   report.   The  report's  treatment  of
uncertainties and the impact of the report are discussed.

          The update  also  compares comments in  the  NAS  report
with comments from  the UK DOE report on the same subjects.

14.   An  Overview  of   Industry  Efforts  to   Investigate   the
      Potential  for Chlorofluorocarbon  (CFC)  Emission Reduction,
      Du Pont, February, 1980.

          This   update   prepared   for    the   EPA   reviews   the
activities  in various  industries   to  reduce  emissions  of CFCs.
Industries  discussed  include  mobile air-conditioning,  flexible
polyurethane   and    packaging   foam,    solvents,    commercial
refrigeration and  air-conditioning,  industrial  gas sterilization
and liquid food-freezing.
                               A-7

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                                          Reports & Submissions
15.    The "Importance of Chlorofluorocarbons and Polyurethane
      Foams, SPI, March, 1980.

          Published by  the  Urethane Division  of  the Society  of
the Plastics  Industry,  this bulletin  addresses  the use of  CFCs
in foams, the essentiality of the products,  the lack  of suitable
alternatives to CFCs and emission control of CFC processes.

16.    A Critique of the Rand Corporation Draft Report, "Economic
      Implications of Regulating Chlorofluorocarbon Emissions
      from Non-Propellant Applications", Du Pont,  March, 1980.

          Du  Font's   critique  discusses   the  Rand   report's
strengths, data  limitations,  analytical  assumptions,  limitations
on the use  of  the findings,  and areas  needing  clarification and
further  work.   Rand's  treatment of  individual  uses of  CFCs and
the theoretical,  methodological,  practical  and legal aspects  of
the economic incentive regulatory approaches are examined.

17.    The Du Pont Development Program on Alternatives to
      Commercial Chlorofluorocarbons, March, 1980.

          This  submission reports  on  the  status  of  the Du Pont
alternatives   program   designed   to   identify   and    develop
fluorocarbon compounds  that  could  be used in place of  the  CFCs,
but which would not contribute significantly  to  potential  ozone
depletion.
                               A-8

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                                          Reports & Submissions
18.   Comments on the December, 1979 Report by the National
      Academy of Science's Committee on Alternatives for the
      Reduction of Chlorofluorocarbon Emissions (CARCE),
      Du Pont; April, 1980.

          Du  Font's  comments  on the  CARCE  report are  divided
into  two  categories:   a  review of  general  concepts  underlying
the  CARCE  report  and  a  review  of  the  data  and  conclusions
developed by the CARCE report.

19.   Fluorocarbon/Ozone Update, Du Pont, April, 1980.

          Du Font's  fourth  edition of the  series  provides brief
discussions of  the  NAS  CISC  and NAS CARCE reports  and includes
comments on international activity.

20.   Summary;  Research Program on Effects of Chlorofluoro-
      carbons on the Atmosphere, CMA, May,  1980.

          This  report  is Revision  13  of  a  summary of on-going
research  programs,  sponsored   by   the   Chemical  Manufacturers
Association, on effects of chlorofluorocarbons in the atmosphere.

          These  industry-sponsored  programs  are   focused   on
developing  information  needed  to   fill  gaps  in  the  existing
scientific  knowledge of the  potential effects  of  CFCs  on ozone
and any subsequent environmental impact.

21.   Energy Consequences of Chlorofluorocarbons Regulation,
      Battelle, May, 1980.

          Battelle  prepared   this  comprehensive analysis  of  the
energy  penalties   of   regulation   of   chlorofluorocarbons  for
Du Pont.
                                A-9

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                                          Reports & Submissions
          The  report   analyzed   four   major   uses   of   CFCs:
automotive air-conditioning, refrigeration,  insulating  foams  and
liquid food-freezing.

22.   Comments on the December,  1979 Report by the Committee on
      the Impacts of Stratospheric Change (CISC)  of the National
      Academy of  Sciences,  Du Pont, May,  1980.

          In  this  submission  to EPA,  Du Pont  comments  on  the
assessment of  the  problem, the  general  conclusions and  the  key
findings  of   the report  by  the  NAS Committee  on  Impacts  of
Stratospheric Change (CISC).

23.   Analysis of the Conclusions of the British and American
      Reports on the Effect of Chlorofluorocarbons on the
      Atmospheric Ozone, EEC, June, 1980.

          This  report  to   the   EEC,  prepared  by  G.   Brasseur,
focused primarily on:   (1)   an analysis of  various  reports on the
CFC/OO  controversy,  including  their  conclusions,  certainties
and  uncertainties,   and  (2)  developing  a  list  of projects  to
reduce the uncertainties in the next five years.

          Side-by-side comparisons  of the NAS Report  and the UK
Report  are   included  as well  as  an  in-depth  analysis  of  the
uncertainties in the science.

24.   Chlorofluorocarbons and the Environment, EEC, June, 1980.

          This report  by  the  EEC Commission  issued  to  the  EEC
Council  was   a  re-examination   of  the  scientific  data  and  a
re-examination of   economic  and  technical  data  on CFC use  in
member nations.
                               A-10

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                                          Reports & Submissions
          The  re-examination of  the  science  was  based  on  Dr.
Brasseur's  [Brasseur,  1980] report, highlighting only  his major
findings.

25.   Some Concerns with Recent EPA Communications on the
      Chlorofluorocarbon/Ozone Issue, Du Pont/ June, 1980.

          This  document  and a  transmittal  letter  from C.  N.
Hasten,   Director   of  Du   Font's  "Freon"   Products   Division,
discusses concerns  over  inaccuracies and  overstatements  made by
EPA in a number of communications.

          The   document   discusses   various   areas   of   the
controversy   including:    CFC   use   projections,   scientific
uncertainties,  detection   of  ozone  depletion   and  depletion
potential of CFC-22.

26.   An Assessment of the Chlorofluorocarbon/Ozone Problem,
      CMA, June, 1980.

          Prepared  by  the  CMA Fluorocarbon  Project  Panel, after
a  review of  the  data  base  used  by  groups  commenting  on  the
subject  of   ozone   depletion,  this  work  examines   the  relative
validity  of  one-dimensional modeling  and ozone  trend  analysis,
through an assessment of the uncertainties of each.

27.   Fluorocarbon/Ozone Update, Du Pont, June, 1980.

          In the fifth issue  of  this series, Du Pont reviews its
development program for  alternatives to  commercial chlorofluoro-
carbons.   Included  in  the   discussion  are:   1)  criteria  for
alternatives,  2)  a listing  of  chlorofluorocarbon  alternatives,
3)  the program status and plans, and 4) the timetables.
                               A-ll

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                                          Reports & Submissions
28.   Uncertainties in Chlorofluorocarbon Effects and
      Stratospheric Ozone,  SRI,  July, 1980.

          EPA sponsored  a  workshop, hosted  by SRI,  to  evaluate
the critical  issues  and  uncertainties that  were  hindering  EPA's
ability  to make  a  fully  supportable  decision  on  further  CFC
regulation.
          Eleven   participants   discussed   the   areas   of   CFC
releases, atmospheric transport  and  chemistry,  climatic effects,
human   health   effects,   biological/ecological   effects   and
economics.

          SRI  compiled  the  results  of  the  workshop  into  this
report.

29.   Research  Program  Directed  by  the Chemical  Manufacturers
      Association  Fluorocarbon  Project  Panel,   Progress  Report,
      CMA, July, 1980.

          A progress  report on the research programs directed by
the  Chemical  Manufacturers  Association   Fluorocarbon  Project
Panel was submitted to UNEP in July,  1980.

          Programs   reviewed   included   Atmospheric   Lifetime
Experiment,  Ozone  Trend  Analysis,   Atmospheric  Measurements,
Modeling and Atmospheric Chemistry.

30.   Fluorocarbon/Ozone Update,  Du Pont, July, 1980.

          In the sixth of  this series, Du  Pont  provides an over-
view  of  the  Battelle report,  "Energy  Consequences of  Chloro-
fluorocarbon Regulation."
                               A-12

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                                          Reports & Submissions
31.   Uncertainties  and  Benefit-Cost  Analysis  of  CFC  Control,
      August, 1980.

          M. J. Bailey, of the University  of  Maryland, assembled
data on the  significant effects of  continued  CFC emissions.  His
report   also   reviews  the   theory,   the   actual   technical
uncertainties and offers an appraisal of the  reliability of data
and derived  estimates.  An  assessment  of  the  risk  against  the
likelihood of narrowing the uncertainties is also included.

32.   Fluorocarbon/Ozone Update,  Du Pont, October, 1980.

          The  seventh, and  most  recent,  issue of   the  series
offers  an  overview  of the  theory  and  a   review  of  the  recent
developments in the science underlying the theory.
                               A-13

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APPENDIX B
                  THE  DU  PONT  DEVELOPMENT  PROGRAM
                          ON ALTERNATIVES
                 TO COMMERCIAL CHLOROFLUOROCARBONS
                                B-l

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                                            Alternatives Program


                         Table  of  Contents

                                                            PAGE
1.  INTRODUCTION                                              3

2.  CURRENT COMMERCIAL CHLOROFLUOROCARBONS                    4

3.  PROPERTIES OF COMMERCIAL CHLOROFLUOROCARBONS              4

4.  CRITERIA FOR ALTERNATIVE PRODUCTS                         5

5.  SCOPE OF DU PONT ALTERNATIVES PROGRAM                     5

6.  ALTERNATIVE CANDIDATES BY POTENTIAL APPLICATION           7

          a.  Refrigerants                                    7
          b.  Foam Blowing Agents                             9
          c.  Cleaning Agents                                10
          d.  Liquid Food Freezant                           11
          e.  Sterilant Gas                                  11

7.  PROGRAM STATUS AND PLANS                                 11

8.  TIMETABLE FOR COMMERCIALIZATION                          13

9.  SUMMARY OF ALTERNATIVES STATUS                           15
                                B-2

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                                            Alternatives Program

1.    INTRODUCTION

          In  response  to  the  issuance  of  the  Chlorofluoro-
carbon/Ozone Depletion  Theory,  the Du Pont  Company  and  others
launched major  research  efforts to  resolve  the  uncertainties in
the  underlying   science  in  order  to  quantitatively  verify  or
disprove the  theory.   However,  as  the outcome  of  this research
could  not   be  predicted,  Du Pont  also  initiated  a  program  to
examine  how  the   hypothetical  stratospheric  chlorine  burden
resulting from  the  emissions  of chlorofluorocarbons  (CFCs) might
be reduced.   This  program  had two  thrusts:   1)   To assess  the
technological and economic  feasibility of  reducing CFC emissions
through  conservation  and/or   recovery/recycle,   and   2)    To
identify and  develop  fluorocarbon  compounds  that  could  be  used
in place of  the CFCs  but  which  would  not  contribute  to  the
hypothesized environmental  risk.   This paper  reports the status
of the alternatives program.
                                B-3

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                                            Alternatives Program

2.    CURRENT COMMERCIAL CHLOROFLUOROCARBONS

          Six  major  chlorofluorocarbons   are  manufactured  in
commercial quantity:

              CFC-11           (CC13F)
              CFC-12           (CC12F2)
              CFC-22           (CHC1F2)
              CFC-113          (C2C13F3)
              CFC-114          (C2C12F4)
              CFC-115          (C2C1F5)

These  compounds   are   key  factors   in   maintaining  important
segments  of  the  national  economy.   Their  applications   include
the energy transfer fluid in  refrigeration and air-conditioning,
the  blowing  agent  and  insulating  gas for  plastic  foams,  the
solvent  cleaning   and   drying  medium  in  the  manufacture  of
electronic and  mechanical  equipment  and  military  hardware,  the
inerting  agent  in sterilizing gases,  and  the  freezing agent in
some  speciality  food  freezing.   Because   the  uses  are dependent
upon  the specific properties  of  the chlorofluorocarbon employed,
the compounds are not interchangeable  among the applications.

3.    PROPERTIES OF COMMERCIAL CHLOROFLUOROCARBONS

          The   commercial  compounds   contain   at   least  one
carbon-fluorine   bond   in  the   molecule   and   have   a   unique
combination  of  properties  including  low   heat  of  vaporization,
nonflammability,  low  chemical   reactivity,   and  low  toxicity.
These  properties  result  in  low  energy  consumption,  very  few
material  compatibility   problems  and  good  safety-in-use.   Also,
they  give rise to a high  degree of  atmospheric stability.
                                B-4

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                                            Alternatives Program

4.    CRITERIA FOR ALTERNATIVE PRODUCTS

          To  justify  consideration as an  alternative  product, a
compound  must   meet  the   technical  performance   of   current
commercial    chlorofluorocarbons    with   regard    to   product
performance,  toxicity,  and   safety-in-use.    It   must  meet  a
criterion  for  environmental  acceptability   (as  yet  undefined)
opposite  its potential  for  ozone  depletion.   In addition,  a
commercial process  for  its  manufacture must  be  available,  or be
developed, an economic  incentive for manufacture must exist and
the   cost   of   the   compound  must   be   compatible   with  its
value-in-use.

          A  commercial  process should  (1) utilize  raw materials
currently available or readily  developed,  (2)  generate a minimum
of  by-products  for disposal  or  treatment to  meet  environmental
regulations,  (3)  meet  health  standards  for  the   protection of
workers,  (4) provide a  product  quality suitable for  end-use
applications, (5)  be  based  on  technology within  the  capability
of  current  materials  of construction and design  knowledge, and
(6)   be   affordable    as    to   total   capital    required   for
construction.   All of  these  parameters  must be  met  with  the
expectation of a suitable return on the investment  required.

5.    SCOPE OF DU PONT ALTERNATIVES PROGRAM

          The most  promising candidates have  been  identified as
either   fluorocarbons  containing   no  chlorine   (since   these
compounds  would   not  contribute  to   the   hypothesized   ozone
destruction)  or  chlorofluorocarbons  containing hydrogen  (since
these  compounds   should  degrade   to  a  large  extent  in   the
troposphere,  through  reaction  with hydroxyl  radicals).  This  led
to    an   examination   of   all   practical    fluorocarbon    and
chlorofluorocarbon  compounds meeting one  or  the other  of  these
criteria.  Only  fourteen compounds  were  found to  comprise  this
category:

                                B-5

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                                            Alternatives Program

                 CFC-21                (CHC12F)
                 CFC-22                (CHC1F2)
                 CFC-31                (CH2C1F)
                  FC-32                (CH2F2)
                 CFC-123               (C2HC12F3)
                 CFC-124               (C2HC1F4)
                  FC-125               (C2HF5)
                 CFC-132b              (C2H2C12F2)
                 CFC-133a              (C2H2C1F3)
                  FC-134a              (C2H2F4)
                 CFC-1415              (C2H3C12F)
                 CFC-142b              (C2H3C1F2)
                  FC-1433              (C2H3F3)
                  FC-152a              (C2H4F2)

          These  compounds  have  been  or  are   being  evaluated
extensively for product  performance  (as refrigerants, foam  blow-
ing  agents  and solvents),  safety  (flammability  and toxicology)
and  manufacturing  capability.   Thus  far, only  CFC-22,  FC-134a,
CFC-141b,  CFC-142b  and  FC152a  have  survived   all  the   tests
performed.   However,  the  results  of  all  long-term toxicology
studies, which would be  necessary before  more broad use of  these
compounds  would  be permitted,   are   not  yet  available.    Only
CFC-22 has a commerical process.*

          Over  the  past  five years,  Du  Pont has  expended  over
$15  million  of technical effort  by its  chemists, engineers  and
toxicologists to:

          •      Make sample  quantities for testing.
          •      Formulate products and evaluate  performance.
          •      Perform toxicological  tests.
  CFC-142b and FC-152a are manufactured in very limited  quantities
                                B-6

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                                            Alternatives Program

          •   Obtain data to calculate atmospheric stability.
          •   Carry out process research for manufacture.

6.     ALTERNATIVE CANDIDATES BY POTENTIAL APPLICATION

          A summary of the status of  the  search  for alternatives
by application follows:

      a.  Refrigerants

          i.  Mobile Air-Conditioning -

              •   CFC-12  is  the   refrigerant   used  in  mobile
                  air-conditioning.

              •   CFC-22  and  CFC-114  mixtures  or  CFC-22  and
                  CFC-142b mixtures potentially  could  be used in
                  present equipment designed  for  CFC-12.   Both
                  CFC-22 and  CFC-142b,  however,  have  been found
                  to  produce  weakly  mutagenic   effects   in  the
                  Ames  Test.   Long-term   inhalation   tests   on
                  CFC-22 and  CFC-142b are  in  progress  in order
                  to ascertain the  significance  of  the Ames Test
                  results.    Additional  problems  with  CFC-142b
                  are  that,   by  itself,  it is   flammable  under
                  some   conditions.    Consequently,   long-term
                  field  testing  would   be  required   prior   to
                  commerciali zation.

              •   The  use  of  CFC-22  alone  would  require major
                  redesign of equipment.

              •   FC-134a  is  a  direct  substitute  for  CFC-12
                  based  on   laboratory   and  wind  tunnel  tests.
                  However,  extensive  field  testing  has  not been
                               B-7

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                                    Alternatives Program

          performed.    More  importantly,   no  commercial
          process  for   its  manufacture  has  been  found
          despite  a  large  research  effort.    Toxico-
          logical studies  are  incomplete  and limited  by
          material availability.

 ii.   Home Appliances -

      •   CFC-12 is the refrigerant used  in home appli-
          ances .

      •   Mixtures of CFC-22 and  CFC-142b could  be  used
          with  little  redesign.   Equivalent  performance
          to CFC-12 has been demonstrated.

      •   The use of  CFC-22 alone  would require  redesign.

      •   FC-134a  is  a  direct   substitute  for  CFC-12
          based on 20 months of performance testing.

      •   Toxicological  testing   and/or  process  limita-
          tions  for   CFC-22,   CFC-142b  and  FC-134a  as
          discussed   above   apply   equally   to   this
          application.

iii.   Store Refrigeration (Non-Frozen Food)  -

      •   CFC-12, CFC-22 and CFC-502 are  all used.

      •   CFC-22  has  caused some performance  problems.
          The industry prefers  CFC-502.

      •   CFC-502 already is replacing the  use  of CFC-12
          in new equipment.
                       B-8

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                                      Alternatives Program

        •   Toxicological  testing  limitations  on  CFC-22
            apply equally to this application.

   iv.  Chillers -

        •   CFC-11, CFC-12 and CFC-114 are all used.

        •   Specific   design    requirements    limit   the
            potential for a single alternative replacement.

b.  Foam Blowing Agents

    i.  Polyurethane Insulating Foam -

        •   CFC-11  is  the   product  used  in  polyurethane
            insulating foam.

        •   The  use  of any  of  the  alternative  candidates
            examined  will  result in  some  decrease  in  the
            insulating value from that of CFC-11.

        •   CFC-123 and CFC-141b  have  been  used to produce
            this  foam and  are   thought  to  be  technically
            feasible  as  replacements  —  but  a  special
            polyol will need to be developed.

        •   No  commercial   process  now  exists  for  the
            manufacture of either compound.   Toxicology of
            both compounds is incomplete.

   ii.  Flexible Polyurethane Foam -

        •   CFC-11  is  the  major CFC product  used  in flex-
            ible polyurethane foam.
                          B-9

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                                      Alternatives Program

        •   CFC-123,  CFC-133a and CFC-141b  are  technically
            feasible  as  replacements.   CFC-133a has  poor
            toxicity.   lexicological  testing  and  process
            limitations  of  CFC-123  and   CFC-141b  apply
            equally to  this application.

  iii.   Polystyrene Insulation and Packaging Foam -

        •   CFC-12 is  the major CFC product in these uses.

        •   CFC-124  and  FC-134a   should   be  technically
            feasible.   No  commercial  process  exists  for
            either  compound.    Toxicological   testing  is
            incomplete.

        •   CFC-22 and  CFC-142b mixtures  were  evaluated
            but performance was poor.

   iv.   Polyethylene  Foam -

        •   CFC-12 and CFC-114 are  the  major  products used
            in polyethylene foam.

        •   We have not  identified  a  promising  alternative
            candidate.

c.  Cleaning Agents

        •   CFC-113  is   the   product  used  in  precision
            cleaning, e.g., electronics and computers.

        •   All  possible  alternatives  either   failed  to
            meet  product  requirements,  are  toxic  or  are
            flammable.   The  closest alternative, CFC-132b,
            is  inadequate in  performance  since  it  is too
            strong a solvent.

                          B-10

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                                            Alternatives Program

      d.  Liquid Food Freezant

              •   CFC-12 is the only fluorocarbon or chloro-
                  fluorocarbon  the  Food  &  Drug  Administration
                  has approved for this use.

              •   There is no market justification  to  develop an
                  alternative product.

      e.   Sterilant Gas

              •   CFC-12  is  the  product   used  as  an  inerting
                  agent in sterilizing  gases.

              •   There is no market justification  to  develop an
                  alternative   product   specifically   for   this
                  use.  However, it is possible  that one or more
                  of the  alternatives, upon passing all testing,
                  could be adopted for  this application.

7.    PROGRAM STATUS AND PLANS

          The research and development effort  on alternatives is
continuing:

          •   Acute  and  short-term  toxicity  tests  have  been
              performed on:
                  CFC-21                    CFC-133a
                  CFC-22                     FC-134a
                  CFC-31                    CFC-141b
                  CFC-123                   CFC-142b
                  CFC-124                    FC-152a

          •   Work  has  been  terminated  on  CFC-21, CFC-31,  and
              CFC-133a due to adverse toxicological findings.
                               B-ll

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                                  Alternatives Program

•   A  long-term   toxicology   study   of  CFC-22   for
    carcinogenecity is under way  in Europe.   A similar
    test  on  FC-152a   is  in  progress  in  the  United
    States  with  results  expected  by mid  1981.   The
    same  test  has  just been  initiated  on CFC-142b  in
    the United  States  with results  expected by  late
    1982.

•   Small  scale field  tests of CFC-22 and CFC-142b  in
    automotive  air-conditioning  are  underway.   Field
    tests  of FC-134a will require production  of  sample
    material.

•   Basic  data  has  been  collected  over  the last  20
    months on  the  performance  of  FC-134a in  a  house-
    hold refrigerator.

•   Basic   data on equipment   modification   needed  to
    replace CFC-12  with CFC-22 or CFC-22  and CFC-142b
    mixtures in refrigeration  and air-conditioning are
    being  developed.

•   Work is continuing on short-term  tests  which would
    enable  the  determination  of  long-term  insulating
    performance of alternatives in polyurethane foam.

•   Work  has  been  terminated  on  CFC-123, CFC-124 and
    FC-125 due to  lack of  an  acceptable manufacturing
    process.

•   Process   research   is  continuing   on   commercial
    routes to FC-134a and CFC-141b.
                     B-12

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                                            Alternatives Program

8.    TIMETABLE FOR COMMERCIALIZATION

          Any  alternative   will  require  up  to  ten  years  for
commercial production  (assuming all  technical  and toxicological
programs yield favorable results)  as follows:

      •   Construction  and  operation of  pilot plant  to  develop
          process  design  data and  to obtain material  (40  to 50
          tons) for toxicity testing:  2 to 3 years.

      •   Long-term chronic toxicity testing:  3 years.

      •   Development of basic  design data  for commercial plant,
          including waste  disposal:   2  years  (can coincide with
          toxicity testing).

      •   Purchase  of   plant  equipment  and  the   preparation  of
          plant site:  2 years.

      •   Obtain  environmental permits:   1  year  (can  coincide
          with site preparation).

      •   Construction of plant:  1 to 3 years.

      •   Start-up to full commercial operation:   1/2 to 1 year.

      •   Prudent  business   decision would  hold  purchase  of
          equipment   and   plant    construction    for   favorable
          toxicological results.
1   Although  processes  exist  for  CFC-22, CFC-142b  and FC-152a,
    significant  expansions  or  new  facilities would  be required
    for  their increased  production and  for their  raw material
    needs.
                               B-13

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                                        9.   SUMMARY OF ALTERNATIVE STATUS
00
I
       Fluorocarbon
            #
       and Formula

       11 CC13F (a)

       12 CC12F2 (a)
  Potential Application

Blowing agent, refrigerant

Refrigerant, blowing agent,
Manufacturing
   Process

     Yes
Flammability   Toxicology

     No             Low

113 CC12FCC1F2 (a)
114 CC1F2CC1F2 (a)
21 CHC12F
22 CHC1F2
food freezant, sterilant
Solvent, refrigerant
Blowing agent, refrigerant
Replacement for CFC-11;
blowing agent
Replacement for CFC-12;
Yes
Yes
Yes
Yes

No
No
No
No

Low
Low
Low
Toxic; Dropped
Weak mutagen, Life-
       31 CH2C1F

       32 CH2F2 (b)
      123 CHC12CF3


      124 CHC1FCF3


      125 CHF2CF3 (b)

      132b CH2C1CC1F2



      133a CH2C1CF3
refrigerant

Aerosol propellant

No primary application; low
boiling compound; Dropped

Replacement for CFC-11;
blowing agent, refrigerant

Replacement for CFC-12;
refrigerant, sterilant

Refrigerant

Replacement for CFC-113;
too strong a solvent;
Dropped

Blowing agent, propellant
     Yes

Not commercial


Not commercial


  No; Dropped


  No; Dropped

  No; Dropped



     No

Not commercial
    in U.S.
     No      time  test  underway

     Yes      Toxic; Dropped


     Yes            Low


     No             Low


     No             Low

     No        Not  known



     No      Very  incomplete

              Embryotoxic;
     No         Dropped

-------
       Fluorocarbon
            f
       and Formula
      134a CH2FCF3  (b)

      141b CH3CC12F




      142b CH3CC1F2

      143a CH3CF3  (b)

      152a CH3CHF2  (b)
                       Potential Application
                       Replacement for CFC-12;
                       refrigerant, others?

                     Replacement  for CFC-11;
                     blowing agent
   Manufacturing
      Process
        No
Yes, developmental
                     Blowing agent,  refrigerant        Yes

                     Refrigerant                 Not commercial

                     Propellant,  refrigerant           Yes
Flammability   Toxicology

           Very incomplete;
              testing  in
    No         progress
     Yes     Weak mutagen

             Weak mutagen;
                Lifetime
     Yes     test underway

     Yes       Incomplete

     Yes   Low; Lifetime test
                underway
i
M
Ul
(a)  existing  products  for comparison;  (b) contains no chlorine.

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X.  APPENDIX C
                    THE ENERGY CONSEQUENCES OF
                  CHLOROFLUOROCARBON REGULATION
                         (BATTELLE REPORT)
                               C-l

-------
                                            Energy Consequences
                                            of CFC Regulation
         The following discussion  on  the energy consequences  of
chlorofluorocarbon regulation  summarizes  work done by  Battelle,
Columbus Division under  contract  to E.  I.  du Pont de Nemours  &
Company.

         The  discussion  is  organized  for  various  levels  of
interest and varying need for detail.

         •   The  first  section  is  the  Summary  and  Conclusions
             which deal only with the  net results and  conclusions
             to be drawn.

         •   Next is  the Introduction describing  the  objectives
             and scope, and methodology.

         •   Following next are brief discussions  of  each  of the
             four major  CFC use areas investigated,  giving  some
             of the rationale involved.
             /
         References and appendices cited  in this  section refer to
the full report from Battelle [Battelle,  1980].  The full report,
including appendices  giving detailed  rationale  and  calculations
as  well  as  tabulation   of  the   results,  is  included  in  our
submission.
                               C-2

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                                            Energy Consequences
                                            of CFC Regulatfon
                        TABLE OF CONTENTS

                                                      Page


Summary and Conclusions                                 4

Introduction                                           10

     Objective and Scope                               11
     Methodology                                       11

Automotive Air-Conditioning                            14

     General Considerations  s                          14
     Energy Penalties                                  16

Refrigeration                                          18

     General Considerations                            18
     Energy Penalties                                  19

Insulating Foams                                       24

     General Considerations                            24
     Energy Penalties                                  24

Liquid Food-Freezing                                   27

     General Considerations                            27
     Energy Penalties                                  27
                               C-3

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                                                               Energy Consequences
                                                               of CFG Regulation
                               FINAL REPORT

                                    on
                          ENERGY CONSEQUENCES OF
                      CHLOROFLUOROCARBON REGULATION
                                    to
                         E.  I.  du Pont de Nemours
                                & Company
                                   from
                                 BATTELLE
                            Columbus Division
                                    by
                       P.  R.  Beck, J.  M. Corliss,
                       M.E.D.  Hillman, J. L.  Otis
                           and  S. G. Talbert
                         SUMMARY AND CONCLUSIONS

          The overall results of this study are presented in Table 1
in summary form and in somewhat greater detail 1n Table 2.   The results
show that there is indeed a significant energy penalty associated with
a ban on chlorofluorocarbons in the various applications studied.
          The results indicate there would be a net energy penalty of
 5.5billion or 9.5 billion gallons of fuel equivalents in the tenth
year of the ban and a cumulative total of 27.9 billion or 49.8 billion
gallons for the first decade following the ban, depending on whether
or not R-22 is adopted as a substitute for the banned CFCs. Adoption
of R-22 leads to the  smaller penalty.
Text continues on page c-7
                                     c-4

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                                 TABLE  1.   SUMMARY OF  ENERGY PENALTIES ASSOCIATED WITH A
                                           BAN  ON USE  OF CHLOROFLUOROCARBONS
                                           (millions of gallons fuel equivalent)
o

Automotive A1r Conditioning
Home & Store Refrigeration'8'
Insulating Foams
Liquid Food Freezing
Total
Using
1981
48
169
231
9
457
R-22 Where Possible
1990
326
2,003
3,169
12
5,510
Decade
2,090
10,371
15,360
106
27,927
Using Next Best
1981
161
446
231
9
847
1990
1,070
5,267
3,171
12
9,520
Alternative
Decade
6,870
27,461
15,365
106
49,802
           (a)
              Includes losses  due to  outdoor  compressor when using ammonia and  Incremental
              effect of elimination of  CFC's  1n  both  refrigerant and foams.
                                                                                                                 9

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                                        Energy Consequences
                                        of CFC Regulation
TABLE 2.  ENERGY PENALTIES ASSOCIATED WITH A BAN
          ON THE USE OF CHLOROFLUOROCARBONS
          (millions of gallons of fuel equivalent)
Using R-22
Where possible
.
Automotive Air Conditioning
Domestic & Commercial Refrigeration
Refrigerators
Freezers
Centrifugal Chillers
Food Store Freezers
Beverage Coolers
Mobile Units
Unit Coolers
Ice Makers
Water Coolers
Insulation
Commercial Construction
Residential Construction
Industrial Construction
Refrigeration
Tanks and Pipes
Transportation
Incremental Combined Effect
Refrigerators
Freezers
Mobile Units
Losses Due to Outdoor Compressor
Liquid Food- Freezing
Totals
1981
48
162
77
19
9
3
39
0
3
11
1
231
117
11
4
68
30
1
7
3
4
0
—
9
457
1990
326
1930
907
200
115
31
540
0
28
128
6
3169
1707
174
52
833
393
10
73
36
35
2
—
12
5510
Decade
2090
9980
4750
1080
600
170
2670
0
.150
660
30
15,360
7740
840
260
4420
2040
60
391
190
191
10
—
106
27,927
Using Next
Best Alternative
1981
161
173
77
19
7
3
39
13
3
11
1
231
117
11
4
68
30
1
7
3
4
0
266
9
847
1990
1070
2084
907
200
90
31
540
154
28
128
6
3171
1707
174
52
833
393
12'
73
36
35
2
3110
12
9520
Decade
6870
10,770
4750
1080
470
170
2670
.790
150
660
30
15,365
7740
840
260
4420
2040
65
391
190
191
.10
16,300
106
49,802
                C-6

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                                                                    Consequences
                                                             or CFC Regulation
           It should first be noted that these penalties describe only
the first  decade of the ban and that the annual penalty will undoubtedly
continue to grow for many decades beyond the first.  This Is because
complete displacement of the more efficient CFCs such as R-ll and R-12
will not be completed within 10 years.  Most of the applications con-
sidered have a useful life beyond 10 years, and particularly 1n the
case of insulation, replacement of the more effective CFCs would not be
complete for several decades.  Thus the energy penalty would continue to
grow well  beyond the first decade.  No attempt has been made to project
the magnitude of these future increases because of the obvious unrelia-
bility of  such long-range forecasts.  Nevertheless, 1t is certain that
the annual penalty will continue to grow well beyond the first decade.
           Alternative projections are given for the first decade because
of the unique characteristics of refrigerant R-22.  Whether or not R-22
represents a viable alternative depends upon EPA actions regarding its
future and  the attitude of industry regarding its economic feasibility.
R-22 differs from other CFCs in that it contains a single hydrogen atom.
The presence of this hydrogen atom makes it susceptible to degradation
by reaction with hydroxyl radicals.  Ironically, this "weakness" causes
it to disassociate in the lower levels of the atmosphere.  Less, there-
fore, survives to diffuse to the upper atmosphere where it may cause
harm to the ozone layer.  The impact is variously estimated to be
10 to 30 percent of the impact caused by fully halogenated CFCs.  While
scientists may not agree on just how much the impact is reduced, 1t
is clear that R-22 is a preferred material from the standpoint of the
impact on  the ozone layer.
           It is also clear that R-22 1s a preferred material in the
refrigeration and automotive air conditioning applications from the
energy conservation standpoint.  It would therefore appear to be a
desirable  compromise in the event that other CFCs are banned in these
applications.
           However, this study has focused only on the energy consequences
of a ban on CFCs, and the economic Impact of a conversion of current
refrigeration systems to R-22 has not been evaluated.  At any given

                                    C-7

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                                                             Energy Consequences
                                                             ot CFC Regulation
temperature R-22 has a substantially higher vapor pressure than R-ll
and R-12 and would require a complete redesign of the refrigeration and
automotive units for future use.  This, of course, would be a costly
procedure which the industry may not choose to undertake.  Further, since
higher pressures would be involved, the redesigned equipment would
undoubtedly be more expensive and heavier than that currently in use
and could be viewed as unsalable.  Finally, although R-22 represents a
substantial improvement with respect to possible damage to the ozone
layer, it is not regarded as completely harmless.  In weighing the sub-
stantial business risks involved, plus the possibility of future
restrictions on R-22, industry may choose to reject 1t as an alterna-
tive to the currently used CFCs.  Rather than speculate further on how
industry will view R-22 as an alternative, Battelle has chosen to simply
present the consequences if R-22 is used or if industry selects the next
best alternative.  The difference in the results is about 22  billion
gallons for the decade and 4  billion gallons in the tenth year.
          Numbers like 50  billion gallons of fuel per decade have some
meaning to petroleum economists and others closely involved with the
magnitude of the numbers relating to the energy crisis.  However, such
numbers need to be related to more familiar benchmarks for those outside
the energy industry.  Following are a few such benchmarks for the energy
penalty associated with the 9 billion gallons of fuel calculated for the
tenth year of a ban on CFCs and R-22.
          •  9.5 percent of our 1978 crude oil imports
          •  38 percent of our 1978 oil imports from Iran
          t  45 percent of the current annual oil production
             from Alaska's North Slope
          •  Energy to supply 11 cities the size of Toledo
             (population about 500,000) for 1 year
             (excluding gasoline)
         -•  Energy output of 29 nuclear power plants
             (nearly half the number in operation)
          •  18 times the expected petroleum savings
             envisioned for 1985 through the use of
             "gasohol"

                                     c-8

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                                                             Energy Consequences
                                                             of CFC Regulation
          •  73 percent of the third quarter 1978 balance
             of payments deficit (assuming oil imports are
             $25 per barrel)
          •  The fuel required to drive 12 million average
             cars (about 10 percent of all U.S. cars) for
             1 year.
          The primary conclusion to be drawn Is quite simple.   If the
use of CFCs is banned in the applications examined, there will  be
additional and serious aggravation of our current energy problems.  The
banning of some CFCs but not R-22 might reduce the Impact of the regu-
lations, provided Industry 1s willing to take the business and  economic
risks involved.
          With more extensive computation, additional data, more detailed
market information, or simply different, but still realistic assumptions,
one might derive a different net total which may be somewhat higher or
lower than presented here.  The calculations leading to these results
are, in fact, presented in some detail in the Appendices to this report
to facilitate an examination of new or different data.  The conclusions,
however, will remain the same:  A ban on the use of CFCs will  have an
adverse and serious impact on an already serious energy problem.
                                    C-9

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                                                             Energy Consequences
                                                             of CFG Regulation
                              INTRODUCTION

          Chlorofluorocarbons (CFCs) constitute a series of specially
designed synthetic fluids originally developed to perform as refrigerants.
They are of low toxicity and chemically Inert.  Over the years, 1n
addition to refrigeration, they have found a number of applications,
including aerosol propel1 ants and blowing agents for Insulating foams.
Most of these applications relate directly to their unique physical
properties and their safety features.
          However, in recent years it has been claimed that the CFCs
diffusing into the upper atmosphere are having a depleting effect upon
the protective ozone layer.  Because of this, the Environmental Protection
Agency has already banned the use of CFCs as aerosol propel!ants and
is considering further restrictions upon their use in other applications.
          In most major applications, the CFCs are used because of their
advantageous thermodynamic properties.  It is therefore logical that
exclusion of their use in such applications would carry an associated
energy penalty.  In 1979 the Freon® Products Division of the E. I. du
Pont de Nemours & Company conducted a preliminary examination of the
energy impact of a ban on CFCs in several major applications.  The results
of  this preliminary study indicated that there would be, indeed, a large
penalty if CFCs were banned and industry was forced to use less optimal
materials.   Based on these indications, Du Pont then decided to have a
more thorough examination conducted by an independent organization, and
Battelle was selected to carry out this work.  This report contains the
results of that effort.
                                     c-io

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                                                             Energy Consequences
                                                             of CFC Regulation
                          Objectives and Scope

          The primary objective of this program was to develop a realistic
estimate of the energy costs associated with a ban on the use of chloro-
fluorocarbons in major applications.  The applications covered are:
          •  Automotive air conditioning
          0  Home and store refrigeration
          •  Insulating foams
          •  Liquid  food  freezants.
                .
          The study focused only on energy consumption.  No analysis of
economics or safety was performed except that these factors were given
qualitative consideration in selection of alternatives to be used for
comparison.
          Only systems and equipment currently in use were considered.
New inventions or developments would have been considered 1f it were likely
they would have a near-term impact.  However, no such developments or
breakthroughs for these applications are apparent.
          Finally, no consideration was given to developing technologies
involving the use of CFCs for other applications such as heat pipes, solar
heating, etc.   These situations represent an additional penalty in terms
of lost opportunity but do not fit well  with the "here and now" analysis
of existing areas.

                               Methodology

          The general approach employed in all cases consisted of five
steps:
          •  Selection of one or more reasonable alternatives
             to the use of CFCs
         _•  Development of appropriate per unit engineering
             parameters
          •  Calculation of the per unit energy penalty
             Involved
          •  Development of market data for the period
            -1981 to 1990
          t  Extension of the total energy penalty for
             e»r:!» year of the decade.
                                      c-ll

-------
                                                             Energy Consequences
                                                             of CFG Regulation
          Implicit 1n the selection of alternatives is the presumption
that there will be no near-term technical breakthrough providing easy
solutions to the problem.  For example, it appears very unlikely that
any new type of refrigeration equipment will be developed over the next
decade.  Therefore, the systems considered are conventional heat pump
or compressor-type refrigeration, absorption systems, and air-cycle
systems.
          Likewise, it is presumed to be highly unlikely that alternative
fluids to the CFCs will be developed.   The CFCs were specifically
designed to optimize their thermodynamic properties in a nonflammable,
nontoxic fluid.  By definition these materials must be simple molecules,
consisting of a very few atoms.  Were there any obvious alternatives
to the current CFCs, they very likely would have been developed long ago.
While scientists are always reluctant to say "It can't be done", they
generally agree development of alternatives to CFCs having equivalent
safety and thermodynamic properties is extremely unlikely.
          Battelle therefore believes the alternatives given consideration
in this report are the most reasonable and appropriate for the time period
being considered.   The development of basic engineering calculations to
determine per unit energy penalties required a certain number of assumptions
regarding typical  systems.  For example, in refrigeration, certain
assumptions are necessary regarding the ambient conditions in which the
unit is operating.  Also, in the case of insulation, certain assumptions
were necessary regarding the overall structure of the insulated surface.
Such assumptions are detailed in the appendices along with the calcu-
lations such that if the reader wishes, he or she may test the impact of
different sets of assumptions.  However, Battelle believes that the
conditions and structures selected for this set of calculations are
reasonably typical and representative of actual situations.  The calcu-
lations themselves are relatively straightforward and follow standard
engineering practice.
*Hydrochlorofluorocarbons, for Instance CHC1F9  (R-22), constitute a special case.
 See page  c-7                        c_12

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                                                             Energy Consequences
                                                             of CFC Regulation
          In most cases market data was derived from generally accepted
authoritative sources, and assumptions were avoided wherever possible.
A 11st of references 1s provided at the end of each appendix.   In a
few cases even the authoritative sources disagreed, and it was necessary
to select one source or develop some compromise.  For example, there
1s considerable disparity 1n the opinions as to what percentage of the
time automobile air conditoners are actually 1n operation, and the
resolution of this disparity 1s detailed in Appendix C.
          Considerable amounts of the market data were derived from the
Rand Corporation draft report on the economic implications of regulating
chlorofluorocarbon emissions.  It should be noted that this  Is a  working
draft dated September 1979, with the finalized version of the  report
to be Issued later this year.  However, it is Battelle's understanding
that there will be no changes between this draft and the final report in
the market data for the applications with which this report 1s concerned
(Reference B-3, Appendix B).  However, should there by any significant
changes, the detail of marketing calculations and forecasts 1s Included
in the Appendices so that they may be incorporated by the reader.
          The time period 1981 to 1990 was selected for the market fore-
casts primarily because of the availability of data for that period,
especially data from the Rand Report mentioned above.  This does  not
necessarily presume that a ban on chlorofluorocarbons would have  an
impact as early as 1981; rather 1t presumes that the Impact during any
10-year period in the relatively near future would be roughly  the same
as those for which the forecasts have been made.
          The results of multiplying the market forecasts by the  penalties
per unit result 1n the total energy penalty for the various applications.
These results are in dissimilar units, I.e., gallons of gasoline, kilowatt
hours, gallons of fuel oil, etc.  For purposes of this report, comparison
and summation were converted to the equivalent gallons of fuel (140,000
Btu energy content) as a common denominator.  This unit was chosen because
of the more universal familiarity of the public with the meaning  of a
gallon of fuel, e.g., gasoline, as opposed to such terms as Btu's, quads
and kilowatt hours.  The actual penalty, of course, if a ban 1s enacted,
will be some mlxutre of gallons of gasoline or fuel oil, tons  of  coal,
units of nuclear power, hydroelectric, etc.
                                   C-13

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                                                             Energy Consequences
                                                             of CFC Regulation
                       AUTOMOTIVE AIR CONDITIONING

          Supporting data, references, and calculations for the discussion
of automotive air conditioning are contained in Appendices B, C, and K at
the end of this report.

                         General  Considerations

          The popularity of automotive air conditioning has grown steadily
since its inception.  Currently,  nearly three-fourths of all  domestically
produced passenger cars, about half of the light trucks, and  half of the
imported automobiles are equipped with air conditioners.  In  addition,
there are substantial after-market sales for installation for nonfactory
installed air conditioners.  These air conditioners,  at present, consume
an estimated 500 million gallons  of gasoline per year and will  consume
naarly 22 billion gallons over the course of the next decade.   The popu-
larity of air conditioning in automotive vehicles is  no longer considered
a matter of personal comfort.  It has come to be regarded as  a necessity
by many, especially those who are subjected to prolonged periods of
driving under heat stress conditions.  The air conditioner, of course,
plays a key role in reducing the  debilitating effect  of heat  stress and
thereby contributes to safety, health, and productivity.  The benefits
derived from automotive air conditioning are quite parallel to those
involved in the air conditioning  of homes and commercial buildings but
with significantly greater emphasis on safety.
          R-12 is the universally used refrigerant in automotive air
conditioning systems.  The systems have been designed specifically for R-12,
and no other refrigerant can be substituted directly  in these systems.
Thus, if the use of R-12 is prohibited, a redesign of the air conditioning
equipment will be necessary.   Prelminiary calculations eliminated absorption
and air-cycle systems as alternatives to the current  compressor CFC units.
Thus, the alternatives considered in this report involve substitution of
other fluids for systems similar to the current R-12  units but appropriately
modified for the substitute fluids.  The use of R-22, ammonia, and propane
were examined.
                                      C-14

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                                                             Energy Consequence^
                                                             of CFC Regulation"^"
          Two penalties are associated with a switch from R-12 to any
of the above three alternatives.  One is associated with the increased
weight of the vehicle.  This is because the alternatives operate under
conditions of higher pressure and will require stronger components
throughout the unit.  Whether, in fact, dependable units can be designed
within the limits of economic feasibility is open to question.  However,
only the energy considerations are within the scope of this study.
          The second penalty reflects changes in the efficiency caused
by the change of refrigerant and by the design requirements necessi-
tated by the use of refrigerants which otherwise expose occupants to
unacceptable toxicological and flammability hazards.
          It should be noted that the penalty associated with the effec-
tiveness of the unit applies, of course, only while the air conditioner
is on, probably one-third of the time on the average, but the penalty
associated with increased weight is, in effect, 100 percent of the miles
driven.
                                    c-15

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                                                             Energy Consequences
                                                             of CFC Regulation
                             Energy Penalties

          Energy penalties associated with a ban on CFCs are shown in
Table 3.  The results show that the increased fuel consumption if R-12
is banned but R-22 continues to be used will be about 2 billion gallons
of fuel for the decade, or about 10 percent more than the current fuel
used for air conditioning if R-12 were continued in use.
          If R-22 should also be banned, the next best alternative
would appear to be an ammonia system.  The penalty here for the decade
is on the order of 7 billion gallons of fuel, which is roughly one-third
more than the current fuel used for air condition'irg if R-12 were to
continue in use.
          The use of propane resulted in higher penalties due to both
cycle efficiency and weight increase.  Therefore, only the ammonia and
the R-22 systems are considered in the summary and conclusions.
          It should be noted that ammonia and propane are both flammable
and that ammonia is also toxic.  Ammonia is a disabling lachrymator.
Conceivably either or both could be prohibited from use in motor vehicles
for safety reasons.   Also, because of these characteristics, systems
employing these fluids are assumed to require a secondary loop (a secondary
heat exchanger) located outside the cab of the vehicle so that the
refrigerant does not enter the area occupied by passengers.  This further
increases both the weight and cost of the system and lowers efficiency.
Thus while ammonia and propane may be viable alternatives from an energy-
penalty standpoint, they may eventually prove impractical on the basis
of economics and safety.
          R-22, on the other hand, is nonflammable and relatively nontoxic
and, therefore, would neither require a secondary loop nor present an
increased hazard on the highway.  Its use would, however, still require
redesign of equipment and undoubtedly additional costs.
                                   C-16

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                        TABLE 3.  ENERGY PENALTIES ASSOCIATED WITH USE OF ALTERNATIVES
                                  TO R-12 VEHICULAR AIR CONDITIONING
                                  (millions of gallons per year or decade)
o
i
Penalties Associated with Refrigeration
Cycle Efficiency (Excluding Weight Penalties)
If Only CFCs
Banned
Use of R-22:
1981 34
1990 226
Decade 1450
1981
1990
Decade
If CFCs and
R-22 Banned
Use of Ammonia:
147
969
6230
Use of Propane:
193
1270
8190
Penalties Associated with Refrigeration*
Cycle Efficiency Combined with Weight*3'
If Only CFCs If CFCs and
Banned R-22 Banned
Use of R-22 Use of Ammonia
48 161
326 1070
2090 6870
Use of Propane:
207
1370
10,100
      (a)  Height penalties for either ammonia or propane systems are likely to be greater than the 12
          pounds estimated for R-22.  However, a 12 pound weight penalty has been assumed for ammonia
          and propane systems.


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                                                             Energy Consequences
                                                             of CFC Regulation
                              REFRIGERATION

          Supporting data, references and calculations for the material
in the discussion of refrigeration are contained in Appendices D, G, J
and K.

                             General Comments

          Refrigeration is the largest and probably the most important
of the current uses of CFCs.  In almost all cases our fresh food supply
1s dependent on some form of cooling, from packing and shipment through
warehousing and retail and into the home.  Even fruits and vegetables
not thought of as requiring refrigeration must be moved through the
distribution system at controlled temperatures.
          In addition to the food industry, there are a host of industrial
applications where chillers or coolers are necessary.
          Of these items, the familiar household refrigerators and freezers
are the largest market segment.  However, this market is largely saturated,
and growth of new sales is proportional to new household formation:
sales are mostly for replacement purposes.  Sales in other segments, notably
beverage coolers and mobile transportation ("reefers"), are more dynamic.
          Refrigerant R-12 is by far the most broadly used refrigerant in
this category.  Some R-22 and R-502 is  used in food store freezers.  R-ll,
R-12, R-500, R-114, and R-22 are used in centrifugal chillers, but R-ll
and R-12 are 90 percent of the total.
          Alternatives to the use of CFCs in these applications include
ammonia, propane, air-cycle, and absorption cycle.  In all cases, ammonia
was found to be the best non-CFC alternative.  Ammonia, of course, is
both toxic and flammable and would not be permitted in homes, stores, etc.,
where it might present a hazard.  Therefore, the compressor unit would
necessarily be remote from the cooling unit, requiring a secondary loop
using a safe fluid to cool the loop within the house or store.  Such units
are not Inconceivable and would resemble current home air conditioning
Installations with an added external heat exchanger.  However, there would
be a substantial economic penalty compared to an ordinary refrigerator or
freezer as well as an energy penalty.
                                    C-18

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                                                             Energy Consequences
                                                             of CFC Regulation
           In addition to the energy penalty associated with the reduced
 effectiveness of ammonia In the case of refrigerators, there 1s also a
 penalty for the lost utilization of waste heat.  A household refrigerator
 1s,  In effect, a heat pump transferring energy from food, air, etc.,
 within the refrigerator to the home.  Thus the electrical energy required
 to operate the refrigerator results In reduced heating fuel demand.  This
 energy, of course,  is wasted if the compressor unit 1s located outside
 the  home.  Of course, the reverse 1s true If the home 1s being air
 conditioned.  The net effect is calculated in Appendices G and J.
           Further,  if there were .a simultaneous ban on use of CFCs in a
 refrigerant and 1n  Insulating foams, the energy penalty associated with
 the  refrigeration cycle would be increased.  That is, because the
 insulating would be less effective, more units of cooling would be required
 from a unit operating at reduced efficiency.  This effect 1s also detailed
 in Appendixes G and J.
           In the event that R-22 were permitted in future refrigerant use,
 a secondary outdoor loop would not be required for safety reasons.  There
 would be a reduced  economic penalty; a higher pressure system would still
 be required, but this would certainly cost less than an exterior loop.
 Also, there would be no net heating penalty for waste heat because the
 unit could safely be within the home.

                            Energy Penalties

           The energy penalties associated with a ban on CFCs and the
 use  of ammonia as an alternative for the refrigeration cycle efficiency
 alone are  shown In  Table 4.  Also shown are the penalties 1f R-22 were
 allowed.   Only in the case of mobile refrigeration is the difference
 significant.  There are other differences 1n food store freezers and
 centrifugal chillers, but the numbers are small and disappear upon
 rounding. ~
           Table 5 shows the additional Impact of a simultaneous ban
 on CFCs for Insulation, as well as refrigeration for refrigerators and
 freezers and mobile units.  The Impact Is the same whether R-22 or
Text continues on page c-22
                                     C-19

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                                                             Energy Consequences
                                                             of CFC Regulation
             TABLE 4.   ENERGY PENALTIES ASSOCIATED WITH A BAN
                       ON CFCs FOR REFRIGERATION
                       (millions  of gallons  of fuel  equivalent)
Using Ammonia

Refrigerators*
Freezers*
Centrifugal Chillers
Food Store Freezers*
Beverage Coolers*
Mobile Units
Unit Coolers*
Ice Makers*
Water Coolers*
Total
1981^
77
19
7
3
39
13
3
11
1
173
1990
907
200
90
31
540
154
28
128
6
2084
Decade
4750
1080
470
170
2670
790
150
660
30
10,770
Using R-22
1981 ~
77
19
9
3
39
0
3
11
1
162
1990
907
200
115
31
540
0
28
128
6
1955
Decade
4750
1080
600
170
2670
0
150
660
30
10,110
^Secondary loop  assumed  when  using  ammonia.
                                     C-20

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                                                         Energy Consequences
                                                         of CFC Regulation
   TABLE 5.  INCREMENTAL IMPACT OF A SIMULTANEOUS BAN ON CFC
             USE IN BOTH REFRIGERATION AND INSULATION
             (millions of gallons of fuel equivalent)
                               Using Either Anmonla or R-22
                                as Alternative Refrigerant
                                 1981     1990     Decade
Refrigerators                      3       36        190

Freezers                           4       35        191

Mobile Units                       0        2         10

          Total                    7       73        391
                               C-21

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                                                             Energy Consequences
                                                             of CFC Regulation
ammonia 1s used, and amounts to an additional 391 million gallons for the
decade.   If data were available, similar calculations for other commercial
refrigeration would probably add another 100 million gallons to the total.
          Finally, Table 6 shows the additional net energy penalty for
refrigerators only if the compressor 1s located outside of the residence,
taking into account the effect on both heating and air conditioning
requirements.
          The total of all of these effects for the decade amounts to
10.5 billion gallons if R-22 were allowed and 27.5 billion gallons if
ammonia were used.
                                    C-22

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                                                            Energy Consequences
                                                            of CFC Regulation
          TABLE 6.   IMPACT OF LOCATING REFRIGERATOR  COMPRESSOR
                    UNIT OUTSIDE OF HOME
For a home not
air conditioned

For an air conditioned
home
                    Net

Average if 61% are
air conditioned
   9.11  million Btu's per year lost heat
   9.11  million Btu's per year lost heat
  -4.70  million Btu's per year lost cooling
   4.41  million Btu's per year lost heat

   6.24  million Btu's per year
  44.6  gallons of fuel equivalent per year
For:  1981
      1990
   266   millions of gallons of fuel equivalent
           per year

  3110  millions of gallons of fuel equivalent
           per year

        millions of gallons of fuel equivalent
16,300    f0r the decade
                                     C-23

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                                                             Energy Consequences
                                                             of CFG Regulation
                            INSULATING FOAMS

          Supporting data, references and calculations for this discussion
of insulating foams are contained in Appendices E, F and G.

                         General Considerations

          CFCs are employed as the blowing agents in rigid polyurethane
and polystyrene (PS) foams, which are used extensively as insulation in
residential and commercial construction, freezers and refrigerators, and
transportation equipment.  The blowing agents generally used are R-ll
and R-12.  In addition to being nonflammable and nontoxic, the CFCs have
lower heat transfer coefficients than other usable gases.
          In the case of residential,  commercial and industrial con-
struction, the insulation may be applied as slabstocki laminated board,
filled spray or poured-in-place.  In transportation, slabstock, spray or
poured are used.  Tank insulation is virtually all sprayed, and refriger-
ation and pipe insulation is poured.
          In the case of polystyrene foams, the use of CFCs is for reasons
of safety and performance.  Pentane is an effective substitute from the
standpoint of producing suitable cell size and foam structure, but its
flammability constitutes a severe production hazard.
          In polyurethane and polystyrene foams used for Insulation, the
CFC is retained in the cells over long periods and contributes materially
to its insulating properties.  Foams blown with CFC have on the order of
twice the insulating value of foams blown with carbon dioxide.

                             Energy Penalties

          Table 7 shows the energy penalties associated  with  elimination
of the use"of CFCs as blowing agents in the various applications listed.
          Insulating materials are only one component contributing to
the Insulating value of a structure.  Masonry, wood, sheathing, etc., all
contribute something.  The structures used as a basis for the table
calculations are detailed in Appendix F, and the alternatives are shown
1n Table E-7.
                                     C-24

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                                                     Energy Consequences
                                                     of CFC Regulation
TABLE 7.  ENERGY PENALTIES ASSOCIATED WITH THE ELIMINATION
          OF CFCs IN INSULATING FOAMS
          (millions of gallons of fuel equivalent)

Commercial Construction
Residential Construction
Industrial Construction
Refrigeration
Tanks and Pipes
Transportation Equipment
Total
1981
106
8
4
68
30
1
217
1990
1565
126
52
833
393
10
2979
Decade
7010
610
260
4420
2040
60
14,403
                            C-25

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                                                             CFC Consequences
                                                             of CFC Regulation
          In most cases, these alternatives presume some thickness con-
straint.  For example, refrigerators cannot be made larger to accommodate
thicker Insulation because of constraints Imposed by 2x1 sting doorway
sizes.  The Interior size could be reduced, but smaller capacity would
result 1n some combination of more units or more frequent trips to the
grocery and greater gasoline consumption.
          Tank Insulation presents a special problem 1n that there is no
real constraint on the thickness of Insulation used.  Fiberglass is not
currently used because 1t requires protection from the elements, especially
rain.  Polyurethane foam is self-protecting.  If one assumes effective
protection for fiberglass can be developed and Is economically practical,
the thickness can be made as great as needed to eliminate any energy
penalty.  Therefore,  the table  shows a range of penalties for equivalent
thicknesses to no loss.  To date the alternative has frequently been
foam or no insulation.
          The uninsulated alternative is unlikely to remain  viable so
was not considered, although it would lead to much larger energy penalties.
                                    C-26

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                                                                 Energy Consequences
                                                                 of CFC Regulation
                           LIQUID FOOD-FREEZING

          Datat  references and  calculations  relating  to  this discussion
of  liquid food-freezing  are contained  in Appendix  H.

                          General  Considerations

          Liquid food-freezing  refers  to the use of a freezant R-12  (IFF)
to  spray foods or directly immerse  them in cold liquid.  The process differs
from cryogenic freezing  with liquid nitrogen or liquid carbon dioxide in
that the freezant is  condensed  and  recovered rather than vented to the
atmosphere.   The liquid  must be therefore easily condensed.  In addition,
it  must be  inert, of  low toxicity,  and, of course, high  purity.
          IFF is used only for  certain rather delicate types of food.  The
air blast technique used for most foods is cheaper but tends to cause
^dehydration  or other  damage to  some products.  Among  the foods where IFF
'is  used are  clams and shrimp, french-sliced  green beans, berries and
similar freeze-fragile items.   For  these products, air blast is not an
alternative  if quality is a constraint.  Therefore, only cryogenic nitrogen
and carbon dioxide are considered as alternatives.

                             Energy  Penalties

          The energy  penalties  associated with discontinuation of the use
of  R-12 in  IFF applications are shown  in Table 8.  These data show there
1s  an  expected penalty of about 12  million gallons of fuel equivalent
in  the tenth year of  a ban and  over 100 million gallons  for the first
decade.
          These  projections have assumed a rather modest growth for LFF.
The growth might well be greater except that the threat  of a ban on the
use of R-12  has  already  had an  impact  on the installation of new systems.
The projections, therefore, reflect the current outlook  rather than
speculation on what the  situation might have been.

                                        C-27

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                                         Energy Consequences
                                         of CFC Regulation
 TABLE 8.   ENERGY  PENALTIES  ASSOCIATED WITH  USE  OF
           LIQUID  NITROGEN AND LIQUID CARBON DIOXIDE
           AS A SUBSTITUTE FOR R-12  IN FOOD  FREEZING
           (millions  of gallons fuel  oil  equivalent)^'
•Year

Fruits
Seafood
Meat


and Vegetables
and Specialties

Total .
1
6
1
1
9
981
.45
.38
.39
.22
1
8
1
1
12
990
.42
.81
.81
.04
Decade
73
15
15
105
.94
.87
.94
.75
(a)  Battelle  calculation  based  on  Tables  H-2  and  H-4,
                 028

-------
X.  APPENDIX D
        - A COMPARISON OF SOME OF THE PRINCIPAL FINDINGS -
             THE NATIONAL ACADEMY OF SCIENCES REPORT
         "STRATOSPHERIC OZONE DEPLETION BY HALOCARBONS:
             CHEMISTRY AND TRANSPORT", NOVEMBER, 1979
                               AND
        THE UNITED KINGDOM DEPARTMENT OF THE ENVIRONMENT
         REPORT "CHLOROFLUOROCARBONS AND THEIR EFFECT ON
                STRATOSPHERIC OZONE", OCTOBER, 1979
                               D-i

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                                      NAS/UK DOE Comparison
Introduction
         The National Academy  of  Sciences'  (NAS)  November,  1979
report [NAS, 1979a]  on  the  effect of chlorofluorocarbons (CFCs)
on the ozone layer  differs  sharply from the conclusions reached
in a  report  released in October,  1979 by the  Department  of the
Environment of  the United  Kingdom  [UK  DOE, 1979].

         The two  reports,  drawn up  by qualified  scientific
bodies,  have arrived at  significantly  different  conclusions  on
matters  ranging  from uncertainties  in  the  calculations  to the
significance of missing  chemistry  in  the  computer model.

         Since  the subject and  conclusions  of  these reports are
matters  of  international  consequence, the  Du  Pont  Company
believes there  should  be  a  resolution  of  these  scientific
differences regarding the  effect of CFCs  on  the ozone layer prior
to further unilateral regulatory action  by the United States.

         A comparison 'of  some  of  the major differences between
these two reports  follows:
                               D-2

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                                       NAS/UK DOE Comparison
NAS REPORT

•There is agreement with
 previous reports that
 continued release of
 halocarbons into the atmo-
 sphere will result in a
 decrease in stratospheric
 ozone.
UK REPORT

•The validity of the hypothesis
 is still in doubt.

•Basic scientific understand-
 ing, although progressing
 rapidly, is still inadequate
 in many respects.

•The  report  concludes   that
 present understanding of ozone
 depletion  is  limited  and  is
 based  on  model  assumptions
 which have not been adequately
 validated.
•New values for some of the
 chemical rate coefficients
 have increased the predicted
 ozone reduction resulting
 from continued release of
 chlorofluoromethanes
 (CFM's).
>The results concur with other
 studies that the predicted re-
 ductions in total ozone amount
 are greater than those estima-
 ted in 1975 at the time of the
 preparation of Pollution Paper
 No. 5.  Whether the statements
 realistically describe what is
 likely to happen  in  the atmo-
 sphere depends on the validity
 of  the  calculations  and  also
 their coverage including the
 simultaneous  effects  of other
 atmospheric pollutants.
•The uncertainties in the chemi-
 cal rate coefficients, in
 atmospheric transport, and in
 the use of one-dimensional
 models have been combined to
 give an overall uncertainty
 range of a factor of 6 within
 a 95 percent confidence
 level.
•The uncertainty range means
 that for the case of continued
 release of CFM's at the 1977
 level there is 1 chance in 40
 that the ozone depletion will
 be less than 5 percent and 1
 chance in 40 that it will be
 greater than 28 percent.
•It is not therefore realistic
 to assign overall uncertainty
 limits to our calculated ozone
 perturbations; deficiencies in
 our basic knowledge of the
 processes establishing the
 composition of the stratos-
 phere and in the modelling
 technology cast doubts on
 their validity.
                               D-3

-------
                                       NAS/UK DOE  Comparison
•There have been considerable
 improvements in the computer
 model and in the laboratory
 and atmospheric measurements,
 which have reduced the uncer-
 tainty range.
•The  STRAC   report   [The   UK
 Stratospheric Research Ad-
 visory Committee]  deals ex-
 tensively with the uncertain-
 ties in the model  results.
 Not all of them could be asse-
 ssed quantitatively and it  is
 not possible  to  assign  error
 ranges to these estimates that
 allow  for  all  the  uncertain-
 ties.     These  have,  however,
 widened  rather  than  narrowed
 since  Pollution  Paper  5  was
 published [1976].
•Even allowing for the best
 professional judgment of the
 possibility that some impor-
 tant chemical reaction has
 been overlooked or that
 there remain large errors
 in the measured chemical
 rate coefficients, we
 believe that there is a 3
 out of 4 chance that con-
 tinued release of CFM's
 at the 1977 level will
 result in an ozone deple-
 tion that lies in the
 range of 9 to 24 percent.
•Any uncertainty analysis would
 be  incomplete  as   it   would
 encompass only quantifiable
 sources of uncertainty.

 In contrast the uncertainty
 from the different assumptions
 made in simulating the trans-
 port processes and in the
 modelling procedures  cannot
 yet be quantified, nor can any
 firm statement be made regard-
 ing the  uncertainties arising
 from possible deficiencies in
 our knowledge of the detailed
 chemistry and photochemistry.
                               D-4

-------
                                      NAS/UK DOE Comparison
•Although there are a few excep-
 tions, the comparison between
 the models and measurements
 of substances in the present
 stratosphere is considered
 to be satisfactory within the
 uncertainties of the measure-
 ments.  We, therefore, believe
 that the projections for
 depletion are valid
 within the stated uncertainty
 ranges.
       •A certain amount of  success  in
        the  simulations  has clearly
        been  achieved   both  in  the
        STRAC programme  and  elsewhere
        but there are major  discrepan-
        cies.  Moreover, unless one  is
        prepared to reject evidence  of
        actual  measurements  in  favor
        of theoretical calculations  it
        must  be  concluded that  there
        are  still   important  gaps  in
        our understanding and know-
        ledge  of  the  process  that
        determine stratospheric com-
        position.  It follows  that  if
        we are  not  satisfied  with our
        present  ability  to simulate
        the   particularly    on  the
        grounds  that  there  may  be
        major  error  or  omissions  in
        current  theory,  we  must  be
        very cautious in accepting
        quantitatively any predictions
        from accompanying perturbation
        experiments.
                                  •These findings,  together with
                                   other  discrepancies  between
                                   model calculations  and mea-
                                   surements  brings into question
                                   the validity of  the models
                                   presently  used to predict
                                   ozone perturbations.
         The  UK  report  concludes  "In  the  light  of  the  many
uncertainties  still  prevailing such  a  reduction  [the  voluntary
steps underway  in the  EEC to  reduce  aerosol  propellant uses of
CFC's by 30  percent  from  the  1976 level by 1982 ] appears to be
adequate  pending  further
warranted at present."
research.    Strict  regulation  is  not
 The  United  States already
 propellant uses of CFCs.
  has  banned  essentially all  aerosol
                               D-5

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X.  APPENDIX E
           CHLOROFLUOROCARBONS AND OZONE - THE SCIENCE
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                        Table of Contents
                                                           Paqe
1.  SUMMARY AND CONCLUSIONS                                  5

    A.  MODELS DO NOT PREDICT FUTURE REALITY                 5

    B.  IT IS UNREASONABLE TO EXPECT ACCURATE                6
        FUTURE PREDICTIONS FROM MODELS

    C.  CURRENT MODEL RESULTS INDICATE A SMALLER             6
        POTENTIAL FOR FUTURE OZONE DEPLETION THAN
        CITED BY EPA; ADDITIONAL REDUCTIONS ARE LIKELY

    D.  REGULATORY ACTION AGAINST CFCS IS NOT NEEDED AT      8
        THIS TIME TO PROTECT STRATOSPHERIC OZONE

2.  CRITICAL REVIEW OF CURRENT CHLOROFLUOROCARBON/OZONE     10
    SCIENCE

    A.  OZONE OBSERVATIONS                                  10
        1.  Statistical Analyses                            11
        2.  Umkehr Measurements                             14
        3.  Tests of Other Model Calculations               15

    B.  CHLOROFLUOROCARBON EMISSIONS AND TROPOSPHERIC       16
        PROCESSES
        1.  Atmospheric Lifetime Experiment                 16
        2.  Tropospheric Sinks                              18
        3.  Chlorine Removal by Rainout                     20
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C.  TRANSPORT IN THE ATMOSPHERE                         21
   . 1.  Local Averaging                                 21
    2.  Eddy Diffusion                                  22
    3.  The Assumptions                                 23
    4.  Testing the Approximations                      23
    5.  Estimating Uncertainty Due to Transport         25
    6.  2-D Transport                                   26

D.  STRATOSPHERIC CHEMISTRY                             27
    1.  Measurement Uncertainty                         28
    2.  Temperature and Pressure Dependence             28
    3.  Product Identification                          29
    4.  Third-Body Dependencies                         30
    5.  Pressure Dependencies                           31
    6.  H0x Chemistry                                   32
    7.  Excited States                                  35
    8.  Solar Flux                                      36
    9.  Unknown Chemistry                               36

E.  STRUCTURE AND SCOPE OF MODELS                       38
    1.  Stratospheric Chlorine Inputs                   39
    2.  Other Time-Varying Chemical Inputs              40
    3.  Coupled Nature of Atmospheric Processes         42
    4.  Atmospheric Variability                         43

F.  MODEL RESULTS                                       47
    1.  Comparison of Calculated and Measured           47
        Concentrations
    2.  Comparison of 2-D and 1-D Model Results         51
    3.  Current Model Ozone Depletion Calculations      52
    4.  The Effects of Postponed Regulations            55

G.  OZONE AND ULTRAVIOLET RADIATION                     57
    1.  Latitudinal Variation in Calculated             57
        Depletion

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    2.   Natural Ultraviolet Radiation                   58
    3.   Action Spectra                                  59
    4.   Dose and Dose-Rate                              61

H.  UNCERTAINTIES                                       62
    1.   Current Uncertainties                           63
    2.   Reduction of Uncertainty                        67
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 1.  SUMMARY AND CONCLUSIONS

        To  appreciate both  the  general   status  of  atmospheric
science and  the  impact of  recent  developments,  some synthesis is
necessary.   The  following conclusions  are supported by  the  de-
tailed discussion in section 2.
 A.  CONTRARY TO A POPULAR MISCONCEPTION, MODELS  DO NOT PREDICT
     FUTURE REALITY.

         Model calculations account only for those aspects  of the
future  which are  specifically  included  as  input.   Thus,  all
fluxes  of  chemical  species to  the  atmosphere are  held  constant
beyond some  given year  (usually  the  present)  in  all steady-state
calculations.   Even for  time-dependent scenarios,  calculations
generally  include  only  changes  in  CFC  flux.    Where  specific
calculations involving more  than one potential perturbation  are
done, the  combined  effects are found not to  be  simply  additive.
Even  if  projected  variations  could  be  included  simultaneously,
the   calculated results are limited by the  accuracy of  the input
projections - none of which are well defined.'

         Model  success in prognostic applications must  neces-
sarily be preceded  by diagnostic success.      Yet, models fail to
reproduce  the current best (if imprecise)  picture of the present
day stratosphere based on measurements.   A  particular example is
lower stratospheric CIO concentrations - overestimated by models,
and directly  responsible  for  much of the model-calculated ozone
depletion.      Ozone measurements also do not confirm the changes
predicted by models for either short- or long-term perturbations.
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 B.  ON THE BASIS  OF  PRESENT KNOWLEDGE, IT  IS  UNREASONABLE  TO
     EVEN EXPECT ACCURATE FUTURE PREDICTIONS FROM MODELS.

         The uncertainties  associated  with models  are  numerous,
large, and often  inherently  unquantifiable.   These uncertainties
arise  from  model  inputs,  model  design,  calculated  simplifica-
tions,  and   incomplete  testing  of  assumptions.    The  chlorine
contribution to  the  stratosphere  from CFCs  is  not  well-known.
Critical reaction  rates are  often  poorly  defined.   The  treatment
of transport is uncertain.

         There  are  also  many potentially  important interactions
which are simply not understood.  New chemistry is still possible
and  indeed being  discovered.   The  1-D approximation  is  only  now
being tested, and  even at  that  it is being tested  only  by a  2-D
approximation.    Local  variability  on short temporal  and spatial
scales is ignored for  lack  of both information and a way to study
it.  Feedbacks  are omitted  or guessed.   It is  simply unreasonable
to ask  more of models  than they are capable  of delivering.  The
failure of models to reproduce the present signals an immediate
caution on any  extrapolations.

 C.  CURRENT MODEL RESULTS, TO WHATEVER EXTENT THEY CAN  BE RELIED
     UPON, NOW  INDICATE A SMALLER  POTENTIAL FOR FUTURE ADVERSE
     EFFECTS THAN THAT GIVEN IN 1979; PRELIMINARY RESEARCH  INDI-
     CATES FURTHER REDUCTIONS TO COME.

         According  to a  recent  publication [Wine  et  al. , 1980],
revised chemical  rate data  has  reduced  the LLL  model  base case
calculated ozone  depletion to  13.9%.   The NAS  [1979a]  reported
the  earlier  LLL  result, 18.6%,  and revised  it downward  to 16.5%,
based  on  expectation of  small  tropospheric  sinks and  feedback
mechanisms.   A  similar treatment prorated to the more recent base
case of  13.9%  would  revise  it  downward  to approximately 12.3%.
However, as  discussed  elsewhere, we believe the NAS treatment  to

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 be  inadequate  (an attempt to quantify the  inherently  unquantifi-
 able) .   Therefore,  we will  use  the 13.9% as  a  base  case model
 calculation for the ensuing  discussion.

         Other revisions, some  to be recommended  in  the next NASA
 revision,  and  others  awaiting  confirmation,  would  improve model
 agreement  with measurements of  CIO  concentrations  by reducing
 lower  stratospheric  OH  levels.    The concomitant  reduction  in
 calculated  steady-state  ozone  depletion  reduces the  figure  to
 below 6-9%.

         Preliminary   Atmospheric  Lifetime   Experiment  (ALE)
 results  [CMA,  1980a] indicate a  lifetime for CFC-11 of half that
 derived  from  known   stratospheric  destruction,   implying  a
 tropospheric sink  equal  to  that in  the  stratosphere.    If  the
 preliminary estimate is correct,  ALE will confirm  the  lifetime of
CFC-11  by   1982.    If  CFC-12  behaves similarly,  as  one  would
 expect,  the  chlorine   contribution  of CFCs-11 and  12,  and  the
 calculated ozone depletion would both be halved.   Along with the
 other likely revisions,  this reduces  the figure  to  less  than  5%
depletion at steady-state.

         The expected  doubling   in  C02  is calculated  to  reduce
 calculated CFC-induced depletion by about 3-5%.   That is, on the
 basis of recent developments and  more  complete  analysis,  the  net
 model-calculated potential future  ozone change due to continued
 release of CFCs at recent levels may  well  be as  low  as  2%  when
 current results are  confirmed by  additional measurements.

         A  2-D  model calculation of  latitudinal  depletion
distribution has  shown  that  the physical amplification factor for
 conversion to a DUV change is near 1 rather than 2 or  more [Pyle
and Derwent,  1980].   Thus  the  risk  of a  44% increase  in  DUV,
estimated a year  ago,  may now be  reasonably assessed as a risk  of
as little as a  2%  change  in  DUV.   (The most recent Du Pont 2-D

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model results suggest that the latitudinal variation in calcula-
ted  depletion  may be  considerably  less  than  that of  Pyle and
Derwent  [1980],  and  the  physical  amplification  factor  may lie
between 1 and 2).

         The reduction from  18.6%  to  as low as  2%  or  below for
steady-state  depletion  implies  a  comparable  reduction  in
calculated present day depletion to a few  tenths of a  percent -
reducing the disagreement with  the  positive  trend observed with
ozone  trend analysis.   Thus, ozone  measurements  lend  further
credence  to the assessment  that the  theoretical  risk is now far
less than that  perceived  in  1979 by  the  NAS panel.

 D.  THE GOAL OF MAINTAINING  STRATOSPHERIC OZONE  CONCENTRATION AT
     NEAR CURRENT  LEVELS  CAN  BE  MET WITHOUT IMMEDIATE REGULATORY
     ACTION AGAINST CHLOROFLUOROCARBONS.

         Significant  reductions in  the  perceived  risk  based  on
model-calculated ozone depletion  reduce the need for  immediate
regulatory  decisions.   Increased  awareness  of  uncertainties  at
the  same  time  decreases  the risk of  a wrong  decision.    Ozone
measurements provide  reassuring evidence  of  the situation  as it
really  exists   at present   -  a  small   long-term  trend   toward
increasing  ozone.    This  result  is  in  sharp  contrast with
now-dated EPA-cited calculations, and  is indirect confirmation of
preliminary  research  results  which  would  further reduce the
theoretical risk.

         The near  future  promises  many  significant tests of the
theory and  improvements  in  modeling  capability.   The additional
depletion  associated with  even  a  five-year  delay in U.S.   regu-
lation was  small  even  before recent model revisions.  Thus, the
benefits of a delayed decision,  scientific as well.as economic,
combined with the likelihood  of  a significantly  better decision

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with  each passing  year,  far outweigh  the  very small  current
estimates of the risk arising from delay.

         And even overriding  those  issues is what appears  to be
the most  significant  development to date.   Refinements  in ozone
trend analysis  have given  us a capable  early warning  system for
long-term changes  in ozone  concentration,  no matter  what  their
cause.  Those changes, if they occur, will be detected at a level
of less than 1.5 percent  [Reinsel  e_t al. ,  1980;  St.  John, 1980a;
1980b;  St  John et  a_l. ,  1980].   If CFCs  are deemed  to be  the
cause,  the  ozone  change  can be contained  to very low  levels  -
levels  below  those  contemplated recently  by EPA  as  potentially
achievable goals  [Jellinek,  1980a;  EPA,  1980d].   No immediate
regulation is required to better this goal.
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 2.  CRITICAL REVIEW OF CURRENT CHLOROFLUOROCARBON/OZONE SCIENCE

         In  each  of  the subsections  which follow,  an area  of
research  is  reviewed.    Particular  attention  is given  to  recent
developments, remaining  uncertainties,  and  conclusions  justified
on the basis of present knowledge.   Specific detailed support for
scientific arguments made elsewhere in the submission is provided
here.

 A.  OZONE OBSERVATIONS

         Measurements of ozone have been  suggested  as a valuable
tool  for  both  scientific  and regulatory  analyses  of  potential
ozone depletion  [CMA,  1980a;  Du Pont,  1978;  1980a; Ward,  1979;
Masten,  1980].  The information  available  from  the  ozone record,
via various analytical and statistical analyses,  provides insight
into  the  factors  affecting  ozone  concentration and a test  of
theoretical predictions.  The  former,  of course,  leads to greater
understanding of  natural ozone variations, simplifying  the  task
of discerning unnatural  changes.  The  latter, both  constrains  to
some  extent  the  confidence  placed  in  predictive  models,  and
potentially  leads  to  insights in modeling  as  well.  Ozone  mea-
surements,  in  and of themselves, do  not  obviate the need  for  a
scientific  resolution  of the  theory  of  ozone  depletion.    The
science must be resolved  to explain what  is or  is not happening.
Nonetheless, the use of ozone  measurements as  an early warning  of
unusual  change in  ozone should be of value in  regulatory analy-
ses , and the existence of an early  warning system  permits  more
time  to  be taken  to  resolve the  underlying  science with confi-
dence that a dangerous problem is not developing.

         Two  recent reports   [NAS,  1979a;  NASA,  1979]   have  con-
sidered the  early warning possibility  in a limited application,
i.e.,  the  potential  for  detecting  a CFC-induced  decrease  in
ozone.  The  implicit premise  in  those  analyses  is that  detection

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of a  trend  (or lack thereof)  is  a  useful exercise only  if  the
trend is large enough to  permit determination of its cause.  This
reasoning  neglects the  value  of  information on the simple
existence or nonexistence of  a  trend.  That information should be
of particular  value to  a regulator  faced  with  inadequate  and
uncertain   information  regarding  potential   (and  calculated
current) changes in ozone concentration.

         The approach  to the regulatory question  chosen  by  the
NAS panel was  direct:    Assuming  the  then-current  model results
were accurate predictions,  could a regulator afford to  wait until
the theory has been verified  by ozone measurements before  taking
action?   Through  arguments,  some  of which  will be  discussed
below,  that  question   was  answered   in  the  negative.    On  that
basis,  any   current value  of  the   measurements   to  regulatory
decision-making was dismissed.   Yet,  the  theory may  not  be
correct;  ozone  may  not  change,  or  it may  increase.    The
regulator need not decide now that regulation  be put off  for 20
years.   He or she must decide  only  whether to regulate now or to
postpone regulation for some  additional  period of research  and
evaluation.       Moreover,  the regulator's  concern should be
protection  of the ozone layer,not protection  from some
calculated inherent danger of CFCs.

         In the following discussion,  this broader application of
ozone measurements  is  discussed,  along with  the recent  develop-
ments  in  their analysis.    Ozone measurements do function as an
early warning system for  long-term change  in ozone concentration.
The importance of  this  contribution  cannot be overlooked.

     1.'  Statistical Analyses

         The  type  of   ozone  observational  data available,  and
developments in  analysis of  this data  through 1979,  have  been
discussed in  some  detail  by  the NAS panel  [1979a].    Several

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averaging techniques for deriving global ozone rely on graphical
and  visual  analysis   for  trend  detection,  e.g.,   [Angell  and
Korshover, 1978;  1980;  Miller e_t  al. ,  1979].    The  more  recent
applications of  statistical   trend  analysis  [Hill  and  Sheldon,
1975; Hill  et.  a_l. ,  1977]  and' spectral  analysis  [NAS,  1979a] to
Dobson ozone measurements  allow  more  specific and apparently  more
sensitive approaches to trend detection.  The most recent work by
three  groups  has  contributed  considerably to  that   relatively
young research  area.

         St.  John   [1980a;   1980b]   has   introduced . several
refinements  to  the  original  methods of  Hill  [Hill  and  Sheldon,
1975; Hill £t al_. f 1977].   Rather than  the  zero trend followed by
linear trend model  for CFM induced depletion, St. John regresses
directly  against  a  1-D  atmospheric-model-calculated  depletion
curve.    The  regression  coefficient  or  CFM-parameter  may be
directly  translated into  a  net  ozone  change  occurring over the
period 1958-79.   In further  testing  of the data, St.  John notes
that differentiation of the  CFM  curve  from other similar  slowly
changing  long-term  trends is  difficult given the near  absence of
any trend.   Thus  the  estimated  trend is better  described as the
overall long-term net  trend  in ozone.

         For the period  1958-1978 St.  John finds a  slight but
statistically insignificant increase in  ozone of 0.3  +  1.2%.
Stated uncertainties are 95  percent confidence limits,   and  are
derived  from  variability  among  the  estimates   for   individual
Dobson   stations.    This   approach  to  uncertainty  defines
statistically  the   uncertainties  associated with  any  long-term
effects that vary from  one station to  the  next,  and furthermore
it  removes  those  effects  as  contribution to the observed  trend,
isolating them  as uncertainties.   It  is not necessary,  therefore,
to  rely  on  estimates  of  those  uncertainties.   Indeed, the NAS
estimates for instrumental  uncertainties, meteorological  bias,
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and geographical biases  all  appear to be  conservative over-
estimates when compared  to the  true data-derived uncertainties.

         Reinsel e_t  al.   [1980] at  the University  of  Wisconsin
have  applied  similar methods  using  the linear  trend  represen-
tation for  the  CFM  trend, and for the  period  1970-1978  find  an
increase  of  0.3  +   1.4%.    Included  in that  uncertainty is  a
conservative estimate  of  correlations  (i.e.,  lack of  indepen-
dence) among  Dobson  stations  clustered geographically.   Other-
wise,  Reinsel's et al.  and St. John's results are comparable  and
in notably good agreement.

         The Wisconsin  group has  also examined  the more complete
satellite data  now  available  in  order   to  test  the  global
representativeness of  their chosen  set  of  36  Dobson  stations.
Satellite  data  display a negative  time  trend with respect  to
ground based measurements.   The  investigators  in  the  satellite
measurement program concur  that a  degradation  in satellite
performance  took  place,  and   that  the satellite  trend   is  not
an  indication  of an actual decrease  in  ozone  [Cunnold,  1980;
Stolarski,  1980].   The  degradation  may, in  fact,  hide  an
increasing  trend   observed  in   the  Dobson  measurements.
Nonetheless,  the global  satellite trend  may  provide  useful
information.    A  comparison  of  Dobson  station  data  with  the
satellite data  for the  same  isolated  geographical regions shows a
difference  identical to  that  found with  the  global  satellite
data.     Thus,  the  Dobson  station  locations  are  shown  to  be
representative  of the global trend in ozone.  While no  inference
is possible regarding absolute calibration,  the Dobson  locations
would   appear  to  reproduce  global  trends  with  no  geographical
distribution bias.

         Watson  [Watson,  G.S.,  1980]   has   also  continued  the
spectral  analysis of the  Dobson  ozone record discussed  by  NAS
[1979a] ,  and reports a change  in  the seventies  of +0.6  +_ 1.9% in

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ozone concentration.   The  uncertainty  stated  here  is  somewhat
broader  than  those discussed  above,  including  some partial
measure  of  the  possibility  a  trend  is  masked  by  natural
variations.   Again,  however,, the  results are similar to those of
other statistical  techniques.

         In   conclusion,  ozone appears to be  increasing,  and none
of the estimated 2v uncertainty  ranges includes the 1979  calcu-
lated "to date" ozone depletion  of 2.1%.    Recent changes  to the
model  (discussed in ensuing  sections) reduce those calculated
figures enough to  move  them  to  within the  confidence range for
measured  ozone.     In  that  sense, the ozone  measurements support
the appropriateness  of  such  model revisions, in which  case the
theory as cited by EPA  overestimates depletion.
                                                                &

         There is,  of  course,  the alternative  possibility  that
another long-term trend may be offsetting CFC induced depletion,
resulting in little  net change  to date  of  global  ozone.   Either
possibility  has  important  regulatory  implications, but must  be
considered  along  with   other  information  available from  ozone
measurements.

     2.   Umkehr Measurements

         As  pointed  out by  the NAS panel [1979a] , Umkehr measure-
ments of ozone vertical concentration profiles provide access to
measurements of local ozone  concentration in  the region where the
percentage  impact  calculated  to  have  occurred   is  largest  -
approximately 5%  near  40 km.   Angell and  Korshover [1980]  have
examined  data through 1979  for  the 32 - 46 km layer and conclude
"there is still  no  evidence  of an anthropogen i ca 1 ly-_i nduc_ed_
decrease  in  ozone  in this sensitive layer."   The Princeton group
has begun analysis  of  the Umkehr  data,  and initially  have noted
an ozone  increase  during  the   1970's.   These  are particularly
interesting   results  in light  of the  general  confidence  often

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expressed  that  stratospheric chemistry  dominates  transport  at
these altitudes, and is  also  well  understood  there.   A  conflict
with model calculations  for  the upper stratosphere is,  therefore,
a more serious challenge  to  the theory.  The significance of  that
challenge will be  better  defined as the analysis is completed and
uncertainty limits  are published within the next year  or  two.

     3.   Tests of  Other Model  Calculations

         Based on  model calculations numerous other stratospheric
perturbations are  thought to influence ozone  concentration.
Aside from the phenomenon known as sudden stratospheric  warming,
the NAS  panel  notes  that "strong  evidence is  lacking for  other
natural  or man-induced  perturbations  to the ozone distribution."
These include volcanic  activity [Steed e_t al. , 1980;  Angell and
Korshover, 1973; 1978], nuclear explosions [Angell and  Korshover,
1973; 1978],  and the 11-year  solar cycle  [Angell  and  Korshover,
1973;  1978].   The accumulated  evidence  suggests that  the
discrepancies-  between  models   and   measurements   for  ozone
perturbations  extend  beyond  the  CFC-effect   to  include  other
aspects  of  model  chemistry  or   feedback through  atmospheric
dynamics ignored completely  in the models.

         Taken together,  the  accumulated evidence  available  from
the  ozone measurement record leads to considerable  skepticism
concerning model calculations  - skepticism  that is justified  by
the  extensive and  increased model uncertainty  at the present
time.

         With this  background we  turn  now to  an  examination  of
the  various  steps  in  the  theory  and  the  status  of  the  model
inputs and results.
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 B.  CHLOROFLUOROCARBON  EMISSIONS AND TROPOSPHERIC PROCESSES

         The  initial  determinant  in  quantifying  potential
stratospheric  ozone  depletion  is,  of  course,   that  amount  of
chlorine contributed to the  stratosphere  by  CFC  emissions.   The
first  controlling  factor  is  production and  release.    Much
attention has been paid to release scenarios  in official studies
[NAS, 1979a;  1979b;  Rand,  1980;  UK DOE, 1979]  and certain factual
errors have been noted [Du Pont, 1980a; Masten,  1980].   The fact
is that 1979  production  of CFCs-11 and  12  is down by 17.5 percent
from  peak  levels  of  1974  [CMA,  1980a;  1980b].    Unrestricted
growth  is  an unrealistic assumption  given  current regulatory
initiatives elsewhere  and  continued expected  regulatory  concern.
Concern over  potential  future  regulation  has a  large  dampening
impact  on  growth because of  the  perceived extremely high  risk
associated  with  any'  significant  capital  investment  in  a
threatened  product.    The only reasonable  conclusion  is  that
growth  in  production  will be  limited  (by current  capacity  and
regulatory  concern)  and  will  be  relatively slow, unless and until
the  science  surrounding   the Chlorofluorocarbon/Ozone Theory  is
satisfactorily resolved.

     1.  Atmospheric Lifetime Experiment

         A  second  factor  influencing  the  stratospheric  chlorine
contribution  is  transport  through  the  troposphere.     NAS
acknowledges   the possibility  of  some  CFC  destruction in  the
troposphere,  and  indeed   revised   its central  value   for
steady-state   depletion  downward to  account, for  its  likelihood
[NAS,  1979a].   However,  the magnitude of  this  "correction"  was
determined  arbitrarily  after  attempting  to  enumerate  all  the
possibilities and assign lov/er  bounds to each.  Given the paucity
of available  research  results,  such a task is formidable.
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         A more direct route to the  answer on the  tropospheric
sink question is available  from the  Atmospheric Lifetime Experi-
ment,  currently  underway under CMA  sponsorship  [CMA,  1930d].
Although no results were available to the NAS Panel, a report of
interim results was made to  EPA [CMA,  1980a]  and the scope of the
program  and   its  goals were  clearly defined  in  the  published
literature  [Cunnold   e_t  al. ,   1978],    In  short,  a   series  of
frequent, carefully calibrated measurements is being made over a
period  of  at  least three years  to  determine the  rate at which
atmospheric  CFC  concentrations  are  increasing.   Along  with
accurate production figures and  use  distributions,  the measured
trend allows  determination  of  the  atmospheric  lifetimes  for the
compounds.   To the extent  that this  lifetime  is smaller than that
calculated assuming only stratospheric destruction, the CFCs are
being destroyed by some other  mechanism.   In the  trend method of
data analysis,  uncertainty  limits rapidly converge  as the data
set  lengthens.   A total of  three years  of  measurements  will be
sufficient to  identify a total  lifetime   significantly shorter
than  the  stratospheric  lifetime  if  current  data  quality  is
maintained [CAP Associates,  1980].

         The advantages indicated  by  the  trend method of analysis
are  both the  rapid   convergence  of  uncertainty  limits  and the
independence  of   the   result  from absolute  calibration  of  the
measurements.   This  becomes  especially important  given the
current  data   which   indicate  more  CFC-11  and   CFC-12   in  the
atmosphere than calculated emissions  would  account for.  Both the
stratospheric sink   and  a  possible  tropospheric  sink  would
increase this  discrepancy.  Nonetheless, the trend method, which
is  independent of  absolute  calibration,  indicates  a lifetime
shorter  than  that  based  on  stratospheric photolysis alone.  The
atmospheric overburden  indicated  by  the  budget  or global  burden
analysis is currently  under investigation to identify  the  source
of the discrepancy.
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         A best fit  of  the trend  in  the  data set  available to
date  (18  months)  indicates a lifetime  approximately one half of
that  due  to known stratospheric  sinks for CFC-11.   CFC-12 is
expected  to  behave  similarly to CFC-11 but  to exhibit somewhat
more  stability  to any  sink  mechanism.   The  uncertainty  range
remains very  wide with  the  short  data  set  available  currently.
However,  the  significance  of  the  method   lies   in   the  rapid
convergence of those limits.  Within  two  more years a  tropo-
spheric sink important  enough to drastically reduce calculated
ozone  depletion  will be  indicated if  its exists—as preliminary
results indicate.

     2.  Tropospheric Sinks

         It will,  of course,  be equally important to  eventually
justify such a result by demonstrating a sink mechanism.  Work by
Ausloos and Rebbert [1980]  has  identified destruction of CFCs-11
and 12  absorbed on  sand and  irradiated with ultraviolet  light.
Interpretational difficulties arise in attempted extrapolation of
the laboratory  results  to  the  real  atmosphere,  however.   The
experimental  rate of destruction  was  found  to be  sensitive to
parameters such as relative humidity.  The appropriate  conditions
for atmospheric encounters  of chlorofluorocarbon and sand are not
known.

         An alternative  approach to an understanding of the sand
mechanism and assessment of  its significance has arisen from the
work of Crescentini  and  Bruner  [1979;   1980].   Bruner  has noted
large  variability  in  CFC-21  measurements as a function of season,
location,  and  wind  direction.   CFC-21  has  been  suggested  as  a
possible decomposition  product  for CFC-11 [Glasgow et al. , 1977]
and its concentration has been measured by several groups [Singh
e±  al. ,   1977;  Penkett  e_t  al.  ,  1980;  Crescentini  and Bruner,
1979] .  The concentration  is often  found to exceed expected upper
limits.   (According to current  understanding, CFC-21 occurs only

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as  a  minor   by-product  in  chemical  manufacturing   processes).
Crescentini and Bruner  [1980] noted  a  correlation of  high  CFC-21
concentrations  with  air  masses  which have  recently  traversed
desert regions  and  of low concentrations  with  clean ocean  air.
The  work  is  currently  being  extended  to  further  define  the
correlation  and  search  for  corresponding decreases  in  CFC-11
concentration.  The  research  also is  information which has  been
made  available  to the  EPA,  although  not  in  advance  of the  NAS
report.

         CFC-22,  which  is a  commercial  product, has also  been
detected   in  the  atmosphere  at  concentrations  well  above  those
expected   on  the  basis  of available production estimates.    In
analogy with  the  possible formation  of CFC-21 from CFC-11,  it is
also  possible  that  CFC-12 decomposes  by  some mechanism to  form
CFC-22.

         The  work  is indicative  of  the  progress being  made  to
determine experimentally whether tropospheric  CFC sinks  do  indeed
exist.   Although the NAS minimized the likelihood of  significant
sinks  by assuming only a  small  one was possible,  the  evidence
supporting the conclusion was  not  exhaustive  by any means  and
represents an element of acknowledged subjectivity  in  the  report.
Other  work in  progress  includes consideration of   a  sink  not
thoroughly examined  previously.   A group at Du  Pont  is  studying
possible   destruction  of  CFCs at  plant surfaces.  The  available
surface  area  represents  over  six   times  the  total  world  land
surface  and provides a  reducing  medium  that may  be capable  of
inducing  reaction of  the compounds.   Even a slow reaction on  such
a scale could have profound  effects.

         The  troposphere is  a  much  more  complicated  chemical
system than  the  stratosphere  and is  correspondingly less  well
understood.  One would expect tropospheric  influence  on  potential
ozone  depletion  to   be  small,  but the  two known areas  of  impor-

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tance contribute to  a  major  uncertainty.     Both the quantity of
CFCs which  reaches the  stratosphere undestroyed and (see below)
the quantity of chlorine  leaving the lower  stratosphere  with
rainfall are open to question.      Current information indicates
preliminarily that as  little  as half the  currently assumed  con-
tribution  of  CFCs is actually realized  in  the stratosphere.
Nonetheless, within as short a time as two  years,  research  will
provide  quantitative  evidence  for  a  tropospheric  sink  if  it
exists.   An understanding  of  the sink,  if  it  is  verified  to
exist,  may be somewhat slower  in coming.

     3.  Chlorine Removal  by  Rainout

         A  final area  of  some  uncertainty   in  stratospheric
chlorine  contribution is  the  rate   and maximum  altitude  for
removal of  soluble  atmospheric  gases  in  rainfall.   The  concen-
tration of  chlorine in the  lower  stratosphere,  where most  ozone
depletion is calculated to take  place,  is tightly  coupled  to the
maximum  altitude  of  rainout  in  the  computer  model  atmosphere
[Miller et  al.,  1980a] .  The  real world  data  available  provides
little  guidance  to  modelers,  leaving  significant  uncertainty  in
this model parameter.
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 C.  TRANSPORT IN THE ATMOSPHERE

         An understanding of how chemical species move around  in
the atmosphere  is  critical  to  any evaluation of the net  effects
of a given species on the atmospheric chemical system.  The  rate
at which any simple chemical reaction proceeds  is governed by the
local concentrations  of  the reacting species.   Those  concentra-
tions are  in  turn  determined by previous chemistry and by trans-
port  into  and  out of the  region of  interest.    Both the  time
increments and  the distance increments  over which large  concen-
tration  fluctuations may  occur   are  small.   In  addition,   the
problem is a three-dimensional  one.   The appropriate  tool  for the
problem is a three-dimensional  model,  with  time increments of the
order  of  seconds,  and  distance  increments  of  centimeters  to
meters  --  a  model  which   is  not  likely   to  be  developed   for
decades.  Thus research on  atmospheric processes  has  necessitated
the development of  simplified models  employing  a  variety  of
approximations.  This section  examines  the  transport parameteri-
zation  of  one- and  two-dimensional  models,  noting  the critical
assumptions and associated  uncertainties.

     1.  Local Averaging

         It is  not feasible to treat  the   extremely  small-scale
variations in  transport  velocities and  species concentrations  in
a computational model of  the atmosphere, although  such  variations
may  be  as large  as  the   average  quantities  (e.g.,  direction
reversal for winds).  With  respect to transport, such  variations
are  primarily  important  insofar  as  they  compromise other
assumptions the  modeler  must make to  deal  with the  variations,
i.e.,  eddy diffusion.   This  subject  is discussed  below.    The
effects  of such  averaging  on  chemical terms  in  the  model  is
addressed in the section  on atmospheric  variability (E-4).
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     2.   Eddy Diffusion

         In  two-dimensional  models,  one averages  not  only  over
local variations  but  also  over  longitude.   The resulting  mass
balance  equations for  each chemical species contain not only  the
mean vertical and latitudinal motions,  but  also  covariance  terms
which are  averages  of  the  product  of  fluctuations  in   wind
velocities and  fluctuations  in  species  concentrations.    If
velocities and  concentrations  are simultaneously large,  net
transport  is  large,  etc.    However,  the true atmosphere has  not
been measured, as the average covariance is not  well defined.

         Reasoning that net  transport occurs only  if the  initial
concentration is  different  in  two  adjacent regions, and  further
that such transport  is  most likely  to  be determined  by  the growth
in  mean  concentration, Reed and  German  [1965]  introduced  the
so-called  "K-theory"  in which  eddy fluxes  (i.e.,  transport  in
addition to mean  flow)  in  the meridional plane  are proportional
to  mixing  ratio  gradients.   The  constants of  proportionality,
Kw' Kw7» K-7w' an(3 %•-„  are  assumed  to  be species-independent,  but
 yy   yz   zy       zz
functions  of  latitude,  altitude,  and  time  of  year.    These
assumptions provide  "closure" to  the mass balance equation.   That
is, they permit calculation without knowledge  of  the fluctuations
themselves  or of  their covariance.    One needs  only averaged
mixing ratios and some information on the magnitude of the  pro-
portionality constants.
                        /
         For one-dimensional models the  averaging is extended  to
include  latitude --  leaving  only altitude  as a  spatial  variable.
The  covariance  terms  now  include  latitudinal  fluctuations,  as
well  as  longitudinal,  temporal, and  small-scale local fluctua-
tions.  Here  the entire set  of covariance  terms  is assumed  to  be
expressible as the product  of a  single  diffusion  coefficient,  KZ,
and the  vertical  concentration gradient.   With this final  stage
of averaging, there  is no  mean flow term  remaining, since  there

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is no overall transport of mass in the vertical direction either
away  from  or  toward  the  earth's  surface.   In one-dimensional
models,  eddy diffusion is the only  transport  to  be  considered.

     3.   The Assumptions

         The National  Academy of  Sciences  report  outlines the
assumptions inherent in eddy  diffusion:

         "...to    justify    the    use    of   the    diffusion
         approximation  in a 1-D  model,  the  mean  correlation
         (between   velocity  fluctuations  and   concentration
         fluctuations)   must   not  only  be  proportional   to  the
         negative  gradient   of  the  mean  mixing  ratio  for  all
         species,  but  the  coefficient  of  proportionalities,
         K, must  also  be  independent of  the  species."    [NAS,
         1979a,  p.  51].
Of course,  a similar  statement may  be made  regarding  two-dimen-
sional  eddies.    No direct tests are available  for these  assump-
tions, but  caution is in order.

         The diffusion  coefficients  are  not  necessarily truly
independent of  the  species.   In recent  theoretical  work on the
two-dimensional  eddy-diffusion  approximation,  Pyle  and  Rogers
[1980a;  1980b]  note that  the  assumption  of independence is valid
only for very long-lived or  inert tracers.  To  the extent that a
species   reacts,   the   diffusion  coefficient  may   be   chemistry-
dependent.   For  very  reactive species,  chemistry could dominate
creating serious  errors.   The principles  apply equally  well to
the further simplified eddies of  1-D  models.

     4.   Testing the Approximations

         The danger of  acccepting  the eddy diffusion  approxima-
                                                \
tion blindly is equally well  noted  by NAS:

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         "It is not very probable that such  stringent  conditions
         [see previous  quotation]  can  be  met in  view of  the  fact
         that photochemical  sources  and  sinks,  vertical  fluxes,
         and chemical  reactions  all  vary with latitude,  longti-
         tude,   and  height  for  each  gas,  giving  rise  to  many
         nonlinear effects."  [NAS, 1979a,  p. 51].
The panel concludes, however, that the approximation would still
be useful (for  1-D)  if K profiles derived  by fitting measurements
of upward moving trace gases are similar in  shape and  comparable
in magnitude to those  derived  from downward  fluxing trace  gases.
In  fact,  for  the  several  long-lived  gases   examined,  the
comparison is reasonably good.

         However,  the rationale presented  has a major flaw.     As
indicated by  Pyle and  Rogers  [1980a;  1980b] , it  is   just these
long-lived  species,  such  as  N-0,  0.,  and  CH4,  for  which  the
approximation   should  be  most  applicable.    Yet  it  is  the
short-lived, highly  reactive  species  that  may  influence ozone
concentrations,  and, therefore,  which must  be accurately  modeled.
It is satisfying  that  upward  and downward moving species  behave
similarly, but not  sufficiently  so to  justify  application  of the
same transport  parameters to all atmospheric species.

         The long-lived species are initially chosen for  the  test
by valid reasoning.   Their concentrations  are largely governed  by
transport and  boundary conditions,  with  fairly  well  understood
chemical sources and sinks.   Shorter-lived  species are  themselves
far more dependent on chemistry,  and  any  fitting  attempt  would  be
as much  a  test of  model chemistry  as of  model transport,  and
therefore of  little  value  as  a test  of  transport parameteri-
zation.    If  eddy  transport  itself  is a function  of chemistry  as
Pyle argues, eddy transport of  short-lived  species remains as  an
untested assumption in current models.
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     5.  Estimating Uncertainty  Due  to Transport

         The uncertainty  in  calculated ozone  depletion  arising
from transport is  taken by NAS  to  be dominated by the effect on
CFC lifetimes.   Since the  CFCs are  long-lived trace species, this
aspect  of  the  uncertainty  has  indeed  been   tested  by  their
analysis and may  well be correct.    That  all other uncertainties
are smaller has  not been demonstrated.

         A change  in the  constant  K profile  for  all species is
said "generally"  to provide a negative feedback on the change in
ozone destruction, so that the  uncertainty  in  A. Q-^ is less than
or equal to that  in K.  This ignores the  uncertainty in K-theory
itself,  i.e.,  the  assumption  that  it  is  a   reasonable way  of
expressing atmospheric  transport.    Also  discarded  is  the
possibility  that  the   theory   is  basically  sound,  but  the
coefficients are  strongly species  dependent.   The NAS reasoning
is as follows:
         "It  is  possible,  however,  if  transport  errors  in
         different species  were  to add  randomly  rather  than in
         the  correlated  fashion  of  the 1-D  models,  that  the
         overall  uncertainty  in  ozone change  could  be somewhat
         larger  than   the  uncertainty  in  CFM  lifetimes.    We
         believe  it likely,  however,  that the uncertainties due
         to  transport  are  smaller  than  the  uncertainty  in CFM
         lifetimes and that  our  error  estimate [a factor  of 1 +_
         0.3] is a conservative  one."   [NAS,  1979a, p. 58].
Although  the results  of  Pyle were not yet  available to the NAS,
the possibility of species-dependent transport  was known, but was
entirely  untested for  the most critical species, and was dis-
carded completely on  the sole basis of  belief.
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     6.  2-D Transport

         The theory of 2-D eddies has been discussed already,  and
the problems  are  similar to  those  of 1-D eddy  diffusion  except
for  those  associated  specifically  with  latitudinal  averaging.
Yet while  the  four-parameter  (K  ,  K  ,  K   ,  K   )  expression of
                                yy   y £   zy   z z
eddy transport perhaps allows for more realism,  it  also requires
the derivation of  four parameters rather than one.   The limita-
tions of the  data  base alluded  to by NAS for  1-D eddy diffusion
therefore  become  more  critical,  and  the individual  parameters
less well defined.

         An additional  requirement  in 2-D modeling  is  a parame-
terization for mean flow in  the  meridional  plane.    It  has  been
argued  [Pyle  and  Rogers,  1980a;  1980b]  that,  in   the  Eulerian
representation, the  eddy diffusion tensor must  be  non-symmetric
(i.e., K   ? Kzv^ *   Tne implied advective transport could instead
be incorporated with  the  mean flow  in  a  Langrangian representa-
tion,  leaving  the K-tensor  symmetric  and  reducing  by one  the
number of necessary parameters [Miller e_t al. ,  1980a, 1980b;  Pyle
and  Rogers,  1980a;  1980b] .    Two-dimensional  modeling  remains  a
very young research area,  though, and it is likely that expansion
of the  data  base  will permit (in the future if  not  already)  2-D
models  to  further  improve  transport representation and,  at  the
same time, provide a  much more  realistic  simulation  of the atmo-
sphere  than  that  in  1-D models.    Both 1-D and 2-D models,  how-
ever, will still be subject to  the  untested assumptions  accom-
panying the eddy diffusion theory.
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 D.  STRATOSPHERIC CHEMISTRY

         While  tropospheric  processes,  transport,  and  model
construction  all   influence  the magnitude  of  calculated  ozone
reduction,   the  process  if  it  occurs  is  a  chemical  one.    The
active catalytic  species are generated  and  lost in chemical and
photochemical reactions,  the  ozone  destruction cycle is chemical,
and  the  chemical   interactions  among  all  the  atmospheric  trace
species  govern  the  degree  of effectiveness  of  the cycle.
Furthermore, despite the  confidence expressed by the NAS Panel on
Stratospheric Chemistry  and  Transport  in  the body  of  chemical
knowledge assembled  for  their   report  [1979a],  it  was chemistry
which  contributed  the major   uncertainty according to  their
analysis.

         Since the 1979  report,  research in  kinetics  and photo-
chemistry  has provided  even more  evidence of the weaknesses in
the current data base.   Several  new results and remeasurements of
"well-known" reactions  underline  the  conclusion of Smith  [1978]
that the uncertainties have been repeatedly underestimated.   Pos-
sible reasons for  the underestimation are not difficult to  find.
Available techniques are  continually pushed to the  limit of their
capabilities.  The  atmospheric  system  is  not amenable to simple
duplication  in  the  laboratory.    Finally,  the  questions  being
asked  of  kineticists  and  photochemists  are  demanding.    The
molecular interactions of radical species  are not nearly so well
understood  mechanistically  as  those of  more stable  molecules, and
conventional extrapolations over temperature  and pressure ranges
may  often be unjustified.   Products are not  always the expected
ones,  and   even  minor  product   branching  may  have   major  con-
sequences.
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     1.  Measurement Uncertainty

         The first source of uncertainty  which  must  be  considered
in any  evaluation  is  simply the degree of confidence  in current
data  --  soundness  of  techniques,  carefulness  of  the  experi-
menters,  and  accurate  expression  of  confidence  limits.    The
number of reactions to be considered makes  this alone a source of
major uncertainty in model-calculated depletion.     To  that must
be added the effect of sensitivity of calculated depletion, both
to  individual errors  and to combination of  errors.   As will be
explained below  for the case of HC^NC^/ a significant error  in
one  reaction  leads  to  underestimated   sensitivities  for   other
reactions.

     2.  Temperature and  Pressure  Dependencies

         Next,  the data  base  itself suffers problems  in its ap-
plication to the stratosphere.     Reaction  rates have rarely been
measured under  the full range of  temperature and  pressure con-
ditions present in the  stratosphere.    The  most  direct, and
presumably most  accurate,  laboratory  techniques  require low
pressures, making the high  pressure, low  tempeprature  conditions
of the  lower stratosphere almost  impossible  to  simulate.  Yet it
is in the lower  stratosphere where the  most complicated chemistry
is  important and  where  most ozone depletion has been  calculated
to take place.   Many reactions  in  the current data  set  have  never
been examined  for pressure dependence,  yet  similar  reactions have
been  (surprisingly)   found  or  postulated  to   exhibit pressure
dependence  (e.g.,  OH  +  CO,  HO-  +  H02).    Unusual temperature
dependencies abound  —  H02  +  H02, H02  +  CIO,  OH  +  HNOj, for
example.   In many  cases,  it  is  apparent  that reaction  mechanisms
are  simply not  well  understood,  and  a  great  deal  of research
remains  needed  to  solidify  the  data  base.   Such  questions are
critical when considering  the  extensive  coupling among chemical
families and  the  fact that  many  of the reactions involved are

                               I? _-.Q
                               ij — £. O

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among those to which calculated depletion is most sensitive.   The
results  of the past  year for OH + H202 [Keyser, 1980;  Sridharan
et al., 1980]  and OH + HN03 [Wine  et al.,  1980]  both  lie  outside
95 percent confidence range given in the NASA [1979a]  evaluation.
The NAS  estimation  of  uncertainty  in A CK was,  of  course,  based
upon such evaluations.

     3.  Product Identification

         A third area of uncertainty minimized in earlier  evalua-
tions is the identification of reaction products.  Sze [1979]  has
noted that if the reaction OH + CIO  has  a  branch of as  little as
10 percent to HCl + 02, the calculated ozone depletion is  reduced
significantly.  Yet model calculations assume the products  to be
entirely H02  + Cl.   Although product  studies   are in  progress,
previous work  limits  that branch only  to  <" 35  percent  [Leu  and
Lin, 1979].   A similar situation exists for a possible HCl  pro-
duct from  the  reaction H02 + CIO,  although an  upper  limit of  3
percent  has  been established  at  room temperatures [Stimpfle et
al. , 1979;  Leek ^t a_l. , 1980;  Leu,  1980].

         The significance of product identification  was  made more
apparent  recently  by  Molina  _et  al. [1980]   in  their  study  of
chlorine nitrate  formation.   Previous  work  [See NASA,  1979]  on
this reaction, CIO + N02 + M,  had measured the rate  by monitoring
reactant disappearance.   Molina  e_t  al.  monitored  formation  of
C10N02  product,   and  observed  a  rate  one   third  that  of  the
previous studies.    It has  been  postulated  that  the  remaining
reactant disappearance  leads  to production of  another  isomeric
product  whose  chemistry  in  unknown,  but which is likely  to be  a
less  effective chlorine  sink  than  chlorine  nitrate.    A  less
effective  sink   could  increase  calculated  ozone  depletion.
Because of the major role played by ClON02 in current  models of
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the stratosphere and the potential  for  significant new  chemistry
involving  any isomer,  the enlarged uncertainty here deserves
rapid attention.

         Identification  of photolysis products has  also  in many
cases  not   been  resolved,  with chlorine  nitrate  again  as  an
example  [See  NASA,  1979].   A  more critical  case is  the possi-
bility  of  HCl  production from  HOCl photolysis, being  studied
currently  by  Birks.  The  examples mentioned  are  by  no  means
exhaustive.   As with  temperature  and  pressure  dependencies,  a
careful  review of  the CODATA summary  [1980]  of  evaluated data,
and  comparison  with  NASA  report  RP-1049  [1979]   reveals  many
inadequacies  in  the  data  base.    The  hundreds  of   references
contained  in  those  documents serve  to  identify  the assumptions
incorporated  in current  models.    As the new  results continue to
point out,  such  assumptions are  all too often  not warranted.

     4.  Third-Body  Dependencies

         Hamilton  and Lii  [1977]  and others  [Lii e_t  al. , 1979;
Cox and  Burrows,  1979] ,  have found the  reaction  rate  for H02 +
H02 to  be  dependent on  the concentration of  water  vapor in the
reaction region  and proposed  that a  complex,  H02«H20,  may
participate in  the  reaction,  effectively  catalyzing   it.   Con-
siderable study will  be  required  to understand the  mechanism of
such action,  but  a  possible role  for  the  complex  in  other H02
reactions is  suggested  by  these  results.   A complex with water,
unless  very strong,  is  of significance  only  in  the troposphere
and  lower   stratosphere,  given  the  relative aridity of  the
stratosphere.

         A  potentially more important complex  has been  postulated
by  Prasad  [1980],    In  examining  laboratory data  on  chlorine-
sensitized  ozone decomposition,  Prasad has found that apparent
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inconsistencies can  be  explained in  terms  of  a C10»02  complex.
The  complex  could   involve  significant  amounts  of  CIO.   The
sensitivity of  such  an  association  complex to  temperature  could
help to  explain  the  large variability among the several  in  situ
measurements  of  stratospheric  CIO by Anderson  ejt  al. ,  [1980a] .
Reactions  of   the complex  might  also  serve  to   decrease the
efficiency of the chlorine catalytic  cycle  through  the  following
"do-nothing" cycle:
                   CIO + 02 + M	* C10»02  + M
                     C10-02 + 0	>-OClO
                      OC10 + hv	»> CIO + 0
A complex involving 02 would not be  limited  by  02  concentration,
but only by the temperature and pressure conditions  required  for
its formation.  Recent work of Anderson  et al.,  [1980b]  suggests
that the role of this complex is very  limited,  but  the  notion of
oxygen complexes,  like that of  water  complexes,  remains  generally
untested.

     5.  Pressure Dependencies

         Negative  temperature  dependencies noted  for several
radical-radical  reactions  also  imply  the  possible  role  of
complexes as  intermediates.   Should  that  be  the  case, product
distributions would  be  strongly influenced  by  the  structure  of
the  complexes,  and   product  identification  becomes  even   more
essential.   Additional variation  of rate  with altitude  again  adds
to rate uncertainty.

         Pressure dependence  of  3-body  reactions   are  also  not
always well defined.   An example  is the reaction for chlorine

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nitrate formation, where the fall-off  in  the  observed  rate does
not fit the theoretical  fall-off curve  [Watson, R. T., 1980].

     6.  HO^ Chemistry
           X ~™   " ••" ' ' " "  '

         One might note  from the  preceding  discussion  that many
of  the major  types   of  uncertainty  in  stratospheric  chemistry
involve HO  species,  OH and HO,.   A review of those reactions to
          X                   £f
which calculated ozone depletion is thought to be most sensitive
indicates that several of those reactions also involve  either OH
or H02«   Finally,  many  of  the  most surprising developments from
research, during the  past year  in particular,  once again involve
the  so-called  odd hydrogen species.    The chemistry  of  these
species,  particularly  HO,, [Watson, R.  T.,  1980], is not  at all
well understood.

         The principal interaction between  odd hydrogen  and odd
chlorine  species is through  the reaction:

                      HO  +  HC1	> H20  + Cl
This reaction controls the  rate  at which chlorine is removed from
the  temporary  sink HC1.    As  HCl,  chlorine  is  isolated  in  a
relatively stable  form,  and does  not contribute  to  depletion.
Chlorine atoms,  on the other hand are  a reactant in the catalytic
destruction  cycle.    A variety  of  atmospheric  measurements
indicate  indirectly that the model-calculated  concentrations  of
OH in the lower stratosphere are too high.  Through the reaction
above,  this  leads to  exaggerated amounts  of  calculated ozone
depletion.  Consequently, special importance has been attached to
the study of  reactions  by  which OH may be  converted  to  H20 and
removed  more  rapidly  from the  stratosphere.    Several  such
reactions are currently being studied.

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         Perhaps  the  most  important,  and  almost certainly  the
most uncertain, of these reactions is:

                      OH + HOj	>H2° + °2

A number of  studies have  been completed,  and  they generally fall
into two  groups:   studies  by relatively  direct  methods at  low
pressure giving a  slow  reaction  rate  [Hack  et al. ,  1978;  Burrows
et al.,  1978a;  1978b;  Chang  and  Kaufman,  1978],  and  studies  by
more  indirect  methods  at higher  (atmospheric)  pressure  giving
rates  up  to  an  order  of   magnitude  faster   [Demore,   1979;
Hochanadel  et  al.,  1972].     Furthermore,  the reaction  is  not
expected  to  be   pressure-dependent,  making  resolution  of  the
differences  difficult.    At  present,  there  is  no direct  method
available for  the  entire  range of pressure necessary.  The most
recent  studies  corroborate   earlier  indirect  results  [Kurylo,
1980; Demore, 1930].   A fast  reaction rate,  even  if  only  at high
pressures  and  low temperatures   (i.e.,  the  lower  stratosphere)
would  significantly  reduce  calculated depletion.    The value  of
such reduction and those  arising from other  recent  developments
will be discussed thoroughly in the section on model  results.

         A  surprising  result  obtained  recently  by Wine  et al. ,
[1980]  is a significantly faster rate  for the reaction OH  + HNOj,
previously  thought to  be  known  quite  well.    In  addition,  a
negative temperature  dependence was observed,  making  the reaction
especially  important  in  the  cool  lower  stratosphere.    Kurylo
[1980]  has  recently  given preliminary confirmation  for the Wine
et  al. ,  result,  although Marinelli  _et  al. ,  [1980]  measured  a
somewhat slower  rate.   The unexpected Arrhenius  parameters have
led the researchers to an investigation  of the products.   The

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products currently  assumed  by modelers  are H20  +  NO-,/  but  the
temperature dependence observed is uncommon for a simple  hydrogen
abstraction reaction.   Other  products such as  H202 and N02  are
possible,  although  Marinelli  e_t  al.  [1980]  have concluded  that
H20 and NO-, are indeed the major  products.   Again here,  the  model
calculations   are  quite  sensitive   to  this  reaction  and  its
products.

         In other HO  chemistry,  Molina  and Molina [1980a;  1980b]
                    X
found  that the  association  complex   between  H02 and N02,  i.e.,
peroxynitric acid (H02N02), photolyzes more slowly  than  previous
results  [Graham  et.  al. ,  1978]  had implied.   As a  consequence,
other  reactions  of  the molecule  assume  greater  significance  in
atmospheric models.    The  LLL  model used  by  NAS,  along  with
several  other  models,  had omitted H02N02  from  earlier  calcula-
tions,  assuming  it  photolyzed  rapidly  back  to   the  initial
reactants.   With the longer lifetime  of  H02N02,  the  reaction OH +
H02N02 may now provide  another route  for removal of  odd  hydrogen
from the lower  stratosphere.   Trevor et al.  [1980]  have used  a
direct method  to determine  a  very fast  upper limit  for  the  rate
of the OH + H02N02  reaction.   Littlejohn and Johnston [1980]  very
recently reported the first actual measurement of this  rate,  as 2
         -12    3
+_ 1 x  10    cm /molecule  -  sec.  — 5 times faster  than  the  NASA
[1979]  recommended  rate.  And  Barker  ejt  al  [1980] , in a  continua-
tion  of  the  Trevor  study  by  an alternate  method,  have  just
                      a
reported rate  measurements of OH + H09N09  in  the range of  4  to 5
    -12
x 10    at  four different temperatures.   A  fast rate for  the OH +
HOpNO-,  like  other  rate  increases  mentioned  in this  section,
again  converts odd  hydrogen  to water more quickly  and  leads  to
decreases in calculated depletion.

         The significance of these developments goes beyond  their
effects on  calculated depletion.    The changes came  in  unexpected
places.  They  belie  the great  confidence expressed in the current
recommended rate set used by modelers  and raise questions about
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the true range of uncertainty  in  calculated ozone depletion which
arises from "known chemistry".

     7.  Excited States

         The role of excited states  in  stratospheric chemistry is
a  question  often  discussed,   but rarely  with  satisfactory
resolution.    Sufficient  excitation   could  produce  dramatic
differences in reaction rates.   Certainly, however, most excited
state  species  produced  as  a  result  of  photolysis  or greatly
exothermic reactions will  be rapidly quenched.  The 0( D) atom is
an  exception   already  incorporated  in models,  although  there
remains  some  doubt  about  the absolute  quantum yields  for  its
production [NASA, 1979;  Chang, 1980].   Electronically excited 02
and 0-,  have  been  proposed, e.g.,  Prasad  and  Burton  [1979],  to
play  a  role,  but  no  examples have  yet  been found.   These  are
particularly   important  in that they may  provide  additional
sources   of  odd  oxygen  (i.e.,  atomic  oxygen   and   ozone).
Vibrationally  excited  OH radical  is a  likely product of several
reactions, but its survival  relative to quenching is likely to be
small,  and  only  a   large   source would   make  this  species
significant.

         There is  also a more indirect way  that excited states
may  relate to  our  knowledge  of  stratospheric  chemistry.    In
laboratory kinetic  studies the radicals of  interest  may also be
produced in excited states.  Failure to equilibrate these species
sufficiently can  lead  to erroneous  reaction  rates.   Ravishankara
and Wine  [1980]  note a likely example  in  their work on the Cl +
CH^ reaction.   The two  spin  states  of the  ground  electronic state
of chlorine atoms are  separated  in  energy by such an amount that
the lower  state  reacts endothermically with methane,  while  the
upper state reaction is exothermic.   Ravishankara postulates that
this  may  explain the difference  apparent  among previous studies
of  the  reaction since  the   measured  rate  will  depend on  the

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relative populations  of  the two  states.   Furthermore,  the  rate
appropriate for  use  in stratospheric models  will depend on  the
stratospheric populations.  Further consideration of  these  ideas
will certainly lead to refinements in  stratospheric  models or  our
confidence  in  them,  but  at  this stage,  the  ideas  represent  an
additional new source of uncertainty.

     8.  Solar Flux

         Recent  efforts  to determine more  accurately the  solar
ultraviolet  flux  reaching the   stratosphere  are  discussed   by
Nicolet [1980] .  Reductions from the  flux levels currently  used
by modelers have been considered.  If  incorporated,  the  rate  of
ozone  production is  decreased,  and  several  other  photochemical
reactions  are affected.   The net  result could be  a  slight change
in  calculated  ozone  depletion.    Once  again  the  point  to  be
stressed is the significant uncertainty  in model inputs.

     9.  Unknown Chemistry

         Several other facets  of  stratospheric chemistry  may have
potential  impacts  on  ozone perturbations, but are  currently  not
well enough understood to  permit  conclusions.   First  among  these
is the  process  of halocarbon  oxidation.   Current  models 'assume
immediate  release  of  all  chlorine atoms  upon  initial photolysis
of CFCs 11  and  12, and most neglect any  subsequent chemistry  of
the fragments.   Indeed, all the  chlorine  from  stratospheric CFCs
11 and 12  is probably released  eventually, and a time  delay  would
be relatively unimportant.  However,  the possibility remains that
a  chlorine-containing   intermediate  would  be  sufficiently
long-lived  to  be  transported   to  the  lower  stratosphere  and
removed directly.    This  would   reduce  the  effective  chlorine
contribution of CFCs to the stratosphere, and thereby reduce  any
ozone depletion which might be  calculated  to  occur.
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         The methane  oxidation  cycle  is  expected  to  provide  a
small source of odd  oxygen  through  interactions with odd hydrogen
and odd  nitrogen  species.   However,  this cycle is not  yet well
understood.     Many  of the  methane  oxidation products included in
current models  have  not been  observed in the atmosphere, so veri-
fication of  the current model chemistry is not possible. The rel-
evance to calculated  ozone depletion lies  in  proper  quantifica-
tion of  the  ozone  source  and in exploring possible interactions
with the chlorine  cycle.

         Likewise,  sulfur chemistry is thought  to  be irrevelant
to  the  ozone depletion calculations,  but again the knowledge is
minimal.   Since  much of  the  sulfur  is  rapidly  converted  to
aerosol,  the  question becomes  one of  heterogeneous  chemistry.
Here again the  neglect  of  this chemistry  in  current models is
based  more  on lack  of  information than  on  confidence  in its
unimportance.

         A  final  note on   unknown  chemistry concerns  ozone
production.   A  variety of  possible  reaction schemes which lead to
production  of  ozone  (or  equivalently, oxygen  atom)  have  been
proposed  [Prasad and  Burton,  1979; Miller  ej:  al. ,  1980c] .   None
have  been  verified,  although  experimental   work  is  still  in
progress.   The  schemes proposed are all  dependent  on  chlorine,
and may provide explanations  for stratospheric measurements such
as  Anderson's  observation of  normal   ozone  in the  presence  of
abnormally large amounts  of chlorine  [Anderson et al., 1980a], or
Dobson and  Umkehr  measurements of increasing  ozone  levels over
the   past   decade    despite   increasing  concentrations   of
stratospheric   chlorine  (discussed  in  the  section  on  ozone
measurements) .   It  is  important either to  verify or  to  rule out
such chemistry  to reduce the very  large uncertainty in "unknown"
chemistry.   Of course  the  very  nature  of  the word  "unknown"
implies  that  the  topics  addressed   here  do  not necessarily
encompass all such chemistry.   Other surprises may exist as well.

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 E.  STRUCTURE AND SCOPE OF MODELS

         The previous sections on the troposphere,  transport,  and
chemistry describe the  foundations  of  our  knowledge  of  the atmo-
sphere  in  general and  the  chlorofluorocarbon  effect  in  parti-
cular.  To  achieve some understanding  of  the  CFC effect requires
synthesis of  this  knowledge.   Computer models of  the atmosphere
provide  the  tool.    One must realize, however, that models  are
only a tool — compilations of knowledge and not duplications  of
the atmosphere itself.

         Modelers attempt  to  verify their  results by comparison
with measurements  made  at  a  point in  time.   However,  the  time
propagation of models  is rarely tested  (few  comparable measure-
ments  exist) ,  and  the  comparisons  are   not  always  successful
[Steed e_t al. , 1980; Angell and Korshover;  1973; 1978].   Indeed,
Prather ej:  al.  [1979]  argue  that  the concept of  the atmosphere
employed in current models may suffer from physical instabilities
such that only minor changes in input, e.g., total  NO ,  may cause
                                                     X
gross changes in the  chlorine  chemistry calculated by the  model.
This is especially true for  high  latitude  conditions.  Given  the
very nonlinear system of equations to be solved,  such a  result is
not surprising.
                                                     •
         Nonetheless, models are an exceptionally useful diagnos-
tic tool.    They  have helped researchers  identify  weaknesses  and
gaps in knowledge and have guided subsequent  research toward  the
more  crucial  problems.    The  dynamical  nature of   models  also
allows a  consideration  of the  time evolution of  the atmosphere
under a given set of conditions.  To the extent that  the "present
day" results of  a  model are correct and  the  dynamical  equations
are correct, one can calculate the changes to  be expected under a
totally specified set of future conditions.
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         However/ as discussed earlier,  the limitations of the
current data base cause concern.     Neither  the  transport  nor the
chemistry in current models is likely  to be complete  or exact.
The  time  propagation  of any errors is also likely  to  exaggerate
them,  particularly  if physical  instabilities   of  the  sort
mentioned by Prather e_t a_l. [1979]  are  present.

         Even without the concern over  data base and  conceptual
uncertainties, true prognostication with  models  is difficult.  As
mentioned, one must make assumptions about  the  "future"  in  order
to do  a calculation.   The simplest,  most  common,  and  probably
most misleading  assumption  is  that all input fluxes of  chemical
species and  solar  energy remain  at their present (or  other well
defined) levels.   From  the point of view of the research scien-
tist, this is a  useful  if  not  essential  exercise.   It  allows the
models  to  achieve  a  steady-state,  i.e.,  a condition where  no
further change  is  noted from  one model-year to  the  next.   Given
numerical differences  in modeling techniques,   this steady-state
condition is  most  amenable to intercomparison  of models.  How-
ever, this is not by any means a  simulation of  the  real  future,
as an experienced modeler will readily  admit.  The model  behavior
is that to be expected if the data base is complete  and accurate,
jLE the  conditions  are  accurately descriptive of the future, and
if the  model  structure  does not  impose  unwarranted constraints.
The  data  base  has  been discussed, and the  latter two  conditions
are addressed in this section.

     1.  Stratospheric Chlorine Inputs

         The sources of  stratospheric  chlorine  are  not all well
defined  [NASA,  1979;  Jesson,  1980] .   Background chlorine levels
in models are based on  estimates  of  known natural sources  (e.g.,
CH-jCl)   and  estimates  of  industrial  sources.    In  "prognostic"
calculations,  estimated  current   sources  of most  compounds are
presumed to  remain constant into the  model "future".   Sometimes

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the  model   flux  of  CFCs-11  and  12   is  allowed  to  change  to
investigate the possible impacts of such changes.   Realistically,
however, the  future  fluxes  (both  natural  and  man-made)  are  not
well known  -  but  are unlikely to remain constant.   An excellent
example is  methyl   chloroform,  for  which   both  industrial
production and  atmospheric  concentrations  are  known  to  be
increasing  at the present time.  Given  nonlinear  effects even  in
chlorine chemistry   itself   [Cook  e±   al.,  1980],  the  marginal
effects of  continued CFC release  are  not accurately  calculated
under such  unrealistic constraints.  Volcanoes  may also provide a
time-varying source  of atmospheric  chlorine [Steed ej: a^. ,  1980],

         It  may   well   be  impossible   to   account for  all  such
variations   in chlorine  release,  and  that  in itself  does  not
demean  the  results   of  model  calculations.    It  does,  however,
provide a  perspective for  viewing  calculations  extrapolated  to
the "future".

     2.  Other Time-Varying Chemical Inputs

         CFCs are not the only stratospheric  perturbation to  have
been considered by modelers.  However,  until recently, each  such
perturbation has  been considered individually with the assumption
that  little  coupling  takes  place among  the  various  chemical
families.   Molecules such as  H02N02, ClON02, and  HOC1  along  with
several fast reactions such as H02 + NO,  CIO + NO, and OH +  HCl
have served to better define  the coupling among HO  ,  NO  and  Cl
                                                   a    j\        x
species and their chemistry.

         NO  perturbations, possibly in the form  of  an increased
           A
N20 source  from  fertilizer  use,  cannot reasonably be  ignored  in
consideration of a CFC  perturbation.   To  the extent that  an  N20
source  is   increased,   the  calculated  CFC   effect  on  ozone  is
decreased  [Miller e_t  al. ,  1980c; NASA, 1979].   A recent  set  of
calculations  [NASA,  1979] shows  the CFC effect  is roughly  halved
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if  the  ^0  source  doubles.    A  "prediction" for the future is
improperly named if  such  changes are not taken into account.    A
"what if" question which  isolates a single perturbation  is  irre-
levant  to the  question  of  appropriate immediate action.   One
reacts with justification to what one expects will happen  taking
all variables into account.  Focusing on a single variable and ig-
noring others is unreasonable.

         Honest evaluation of  the  future  has become increasingly
difficult as our knowledge has improved.   A case  in point is the
carbon  dioxide  perturbation.   The  primary  effect  of  the  well
documented increases in  C02  [NASA,  1979;  NAS , 1979a]  is  on the
radiative  and  thermal  properties  of  the  atmosphere.   Chemical
effects,  although  potentially  large,  are  secondary.    Most
chemical  models  parameterize   radiation  and temperature  fields
rather than calculating them explicitly, and the radiation models
generally use only simplified  chemistry not capable of accounting
for  a  possible  CFC  effect.    Recently,  however,  modelers  have
begun to combine the two  more  effectively  [Penner, 1980a;  1980b;
Haigh  and Pyle,  1980;  Callis and  Natarajan,  1980].   The  new
calculations show that  a  CC^-induced  cooling of the stratosphere
may well  cause  increases  in ozone  concentration  of  up to  6 per-
cent.   Taken in conjunction  with a CFC  perturbation,  the net
effect  is a  reduction  of CFC-induced depletion (by approximately
3-5 percent with current  model  chemistry) .   [Penner, 1980b] .
         A doubling  of  both N^O and  COp/  the first of which is
not unexpected and the  second of which  is  likely,  reduces  the
calculated CFC effect on ozone  by well over half.    Yet both are
customarily ignored in discussing the  "dangers" of CFCs. Calcula-
tions  of  a postulated CFC  scenario  continue to be referred to as
"predictions of the future" despite the  obvious fact  that  they
are neither predictions  nor an  accurate account of the future.
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     3.   Coupled Nature of Atmospheric  Processes

         The  atmosphere  is  a  complex  coupled  system  involving
inputs of  chemicals  and  subsequent  reactions,  radiation  inputs
and  radiative processes,  and  transport.   Radiation  influences
chemistry both  through  photolysis  and  temperature.   Dynamics  is
influenced by radiation  via  heating and  convective processes and
in  turn   serves to  transport  and  distribute   thermal  energy.
Dynamics   as  well alters  local  chemical  composition,  which,  in
turn, both drives chemical  reactions  and influences  the  flux  of
radiation through the  atmosphere.   Finally the chemistry of the
atmosphere itself determines the  chemical composition  under the
influence of all the  other processes.

         In attempting  to model  the atmosphere with a  1-D model,
these processes  are  not all treated.     Horizontal  transport   is
ignored   and  vertical  transport  is   paramaterized  and  not
interactive with other  changes.   In particular, the coupling  with
dynamics   and  radiation  is  omitted.    The difficulty  with  such
approximations lies  in the  tacit  neglect of  feedback  mechanisms.
The  lack  of  calculational  experiments  has  limited  ability  to
estimate   the  magnitude  of these  effects.   They  have been noted
and subjective guesses  as to their magnitude  have  been  made  [NAS,
1979a; UK DOE,  1979].   For the  moment,  however,  they  remain not
well understood, and not  at  all  rigorously quantified -  even  to
the extent of establishing confident  upper limits.

         Feedbacks  are,  of course,   second order  effects  --
responses to  a   response.   Thus,  for  very small perturbations,
they  may be  reasonably given  proportionally  less  emphasis.
However,   the  sorts  of  chemical  change  postulated  to arise  from
CFCs  are  large  enough   to  lead   to  more  serious  errors.   The
severity   is  compounded  by  the   basic  lack  of  understanding  of
feedbacks as much as  by the computational difficulty  of  including
them.
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     4.  Atmospheric Variability

         As  models   are  designed,  calculated  chemical  species
concentrations are slowly varying functions of altitude and time
(and latitude  in  2-D models).    The  realistic behavior, however,
is far removed from  the model  representations.    Water has  been
observed  to  exhibit  significant  stratification  on   relatively
small  altitude  scales  [Kley  £t  al.,   1979].    Total  column
fluctuations  occur  for N0?  (Noxon,  1979)  and  OH  [Burnett  and
Burnett, 1979].   I_n  situ  measurements  of CIO  also  show marked
variability  at  all   altitudes  [Anderson   e_t  al. ,  1980a;  1980b;
Parrish £t  al,  1980].  Even source  molecules such as ^0,  CH^,
and CFCs are  found  to exhibit  variability [Ehhalt, 1978; Goldan
ert  al. ,  1980].     These  measurements   are  all  examples  of
variability on time  and distance  scales which  models are unlikely
to  be  able  to  account for,  since  models necessarily calculate
averaged concentrations.

         Beyond this sort  of  variability, there are  the longi-
tudinal,  latitudinal,  and seasonal  variations,  all of which are
ignored  by 1-D models.   Such  fluctuations and  gradients  in
species concentration can  become  significant  in the reaction rate
calculations performed by models.  To take  the  case  of a simple
bimolecular reaction, the  rate  is conventionally  expressed as:

                           k  •  A •  B
where k  is  the  temperature  dependent  rate  constant,  and A and B
are  the  local  reactant  concentrations.    In  a one-dimensional
model, what  we  want is the  average  rate  of  reaction,  i.e., the
average  of   that  product  over   time,  latitude,  longitude,  and
altitude increment.   We denote the  average  by:
                               V _ f '3
                               1J  1 -I

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                           k •  A •  B

To get  that  result, one  needs  a value for  the  product at  each
time  and  point  in space  --  unavailable   information.   The
information  we  can approximate,  however,  is  the  individual
averages of  those quantities,  i.e.,  k, A and B,  so  the  models
employ the product:

                           k" •  A •  B

The  two  expressions of  the product  are  not necessarily  equal.
Suppose one considers the averages for two nearby locations.   At
the first,   k,  =  1, A,  = 2, B,  = 0; at the second, k~ = 1,  A2  =
0, and B  = 2.   Now:
      k •  A  •  B = 1/2 (kj_ •  A! •  Bj_   +  k2  •  A2  •  B2)
                  = 1/2 (1 • 2 • 0  +  1 • 0  • 2)
                  = 1/2 (0 +  0)
                  = 0
This is  true  average reaction  rate in  that  region.  The  model,
however, performs a slightly  different  calculation:

     "k • "A  •  "i = 1/2 (kj_ +k2) • 1/2  (Aj_  + A2) • 1/2 (El  +  B2)
                  =1/2 (1+1)  •  1/2  (2  + 0) •  1/2  (0  +  2)
                  = 1 •  1 •  1
                  = 1

This sort of  averaging error  can,  and does, take place with  each
of the  kinds  of averaging incorporated into model  calculations.
That much is  known.  What is not known is the  magnitude of  such
errors.

         Furthermore, that magnitude is very  difficult  to check
against reality.  One is  forced  to  compare model with  model.   For
example, a  2-D  model  can be averaged  over  latitude  to give  a

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"1-D" result, which can then be compared to 1-D models.   In fact,
Tuck  [UK  DOE,  1979], has  compared  3-D model results with  a  2-D
simulation for particular reactions and found that the errors  may
indeed  be very  serious.    It  is, of  course,  possible  that  the
errors  will  tend  to cancel  each other,  but  for  an  extremely
nonlinear system that is an improbable outcome.

         Spatial variability also  presents  difficulties  for
interpreting model results and comparing them with field measure-
ment data.   Any  atmospheric field quantity, X, may  be  expressed
as  the  sum  of  an average  over  longitude,  X,  and the  deviation
from  that average, X1,  i.e.,  X  =  X  +  X1.   Now a  measurement
provides  the quantity X,  whereas a model  calculates X.   For  a
valid  comparison,  one must either  know  X1  or have sufficient
measurements to establish a reliable X from field  measurements of
X.

         Carrying  the situation  to 1-D models, the  situation is
further complicated by latitude.   The  longitudinal average X  may
be further broken down into a global average X and a  deviation of
the longtudinal average from the global average X" so that

                            "x = X~ + X"

                       and X = * + X1 + X"
In analogy to  the  2-D  situation,  a  comparison  of  1-D  results for
1(  requires either  knowledge  of  both X1  and X"  or  sufficient data
to  provide  a   reliable  average  field  measurement   of  X.    In
general,  field data are simply  not sufficient to define  either
the fluctuation terms  or the  necessary  averages,  and  the desired
comparison is  not possible.

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         An  appreciation  of these problems  is  essential  to any
comparison of  model  results  with  field  measurements.    Thus,
statements that  current agreement is reasonably  good  [NAS, 1979a]
are implicitly  qualified by the knowledge  that  only  gross errors
in magnitude  or  errors in shape are likely  to be detectable.  The
calculated  averages may well  be quite different  from either
individual measurements or  the  real averages  occurring in the
stratosphere.
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 F.  MODEL RESULTS

         Despite the extensive uncertainty  associated with models
and the data upon which they  are based, models are indeed useful
and their  results  are important.    The  dangers lie in the inter-
pretation of the results  without  appropriate caution.     The
principle applications lie  first,  in  using  comparisons  of
calculated and  measured  results to give  general  indications of
model  inadequacy or  adequacy,  and  second,  in providing qualita-
tive,  if  not quantitative,  information  on  impacts of changes in
either model input (e.g.,  release  scenarios)  or data  base (e.g.,
rate constants).  In either  case, appropriate  attention to uncer-
tainty is a necessity.

     1.   Comparison of Calculated and  Measured Concentrations

         Numerous reviews comparing theoretical and experimental
profiles  of  chemical species mixing  ratios  (or   concentrations)
have  been  published.   NASA [1979], NAS  [1979a],  and  the  UK DOE
[1979]  have all addressed  this   subject,  and  the  citations
contained in those  documents  provide  an even more complete body
of information.   Miller e_t  al. [1980c]  reviewed the situation for
one-dimensional  model  results,  and later  [Miller jit:  al.  1980b]
for 2-D results based on the  Du Pont models.   These models agree
well with others  [see NASA,  1979]  and,  taken together, have the
further  advantages  of  containing   identical  treatments   of  the
chemical  scheme,  and  hence   providing  some   information  on  the
effects of  including  the  latitudinal  dimension.    The following
discussion summarizes the current situation.

         a).   OH, H02, H202.   For  the odd  hydrogen  species,  the
available field measurement data are very limited.  For both 1-D
and 2-D  models, where  information is  present,  the  comparisons
between  model  and  measurement  are  quite  good.    The  major
difficulty is the lack of experimental  profile measurements below
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30 km,  the  lower limit of  measurements  by Anderson  [1976],   In
the section  on  chemistry,  a  reference  was  made to  the implied
discrepancy in the lower stratosphere.  OH concentration strongly
influences  the  ratios  N02/HN03  [Harries, 1978;  Evans jjt_ al.,
1976;  Loewenstein ej:  al.,  1978]  and HC1/C10  [see Miller ^t al. ,
1980a;  1980b;  1980c],  both of which  appear  to be underestimated
in model  results.   Such a comparison  is  difficult,  however,  due
to the  different techniques  and concomitant  different absolute
accuracies of measurements for each separate species.  The ratios
are often  derived  from data  taken  at different  times,  and even
different  locations.    Decreased  concentrations  of  OH at  low
altitudes  in  model  calculations  would nevertheless  improve  the
comparison by  increasing  the  model  ratios.   Recent  changes lead
to some, but relatively insignificant  improvement.

         b) .   Total  NO .    Calculated  total  odd  nitrogen  in  the
                       A,
upper  stratosphere  (approximately  35-45  km)   is  near  25 ppb with
NASA RP  1049  [1979]  model chemistry.   Expected  increases  in  the
recommended photolysis  rate for NO  and  other  recent  changes  in
chemistry  [Chang,   1980],   may  improve  this  situation to  some
extent,   but do not  remove  the problem.   (Before the  recommended
NO photolysis  rate was slowed in 1979, the model-calculated total
odd nitrogen in  this region was 15-18 ppb  [Miller e_t aj^. , 1980c] ,
whereas  measurements  indicated less  than  15  ppb  [e.g., Horvath
and Mason,  1978].    The  difference  occurs  in both  1-D  and  2-D
models.

         c) .  HNO-j.   Nitric acid remains greatly overestimated by
models  in the  upper  stratosphere   [NASA,  1979].   The problem
persists  in 2-D calculations  [Miller  et  al. ,  1980a] , and  in
calculations with the most recent chemistry.

         d).   N02.  The underestimation  of N02 below 30 km noted
by NASA  [1979]  is still characteristic of model results, and like
other  NOX discrepancies is  unimproved  in  2-D  models.   Calculated
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profiles between  20  and  30 km lie  below  measured  values at  all
latitudes,  but particularly the higher latitudes.   This  deviation
is  consistent  with calculated total  column NCU which  does  not
show  the  variation  with  latitude  characteristic  of   measured
values.  Like other discrepancies,  it  is  not removed with  recent
chemistry.

         e).    HO^NOp.    Employing  reduced  photolysis  cross
sections of  Molina [1980a; 1980b]  in recent model  calculations
has led  to an  additional  discrepancy.   Whereas Murcray e_t  al.
[1973]  have  given an  upper  limit of  0.4  ppb  at  25 +  4 km,  64
degrees N  latitude,  model  results  for that location range  from
1.5 to 2.0  ppb.   Although the  Littlejohn and Johnston [1980]  rate
for  the reaction  OH +  H02N02  reduces  the  calculations  to
approximately 0.5  ppb, Murcray  [1980]  claims  recent  measurements
reduce his  upper   limit  to  approximately  0.1 ppb.   Thus,  other
HC^NC^ reactions may well be  important.

         f) .  0-j.   While  1-D  model  results indicated a  possible
underestimate of  ozone at  high altitudes  (50 km) , the  represen-
tation appears to be improved  in  the current 2-D simulation.   New
chemistry recommendations lead to small overestimates in ozone.

         g).  C10N02,  Cl.  Information on these  critical chlorine
species is  limited, but  agreement appears  to be reasonable  where
comparison  can be made.

         h) .  HC1.  Although  the calculated profiles for HC1  in
both 1-D and 2-D models lie near  the measured profiles  throughout
the stratosphere,  the qualitative  comparison  reveals  a  signif-
icant discrepancy.  (A detailed explanation is  given  by  Miller
et  al.,   [1980a]).   Whereas  the  measured  profiles   generally
display  a  monotonic  increase  of mixing  ratios with  increasing
altitude, the calculated  profile  shows a rather  steep increase in
the  lower   stratosphere  with  relatively  constant mixing  ratio
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above approximately  25  km.   The result  is  an underestimate  by
models  at  higher altitudes,  reasonable  agreement  in the  middle
stratosphere, and an  overestimate  below 25 km.  The improvement
anticipated with the development of  2-D modeling  [MAS, 1979a]  has
not materialized, and the discrepancies seem  to be  indicative  of
problems  with model chlorine chemistry,  rather than  a phenomenon
of meridional transport [Miller et  al., 1980a].   The most  recent
reaction rate revisions significantly increase  the  disagreement.

              i. CIO.    Qualitatively,  the comparison  of  calcu-
lated and measured CIO profiles  is similar to  that for HCl.   For
CIO, however, the best agreement seems  to come  at slightly  higher
altitude.   Near 40 km, the calculated profile  lies  near the lower
end of  the  so-called  "normal"  range  of CIO profiles measured  by
Anderson  e_t al. ,  [1980a] .   At  lower  altitudes,  however,  the
calculated profile exceeds measurement.  More  significantly,  the
decrease in mixing ratio with  decreasing latitude below 30  km  is
not nearly  so  steep  in  the calculated  profiles as that observed
in the  measurements.  Thus,  at  25 km,  the  calculated profiles  in
the NAS report  [1979a]  exceeded the  measurements  by  over  100
percent.  Furthermore, those  models  also calculated  the majority
of ozone depletion to  take place between 20  and  30  km, and  that
depletion is directly related  to these overestimated CIO concen-
trations.      Just as with HCl, NAS  [1979a] expressed expectation
that  improvement would  be forthcoming with  inclusion of latitu-
dinal transport in 2-D models; and  again, the  2-D treatment at  30
degrees N  latitude  using equivalent  chemistry  is very similar  to
the 1-D result [Miller et al., 19SOa].      The most  recent model
chemistry  significantly decreases both this discrepancy and
calculated ozone depletion.  Complete removal  of  the  discrepancy
will lead to still lower  calculated  depletion.

               A problem  which has  as yet found no  model solution
is  that of  the  very high  CIO measured on_p,ne_  occasion  by
Anderson et al., [1980a].   While this   represents  only  a  single
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balloon  flight,   the  unique  results   remain  significant.   The
possible explanations have  been discussed often, e.g., Anderson
et al. ,  [1980a; 1980b] and Miller e_t al. ,  [1980c] .  However, the
crucial  point  is  the simultaneous measurement  of  ozone made on
the  same flight.    Ozone levels were  found to  be normal in  spite
of the elevated chlorine monoxide.   The measurements were  made up
to 40 km where one ordinarily assumes  the chemistry to  be  simpler
and  relatively   better  understood   than that in   the   lower
stratosphere.  Yet,  the  facts don't fit  the theory.   Here,  as in
other  cases of real  world- measurements which conflict with the
theory,  it has seemed more appropriate to some to  discard the
evidence rather than to  question the theory.

     2.  Comparison of 2-D and 1-D Model Results

         In  the preceding  section,  several instances  were  noted
where calculated  two-dimensional model  vertical mixing  ratio pro-
files for 30 degrees N latitude  are in  substantial agreement with
1-D results.  As  mentioned,  a more complete comparison  is  made by
Miller e_t a^. , [1980a, 1980b] .  Complete evaluation of  the newest
calculations  is  still in progress.   While  this conclusion may
provide  some  support for the contention that  1-D  models may be
most representative at that  latitudinal zone,  it also dispels the
notion  that the  major  discrepancies  in  C1X  species  are  minor
transport  effects  with  little  implication for  calculated  ozone
depletion.     On  the  contrary,   those  discrepancies  will  merit
greater  attention  with  regard to determining their true  origin.
The  revisions of  several  reactions,  particularly  those  of OH
radical, are  merely the  beginnings  of  that work,  and will not
solve the problem completely.

         Two-dimensional  models are  also capable  of  providing
more complete  information regarding calculated  ozone  depletion.
While  it is not  obvious for  1-D results whether the  calculated
depletion represents a global average  or the  results  for a parti-
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cular latitude,  the 2-D model  provides a  latitudinal distribution
of  depletion.     Pyle and  Derwent  [1980]  £ind that the depletion
calculated by their model occurs  primarily at high latitudes in
winter.   This coincides with  the measured maximum in the annual
ozone  variation  [NASA,  1979] .   The  minimum  in solar ultraviolet
flux,  which occurs simultaneously,  implies that the link between
global average ozone depletion and  global  average  increase  in UV
is not  likely to  be  one of  amplification to the  extent expected
at the time of the 1979 NAS reports.    Pyle  and Derwent find a 1
to 1  relationship  between the percentage changes, half of that
estimated in 1979.   Other  models will soon  be  capable  of  pro-
viding confirmation for this  result, and  of assessing the effect
of  new  recommendations  in  chemistry,  which may decrease  the
latitudinal variation somewhat.

         The  additional  information  in the  latitudinal  and
temporal variations in the theoretical ozone depletion will also
allow for more sophisticated  analyses of  ozone measurements, with
the aim  of  identifying  any trends  in ozone concentrations which
may be related to model calculations.  In  summary, 2-D models, as
they  reach  greater  levels  of  sophistication  and  validation,  are
likely to provide considerably more  complete  information than 1-D
models.   Such  information allows  better understanding of  the
theorized depletion and its implications  for  biological systems.

     3.  Current Model Ozone  Depletions Calculations

         Perceptions of potential ozone  depletion according to
theoretical calculations have  changed significantly over the past
year among scientists who have followed the  recent developments
in chemistry.    The  of ten-referred-to  figures  quoted by  NAS
[1979a]  were  calculated  with the  Lawrence  Livermore  Laboratory
(LLL)   model.    A  recent  paper  [Wine  et al. ,  1980]   notes  the
changes in those results that  came  with adoption of the chemistry
recommended  in  1979  by NASA,  along with other  minor  revisions
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(such as the change in OH + H2°2^ *   Rather  than  18.6%  calculated
steady state depletion as the  base case,  the model  now  calculates
13.9% ozone depletion  for continued release  of  CFCs-11  and 12 at
1977  release rates.   The NAS figure  was adjusted  from  18.6% to
16.5% based on some expectation of tropospheric  sinks  and nega-
tive  feedback mechanisms, and a  proportional adjustment  might be
applied to the 13.9% figure with  the  same   assumptions  (yielding
approximately 12.3%).

         Several newer reaction rate measurements may reduce  this
figure much  further.   Wine et al. ,  [1980]  have  reported a  rate
for  OH  + HNOo  which,  when included  in  the LLL model,   reduces
calculated depletion to  9.5%,  if  the reaction  products are those
currently assumed (H20 +  N03).  (NASA recommends  use of this  rate
in  its  latest  evaluation [Chang,  1980]).   Despite  this large
revision due  to the  change  in this  reaction  rate, it  was not
identified in  the  NAS list of  reactions to which    03  is  most
sensitive.   Should the reaction produce an  alternative,  and  less
likely,  set of  products  (H200  + N02^'  calculated depletion would
be reduced from the 13.9% figure  to near  12%.

          Further,   a  change  from the estimated  rate  for  OH  +
H02N02 to  the  measured  value which  is now  available [Littlejohn
and Johnston,  1980] also reduces  the 13.9%  figure  to below  12%.
Also, without including changes in the  other OH reactions, a  move
to the fast  rate  for  OH  + HO- would reduce  calculated depletion
from 13.9% to below 11%.   Several  other reaction  rates,  including
H02N02,   are  revised  in  the   latest  NASA recommendation  [Chang,
1980].   As a  group  they  also tend  to  lower calculated ozone
depletion.

         In combination,  these latest revisions shift the calcu-
lated result to approximately 7%  or even less, a dramatic change
from the 18.6% reported only  a year ago.   (Using  a  similar set of
r.eaction  rates, Penner [1980b]  reports  5.5%, but notes  that
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necessary changes in transport rates will  increase this  figure
somewhat).   (A change in  OH  +  HO^ would further reduce calculated
depletion).       In retrospect,  the concerns generated by the NAS
report [1979a]  and the increase  in calculated depletion since the
previous report [NASf 1976]  were somewhat excessive.     Only one
year  later  the model  results are near those of the first report
[NAS,  1976]  and are likely to  move to well below that level.   At
the same  time, the confidence in models themselves has been con-
siderably  shaken, both  by  2-D  results/ and  by the  increased
awareness of critical and unjustified assumptions in the models.

         The  preliminary reports  of  the  ALE  program  provide
initial  evidence  contrary   to the assumption  in  all  depletion
calculations that CFCs are not destroyed in the troposphere.  If,
for instance, CFCs-11  and 12  are  both  found  to have atmospheric
lifetimes,  equal  to  half the  stratospheric  photolysis  lifetime,
calculated depletion  would  likewise  be  reduced  by half,  i.e.,
from the most recent values  of 6-9% down to 3-4.5%.

         The  observed  trend  in C02  concentrations,  should  it
continue until CC>2 has doubled as  expected,  would  imply  a growth
of ozone estimated  at  4  to  6% [Penner,  1980b].   This additional
factor  (perhaps  slightly reduced  to  3-5% by  interaction  with  a
chlorine perturbation) may  be applied  to any  of  the  calculated
figures mentioned previously.   Any  trend  in ^0 is calculated to
further reduce the potential impacts of CFCs.

         To claim  the current  evidence  proves CFCs  to  have  a
negligible effect on  the ozone  is  an  exaggeration,  but  the evi-
dence   indicates  that such  an outcome  is  highly possible.   And
very  definitely,  the  evidence shows  that  the large  effects
"predicted"  so confidently and so recently  are now much  less
likely.
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     4.  The Effects of  Postponed Regulations

         A  proper   regulatory  assessment  of   a  potential,  but
ill-defined and  unverified,  threat  to the  environment  requires
attention  to   the   time  dependence  of  the  potential  effects.
Specifically,  the  reliance on  calculated steady-state  ozone
depletion  numbers  can distort  the  perception  of  how  fast  the
potential  problem  is developing  and  how  urgent  the  need  for
action.    It   is  illustrative   to  consider how that  potential
predicted effect would be changed by  a regulatory  decision made
now as compared to one made at  some future  time.  That point was
made  in  an earlier  Du Pont  submission to  EPA  [Du  Pont,  1980b]
regarding  the  NAS  CISC  report  [1979b].    Assuming  an  extreme
regulatory  response  of   a  total  U.S.  ban  on  CFCs-11  and  12,
combined  with  constant   continued  release   by  the  rest of  the
world, Du  Pont 1-D  model  results  showed  that deferral of such
action from  the end  of  1980  to  the  end  of  1985  would have  a
calculated maximum incremental  effect  of  0.2 percent on  the time
dependent  ozone  depletion  curve.   That is, the depletion at any
time in the future  is calculated to  increase  by less  than  0.2
percent  as a  result of  deferring the  regulation for five years.
That maximum difference  would occur while depletion is calculated
to  be  still  relatively  small;  ultimate depletion  would be
Identical at steady-state.   This would be  true  of  any reduction
in emissions by  a  comparable amount  (approximately  30%).   It is
important to realize too  that, those calculations were made with a
model chemistry which calculated  18.3%  steady-state depletion for
continued release at 1975 rates,  well  above current LLL results.
These  calculations  represent  an overestimate based  on  best
current knowledge.

         The significance of  those  results  lies not in arguments
for arbitrary  deferral,   but  in  support of  a cautious regulatory
position  in the  face  of  severe   uncertainties  which  can  be
resolved  by the  ongoing  academic,  government,  and  industry
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research programs.  Regular  evaluations  can be made  to  reassess
the situation.

         It may,  therefore,  be  concluded that  premature  regula-
tion has  virtually no  tangible  or calculated  benefits  to  the
environment, yet  it may entail  serious costs  addressed  elsewhere
in this document.   At  the  same time, the  likelihood of a  more
soundly based decision increase with each research result  as more
aspects of the atmospheric system are better defined.   Several of
the numerous results  to be expected in  the next few years  have
been mentioned  above  and will  be  more completely  considered in
section H  on uncertainties.
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 G.  OZONE AND ULTRAVIOLET RADIATION

         A persistent problem with understanding theorized ozone
depletion lies  in  determining  its significance.  Qualitatively,
it is understood that less ozone will result in more ultraviolet
radiation reaching  the  surface  of the  earth.   Increased ultra-
violet may  be related to  certain  biological  effects.   However,
neither of  the  relationships  is  well-defined.   Moreover, worst-
case  scenarios   differ  tremendously  from  other  possibilities.
Lack  of   data  frustrates  confident  differentiation  among  the
possibilities.    Below we highlight  key  variables;  detailed
discussion appears in Appendix F.

     1.  Latitudinal Variation  in  Calculated Depletion

         Potential   ultraviolet  changes  have  generally  been
calculated in terms of a global  average  depletion calculated with
1-D models,  and a  relative amplification  factor  based on solar
spectrum and global average ozone  concentration.  Two-dimensional
models have  now  demonstrated  a  correlation  between  calculated
depletion  and  natural  seasonal   and  latitudinal variations   in
ozone concentration [Pyle  and  Derwent, 1980].   The correlation  is
such  that  a  calculated global average change  in ultraviolet flux
is considerably less than that  calculated in  the one-dimensional
approximation, even when the global average ozone depletion from
the  2-D  model  is  equal  to  that  in the  1-D  model.   Accurate
quantitative  evaluation of this  correlation is  a  priority task
for the newly developed 2-D models.

         To  assess  the  importance  of  any  change   in  ozone
concentration, one  must understand just what the change  implies,
i.e., how does  ultraviolet vary in each location.  Then one must
further understand the importance  of  such  changes in  ultraviolet.
Just how large are the changes compared  to actual latitudinal and
temporal variations?
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     2.  Natural Ultraviolet Radiation

         Natural ultraviolet  fluxes  to the earth's  surface  have
been both measured  and  calculated.   Field measurements  are  made
difficult both  by  instrument  sensitivity  and by  meteorological
considerations [See Appendix F-2].  In order  to  determine  either
average or representative daily  fluxes, one must consider  normal
patterns of cloud cover and associated meteorology as  a  function
of season and location.

         Calculations based  on solar  UV flux  and  ozone  concentra-
tions  are most  often based on clear  sky  conditions,  neglecting
the attenuating effect of clouds.  Occasionally,  however, a cloud
cover  correction  is applied  and  comparison  of  measured  and
calculated data  is  possible.    Such  comparisons  reveal  discre-
pancies of up to 25 percent.  A more  thorough  discussion  of these
issues  is  given by Klein  [See  Appendix   F-2]  and  much of  the
following discussion relies  on that analysis.

         Despite the difficulties and  associated  uncertainties,  a
picture of  the  UV  radiation  flux to  the  earth  is  beginning  to
emerge.  An almost  startling  discovery is  the  range  of variation
in UV flux with both latitude  and season.   Measurements discussed
by Klein have been  made in  Panama (9  degrees N  latitude)  and  in
Rockville, Maryland  (39 degrees  N  latitude).   UV  input  was  mea-
sured  in 5 nanometer intervals.  The  measured  radiation in Panama
was found to  be  more than twice that occurring  in Rockville for
representative  days  of  each  season.    Using  the   DNA  action
spectrum of  Setlow  (1S74) ,  the  UV  flux  was weighted  and  summed
according to the NAS [1979b] definition of  "damaging" ultraviolet
(DUV) .  The  inferred  DUV  dose at Panama was found to  be four  to
five  times  as large  as  that  received in  Maryland,  a  dramatic
change over only 30 degrees of  latitude.   As  Klein notes:   "This
certainly would imply that one should  be cautious about predicted
effects  of  20-45  percent  increases  in UVB  in  temperature
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latitudes."    Even  such  seemingly  significant  changes  are
literally  small  compared to  natural latitudinal variations.
Furthermore,  as  noted  elsewhere in this  document,  such changes
are based on  calculated  depletion levels which are beyond current
estimates and which represent  a  steady-state situation  which is
neither realistic nor likely to  occur.

         The  natural latitudinal variations are not  cited  to
imply  that a geographic redistribution of population would be an
appropriate or an adequate response to ozone depletion.   They do,
however, give some perspective  on changes  in UV levels.    Also,  a
better knowledge of such variations, both  in UV and DUV  (or other
appropriate  weighting),  allows  realistic  interpretation  of
effects research in biological  systems - both epidemiological and
experimental  studies.  An accurate picture of normal latitudinal
and seasonal  variations  must  also  be  used  with time and latitude
dependent calculations  of ozone  change  in order  to  determine
realistic effects of  diminished   ozone   levels.    The  several
correlations  and  nonlinear  variations of  calculated  depletion,
ozone  itself,  and  incident  solar UV all  introduce   errors  in
estimated overall  effects when each  step  in  the sequence  is
treated  using  global  annual   averages.    As   a   simple  obvious
example, large  depletion at  the  poles  during polar  night  has
virturally  no effect on  incident UV at the  pole,  whereas  a much
smaller ozone change at the equator in summer may cause a rather
large absolute change in local  UV flux.

     3.  Action Spectra

         One  might very reasonably  assume  that  different  wave-
lengths  of   ultraviolet  light  will   interact  differently  with
biological  systems.    Therefore,   in   studying  the  effects  of
changes in ultraviolet  it is  appropriate to consider  a UV flux
weighted by  some  action  spectrum.    It   is  also  reasonable  to
believe  that different  biological  effects  occur  by  different
                               E-59

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                                               Science
mechanisms  and,  therefore,  would  exhibit  different  action
spectra.    Therein lies  the  major problem  in interpreting  the
effects of even  well-defined changes in incident UV.  For most of
the postulated  potential  effects,  no action  spectrum  has  been
determined [NAS, 1979b].    For  others,  arguments  have  been  made
that a  given measured action  spectrum is  appropriate,  but  no
actual  relationship has been demonstrated.

         In  the face  of  this  lack of  certainty,  the  term
"damaging ultraviolet" has been used  by NAS [1979b]  to describe
UV changes weighted by the DNA action spectrum  given  by Setlow
[1974].   At the same time, Appendix D of the NAS report  [1979b]
makes  clear the very  large differences  in  percentage  change  of
weighted  UV which  may be  derived using different action spectra
but identical ozone depletion.   Thus, the magnitude of an effect
depends  not  only  on the  magnitude of ozone depletion  and  the
change from  normal UV levels but also on the  appropriate action
spectrum.  A review of the NAS  appendix  makes  clear  that  the
DNA-damage action spectrum  is  a  worst-case among the  various
action spectra  considered thus  far.   The DNA-damage  action
spectrum  has  not  been directly  related to any  of  the effects
discussed by NAS,   but only chosen as a plausible relationship.
The arbitrariness of the  "folklore"  value  of  2 for a biological
amplification factor  (relative change in biologically  effective
ultraviolet  for a given  change  in ultraviolet  itself) is made
quite  clear by NAS.

         As summarized by  the authors of the NAS CISC report:

         "The  complex  relationships  between   RAF   [relative
         amplification factor] and  latitude, season,  percen-
         tage ozone-layer  reduction,  and   weighting   function
         create  considerable uncertainty in  any simple  statement
         about  the DUV dose  change expected for  any particular
         ozone depletion.  This uncertainty  is  compounded with
                              E-60

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                                                 Science
         the  uncertainty  in the  relationship  of the  biological
         response  to  the  DUV  dose  in  assessing  the  ultimate
         biospheric impact."  (emphasis added).   [NAS,  1979b,
         p. 311].
Yet such a "simple statement" is included as Key Finding No.  7  of
the same  report!   Reiteration of the Key Finding No.  7 statement
is now cited as partial justification for regulatory action, and
the numerous strong caveats which should  be applied  are virtually
ignored.

     4.  Dose and Dose-Rate

         A  final  potentially important  factor   in  understanding
changes  in  ultraviolet  flux  is  an appreciation of natural
temporal variations in ultraviolet on a daily basis.  UV flux,  of
course, follows  the diurnal  variations  of sunlight in general.
As such, the  maximum  occurs  in  the mid-day hours with decreased
levels toward  morning  and  evening.   As a  consequence,  it  may  be
appropriate to'consider  not total daily dose  or annual dose  of
UV, but  changes in  peak  dose,  peak  dose  rate, or average  dose
rate.

         It has been argued (Damkaer, See Appendix F-4) that  dose
rate  may  be  equally  or  more   important  than  total  dose  in
determining biological effects.   Again, this suggestion should  be
acknowledged  and  accounted  for  in any  attempt to  quantify the
effects of calculated ozone depletion.
                               E-61

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                                                Science
 H.  UNCERTAINTIES

         An uncertainty is  almost  always more easily defined than
quantified.   Despite their mention  of most of  the significant
uncertainties,   the   NAS  Panel  on  Stratospheric  Chemistry  and
Transport  has   been  severely   criticized  over  its  attempts  to
quantify those  uncertainties  [Du  Pont, 1980a;  CMA, 1980].   The
criticism addressed  both  the propriety  of certain quantifications
and the estimates themselves.

         Faced  with  an uncertainty  for  which  either  theory  or
experiment provides  well  defined limitations, it is  reasonable to
report a range  of uncertainty.  For  other  cases,  however, where
uncertainty centers  around a  plausible  but  otherwise untested
assumption,  only  subjective considerations  will  allow  the
assignment of a  numerical  value  to uncertainty.   Such estimates
are often useful to  an investigator determining the  future course
of research,  but only with the full  realization that they do not
constitute scientific evidence.    Use  of  subjective uncertainty
ranges easily can be misleading — a decision  which seems to be
justified by the evidence may  in fact not be so.

         The fear of inadvertent  misuse of the uncertainty esti-
mates prompted a portion  of our earlier criticism and now appears
to be well-founded.   Despite statements by the NAS panel that the
question of unknown  chemistry  broadened the 95 percent  confidence
limits on  calculated  steady-state  depletion  to  3  to 30 percent,
the principal findings' statement  of  5 to 23 percent  is  the one
which is cited.   Not only  is  that estimate  given undue credence
(it already includes some "unquantifiable" uncertainties), but an
acknowledged   (if   underestimated)  source  of  uncertainty  is
summarily ignored.

         In short,  a regulator must be  aware  of the distinction
between what  has  been  scientifically  demonstrated  -  via the
                               E-62  .

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                                                Science
scientific method -  and what  are subjective  or intuitive
conclusions of  the  scientists themselves.   This  applies both  to
atmospheric science in  general and to evaluations of uncertainty.
Although some  caveats  were  included  in the NAS report  [1979b],
the distinctions were  apparently  not  sufficiently  clear, and  the
uncertainty estimates were in general not well supported.

     1.   Current Uncertainties

         A  brief  review of  general  areas  of  uncertainty will
demonstrate the significance  of  several major  concerns  which  may
be hidden by the assignment of.subjective estimates.

         a).    Known Chemistry.   Previous estimates of   the
uncertainty in  calculated  ozone depletion due to uncertainties in
known chemistry have  generally relied  on model sensitivity
studies, coupled with confidence  ranges for individual  reactions.
Despite  evidence by Smith  [1973]  that  such methods have  in  the
past led  to underestimation, the caution  was unheeded.   Again,
remeasurements of  "known"  reactions  (OH + HgOp  an<3  OH + HNCU)
have found rates outside previous  uncertainty  ranges, with
consequent larger effects  on  calculated ozone  depletion than
anticipated.  Not only uncertainty,   but also the  sensitivity  of
calculated  ozone depletion  to  given  reactions  have been  under-
estimated.  Although the calculated depletion still falls  within
the  range   suggested for  errors  in  known  chemistry,  one must
remember that only  a few  remeasurements have been made.  The fact
remains  that the premises  (individual reaction rate uncertainties
and sensitivities)  supporting the overall estimated range have
not held up under scrutiny.

         A further  example is found  in  the  case of peroxynitric
acid  (PNA).    Based   on  the  previously  "known"  ultraviolet
absorption  cross sections, PNA  and   its "unknown"  chemistry  was
omitted   from  both  model  calculations  and  uncertainty analyses
                              E-63

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                                                 Science
used by MAS.   The molecule was deemed  to  have little  potential
influence on results.   However,  a  remeasurement of  its  photolysis
cross sections  [Molina  and Molina, 1980a;  1980b]  has  implied a
significantly longer photolysis  lifetime in  the stratosphere, and
has  made  other  reactions  more  important.    In  particular,
calculated depletion varies by over a factor of two  depending on
the  chosen  rate for the  reaction OH + H02N02, which has only
recently  been  measured to  be 5  times  or  more  faster than the
estimated value modelers have  had  to  rely on.

         b).  Transport.  The  uncertainties  due to  transport have
been evaluated  on  the   basis  of  changes in calculated A 0-, only
with respect to  changes in the eddy diffusion parameterization.
The  changes  in parameters  were  restricted   by   assuming that
changes  in  calculated CFC   lifetimes  dominated  other  errors.
These assumptions have  been challenged,  and indeed it  may  be the
applicability  of  the  eddy  approximations  themselves  to
short-lived species which  introduces  the major uncertainty.   In
any case,  such factors  have been ignored in  the NAS estimates.

         c).  Tropospheric Sinks.   Uncertainties in  the chlorine
contribution to the stratosphere  from CFC release  have  been eva-
luated by attempting to quantify, on a  case-by-case  basis, every
previously  postulated   mechanism  for  a  tropospheric  sink.   An
estimate  is  then  made   of  an  arbitrary  and unspecified  "likely"
sink and  possible limits  to its  effectiveness.  This approach is
valid only if all possible sinks have  been considered;  complete-
ness has not been demonstrated,  and without  it  the  uncertainty is
unquantifiable without  information directly  from atmospheric CFC
concentration changes.

         d).  3-D Chemistry and  Feedbacks.   The problem with this
potential source of error is, of course, that  it  is unquantifi-
able.  While  the  possible sources of  error have  generally been
identified,  quantitative  tests of  many  assumptions regarding 1-D
                               E-64

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                                                Science
model construction and omitted  feedback  mechanisms are simply not
yet available.   Although  the  NAS expects that some reduction of
calculated depletion  will take  place  (the  "correction factor"
applied to  calculated depletion),  the  chosen  range  of possible
effects is necessarily arbitrary.  At the same time,  the spatial
and  temporal  averaging   assumptions  in  1-D  models  are  fully
capable of leading to severe  errors  in chemical treatment.

         e).   Systematic Errors and Omitted Chemistry.    The
question  of  systematic errors  and   omissions  in  chemistry  was
discussed  briefly by NAS  [1979a] , and an "educated guess" of the
associated uncertainty was  given,  but  not  included  in  a  table
purporting to  be a  summary of  contributions  to  predicted  ozone
change and error estimates.   Perhaps such "guesses" were omitted
because of  concern  over  their  arbitrariness,  but  other equally
subjective estimates were included in the  table.   This contrib-
ution to uncertainty is actually a critical one.   As an example,
possibilities for chlorine-catalytzed ozone production have been
suggested  in  the literature, but not disproven scientifically.
No matter  how doubtful they may  be in someone's educated opinion,
the  possibilities  still  exist.    Unknown  chemistry   involving
H02N02  (now  demonstrated  to  be  important by  an unexpected
revision in "known" chemistry) accounts  for the entire factor of
2  range  given   by  NAS   for  this  error  contribution.    Other
contributions,  appropriately  included,  would  broaden  this  range
in a  realistic  assessment.   It  may  be  argued that  the overall
range  for possible  calculated  steady-state  ozone change  must
include the potential for positive changes  in  ozone  levels.   In
any case,  the unknown  is a  major source  of potential error in
ozone  depletion calculations and should  not be considered as
subordinate to, or less real  than, other sources of error.

         f).    Ozone Trend Analysis.    In  its  chapter  on  ozone
change  projections   (a  far   better  choice  of  words   than
predictions), the NAS Panel notes that  all  change estimates are
                               E-65

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                                                 Science
made independently of ozone  trend  estimates.   Also  mentioned  is
the possibility  "to  improve"  our estimates by making use  of  the
information  given by  the  observed  ozone  change."    (emphasis
added).  [NAS, 1979a, p.  194].

         It  is  possible  to   repeat  the  analysis  using  current
results for  both ozone  trend  and  model calculations.   Further-
more,   the  improved  ability to  analyze  ozone measurements  makes
the exercise  much more meaningful  now than  in  its  application  by
NAS.   The  exercise  makes use of  all  information,  rather  than
relying solely  on  the  theoretical  computer  model  results  and
neglecting the measured  real-world  data.

         In this exercise  the variance and central  value of trend
estimates  are combined with those  of  model  calculations covering
the same time period to give  a  "best  estimate" of  the  1973 ozone
change based  on both trend analysis and  the model  prediction"  of
-1.3%   [NAS,   1979a,  p.  195]   (emphasis  added).    Since  several
                                                               2
contributions to  the ozone  trend  variance estimate,  [(1.75%)  ]
have  now   been  determined  statistically,  (measured  variance
                   2
approximately (0.7)   ), it  is  appropriate to redo  that  analysis.
The best  trend  estimate  now is  +0.3%   (through  1978).    Model
calculations  for  depletion  through  1973  recently hovered  near
-1.5%   (corresponding  to  approximately -13% depletion at  steady-
state) , and the variance assumed can  be  taken  from the  NAS error
analysis.    (The  latest  calculation would  give  a  still  smaller
present day figure).   One standard deviation = 0.35  x  calculated
depletion  =  0.35 x  1.5%  = 0.53%.   The variance  is,  therefore,
       2
(0.53%) .   The derived combined  "best estimate"  for  ozone  change
through 1978  is,  therefore,  now about  -0.84% or lower  according
to this "best estimate".

         In  an   extension  of  that analysis,  according  to  NAS
[1979a], all  other   estimates can  be multiplied  by the  propor-
tionality  factor, in this  case 0.84/1.5  =  0.56,   to account  for
                               E-66

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                                                Science
the current information given by trend analysis.   Applied to the
steady-state calculated depletion of  13%  used  here (revised LLL
model plus minimal correction for  OH + HNCU), the  "best estimate"
for steady-state depletion  by this method  is 7.3%.  This analysis
still ignores many other recent  developments which  further reduce
the model  estimate,  and,  therefore,  the  "best  estimate," but is
given to demonstrate the information contained  in  trend analysis
estimates - information that  should  not be  overlooked.

         The  NAS  Panel   chose  to  call  such   a   correction
speculative because of  the uncertainty in  their own estimates of
variance.    The  comparable  variance has now,  however,  been
determined  from the  ozone  data,  and indeed,  the  present day
variance in  ozone  data is  found  to be similar  to that in  model
calculations.  This is especially  true when one realizes that NAS
has  likely underestimated  the  model  variance  by  a   significant
amount.
 2.  Reduction of Uncertainty

         In pondering the necessity  of  a  regulatory decision, one
must pay  attention  not  only to  current  uncertainties but to the
time scale on which  they may be diminished.   Attendees  at  a
Stanford Research Institute Workshop considered  such questions on
a very broad scale [SRI,  1980].  It  is also,  of  course,  relevant
to consider  research  in  a more detailed  sense,   i.e.,  to examine
likely  near-term  research  results.   For  major developments
affecting major uncertainties,  such  analysis  is  a necessity.

         a).  An experiment  intended to  determine experimentally
the quantitative  relationships between  catalytic  species   (CIO,
OH, H02 and N02)  and  odd  oxygen (0 and  O-.)  in the stratosphere is
currently being developed by J. G. Anderson.   All species will be
measured simultaneously  as  a  function of  altitude  in  the  upper
                               E-67

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                                                 Science
stratosphere (approximately 28 to 38  km).   The  upper  stratosphere
has  been  chosen  because   relative  species  concentrations  are
determined  primarily  by  chemistry,  due  to the  long  transport
lifetimes  in  that  region.    Measurements  will be made with  an
instrument package  that  is  raised  and  lowered  repeatedly
(approximately  10  times)  through  the  relevant  altitude  range.
Variability of concentrations over the time and spatial  scale  of
the measurements will  be sufficient to establish  the  sought-after
relationships,  independent  of any model  results.   A  comparison
with the  relationships  derived  from  models  for the same altitude
range will  help to define  the  accuracy  of the  models in  that
region.   By accounting  in some  way for the  role of transport,  it
is possible to extend the measurements into the middle  and  lower
stratosphere.   In theory, this experiment  is capable  of providing
definitive information regarding the stratospheric  chemical
aspects of ozone depletion.    The  reel-up-reel-down   engineering
will be  tested  in a flight planned  for  the spring of  1981,  and
a  flight  of the full  instrument package  flown is planned  later
that  year.    Analyses  and  more  flights   should  follow  shortly
thereafter.

         b) .   The  Atmospheric  Lifetime  Experiment  enters  its
third year  in 1981.   Analysis of its  results will  address  the
question of tropospheric sinks for CFCs,  a second  major aspect  of
the theory.   A  sink important  enough  to  have  a  major  impact  on
calculated depletion would be evident  in  the complete  three-year
data.   Thus, an  answer should  also be available in 1982.

         c) .  The rapid  further development  of  two-dimensional
models in the near  future  promises to be  a third major  event  of
the  next  few  years.     The  ability  to  test directly  certain
currently  unquantifiable uncertainties  of  modeling  answers   a
critical need.  One-dimensional models are being  increased  in
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                                                 Science
sophistication, with radiative-convective  models  being  coupled to
photochemical models for  investigation of  feedbacks and  combined
perturbations.

         d).   Research in kinetics and  photochemistry  is  expected
to continue  at  its  customary  rapid pace.   However, even in  this
area, the near  future  is  an  especially important time given the
several  high-sensitivity, critical  reactions  currently under
study, e.g.,  OH + H02N02,  OH  + CIO, OH  + H02  and  others.

         e).    In the  area of field measurements, concentration
profiles for a  number of  species will  no  doubt be  better defined
by ongoing programs  of  experiments.   Of special interest  is the
increased development  of  ground  based techniques.   [Parrish et
al.,  1980] have  utilized  such  a  technique  to measure CIO radical
column  densities  (finding  results  in  near  agreement  with
Anderson's  "normal"  range  for  CIO),  and are   also  capable of
measuring 0-,.   Vertical  profiles can  be  derived from the data.
The  ability  to  take measurements  on  almost  a daily  basis is a
great advantage of  this  method  over  infrequent balloon  flight
measurements, and  leads  to much  more  rapid building  of a  data
base suitable for model validation or  invalidation.

         f) .    The  improvements  to be expected  in  ozone trend
analysis have already been quite fully described.  The principal
efforts  of future research will be to  devise  new  ways of  removing
explainable variations from the ozone  record  to better  expose the
existence or  nonexistence of  a  trend.   Already the method  pro-
vides the desired margin  of safety  to  permit a  postponement in
regulations until a better decision can be made.
                               E-69

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                                                  Effects—Skin Cancer
            Potential Effects on Humans of Alteration  of  the




                       Stratospheric Ozone Layer.




           A Critical  Review  of  the  Report of the Committee on




   Impacts of Stratospheric Change of the National Academy of Sciences




               Entitled:  Protection Against Depletion of




               Stratospheric  Ozone by Chlorofluorocarbons,




                         Washington, B.C., 1979









                                   by




                    Frederick Urbach, M.D,,,  F.A.C.P.




                 Director, The Center for  Photobiology,




                Skin  and Cancer Hospital of Philadelphia




            Professor  and  Chairman,  Department  of Dermatology




                  Temple University School of Medicine
The Skin and Cancer Hospital




3322 North Broad Street




Philadelphia, PA  19140




(215)221-3924




                            (APPENDIX  F-l)










                               F-l-1

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                                                               Transraittal letter for
                                                                   Appendix F-l
                       TEMPLE  UNIVERSITY
                       SCHOOL OF MEDICINE
                       PHILADELPHIA, PENNSYLVANIA 19140
   THE CENTER FOR PHOTOBIOLOGY
      FREDERICK URBACH, M.D., F.A.C.P.
      PROFESSOR AND DIRECTOR
      215-221-3924

      P. DONALD FORBES, Ph.D.
      ASSOCIATE DIRECTOR
      215-221-3920

      DANIEL BERGER, M.S.E.E.
      215-221-3937
      HAROLD F. BLUM. Ph.D.
      215-221-3924
      RONALD E. DA VIES, Ph.D.
      215-221-3960
      MAHENDRA K. LOGANI, Ph.D.
      215-221-3961
      STANLEY S. MANN, Ph.D.
      215-221-3916
      THOMAS R. C. SISSON, M.D.
      215-221-3071
      WILLIAM H. COLE
      ADMINISTRATOR
      215-221-3926
                                                SKIN AND CANCER HOSPITAL
                                                     3322 N. BROAD STREET
                                                    PHILADELPHIA, PA. 19140
                                                December  12,  1980
Dr. Richard B. Ward
E. I. DuPont de Nemours  & Company, Inc.
Petrochemicals Department
Wilmington, Delaware   19898
      Dear Dr. Ward:
           Enclosed please find  my  report entitled, "Potential Effects  on Humans  of Al-
      teration  of the  Stratospheric  Ozone Layer:   A Critical  Review," which  was prepared
      at your request for  use  by  E. I. DuPont  de Nemours &  Company, Inc.

           Please  feel   free   to  use  this  report  in any  way  that you  deem  appropriate.

           I  propose to  submit all or part of this report  to scientific  journals for pub-
      lication,  and  will  keep you informed  of the  contents  and the  journals  to  which  I
      will submit the material for publication.

           If you have  any questions or  comments, please  do  not hesitate  to  let me know.

                                                                       Sincerely,
                                                                       Frederick Urbach ,  M.D.
      FU/jbh
      enclosures
Z-967

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                                                        Effects—Skin  Cance.
                            TABLE OF CONTENTS




                                                                   Page




     A.I.  Summary                                                 F-l-5




     A.2.  Recommendations                                         F-l-11




B.   Historical Review of the Problem                              F-l-14





C.   Potential Changes in "Biologically  Effective"  UVR  Reaching




     Earth Secondary to Anthropomorphic  Alteration  of the




     Stratospheric Ozone Concentration                              F-l-28




     C.I.  Conclusions and Recommendations                          F-l-28




     C.2.  Action Spectra for Some Effects  of  UVR on the Skin       F-l-28




           C.2.1.  The Human Erythema Action Spectrum               F-l-28




                   C.2.1.2.   Physiologic Mechanisms Involved in




                             Skin Erythema  Development              F-l-33




           C.2.2.  The Skin Carcinogenesis  Action Spectrum          F-l-37



     C.3.  The Effect of Weighting of Solar (Earth) Level UVR with




           Various Action Spectra                                  F-l-40




     C.4.  Comparison of Effect of Various  Skin Action  Spectrum




           Weighting of Solar UVR with  "Real," i_n vivo  Experiments  F-l-44




D.   The Risk of Increase in Nonmelanoma Skin  Cancer Due to




     Increased Earth-Level Solar UVR                               F-l-48




     D.I.  Conclusions                                             F-l-48




     D.2.  the Natural History of Nonmelanoma  Skin  Cancer           F-l-51




           D.2.1.  Anatomic Distribution of Basal Cell  and Squamous




                   Cell Skin Cancer                                F-l-54




           D.2.2.  Age and Duration of  Exposure and Nonmelanoma




                   Skin Cancer                                     F-l-57
                             F-l-2

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                                                     Effects—Skin Cancer
           D.2.3.   Race  and Ethnic  Extraction                    '   F-l-63



           D.2.4.   Geographic  Distribution                          F-l-65



           D.2.5.   Relationship  to  Environmental  Exposure  and



                   Changing Incidence  with  Time                     F-l-77



     D.3.   Experimental  Sk-in Carcinogenesis                        F-l-82



           D.3.1.   Mechanisms  of UVR Carcinogenesis                 F-l-83



           D.3.2.   Tumor Types                                     F-l-83



           D.3.3.   Ultraviolet Radiation  as an Initiating  Agent     F-l-88



           D.3.4.   Interactions  between Ultraviolet  Radiation  and



                   Chemicals                                       F-l-89



           D.3.5.   Physical and  Quantitative Aspects  of UV



                   Irradiation in Animal  Studies                    F-l-91



           D.3.6.   Dose  Response Relationships                      F-l-93



           D.3.7.   The Immune  Response to Tumor Induction           -p-I-95



E.   The Risk of Increase of Malignant Melanomas  of  the Skin Due to



     Increases Earth Level Solar UV Radiation                       F-l-98



     E.I.   Conclusions                                             F-l-98



     E.2.   The Natural History of Malignant Melanoma  Skin  Cancer    F-l-102



           E.2.1.   Anatomic Distribution  and Histopathology         F-1-104



                   E.2.1.1. Lentigo Maligna Melanoma              F-l-104



                   E.2.1.2. Superficial  Spreading Melanoma         F-l-105



                   E.2.1.3. Nodular Melanoma                       F-l-106



                   E.2.1.4. Classification of Malignant Melanoma   F-l-108



                   E.2.1.5. Acral  Lentiginous Melanoma             F-l-110



           E.2.2.   Age,  Sex and  Site Distribution of  Malignant


                   M i                                             F-l-111
                   Melanoma
                              F-l-3

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                                                      Effects—Skin  Cancer
           E.2.3.   Race,  Ethnic Extraction  and  Heredity             F-l-117




           E.2.4.   Malignant  Melanoma  and Exposure  to  Chemical




                   Agents                                          F-l-121




           E.2.5.   Geographic Distribution  of Malignant Melanoma    F-l-122




           E.2.6.   Sunlight and Malignant Melanoma                  F-l-128




     E.3.  Experimental Models for Malignant Melanoma               F-l-135




     F.I.  Forecasting the Effects of  a  5-Year  Delay in Regulation




           of CFC  Emissions in the U.S.                             F-l-137




           F.I.I.   DuPont's Comments on  the NAS (1979) Report       F-l-140




G.   Critique of the NRC Report:   Protection Against Depletion of




     Stratospheric Ozone by Chlorofluorocarbons                    F-l-155




     G.I.  Chapter 3 - Human  Health Effects                        F-l-155




     G.2.  Appendix C - Solar UV Irradiation at the Earth's




           Surface                                                 F-l-164




     G.3.  Appendix D - The Biologically Effective  UVR             F-l-164




     G.4.  Appendix F - Factors in UV  Dose-Response of




           Npnmelanoma Skin Cancer and Malignant Melanoma           F-l-164




     G.5.  Appendix G - Further Detail on Malignant Melanoma        F-l-166




     G.6.  Appendix H - Preventive Measures Related to Malignant




           Melanoma                                                F-l-167




H.   Recommendations for Further Research                          F-l-169




I.   References                                                    F-l-175
                             F-l-4

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                                                         Effects—Skin Cancer
                              A.I.   Summary




     The  high  energy,  short  wavelength portion  of  the solar  electro-




magnetic  spectrum (wavelengths  shorter  than  320 nm)  is  potentially  very




detrimental to living  cells  and tissues.   A  low  concentration  of ozone




formed  in the  stratosphere  absorbs  most  of the  photons of  ultraviolet




radiation  (UVR)  and  thus  prevents  most  of  them from reaching earth.




However,  even  in  the presence  of  this  ozone  layer,  which varies  in




thickness  in various   latitudes  and  at  various seasons, a biologically




significant amount  of  UVR reaches the surface of the  earth.




     It  is  a  working  assumption  that byproducts  of  human  activity  in




recent  years and in  the  foreseeable future  may penetrate  to the level




of ozone  formation  in  the  stratosphere  and could  result in  a depletion




of this important "ozone shield."




     Model calculations  performed  in the  past decade have  resulted  in




the  suggestion  of  a   parametric  range  for  the  potential  decrease  in




stratospheric  ozone  due  to  various  causes  of from  1%  to  50%  (median




15%).   A recent report  of the  National  Academy of  Sciences (NAS)  en-




titled, "Protection against  Depletion of  Stratospheri.c  Ozone by Chloro-




fluorocarbons"  (NAS,  1979) estimates a  median decrease  in stratospheric




ozone at  equilibrium  of  16.5%,  assuming continuing discharge of chloro-




fluorocarbons  (CFC)  into the  atmosphere.




     The major  effects on humans of UVR  in the UVB (320  to 280 nm) range




are  on  the skin and  the eyes.   Acute effects consist of "sunburn,"  an




inflammatory response  of  the tissues  which  may be  no  more than  mild




redness, or slight  stinging of the  eyes, or may develop  into  the equiva-




lent of second  degree  (blistering)  "burns."  The acute effects of single
                             F-l-5

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                                                         Effects—Skin Cancer
overdoses of UVB  are  transient,  heal  without scarring, and in the  skin




lead  to  adaptive  changes  of  skin thickening  and pigmentation, which




afford some degree  of  protection.   The  only established positive  (bene-




ficial) effect of  UVB  in  humans  is the production of  vitamin D  precur-




sors  in  the skin,  which  are  absorbed into the bloodstream and  prevent




rickets,  a  serious  vitamin  deficiency disease.   It should  be recognized




that  most  work has been on the  harmful  effects of UVB, and relatively




little attention has been  given to  possible beneficial  effects, however.




     Repeated  UVB  exposure, prolonged  over many  years,  can  result  in




chronic  degenerative  changes  in  skin,  characterized  by  skin   "aging"




and the  development of premalignant  and  malignant ski.n  lesions.   The




skin  cancers of man can be  broadly divided into two types:  nonmelanoma




skin cancer (NMSC) and malignant  melanoma  (MM).




     There  is  excellent,  although circumstantial, evidence  that  NMSC




is  primarily  due  to repeated  exposure  of  the  skin  to UVB.   The major




arguments in favor of such a causal role  of UVR in  NMSC are:




•    The   most  frequent location of  NMSC  is on the most  exposed  skin




     sites (head,  neck, arms,  hands).




•    Pigmented  races,  who  sunburn much  less  readily  than people  with




     white  skin,  have  much less NMSC and  when it does occur,   it  does




     not  affect the sun exposed sites.




•    Among  white  skinned  people,  those  who spend more  time outdoors




     and   live  in  areas of  greater UVR exposure  (near the equator and




     in  tropical  and  semitropical  areas)  have much  greater  risk for




     NMSC.




•    Genetic  diseases  resulting  in  greater  sensitivity   to  solar UVR




     are  associated with premature  NMSC  development (albinism).
                            F-l-6

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                                                       Effects—Skin Cancer
•    Skin cancers  of  the NMSC type can  readily  be induced in the  skin




     of experimental  animals,  and the  upper  wavelength limit for  this




     is 320 nm,  similar  to  the spectral,  range  producing  sunburn  in  man.




     Recent epidemiologic research  has  resulted  in  the development  of




a  preliminary  dose-response relationship  of  NMSC to  UVB.    Reasonable




assumptions, based on tissue  culture and  animal  experiments,  for  the




relationship of various wavelengths of  UVR to  NMSC induction have  been




proposed.   While there is still discussion  about  the exact  relationships




of  various  parts  of  the UVR  to carcinogenesis,  existing data  appear




reasonably  sufficient  for  the  development  of  model  systems  that allow




for some  predictions  as  to  the  effect  of  reductions  of  stratospheric




ozone   to  the  probable increases  in the  incidence of  NMSC secondary  to




increase in UVB.




     Because of  uncertainties  in  the amount  of  UVB  actually reaching




various populations,  and because parts  of any population are signifi-




cantly  more sensitive (for  inherited reasons) to  the chronic  effects




of  UVR,  estimates  of possible NMSC  increases have ranged  from a  few




thousand  to many  hundred  thousand of additional cases  i.n   the  U.S.A.




alone.   Projected estimates are.  based  on  available  data (which  is  im-




proving)  and best estimates of  their meaning (where considerable,  dif-




ferences of opinion still exist).




     In summary,   there  is  reason to  believe  that most  NMSC (but  not




all,  for  about  one-third of basal cell  cancer occurs  in areas not  re-




ceiving much  UVB  and not  showing  other  sunlight  damage) is causally




related to  chronic,  repeated  UVB  exposure,   and  that a  dose-response




function  exists  that  can, with considerable future refinement, be  used
                             F-l-7

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                                                        Effects—Skin Cancer
to predict  changes  in  NMSC incidence given alterations of the  UVB  cli-




mate.




     The  situation  is  somewhat  different  where  MM  is  concerned.    The




NAS  report  (NAS, 1979)  uncritically suggests that  the relationship  of




MM to  solar UVR exposure is basically similar to that  of  NMSC,  and  that




the  same  model  systems apply equally to NMSC and MM for predictive  pur-




poses.




     There  is  considerable  evidence  that such assumptions are  not  ten-




able.   The  matter is of great  importance, since  MM is  a  serious, often




(40%)  fatal  cancer.  Although much  less frequent  in incidence,  its po-




tential  ability to  cause  death makes it of greatest importance to at-




tempt  to  develop a  model for its causation,  which may  allow  predictions




as to  future incidence  to be made.




     Because of its seriousness,  recording  of cases of  MM  is  usually




very  good,  so   that  epidemiologic. studies  that are  quite  reliable  have




been  carried out in many countries  in  the  past  three  decades.   Very




briefly, the following  are the. salient findings:




•    There  has  been a  consistent,  worldwide  increase  in  MM,  incidence




     rates  increasing  3  to  7% per  year,  leading  to a doubling in  10




     to 15 years.  This trend for increasing incidence  began  with people




     born at  or  before  the.  turn of  the century, and has  been  progres-




     sively  accelerating,  so that younger  persons have  a greater  risk




     for  development of MM  than  older  ones.   This  is  very  unusual  be-




     havior for  a malignant tumor.




•    There are  striking  differences in  anatomic  distribution by  sex




     -  MM is much more frequent  on  the.  backs  of men and  the lower  legs
                            F-l-8

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                                                    Effects—Skin Cancer
of women.   The  incidence  in those areas has been increasing  rapid-




ly, in contrast  to  MM of  the head and  neck area,  and on the feet,




which rose  only  slightly.   This distribution is  entirely different




from that of NMSC.




Most MM  is  a  disease of young adults.   In  contrast  to NMSC, inci-




dence of  MM rises  sharply  during adolescence,  plateaus  in  middle




age, and  rises  again  in  old age.   NMSC begins  to appear in  late




middle age and rises sharply in old age.




In contrast to NMSC,  only  about 10% of  MM  (a  subtype that closely




resembles squamous  cell cancer  in its biologic behavior) show  sig-




nificant evidence, of chronic solar skin damage.




While there  are   latitude gradients  for MM within some  countries,




the normal  gradient of increasing  incidence  from higher to lower




latitudes is  reversed  in  central Europe, and, particularly  in  the




Scandinavian  countries,  show  incidence  rates  greatly  in  excess




of  those  expected based on  relative UVB intensity found at  their




latitude.




From available  data,  it  appears  that  the  latent period  for  MM




development is short, perhaps even 3  to 5 years.   The  latent  period




for NMSC is certainly in excess of 20 years.




In  contrast to  NMSC,  which affects  mainly those chronically  ex-




posed to  sunlight,  i.e.,  outdoor workers, MM is  much  more frequent




in white collar,  educated,  more affluent city dwellers.




As  yet,  no  animal  model  for experimental production  of  MM  exists




using UVR.   Only recently  has  it been possible  to produce  MM  ex-




perimentally in guinea pigs, using a  chemical carcinogen.
                       F-l-9

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                                                         Effects—Skin Cancer
     From the  foregoing  it  is  obvious that there are major  differences




in most features of NMSC and MM.




     It is obvious  that,  if UVR  is causally related to  the  development




of MM,  the  mechanisms  are  very  different.   Certainly,  except for  the




10% Lentigo  Maligna Melanoma that appears  on  the  head  and neck of  old




persons, most  MM  can  not reasonably  be caused by the cumulative effect




of repeated  exposures to UVR,  as  is  the  case with NMSC.   The various




theories that have been proposed  for  its  etiology are:




Related to UVR:




•    Exposure  to  intermittent,  high  dose  exposure,  presumably due  to




     social  changes,  i.e.,  sunbathing, weekend gardening,  golf, tennis,




     etc.  and  vacation  trips  to  sunny places  (Spain, North Africa,  the




     Caribbean, etc.).




•    Production by  UVR of  a  "circulating  factor" which causes distant




     effects on precursor lesions.




•    "Initiation"  of  melanocytes,  either  by chemicals  or UVR, with  ei-




     ther UVR  or  chemicals  acting  as  a "promoter"  (i.e., two  stage  car-




     cinogenesis).




•    "Promotion"  of preexisting,  abnormal  precursor cells  or lesions




     by UVR (precursor lesions perhaps genetically  determined).




     In any  case, it is obvious that  at  this  time, there is no possi-




bility  of  assuming  a reasonable  dose-response  relationship  of UVR  to




MM development.  In the absence of  such information,  attempts  to predict




what changs may take  place  in MM incidence if  the  intensity  or  spectrum




of UVR changes are not appropriate.




     There is  certainly  no  rationale  for using the models proposed  for




NMSC development secondary to UVR exposure  for  evaluation of  MM  changes.








                            F-l-10

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                                                        Effects—Skin  Cancer
     It is  in making  such assumptions that  the NAS  report  errs  serious-




ly.   There are  a  number of  technical  errors  in the report.   The  most




glaring are:  e.g.,  the  wrong dose for production  of minimal erythema,




the uncritical  use of the  deoxyribonucleic acid (DNA)  action  spectrum




used  to  derive  the term "DUV" (damaging ultraviolet),  the neglect  to




heed  warnings   from  agencies  and  investigators  that  the  relationship




of MM  to  UVR differs significantly from  that  of NMSC,  and that a  com-




plicated mixture  of  environmental and  host factors relate to  MM,  etc.




     There are  other  technical  problems  - fabrics do not allow  signifi-




cant amounts of  UVB  to  pass, thus the assumption that such transmission




allows exposure  of lightly clad backs  is faulty.




     The authors frequently  confuse intensity  and dose.   There  are  fre-




quent  speculations for which no real data exist,  e.g.:




     "MM  does  not correlate with cumulative  lifetime   exposure, which




     suggests that intermittency  of  exposures  may be important." (NAS,




     1979, p. 325)




The first  clause of that  sentence  is correct; the conclusion is  a specu-




lation for which no real  evidence  exists.




     Finally, calculations,  using worst  case  assumptions  based on  NAS




data,   strongly  suggest  that  a  5  year  delay  in regulation of  CFG  will




not have a  discernible effect on  increases  in incidence of  NMSC or MM.




                          A.2.  Recommendations




     1.  Measurements  of  Actual Skin UVB Dose




     In order  to  establish  more  accurate  dose-response  relationships




between incidence  of  skin cancer  and UVR exposure, it   is  necessary  to




develop,  test  and use  personal  UVR  dosimeters  that  allow estimation




of actual  received dose  of various populations.










                             F-l-11

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                                                          Effects—Skin Cancer
     Two prototypes,  based  on  the Robertson-Berger system for measuring




erythema effective  UVR,  are being  developed at present.   Such  instru-




ments are urgently needed and should be used by persons of various  types




of outdoor exposure, and at various latitudes.




     2.  Continuation and Extension of Actual UVB Climatology




     While  hardly perfect,  data  obtained from  the  present  network  of




Robertson-Berger  meters  has been most  useful  for modeling of UVR  dose




by  latitude.   Additional stations need to be  established,  particularly




in  the  tropics and  at  high latitudes.   The data obtained needs to  be




acquired and  disseminated  on  a more  rapid and regular basis  (at  least




yearly) and be accessible to all investigators  interested in these  prob-




lems .




     3.  Animal Experiments  investigating effects of  dose rate,  frac—




tionation of  dose effects  and  interaction between wavelengths need  to




be performed.   The  use  of  appropriate solar simulators  and instruments




allowing tests  of interaction  of  various wavelength  bands is of  con-




siderable importance.




     Investigation is needed of the influence  of change  in flux of UVB




on  skin  carcinogenesis.   Preliminary experiments show  that protracting




the delivery  of  a  dose  of UV  (i.e.,  altering flux) has  a significant




effect on  skin carcinogenesis.   The  direction  of  the effect is  unex-




pected - lower flux can  be  more effective.




     It  is   recommended  that  the  effect  of  varying  interval periods




during  carcinogenesis experiments  be  studied  in  detail.   The  dose-




response model  of Blum  and  the model  for  effect  of "effective exposure"




of Robertson  demonstrate that   intervals  of  exposure are  of  importance
                             F-l-12

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                                                          Effects—Skin  Cancer
in skin carcinogenesis.   This  may be one of the  most  important experi-




ments, since  in nature,  change  in  ozone will  affect flux and spectral




distribution of  UV but not  the  time relationship  during which people




will be exposed.




     At present,  the  only workable  animal  model for  MM is the guinea




pig system  reported by  Pawlovski  et al.  (1980).   However, this utilizes




chronic skin  painting with  a  chemical  carcinogen only.   It is recom-




mended that  experiments using the  same  guinea pigs  but using UVB ex-




posure be performed.   In  addition,  the  interaction  of  chemical carcino-




gens and UVR should be investigated.




     4.  A Central Laboratory for measurement,  calibration and reference




standards  for UVR light sources and  measuring devices  needs to be estab-




lished, so  that data  obtained  by various investigators with different




equipment  can be appropriately compared.
                            F-l-13

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                                                           Effects—Skin Cancer
                   B.   Historical  Review  of  the  Problem




     Solar  radiation   is  a very  important  element  in  our  environment,




and  yet,  because  of  its  ubiquity,  the  wide scope of  its  chemical  and




biological effects  is  often not fully appreciated.   The fact that solar




energy  fixation makes  life possible  is widely  known.   It is  not  so




generally  appreciated  that many  of  the effects of solar  radiation  are




detrimental.  Most people are aware that a painful sunburn can be caused




by  excessive  exposure to  the  sun.   There are  also more  subtle  effects




of  sunlight  on  living cells,  including the  production  of mutations.




The  development  of skin  cancer may follow  sufficient  chronic  exposure




to sunlight.




     The  shortwave portion  of  the  solar spectrum  is  potentially  very




detrimental to  plant   and  animal  cells.   A low concentration  of ozone




in  the upper  atmosphere   filters  out  these harmful  wavelengths of  UV




radiation  and  thus  prevents most of  it from  reaching the  surface  of




the  earth.   The  formation of  this  ozone shield  in  geologic time  was




most  likely  a  prerequisite for  the evolution of  terrestrial  life  as




we know it.   However,  even in  the presence  of  this ozone layer, a  bio-




logicaly  significant  amount of UV  radiation does reach  the surface  of




the earth.




     It is a working assumption that  human activity  has  not yet  appreci-




ably modified  the  earth  level  solar spectrum.   Initially,  concern  was




raised that exhaust products from a large fleet  of supersonic transports




(SSTs) might seriously reduce the stratospheric  ozone  layer that  shields




the earth's surface from  solar  UV radiation (CIAP,  1975).   More  recent-




ly, calculations  of rate  constants  for an  important chemical,  reaction
                          F-l-14

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                                                          Effects—Skin Cancer
(H09 + NO),   using  improved techniques,  suggest that NO   injection  will
   £-                                                   X


not  cause  a  serious perturbation  of ozone.   However,   data  presented




to  a  very  recent  conference  on stratospheric 0~ have  again  changed the




predicted effect of NO  on ozone.




     More recently,  it  has  been  reported that continuing discharge  of



chlorofluorocarbons  (CFG)  into  the  atmosphere or  a major  series  of




atomic  explosions  above  the earth's  surface could have an even  more



significant effect on the ozone layer (Hampson,  1974;  NAS, 1979).



     Recent  computer calculations  suggest  that  if  chlorofluorocarbon



releases were to continue at  the 1977 rate, a stratospheric ozone  deple-



tion  of  about  16.5%  could  eventually occur,  with  about half  this  deple-



tion  (or 8%)  attained  in 30  years (e.g.,  Stief et  al. ,  1978;  Dickinson



et al., 1978; Crutzen et al., 1978;  NAS,  1979).



     The shortest  wavelength  of  solar  radiation observed  on earth  at



sea  level,  at  the  time of  maximum  solar elevation,  is  about 288  nm,



although the photosphere  of the  sun radiates  significant  amounts  of



very  much  shorter UV radiation,  since  it corresponds to a  brightness


                          r*
temperature of about 5,000 K.



     The available UV solar  radiation is  depleted as  it  penetrates  the



earth's upper atmosphere.  This depletion  is, in part,  due to  scattering



by air molecules,  but it is mostly due to  absorption by molecular  oxygen



and  ozone  which is  further  enhanced by  scattering.   Molecular  oxygen



absorption becomes strong  at wavelengths  below 200  nm and is  important



to  the  thermal balance  of the  upper  atmosphere above  50 km.  The  sig-



nificant spectral  regions  for  ozone  absorption in  the UV are the  con-



tiguous  Muggins (320-360  nm) and  Hartley  (220-320 nm)  bands.    These
                           F-l-15

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                                                        Effects—Skin Cancer
bands  absorb  quite weakly  at  360  nm,  but rapidly increase  in  strength




with  decreasing  wavelength, reaching an  absorption  maximum at  255  nm.




At sea  level,  the  effect of atmospheric ozone becomes  significant  below




325  nm,  and there  is  a  very sharp drop  in transmission,  from  approxi-




mately  9070 of extraterrestrial  UV radiation  at  325 nm  to  170  or  less




at 295  nm.  Thus,  the absorption  of UV radiation by ozone  occurs  pri-




marily  in  a wavelength  region shown to be effective in  the production




of skin  erythema,  chronic  skin and eye damage, and  skin  cancer.  Thus,




if a  reduction  in  atmospheric  ozone would occur  secondarily to  altera-




tions of conditions in the stratosphere,  concern  arises as to  potential.




increases  in  the  incidence  of sunburn, degenerative skin and  eye  dis-




orders,  and skin  cancer  in man (CIAP,  1975;  NAS,  1973, 1975,  1979).




     A  parametric   range  for  the  potential  decrease   in  stratospheric




ozone  due  to various  causes of from  1 to 50 (median  15)  percent  has




been  assumed by  various  authors (CIAP,  vol.  5, 1975; NAS,  1975, 1979).




Based  on the admittedly  inadequate  epidemiologic data,  this has  given




rise  to  estimates  of increases in skin cancer  ranging  from  a  few  thou-




sand  to  many hundreds of  thousands of  additional  cases  in the United




States  alone.    The huge  range  in estimates   results  in  part   from  the




present  uncertainty about   the  shape of  the  "biologic  action  spectrum"




for skin cancer induct ion and the lack of precise knowledge of the amount




of  "carcinogenic"   UV  radiation reaching  populations   at  risk.   It  is




important  to  recognize that projected estimates  are based on  available




data and best estimates of their meaning.   Additional surveys of natural




UV  insolation,  analyses  of  additional  epidemiologic data,  and further




experiments with animals would greatly reduce  some  of  the uncertainty.
                            F-l-16

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                                                           Effects—Skin  Cancer
     Although potential  effects of  increased  solar irradiance  on  man,




particularly  in  the form  of  skin  cancer, is a prominent  and sensitive




issue, impacts of  this  increased irradiance on organisms of terrestrial




(both agricultural and nonagricultural) and aquatic ecosystems may ulti-




mately be  of  much  greater concern.   Certainly  our  understanding of the




sensitivity  of  plants,  invertebrates  and  vertebrates  to  increases  of




UV irradiance  is not  nearly as well  developed  as  is  the case  for  homo




sapiens.    Without  a  reasonable  understanding  of  what  a unit  decrease




in  ozone  means  for  the  biosphere,   there  is  no perspective  upon which




to base decisions concerning acceptability of  "allowable" change.




     Depletion  of   stratospheric  ozone and  consequent  increase of  UV




irradiance  attributable  to SSTs of  the  size and configuration  of  Con-




corde are  now contemplated to  be  rather small compared  to present-day




ambient fluctuations or to the diminutions of  ozone postulated to result




from  other  activities of  man  (NAS,  1979).   On the other  hand,  present




estimates of  ozone  reduction  due to CFC release are  estimated  to reach




as  high  as 16.5%  (NAS,  1979).   Thus  there exists  a critical  need  to




investigate  the  effects  of enhanced  UV irradiance  on  organisms.    It




would not  be  unreasonable  to  postulate  that  the  added  stress  imposed




by  UV radiation  increase  due to any one agent, though  small,  could  be




a critical  amount  when  added  to that  increase  of  UV  resulting  from ef-




fluents  of super-  and  subsonic  aircraft, diffusion  of  chlorofluoro-




carbons  into  the   stratosphere,  release of  nitrogen oxides into  the




stratosphere by nuclear  explosion,  etc.   Since chemical  injectants  from




several sources  may be  producing  additive effects on ozone  depletion,




that  increment  of  diminution resulting  from  any  one  activity  must  be










                            F-l-17

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                                                         Effects—Skin Cancer
evaluated  in  a  biological context in light of  other  potential  changes.




For  example,  the  effects of a 1%  decrease  of  ozone  from current levels




can  not  be compared with the effects of a 1% decrease for an atmosphere




already partially depleted by other causes.




             State of Current Knowledge Involving Effects of




                    Enhanced UV Radiation  on Organisms




     Photobiological  research  involving that  region of  the  UV  spectrum




under consideration (280-320 nm,  referred to as UVB)  has received little




attention.  Most  UV photobiology has employed  254 nm  radiation  because




it  is  easily generated  by  low pressure mercury vapor  lamps and  is  ef-




ficiently  absorbed  by  nucleic  acids.    Since  wavelengths  shorter  than




285  nm are effectively  absorbed  even by an  atmosphere severely  depleted




of  ozone,  this  "254  nm photobiology"   is of  little value  in quantita-




tively assessing  the  impact of  increased  solar  UVB  irradiance  (NAS,




1973).   Only recently  have experiments been  initiated to  specifically




address the question  of the biological  effects of increased UVB  irradi-




ance as would occur with stratospheric  ozone depletion.  This work  was




sponsored  initially by  the  Department  of Transportation Climatic Impact




Assessment  Program  (DOT/CIAP)  and continued by the Biological and  Cli-




matic  Effects  Research  (BACER)  program, now  Stratospheric Impact  Re-




search and Assessment  Program (SIRA) of the U.S.  Environmental  Protec-




tion Agency.




     These  preliminary  experiments   and the   earlier  photobiological




literature  indicate that:   (1) Most  observed biological effects  of  UVB




radiation  are decidedly detrimental; (2) Most  organisms have developed




a capacity  to avoid excessive normal solar  UVB radiation by absorption
                            F-l-18

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                                                         Effects—Skin Cancer
of Che radiation before it reaches sensitive  physiological  targets  (e.g.




by cuticular  waxes  and pigment  on plants;  by feathers, fur,  pigments,




etc.  of animals), to avoid exposure by behavioral  patterns,  or  to toler-




ate a certain  UVB  radiation  stress such as by molecular, repair mechan-




isms;  (3) CIAP  (1975)  indicated  that  the capacity to avoid  or tolerate




this   UVB  radiation  may  be  limited  for most organisms,  and  that  some




organisms may  be already  existing  near a threshold where  an  increased




UVB irradiance  regime would be  detrimental.    However,  the  relevance




of such experiments  to  field conditions on  land  and  in  oceans  is uncer-




tain,  because of difficulty in simulating appropriate conditions.




             Biomedical Implications of UV Radiation  Changes




                               for Humans




     Acute  Effects  on  the Skin.   Erythema solare,  or more  commonly,




sunburn, consists in  its  mildest  form of a reddening of the skin  which




appears one to  six  hours  after exposure to erythemogenic UVR  and  grad-




ually  fades  in one to three  days.   In its  more  severe forms, erythema




solare  causes  inflammation,  blistering  and  peeling  of  the  skin;   it  is




followed by  tanning of the  skin, which  becomes  noticeable within  two




or three days following irradiation (Giese,  1965).




     Although sunburn will occur  with  shorter  exposures  if  stratospheric




ozone  is reduced, protective  measures  now available  (clothing, chemical




sunscreens,  etc.) will  prevent  this from becoming a  seriously limiting




factor for human activities.




     Acute Effects  on the Eye.   That  the biologic effect  of  UVA  (320-




400 nm)  and  UVB on living tissue was  known  in  very  early  times is  in-




dicated by Xenophon's mention of  snow  blindness  in his treatise Anabasis
                          F-l-19

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                                                          Effects—Skin  Cancer
(379-371 B.C.)-   Coordinated  studies  on the harmful effects of  UV were




begun  in  the nineteenth  century,  but were  directed  at the effects  of




the electric light on the eye.




     Although more  energetic  than the  visible  portion of the electro-




magnetic spectrum, UV  radiation  is  not  detected by  the  visual  receptors




in mammals,  including  man.   Thus, exposure  to  UV may  result  in  ocular




damage  before  the  recipient  is  aware  of the  potential  danger.   Many




cases  of  keratitis  of  the  cornea and  cataracts  of the lens due to  UV




exposure have  been  reported.    The  UV  radiation  involved was produced




by welding arcs,  high-pressure pulsed  lamps,  and the reflection of solar




radiation from snow and sand.




     In the  UVB  region reaching  earth from the  sun, which  has  most bio-




logical effectiveness  (290-320  nm),  the action spectrum  for photokera-




titis  is almost  identical to  that for skin erythema.  Thus all the con-




clusions about increased hazard from  a change in this UV band applicable




to  acute  effects  on  the  skin  apply  equally well  to  the eye  (Pitts,




1970).




     Vitamin D.  Sunbathing is popular and there is  a widespread  feeling




that  "sunlight  is good  for  you," but  the physiological   benefits that




presumably  underlie  the  feeling  of wellbeing have not been adequately




explained  or studied.     Since  recent concerns have  centered  on ozone




depletion  and  UVB  increases, most  recent research  on the  effects  of




UVB has examined potential detrimental effects of  increased UVB.




     The only  thoroughly established  beneficial effect  of UV  radiation




on  the skin is  the  conversion  of 7-dehydrocholesterol to vitamin  D3.




Renewed interest  and recent progress  in understanding of  the mechanisms
                            F-l-20

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                                                         Effects—Skin Cancer
of  vitamin  D production  and  its metabolism  and  functioning have  been

made  by  several investigators,  including  DeLuca's  (1971) group  at  the

University of Wisconsin, where Steenbock did the classic work on conver-

sion  of  ergosterol in  plant  foods  to dietarily effective vitamin  D  by

UV  radiation.   Steenbock's  work was done in  a  period  of rapid  progress

in  biochemistry and nutrition.   However, as DeLuca has  said, the clin-

ical  existence  of  rickets  and  designation of  vitamin  D as  a  vitamin,

rather than a prohormone,  is a "complication of  civilization."  Through-

out most  of human existence  7-dehydrocholesterol  was converted  in  the

skin  by  UV radiation  to  vitamin D.j.   Only in northerly climates,  and

particularly with  the  advent  of cities, was  the sun-produced vitamin 0

insufficient  to prevent  rickets in  growing  children and  osteomalacia

in  adults.   Both  of  these diseases are  produced by  defective bone  cal-

cification.   Loomis  (1967)  describes  the particular  cruelty  to  poor

children inflicted by  a tax on windows in  urban housing. There is  also

a  claim  that Neanderthal man was  rachitic  at a time of  rapid  climatic

change.

     Anthropologists  have  long  looked upon white skin as an adaptation

to  low levels  of  UV  radiation,  with  selection  for lighter  skin perhaps
                                                    \
occurring very rapidly during  cloudiness associated with glacial periods

because of  the impossibility of  a woman  with  a rachitically  deformed

pelvis to  give birth.    (This  assumption  is open  to many  questions.)

     Loomis (1967) endeavored to  extend the implications of  the vitamin

D  theory of  skin  color to the idea that white man  in  the tropics  should

be  expected to  suffer  from vitamin D intoxication.  This idea was chal-

lenged in  a series of  letters  to  the editor of Science (Blois,  1968;
                               F-l-21

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                                                         Effects—Skin  Cancer
Blum,  1968)  and elsewhere  (Daniels  et al.,  1972)  on the  grounds  that




such  intoxication  had  not  been  observed  in white men  in the  tropics




and  that  Loomis was assuming  higher exposures  and efficiencies  than




were likely.




     There  is evidence  that  increased dietary intake of vitamin  D  (al-




most always  vitamin D,,)  can  produce  vitamin  D  intoxication.    Whether




this represents  a  difference  in route of  administration  or a  difference




between vitamins D? and  D^  does  not  appear in  the  literature  and  is




an  important  area  for  urgent  investigation.   We  know  that  vitamin  D




intoxication can be produced by  oral administration, and  we know  that




this effect appears  to  summate  with UV effects on  the  skin,  but we can




not  at  present  answer  the question, "Would an increase  in  environmental




UV  radiation lead  to vitamin D intoxication or poisoning  in  normal man




or  other animals?"




               Chronic Detrimental Effects of UV Radiation




     UV Radiation  and Skin  Aging.    Solar  or actinic changes  in human




skin  (farmers'   skin,  sailors'  skin)  are  shown  by  atrophy,  freckling




with  hyper- and hypopigmentation,  dilated  blood  vessels   and  a  yellow




discoloration due  to increases of abnormal elastic  tissue.   Wrinkling




is  also a  prominent feature.   Most  attention  related to hazards of in-




creased UV radiation  in man's  environment has  been centered  on  skin




cancer, but for every  patient  who  develops  actual  cancer,  there are




probably  hundreds  who  develop  readily visible  actinic  changes.   This




may  be  no  problem  in a  "weather-beaten sailor" or  a  "red-neck farmer,"




but  it can be  a devastating problem in  a  woman who likes  golfing or




boating and may look in  some ways  as if  she were 70 years old when she
                               F-l-22

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                                                        Effects—Skin  Cancer
is  50.   Significant  increases  in UV  radiation will make  this a  much




more  common  problem  that  can not  be  treated  adequately  or cured  the




way skin cancer  can  be,  and may  lead to  more psychological  effects  than




skin cancer itself.




     Nonmelanoma Skin Cancer.  In section C of this  report,  the  existing




data  for etiology, epidemiology  and  experimental  production of  nonmela-




noma skin cancer are  described in detail.




     Human Skin  Cancer Production by UV.   Examination of  the sun's  role




in  the  production of human  skin  cancer  does not  lend itself to  direct




experimentation.   However,  extensive astute  observations have  strongly




suggested  the  etiologic  significance of  light energy in the induction




of  these  tumors.  Skin  cancers  in.Caucasians in  general are most  pre-




valent in geographical areas of  the  greatest insolation  and  among  people




who receive  the most exposure,  i.e. men  who work  outdoors.   They  are




rare  in  Negroes  and other  deeply   pigmented  individuals  who have  the




greatest  protection  against  UV  light  injury.   Further,   the  lightest




complexioned individuals, such as  those  of Scottish and Irish  descent,




appear to  be most susceptible to  skin cancer formation when they  live




in  geographic  areas  of  high UV  exposure.   When  skin cancers  do occur




in  the  darkly  pigmented races,  they are  not distributed  primarily  in




the sun-exposed  areas as they are in light  skinned people.   The  tumors




in  these  pigmented  individuals  are  more  commonly  stimulated by other




forms of trauma,  such  as chronic leg ulcers, irritation  due to  the  lack




of wearing shoes, the use of a Kangri (an earthenware pot  that is  filled




with burning charcoal and strapped to the abdomen  for warmth), the wear-




ing of a  Dhoti  (loin cloth), and so on.   In contrast,  the  distribution
                            F-l-23

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                                                      Effects—Skin Cancer
of skin cancer  in  the Bantu albino and in  patients  with  xeroderma pig-




mentosutn follows sun exposure patterns.




     Blum  (1959),  Urbach  et  al.  (1969,  1972)  and most recently  Emmett




(1974) have  reviewed the evidence  supporting  the role  of sunlight  in




human skin cancer development.  Briefly,  the main  arguments are:




•    It is clearly  established  that  superficial skin cancers  occur most




     frequently  on  the  head, neck,  arms  and hands,  parts of the body




     habitually exposed to sunlight.




•    Pigmented  races,  who  sunburn  much  less readily  than people with




     white skin, have very much  less skin  cancer and  when  it does  occur,




     it affects areas not  exposed to sunlight most frequently.




•    Among Caucasians  there  appears  to  be much  greater incidence  of




     skin  cancer  in those  who  spend  more  time  outdoors than those who




     work predominantly indoors.




•    Skin cancer is  more  common in white  skinned  people  living in areas




     where insolation is greater.




•    Genetic   diseases  resulting in greater  sensitivity  of skin  to the




     effect  of  solar UV radiation are associated with marked increases




     and  premature   skin  cancer development  (albinism,  xeroderma pig-




     mentosum).




•    Superficial  skin  cancers, particularly  squamous  cell  carcinoma




     of the skin, occur predominantly on  the areas receiving the maximum




     amounts   of solar  UV  radiation and  where   histologic  changes   of




     chronic  UV damage are most  severe.




•    Skin  cancer can be produced readily  on the  skin of mice and rats




     with repeated  doses  of UV  radiation  and the  upper wavelength limit
                            F-l-24

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                                                       Effects—Skin Cancer
     of the most  effective  cancer  producing radiation is about 320  nm,




     that  is  the  same  spectral  range that produces erythema  solare  in




     human skin.




     Though  these arguments  do  not  constitute absolute  proof,   there




is  excellent  epidemiologic  evidence supporting  the role  of  sunlight




in nonmelanoma skin cancers.




     Malignant Melanoma.    In section  D of  this  report,  the  existing




data for etiology, epidemiology and experimental production of  malignant






melanoma are described in detail.




     Suffice it to state  here that,  while malignant melanoma  as  an  en-




tity has been known and described  for over 150 years,  the possible  etio-




logic  relationship  to  solar  ultraviolet radiation has  only been sug-




gested  in  recent  years.   Until  1948,  MM was not separated from  other




skin tumors in international statistical classifications, and thus  know-




ledge  of  its variation from population  to  population  was  effectively




prevented.   An  equally  important  factor is  the  lack of concentration




of MM on light-exposed skin surfaces, in obvious contrast to  the distri-




bution of nonmelanoma skin cancer.




     The original and  strongest  evidence  for  the possible  importance




of  exposure  to sunlight  as a causal  factor for  development  of  MM  in




white people is the  apparent  influence  of'latitude of residence  on  the




incidence and mortality  of  MM.  As will be seen in section D,  this phe-




nomenon is  not  simple,  or  even  realistically  similar  to  the  latitude




gradients found regularly for nonmelanoma skin cancer.




     However,  since  35 to  40% of all  patients affected by  MM die  of




their disease,  and since the incidence rate of MM is  rising at  an  alarm-




ing  rate,  the need  to  determine  etiologic  factors  in  this  malignant




tumor is urgent.




                              F-l-25

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                                                       Effects—Skin Cancer
                                 Summary




     Solar ultraviolet  radiation  shorter  than wavelength 320 nm is  bio-




logically  highly  effective,  and  the  majority of  the  effects  on  living




organisms  are  detrimental.   Most  of the UVR  emitted by  the photosphere




of  the  sun is  effectively  absorbed by  a  thin layer  of  ozone produced




photochemically from  oxygen  in  the stratosphere.   There  is considerable




concern  that   anthropomorphic  effluents,  particularly NO ,  Cl and  Br,




can  alter  stratospheric ozone  concentrations.  Concern  in  recent years




has  been  primarily  directed at  NOx emitted  from aircraft capable  of




stratospheric  flight,  and Cl derived from destruction of chlorofluoro-




carbons  in the stratosphere.   Estimates of a calculated  16.5% reduction




in  stratospheric  ozone concentration (at  equilibrium) have  been made,




based  on  incomplete  knowledge  of  stratospheric  chemistry  and  various




model systems.




     It  should be noted, however,  that preliminary calculations using




two  dimensional modeling  (Pyle  and  Derwent, 1980) suggest  calculated




ozone depletion and calculated DUV increase is not uniform with latitude




and  season.    If  this  is correct,  estimates of  effects  would have  to




be revised downwards.




     It is certain that a reduction in stratospheric ozone concentration




will result in an increase of biologically effective UVR  reaching earth.




Among the known effects of chronic exposure of skin to  UVB are degenera-




tive  changes   in  the  connective  tissue of  the  skin  leading  to "skin




aging"  and the  induction of nonmelanoma  skin cancer.   The  degree  to




which  such changes take  place  is markedly  affected  by   dose  and dose-




rate of UVR,  as well as pigmentation and genetic predisposition.
                             F-l-26

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                                                      Effects—Skin Cancer
     Much  less clear  is  the relationship of UVB  exposure  of  skin to




the  incidence  of  malignant  melanoma,  a  potentially  fatal  skin malig-




nancy.
                           F-l-27

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                                                        Effects—Skin Cancer
          C.  Potential Changes in "Biologically  Effective"  UVR

          Reaching  Earth  Secondary  to Anthropomorphic Alteration

                 of the Stratospheric Ozone Concentration

                  C.I.   Conclusions and Recommendations

     Of  the various  action  spectra proposed  for skin  carcinogenesis,

the  portion of  the  DNA  action  spectrum  up  to  about  280 nm published
                                  •
by  Setlow  (1974)  appears  to  be  closest  to experimental  observations

in mice.

     The  exact  shape of an  action spectrum used  to weight  calculated

or  measured spectral data of  solar UVR  is  of  critical  importance  for

the  estimation  of  any effects  attributable  to  changes  in  quality  and

quantity of solar UVR reaching biologic targets.

     Recommendations

1.   In any calculations  concerning biologic  effects  of  UVR  it is  neces-

sary to check with known  observed biologic reactions  by  utilizing  actual

values  substituted  in  any  model  system, to determine whether  the  effect

matches the prediction.

2.   Considerable  further  experimentation is  needed  to determine  the

exact shape of  a skin  carcinogenesis  action  spectrum,  particularly with

wavelengths between  300  and  280  nm.  Animal  experiments, using  filtered

light sources simulating  field conditions, are  feasible.

         C.2.   Action Spectra  for  Some  Effects of UVR on  the Skin

             C.2.1.  The  Human Skin Erythema  Action Spectrum

     During the  1920's and early  1930's, the relationship between  the

degree  of  erythema  produced  and  a given  wavelength of UV was  studied

by  several  teams of scientists.   Hausser and Vahle  (1927)  reported  the
                             F-l-28

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                                                      Effects—Skin Cancer
first  precise  determination  of  the  action spectrum  for the  erythema




of human  skin;  a  double  peak was  shown  with maxima  at  about  250  and




297  nm  and a minimum  at  about  280  nm.   In these and  related  studies,




the  skin of  several  individuals  was exposed to UV radiation  from a mer-




cury  lamp  passed  through a  double-quartz-prism monochromator,  and  the




influence  of wavelength,  exposure  time  and exposure rate upon  the  na-




ture, degree and  course of  erythema was  examined.   Similar action spec-




tra  were  published by Lukiesh et  al.  (1939),  using a mercury  arc lamp




and  filters,  and  by Coblentz  and Stair  (1934),  using a quartz-prism




monochromator.




     Coblentz and Stair (1934) formulated a standard  skin  erythema curve




(Fig.  1).   This  curve  represented the relative effectiveness  of equal




amounts of  energy at  different  UV wavelengths for  producing  erythema.




The  most  effective wavelength in  the then accepted standard curve  was




297  nm;.  250 nm being  60% and 280  nm  about  5% as effective  as  297  nm.




Recent reports  have  shown that,  although 280  nm  is somewhat  less  ef-




fective than adjacent wavelengths  in  producing erythema,  this  reduction




in efficiency is  by  no  means as  low as the old standard curve  suggests.




In  addition,  doubt has been cast  on  the peak of  efficiency being  at




297  nm.   A comparison of various  action  spectra  for UV erythema up  to




1966  has  been  carried out  by Johnson et al.  (Fig.  2).  One  important




factor to  consider when  comparing  results from  different laboratories




is the  region  of  the  skin   that  was  used as  the  test site.   Olson  et




al.  have reported  that  the  minimum erythemal  dose  may  vary considerably




with different  anatomical  locations.




     Recently,  Magnus,  Everett  et  al.,  Freeman et  al.,  and Berger  et




al. have reported UV  action  spectra that  have  several features  in common









                             F-l-29

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                                                          Effects—Skin Cancer
               240  250  260  270  280   290   300   310   320
                               Wovelengths (nyim)
Figure 1.   Action  spectrum for erythema production.   L,  H and T,  1930;
Luckiesh,  Holladay  and  Taylor (1930).   H &  V,  1927; Hausser  (1928).
C, S & H,  1931;  Coblentz, Stair and Hogue (1931).   H & V,  1922;  Hausser
and Vahle (1922).  [From W. W. Coblenz, R.  Stair and J. M.  Hogue,  Bureau
of  Standards  Journal  of  Research,  8, p.  541  (1932).] (From  Coblentz
and Stair, 1934.)
                            F-l-30

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                                                            Effects—Skin Cancer
                             250  270  290   310
                             •Standard curve'I.C.I. Berlin (1935)
                                            Luckiesh, Hoiladay S Taylor (1930)
                  Luckiesh 8 Taylor (1939)
    CoWentz, Stair a Hogue (1932)
                 250   270  290  310
                  Freemen et al. (1966)
    250  270  290
    Everett eto/.( 1965)
                                                         310
                                 Wavelength (nm)
Figure  2.    Action  spectra for  UV erythema.   Hausser  (1928):   Forearm
skin.   Spectral  lines  from medium  pressure mercury  arc separated  with
quartz  prism.   Luckiesh et al.  (1930):   Back skin.  Spectral  lines  from
medium  pressure mercury arc separated  with filters.   Mathematical  cor-
rection  for spectral  contamination.   Luckiesh and Taylor (1939):  Upper
arm, inner  aspect.   Source and corrections  as for Luckiesh et  al.  (1930)
Coblentz et  al.  (1932):  Forearm  skin.   Spectral lines from medium pres-
sure mercury arc  separated  with quartz  prism.   Freeman et  al.  (1966):
Abdomen  skin.   Continua from three  high pressure  xenon  arcs,  dispersed
through  Bausch and  Lomb  grating monochromators to single  focus.   Slit
widths:   2.7 mm  1.5 mm.   100%  = 8.0 x  10^ ergs  cm"  .   Everett  et  al.
(1965b):   Back  skin   Continuum  from high  pressure xenon arc  dispersed
through  Bausch and  Lomb  grating monochromator.   Slit   widths:    5.4  mm
3.0 mm.   100% = 6.6 x 10  ergs cm~
(From Johnson et al.,  1968.)
                             F-l-31

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                                                         Effects—Skin Cancer
but also  show  some  major  differences.   Cripps et al. were  in agreement




with these  authors  that  the  most  effective wavelengths  are in the 250-




260  nm range  and that effectiveness  falls  off rapidly  above  300 nm.




In  the  region  of 270-280  nm,  Magnus  found  270  nm  to be the least ef-




fective wavelength.    Freeman  et  al.,  who used abdominal  skin  as the




test  site,  showed  a  marked depression  at 280  nm,  whereas Everett  et




al. reported a plateau between 280-290  nm.   However, these latter au-




thors, although using  the  skin  of  the  back of  the trunk,  recorded their




observations at  8  hours  after the  exposure rather  than  at  24 hours.




The results of Cripps  et  al.  show a definite  depression  in the 270-280




nm  region,  with  the  least  effective wavelength  appearing at  275 nm at




24  hours  and  280 nm  at  8  hours.   Berger et  al.  showed that the time




of  determining erythema after  irradiation  had  a  great influence on the




shape of the action  spectrum,  particularly  on the relative  effectiveness




of  the  250  and 297  peaks, with erythema due  to  250 nm  peaking 8 hours




after irradiation and that due  to  297 nm at 24  hours.




     The  shortest wavelength  that  appears  at  present  in terrestrial




sunlight  is approximately  288  nm.   Thus, in a normal person, the solar




erythemogenic  region may be  considered to  extend from about 290 to 320




nm,  but  the  lower  wavelength  limit  is of  course  asymptotic.   Cripps




et al. reported that,  in  the wavelength interval  between  292.5 and 298.5




nm,  the  most  effective  wavelengths  for producing  erythema were 292.5




and 294 nm.   Freeman et al.,  using  rabbit skin  and human  abdominal skin,




found  292  nm  to  bethe most  effective,  and  the  preliminary results of




Berger et al.  suggest  that the most  efficient  wavelength  in this region




is between 290  and 294 nm.
                              F-l-32

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                                                          Effects—Sk.in Cancer
     A reexamination of the erythema response of human skin to  UV  radia-




tion was  carried out  by  Berger  et  al.  (Fig. 3).   Using  high-intensity




monochromatic radiation  with minimal stray-light  characteristics,  they




found  that  stray  light  significantly affected  the measurement of  the




minimal erythema dose  at  wavelengths  between 303 and 313  nm.   Utilizing




the skin  action  spectrum  cited above and the solar  UV  output  spectrum,




the most effective radiation for producing erythema from solar  radiation




was calculated  to be  between  305  and 310 nm, depending on solar  alti-




tude.




     The  type of erythema produced depends somewhat  on the wavelength.




Erythema  from shorter  wavelengths appears  earlier  and  fades  quicker




than  that produced  by longer wavelengths.   Further,  short wavelength




erythema  is pink in  contrast to the deeper red  from longer wavelengths.




Blum  and  Terus  (1945) found  that  large  doses  of  deeper penetrating




radiation around 300  nm  inhibited  the action of wavelengths at  254 nm,




probably by injuring superficial  blood vessels.




  C.2.1.2   Physiologic Mechanisms  Involved in Skin Erythema Development




     Erythema caused by ultraviolet radiation is confined  to the exposed




areas  and reflects blood  vessel  dilation and  increased  blood flow  in




the dermis.   It  is often assumed that the initial photochemical reaction
                              F-l-33

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                                                        Effects—Skin Cancer
          per
          cent
           220
           140
           100
            70
            30
                  8 hrs MED
                  74 hrs MED
                  24 hrs 30 R
                       \
                          N
                nm   254
                                   280
297 303   313
Figure  3.   "Action  spectrum"  of human  skin.   Averages  of  values for
five subjects, abdominal  skin,  second  exit  slit.   Note great  similarity
for wavelength from  297  to  313 nm,  and marked differences for 8 h MED,
24 h MED  and  a curve constructed by using  values  for moderate erythema
(Kodak Color Balancing filter 30 R)  (From Berger et al.,  1962.)
                             F-l-34

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                                                         Effects—Skin Cancer
is in  the  epidermis,  where photon absorption by keratinocytes may  lead




to liberation  of  intracellular  substances  which diffuse into the papil-




lary dermis  to cause  vasodilation.   This diffusion theory  is  supported




by the  existence  of  a latent period between exposure  and  erythema,  and




by the  fact  that  much of the radiant energy of the erythemogenic wave-




length  region  is  absorbed  by  the epidermis.   However, there may  also




be direct  injury  to  the  vascular  endothelium  or to other  sites  in  the




dermis.




     Most  studies of  the mechanism of  "sunburn"  have used  artificial




sources  of  UVB or sources  in which the spectral  distribution  is  such




that  UVB is assumed  to  provide  the major erythemogenic influence.   In




experimental animals,  the  vascular  response  to ultraviolet  radiation




is biphasic.   A transient immediate vasopermeability  is followed, after




a  latent period  of  2 to  8  hours,  by  a delayed,  prolonged,  increased




vasopermeability  and  vasodilation.   In  some animal models  the  initial




vasopermeability  is  accompanied  by  a  faint erythema  which may begin




during exposure.  This immediate  effect  has been attributed to  histamine




release possibly due  to a direct  effect  of  photons on  dermal mast cells.




There is evidence that  serotonin may also play  some  role.   In rats  and




guinea pigs, serotonin and  histamine antagonists suppress  the  immediate




phase  of UV vascular  responses.   In vivo studies of  human skin  have




shown transient appearance of kinins within minutes  after ultraviolet




radiation.    Kinin was not  found after  the  onset  of  delayed  erythema.




     The mediators of  the delayed  phase of ultraviolet  induced vascular




response have  been difficult  to  define.   Antihistamines do not  suppress




the  delayed erythema  phase  of  the  vascular   response to  ultraviolet











                               F-l-35

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                                                        Effects—Skin  Cancer
radiation  in guinea pig,  rats  or man.   Kinins have been stated  to  be




absent  or  not elevated.   Delayed erythema was not  suppressed by  using




various  inhibitors  of  proteases,  plasminogen activators,  or  kallikrein.




Serotonin  has been  found in urine  following ultraviolet exposure but




the significance of this finding is not clear.




     More  recently prostaglandins,  a group  of long-chain  fatty  acids




with  yasoactive  properties,  have been implicated as  possible mediators




of the  delayed  phase  of erythema.  Prostaglandins  are produced  in  human




and  animal  skin  (PGE  and  PGF  groups  of prostaglandins),  intradermal




injection  of prostaglandins  produces erythema  (PGE mainly, PGF  group




are much less active)  and furthermore the production  of  prostaglandins




increases  following UV  exposure.   Indomethacin is  a potent  inhibitor




of the  conversion  of  arachnidonic acid to active prostaglandin,  a  reac-




tion  catalyzed  by the  enzyme  prostaglandin   synthetase.   Topical  indo-




methacin in  both humans  and  guinea  pigs  produces  a profound and  pro-




longed blanching of UVB induced delayed  erythema,  and in  humans  intra-




dermal  indomethacin has  been  shown  to  consistently decrease  erythema




from UVB but not from all sites irradiated with UVC  (wavelength  280nnm);




these  effects  appear  to  be  due to inhibition  of prostaglandin  synthe-




tase.




     It  has  been  suggested  that the complex  reaction known as  "sunburn"




may result  from hydrolytic  enzymes  and  possibly  other substances re-




leased by  lysosomes within  keratinocytes.  Johnson  found  that  irradia-




tion with  wavelengths  shorter  than 320 nm reduced the extractable  acid




phosphatase  in  mouse  ears, but  did  not  deplete histochemically  demon-




strable  succinic dehydrogenase.   He felt  this was evidence  for  lysosomal




labilization  in  the absence  of  nonspecific  leakage due to  cell  death.








                             F-l-36

-------
                                                       Effects—Skin Cancer
     Histochemical  studies  of  human  skin  exposed to  ultraviolet  light




were consistent with  the  theory  that specific damage  to  lysosomal  mem-




branes caused partial to complete rupture and release of  enzymes.




     The  release  of  lysosomal enzymes  may not  only lead to  damage  of




the keratinocytes but  may  also release enzymes,  vasodilator  substances,




or  subsequently  formed cell-breakdown  products  into the  dermis,  where




they may directly or indirectly lead to erythema.  It has been  suggested




that  the  immediate  erythema which  results  from ultraviolet  radiation




results from  disruption of lysosomes of endothelial  cells with  release




of  chemical  mediators.    The  delayed  erythema  could then result  from




secondary diffusion of proteinases from the epidermis secondary to  lyso-




somal  rupture.   It  is also possible  that direct photon  damage to the




lysosomes of  mast cells of  the   dermis  or endothelial  cells  of dermal




blood vessels may play a role in  the delayed erythema of  sunburn.




     Multiple  chromophores may  exist  in  skin,  and  radiation  probably




leads  to  activation of  a  complicated cascade of mediators whose  final




endpoint is erythema.  Multiple pathways may exist.   It is also possible




that photons  have direct  effects on blood  vessels  or  nerves.  Ultra-




violet light causes dilatation of isolated exposed dermal blood vessels.




Dermal proteins may be directly changed by radiation.




   C.2.2  The Skin Carcinogenesis Action Spectrum




     Human  skin  cancer, especially  basal cell  and  squamous  cell  car-




cinoma, are  closely associated  with chronic repeated exposure  of  skin




to solar ultraviolet radiation (cf.  D.2 below).   Three types  of evidence




indicate that the most effective  wavelengths are  shorter  than wavelength




320 nm:   (1)  extensive experiments  in mice show  that wavelengths longer
                              F-l-37

-------
                                                        Effects—Skin Cancer
 than  320 nm are almost  ineffective  for  induction of skin cancer (Blum,




 1959;  Forbes  et al.,  1978; Freeman, 1978);  (2) Wavelengths shorter than




 320  nm  are highly effective  in  inducing photochemical  changes  in DNA




 and killing of  cells  in  tissue culture (Setlow, 1974; Rothman and Setlow




 1979).   Furthermore,  damage to DNA is considered  to be one of the events




 leading  to carcinogenesis  (Smith,  1976), and  a  number of carcinogenic




 chemicals  mimic UVR  damage  to  DNA (Regan  and  Setlow,  1973);  (3) The




 effective  wavelengths for human  skin erythema  production are below 320




 nm.    Also,  individuals  who  sunburn easily  and  have  high  exposure to




 solar  UVR  have a much higher  incidence  of nonmelanoma skin cancer than




 those  who  sunburn  rarely and  have little  exposure to the sun (Vitaliano




 and Urbach, 1980).



     This  last  observation  has  been used  as  a  basis  for assuming  that




the human  skin  erythema action  spectrum and  the skin  carcinogenesis




action spectrum are closely related (CIAP,  1975, vol.  5).




     In  1974, Setlow  suggested that  a  slightly  altered  DNA action spec-




trum  would be  a  better  representative  than the skin erythema action




spectrum for  skin  carcinogenesis.   He  compared  data  obtained  in  bac-




teria, and  later in  cultured  mammalian  cells (Rothman and Setlow, 1979)




to the skin erythema  action  spectrum,  and found that  below 297  nm these




two action  spectra differ by  less than  20% provided the spectra  were




appropriately  normalized (Fig.  4).    Given   present  day conditions of




stratospheric ozone,  the erythema action  spectrum would only  slightly




underestimate the carcinogenic effect if   DNA were  the  target,  since




almost no  radiation shorter  than 297 nm reaches  earth.   The  major  dif-




ference  of  importance  is that  the erythema action spectrum turns down-




ward  in  effectiveness   below  292  nm,  while  the DNA  action  spectrum








                               F-l-38

-------
                                  Effects—Skin Cancer
 I   |i  I   I  I   I   I  I   I	I
i 1-° -


o 10-'.
UJ
QL

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% 10-3-
5.
o
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g io-4-
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g 10-=-
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__1
UJ
" 10-'-

^V O ^^
\ /
°\ / 	 	 SUNLIGHT
V
o /
\l
fc
k.
j \ .
/ \'
\ '•
1 \ \ 	 	 ERYTHEMA
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-10"


-1011 I
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-109 <
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-108 —
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-106
       i  r   iiiiir
260  280   300   320  340  360
        WAVELENGTH (nm)
           Figure 4
       (from Setlow, 1974)
       F-l-39

-------
                                                         Effects—Skin Cancer
continues to rise  steeply  in  effectiveness  to 265 nm.   This  difference




in shape  is  of  considerable  importance  if  stratospheric ozone were  to




decrease -  associated with an  absolute  increase  in  solar UVR  shorter




than 320 nm is  a shift to lower  wavelengths  (Fig.  5).




     That there  is  indeed  justification  for using the DNA  action  spec-




trum  in  some form  is strongly  suggested by  the  experiments  of  Forbes




(1978).   Utilizing a  xenon  arc filtered so  as to represent  the  solar




spectrum  of  thinner  and thinner  layers of  atmospheric ozone,  Forbes




showed  in  mouse carcinogenesis  experiments  that   the addition  of  small




amounts  of  radiation  of  wavelengths shorter  than  300  nm very  signifi-




cantly increased experimental skin  cancer  induction.   These experiments




strongly  suggest  that the DNA  action spectrum indeed is  applicable  to




this problem rather  than  the  erythema action spectrum (Fig. 6).   Never-




theless,  there  is  a  caveat  -  experiments  using  UVR of 254  nm  (Forbes




et al.,  1975)  show very  little  carcinogenic  effectiveness.   Thus,   ab-




sorption by overlying  dead  layers  of skin must have  an  effect.   At  this




time  it  is  not  known just where the  peak effectiveness  of UVR even for




mouse  skin  is  located,  except that it is shorter than 297  nm and longer




than 254 nm.




          C.3.   The Effect of Weighting  of  Solar (Earth) Level




                     UVR with Various Action Spectra




     It  has  been pointed out above  that some reasonable representation




of  the DNA  action  spectrum,  obtained in vitro, appears to be  on theo-




retical  and experimental  grounds  the  most  likely weighting  function




for estimation of the carcinogenic effect of  solar UVR.
                              F-l-40

-------
                                                Effects—Skin Cancer
      100.0
p
35
in
(A
111
       10.0-
        1.0-
        0.1-
       0.01-
      0.001
     0.0001
   0.00001
                _j	I	i	I	I	I
                      ACTION  SPECTRA
                       DNA t ERYTHEMA
                       - Normalized to297nm
                   ERYTHEMA -
                   Normalized to
                   297nm
          /
DNA - Normalized
265 nm
          265  275  285  295  305 315  325  335
                           nm
                        Figure  5  .
           F-l-41

-------
                                                      Effects—Skin  Cancer
                 10
15         20
   Weeks
Figure  6.   Tumor  yield  vs. time (expt.  E).  (From Forbes et al., 1978.)
                          F-l-42

-------
                                                      Effects—Skin Cancer
                280  290
300    310
    x (nm)
320
330   340
Figure 7.   Comparison  of  some measurements  of  the  spectral  efficiency
for erythema and analytic  representations  of  the  data  by  least-squares
fitting.   CS, BUD and CR denote data  by Coblentz and Stair (1934); Ber-
ger et al.  (1968),  and Cripps and Ramsay  (1970), respectively.  (From
Green et  al.,  1974.)
                            F-l-43

-------
                                                          Effects—Skin Cancer
     It  has  been  shown  that  for wavelengths  longer than 297  nm (which




includes  virtually all  present  solar  UVR reaching  human  populations)




there is a great similarity in slope and only 20% difference in quantity




between  these  two action  spectra.   As  a matter  of fact,  if  one  goes




from 30  N  northward,  the DNA weighted  irradiance  decreases  faster  than




the erythema weighted irradiance (see Table 2 below, C.4 ).




     However,  numerical  results of weighting of  calculated  or measured




solar  spectra  indicate  a very considerable sensitivity  to  the specific




choice  of  action  spectrum.   This  has  been elegantly shown by Green et




al.  (1974),    These  authors  compared  calculated  dose  rates  vs.  solar




zenith  angle  for  four   different  erythema action  spectra.   In  Fig.  7




are compared the  action  spectra obtained  by Coblentz and Stair (1934),




Berger et  al.  (1968)  and Cripps and Ramsay  (1970)  respectively.   Table




1  shows  the  results of such a  study.    Dose  rates obtained  with  the




Berger et  al.   (1968) action  spectrum were  approximately 80%  of  those




calculated  from the  Coblentz  and  Stair  (1934)  data.    This  indicates




that  the marked  differences  between  these response  functions  in  the




320 to 297  region  have  very little effect on the erythema dose calcula-




tions.   However,   for the  "long tailed"  Cripps-Ramsay  spectrum and  for




the "sharp"  Green  and Mo (1974)  spectrum,  significant  relative changes




with  latitude  and declination  of  the  sun will arise  (see  also below,




C.4).




  C-. 4 .  Comparison of Effect  of Various Skin Action Spectrum Weighting




               of  Solar UVR  with  "Real"  In-Vivo  Experiments




     In  almost  all  calculations  made for modeling purposes,  either  only




relative  (or  ratio)   increases  of  biologically effective UVR  have  been
                              F-l-44

-------
                                                        Effects—Skin  Cancer
                                 Table 1









                         Erythema Radiation Doses




   Dose rate  vs.  solar zenith angle for different erythema action spectra
Angle
(deg.)
0
10
20
30
40
50
60
70
80
Coblentz & Stair
(1934)*
i
2.56 x 10
2.45 x 10"1
1
2.12 x 10
1.65 x 10"1
1.11 x 10"1
6.11 x 10~2
2.47 x 10~2
6.17 x 10~3
8.90 x 10~4
Berger et al.
(1968)**
0.799
0.799
0.800
0.801
0.802
0.804
0.804
0.802
0.796
Cripps & Ramsay
(1970)**
0.869
0.877
0.902
0.953
1.049
1.233
1.625
2.560
4.787
Green & Mo
(1974)**
0.540
0.538
0.529
0.514
0.491
0.454
0.390
0.258
0.057
*Dose rate in erythemal-effective W/m .




**Dose rate relative to Coblentz-Stair value.




                        (From Green et  al.,  1974)
                               F-l-45

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                                                           Effects—Skin  Cancer
used or  dose-rates have  been  calculated and annual doses based  on  such

calculations have been compared,  without  any  one  having  put  "real"  num-

bers to such models.
         *t        i
     To give examples:

     A.   Using  a  reasonable  calculated irradiance for  noon  summer solar

     UVR  at  30  N latitude  and the  Cripps-Ramsay  action spectrum,  and

     the  data  for minimal  erythema  doses  (MED)   at  their  peak value,

     a minimal erythema  dose  for  untanned human skin should be  obtain-

     able  in  111  seconds,  or less  than  2  minutes.   All  known actual

     observations  show that at  least 10-12  minutes are required  (Nacht-

     wey, personal communication).

     B.   Using  a typical  skin erythema spectrum  in which relative ef-

     fectiveness  is  related  to wavelength by an  analytical  representa-

     tion determined by  a  nonlinear  least square  analysis of five  pub-

     lished erythema action spectra,  and  an MED aft 300  nm  of 206 J/m2,

     the  time necessary  to produce  an MED  at 30°N is 12   minutes, or

     a  time  consistent  with  actual  observation  (Nachtwey  and  Rundel,

     in press).

          Using  the  same MED,  but the doses calculated  for various ac-

     tion spectra  by  Green  et  al.  (1974)  one finds (assuming  a sun angle

     of 20°):

          Coblentz &  Stair                     16.19 minutes

          Berger et  al.                        12.96 minutes

          Cripps and  Ramsay                   14.61 minutes

          Green  and Mo                           8.57 minutes

          Again,  the Berger  et al.  spectrum,  most similar  to  the  one

     used above, gives  reasonable  results.




                          F-l-46

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                                                        Effects—Skin Cancer
     Finally,  Table 2 below  is  instructive  in  terms  of  the actual  ir-

radiances  under  simulated  field  conditions.   (Parenthetic irradiances

are normalized  to 30°N.)

                                 W/M2
Source
Sun 0
Sun 30° N
Sun 40° N
Sun 50° N
Unweighted
Irradiance
270-360 nm
34.5
33.6
31.7
28.6
Erythema
Weighted
Irradiance
386 x 10"3 (1.31)
294 x 10~3 (1.0)
238 x 10~3 (.81)
_3
178 x 10 (.61)
DNA
Weighted
Irradiance
11.14 x 10~3 (1.51)
7.39 x 10"3 (1.0)
5.53 x 10~3 (.75)
3
3.77 x 10 (.51)
DNA + Skin
Transmission
Irradiance
1.84 x 10~3 (1..41)
1.3 x 10~3 (1.0)
1.01 x 10~3 (.78)
0.72 x 10~3 (.55)
                               Table 2.
             (Modified from Nachtwey and Rundel, in press)
                         F-l-47

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                                                         Effects—Skin  Cancer
           D.   The Risk of Increase  in  Nonmelanoma  Skin Cancer




                  Due to Increased Earth-Level Solar UVR




                            D.I.   Conclusions




     From a  few  detailed  epidemiologic  investigations  and  the  data




available from a world  compilation  presented  in  Cancer  Incidence  in Five




Continents some  figures  for  incidence  of  basal cell and squamous cell




carcinoma can be  obtained  which  show a geographic  variation  from annual




skin cancer  incidences as  low as  5/100,000  to  over 200/100,000.  From




these data  it  is also possible  to  estimate  that  the incidence  of skin




cancer approximately doubles  for every 10  degrees  of  latitude, provided




that the population is  of  reasonably similar  genetic  stock.




     Various models have  been proposed,  relating  a decrease in  strato-




spheric ozone to  potential  increases  in  NMSC.   Most of  these  are based




on two steps:   a calculation of  the expected increase of "biologically




effective"  ultraviolet  radiation,   and then  a  number  relating  UVR  to




increase in NMSC.




     Existing models suffer from several major uncertainties which  can




significantly affect the  resultant  estimates:   The choice of the appro-




priate action spectrum  to  determine  the magnitude  of  the  physical ampli-




fication  factor  (0, to UVR);  the  choice of  the configuration and data




source  for estimation  of  dose-response  relationships  leading  to   the




biologic amplification  factor (UVR  to cancer);  the  potential  confounding




effects  of  age,  genetic   background,  occupation,  etc.,  etc.  affecting




actual dose of UVR received by the  skin.




     At this  time,  an overall amplification factor  (0^  to cancer)   of




approximately 4  times  is  predicted  by  the  most  recent  models.  However,
                             F-l-48

-------
                                                         Effects—Skin  Cancer
no separate analyses have as yet  been performed  for  basal  cell carcinoma




and squamous cell carcinoma, which  have  clearly different  relationships




to  UVR.    Additionally,  preliminary two  dimensional  modeling  of ozone




depletion  (models  in  which the  north-south  or  latitude dimension  is




expressed) suggest this  factor may  be substantially reduced due to the




distribution of  ozone  depletion towards  the  poles  and  to the winter




season (Pyle and Derwent, 1980).




     It has  been suggested many  times  that prolonged exposure to  sun-




light can result in  the development  of skin cancer  in  man.   Furthermore,




the person  most  likely  to  develop  skin  cancer  has been  characterized




(mostly by inference)  as  having  a light  complexion, blond or red hair,




and blue  eyes.   He  or  she  supposedly sunburns  and freckles easily and




is often of Celtic ancestry.




     As a  result of  the  early  studies  of  Unna and Dubreuilh and  many




others since the  turn of the  century, a number  of  arguments support the




belief that  sunlight is  a  causal factor  in human  skin cancer.  Among




the main arguments in favor  of  this  assumption are:




     1.  It  is  clearly  established  that skin   cancer  occurs  most   fre-




         quently on  head, neck,  arms and  hands.




     2.  Pigmented races, who sunburn much less readily than do people




         with white   skin, have much  less skin  cancer, and when it  does




         occur,   it  is not  predominantly  found  on  light-exposed areas.




     3.  Among  Caucasians there  appears  to be  a greater prevalence  of




         skin cancer in those who spend more time outdoors  than  in those




         who work predominantly  indoors.




     4.  Skin cancer  is more common  in  white-skinned people living  in




         areas where insolation  is greater.











                            F-l-49

-------
                                                           Effects—Skin Cancer
     5.  Skin cancer  can be produced  readily  on  the  skin of mice  and




         rats with  repeated doses of  ultraviolet  radiation;  the  upper




         wavelength  limit  of  cancer-producing  radiation  is  about  320




         nm,   i.e.,  the  same  spectral  range  that  produces sunburn  in




         human skin.




     Although statements asserting one  or  more  of  the  above assumptions




have  been  frequently published,  adequate  epidemiologic information  to




substantiate  them has been  found  difficult to obtain.   The main  reasons




for this difficulty  are  due to the fact that cancer of the skin  is  ex-




tremely  common  in whites  (amounting  to 1/3 to 1/2 of  all cancers  of




all sites in  the United States) and that it is rarely fatal.




     Unlike cancer  of most  other  sites, most skin  cancers  are diagnosed




and treated in physicians'  offices and the  apparent diagnostic advantage




of accessibility of the lesions can be nullified by the need for  compre-




hensive coverage of many sources of reports outside hospitals that  main-




tain different practices for the  recording of  data.   Records in  physi-




cians' offices  often may  indicate  little  more  than the patient's name




and omit  such items as  age  and residence  that  are helpful for  identi-




fication of  individuals in  order to  eliminate  duplicate  case  reports




and are  necessary  for  the  calculation  of rates  specific  for  age  and




other   demographic  factors.    Also,  many  specimens  escape microscopic




examination  and,  what  is  worse,  the percentage  not  so examined will




vary  among communities  and  with  such host characteristics as  age  and




site of  the  lesion.   Skin  cancers are usually not  lethal,  and mortality




data can not  be  relied  on  to yield information  on  differentials  in risk




by  age,  sex,  race   and  other   characteristics   with  the same  precision




as for other  sites with less favorable prognoses.









                            F-l-50

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                                                          Effects—Skin Cancer
     Despite these  difficulties,  certain facts  about  skin cancer  seem




to be established beyond dispute.   These include  the  low  risk  in  heavily




pigmented  peoples,  the  continued rise  in  incidence  rates  throughout




the life span,  and  the  higher rates  among people  living  in subtropical




and tropical latitudes.




           D.2.   The Natural History of Nonmelanoma Skin Cancer




     There  has  been a  recent  reawakening of  interest  in  the field  of




photobiology.   This has been  largely due to  rapid advances  in  photo-




chemistry,  particularly due to  a  much better understanding of photobio-




logic phenomena  occurring  at  the  molecular level, and a  recent  concern




about potential  alteration  of  the ozone layer.   Furthermore,  the  great




improvement in design, versatility and intensity  of modern light  sources




and the development of accurate measuring devices capable of determining




intensity  of very  narrow  bands  of light even  in the ultraviolet region




of the electromagnetic spectrum have  made more elegant  studies possible.




     That  sunlight can  cause  demonstrable  acute  and  chronic  changes




in  apparently  normal  skin certainly  has been  known since  antiquity.




"...I am dark, because the sun has scorched me."  (Song     of   Solomon).




Charcot  (1859)  determined that ultraviolet radiation caused  acute  ery-




thema  and  Unna  proved  that pigmentation can  be  induced  by ultraviolet




radiation.   It  soon became  apparent  that the  capability of the  skin




to react  to light  by pigmenting was  most variable, and  that this varia-




bility  pertained not only  to different races but also  to individuals




of apparently similar ancestry.




     Unna  (1894) noted severe degenerative skin changes  on exposed areas




of  the  skin  of sailors  and  associated  these with the  development  of




skin cancer which  was seen with  great  regularity in his clinic  in Ham-




burg,  an  old Hanseatic  seaport  town.   Dubreuilh (1896,  1912), studying






                            F-l-51

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                                                         Effects—Skin Cancer
skin  diseases  in  the  Bordeaux region of France, noted  the  frequent  oc-




currence  of  keratoses and  skin  cancer in  vineyard  workers, while  the




nearby city  dwellers  showed few  such lesions.  These observations were




soon  confirmed by  Shield  (1899),  Hyde (1906), and  others, who  noted




a high  incidence  of skin cancer  in  rural areas of  the  U.S.  and  Austra-




lia,  where  light  exposure was much more intense than  in central  Europe.




It  is interesting  (and  almost  prophetic)  that Bruusgaard in 1922 con-




sidered the  sailors'  skin cancer as being due  to a combination  of sun-




light  and coal  tar  (to  which  sailors  were  heavily  exposed in  those




days).




     Following  the  clinical  observation  of  a relationship  of  chronic




sunlight  exposure to  skin cancer,  there was much discussion  among der-




matologists  as  to whether this  association  applied  to all white-skinned




people or,  as Haxthausen  (1929)  had proposed, really  occurred  only  in




those  carrying a  fo rme   fruste  trait of xeroderma  pigmentosum.  This




view  began  to  change  when Findlay in 1928  showed that daily  irradiation




of mice with ultraviolet  radiation from a mercury arc caused the induc-




tion  of skin cancers.   Incidentally, Findlay  also noted that when mice




were  tarred  prior  to  ultraviolet radiation exposure,  the period neces-




sary  for  the induction  of skin cancer was  reduced.  In  1933  he was able




to produce  skin cancer  in rats with ultraviolet light,  and his findings




were  soon reproduced  by  Putschar  and Holtz.   In a  series  of  studies




between 1930 and  1936,  Roffo showed that  skin cancer  could  be  induced




in rats with natural  sunlight  as well as  with mercury arc  radiation,




and carried out the first real epidemiologic study of human skin  cancer.




As had  Dubreuilh,  he pointed out  that  the  same skin areas most  likely




to develop  skin cancer  also  showed a great tendency to develop hyper-




keratoses,  and  considered  these   keratoses   as  premalignant lesions.





                            F-l-52

-------
                                                          Effects—Skin Cancer
Finally, Roffo  carried out  the  first  action  spectrum  studies of  skin




photocarcinogenesis:    he  showed  that  clear window glass was  sufficient




to  stop skin  cancer  production  by both  natural  sunlight and mercury




arc radiation,  thus  setting an  approximate  limit  for the effective  UV




radiation of shorter  than 320 nm.




     Classical evidence in support of  the role  of  sunlight, particularly




of ultraviolet  radiation,  as  a  causal  factor in human skin cancer  com-




prises  a  number of  factors.  • Most of  these factors may  be  summarized




by six associations of skin cancer:




     1.  Association with  exposed areas  of the skin.  Among Caucasians,




     skin cancers  occur  most frequently  on  parts  of the body most  ex-




     posed  to  sunlight -  the head, neck,  arms and hands,  and the   up-




     per back.




     2.   Association  with  protection  against  ultraviolet   radiation.




     Among races with  dark skin,  in which pigment  filters  UV  radiation,




     there  is  very  little skin  cancer  and  the disease  does not  pre-




     dominantly occur  in  areas of the  skin exposed to the  sun.  Sunburn




     and skin cancer  arise in the  same  tissue,  and  UV radiation is known




     to cause sunburn.   It appears  that  those who  are more susceptible




     to skin  cancer  sunburn more  easily.   Caucasians of  Celtic origin




     are more  susceptible  to  both skin cancer and  sunburn; those  of




     Latin origin,  less.




     3.   Association with  the  amount  of  exposure to the sun.   Among




     Caucasians there  appears to  be a  greater  prevalence of skin cancer




     among those who  spend more  time outdoors.




     4.   Association with  intensity  of  solar  insolation.   As one  ap-




     proaches the  equator, measures of  incidence  of skin cancer among











                           F-l-53

-------
                                                           Effects—Skin  Cancer
      white-skinned people increase, as do the amount of solar radiation




      and intensity of  UV  radiation.




      5.    Association  of  ultraviolet  radiation  in  laboratory studies.




      Skin  cancer  can  be  produced in  mice  with  repeated doses  of  UV




      radiation  in  the  same spectral range that produces sunburn in human




      skin.





      6.    Association  with  insufficient  ability  to repair DNA  damaged




      by  ultraviolet radiation.    Those  with the  recessively  inherited




      disease  xeroderma pigmentosum, who  consequently  have a  defect  in




      the  repair of  DNA  damaged by UV radiation,  have  a  predisposition




      to  the  development  of skin cancer.   Such victims  are often photo-




      sensitive,  and  their tumors  appear  to be induced  by  sun  exposure.




      They  usually  die  as  a result  of  skin malignancies before reaching




      adult life.





   D.2.1  Anatomic Distribution of Basal  Cell and  Squamous  Cell Cancer




     Numerous studies  have shown  that  skin cancers arise  (in  those sus-




ceptible,  i.e., white skinned people)  primarily  on  sunlight  exposed




sites.   From these  studies  it is  demonstrable  that  about  90% of  all




basal  cell carcinomas  (BCC) and  more  than half  of  all   squamous  cell




carcinomas  (SCC) occur on  the head and  neck.    The  majority of  those




squamous cell  cancers  not occurring on  the  head  and neck are found  on




hands  and  forearms,  and  the  ears of  females are markedly  protected




(Table 3).




     Comparing  the  sites  of. non-melanoma  cancers  with studies made  of




the geometry of  insolation of  the head and neck areas,  it  becomes  clear




that  2/3 of all  basal  cell carcinomas  occur  on the  skin sites  receiving
                             F-l-54

-------
                                                                    Effects—Skin Cancer
                                            Table 3
                        Anatomical Distribution of Keratoses, Basal Cell

                            Carcinomas  and  Squamous Cell Carcinomas

Anatomical Site




Forearm and Wrist
Hands and Fingers
Side of Face
Ears
Scalp, Temple,
Forehead
Nose
Neck
Lower Limb
Upper Arm and Shoulder
Trunk & Elsewhere
Circumocular Region
Lower Lip, Chin
Upper Lip
Keratoses



Males
7,
47.7
19.0
7.3
6.4

5.0
4.9
2.8
2.6
1.6
1.1
0.9
0.5
0.2
Females
7o
39.3
22.7
11.5
0.5

8.4
8.7
1.1
2.6
0.8
1.0
1.8
0.9
0.7
Squamous Cell
• Carcinomas


Males
7o
22.9
15.3
13.7
8.8

5.5
7.2
8.0
5.0
1.5
3.1
3.3
4.1
1.6
Females
7.
15.8
19.5
17.4
1.6

12.5
12.5
4.9
3.3
0.5
2.2
4.3
3.3
2.2
Basal Cell
Carcinomas


Males
%
5.2
1.0
28.9
4.7

12.5
16.7
9.1
0.7
1.9
4.0
11.5
2.2
1.5
Females
7o
2.7
1.8
24.0
1.7

16.2
27.4
4.4
0.5
1.6
2.1
9.8
4.6
3.2
Ratio of Basal
Cell Carcinomas
to Squamous Cell
Carcinomas
Males

0.9
0.3
7.9
2.0

8.5
8.8
•4.3
0.5
5.0
4.9
13.3
2.0
3.5
Females

1.0
0.5
8.0
6.0

7.6
12.7
5.2
0.8
1 7 . 0*
5.5
13.9
8.1
8.5
1
 Sources:  Keratosis data from three regional  surveys,  cancers from Queensland Radium Institute
          records
 Only one  squamous cell carcinoma was found at this  site.

                               (From Silverstone & Searle,  1970)
                                       F-l-55

-------
                                                        Effects—Skin Cancer
the highest UVR doses, and that virtually all  squamous  cell  carcinomas




occur at  these  sites  (Tables 3 and 4).




                                Table 4

Area
BCC
Head & Neck
(unshaded)
Head & Neck
(shaded)
sec
Head & Neck
(unshaded)
Head & Neck
( shaded)
Skin & Cancer Hospital
(Urbach 1972)
Male %
63.3
36.7
100.0
0
Female %
63.0
37.0
88.0
12.0
Total
63.2
36.8
94.0
6.0
Radiumhemmett
(Magnusson, 1935)
Male %
57.1
42.9
84.2
15.8
Female %
67.3
32.7
90.0
10.0
Total
1
62.2
1
37.8
86.5
13.5
  Comparison of  distribution of BCC  and  SCC over protected and  unpro-




  tected areas of  head  and neck.   (The  6 and 13%  incidence  in  shaded




  areas  at   Skin   and   Cancer  and  Radiumhemmett  represents  1  and 3




  patients  respectively.)
                            F-l-56

-------
                                                          Effects—Skin
     D.2.2 Age  and  Duration  of  Exposure  and  Non-Melanoma Skin  Cancer

     Age  specific  incidence  races  have been obtained in  several  recent

skin cancer  surveys.    In Figs. 8&9 are  given such  data  for the  results

of  the  Third National  Cancer  Survey,  carried  out in four  locations  of

the U.S.,  and  in Table 5 the  data  collected by Gordon  et  al. from  the

literature for  widely  geographically  separated areas.  All figures  are

for white  skinned Caucasians  only.   In   Figure 10 A & B  ,  the  graphs

are recorded  on a  log-log  scale (log  incidence  against  log age).   If

the graphs  for  the various  countries were parallel,  this would mean

that their relative incidence  rates were  independent  of age.  The graph

for Queensland  has  a  distinctly  more  shallow slope,  indicating  a rela-

tively greater spread  of skin cancer into  the younger  age  groups.

     The  most   recent   age  specific incidence  rates  have  recently been

published  for   1977-78  and  eight  areas  in  the U.S.  by  Scotto   et  al.

(1980).   These are given in  Table 5 following.

     From the  factors  listed  in  the  introduction  to this section  and

studies   utilizing  Robertson  type UVR meters in Australia,  Philadelphia

and Galway,  it   is  possible  to arrive  at some very  crude  estimates  of

the amount of UVR  required  for susceptible individuals to  develop skin

cancer.    Clearly such an estimate  has  to be,  at this  time,  considered

to  be  extremely  crude and  very preliminary.    Robertson  estimates  as

follows:
Individual
Child (Goroka)
Outdoor
(North Queensland)
Outdoor (Victoria)
Outdoor (Galway)
| Fraction
I in Sun
I 3/5
1
1 2/5
1
1 1/2
I 3/5
Duration
(years)
6
20
30
50
S.U.
(per year)
4000
2600
1600
1000
Total
S.U.
24,000
52,000
48,000
50,000
    S.U. - "Sunburn" unit is equivalent to 12-15 minutes of noon
    equatorial clear day solar UVR.
                               F-l-57

-------
                                                        Effects—Skin Cancer
   0-
   o
   a.

   o
   o
   o
    •
   o
   o
   oc.
   UJ
   a.

   VS
3200




2600




2400




2000




1600




1200



800




400




0
                                                        OflLLRS
                 IS-   25-  35-   45-  55-
                  24    34   44    54   64

                               flG€   CROUP
                                    65-  75-
                                     74   84
85 *
Figure 8.   Age-specific  incidence  rates of nonmelanoma skin cancer among

Caucasian  males.   (From  Scotto  et  al., 1974.)
                        F-l-58

-------
                                                         Effects—Skin  Cancer
  ae.
  
  CL
  O
  0.

  O
  O
  O
   •
  O
  O
  oc
  UJ
  d.

  (O
  *-

  UJ
  UJ
  h-
  a
  QC
3200


2800


2400


2000


1600


1200


800


400


0
    OflLLflS
    niNN
   -SflN FRflN
, - JOWfl
                15-
                 24
                25-  35-   45-  55-    65-   75-
                 34   44    54   64     74    84
                        nee   GROUP
                                                        85*
Figure 9.   Age-specific  incidence rates of nonmelanoma  skin  cancer among
Caucasian  females.   (From Scotto et al., 1974.)
                            F-l-59

-------
                                          'inofe  j

                        Nonmelanoma Skin Cancer in the United States — NCI Incidence Surveys
TABLE 7, ANNUM. ACS-SPECIFIC, CRUDE, AGE-ADJUSTED (1970 0 S STANDARD)  CKIK CANCER INCIDENCE KATES
          PEB  100,000 POPULATION BY GEOGRAPHIC AREA,  1977 - 1970, ALL ANATOMICAL SITES - HHITE, DOTH SZXE3


                                                            SAH

OY-3 RADIATION INDEX" .
DEGREES N LATITUDE
<15
15-21
25-31
' 35-11
1
V 55-61 •
o 65-71
75-01
05 +
CRUDE RATE
ACE-ADJUSTED RATE
STANDARD ERROR X 1.96
SEATTLE
{MUG CO) .
101
'47.5
0.1
1.6
36.0
121.7
303,5
516.1
712.6
1125.7
1100.0
200.6
100.7
0.0
KINN-
ST PAUL
106
11.9
0.7
5.9
21.1
95.7
2 96.. 5
190.1
806.3 .
1200.9
1559.7
105.2
193.3
6.6
DETROIT
(SMSA)
110
12.2
0.3
3.5
1fi.7
ns.7
206.9
361.1
503.5
005.7
036.0
138.0 '
135.6
. 1.0
UTAH mucisco-
(STATE) OAKLAND
(SHSA)
•10. 7 t
0.8
8.5
56.2
213.2
517.9
881.9
1U12.2
1962.1
2323.1
271.5
337.6
11.3
151
37.8
1.3
5.7
30.1
133.1
311.0
61U.6 • -
871.6
1009.7
993.6
212.1
213.0
5.3
• ATLANTA
(SHSA)
33.7
***
8.1
70.0
219.9
639.2
1120.5
1676.0
2062.2
2027.7
330. U
393.0
12.3
NEV
ORLEANS
(HETRC)*
17C
30.0
1.3
5.5
. 60.5
212.0
629.9
1089.8
1505.3
2165.2
2350.2
399.1
301.2
11.3
NEV
MEXICO
(STATE)
197 t
35. It
1.1
1.S
38,5
107.9
515.7
917.3
1150.0
2071.9
2079.3
295.6
336.7
11.7
ALL
SURVIJ
AREAS
(101-197)
(17.5-30.0)
0.7
5.6
37.1
113.1
361.9
638.8 .
977.2
1305.2
• 1357.0
229.1
231.3
2. .6
  •INCLUDES THBEE PARISHES:  JEPFEItSON,  ORLEANS,  AND ST BERNARD

 ••INDEX «  ESTIMATED OV-D  COUHTS  PER  10,000 PER  ANHDH

  tUYD COUNTS AHD LATITUDES  ARE FOR  ALBUQUERQUE,  NEW HEXICO  AND  SALT LAKE CITI,  UTAH  RESPECTIVELT
 W
 Hi
 Hi
 fl>
 O
 rt
 en
 I
 I
 tn
                                          (From Scolito  cl. ;i I . ,
n
m

5
D

-------
                                                    Effects—Skin Cancer
INCIDENCE
   PER
 MILLION
 10,000
  5,000
                                                      0-31%
                           (1) Queensland Coastal  Regions
                           (2) El Paso/Texas (Non-Latins)
                           (3) Cape Province, S.A.  (Whites)
                           (4) South-west England.
                    30
    40      50
AGE IN YEARS
60
70  80
                          Figure  10A
            (From Gordon and  Silverstone,  1976)
                        F-l-61

-------
                                                        Effects—Skin Cancer
INCIDENCE
   PER
 MILLION
 10.000
 5,000
  1000

   500
   100

    50
    10

     5
     1 *
     20
           (1) Queensland Coastal Regions
           (2) El Poso,Texas (Non-Latins)
           (3) Cape Province, S.A. (Whites)
           (A) South-west  England
30       40      50
     AGE IN YEARS
60
70  80
                           Figure 10B
              (From Gordon and Si 1verstone,  1976)
                      F-l-62

-------
                                                         Effects—Skin  Cancer
     D.2.3  Race and Ethnic Extraction




     It has  long  since  been known that whites have  a  much higher inci-




dence  of  skin cancer than pigmented races (Urbach, 1963).   The  higher




incidence  observed  in sun  exposed  areas  of skin of whites  and  albinos




is  attributable  to  the  chronic  effects of  UVR.    Basal  cell carcinoma




in  particular  is  very  rare  in pigmented  races  (Higginson  and  Oettle,




1960; Urbach, 1963).




     In contrast to  the  anatomic  distribution of  squamous  cell carcinoma




in  whites  (70% on  head and neck),  Isaacson (1978) found only  1/3  of




squamous cell  carcinomas  in urban blacks  in  South  Africa to be  on  the




head and  neck.    Furthermore,  the male-female ratio was  60/40,  as  com-




pared  to  85/15  in  whites.    Basal  cell  carcinoma was  almost  absent.




Furthermore, the  age  of onset was  much earlier  in  blacks  than  whites,




50% of squamous cell carcinomas occurring before  age 50!




     In several  carefully  controlled studies, comparing  white  patients




with non-melanoma skin  cancer  to  age-sex matched controls from the  same




populations, it has been shown that  patients with skin cancer have  much




greater frequency of  certain genetically transmitted  traits  than those




without skin cancer  (Urbach et  al.,  1972;  Gellin  et  al.,  1966).




     Skin cancer patients,  as a group, had  greater  frequencies  of light




eyes, complexion  and  hair  color  than did the controls.   They also  sun-




burned more  frequently   and  tanned  less easily  than did  the  controls,




though the degree of tan achieved  was only marginally less.  Male  cancer




patients had  experienced greater cumulative  outdoor exposure than  had




male controls.   The  proportion  of   Irish  and English  (including  Scots




and Welsh)  ancestry was greater  in  cancer  patients,  while  the  Slavic




and "other" categories of national origin were smaller.











                            F-l-63

-------
                                                          Effects—Skin  Cancer
     Patients with  basal  cell  and squamous cell carcinoma differed with


respect  to  age and  sex  distribution.   In the case of basal  cell  car-


cinoma,  the  two sexes were  almost equally  represented;  almost 15%  of


the  patients  were  less than 50  years of age, and nearly 65%  were  less


than 70  years  old.   In the  squamous  cell  carcinoma  group,  on  the  other


hand,  males  outnumbered  females  by more than 6 to 1, and  all patients


were at  least  50  years  of  age,  with more than 70% of them being  over


70  years of age.   Light  (blue  or green) eye  color was  also somewhat


more frequent  in the  squamous  cell  carcinoma  group,  but  in  the  other


coloring  characteristics,  complexion  and  hair,  the  two cancer groups


were not significantly different.   The two  groups were  also  indistin-


guishable with  respect  to  tanning  and sunburning characteristics  and


national  origins.    They  differed significantly  with  respect   to  total


outdoor exposure, with a  much larger fraction of the  squamous cell  group


appearing in the maximum  exposure category (Vitaliano and  Urbach, 1980).


     These  studies  and the  clinical  impressions of many  astute physi-


cians  show  a  distinct  association of skin cancer with  light color  eyes,


fair complexion,  light hair color,  poor  ability  to  tan,  ease of  sun-


burning and a history of  repeated severe sunburn.  Furthermore, whenever


looked  for,  there  is an  increase  in  Celtic  stock  among skin cancer


patients.


     But  this  clearly is  not  the whole  story.   There are many people
         o

with origins  other  than  Celtic  who match  these characteristics,  and


it  is  apparent that  the  Celts  inherit,  but are by  no  means  the  sole


possessors of,  a sun-sensitive,  poorly  adapting skin.   Yet  it is  clear


that genetic  factors  are of  great  importance.   In  the three careful
                             F-l-64

-------
                                                          Effects—Skin Cancer
prevalence studies of Silverstone (1960), Macdonald and Bubendorf (1964)


and  O'Beirn  et  al.   (1968),  the prevalence of  skin cancer  rises  with


advancing age  at  about  the same rate  in  Queensland  and in Galway,  dif-


fering primarily  by  age  of first lesion.   In  El Paso the lesions begin


early, but  the slope  of the prevalence  curve  is much less.   This  is


probably the result  of  genetic  differences since the population studied


in Queensland and Ireland is mainly Celtic, while the El Paso population


has few Celts and probably much Mexican admixture (Urbach et al., 1972).


     D. 2.4  Geographic distribution


     Incidence  data   for  skin  cancer,  other   than   melanoma,  must  be


treated  with  considerable reserve.    Many cancer   registries  do  not


register non-melanoma  skin cancer  at  all, and  those that  do  are  uni-


formly incomplete,  since most  of  these tumors  are  treated  in  doctors'


offices  and  either not  at  all  reported or reported  without histologic


verification.


     The best  overview  of geographic  distribution   has  been given  by


Gordon and Silverstone  (1976) and  is shown in Tables  6 and 7.   The re-


sults  are  shown  in  the  form of a  cross  classification of  skin cancer


rate against latitudinal  "zone."   The tabulation is  based  on data  for-


mulas, but in  each cell  of the  table  a  figure is given for the average


ratio  of  female  to  male rates   for  the  countries listed  in that  cell.


     Some indication  of the correlation between latitude and skin cancer
                                                                4

incidence is  obtained by  observing  the "diagonal" pattern  made  by the


group  of ethnically  similar  peoples  starting  with Sweden at  "top  left"


and running  down  to Queensland  at  "bottom right."   On  the  other  hand,


the more  pigmented groups  tend  to  be  concentrated  at  the  "top right"


of the tables.






                            F-l-65

-------
                                                              Effects—Skin  Cancer
Average Incidence
of Skin Cancer per
100.000
(both sexes)
0.0-4. '.1





5.0- m.ii



20.0- 24. !l


30.0-4'.). VI


A B






Sweden** Poland
Rumania
Denmark
F/M = 0.48 F/M = 0.84*
Finland United Kingdom
German Dem. Rep.
F M = 0.88 F, M = 0.725
Canada

F. M =.0.r>7
Zone6
C
Japan




F/M = 0.80
Yugoslavia


F'M = O.Sli
New York Stale**

F. M = o.iili
Ne\ ad.i

F'M = (l.(>4
D
S.A. Cape Bantus
S. A. Cape Colored
Natal Africans
Natal Indians
Bulawavo Africans
F/M= i.27
Texas (Latin)


F/M= 1.01






E
Bomha\
Nigeria



F/M = 1.4>l
Jamaica


F/M = 0.94



Colombia
Puerto Rito
F/M = O.H5
    50.0-W.9
    100 and mcr
                                           Victoria (Australia)
                                           Tasmania (Australia)
                                           F M = 0.4!l
                                                          S. A. Cape (whites)
                                                          Texas lnon-l.alin)<
                                                          Queensland (whiies)J
                                                          F;M = O..V.I
"Zonal latitudes are: A. ah
'''Zoning based on male ra
^Poland = (1.84: Rumania
ttExcludiriK New York Cit
§L'.K. = 0.38; G.D.R. = <>.-
UMales. 133.0: females. 72
T.Males. 168.2: lemales. 10
JMales. 265.1; females. 15
ve till": B. 4ric-till=: C. H;>°-4.ri°: 1). u'll'-:!.')°; E. II*- 20°.
es onh.
I.Oil: Denmaik = O.S'.I.
1; HungaiA = 0. 88.
1.
8.
Table  6.   Global  distribution of  skin cancer  incidence  other than mela-
noma;  male  data  with  corresponding  female  to  male  ratios  (F/M)  (From
Gordon  and Silverstone,  1976.)
                                F-l-66

-------
                                                                     Effects—Skin  Cancer
Average Incidence
of Melanoma per
100,000
(both sexes)
0.0-O.tl
1.0-1.9
2.0-2.9
3.0-3. SI
4.0-4.9
5.0 and over
A B
Rumania (Banal)
F/M = 0.5(1
United Kingdom
Poland
Hungan
F/M= 1.51
Finland Canada
Denmark
German Dem. Rep.
F/M = 0.83 F/M = 1.3'.'
Norwav
Sweden
F/M= IJ2


Zone*
C
Japan
F/M = 0.83
Yugoslavia
F/M = 1.47
New Zealand Maoris
New York Staiet
F/Mtt
Nevada
Connecticut
Victoria (Australia)
F/M = 1.28

New Ze.iland§
(Europeans)
F/M = 1.47
D
S.A. Cape Colored
Natal Indians
Bulawayo Africans
California Negroes
Hawaiian
F/M= 1.92
S. A. Cape Bantu
Natal Africans
Texas Latins**
F/M = 2.84
Israel (Native
News)
F/M = 1.55
Texas (non-Latin)
California (whites)
S.A. Cape (whites)
F/M= 1.30
Hawaii (Caucasian)
F/M = 0.78
Queensland (whites)||
F/M- 1.22
E
Bombay
Puerto Rico
F/M" 1.81
Jamaica
Nigeria
F/M= 1.24
Colombia
F/M = 0.45



   •Zonal latitudes are: A. above 60°; B. 45°-60°; C. 35°-45°; D. 20°-35°; E. ()°-20°.
   "S.A. Cape Bantus = 4.71; Natal Africans = 3.00; Texas Latins = 0.80.
   tExtluding New York City.
   ttN.Z. Maoris = 4.38; N.Y. State = 1.13.
   SMales. 6.2; females. 9.1.
   [[Queensland is half in zone D and half in zone E: male;.. 14.3; females, 17.4.
Table  7.     Global  distribution   of  melanoma  incidence;  male  data  with
corresponding  female to  male  ratios  (F/M)  (From Gordon  and  Silverstone,
1976.)
                                     F-l-67

-------
                                                         Effects—Skin Cancer
     U.S.A.




     The  main sources  for incidence  data  of skin  cancer  in the  U.S.




came from  the National  Cancer Survey performed in eight cities in 1947,




a  survey in  Iowa  performed  in  1950 and in  New York  state  (excluding




New  York city) in i960.   The  most  extensive  data is that of  the Texas




Tumor  Registry,  obtained by  McDonald,  and covering  the  years 1944  to




1966,  and  the most  recent  survey  is that of the  Third National  Cancer




Survey,  performed  in 1974, and  a  special  survey of the U.S.  National




Cancer Institute performed in  1977-78.




     All  these data  show a  marked increase  in  the incidence of  skin




cancer in the past three decades   and a pronounced north-south gradient.




Table  8 shows data  obtained  by  -Hocnszel in the years  1947-60.   Tables




9 and 10 show the  data of McDonald  for  six  regions in Texas  (1964),  and




Table H shows the data  of  the Third National Cancer Survey  (Scotto  et




al., 1974).   Table  12 shows that in the U.S., skin cancers make  up from




40  to  116%  of  all other  cancers of all  sites  in  Caucasians  (Scotto




et al., 1974).




     Thus it  appears  that  in  Iowa,   for instance,  the  incidence  of skin




cancers  in males  rose from 61.4/100,000 in 1950 to 174/100,000 in 1972.




This roughly  threefold  increase is  also noticeable  in all  areas  in




Texas,  with  the exception  of  El  Paso, where the incidence  rate actually




decreased, and Houston,  where the  increase apparently  represented  only




a  doubling.    The Texas  data show  that  incidence rates  increase  with




descending latitude,  but  not  in  a stepwise  fashion.   In the  most  recent




five-year period  (1962-1966)  the rate for El  Paso was 183/100,000,  that




for  San  Antonio  (1   further  south) 147.35/100,000.   In San  Antonio,
                            F-l-68

-------
                                                         Table  8
  Age-adjusted"-'-  skin cancer incidence per 100,000 population by sex for selected characteristics:   8 U.S.  cities"""'' (1947),

                           Iowa (1930),  and  New  York  state,  exclusive  of  New York  city (1958-60)
Characteristics
All skin cancers***
Region
North
South
Residence
Urban
Rural
Site
Face, head and neck
Upper extremities
Trunk
Lower extremities
Histologic type
Melanoma
Basal and basosquamous
eel 1 carcinoma
Squamous cell
carcinoma
Male
8 Cities**
48.2

33.4
143.3

48.2


39.4
3.7
2.8
1.4

1.7

21.8

12.1
Iowa
61.4




72.1
52.1

48.6
5.3
}3.4
•J

Not
com-
puted


New York
41.3




45.6
42. 3 +

30.3
3.1
3.0
1.0

2.3

26.8

7.2
Female
8 Cities"""'f Iowa
34.9

25.4
88.0

34.9


28.2
1.8
2.9
1.5

2.2

16.7

6.7
35.3




45.4
24.9

27.4
2.1
13 7
_}

Not
com-
puted


New York
27.6




31.1
25. 8+

20.5
1.4
2.3
1.4

2.6

19.4

2.9
Ratio: Male/female
8 Cities-'--"
1.38

1.31
1.63

1.38


1.40
2.1
0.97
0.93

0.77

1.31

1.81
Iowa
1.74




1.59
2.1

1.77
2.5
?0.92
(w • ^
"'






New York
1.50




1.47
1.64

1.48
2.2
1.30
0.71

0.80

1.38

2.5
(Ti
  *Age-adjusted to total population of continental United States, 1950.

  —Whites only

  ***Includes newly diagnosed cases of all types and sites, with or without microscopic confirmation.

  +Residents of rural areas of nonmetropolitan counties in New York State


  Sources:  8 cities - unpublished tabulations from 10-city cancer morbidity surveys.  Iowa -  supplemented by unpub-

  lished tabulations.  New York - unpublished tabulations furnished by Bureau of Cancer Control,  New York State

  Department of Health.


                                                  (from Haenszel, 1963)
M
H,
Ml
fl>
O
rt
(A

I
en
O
                                                                                                                             O
                                                                                                                             n>
                                                                                                                             H

-------
                                                    Effects—Skin Cancer
                        Table  9

AVEKACE ANNUAL ACE-AUJUSTF.D IXClDKXCt KATES
                    PEU 100.000'
               SIX REGIONS  IN TEXAS
                      1944-1955
MAl.CS
\V>UTE NONVVIIITt M'AMMl >UKNAM_t.l>
KUMDEH HATE NOV.SKK K-\T£ NUMHKIt RAT*.
Replon A}
(El Paso)
1944-48
19-19-53
19S-1-5S
1959-63
1944-60
• 1949-65
1952-65
Region D
(San Antonio)
1944-45
1949-53
1954-58
1959-63
1944-65
1949-66
1962-65
Region El
(Laredo)
1944 -4S
! 1949-53
I. ' 1954-58
. 1959 -G3
1944-6G
1949-G5
1952-66
Region F}
(Harlingen)
, 1944-48
1 1949-53
. 1954 -5S
1959-63
,. 1944-6G .
1949-65
1952-65
Region G
•(Corpus Cliristi)
1944-48
1949-53
19.54-58
1959-53
•1944-65
1949-55
1952-G6
Region It
(Houston)
1944-48
1949-53
1954-5S
1959-63
'. 1944-66
1949-65
1952-66
326 215.G
493 ' 254.3
494 19S.S
566 201.3
2207 205.8
15S1 203.5
579 183.0

SIS 5S.-2
765 71.2
872 70.9
1807 131.3
539S 97.8
48SO • 106.3
2137 147.4
•

16 ' 34.4 '
39 63.5
69 93.5
1GO 214.2
412 - 135.4
396 154.8
209 25G.G
•

31 16.1
224 93.5
729 274.8
796 277.9
2251 193.8
2230 '229.6
&41 284.6 .
•
276 105.5
615 180.0
11G3 • 273.4
1577 323.9
4900 264.5
4624 293.1
1916 371.0
. *
ftf~A 4rt 1
**6* 4U-i
503 52.2
896 73.3
1354 . 84.6
4032 71.5
3S1S 7G.9
1G5G 92.7
• 29
30
31
41
159
130
45

1 £ 26
5 4.7 35
-•> 20 51
5 3.8 67
14 2.7 247
13 3.1 221
3 2.4 91

3'
12
15
50
117
H'
^
R7
0 1

5
19
M&
86
' '95
2S2
277
' • . - 125
. *
0 0 18
2 5.6 ' 36
5 17.2 46
6 17.6 59
17 11.5 195
17 13.7 ISO
7 13.9 63

B 38 1
° ~
. 12 4.3 . 3
14 4.4 4
15 ^ is
59 4.0 29
51 4.0 25
14 2.7 »
30.7
22~6
26.0
25.6
2-1.7
24.5

6.9
10.4
12.S
13.1
13.1
14.4
' 1S.3

3.6
9.4
12.3
32.9
19.3
22.8
430
"»fc^.\^

2J3
98
36.9
34.4
26.2
31.2
42.8

18.1
29.7
30.3
36.2
30.2
32.7
34.2

1.S
4.8
6.7
14.7
9.9
11.1
20.5
1970 Standard population.
    figured for Spanish surname* and non
       oxists" ofKces not iiicluUed.
                                        sotiwme
                                        >uriu
                                              
-------
                      Effects—Skin Cancer
Table 10
GANGER OF THE SKIN EXCLUDING MELANOMA
AVERAGE ANNUAL AGE-ADJUSTED INCIDENCE KAILS

.

PEK 100.000*
SIX REGIONS IN TEXAS
1944- 19 5S






FFV.\:.F:S 	 -

WHITE . NON-.-'illTE
SI'AMSM >CI
NUMD'EK RATE NUMBES RATE NUMi-.iiK
Region A}
(El Paso)
1944-48
. 1949 -53
1954-55
1959-63 '
1944-65
1949-66
' 1952-65
Region D
(San Antonio)
1944-45
1949-53
1954-55
1939-63
1944-65
1949-65
1952-65
Region Et
(Laredo)
1944-4S
1949-53
1954-5S
1959-63
1944-65
1949-65
1952-65
Region Ft
(Harlingen)'
1944 —IS
1949-53
1954-5S
•1959-63
. 19-14-66
1949-65
1952- 6G
Kegion C .
(Corpus Christ!)
1944-48
1949-53
1954-5S
1959-63
• 1914-65
1949-65
1962-66
• lli-pun II
(Houston)
1044-43
. 19-19-53
1954 -5S .
1939 -Go
1044-CG
1949 -.GO
19G2-Gr,
• 1970 St:ti»d»nt pi
IK»(cs figured for

173 105.6
240 119.8
326 120.2 '
380 122.3
1349 117.3
1176 119.2
36S 105.9

359 .35.6 2 1.7
516 41.4 4 3.6
595 41.1 10 7.6
1310 78.5 " 6 3.8
3SS2 59.8 25 4.3
3523 64.3 24 4.8
1621 90.2 8 4.9


8 23.1
• •* ft I C
lo 24.6 .
33 49.4
' 94' 124.2
213 71.8
205 81.1
112 131.2

13 7.9
124 55.5
399 146.1
411 132.9
1237 104.3
1224 120.8
453 139.3

125 ' 47.1 0 ' 0
370 105.6 2 . 3.-.
6G5 15-5-0 1 2-0
1007 .193.7 < 9-S
2035 1S3.4 S 4.3
28 11 H0.3 S 5.-
1176 20G.9 4 5.3
•
- 153 19.3 J2 '5-3
259 23.5 10 4.3
' 5G9 39.5 9 2.4
HUO 43.1 1* 3.1
S3S2 3G.O =*> 3.6
2229 3S.7 4o J^
932 -M— 'G
SS^rnanv.a ««d ,:o,WSp.nW, >«

25
31
35
44
174
149
f\
50

25
35
52
77 •
257
241
105

4
16
20
40
104
100 •
41

6
IS
70
S4
260
" 254
120

22
: 3S
.J9.
44
192
170
60

3
5
S
S
35
32
13
niamccl.
CNAMKP
KATE
'
20.7 - .
2G.4
f\ "1 O
22.5
m f\
2^.0 •
24.0 .
24.7
rj t "T
^.-t.l

7.4
10.0
11.4
15.5
13.2
14.4
15.7

4.1
10.S
145
22.7
15.3
17.5
21.7

3.1
8.5
29.9
29.2
23'i
27.5
37.7

24.5
33.1
3-1.9
' 24.6
30.1
31.2
3i3

12.4
7.3
S.5
9.9
11.4
1U
13.1

J|)cm.;iU.I<>psts- Olliccs •«« incmuw-
(From MacDonald anH Rnbendorf,

F-l-71
1964)




-------
                                                                 Effects—Skin Cancer
                                         Table 11

          Annual Age-Adjusted  Skin  Cancer Incidence Rates* for Caucasians by Sex,
                               Cell Type, and Area,  1971-72
    Cell type
                 Dallas-Fort Worth
M
A.
T
 Iowa
Patients
  M   I  F
 Minneapolis-
   St.  Paul
T  I   M  I   F
|  San Francisco-
|     Oakland
!  T   I  M   I  F
All patients    |  379  j  539  | 259  |  124   174  | 83  | 151 1  201 |  115 |  184 ]  250  |  133
Basal cell      |  286  |  394  | 205  |   93  j 123  j 69  j 129 j  165 |  103 j  153 j  198  |  117
Squamous cell   |   83  |  124  j   51  j   28  |  47  | 13  |  21 j   35 j   12 j   28 j   45  |   15
Both basal and  j       I      j      I      I      I     I     I      I      I      I      !
  squamous	|   10  j   21  j    3  |   3  j   4  j  1  |   1 j    1 j    0 j    3 |    7  j    1

                                (From Scotto et al., 1974)
                                        Table 12

            Age-Adjusted Incidence  Rates'" Among Caucasians for Nonmelanoma Skin
                 Cancers and Cancers of All Other Organs Combined  by Area

Dallas-Ft. Worth
Iowa
Minneapolis-
St. Paul
San Francisco-
Oakland
All cancers excluding
nonmelanoma skin
cancers, 1969-70**
326
297
320

355
Nonmelanoma
skin cancers
379
124
151

184
Nonmelanoma skin
as percent of al
cancers
116
42
47

52
cancers
1 other





    *Per 100,000 population standardized to the population of the U.S.  for 1970
    **Preliminary,  unpublished  data  from the Third National Cancer Survey.
                                   (From  Scotto et al., 1974)
                                        F-l-72

-------
                                                          Effects—Skin Cancer
•a  large pare  of  Che permanent population consists  of  retired military




personnel  and  their  families.   Most  of these  people  spent  much  less




time  in the  sunny south than  the  permanent  population  in El Paso.   The




highest  incidence rate  was  found at Corpus  Christi  at  28  N latitude




(371/100,000).    This  is  significantly  greater  than  the  incidence  at




Harlingen  (284.5/100,000)  at  26°N  latitude.   At Corpus  Christi  an ad-




ditional  factor  to  exposure  is  operating:    a great  preponderance  of




Celtic  inhabitants which  migrated to  that  area  about a  century  ago.




Thus  the  disproportionately  high  incidence  of  skin  cancer  in  Corpus




Christi  is due to a combination of intense  insolation,  and a very  sus-




ceptible population, a situation similar to that existing in Queensland,




Australia.




     Europe




     The  data  available  for  incidence  and  prevalence  of  skin  cancer




in  Europe  are fragmentary  and extremely difficult  to  interpret,  since




surveys, such  as they are, were performed by  variously rigorous methods,




and  over  at  least three  decades,  during which  the incidence of  skin




cancer  has greatly  increased.   However,  it  is clear  that just as  in




the U.S. and Australia, a marked north-south  gradient exists.




     In  1967,  Ball et  al.  reported skin cancer  incidences as follows:




Sweden  - males 7.4,  females 4.5/100,000; Denmark - 26.7/18.0; German/ -




12.9/9.5;  Yugoslavia -  15.8/23.4; England  -   34.9/15.9.   More  recent




reports  suggest  incidences  in the German Democratic  Republic of  43.9




for males  and 40.3 for females, in Bulgaria of  42.2 for rural and  25.0




for  urban people,  and  a  staggering  incidence  for precancerous  skin




lesions of 2450/100,000 in the Kirghiz S.S.R.
                           F-l-73

-------
                                                        Effects—Skin Cancer
     Africa, India, Japan




     Information relating  to  skin  cancer in Africa, gathered  from  var-




ious sources, mainly  the  reports  of Oettle and J.N.P. Davies, show  that




the native  Africans have  extremely  low rates  of  non-melanoma as  well




as melanoma skin cancer.




     The  incidence  rates  in  the  Johannesburg Bantus and in  Uganda  are




of  the  order of 1-2/100,000  for  non-melanoma  skin  cancer  (almost  all




squamous  cell  carcinomas  of  the  lower  extremities).   Isaacson  (1979)




reported  an incidence of  1/100,000 for Soweto (South Africa) blacks.




     The exceptions are albino  natives,  who are extremely prone  to  the




development of skin cancer.   In South Africa,  albinism is  quite  common




among the  Bantus.   Oettle  estimated a  crude  annual incidence rate  of




579  for male  and  408 for  female  albino Bantus for  squamous cell  car-




cinomas of  the  skin.   Interestingly, the rates for basal  cell carcinoma




were only  36/100,000  for  both albino sexes combined  (actually only one




case was found!).




     India




     Incidence data for skin cancer  in India is not  available.   However,




it  is clear  that the  majority of  skin cancers  seen  in hospitals  occur




in  whites.   Among  native  Indians,  special types  of squamous  cell  car-




cinomas of the skin are found, which are presumably  due to extreme heat,




combustion and chronic friction such as Kangri, Dhoti  and Chutta  cancer




(Urbach, 1963).




     Japan and Taiwan




     While again incidence  figures  are  not available,  it  is  clear  that




skin cancer  is  uncommon  in  Japan  and  Taiwan.  This is  also  borne  out
                           F-l-74

-------
                                                          Effects—Skin  Cancer
by a  reversal in Japan  and  Taiwan of  the  usual basal cell to  squamous




cell carcinoma ratio seen in whites.    Squamous cell carcinomas are two




to three  times  more common  than basal cell  cancers,  and may arise at




the  site  of premalignant skin  changes  such  as  burns,  chronic trauma,




or secondary to  arsenic ingestion (Urbach,  1963).




     Australia and New  Zealand




     Probably the  best  skin  cancer  surveys  of recent  years  have been




carried  out  in  Australia,  particularly in  Queensland,  by Silverstone




and Searle  (1970).   In  Table 13 are  reported  their  values  for  incidence




of skin cancer in various parts  of Australia.




                                Table 13




                        Skin  Cancer in Australia
          Annual  Incidence  per  100,000 population of sex stated

State

Victoria
Queensland
Brisbane
Townsville


Crude
Crude
68.5
265.1
242
466
Male

Age
Standardized
66.6
265.1




Crude
50.5
174
170
300
Female

Age
Standardized
38.5
155.8


     How do these incidences  in Queensland  compare with  those elsewhere?




One has  to look for comparable  demographic  data  in those areas of the




world  which  are warm  and  sunny and  to  which people  from the British




Isles and northern Europe migrated.
                            F-l-75

-------
                                                           Effects—Skin Cancer
                Examples  of  High  Incidences of Skin Cancer




            Skin Cancer - Annual Incidence per 100,000 by Sex
| Country
JS.W. England
| South Africa - Cape Whites
[Texas (Non-Latin)
1
[Queensland -''(Whites)
Male
28
133
168
265
Female
15
72
106
156
               "'This means that in Queensland about 3,500 to




               4-,000 people develop a skin cancer for the




               first time each year.




     When  age  specific incidences  for  these regions are  calculated  it




can be  shown  that  skin cancer tends to appear  at  an earlier  age  in  the




Queensland population than in those dwelling  in  other areas.




     The percentages of the  aged  male  population who  develop  skin  cancer




per year are:   southwest England  3.1;  non-Latins, Texas  7.5;  Cape  Whites




10.2; Queensland  17.0.   The corresponding prevalence rates for  females




are:   1.5%,  5.6%,  5.2%,  10.5%.    For  long  it  was said that  the  Celtic




and Anglo-Saxon population  of north Queensland was  the only  successful




northern European  settlement  of  a permanent  kind in the tropics,  hence




one must expect to find a high incidence of  skin cancers.




     What  is the  effect  of  latitude within Australia?   An  approximation




can be  made.   If  the  male  incidence  in Hobart  is  unity, in  Brisbane




it  is  four and in Townsville  it  is eight.   These places  correspond  to




south latitudes of  about  43 , 28  and 19   respectively.  The  proportion




of males  in Queensland between 20 and 80 years  who  would  be  found with
                            F-l-76

-------
                                                           Effects—Skin Cancer
at  least  one skin  cancer  or history  of  same,  varied between 5%  or  6%




in  the  subtropical  areas  around Brisbane  to 12%  to  13%  in the tropical




north of  the  state.   As a generalization  the proportion  of females with




skin  cancer  in the  various  parts  of  Queensland was  about  60% of  the




proportion found in males.




     If one  plots  the  global distribution of annual UV  solar  radiation




as  put  forward by  Schulze  and Grafe  (1969)  against  incidence  of skin




cancer on a global basis a case can be made that a doubling of  incidence




occurs  for  every  10   decrease  in latitude.   The Australian data  would




approximate  to  this,  particularly in  Queensland where  the  difference




in  incidence  between Brisbane  and Townsville  is  about  two to  one  and




the  difference  in  latitude  about  9  .    (A  doubling effect with  every




8   to  9  decrease  in  latitude  would  fit  Australian estimates of  inci-




dences more accurately.)




     In New  Zealand, not  as much  work has been  done on  skin  cancers




as    in Australia,  however, good  estimates of  skin cancer  incidence




have been reported by Eastcott.   These are:




     For  basal  cell carcinoma 113/100,000, for  squamous cell  carcinoma




38/100,000,  and for malignant  melanoma  5.5/100,000.   These  rates  are




considerably lower  than Australia,  but  New Zealand is  much further from




the equator  and thus receives less UV radiation.




     D. 2.5   Relationship  to  Environmental  Exposure  and Changing  Inci-




     dence with Time




     All available evidence suggests that  virtually all human skin  squa-




mous cell cancer  but only  2/3 of  basal cell  cancer  are  related  to total




accumulated  lifetime dose of  biologically effective  solar  ultraviolet
                          F-l-77

-------
                                                         Effects—Skin Cancer
radiation  (Urbach,  1969;  O'Beirn et  al.,  1968;  Gellin  et al.,  1966;




Scotto  et  al.,  1974;  Vitaliano and Urbach,  1980).    It  is also  clear




that pigmentation of the skin confers a marked protection  and that  there




is considerable  variation  in  the  sensitivity  to UVR among  "white"  peo-




ple,  and that much  of this  variation  is genetic  (Urbach,  1969).    It




is  highly   associated  with  "ease  of   sunburning"  and ability  to  tan




(Vitaliano  and  Urbach, 1980).   However,  given  sufficient  UVR  exposure




for  sufficient   time,  most white people  can  develop  NMSC.   The  great




difference in susceptibility,  which  is  by  no means  regularly distributed




geographically,  is  one of  the  major confounding factors for any  dose-




response calculation in man.




     All investigators who have attempted  to model  dose-response  effects




for  NMSC agree  that  there are  also a number of latitude-related  vari-




ables which modify  the relation of  actually received  UVR dose  to  inci-




dence of NMSC.   This  conclusion  is  based in  part  on  the indication  of




non-linearity  in incidence-latitude  figures,  and in part on the  intui-




tive concept  that  latitude-related  climatic and behavioral  effects  must




modify the  UVR  dose  actually  reaching  the skin  of  a  target population.




     There is obviously a relationship  between latitude and  solar  energy




intensity,   and  this gradient  is  exaggerated  in the  UV portion of  the




spectrum.  Although the shape of this relationship  is  relatively  complex




and  dependent on a  number of variables (altitude,  albedo,  cloud  cover,




aerosols,  etc.)  for  a range  of  northern mid-latitude  values  (30   to




50 .  N) ,  the  form  closely  approximates a straight  line for  calculated




(Green,   1978) and  integrated  skin  erythema  action   spectrum weighted




values (Scotto et al., 1980).
                          F-l-73

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                                                         Effects—Skin Cancer
     The relative effects of the "lifestyle" factor are  largely  specula-




tive.  MacDonald  (1971)  suggested that it contributes about  507»  of  the




gradient,  and  van der Leun  and  Daniels  (1975)  considered this  not  an




unreasonable estimate.   To  accept such an estimate in conjunction with




an exponential dose-incidence  relationship,  however,  implies  that these




"other  factors"  are  also exponentially  related to  latitude.    If  the




assumed magnitude  of  these  factors is speculative, an assumed  exponen-




tial relationship is considerably more so.




     If  the  input of  potentially effective UVR  is linearly  related to




latitude, and if the factors relating this input to NMSC are nonlinearly




latitude  dependent,  it  follows  that  the  relationship  of skin  cancer




incidence  to  latitude must  be  nonlinear.   Indeed,  the  epidemiologic




evidence  available  (Gordon,  1976;  Scotto  et al.,  1980)  shows this  to




be the case.




     In order to  obviate the unknown "other factors," various  modelers




have  used a  two   step procedure:   in  the  first  step,  the  amount  of




average  stratospheric  ozone  is  related  to  the biologically effective




UVR dose  (physical  amplification  factor);  in the second  step  the  annual




UVR dose  is related to  estimates of skin cancer  incidence (biological




amplification factor)  (Green and Mo,  1975;  Urbach et al., 1975;  Scott




and Straf, 1977).




     The advantage of  this  approach is that one can  explicitly account




for  dose  differences  which  are  not  related to  the  amount of strato-




spheric  ozone.    No  attempt was  made to  account  for possible genetic




or behavioral differences between the various populations.




     A  fundamentally  different  approach  is  to  evaluate  the  effect  of




an  ozone  reduction  indirectly  by  using  a  dose-response  theory   to
                          F-l-79

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                                                          Effects—Skin Cancer
describe the  effect  of  an increment in the  annual  UVR  dose (Rundel  and




Nachtwey,  1978).   This  approach resembles the  aforementioned  "two  step




approach."   It also  uses the  same  two steps.   The  difference  is  that




the  step  in which  the  annual  UVR  dose is related to  the  incidence  is




not based  on  epidemiologic  data,  but on a dose-response  model inferred




from  animal  experiments.    The  advantage  of  this  approach  is  that  one




deals with  one  population (hairless mice)  and does not  have the problem




of genetic, environmental and  behavioral  differences  at different  loca-




tions (Rundel and Nachtwey,  1978).




     Finally and most recently,  De  Gruijl  and van  der  Leun (1980)  have




developed  a dose-response  model  based  on  animal  experiments.   Using




this model they derived  a mathematical  formula which gives the  relation-




ship between  a  fractional increment in the animal  UVR dose and the  cor-




responding fractional increment in skin cancer incidence.




     For such model  calculations,  estimates  of the "physical amplifica-




tion" factor  are necessary.   Extensive calculations have  been  made  by




Green et al.  (1974),  Mo and Green  (1974), Johnson  et al. (1976),  Scott




and  Straf   (1977).   These  calculations are  based mostly  on  extensive




UVR measurements  performed  by Bener (1972),  estimates  of  local  average




0., concentrations, estimates for effect of  cloud cover,  etc.  With  minor




variations, amplification factor  (optical) has  been found to be approx-




imately  1.7  (Green and Mo,  1975)   based on  an  action  spectrum similar




to DNA.




     There  is  still  extensive  discussion  among  modelers  whether  the




biological dose response  relationship  follows  an exponential or a  power




law  relationship.    Nevertheless,  irrespective  of  the  model  used,  the
                           F-l-80

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                                                        Effects—Skin
"biological  amplification  factor"  ranges  in the vicinity of  2x  (Urbach



et  al.,  1975; Green  et al.,  1976;  Green,  1978;  Scotto  et  al.,  1980;



de Gruijl  and van  der Leun, 1980).   It  should,  however,  be pointed out



that, particularly  if  the  power law applies,  the "biological amplifica-



tion  factor" (AFg) will,  be less  away  from the  equator  and more  near



the  equator   (e.g. , Seattle, 47.5 N,  AF_  1.47;  New  Orleans,  30 N,  AFn
                                       B                               o


2.57) (Scotto et al.,  1980).



     Thus, the  general  estimate  for  the  overall amplification  factor



obtained from the  most  recent  models remains  at 4x,  i.e.  a  170 reduction



in ozone may result  in a 4% increase  in nonmelanoma skin cancer.   Pre-



liminary results  from two  dimensional  modeling suggest  the  nonuniform


               °3
distribution  ofAdepletion  could result  in  a lower factor  (Pyle  and Der-



went, 1980).



     One other point  needs  to  be made before the  above  described  dose-



response relationships  are put  to  general  use.   That is that  there  is



a  significant difference  in risk for developing basal cell  or  squamous



cell cancer  of  the skin.    It has  been  pointed  out before that  of  basal



cell carcinomas, about  1/3  seem to have no relationship  to UV  exposure



(Urbach  et  al.,  1972;  Gellin  et  al.,  1966).   Also, unpublished  data



of the most  recent epidemiologic survey performed by NCI (Scotto,  per-



sonal communication)  show a much  shallower north-south incidence  slope



for basal  cell  carcinoma  than  squamous cell carcinoma.  Finally, Vital-



iano and Urbach  (1980)  have found that the increased risk  for  the most



susceptible  population  is  very  much greater for development of  squamous



cell carcinoma than basal cell  carcinoma,  and  that, given  the same  level



of cumulative  lifetime  solar  exposure,  subjects  over 60 years of  age



had  a  higher risk  for  development  of NMSC  than those at younger  ages.







                              F-l-81

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                                                         Effects—Skin Cancer
     Clearly,  the  existing  models  need  considerable  refining before

realistic  risk  estimates  relating  reduction  in  ozone  to increase  in

NMSC can  be made,  and  present models certainly overestimate the  risk.

     Finally, as  far as changing  incidence  of NMSC  with time is  con-

cerned,  there  is a  small  amount of  data that the  incidence has  been

increasing  by  2-3%  per year  in  the  past decade (Scotto et al., 1980).

This has been happening  although there  has been no measurable  decrease

in  ozone  in that time  period (Berger,  personal communication; London,

1980).    It may be  the  reflection  of a continuing increase in  exposure

for sociologic reasons - i.e., "a tan is  beautiful."

                  D.3  Experimental  Skin  Carcinogenesis

              Effects of Long-Term Exposure of  Skin to UVR

     UV  irradiation  induces   an  inflammatory  response  and  ulceration

in  both the  epidermis  and  the dermis, the latter being  infiltrated  with

leukocytes  in  the region  of  the lesions, and  to  a much  lesser extent

between them.   These lesions  ulcerate  and the epidermis may disappear

for a  time  in  the center.   However,  peripherally there  is  particularly

active hyperplasia.    The basal membrane  (between  the epidermis and  the

dermis) may disappear for a time  in the  regions  of these  "open"  lesions.

Between  the  lesions,  the  infiltration  of  leukocytes  is  relatively

slight.

     Injury  to  the  epidermis and  dermis, brought  about by long-term
            i
exposure  to UVR, leads  to dermal  alteration,  fibrosis  and  elastosis,

as  well  as to epidermal  atrophy.   However,  experimental production  of

cutaneous  elastotic changes  in  animals  by   artificial  UV  irradiation

has only  been reported  rarely.   Using  histochemical  methods,  Sams  et

al. (1964)  demonstrated  focal dermal  elastosis in mice  after prolonged

exposure to artificial  UVR.   UVR-induced changes in connective tissue

were also seen in rat skin  by Nakamura and Johnson (1968).




                              F-l-82

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                                                          Effects—Skin Cancer
                  D.3.1  Mechanism of UVR Carcinogenesis




     In  order  to  understand the  possible mechanisms  of UVR  carcino-




genesis,  it  has  been  necessary  to study the formation and  excision  of




pyrimidine  dimers,  unscheduled  DNA  synthesis,  and  all  the data  valid




for the range from bacteria to mammalian cells.




     It  is  now  generally believed that UVR carcinogenesis  results  from




a  succession of  events originating  in a  photolesion of  the  genetic




material.




     From the numerous  studies  that  have led to an  elucidation  of  some




of  these  mechanisms,  it emerges  that faulty  DNA  repair can  increase




the frequency of  carcinogenesis  in the following ways:   by  causing al-




terations in DNA, which also find expression in an  increased  frequency




of  chromosome  aberrations  and a  rise in  mutation  rate;  by  increasing




the rate  of transformation  of  normal cells  into  cancer  cells; and  by




facilitating the  expression  of  latent oncogenic viruses able to  trigger




cancerous growth (Setlow, 1973;  Trosko and  Chu,  1973).




     Errors  induced  by DNA  repair during  the  initiation phase  of  car-




cinogenesis seem to be the most  likely mechanism leading to  UVR cancers.




                            D.3.2  Tumor  Types




     Epidermal  tumors.   The  first visible  step  in  UVR-induced  epidermal




tumor  formation  in  animal  skin  consists  of  cell  proliferation,  i.e.,




an  increase in  the  number  of   squamous  cells   and  cell  layers,  which




gradually  become papillomatous  in  character  (Stenback,  1978).    This




is  accompanied by an increase in  cellular atypia, 'nuclear  enlargement,




hyperchromatism,  indentation, and prominence  of  nucleoli.  This basical-




ly  proliferative  response  is   frequently  replaced  by  a  dysplastic
                              F-l-83

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                                                           Effects—Skin Cancer
pleomorphism,  occasionally  with  pseudoepitheliomatous  hyperplasia-like




features, which  ultimately  invade  the  dermis.    The  tumors first  seen




are acanthomatous papillomas  (trichoepitheliomas) , with  a predominantly




epithelial  component  or  fibropapillomas  in which the tumor  is  composed




of a fibrous stroma covered  by squamous epithelium.




     The  malignant  tumors  that  ultimately  develop  are  squamous  cell




carcinomas  of  different  types  including:    solid  keratin  containing




tumors;  moderately  differentiated,  individually  keratinizing  tumors




with  distinct  intercellular  bridges;  and  less-differentiated,   non-




keratinizing  spindle   cell  tumors,  in  which  ultrastructural  analysis




reveals squamous cell  patterns.




     Keratoacanthomas,  i.e.,  proliferating  epithelium  on a  cup-shaped




base,  are relatively more frequent  in animals of different  species  re-




ceiving  large  doses of UVR  than  in animals treated with  chemical  car-




cinogens.




     Epidermal  tumors  are easily induced  by  different  agents  in  mouse




skin (Stenback, 1969).  Winkelman et al. (1960)  reported  the production




of  squamous  cell  carcinomas  on  the backs  of  hairless  mice exposed  to




UVR.   Further studies  established  that  carcinomas  could be  induced  in




this animal  almost  to  the  exclusion of sarcoma  formation  (Epstein  and




Epstein,  1963).   In  early  studies, epithelial tumors were  reported  in




both rats  and mice (Findlay,  1930; Herlitz et al.,  1930;  Putschar  and




Holz,  1930), but in later  studies  the deeper lying dermal  tumor  response




to  UVR  predominated.    No mention  of  skin sarcomas was  made,  however,




in the studies of Beard et al. (1936) on  albino rats  in  which 12 animals




exhibited 9  carcinomas of the  external  ear,  6 sarcomas of  the  eye  and




1 carcinoma of the skin of the nose.
                              F-l-84

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                                                            Effects—Skin  Cancer
     The difference in the distribution of tumor types,  with sarcomatous




growth predominating in haired mice and carcinomas in man (Urbach,  1969)




may,  in  part,  be explained  by  the difference  in  penetration of  UVR,




a greater  amount  reaching  the dermis in mice (Kirby-Smith et al.,  1942;




Everett et al., 1966).




     Dermal  tumors.    Another type  of  neoplastic  progression seen  in




mice,  particularly after  intensive  treatment with  large doses of  UVR




over a short  time period,  consists of ulceration, scarring  and  the  sub-




sequent  formation of  dermal  tumors.   These  tumors  begin as aggregates




of  regularly  built,  elongated  cells  with  small  monomorphic nuclei.




Epithelial proliferation  is occasionally  observed  as a  secondary  phe-




nomenon.    The  tumors rarely  extend  grossly through the surface.    In




the  early  stages, they  appear to be papillomas, although  they consist




entirely of  fibroblastic  cells.   Some tumors are remarkably acellular,




with a prominent  fibrillary pattern.   The tumors are composed  of  large,




polymorphic cells with prominent  nuclei.   Ultrastructural analysis  shows




the  predominant cellular components  -  a dark cell type,  with hyperchro-




matic  nuclei  and  scanty cytoplasm,  and a  light  cell type,  with  large




nuclei and abundant  cytoplasmic  ribosomes (Stenback, I975a).   The  same




cell  types are  also  seen  in malignant tumors,  in which  the  cellular




polymorphism  frequently  is considerable,  with  nuclear  atypism and  en-




largement, numerous  nucleoli  and a generally disorganized  arrangement.




Sarcoma  induction is  partly species-specific, as these  tumors  were  not




seen in  UV-irradiated  Syrian  golden  hamsters (Stenback,  1975b)  nor  were




they seen  in  hairless  mice (Epstein and Epstein, 1963)  or  guinea  pigs,




susceptible to chemical sarcoma induction (Stenback, 1969, I975b).
                              F-l-85

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                                                           Effects—Skin Cancer
     An  infrequent  neoplastic  alteration  in  several  animal  species  is




the vascular tumor (Stenback,  I975b).   This  begins  as a  proliferation




of  dilated  vascular  spaces  with regular  endothelial  lining.   Rarely,




the  endothelium proliferates  to  the  point  of  forming  angiosarcomas,




or  invasive  tumors  composed  of  large,  atypical  cells  arranged  in  a




nodular pattern.




     The role of the dermis in epidermal  tumor formation has been empha-




sized by numerous  investigators  (Orr,  1938; Mackie and McGovern, 1958).




A  proliferation of elastic  tissue  was  induced experimentally  in  mice,




by  Sams  et  al.  (1964),  through repeated  exposure to UVR.   Similarly,




Magnus  and  Johnson  (1965)  stimulated formation  of  elastotic  tissue,




following early  destruction  of elastic fibers,  with radiation of 300  nm




from a monochromatic  source.   Nakamura and Johnson (1968)  reported that




dermal  elastic  tissue  proliferation occurred  in  albino  rats  after




chronic  irradiation  with UVR,  only  after   discontinuation  of  the  expo-




sure.  It was  postulated by Johnson et  al.  (1968) that  this change was




the result of photochemically-induced alterations  in fibroblast function,




rather than  the degradation of  normal elastic  fibers.    In  support  of




this concept, Epstein et al.  (1969) noted that unscheduled DNA synthesis




occurred in connective  tissue  cells  of the upper  dermis within  minutes




of  exposure  to UVR  shorter  than 320 nm,  demonstrating a  direct effect




of UVR on dermal fibroblasts.




     Because  of its  frequent  association  with  skin  cancer  formation,




actinic elastosis has been considered to  play an important  role in tumor




development.   However,  Sams and his  co-workers  (1964)  and  Graham  and




Helwig  (1965)  demonstrated  that  actinic  elastosis  was  not  essential
                               F-l-86

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                                                           Effects—Skin Cancer
for Che development of epidermal malignancies.   Furthermore,  the  experi-




mental production  of  elastosis  in animals has not been  associated  with




cancer formation,  nor has  UVR-induced  experimental  cancer  depended  on




the presence of this change (Epstein and Epstein,  1963).




     Adnexal  tumor formation  is  not as  common in UVR-treated  animals




(Stenback,  1975) as  in,  for example, carcinogen-treated  rats (Zackheim,




1964;  Stenback,  1969).   Hyperplasia and  cystic disorganization  of  hair




follicle walls  is  very  common,  but rarely progresses  to  grossly  visible




neoplasia.   Trichoepitheliomas with barely visible follicular  arrange-




ments  are  rarely  seen.   Even  more  uncommon  are  hamartomatous  tumors,




hair  follicle-derived trichofolliculomas   and sebaceous  gland  tumors.




Sebaceous gland  epitheliomas  and  carcinomas are even  rarer.   In  a study




in  1930,  Putschar  and Holtz reported only  a  very  small  number  of basal




cell carcinomas in rats.




     Species-Specificity




     Three  specific factors - pigment, hair and thickness of  the  stratum




corneum  - have been  found to  alter  susceptibility to  tumor induction.




It  was found that  pigmented mice  required  significantly more radiation




to  induce tumors than albino animals.  Hair offered even greater  protec-




tion  (Blum  et  al.,  1959), and thus the hairless rat appeared  to  be a




likely  subject  for  tumor  induction studies.   However,  the results  of




Hueper's  (1941) extensive  studies  indicated  that  this  animal  was,  in




fact,  quite  resistant  to  UV   penetration  because of  its  thick  stratum




corneum.    Since  pigment,  hair and  the stratum  corneum  were  limiting




factors,  the ears  of  albino mice and  rats became the  traditional  test




sites  for  experimental  production of cancer by UV irradiation.   A re-




markable  amount of  quantitative   data  has  been accumulated  using  this











                                F-l-87

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                                                            Effects—Skin Cancer
 system.  The  usual  tumor  produced in this tissue was  a  sarcoma  (Roffo,




 1934;  Grady  et  al.,  1943b).   Thus,  the  albino  ear model could not be




 used for  evaluating qualitative  changes associated with  epidermal car-




 cinogenesis,  which  is the  primary process induced by UVR in human  skin.




      Winkelman  and  his  co-workers  (1960)  reported the  production  of




 squamous cell carcinomas on  the  backs of  hairless mice  exposed  to UVR.




 Further  studies  established that  carcinomas  could be  induced in this




 animal  almost to  the  exclusion of sarcomas (Epstein and  Epstein,  1963;




 Epstein, 1965).   In  addition, UVR-induced  pigmented  tumors were reported




 in pigmented hairless mice  (Epstein  et  al.,  1967).   Thus, the hairless




 mouse  has  provided  a model for  both the  qualitative  and quantitative




 examination of the carcinogenicity of UVR.




      Though penetration  of  UVR  appears  to  be  of  obvious importance,




 other  factors also  influence  the  type of  growth induced  by UVR.   Grady




 et  al.  (1943a)  found that  the  size  of individual  doses  did  not have




 any  effect on the  carcinoma/sarcoma  ratio in the  albino,  hairy mouse




 but  that  reduced intervals  between  exposures increased  the  number of




 epidermal carcinomas.  These findings suggest  that  various tissues re-




 spond  differently to  the carcinogenic  effects  of UVR (Stenback,  I975a).




 In part, this may be  associated  with differences  in penetration  of var-




 ious wavelengths of UVR.   Furthermore,  there  are great  species  differ-




 ences in the  repair  capability of  cells.




D.3.3 Ultraviolet  Radiation  as an  Initiating Agent




      The two-stage  concept  for skin  tumor formation proposed by Beren-




 blum and  Shubik  (1947)   supposed  formation  of dormant  tumor  cells by




 a  single  application  of a  carcinogen.    These  latent  tumor cells were
                              F-l-88

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                                                           Effects—Skin Cancer
provoked  by  the subsequent  application  of a  promoter  to  form  visible




tumors.   In his  studies on  the  induction of  skin  cancer by  exposure




to UVR, Blum  (1969)  indicated that the process was continuous  beginning




with  the  first  exposure and progressing  to  ultimate tumor  formation.




Blum's conclusions were  based on  experiments  in which he  (Blum  et  al.,




1943) and Rusch et al. (1941) could not produce tumors,  unless  exposures




were carried out  over a  minimum of 1\ months,  regardless  of  the amount




of energy used.   Blum's  experiments suggested that, with  shorter  expo-




sure  periods,   tumor   formation  was not  accelerated enough  to  become




visible within  the lifetime  of  the experimental  animal.   Epstein  and




Roth (1968), using a  single exposure  to UVR as  an initiator  and treat-




ment with croton oil  as a promoter, concluded  that  croton oil  stimulated




tumor  formation,  the  characteristics  of which  were  established  by




initial exposure  to  UVR.   The results  of these  studies  were  signifi-




cantly different  from those encountered when  a  chemical carcinogen  was




used as the initiator (Stenback,  1969).




D.3.4    Interactions  between Ultraviolet Radiation and Chemicals




     Chemically-enhanced  photocarcinogenesis




     An  equally  significant problem  concerns  photo-induced  carcino-




genesis following the application to the skin  of agents  which  are photo-




toxic, but not in themselves carcinogenic.




     A portion  of the sunlight  spectrum  is carcinogenic,  even in  the




absence of an  exogenous  photosensitizer.   At  the current rate  of intro-




duction of  new compounds  into  the environment, it has  become  increas-




ingly  important  to determine whether  a readily demonstrable  property,




such  as  phototoxicity,  can  be  used to  predict  compounds  or  treatment




regimes that could enhance photocarcinogenesis.










                             F-l-89

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                                                           Effects—Skin Cancer
     Concepts  of  chemical interaction with  UVR-photocarcinogenesis  are
of  recent  origin.    Blum  (1969)  and Emmett (1973) reviewed a  number  of
reports  dealing  with the  influence of phototoxic substances  on  photo-
carcinogenesis.  The  results  frequently  appeared to  be in disagreement,
a  situation  possibly reflecting   differences  in technique,  including
solvent,  routes  of  administration, light  sources,  criteria  for  tumor
recognition,  and  in  statistical  evaluation (Blum, 1969).   In  addition,
characteristics  of  some  compounds  (toxicity,  carcinogenicity,  insta-
bility)  rendered their  interactions with  light  complex and their  analy-
sis difficult.
     The relative enhancing effects on photocarcinogenesis of  two  widely
recognized photoactive compounds,  8-methoxypsoralen  (8-MOP)  and  anthra-
cene, were  studied by Forbes  et  al. (1970).   Both compounds were  photo-
toxic,  but  only  the  8-MOP  solutions markedly  enhanced  photocarcino-
genesis.   Thus,  the  ability  of  a  chemical  to  induce  phototoxicity  is
not always sufficient to augment  photocarcinogenesis.
     Interactions Between Light and Chemical  Carcinogens
     The fact that UVR can alter  several  phenanthrene  carcinogens  photo-
chemically has been  known for  some time.   The  studies  of Davies  et  al.
(I972a,b) showed that the carcinogenicity  of  7,12-dimethylbenz(a)anthra-
cene  (DMBA)  was  reduced  by  light   according to  the  demonstrable  photo-
chemical  lability  of  the compound.   There  was  also  evidence that  an
additional  time-dependent factor  could  influence this effect.    Thus,
it  appears  that,  at  least  in the  case  of DMBA-treated  animals,  light
may contribute in two opposing ways:  (a)  by  degradation of the carcino-
gen  to  noncarcinogenic  products,  and (b) by stimulating  a  phototoxic
response  that appears  to coincide  with   a  relatively  increased  tumor
yield.
                              F-l-90

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                                                           Effects—Skin Cancer
     Depending on  the wavelengths  of  the UVR used, carcinogens can  be




photodegraded  to  a  less carcinogenic  compound,  or  can induce photo-




toxicity which may  augment  carcinogenesis or cause such a  severe  local




phototoxic  reaction  that the  epithelial  skin cells are nearly all  de-




stroyed.  Thus, either  enhancement  or inhibition  of skin carcinogenesis




may occur, depending upon the carcinogen and the wavelength  of  the  light




source used.




     UVR-induced carcinogen formation




     The photochemical conversion of  sterols to carcinogenic  substances




has  been  proposed  as a  potential   explanation  for the  cancer-causing




effects of  light upon skin  (Black and Douglas, 1973).   It  has recently




been  demonstrated,  in  vitro,  that  one  such compound,  cholesterol-5a-




oxide,  which  possesses  carcinogenic  properties   (Bishoff,  1969),   is




formed in human skin exposed to UVR  (Black and Lo,  1971).




D.3.5  Physical and  Quantitative Aspects of  Ultraviolet Irradiation




                            in Animal Studies




     Carcinogenic  action spectrum




     Determination   of the  effective wavelengths  or  "action  spectrum"




is  one  of the primary  objectives  in  the study  of photobiological  re-




sponses.   However,  data  are  not  available  for  the action spectrum  of




UVR-induced cancer  formation.   The  paucity of this information for  one




of  the  most  extensively studied  photobiological   reactions  is due  to




a  number  of  factors, including  the  large  number of  potential   wave-




lengths,  the  considerable  number  of animals necessary  and the length




of  time (a matter  of many months  or years) required  for  exposure  to




each wavelength, the  difficulties  in immobilizing  experimental animals,
                              F-l-91

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                                                            Effects—Skin Cancer
and  the  need  for  an  especially good monochromator with  practically  no




stray  light  contamination.    Though  the complete curve of  the  carcino-




genic  spectrum is not  known,  certain  aspects  have  been determined  by




less  sophisticated methods.   Roffo  (1934)  reported  that window  glass




filtration  eliminated  the  carcinogenic effects  of  sunlight  on  white




rats.  Thus  the  offending rays of the  sun  would  be  found approximately




between  290-320  nm.    A number of  investigators  using mercury  arc  and




fluorescent  sun   lamps  with  filters  have   confirmed  that,  under  their




experimental conditions,  320  nm  represented the longer wavelength  limit




for cancer  formation  (Griffin et  al., 1955; Blum, 1969).   Furthermore,




carcinogenic responses have  been produced by radiation as  short  as  230.2




nm  (Roffo,  1934), and  skin cancer has  long been known  to be  induced




by UVC and UVB.  Thus the action spectrum appears  to  include wavelengths




between  230 and  320  nm, but  wavelengths  between 290  and  320  nm have




been  shown  to  have significantly greater carcinogenic  effects  than  UVR




shorter than 260 nm (Rusch et al.,  1941; Blum,  1943;  Blum  and  Lippincott




1943; Kelner and Taft, 1956).




     Freeman (1978)  performed a series  of experiments to  provide more




specific  comparative  data  by testing  the hypothesis  that the action




spectrum  for   carcinogenesis  parallelled  that   for erythema.   In  these




studies,   squamous  cell carcinomas developed  at approximately  the same




rate and  frequency, when UVR  exposure was  proportional to that  for ery-




thema, with a decreasing potency from 300 to 320 nm.   No tumors  occurred




in mice  exposed  to 290 nm.   These  cancer-producing wavelengths  are also




responsible for  the normal  phototoxic sunburn  reaction.  Longer UV  and




visible  light   are neither  erythema-producing nor  carcinogenic  under




ordinary conditions.
                              F-l-92

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                                                             Effects—Skin Cancer
     It can not  be  assumed that the action  spectra  for  human skin  ery-




thema  and  mouse skin  photocarcinogenesis  are similar, unless  a  common




chromophore or  action  mechanism  is involved.   Setlow (1974)  proposed




that the common  denominator  was the action  spectrum for  affecting  DNA.




Making some allowance  for  the  skin transmission of UVR,  he  showed  that




the shapes of action  spectra for  DNA,  erythema and possibly  skin  cancer




production were  similar and could  be made to coincide.




                    D.3.6   Dose-Response  Relationships




     The second  law of photochemistry  (the law of  reciprocity of  Bunsen




and Roscoe) states that photochemical action depends  only  on  the product




of the light  intensity and the  duration of exposure.  This law,  however,




holds  only for  primary photochemical  action, and  can  not   be applied




to  secondary  reactions.   Since  the biological endpoints  that can  be




observed,  such  as erythema,  pigmentation,  skin cancer production,  etc.




are certainly  indirect effects, and  since we  still  know little about




the primary photochemical  reactions  that underlie  them,   it  is  not  sur-




prising that "reciprocity" holds  only  for some of the effects  studied.




     In  the   first  quantitative  photocarcinogenesis  experiments  ever




performed, Blum  (1969)  found that,  within relatively narrow  limits  (ap-




proximate  factor of 5),  differences  in dose,  intensity or interval  be-




tween  doses did  not  alter  the  shape or slope of tumor  incidence curves,




but only their positions on the log-time axis.  Blum, however, was care-




ful to point  out that this  was  only  true as long as the experimental




conditions remained  the same  until the  time the tumors  appeared.




     With  the   accumulated  data,  he  surmised  that  UVR-induced  cancer




formation was a  continuous process  that began with the initial  exposure
                              F-l-93

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                                                            Effects—Skin  Cancer
and  that  the  appearance of  tumors  within the  lifetime  of the  animal




depended on sufficient acceleration of the growth process.




     In  the majority  of  studies  on  photocarcinogenesis,  fixed  doses




of  UVR  have been given  at  a  fixed dose rate, and the  interval  between




doses altered,  but  in  increments  of  at  least  24 hours.   Such  experi-




ments, while  very valuable,  are  far  removed from the  conditions  found




in  nature under  which  human skin is exposed.   Man is exposed  to  a  rela-




tively  low  UVR  flux that  varies with time of day,  season  and environ-




mental  conditions,  such as cloud  cover,   and  also  during  the exposure




period.




     Two  recent   animal  experiments   have  shown   that  both varying  the




UVR dose increment and varying the  dose-rate while the daily dose  remains




constant affect UVR-induced skin carcinogenesis.




     In the  first experiment,  groups of  hairless mice were exposed  to




doses of UVR  from a bank of  "fluorescent  sun" (FS)  lamps  known  to pro-




duce  skin  cancer in these  animals.   Equal doses of UVR were  delivered




in  periods  of 5 minutes, 50 minutes  or  500 minutes.   Thus,  while  the




doses (given 5  times  weekly)  were  the same, the  flux  varied by a factor




of  10 or  100.    Striking differences  in both  tumor  development time and




tumor yield were  noted.   The animals given  the total UVR  dose  in  5




minutes developed tumors  later and in smaller numbers  than those  given




the  same  total  dose  in 50 or 500 minutes  (Forbes,  personal  communica-




tion).  Thus, protracting the  UVR dose over longer time periods resulted




in  a  striking increase  in the carcinogenic  effects of the  radiation.




     In another  experiment, mice were exposed to UVR doses per day dif-




fering  by  a factor  of two.   As  Blum  had found previously,   the  lower










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                                                             sttects—Skin Cancer  |
daily  dose  resulted in  the  delayed onset of first  tumors  without  sig-


nificantly  changing the  shape  of  the  response  curve  (Forbes,  1978).


     Physical factors influencing UVR carcinogenesis


    Although  the  tumor-promoting  properties  of  such physical  factors


as  freezing,  scalding  and wounding  have been  described  for  chemical


carcinogenesis  systems,  little  information is  available about  the  ef-


fects of  these  factors  on UVR-induced cancer formation.  Bain  and  Rush

                                                         o
(1943)  reported that  increasing  the temperature to  35-38 C accelerated


the tumor growth  rate.   The  stimulating effects of heat  on  UVR  carcino-


genesis were  confirmed  by Freeman and Knox (I964b).  Heat  also  enhanced


the acute injury response to  UVR.


     Temperature does not affect  the photochemical  reactions that follow


UV  irradiation, but it  does  affect many  of  the  biochemical  reactions


that  follow the initial  photochemical  change (Blum, 1941,  1969).   Al-


though  it is  known  that heat adversely affects  photosensitivity (Lipson


and Baldes,  1960) and  other  phenomena of light  injury (Bovie and Klein,


1919;  Hill  and  Eidenow,  1923), and that heat alters the effects of  x-


ray (Carlson and Jackson, 1959),  the influence of heat on burns  produced


by sunlight  or UVR has rarely been considered  (Freeman and Knox, I964b).


     Other studies have  shown  that  high  winds  and high humidity  signifi-


cantly increase  tumor incidence  (Zilov,  1971;  Owens et al.,  1977).


            D. 3.7  The  Immune  Response  to  Tumor Induction


     A number of  studies  have shown that the immune  status of  the  host


and  tumor  induction  are potentially  interactive  processes.   Chemical


carcinogens   cause  alterations  of  the  host   immune-response,  the  type


and extent  of which depend on the  tumor-inducing  agent  (Curtis,  1975).
                           F-l-95

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                                                           Effects—Skin  Cancer
UVR  also  profoundly affects  immunological  reactivity,  particularly  the




immune response  to  skin  tumors induced by UVR.   Studies leading to this




conclusion were  prompted  by  an observation by Kripke (1976)  that tumors




induced by  UVR  in  CoHf mice  were highly antigenic  and  are  usually  im-




munologically  rejected  when  transplanted to  normal,  nonirradiated syn-




genic recipients.   This  raised the question as  to why these  tumors were




able  to  grow  progressively   in  their  primary  host  without  succumbing




to  immunological rejection.    In  an  extensive  series  of  experiments,




Kripke and  Fisher  (1976)  found  that pretreatment of mice with  UVR  for




periods of  time  too  short to  induce  skin tumors  made them unable  to




reject transplants  of UVR-induced  tumors,  even though  such  transplants




were  immunologically rejected  by  unexposed  animals.   This  indicates




that  UVR—exposed mice are systemically altered in  a way  that  prevents




immunological rejection of highly antigenic UVR-induced tumors.




     Similarly,  inability  of  unexposed  secondary  hosts to  reject UVR-




induced tumors  after transfer of. lymphoid cells  from  UVR-treated mice




has  been  established and  demonstrates  the immunological nature  of  the




systemic  alteration in  the UVR-treated mice  (Fisher  and Kripke,  1977).




Furthermore,  the failure  of   lymphoid  cells  from UVR-exposed mice  to




react against  UVR-induced tumors  is due to  the presence  of  suppressor




T lymphocytes  in the  lymphoid organs of UVR-treated  animals.   In spite




of  their  inability  to reject  highly antigenic UVR-induced tumors,  UVR-




exposed mice  respond normally to most other antigens  (Kripke,  et al.,




1977; Norbury et  al.,  1977).   The one  exception is  that  UVR-treated




mice  have  a transient  defect  in antigen processing  in  the  skin,  which




is  reflected  in their  inability to  develop contact  hypersensitivity




reactions (Jessup et al.,  1978).









                             F-l-96

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                                                         Effects—Skin  Cancer    I
     The finding that  a  selective  immunological  defect  precedes  the




appearance of UVR-induced primary  tumors  suggests that the immune system




might control early  UVR-induced skin  cancers  and that tumors ultimately




appear because of this interference  by UVR with host defense mechanisms.




     The  carcinogenic  action of  polycyclic hydrocarbons has  been as-




sociated with their  immunosuppressive action  (Stenback, 1969).  Immuno-




deficiency  states  and   immunosuppression therapy  are  both  associated




with  an  increased  tumor  incidence.   Immunosuppressive  agents, such as




antilymphocyte  serum,  enhance both  chemically-  and  UVR-induced tumor




formation (Nathanson  et  al.,  1973,  1976).
                              F-l-97

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                                                           Effects—Skin  Cancer
        E.   The Risk of Increase  of Malignant Melanoma of the Skin




             Due to Increased Earth-Level Solar UV Radiation




     E.I.   Conclusions




     There  appear  to  be significant  differences in the age/sex  ratios,




incidence,  geographic  distribution  and  anatomic  location  between NMSC




and MM.




     NMSC is a  disease increasing  sharply with advancing age,  beginning




in the  50+  year olds.   It is significantly more frequent in males  (par-




ticularly squamous  cell cancer), affects  primarily  the head  and  neck,




and  to a much lesser  extent  the  shoulders,  upper  chest  and  forearms




and  hands.   It  is  very uncommon below  the  midchest.   There   is a dis-




tinct,  striking latitude  gradient  both  within and  between countries,




following the  intensity  pattern  of  solar UVR.   The disease is uncommon




in heavily  pigmented persons,  even  in  areas of intense insolation',  and




usually occurs  in  these  at  sites  of  chronic  trauma.   There  is almost




always evidence of  severe  solar  elastosis (sunlight  damage to  the con-




nective tissue) in  the skin  in which the  tumors  arise.  Lesions clini-




cally,  histologically  and biologically  almost  identical  with  squamous




cell carcinoma occur spontaneously  in animals on exposed skin in heavily




insolated  areas,  and  can be  reproduced  with  excellent   dose-response




characteristics  in  experimental  animals exposed  to  appropriate  wave-




lengths of UVR.




     In contrast,  MM is a relatively  uncommon tumor, primarily  occurring




in man.   The  sex  ratio varies  from 1:1  to 1:1.2 in favor of  females.




In contrast  to NMSC,  the  anatomic  distribution  of MM  does not follow




the most UVR exposed  sites.   About  10%  of MM  are on the head  and  neck.




This  type  of lesion most  often  represents  LMM,  and  has  basically  the




same characteristics as  squamous cell  carcinoma:   location on most  ex-




posed  sites of  head  and neck,  low  incidence  before age  50,  with  a  rapid







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                                                           Effects—Skin  Cancer
and  progressive rise  in frequency with  advancing age,  almost  uniform




presence of solar elastosis in the adjacent skin and low aggressiveness.




     While  NMSC is  extremely uncommon  in pigmented  races, MM  occurs




about  one-fifth as frequently  in  such people  as  in white-skinned  pa-




tients,  and there  is mostly  found (75-85%)  on the foot  and  lower  leg.




     Another 6  to  11%  of MM appear to be of  genetic origin,  as  evidence




by  familial  and multiple  lesions,  and peculiar precursors  found  early




in life  (B-K mole).




     The remaining approximately  75  to 80% of MM  in white  persons  have




interesting attributes:   The  incidence  rises sharply  from  adolescence




to  early  adult life  (particularly  on  the  legs  of  women),  plateaus




through  middle  age,  and  rises  again in old age (because of  appearance




of LMM).   The  male/female incidence shows a preponderance of young fe-




males  (less than 40  years old) and the sites  of greatest incidence  dif-




fer, being  trunk in males  and lower  leg in  females.   Of  interest  is




the  observation that,  although  the  various  populations studied   live




in such  disparate  areas  as  Finland (north of  60   latitude)  and Queens-




land,  Australia  (25 -15   south latitude)  and  thus  are  exposed to hugely




different amounts of solar  UVR,  the relative  proportion of MM affecting




various  body  sites  has  remained  quite  stable until  recently.   In  at




least  two   areas  (Norway and  Hawaii)  the differences  in incidence  of




MM between  males and  females  on   the  most  affected sites (back  in  men




and  legs in women)  seem to be  disappearing  in the  past decade  only.




     The latitude  gradients for  incidence  (and mortality)  of MM  exist




within certain  countries, but  not  in others.   Thus there are  real  lati-




tude gradients  for MM  in Norway,  Sweden, Great Britain  and  the  U.S.A.,
                          F-l-99

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                                                          Effects—Skin Cancer
but  less  striking,  or even  reversed gradients  in Western  Australia,




across  central  Europe and  a  partial latitude gradient in eastern  Aus-




tralia, where  in  Queensland the  incidence of MM is  less  in  the  tropics




than in the subtropical areas.




     In contrast  to  NMSC,  the  populations  most  affected  are not  the




outdoor workers,  but rather  the  white-collar,  more educated, more  af-




fluent  people,  and  the  demonstrable  concentration  of MM in  large  cities




cancels out  a  latitude gradient  in  such places as  Finland  and Western




Australia, where this has  been investigated.




     The worldwide  rapid  increase in  the incidence of MM (and,  inter-




estingly,  much  slower increase  in mortality rates, as  if   the MM  were




becoming  less  aggressive)  has been  attributed to  changes in lifestyle,




with greater  exposure  to  solar UVR  during leisure  activities  and  vaca-




tions.   Since  the  more  affluent can  be considered to  be   more  likely




to  partake  in  such  activities,  the reasoning  goes that men  removing




their  shirts  outdoors, and women wearing shorter skirts,   account  for




the peculiar anatomic distribution of MM.




     The  lack  of  evidence for  chronic  solar damage  of  skin in  which




MM  appear,  the young  age  of  a  majority of  patients,  the variation  in




latitude  gradients,  the  peculiar  anatomic   distribution  not matching




most exposed  skin  areas and the  preponderance in  city  dwellers  suggest




very strongly  a significant difference  in pathogenesis of NMSC and  MM,




at least as far as the significance  of solar  UVR is concerned.




     Except  for LMM,  other MM  are  certainly  not related   to  chronic,




repeated solar UVR damage  resulting  from  accumulated dose.




     Whether the  suggestions  that acute, intermittent  exposure to  solar




UVR, or some dependency on intensity  of irradiation, or some  interaction







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                                                          Effects—Skin Cancer
of UVR with chemical or precursor lesions are the basis of MM etiology




needs yet  to be  determined.




     The  absence of a good animal model for MM, at  least for the rela-




tion of UVR to MM,  makes such studies difficult.
                            F-l-101

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                                                            Effects—Skin  Cancer
     E.2.   The Natural History of Malignant Melanoma Skin Cancer




     The  first  case of  malignant  melanoma ever recorded  seems  to  have




been  treated  by John  Hunter  in 1787,  although he  never  described  the




disease  as  such.   Laennec first reported what we now know as MM in 1812,




and coined the term "melanoses" (melas - Greek = black).




     The classic and prophetic reports in the English language are those




of Norris  (1820,  1857).   His description of  eight  cases is fascinating




(Norris,  1857):   "The  disease  often  occurs  in  those  persons who  have




moles  on various  parts  of the body,  most resided  in  very  smoky  coal




and iron  districts,  there is  a strong tendency  to  hereditary predispo-




sition and it is a disease allied to cancer."




     He  noted that  his patients had light colored  hair  and a fair  com-




plexion  and  that trauma  may  accelerate  the growth  of a  melanoma,  that




while  often  black, the  lesions could be almost lacking  in  pigment  and




have  blue,  pink or  grey areas, and  may disseminate widely  throughout




the body.   In  other  words,  Norris,  150 years  ago,  had made the  most




salient  observations  regarding this  uncommon,  but   serious  skin cancer




(Davis, 1980).




     There  are  significant differences between many aspects  of  natural




history  of  nonmelanoma and melanoma skin cancer.  For  NMSC, three kinds




of evidence - latitude  dependence,  body location and relation to  outdoor




sunlight dependence- all combine  to point closely  to  exposure to solar




UVR as the prime cause.
                                F-l-102

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                                                            Effects—Skin Cance;
     The situation is  different  for  malignant  melanoma,  as  will  be  seen




in the  following.    The  latitude dependence,  only  recently pointed  to




as the  prime  indicator  of  relationship  to  solar UVR, is becoming  less




striking, indeed in  some  areas  invalid,  as  better  epidemiologic  studies




become available.  The body location  does not fit areas  of maximal  solar




exposure, and differs greatly from NMSC.   In contrast  to  NMSC,  malignant




melanoma  appears to  have a  predilection  for  middle class,  primarily




indoor workers and their wives.




     There  is  general  consensus of  those   having  studied  the  natural




history of malignant  melanoma  that,  if there is a  relationship to  solar




UVR exposure, the mechanisms  involved  must  be  very different  from  those




operating in NMSC, and that  the cumulative  effect of chronic, repeated




UVR exposure can not  be  held  responsible for malignant  melanoma  induc-




tion.




     The  present lack  of an  animal model   for malignant  melanoma  and





the uncertainties  regarding  dose-response  characteristics prevent  the




conversion of  projections of  change in  UVR  intensity   to  estimates  of




extra deaths.
                             F-l-103

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                                                            Effects—Skin  Cancer
E.2.1   Anatomic  Distribution  and Histopathology




     E.2.1.1   Lentigo  Maligna Melanoma




              (Hutchinson's  melanotic freckle, circumscribed precancerous




              melanosis of Dubreuilh)




       This  kind  of  malignant melanoma  begins  as  a  small,  irregular




  freckle-like lesion, almost  always located on  the  head  and  neck,  and




  then  evolves over many  years in  a  distinctive way to become an invasive




  malignant  melanoma  distinguishable from other  forms  of malignant mela-




  noma.   The  early,  noninvasive stages  are referred  to  as "Lentigo Ma-




  ligna"  and  the  late,  invasive stages as L-M melanoma.  This has a better




  prognosis  than  other forms  of melanoma (Clark et al., 1969).




       L-M  melanoma occurs primarily on the  exposed  surfaces  of the body




  of  elderly patients with white skin,most of whom have fair complexions.




  The  early,  noninvasive  lesion  is  an  irregular,  tan, freckle-like pro-




  cess,  from  0.3 to  as  much  as 4  cm in diameter, most commonly found on




  the  temples or  cheeks,  particularly of  females.   Histologically there




  is  a distinct  increase  in the  number  of  epidermal  melanocytes, which




  vary  from normal  to distinctly  atypical,  to  frankly bizarre  in struc-




  ture.   When  invasive L-M melanoma develops, usually after  10 to 30 years




  of  a slowly growing Lentigo, the  appearance  changes.    The outline of




  the  lesion  becomes  irregular  and develops  a kaleidoscope  of   colors,




  including  tan,  brown, black,  elevated blue-black nodules, and sometimes




  translucent  whitish-blue areas.    These  latter  represent  areas of spon-




  taneous regression  in parts of the  lesion,  which  however is not a sign




  of  cure;  the   lesion  continues  to develop  in  adjacent  areas.   Histo-




  logically,   the  L-M melanoma is  identical to  lentigo  maligna   except




  for  invasion of the dermis  by malignant melanocytes.








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                                                            Effects—Skin Cancer   I
     There is also almost uniformly histologic evidence of severe  "solar




elastosis," dermal connective  tissue  changes  typical of chronic,  severe




sunlight exposure.  Patients with lentigo maligna and L-M melanoma often




have a  history  of solar keratoses, basal cell and squamous cell cancers




of  exposed  areas (McGovern, Little,  Freeman, Robertson,  personal  com-




munications; Larsen and Crude 1979).




     The  distribution  (78% on head,  neck  and upper trunk -  Larsen  and




Crude,  1979),   the  almost   uniform  presence  of  severe  solar  elastosis




of  'the  adjacent  skin,  the slow progression  and good  prognosis  (Wayte




and Helwig,  1968) clearly  separate this form  of  malignant melanoma from




all .others.




     The  anatomic location,  incidence   in  the   older  (60+)   age  group,




associated  solar dermal  damage  and  slow  development  strongly suggest




an  etiologic  relationship  to  chronic  solar UV  exposure.   In terms  of




frequency,  approximately  10 to  1570  of   all malignant  melanomas   are  of




the L-M melanoma type.






                 E.2.1.2  Superficial Spreading Melanoma







     Superficial  spreading melanoma  (SSM)  is the  most  common   of  the




four clinical  types  of malignant  melanoma.   It  constitues   from  35  to




45% of all such tumors (Larsen  and  Crude, 1979).




     SSM is a  complex  lesion  that  presents two quite  distinct patterns




of  growth,  which have  been described  as  the radial  and the vertical




growth phase.   The radial  growth  phase is a period of gradual  peripheral




enlargement ("spreading")  of a  relatively flat pigmented lesion.




     Sooner or  later,  usually after  a   period of  one to  five years,  a




nodule may develop in SSM and this  constitutes the onset of the vertical
                            F-l-105

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                                                          Effects—Skin Cancer
growth phase  (VGP).   This appears to  be  caused by growth of a morpho-




logically distinct new  type  of  cell,  with a capability  for  deeper  inva-




sion and metastasis.




     Examination  of  the cut  surface  of the lesion with  the  dissecting




microscope  usually  shows  pigment  filling  the  papillary dermis  (much




of the pigment  will  be  in melanophages deep to  the  tumor).   The nodule




(or  VGP),  if  present,  consists  of  a  pigmented  or,  more  frequently,




amelanotic,  soft fleshy  tumor that  may  extend  into the  reticular  dermis.




Wherever one  judges  invasion  to be the deepest,  levels of  invasion  and




thickness are determined.




     The hallmark  of  SSM  is  the large epithelioid cell.   Proliferation




occurs initially  in  the  basal  keratinocytic  layers, and  although dis-




positions of  individual  cells  are  frequent  at  the lesional margins,




nests of melanocytes  are invariably present  elsewhere within the  lesion.




These nests differ from those of nevi  in the following  ways:




     1.  Variation in size and shape.




     2.  Tendency  to fuse  with adjoining  nests and to  spread  up  the




         sides of rete ridges (McGovern, 1976).




     3.  Indistinct  margins  with  an   ill-defined  separation   between




         melanoma cells  and keratinocytes (Price et al., 1976).




     A.  Separation  of  nests  or single cells  from the  basal lamina with




         upward  migration to  produce   a  pattern  of  large,  relatively




         pale  cells  in the  epidermis  which  resembles  that  of  Paget's




         disease (McGovern, 1970).




                   E.2.1.3  Nodular Malignant  Melanoma




     Nodular  malignant  melanoma (NMM)  is, by definition,  pure vertical




growth phase  disease.   More specifically, nodular melanoma  is  invasive




melanoma  without  the preceding and  adjacent   intraepidermal  component.









                             F-l-106

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                                                           Effects—Skin  Cancer
It is a tumor that arises by direct tumor progression without a discern-




ible evolution through demonstrable lesions analogous with radial growth




phase disease.





     A nodular  melanoma  presents  as  a mass that expands  only  slightly




in radial axes  as  it becomes progressively elevated.   Growth is usually




rapid  and  the  history commonly  short  (under  12 months).   Although  a




history of preexisting nevus may be obtained,  the  spreading  variegated




lesion of  the  radial growth  phase distinctive  for  most melanomas  is




not  present,  and  the lesion  is  relatively  symmetrical with  discrete




borders.    Even  in the so-called amelanotic melanoma,  a few flecks  of




pigment are  usual,  and the  total absence of melanin  (to  careful  hand-




lens  inspection)   suggests   another  diagnosis,  especially  Spitz  tumor




or pyogenic granuloma.  Ulceration is  a frequent  but by no means invari-




able finding.   The  epidermal  fine surface  marking pattern is  usually




obliterated as  a  result  of  stretching of  the  epithelium by growth  of




the  tumor  in the  papillary  dermis or  because  of  epidermal  invasion.




Ulceration may occur  with  spontaneous  hemorrhage  in  the form of  a bloody




ooze or with  crusting.




     As in SSM,  epithelioid cells  are usually  predominant.   They  are




usually pigmented  but sometimes the  majority are  amelanotic.   A  few




pigmented cells are  almost  invariably  present,  and they  contain  dusty




fine melanin  granules that  represent  abnormal  melanosomes.  The  tumor




cells  commonly  invade the  overlying  epidermis  in  a pagetoid  fashion,




and  if  these  cells extend a short  distance lateral to  the  deep  dermal




component,  SSM may  be simulated.   The  invasive  cells may extend  through-




out the full  epidermal thickness to produce frank  ulceration.   Neither
                                F-l-107

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                                                           Effects—Skin  Cancer
epidermal invasion  nor  ulceration  is  an  invariable  finding,  however;




a "grenz"  zone  of uninvolved dermis may separate epithelium  and  dermal




component, and in some such cases, it may not be possible to demonstrate




an origin of the tumor in the overlying epidermis.




     The  dermal  component  of  a  nodular melanoma  is almost  invariably




level  III  or IV.   The cells  are arranged in  large nests  within  which




there  is  no  stromal response.   Between the nests,  fibrosis  and new ves-




sel  formation  are  usual,   and  there  is  a  scattered  lymphohistiocytic




infiltrate with melanophages and, quite frequently,  plasma cells.




   E.2.1.4  Classification of Malignant Melanoma




     The  better  prognosis  of superficially  invasive melanomas  has  been




appreciated  by  a number of writers (Mehnert and Heard,  1965;  Lund and




Ihnen, 1955; Clark  et  al.,  1969; Nicolle et  al., 1960).  Clark in 1967




proposed a classification of melanomas in terms of the  level of invasion




in relation  to  the  interface between the papillary  and  reticular  dermis




(Clark,  1967;  Clark et  al.,  1969).   This  classification  was  accepted




by  an international  group  of  pathologists  in  1973  (McGovern et  al.,




1973)  and  remains  in  wide  use today.  The  basis of classification into




five  levels  of   invasion is generally understood,  although problems  of




interpretation  arise  from  time   to  time.   The  levels  are  as  follows:




     Level I:  Confined to the epidermis (in situ)




     Level II:   Invasive into the papillary zone of  the  dermis




     Level III:   Tumor fills and expands the papillary  dermis




     Level IV:   Invasion of the reticular dermis




     Level V:  Invasion of the subcutaneous fat




     The classification above  is useful,  in that the prognosis for sur-




vival  is  excellent  in  level  I  and II melanoma, but becomes  materially









                              F-l-108

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                                                          Effects—Skin Cancer
worse when the  tumor  reaches  the reticular  dermis  (level  III), probably




because of  emergence  of a new  type  of  tumor cell with altered  proper-




ties constituting  the vertical  growth  phase of the disease  (Wanebo et




al., 1975; Foulds, 1979).




     The  major  histologic  features of  malignant  melanoma are shown in




the table below.




                                 Table 14




Histologic features of Malignant Melanoma




Pagetoid spread




Dermal invasion




Lack of maturation in  dermal  component




Dusty pigment




Pigment in deep dermal lesional  cells




Inflammatory response  and  regression




Mitotic activity




Cytologic atypia




Variable cytologic patterns within the  lesion




Ulceration




Epitheloid or spindle  cells;  large nucleoli




Nuclear hyperchromatism and pleomorphis




Irregular nests:  Size variation




                  Poor definition




                  Fusion




                  Dyshesion
                               P-l-109

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                                                         Effects—Skin Cancer
   E.2.1.5  Acral Lentiginous Melanoma




     Melanomas of the hands and feet are an uncommon variety,  accounting




for  about  5%  of malignant  melanomas  in white  skinned  people, but  50




to 75%  of all  malignant melanomas in genetically  deeply  pigmented  per-




sons (see below, Section E.2.3).




     In  contrast  to the more common varieties,  acral  lentiginous mela-




noma shows distinctive clinical and histological changes.




     The  typical clinical  appearance   is  of  a  black, rounded  nodule.




Many of  the  tumors  are exophytic  , and ulceration is common.   Most  les-




ions are  accompanied  by a peripheral macular hyperpigmented halo, which




may extend for several centimeters about the nodule or ulcer.




     Histologically,  the  macular  portion  shows  the pattern  of  radial




growth phase, with a diffuse lentiginous hyperplasia of atypical melano-




cytes  in the  basal portion  of the epidermis,  which itself  is  hyper-




plastic,  with  elongated  rete  ridges.    The dysplastic melanocytes  are




separated  from  neighboring cells  by clear areas,  the papillary dermis




shows a dense, lymphohistiocytic infiltrate.




     In  the  nodules,  vertical  growth of pigmented, spindle celled mela-




nocytes  infiltrates  the dermis.   When  found,  most lesions are  deeply




invasive  (Clark level 3).




     Acral  lentiginous  melanoma  is  more common in males  (M/F  ratio  2:1)




and  the  duration of  the  lesions  prior to  diagnosis  varies from months




to a few years.   Most common age group is 50-60 years.




     In  a recent  series  (Coleman  et  al., 1980),  50% of  patients, had




melanoma  metastatic to  the  inguinal nodes, and  a  poor  life expectancy.
                               P-l-110

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                                                         Effects—Skin Cancer
                  E.2.2  Age,  Sex and Site  Distribution

     In recent reports of several  large  series of cases of MM,  certain


observations  occur  uniformly.   These  are:    a consistent,  world-wide

increase in MM,  primarily  in  lesions involving the back of men  and  the

lower legs  of  women  (Magnus,  1977;  Holman et  al.,  1980);  a progressive

decrease of  age  of  onset  (Malec and  Eklund,  1978; Lee et al.',  1979),

again world-wide,  in  the same anatomic locations;  and  great  difference

in incidence  and  localization  of MM between white  and  nonwhite  popula-

t ions.

     As will  be  shown,  it  is  important to examine  not  only age  and  sex

incidence  ratios,  but to compare  such factors in  relation to  location

of the MM  lesions.   There  is  uniform agreement that,  with  the exception

of LMM, MM is a  type of tumor which  attacks  younger  age groups.   There

is,  among  white  populations,  a  greater  incidence in  females than  in

males (particularly  England  and Wales).   The male to  female  incidence

ratios  vary  from 1:1  to 1:1.2  in several studies  (McDonald,   1948;  Lee

et al.,  1971; Beardmore, 1972;  Shaw  et  al.,  1977; Sober et  al.,  1979;

Jensen  and Bolander,  1980).

     The differences  between  males  and  females  are  markedly  affected

by age  group; for instance,  E.  McDonald  (1948)  found  a  preponderance

of females in the under 40  year old age group.
                      |    Age    |  Male  |  Female
                      I           I        I
                      |  20 years |   2.9% |   6.270
                      I           I        I
                         20-40   |  12.2% |  22.6%
                                 I        I
                         40-60   |  44.8% |  32.2%
                                 I        I
                          60 +   |  40.1% |  39.0%

                         (From MacDonald, 1948;
                        Connecticut, 1935-1946)

                            F-l-111

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                                                        Effects—Skin Cancer
     Similarly, Beardmore (1972)  finds  in  Queensland,  Australia between



1963 and  1969 45% males  and 5.5%  females  with MM.   The age breakdown



is given below for the incidence of MM in  tropical  and  subtropical  areas



of Queensland:



                            Tropical	|  Subtropical
                   Age   | Male  | Female
Male |  Female
10 -
20 -
30 -
40 -
50 -
60 +
0.9 | 2.3
8.4
14.7
28.5
19.2
11.7
22.0
1.2 | 2.3
7.8
17.4
21.9 | 23.5
21.8
25.6
28.5 | 24.2 | 29.5
14.3
25.7
30.0
25.2
29.2
                Incidence/100,000 adjusted to Australia

                              population.



    Notable again is the preponderance  of young  females  (40 years old or



less), and  the  absence  in  increase  in MM as solar  intensity  increases



(i.e., tropical  vs.  subtropical  areas).



     The   age  difference becomes  even  more  striking  when one  examines



the various sites of  appearance  of  the different types of MM.  For in-



stance, Bakes and McMillan  (1973) report:   LMM,  11%,  age  group  affected



70 to  79; SSM,  50%,  age group affected,  40  to  49;  NMM 39%, age group



affected,  30  to 70.   Sober et  al.,  in 1130 cases  of MM,  found 69.6%



SSM,  15.7% NMM  and  4.7% LMM,  with mean  ages  of  47.3,  50.4 and  69.4 re-



spectively.   The most  extensive  analysis of site,  sex  and age  relation-



ships of  MM has  been carried out  by  Beardmore (1972).   It  is  instructive



to compare  the  sex and  site  analysis  in two widely separated  areas of


                                              o       o
the world - Queensland, Australia (latitude 28  to  17   south)  (Beardmore



1972)  and Finland  (latitude 60°  to 70°  north)  (Teppo et  al., 1978).



The data  are given  below:
                          F-l-112

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                                                            Effects—Skin  Cancer
     Some  of  the above  observations  can be  explained  on the basis of




the  different  biologic behavior of the  different  types  of MM.  LMM is




a very slowly progressing neoplasm,  developing over a period  of decades.




It  is  the most  common melanoma found  on  the face  and  neck  area, and




clearly related  to  chronic  solar  UVR  exposure, as evidence  by the  uni-




form presence  of dermal solar elastosis, and  frequent association  with




NMSC (Teppo  et  al.,  1978;  Larsen  and Crude,  1978).   This explains the




low  incidence  in younger  patients and  the  inexorable  continuing  rise




in  incidence in  older age.   The frequent location on the ears of males




(Beardmore,  1972)  is  also  due  to the  exposure  of this  area  in males,




given the hairstyles existing until  recently.




     The most  recent  and  fascinating  study  has been prepared  by Magnus




(Cancer,  in  press),  reviewing  the very extensive  MM  material  of the




Cancer Registry  of  Norway.   Between 1955 and  1977,  over  5000  new cases




of  MM  were registered,  allowing  significant  analyses according to co-




hort, sex, age and  primary  site.   Magnus finds:   a continuous, exponen-




tial rise  in the incidence  of  MM  over  three decades,   at the rate of




about 77o  per year;   a change in  incidence  over  time by  anatomic sites




in the most recent decade and a  striking cohort effect.




     Significant  changes  took place  between  the  1955 to  1970 and  1970




to  1977  periods.   There  was a reduction  in the  annual  percentage in-




crease  for  MM  of the trunk  in males coupled with an increase in  this




body site  in females,  and  the  reverse  was  found for MM of  the lower




limb.   In other words,  the  incidence  trends  for these  two sites  have




now become almost identical,  in contrast to  the  situation a  decade  ago.




     Magnus1  cohort   analysis  strikingly  shows  a marked cohort  variation




on  the  trunk  and  lower limb,  with the incidence being  higher  in the




younger generation.




                             F-l-114

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                                                           Effects—Skin  Canceq
     Also, the  incidence  in the  face/neck  area  is  markedly higher  in




persons born  1890-1909,  and lower  in  those  born in 1930-1939 than  the




incidence on trunk in males and lower leg in  females.




     Although Magnus  concludes  that  the most   likely  cause for  these




observations  is  a change  in  lifestyle,  leading to greater  exposure  to




solar radiation  in  the  younger cohorts,  he  warns that  there  can  hardly




be  a  simple  relationships  between  the  cumulative dose of sunlight  and




MM.   He points  out that  the predominant incidence  of  NMSC on the  face




of  old  people suggests that total  dose  rather  than intensity of  solar




radiation  is  essential.    However,  since it can reasonably  be assumed




that sun  exposure  to  the  face/neck  area is reasonably  stable  to  an  ad-




vanced age, and  since  the shape of  the  incidence curves for  trunk/lower




limb deviates from  that  of the face/neck,  this  must  imply  that the  car-




cinogenic  exposure  on  these   sites  can  not  be  stable,  but  increases




during adolescence and early life.   Thus in MM,  assuming UVR is causal,




it  is  not solely  a  question of accumulated dose, particularly in  view




of  the  almost total absence of  evidence of  solar elastosis  in the  ad-




jacent dermis, and  the  absence of association with NMSC (Teppo,  1978).




Thus, the pathogenesis of  NMSC  and MM skin cancer may be quite  different




as  far  as the role of solar radiation is concerned,  and the  latent per-




iod  for MM must  be significantly shorter than  that  of  NMSC  (Lee, 1972;




Elwood and Lee,  1975; Fears et  al.,  1976).




     The  striking  predilection of  SSM  to affet  the  legs of  women  and




backs of  men  is  not so easily  explained.   Since both,  and particularly




the  former,  appear  quite  early  in  life,  it  must  be   assumed that  the




precancerous  period  is short,   of the order  of a few  years.   Clearly,
                             F-l-115

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                                                         Effects—Skin Cancer
this  type  of  lesion  is not  reasonably  due  to chronic  repeated  solar




UVR exposure, particularly in view of  the  almost  total  absence  of evi-




dence  of  solar  elastosis  in the adjacent  dermis,  and the  absence  of




association with NMSC (Teppo  et  al., 1978).  The nature of the carcino-




genic process causing  this  most  common  type of MM is not obvious.
                           F-l-116

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                                                        Effects—Skin Cancer
               E.2.3  Race, Ethnic Extraction and Heredity




     The susceptibility of  Caucasians  with  fair, poorly tanning,  easily




sunburned  skin  to develop  nonmelanoma  skin cancer has  been  documented




frequently  (Molesworth,  1927;  Urbach  et  al.,   1976).   That  a  similar




effect  may exist  in malignant  melanoma has been  reported  in  various




ways.   Gellin  et  al. (1969) in a  case-control  study  showed that,  while




there was  no  significant  association with complexion  or ability  to tan,




there were significant  correlations of  malignant  melanoma with  light




eye color,  light  hair  and  estimated outdoor exposure.   However,  Gellin




et al. found that patients  with MM were much less likely to  have  another




skin  cancer  than patients  with  BCC, where development  of  another  skin




cancer was  very  frequent.   Bart and Scholl  (1973)  also found light  eye




color in malignant melanoma patients.




     Lane-Brown et al.  (1971,  1973) found a  disproportionate representa-




tion  of  persons  with a  Celtic genetic  heritage  among  malignant melanoma




patients  in Australia, with  50%  of malignant  melanoma patients  being




at  least  one-half Celtic extraction (as  compared  to  23 to 28% of  non-




cancer  controls).   This was as high as  the Celticity found  in NMSC  in




the same study.




     Among  non-Caucasians,  malignant  melanoma  is much less frequent




than  among white-skinned people,  Scotto  et  al.  (1974) reported an  inci-




dence in the U.S.  of 4.47/100,000 in whites,  and 0.8/100,000  in blacks.




Thus, the  incidence in  U.S.  blacks was  about  20% of  that  in whites,




a relatively much higher proportion than  that  found  for  NMSC.




     In   sharp  contrast  to  the  distribution in  whites,  non-Caucasians,




and blacks  in particular,  have  a very  high  incidence  of malignant  mela-




noma  on the  foot  (whites,  10-15%;  blacks, 60-75%;  Asians, 30-35%).










                          F-l-117

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                                                        Effects—Skin Cancer
Crombie  (1979)  in an  extensive  analysis of 59 population  based  regis-




tries, showed again that malignant melanoma occurs in Africans primarily




on the  foot.   He found marked heterogeneity among  the  nonwhite groups.




The tumors  in  Africans were mostly on the  lower  limb,  particularly  the




foot  (60-75%  of total  MM)  (Oettle,  1966;  Lewis,  1967; Davies, et al.,




1968;  Camain et al.,  1972).




     In Asian  populations 40%  of MM are of the acral  lentiginous type,




and are  rising  at  a  rate of 57G  per  year in reasonable  accord with wes-




tern  trends.   Haverkamp  and  Radman (1979) reviewed the experience  of




American blacks  - in  a series  of  reports dating  back  to  1939, 50  to




76.5% of all malignant melanoma  occurred on the  foot.   It has been sug-




gested  that  this  disproportionate incidence  on  the foot  is due to  a




relative absence of  nevus-cell nevi  on the skin  of  non-Caucasians,  ex-




cepting palms  and  soles (Coleman et al.,  1980; Van  Scott et  al., 1957;




Kenny,  personal communication).   Thus,  if nevus-cell  nevi  sometimes




are precursors  or  can  be stimulated to develop MM,  this  maldistribution




could in part account for this phenomenon.




     Instructive is  the recent report  of Hinds (1979) concerning inci-




dence in the non-Caucasian  population  of Hawaii.    In contrast  to rela-




tive incidence of 2.6% on feet in white males  and  2.7%, in white females,




the relative  incidence of  malignant  melanoma  in non-Caucasians  on  the




feet was 41.5%, for males and 21.7% for  females.




     Finally,  a  report by  El  Bolkainy  and Ebeid (1973) from  Egypt  is




instructive.   Egyptians  are racially Caucasians,  but are of much  darker




skin color  than  Europeans.   In spite of the high  solar  exposure of most




inhabitants, malignant melanoma  appears to be  rare in Egypt.   As  in
                            F-l-118

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                                                         Effects—Skin Cancer
non-Caucasians, 43%  of malignant melanomas  occurred on  the  feet.    In




contrast  to  blacks,  where  malignant  melanoma is  rare  on the head  and




neck, 26%,  occurred  in  this area, about the same  as in whites.  However,




in  contrast  to  whites,   lentigo  maligna melanoma  is rarely,  if ever,




encountered  in Egypt.   Since  this  latter lesion  is the one commonly




associated with  chronic  UVR exposure  in whites,  it appears  that  the




heavy pigmentation of  the  Egyptians  protects  their skin (also  evidenced




by  the  rarity  of NMSC in  native Egyptians).   If that  is the case,  it




is  difficult  to  conclude  that  the  other malignant melanoma of  the  ex-




posed head and neck skin are due to  solar UVR.




     There is  now clear  evidence that a real genetic  element is among




the factors responsible  for the causation of  malignant  melanoma.  Esti-




mates for 6 to 11% of malignant  melanoma lesions  to be of  genetic  origin




have been  made by various authors (Andersen  et  al.,  1970,  1971;  Wallace




and  Exton, 1972; Wallace  et  al.,  1973).   Familial patients manifest




a younger age distribution, a significantly earlier average  age at first




diagnosis, increased frequency  of multiple primary melanomas and a sig-




nificantly higher survival  rate.   The  genetic  mechanisms underlying




the  familial  type  of  melanoma  is  apparently  complex  and may  involve




several  autosomal  gene  loci,   in  addition to  a  cytoplasmic  component




transmitted by  an  affected or  carrier  female.    Neither  the  site  nor




the  type  of  lesion  is  specific, except  that   patients  with familial




malignant melanoma and their  relations seem  to  have  distinctive  melano-




cytic nevi, designated by  Clark et  al. (1978) the "B-K mole syndrome."




Such peculiar  nevi  begin  in  childhood,  but  the progressive cellular




atypia  described  occurs later,  possibly because  such  genetically  altered
                             F-l-119

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                                                        Effects—Skin  Cancer
nevi  are  more  susceptible  to neoplastic transformation than the common




acquired melanocytic nevi.   There are  doubtless  other  phenotypes associ-




ated  with familial  melanoma,  and  additional  studies need  to  be done




before this syndrome can be understood.




     However, the various  hereditary  and  ethnic factors affecting  inci-




dence and distribution of malignant  melanoma  can not  be  only or even




primarily  related  to the  effect  of UVR  on  the skin.   Although   it is




tempting  to  read  into the  lesser frequency of  malignant  melanoma in




non-Caucasians the  simplistic  idea that  such  is due  to  protection by




pigment,  clearly  the matter is  more  complicated.   The  very high fre-




quency of  malignant  melanoma on  the feet  of non-Caucasians, the normal




distribution of malignant  melanoma  on  the head  and neck of  pigment pro-




tected Egyptians and  the  frequency  of familial  incidence are not easily




explainable in this fashion.




     Furthermore,  American blacks have  lower rates than American whites




for  MM  of  the  ureal  tract  and  the  mucous membranes  (Scotto  et al.,




1976).
                           F-l-120

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                                                         Effects—Skin Cancer
        E.2.4  Malignant Melanoma and Exposure to Chemical Agents


     The  evidence  for a causal association between chemical  agents  and


MM is meager.  Isolated cases or small clusters of MM  apparently related


to exposure  to  a variety of chemical agents  have  been reported.  Levo-


dopa  used for  therapy  of  Parkinson's   disease  has been  incriminated,


primarily  because  it  is  a  common intermediate  in the biosynthesis  of


catecholamines and melanins.   Skibba et al.  (1972) reported   a patient


who developed a  recurrence  of  previously excised MM,   and  multiple  pig-


mented  skin   lesions,  some  of which  were histologically primary  MM.


On the other hand,  Sober and Wick (1978) found only one patient of  1,099


MM cases  of  the  melanoma cooperative group who ingested Levodopa.   They


concluded  that  if  this  drug  played  a  part in the induction  of MM,  it


must be inconsequential.


     Beral et  al.  (1977) noted  higher   incidence  rates  of MM  in women


who had  used contraceptives,  particularly longterm users.   They  sug-


gested that  the  known effect  of estrogen,  augmented by the simultaneous


administration of  progesterones,  as  stimulant of melanogenesis  was  the


effective mechanism.


     More  recently,  Bahn et al.  (1976) found a  very  small MM  cluster
                                   f

(2/31  exposed) in men heavily  exposed to PCBs.  However,  further study


of this  possible carcinogenic  association is warranted,  and the  epi-


demiological  significance of  this  apparent relationship between MM  and


occupational  exposures to chemicals is not  known.


     Pell et  al. (1978)  in  a  careful and detailed  study of cancer inci-


dence  and mortality  in  the  DuPont  Company found a  significant  increase


in the  standardized  incidence  ratio for  MM  in male  employees (SIR =
                              F-l-121

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                                                        Effects—Skin  Cancer
123).   This held for both  wage  and salaried employees.   While the  SIR




for females was also increased,  it did not  reach  levels of significance,




lagging considerably behind cancer of the cervix  and  leukemia.




     The  excess  of  incidence in  male  employees  was slightly greater




in  the  salaried  group.   One possible explanation offered was the  com-




paratively  high  concentration  of  employees  in  the  southeastern U.S.,




where mortality from MM is especially high.




     Of interest also  is  that the standardized mortality  ratio was  sig-




nificantly  less .than  expected in males,  and less,  but not significantly




so, in females.




     It may  be suggested  that this phenomenon is  due  to  early recogni-




tion and treatment of lesions.




     No  discernible  relationship  to  any  specific  chemical  agent   was




found in this study.




           E.2.5  Geographic  Distribution of Malignant Melanoma




     The  two major  findings  that  support  the contention  that  NMSC  is




primarily caused by chronic  exposure to  solar UVR  are the anatomic  dis-




tribution of  the cancers  (on sun exposed  areas)  and  the  striking lati-




tude gradient of  their incidence.




     It has  been  pointed  out in a  previous  section that the anatomic




distribution of MM does not clearly parallel the  presumed  sites of maxi-




mum solar exposure.   In  the case of one  type of  MM,  LMM,  the  character-




istics of  age distribution,  anatomic  distribution and histologic  evi-




dence of solar connective  tissue damage all  seem,  for  practical purposes,




to be  identical to  the  features of squamous cell carcinoma  of the skin.




It must  thus be assumed  that solar  UVR exposure is the primary cause




of LMM. However, this then applies to only  about  10% of  MM  (Larsen and




Crude, 1979).




                             F-l-122

-------
                                                         Effects—Skin  Cancer
     Cutchis  (1978)  was one  of  the first  to  point out  that  the geo-




graphic distribution  of MM,  reported  in  Vol.  Ill  of  Cancer Incidence




in Five  Continents  (Doll et  al.,  1976)  shows  significant anomalies if




the assumption is made  that  exposure  to  solar  UVR  is the most signifi-




cant  factor in the causation of MM.




     The major  discrepancies found  at that  time  were  the relatively




large incidence of MM in the Scandinavian  countries, particularly Norway




(Magnus, 1975,  1977)  and Sweden  (Malec and Eklund, 1978),  the lack of




any evidence  for  a  latitude  gradient  (or  even  a  reversal  from the usual




N/S  increase)  for central European countries  (Crombie,  1979);  and the




peculiar male-female  ratio  for  MM, which usually remains below unity,




in sharp  contrast  to  NMSC,  where  the M/F ratio  exceeds  4:1  or more




(Urbach, 1972).




     The data described above have been accumulated  by the International




Agency  for  Research  in  Cancer (Doll et al., 1976) from worldwide cancer




registries.   They certainly  represent  information based on  various time




periods  and  acquired  by different means.   Since  the  incidence  of MM




has  been  rising  sharply  world  wide,   it  may  not be  too  surprising if




these data did not represent strictly  comparable  enumerations.




     If solar UVR is the primary cause of  MM,  then,  as  in NMSC, there




should  exist  recognizable latitude  gradients for the  incidence and mor-




tality  of MM,  with  rates increasing toward the  tropics.   The existence




of such latitude gradients has been  reported from Norway (Magnus, 1975),




Sweden  (Magnus,  1977; Eklund and  Malec,  1978),  Finland (Teppo et al.,




1978),  and the  U.S.A.  (Cutler  and Young,  1975; Fears et  al.,  1976).




     There  are,  however,  inconsistencies  in a number of these studies




which  have  recently  been noticed.   Of major  importance  have been the











                             F-l-123

-------
                                                        Effects—Skin Cancer
observations that major  cities  show  a .disproportionately  high  incidence




of MM,  which could  not  be explained on  latitude alone,  and  that most




Nordic  countries  show incidence rates  for  MM greater  than can be  ex-




pected  based on  their  latitude  (Lee and  Issenberg,  1972; Eklund  and




Malec,  1978; Crombie,  1979; Viola  and Houghton,  1978; Houghton et al.,




1980; Jensen and Bolander, 1980).




     For  instance,  Teppo  et  al.  (1978)  found  a distinct  north-south




gradient  for MM incidence along  Finland,  with the incidence  rates  30%




or more greater  in  the south  of that country.   However,  when  the  inci-




dence rates were adjusted to  urban/rural  population ratios,  the latitude




gradient  markedly  diminished for  the 1953-59 time  period, and disap-




peared  for  1961-73.    They concluded  that  there  was a marked  effect  of




urbanization and that  factors other  than latitude operate.   Eklund  and




Malec (1978) performed an epidemiologic  study similar to that  of  Teppo




(1978)  and  Magnus  (1975, 1977).   Their major  findings  were:  Sweden




has  a much  higher  incidence  rate for MM  than  central  Europe.   There




was  a distinct  north/south gradient  along  Sweden, but the  major cities




had  a  disproportionately high  incidence of  MM.   The difference in  the




cities  was  primarily due  to  increases  of MM of the  trunk and arms  of




men and the arms and legs of women.   There was no disparity  in  incidence




of MM of  the head and neck between  rural  and city areas.  The differ-




ences could not be explained  on  latitude  alone.




     In contrast to the above, Beardmore  (1972) and Little et al. (1980)




noted that in Queensland, Australia,  MM was  more  frequent  in subtropical




than in tropical  areas,  and  Holman noted a  reverse gradient (i.e., away




from  the  equator)  in  Western Australia.   This finding was  ascribed  to




the above noted increased incidence of MM in  large cities.









                            F-l-124

-------
                                                            Effects—Skin Cancel
     Most recently, Crombie  examined  data  from a large series  of  tumor




registries for Europe  (Doll  et  al.,  1976)  and concluded  that  the  inci-




dence  of  MM  increased with  increasing latitude in central  Europe  from




Italy  to  Germany,  the reverse  of  that  found in England  and Wales,  the




Nordic countries  and  the U.S.A.   He  investigated  possible  confounding




effects and  concluded  that  the  result was  highly  significant and  not




due  to  confounding factors.    He also noted the apparently  excessively




high  incidence  of MM  in  Scandinavia  and  the  excess found  in  large




cities.   Crombie  concluded  that  this  latitude  reversal  may be due to




darker pigmentation of  southern Europeans'  skin,  but pointed  out  that




the  effect of  change  in susceptibility would  have  to be very  large to




overcome a latitude effect.




     Jensen and Bolander (1980)  reviewed again the  IARC  and  newer  inci-




dence data.   They  comment on  great  variation  in incidence  of  MM by  coun-




try, the low  incidence  in countries with predominantly pigmented inhabi-




tants and point out that there  are latitude gradients within  countries




(England  and  Wale's, Sweden, Canada,  U.S.,  Norway)  which  increase as




latitude decreases and  exceptions to  this phenomenon (Western Australia,




Texas, Finland)  (Table  18).




     Lee  (1977) was the first  to  point out a  peculiar  association of




incidence of MM with certain,  unexpected,  occupational groups.  He  ob-




served, first  in   England and  Wales,  that  the occupational  groups  that




suffered the highest mortality  from  melanomas  of the  skin were clerical




and  professional  workers  and   their  wives.    This  initial  finding  has




been confirmed by  Viola  and  Houghton (1978)  for Connecticut,  by Holman




et al. (1980) for  Western Australia and summarized  by  Lee  and Strickland




(1980).












                             F-l-125

-------
                                                                               Effects—Skin Cancer
                Am
                Zone
 M*le*
Hommn
Femil**
Femmn
AFRICA,—AFRIQUE

Nigeria, Ibadan — Nigeria, Ibadan
South Africa, Cape
Afrique du Sud, Le Cap
  White —Blancs	
  Coloured—Metis	
  Bantu—Bantous  	,
Natal
  African—Africains	,
  Indian — Indiens	
Southern Rhodesia, Bulawayo (African) .
Rhodesia du Sud. Bulawayo (Africains)
AMERICA — AMERIOUE

Brazil — Bresil
  Recife	
  S3o Paulo  	
  0.9
  3.1
  0.2
  0.7

  0.8
  0.9
  3.0
Canada
  Alberta	
  British Columbia 	
  Colombia britannique
  Manitoba	
  Maritime Provinces	
  Provinces maritimes
  Newfoundland—Terre-Neuve
  Quebec—Quebec 	
  Saskatchewan  	
Colombia, Cali —Colombie, Cat!
Cuba	
Jamaica,Kingston ..<	
JamaTque, Kingston
United States of America
Etats-Unis d'Amerique
  Alameda, White—Blancs  	
           Black—Noirs	
  Connecticut  	.'	
  Detroit — Detroit       '
    White—Blancs	
    Black—Noirs	
  El Paso
    Spanish—Espagnols 	
    Other White—Autres Blancs 	
  Hawaii
    Hawaiian—Hawaiiens  	
    Caucasian—Caucasians  	
    Chinese—Chinois 	
    Filipino—Philippins  	
    Japanese—Japonais 	
  Jpwa  	
  New Mexico — Nouveau-Mexique
    Spanish — Espagnols 	
    Other White—Autres Blancs 	
    Arher. Indian — Indiens d'Amerique
  New York State — Etat de New York .
  Puerto Rico—Porto Rico	
  San.Francisco Bay Area
  Bate de San Francisco
    White—Blancs	
    Black—Noirs	
    Chinese—Chinois 	
  Utah 	
 ASIA — ASIE
 India.Bombay—Inde.Bombay  .....
 Israel — Israel
  All Jews—Population juivetotale
  Bom in Israel—Natifs d'lsrael ....
  1.6
  2.2

  2.2
  3.6

  2.6
  2.0

  1.6
  1.4
  23
  2.1
  0.5
  1.4
  5.4
  0.7
  45

  2.7
  0.5

  0.0
  3.8

  0.9
  6.8
  0.0
  0.3
  0.3
  3.2

  0.8
  4.8
  0.7
  3.4
  0.7
  6.3
  0.9
  0.7
  55
  0.2

  3.4
  4.7
  2.2
 5.2
 1.0
 3.3

 2.4
 0.0
 2.6
  1.2
  13

  2.7
  4.8

  3.4
  2.7

  1.9
  13
  3.4
  2.0
  0.3
  1.1
  5.9
  0.5
  4.3

  3.1
  0.6

  1.0
  4.8

  1.0
  5.7
  0.0
  0.0
  0.3
  2.7

  0.9
  5.3
  1.2
  3.0
  0.8
  6.6
  0.6
  0.0
  5.1
  0.2

  4.5
  7.0
Ana
Zone
ASIA(concl.) — ASIE(fin)
Israel IconcU — Israel (fin)
Born in Europe or in America 	
Natifs d'Europe ou d'Amerique
Born in Asia or in Africa 	 	
Natifs d'Asie ou d'Afrique
Non-Jews — Non-Juifs 	
Japan — Japon
Miyagi 	 	 	
Okayama 	
Osaka 	 	 	
Singapore — Singapour
Chinese — Chinois 	
Malay — Malais 	 .'.'.....
Indian — Indiens 	
EUROPE
Denmark — Danemark 	
Finland — Finlande ..' 	
German Democratic Republic 	
Republique dsmocratique allamande
Germany, Federal Republic of
Allemagne. Republique federate d'

Saarland — Sarre 	
Hungary — Hongrie
Szabotcs 	
Vas 	 •- 	
Iceland — Islands 	
Malta — Malte 	 	

Urban — Population urbaine 	
Rural — Population rurale 	
Poland — Pologne
Cieszyn, Nowy Sacz 	
Cracow — Cracovie 	
Katowice 	
Warsaw, City — Varsovie, ville 	
Warsaw, Rural — Varsovie. campagne
Romania — Roumanie
Timis 	 .' 	
Spain — Espagne
Zaragoza — Saragosse 	
Sweden — Suede 	 	
Switzerland — Suisse
Geneva — Geneve 	 	
United Kingdom — Royaume-Uni

Oxford 	
Sheffield 	
South Metropolitan Cancer Registry . .
Registre sud-metropolilain du cancer
SouthWest— Sud-Ouest 	
Liverpool 	 	
Ayrshire 	 	
Yugoslavia — Yougoslavie
Slovenia — Slovenie 	
MJI«»
Homm<»


3.4

0.9

0.7

0.3
0.1
0.3

0.6
0.4
0.4

2.9
23
2.1



2.4
2.3

1.6
1.8
1.6
05
5.4
6.7
4.5

0.6
1.7
1.2
2.3
03

IS

0.3
4.1

33

1.3 '
2.2
1.1
1.6

1.6
0.9
2.0

13
Fem^j
FBmr^


4.8

05

0.1

0.1
0.0
0.2

0.3
0.0
0.9

43
2.8
2.3



1.3
2.3

1.4
2.1
3.6
0.9
5.7
65
5.1

2.5
2.0
15
2.1
0.3

1.4

0.3
- 43

13

2.2
3.1
15
23

4.0
2.0
23

23
                         OCEANIA — OCEANIE

                         New Zealand — NouveHe-Zelande
                          Maori—Maoris	   1-9
                          Non-Maori—Non-Maoris	   9.4
• World Standard ?opulJt:on (DOLL. R. ET Al_ 19701. and
 Sowct: WATERNOUSE. J. ET At, 1976).
                                                                                                            15
                                                                                                           11.7
     Table   18.    Age  standardized  incidence  rates  of  malignant  melanoma  of
     skin.   (From Jensen and Bolander, 1980.)

                                          F-l-126

-------
                                                          Effects—Skin Cancer
     The  size  and consistency  of  the  relationship of MM risks to  some
                                                   i

factors  associated  with better  education,  high social status, or  more


money,  and  the presence  of  the relationship  in  both employed men  and


among  their  wives suggest that  the effect  is  real.   It suggests  that


the relationship  is  a  biological one between MM incidence and some  fea-


ture of  life  associated with education or economic status.   It may  also


explain  the  above noted preponderance  of MM incidence to large cities,


since  the more affluent  are more  likely  to live  in  cities and their


suburbs.


     Teppo,  Pukkala  et  al. (1980) in a remarkable  study of the relation-


ship of  "Way  of  Life and Cancer Incidence  in  Finland"  confirm the  pre-


dominance of  MM  in  the towns and  low  rates in rural  areas.  They  show


a  consistently  positive  association  with parameters  describing   the


socioeconomic  level  of the  municipality,  particularly for  MM in rural


areas.   A negative  association  was seen  between  farming  and forestry


and MM.


     In contrast,  for cancer  of the lip (the best  reported form of NMSC)


a strong  inverse  association was seen between the  incidence  of lip  can-


cer  and  that  describing the  standard of  living  of  the municipality.


No  other primary  cancer site displayed suchstrong negative  associations


than  that found  for lip  cancer.   The risk for lip cancer was highest


in  the  farming,  forestry and  fishing occupations, and in rural areas.


Thus  a  striking  difference  between MM and lip cancer was  found as  far


as income, city dwelling and  outdoor occupations are concerned.


     It  has  been  previously   pointed  out that  the incidence of MM  has


been rising  rapidly  in white populations for many years.   For example,
                          F-l-127

-------
                                                         Effects—Skin  Cancer
in  Norway  a continuous rise  in  incidence of about  7°/c per year has been




observed since  1955  (Magnus,  1980).   A major component  of  the  causation




of  this  rising incidence  is  a systematic  increase  in  risk of  succes-




sively later born  cohorts  (Lee and Carter,  1970; Elwood and Lee,  1974;




Magnus, 1975;  Eklund  and  Malec,  1978;  Lee,  et al.,  1979; Holman  et al.,




1980).  This cohort  increase  began as early  as  the  last quarter of  the




nineteenth  century  in Australia  (Holman  et al., 1980)  and about 1900




in  Norway  (Magnus, 1975).   It is  of  interest that cohorts born  since




1925-30 show  a stabilization  of  this increased risk,  but at a higher




rate  (Elwood  and  Lee,  1975;  Holman et  al. ,  1980).  The   increase  and




cohort variations  seem to  be much greater  for MM  of  trunk and  lower




limbs than  for  MM  of  the face-neck area (Magnus,  1980).  This  indicates




that  the  trend in carcinogenic  exposure  through life may  be  different




for face-neck and trunk-leg areas.  Why people born  5 years  later should




go  through  life with  a  substantial increase  in  risk of dying  from MM




compared with   their  elder peers  in  the  same  population  is not  known




(Lee et al.  , 1979).




                   E.2.6   Sun Exposure and  Risk of MM




     In addition  to  the   above  described  geographic variations of MM




incidence and  mortality,  several other observations have  been proposed




so as to relate the risk of MM development to sunlight exposure.




     Anaise et  al. (1977)  and Movshovitz  and Modan  (1973)  reported that




MM was found more  frequently  in European Jews  than  in  African or Asian




Jews  in Israel;  that  the  incidence was higher in Israeli born, European




descended Jews than  recent  immigrants and  attributed  this to  greater




UV exposure in  a  sunny country.   However,  Hinds and Kolonel (1980)  and
                           F-l-128

-------
                                                         Effects—Skin Cancer
Holman  et  al.  (1980)  noted  reverse  conditions,  i.e.  more MM in  recent




immigrants  to  Hawaii  or Western  Australia  than  in  the  native  born,




European  descendants.   Houghton et  al.  (1978) noted a cyclic  increase




in  MM  superimposed  on  the  previously reported continuing  rise in MM




incidence  two  to three  years  after  sunspot  maxima in Connecticut, New




York and Finland, but not in Norway.   Wigle (1978)  confirmed  this  obser-




vation  in Canada.   Houghton  et  al.  ascribed  this  to  a  decrease in




stratospheric  ozone  associated with  increases in galactic cosmic  rays.




They  suggested ozone  decreases  of the order  of 1 to  3% secondary to




sunspot  influence.    However,  no  such evidence of  ozone decrease has




been  observed  in the  long  term Dobson measurements reported by  London




(1980),  nor  have such  changes  in  ozone  been noted in association  with




sunspot activity (London and Reber, 1979).




     Scotto and  Nam  (1980)  observed  a strong seasonal pattern with sum-




mertime peaks  for MM of females (particularly legs),  and  a similar peak




for MM  of upper  extremities of men.    This was also noted by Malec and




Eklund  (1978).




     On  the  other  hand, Leach  et al.  (1978) observed:   A consistent




increase  in  stratospheric  ozone over  England (in  keeping with the re-




sults of  London, 1980), an  accompanying   fall in  NMSC  in Bristol, but




a  steadily  rising incidence of  MM opposite  to  the ozone concentration




in the stratosphere.




     It  has  been suggested  by  a number  of observers (Lee,  1972;  Fears




et  al.,  1976;  Magnus,  1975,  1980) that the  increase in the incidence




of  MM,  particularly among the  affluent  population in  the  cities, may




be  due  to unaccustomed, intermittent  overexposure  to sunlight  on  vaca-




tions, weekends, etc.   Furthermore,  the changes  in  clothing  and outdoor












                            F-l-129

-------
                                                         Effects—Skin  Cancer
recreation  habits  in the  decades  since World War  II would allow more




exposure  (men  going shirtless,  women with  shorter  skirts  and nylon




stockings, more sun exposure for cosmetic  tanning  purposes,  etc.).




     To  test  this  hypothesis,  Eklund and Malec (1978) investigated  the




issuance  of  passports in  Sweden,  reasoning that  to get to a sunny area




one had  to  leave Sweden and go  south.   Indeed,  it was found that more




passports were  issued in  cities than in rural  areas,  but  the difference




in passport  issue  could  at  most explain  25%  of  the increase  of MM  in




Swedish  cities.   Furthermore,  Brodthagen  (personal communication)   in-




vestigated  the  frequency  of Danes participating  in charter tours since




1950  (Fig.  11), the number  of  persons  in  organized tours of more than




three  days'  duration traveling  to  areas  35   to  40   latitude  by year




since  1970  (Fig.  12),  and  the  number of persons traveling to various




areas  on  these  tours (Fig.  13).  As can be seen,  the  frequency of Danes




leaving  the  country  has   increased  dramatically  (Fig.  11),  but there




has been little change in the past decade  in  those  going to  sunny areas,




the greatest  increase had  been  in travelers  to England (i.e., the same




latitude),  probably  because of  favorable  foreign  money  exchange.    It




thus  appears  that  greater  exposure  to  sunlight  in the south,  at least




for Danes,  is not  likely  to be  the  major cause  of the  increase in  MM




incidence.




     In  summary,  it  appears that  the pathogenesis of NMSC and MM  may




be quite  different   as  far  as  the  role of UVR is concerned.   The pre-




dominance of  NMSC  on the  head  and  neck of older persons strongly sug-




gests that cumulative, total UVR does is involved.   The relatively early




onset  and different  distribution  of MM, as well  as the secular changes
                             F-l-130

-------
                                            Effects—Skin Cancer
Number of Persons on Charter Tours from Denmark
        (Company:  Sterling Airways Ltd.)

     Log Scale
   10x10 -
                                     614,507
            50  54  58  62  66  70  74 78 YEAR
                   Figure  11
               F-l-131

-------
                                         Effects—Skin Cancer
     Number of Persons  in Organized Tours
         (duration more  than  3 days)
number x 10
     i

  400-

  350-

  300-

  250-

  200-

  150-

  100-

   50
Latitude 35-40°
                      'Spain
                                   Yugoslavia
       70  71  72  73  74  75  76   77  YEAR
                    Figure 12
                  F-l-132

-------
                                                   Effects—Skin  Cancer
number xlO
    12-

    10-


    8-

    6-

    4


    2
          sr=r--: Latitude 25-35u
          -.-•-:- Latitude 45°
                 Latitude 45-50°
     ,England
    .-Austria
 "**--Africa
	 France
  ^-Middle East
              1 - 1
                         [— —  i     i     i     i
        70   71    72   73   74   75   76    77  YEAR
                          Figure 13
                        F-l-133

-------
                                                           Effects—Skin Cancer
described above  (cohort  effects),  strongly  suggest  that  the  latent  per-




iod for MM  is  very much shorter than that  for  NMSC (Lee,  1972;  Magnus,




1980).




     Lee  (1972)  in an  elegant  analysis of the potential mechanisms  of




MM induction suggested:




     (1)  that  the  causative  mechanism  for  MM is complex and  specific,




          and  certainly  not  "chronic irritation" (i.e., cumulative UVR




          damage);




     (2)  that  exposure  to the  eliciting agent  operates  with  a  short




          latent  period, so that MM  develops  in the susceptible  persons




          reasonably  soon  after  they have  a  possibility of  developing




          the tumor




     (3)  that  either  a "systemic agent"  which operates at  a  distance




          is involved, or  that  the skin of  susceptible persons  contains




          "dominant  precursors,"   i.e.  something akin to premalignant




          clones  of cells  that  are stimulated into  fully developed  can-




          cers  by an environmental  agent,  of which UVR may  be  one.




     In  summary,  the  geographic   variation of  the  incidence  of MM  is




not nearly as clear-cut as is  that  of NMSC.  While there  are  respectable




latitude  gradients  within  some  countries, these  are  affected by the




very  real  increase in MM  incidence  in big  cities, which, at  least  in




Scandinavia, are  located  in  the  southern  portions  of the  countries.




In contrast to  this is a reverse latitude  gradient along  central  Europe,




which  appears  to be real.  Further  studies will  be needed to  sort out




the degree  to  which exposure  to solar radiation  is  responsible  for the




development of  MM.
                             F-l-134

-------
                                                         Effects—skin
             E.3.   Experimental  Models  for  Malignant Melanoma




     Although malignant melanoma occurs spontaneously  in  most  vertebrate




animals,  only  a  few experimental models  exist,  of which  only in  one




case the induction of MM has been associated with  UVR.




     The genetic  regulation of MM has been studied in the platy  fish,




in which  a tumor  producing gene and  associated  regulatory genes  have




been identified (Vielkind,  1976),  in  the  Sinclair  swine  system,  in




which  the  development  of  MM is  also  genetically determined  (Millikan




et  al., 1974).   In neither case  is  the  development  of MM  associated




with exposure to UVR.




     What  appears  to be a  realistic model  for  MM has been reported  by




Pawlovski  et al.  (1980).   40%  of 65  albino guinea pigs,  painted chroni-




cally with 7,12 dimethylbenzanthracene  (a known, potent skin carcinogen)




developed metastasizing MM  which  apparently arose by  a malignant trans-




formation  of carcinogen  induced  junctional  nevi.   The  clinical  and his-




tological events leading to the  development of MM  were  found to  be  quite




similar to human  MM in most aspects.  No  UVR exposure was  used in this




system.




     Melanomas have been induced in  several  different  rodent   systems.




     Isolated  lesions  of  MM were produced by  carcinogen  painting  of




skin  in guinea pigs  by  Berenblum (1949).   In  the  studies of  Edgcomb




and Mitchelich (1963)  and  Clark  et  al.  (1976),  again, no UVR was  used.




     The neonatal  administration of  urethane caused  a  high  incidence




of melanoma  in non-inbred Syrian hamsters  (presumably malignant trans-




formation  of  the  "pigment  spot" in these  animals)  (Vessilinovitch  et




al., 1970).
                               F-l-135

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                                                          Effects—Skin  Cancer
     In mice, two  reports  of  what  appears  to be UVR related production




of MM have  appeared.   Epstein et  al.  (1967)  induced "blue nevi" in pig-




mented hairless  mice  by painting with a single  dose  of DMBA,  and pro-




moted with  chronic  administration of  UVR.   They produced many squamous




cell cancers, and  late  in  the life  of the treated animals very few lo-




cally invasive  MM  lesions appeared.   Kripke  (1979)  reported that 1 of




40 animals  used  in  a  modified initiation-promotion experiment developed




a pigmented  lesion, apparently a  MM.   In this experiment, UVR was used




as initiator and croton oil as promoter (basically the reverse situation




from Epstein et  al.'s  experiment, where  carcinogenesis was induced with




a chemical [DMBA] and  UVR was  used as  "promoter"  ).




     Finally, Kripke   and  Lill  (1979)  have  observed  potentiation  of




growth rate  to  a  B16  melanoma line  in  UVR  treated  mice.   This  effect




could be  due to  immunologic  alteration of the host animals,  as has been




reported by Kripke  (1977) for  UVR  induced skin sarcomas.
                                F-l-136

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                                                          Effects—Skin  Cancer
             F.I.    Forecasting  the  Effects  of  a  5-year Delay




                in Regulation of CFC Emission in the U.S.




     Even  assuming  that the  data  given in  the NAS report  are  correct




(and  it  appears  that  due  to recent changes  the  overall depletion  of




ozone  and  increases  in  DUV are overestimated), the effect  of a  5-year




delay  in regulation of CFC emissions in the United  States  on  skin  cancer




incidence is not likely to be noticeable.




     In DuPont's comments  (DuPont,  1980)  on the NAS report (NAS,  1979),




an  appendix  A calculated  the differential  ozone  depletion  which  would




follow a ban on all production of CFC-11 and CFC-12 in  the United  States




in  1980 or  1985.   The  calculation  assumes  continued constant  emissions




abroad, and  calculates that  U.S.  emissions would  reduce  gradually  and




terminate 20  years  after  the ban.   The appendix follows  (Section  F.I.I,




pp. F-l-140 to F-l-154) and  contains details of  the calculation  method-




ology and results.




     The calculation  shows  that the  difference due to  a 5-year  delay




is  always  small.    During  the first 30 years  (to  2010),  the  difference




in  ozone  depletion increases to  0.2%,  and  thereafter slowly  declines,




by 2100 the difference due to the 5-year delay  is 0.06%.




     DuPont used the  Setlow DNA action spectrum (by analogy to  the  NAS




procedure)   to  calculate   the  incremental   DUV from the  5-year  delay.




The  incremental  DUV  from  a 5-year delay  changes  with the  incremental




ozone  depletion,  reaching a  maximum  of 0.6%  by 2010  and declining  to




0.2%, by  2100.  For  the reasons discussed  in  Section C,  this  overesti-




mates the effective DUV.
                         F-l-137

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                                                         Effects—Skin Cancer
     In  Section  D.2.5 we  noted  that existing data  indicates  that  NMSC




incidence is increasing by 2-3% per year.




     Using  the  2-fold biological  amplification  factor - again  a  worst




case "model"  which overestimates  any  calculated changes in NMSC  inci-




dence due to  ozone depletion and DUV increase -  the incremental effect




due  to  the  5-year  delay  may be  crudely translated  into an  increase  in




NMSC which  gradually  increases  to 1.2% over the  period 1980-2010 (while




the  estimated present trend would presumably increase  incidence by  60-




90%, at  2-3%  per  year),  and then  declines through  the  rest  of  the




twenty-first century  (while  the  present trend would presumably increase




incidence by a further 180-270%). <•




     The  natural  variations  are such  that  analyses of NMSC  incidence




figures  over many  years  are necessary to  detect  and quantify the exist-




ing  incidence trend of  2-3% per year.  A  superimposed increase  of less




than 1%  in  the  incidence of NMSC  over a human  lifetime would  be  lost




in the natural variations and would not be discernible.




     For the reasons  given in Section E of the  text, it is  not possible




to  relate  any change in  MM  incidence  to  the small  change in  DUV  which




would be  associated with  the 5-year delay.  MM  incidence  is  also rising




worldwide at a  rate of  3-7%, and  as  for  NMSC,  these increases in  inci-




dence are  in  the  absence of any  measurable decrease  in  stratospheric




ozone.
*It  should be  immediately evident  that this  use  of statistical  data




is  not  appropriate  from  any  rigorous  statistical  or  epidemiological




viewpoint.   It does,  however,  indicate the  relative  magnitude of  the




effect  of  current trends  compared  with changes  in  incidence  due  to  a




small increase in DUV.



                           F-l-138

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                                                        Effects—Skin Cancer
     Thus,  the  calculated  effect  of  a  5-year  delay in regulation of




U.S.  emissions of  CFCs,  even  if it were  to  actually occur, would not




produce noticeable  increases in MM  or NMSC  incidence.
                            F-l-139

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                                                Effects—Skin Cancer
F.I.I  DuPont's  Comments on the Report by the Committee




    on  Impacts of Stratospheric Change (CISC)  of  the




             National Academy of  Sciences




      (E.  I.  DuPont  de Nemours & Co., Inc., 1980)




                      Appendix A




  Effect on Calculated Ozone Depletion of a Five-Year




 Postponement in U.S. Regulation of Chlorofluorocarbons
                     F-l-140

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                                                    Effects—Skin Cancer
                           VI.  APPENDIX

        Effect on Calculated Ozone Depletion of a Five-Year
    Postponement in U.S. Regulation of Chlorofluorocarbons (CFC)


          The Du Pont one-dimensional atmospheric model has been
used to calculate the changes in ozone concentration and flux of
damaging ultraviolet radiation (DUV) predicted to result from
emissions of CFC-11 and -12 for the following three scenarios:

          Case A.  Continued release at 1978 levels.

          Case B.  U.S. production halted at the end of 1980.

          Case C.  U.S. production halted at the end of 1985.

The calculations permit the determination, as a function of time, of
the differences in calculated ozone depletion and in DUV flux which
would result from a five-year postponement in a ban on U.S. fluoro-
carbon production.  Cumulative dosage information is also available
from the calculations.

1.  Results and Discussion

    A.  Ozone Depletion

          Calculated cumulative ozone depletion for the three cases
is presented graphically in Appendix Figure 1 [p. 25]  through the
year 2080.  A U.S. cutoff is seen to reduce the calculated depletion
by an amount which increases slowly until the steady state values
(asymptotes) are reached.  The difference between Cases B and C
reaches a maximum at about 2010 and decreases thereafter.  The lat-
ter two cases are identical at steady state.  This is seen more
clearly in Appendix Figure 2  [p. 26], where the calculated additional
ozone depletion due to a five-year postponement is plotted by year.
The maximum difference in calculated ozone depletion is 0.2 percent,
from 5.7 percent to 5.9 percent, in the year 2010.  By 2080,  a U.S.
cutoff in 1985 is calculated to lead to 0.08 percent more ozone
depletion than the 9.2 percent calculated for a cutoff after 1980.

    B.  Increase in DUV

          As explained in more detail later, the calculated changes
in stratospheric ozone content have been used to calculate changes
in the ground-level flux of DUV.  Appendix Figure 3 [p. 27] presents
that change as a function of time analogously to Appendix Figure 1
IP- 25].  The same general comments regarding the effects apply here,
since the DUV flux is implicitly related to ozone content.  The
average value of a given curve during some time interval represents
the percentage increase in calculated cumulative dose relative to
exposure to the pre-CFC DUV flux for the same number of years.

          Appendix Figure 4 [p. 28] is a plot of the calculated
additional DUV flux attributable to a five-year postponement in


                            F-l-141

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                                                     Effects—Skin Cancer
    the assumed U.S. cutoff (analogous to Appendix Figure 2  [p. 26]  for
    ozone depletion).  The maximum difference is  0.6  percent in about
    2010 and the difference declines slowly to no difference at steady
    state.  By 2090, the difference is 0.25 percent.   Again, the  area
    under the curve may be used to determine the  calculated  difference
    in cumulative dose due to a five-year postponement.   For example,
    the increased DUV dosage for a 30-year period is  the average  value
    of the curve during that 30-year period.

    C.  Steady State Changes

              Assuming both U.S. and world production remain constant
    up to the point of a U.S. cutoff and world production remains
    constant thereafter, the steady state changes in  ozone concentration
    and DUV flux are independent of the date of the U.S. cutoff.   The
    steady state results are summarized in the following table.

                      Calculated Steady State Results

                                          AOp (percent)   ADUV (percent)

          No Cutoff  (1978 Release)            -16.5          55.7

          U.S. Cutoff                         -11.8          36.0

2.  Details of the Calculations

              The following sections describe the model  used, the
    calculation of DUV flux, and the release scenarios employed in
    the calculations.

    A.  Model

              The model is essentially the same as that  employed  in the
    1979 NASA stratospheric workshop12, with a few minor modifications.
    The photolytic behavior of NO is calculated on the basis of the
    recent results of Frederick and Hudson1-^, rather  than the* earlier
    evaluation of Cieslik and Nicolet-1- .  This leads  to  a greater amount
    of NOy in the stratosphere.  In addition, the mixing ratio of water
    vapor at the tropopause has been increased from 3ppm to  4ppm.  The
    NO modification tends to decrease the sensitivity of stratospheric
    ozone to a chlorine perturbation, while the water vapor  change tends
    to increase the sensitivity.  The net effect  of both is  an increase
    in sensitivity by less than a factor of 1.1.   The calculations for
    the NASA workshop employed so-called "standardized"  1975 chloro-
    fluoromethane (CFM) release rates totalling 750 million  Kg/yr world-
    wide.  The worldwide release rates in 1978 were a factor of *1.2
    lower than the standardized 1975 values, and  form the basis for the
    present release figures.
                                F-l-142

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                                                   Effects—Skin Cancer
B.  DUV Calculation

          The amount of destructive ultraviolet radiation at ground
level, or DUV, is defined in terms of its biologically harmful
effects on DNA molecules.  DNA molecules exhibit varying degrees of
sensitivity to monochromatic light at different wavelengths.  This
sensitivity is characterized by the so-called "action spectrum" of
the molecule, which provides a weighting factor as a function of
wavelength for the imposed radiation flux.

          In the present calculations, the DNA action spectrum
developed by Setlow15 serves as the basis for the calculation of
the DUV flux.  The calculation includes the effects of Rayleigh
scattering of solar radiation and diffuse reflection at the ground
with an albedo of 0.25.  The fluxes calculated in this manner are
the integrals over all solid angles of the so-called radiation
intensity I.  Procedures for performing the radiation transfer
calculation with Rayleigh scattering and albedo are described in
Miller et_ al_.16'17  In effect, the DUV flux is treated exactly as
if it were a photolytic reaction rate in the model, with the photo-
dissociation cross section replaced by the product of hJ and the
action spectrum.  In the present evaluation we calculate globally
averaged values of the DUV fluxes, although, because the model is
one-dimensional, the effects of ozone column variations with .latitude
are not accounted for.

C.  Release Rates

          Release rates for CFC-11 and CFC-12 follow the standard
data for release through 1978 as compiled by Alexander Grant for the
Chemical Manufacturers Association.  It is assumed that, if U.S.
production were to continue unaltered, the worldwide release of CFC-
11 and CFC-12 would proceed at their 1978 levels (283.6 million
Kg/yr CFC-11 and 340.9 million Kg/yr CFC-12) indefinitely.   The U.S.
production rates of CFC-11 and CFC-12 just prior to the halt in
production are taken as 60.0 million Kg/yr and 125.0 million Kg/yr
respectively.  These estimates are based on the non-aerosol
production figures for 197812'18, together with estimates of the
residual aerosol production following the 1979 ban.  The distribution
by uses of CFC-11 and CFC-12 prior to the assumed halt are taken to
be as follows:

                                   CFC-11 Production   CFC-12 Production
                Use                 (million Kg/yr)     (million Kg/yr)

      Hermetic Refrigeration              3.5                 33.1

      Non-Hermetic Refrigeration          5.5                 59.9

      Closed Cell Foams                  25.9
                                                "              25.9
      Open Cell Foams & Other            20.8

      Aerosol                             4.3                  6.1

      Total                              60.0                125.0
                             F-l-143

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                                                   Effects—Skin Cancer
    above distribution is based on that which existed for non-aerosol
     during the years 1977 and 1978,  and on the assumed residual
        production.
          The assumed U.S.  production rate of CFC-11 represents 21
        of the worldwide CFC-11 release rate, while that of CFC-12
 ,-ii-esponds to 37 percent of the worldwide CFC-12 release.  The
 .
-------
                                                    Effects—Skin Cancer
the production halt.  These are listed in Appendix Table 1 [p.  24]
and plotted graphically in Appendix Figures 5 and 6 [pp. 29,  30].
The results in the table can also be used to determine the implied
total accumulation of U.S. production in existing equipment prior
to the cutoff.  The value obtained is equal to ^5 years of assumed
U.S. production for both CFC-11 and CFC-12.  This is rather large
compared to the ^2 years production in existing equipment worldwide
calculated for the year 1978.  The larger value of the accumulation
was anticipated, and is attributable to the assumed constant U.S.
production rate and distribution by uses.  Worldwide,  the
accumulation has been increasing rapidly over the past decade owing
to the influence of the distributional changes that have occurred
in the U.S.  The release of *5 years of U.S. CFM production during
the 20 years following the cutoff is realistically an upper bound
to the actual discharge that would occur.  The release figures  in
Appendix Table I [p. 24] can, in this sense, be considered to be
conservative, since they will result in a maximum amount of esti-
mated ozone depletion.  A lower bound to the release is of course
provided by assuming no accumulation, and a release rate which
responds instantaneously to the production rate.  The actual release
rate is expected to reside between these two limiting situations
(assuming no further growth in U.S. production).
                              F-l-145

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                                                    Effects—Skin Cancer
                         APPENDIX TABLE I
         CFC-11 and CFC-12 Releases Following U.S. Cutoff
Year

  0
  1
  2
  3
  4
  5
  6
  7
  8
  9
 10
 11
 12
 13
 14
 15
 16
 17
 18
 19
 20
CFC-11 Release
(million Kg/yr)

     283.6
     266.7
     252.6
     250.5
     248.4
     245.9
     244.0
     242.1
     240.6
     239.0
     237.7
     236.1
     234.6
     233.0
     231.6
     230.3
     228.8
     227.6
     226.2
     225.0
     223.6
CFC-12 Release
(million Kg/yr)
        ,7
        ,3
340.9
320.0
298
289
277.6
265.6
255.9
249.2
244.6
241,7
239.0
236.0
232.1
228.8
225.8
223.2
221.2
219.2
218.2
217.2
215.9
                              F-l-146

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o
c
nl
CJ
                                                      T	1	1	1	T

                                                            STEADY STATE - CASE A	
   15
          APPENDIX FIGURE 1
          CALCULATED OZONE DEPLETION
   10
                                                           STEADY STATE - B AND
                                               CAS
    o
                                                                             CASE B
      I960
1980
2000
2020
2040
2060
2080

-------
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                 APPENDIX FIGURE 2


                 CALCULATED OZONE DEPLETION

                 FOR FIVE-YEAR POSTPONEMENT
     0.2
en

o
                                                                                                         CO
Q_
UJ
(=3
LU
Q_
     0.1
        1980
                          2000
2020
2040
2060
2080
                                                YEAR

-------

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-------
   0)
   o
   c
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   U)
   -p
   o
   OJ
00
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290
       280
       270 -
       260 '
       250
       240
       230
       22Q
           0
APPENDIX FIGURE  5


CFC-11 RELEASE FOLLOWING U.S.  CUTOFF
                                            10
                                              15
20
                                           YEARS  AFTER CUTOFF

-------
  J-l
  0)
  u
  £
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  u

  c
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  I
  I
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       350 -
       300*
       250
APPENDIX FIGURE  6

CFC-12 RELEASE FOLLOWING U.S. CUTOFF
      200
                                                                                  m
                                                                                  H
                                                                                   I
                                                                                  H
                                                                                   I
                                                                                  Pn
                                                  10
                                               15
                                                                                            20
                                         YF4RS,

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                                                      Effects—Skin Cance
VII.  REFERENCES
      1.  National Academy of Sciences:   Protection Against Depletion
          of Stratospheric Ozone by Chlorofluorocarbons, Part I,
          Report of the Committee on Impacts of Stratospheric
          Change, 1979.

      2.  National Academy of Sciences:   Stratospheric Ozone
          Depletion by Halocarbons:  Chemistry and Transport,
          Report of the Panel on Stratospheric Chemistry and
          Transport, 1979.

      3.  Du Pont:  "Comments on the National Academy of Sciences
          Report, Stratospheric Ozone Depletion by Halocarbons:
          Chemistry and Transport."  Submitted to EPA, January,
          1980.

      4.  Reference 1, Part II, Report of the Committee on Alter-
          natives for the Reduction of Chlorofluorocarbon Emissions,
          1979.

      5.  Du Pont:  "Comments on the December 1979 Report by the
          National Academy of Sciences Committee on Alternatives
          for the Reduction of Chlorofluorocarbon Emissions  (CARCE).
          Submitted to EPA, April, 1980.

      6.  National Academy of Sciences,  Halocarbons:  Environmental
          Effects of Chlorofluoromethane Release, Report of the Com-
          mittee on Impacts of Stratospheric Change, 1976.

      7.  Cutchis, P.  On the Linkage of Ultraviolet Radiation to
          Skin Cancer.  Institute for Defense Analysis.  Report to
          the Federal Aviation Administration, Department of
          Transportation, Report No. FAA-EQ-78-19, September 1978.

      8.  D'Arge, R.C., Daly, G., and Patten, C.W.  Economic and
          Social Measures of Biologic and Climatic Change.  Climatic
          Impact Assessment Program (CIAP) Monograph 6.  Department
          of Transportation DOT-TST-75-56 (1975).

          Technology Assessment of the Fluorocarbon/Ozone Depletion
          Problem, Systems Control, Incorporated.  Report under
          Grant No. ERS 77-09248 to the National Science Foundation
          (1979).

          Hoch, I., Climate, Energy Use and Wages.  Chapter 4 in
          Some Economic Aspects of Controlling Ozone Depletion,
          A Report to the Environmental Protection Agency from
          the University of Maryland.  EPA Grant R 805411-01
          (SR-EDAF), October'1979.
                              F-l-153

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                                                  Effects—Skin Cancer
 9.  Reference 1, p. 118, Table 4.2.

10.  Ward, R.B., (Du Pont) to Klauder, D. (EPA).  "Chemical
     Manufacturers Association Fluorocarbon Project Panel
     Research Program and Scientific Uncertainties".
     November 19, 1979.

11.  Summary:  Research Program on Effect of Chlorofluoro-
     carbons on the Atmosphere - Revision 12.  Chemical
     Manufacturers Association.  November 30, 1979.

12.  National Aeronautics and Space Administration.  "The
     Stratosphere:  Present and Future," NASA RP1049, 1979.

13.  Frederick, J.E. and R.D. Hudson, J. Atmos. Sci. 36, 737-
     745, 1979.

14.  Cieslik, S. and M. Nicolet,  Planet. Space Sci. 21, 925-
     938, 1973.

15.  Setlow, R.B., Proc. Nat. Acad. Sci. U.S. 71, 3363-3366,
     1974.

16.  Miller, C., P. Meakin, R.G.E. Franks, and J.P. Jesson,
     Atmos. Environ. 12, 2481-2500, 1978.

17.  Miller, C., D.L. Filkin, and J.P. Jesson, Atmos. Environ.
     131, 381-394, 1979.

18.  McCarthy, R.L., F.A. Bower, and J.P. Jesson, Atmos. Environ.
     11, 491-497, 1977.
                          F-l-154

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                                                             Effects—Skin Cancer
           G.  Critique of the NRC Report:   Protection Against




         Depletion of Stratospheric Ozone by Chlorofluorocarbons




                 G.I.   Chapter 3 - Human Health Effects




To:  Introduction (NAS, 1979, pp 74-75)




     It  is  correct   that  "the epidemiologic evidence  for  the causative




role of damaging UVR (DUV) in the development of nonmelanoma skin cancer




of the  exposed  areas (the face and neck)  is  indisputable." (NAS,  1979,




p  74).   However, the exposed  areas of  skin in people are  not  only  the




face  and neck,  but also  the upper  back  and  the  dorsae  of the  hands




and  forearms,  where SCC  is  commonly  found  but BCC  is  quite uncommon.




     It is correct that "the susceptible population includes (one should




really  say:    consists of...)  white,  fair  skinned  persons "ho sunburn




easily and who receive  prolonged occupational or recreational exposure."




There  is  only the  most  preliminary  data  that  "a  subset  of  this  white




population  [has]...  a  deficient  DNA  repair mechanism"  (NAS,   1979,  p




74)  -  this  is  based  on  two  small  studies on  the repair  capacity  of




lymphocytes circulating in the blood of patients with actinic keratoses.




The  meaning  of  these  preliminary  observations is  by no  means  clear.




It is  of interest that the  same  authors have not  found such an abnor-




mality of DNA repair capacity in patients with malignant melanoma.




     None of the above  detracts from the clear and indisputable  associa-




tion of  most  (but   not  all  — see below)  nonmelanoma skin  cancer  and




the cumulative effect of repeated, chronic exposure to solar UVB.




     The  situation   is  much   less  clear as  far  as malignant  melanoma




(MM)  is concerned.   In contrast to the  statement  "recent  evidence sup-




ports the previous conclusions of  CISC that the  development of malignant
                       F-l-155

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                                                          Effects—Skin Cancer
melanoma  of  the skin  of  man  is  related to DUV  exposure,"  (NAS,  1979,




recent  evidence casts  doubt on  a  direct relationship  of  MM  to  solar




UVR exposure.




     The  latitude  gradients  vary  from country to country, and in Europe





are even reversed.   While the incidence of MM has been increasing world-




wide,  the one  body site  where  there  has been  no or  little  increase




has been  on  the most exposed area,  i.e. the  head and neck.   The assump-




tion  that females'  legs  are  more   exposed  than  men's  because of  the




wearing  of   skirts  is  not  really  borne  out,  when one  considers  that




the amount of  UVR  (excepting when on snow or  ice,  where UVR reflection




is high)  that   reaches the  legs  in  the upright position  is  only 15-20%




of that reaching the head and neck.




     The  cohort effect described  is real,  but,  on  closer  inspection.




began  at  least about  the  year 1900, and perhaps  earlier  in Australia.




It thus appears dubious that this  can be primarily ascribed to increased




recreational  exposure.




     The  only   certain things  about malignant  melanoma  are  that  there




has been  a   real worldwide  increase in  incidence (incidentally in  the




absence of any  change  in  stratospheric ozone), and that  it  is primarily




the middle   class  males  and  their  wives who  show this  increase,  i.e.




not those habitually and  occupationally exposed to UVR.




To:  General  Aspects of Sunlight Exposure (NAS, 1979,  pp  75-77)




     It  is true that "a single 15  to  20 minute  exposure of  white  skin




to  the sun  at noon  in  middle  latitudes during  summer can produce  a




slight  sunburn" (modifications  underscored,  NAS, 1979,  p  75).    The




figure  given for  the  dose  for  such an  exposure is peculiar.   1.2  x




10   J/m  is about  the total solar  exposure,  assuming a  solar  constant









                          F-l-156

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                                                          Effects—Skin Cancer
            0
of  1333  w/m  and  15  minutes of  exposure.    This  figure is  misleading


and meaningless -  unless  the  UVB dose is given  (200-250  J/ro  of  energy


equivalent  to  the  effectiveness  of  wavelength 297  nm),  the number  is

                                                     /•    o
not useful.   One  could  be exposed  to  the  1.2 x 10  J/m   dose  through


3 mm of window glass and have n_o biologic effect.


     The  statement  that  1/3  of  the white  population  will   not  develop


a  protective  tan  has  to  be  taken  with  a  great  deal  of  caution.    In


the U.S.,  it  is  more  like 15%,  in central Europe  perhaps 5%, in  Ireland


and Scotland perhaps 50%.


To:   Skin Cancer  Caused  by  Exposure  to Sunlight   (NAS,   1979,   pp  77-


      79)


     The  statement  that  "...the  evidence associating UVB with malignant


melanoma  is not  so strong as for nonmelanoma, we  believe  that the  only


action spectra that we  can prudently use for  any  quantitative  estimate


of  the potential hazard  arising from an increase in UVB are those given


in  (figure location)"  (NAS,  1979,  p  79)  is  certainly true, at  least


in  .part,  if the assumption is  made  that UVB is  the  predominant cause


of  MM.   Whether  this  assumed conclusion  is  tenable  is  discussed  below.


     Comment  should be  made on  the uncritical  use  of the  DNA  action


spectrum  that  is used to  derive  "DUV"  in this monograph.   It  is clear


that  the  known DNA action  spectra  in  the UVR have  a  slope similar  to,


but somewhat  steeper  than, the  accepted  skin  erythema  action spectrum.


The major difference  occurs  at  wavelengths shorter than 295 nm, where


the  erythema  effectiveness  becomes  less,  while  the  DNA  effectiveness


continues to rise.


     Since  the only cells in human  skin  normally  capable  of cell divi-


sion  (and thus capable  of being transformed  to cancer  cells)  are  the





                           F-l-157

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                                                            Effects—Skin Cancer
basal  cells  and  possibly  the melanocytes,  the  radiation  must  reach

the  nuclei  of such  cells to be effective.   These cells are  located  at

the  bottom  of  the  epidermis,  and  effective radiation must pass  several

cell layers (containing DNA in their nuclei,  but  being unable  to  divide)

before  it  can reach  its  target.    Since shorter  UV  radiation  is  more

absorbed  than  longer  UVR,  the  "real"  effective  action  spectrum  for

susceptible  cell  damage  will have  a shape  somewhere  between  the  DNA

absorption  spectrum  and the  erythema  action spectrum.  Our own  experi-

ments in hairless mice, showing a  strikingly increased photocarcinogenic

effectiveness  of  wavelengths  shorter than  295   nm,must  be   taken  with

caution, since the  mouse  skin averages 2-3 cell  layers above the basal

cells,  and  human skin  has  5-10  cell  layers  able  to  absorb  radiation.

Studies to  determine  actual  transmission of UVR  to the basal  cell layer

of human skin  are  of critical importance, since, as pointed  out  before,

the  shape  of  the  action spectrum  can have a striking effect  on calcula-

tions  of "DUV" (which is  an  action  spectrum-weighted  number),  particu-

larly when solar UVR increase is being considered.

To:  Evidence for Sun-Induced Skin Cancer (NAS,  1979,  pp 80-85)

     The logic of  the  introductory statements as far as NMSC  is  reason-

able  and   in  keeping with  best  present  knowledge.   It is  unfortunate

that  basal cell  carcinoma,   as  described  in  NAS,  1979,  p  84,  Figure

3.4,  should have been  used  as the example for  documentation that  "the

skin  cancers  should be heavily  concentrated on  the  parts of  the  body

most  exposed  to the  sun,"  (NAS,   1979,  p.  81)  since  1/3  of  the basal

cell  carcinomas  on  the  head and  neck   occur  in areas receiving,  for

anatomic  reasons,   very  little UVR  and  where  the adjacent  skin shows

little  or  no  solar  damage  (inner  and  outer canthus,  upper  lid, post-

auricular area, etc.).
                            F-l-158

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                                                         Effects—Skin Cancer
     Whether  solar  radiation  alone  causes  skin  cancer ("pattern  1")




or whether  the dependence  on  exposure is  more  complex  ("pattern  2"),




the  logical  reasoning  is  consistent, but  the  arguments are  circular:




Since  all  the  evidence  strongly  points  to major  differences  in  causal




mechanisms between NMSC  and MM,  and since considerable  data  as  to  what




is happening  is  available,  it  is not difficult  to  determine  criteria




and  then  show  that  the  observations  match the proposed  criteria.   So,




the  criteria  become  self-fulfilling  prophecies,  since  they  were  drawn




from existing data.




     Nevertheless,  if  the  assumed  criteria  are  correct  (and  of  course




they fit present day data), it must be clear that  predictions of  future




effects  are  at  best very  difficult   (e.g.,  the  most  recent  statement




in  the 2nd  Biennial Report to  Congress  of NCI  - 1979:   "A study  of




skin melanoma  incidence  data  from 10 locations   in  the U.S. has  also




produced preliminary results.    Although  incidence  is  increasing,  the




dose-response  relationship  between UVB radiation  and  melanoma  suggests




a  complicated  involvement  of  environmental  and  host  factors  requiring




further investigation.").




     The NAS report, nevertheless, states further, "(for MM)  the  lati-




tude dependence  appears well  established"  (NAS,  1979,  p  82).    Data




quoted  above  (section  E) shows that  this  statement  is at best a half-




truth.    Latitude  gradients  are reversed  in  Europe,   Western  Australia




and  not  present  in  Finland,  and  incidence  maxima  do not  correspond




to latitude -  e.g. higher  in Stockholm than in England or  Connecticut.




     The anatomic distribution  of  MM only  vaguely  corresponds  to  insola-




tion -  the  greater  frequency  of   MM  on head  and  neck  in males is  con-




siderably weighted by  the  presence of lentigo maligna  melanoma, which,










                           F-l-159

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                                                          Effects—Skin Cancer
while  comprising only  10%  of  MM,  really  seems to  be  due  to  chronic




insolation.   MM on  the  scalp has  nothing  to  do  with UVR,  since  hair




is  an almost  perfect neutral density  filter,  and  MM does  not  appear




excessively  on   bald  scalps.   The  unlikeliness  of  the really  greater





incidence  of MM  on  the  legs of  women  to  be  related to  sunlight  has




been commented on - unless all these ladies  sunbathe  in skirts.




     The  putative  relationship  between  clothing  styles  and incidence




of  MM on  legs   is  at best   tenuous,  since  north  Australian men,  who




habitually  wear  shorts  all   year  long,  have  low  incidence  of  leg  MM,




while  both  in  Hawaii and  recently  in  Norway,  the difference  in  the




incidence  of MM  on  legs  between  males  and  females has  almost  disap-




peared.




     It  is  certainly  true  that  there  has  been  a  worldwide  increase




in  the  incidence of  MM.   To ascribe this mostly to  changes in  exposure




patterns  appears premature.   It  is also  true that  the  dose-response




relation to  DUV  is  complicated  and unlikely to involve many other vari-




ables.




To:  Body Location (NAS,  1979, pp 86-89)




     There  are   several  statements  where  knowledge   is  implied  but  no




good data to back the statements  exists:




     E.g.:   "Most  (MM)  occur  on  lightly  covered  or occasionally  un-




             uncovered regions  of  the  body...Very  few  have been  seen




             (either  in  males  or  females)  on  the  regions  ordinarily




             covered  by  bathing  suits"  (NAS,  1979,  p 87).   If  the  in-




             duction  period  is  short  (5  years or less),  where  are  the




             MM  on  the abdomen  and  lower back  of  women  who,  at least




             in  the  U.S.,  have  been  wearing  two—piece   bathing  suits




             at  least since 1950?






                            F-l-160

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                                                         Effects—Skin Cancer
             .Is  there  data  on  the  frequency  of men  exposing  their




             trunks to the sun during  recreation?




             .The  data  quoted  on  transmission  of  UVR by  fabrics  of




             Infante and  Daniels  (NAS,  1979,  p  87)  is  wrong.    Unfor-




             tunately,  they neglected  to  remember the  almost universal




             use  of  optical   brighteners  which  resulted  in  spurious




             measurements  not  due  to UVR.




                 Realistic  studies   show  maximal  transmission  of  even




             thin woven cloth on the order  of less than 10% below  320




             nm (Herskowitz and Dobes,  in  press).




             .Why  does  lack  of  change of   incidence  on face  or  feet




             in Norway (and other areas)  during  a period of  rapid  rise




             in  incidence  on  other areas support  the hypothesis  that




             "change  in  behavioral  pattern  is an  important factor  in




             the  striking  increase  in  incidence  of  MM since World  War




             II" (NAS,  1979, p 89)?




                 Even if one  assumes  that  some factor in  the skin (pre-




             cursors,  nevi,  etc.)  are rate-limiting  for  the  effect




             of  solar  UVR,  it  is  unreasonable  to  expect   that  indoor




             workers and their wives  have  already had maximal effective




             UVR  doses  to  the  face,  and certainly  they receive  more




             UVR  to  the  face than  in the  past if their backs  and  legs




             now have more "recreational"  exposure.




To:  Forecasting the Effects of DUV  Increase  (NAS,  1979, pp  96-99)




     The best  present estimates  suggest that the  biologic amplification




factor  (to convert  from DUV increase  to an  increase  in NMSC incidence)




is 2.   In other words,  for  a  1%  increase  in DUV,  it may  be  expected









                              F-l-161

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                                                             Effects—Skin  Cancer
that  there  will be a  2%  increase,  at equilibrium, in NMSC.   It  should




be  noted,  however, that  the  overall effect of ozone  depletion  on  NMSC




incidence may  be  reduced  when  two  dimensional  modeling is  used  (Pyle




and Derwent, 1980).




     The  same   relationship  does not  hold  for  MM.   At this time,  no




reasonable  calculations  for  the  biological  amplification  factor  for




MM  can  be calculated.  Even  for NMSC,  a simple number  for this  factor




is an oversimplification.




     It  is  true  that, given  a  decrease  in 0.,,  the  intensity of  DUV




will  build  up  at  higher  latitudes, towards  that previously found  at




lower  latitudes.   However, the  dose received by  an individual  at  risk




will be smaller at  the higher  latitudes  even then.




     This  is  due  to   the  fact   that the dose  (i.e.  intensity x  time)




varies  so  strikingly  with sun  angle;  the  sun angle of  course will  not




change  with  ozone  concentration.   Also, since  the time each day  that




the  sun angle  exceeds  55  from the vertical  varies  with  latitude  by




season,  and  since ozone  concentrations vary  with latitude  by  season,




the effects  of  a  per  cent decrease  at one latitude can not  simply  be




equated with a shift  to a  lower  latitude.




     The  final  paragraph  of  this  section contains a  peculiar set  of




arguments:




     ."An increase  in MM  deaths...,  if it occurred, would be  delayed,




     well beyond  the  onset  of  a DUV  increase,  while  the accumulated




     dose builds up in individuals"  (NAS,  1979, p  99).   If the  assump-




     tion is that  MM  has  a short incubation  period, and is not  related




     to  chronic,  repeated UVR   exposure,  but  is  due  to  "intermittent




     overdoses," then  that  statement  is   peculiar.   Perhaps  that  is











                            F-l-162

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                                                          Effects—Skin Cancer
     quibbling,  because  technically  there  will  of  course  in  either




     case  be  a delay.   However,  the deaths due to MM  should  rise then




     much  faster than the incidence  in NMSC.




           In  any   case,  the  proposed  calculation  is  not correct.   If




     a  reduction   of  ozone  by  16%  causes  a  44%  increase  in  DUV,  and




     the  biologic  amplification   factor  (DUV  to   skin  cancer)  is  x2 ,




     the  final  increase would be  88%  (i.e.,  2 x 44%),  not  64%.   Table




     3.5  (NAS,  1979,  p  102), attributed to Scott  and  Straf, shows that




     for  MM mortality,   an  estimated 20% reduction of  ozone  would,  by




     their  calculations,  result  in an  increase of 1.5 to 2 times (HANES




     TCNS  or  TCNS  only)  in Minneapolis-St.   Paul  (northern  U.S.)  and




     a  1.5 to  4  times  increase  for the same  data  in  Dallas-Fort Worth




     (southern U.S.).  All these figures,  from the best estimates avail-




     able  at   present,   are   significantly  below  the   overall  estimate




     quoted above in the chapter.




          All  data  available  suggest that   the  north-south  increase




     in skin  cancer  has a nonlinear relationship -  a  considerably dif-




     ferent assumption  from the one used in  all  predictions,  including




     those  in this monograph.




     In  summary,   the descriptions of  available  data   fit best  present




knowledge  as  far  as NMSC  is  concerned.    There  are  serious  problems




in  trying  to  relate the  incidence of  MM  in any  straightforward  way




to  DUV  exposure.    The  obvious  evidence for  the  interaction of factors




other than DUV exposure  makes  risk calculation at  this time  extremely




hazardous.   Certainly  it is not  reasonable  to  use  the  same  transfer




functions  which are  appropriate   for  NMSC to  estimates of changes  of




MM.









                              F-l-163

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                                                         Effects—Skin  Cancer
     It  is  unfortunate that,  at  this time, a more  reasonable  approach




to  this  important problem  does  not suggest itself.  However,  as  Lewis





Thomas once wrote:




     "The  skeptics  in  medicine  have  a  hard  time  of it.   It  is  much




     more difficult to  be  convincing about ignorance concerning disease




     mechanisms  than  it is  to make claims for  full  comprehension,  es-




     pecially when  the comprehension  leads,  logically  or not,  to  some




     sort  of  action.   When  it  comes  to  serious  illness,  the  public




     tends,  understandably,  to  be   more  skeptical  about  the  skeptics,




     more willing  to  believe the true believers."  (Nature 284:298-299,




     1980)




       G. 2  Appendix C, Solar UV  Irradiance at  the Earth's Surface




                         (NAS,  1979, pp 300-303)




     Excellent,  simple  description  of   a  very  complicated   problem.




Does  point  out   the  difficulties   inherent  in  making  calculations  of




spectrum  and  amount  of UVR  reaching earth, and the uncertainties  in-




herent in all calculations.




 G.3  Appendix D, The Biologically  Effective UVR  (NAS, 1979,  pp 304-318)




     Excellent,  competent  description  of  the   problems  inherent  in




weighting  solar  UVR  to obtain  a   "biologically  effective"  unit.   The




magnitude  of  the differences  due  to different  action  spectrum assump-




tions  is clearly  shown,   as  is  the  problem  inherent  in normalization




of various action spectra.




       G.4  Appendix F, Factors in  UV Dose-Response  of NMSC and MM




                         (NAS,  1979, pp 325-334)




     It  is correct that "NMSC  appears to correlate  best with cumulative




lifetime  UVB  exposure,  therefore,  older  persons  will have more cumula-




tive effects" (NAS, 1979,  p 325).







                            F-l-164

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                                                         Effects—Skin Cancer
     Again,  a  generalization.   Obviously,  one  has to live  long  enough




to accumulate  enough  DUV  to  have an  effect, but  age alone is not  the




criterion -  it  is  exposure  -  in one  of our  studies  (Urbach et  al.,




1976) people  of  the  same  age can have  as much as 25-fold  differences




in outdoor exposure.




     "Melanoma does not  so  correlate,  which suggests  that  intermittency




of exposures  may be  important"  (NAS,  1979,  p  325).   The  first  clause




of that  sentence  is  correct;  the  conclusion  is  a  speculation.   One




might equally well conclude that  therefore:




•    DUV is not causally related  to MM




•    Predisposed  skin  requires  much  less  accumulated  dose  to  cause




     MM  (e.g.  if there  is  an "initiated" skin  area  that  is "promoted"




     by UVR).




•    Interaction  of DUV  with some  other  agent  (chemical? viral?)  is




     effective.




•    Etc.




     Effect of Skin Color (NAS,  1979, p 328)




     While people  with genetically  dark  skin have indeed  less MM,  the




difference  in incidence  is not  as  striking as  in NMSC  (1:5  compared




to less than 1:50, with almost no basal cell carcinoma).   When MM  occurs




in pigmented  people,  50+%  occurs on  the  foot  -  indeed a  lighter skin




area,  but  one that does  not  receive any solar  UVR,  and both  palms and




soles are so heavily keratinized that it is almost impossible to sunburn




these  areas  because of  the thick keratin layer  that is dead and absorbs




virtually all  UVR.




     Precursor Lesions  (NAS, 1979, p 330)




     Familial  incidence,  of  genetic  origin,  occurs in  about  10%  of









                            F-l-165

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                                                           Effects—Skin Cancer
all MM.   These  are mainly in younger groups and multiple lesions occur.





UVB can not be incriminated.




     UVA-Induced Carcinogenesis (NAS, 1979,  p 331)




     The  first experiment  quoted  was indeed reported in 1973.   However,




it has  since been  found  by  Forbes  (and  reported at meetings  where  at




least two of the  committee  members were present)  that  this  effect  of




UVA potentiating  UVB effects  was  due to the phenomenon  of  protraction




(Forbes,  1978).




     It was  found  that, when the  same dose  (and  spectrum)  of  UVR,  from




the same  light  sources,  was  given  over  a  5 minute,  a  50 minute  or  a




500 minute   time  period  each  irradiation  day,  the  dose delivered  in




500 minutes  was very much more effective than  that  given in 5 minutes.




     Repetition of  the  original experiment,  with the original  two light




sources,  adjusted  to deliver  the  daily UVB  dose at  the  same  rate showed




that additional  UVA had  n_o  potentiating effect (Forbes  et  al.,  1978).




     While it is  possible to produce skin cancer in  hairless  mice  with




UVA (filtered  to   remove  all  UVB)  it  takes  about 1600  times  the daily




UVB dose  to produce  such effects.




     Sunlight ('1  July 1976  -  cloudless day, actual  measurements,  40°N




latitude) delivers  from sunrise to sunset 31 times  as  much  UVA as  UVB.




     In  terms  of   skin  minimal erythema doses,  that amounts  to  17  MED




UVB and  2.25  MED  UVA to  a horizontal  observer.   Clearly, the  contribu-




tion of UVA to NMSC  induction in nature is negligible.




          G.5  Appendix G, Further Detail on Malignant Melanoma




                          (NAS,  1979, pp 335-341)




     Cohort  Experience  (NAS, 1979,  p 336):   Recent  reports (see section




E) show that the  increase in incidence  in MM began with cohorts  born




before  1900,  possibly as early as  1885 in Australia.







                             F-l-166

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                                                          Effects—Skin Cancer
     Geographic Variation (NAS,  1979,  p 337)




     More recent reports show that latitude gradients for MM vary great-




ly in various  parts  of the world.  In  part  this is due to the peculiar




predilection of  MM to  occur  in white collar, affluent  people,  who  are




mostly city dwellers.   In Finland,  Norway and Sweden,  the major cities




are  in  the  south.   In  Western  Australia,  the gradient  is  reversed,




apparently  because of the  major  city,  Perth, being  much  further  from




the equator than the rest of the state.




     Even in Queensland,  the  MM incidence is higher  in  the subtropical




than in the tropical regions.




     That these "deviations" are not just due to  such factors as suscep-




tible population,  climate,  etc.  is  shown by the  fact that the gradients




for NMSC show very little "deviation."




     Types of Melanoma (NAS, 1979, p 337)




     The  four  major  types of  MM  are  described.    No mention  is  made




of  the  fact  that of  these,  lentigo  maligna melanoma  behaves  exactly




as  a UVB induced  skin cancer,  i.e.,  squamous  cell  carcinoma.   It  is




most frequently  found  in  the  elderly, on  the most  light exposed areas,




develops  slowly,  and  metastasizes  late.    Histologically,   solar  UVR




induced changes  are  almost always present, and,  in  the  opinion of  most




expert pathologists,  a sine-qua-non  for the diagnosis  of this lesion.




     Again,  much  is made  of  the localization  in  areas  that  are light




exposed,  including legs  of women.   The  problems  that this attribution




causes have been discussed before.




         G.6 Appendix  H,  Preventive Measures  Related  to  Melanoma




                          (NAS, 1979, pp 342-344)




     This brief chapter should be entitled:  Preventive Measures Related




to Skin Cancer (modification underscored).




                            F-l-167

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                                                         Effects—Skin  Cancer
     The program  outlined  is reasonable  and  objective.   It  certainly




will lower  the  incidence  'of NMSC.   Whether it will affect MM  (except




for the self-examination, which can successfully lead to early  diagnosis




and treatment)  depends  on  the degree to which MM  incidence is  related




to UVB  exposure.
                            F-l-168

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                                                           Effects—Skin Cancer
                 H.   Recommendations  for  Further Research



Recommendation 1;  Present Ozone Levels




     That more accurate  data  on present  ozone levels be  obtained,  par-




ticularly near sites  where  epidemiologic data have  been or  will  be  col-




lected.




     Present  Dobson  ozone  stations  are  scattered  and  make a  limited




number  of  observations.   Satellite ozone estimation offers  greater  in-




formation over wider  areas  and longer  periods.  Comparison  of relative




pertinent usefulness  of  Dobson  and  satellite ozone measurement  is  re-




quired.




     It  must  be  anticipated   that  there will be  processes other  than




the  SSTs  which  may  perturb  the steady  ozone  state.   There is  thus  an




urgent  need  for  ozone baseline  data which are reliable, accurate,  and




continuous.    It  is  important  to attribute any changes reliably  to  the




correct cause.




Recommendation 2:  UV Radiation Reaching  Earth




     That accurate measurement be continued of the UV radiation reaching




earth from sun and sky:




     (a)  To establish baseline levels.




     (b)  To establish the range of existing natural variation.




     (c)  To monitor  for possible  steady change  resulting  from  various




          causes.




     (d)  To  establish   more  reliably  the relationship  between ozone




          and effective UV for various  results.




     Two useful  classes   of  measurement  have  already  been  instituted:




     A.   Spectroradiometer




     Bener  at  Davos has completed extensive  studies  on sun and sky show-




ing  absolute  intensities  at all  UV wavelengths and indicating apparent




                           F-l-169

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                                                           Effects—Skin Cancer
influences of  altitude,  ozone  and elevation of the  sun  above  the  hori-




zon.   It  is  recommended that further work should proceed at  this exist-




ing observatory.  (Other sites may also be desired.)




     B.   UV-B Meters




     A network  of  UV-B  meters  (based on the design  of Robertson as  im-




proved by Robertson  and Berger)  has been established under the auspices




of  the  CIAP  and  NOAA.   These  instruments  automatically integrate  the




intensities of all UV-B wavelengths weighted to closely match the action




spectrum for production  of  erythema in untanned white human  skin.  They




are rugged,  operate  continuously  with minimum  attention,  are relatively




inexpensive  and stable  and  give  an  immediate  approach  to   the overall




effectiveness  of  the  sun's radiation  as  regards  long-term  damage  to




human skin.




     Present UV-B meters are  located (usually  at  weather   bureau sta-




tions) at the following locations:  Philadelphia (Base),  PA;  Des Moines,




IA;  Minneapolis,   MN;   Bismarck,  ND;  Tallahassee,  FL;   Mauna  Loa,  HI;




Brisbane, Australia; Aspendale, Australia;  Davos,  Switzerland.  Further




stations will  be  established within the next  three months   at:  Honey-




brook,  PA;  Tucson,  AZ; Rochester,  MN;  Hamburg,  Germany;   Poland (2);




Italy,   It is  recommended  that this  network be  continued and  that con-




tinued assessment  of results be supported.




Recommendation 3;   UV Measurement  Stations




     That UV measurement  stations  be  established  at additional  sites




with  significance to  the   predictions  desired  for  the  ozone  program.




Recommendation  4:    Appropriate   Improvement  of the  UV-B Meter System




     The present  UV-B meters  (provided  to meet the  urgent  demands  of




the CIAP program)  include minor instrumental errors which can and should












                          F-l-170

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                                                           Effects—Skin  Cancer
be reduced to meet the more exacting requirements  of  a  program  ext.ending




forward for a longer period.




     (a)  Cosine  error  resulting from  flat  filters can  be reduced by




          hemispherical filters and  changes  in  phosphor geometry.




     (b)  Temperature  errors   can  be  reduced  by  thermostatic  control




          to nearly constant  temperature.




     (c)  Safer and quicker handling of  data  can be  provided by improved




          computer  access  through  a process  such   as  tape recording.




     (d)  Ensuring greater long-term reliability of  results by improved




          calibration procedures.




Recommendation 5:   Personnel  Monitors




     Studies with personnel monitors  (such  as  the KPR type  already  ap-




plied  in  Switzerland)  are needed to relate variations in  personal  be-




havior and  orientation with  the indications  of fixed outdoor detectors.




     This  factor  does  vary  from  one community to  another  and  present




lack of  knowledge on  it  acts  to confuse  application of  existing  data




on chronic skin damage.




Recommendation 6;   Incidence  of Skin Cancer




     A better  baseline for present  incidence  of  skin cancer  in man is




required:




     (a)  To make  more reliable predictions  of  possible change.




     (b)  To attempt  to  recognize  change  in years  hence data  on  inci-




          dence (or prevalence) of skin  cancer. This should be obtained




          in at least  6-8  areas separated  by at least 300  miles north-




          south over a latitude span reaching  beyond the  most  populated




          areas.   Similar  data are  needed  nearer the  equator.  It is
                          F-l-171

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                                                          Effects—Skin  Cancer
          of  paramount  importance  that  all  these studies  be  peformed




          according to the  same  protocol  so  that  valid comparisons  may




          be made.   Promising areas  for  such  studies, in  addition  to




          the U.S., are Australia (particularly Queensland), Scandinavia




          and South Africa.




     Recommendations:  Animal Experiments Associated with Development




                             of  Skin Cancer




Recommendation 7:   UV-B/Solar  Spectrum Interaction




     Animal  experiments  associated  with  development  of   skin  cancer.




Some of these are  already planned  and to some  extent operating as pre-




liminary trials.   They should  lead  to  a  separation of the relative quan-




titative significance  of  differences  in:




     (a)  Total  dose




     (b)  Dose rate (flux)




     (c)  Diurnal  and  overall  fractionation




     (d)  Action spectrum




     (e)  Combination  of  longwave  UV  and visible  radiation with  the




          active "carcinogenic"  wavelengths.




Separation  of  these  different  factors   is  necessary  to  permit  proper




evaluation  of even existing dose-response information, and  to  make  it




possible  to enhance  predictability  of   effects  due  to changes  in  the




radiation climate.




     A study  is required of the  effect  of interaction  between  UV-B and




the  rest  of the solar spectrum  in  relation  to  skin  tumor development.




      Experiment  has already shown  that this effect exists.
                         F-l-172

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                                                           Effects—Skin Cancer    |
It  is particularly  pertinent in  this  field  where  ozone reduc-


tion  will  affect UV-B only.


Recommendation 8:   UV-B Flux


     Investigation is needed of the influence of change in  flux of UV-


B on skin carcinogenesis.   Preliminary experiments show that  protracting


the delivery  of  a dose  of UV (i.e., altering  flux)  has  a  significant


effect on  skin  carcinogenesis.   The  direction  of  the  effect  is  unex-


pected - lower flux can be  more effective.


Recommendation 9;   Intervals  of UV Exposure


     It  is  recommended  that the  effect of  varying interval  periods


during  carcinogenesis  experiments  be studied  in  detail.   The  dose-


response model of  Blum,  and the model  for effect of "effective exposure"


of  Robertson, demonstrate  that intervals of  exposure  are  of importance


in  skin  carcinogenesis.  This may be  one of the most important experi-


ments, since  in  nature, change in  ozone will affect  flux and  spectral


distribution  of UV but not  the  time  relationship  during which people


will be exposed.
                  \

Recommendation 10: Animal  Models for Malignant Melanoma


     At  present,  the  only  workable animal  model  for MM  is the guinea


pig system reported by  Pawlovski et al.  (1980).   However,  this  utilizes


chronic  skin  painting  with a chemical  carcinogen  only.   It  is recom-


mended that experiments  using the  same  guinea  pigs  but  using  UVB ex-


posure be performed.    In addition,  the interaction of chemical  carcino-


gens and UVR should be  investigated.


                    Training and Reference  Standards


Recommendation 11:   There  is a  dearth  of  trained  photobiologists  in


the world.   Primarily  this  is  due  to the  fact  that  photobiology  is  a





                           F-l-173

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                                                           Effects—Skin  Cancer
very young branch  of  science,  and that  at  this  time  no  real Departments




offering graduate  training exist  in  this  field.   This is particularly




true of the animal experimentation area.




     It is recommended  that  efforts  be  made to develop and support one




or two  centers  capable  of  offering such graduate training.  Nuclei for




such centers exist at Harvard and Temple  Universities.




Recommendation  12:   A serious  problem exists due to' the  fact  that var-




ious investigators use  a wide  variety- of UVR sources and  measuring de-




vices  which  are  not "standardized"  in  the usual sense  in  which this




word is used.




     It is  recommended  that  a  central radiometric laboratory  be  estab-




lished  and supported, capable  of making  accurate  spectral  and  intensity




measurements of varius  light sources, of developing and  supplying ref-




erence  sources,  and   of calibrating  and  testing measurement devices  in




the  UVR.    Such activities  would make  it  possible  to  compare  results




obtained in  many laboratories  critically  to each  other, something which




is not possible at present.
                            F-l-174

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                                                            Effects—Skin  Cancer
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                             F-l-199

-------
           COMMENTS ON THE NATIONAL ACADEMY
       OF  SCIENCES REPORT:   "PROTECTION AGAINST
         DEPLETION OF STRATOSPHERIC OZONE BY
                CHLOROFLUOROCARBONS."
PREPARED FOR E.  I.  DU PONT DE NEMOURS &  COMPANY,  INC,
                         BY
                   DR.  W.  H.  KLEIN
                      DIRECTOR
SMITHSONIAN  INSTITUTION RADIATION BIOLOGY LABORATORY
                 ROCKVILLE,  MARYLAND
                   DECEMBER, 1980

                   (APPENDIX F-2)



                        F-2-1

-------
                                                Transmittal letter for
                                                   Appendix F-2

+                  '                                     12291543-45605-0849R
**TLX MSG RCVD**
WASHINGTON DC   12-29-80
SMITHSONIAN INSTITUTION
FROM  WILLIAM H KLEIN   DIRECTOR
       SMITHSONIAN RADIATION BIOLOGY LAB.
TO  RICHARD^VAPD _ PETRO CHiMlCAL DEPT.
THIS WILL ACKNOWLEDGE MY COMMENTS ON THE NAS REPORT.

-------
                                       Effects  - UV-B Measurement
                 COMMENTS ON THE NATIONAL  ACADEMY
             OF SCIENCES REPORT:  "PROTECTION  AGAINST
               DEPLETION OF STRATOSPHERIC OZONE BY
                      CHLOROFLUOROCARBONS."
                        TABLE OF CONTENTS
                                                        Page


1.  INTRODUCTION                          ,              F-2-3

2.  DIFFICULTIES IN THE MEASUREMENT OF UV-B

    A.  UV-B Measurement as an Experimental
        Complication                                    F-2-3
    B.  Laboratory Measurements                    .     F-2-A
    C.  Field Measurements                              F-2-A
    D.  Weather Corrections                             F-2-A
    E.  Significance of UV-B Measurement Difficulties    F-2-6

3.  LATITUDINAL VARIATION OF UV-B AND ACTION SPECTRUM  SELECTION

    A.  Projected UV-B Changes versus UV-B Changes
        with Latitude                                   F-2-6
    B.  Comparison of Measurements at Various Latitudes F-2-6
    C.  Calculating DNA Dose from Five Nanometer
        Energy Integrals                                F-2-8
    D.  Action Spectrum Choice                          F-2-11
    E.  Action Spectra other than DNA                   F-2-11
    F.  Si-gnificance                                    F-2-13

A.  SUPPLEMENTATION OF UV-B WITH LAMPS

    A.  Experimental Limitations and Sources of Error    F-2-15
    B.  Physical Characteristics of Lamps               F-2-16
    C.  Experimental Factors in the Use of Lamps        F-2-16
    D.  Significance of Difficulties in Supplementing
        UV-B with Lamps                                 F-2-16

5.  REFERENCES                                          F-2-19
                              F-2-2

-------
                                         Effects  -  UV-B  Measurement
        COMMENTS BY DR.  W.  H.  KLEIN ON THE  NATIONAL  ACADEMY OF
    SCIENCES REPORT,  "PROTECTION AGAINST DEPLETION OF STRATOSPHERIC
                    OZONE BY CHLOROFLUOROCARBONS."
1.   INTRODUCTION

         I have examined the National  Academy  of  Sciences  (NAS)
Report entitled, "Protection against Depletion of Stratospheric
Ozone by Chlorofluorocarbons" (NAS, 1979)  with particular  emphasis
concerning measurements of UV-B (285-320 nm) and  techniques of UV-B
supplementation.  The comments concerning  this aspect of the report
are my opinion and can only be attributed  to me and no other person
or organization.

         The report,  in its entirety,  is a rather comprehensive and
very good review of the ozone and UV-B situation.  However, the
effort to summarize the complex problems does  oversimplify and
possibly results in statements that may be misleading.

         The following comments (Sections  2-4) are intended to be
constructive and informative, so that  future experiments can be
improved.


 2.  DIFFICULTIES IN THE MEASUREMENT OF UV-B

     A.  UV-B Measurement as an Experimental Complication

         NAS acknowledged the difficulties in  the measurement of UV
radiation:

              "Measurement of the UV radiation itself introduces
         additional complications, which were  especially troublesome
         in earlier experiments.   While spectroradiometric
         measurements (that is, absolute measurements of the
         radiation per unit area and unit  spectral bandpass at a
         sufficient number of representative wavelengths)  have been
         made recently by most investigators,  this was not done in
         most of the  earlier studies.   Instead, simpler dosimeters
         were utilized, such as the Robertson-Berger meter, which
         characterizes a broad waveband with respect to a  weighting
         function that may not be biologically correct.  The
         uncertainty  introduced by meters  of this  kind is  discussed
         in Appendix E."  (NAS, 1979,  p. 66).

         However, definitive information about the magnitude of the
difficulties was not  provided.


                                F-2-3

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                                         Effects  -  UV-B Measurement

     B.  Laboratory Measurements

         The best spectral irradiance measurements  that can be made
today between 250 and 350 nm are accurate to about  3  to 5 percent in
a rigidly controlled laboratory measurement.  Depending on what kind
of standard source is used, calibration accuracy  of UV-B instruments
can vary from less than 5 percent to about 10 percent (National
Bureau of Standards, 1977).  Argon mini arcs have an  uncertainty in
their irradiance of an estimated 6 percent for wavelengths greater
than~140 nm.  The National Bureau of Standards (NBS)  synchrontron UV
radiation facility can calibrate'spectrometer and photometer units
to better than 5 percent.

     C.  Field Measurements

         The measurement of UV-B radiation under  unfavorable field
conditions can .vary by as much as 25 percent (National Bureau of
Standards, 1977).  Temperature, depending on the  detector, has an
important effect on the accuracy of a measurement and normally under
field conditions this is not controlled.   Therefore,  some kind of
compensation is required for temperature-sensitive  detectors.  The
cosine correction and the transmission factors of a diffuser can
introduce sizeable errors if not determined and evaluated.  Stray
light problems associated with unwanted visible light not being
sufficiently blocked out in daylight field measurements can
introduce significant errors.

     D.  Weather Corrections

         If atmospheric conditions were always clear  and
pollution-free, there would not be the need for accurate
measurements of UV-B, since the amount of energy  would be primarily
dependent upon ozone concentration.  However, there are not too many
clear days; therefore, clouds, aerosols,  dust and other pollutants
such as sulfur dioxide should be considered.  Table 1 shows a
comparison of the measured* Radiation Biology Laboratory (RBL) daily
averages of UV-B centered at 305 nm at 40°N latitude  and calculated
values.  In addition, the cloud correction figures  used by Mo and
Green (1974) were applied to the calculated values.  It is obvious
that deviations of calculated values from measured  values under the
best of conditions range up to 25 percent.  There is  little doubt
that meterological conditions have a strong influence on the
quantity of UV-B reaching the surface of the earth, indicating that
monitoring of UV-B should be performed in order to  evaluate properly
UV-B energy doses received by biological organisms  (Klein and
Goldberg, 1978).
     Instrument accurate to +_ 5 percent based on a NBS  referenced
     standard lamp.
                                F-2-4

-------
                                         Effects - UV-B Measurement
                                Table  1
     The calculated integrated daily global UV radiation for 5  nm
      centered at 305  nm at  sea  level  for  a clear sky in units of
     joules m-2.   Average amounts  of ozone  for latitude  and  season
     have been used in the calculations  (Mo and Green, 197A).  The
           measured values are daily averages  for the month.

                                  Latitude AO°N
Month
Jan.
Feb.
Mar.
Apr.
May
-Dun.
July
Aug.
Sept.
Oct.
Nov.
Dec.
Calc.
62.78
15A.5
350.6
665.8
957. A
1163.
1230.
1087.
731.2
351.6
121. A
55.88
Meas.
A2.6A
137.6
239.2
532.9
5A3.0
687.2
NO DATA
NO DATA
NO DATA
271.8
10A.7
AA.78
Calc
Meas.
1.A7
1.12
1.A7
1.25
1.76
1.69
-
-
-
1.29
1.16
1.25
Cloud
Correction
.66A
.66A
.630
.759
.614
.6A7
-
-
-
.619
.670
.608
[Calc]
Meas.
Corrected
.98
.74
.93
.95
1.08
1.09
'
-
-
.80
.78
.76
                               Table 2


      Comparison of relative DMA dose, daily total UV from 280 nm
    to 322.5 nm (J m-2),  and daily total  insolation  from  280  nm  to
       2800  nm  U  m-2)  for representative days in Rockville, MD.

                 29 Mar 76     29  Jun 76     20 Sept  76    13 Jan  76

Daily DNA dose   24.12         45.34        30.10        4.60

Daily total UV   3.95 x 10*     5.6A x 10A   A.60 x 10A    l.AA x  104
Daily total
  insolation
1.16 x 107    1.98 x
                                                   107    6.95  x  106
                                F-2-5

-------
                                         Effects  -  UV-B Measurement


     E.  Significance of UV-B Measurement Difficulties

         It is essential that instruments and  standards be  developed
to enable researchers to measure changes  in UV-B  with  an  accuracy
that will provide the data needed to follow changes to which
biological organisms will be exposed at the surface of the  earth.
These measurements must be sensitive and  accurate enough  to indicate
relatively small changes in ozone,  or to  indicate small changes  in
ultraviolet irradiation to which biological material will be
exposed.  Calculations are only valid for essentially  clear days.
They should not be used to determine UV-B exposure  since  the error
can be large.

  3.  LATITUDINAL VARIATION OF UV-B AND ACTION SPECTRUM SELECTION

     A.  Projected UV-B Changes Versus UV-B Changes With  Latitude

         The MAS Report commented:

              "Recognizing all the  above  uncertainties, Figure 2.1
         indicates the increases in the annual DNA-damaging UV at
         40°N latitude expected from possible  ozone-layer reductions
         over the next century (assuming  continued  release  of
         chlorofluorocarbons at the 1977  rates).  A 7.5 percent
         ozone-layer reduction would, for example,  lead to  about a
         19 percent increase in DNA-damaging UV,  and a 16 percent
         reduction to about a 44 percent  increase.   (These  values
         will be somewhat less at latitudes toward  the equator and
         greater at higher latitudes). The increase in DUV for  a
         given decrease in ozone concentration is larger  than the
         figure estimated in earlier reports,  but this is hardly a
         significant change in the  light  of remaining  uncertainties
         about the proper weighting function.   The  change arises
         from more recent knowledge of the solar  intensity
         distribution at the shorter wavelengths, coupled with a
         presumably better action spectrum (Appendix C)."  (NAS,
         1979, p. 62)

     B.  Comparison of Measurements at Various Latitudes

         It is estimated, considering all the  uncertainties during
continued 1977 releases of chlorofluorocarbons, that an increase in
UV-B reaching the earth's surface would be of  the order of  19 to 44
percent.  This is small compared to existing differences  at latitude
39°N (Rockville, MD), 30.4°N (Tallahasee, FL)  and 9°N  (Panama),  all
from actual UV-B totals and from DNA dose equivalents that  follow
(see Table 4).


                                F-2-6

-------
                                         Effects - UV-B Measurement
                                Table  3
    Comparison of relative DNA dose and daily total UV from 280  nm
    to 322.5 nm (3  m-2)  for  representative days in  Tallahassee, FL.

                 20 Mar 76     21 Jun 76 28  Sept  76      06 Jan  76
Daily DNA dose   45.68         55.54     36.75,           16.00
Daily total UV   4.60 x 10*    4.57 x 10*   3.01  x 10*   2.42  x
No totals
  available          -                       -
                               Table 4
    Comparison of relative DNA dose,  daily  total  UV  from  280 nm to
      322.5 nm  (J m-2), and daily total insolation from 280 nm  to
       2800 nm (J m-2) for representative days  in  Panama,  and  a
      comparison with  corresponding quantities for Rockville,  MD.

                 23 Mar 76     30 Jun 76     27  Sept  76    18 Dec 75
Daily DNA dose   130.96        112.25       124.85       90.24

Daily total UV   1.02 x 105    9.50  x 104    1.01  x 105    8.32  x 10A
Daily total
  insolation      2.12 x 10?    1.66  x 107    1.54  x 107    1.50  x 107
Ratios,  Panama; Rockville
Daily DNA dose   5.4           2.5           4.1           19.6
Daily total UV   2.6           1.7           2.2            5.8
Daily total
  insolation      1.8           0.8           1.0           2.2
                                F-2-7

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                                         Effects - UV-B Measurement
     C.  Calculating DNA Dose  from  Five  Nanometer Energy Integrals

         A necessary part of doing  UV  mutagenesis studies is to
determine the dose of radiation received by  the organisms of
interest.  There are two ways  to measure this  dose with radiometric
instruments; either measure with an instrument that has the same
spectral sensitivity of DNA, or measure  with an instrument of
different sensitivity and use  the DNA-sensitivity relationships to
convert these measurements to  some  relative  dose measure.  In this
case, we have chosen the latter method,  using  an eight channel UV
radiometer that measures the integrated  energy in a nominal
bandwidth of five nm, centered at 285, 290,  295, 300, 305, 310, 315,
and 320 nm (Goldberg and Klein, 1974).   For  the DNA sensitivity
curve (action spectrum) we have used the one from Setlow (1974), as
used by NAS.  The choice of action  spectrum  represents a major
uncertainty itself, as discussed in 3.D  and  3.E below.

         Given a relative sensitivity  function, the dose (D) is
defined:
                   °  •  J
E(x)  I(X)   dX
         where     E(X)    is the relative  sensitivity  curve
                   I(X)    is the spectral  density  of the  light input
           and     X      is the wavelength

Since we do not measure  I(X) directly,  but rather  measure the energy
integrals over the eight channels (each 5  nm  wide), we  approximate:

               8              Xi + 2.5

         D =   I  (E (X^    ji(x)   dx;   Xi  =  285, 290,..., 320

             i = 1             Xi - 2.5

A further assumption is  that dose and radiant flux are  linearly
related with respect to  time; doubling  the exposure time  while
cutting the flux in half should give the same dose.  'Dose units used
here are arbitrary; one  dose unit is the equivalent of  1000 Jm-2
of 310 nm light.  In terms of flux, one dose  unit  is equivalent to
10 W m-2 of 310 nm light for 100 seconds (or  5  W nr2 of 310 nm
light for 200 seconds).

         The tables presented here show total dose, total UV (280 nm
- 322.5 nm), and total insolation (280  nm  -2800 nm) for three sites
at four times of the year for representative  days.  Hourly totals
are given for dose and UV.  Days are deemed representative on the
basis of having a daily  total insolation that is near  average for
the location and season.  Tables 5-7 show  hourly totals,  and are
summed to provide the daily totals in Tables  2-4.   Table  4 also
compares the ratios between Panama and  Rockville,  MD.   Using the
Setlow DNA action spectrum the average  DNA daily dose  is  340 percent
larger in Panama, while  the average daily  insolation is only 28
percent larger in Panama.


                                 F-2-8

-------
         Effects - UV-B Measurement

Table 5

Hourly totals for relative DNA dose and tc
322.5 nm (J m-2) for representative daj
(1976).
29 Mar 76 29 Jun 76 20
Hour
4-5
5-6
6-7
7-8
8-9
10-11
11-12
12-13
13-14
14-15
15-16
16-17
17-18
18-19
19-20
Dose

0.00
0.02
0.25
0.86
3.23
4.40
5.06
4.58
2.53
0.92
0.30
0.04
0.00

Total
UV

1
192
1257
2559
4988
5956
6602
6432
4217
2078
1083
297
15

Dose
0.0
0.02
0.21
0.91
2.66
4.60
8.59
10.41
8.83
4.41
1.27
1.09
0.37
0.07
0.00
Total
UV
4
191
1068
2571
3880
5478
8632
9917
9029
5416
2328
2494
1416
442
31
Dose

0.00
0.02
0.28
3.04
5.20
6.71
6.27
4.31
2.45
0.61
0.05
0.00


Dtal UV from 280 nm to
fs in Rockville, MD
Sept 76
Total
UV

1
198
1201
5408
7397
8489
8033
6232
4381
1497
223
27


13
Dose



0.02
0.31
0.74
1.06
1.22
0.77
0.34
0.04
0.01
0.00


Jan 76
Total
UV



26
1428
2548
3001
3335
2232
1185
243
56
2


F-2-9

-------
                                         Effects - UV-B Measurement
                               Table 6
 Hour

 5-6
 6-7
 7-8
 8-9
 9-10
10-11
11-12
12-13
13-14
-14-15
15-16
16-17
17-18
18-19
19-20

Note:
totals for relative DNA dose and total UV from 280
nm (J m-2) for representative days in Tallahassee,
20 Mar 76 21 Jun 76 28 Sept 76
Dose

0.00
0.10
0.77
2.63
4.33
5.68
10.02
8.61
7.56
3.93
1.65
0.39
0.02

Total
UV

9
403
1782
3683
4474
4979
7956
7014
7024
4560
2857
1138
113

Dose
0.00
0.06
0.54
2.13
5.09
7.47
9.45
8.55
9.44
6.04
3.23
2.47
0.89
0.16
0.01
Total
UV
6
261
1214
2924
4849
5678
6290
5557
6261
4368
3050
3003
1668
508
40
Dose

0.00
0.10
0.76
3.64
2.81
7.41
7.45
6.42
3.72
2.90
1.16
0.08
0.00

Total
UV

16
488
1364
3587
2200
5008
4899
4272
2887
3014
1934
423
9

nm to
FL.
06 Jan 76
Dose


0.00
0.04
0.27
1.27
2.95
3.93
3.63
2.45
1.13
0.31
0.03


Total
UV


8 '
198
745
2299
4183
5047
4766
3718
2260
903
116


The instrument used at Tallahassee  differs  from  the others
in that instead of measuring a  5  nm wide  integral centered
at 300 nm, it measured a ten nm wide integral  at 297 nm.
This measurement is used with the 295 nm  integral to
estimate the 300 nm integral.
                                F-2-10

-------
                                         Effects  -  UV-B Measurement


Table 7




Hourly totals for relative DNA dose and total UV from 280 nm to
322.5 nm (J m-2) for representative days in Panama.
23 Mar 76 30 Jun 76 27
Hour
6-7
7-8
8-9
9-10
10-11
11-12
12-13
13-14
14-15
15-16
16-17
17-18
18-19
Dose
0.01
0.47
3.15
6.57
14.45
25.54
25.14
24.92
18.29
8.98
3.02
0.42
0.01
Total
UV
72
1361
497.1
6834
10892
16533
15552
16144
13898
9143
4788
1345
49
Dose
0.03
0.71
3.14
8.14
18.77
28.47
22.43
14.81
6.48
5.80
3.05
0.41
0.02
Total
uv •
205
1952
4732
8401
15056
19586
15039
10758
5928
6783
5176
1269
100
Dose
0.02
0.60
1.26
3.57
11.95
33.99
32.36
25.61
9.97
4.11
1.33
0.09
0.00
Sept 76
Total
UV
98
1645
2155
3899
9918
24206
22381
19123
9335
5531
2661
390
2
18 Dec
Dose
0.00
0.34
2.53
8.41
14.84
23.51
18.53
14.16
5.74
1.55
0.57
0.05
0.01
75
Total
UV
50
1319
4889
10121
13516
18229
13948
11513
5643
2217
1519
239
7
     D.  Action Spectrum Choice

     The relative response of a  system  to  various-wavelengths of the
visible and near-visible light spectrum is termed an action
spectrum.  A particular action spectrum is a  very specialized thing
and may apply only under the  conditions used  to obtain it.
Therefore,  it is probably more appropriate to indicate that this is
an action spectrum and not the action spectrum.

     E.  Action Spectra Other than  DNA

         Figure 1 shows the weighting functions in current use for
biological  effects.  For our  comparison of measured UV-B values and
calculated  DNA dose for each  latitude,  we  have used, and NAS used,
the most effective action spectrum  for  biological material.
Therefore,  the maximum effect is shown  and all the other weighting
functions will generally be considerably less.
                                F-2-11

-------
                                    Effects - UV-B  Measurement
    z
    LU
    UJ
    u.
       -1
       -2
       -3
    UJ
    cr

    O
    O  -4
       -5
        280    290    300     310     320


                         WAVELENGTH (nm)
                                          Photosynthesis

                                          Inhibition
330
       340
Weighting functions in current use for  biological UV effects.
                        FIGURE 1

              (from MAS,  1979,  p. 307)
                         F-2-12

-------
                                         Effects  -  UV-B Measurement


     F.  Significance
                                                      /
         There is already a natural variation with  latitude  that
greatly exceeds the anticipated change in UV-B due  to  ozone
changes.  My opinion is that comparisons  can be made between
latitudes using modern controlled environment facilities  in
ultraviolet transmitting glasshouses.   In fact, it  is  recommended in
the Report under Major Research Issues (MAS,  1979,  p.  71)  that such
a monitoring facility be established at various locations.   The
action spectra for most biological effects of ultraviolet  radiation
are not well known and caution should  be  used when  using  generalized
action spectra for estimating effects. Use of the  DNA or  Setlow
action spectrum represents a "worst case" choice.

              "Another type of natural ozone variation offers an
         opportunity to set limits on  the magnitude of
         ozone-depletion effects.   These  are cyclic variations,
         amounting to approximately 5  percent total amplitude at
         temperate latidudes, over a period of about a decade
         (Angell and Korshover, 1973). Weighted  for DNA-damaging
         effectivenss, such ozone variations would  produce roughly a
         13 percent change in DUV.  The common experience  of
         temperate areas of the world  (which have repeatedly been
         through such cycles) shows that  changes  of this  magnitude
         do not produce any spectacular effects on  plants  or animals
         over the relatively few years of their duration.  (Small
         effects would, of course, tend to be blurred  by  the
         ordinary variations in weather and other factors.)  While
         there seems to have been no concerted effort  at  detecting
         effects due to these changes, it would seem safe  to say
         that most organisms can reasonably accommodate decade-long
         oscillations in ozone concentration,  of  the order of one
         third of the 16 percent change expected  from  continued CFC
         release at current rates."  (NAS,  1979,  p. 64)

         I agree with the above statement about cyclical  variations
and according to Figure 2 (World Meterological Organization, 1977)
this kind of variation in ozone has been  occurring  for twenty or
more years.  It would seem to me that  most organisms could safely
handle a two or three percent change in ozone with  little  or no
detectable effect.  It would probably  not be  a measureable
biological response with current techniques and methods.
                                F-2-13

-------
                                              Effects -  UV-B  Measurement
 30r-
 20
 10
-10
-20
  6
  4
  2
  0
 -2
 -4
 •4
  2
  0
 -2
 -4
  A
  2
  0
 -2
 -4
  4
  2
  0
 -2
 -4
 -6
 -8
UJ
O
z
UJ
o
cr
UJ
a
        (Note different  scale
         compared with other
         regions  below)
-10
                                                 TJ.S.S.R.
                                             (7 stations)
                                                                                EUROPE
                                                                            (14 stations)
                                                                                 WORTH  -
                                                                                AKEEICA
                                                                            (11 stations)
                                                  JAPAN
                                              (3 stations)
                                                                                 INDIA
                                                                             (5 stations)
  1950
                 1955
iyoo
I9G5
1970
I97D
I960
    Tine variation in  total ozone in north temperate latitudes expressed as a percentage
    deviation from the mean for the total length of record (the annual  oscillation has
    been removed).   A 1-2-1 smoothing (divided by four) has been applied twice to the
    successive seasonal values.
    Vertical bars  represent two standard errors of estimate based on  individual station
    values within  the  regions.  Single-shafted arrows indicate occurrence of quasi-
    biennial west  wind maximum at 50 mb in the tropics;
         A = Exuption  of Mt. Agung (Indonesia)  F = Eruption of Kt. Fuego (Guatemala)
         N •» Large nuclear explosions          S = Large solar proton  event.
                                      FIGURE 2
               (from  World  Meterological  Organization, 1977)
                                       F-2-14

-------
                                        Effects - UV-B Measurement


 A.  SUPPLEMENTATION OF UV-B WITH LAMPS

     A.  Experimental Limitations and  Sources of Error

         The NAS report acknowledges difficulties associated with
experimental supplementation of UV-B with  lamps:


              "The measured spectral composition of radiation from
         the lamp sources is not the same  as that of sunlight over
         the biologically effective wavelengths (Figure E.I,
         Appendix E).  Consequently, in  comparing its effects on
         plants and animals with those of  natural sunlight, a
         weighting function based on the proper action spectrum must
         be applied to the spectral distributions of both sources.
         If the biological action spectra  for UV radiation damage to
         plants and animals were known precisely, one might make an
         accurate comparison by this means and be able to predict
         the consequences of ozone depletion from the lamp
         experiments.  However (as explained above and in Appendix
         D), the action spectra for most biological effects of UV-B
         radiation are not well known, and one must usually surmise
         their form approximately. This can introduce an
         uncertainty of as .much as twofold in predicting the
         increased biological damage accompanying a 16 percent
         reduction in the ozone layer."  (NAS, 1979, p. 65)
and:
              "Finally,  the environmental  conditions under which
         many of the experiments  have  been performed may in some
         cases have altered the sensitivity of  plants  and animals to
         UV-B radiation.  For example,  the UV sensitivity of plants
         appears to be as much as fourfold greater in  the artifical
         illumination of plant environment growth chambers or in
         greenhouses, than in the open-field environment, possible
         because of the  different level of photosynthetic
         illumination.  Unfortunately,  this means that the
         experiments providing the most completely controlled
         conditions (which should therefore allow more refined
         testing) are not by themselves able to evaluate the
         consequences of increased solar UV on  plants.  Also, in
         most experiments, plants and  animals have been subjected to
         environmental conditions free  from other stresses besides
         the UV radiation.  Thus, the  interaction of such other
         stresses with the UV-B has not yet been evaluated." (NAS,
         1979, p. 66)
         Further justification  for  these concerns follows below


                                F-2-15

-------
                                         Effects - UV-B  Measurement

     B.  Physical Characteristics

         Experiments using fluorescent lamps to provide  supplemental
UV-B must be carefully examined before accepting the  results,  even
on a qualitative basis.  Lamps age and filters  change and  the
shortwave cutoff (Figure 3) often is not appropriate, as well  as the
spectral quality and intensity of the rest  of the spectrum.  Figure
4 presents the aging effect on the emission of  a UV-B lamp.  Forty
percent of the energy is lost at the end of 2000 hours and the
decrease is relatively uniform after the first  10 hours  of use.
This loss associated with the slow darkening of the filters
introduces significant errors in doses unless measured and adjusted
practically every day.

     C.  Experimental Factors in the Use of Lamps

         One of the serious defects in UV-B supplemental lamps is
the inability to irradiate in the natural min-max-min mode as  occurs
in natural daylight.  This produces an improper dose  rate  and  could
cause a completely different response to occur.   Tables  5-7 show the
hourly doses of UV-B and also equivalent DNA dose at  three latitudes
for a representative day, indicating change with time of day.  It is
evident that a fixed intensity for four to  six  hours  would not
simulate the natural exposure conditions.   The  lamp position is
fixed and usually produces a non-uniform source of UV-B  energy, with
also a fixed shade over certain portions of the plant canopy.  This,
then, results in less uniform visible light for photoreactivation
effects to occur.  Most growth chambers cannot  simulate  the natural
daylight, neither from the spectral distribution nor  intensity
standpoint and, therefore, results cannot be used to  predict field
responses unless an appropriate transfer function is  first
determined.   It is plausible that this light quality  and intensity
difference is the reason for a 4-fold difference in UV-B sensitivity
of plants grown in growth chambers versus natural conditions.

     D.  Significance of Difficulties in Supplementing UV-B with
         Lamps

         Extreme caution should be used in  attempting to extrapolate
UV-B effects from growth chamber results to natural conditions
because of the inability to reproduce natural conditions.  Even
experiments unde'r natural conditions with supplemental UV-B lamps
should be evaluated with the full knowledge that lamps and filters
change on a daily basis.  Experiments should be conducted  in which
monitoring of these factors are performed on a  daily  basis.
                                F-2-16

-------
                                 Effects  - UV-B  Measurement
        10
       10'
       10'
       10'
                                      Solar Irradiancv
           fl'lO  0.20 / / 'OSO  •<"> • cm Oione
               I  Q.30'0.401	|	
        280    290    300    310    320

                      WAVELENGTH (nm)
                                      330
Spectral irradiance  at  a  distance of 16.5 cm
from six FS40 sunlamps, filtered with 5-mil cellulose
acetate, superimposed on  the  solar spectral irradiance
(sun 30° from zenith) with different ozone thicknesses.
                     FIGURE 3
           (from  NAS,  1979,  p.  320)
                       F-2-17

-------
 c
 0)
 CD
 (H
 CD
 0)
z:

CD
 I
      FIGURE  4.   DECAY CURVE FOR SYLVANIA UV-B LAMP #2021


            GTE  SYLVANIA UV PHOSPHOR  F48T12/2021/VHO
          Test duration  2000.h  (2 May 80 - 24 July  80)
en
4->
o

-------
                                         Effects  -  UV-B  Measurement

5.  REFERENCES

         Copies of the cited references appear  in the  Reference
Volumes.


Goldberg, B.  and Klein,  W.  H.  (197A).   Radiometer to monitor  low
     levels of ultraviolet  irradiances.  Appl.  Opt., jj  (3),  493-496.

Klein, W. H.  and Goldberg,  B.  (1978).   Monitoring UV-B spectral
     irradiances at three latitudes.   Proc.  Internatl. Solar  Energy
     Soc. Congress (Pergamon Press)  !_,  400-413  (New Delhi,  India,
     January).

Mo, T. and Green, A.E.S. (1974).   A  climatology of  solar erythema
     dose.  Photochem. Photobiol.,  20,  483-496.

NAS - National Academy of Sciences  -  (1979).  Report of  the Committee
     on Impacts of Stratospheric  Change,  ir\_  "Protection  Against
     Depletion of Stratospheric Ozone  by  Chlorofluorocarbons."
     December, Washington,  D.C.

National  Bureau of Standards (1977).   Symposium on  Ultraviolet
     Radiation Measurements for Environmental Protection and  Public
     Safety,  June 8-9, Gaithersburg,  MD.

Setlow, R. B. (1974).  The  wavelengths in sunlight  effective  in
     producing skin cancer:  a theoretical analysis.   Proc. Nat.
     Acad. Sci. USA. 73.  (9), 3363-3366.

World Meteorological Organization  (1977). UNEP Meeting  of  Experts:
     Atmospheric Ozone.   A  survey  of  the  current  state of knowledge
     of the ozone layer, March 1-9.   Washington,  D.C.
                                F-2-19

-------
           COMMENTS  ON  THE NATIONAL ACADEMY
       OF  SCIENCES REPORT:   "PROTECTION AGAINST
         DEPLETION OF STRATOSPHERIC OZONE BY
                CHLOROFLUOROCARBONS. "
PREPARED FOR E. I.  DU PONT DE NEMOURS & COMPANY,  INC,
                         BY
                   DR.  R.  H.  BIGGS
                      PROFESSOR
     INSTITUTE OF FOOD  AND AGRICULTURAL SCIENCES
                UNIVERSITY OF FLORIDA
                GAINESVILLE, FLORIDA
                   DECEMBER, 1980


                   (APPENDIX F-3)
                        F-3-1

-------
                                                           Transmittal  letter for
                    UNIVERSITY OF FLORIDA         Appendix F-3

                    INSTITUTE OF FOOD  AND AGRICULTURAL  SCIENCES
                                                                 •


                                                               GAINESVILLE. FLORIDA 32611
FRUIT CROPS DEPARTMENT
     1172 MCCARTY
TELEPHONE: 904-392-1996
                                              December 15, 1980
         Dr.  Richard B, Ward
         Research Associate,Environmental
         E.I.  duPont de Nemours  & Company
         Wilmington, Delaware  19898
         Dear  Dr. Ward:

              Enclosed please  find my comments on the National Academy of
         Science Report: "Protection against depletion of stratospheric
         ozone by chlorofluorocarbons."  I understand it will be appended
         to a  report  you will  be  submitting to EPA.

              I hope  the comments are useful.
                                              Sincerely,
                                              Dr. R, H. Biggs
                                              Professor (Biochemist)

-------
                                                   Effects  - Crops
                 COMMENTS ON THE NATIONAL ACADEMY
             OF SCIENCES REPORT:  "PROTECTION AGAINST
               DEPLETION OF STRATOSPHERIC OZONE .BY
                      CHLOROFLUOROCARBONS."
                        TABLE OF CONTENTS



                                                       Page


1.  INTRODUCTION                                       F-3-3


2.  SUMMARY                                            F-3-3


3.  SPECIFIC COMMENTS ON THE REPORT                    F-3-A

    A.  General observations on an inadequate  data
       base for prediction.                            F-3-A

    B.  Biological Responses to UV-B radiation.          F-3-A

       (1) Action spectra and biological weighting
           functions                                   F-3-A
       (2) Shielding and orientation                   F-3-5
       (3) Field and environmental  chamber  problems     F-3-6
       (A) Significance of UV-B change                 F-3-10
       (5) Major research issues                       F-3-10


A.  REFERENCES                                         F-3-13
                              F-3-2

-------
                                                     Effects  - Crops
        COMMENTS BY DR. R.  H.  BIGGS ON THE  NATIONAL  ACADEMY OF
    SCIENCES  REPORT,  "PROTECTION AGAINST DEPLETION OF STRATOSPHERIC
                    OZONE BY CHLOROFLUOROCARBONS."
1.  INTRODUCTION

         In studying the new National  Academy  of Sciences  (NAS)
report, "Protection against depletion  of  stratospheric ozone by
chlorofluorocarbons" (NAS,  1979)  with  particular emphasis  on higher
plant systems, I had the reactions noted  on  subsequent pages.  I
appreciate the opportunity  to study this  report and  am hopeful that
my reactions to an extremely complex problem are useful.   The
comments reflect my efforts, and  so opinions stated  can only be
attributed to me and no other person or organization.

         Periodical review  of this complex problem by the  National
Academy of Sciences Committee on  Impacts  of  Stratospheric  Change is
extremely useful,  and indeed, the present document is a valuable
general review of  the UV-B  radiation problem as it is envisioned
today.  Careful reading of  each section of the document does
indicate that conclusions based on facts  are fair in light of my
knowledge of the problems.   It is the  "summaries of  summaries," the
attempt to boil down the complex  problem  to  a  socially manageable
one, that I would  criticize.  Specific suggestions will be related
to the sections of the report dealing  with higher plants and will
contain some suggestions as to future  research endeavors that may
lend insight into  plant responses to UV-B radiation  that may have
some predictive value as applied  to both  cultivated  and
non-cultivated ecosystems.
2.  SUMMARY
             There is no data base  to  predict that a catastrophe
             will occur with  crop plants  as  a result of decreasing
             ozone predicted  to  occur  at  present chlorofluorocarbon
             release rates  or those after 5  years.

             Growth chamber and  greenhouse studies of cultivated
             plants cannot  be used  at  the present time to predict
             yields under field  conditions.  These types of studies
             should be continued along with  field studies.

             We need a much larger  data base to predict effects of
             increasing UV-B  radiation on crop yields.  Top priority
             should be placed on field studies, action spectra, and
             real-world documentation  as  related to changes in UV-B
             irradiance in  cropping systems  and in non-cultivated
             ecosystems.
                                F-3-3

-------
                                                     Effects - Crops


3.  SPECIFIC COMMENTS ON THE REPORT

         (NAS, 1979 - Chapter 2: Nonhuman Biological Effects,  pp.
         58-73; Appendix D:  The Biologically Effective Ultraviolet
         Radiation, pp. 304-318.)

      A. General observations on an inadequate data base for
         prediction

         From my assessment of the Terrestrial effects, non-human
research, there is not a data base at this point to do much
predicting of the biospheric consequences of a stratospheric ozone
reduction.  Although it is limited, the better data base is for
cultivated plants, and in this case,  there is no reason to
anticipate an immediate catastrophe.   In fact, what is evident is
that there are alternative ways to cope with this environmental
stress factor just as there are for high solar irradiances, drought,
winds, unfavorable temperatures, etc.  Plants have mechanisms  to
cope with UV-B radiation (285-320 nm) to varying degrees.   The real
question that must be addressed is:  when does the UV-B radiation
exceed a certain threshold that will  affect yield, or some other
desirable plant trait of a crop or ecosystem?  we cannot predict the
answer to this question with any precision as to yields from any
higher plant at the present time, nor can we predict what  will
happen on specific ecosystems.  Therefore, the position at this
point should be that there is the possibility of an additional
stress load on terrestrial plants, both cultivated and
non-cultivated, from an increase in UV-B radiation in the  biosphere
should a 16% reduction in ozone ultimately occur.  However, the
degree of uncertainty that is associated with the possibilities
would seem to indicate that the best  course of action would be to
proceed for a limited period of time  to mount a good research  effort
to reduce (a) the uncertainties associated with knowing the degree
of stratospheric changes expected in  relation to time, say five
years when some verification of whether stratospheric ozone changes
predicted by atmospheric scientists is actually occurring, and (b)
those uncertainties associated with biological effects of  UV-B
radiation on plants.  The latter will be dependent on rates of
changes, i.e., seasonal and long-term patterns of change in
stratospheric ozone.

      B. Biological Responses to UV-B Radiation
         (NAS, 1979, pp. 58-63)

         (1)  Action spectra and biological weighting functions

             While there is no question that if DMA and proteins
absorb UV-B radiation there could be  damage, there is a question
about how much UV-B radiation is actually absorbed by nucleic  acids
and proteins that control plant growth and development, and the
relation of this absorbance to actual damage.


                                 F-3-4

-------
                                                     Effects  - Crops


             We do not have a way at the present  time of  estimating
this damage directly and indirect methods are  encumbered  by many
sources of error, i.e., reflective and absorbance properties  as
related to overall geometry of the plant;  shape,  structure and
orientation of individual organs; and internal structure  of organs,
particularly as related to protective absorbers.

             Biological weight functions are extremly important.
Our knowledge of how to make equivalences across  the  UV-B radiation
wave-band are based on only a few action spectra  for  biological
responses in this wave-band and these differ greatly  (Caldwell,
1977).  Since all quantitative predictions rely heavily on the
choice of the weighting function for evaluating potential damage,
there is reason for caution and a vital need for  a better data base
in this area, particularly between the correct weighting  function to
use as related to limiting factors in crop production or  in
competititon between species in ecosystems.

             Appendix D (NAS, 1979,  pp. 304-318)  is a good treatment
of the necessity for using biological weighting functions when
relating biological responses to the UV-B radiation wave-band.  As
more data becomes available, i.e., photosynthesis,  phytohormone
changes, partitioning of substrates  between plant organs, etc., it
will be essential to supply the appropriate weighting function to
each response.  The use of the weighting function that is based on
DMA has utility only because we lack the data  based on action
spectra as related to specific physiological processes that may be
limiting factors under natural conditions.  This  demonstrates an
area of research that is vitally needed, that  is,  action  spectra as
related to plant physiological responses to UV-B  radiation.

         (2) Shielding and orientation

             Meristematic and other  regenerative  cells are generally
well shielded in most cases from UV-B radiation.   In  view of  this,
it would seem important to stress avoidance mechanisms in more
detail than dealt with in the report, particularly as related to
photoprotection and future experimentation.  For  example, it  could
be that the phototropic responses of leaf orientation as  related to
incident radiation is an important factor in avoidance mechanisms.
The same would be true for orientation of meristematic organs.  If
the phototropic response is heliotropic in nature,  and this is the
case with certain varieties of soybeans, then  comparisons between
controlled environmental growth chambers and field conditions will
have another confounding parameter.   This may  seem like a small
point but in models to predict yields of soybeans,  leaf angle is a
major component (Duncan, 1971).  Knowledge of  these types of  plant
responses lends further credence to  implications  in the report that
controlled environmental chambers data cannot  be  used to  predict
plant responses, particularly yields in the field.   Related to this
problem is the statement in the NAS  report (NAS,  1979, p. 66) as
follows:


                                 F-3-5

-------
                                                     Effects  - Crops


                 "Finally, the environmental conditions  under which
             many of the experiments have been  performed may  in some
             cases have altered the sensitivity of plants and
             animals to UV-B radiation.   For example,  the UV
             sensitivity of plants appears to be as much as fourfold
             greater in the artificial illumination of plant
             environment growth chambers, or in greenhouses,  than in
             the open-field environment,  possibly because of  the
             different level of photosynthetic  illumination.
             Unfortunately, this means that the experiments
             providing the most completely controlled conditions
             (which should therefore allow more refined  testing) are
             not by themselves able to evaluate the consequences of
             increased solar UV on plants.  Also, in most
             experiments,  plants and animals have been subjected to
             environmental conditions free from other stresses
             besides the UV radiation.  Thus, the interaction of
             such other stresses with the UV-B  has not yet been
             evaluated."

It should be noted that even the "fourfold greater" estimate  of
sensitivity is at this point only a rough guess, and this is  for dry
matter production, not seed yields.


             A listing of other avoidance mechanisms identified as
important to the UV-B radiation assessment as to damage, namely,
pigment changes (Caldwell, 1977) phytohormones  (Lindoo e_t a.1. , 1979)
cuticles (Robberecht and Caldwell, 1978;  Kossuth and Biggs, 1978)
and changes in plant forms (Biggs and Kossuth,  1978) also reinforces
the idea that we have very little knowledge at  the present time of
transfer functions between growth and development of plants in
controlled environmental chambers and under field conditions  when
exposed to enhanced UV-B irradiance levels.  Thus a diligent  and
consistent effort should be made by biologists  and theoreticians to
establish the nature of these transfer functions, if they exist.

         (3) Field and environmental chamber problems

             I would agree with the last  sentence of the
introductory paragraph (MAS, 1979, p. 63) "only beginnings have been
made in this direction," meaning in relation to experimental  studies
on the general nature of biological responses both under field and
controlled chamber conditions.  (Using the word damage at this point
could prejudice the research before it is conducted.)

             While I would agree in principle with the idea that
"the epidemiological approach" would seem unworkable for estimating
effects of ozone depletion on plants because of many natural
uncontrollable factors, stratified experiments  could take advantage


                                F-3-6

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                                                    Effects - Crops


of the natural variation in UV-B radiation  at  ground level to assess
plant responses.   With many crop plants,  we  are  able to optimize
water, mineral elements, temperature,  gases  (quantities and quality)
and in fact most  factors except radiation.   Optimization and
characterization  of radiation for control environmental climate
chambers and greenhouses has been the  single most troublesome
component.   The use of natural solar  fluences  with UV-B radiation as
high as, or higher than, what would accompany  a  16% ozone reduction
at 40°N latitude  (for example, high altitude in  Hawaii or other low
latitude and high altitude locations)  to  irradiate plants while
keeping other factors optimized would  seem  to  be a good experimental
approach,  especially if this is properly  interfaced to conventional
controlled  environmental phytotron and field experimentation.  For
this integrative  physiological approach,  systems analyses will be
very critical to  its success as a predictive tool.

             As has been pointed out  by Dr.  w. H. Klein in his
comments*,  experiments using fluorescent  sun lamps to supplement
UV-B radiation, spectral quality and  intensity,  and the ON-or-OFF
mode of actuating the lamps leads to  an unnatural exposure of plants
to UV-B irradiances.  In addition to  these  factors inherent in lamp
enhancement studies, there is the problem of an  unnatural albedo in
controlled  climate chambers with highly reflective walls.  This
enhances the albedo of UV-B irradiance over  the  direct component to
a much greater level than would generally occur  in nature.  This
could seriously hamper photo-control  avoidance mechanisms and could
lead to an  over-estimate of potential  damage.  The Duke Phytotron
study in the "C"  type chambers by Biggs and  Kossuth (1978) provided
much of the data  for the NAS summary  statement No. 1 (NAS, 1979, p.
67) as follows:

             11 1.  Tests of more than  100 species or varieties of
         species  in controlled environment  growth chambers indicate
         that approximately 20 percent are  sensitive to daily UV-B
         doses of the order of those  delivered by Florida sunshine
         at present ozone levels,  while 20  percent were resistant to
         doses four times greater than this, and the remaining 60
         percent  showed some intermediate sensitivity.  These tests
         would indicate that a significant  fraction of the present
         agricultural varieties are at present under UV stress and
         would suffer decreased production  with  a 16 percent ozone
         reduction."

             This research was done in chambers  with highly
reflective  walls  of polished aluminum. While  enough caveats were
placed in the detailed accounts on these  experiments, this summary
statement implies a level of damage that  could lead to an
over-estimate of  the problem. This means  that  summarizers should
make every  effort to guard against misleading  interpretation that
might arise in summary statements. For example, in the NAS Appendix
B (NAS, 1979, pp. 283-284):
*Note added by Du Pont.   See Appendix F-2,


                                F-3-7

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                                                     Effects - Crops


             "Over 100 species and varieties  of  agricultural plants,
         as well as some nonagricultural  higher  plant species, have
         now been tested for their comparative sensitivity to UV-B
         radiation in controlled environmental growth chambers.  A
         short-term,  but extensive screening  program  of 82 species
         and varieties was recently undertaken at  the University of
         Florida in Gainesville (R. H.  Biggs  and S. V. Kossuth,
         unpublished  BACER report).  Approximately 20 percent of the
         species were classed as highly UV-B-sensitive species.
         Many exhibited significant reductions in  yield when exposed
         daily to the lowest UV-B dose  employed, which is
         approximately equivalent to the  amount  of UV-B radiation
         received in  a half day of normal sunshine in the summer in
         northern Florida.   On the other  hand, 20  percent of the
         species suffered no apparent reduction  in yield at even the
         highest daily doses employed,  which  would correspond to
         roughly twice the amount of solar UV-B  radiation currently
         received during a summer day in  northern  Florida.  The
         remaining 60 percent exhibited intermediate  degrees of
         sensitivity  to UV-B radiation.   Apart from reductions in
         plant dry weight or yield, UV-B  radiation also affected the
         proportion of plant material represented  in  various plant
         organs such  as roots, shoots,  and leaves.  Although these
         alterations  might not necessarily be detrimental
         themselves,  they could result  in undesirable consequences
         for agricultural utilization of  the  plants." (Emphasis
         added).

             The word yield in this sense means  reductions in the
dry weights of plants grown under these rather stratified conditions
in the phytotron.  In subsequent summaries, there  is  the real
possibility that soybean will become the  modifier  and yields the
subject with a very active verb.  A case  in point  is  the fourfold
estimate statement in the second summary  of findings  (MAS, 1979, p.
677!

             11 2.  However,  15 species  and varieties  tested in the
         open field appeared more UV resistant than plants grown in
         laboratory environmental growth  chambers.  Where it is
         possible to  make comparisons of  the  same  plants, the
         differences  in resistance are  on the order of fourfold.  If
         this result  turns out to be general, the  higher sensitivity
         indicated in the growth chambers does not represent
         open-field behavior,  and the expected consequences of ozone
         depletion become considerably  less than those tests would
         indicate.  Nevertheless, some  species (sugar beets,
         tomatoes, mustard,  corn) still appear to be
         affected—although the field experiments were necessarily
         less well controlled, and the  results less clear-cut, than
         were the chamber studies."  (Emphasis added).


                                F-3-8

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                                                     Effects - Crops


             This was estimated from plant  growth  parameters so it
cannot be applied to yields.   If anything this  should be  viewed as
an over-estimate in terms of effects on crop  yield,  particularly as
applied to seed crops.

             Controlled environmental chamber studies cannot be used
to extrapolate to field conditions.   They do  provide a data base for
an identification of symptoms that might be encountered by higher
plants under stress from UV-B radiation.  It  may be  that  in
retrospect, after a sufficient comparative  data base between plants
grown in controlled environmental growth chambers  and under field
conditions have become available, that these  and other controlled
environmental studies could be the basis for  establishing transfer
functions for extrapolation between  highly  stratified studies and
field conditions, particularly biomass and  form.   At the  present
time there is a lack of field related studies to establish any
transfer functions especially for yields or organs associated with
reproduction.

             From our experience with field studies  and analyzing
the data of others there are many variables encountered.  One fact
noted from the CIAP studies (Biggs e_t al.,  1975) was that plants
become more sensitive to UV-B radiation as  irradiances in the UV-A
and visible portion of the spectrum  are decreased.

             Knowing this, our objective in the phytotron screening
test was to demonstrate the UV-B radiation  at moderate fluence
levels, but under stratified conditions to  demonstrate sensitivity,
does affect plants.  These tests were designed  to  study the
responses of the various species to  UV-B radiation stress to provide
a diagnostic symptoms base.  It was  assumed that plants that did not
demonstrate obvious symptoms of stress might  be very tolerant under
field conditions.  This latter is still a hypothesis.   Even though
it would seem logical, it must be substantiated by fact in the
integrative physiological reactive mode under field  conditions.  A
further hypothesis was that it may be possible  to  establish the
degree of sensitization to UV-B radiation that  arises as  a result of
the stratified conditions.  Verification of such a transfer function
has not been established but is seemingly related  to low  vs. high
irradiance in the visible portion of the spectrum.

             No studies of plant responses  under phytotron or
controlled environmental conditions  per sje  have ever been used
successfully to quantitatively predict crop yield  under field
conditions (Loomis ejt al. , 1979).  They have  been  used to
demonstrate that a certain parameter is critical to  growth and
development and should be considered at some  point in the hierarchic
levels of integration of a number of factors  to predict the output
of the yield of a crop from a plant  community.


                                 F-3-9

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                                                     Effects  - Crops


             A good realization of the limitation  of  controlled
environmental growth chambers was outlined  in  a  recent  report on how
to make comparisons between laboratories as to reliability  of growth
chamber generated data (Ormond et_ al., 1980).

             It was once hoped that phytotrons would  fill the role
of being a powerful tool for the integrative physiology of  plants as
adaptive control systems.  This has not been the case and it  now
seems that crop modelers will be the principal consumers of plant
responses under phytotron,  or control  environmental conditions and
that models or system analyses will be the  integrative  tool (Loomis
£t al., 1979).  If this is  so and certain models have been
successfully applied to predict yields (Evans, 1977), experiments in
controlled environmental conditions, stratified  greenhouse  and field
tests and natural tests, should be interfaced  to maximize
establishment of interfacing components for system analyses.  Thus
an integrative approach would seem to  have  great merit  to study the
problem.

         (4) Significance of UV-B change

         My best estimate at this time from my own studies  and
reviewing others is that a  5 percent change in ozone, i.e., 13
percent UV-B irradiance increase, can  be tolerated by most
cultivated plants adapted to grow in full sunlight.   There  may be
minimal effects on yields of some crops, particularly those related
to biomass production, but  the data base does  not  allow for
quantitation in parameterizing the degree of effects  on yield.  One
would expect that the first observable changes would  be at  the low
latitudes where a predicted 5 percent  ozone would  be  super-imposed
on a cyclic variation around a nodal point  of  less ozone in the
stratosphere.

         (5) Major research issues: (MAS,  1979, pp.  70-72).

         I would concur with the NAS statement number 1 (NAS, 1979,
p. 70) on recent research advances:

             " 1.   Larger numbers of agricultural  plant varieties
         have been experimentally tested by radiation supplement for
         their sensitivity  to UV-B.  These  tests have confirmed the
         wide variation in  sensitivity among different  plant
         varieties that was suspected  earlier  and  have  also
         indicated that the sensitivity depends  on conditions of
         testing,  but the tests leave  the true sensitivity  profile
         of the most important agricultural plants in doubt."

             A concerted effort should be made as  I indicated in the
final paragraph of III.2.C, (page 10 of this Appendix).


                                F-3-10

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                                                    Effects - Crops


             I would wholeheartedly  support  the suggestion that
action spectra are very much needed  (NAS,  1979, p. 70) and would
make the task of constructing integrative  physiological systems as
related to changes in cropping and ecosystems much easier than would
an empirical approach.  To give proper  biological weighting between
UV-B radiation increases and functional disorders, action spectra of
limiting processes are a must.

             Both high-intensity, solar-simulators and
UV-transmitting greenhouses at high  altitudes in low latitudes are
excellent suggestions (NAS, 1979, p.  71).  My expansion on these
ideas would be to validate these tests  further with field tests in a
system analysis approach.

             A study to evaluate the  feasibility of crop breeding to
develop more UV-resistant cultivars  would  not only provide more UV-B
resistant selections but would give  some indication of the genetic
basis for adaptability (NAS, 1979, pp.  71-72.) and physiological
systems involved.  Plants have evolved  along with an evolution of
the atmosphere.  There were earlier  periods  when there were much
higher fluences of UV-B radiation.   Therefore, there are biological
mechanisms available for coping. The question is the rate of change
that can be handled by natural ecosystems.   As viewed for cultivated
plants, what is the feasibility of crop breeding to aid in coping
with increased UV-B irradiances and  genetically can these systems be
identified?  Allied to this would be  to address the question of how
many crop introductions in the tropics  in  high UV-B areas have
failed, or do poorly, because of this additional stress factor.
This could be a strategy to encourage research in this vital area
today which would lead to a better data base on the UV-B radiation
problem in general.

             NAS1 last paragraph on  major  research issues (NAS,
1979, p. 72) is well stated.  There  must be  a long-term commitment
to critical mass experimentation in  this area.  Facilities and
financial support must form part of  a consistent and sustained
research program.  The report of past efforts in this area, at best,
can only be viewed as the first stage of research.  It was
constructed to ask the questions:  Do we have a problem and what are
the possible effects?  There is a several  "quantum jump" required to
answer the question.  Given a certain percentage depletion of ozone
what will be the real effects on plants in the biosphere?  Thus, I
would agree with the general context  of the  concluding paragraph
(NAS, 1979, p. 72).  Time is required for  the development of a sound
data base.  A "gearing up" and "gearing down" on a short turnaround
time has produced experiments that were hastily conceived and
conducted to assist in parameterizing the  range of problems that
could be encountered by increased UV-B  in  the biosphere.

             In addition to the suggestions  in the report, I would
like to add the following from my perspective.


                                F-3-11

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                                            Effects  - Crops
Biologists need three critical items to address  many
questions relevant to effects of the UV-B radiation on
plants (or animals):

a)  Good irradiance sources of high intensity  with proper
    attentuating filters to simulate expected  solar
    irradiance in the UV-B wave-band.

b)  Reliable and rugged spectroradiometers to  validate
    conditions in tests.  This has to be coupled to
    dependable calibration standards.

c)  Systems capable of real-time analysis of variable
    integrative physiological components that  provide a
    basis for predictive purposes.

Examination of UV-B radiation reflectors, e.g.,  dichroic
filters, for enhancement studies in the field  should be
made.  They could possibly simulate ozone depletion better
than currently available lamps.

When a space laboratory becomes  a reality,  priority should
be given to the testing of higher plants to
extra-terrestrial solar radiation using attenuating filters
to approximate ozone depletion.
                       F-3-12

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                                                     Effects  -  Crops

4.  REFERENCES

      Copies of the cited references appear in the  Reference  Volumes.

Biggs, R. H. and Kossuth, S.  V. (1978).   Impact of  solar  UV-B
    radiation on crop productivity,  Final report of UV-B  biological
    and climate effects research.   Terrestrial.  FY 77.   Univ.
    Florida, Gainesville, FL.

Biggs, R. H., Sisson, W. T.,  and Caldwell,  M.  M. (1975).   Response
    of higher terrestrial plants to  elevated UV-B irradiance.   In:
    Nachtwey, D. S., Caldwell,  M.  M., and Biggs, R. H.  (eds).
    Impacts of climatic change  on the biosphere, CIAP Monograph 5,
    Part 1:  Ultraviolet radiation effects.  U.S. Dept. Trans.,
    Springfield, VA, pp. 4-34 to 4-50.

Caldwell, M. M. (1977).  The  effects of  solar UV-B  radiation
    (280-315 nm) on higher plants:  Implications of stratospheric
    ozone reduction.  In:  Castellani,  A. (ed).  Research in
    photobiology.   Plenum Publishing Corp., New York, pp. 597-607.

Duncan, W. G. (1971).  Leaf angles,  leaf area, and  canopy
    photosynthesis.  Crop Science 11, 482-485.

Evans, L. T. (ed)  (1975).  Crop Physiology.  Cambridge  Univ.  Press,
    pp. 374.

Kossuth, S. V.  and Biggs, R.  H. (1978).   Sunburned  blueberries.
    Fla.  State Hort.  Soc.  Proc. 9J.,  173-175.

Lindoo, S. J.,  Seeley, S. B.,  and Caldwell, M. M. (1979).  Effects
    of ultraviolet-B radiation  stress on the abscisic acid status of
    Rumex patientia leaves.  Physiol. Plant. 45, 67-72.

Loomis, R. S.,  Rabbinge, R.,  and Ng, E.  (1979).  Explanatory  models
    in crop physiology.  Ann.  Rev. PI.  Physiol. 30, 339-367.

NAS - National Academy of Sciences - (1979).  Report of the Committee
    on Impacts of  Stratospheric Change,  ijn  "Protection  Against
    Depletion of Stratospheric  Ozone by  Chlorofluorocarbons."
    December, Washington, D.C.

Ormond, P., Hammer, A., Krizek, D. T.,  Tibbitts, T. W., McFarlane,
    0. C., and Langhans, R. W.  (1980).   Base-line growth  studies of
    "First Lady" marigolds in controlled environments.  J. Am.  Soc.
    Hort. Sci.  105, 632-638.

Robberecht, R.  and Caldwell,  M. M. (1978).   Leaf epidermal
    transmittance  of ultraviolet radiation  and its  implication  for
    plant sensitivity to ultraviolet-radiation induced  injury.
    Oecologia 32,  277-287.


                                F-3-13

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           COMMENTS ON THE NATIONAL ACADEMY
       OF SCIENCES REPORT:  "PROTECTION AGAINST
         DEPLETION OF STRATOSPHERIC OZONE BY
                CHLOROFLUOROCARBONS."
PREPARED FOR E. I. DU PONT DE NEMOURS & COMPANY, INC,
                          BY
                 DR. DAVID M. DAMKAER
            AFFILIATE ASSISTANT PROFESSOR
              DEPARTMENT OF OCEANOGRAPHY
               UNIVERSITY OF WASHINGTON
                 SEATTLE, WASHINGTON
                    DECEMBER, 1980


                    (APPENDIX F-4)
                        F-4-1

-------
                                               Transmittal  letter for

                                                    Appendix F-4
                                     University of Washington
                                     WB-10
                                     Seattle, WA  98195
                                     December 16, 1980
Dr. Richard B.  Ward
Research Associate
E. I. DuPont DeNemours  & Company
Wilmington, Delaware  19898

Dear Dr. Ward:

     As I mentioned in  our conversation today,  I have read and
approved the most recent draft  of my  comments on the National
Academy of Sciences Report (1979)  "Protection against Depletion
of Stratospheric Ozone  by Chlorofluorocarbons."  You may con-
sider this the  final transmittal  of these comments.  I trust
that they will  shed light on  at least my opinions of the NAS
review.

                             Sincerely yours,
                             David  M.  Damkaer

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                                            Effects - Marine
                COMMENTS ON THE NATIONAL ACADEMY
             OF SCIENCES REPORT:  "PROTECTION AGAINST
               DEPLETION OF STRATOSPHERIC OZONE BY
                      CHLOROFLUOROCARBONS."
                        TABLE OF CONTENTS


                                                           PAGE

1.  INTRODUCTION                                           F-4-3

2.  SUMMARY                                                F-4-3

3.  SPECIFIC COMMENTS                                      F-4-4

    A.   Marine Phytoplankton - Natural communities
         in situ                                           F-4-5

    B.   Marine Phytoplankton - Single species
         in laboratory culture                             F-4-6
      I
    C.   "Aquatic Microorganisms, protozoa, algae,
         and small invertebrates"                          F-4-7

    D.  Marine Zooplankton -  (invertebrates)               F-4-8

    E.  Marine Zooplankton (fish eggs and larvae)          F-4-9

4.  CONCLUSIONS                                            F-4-11

5.  REFERENCES                                             F-4-13

6.  CITATIONS FROM THE NAS REPORT                          F-4-14
                              F-4-2

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                                           Effects - Marine
   COMMENTS BY DR.  DAVID M.  DAMKAER  ON THE NATIONAL ACADEMY OF
 SCIENCES REPORT,  "PROTECTION  AGAINST DEPLETION OF STRATOSPHERIC
                  OZONE BY  CHLOROFLUOROCARBONS."
1.  INTRODUCTION

         I  have  examined  the  title  report,  particularly  the
sections  on  aquatic  ecosystems.   The  comments  that  follow
represent my opinion and do not necessarily reflect the opinions
of  the National  Oceanic  and  Atmospheric  Administration  (my
employer), the Environmental  Protection Agency  (the supporters of
our research  on UV  effects) ,  or of the University of Washington
(with which I have a faculty affiliation).  That said, I believe
that the National Academy  of  Sciences  report (NAS)  was an even-
handed,  excellent  review of  the ozone/ultraviolet  radiation
concern, and  most of the  real  conclusions  were  fairly based on
what is known.  It is unfortunate that some of these  conclusions
were summarized and  oversimplified  in  sections  removed from the
more-detailed  reviews.   And  I  would  criticize  those  areas
particularly  since it  is  the  summary sections  that will be most
widely read by the bureaucracy  and legislators.

2.  SUMMARY

         The compilers of  the  NAS  report  frequently  admit  to an
unfortunate lack  of  knowledge  in  the area of effects on aquatic
ecosystems.    If  the  present  observations were  overwhelming,
consistent,  and  theoretically  sound,  perhaps  the  potential
consequences of  increased biologically  damaging  ultraviolet
radiation  (DUV)  could  be  predicted.   In  the  aquatic  area,  at
least, I believe that the  studies as a whole do not yet permit a
conclusion  one  way  or the other,  and  at this moment I  tend to
believe  that  the  effects  will not  be  as  severe  as  some have
concluded.   Because  there is  much  emotion  connected with this
issue,  I  feel obliged also to state that  I consider myself an
environmentalist,  and not  a  tool  of the establishment  (whatever
that is).   So I am especially  concerned that certain  unqualified
statements, like those implying that half  or more of  a population
will   die   with   predicted  DUV  increases,  might   jeopardize
evaluations of any evidence.   If subsequent  research  demonstrates
that there may be a  serious problem, I hope I am among the first
to  say  so.    In  the  meantime,   I  trust  that  the  scientific
community will retain its credibility.

         What  information  there  is  on  UV effects  on  aquatic
ecosystems  is the result  of  a  "crash program," however laudable
certain facets  have  been.  Probably  the most valuable outcome of
the  crash  program   has  been  the  development  of   instruments.
Beyond  that,  in  the application  of  instruments  to   the aquatic
area,  there have arisen inevitable comparison gaps, and the total
effort cannot yet come up to  the sum of  its  parts.

                              F-4-3

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                                            Effects  -  Marine
         Periodic NAS  reviews  will  be indispensable in  unifying
the experimental  approach,  techniques,  and interpretations.   In
some respects the inevitable diversity of  initial  investigations
has been good,  but  perhaps  the time has come to determine  which
areas  and  approaches  will  yield the  more timely  and  the  more
useful  results.    Comparison  gaps  will narrow  as  publications
become  available,  and  as researchers meet and  compare  results.
Behind  whatever  factors  that have contributed to this,  I  suppose
lack of money is the most mundane yet most  important.

         In short,  one is frustrated when comparing the  results
of  different  investigations.    We  are   not   yet  near   to
extrapolating the effects on one species  to those of another,  nor
can we  say  with  much assurance how the same species might  react
to UV  in another  locality.   This  is  also true in studies  of most
other  parameters.   But there are  "standard methods"  available  in
traditional research areas,  and UV effects research has  not  yet
reached that  level.   Consequently,  there   is variability  in  many
basic  elements  like types,  combinations,  geometry,  filters,  and
time-schedule-s  of  radiation  sources; weighting   factors;  and
experimental  design and   interpretation.   It is no wonder  that
comparisons are  difficult.   An impression  might  be given by  the
NAS report  that  there  is a mass  of  corroborative  data.  But  it
needs  to  be  stated that  there  is  perhaps  not  yet a  body  of
knowledge regarding UV effects on aquatic  ecosystems.

3.  SPECIFIC COMMENTS

         In the NAS report,  Key Finding 13  states:

         13.  Larval forms  of  several  important seafood  species,
         as well as microorganisms at the  base of the marine food
         chain, would suffer appreciable  killing as a result of a
         16 to 30 percent ozone depletion.  Present  ignorance  of
         ultraviolet  penetration  into  the  waters that   they
         inhabit  and of  the depth distribution  of  the  organisms
         precludes an estimate of actual  losses.   (NAS,  1979,
         p. 7).

Presumably this statement is based on the  investigations reviewed
in  the main  body  of  the report.   The Summary of  Findings  with
regard  to aquatic  ecosystems   (NAS,  1979,   pp. 68-70)* seems also
to be  based on the same  investigations.  These investigations are
outlined   in  the  NAS  report's  Appendix B  (NAS,  1979,  pp.
288-297)*, and include studies on:

         A.  Marine phytoplankton - natural communities  in situ,

         B.   Marine phytoplankton - single species in laboratory
             culture,
 Cited pages from the NAS report are attached to these comments
 as Section 6.

                              F-4-4

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                                            Effects  -  Marine
         C.  "Aquatic microorganisms,  protozoa,  algae,  and  small
             invertebrates,"

         D.  Marine zooplankton (invertebrates),  and

         E.  Marine zooplankton (fish  eggs  and  larvae).


     A.  Marine Phytoplankton - natural communities  in  situ.

         The  first  group  of  studies  is represented  by the
observations of Jitts  e_t  al.  (1976)  and Lorenzen (1979).   These
investigators  observed  that  (a)  the  photosynthetic  activity  of
phytoplankton  increased when natural solar  incident  UV was
removed  by  proper  filters.    The  NAS  conclusion  is  that  (b)
natural  solar  UV  decreases  photosynthesis.   Statements (a) and
(b)  are  quasi-equivalent,  but  the  conclusions  drawn  from  each
need not be  the same.   First  of all,  the experimental  conditions
were  not  natural  (over  and  above  the fact  that  experimental
conditions  never   can   be),   in  that  UV,   which  is   a natural
environmental component, was removed.   This created some level  of
optimal  conditions  and  productivity   increased.    Implicit  in
statement   (b) ,  as  it  stands  unqualified,   is  that  further
increases  in DUV  will  further decrease photosynthetic  activity.
This  is  not necessarily  true.   Though plant  systems are  well
tuned  to  radiant  energy,  and  usually  respond  rapidly and
predictably, there have not  yet been  sufficient  experiments  with
phytoplankton at elevated UV  levels to  eliminate the possibility
of  threshold  UV  doses and  dose-rates.   That  the  activity  of
phytoplankton increases as  their environment goes from  "natural"
to  improved, does not  necessarily mean that  this  activity  will
decrease  at the  same  rate  while  culture  conditions  go  from
"natural"  to somewhat  worse.   Depending on species and  the  many
plant pigment possibilities, there may be  threshold levels  beyond
current  ambient levels,  toward which UV  and  activity will not
change  in   the  same  degree.   Thomson ^t  al.  (1980)  show   a
relationship between laboratory enhanced-UV and  growth-rate  of a
diatom (Melosira nummuloides) .  They have  estimated this to  be a
linear relationship.  But the regression is not  particularly good
(r   =  0.68) , and  the  individual observations  might  better  fit a
parabolic  or  other  regression,  suggesting  the existence of  a
threshold  (more about this under 2,  below).

         The NAS  report points out  in another  section, 'that  if
DUV weighting factors other  than erythema  (Lorenzen,  1979)  or DNA
(Thomson et al.,   1980)  are  used,  predictions  of  increased DUV
(through ozone  depletion)  might be much  less,  as,  for  example,
with  the  application  of  a  photosynthetic  inhibition  action
spectrum   (NAS, 1979,   p.  307-309)*.    So that  predictions  of
decreased  photosynthesis  (even assuming  a constant dose/effect
relationship) would also be  less.
*See footnote on p. 4.

                              F-4-5

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                                            Effects - Marine
         In addition, there are a number  of  other  uncertainties,
including  the lethal  limits  of  UV-B  to algal  cells,  genetic
resilience, repair  capability,  the  proportion of  photosynthesis
at various depths and times, and the magnitude of  vertical mixing
and exchange of UV-exposed populations.

     B.   Marine  Phytoplankton - single species  in laboratory
         culture.

         The  NAS  report  refers  to  two  studies  on  individual
phytoplankton species:  Thomson, e_t  aj^.  (1980), and R.  C.  Worrest
(unpublished).    The  first  study  used   diatoms  that  had  been
pre-stressed  by  UV  in  an  experiment on  responses   of  an
attached-algae  community.    Therefore,   there may have  been  a
danger in  underestimating  responses if_  there is some  individual
variability in UV  resistence  (as  is likely).  The investigators
derived   a   relationship   between  DUV   (DNA-weighted)   and
growth-rate.    As  mentioned  above,  the  observations  are   not
inconsistent with some threshold in  the  dose/effect relationship.
This  would  alter  predictions  based  on the  author's   linear
regression.  Also,  as in the _i_n situ  studies,  they have included
data  on   enhanced  growth-ratesBy"  excluding  UV.    This,  as
mentioned  above,  alters   the  perception  of  the  dose/effect
relationship; if those (unnatural)  levels are omitted,  the linear
relationship would have a distinctly different slope,  with a  much
smaller predicted  decrease  in growth-rate,  for  increases in  UV
through the levels of concern.

         The  experiments  of Thomson e_t  al.  (1980) bracketed  UV
irradiance levels and daily doses  that wo~uld  occur  off the Oregon
coast  (where  the  experiments  were  conducted).    However, their
conclusions seemed  to  be based on  comparisons w.ith  a  calculated
UV-| surface daily dose for June at  30 degrees NU) (Mexico), 141
Jm   DNA*   T^e  autnors  indicate  that M. nummuloides has  a  wide
distribution.    But  the  possibilities   olgenetic,  behavioral
(depth),   and  physiological  adaptation with latitude may  be  very
important  (as  it is with temperature, for example), so that the
Oregon-derived dose/effect curve may not be valid  for subtropical
populations.    Beyond  possible latitudinal  biological  effects,
calculations based on higher daily doses may  be misleading, since
fixed percentage  increases  at high  doses  involve  larger absolute
increments, and, therefore, larger growth-rate increments  because
of  the  reported linear  relationship.   Using the  "average clear
spring-summer" daily  surface  dose at  45  degrees N  (Oregon) given
by  the _aame authors  in  another paper  (Karanas,  e_t al.,  1979),
55.9 Jm   DNA» as t*ie base^*ne ^or calculating the predicted
 (l)The NAS  report,  based  on  the  Thomson  et  al.,  manuscript,  says
 40 degrees N=-but  the published paper says 30 degrees N.   I  feel
 that 141 Jm~  DNA  is too high for Oregon, and have assumed that
 30 degrees N is meant.
                              F-4-6

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                                           Effects - Marine
growth-rate declines (using the relationship of Thompson et al.,
1980)  a  15 percent DUV  increase  would result  in  a  3.2 percent
decrease in growth-rate  (not 8 percent), while  a  32  percent DUV
increase would result  in  a 7 percent growth-rate reduction (not
16 percent) .

         The  authors  do  not  show their  calculations  for the
estimated  reduced  productivity throughout  the  upper  two meters
off the  Oregon  coast   ("integration of  the  percent reduction  in
productivity for  all depths throughout  the upper two meters...").
But if they based these calculations on the percentage  decreases
from a 30 degree  N base DUV, certainly  these  integrated  estimates
would also be high by  about 2X.

         I  have  not  seen  Worrest's  (unpublished)  report   on
photosynthesis  in  the  diatom Chaetoceros  didymujs,  which   is
referred  to in  the NAS  report.    Reference  is  again  made   to
"reductions" of  photosynthesis by natural  UV,  when  compared  to
controls  receiving  n£ UV.   It  may be  more than  semantics   to
prefer  that it  be  said  that  the  unnatural  lack of  UV allows
increased  photosynthesis.   The choice  of DUV weighting  factors,
and the  choice  of  curve  fitting  the data,  would  likely have a
great impact on the conclusions.

     C.   "Aquatic  Microorganisms,  Protozoa,  Algae,  and  Small
         Invertebrates."

         The NAS report  (NAS,  1979,  p.  289)*  refers  to  a series
of observations on  dose/dose-rate  responses  in  a  large  number  of
aquatic  organisms  (e.g.,  Nachtwey,  1976).   It is stated that  UV
doses  "comparable"  to present solar  doses  can kill  appreciable
percentages of these populations.   In subsequent text  (NAS,  1979,
p. 323)*  it is  stated unequivocally that the dosimetry  in  these
early experiments was  misleading,  and  that  the solar doses were
significantly  overestimated.   These  experiments   should   be
repeated with spectroradiometric measurements.  It is  unfortunate
that  the   dose/dose-rate   relationships  suggested   in   these
experiments have not been  pursued.   It  is becoming more  and more
certain, I  believe, that dose-rates or doses by themselves cannot
lead  to  reasonable predictions,  but  that  it  is  necessary  to
consider  dose/dose-rate  responses.    That  is,  since  there  are
repair mechanisms,  effects  are determined not only by  dose, but,
beyond a certain threshold, also by dose-rate.
*See footnote on p. 4.
                              F-4-7

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                                            Effects  - Marine
     D.  Marine Zooplankton (invertebrates).

         The report by Damkaer e_t al.  (1980) deals with a number
of common  marine  zooplankton species  found  near  the surface at
least during  some  time in their  life-cycle.   At  that time  they
are  presumably vulnerable  to  DUV.    This  report  describes   a
threshold  level up to which  np_  deleterious  effects  were noted.
In this respect, qualitatively,  these observations  agree with the
low dose-rate observations of Nachtwey (1976).   These experiments
bracketed natural  DUV doses and dose-rates throughout the season
of surface-occurrence.   If only  the  higher  dose-rates  had  been
utilized,  no  "thresholds" would  have  been  observed.   Damkaer
chose  an  erythemal  weighting  factor,  which,  in   the  ranges
considered,  has   nearly  a   linear   relationship   to  the  DNA
weighting, so that  those  results  can  be qualitatively and roughly
quantitatively compared  to  other  observations  using  DNA-weight.
Probably the  most  serious short-comings of  those  investigations
are  the  lack of  precise knowledge  of penetration  of  DUV  into
local seawater, and  of the  lack  of  information on  the vertical
distributions of the organisms.   The  conclusion  of  Damkaer
et £l.(1980) , and  of the  NAS  report,  is that  the tolerance levels
oT some of  these zooplankton  would be exceeded  (at  the surface)
toward the  end  of  the near-surface  cycle.   This  does not  imply
catastrophe;  some  mechanism   already  limits   this   surface
occurrence,  and perhaps  it  is   UV  even  now.     If  so,   or if
increased UV becomes a limiting factor, much more  research  needs
to be done before  the extent  and  implications of those limits can
be  determined.    (More  about  such  things  below).    Recent
evaluation  of  these data, in light  of dose/dose-rate  responses
and the estimated  attenuation of  DUV in seawater, suggests  that
there would be a significant  margin of safety from  DUV,  unless it
is  only  the late-occurring  populations   that  are  typically
successful, a determination of which  is beyond present knowledge.

         Another   publication    concerning   marine   plankton
invertebrates is that  of Karanas et  al.,  (1979).   This was not
referred to  in  the NAS report, but  Karanas1 paper  will receive
wide distribution  and  doubtless  will be considered  by  those who
must make decisions on the fate  of CFCs.

         Karanas  studied  the  responses of the  developmental
stages  of  the copepod  Acartia  clausii,  the  adult  of   which
approaches  the  morphological  grade and  size  of  the shrimp  larvae
observed  by  Damkaer  e_t_  al.    Therefore,   the  two  studies are
potentially  complementary.    Unfortunately,  the  DUV dose-rates
used  for  stressing  the  Acartia  were  unrealistically  high  (by
about 5X), even though the daily doses were  comparable to natural
(Oregon)  daily  doses.    If  there  were complete reciprocity  this
would not  matter,  but  it  is  doubtful  if  reciprocity  is  the  rule,
particularly at lower  (the natural)  daily doses.  Karanas et al.,
do  not  discuss reciprocity or  its  assumptions.   I  believe  tTTat
they have  misapplied  Beer's  Law,  when they  calculate the  depths
of  certain daily  doses  (Karanas  et   al., 1979,  p.  1113).    They
assume Beer's  Law  holds  for  doses as well as  intensities,  which

                              F-4-8

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                                            Effects  -  Marine
may be true if the doses are given for  the  same  time  period.   But
I do  not  believe that  they can equate their experimental doses
over less  than  an hour with a  natural  daily dose obtained over
(say)   6  hours.   There  are no  depths at  which  the  laboratory
intensities are  reached, or  at  which  the  necessary  doses   are
reached  in the  given  experimental  time.    The  conclusions  of
Karanas e± al.,  should  be  re-examined.    Namely,  that  "enough
radiation  penetrates  to  a  depth of about  1 m during every clear
summer day  to  eliminate about  50 percent of  the  early and late
naupliar   developmental  phases."   What   is  the  fate  of   the
remaining 50 percent, which may be somewhat  weakened, on  the next
day?  Why are  there still so many copepods?

     E.  Marine Invertebrates (fish eggs and larvae).

         Hunter  e_t  al. , (1978)  studied the sensitivity of eggs
and larvae  of  anchovy and  mackerel.   The  anchovy were the more
sensitive,  and  most  attention  was  given  to  these.    I  have
difficulty  evaluating  the  reported  LD    values,  especially when
the "survivors"  showed  retarded growtn and development and when
it seemed  "unlikely that any of the damaged  survivors,  regardless
of dosage,  would be  able  to  feed successfully."   This  suggests
that  the  experimental doses  were  much  too  high.   In  an
unpublished study  cited in  the  NAS report,  Hunter  £t_ al.,  did
lower  dose-rate,  and  found  a   lower  LDcnf  indicating  that   the
effect  of  total  dose  depends  on  dose-rate  and,  therefore,
reciprocity would  not apply.   This unpublished study  indicated,
but the  NAS report  did not mention,  that,  as  before, even  the
"surviving" larvae at  "low" doses would probably  not survive.   I
believe  that  more  research  needs to  be  done  with  fish larvae
which would relate total lethal doses to dose-rates.

         The NAS  report  states  that  the responses at these doses
probably  represent  a  "worst  case,"  say   at  June  surface   DUV
levels.  That the anchovy eggs  and larvae  are at the  surface  from
January to June would indicate  that earlier hatchings might avoid
UV stress.  Therefore,  the  situation with  anchovy larvae  appears
analogous  to  that of the shrimp larvae  (Damkaer  et al. ,  1980).
Recalculating  the erythemal  threshold  levels  Frombamkaer's
report  (line  A), to  compare,  in  the  following  table, with  the
lowest doses  of  Hunter  et al.,  (line  B)   (at  which  significant
morphological damage  occurs), I  find:
                              F-4-9

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                                            Effects - Marine
                   DNA-weight-Dose-rate     DNA-weight  Dose
                            "^)                  (Jm ^)
         A                 .002                   190

         B                 .002                   530

There is remarkable agreement.

         But it should be stressed that Hunter's June  DUV  levels
are "worst case," and so would have  been  that  of Damkaer et  al. ,
if they had  only  considered  end-of-the-season  UV levels.  There
is no natural law that says all those shrimp and fish larvae  must
survive.  Organisms place their bets on a  lot  of squares,  and  as
the season progresses not all  bets will pay off.   Populations  do
not need  to  be winners  on  all squares;  some  squares never pay
off, and some only pay off once in awhile.   All that is  required
is a reasonable game.   It  appears that UV  might be  an important
regulator  at some  times.    Perhaps  increases  will  shorten the
seasons and  decrease the odds  then for population success, but  I
do not  believe  that  a case can be  made  one way or  the other  at
present.

         This work of Hunter  et  al . , shows  one very commendable
aspect, and  that  is  the advantage taken  in cooperation with the
adjacent  Scripps  Visibility  Laboratory,  so that  these studies
amount  to  a  joint effort  of  excellent biologists and  excellent
physicists and instrument designers.  One can  expect  good  things
from such a combination.

         Another hazard  and uncertainty in laboratory work  should
be  mentioned here,  and  that  is  the  difficulty  of  maintaining
certain organisms in good condition.   For  some  common animals,  it
is  not  yet  possible  to keep  them   alive,  much less  experiment
meaningfully  with them.   For  most  of  the other  animals,  the
laboratory  conditions   themselves  exert  a powerful negative
influence, so that a "true" and isolated  measurement  of UV  stress
is not attainable.  This can be seen in the high mortality  in the
controls  for anchovy larvae,  which were   kept  in   small  closed
containers, a poor but necessary approximation  of  the open  ocean.
Karanas et al. , mentioned high temperature  as  a possible flaw  in
their experiments, wherein the Acartia were kept  at  temperatures
near or exceeding reported optimum limits.   No  doubt the animals
would  do  better  if  kept  in  the field, but  the  technical
difficulties  of  experimenting  with  most of  them  there are
overwhelming^   As  in some  agricultural   field  tests  * '   (NAS,
1979, p.  67)  i  actual field  tolerance  of UV is likely more  than
that determined in the laboratory.
 See footnote on p. 4.
        added  by  Du  Pont:   This point  is  discussed  by  Dr.  Biggs
   in Appendix F-*3.
                              F-4-10

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                                            Effects - Marine
         The NAS  report also  points  to possible  UV dangers  to
aquaculture,  and  the  lack  of  information  in  this  area  is
mentioned.  Since most aquaculture is in shallow bodies  of  water,
increases  in  UV  may well  become  a  serious  problem.    In  the
manipulation of  nature,  normal  developmental  cycles  are  often
circumvented,  and untimely  exposures  to  UV  might  become  the rule
in this area.  However,  especially in the smaller-scale  projects,
there may  even now  be the  possibility  to increase  production  if
ponds  are screened  from UV.    Removal  of   UV  might add   a  new
dimension toward optimizing growth conditions.

         Finally, the NAS report raises  two issues of  possible
relief for UV-affected organisms.  The first is  simply  behavioral
change,  and  in  the aquatic  ecosystem this  means  avoiding  the
near-surface layer.   That this is not so simple  is acknowledged.
In the first place,  the  UV  would have to be sensed, and this  is
not  likely.    Some  recent  experiments of our own have  indicated
that some shrimp and crab larvae, euphausids, and  copepods  cannot
detect harmful doses of UV,  and  do  not increase their  depth  in
large  (2 m  deep)  cylinders.   Even  if they  did  alter   their
preferred depth, they would likely lose some advantages  which the
"normal" depth has offered them.

         The second  "strategy" to live with  UV stress would be  to
evolve protective coverings or to  evolve new behavioral  patterns
(by  natural  selection  rather than by active sensing as above).
This could lead to  new  depths of  occurrence or  to new  seasons  at
the  surface.    For  the  larger  organisms (above  algae and
bacteria) ,  projected  UV  increases  would probably  occur  in  too
short a  time to  allow  evolutionary changes.  There  is,  however,
the  famous  case  of  the darkened moth  in  England,  responding (by
natural  selection)  to increased  air  pollution.    The time  scales
here are not vastly different.  However, not every organism would
find a way (or time) to cope.


4.  CONCLUSIONS

          In  summary, the  data available to   the compilers  of the
NAS  report  are not conclusive  one  way or   the  other.   This  is
admitted  in  the  report,  but  some statements,  (e.g.,  Key Finding
13)  out  of  context  might suggest a  stronger foundation  in fact.
UV does  affect aquatic  organisms adversely.   To what  extent  it
will  do   so  in nature,   to  individual  species, populations,  and
communities, cannot  yet  be  predicted.  There is  enough  evidence
to warrant  (even  demand)  additional  research,  and  pointing this
out  may  be  the  most important  contribution of  the NAS  report.
Periodic  reviews  can serve to reevaluate new  information  and  to
focus  the   investigative  approach.    I  believe  this   is  an
extraordinarily  exciting  research   area, and  one   that  is
potentially  too important to  ignore.
                              F-4-11

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                                           Effects - Marine
         The present  information on the effects of enhanced  solar
UV  on  aquatic  ecosystems  is clearly  subject to  differing
interpretation.   With phytoplankton,  the  experiments  under
decreased   DUV probably  should  not  be  taken  to mean  that
productivity  under  enhanced  UV  will  change  with  the  same
magnitude.     More  serious   is   the   lack   of  knowledge  of
phytoplankton  action  spectra,  and  applying  action  spectra
applicable  to  other  organisms  can  suggest a  very wide  range of
effects,  from  negligible  to  large.    For  zooplankton,  some
experiments have not used DUV  doses  or  dose-rates comparable to
solar UV doses, and have greatly  underestimated  experimental DUV
doses and,  therefore,  have overestimated  the  effects.   Recent
experiments  have  yet  to  deal  thoroughly  with  the  likely
differences between reactions   in  the laboratory  and  nature, the
real  decreases  in  UV with  depth,  the  vertical  distribution of
organisms,  and  the probabilities  of UV  levels  with season and
seasonal occurrences  of  organisms.

         If there can be any conclusion  regarding UV effects on
natural  populations,  I  believe  it would be to  say that the season
of near-surface occurrence might be shortened.   This  could become
a  common  factor in  fluctuations  of  local  populations  in  some
years,  and  may even  lead  to  geographic  restrictions  for  some
species.  Against  the  other   natural  variability  in aquatic
ecosystems,  it would  be  very difficult  to  measure  UV-caused
fluctuations.   In  the  Earth's  past,  the  rule  has been  expansion
and contraction of  populations, so  that  in itself does  not  spell
catastrophe.    As  in  other  environmental questions,  one   must
decide  what to  trade.    Might the  UV  question boil  down to
refrigerators vs. shortened  seasons and restricted distributions?
The same question arises with corn, coal and condominiums.
                              F-4-12

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                                           Effects - Marine
5.  REFERENCES
         Copies of the cited  pages  of  the NAS  report appear in
Section 6  of  this appendix.   Copies of  other references below
appear in the  Reference Volumes.


Damkaer, D. M.,  Dey,  D. B.,  Heron,  G.  A., and  Prentice,  E. F.
     (1980).     Effects  of   UV-B  radiation  on  near-surface
     zooplankton of Puget Sound.   Oecologia, 44,  149-158.

Hunter, J.  R., Taylor, J. H.,  and  Moser, H. G.  (1979).  Effect of
     ultraviolet irradiation  on eggs  and  larvae  of the northern
     anchovy,  Eugraulis mordax,  and the  Pacific mackerel, Scomber
     japonicus^duringtheembryonic  stage.    Photochemistry and
     PhotobioTogy, 29, 325-338.

Jitts, H. R.,  Morel,  A.,  and  Saijo,  Y.  (1976).  The relation of
     oceanic  primary  production  to available photosynthetic
     irradiance.  Aust. J.  Mar.  Freshwater Res.,  27, 441-454.

Karanas,  J.   J.,  Van  Dyke,  H.,  and  Worrest,   R.  C.   (1979).
     Midultraviolet   (UV-B)   sensitivity  of  Acartia  clausii
     Giesbrecht (Copepoda).  Limnol.  Oceanogr., 24 (6) ,  1104-1116.

Lorenzen, C.  J.  (1979).  Ultraviolet  radiation and phytoplankton
     photosynthesis.   Limnol.  Oceanogr., ^4_(6) , 1117-1120.

Nachtwey, D.  S.  (1976).  Potential effects on  aquatic  ecosystems
     of  increased UV-B  radiation.   Proceedings of  the  Fourth
     Conference on the Climatic Impact Assessment Program, Hard,
     T.   M.    and  Broderick,   A.  J.,   eds.,   pp.   79-86.
     DOT-TST-OTS-75-38,  U.S.  Department  of  Transportation,
     Washington, D.C.

NAS-National  Academy of Sciences-(1979).   Report  of the Committee
     on  Impacts  of Stratospheric  Change  jri  "Protection against
     depletion  of stratospheric  ozone  by chlorofluorocarbons.
     Washington, D.C.

Thomson, B.  E.,  Worrest, R.   C.,  and Van Dyke,  H.  (1980).   The
     growth repsonse of an estuarine diatom  (Melosira nummuloides
     [Dillw.]   Ag.)  to UV-B (290-320  nm)  radiation.Estuaries,
     3(1),  69-72.                                      	
                              F-4-13

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                                          Effects -  Marine
6.  CITATIONS FROM THE  REPORT OF THE NAS COMMITTEE on Impacts of
StratosphericChange,"ProtectionAgainstDepletion  of
Stratospheric  Ozone by Chlorofluorocarbons."   (Pages  67-70,
288-299,  307-309,  322-324).
                             F-4-14

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                                                          Effects -  Marine
                                                       67

 SUMMARY  OF FINDINGS

 The  major  information  available  on UV sensitivity of
 organisms,  which  is  helpful  for  evaluating the possible
 effects  of ozone  depletion,  is reviewed in Appendix B.
 This information  covers  agricultural crops and land vege-
 tation,  domestic  and wild  animals, nonagricultural land
 ecosystems,  and aquatic  organisms and ecosystems.  The
 information is summarized  briefly here for reference.


 h'ith Regard to Agricultural  Plants

   I.  Tests of more than  100 species or varieties of
 species  in  controlled  environment growth chambers indi-
 cate that  approximately  20 percent are sensitive to daily
 UV-B doses  of the order  of those delivered by Florida sun-
 shine  at present  ozone levels, while 20 percent were re-
 sistant  to  doses  four  times  greater than this, and the
 remaining  60 percent showed  some intermediate sensitivity.
 These  tests would indicate that a significant fraction of
 the  present agricultural varieties are at present under
 UV stress  and would  suffer decreased production with a
 16 percent  ozone  reduction.
   2.  However, 15 species and varieties tested in the
 open field  appeared  more UV  resistant than plants grown
 in laboratory environmental  growth chambers.   Where it is
 possible to make  comparisons of the same plants, the
 differences  in resistance  are on the order of fourfold.
 If this result turns out to  be general, the higher sensi-
 tivity indicated  in  the growth chambers does not repre-
 sent open-field behavior,  and the expected consequences
 of ozone depletion become considerably less than those
 tests would  indicate.  Nevertheless, some species (sugar
 beets, tomatoes, mustard,  corn)  still appear to be af-
 fected—although the field experiments were necessarily
 less well controlled, and  the results less clear-cut, than
 were the chamber studies.
   3.  The  existence of relatively more resistant varie-
 ties of the  same species offers the possibility of select-
 ing  plants better adapted to UV-B stress.   Efforts could
be made to  combine the UV resistance trait with the other
 characteristics desired in these plants (high crop yields
 and  resistance to certain diseases, for example)  through
systematic breeding.   However, in much of the agriculture
of undeveloped countries, introduction of new varieties
would be difficult,  and any emergence of more UV-resistant
                         F-4-I5

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                                                Effects  - Marine
68

varieties might have to depend on the slower process of
natural selection after the ozone decrease had occurred.
Kith Regard to Domestic and Wild Animals

   4.  The very incomplete information suggests that the
impact of ozone depletion on domestic and wild animals
would not be large.  An increase in conjunctival carci-
noma (cancer eye)  affecting some cattle breeds could be
expected, but the fraction of cattle affected would be
small.

h'i th Regard to Nonagricultural Land Ecosystems

   5.  Perturbations of nonagricultural ecosystems could
ultimately be as important as more direct effects on
human health or human food supplies, but .there is almost
no information with which to assess the consequences of
increased solar-UV radiation on such ecosystems.  Because
nonagricultural plants show about the same range of sen-
sitivity as crop plants, reduced productivity of some
forest and grazing-land plants might occur.   However,
change in the species composition of these systems seems
a more likely response.  Such a change would alter the
character of the vegetation and might qualitatively change
the products provided.  However, UV sensitivities and
their range of variation in wild species are known in so
few cases, and the theoretical modeling of ecosystems is
at present so primitive, that such changes cannot be pre-
dicted confidently.
   The fact that ozone depletion would be a  worldwide
perturbation makes its consequences more worrisome than
effects on simply a local environment.  The  presumed
effectiveness of past evolutionary adaptation, which de-
veloped over millennia, and the human need for a stable
framework in which to operate, argue that widespread
changes,  occurring rapidly compared with the usual evo-
lutionary time scale, would be more likely to be harmful
than helpful.   Consequently, where a prospective man.-made
change cannot be proven unequivocally beneficial, it
should be viewed with some suspicion.

With Regard to Aquatic Ecosystems
   6.  Experimental studies on over 60 aquatic micro-
organisms, protozoa, algae, and small invertebrates
                      F-4-16

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                                                            Effects -  Marino
                                                        69

 indicate  that roost of them are sensitive to current water-
 surface levels of DUV radiation.  Because they currently
 thrive in nature, attenuation of DUV by natural waters,
 especially  in productive areas, may play an important
 role  in their survival.  (The degree of penetration of
 DUV into  such waters is not well characterized.)
   7.  UV-B irradiation of young anchovies by means of
 lamps indicates that in surface waters this commercially
 important species lives normally near its UV tolerance
 limit.  UV  increases similar to those expected with a 16
 percent ozone-layer reduction would, as a "worst case,"
 kill over 50 percent of the anchovies in the top 10 m of
 the clearest ocean water or else would require them to
 substantially readjust their usual water depth to dimin-
 ish UV exposure.  Such avoidance, if it were to occur,
 would result in a substantial shift in ecological rela-
 tionships .
   Similar  studies show that mackerel are more UV resis-
 tant than anchovies. .The "worst case," corresponding to
 organisms exposed near the water surface, indicates essen-
 tially no losses.
   Analogous studies of crab and shrimp larvae indicate
 that they too are near their DUV tolerance limit, con-
 sidering their location in the water column (near surface)
 and their reproduction/development season (late winter,
 early spring).  A 16 percent ozone-layer reduction might
 substantially shorten their reproductive/development
 season with unknown, but probably detrimental, conse-
 quences to productivity.
   This very limited sampling gives little perspective on
 the UV sensitivity range of commercially important aquatic
 organisms.  If we presume that such a small sample is
 roughly representative,  an appreciable fraction of fishery
 species young would be vulnerable to the DUV levels ex-
 pected with a' 16 percent ozone reduction.  They would
 either be injured or would have to seek deeper water,
with unknown consequences on their subsequent prosperity.
   8.   The final conclusion depends on where the burden
of proof is presumed to lie:   one cannot convincingly
demonstrate that a 16 percent ozone reduction would cause
 significant decrease in yields from agricultural crops or
 from nonagricultural land or aquatic ecosystems.  Neither
is it clear that a 16 percent ozone reduction would not
entail important losses in these yields.  The uncertainty
stems partly from ignorance of the proper weighting func-
tion for different wavelengths (i.e.,  action spectrum) to
be used in comparing solar and artificial source
                           F-4-17

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                                                        Effects  -  Marine
70

 irradiations but mostly  from  the limited scope, and in
 some  cases  incomplete design, of experiments and the lack
 of  corroboration by  independent investigators.  These
 lacks,  in turn, stem from the haste with which the re-
 search  efforts have  been put  together and the absence of
 a systematic longer-range program to answer well-defined
 Questions.
MAJOR  RESEARCH  ISSUES

Progress has been made on several questions since the last
full CISC report was published in 1976, although less than
could  have been made, considering the need for information
to evaluate the biological effects of DUV.
   The recent advances are:

   1.  Larger numbers of agricultural plant varieties
have been experimentally tested by radiation supplement
for their sensitivity to UV-B.  These tests have confirmed
the wide variation in sensitivity among different plant
varieties that was suspected earlier and have also indi-
cated  that the sensitivity depends on conditions of test-
ing, but the tests leave the true sensitivity profile of
the most important agricultural plants in doubt.
   2.  Tests with larval forms of several fishery species
also indicate that wide variation in sensitivity occurs
from one to the other and that some species have signifi-
cant sensitivity.  The very small numbers tested, and
uncertainty about the likelihood of UV adaption or UV
avoidance by the animals under natural conditions, as
discussed in Appendix B, leaves the significance of these
results still unclear.

   The points stated above need further investigation by
a sufficient number of independent investigators and need
to be pursued over a sufficient time to overcome the
spotty sampling, the possible statistical fluctuations in
small experiments, and,  in some cases,  the deficiencies
of experimental design that now limit interpretation of
the results.  The effect of environmental conditions on
the UV sensitivity of plants needs to be explored.
   Because the action spectra for different UV effects on
most higher plant and animal species are at present not
known,  emphasis should be directed to their determination.
The results are needed to establish the weighting func-
tions for predicting consequences of ozone depletion.
                      F-4-18

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                                                    Effects  - Marine
286

of those that are more sensitive (Caldwell, 1977; Fox and
Caldwell, 1978).  Such changes in competitive balance
might amplify rather small sensitivity differences, af-
fecting subtle processes  (pollination, relationships be-
tween predators and their prey, and biological fixation
of nitrogen, for example).
   Changes in the competitive balance of plant species
have actually been demonstrated, using UV-B-producing
lamps to supplement normal sunlight (Fox and Caldwell,
1978).  Although these supplements were greater than the
UV-B increase that would accompany currently expected de-
creases in stratospheric ozone, the results indicate some
of the processes that may be involved in species replace-
ments.  Recently, A. Bogenrieder, B. Bruzek, and S. Kiliani
(University of Freiburg, unpublished data)  showed that the
balance between plant species can also be altered when both
UV-B and the longer-wavelength, less biologically active
UV-A are filtered out of normal sunlight.  This occurred
even at 50° N latitude,  where the DUV dose  rate is con-
siderably smaller than at lower latitudes.   Such experi-
ments suggest that changes in nonagricultural ecosystems
may accompany small UV-B increases; but because so few
nonagricultural plant and animal species have been evalu-
ated, it is impossible at this time to predict which spe-
cies might benefit at the expense of others.
   It is usually not easy to decide whether a specified
change in the species balance of an ecosystem should be
considered detrimental or beneficial to human welfare.
However, the presumed effectiveness of past evolutionary
adaptation, and the human need for a stable framework with-
in which to operate, make it prudent to regard any wide-
spread changes as likely to be harmful.
AQUATIC ORGANISMS AND ECOSYSTEMS

Marine and freshwater ecosystems are a vital element in
the complex environment that makes life as we know it pos-
sible.  The finfish and shellfish used for human food,  and
the organisms on which they feed, are obviously important.
In addition,  aquatic organisms decompose organic wastes
(thus depolluting the waters),  and marine algae serve as
a source of oxygen and as a sink for carbon dioxide.
Amounts of the latter gas in the atmosphere are measurably
increasing at this time,  because of the very heavy,  world-
wide combustion of fossil fuels.
   Current levels of solar-UV radiation at the water sur-
face can be lethal to marine bacteria, and current surface
                         F-4-19

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                                                           Effects  -  Marine
                                                       289

 UV levels,  at  wavelengths  shorter  than  the  cutoff point
 for glass or Mylar  (below  340  or  315  nm,  respectively),
 significantly  reduce  photosynthesis  in  marine  algae when
 these  organisms  are collected  at various  depths  and brought
 to the surface (Jitts et al.,  1976;  Lorenzen,  1975).   Labo-
 ratory studies on a variety  of aquatic  organisms support
 these  sunlight studies.  Simulated doses  of DUV  radiation
 at the water surface,  produced by  fluorescent  sunlamps with
 filters (see Appendix E),  indicate that only a few hours of
 radiation comparable  with  that in  the near-noon  summer sun-
 light  can kill 50 percent  of the population in most of the
 60 or  so species tested  (bacteria, .algae, protozoa, small
 invertebrates)  (Calkins, 1975;  Calkins  et al., 1978; Nacht-
 wey, 1976).  These studies thus suggest that aquatic eco-
 systems may be extremely vulnerable to  ozone depletion/
 increased UV-B.  However,  the  dosimetry for these experi-
 ments  was done with a  Robertson-Berger  Sunburning Ultra-
 violet Meter (R-B Meter).  As  discussed in  Appendix E, the
 use  of this meter for  comparing DUV from  filtered fluores-
 cent sunlamps  with that of sunlight may significantly over-
 estimate sunlight sensitivity.
    Most recent studies have  employed better dosimetry, in-
 volving spectroradiometric measurements weighted by either
 an  erythema or DNA-effective weighting  function  (see Appen-
 dix  D).  Several of these  studies provide quantitatively
 useful  data for assessment.
    Photosynthesis in a marine diatom  (Chaetoceros djdymus)
 decreases exponentially with increasing DNA-weighted dose
 (R.  C.  Worrest, Oregon State University,  unpublished).
 Recalculations of these data indicates  that current summer-
 time daily surface DUV doses at 40° N latitude at the water
 surface can reduce photosynthesis  (carbon dioxide uptake)
 by 40 percent  relative to  controls receiving no UV-B.  A
 44 percent increase in DUV (such as would accompany a 16
 percent ozone  layer reduction at 40° N  latitude)  would de-
 crease photosynthesis by 28 percent from that expected in
 nature with current summertime daily surface doses.   These
 results assumed that the DNA-effective  dose  is the appro-
 priate one to use,  but this may not be  the  correct weight-
 ing  function for photosynthetic inhibition.   Most important,
 however, is the protection these organisms  receive from
being located at some depth in the water.
   Similar studies  by Thompson et al. (1979) examined the
effects of simulated solar UV-B on the  growth rate (cell
divisions/day)  in an estuarine chain-forming diatom (Melo-
 sira nurnnuloides),  which attaches to surfaces and floats
 in the water column.   DUV doses comparable with current
                        F-4-20

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                                                         Effects  -  Marine
 290

 summer  daily surface  doses  at  40°  N latitude  reduced  the
 growth  rate by 35 percent relative to  controls  receiving
 no UV-B.   Any considerable  increase in this DUV dose  would
 then be expected  to reduce  the growth  rate for  organisms
 at the  water surface.
    These  two studies  indicate  th?.t,  with current  surface
 doses,  these organisms  are  under UV radiation stress.   Yet
 they thrive in nature.   This may mean  that they must  con-
 stantly contend against the UV radiation in order to  exist
 in environments having  other advantages and are consequently
 not producing at  the  maximum possible  rate.   The  situation
 could be  analogous to that  of  some terrestrial  plants,
 which show spectacular  increases in yield if  grown hydro-
 ponically under optimum conditions.
    In another quantitatively useful  study, D. M.  Damkaer
 (NOAA Pacific Marine  Environmental Laboratory,  Seattle,
 unpublished BACER report) examined the DUV sensitivity  of
 larval  forms of shrimp  and  crab (two species).  These or-
 ganisms appear to be  less sensitive  than the  bacteria,
 protozoa,  and algae mentioned  above, in that  several days
 rather  than several hours exposure are required to produce
 an effect.   Moreover, the organisms  show a threshold of
 tolerance to the  killing effects of  DUV, with no reduction
 in rates  of development at  sublethal doses, compared with
 control organisms.  The  various tolerance doses (weighted
 with an erythemal  weighting function)  are plotted in Figure
 B.I.  In  this plot, a short, horizontal line  is positioned
 vertically  to show the  tolerance dose  of the  organisms
 (measured at  the  water  surface) and  horizontally to show
 the  period  of the  year  during  which  the larval  forms de-
 velop.  These tolerance  doses  are  superimposed  on curves
 showing the  annual  DUV  cycle of average daily doses at
 the  location  of the experimental studies, assuming various
 ozone-layer  reductions.
    During most  of  the reproductive/developmental period,
 the  tolerance  threshold  daily  doses determined  for these
 organisms are  greater than  the average daily  doses experi-
 enced at  current ozone  levels, but there is not much margin,
 the  organisms  being near their limits of tolerance.   Al-
 though  daily  DUV doses resulting from ozone-layer reduc-
 tions as  large as  40 percent would not exceed the daily
 tolerance limits for part of reproductive/development
period  (and would  thus  leave a window of safety at the
beginning of  each  group's surface dwelling season),  this
surface-tolerating season could be significantly shortened.
There would be some shortening of it even at a 16 percent
ozone-layer reduction.  Whether or not the populations
                       F-4-21

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                                                          Effects  - Marine
                                                       291
     4.0 f-
   O
   o
   <
   o
1.0-
           FEB
                MAR
                               JUNE  JULY
                                          AUG
                                               SEPT
                                                    OCT
FIGURE B.I  Daily solar DUV dose at the water surface
 (erythermal action spectrum) in arbitrary units for vari-
ous ozone thicknesses at Manchester, Washington.  Horizon-
tal bars, showing the time of year during which larvae of
various species develop, are positioned vertically to in-
dicate the tolerance daily dose.
could endure substantially reduced periods of reproduction/
development is not known.  Success of any year's group of
larvae  (the "year-class") depends on the timing of a great
number of factors besides UV-b levels (e.g., weather, food
supplies, and predators).  Early larvae may do well one
year, but only late larvae may survive in a subsequent
year.  An additional stress like increased UV-B is not
likely to be beneficial.
   Hunter et al. (1979) examined the sensitivity of the
eggs and larvae of the northern anchovy and the Pacific
mackerel during their embryonic stages when they dwell
near the water surface.  Using different types of filters
they established that the killing effect of UV-B was con-
sistent with a DNA-damage action spectrum.  The doses
lethal to half the population (LDsg's) for fish embryos
irradiated at varying dose rates 7 hours per day for 4 to
5 days were 1150 J m~2  (joules per square meter) for an-
chovy and 1576 J m~2 for mackerel weighted for DNA damage
effectiveness,  as described in Appendix D.  Anchovy sur-
viving the lowest dose used (760 J m~2)  showed brain and
eye lesions and retarded growth and.development.  These
                     F-4-22

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                                                        Effects -  Marine
292

results are compared in Figure B.2 with the DNA-effective
radiation penetrating into various natural waters in mid-
June at San Diego, California  (33° N latitude)  (Smith and
Baker, 1979).  The comparisons indicate that brain and eye
damage and retardation of growth should occur in anchovy
larvae at the surface in about 4 days in June if the ozone
layer were reduced by 25 percent.  Since spawning of these
creatures occurs mostly over a period (January-June) in
which the solar DUV dose rate increases by a large factor,
this represents a worst case.
   In a subsequent study J. Hunter, 0. Taylor, and H. .G.
Moser (National Marine Fisheries Service, La Jolla, Cali-
fornia,  unpublished BACER report) have extended their
studies with anchovy past the embryonic stage and into
the feeding stage.  They employed a similar experimental
protocol but with lower daily dose rates, expecting that
the same total dose given over a longer period of time
might allow some repair and thus yield a higher 1,059.
Surprisingly, they found that exposures over 12 days at
6 h/day at various low dose rates yielded a lower 1,050,
675 J m   (with a DNA damage weighting function).   Refer-
ence to Figure B.2 indicates that the LD^o level is reached
at 4 m in clear ocean waters with current irradiances.   If
a 25 percent ozone-layer reduction were to occur,  the LDso
level is reached at about 7.5m.   Growth inhibition, which
occurs at doses greater than 530 J m~^ (DNA-effective)
given over 12 days could be expected to occur under present-
day irradiances down to 5.5 m,  and down to 8.5 m with a 25
percent  ozone-layer reduction.   Eggs and larvae of anchovy
commonly occur at these depths during this period  of their
development.   These calculations, made for a somewhat larger
ozone depletion than now envisaged, need to be repeated for
the 16 percent depletion figure but give some indication
of the general magnitudes of effects that might occur.
   At first glance the large effects observed with doses
simulating current surface levels seem incompatible with
the productivity observed in nature.  However, other fac-
tors,  such as predators or food supply,  may so limit the
population that UV-B becomes less important.   Also,  there
are reasons why these data may overestimate the- UV sensi-
tivity of the organisms tested.  An obvious one is that
the organisms probably spend part of their time well below
the surface,  where DUV is attenuated (Figure B.2).   Another
is that  in nature photoreactivating light is available  at
an intensity  more than an order of magnitude above usual
laboratory levels,  which might increase photorepair of
DNA damage.
                         F-4-23

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                                                            Effects -  Marine
                                                       293
                     (aim • cm! • 0.24
                                      ?88 I X 4 days- 1150)
        o
        o
        o
        Q
        i
        g
        UJ
        5
        <
        Q
                          DEPTH (m)

FIGURE B.2  Daily DUV dose  (in mid-June at 33° N latitude
DNA-damage action spectrum) as a function of water depth in
three different types of ocean water.  Curves show the dose-
depth relation with "standard ozone" thickness (0.32 atm cm)
and a 25 percent depletion of this value  (0.24 atm cm) in
clear open ocean waters of low productivity  (i.e., chloro-
phyll-a content 0.025 mg m~^  (	); in moderately produc-
tive waters  (chlorophyll-a content 0.5 mg itT^) (---); and
in the latter waters when a high concentration of dissolved
organic material_is also present (	).  The horizontal
line at 288 J m~^ day"1 shows the daily dose killing half
of an anchovy larval population in 4 days (LDso = 1150 J
m~2).  The horizontal line at 190 J m~2 day"1 shows a daily
dose producing retardation and damage of these larvae in
4 days (760 J m~2).  The horizontal line at 56 J m~2 day"1
shows the daily dose killing half of an anchovy larval
population irradiated for 12 days (LDso = 675 J m~2), a
time extending beyond the embryonic into the feeding stage.
The horizontal line at 44 J m~2 day"1 shows the daily dose
producing significant growth inhibition in 12 days (530 J
m"2).
                         F-4-24

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                                                        Effects -  Marine
 294

   The  actual  location  of  organisms  in the water column
 and  the amount of penetration of UV-B into natural waters
 are  not well known.   In the  case of  anchovy  irradiated for
 12 days at  current DUV  irradiances,  50 percent would die
 if they remained at  a depth  of 4 m or less in clear ocean
 water or if they existed for the same period at 0.8 m or
 less in the most UV-attenuating waters studied  (Figure B.2)
'Even though the larvae  of  these animals occur through the
 upper mixed layer, from the  surface  to the therrnocline,
 the  proportion of the population at  various depths is not
 known,  and  the effect on the population cannot now be pre-
 dicted.   Moreover, although  the calculated irradiances of
 Smith and Baker  (1979)  provide some  indication of penetra-
 tion of DUV radiation,  their values  are based on extrapo-
 lations of  measurements in only four water types at 310 nm
 and  above,  and there  have  been no measurements in the more
 effective spectral region  for DNA-damage.  The biological!}
 important estuarine  and near-coast environments have also
 not  been adequately  studied.  The near-coast measurements,
 made in moderately productive waters, with a relatively
 high concentration of dissolved organic material, indicate
 a very  strong  attenuation  of DUV (dotted lines, Figure B.2).
 The  extent  to  which  this measurement is typical of the pro-
 ductive  regions of the  globe is not known.  Information on
 the  penetration of DUV  into  the waters where organisms
 actually exist is critically important to the assessment
 of the  impact  of increased DUV on seemingly very sensitive
 aquatic  organisms.
   The  impacts of ozone depletion on fishery species raise
 a concern for  supplies  of  human food derived from aquacul-
 ture.   Half the total protein intake for over 200 million
 people  in Southeast  Asia,  and additional millions in other
 regions,  is derived  from pond-grown  fish and shellfish
 species.  These organisms  are reared in shallow ponds and
 are  dependent  on microscopic plankton for food supply.
However,  there has not  been  any experimental work to ex-
plore this  potential  problem.
   The  effect  of more intense photoreactivating light will
depend  on the  degree  to which DNA repair is light-limited
 in the  species in question.  This is not known at present.
 Directly determining  whether photoreactivating light as
 it occurs in nature  strongly affects the sensitivity to
DUV  has  been difficult.  The most practical source of pho-
 toreactivating light  of solar intensities is the sun it-
 self (full-scale solar  simulators being quite expensive
both to  construct and maintain).  Yet experiments in green-
houses or in the field  suffer from considerable variability
                      F-4-25

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                                                           Effects  - Marine
                                                       295

 in  environmental parameters, particularly  temperature.
 R.  C. Worrest, Oregon  State University  (unpublished) was
 unable  to verify, in a greenhouse study, results obtained
 in  the  laboratory, because of the substantial lack of re-
 producibility from one greenhouse experiment to another,
 and the question remains open.
    In any event, we can say that any ozone-layer reduction
 will lead to an increase in DUV at all depths in the water
 column.  Moreover, because photosynthetically active radia-
 tion  (PAR) will not change appreciably with ozone reduction,
 the ratio of DUV to PAR will also increase at all depths in
 the water column, with potential consequences to phytoplank-
 ton.  This would be true even if these organisms could mi-
 grate deeper to avoid the increased DUV.  Thus, on the basis
 of  current knowledge, we must accept the possibility that
 ozone depletion could seriously affect the aquatic biosphere.
AVOIDANCE AND ADAPTATION

Most of our quantitative discussion has tacitly assumed
that the effects of a long-term depletion of stratospheric
ozone on plants and animals would be determined entirely
by the average increase in solar UV-B at the earth's sur-
face, i.e., that neither compensating behavioral changes
to reduce UV exposure nor adaptations to decrease sensi-
tivity would take place.  Clearly, many organisms have
evolved strategies that reduce the UV exposure of their
sensitive structures.  One example is protective outer
coverings, such as fur, feathers, or special pigments.
Some desert reptiles avoid daylight altogether and are
active only in the evening and nighttime hours, but those
species that are active by day have melanin accumulations
in their outer tissues that can prevent UV-B penetration
to physiologically sensitive points (Porter, 1967; 1975).
However, it is not clear how rapidly additional protective
strategies might emerge.
   Aquatic organisms in water of sufficient organic con-
tent could readily find a much more protected environment
only a few meters deeper (cf. Figure B.2), but increased
UV-B radiation may not be directly sensed by these organ-
isms.  Instead, they may (like human beings) respond to
concomitant visible light or radiant heat and rely on this
cue for avoidance of excessive UV exposure in normal sun-
light.   Since changes in the amount of ozone in the atmo-
sphere  would affect essentially only the UV-B radiation,
without an accompanying change in the directly perceived
cue, behavioral avoidance might be slow to evolve.
                           F-4-26

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                                                     Effects  - Marine
296

   Even if such avoidance did occur, changing the time of
day that an organism was active (in the case of animals),
or changing its location within an ecosystem, would alter
its relations with other species and might change the com-
petitive balance of species, the susceptibility of the
organism to predators or parasites, or, in the case of
plants, the availability of pollinators.  Since most spe-
cies have .evolved over millenia to their niche in an eco-
system, such changes in relationships with other species
would probably not be advantageous.
   Adaptation might occur as either a short-term physio-
logical response or as a longer-term evolutionary change.
An example of the former is the tanning of light-skinned
humans, in which the aggregation of melanin pigments in
outer layers of the skin, in response to a UV stimulus,
provides an improved barrier to subsequent UV-B penetra-
tion.  Such protection is limited,  compared with the
screening regularly available to dark-skinned races but
is nevertheless significant, as increased sunburn resis-
tance after tanning shows.   There is limited evidence that
some plant species similarly respond to UV radiation by
increasing the amounts of certain pigments in their leaves
to provide an analogous protection (Robberecht and Caldwell,
1978).   The increased physical screening in plants seems
to vary considerably from species to species and is also
very likely limited (Van et al., 1977;  Robberecht and Cald-
well, 1978) .
Evolutionary Response to Increased UV-B Radiation

Considering that plants and animals have evolved effective
and sometimes very intricate mechanisms to cope with pres-
ent levels of solar UV-B radiation, the possibility exists
that some species could evolve an increased resistance.
Most natural species of plants and animals carry a certain
genetic variability, which provides the background on which
natural selection can act in the face of a new stress to
evolve a better adapted species.  If all circumstances are
conducive, a rather rapid evolution of resistance can take
place,  as in the case of the 250 species of insects and
crop pests that have evolved increased tolerance to widely
used insecticides—sometimes in periods of a few years
(Brown, 1960).   Some plants have evolved tolerances toward
heavy metals, such as lead in mine tailings (Antonovics,
1975).   On the other hand, many species have failed to
evolve resistance to new environmental perturbations—
                      F-4-27

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                                                           Effects -  Marine
                                                      297

especially where these occurred rapidly—as exemplified
by continued sensitivity of falcons and ospreys to DDT.
For some organisms, the 35 years in which half the ozone
reduction may take place would only span a few generations
and is too short for such a mechanism to respond.
   The time available for change is a crucial factor
(Antonovics, 1975), and in general, a higher probability
of evolving resistance is expected for species that are
very short-lived, have very large population numbers,  and
naturally engage in crossbreeding.  These characteristics
account for the success of insects in increasing their
resistance to insecticides, compared with the failure  of
comparatively long-lived predatory bird species to do  this.
However, no assured statements can be made beyond  these
general expressions of probability.
REFERENCES

Antonovics, J.  1975.  Predicting evolutionary response of
  natural populations to increased UV radiation.  CIAP
  Monograph 5, Impacts of Climatic Change on the Biosphere,
  Part 1, Ultraviolet Radiation Effects, D. S. Nachtwey,
  M. M. Caldwell, and R. H. Biggs, eds.  pp. 8-3 to 8-26.
  DOT-TST-75-55, U.S. Department of Transportation, Wash-
  ington, D.C.
Bogenrieder, A., and R. Klein.  1977.  Die Rolle des UV-
  Lichtes beim sog.  Auspflanzungsschock von Gewachshaus-
  setzlingen, Angew. Hot. 51:99-107.
Brandle, J. R. , W. F. Campbell, W. B. Sisson, and M. M.
  Caldwell.  1977.  Net photosynthesis, electron transport
  capacity, and ultrastructure of Pisum sativum L. exposed
  to ultraviolet-B radiation,  Plant Physiol. 60:165-169.
Brown, A. W. A.  1960.  Mechanisms of resistance against
  insecticites, Ann. Rev. Entomol. 5:301-326.
Caldwell, M. M.  1977.  The effects of solar UV-B radiation
  (250-315 nm) on higher plants:  implications of strato-
  spheric ozone reduction, in  Research in Photobiology,
  Plenum Press, N.Y.  pp. 597-607.
Calkins, J.  1975.  Effects of real and simulated solar
  UV-B in a variety of aquatic microorganisms—possible
  implications of elevated UV  irradiance.   CIAP Monograph
  5, Impacts of Climatic Change on the Biosphere, Part 1,
  Ultraviolet Radiation Effects, D. S. Nachtwey, M. M.
  Caldwell, and R. H. Biggs, eds.   pp. 5-33 to 5-71.  DOT-
  TST-75-55, U.S. Department of Transportation, Washing-
  ton, D.C.
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                                                    Effects  - Marine
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Calkins, J., J. A. Barcelo, P. Grigsby, and S. Martin.
  1978.  Studies of the role of solar ultraviolet radiation
  in "natural" water purification by aquatic ecosystems.
  Research Report No. 108, University of Kentucky Water
  Resources Research Institute, Lexington, Kentucky.
Dickson, J. G., and M. M. Caldwell.  1978.  Leaf develop-
  ment of Rumex patientia L.  (Polygonaceae) exposed to UV
  irradiation  (280-320 nm), Am. J. Bot. 65:857-863.
Fox, F. M., and M. M. Caldwell.  1978.  Competitive inter-
  action in plant populations exposed to supplementary
  ultraviolet-B radiation, Oecologia 36:173-190.
Hunter, J. R.,  J. H. Taylor, and H. G. Moser.   1979.  Ef-
  fect of ultraviolet radiation on eggs and larvae of the
  northern anchovy, Engraulis mordax, and the  Pacific
  mackerel, Scomber japonicus, during the embryonic stage,
  Photochem.  Photobiol.  29:325-338.
Jitts,  H. R., A. Morel,  and Y. Saijo.  1976.   The relation
  of oceanic primary production to available photosynthetic
  irradiance, Aus. J. Marine Freshwater Pes.  27:441-454.
Lorenzen, C.   1975.  Phytoplankton responses  to UV radia-
  tion and ecological implications of elevated UV irradi-
  ance.  CIAP Monograph  5, Impacts of Climatic Change on
  the Biosphere, Part 1,  Ultraviolet Radiation Effects,
  D. S. Nachtwey, M. M.  Caldwell,  and R. H. Biggs, eds.
  pp. 5-83 to 5-91.  DOT-TST-75-55, U.S. Department of
  Transportation, Washington,  D.C.
Macdonald, E.  J.  1975..   Association between cancer eye
  and solar radiation.   CIAP Monograph 5,  Impacts of Cli-
  matic Change  on the Biosphere,  Part 1, Ultraviolet Radia-
  tion Effects, D. S. Nachtwey, M. M. Caldwell, and R. H.
  Biggs, eds.  pp. 6-20  to 6-22.   DOT-TST-75-55, U.S. De-
  partment of Transportation,  Washington,  D.C.
Nachtwey, D.  S.  1976.   Potential effects on  aquatic eco-
  systems of increased UV-B radiation, in Proceedings of
  the Fourth Conference  on the Climatic Impact Assessment
  Program, T.  M. Hard and A. J. Broderick, eds.  pp. 79-86.
  DOT-TST-OST-75-38, U.S. Department of Transportation,
  Washington, D.C.
Pitts,  D. G.,  and A. P.  Cullen.  1976.  Ocular ultraviolet
  effects from  300 nm to 400 nm in the rabbit  eye.  NIOSH
  Report for Contract CDC-99-74-12, October.
Porter, W. P.   1967.  Solar radiation through  the living
  body walls of vertebrates with emphasis  on desert rep-
  tiles, Ecol.  Monogr.  37:273-296.
Porter, W. P.   1975.  Ultraviolet transmission properties
  of vertebrate tissues,  CIAP  Monograph 5, Impacts of Cli-
  matic Change  on the Biosphere, D. S. Nachtwey, M. M.
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                                                          Effects  - Marine
                                                      299

  Caldwell, and R. G. Biggs, eds.  pp. 6-3 to 6-15.  DOT-
  TST-75-55, U.S. Department of Transportation, Washington,
  D.C.
Robberecht, R., and M. M. Caldwell.  1978.  Leaf epidermal
  transmittance of ultraviolet radiation and its implica-
  tions for plant sensitivity to untraviolet-radiation
  induced injury, Oecologia 32:277-287.
Sisson, K. B., and M. M. Caldwell.  1976.  Photosynthesis,
  dark respiration, and growth of Rumex patientia L. ex-
  posed to ultraviolet irradiance  (288 to 315 nanometers)
  simulating a reduced atmospheric ozone column, Plant
  Physiol. 58:563-568.
Sisson, W. B., and M. M. Caldwell.  1977.  Atmospheric
  ozone depletion:  reduction of photosynthesis and growth
  of a sensitive higher plant exposed to enhanced UV-B
  radiation, J. Exp. Bot. 28:691-705.
Smith, R. C., and K. S. Baker.  1979.  Penetration of UV-B
  and biologically effective dose-rates in natural waters,
  Photochem. Photobiol. 29:311-324.
Thompson, B. E., R. C. Worrest, and H. van Dyke.  1979.
  The growth response of an estuarine diatom (Melosira
  nummuliades [Dill.] Ag.)  to UV-B (290-320 nm) radiation,
  Estuaries (in press).
Van, T. K., L. A. Garrard,  and S. H.  West.  1976.  Effects
  of UV-B radiation on net  photosynthesis of some crop
  plants, Crop Sci . 16:715-718.
Van, T. K., L. A. Garrard,  and S. H.  West.  1977.  Effects
  of 298 run-radiation on-photosynthetic reactions of leaf
  discs and chloroplast preparations  of some crop species,
  Environ. Exp. Bot. 17:197-112.
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                                                             Effects  - Marine
                                                       307
                                            Photosynthesis
                                            Inhibition
    LLJ
    z
    UJ
    o
    01
    cc
    o
    O
       -4 -
       -5 -
        280
               290
300     310     320

    WAVELENGTH (nm)
                                                    340
FIGURE D.3  Weighting functions in current use  for  biologi-
cal UV effects.
latitude, season, and other factors.  These tables became
the starting point for various investigations  into biologi-
cal effects other than human skin response.  It was  believed
that, although human sunburn is not itself relevant  to  ef-
fects in other organisms, use of an erythemal  weighting
function yielded a reasonable, relative DUV radiation mea-
surement for a typical biological effect.  This use  was
reinforced by the availability of the fairly inexpensive
                          F-4-31

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                                                      Effects  - Marine
 308

 Robertson-Berger  Sunburning Ultraviolet Meter, which was
 reputed  at  that time  to have a response spectrum  (Figure
 D.3,  Curve  B)  sufficiently similar to the erythemal action
 spectrum to serve as  a practical dosimeter.  However, as
 is clear from  the figure, the response spectrum of this
 meter is really somewhat different from the erythemal
 action spectrum.
   Caldwell (1971) developed a generalized plant  action
 spectrum from  a number of action spectrum studies with
 plant material  (Figure D.3, Curve C).  Setlow  (1974) com-
 bined the results of  action spectrum studies with bacteria
 and viruses (where injury to DNA is known to be responsible
 for the  effects) to give a generalized DMA-damage action
 spectrum (Figure D.3, Curve D).  In unpublished studies
 conducted for  the EPA-BACER (Biological and Climatic Ef-
 fects Research) Program, investigators at the USDA Agri-
 cultural Research Center, Beltsville, Maryland, employed
 a simplified weighting function, termed AI9 (Curve E), which
 approximates the Setlow DNA-damage action spectrum.  Inves-
 tigators at the University of Florida (R. H. Biggs and
 S. V. Kossuth, unpublished BACER report)  employed an aver-
 age weighting  function, termed /5I21  (Curve F), that falls
 between  the DNA-damage action spectrum and the Caldwell
 action spectrum in the short-wavelength portion of the
 UV-B  region.  Figure  D.3 also shows a weighting function
 (Curve G) for  inhibition of part of the photosynthetic
process  occurring in  isolated chloroplasts (Jones and Kok,
 1966).   This study is the only one known that has critically
 examined the spectral influence of UV (and visible) radia-
 tion  on  the photosynthetic reaction, independent of influ-
 ences on cell growth  and metabolism.  Recent studies by
 R. C. Smith, K. S. Baker, 0.  Holm-Hansen, and R. Olson
 (Scripps  Institution  of Oceanography, unpublished) have
 shown that photosynthesis by phytoplankton exposed to solar
radiation through various filters is inhibited in a manner
consistent with the Jones and Kok action spectrum.
   To understand the effect of the weighting-function
choice on the calculated DUV dose one may note in Figure
D.I that a given ozone-layer depletion increases the UV-B
irradiance by different amounts at different wavelengths.
The increase at a short wavelength (like  290 nm),  where
J(X)   is  low may be over an order of magnitude  more than
that  at a longer wavelength (like 320 nm),  where J(A)  is
larger.  Because of this fact the effect  of decreased ozone
thickness on the DUV dose rate depends very much on the
relative values of E(X)  at these longer  and shorter wave-
lengths.   For a given ozone change,  the  calculated change
                      F-4-32

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                                                             Effects  -  Marine
                                                       309

 in DUV dose  rate will be generally greater with weighting
 functions  that  increase more toward the short wavelengths
 than  those that increase less.
   Different weighting functions shown in Figure D.3 give
 very  different  predictions of the effects of ozone deple-
 tion.  For example, about 50 percent of the inhibitory
 effect of  UV on the photosynthesis reaction results from
 radiation  greater than 390 rim, and 25 percent from radia-
 tion  between 340 and 390 nm  (Curve G).  Thus, 75 percent
 of the photosynthetic inhibition by solar radiation results
 from  wavelengths that would not change with ozone-layer
 reduction.   Consequently, if this weighting function is
 applicable to intact plants, a moderate ozone depletion
 would not  be likely to have a serious impact on photosyn-
 thesis over  that already being experienced.  This contrasts
 greatly with the predictions using an erythemal or a DNA-
 damage weighting function (Curve A or D), which would pre-
 dict  a much  larger effect.
   The Robertson-Berger  (R-B) meter reading also changes
 less  with  a  given change in ozone amount than does the DUV
 dose  rate  calculated with an erythemal or DNA-damage weight-
 ing function.   One consequence of this fact is that an R-B
 meter reading is less sensitive to the latitudinal change
 of UV-B than is the DUV dose rate calculated with a DNA
 damage action spectrum.  Such a difference in the estimated
 latitudinal  gradient is important because some epidemiologi-
 cal studies  correlating human nonmelanoma skin-cancer inci-
 dence with DUV  have used R-B meter readings at different
 cities to  indicate the local UV environment.  From such
 correlations, projections of increased skin cancer for   ~
 particular ozone-layer depletions have been made.  However,
 if the DNA-damage weighting function is more appropriate
 for skin cancer than the R-B meter response, and there is
 preliminary  evidence that this is so for skin-cancer induc-
 tion  in hairless mice (P. D. Forbes, F. Urbach,  and R. E.
 Davies, Temple  University Skin and Cancer Hospital; R. D.
 Rundle and D. S. Nachtwey,  NASA Johnson Space Center,  un-
 published) ,  the latitudinal  DUV dose gradient is actually
much steeper than the value  measured.   This would change
 the estimated increase in skin-cancer incidence  accompany-
 ing a given  ozone-layer depletion.
   As shown  in Figure D.4,  a rather different latitude
dependence of solar-DUV dose rates is calculated with dif-
 ferent action spectra,  using the average values  of ozone-
layer thickness appropriate  for the season (the  summer
 solstice)  and latitude.   (To facilitate comparison, all
these curves are normalized  to 30° N latitude, corresponding
                           F-4-33

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                                                      Effects  - Marine
 322

 at the  approximate latitude  (30° N) of Gainesville,
 Florida, where  the experiments were performed.*  Column 4
 shows the percentage increase in this dose rate, with a
 15 percent ozone reduction.  Column 5 shows the corres-
 ponding increase in weighted daily DUV dose rate in
 J • m~2 • day~^  (the product of the values in Columns 3
 and 4), and Column 6, the percentage reduction in yield
 for a 15 percent ozone-layer reduction (the product of
 Columns 5 and 2) .
   It may be noted (Column 4) that the percentage increase
 in DUV  is lower with the Caldwell weighting function than
 with the DNA-damage function, and still lower with the'
 AI21 function.  However, the yield reductions expected
 with 15 percent ozone depletion (Column 6) are higher with
 the AI21 and Caldwell weighting functions than with the
 DNA-camage function.  This seemingly paradoxical situation
 arises because weighting functions like ^121 and Caldwell,
 which give more emphasis to the longer UV-B wavelengths,
 make the DUV dose rates for sunlamp radiation considerably
 lower, relative to sunlight, than those calculated with a
 DNA-camage weighting function.  Consequently, in order to
 simulate a certain increase in solar-DUV dose rate on the
 basis of these weighting functions, more actual sunlamp
 exposure is required than if the DNA-damage function were
 employed.   Hence the larger biological effect.  Use of the
 photosynthesis inhibition weighting function (Curve G of
 Figure D.3, Appendix D), instead of the Caldwell curve,
 would make even a larger difference.  The question is, of
 course, which of these Column 6 numbers is correct (i.e.,
 what weighting function should be used)?
   An analogous problem arises when a dosimeter, such as
 the Robertson-Berger meter, is used to compare sunlight
 with UV from sunlamps in an experimental setup.  If the
 DUV dose rate from sunlight  (say,  at noontime on the sum-
 mer solstice, at 30° N latitude, with 0.29 atm • cm of
 ozone overhead) were the same as that from a particular
 set of filtered sunlamps, according to the R-B meter read-
 ing,  it would then be about sixfold less than the lamp
 dose rate if recalculated on the basis of a DNA-damage
weighting function.  That is, the sunlamp radiation would
 actually contain six times the DNA-damaging UV of sunlight
*Note that, for the reasons explained at the beginning of
Appendix D, the raw DUV doses for different action spectra
in Column 3 cannot be directly compared  (although the final
numbers in Column 6 can be).
                          F-4-34

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                                                           Effects  - Marine
                                                      323

when adjusted to make the two give the same R-B meter read-
ing.  This creates a large uncertainty in how experiments
should be set up and interpreted, which cannot be elimi-
nated until the correct weighting functions are known.
   The instantaneous DUV dose rate may be an important
parameter in determining the biological effect, since high
rates of UV damage may overwhelm repair processes.  Nacht-
wey  (1975) has demonstrated a strong dependence on dose
rate of the effectiveness of filtered sunlamp radiation
for killing the alga Chlamydomonas reinhardi  (Figure E.2).
These experiments employed a range of R-B meter readings
(expressed in "Sunburn Units," or SU) corresponding to sun-
light with present to moderately depleted ozone levels.
However, if the DNA-damage weighting function  (rather than
the R-B meter response spectrum) is actually the appro-
priate one for killing of this organism, almost all of the
dose rates studied were greatly in excess of those given
by the sun, even with extreme ozone-layer reductions.  Only
the points around 1 SU • h"1 are close to current noontime
                       2     3    4    5
                         DOSE RATE (SU • h"1)

 FIGURE E.2   Lethal doses  for 50 percent killing  (LD50)  and
 90  percent  killing  (LDgg) of Chlamydomonas  reinhardi  ex-
 posed  to filtered fluorescent sunlamp  radiation  at  differ-
 ent dose rates.  Doses and dose rates  are given  in  terms
 of  R-B meter readings  ("Sunburn Units," or  SU) .
                     F-4-35

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                                                      Effects  - Marine
324

irradiances on a DNA-damaging dose-rate basis, and at this
rate the time required for 90 percent kill amounts to a
full daylight period at noontime dose rates--i.e., it ex-
ceeds the daily dose naturally available.   Since irradia-
tion protracted over a period of days might well give a
different dose response because of the better opportunity
afforded for repair, reports of biological effects result-
ing from a few SU delivered by fluorescent sunlamps must
be reevaluated with better information about the weighting
function.  The conclusion that the organisms can be killed
by a few hours of summer sunlight under current irradiances
may or may not be valid.
   An additional complication in experimental studies is
that, in most situations, the sunlamps are turned on for
from 4-6 h to obtain a given daily dose comparable with
that from the sun.  This is obviously unnatural and sub-
jects the organisms to much higher intensities than the
sun delivers at some times of day (e.g., in midmorning
and midafternoon) but to lower intensities than the sun
delivers at noon.  Only a few investigators have used the
more natural upward and downward stepping of irradiance,
which is a better practice.
   Another problem is that the UV-A and visible components,
even with supplemental white fluorescent lamps, are gener-
ally more than an order of magnitude less intense than
that in sunlight.  This unnatural situation may eliminate
some significant synergisms, positive or negative, between
radiations of different wavelength that are present in
sunlight.
REFERENCE

Nachtwey, D. S.  1975.  Dose rate effects in the UV-B in-
  activation of Chlamydomonas and implications for survi-
  val in nature, in CIAP Monograph 5,  Impacts of Climatic
  Change on the Biosphere, Part 1, Ultraviolet Radiation
  Effects.  D. S. Nachtwey, M.  M. Caldwell,  and R. H. Biggs,
  eds.  pp. 3-105 to 3-119.  DOT-TST-75-55,  U.S. Dept.  of
  Transportation, Washington, D.C.
                            F-4-36

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