Phone (419) 475-6458
MEDICAL  COLLEGE OF OHIO
        AT  TOLEDO
P. 0. BOX  6190, TOLEDO,  OHIO 43614
DEPARTMENT OF PHARMACOLOGY
     AND THERAPEUTICS
                                                   6 July 1971
 William D. Ruckelshaus
 Administrator
 Environmental Protection Agency
 1626 K Street, N.W.
 Washington, D. C.  20460
 Dear Mr.  Ruckelshaus:

           Your Mercury Advisory Committee has completed its report.
 If we can help further please feel free to call upon us.
                                                  Sincerely,
                                                                          r f
                                                  Edward J. Cafruny, M.D.,  Ph.D.
                                                  Chairman, Mercury Advisory
                                                    Commi ttee
 EJC.m
EPA 540/5-71-003

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REPORT OF THE MERCURY ADVISORY COMMITTEE


 OF THE ENVIRONMENTAL PROTECTION AGENCY


         TO THE ADMINISTRATOR
                    Submitted for the
                      Mercury Advisory Committee
                      of the Environmental Protection
                      Agency
                        /.-              .        / .
                             •  . „  -   ...'••       -; ./

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                                                                     -1-

                          INTRODUCTION

     On receipt of notices of cancellation of registration of
Algimycin 200, Algimycin 300, and Industrial  Algimycin MT-4,  the
registrant, Great Lakes Biochemical  Company,  exercised its rights
(under Section 4.c. of the Federal  Insecticide,  Fungicide, and
Rodenticide Act) to request that an  advisory  committee review the
cancellation action.  A Mercury Advisory Committee was appointed by
William D. Ruckelshaus, Administrator of the  Environmental Protection
Agency.  The committee reviewed published literature and considered
all relevant factors pertaining to its charge.  Members then assembled
in Washington, D. C. on May 3-4, 1971.  During these two days, the
committee met with representatives from Great Lakes Biochemical,
expert witnesses, and representatives of various governmental
agencies.  On completion of these hearings, the Mercury Advisory
Committee  considered all relevant factors and prepared to submit
recommendations to the Administrator of the Environmental Protection
Agency.
     The committee's recommendations are contained in this report
which comprises
               Section I   -  Summary
               Section II     Efficacy of Mercurial Algicides and
                              Non-mercurial Substitutes
               Section III -  Risks to Handlers and Swimmers
               Section IV  -  Contribution to Environmental
                              Pollution  and  the Need  for Control

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                                                     -2-
Section V  -  Appendix A - Members of the
                           Mercury Advisory Committee
              Appendix B - Discussants at May 3 and 4
                           meeting
              Appendix C - EPA staff at May 3 and 4
                           meeting
              Appendix D - Special Exhibits
                           1.  List of chemical  algicides
                           2.  Letter from Mr. McNew,
                               Managing Director,of the
                               Boyce Thompson Institute
                               for Plant Research, Inc.
                           3.  Letter from Dr. Robert
                               G. Tardiff, Chief,  Toxicology
                               Division of Water Hygiene

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                                                                     -3-
                       Section  I  - Summary
     The Mercury Advisory  Committee disapproves the use of Algimycin
products which contain  mercury.   Accordingly, it recommends that the
cancellation of registration  of Algimycin 200 and Algimycin 300, July 22,
1969, and Industrial  Algimycin  MT-4,  August 7, 1970 be sustained.  As
a basis for this recommendation,  the  committee cites three major points:
          1.  Effective substitutes which do not contain mercury
              are available.
          2.  Although  algicides  containing phenylmercuric com-
              pounds  have  not permanently injured or killed
              swimmers  or  handlers of such compounds, there are
              not enough data in  the  open literature to warrant
              the conclusion  that mercurial algicides are  free
              of risk.   Granted that  any risk  involved  is
              generally of a  low  order,  there  are  certain  groups
              (e.g.,  people with  renal disease,  others  with various
              infirmities) who may  be especially susceptible  to
              the deleterious effects of mercurial  compounds.
              Moreover, the hazards  of long-term exposure over
              periods of years have not been  weighed.
          3.  Phenylmercuric  compounds added  to swimming pools
              or water cooling towers do not remain confined
              at loci of addition.   Sooner or later, mercurial
              residues are disseminated widely into the soils
              and v/aters of the earth.  As mercury levels in
              the environ.~ant rise,  "en end beneficial  am>a1s

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                                                                    -4-
              must suffer the consequences of mercurial toxicity.
              Since it has been clearly shown that free mercuric
              ion is released in the tissues of vertebrates
              injected with phenylmercurials and that bacteria
              can convert inorganic mercury to methyl mercury,
              the toxicity of phenyl mercurials in the pharma-
              cological sense cannot be separated entirely from
              the lesser or greater toxicity of its conversion
              products.  It is important to note that the
              metabolic fate of phenylmercurial compounds
              added to swimming pools or water cooling towers
              is entirely unknown.  The possibility that
              bacteria or algae in pools alter the chemical
              form of the added mercury has not been excluded.

     The Mercury Advisory Committee considers point 3 above to
contain the most cogent and compelling arguments against the use of
mercurial algicides, and sufficient, in itself, to sustain cancella-
tion orders for the registration of Algimycin products.
     The committee further recommends that all appropriate agencies
of the Federal. Government mobilize forces so as to mount a concerted,
coordinated campaign against the unnecessary contamination of man's
ecosystem with mercury and its compounds.  Tha elimination of mercury-
containing algicides only slightly reduces the environmental burden,
and will  have little impact unless all known and potential sources of
mercurv are controlled.

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                                                                    -5-
               Section II  - Efficacy of Mercurial Algicides
                              and  Non-Mercurial  Substitutes
     Algal growths in swimming  pools  are  common occurrences  in many
private, residential-type swimming  pools  located outdoors.   The
presence of these plankton in swimming  pool water  is  not  consistent
with good design and  proper operation 'of  swimming  pools.  Algal
growths in swimming pool  water  are  usually  indicative of:
     1) improper design and/or  location of  the inlets and
        outlets as to provide poor  circulation of  the water
        through the pool;
     2) lack of continuous maintenance  of a residual  amount  of
        the disinfectant in the swimming  pool water so  as to
        maintain bactericidal conditions  in all areas of  the
        swimming pool at all times;
and/or
     3) inadequate maintenance  and  cleaning of the swimming  pool.
     The presence of algal growths  in swimming pool water is
dependent also upon the presence of  sufficient nutrient  materials,
particularly phosphates and nitrates, in  the  water to support the
growth of microscopic plant and animal  life.   Some community water
supplies have relatively high levels  of these nutritive compounds
naturally.  Continuous use of swimming pool water over a  period of
several months with only a small volume of make-up water added,
usually results in the provision of sufficient nutritive materials
to support algal growths.

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                                                                     -6-
     Most algal growths require sunlight or a very high level  of
artificial illumination.  Most outdoor swimming pools are located so
that all or a major portion of the water surface is exposed to direct
sunlight.  Hence, the sunlight requirement for algal growth is
provided.
     The most common condition, and the most difficult to correct,
which leads to algal growths in swimming pool water is the failure
to maintain continuously in all areas of the pool a residual level
of the disinfectant sufficient to be bactericidal.  Strong sunlight
destroys quickly the residual portion of most disinfectants used in
swimming pool water treatment.  Also, most private, residential-type
swimming pools are not equipped with devices to permit continuous
application of the disinfecting chemical.  Without such apparatus,
it is impractical, if not impossible, to maintain continuously in
all areas of the swimming pool a residual concentration of the
disinfectant of any detectable amount, much less of a level that is
bactericidal and algicidal or algistatic.
     There is, therefore, a practical need to apply an algicidal
chemical to the water of a large number of swimming pools on a regular
basis to prevent the growth of algae.  From the public health point
of view, there Is a need to keep swimming pool water relatively free
of algae.  Algae interfere with the disinfecting action of the
bactericidal agents used in swimming pool water treatment.  Usually,
a greater amount of the bactericide is needed to achieve a satisfactory
level of disinfection.  Algae may contribute to accidental injury as

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                                                                    -7-
they may cause the bottom, side-walls,  steps,  etc.  to  become slippery.
Also, algae, if present in sufficient numbers, may  cause  the swimming
pool water to become opaque.   This  condition may  contribute to  injury
or drowning by the inability  to see someone in the  water  who may  need
assistance.  While the presence of  algae in swimming pool water is
indicative of poor or inadequate design,  operation, and/or maintenance,
practical considerations make it necessary to  accept the  need for the
routine application of algicides to swimming pool water in many
instances.
     There is no question that compounds  containing phenylmercuric
acetate are effective algicides in  swimming pool  v/ater.   However, there
are many other compounds that are considered to  be  equally effective.
For example, many of the quaternary ammonium compounds, if used properly,
are effective in the control  of algae in swimming pools.
     It is also possible and  practicable to use  periodic  (once  every
7-10 days) "super-chlorination" as  a means of  controlling algae in
swimming pools.  The benefit  of "super-chlorination"  is  not  limited
to control of algae.  "Super-chlorination"  is  a  desirable practice
to inactivate resistant bacteria, viruses,  and other microscopic
life and to reduce the concentration of chloro-ammonia compounds  in
the swimming pool water.  These compounds frequently cause eye
irritation and have reduced efficiency as a bactericide.
     In summary, it may be said that for practical reasons, there is
a need for algfcides in swimming pool operation, particularly  for
use in many private, residential-type pools.   However, there are

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                                                                    -8-
"safe" compounds that may be used to control algae.  Similarly,
there is a method of swimming pool operation, namely periodic
super-chlorination, that will control algal growths in swimming pools
under most circumstances.  Super-chlorination may be used in conjunc-
tion with other algicides to obtain greater efficiency.  It is
acknowledged that compounds containing phenylmercuric acetate, such
as "Algimycin 200" and Algimycin 300", are effective algicides in
the treatment of swimming pool water, but it must be acknowledged
also that phenylmercuric acetate compounds are not superior to other
agents or processes.  A number of effective algidical agents is
listed in Appendix Dl.  Additional information concerning the effective-
ness of algicides is presented in Appendix D2.

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                                                                   -9-
               Section III  - Risks  to Handlers  and  Swimmers

     There appears to be no clinical  or laboratory  evidence  that
phenylmercuric compounds,when used  properly  and according  to instructions
in swimming pools, constitutes a health hazard  to either swimmers or
handlers.  An epidemiologic and health status study of workmen  exposed
to phenylmercuric compounds for as  long as six  years  has demonstrated
no evidence of adverse health effects except cutaneous reactions which
were not classified.  T>2   it is very likely that these were primary
irritant reactions, since the degree  of exposure was  such  that  this
type of reaction would be expected.   Studies, which cannot be regarded
either as adequate or complete, of  swimmers  and users of PMA as a
swimming pool algicide have not revealed any adverse health  effects.3
However, phenylmercuric compounds when used  as  weed killers, contra-
ceptive agents, and topical anti-infectives, have been  reported to
cause allergic contact dermatitis.4   Among  the allergic dermatoses,
cases of cell mediated hypersensitivity of this kind to phenylmercuric
compounds are rare problems.  There is also  one well documented case
in the literature of allergic asthma  and urticaria  from phenylmercuric
proprionate in a person with a previous history of  atopy.5   It would
appear, then, that both cell mediated and immediate types  of hyper-
sensitivity are infrequently provoked but known to occur.    Such cases
have not been reported among swimmers in pools using PMA as an algicide
or handlers of PMA used as a slimicidefor industrial cooling systems.
     On the other hand, nercurial algicides cannot be considered to
be entirely  innocuous.  The  rubber of  s^ir'-ing pools in the United States

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                                                                    -10-
continues to increase yearly.  For many people, exposure to waters
treated with mercurial algicides has become a frequent event, repeated
periodically over a period of many years.  Dose-effect and time-effect
data are not available.  Total intake of mercury must be considered.
There are multiple avenues for intake .(e.g., inhalation, ingestion  of
pool waters, absorption through intact or abraded skin).  Whatever
amount is absorbed by these routes is simply added to the total  body
burden of mercury derived from an already contaminated ecosphere.
Whether this additional exposure to mercurial algicides will prove
to be injurious to various organs and tissues is an unanswerable
question at this time.  The question certainly merits attention, for
mercurials are persistent in human tissues and may accumulate to
dangerous levels especially in individuals whose renal function is
impaired.

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                                                                     -11-


                     Section III -  References
1.  Goldwater, L. J., Jacobs,  M.  B.,  and Ladd,  A.  C.:  Absorption
         and Excretion of Mercury in  Man.   IV.  Tolerance to Mercury,
         Arch. Environ. Health 7:568-573,  1963.

2.  Ladd, A. C., Goldwater, L. J., and Jacobs,  M.  B.:  Absorption
         and Excretion of Mercury in  Man.   V. Toxicity of Phenyl-
         mercurials.   Arch. Environ.  Health 9:43-52,  1964.

3.  Wisconsin Alumni  Research  Foundation:  Algimycin 200 in Swimming
         Pools, Exhibit 7.

4.  Morris, G. E.: Dermatoses  from Phenylmercuric  Salts.  Arch.
         Environ. Health 1:53-55, 1960. '

5.  Matthews, K. P.:  Immediate Type Hypersensitivity to Phenyl-
         mercuric Compounds.   Am. J.  Med.  44:310-318,  1968.

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                                                                     -12-
             Section IV - Contribution to Environmental Pollution
                            and the Need for Control

     There is now overwhelming evidence that man has contributed
significantly to the increasing amounts of mercury found in the
environment, particularly in water. foods, and airj  In streams
and oceans, the levels reached are such as to render certain fish
inedible, and in some countries undesirable concentrations of mercury
are found in staple foods, such as rice, fruits, eggs, and meat.
Since inorganic mercury may be transformed by anaerobic microbial
systems in the sediments of waterways to methy!mercury, both
discharges of methylmercury as well as inorganic mercury into streams,
estuaries and oceans, contribute significantly to the depot of
methylmercury to the earth's waters.  There is convincing evidence
that phenylmercuric compounds may be converted by vertebrate biological
systems to the inorganic form and then by microbial metabolism into
methylmercury.  Hence, phenylmercuric compounds which are eventually
discharged from sewer outflows into streams or other bodies of water
probably add to the depot of methylmercury in our waters.  At this
point in time it is, therefore, urgent that all controllable sources
of mercury, including phenylmercuric compound uses, be eliminated or
maximally reduced.  Mercurial algicide is an identifiable and an
easily eliminated source of contamination.  While its use may represent
a minor item in the world's total use of mercury and a small contributor
as compared with the nercury used in chloralkali plants, electrical
equipment, and exterior paints, it is essential that phenylmercuric

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                                                                   -13-
discharges as well  as the major contributors  to mercury contamination
of the environment be eliminated.   It is  essential  that a  coordinated
effort to avoid discharge of mercury compounds into water,  air, or
landscape be undertaken.   Phenylmercuric  acetate may  be eliminated
by substituting equally effective  compounds which  are less  toxic  for
man and animals.  For this cogent  reason  above, the registration  of
PMA as an algicide for swimming pools and slimicide for cooling
systems be cancelled.
     If algicides are needed in a  swimming pool,  it is likely that
chlorination is not - or cannot be - effectively  utilized  (see
Section II).  If chlorination is not effectively  used, there is  likely
to be a host of bacteria in the pool waters.   This is an  important
observation in any consideration of the mobility  of mercury in the
environment.  It is the microbial  transformation  of inorganic mercury
to methylmercury that so stunned scientists and demanded  a new look
into the whole mercury problem.  It now appears that  all  forms of
mercury may be directly or indirectly capable of  conversion to methy!-
mercury.2  It has even been stated that certain  bacteria  appear
capable of converting mercury compounds into metallic mercury vapor.3
Insofar as the phenylmercurials used in swimming  pools is concerned,
Jernelov suggests that they are more efficient sources of mercury for
subsequent methylation than is inorganic mercury. ^
     In evaluating the mobility of mercury in the  environment and its
ecological effects,  it is necessary  to look  at the transforming

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                                                                   -14-
reactions that occur.  For phenylmercury,  Jernelov4 cites the
fol1owi ng:
               (C6H5)2 Hg
                  II
                                                (CH3)2 Hg
                                                 J1
                  Hg
     The above conversion of phenylmercury to mono- and dimethyl -
mercury in bottom sediments has been demonstrated.  In this work",
however, Jernelov notes that it has  been  very difficult to
quantitatively repeat these experiments.   This may be a manifesta-
tion of the loss of the more volatile dimethylmercury and perhaps
other volatile intermediate forms.   A great deal of the mercury
"cycle" needs yet to be pieced together.   We do not know all the
environments in which methyl ation can occur.
     Phenylmercury, when used in swimming pools for algae control,
must be repeatedly brought up to strength.5 Quite obviously, mercury
is lost from the pool.  Some may be  volatilized directly to the
atmosphere.  Some will be splashed out onto the ground.  In some
locations, swimming pool  waters can  be discharged directly into a
sanitary sewer system, thence going  to the sewage treatment plant.
In other locations it is possible to get  a permit to empty a
swimming pool  into a storrcwater drainage  system.  The important
point is that the -swimming pool  is  not a  mercury sink - mercury

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                                                                    -15-
moves from the pool  into the environment.
     Although it has been stated that phenylmercury  is  an efficient
form of mercury for subsequent methylation, mercury  need not be  in
the phenyl form to migrate.   Jonasson and  Boyle  of the  Geological Survey
of Canada suggest that mercury can  migrate as  sulfate,  nitrate,  various
chloride complexes,  carbonate complexes, hydroxide complexes,  ammonia
complexes, and as a variety  of chelated and other organo metallic
complexes. *>
     Although the quantification of the various  pathways followed by
mercury in the environment requires much additional  study,  available
evidence indicates that little, if  any, methylation  occurs  in  soils.2
However, Thompson, in. his chapter on Airborne  Mercury?, states that
both dimethylmercury and elemental  mercury are volatile at  ordinary
outdoor temperatures, and that atmospheric variations might be
associated with warming and  drying  of the  soil.   Hence, mercury
deposited on land may not methylate directly  at  that point, but
some will certainly evaporate and be transported to  aquatic
environments where methylation can  proceed.   Thompson cites
unpublished data from Sweden showing the  concentrations of mercury
in precipitation, varying from a December low of 0.08ug/l  to a July
high of 1.45pg/l.
     It is characteristic of mercury that water concentrations are
seldom high.  The waters of Minamata Bay - so seriously affected
by pollution - contained only 1.6  to 3.6 ppb.  Surveys in  the U.S.
show mercury to be generally associated v/ith suspended particles.

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                                                                   -16-
Oceanic mercury is generally present as an anionic complex (HgCl42~)
which does not have  so pronounced a tendency to adhere to particu-
lates as do forms of mercury found in fresh waters.3   Even today,
most waters of Sweden need not be monitored.8
     Attempts have been made to establish limits or standards for
mercury discharged to aquatic environments.  These have revealed that
the mercury compounds tested were quite toxic even at low concentra-
tions, and a level of no effect is difficult to arrive at.  For
example, ethylmercury at 60 ppb (parts ethylmercury per billion
parts of water) was found to be lethal to marine phytopiankton, .but
as little alkylmercury as 0.1 - 0.6 ppb measurably reduced photo-
synthesis and growth.  In another study, goldfish exposed to mercuric
chloride at 820 ppb died in seven days, but only two days exposure
to 3 ppb impaired their "learning".-*  Harriss et. al., after their
studies on phytoplankton, concluded that effects below 1 ppb must
be determined in order to establish adequate water quality standards.^
By comparison, drinking water standards in both the U.S. and the U.S.S.R.
currently recommend a value of 5 ppb.
     Swedish studies (Johnels and Westermark) have documented the
increasing mercury content of the biosphere.  In this unique work,
the accumulation of mercury in feathers of the goshawk in both
freshly killed birds and in museum collections covering a period of
more than 100 years shows nearly constant mercury levels from the
middle 1800's until 1940.  In 1940, alkylnercury seed dressings
were first '.ise'i and tha nrarcury concentration in feathers began an

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                                                                    -17-
upward trend to a level  10 -  20  times  that  of  the constant period.10
     Most of the mercury found in  animal  tissues is methyl mercury.
Other forms of mercury are able  to pass  into the methyl form  in
nature owing to microbial  action in bottom  sediments.  The process
is not well understood and requires far  more study to determine
the conditions that permit methyl ation and  demethylation and  the
rates at which these processes occur.  It is evident, however, that
methylation is a common and natural occurrence.8  Jernelov^ states
that if the rate of conversion of  inorganic to methylmercury  is the
rate-determining step in the  removal of  mercury from bottom sediments,
it is calculated that this removal  would take  from 10 to 100  years.
     Methylmercury is the form best absorbed and most slowly  lost
from animal tissues.  It accumulates in  the brain where  it destroys
cells and causes neurotoxicity.   It passes  the placenta  and damages
the fetus.   It accumulates so that repeated minute doses over prolonged
periods can disable.  These points are documented  for man  but apply
more pointedly to animals, because animals  living  in contaminated
areas are exposed to polluted food such  as  man only  rarely is, and
because some animals excrete mercury more slowly  than  does man.
Animals that live in polluted water can  pick  up much mercury directly
from the water - in some instances more  than  they get  from their food.8
     The mercury contamination in bottom sediments of waterways
constitutes a depot which, through the methylating process,  represents
a continuing source of methyl mercury.   All  discharges  of inorganic
and organic mercury can presumably contribute to this depotJl

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                                                                   -18-
Phenylmercuric compounds used in swimming pools for algae control  are
no exception.
     That radiation causes genetic damage has been known for many
years and the need for appropriate protection of the American
population has been widely recognized.  The principle that exposure
to radiation be kept at the lowest practical level and that there be
no additional exposure unless the harmful effects are outweighed by
anticipated benefits is now well established in the public policy
of this country. The concern is not only for the health and welfare
of contemporary populations but even more important for future  •
generations.  There is reason to fear that some chemicals and drugs
also may constitute as important a genetic risk, possibly a more
serious one, as radiation.  In humans, genetic defects are not
uncommon and are a serious problem.  All agents that are introduced
into the environmental microcosm should be seriously considered
and examined for mutagenic effects.
     It has been stated on page 567 of "Report of the Secretary's
Commission on Pesticides and Their Relationship to Environmental
Health," Parts 1 and 2, published by the U.S. Department of Health,
Education, and Welfare in December 1969,12 "among the plethora of
new chemicals in our increasingly complex environment, a number
are already known to be mutagenic, i.e., capable of producing
genetic damage.  When genetic damage occurs the burden of hereditary
defect in future generations is increased.
     One potential- genetic hazard comes from pesticides.  Although

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                                                                    -19-
we can point to no pesticide now in wide use that has  been  demonstrated
to be mutagenic, the overwhelming majority have,  however, not-been
adequately tested, although appropriate methodologies  are now available.
     We define mutations as any inherited alteration in the genetic
material.  Such alterations in exposed individuals may lead to cancer
and toteratological effects.  Our main concern, however, is for their
descendants; for such changes lead to a wide range of abnormalities,
mental retardation, physical and mental disease,  and all the other
inherited weaknesses and debilities to which man  is susceptible.
Since these effects will occur in future generations and may be .
apparent only many generations removed, by the time the effect is
noticed, the damage is already irreversible.  It  is therefore urgent
that any mutagenic chemicals to which the population is exposed be
promptly identified."
     In fact, that report went on to recommend that "all currently
used pesticides be tested in the near future...  And no new  pesticides
should be registered until tested for mutagenicity."
     There has been a substantial amount of evidence to indicate
that mercury compounds, including those used as pesticides, also
induce chromosome breaks and mitotic aberrationsJ3   The  reasons
for these effects of mercury are not known, except that mercury does
bind to the purines in DNA and this, of course, could change
the genetic message that is synthesized from the  DNA  template.
     On page 39 of the report entitled "Mercury  in  the  Environment:
The Human Element" by Wallace, Fulkerson, Shults  and  Lyon  (ORNL
NSF-EP-1)14, the question of mercury as  a nutagen is  presented.

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                                                                    -20-
In a section entitled Genetic and Long-term Effects  of Mercury
Exposure, it is stated "cytological  investigations  on plant and  animal
cells have shown that mercury compounds give rise to chromosome
breakage and act as inhibitors of the mitotic spindle mechanism, with
the result that polyploidy or abnormal distribution of single
chromosomes occurs.  As spindle inhibitors, methyl  and phenylmercury
compounds are more potent than any other substance knov/n,  including
colchicine.   Such preliminary observations would imply that both  an
increased genetic load of mutations within living populations and
long-term effects such as carcinogenesis may be influenced by mfircury
in the environment."  The report goes on to state that further
investigations should also be undertaken on the various mercury
compounds used in pesticides and Pharmaceuticals.
     Organic compounds of mercury have been found experimentally
to produce genetic mutations and chromosomal aberrations in certain
systems of plants and Drosophila.13~16   Such changes, however,  have
not been demonstrated in mammals as yet.  C-mitosis, defined as
the characteristic appearance of chromosomes which have contracted
more than is usual for mitotic metaphase and lie scattered within
the nucleus, has been demonstrated in cells of Alii urn cepa exposed
to concentrations of phenylmercury compounds at levels as low as
15 x 10-7M (about 0.05 ppm).  Some of these compounds also cause
c-mitotic tumors, and hook-like growth of the roots is also observed.
Methylmercury and phenylmercury are among the most active c-mitotic
agents known, being 200-1000 times -ore effective than colchicine.

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                                                                    -21-
     In a study with Drosophlla  melanogasterl5,16, treatment of
female larvae and adults  with  phenylmercury acetate resulted in a
significant increase in the number  of  exceptional daughter offspring
(XXY), showing irregularities  of meiotic  chromosomal disjunction.
Chromosomal effects and developmental  disturbances (mutant gene and
outstretched and bent wing) occurred.  There has only been one
report on mammals.  These studies with inbred  CBA mice failed to
demonstrate dominant lethal mutations  after administration of organic
mercurial compoundsJ5  However, although pregnant female CBA mice
that received single doses on  day 10 of the gestation period did  not
appear to be affected, there was in these animals a high frequency
of resorbed litters and an increased percentage of dead fetuses.
It should be pointed out also  that  Skerfving et. alJ? showed-a
statistical increase in chromosomal breaks in  blood cells of human
consumers of large amounts of  fish  containing  methy!mercury.  No
such study is available for phenylmercuric acetate.   Methyl mercury
phosphate has been shown to have teratogenic effects  in pregnant
mice resulting in a 31.6% incidence of cleft palate.^   It  is
obvious that in the case of phenylmercuric acetate  there  have  been
very limited, if any, significant experiments  dealing with  the
mutagenic and teratogenic effect of this  agent with the exception
of the work of Ramel.
     It must be kept  in mind that  phenylmercuric acetate does produce
genetic damage in Alii urn cepa roots and  Drosophila and,although
the genetic effects have not been  studied to  any extent in rar:.:alici

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                                                                   -22-
systems,they may occur.  It is also well to keep in mind that when
                                                               •
swimming pool water containing phenylmercuric acetate is emptied,
the mercury compound enters the ecosphere, and by simple forms of
life taking it up, mutations are not only possible in these simple
life forms but also in the higher forms of life that eventually
ingest the simpler forms.
     Thus because of the known genetic effects of phenylmercuric
acetate in Aliiurn cepa and Drosophila, even though the experiments
are limited in number, a strong possibility exists that this agent
would have harmful genetic effects in humans.
     The present problem regarding environmental Hg contamination
has stemmed from a lack of understanding that discharge of this
element in its various forms into ecosystems presented a potential
for unforeseen transformations of a hazardous nature.  This was
particularly true of the discharge of the elemental, metallic form,
which had been considered as relatively chemically - and therefore
biologically - inert.  The elemental form is known to be under
most conditions inaccessible to biological systems except in its
volatilized or vapor state; therefore being relatively unavailable
to living systems, metallic mercury was considered to be of low
toxicity with the exception noted regarding its vapor.
     A parallelism between our consideration of the aryl mercuric
forms of mercury as compared with elemental contamination is
discomforting.  That is, once again, the aryl mercury compounds
                      i
are of relatively-lo1'/ toxicity compared to the alkylmercury compounds.

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                                                                     -23-
Furthermore, whereas the literature is replete with  human  and  animal
toxicity data concerning deleterious effects  of alkylmercurials,  there
are relatively few reports of similar problem of toxicity  due  to  the
aryl forms - with the exception of some cases with suicidal  intent.
Thus there could be a similar tendency, to write off  concerns with the
aryl mercurials as a class, if direct human and animal  toxicity
were our sole criteria.
     It is hoped that the lessons learned regarding  elemental  mercury's
biotransformation will not be forgotten, especially  in  view  of nature's
almost limitless capabilities for chemical  synthesis and transforma-
tion.  It would appear that presently available information  provides
us with more than a suspicion that the aryl mercurials  may be  trans-
formed to mono- and dimethyl mercury in experimental systems.   Swedish
investigations^  have noted that discharge of phenylmercury  appears
to have a more pronounced effect upon mercury build-up in fish than
is the case for discharges of inorganic mercury.
     With such a strong suspicion, it would appear prudent to delimit
the discharge of aryl mercurials through relatively uncontrolled use
into the environment.  Certainly such discharge increments of the
aryl mercurial slimicidal compounds represents one additional  potential
source for methylmercury formation and entry  into the food chain.
This would argue for discontinuance of the use of this  class  of
compound wherein its use is uncontrolled and  its discharge considerable
in magnitude.
     Such a  position  should be  balanced against the possible harm

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                                                                   -24-
to society of making the compound unavailable.  In another portion
of this report the question of appropriate substitutes for the use
in question is considered: it appears that equally effective non-
mercurials are available to achieve the same ends.  Accordingly,
the loss to society of Algimycin products would appear to be minimal
compared to the incremental burden these phenylmercurials place
upon the environment.
     However, if we are to consider the question in its proper
perspective this discharge of phenylmercuric acetate is a relatively
minor source of environmental contamination.  Therefore, for the
proposed action to have any degree of consistency, if the proposed
action stems from a desire to minimize ecosystem mercury burdens,
then other more extensively used phenylmercurials should be similarly
removed from uncontrolled use.  Otherwise, the gain to society of
stemming discharge of mercurial algicides from swimming pools would
seem to be minimal.
     At this point it is most appropriate to cite the major
recommendations of the special report to the Secretary's Pesticide
Advisory Committee of the Department of HEW of November 1970 on the
Hazards of Mercury:^
          "5. . CONTROL.
               All controllable sources of mercury contamination
          should either be eliminated or maximally reduced.
               Thus, (1) the use of all alkylmercury pesticides
          should be terminated and all other mercurial pesticides
          should be severely restricted to usage on the basis
          of demonstrated need only.  Safe substitutes should
          be soun-'it for those rer:dinihg in use and not now possible
          to eliminate.

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                                                                   -25-
               (2)  Further  safeguards should be developed for the
          manufacture,  packaging, distribution and field use of
          seed treated  with organic mercurials and for the
          disposal  of unused treated seed and its containers to
          avoid mercurial poisoning through accidents or misuse
          of such materials.

               (3)  All  industrial users of mercury, particularly
          those operating chlorine and alkali production plants
          and those using mercury catalysts, should be required to
          reduce their  discharges of mercury into the environment
          to levels approximating background levels.

               (4)  Other sources of mercury contamination or
          exposure  - for example discarded electrical equipment,
          chemicals, paints, cosmetics, Pharmaceuticals, sewage,
          and fossil fuels  - must be identified and brought
          under control. The urgency of this is emphasized by
          the circumstance  that although mercury in any form is •
          hazardous, all forms of mercury have the potential to
          be converted  into the highly toxic form of methyTT
          mercury."
     The control of mercury contamination from all  manmade sources

requires the coordination of efforts  by every government agency

empowered to regulate the use and discharge of mercury.   In order

to fulfill the recommendations of HEW Committee, it is urgent that

plans be developed collectively by the several national  health

agencies responsible for the safety of industrial and consumer

environments - air, water, solid wastes, agricultural uses, forestry

uses, food, drugs, cosmetics, etc. - for the surveillance and control

of the uses and environmental contamination of mercury.  In this

planning, it is essential that not only the adverse health effects

on man be considered, but the effects on all  forms of life essential

to man's ecosystem.  It would appear, then, that effective liaison

for planning and control be developed by the  FDA,  EPA (for air, v/ater,

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                                                                    -26-
solid wastes, and pesticide regulation), NIOSH and the Department
of Labor, NIEHS, etc.  Not until such working liaison is established
will it be possible to reduce the hazards of environmental mercury
to man and his ecosystem.

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                                                                    -27-
                      Section  IV  -  References
 1.   Special  Report to the Secretary's  Pesticide Advisory Committee,
          Dept.  of HEW,  Nov.  1970,  Hazards of Mercury.  Environ.
          Res.  4:1-69, 1971.

 2.   Shibko,  S.  I., and  Nelson,  N.: Microbial transformation of
          mercury.  Hazards of Mercury,  Environmental Research
          4(1):23-31,  1971.

 3.   Wallace, R. A., Fulderson,  W., Shults, W. D., and Lyon, W. S.:
          Mercury in the environment, the human element.  Oak Ridge,
          Tenn., January,  1971.

 4.   Jernelov,  A.: Conversion of mercury compounds.   Chemical Fallout.
          Charles C. Thomas,  Pub!., Springfield,  111. (1969), pp.  68-74.

 5.   See manufacturer's  label and recommendations for use.

 6.   Jonasson,  I. R.,  and Boyle, R. W.:  Geochemistry  of mercury.
          Geological Survey of Canada,  Dept. of Energy, Mines and
          Resources, Ottawa,  Canada (1971).

 7.   Thompson,  J. E.:  Airborne mercury.  Hazards  of Mercury.
          Environ. Res.  4(1):50-53, 1971.

 8.   Stickel, W. H.: -Ecological  effects of methyl mercury  contamina-
          tion.   Hazards of Mercury.   Environ.  Res. 4(1):31-41, 1971.

 9.   Harriss, R. C., White, D. B.,  and  Macfarlane,  R. B.:  Mercury
          compounds reduce photosynthesis by  plankton.  Science 170:
          736-737, 1970.

10.   Johnels, A. G., and Westermark,  T.: Mercury  contamination  of the
          environment in Sweden.  In  Chemical  Fallout,  Charles  C.
          Thomas, Pub!., Springfield, 111.,  pp.  221-239.

11.   Nelson,  N.: Introduction and Summary  of conclusions  and recommenda-
          tions.  Hazards of  Mercury.  Environ.  Res.  4(l):4-9,  1971.

12.   Report of the Secretary's  Commission  on Pesticides and Their
          Relationship to  Environmental Health, U.S.  Department of
          Health, Education,  and Welfare,  1969.

13.   Ramel, C.: Genetic effects  of organic mercury compounds.  I. Cyto-
          logical investigations on allium roots. Hereditas 61:208, 1969

14.   Wallace, R.  £.;  Fulkerson,  II., Shults, V!. D., and Lyon, V,1.  S.:
          Mercury  In  the  Environment:  The K'j.^an  Eler^nt, OR.'.'L '1SF-EP-1.

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                                                                     -28-
15.   Ramel,  C.: Genetic effects of organic mercury compounds.
          Hereditas 57:445, 1967.

16.   Ramel,  C., and Magnusson, J.: Genetic effects of organic
          mercury compounds.  II. Chromosome segregation in
           Drosophila  melanogaster.   Hereditas 61:231,  1969.

17.   Skerfving, S., Hansson, K., and L.indsten, J.: Chromosome
          breakage in humans exposed to methyl mercury through
          fish consumption.  Arch. Environ. Health 21:133,  1970.

18.   Oharazawa, H.: Effect of ethyl mercuric phosphate in the
          pregnant mouse on chromosome abnormalities and fetal
          malformation. J. Jap. Obstet. Gynecol.  Soc. 29:14, 1968.

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                                                          -29-
                 Section V


Appendix A - Members of the Mercury Advisory Committee
      Edward J. Cafruny, M. D.,  Ph.  D., Chairman
           Professor and Chairman
           Department of Pharmacology
             and Therapeutics
           Medical College of Ohio
           P. 0. Box 6190
           Toledo, Ohio  43614
      H. V. Aposhian, Ph. D.
           Professor, Cell Biology and
             Pharmacology
           Department of Cell Biology
             and Pharmacology
           University of Maryland
           School of Medicine
           Baltimore, Maryland  21201
      Bertram D. Dinman, M. D., Sc. D.
           Director, Institute of
             Environmental and Industrial Health
           University of Michigan
           School of Public Health
           Ann Arbor, Michigan  48104
      Eric W. Mood, Jr.
           Associate Professor of Public Health
             and Chief, Environmental Management
             and Control Section
           Department of Epidemiology and
             Public Health
           Yale University
           School of Medicine
           60 College Street
           New Haven, Connecticut  06510

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                                                     -30-
Raymond R. Suskind, M. D.
     Director, Kettering Laboratory
     Department of Environmental Health
     University of Cincinnati Medical Center
     Eden and Bethesda Avenues
     Cincinnati, Ohio  45219
Harold W. Wolf, Ph. D.
     Director
     Dallas Water Reclamation Research Center
     Dallas, Texas  75216

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                                                               -31-
                   Section V


Appendix B - Discussants at May 3 and 4 Meeting
          Mr. James F. Stern, Attorney
               Executive Vice President,
               Great Lakes Biochemical Company

          Dr. Robert M. Stern, President
               Great Lakes Biochemical Company

          Dr. Paul 0. Nees
               Wisconsin Alumni Research  Foundation

          Dr. Leonard J. Goldwater


          Dr. George P. Fitzgerald

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                                                          -32-
                Section V


Appendix C - EPA Staff at May 3 and 4 Meeting
     Mr. Harold 6. Alford, Acting Director
          Pesticides Regulations Division

     Mr. David L. Bowen, Secretariat
          Pesticides Regulations Division

     Mr. Edward Carter
          Pesticides Regulations Division

     Mr. Robert Caswell
          Pesticides Regulations Division

     Mr. Joe Cummings
          Pesticides Tolerances Division

     Dr. Lamar Dale
          Pesticides Regulations Division

     Mr. Thomas Kemp
          OGC

     Miss Harriett Lewis, Stenographer
          Pesticides Regulations Division

     Dr. Thomas McClure
          Pesticides Regulations Division

     Dr. Ernest Walker
          Pesticides Regulations Division

     Mr. P. W. Whiteaker
          Pesticides Regulations Division

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                                                                    -33-
                                               APPENDIX  D1
   Chemicals Used for Algae Control  in Water  Cooling Towers


Quaternary Ammonium Compound

Quaternary + TBTO

Na salt of pent^chlorophenate

K salt of       "

Na salt of trichlorophenate

K salt of       "

Mixtures of phenates

Sodium ethyl mercury thio salicylate

Potassium permanganate

Copper sulfate chelated

Chlorine as cyanurates

Na hypochlorite

Dehydroabietylamine acetate

Na salt of 0-benzyl-p-chlorophenol + K and Na salts

K salt of

Chlorinedioxide

1,3-dichloro-e,5-dimethy1  hydantoin

Dodecyl guanidine hydrochloride

Methylene bis  thiocyanate

Bis  trichloro methyl sulfone

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                                                                       -34-
                                               APPENDIX D2


        BOYCE THOMPSON INSTITUTE FOR PLANT RESEARCH, Inc.        .
                        IO86 NORTH  BROADWAY                  \V>^
                         YONKERS. N. Y. 107OJ              V^

GEORGE  L.  McNEW                               „        _
       DIRECTOR                                     May 7, 1971
Dr. Edward J. Cafruny
Dept. of Pharmacology
Medical College of Ohio
Toledo, Ohio £3614-

Dear Dr. Cafruny:

        Dr. Susskind asked ;bhat I write you regarding the potential hazard
to the environment from use of phenylmercuric acetate as an algicide for
swimming pools.  My experience with this material has been primarily for
use as a seed disinfectant and spray material for eradication of apple
scab (Venturj.a inaequalis) on foliage early in the season before fruit
began to enlarge.

        I do know, however, that the material has been used very satis-
factorily under the name of Algimycin for treating swimming pools.  If
I recall correctly, a solution of 5% or less is diluted to about .09 ppm.
of water.  The material quickly (8 to 12 hours) reduces in concentration
to about 10^ of this level.  Presumably this is due to its rapid uptake by
algae or other microorganisms but I assume a minor source of less - and a
very inconsequential one - would be by volatilization.  The residual
amounts discharged when the pools are cleaned could go into drainage lines
or into soil.  In my opinion it would be quickly bound to organic matter.
The only potential hazard I could visualize would be its conversion to
methyl mercury but it would seem to be of such minor occurrence that it
should not be of substantial hazard.

        As you know, there are a number of fungicides that are algicides
which would be free of toxic effects.  For many years copper sulfate was
used in ponds for this purpose.  I believe Phelps Dodge Co. has a sub-
stantial file on this use.  Another prospect would be Dichlone (Phygon of
U. S. Rubber Co.) or 2,3-dichloronaphthoquinone.  I know the Maugatuck
Chemical Division of U. S. Rubber Co. made some extensive tests against
algae in Wisconsin lakes when eutrophication set in about 20 years ago.
I do not recc.ll v'.-.o collaborated with then at the University but I suspect
Dean Glenn Pound of the College of Agriculture might recall the individual.
I suspect the copper would cause some ninor irritation in pools and
Dichlone night cause skin irritation since an occasional rare individual
reacts to it.  A very logical fungicide would be Captan cut I know of no
tests against algae.

                                            Sir.ceraly yours,
                                            Georga L.- ^Icw
                                            Managing  Director

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                                                                           -35-
                                                    APPENDIX D3
                 ENVIRONMENTAL PROTECTION AGENCY
                         WATER QUALITY OFFICE
               5555 Ridge Avenue,  Cincinnati, Ohio 45213
                             May  7,  1971
Mr. David Bowen
Secretariat
Mercury Advisory Committee
Pesticides Regulations  Division
Environmental  Protection Agency
Room 21kk
South Agricultural  Building
12th and Independence,  S.W.
Washington, D.  C.  2002^

Dear Mr. Bowen:

In the past,  the Division of Water Hygiene, V/0.0, EPA,  (formerly  the
Bureau of Water Hygiene, U.S.P.H.S.)  has  been asked  by other  federal
agencies and  by some  state health agencies  to evaluate the  toxicity
of phenyl  mercuric  acetate (PKA) for  use  in swimming pools  and-to
render an opinion as  to its acceptability from a public health stand-
point.   As the Division's toxicologist,  I was assigned these .evalua-
tions.   In each case, my professional judgement led me to conclude
that PMA v/as  not acceptable from a public health standpoint for use in
swimming pools.  The  reason for my decision was based on the  following:

     1.   The  relatively high acute and subacute toxicity of PMA to
         experimental animals;

     2.   The  degree of  absorption of  PMA  via the cutaneous and
         gastro-intestinal routes of  those  individuals swimming in
         the  PMA treated water, including the likelihood of
         Ingesting  the  pool v/ater while swimming;

     3.   The addition to the total body burden of mercury from
         the absorption of PMA;

     k.   The possible conversion of PMA to other more  toxic forms
         of mercury by  aerobic bacteria;  and

     5.   Other less toxic algicides were  available for use  in
         swimming pools.

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                                                                         -36-
Page 2 - Mr. David Bowen
Currently, the Drinking Water Standards  Committee  of  the  EPA  is
proposing a drinking water standard for  mercury  at 0.005  mg per
liter (ppm).   In reconrmending this limit,  it  is  the intention  of
the Committee that the standard pertain  to unintentionally present
mercurials and that the limit should not constitute a  license  to
deliberately  add mercury to water which  is for human  use  (i.e.,
drinking and  bathing).
                                   Sincerely  yours,



                                   Robert  G.  Tardiff,  Ph.D.
                                   Chief,  Toxicology
                                   Division of Water Hygiene
                                                               EPA 540/5-71-003

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