United States
                Environmental Protection
                Agency
                Office of Water
                Regulations and Standards
                Criteria and Standards Division
                Washington DC 20460
EPA 440/5-80-058
October 1980
oEPA
Ambient
Water  Quality
Criteria for
Mercury

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      AMBIENT WATER QUALITY CRITERIA FOR

                 MERCURY
                 Prepared By
    U.S. ENVIRONMENTAL PROTECTION AGENCY

  Office of Water Regulations and Standards
       Criteria and Standards Division
              Washington, D.C.

    Office of Research and Development
Environmental Criteria and Assessment Office
              Cincinnati, Ohio

        Carcinogen Assessment Group
             Washington, D.C.

    Environmental Research Laboratories
             Corvalis, Oregon
             Duluth, Minnesota
           Gulf Breeze, Florida
        Narragansett, Rhode Island

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                              DISCLAIMER
     This  report  has  been reviewed by the  Environmental  Criteria and
Assessment Office,  U.S.  Environmental  Protection  Agency,  and approved
for publication.  Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
                          AVAILABILITY  NOTICE
      This  document  is available  to  the public through  the National
Technical Information Service, (NTIS), Springfield, Virginia  22161.
                                   11

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                               FOREWORD

    Section 304  (a)(l)  of  the Clean Water Act  of  1977  (P.L.  95-217),
requires the Administrator  of the Environmental Protection Agency  to
publish criteria  for water  quality  accurately reflecting  the  latest
scientific knowledge on  the  kind  and extent of all identifiable effects
on  health  and  welfare  which  may be  expected from  the presence  of
pollutants in any body of water, including ground water.  Proposed water
quality criteria  for the 65  toxic  pollutants  listed  under  section 307
(a)(l) of  the  Clean Water  Act  were  developed  and  a notice  of  their
availability was published for public comment on March 15,  1979 (44  FR
15926), July 25,  1979 (44 FR  43660), and October 1,  1979  (44 FR 56628).
This document  is  a revision  of  those  proposed criteria based  upon  a
consideration of  comments received from  other  Federal Agencies,  State
agencies,   special  interest  groups,  and  individual  scientists.   The
criteria contained in this document replace any previously published EPA
criteria for  the  65 pollutants.   This  criterion  document  is  also
published  in satisifaction of paragraph 11 of the Settlement Agreement
in Natural  Resources  Defense Council,  et.  al.  vs. Train.  8  ERC  2120
(D.D.C. 1976),  modified, 12 ERC 1833 (D.D.C.  1979).

    The term "water  quality criteria"  is used  in  two sections  of the
Clean Water Act, section  304  (a)(l)  and section 303 (c)(2).  The term has
a different program impact  in each section.   In section  304,  the  term
represents a non-regulatory,  scientific  assessment of ecological ef-
fects. The criteria presented  in  this  publication  are such  scientific
assessments.   Such water  quality criteria  associated  with  specific
stream uses when  adopted as  State water quality standards under section
303 become  enforceable  maximum  acceptable  levels  of  a pollutant  in
ambient waters.  The water quality criteria adopted in the  State water
quality standards could  have the same numerical limits as the  criteria
developed  under section  304.  However, in many situations States may want
to adjust  water quality  criteria  developed under section 304 to reflect
local   environmental  conditions  and human exposure  patterns  before
incorporation  into  water  quality  standards.    It  is not until  their
adoption as part of the  State water quality standards that the  criteria
become regulatory.

    Guidelines  to assist  the  States  in  the modification of  criteria
presented   in   this  document,  in  the  development  of  water   quality
standards, and  in  other water-related programs of this Agency, are being
developed  by EPA.
                                    STEVEN SCHATZOW
                                    Deputy Assistant Administrator
                                    Office of Water Regulations and Standards
                                   111

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                                 ACKNOWLEDGEMENTS
Aquatic Life Toxicology:

    Charles E. Stephan, ERL-Duluth
    U.S. Environmental Protection Agency
John H. Gentile, ERL-Narragansett
U.S. Environmental Protection Agency
Mammalian Toxicology and Human Health Effects:
    Tom Clarkson (author)
    University of Rochester

    Christopher T.  DeRosa (doc. mgr.)
    ECAO-Cin
    U.S. Environmental Protection Agency

    Si Duk Lee (doc. mgr.) ECAO-Cin
    U.S. Environmental Protection Agency

    Patrick Durkin
    Syracuse Research Corporation

    James P. Kariya, OTS
    U.S. Environmental Protection Agency
    Leonard T. Kurland
    Mayo Clinic

    Paul Mushak
    University of North Carolina

    H. Schumacher
    National Center for Toxicological
       Research

    Samuel Shibko
    U.S. Food and Drug Administration

    Robert Tardiff
    National Academy of Science
Edward Calabrese
University of Massachusetts

Richard Carchman
Medical College of Virginia
Joan Cranmer
University of Arkansas

Dr. Frank D. Itri
Michigan State University

Dinko Kello
Institute for Medical Rese^ch
Zagreb, Yugoslavia

Steven D. Lutkenhoff, ECAO-Cin
U.S. Environmental Protection Agency

Rudy J. Richardson
University of Michigan

Ray Shapiro
National Institute for Environmental
   Health Sciences

Jerry F. Stara, ECAO-Cin
U.S. Environmental Protection Agency

Norman Trieff
University of Texas Medical Branch
Technical Support Services Staff:  D.J. Reisman, M.A. Garlough, 8.L. Zwayer,
P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper,
M.M. Denessen.

Clerical Staff:  C.A. Haynes, S.J. Fashr, L.A. Wade, D. Jones, B.J. Borcicks,
B.J. Quesnell, P. Gray,  B. Gardiner.
                                     IV

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                                TABLE OF CONTENTS

                                                                    Page

Criteria Summary

Introduction                                                        A-l

Aquatic Life Toxicology                                             B-l
     Introduction                                                   B-l
     Effects                                                        B-4
          Acute Toxicity                                            B-4
          Chronic Toxicity                                          B-6
          Plant Values                                              B-7
          Residues                                                  B-7
          Miscellaneous                                             B-12
          Summary                                                   B-13
     Criteria                                                       B-15
     References                                                     B-56

Mammalian Toxicology and Human Health Effects                       C-l
     Introduction                                                   C-3
     Exposure                                                       C-16
          Ingestion from Water                                      C-16
          Ingestion from Food                                       C-18
          Inhalation                                                C-28
          Dermal                                                    C-30
     Pharmacokinetics                                               C-30
          Absorption                                                C-32
          Distribution and Metabolism                               C-36
          Excretion                                                 C-48
     Effects                                                        C-61
          Acute, Subacute, and Chronic Toxicity                     C-61
          Teratogenicity                                            C-90
          Mutagenicity                                              C-91
          Carcinogenicity                                           C-92
     Criterion Formulation                                          C-93
          Existing Guidelines and Standards                         C-93
          Current Levels of Exposure                                C-93
          Special Groups at Risk                                    C-94
          Basis and Derivation of Criterion                         C-94
          Calculation of Criteria in Natural Waters                 C-99
          Comment on Criteria                                       C-106
     References                                                     C-107

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                              CRITERIA DOCUMENT
                                   MERCURY
CRITERIA
                                 Acuatic  Life
    For total recoverable mercury the criterion to protect freshwater  aouat-
ic life as derived using the  Guidelines  is  0.00057 ug/1  as  a 24-hour average
and the concentration should not exceed 0.0017 ug/1 at any time.
    For total recoverable mercury the criterion to protect  saltwater aauatic
life as derived using the Guidelines  is  0.025 ug/1  as a  24-hour  average  and
the concentration should not exceed  3.7 ug/1 at any time.

                                 Human Health
    For the  protection  of  human health  from  the toxic properties  of mercury
ingested through water  and contaminated  aauatic organisms, the ambient  water
criterion is determined to  be 144 ng/1.
    For the  protection  of  human health  from  the toxic properties  of mercury
ingested  through  contaminated  acuatic  organisms alone,  the  ambient  water
criterion is determined to  be 146 ng/1.

    Note:  Criteria reflect  ingestion  of marine organisms  as well  as  fresh-
          water and estuarine fish and shellfish.
                                    VI

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                                  INTRODUCTION

    Mercury, a silver-white metal which  is  a liauid at room temperature, can
exist  in  three  oxidation states: elemental, mercurous,  and  mercuric;  it can
be part of both inorganic and organic compounds.
    Mercury  is a  silver-white metal,  atomic weight 200.59.   A liquid at room
temperature, its  melting point  is -38.87°C  and  its boiling  point ranges from
356 to 358*C.   The  metal  is insoluble  and is  not attacked by  water.   At
20°C, the specific gravity is 13.546  (Stecher,  1968),  and the vapor pressure
is 0.0012 mm Hg (Stecher, 1968).
    Mercury  exists  in a number  of  forms in the  environment.  The  more com-
monly  found mercuric  salts   (with  their  solubilities  in  water)  are  HgClo
                            2
(lg/13.5  ml  water),  Hg(N03)   (soluble  in  a "small  amount" of  water),  and
Hg(CHjCOO)2  (1.0  g/2.5  ml  water).   Mercurous  salts  are much  less  soluble
in water.   HgN03  will  solubilize only  in  13  parts water containing  1  per-
cent   HN03.    Hg2Cl2   is  practically   insoluble  in   water.    Because  of
this, mercurous salts  are  much  less toxic  than  the mercuric forms  (Stecher,
1968).
    The Department  of the Interior carried out  a  nationwide reconnaissance
of mercury  in  U.S.  water in the  summer  and fall of 1970 (Jenne, 1972).   Of
the samples  from the industrial wastewater  category,  30  percent  contained
mercury at  greater  than 10 yg/1; nearly 0.5 percent  of the  samples  in  this
group  contained more than 1,000  wg/1.   Only 4 percent  of  the surface  water
samples contained more than  1,000  wg/1.   The  higher  mercury concentrations
were  generally  found  in  small  streams.   About  half  of the  43  samples  from
the Mississippi River  contained  less  than  0.1  ug/1.   The mercury content of
lakes and reservoirs was between  0.1  and 1.8 pg/1.   With few exceptions, the
mercury content of groundwater samples was  below detection (0.1 ug/1).
                                     A-l

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    In  a  survey  by the  Environmental  Protection Agency  (EPA) Division  of
Water  Hygiene,  273  community,  recreation,  and  Federal  installation  water
supplies were examined.   Of  these,  261  or  95.5  percent,  showed either no de-
tectable  mercury  or  less than  1.0  yg/1   in  the  raw  and  finished  water.
Eleven of the supplies  had mercury  concentrations  of  1.0 to  4.8 yg/1  and one
supply exceeded 5.0 wg/1.  When  this one  supply  was  extensively reexamined,
the mercury  concentration was found  to  be less than  0.8  yg/1  (Hammerstrom,
et al. 1972).
    Seawater contains  0.03  to 2.0  wg/1,  depending on the sampled  area,  the
depth, and  the  analyst.  In  a study of  Pacific  waters, mercury  concentra-
tions were found  to  increase  from surface  values  of  about  0.10 yg/1 to 0.15,
to 0.27 ng/1 at greater depths.   In an area seriously affected by pollution
(Minamata Bay, Japan),  values  ranged  from  1.6 to  3.6  yg/1.   The National  Re-
search Council  (1977)  has shown typical  oceanic  values for  mercury to  be
0.01 to 0.03  wg/1.   Oceanic  mercury is generally  present  as  an anionic  com-
plex  (HgCO~),  which  does  not  have  as  pronounced   a  tendency to bind  to
particulate substances  and then  settle  out as  do mercury compounds found  in
freshwater (Wallace, et al.  1971).
    A major use of  mercury has been as  a  cathode  in  the  electrolytic  prepar-
ation of  chlorine and caustic soda; this  accounted for  33 percent of  total
demand in the United  States  in 1968.   Electrical  apparatus  (lamps,  arc  rect-
ifiers, and mercury battery  cells)  accounted for 27  percent,  industrial  and
control  instruments  (switches,  thermometers,  and  barometers), and  general
laboratory applications  accounted for  14 percent  of demand.   Use  of  mercury
in antifouling and  mildew proofing  paints  (12  percent)  and mercury formula-
tions used to control  fungal  diseases of seeds, bulbs,  plants,  and vegteta-
tion (5 percent) were other major utilizations, however, mercury is no  long-
er registered by the EPA for use in antifouling paints or for  the  control  of
                                     A-2

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fungal  diseases  of bulbs.   The remainder  (9  percent)  was for  dental  amal-
aams, catalysts, pulp and  paper manufacture,  Pharmaceuticals,  and metallurgy
and mining.
    Several forms  of  mercury, ranging from elemental to  dissolved inorganic
and organic species,  are  expected  to occur in the  environment.   The  finding
that certain microorganisms have the  ability  to  convert  inorganic and organ-
ic forms of mercury to  the highly  toxic  methyl or  dimethyl mercury has  made
any form  of  mercury highly hazardous  to the environment  (Jensen and Jerne-
lov, 1969).   In  water,  under naturally  occurring  conditions  of  pH and  tem-
perature,  inorganic  mercury can   be  coverted  readily  to  methyl   mercury
(Bisogni and Lawrence, 1973).
    Mercury is able to  form a series  of  organometallic  compounds with alkyl,
phenyl, and methoxyethyl  radicals.   Short-chained  alkyl  mercurials are  tox-
icologically  important  because  the  carbon-mercury bond  can  be broken  _iji
vivo, with the subseauent disappearance of the organic  radical.
                                     A-3

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                                  REFERENCES

Bisogni,  J.J.  and A.W. Lawrence.   1973.   Methylation of mercury  in  aerobic
and  anaerobic  environments.   Tech.  Rep.  63.   Resour.  Mar.  Sci.  Center,
Ithaca, New York.

Hammerstrom,  R.J.,  et  al.  1972.   Mercury  in drinking water  supplies.   Am.
Water Works Assoc.  64: 60.

Jenne, E.A.   1972.  Mercury in waters of  the  United States,  1970-1971.  Open
file rep.  U.S. Oep. Inter. Geol. Surv.  Menlo Park, California.

Jensen,  S.  and  A. Jernelov.    1969.    Biological  methylation  of  Nature.
223: 753.

National  Research Council.  1977.   An  assessment of mercury  in  the  environ-
ment.  Nat. Acad. Sci., Washington, D.C.

Stecher,  P.G.  (ed.)  1968.  The  Merck  Index.  8th ed., Merck and  Co.,  Rah-
way, New Jersey.

Wallace,  R.A.,  et  al.   1971.   Mercury in the  environment:  the human  ele-
ment.  Oak Ridge, Tennessee.
                                     A-4

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Aquatic Life Toxicology*
                                 INTRODUCTION
    Mercury  has long  been  recognized  as  one of  the  more toxic  metals  but
only recently was  it  identified  as a serious pollutant  ir\  the  aauatic envi-
ronment.   Elemental  mercury, which  is  a  heavy  liauid  at  room temperature,
was considered  relatively  inert.   It was thought  that  it  would auickly set-
tle  to the  bottom of a  body  of  water  and remain  there in  an innocuous
state.  However,  elemental  mercury  can  be oxidized in  sediment  to divalent
mercury (Wood,  1974).   Furthermore,  both aerobic and anaerobic  bacteria have
been found capable of  methylating  divalent mercury in  sediments (The Nation-
al Research  Council,   1978)  and  estuarine  areas  (Jernelov, 1971).   This  me-
thylated form  is  more  water soluble  and  more biologically active  than ele-
mental  and  inorganic  divalent  mercury  (Fromrn,   1977;  Armstrong  and  Scott
1979;  Jernelov,  et al.  1975).   Largely because  of bacterial  methylation,
mercury is much more of a  serious  threat to the  aauatic environment than  was
suspected.  Mercury  is one  of  the  few  pollutants that,  at  about the  same
concentrations  in  water,   adversely affects aauatic   life  through  direct
toxicity and  affects  uses  of aauatic  life through  bioaccumulation.   Bioac-
cumulation has  received more attention  because of potential  adverse  effects
to humans.  Methylmercury is more toxic  than  inorganic  mercury  to mammals as
well  as aauatic life,  and  mercury has no known physiological function.
    The toxicological   data  base  and  environmental  chemistry of  mercury sug-
gest that divalent inorganic mercury (inorganic  mercury) and  monomethyl mer-
cury  (methylmercury)   are  the forms that  are  most directly  hazardous  to
*The reader  is  referred  to the Guidelines for  Deriving  Water Quality Crite-
ria for the  Protection  of  Aauatic Life and  Its  Uses  in  order to better  un-
derstand the  following  discussion and recommendation.   The  following tables
contain the  appropriate  data  that were found in  the  literature,  and  at  the
bottom of each  table  are calculations for deriving various  measures  of  tox-
icity as described in the Guidelines.
                                     8-1

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aquatic systems.   Even  in situations  in  which no organic mercury  was  known
to have been discharged, methylmercury was the dominant  form  in  tissue  resi-
dues  (Jernelov  and Lann, 1971).The methylated form  is  of great  concern  be-
cause it comprises most  of the  mercury residue in tissues of  anuatic  organ-
isms  (Hattula,  et  al.  1978;  Cappon and Smith, 1979)  and tissue  residues  are
a potential hazard to  consumers of aquatic  life.   Defining  the  toxicity  of
mercury residues to humans, and probably  other consumers of  aouatic life,  is
complicated by the effect of  selenium  on  the toxicity of mercury  (Strom,  et
al. 1979;  Friedman, et  al.  1979;  Cappon  and  Smith,  1979;  Speyer,  1980; Gan-
ther,  et al. 1972a, 1972b,; Luten,  et  al. 1980,  and  Rudd, et  al.  1980),  es-
pecially when it is known that  aauatic  organisms  from different  sources have
substantially different  selenium to mercury  ratios.   The FDA  action level  of
1.0 rug/kg  based  on saltwater  fish may be too  high for freshwater fish  which
have significantly different  selenium to mercury  ratios.
    Once methylation takes place, uotake  by  aouatic  life is  extremely  rapid,
and demethylation is a very slow process  (McKim et al.  1976).  Deouration  by
excretion  through  the  kidney reportedly  reouires demethylation  (Burrows  and
Krenkel, 1973).   Apparently  the  slow  rate  of  demethylation  is  responsible
for mercury's biological  half-life  of  approximately  2 to  3  years  (Lockhart,
et al. 1972; McKim, et al. 1976).   In  freshwater  fishes, initial  elimination
of  mercury just  after  the   end  of  exposure is  relatively  rapid,  due  to
sluffing of the slime coat  (Burrows  and  Krenkel, 1973) and  elimination  of
non-methylated mercury.   Once methylmercury becomes   securely  bound to  sulf-
hydryl groups in muscle  proteins, subsequent  loss proceeds at  a  much reduced
rate.   In  fact,  long  term reduction of the  concentration  of  mercury in fish
tissue is  largely  due  to dilution  by  tissue addition resulting  from  growth
(Lockhart,  et al. 1972; McKim, et al.  1976).
                                     8-2

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    Methylation of  inorganic mercury  has  been demonstrated in  the  environ-
ment, in the  slime coat  of  fishes,  and in the intestines of fish  (Jernelov,
1968),  but  has not been  demonstrated  to occur once the mercury is  absorbed
into  tissues  of fish (Pennarcchioni,  et  al.  1976;  Huckabee,  et  al.  1978).
High mercury  concentrations  in slimy freshwater fishes  such  as  burbot,  eels,
and northern  pike,  and  in  the  skin of  acutely-exposed fishes  are  believed
due  to  the methylating  activity of  bacteria prevalent  in  the mucous  coat
(Jernelov,  1968).   Acutely  toxic  concentrations   of  mercury  have been  re-
ported  to stimulate mucous  secretion (McKone,  et  al.  1971;  Baker,  1973), re-
sulting in the  belief by some that  the skin and its mucous coat are  propor-
tionately  greater  mercury  sinks  than   other fish tissues  (Burrows,  et  al.
1974).  However, these are the layers  of the fish  that  are  first encountered
as  mercury  moves  from the  environment into  a fish,  and in acute exposures
the mercury does  not have  time  to  be  transported  to  the final sink -  the
proteins whose greatest mass are in the axial muscle (McKim,  et al. 1976).
    Numerous data are available concerning  the effect of  phenylmercuric  ace-
tate  (PMA)  on anuatic organisms, because  of its  use as a fungicide  and its
use to treat fish diseases.  Many tests have been  conducted on  different PMA
formulations  which  contain  various  percentages of  active  ingredient.   The
percentages of  active  ingredient  given by  the authors  were used  to  convert
to  concentrations of  mercury.   When the percentage of  active  ingredient was
not given, 80 percent PMA was assumed (Allison, 1957).
    Of  the  analytical measurements  currently available, water  duality crite-
ria for mercury are probably best  stated  in terms of total recoverable  mer-
cury, because of the  variety of  forms  of  mercury  than can exist in bodies of
water and the  various  chemical  and toxicological  properties of  these forms.
The forms of  mercury  that are commonly found  in bodies of water and  are not
                                     B-3

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measured  by  the total recoverable  procedure,  such as the mercury that  is  a
part of minerals, clays  and  sand,  probably  are forms that are  less  toxic  to
aauatic  life  and probably will  not be  readily  converted to the more  toxic
forms under  natural  conditions.   On  the other  hand,  forms  of mercury  that
are commonly found in  bodies  of  water and are measured by the total  recover-
able procedure, such  as  the  free ion, the  hydroxide,  carbonate,  and sulfate
salts, and the  organic compounds,  probably are  forms  that  are  more  toxic  to
aauatic life or can be converted to the  more toxic forms under  natural  con-
ditions.  Because the  criteria for  mercury  are  derived on the basis  of tests
conducted on soluble  inorganic salts  of  divalent inorganic  mercury  and  mono-
methylmercuric  chloride,  the total  and  total recoverable  concentrations  in
the test  should be about  the same.   Except as noted,  all concentrations  re-
ported herein are expected to be essentially  equivalent  to  total  recoverable
mercury.  All concentrations  are expressed as mercury, not as the compound.
                                    EFFECTS

Acute Toxicity
    Table  1  contains   the  primary  acute   toxicity  data for three classes  of
mercury compounds:  inorganic mercuric salts, methylmercuric compounds,  and
other  mercury  compounds,  chiefly  organic.   The  latter information  exists
principally  because  many  of these  compounds  have  been used  for  disease
treatment  and  parasite  control   in  fish cultural  practices,  though  their
source for  environmental  concern  is  from  industrial  and agricultural  uses
for  fungus  control.    A  striking feature of the  freshwater acute  toxicity
values is that  the difference  in sensitivity between different types of  or-
ganisms to a  particular  mercury  compound is far greater than the difference
in  sensitivity  of a  particular  species   to  various  mercury  compounds.   For
                                     8-4

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inorganic  mercury,  the  reported 96-hour  LC5Q  values  range  from  0.02  yq/1
for male crayfish to  2,000  yq/1  for larvae of a caddisfly, with  a continual
gradation  in  sensitivity  among  species  with  intermediate  sensitivities
(Table  3).   Data are  insufficient  to  make  such comparisons  for  other  two
classes of mercury  compounds.   Rainbow trout are the  most  acutely sensitive
of  the tested  fish species  to  all  three  kinds  of  mercury compounds  and
methylmercuric  chloride is  about ten  times more  acutely  toxic  to  rainbow
trout than is mercuric chloride.
    MacLeod and  Pessah  (1973)  studied  the  effect  of temperature  on the acute
toxicity of  mercuric chloride  to rainbow trout.   At  5, 10,  and  15*C,  the
LC50  values  were 400,  280, and  220  yg/1, respectively.  Clemens  and Sneed
(1958) found similar temperature  effects with mercury  exposures  at 10, 16.5,
and  24°C   (Table  6).   Their  acute  values for  phenylmercuric  acetate  were
1,960, 1,360, and 233 yg/1, respectively, with juvenile channel  catfish.
    A freshwater Final  Acute Value  of  0.0017 ug/1 was  obtained  for inorganic
mercury using the  species  mean acute values  in  Table  3 and  the  calculation
procedures described in  the Guidelines.  This value should  be useful  because
it  is based on  data for  eleven species,  even though  acute data are  not
available for any non-salmonid fish.
    Acute values for mercuric  chloride  are available for 26 species of salt-
water animals from  5 phyla  (Table 1).   Species  mean acute values  in Table  3
show  that  winter  flounder  is  the  most  resistant  species  tested (LC,-Q  =
1,680  yg/1)  and  the mysid shrimp   the most  sensitive (LC5Q  =  3.5  yg/1).
Fishes were  generally  more resistant to mercuric  chloride  than  the crusta-
ceans and molluscs.   The saltwater  Final Acute Value  for inorganic mercury,
derived from the species mean  acute  values in Table 3  using  the  calculation
procedures described  in  the Guidelines is  3.7 uq/1.   Only  one test with  me-
                                     B-5

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thylmercuric chloride has  been  reported with an acute  value  of  150 ug/1  for
the amphipod, Gammarus duebeni.
Chronic Toxicity
    Chronic  toxicity  tests with Daohnia magna  have been conducted  on  three
different kinds of mercury compounds and the  chronic  values were all between
1.0 and  2.47 ug/1 (Table  2).   In  addition,  a chronic  test with brook  trout
yielded  a  value  of  0.52  ug/1  for methylmercuric  chloride.   Of the  three
available acute-chronic ratios, values  of  2.7 and  3.9 were  obtained for mer-
curic chloride with  Daphm'a  magna,  whereas 140 was found for methylmercuric
chloride with brook trout.
    A chronic  value  of 1.2  ug/1 has  been  determined  (Table  2)  from a  flow-
through  life-cycle exposure  of the mysid  shrimp  to mercuric  chloride  (U.S.
EPA,  1980).   Grouos  of 30 juvenile shrimp were reared in each  of  5 concen-
trations for 36  days  as 2l"C and 30  g/kg  salinity.  Responses  examined  in-
cluded time  of appearance  of first brood, time of first spawn,  and produc-
tivity (total  number  of young/number of  available  female spawning  days  and
total number of  spawns/number of available female  spawning  days).  No spawn-
ing occurred at 2.51 ug/1.   Time to spawn  and productivity  were  significant-
ly  (P<0.05)  different  at  1.66  ug/1 compared  to controls.  The  highest con-
centration at which no  adverse  effect on reproductive processes  was detected
was 0.82 ug/1.  The chronic  limits  are 0.82  and  1.66 ug/1  and  the chronic
value  is 1.2  ug/1.   The  96-hour  LC,-g for  this  species  in  the same  study
was 3.5 ug/1 giving an acute-chronic ratio  of 2.0.
    The  species  mean  acute-chronic  ratio  for Daphnia magna  is  3.2,  whereas
that for mysid shrimp is 2.9, and  these are both  sensitive soecies  in  fresh
and saltwater,  respectively.   All  of  the  reported  acutely  sensitive species
in  both  waters  are  invertebrate species.   Thus  the   absence of an  acute-
                                     B-6

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chronic  ratio  for a fish species  should  not  be too serious, and  3.0  can be
used  as  the Final  Acute-Chronic  Ratio  (Table  3).   Division  of  the  Final
Acute  Values by 3 results  in  freshwater  and  saltwater  Final  Chronic  Values
of 0.00057 and 1.2 uq/1, respectively.
Plant Values
    Data concerning  the toxicity of mercury compounds to  freshwater aauatic
plants are  contained in  Table 4  with  some additional  results  in  Table  6.
Whereas  plant  values for inorganic mercury range from 80 to 2,600  uq/1  ef-
fects  due  to  methylmercury occur at  concentrations  as  low  as  4.8  wg/1.
Another form of methylated  mercury cause  effects  at  concentrations less than
0.3 uq/1  (Table  6).  Although freshwater  plants are  relatively  insensitive
to inorqanic mercury and  sensitive to  some of  the methylated forms, they do
not appear to  be more sensitive  to the  respective forms  of mercury  than  are
freshwater animals.
    Data describing  the  toxicity  of mercuric  chloride  to saltwater  plants
are from two studies with seven species of  algae.  In  both cases,  growth  was
the  response  parameter  investigated.    The  EC5Q concentrations  (Table  4)
indicate reduction in growth at  concentrations ranging from  10 to  160  wg/1.
No data  were  found concerning the toxicity of organic mercury compounds  to
saltwater plant life.
Residues
    Bioconcentration  is a  function of  uptake  rate  relative to  depuration
rate.   The  bioconcentration factor  for  mercury  is  high  because  uptake  is
fast  and elimination is very  slow.  Temperature accelerates  uptake of mer-
cury  by  increasing  the  metabolic  rate and  the respiratory volume.   Because
the gills are  the primary surface  for absorption  of  waterborne  substances  by
freshwater  aouatic  organisms,  uptake  increases  as  respiratory  volume  in-
                                     B-7

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creases.  Increased metabolic rate also  increases energy  demand  and  thus  in-
creases food consumption.  With  greater  rates of food cornsumption,  exposure
to  mercury  through  the food  chain  is  accelerated  (Sharpe,  et al.  1977).
Studies have  shown  that  uptake through  both the  gills  and  the digestive
tract  are significant  for fish, and  some data suggest that tissue  residues
are higher  in  organisms exposed via  both  routes  than via either  separately
(Boudou, et  al. 1979; Phillips and  Butler, 1978).
    Because  metabolic rate is  important  in mercury uptake, dissolved  oxygen
concentration could  also be  expected  to  influence uptake  by increasing  res-
piratory volume.   In a  recent  study,  low dissolved oxygen concentration  in
an eutrophic lake forced fishes  into  warmer  surface  water to  secure  adeouate
oxygen.  In the warmer  surface  water  the  stimulated  metabolic  rate apparent-
ly increased mercury uptake (Larson, 1976).
    Temperature may  significantly affect uptake during episodic  exposures  to
mercury in  which  steady-state  is  not reached  in  the organism.   Under  such
conditions tissue residues are  directly  related  to temperature  (Reinert,  et
al. 1974).   In addition,  a  direct  relationship  seems to  exist  between  tem-
perature and tissue  residues after steady-state has  been  reached (Cember  and
Curtis 1978; Boudou, et al.  1972).  The  latter  is  difficult  to understand  if
steady-state occurs at  saturation of  available bonding sites,  but  empirical-
ly is  does  seem to be the case  (Murray,.  1978).  Apparently not  only are  up-
take and depuration  accelerated  by termperature but,  because of  the  dispari-
ty in  rates  between the two  processes, higher tissue  residues accumulate  at
higher temperature.
    The differences in  bioconcentration  between  different  species  of  fish
are thought  to result from  a  number  of  causes:  concentration  in  the  food
(Phillips  and  Buhler, 1978);  the ouantity of food consumed; the temperature
                                     B-8

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at  which the  fish  is  living;  and  the  differences  in  the  mucous  coat  of
different  species  (Jernelov,  1968).    However  within  a  given  environment,
bioconcentration  factors  for both forage and game  fish  tend to  be  similar
(Huckabee, et al. 1974).
    Distribution  of  mercury  within  a  fish can conceptually be considered  as
a flowing system  in which the flow pattern moves  from the absorbing surfaces
(the  qills,  skin, and gastrointestinal  tract),  into the blood, then to  the
internal organs and  eventually  either  to the kidney  or bile  for  elimination
or  to  the  muscle  for  long-term  storage.   The  later storage  site  can  be
considered  to  have  a   small   leak  whereby  mercury,  after  demethylation,
re-cycles back to the kidney for excretion  (Burrows  and Krenke,  1973).  This
leak  appears  to  be responsive  to  internal  mercury  "pressure"  because,  as
steady-state is approached,  accumulation rate  is slowed  either by a  reduced
uptake  rate or an increased  discharge  rate.   Internal "pressure"  may inhibit
membrane transport  rates  or, for  a  lack of storage  sites, shunt  mercury  to
elimination.
    At  steady-state, when tissue  residues are  relatively  stable  in the vari-
ous organs, muscle mass composes  such  an  important portion of  the  total  fish
mass  that mercury concentrations in  the portion of  the total  fish mass  that
mercury concentrations in the whole fish  are similar  to those  in  edible  por-
tions alone (McKim,  et al. 1976;  Huckabee, et  al.  1974).   However, acute  ex-
posures result in disproportionately  high levels of  mercury  in  the  skin  of
fishes.  This is  probably due at least in part  to the large  amount of mucous
which  is  secreted during acute  exposures.   In  addition,  in  acute exposures
the mercury is not  given sufficient time to  move  from the absorbing surfaces
to the muscle depot, as would be  the case in most naturally occurring situa-
tions.  When the  acutely exposed fish are  moved to  mercury-free  water,  the
                                     B-9

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skin auickly  loses  mercury (Burrows, et  al.  1974) probably because most  of
the mercury  associated  with the  tissue  is  being  sluffed  off,  metabolically
eliminated, or moved to a more enduring destination in protein  storage.
    The available freshwater bioconcentration factors  (BCF) are  contained  in
Tables  5  and  6.   Table  5  contains BCF  values only  from those  studies  in
which  the  exposure  concentrations were  measured  and the  tissue  residues
reached steady-state.   The  BCF data presented  in  Table 6 do not  meet  these
stringent conditions but  are  used to provide  information  on  BCF  values  for
plants  and to  illustrate  the  very important  influence  of  temperature  on
uptake and bioconcentration factors.
    With brook  trout the BCF  for muscle  is  about the  same  or higher  than
that for whole body (McKim,  et al. 1976).  The  BCF  for muscle of brook  trout
at  273 days  is the  geometric mean  of  three  values,  17,000,  21,000,  and
33,000  at  water concentrations of 0.29,  0.09,  and 0.03  ug/1  respectively.
Those  derived  at concentrations  of 0.93 ug/1  and  above were omitted  because
the fish were  adversely  affected.   The  decrease in BCF as the  concentration
in water increases may be largely an artifact of  the  mathematical  derivation
of the BCF.  If the protein binding sites are saturated at all  three  concen-
trations,  as  would  be  expected  at steady-state  (Cember  and  Curtis,  1978),
then the concentration of mercury  in the tissue would  be same at all  concen-
trations of mercury  in  water.   In this situation  the  BCF  would  be inversely
proportional  to the concentration in water.
    Olson, et  al.  (1975) obtained a BCF of  63,000 with  fathead  minnows  at
25*C.  The contrast  between fathead minnows (Olson,  et  al.  1975)   and  brook
trout  (McKim, et al. 1976)  is  one of considerable  interest and  potential  im-
portance.  The  trout were  fed pelleted feed, and  so  little opportunity  ex-
isted  for food  chain input  to  the trout.   In  contrast, the fathead minnow is
                                     B-10

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a  browser  and had  the  opportunity not only  to  feed on the  introduced  food
but  also on  the  Aufwuchs growing within the  mercury-enriched  environment of
the  exposure  chamber.   The  higher bioconcentration factor of  63,000  for the
fathead minnows may be more  representative  of field  situations in which  fish
are  exposed  to  mercury via  both the  water  and  food  routes  (Phillips  and
Buhler, 1978; Phillips and Gregory,  1979).  Furthermore, the  fathead  minnows
were  exposed  at  a  temperature  that  would  provide uptake  and  tissue  residue
values representative of  the higher range  of  temperatures for fish commonly
consumed by  people.  On the  other hand,  if the concentration  of mercury in
fish  tissue  at steady-state  is solely  dependent  on  the number  of available
binding sites, then such things as temperature should not affect the BCF.
    Boudou et  al.   1979,  also provide  data demonstrating  the  importance  of
both  routes  of  exposure  on  resulting  BCF values  (Table  6).   In addition,
they  studied  the influence  of  temperature on  uptake when both  respiratory
and  feeding  rates  are  accelerated by increased metabolism.  Reinert,  et al.
(1974) reported  84-day BCF  values  of  4,530, 6,620,  and 8,049  in  rainbow
trout  exposed  to virtually  eoual concentrations  of  methylmercury at 5,  10
and  15"C,  respectively,  although  residue  concentrations were  still  increas-
ing  at the end of  the test.  Cember  and Curtis,  (1978)  obtained similar ef-
fects  when bluegills  were exposed for  28.5 days.  BCF  values of  373,  921,
and  2,400  were obtained  at  9, 21,  and 33*C, respectively.   They suggested
that a 010 relationship exists between temperature and BCF.
    The  FOA  action level for  mercury in  fish and  shellfish is  1.0 mg/kg
(Table 5).   According  to the Guidelines  for  freshwater organisms the  only
appropriate BCF available for use with this maximum  permissible  tissue  con-
centration is  the   value  of  23,000  for muscle of  brook  trout.  Thus  the
freshwater Final  Residue Value  is  (1.0 mg/kg)/23,000  =  0.000043 mg/kg  or
0.043  yq/1.    This   value,   however,  probably  should  be  lower.   At  this
                                     B-ll

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concentration  half  of  the  exposed  brook  trout  would have  concentrations
which  would  exceed the FDA  action level.  Also  the BCF  of 63,000 for  the
fathead  minnow is  cause  for concern.   McKim et  al.  (1976) found  that  the
concentration  of  mercury  in muscle was  eoual to  or  greater than  the  whole
body concentration.   Also,  Huckabee,  et  al.  (1974) found  that  all  fishes in
a particular  environment  acouired about  the  same concentrations of mercury
in  both  whole body  and muscle  tissue when they  were chronically  exposed to
low concentrations  of mercury.  Thus  the BCF  for the edible portion of some
consumed species may be eoual to or higher than 63,000.
    Information  on  the  bioconcentration  of   various  mercury  compounds  by
saltwater animals  is  included  in  Table  5 and  by  saltwater plankton in  Table
6.   For mercuric   chloride,  bioconcentration  factors   ranged  from  853  to
10,420 for aloae.   For  the same compound the  BCF values with  animals  ranged
from  3.5 for  the  bloodworm  to  10,000  for  the  oyster.   In  contrast,  BCF
values  of  2,800,   40,000,  and  40,000  were  obtained  with the  oyster  for
mercuric  acetate,  methylmercuric  chloride   and  phenylmercuric   chloride,
respectively.
    To  protect the marketability  of  shellfish for human  consumption,  Final
Residue  Values can  be calculated  based on  the BCF values for the  oyster  and
the FDA  action level of  1.0 mg/kg.   Accordingly,  the  Final Residue  Values
for mercury,  based  on data for mercuric chloride, mercuric  acetate, methyl-
mercuric  chloride,  and ohenylmercuric  chloride  are  0.10,  0.36, 0.025,  and
0.025  ug/1 resoectively.   However,  at these concentrations fifty percent  of
the exposed oysters would probably exceed the  FDA action level.
Miscellaneous
    Most of the significant freshwater and  saltwater  results  in  Table  6 have
already  been  discussed in connection  with data  in Tables 1-5,  but  a few  ad-
                                     B-12

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ditional  items  deserve special mention.   The  data of Birge  and  Just (1973)
illustrate  life  stage   influences  on   sensitivity   with   four   orders  of
magnitude  difference  in  sensitivity between  the embryonic and  adult stages
of the frog, Rana pipiens.
    Another  point  of  interest and possible  considerable importance  is  the
work of Heinz (1976)  in  which  mallard  ducks were fed  food  contaminated  with
methylmercuric  dicyandiamide.   These  feeding studies  extended over  two  gen-
erations  and  demonstrated  reduced  fertility and  inhibited food  conversion
efficiency at a mercury  concentration  that was  estimated  to be eauivalent to
0.1 mq/kg in the natural succulent food  of the  wild duck.   These  results
were not  used  to estimate  a Final  Residue Value based on  food  for  wildlife
because  the  dicyandiamide  compound   may  not  represent  the  toxicity  of
methylmercury alone.
Summary
    Freshwater  acute  data for  divalent  inorganic mercury  span  nine taxonomic
orders from rotifers  to  fish.   These  acute  values  range  from 0.02  to  2,000
ug/1 and  the Final  Acute Value is 0.0017  ug/1.  Acute values  for methylmer-
cury and other mercury compounds are only  available for fishes;  conseauently
an estimate  of  the  range of species  sensitivity for  these compounds  is  not
possible.   However,  methylmercuric chloride  is about ten  times more  toxic to
rainbow trout than mercuric chloride.
    Available chronic data indicate  that  the methylmercury is  the  most
chronically toxic of  the tested mercury  compounds,  with  the chronic  values
for Daphnia  maqna  and brook  trout being  1.00  and 0.52  yg/1,  respectively.
For inorganic  mercury  the  chronic value  obtained  with   Daphnia  magna  was
about  1.6  and the acute-chronic ratio was  3.2.
                                     B-13

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    Plant  values  indicate  that  they  should  be  adequately  protected  by
criteria derived to protect aquatic animals.
    Based on  the FDA action  level  of 1 mg/kg and  a  bioconcentration  factor
of 23,000 the  Freshwater Final   Residue  Value  is  0.043 ug/1.   However,  this
concentration  may not  adequately  protect  the marketability of  freshwater
fish because,  on the average, half of  the  individuals  in  a  species such  as
brook  trout  will exceed  the  limit.   In  addition,  data suggest  that  higher
bioconcentration  factors  may be  obtained  with the  edible  portion of  other
consumed species.
    Data  on  the  acute  toxicity  of  mercuric chloride  are  available for  26
species  of   saltwater animals   including  annelids,  molluscs,  crustaceans,
echinodemis, and  fishes.   Species mean acute values range  from  3.5  to  1,680
ug/1.  Fishes  are more  resistant than average, whereas molluscs  and crusta-
ceans  are  more  sensitive  than  average  to  the acute  toxic effects of  mer-
cury.  Concentrations of mercury  that  affected growth  and photosynthetic ac-
tivity of one  saltwater  diatom  and six  species of  brown algae  range from  10
to 160 gg/1.
    Results  of  a life-cycle  exposure  with the mysid shrimp  show  that  an in-
organic mercury  at a  concentration of  1.6 ug/1 significantly influenced  time
of appearance  of first  brood, time of first spawn,  and productivity and the
resulting acute-chronce ratio was 2.9.
    A bioconcentration factor of  40,000  has  been  obtained for methylmercuric
chloride with  an oyster,  which  results in  a  Final Residue  Value of  0.025
ug/1  when used with  the  FDA  action  level.  At  this concentration, half  of
the oysters  would exceed the action level.
    For  both  freshwater and  saltwater  species many acute  tests have  been
conducted on  inorganic  mercuric  salts,  but  few  acute  tests  have been  con-
ducted on  other  compounds  of mercury.  Although  methylmercury  is  probably
                                     B-14

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more acutely toxic  than  inorganic  mercuric salts, few acute  or  chronic  tox-
icity tests  have  been conducted on  methylmercury and it  apparently is  re-
moved from  water  rapidly.   On the  other hand,  inorganic mercury  is  readily
converted  to methylmercury  which   can   become  a  major  residue  problem  in
aouatic organisms.
                                   CRITERIA
    For  total   recoverable  mercury  the  criterion   to  protect  freshwater
aouatic  life  as derived using  the Guidelines is  0.00057  ug/1  as a  24-hour
average, and the concentration should not exceed  0.0017 ug/1  at  any time.
    For total recoverable mercury the criterion to protect saltwater  aauatic
life as derived using the Guidelines is 0.025 ug/1 as  a  24-hour  average,  and
the concentration should not exceed 3.7  ug/1  at  any time.
                                     B-15

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                                     Table t.  Acute values for Mercury
Species
                           Method*
Chemical
                                                                        Species Mean
                                                          LC50/EC50**    Acute Value**
                                                                                         Reference
Rotifer,
Ph 1 1 od 1 na acut 1 cor n 1 s
Rotifer,
Phllodlna acut 1 corn Is
Brlstleworm,
Nals sp.
Cladoceran,
Oaphnla magna
Scud,
Gaimarus sp.
Crayfish (males only,
mixed ages),
Faxonotla cylpeatus
Crayfish,
Orconectes llmosas
Stonef ly,
Acroneurla lycorlus
Mayfly,
Ephemeral la subvarla
CaddlsNy,
Hydropsycho better 1
Coho salmon (juvenile),
Oncorhynchus klsutsch
Rainbow trout (juvanl le)
Sa Imo qalrdner 1
Rainbow trout (juvenile).
s.
s,
s,
R.
s,
R,
s,
s,
s,
s,
s,
FT.
FT,
U
U
M
U
M
M
M
U
U
U
M
U
U
Salmo gairdnerl
FRESHWATER SPECIES
Inorganic
Mercuric
ch lorlde
Mercuric
ch lorlde
Mercuric
nitrate
Mercuric
ch lorlde
Mercuric
nitrate
Mercuric
chloride
Mercuric
chloride
Mercuric
ch lorlde
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
ch lorlde
Mercuric
chloride
Mercuric Salts
518
1,185
1,000
5
10
0.02
50
2,000
2,000
2,000
240
400
280
-
784
1,000
5
10
0.02
50
2,000
2,000
2,000
240
-
-
Bulkema, et al. 1974
Bulkema, et al. 1974
Rehwoldt, et al. 1973
Bleslnger &
Chrlstensen, 1972
Rehwoldt, et al. 1973
Halt 4 Flngerman,
1977
boutet &
Chalsemartln, 1973
Warnick & Bel 1, 1969
Warnlck & Bel 1, 1969
Warnick & Bel 1, 1969
Lor/, et al. 1978
MacLeod 4 Pessah,
1973
Macleod 4 Pessah,
1973
                                                    B-16

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Table 1.   (Continued)
Species
Method*
                                        Chemical
             Species Mean
LC50/EC50"    Acute Value"
 (ug/l)           (ug/l)
                                                              Reference
Rainbow trout (juvenile).
Sal mo gairdnerl
Rainbow trout (juvenile).
Sal mo gairdnerl
Rainbow trout (larva).
Sal mo gairdnerl
Rainbow trout (juvenile).
Sal mo gairdnerl
Rainbow trout (juvenile),
Sal mo gairdneri
Brook trout (juvenile),
Sa 1 ve 1 1 nus font I na 1 is
Drook trout (yearling),
Sa 1 ve 1 1 nus font 1 na 1 1 s
Rainbow trout (juvenile),
Salmo gairdnerl
Goldfish,
Carasslus auratus
Fathead minnow
Pimep hales promelas
Fathead minnow
Plmephales promelas
Channel catfish (juvenile),
Ictalurus punctalus
FT, U
R, U
R, U
R. U
R, U
FT, M
FT, M
R, U
S, U
R, M
R, M
S. U
Mercuric
ch lorlde
Mercuric
ch lorlde
Methy Imercurlc Compounds
Methy Imercurlc
chloride
Methy Imercurlc
ch lorlde
Methy Imercurlc
ch lorlde
Methy 1 mercuric
ch loride
Methy Imercurlc
ch loride
Other Mercury Compounds
Pheny (mercuric
acetate
Pheny [mercuric
lactate
Mercuric
acetate
Mercuric
th iocyanate
Ethy Imercurlc
phosphate
220
155
24
42
25
84
65
5
82
190
150
48***
Mac 1 eod
1973
249 Matida,
Wobeser
Wobeser
29 Matida,
McK 1 m,
74 McKIm,
5 Matida,
82 Ellis,
190 Curtis,
150 Curtis,
48 Clemens
4 Pessah,
et al. 1971
, 1973
, 1973
et al. 1971
et al. 1976
et al. 1976
et al. 1971
1947
et al. 1979
et al. 1979
& Sneed, 19!
                                                   B-17

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Table I.   (Continued)
Species
Method*
Chemical
             Species Mean
LC50/EC50"    Acute Value"
 (yg/l)           (yg/l)
Reference
Channel catfish (juvenile), S, U
Ictalurus punctatus
Channel catfish (juvenile), S, U
Ictalurus punctatus
Channel catfish (juvenile), S, U
Ictalurus punctatus
Channel catfish (juvenile), S, U
Ictalurus punctatus
Polychaete (larva), S, U
Cap 1 te 1 1 a cap 1 tata
Polychaete (adult), S, U
Neanthes arenaceodentata
Polychaote (Juvenile), S, U
Neanthos arenaceodentata
Sandworm (adult), S, U
Nereis vlrens
Bay scallop (juvenile), S, U
Argopecten Irradlans
Oyster, S, U
Crassostrea virgin lea
Oyster, S, U
Crassostrea virgin lea
Oyster, S, M
Crassostrea glgas
Ethy (mercuric 51***
p-toluene
su 1 fonanl 1 Ide
Pheny (mercuric 35***
acetate
Pheny (mercuric 1,158****
acetate
Pheny (mercuric <176***"
acetate
SALTWATER SPECIES
1 nor panic Mercuric Salts
Mercuric 14
chloride
Mercuric 96
ch lorldo
Mercuric 100
ch lor ide
Mercuric 70
ch lor ide
Mercuric 89
ch lorlde
Mercuric 5.6
ch lor ide
Mercuric 10.2
ch lorlde
Mercuric 5.7
ch lor ide
51 Clemens & Sneed, 1959
Clemens & Sneed, 1959
201 Clemens & Sneed, 1958
Clemens & Sneed, 1958
14 Reish, et al. 1976
Relsh, et al. 1976
98 Reish, et al. 1976
70 Elsler & Hennekey,
1977
89 Nelson, et al. 1976
Calabrese, et al.
1977
7.6 Maclnnes & Calabrese,
1978
Glicksteln, 1978
                                                    B-18

-------
Table 1.   (Continued)
Species
Oyster,
Crassostrea glgas
Soft-she 1 1 clam (adult).
My a arenarla
Hard-she! 1 clam,
Mercenarla mercenaria
Clam (adult).
Rang la cuneata
Clam (adult).
Rang la cuneata
Copepod (adult),
Acartia tonsa
Copopod (adult),
Acartia tonsa
Copepod (adult),
Acartia tonsa
Copepod (aduH ),
Acartia tonsa
Copepod,
Acartia clausl
Copepod,
Eurytemora affinis
Copepod,
Nltocra splnlpes
Copepod,
Pseudod laptomus coronatus
Method*
S. M
S, U
S. U
S, M
S. M
S, U
S, U
S, U
S, U
S, U
S, U
S, U
S, U
Chemical
Mercur 1 c
nitrate
Mercuric
ch lorlde
Mercuric
ch lorlde
Mercuric
ch lorlde
Mercur 1 c
ch loride
Mercuric
ch lorlde
Mercuric
chloride
Mercuric
ch lorlde
Mercuric
ch lorlde
Mercuric
ch loride
Mercuric
ch loride
Mercuric
ch loride
Mercur I c
ch lorlde
                                                                      Species Mean
                                                         LC50/EC50**    Acute Value**
                                                                                        Reference
5.5
400
4.8
58
122
10
14
15
20
10
158
230
79
5.6 Gllcksteln, 1978
400 Elsler A
1977
4.8 Calabrese
1977
Hennekey,
, et al.
Dl 1 Ion, 1977
84 Dillon, 1977
Sosnowski
1978
Sosnowsk i
1978
Sosnowski
1978
14 U.S. EPA,
10 U.S. EPA,
156 U.S. EPA,
230 Bengtsson
79 U.S. EPA,
& Gentl le.
& Gentile,
& Genti le.
1980
1980
1980
, 1978
1980
                                                 B-19

-------
Table 1.  (Continued)
                            Method*       Chemical

Copepod,                     S, U         Mercuric
Tlgriopus Japoriicus                       chloride

Mysld shrimp,               FT, M         Mercuric
Mysldopsls bah I a                          chloride
Crab (larva),                S, U         Mercuric
Carcinus maenas                           chloride

Crab (larva),                S, M         Mercuric
Cancer maglster                           chloride

Hermit crab (adult),         S, U         Mercuric
Paqurus longlcarpus                       chloride

White shrimp (adult),        S, U         Mercuric
Penaeus setlferus                         chloride

Starfish (adult),            S, U         Mercuric
Aster I as forbesl                          chloride

Haddock (larva),             S, U         Mercuric
Melanograrmms aerjleffnus                  chloride

Mummlchog (adult),           S, U         Mercuric
Fundulus heteroclltus                     chloride

Mummichog (adult),           S, U         Mercuric
Fundulus heteroclltus                     chloride

Fourspine stickleback        S, U         Mercuric
(adult),                                  chloride
Apeltos quadracus apeltes

Atlantic silverside          S, U         Mercuric
(I arva),                                  chlorlde
Men Id la menldla

Atlantic sllvorside          S, U         Mercuric
(larva),                                  chloride
Menldia nienidia
                                                                          Species Mean
                                                            LC50/EC50"    Acute Value""
(ug/D
223
3.5
14
6.6
50
17
60
98
800
2,000
315
(ug/l)
223
3.5
14
6.6
50
17
60
98
-
1,260
315
Reference
U.S. EPA, I960
U.S. EPA, 1980
Connor, 1972
Gllcksteln, 1978
Eis ler i Hennekey,
1977
Green, et al. 1976
Els ler & Hennekey,
1977
U.S. EPA, 1980
Els ler & Hennekey,
1977
Klaunig, et al. 19
U.S. EPA, 1980
144
125
U.S. EPA, 1980
                            U.S.  EPA,  1980
                                                    B-20

-------
Table t.   (Continued)
                                                                      Species Mean
                                                        LC50/EC50"   Acute Value"
Species Method*
Atlantic sllverslde S, U
( juvenl le),
Men id la men Id la
Winter flounder (larva), S, U
Pseudop 1 euronectes
amerlcanus
Winter flounder (larva), S, U
Pseudop leuronectos
amerlcanus
Winter flounder (larva), S, U
Pseudop 1 euronectes
amerlcanus
Winter flounder (larva), S, U
Pseudop 1 euronectes
amer icanus
Winter flounder (larva), S, U
Pseudop 1 euronectes
amer icanus
Amphipod (adult), S, U
Ganvnarus duebenl
Grass shrimp (adult), S, M
Pa 1 aemonetes puglo
Grass shrimp (adult), S, M
Pa 1 aemonetes purjlo

Chemical
Mercuric
ch lor 1 do
Mercuric
ch lorlde
Mercuric
ch loride
Mercuric
chloride
Mercuric
ch loride
Mercuric
ch loride
Methy Imercurlc
Methy Imercurlc
chloride
Other Mercury
Mercuric
acetate
Mercuric
th locyanate
(ug/l)
86
1,820
1,560
1,610
1,320
1,960
Compounds
150
Compounds
60
90
(|ig/l) Reference
116 U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
1,680 U.S. EPA, I960
150 Lockwood & Inman,
1975
60 Curtis, et al. 1979
90 Curtis, et al. 1979
                                                 B-21

-------
Table 1.  (Continued)
*    S - static,  R = renewal,  FT  =  flow-through, U » unmeasured,  M - measured.



**   Results are expressed as  mercury, not as the compound.



••»  19-20'C



••*« 10'C



»»»»»I6.5 & 24*C
                                      B-22

-------
                                Table 2.  Chronic values for mercury


                            Test-          Chemical
Limits**   Chronic Value**
              (yg/D
Reference
Cladoceran.
Daphnla^ magna
Cladoceran,
Daphnl
-------
Table 2.   (Continued)
                                        Acute-Chronic Ratio
Species
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Mysld shrimp,
Mysldopsls bah la

Brook trout
Salvellnus font! nails

Chemical
1 norqan 1 c I
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Methyl mercuric
Methy (mercuric
chloride
Acute
Value

-------
Table 3.   Speclos mean acute values and acute-chronic ratios for  mercury
Rank*

Species
FRESHWATER
Species Mean
Acute Value
(ug/l)
SPECIES
Species Mean
Acute-Chronic
Ratio

Inorganic Mercuric Salts
11
!0
9
8
7
6
5
4
3
2
1
Caddisf ly,
Hydropsyche batten i
Stonef !y,
Acroneurla lycorlas
Mayfly,
Ephemeral la subvarla
Brlstleworm,
Nais sp.
Rotifer,
Philodlna acutlcornls
Rainbow trout,
Sal mo gairdneri
Coho saimon,
Oncorhynchus klsutch
Crayf Ish,
Orconectes ! 1 tnosus
Scud,
Gammarus sp.
Cladoceran,
Daphnla magna
Crayfish,
Faxone 1 1 a c 1 ypeata
2,000
2,000
2,000
1,000
784
249
240
50
!0
5
0.02
3.2
                                   B-25

-------
Table 3.  (Continued)
Rank*

Species
SALTWATER
Species Mean
Acute Value
<|iq/l)
SPECIES
Species Mean
Acute-Chronic
Ratio

Inorganic Mercuric Salts
26
25
24
23
22
21
20
19
18
17
16
15
14
Winter flounder, 1,680
Pseudopleuronectes amorlcanus
Mummichog,
Fundulus heteroclltus
Soft-shell clam,
Mya arenarla
Foursplne stickleback,
Apeltes quadracus
Copepod,
Nltocra splnlpes
Copepod,
Tlqrlopus japonlcus
Copepod,
Eurytemora afflnls
Atlantic si Iverslde,
Men Id la men Id la
Haddock,
Melanogrammus aeqlefinus
Polychaete,
Neanthes arenaceodentata
Bay seal lop,
Argopecten irradlans
Clam,
Rang I a cuneata
Copepod,
Pseudodi apt onus corona t us
1,260
400
315
230
223
158
116
98
98
89
84
79
-
                             3-26

-------
Table 3.  (Continued)
Rank*
13
12
It
10
9
8
7
6
5
4
3
2
1
Species
Sandworm,
Nereis vlrens
Starfish,
Aster las tor best
Hermit crab,
Papyrus longlcarpus
White shrimp,
Penaeus sotlferus
Copepod,
Acartla tonsa
Polychaete,
Capitel la capltata
Crab,
Carclnus maenas
Copepod ,
Acartla clausl
Oyster,
Crassostrea virgin lea
Crab,
Cancer maglster
Oyster,
Crassostrea glgas
Hard-shell clam,
Mercenaria mercenaria
Mysld shrimp,
Mysldopsls bah la
Species Mean
Acute Value
(liq/l)
70
60
50
17
14
14
14
to
7.6
6.6
5.6
4.8
3.5
Species Mean
Acute-Chronic
Ratio
2.9
                               B-27

-------
Table 3.  (Continued)
* Ranked from least sensitive to most  sensitive  based on species mean
  acute va I tie.

  |norqanI c mercurI c SB Its

        Freshwater Final  Acute Value = 0.0017  vg/l

        Saltwater Final Acute Value -  3.71  M9/I

             Final Acute-Chronic Ratio a 3.0

        Freshwater Final  Chronic Value = (0.0017 ng^D/3.0 = 0.00057 ug/l

        Saltwater Final Chronic Value  = (3.71  ug/D/3.0 =  1.2 ug/l
                        B-28

-------
                                Table 4.  Plant values for Mercury
Species
Chenlcal
Effect
FRESHWATER SPECIES
Alga,
Chi orel la vulgarls
Water milfoil,
Hyrlophyl lum splcatum
Seaweed,
Ascophy 1 1 um nodosum
0 i atom,
Dltylum brightwellll
Seaweed,
Fucus serratus
Seaweed,
Fucus spiral Is
Seaweed,
Fucus vesiculosus
Giant kelp,
Macrocystls pyrlfera
Seaweed,
Pel vet la canaliculate

1 norgan 1 c
Mercuric Salts
Mercuric 32-day EC50,
chloride eel 1 division
inhibition
Mercuric 32-day EC50,
chloride root growth
Inhibition
SALTWATER SPECIES
1 norgan i c
Mercuric
ch lorlde
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric Salts
10-day EC50,
growth
10-day EC50,
growth
10-day EC50,
growth
10-day EC50,
growth
10-day EC50,
growth
10-day EC50,
growth
10-day EC50,
growth
Result*
(H9/D
1,030
1,200
100
10
160
80
45
50
130
Reference
Rosko & Rachlin,
1977
Stanley, 1974
Stromgren, 1980
Canter ford &
Canterford, 1980
Stromgren, 1980
Stromgren, 1980
Stromgren, 1980
Clendennlng & North,
1959
Stromgren, 1980
* Results  are expressed as mercury,  not as the compound
                                                  B-29

-------
Table 5.  Residues for Mercury
Species
Brook trout,
Salvellnus font! nails
Brook trout,
Salvelinus font! nails
Brook trout,
Salvel Inus fontlnal Is
Fathead minnow,
Plmephales prone las
T 1 ssue
muscle
whole fish
nuscle or
whole fish
whole fish
Chemical
FRESHWATER
Methy 1 mercuric
Methy (mercuric
ch lorlde
Methy (mercuric
ch lorlde
Methy (mercuric
ch lor 1 do
methy (mercuric
ch lorlde
SALTWATER
Bloconcentratlon Duration
Factor (days) Reference
SPECIES
Compounds
23,000 273 McKIm, et al. 1976
15,000 273 McKIm, et al. 1976
12,000 756 McKIm, et al. 1976
63,000 336 Olson, et al. 1975
SPECIES
Inorganic Mercuric Salts
Blood worm,
Glycera dl branch lata
Lobster (adult),
Homarus amerlcanus
Oysfor (adult),
Crassostrea vlrglnica
Oyster (adult),
Crassostrea vlrglnlca
Oyster (adult),
Crassostrea vlrglnlca
Oyster (adult),
Crassostrea vlrglnlca

Whole animal
Tal 1 muscle
Soft parts
Soft parts
Soft parts
Soft parts
Mercuric chloride
Mercuric chloride
Mercuric chloride
Methy (mercuric
Methy (mercuric
chloride
Other Mercury
Phony (mercuric
ch 1 or 1 de
Mercuric acetate
3.5 3 Medelros, et al. 1980
129 30 Thurberg, et al. 1977
10,000 74 Kopfler, 1974
compounds
40,000 74 Kopf ler, 1974
Compounds
40,000 74 Kopf ler, 1974
2,600 45 Cunningham & Trlpp,
1973
               B-30

-------
Table 5.  (Continued)
Maximum Permissible Tissue Concentration
Species
Man
Mink,
Mu stela vlson
Brook trout,
Salvellnus fontlnalls

Concentration
Action Level or Effect (mg/kg)
edible fish or shellfish 1.0
hlstologlcal evidence t.l
of Injury
death (700 days) 5-7
References
U.S. FDA Guideline
7408.09, 1978
Wobeser, 1973
McKIm, et al. 1976
Methylmercury;
     Freshwater Final  Residue  Value =  (1.0 mg/kg)/23,000 = 0.000043 mg/l  - 0.043 wg/l
     Saltwater  Final Residue Value =  (1.0 mg/kg)/40,000 = 0.000025 mg/l = 0.025 ug/l
                                                     3-31

-------
       Table 6.  Other data for
                                  rcury
Chen leal
Duration
                                                 Result*
Effect
FRESHWATER SPECIES
RESIDUE DATA
Inorganic Mercuric Salts
Alga,
Synedra ulna
Alga,
Scenedesmus obllquus
Alga,
Mlcrocystls Incerta
Rainbow trout (juvenile),
Sdl mo galrdner 1
Rainbow trout (juvenile).
Sal mo qalrdneri
Rainbow trout (juvenile),
Su (mo gairdner 1
Bluecjill (juvenile),
Lepomis macrochlrus
Bluegill (juvenile),
Lepomis macrochlrus
Bluoglll (juvenile),
Lepomis macrochlrus

Mercuric
chloride
Methy (mercuric
chloride
Methy (mercuric
chloride
Methy (mercuric
chloride
Mot hy (mercuric
chloride
Methy (mercuric
chloride
Methy 1 mercur 1 c
chloride
Methy (mercuric
chloride
Methy (mercuric
chloride
0.29 days
Methy 1 mercur Ic
14 days
14 days
84 days***
84 days***
84 days***
28.5 days
28.5 days
28.5 days
BCF=29,000
Compounds
BCF=761-2,100 (Max-
imum by third day)
BCF«461-990 (Maxi-
mum by third day)
DCF=4,530
(whole fish)
BCF=6,620
(whole fish)
BCF=8,049
(whole fish)
BCF=373
(whole fish)
BCF=921
(whole fish)
BCF=2,400
(whole fish)
0.25
60**
60**
0.263,
at 5 C
0.258
at 10 C
0.234
at 15 C
0.2****
0.5
at 9 C
0.5****
5.0
at 21 C
0.2****
5.0.
at 33 C
Reference
                                                            Fujlta & Hashizume,
                                                            1972
                                                            Havlik, et al. 1979
                                                            Havl ik, et al. 1979
                                                            Re Inert, et al. 1974
                                                            Re Inert, et al. 1974
                                                            Re inert, et al. 1974
                                                         -  Comber, et al. 1978
                                                         -  Cember, et a I. 1978
                                                         -  Comber, et a I. 1978
                      B-32

-------
Table 6.  (Continued)
SpecIes
MosquitofIsh,
Gambusia afffnis
Mosquito fish,
Gambusia afffnis
Mosqul tofish,
Gambusia affinis
MosqultofIsh,
Gambusia affIn Is
Alga,
Scenedosmus obiIquus

Alga,
Mlcrocystls incerta
Chemical
Duration
Methyl mercuric   30 days
ch loride
MethyImercuric   30 days
chloride
Mothy (mercuric   30 days
chlor I do
MethyImercuric   30 days
chloride
     Effect

BCF=2,500
(whole fish)
             BCF=4,300
             (whole fish)
             BCF=3,000
             (whole fish)
             BCF=27,000
             (whole fish)
Result*
(ug/l)     Reference
                                              Other Mercury Compounds
PhenyImercuric   14 days
chloride

PhenyImercuric   14 days
chloride
             BCF=553-1,300 (Maxi-
             mum by third day)

             BCF=252-400 (Maxi-
             mum by th Ird day)
0.8 ug/l   Boudou, et al. 1979
water, at
10"C

0.8 ug/l   Boudou, et al. 1979
water, at
IB'C

0.8 ug/l   Boudou, et al. 1979
water,
164 mgAg
food, 10'C

0.8 ug/l   Boudou, et al. 1979
water,
238 mgAg
food, 26*C
                        60      Havllk, et al. 1979
                        60      Havl Ik, et al. 1979
                                                 NON-RESIDUE DATA
Alga,
Spring assemblages
(predominately diatoms)
Alga,
Ankistrodosmus brauni I
Alga,
Euglena gracl 1 is
Sludge worm,
Tubifex tubifex
Mercuric
chloride
Mercuric
chloride
Mercuric
ch loride
Mercuric
chloride
Inorganic Mercuric Salts
2 hrs Photosynthetlc
activity EC50
336 hrs Llpid biosynthesis
Inhibition EC50
240-336 hrs Llpid biosynthesis
inhibition 
-------
Table 6.   (Continued)
Sludge worm,
Tublfex tublfex

Snail (embryo),
Amnlcola sp.

Snail (adult)
AmnIcoIa sp.

Cladoceran,
Daphnla maqna

Crayfish (mixed ages,
males only),
Faxonella clypeatus

Crayfish (mixed ages,
males only),
Procambarus cIark I

Crayfish (0.2 g),
Procambarus cI ark I

Crayfish (1.2 g),
Procambarus clarkj^

Crayfish (adult),
Orconectes I Imostis

Crayfish (juveni le),
Orconectes llmosus

Crayfish (juvenile),
Orconectes llmosus

Midge,
Chironomus sp.
Chenlea I

Mercuric
chlorlde

Mercuric
nitrate

Mercuric
nitrate

Mercuric
nitrate

Mercuric
nitrate
Mercuric
nitrate
Mercuric
nitrate

Mercuric
nitrate

Mercuric
chloride

Mercuric
chloride

Mercuric
chloride

Mercuric
nitrate
Duration

 48 hrs


 96 hrs
                                                                   Effect
LC50
LC50
 96 hrs      LC50


 Life cycle  LC50


 72 hrs      LC50
 72 hrs
 24 hrs
672 hrs
 96 hrs
LC50
LC50
             LC50
LC60
 30 days     LC50 (unfed)
 30 days     LC50 (fed)
Result11
(ug/l)

  100
                                  2,100
                        80
Reference

Br kovIc-PopovIc &
PopovIc, I977b

Rehwoldt, et at. 1973
           Rehwoldt, et al. 1973
 96 hrs
             I.C50
                         4.8    Bleslnger &
                                Chrlstensen, 1972

                         0.2    Helt A Flngerman,
                                1977
                                      0.2    Helt & Flngerman,
                                             1977
   10      Helt & Flngerman,
           1977

   10      Holf & Flngerman,
           1977

  740      Doyle, et al.  1976


    2      Boutet &
           Chalsemartin,  1973

   <2      Boutet &
           Chalsemartin,  1973

   20      Rehwoldt, et  al.  1973
                                                    B-34

-------
Table 6.  (Continued)
Freshwater community
(preliminary producers,
herbivores and
carnivorous midges)
Pink salmon (embryo),
Oncorhynchus gorbuscha
fMnk salmon (pro-eyed embryo),
Oncorhynchus gorbuscha
Pink salmon (larva),
Oncorhynchus gorbuscha

Sockeye salmon (embryo),
Oncorhynchus norka
Sockeye salmon
(pre-eyed embryo),
Oncorhynchus nerka

SocKeye salmon (larva),
Oncorhynchus nerka

Sockoye salmon (juvenile),
Oncorhynchus nerka

Rainbow trout (juvenile),
Sal no yalrdnorl

Rainbow trout (juvonile),
Sal mo galrdnerj^

Rainbow trout (juvenile),
      ([ulrdnerl
Chemical

Mercuric
ch loride
Mercuric
sul fate
Mercuric
su I fate
Mercuric
suI fate

Mercuric
sul fate
Mercuric
suI fate
Mercuric
sul fate

Mercuric
sul fate

Mercuric
chloride

Mercuric
chloride

Mercuric
chloride
   Duration          Effect

    I yr     Reduced algal numbers,
             standing stock, and
             diversity, numbers of
             species, evenness of
             distribution; no
             evlcence of signifi-
             cant effects on midges

2 days 

-------
Table 6.  (Continued)
Species
Brook trout,
Salvellnus font! nails
Carp (embryo),
Cyprfnus carplo
White sucker (adult),
Catostomus common son 1
White sucker (adult),
Catostomus commersonl
Threesplne stickleback,
Gasterosteus aculeatus
Threespine stickleback,
Gasterosteus aculeatus
Mosqultof Ish,
Gambusia off In is
Leopard frog (cleavage embryo),
Rana pip lens
Leopard frog (blastula embryo),
Rana pfpiens
Leopard frog (gastrula embryo),
Rana pi pi ens
Leopard frog (neurula embryo),
Rana piplons
Leopard frog (tall bud embryo),
Rana plpions
Leopard frog (larva),
Hana pip lens
Leopard frog (adult),
Rana piplens
Chemical
Mercuric
ch lorlde
Mercuric
ch lorlde
Mercuric
ch lorlde
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
ch lorlde
Mercuric
chloride
Mercuric
ch lorlde
Mercuric
ch lorlde
Mercuric
chloride
Mercuric
ch lorlde
Mercuric
chloride
Mercuric
ch lorlde
Duration
48 hrs
60-72 hrs
6 in in
16 mln
10 days
110 mln
>10 days
96 hrs
96 hrs
96 hrs
96 hrs
96 hrs
5 days
96 hrs
Result*
Effect (uq/l)
Increased cough >3
frequency
Reduced hatching ^L3-000
success
Blood enzyme (LOH) 8,000
Inhibition 20%
Blood enzyme (GOT) 10,000
Inhibition 20%
LCO >8
Death 4,020
LC50 500
LC50 >1.0-<10
LC50 >1.0-<10
LC50 >1.0— OO
LC50 >0. 1— OO
LC50 >0. !-7,500-
-------
TabI* 6.  (Continued)
Species
Alga,
AnkIstrodesrous braun11

Alga,
Coelastrum mIcroporum

Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Salmo qalrdnerl
Rainbow trout,
Salmo galrdnerl

Brook trout (embryo),
Salvellnus fontlnalls

Brook trout (a lev In),
Salvolinus fontinalis
Brook Irout (alevlns),
SalvelInus fonlInalIs

Brook trout (juvenile),
Salvolinus fontlnalls

Brook trout,
Salvo IInus fontinalIs

Mosquilotish,
Gambusla aft in Is
Chealcal
Duration
Methyl mercuric
Methy (mercuric
chloride
Methy (mercuric
chloride
Methy (mercuric
chloride
Methy (mercuric
ch lorlde
Methy (mercuric
chloride
Methy Imercurlc
chloride
Methy (mercuric
ch lorlde
Methy Imercurlc
chloride
Methy Imercurlc
chloride
Methy Imercurlc
ch lor Ida
Methyl mercuric
chloride
Methy Imercurlc
ch lorlde
336 hrs
Effect
Compounds
Lip Id biosynthesis,
>EC50
Not stated Growth Inhibition,
EC50
>64 days
120 days
269 days
30 mln
16-17 days
Incubation
period
+ 21 days
30 days
14 days
8 days
<24 hrs
Growth inhibition
Loss of appetite (as
Mg of Hg In total
ration consumed,
1/3 as CHjHgCI)
Loss of nervous
control (as Mg/l
of Hg In total
ration of consumed,
1/3 as CHjHgCI)
Reduced viability
of sperm - EC 50
Decreased enzyme
(GOT) activity
Reduced growth
Increased enzyme
(GOT) activity
Increased blood
plasma ch lorlde
Increased cough
frequency
LC50
Result*
(uq/l)
1,598
>2.4-<4.8
2.0.04
860
1,600
1,000
0.88
0.79
0.79
2.93
^3
500
Reference

Mat son, et al

. 1972
Holderness, et al.
1975
Mat Ida, et al
Matida, et al
Mat Ida. et al
. 1971
. 1971
. 1971
Mclntyre, 1973
Christensen,
Christen sen.
Christensen,
Christensen,
1977
Drummond, et
1974
Boudou, et al
1975
1975
1975
et al.
al.
. 1979
                                                        8-37

-------
Table 6.   (Continued)
Species
                                Chemical
Duration
Effect
Result*
(ug/l)     Reference
Newt ,
Trlturus viridoscens
Newt,
TrMurus vlrldesccns
NowT.
Triturus virldescens
Leopard frog (tadpole),
Rana pip fans
Leopard frog,
Rana plplons
Leopard frog (blastula embryo),
Kana pipiens
Leopard frog (gastrula embryo),
Rana pipiens
Leopard frog (nourdl plate
tsnbryo),
Rana oijiiens
Leopard frog (blastula embryo),
Rana pipiens
Leopard frog (gastrula embryo),
Rana pipiens
Leopard frog (neural plate
eml>ryo),
Raiu pipiens
Mink (adult),
Mustcla vison
Mink (adult),
Mustola vison
Methylmer curie
ch lorlde
Mothy Imercurlc
ch lorlde
Methy Imercurlc
choride
Mothy Imercurlc
ch lorlde
Methy Imercurlc
ch lorlde
Methy (mercuric
ch lorlde
Methy Imercurlc
ch (orlde
Methy 1 mercuric
chloride
Mothy Imorcur ic
ch loride
MeThy Imercurlc
ch loride
Methy Imercuric
ch loride
Mothy Imercuric
ch lor Ido
Mfthy Imercurlc
chloride
>2 days
17 days
8 days
48 hrs

-------
Table 6.  (Continued)
Spec Ies
Alga,
Florida Lake assemblage

Alga,
Florida Lake assemblage
    Chemical        Duration

                 Other Mercury
                Effect

         Compounds
                     Result1
                     (ug/l)
Alga,
CIadophoraceae

Alga,
Ulothr ichaceae

Alga,
Florida Lake assemblage

Alga,
Florida Lake assemblage

Louisiana red crayfish
(juvenile),
Procambarus cIark I

Chinook salmon ( f Ingerl ing),
Oncorhynchus tshawytscha

Chinook salmon,
Oncorhynchus tshawsytscha

Sockeye salmon (juvenile),
Oncorhynchus nerka

Sockeye salmon (juvenile),
Oncorhynchus nerka

Sockeye salmon (juvenile),
Oncorhynchus nerka
    Methy Imercur ic    24 hrs
    dicyandI amide

N-MethyImercurIc-     24 hrs
1,2,3,6-tetrahydro-
3,6-methano-3,4,5,6,
7,7,-hexachloro-
phthalI mi do

    Ethy(mercuric      1 hr
    phosphate

    EthyImercuric      1 hr
    phosphate

    PhenyImercuric    24 hrs
    acetate
    Diphenyl
    mercury
24 hrs
    Methy Imercuric   110 hrs
    dicyandlmide
    EthyImercuric
    phosphate

    EthyImercuric
    phosphate

    PyridyImercuric
    acetate

    PyridyI mercuric
    acetate

    PyridyImercuric
    acetate
                       1 hr
           Growth of population    _<0.8
           inhibition

           Growth of population    _<0.3
           Inhibition
           Nuisance control
           Nuisance control
Growth of population    _<0.6
inhibition

Growth of population   j<28.3
inhibition
           LC50
           Distress
 20 hrs    Safe for disease
           control

  1.5 hrs  LC50
  1.5 hrs  Safe for disease
           control

  1 hr     Safe for disease
           control
                        53.6
                                                         77
                        39
                    10,600-
                    15,800

                      <954
                    <4,752
Reference
                                Harrlss, et al. 1970
                                Harrlss,  et al. 1970
                        38.6    Burrows & Combs, 1958
                        38.6    Burrows & Combs, 1958
                                           Harriss, et al.  1970
Harrlss, et al. 1970
Hendrlck & Everett,
1965
                                Burrows & Combs, 1958
                                Burrows & Combs, 1958
Burrows & Palmer,
1949

Rucker, 1948
Rucker & Whlpple,
195)
                                                       3-39

-------
Table 6.  (Continued)
Species
Rainbow trout (juvenile),
Salmo galrdnerl

Rainbow trout (juvenile),
Salmo galrdnerl

Rainbow trout (juvenile),
Salmo galrdnerl

Rainbow trout (juvenile),
Salno galrdnerl

Rainbow trout (a lev In),
Salmo galrdnerl

Rainbow trout (juvenile),
Salmo galrdnerl

Rainbow trout,
Salmo galrdnerl
                Duration
Rainbow trout (juvenile)
Salmo galrdnerl

Rainbow trout (juvenlle)
Salmo galrdnerl
Rainbow trout (juvenile),
Salmo galrdnerl

Rainbow trout (juvenile),
Salmo galrdnerl

Rainbow trout (juvenile),
Salmo galrdnerl

Rainbow trout (juvenile),
Salmo galrdnerl
Chemical
acetate
acetate

PyrIdylmercuric    1 hr
acetate

Pyr Idyl mercuric    1 hr
acetate

PyrIdy(mercuric    1 hr
acetate

PyrIdy(mercuric    1 hr
acetate

Pheny I mercuric   _>64 days
acetate

Ethy(mercuric     48 hrs
phosphate

EthyImereuric
p-toluene
su I fonan111 da
Pheny (mercuric    24 hrs
acetate

Pheny Imercur Ic    48 hrs
acetate
     Effect
Merthlolate
Mercurous
nltrate
                  48 hrs
                  96 hrs
 Result*
 (tig/1)      Reference
1 hr
1 hr
LCI 00
LCO
1,030
967
Allison, 1957
Allison, 1957
                             LC50
                             LC16
                     4,750      Rodgers, et al.  1951
                     2,380      Rodgers, et al. 1951
                             Safe for disease    _<4,750
                             control
                                Rucker & Whlpple,
                                1951
                             LC60
                             Growth
                             LC50
                       517      Allison, 1957
                     0.11-1.1    Mat I da, et al.  1971
                        43      Mat I da, et al.  1971
                             Retarded learning   5 ug/g In   Hart man, 1978
                                                 feed da 11y
                                                 or 10 ug/g
                                                 feed every
                                                 fifth day
                                                              LC50
                             LC50
LC50
                             LC50
                        25      MacLeod & Pessah,
                                1973

                     1,780      Wlllford. 1967
10,500      Hi I I ford,  1967
                                                     33
                                Hale, 1977
                                                      B-40

-------
Table 6.  (Continued)
Species
Brown trout (juvenile),
Salmo trutta

Drown trout (juvenile),
Salmo trutta

Brown trout (juvenile),
Salmo trutta

Brook trout (juvenile),
SalvelInus fontlnalIs

Brook trout (juvenile),
SalvelInus fontlnalIs

Brook trout (juvenile),
SalvelInus fontlnalIs

Brook trout (juvenile),
SalvelInus fontlnalIs

Lake trout (juvenile),
Salvelinus namaycush

Lake trout (juvenile),
SalvelInus namaycush

Channel  catfish (juvenile),
Ictalurus punctatus

Channel  catfish (juvenile),
Ictalurus punctatus

Channel  catfish (juvenile),
Ictalurus punctatus

Channel  catfish (yolk sac fry),
Iclalurus punctatus

Channel  catfish (1 wk-olJ),
Ictalurus punctatus
Chemical
Duration
Effect
Result*
(ug/l)     Reference
Pheny Imercurlc
acetate
Pyrldy Imercurlc
acetate
Merthlolate
Pheny Imercurlc
acetate
Pheny Imercurlc
acetate
Pyrldy Imercurlc
acetate
Merthlolate
Pyrldy Imercurlc
acetate
Merthlolate
Pheny Imercurlc
acetate
Pheny Imercurlc
acetate
Pheny Imercurlc
acetate
Pheny 1 mercuric
acetate
Pheny Imercurlc
acetate
1 hr
48 hrs
48 hrs
1 hr
1 hr
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
48 hrs
24 Mrs
Safe for disease
LC50
LC50
Safe for disease
control
Safe for disease
control
LC50
LC50
LC50
LC50
LC50 6 10°C
LC50 6 16.5'C
LC50 6 24'C
LC50 6 24°C
LC50 6 23°C
4,750
2,950
26,800
2,070
4,750
5,080
39,900
3,610
1,060
1,960
1,360
233
178
1,010
Rodgers,
Wll Iford
Wll Iford
Al II son,
Rodgers,
Wll Iford
Wll Iford
Wll Iford
Will ford
Clements
1958
Clemens
1958
Clemens
1958
C 1 emens
1958
C 1 emens
1958
et al,
, 1967
, 1967
1957
et al,
, 1967
, 1967
, 1967
, 1967
A Sne.
A Snea
4 Snea
A Sneec
A Sneoi
                                                       3-41

-------
Table 6.  (Continued)
Species
Channel calflsh ( juvenl le 3"),
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Blueglll (juvenile),
Leponils macrochirus
Blueglll (juvenile).
Loponils macrochirus
Mai lard duck.
Anas platyrhynchos

Chemical
Pheny (mercuric
acetate
Pheny Imercur Ic
acetate
Merthlolate
Pyrldy Imercur Ic
acetate
Merthlolate
Methyl mercuric
dlcyandl amide
Duration
24 hrs
46 hrs
48 hrs
48 hrs
48 hrs
2 genera-
tlons
SALTWATER
Effect
LC50 g 23*C
LC50
LC50
LC50
L£50
Reduced fertllHy
and food conver-
sion efficiency
SPECIES
Result*
(ug/l)
1,780
1,370
2,800
7,600
32,000
0. 1 mg/kg
In food
Reference
Clemens & Sneed
1958
Will ford, 1967
Will ford, 1967
WIN ford, 1967
WIN ford, 1967
Heinz, 1976
r
Inorganic Mercuric Salts
Red alga,
Antlthamnlon plumula
Alga,
Cliaetoceros glavestonensls
Alga,
Chaetoceros galvestonensls
Alga,
Cliaotoceros galvestonensls
Alga,
Chi or el la sp.
Alqa,
Croonionas sal Ina
Alga,
Cyclotel la sp.
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
ch 1 or 1 de
Mercuric
chloride
Mercuric
chloride
30 mln
4 days
4 days
4 days
2 days
3 days
LC50 after 7 days
About 30J reduction
In growth
No growth of
culture
BCF=10,920
66% reduction In
co2
DCF=853
No growth of
culture
5,000
10
100
10
2,500
164
100
Honey & Corner,
Hannan, et al.
Hannan, et al.
Hannan, et al.
Ml Ms & Colwol 1
Parrlsh & Carr,
Hannan i Patoul
1972
1959
I973b
I973b
1973b
, 1977
1976
1 let.
                                                B-42

-------
Table 6.  (Continued)
Species                          Chemical.

Alga,                            Mercuric
Puna I lei la sp.                   chloride

Alga,                            Mercuric
Uunaliella tertlolecta           chloride
Alga,                            Mercuric
Dunallet la tertlolecta           chloride
Alga,                            Mercuric
Puna 11 el I a tertlolecta           chloride

Alga,                            Mercuric
Puna 11e11 a ter11oIecta           chloride

Alga,                            Mercuric
IsochrysIs pa I bana               chloride

Alga,                            Mercuric
Isochrysls galbana               chloride

Alga,                            Mercuric
Isochrysls galbana               chloride
Kelp (zoospores, gametophytes.   Mercuric
sporophytes),                    chloride
Laminaria hyperborea

Kelp (zoospores, gametophytes.   Mercuric
sporophytes),                    chloride
Laminaria hyperborea

Kelp (zoospores, gamefophytes.   Mercuric
sporophytes),                    chloride
Laminar I a hyperboroa
Duration          Effect

             752 reduction In
             C02

   8 days    About 102 Increase
             in maximum chloro-
             phy 11 a^ concentra-
             tlon

   8 days    About 452 increase
             In max I mum chIoro-
             phy 11 e_ concentra-
             tion

   3 days    About 152 reduction
             In growth

   8 days    No effect on growth
Result*
(ug/l)

2,500


  100




  220




   10
  15 days    About 102 reduction      5.1
             In growth

  15 days    About 602 reduction     10.5
             in growth

  28 days    Growth rate recover     10.5
             to near normal
             after day 5

  28 days    Lowest concentrat ion    10
             for growth
             inhibition
Reference

Mills & Colwell, 1977


Betz, 1977
Betz, 1977




Da vies, 1976


Da vies, 1976


Oavies, 1974


Davies, 1974


Davies, 1974



Hopkins 4 Kain, 1971
  22 hrs     EC50 respiration     about 450  Hopkins & Kaln, 1971
  28 days    About 802 reduc-    10,000      Hopkins & Kain, 1971
             t ion In respiration
                                                    B-43

-------
Table 6.  (Continued)
Species
A Iga,
f'haoodacty lum trlcornutum
Alga,
Hhaeodacty lum trlcornutum
Alga,
Phaeodacty lum trlcornutum
Red alga (sporl Ing),
Plumarla elegans
Ked alga (sporl Ing),
Plumarla elegans
Red alga (sporting),
Plumarla elegans
Ked alga,
Plumaria elegans
Red alga,
Polyslphonla lanosa
Alga (mixed),
Asterlonel la japonlca plus
Diogenes sp.
5 seaweed species,
Ascophyllum nodosum,
Fucus spiral Ks,
F. versiculosus,
T. serra+us,
P'e Ivetia cana 1 1 cu 1 ata
Algae,
18 spoctes
Algae,
10 Gpecles
AllJdO,
(three species)
Chemical
Mercuric
chloride
Mercuric
ch lor Ide
Mercur 1 c
chloride
Mercuric
ch lor Ide
Mercuric
chloride
Mercuric
ch lor Ide
Mercuric
chloride
Mercuric
ch lor Ide
Mercuric
chloride
Mercuric
ch lor Ide
Mercuric
ch lor Ide
Mercur Ic
chloride
Mercuric
ch lor Ide
Duration
4 days
4 days
4 days
24 hrs
1 hr
18 hrs
30 mln
30 mln
8 days
10 days
17 days
17 days
Effect
About 50? reduction
In growth
No growth of
cul ture
BCF=7,120
40? reduction In
growth over 21 days
40? reduction In
growth over 21 days
LC50 after 7 days
LC50 after 7 days
LC50 after 7 days
BCF=3,467
10-30? reduction In
growth
Growth Inhibition
Letha 1
Depressed growth
Result*
(U9/D
50
120
10
120
1,000
3,170
6,700
8,000
15
10
<5-l5
10-50
30-350
Reference

Hannan, et al. 1973b
Itannan, et al. 1973a
Hannan, et al. 1973b
Boney, 1971
Boney, 1971
Boney, et al. 1959
Boney & Corner, 1959
Boney I Corner, 1959
Laumond, et al. 1973
Stromgren, 1980
Borland, et at. 1976
Oerland, et al. 1976
Sick 4 Wlndom, 1975
                                                     B-44

-------
Table 6.  (Continued)
Species

Algae,
(throe species)

Algae,
(three species)

Sandworm (adult),
Nereis vlrens

Sandworm (adult),
Nereis vlrens

Polychaeto (adult),
Ophryotrocha dladema

Polychaete (adult),
Ophryotrocha dladema

Polychaete (adult),
Ophryotrocha dladema

I'olychaete (adult),
Ophryotrocha dladema

Holychaete (adult),
Ophryotrocha labronlca

Oyster (larva),
Crassostrea glgas

Oyster (embryo),
Crassostrea virgin lea

Oyster (embryo),
Crassostrea virgin lea

Oyster (embryo),
Crassostrea virgin lea

Oyster (embryo),
Crassostrea virgin lea
Chemical

Mercuric
chloride

Mercuric
chloride

Mercuric
chloride

Mercuric
chloride

Mercuric
chloride

Mercuric
chloride

Mercuric
chloride

Mercuric
ch lorlde

Mercuric
chloride

Mercuric
chloride

MercurIc
chloride

Mercuric
chloride

Mercuric
chloride

Mercuric
chlorlde
Duration
 168 hrs


 168 hrs


  96 hrs


  96 hrs


  96 hrs
     Effect

No further
bloaccumulat ion

Changes in eel I
chemistry

LC50
LCI 00


LCI 3


LC60


LCI 00
  21 days    No growth of
             population

   0.5 hrs   LC50
  24 hrs     Abnormal
             development

  12 days    LC5
  12 days    LC50


  12 days    LC95


  48 hrs     LCD
Result*
(ug/1)     Reference

   40      Sick & Wlndom, 1975


30-350     SIcK & Wlndom, 1975
   60      Elsler & HenneKey.
           1977

  125      Elsler & Hennekey,
           1977

   50      Relsh & Carr, 1978
  100      Relsh & Carr, 1978
  500      Relsh & Carr, 1978
                       too
           Relsh & Carr, 1978
                     1,000      Brown & Ahsanullah,
                                1971

                        32      Oku bo & Okubo, 1962
                         3.3    Calabrese, et al.
                                1977

                        12      Calabrose, et al.
                                1977

                        20      Calabrese, et al.
                                1977

                         I      Calabrese, et al.
                                1973
                                                      B-45

-------
Table 6.  (Continued)
Oyster (adult),
Crassostrea virgin lea

Hard-shell clam (larva),
Mercenarla morcenarla

Hard-shell clam (larva),
Mercenarla mercenarla

Hard-shell clam (larva),
Mercenarla mercenarla

Hard-shell clam (larva),
Mercenarla mercenarla

Soft-shell clam (adult),
My a arenarla

Soft-shell clam (adult),
Mya arenarla

Soft-she)I clam (adult),
Mya arenarla

Blue muss Ie (larva),
MytlI us edulls

Clam,
Rang Ia cuneata

Copepods  (adult),
5 genera

Copepods  (adult),
5 genera
Copepods (adult),
5 genera
Copepod (adult),
Acartla clausl
Chemical

Mercuric
chlor Ida

Mercuric
ch lorlde

Mercuric
chloride

Mercuric
chloride

Mercuric
chlorlde

MercurIc
chloride

Mercuric
chloride

Mercuric
ch lorlde

Mercuric
ch lorlde

Mercuric
chlorlde

Mercuric
ch loride

Mercuric
chlorlde
Mercuric
chloride
Mercuric
chloride
                                                 Duration
                  Effect
  19 days    Trace metal  upset
 8-10 days   LC5
 8-10 days   LC50
 8-10 days   LC95
12-18 hrs    LCO
 168 hrs     LCO
 168 hrs     LC50
 168 hrs     LCI00
  24 hrs     Abnormal  development
  14 days    BCF»1.I30
             Whole animal
Result11
(pg/I)     Reference

   50      Kopfler, 1974
    4      Calabrese, et al.
           1977

   14      Calabrese, et al.
           1977

   25      Calabrese, et al.
           1977

    2.5    Calabrese, et al.
           1973

    I      Elsler & Hennekey,
           1977

    4      Elsler & Hennekey,
           1977

   30      Elsler & Hennekey,
           1977

   32      Oku bo & Okubo, 1962
   34      01 I Ion & Neff, 1978
  10 days    =90£ decrease in egg    10      Reeve, et al. 1977
             product Ion
  10 days    =70)1 decrease In
             faecal  pel let
             product ion
   10
Reeve, et al. 1977
  48 hrs     Hg-Cu Interactions      17      Reeve, ot al. 1977
             on LC50              (Hg In
                                  mixture)
   1.9 hrs   LC50
   50      Corner & Sparrow,
           1956
                                                      B-46

-------
Table 6.   (Continued)
Species
Chemical
Duration
Effect
Copepod (adult),
Pseudocalanus mlnutus
Copepod (adult),
Pseudocalanus mi nut us
Barnacle (cyprld),
Balanus improvlsus
Barnacle (adult),
Balanus balanoides
Barnacle (cyprid),
Balanus balanoides
Barnacle (cyprld),
Balanus balanoides
Barnacles (nauplius),
Balanus crenatus
Isopod (adult),
Jaora alblfrons
Isopod (adult),
Jaera nordmanni
Isopod (adult),
Jaera alblfrons sensu
Isopod (adult),
Idotea neglect a
Isopod (adult),
Idotea errurglnata
Grass shrimp (larva),
Palaemonetes vulgar Is
Grass shrimp (larva),
Palaemonetes vulgar is
Mercuric
ch loride
Mercuric
ch loride
Mercuric
chloride
Mercuric
ch loride
Mercuric
ch loride
Mercuric
ch loride
Mercuric
chloride
Mercur 1 c
ch lor i de
Mercuric
ch 1 or i de
Mercuric
ch loride
Mercuric
ch loride
Mercuric
ch loride
Mercuric
chloride
Mercuric
ch lor 1 do
70 days
70 days
48 hrs
48 hrs
6 hrs
6 hrs
6 hrs
5 days
57 days
<24 hrs
<24 hrs
<24 hrs
<24 hrs
48 hrs
No growth of culture
No growth Inhibition
About 50? abnormal
development
LC90
About \0% reduclton
in substrate attach-
ment over 19 days
LC50
LC50
Osmoregu latlon dis-
ruption In lowered
salinity
LC95
LCI 00
LCI 00
LC90
LCI 00
LCO
5
1
16,600
1,000
10
90
60
100
100
100
100
100
56
<5,
Result"
(ug/l)     Reference
                                                                                            Sonntag i Greve,  1977


                                                                                            Sonntag & Greve,  1977


                                                                                            Clarke, 1947


                                                                                            Clarke, 1947


                                                                                            Pyefinch & Mott,  1948



                                                                                            Pyefinch & Mott,  1948


                                                                                            Pyefinch & Mott,  1948


                                                                                            Jones, 1975



                                                                                            Jones, 1973


                                                                                            Jones, 1973


                                                                                            Jones, 1973


                                                                                            Jones, 1973
                                                                                    56      Shea Iy & Sandifer,
                                                                                            1975

                                                                                      .6    Shea I y & Sandifer,
                                                                                            1975
                                                         B-47

-------
Table 6.  (Continued)
Species
Grass shrimp (larva),
Palaemonetes vulgar is
Grass shrimp (larva),
Palaenenetes vulgar is
Crab (adult),
Carcinus maenas
Crab (adult).
Carcinus maenas
Crab ( larva),
Carcinus maenas
Crab ( larva),
Carcinus maenas
Crab ( larva),
Carcinus maenas
Crab ( larva),
Carcinus maenas
Crab ( larva),
Carcinus maenas
Crab ( larva),
Carcinus maenas
White shrimp (adult),
Penaeus setlferus
Hermit crab (adult),
Pagurus longlcarpus
Hermit crab (adult),
Pagurus longlcarpus
Hermit crab (adult),
Paqurus 1 png i carpus
Chemical
Mercuric
ch lorlde
Mercuric
ch loride
Mercuric
chloride
Mercuric
ch lorlde
Mercuric
ch lorlde
Mercuric
ch lor 1 de
Mercuric
chloride
Mercuric
chloride
Mercuric
ch lorlde
Mercuric
ch lorlde
Mercuric
ch loride
Mercuric
ch loride
Mercuric
ch loride
Mercur Ic
ch 1 or i de
Duration
48 hrs
46 hrs
48 hrs
48 hrs
47 hrs
20-30 hrs
4.3-13.5 hrs
2.7 hrs
0.5 hrs
0.22 hrs
60 days
168 hrs
168 hrs
168 hrs
Effect
LC50
Abnormal
development
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
No effect on
resp 1 rat Ion ,
or molting
LCO
LC50
LC100
Result"
(ug/D
10
10-18
1,000
1,200
10
33
100
1,000
3,300
10,000
1
growth,
10
50
125
Reference
Shealy & Sandifer,
1975
Shealy & Sandifer,
1975
Portmann, 1968
Connor, 1972
Connor, 1972
Connor, 1972
Connor, 1972
Connor, 1972
Connor, 1972
Connor, 1972
Groen, et al. 1976
Eisler & Hannekey,
1977
Eisler & Hannekey,
1977
Els ler & Hennekey,
                                               B-48

-------
Table 6.   (Continued)
Species
Chemical
Fiddler crab (adult),
Uca pugi lator
Fiddler crab (adult),
Uca pugl lator
Fiddler crab (adult),
Uca pugl lator
Fiddler crab (zoea),
Uca pugi lator
Fiddler crab (zoea),
Uca pugi lator
Fiddlur crab (zoea),
Uca puyl lator
Shiner perch,
Cymatogaster aggregate
Haddock (embryo),
Melanogrammus arglofinus
Murnriichog (adult),
fundulub hot croc litus
Mummichog (adult),
Fundulus lieterocl Itiis
Munimicliog (ddult),
Fundulus heteroclitus
Mummichog (adult),
Fundulus heterocl it is
Mun»nlchog (adult),
Funduliis hoteroclitus
Mercuric
ch loride
Mercuric
ch 1 or 1 de
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
ch loride
Mercuric
chloride
Mercuric
chloride
Mercuric
ch loride
Mercuric
ch loride
Mercuric
ch loride
Mercuric
ch loride
Mercuric
ch loride
28 days
6 days
24 hrs
8 days
24 hrs
5 days
96 hrs
168 hrs
168 hrs
168 hrs
24 hrs
28 djys
Duration
28 days
6 days
24 hrs
8 days
24 hrs
5 days
—
96 hrs
168 hrs
168 hrs
168 hrs
24 hrs
28 djys
Effect
Low survival. In-
hibited limb
regeneration
20-25$ reduction
In percent survival
1 ncr eased oxygen
consumpt ion
LC50
20-100? Increase In
metabol Ic rate
after stage 1 zoea
About 40jC increase
in swimming activity
of stage V zoea
45? reduction of
brain cholinester-
ase act 1 v 1 ty
LC50
LCO
LC50
LCI 00
Disrupted osmoreg-
u lat Ion
Up to 40% reduction
Result*
(U9/I)
1,000
180
180
1.8
1.8
1.8
33,900
918
100
800
1,000
125
12
Reference
Weis, 1976
Vernberg & Vernberg,
1972
Vernberg & Vernberg,
1972
Decoursey & Vernberg,
1972
Decoursey & Vernberg,
1972
Decoursey & Vernberg,
1972
Abou-Donla &Menzel,
1967
U.S. EPA, 1980
Elsler i Hennekey,
1977
Elsler & Hennekey,
1977
Eisler & Hennekey,
1977
Renfro, et al. 1974
Jackim, 1973
                                                            in enzyme activity
                                                            before  recovery
                                                     B-49

-------
Table 6.   (Continued)
                               Chemical
DuratIon
Effect
Result*
(yg/l)    Reference
Murnmichog (embryo),
Fundulus lieterocl ilus
Mummlchog (embryo),
fundulus lieterocl I tus
Mummlchog (embryo),
fundulus hetoroclitus
Munimichog (adult),
F undu I us heteroc I I tus
Mummichog (adult),
Fundulus heteroc 1 1 tus
Mummlchog (adult),
Fundulus heteroc 1 1 tus
Muinmichog (adult),
Fundulus heteroc 1 1 tus
Winter flounder (adult),
Hseudopleuronectes amerlcanus
Striped bass (adult),
Morone saxat Ills
Sea urchin (spermatozoa),
Arbacia punctulata
Sea urchin (spermatazoa),
Arbdda punctulata
Starfish (adult).
Aster las forbesl
Starfish (adult),
Astorlas forbesi
Mercuric
ch lor Ide
Mercuric
ch lor Ide
Mercuric
ch loride
Mercuric
ch lor I de
Mercuric
chloride
Mercuric
chloride
Mercuric
ch loride
Mercuric
ch loride
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
3 days
3 days
12 hrs
96 hrs
48 hrs
96 hrs
60 days
30 days
8 mln
24 mln
166 hrs
168 hrs
Many developmental 30-40
abnormal It les
Some developmental 10-20
abnormal It les
Some developmental 30-40
abnormal (ties
Mercury red is- 1,000 ug Hg/
tr! but Ion organs Kg body wt
following Se plus 400 ug
pretreatment SeAg body wt
Cellular 250-5,000
degeneration
LC100 2,000
Sluggish uncoor- 1,150
dlnated swimming
Decreased resplra- 10
tlon
Decreased resplra- 5
tlon 30 days post
exposure
About I50J Increase 20
in swimming speed
About 80$ decrease 2,000
In swimming speed
LCO 10
LC50 20
We is & Wels, 1977
Wels & Wels, 1977
Wefs 4 Weis, 1977
Shel Ine & Schmidt
Nlelson, 1977
Gardner, 1975
Elsler, et al. 1972
Klaunlg. et al. 1975
Calabrese, et al.
1975
Dawson, et al. 1977
Young & Nelson, 1974
Young & Nelson, 1974
Eisler & Hennekey,
1977
Elsler & Hennekey,
1977
                                                   B-50

-------
Table 6.  (Continued)
Species
Starfish  (adult).
Aster las  forbesl

Sea urchin (embryo),
Arbacla punctulata

tchlnoderm (larva),
Paracentrotus llvldus

Protozoan,
Crist In^ra spp.

Protozoan,
Euplotes  vannus
Alga.
Puna I lei la tortlolecta

Alga,
PhaeodactyI urn trlcprnutum

Red alga (Sperling),
Plumarla elenans

Mummlchog (adult),
Fundulus heteroclItus

Oyster (adult),
Crassostrea virgin lea

Amphlpod (adult),
Gammarus duebenI

Fiddler crab (adult),
Uca spp.

Fiddler crab (adult),
Uca spp.

blue mussol (adult),
Hytllus edulIs
Chemical

Hercurfc
chloride

Mercuric
chloride

Mercuric
chloride

Mercuric
chloride

Mercuric
chloride
Duration

 168 hrs
Effect
                                      Result*


                 LC100                  125


      13 hrs     Abnormal development    92


                                          3


      12 hrs     Reduced growth       2.5-5


      48 hrs     Inhibition           1,000
                 reproduct Ion

MethyImercurlc Compounds
  40 hrs     Retarded growth &
             development
Methy Imercurlc    JOmln     EC50 photosynthesis  about 170
chloride

MethyImercurlc    25 days    EC50 photosynthesis  about 190
chloride
MethyImercurlc    18 hrs
chloride

MethyImercurlc    24 hrs
chlor I do
             LC50 after 7 days       44
             Disrupted              125
             osmoregulatIon
Methy(mercuric    19 days    Trace metal upset       50
chloride
MothyImercurlc
chloride
   3 days     Induced diuresis        56


                                300-500
MethyImercurlc    32 days    No limb
chloride                     regeneration

MethyImercurlc    32 days    Melanin absent In      100
chloride                     regenerated limbs

Methy I mercuric    24 hrs     About 90? reduced      400
chloride                     feeding rate
Reference

Elsler & Hennekey,
1977

Waterman, 1937
                           Soyer, 1963
                                             Gray & Vent 11 la, 1973
                                             Persoone 4
                                             Uyttersprot, 1975
                           Overnell, 1975


                           OvernelI, 1975


                           Boney, et al. 1959


                           Renfro, et al. 1974


                           Kopfler, 1974
                           Lockwood & Inman,
                           1975

                           Wels, 1977
                                             Weis, 1977
                                             Dorn, 1976
                                                        B-51

-------
Table 6.  (Continued)
Species
01 atom,
Nitzchla del Icatlsslma
Alga,
Chaetocoros sp.
Alga,
Cyclotel la sp.
Alga,
Phaeodacty lum sp.
Red alga (sporllng),
P lunar la e lagans
Dlnof lagel late,
(jymnodl nlum spendens
Dinof lagel late,
Gymnodlnlum spendens
Dlnof lagel late,
Scrippslel la faeroense
Ulnof lagel late,
Scrippslel la faeroense
Oyster (adult),
Crassostroa virgin lea
Oyster (adult),
Crassostrea vlrglnlca
Copepod (adulD,
Acartla clausl
Red alga (sporllng),
Hliimarla efejjans
Chemical Duration
Methy (mercuric
d Icyand iamlde
Dl met hy Imer cury
Dlmethy Imercury
Dlmethylmercury
Methy (mercuric
ch lorlde
Other
Mercuric
acetate
Mercuric
acetate
Mercuric
acetate
Mercuric
acetate
Mercuric
acetate 1 2
Mercuric
acetate
Mercuric
acetate
Mercuric
Iodide
Result*
Effect (lig/O
24 hrs EC50 photosynthesis 0.4
3 days About 75$ reduction 100
In growth
3 days About 15$ reduction 500
In growth
3 days About 45$ reduction 500
In growth
25 mln EC50 growth over 40
21 days
Mercury Compounds
11 days
4 days
25 days
14 days
15 days
hrs da! ly
60 days
1.9 hrs
18 hrs
55$ reduct Ion In
growth
No growth of
culture
45$ reduct Ion In
growth, morphological
varlat Ion
No growth of
cu Iture
33$ reduction In
slwl 1 growth
LC55
LC50
LC50 after 7 days
10
100
10
1,000
10
100
50
156
Reference
Harrlss, et al. 1970
llannan & Patoul 1 let,
1972
Kan nan & Patoul 1 let,
1972
Hannan & Patoul 1 let,
1972
Boney, 1971
Kayser, 1976
Kaysor, 1976
Kayser, 1976
Kayser, 1976
Cunningham, 1976
Cunningham, (976
Corner & Sparrow,
1956
Doncy, et al. 1959
                                                  B-52

-------
Table 6.  (Continued)
Species
D 1 atom,
Nitzchla del Icatisslma
Red alga (sporting),
Plumarla elegans
Copepods (adult),
Acartla clausi
Alga,
Chi orel la sp.
Alga,
Chloral la sp.
Alga,
Ounallella euchlora
Alga,
Dunalietla euchlora
Alga,
Monochrysis lutherl
Alga,
Monochrysis lutheri
Alga,
Phaeodacty turn trlcornutum
Alga,
Phaeodacty 1 urn trlcornutum
Alga,
Protococcus sp.
Alga,
Protococcus sp.
Chemical Duration
N Methylmercurlc-
1, 2,3,6- tetrahy dro-
3,6-methano-3,4,5,6,
7, 7-hexach loro-
phtha 1 Imlne
Ethy Imercurlc
ch lorlde
Ethy Imercurlc
chloride
Ethy Imercurlc
phosphate
Ethy 1 mercuric
phosphate
Ethyl mercuric
phosphate
Ethy Imercurlc
phosphate
Ethy Imercurlc
phosphate
Ethy (mercuric
phosphate
Ethy Imercurlc
phosphate
Ethy Imercurlc
phosphate
E1hy (mercuric
phosphate
Ethy Imercurlc
phosphate
24 hrs
18 hrs
1.9 hrs
10 days
10 days
10 days
10 days
10 days
10 days
10 days
10 days
10 days
10 days
Result*
Effect 
-------
Table 6.  (Continued)
Red alga (sporting),
Plumarla elegans

Oyster (adult),
Crassostrea vlrglnlca

Diatom,
Nltzchla delIcatlsslma

Stickleback (adult),
Gasterosteus aculeatus

Red alga (sport Ing),
Plumarla elegans

Diatom,
Nltzchla delicatlsslma

Sockeye salmon (juvenile),
Oncorhynchus nerka
Sockoyo salmon (adult),
Oncorhynchus nerka
Sockeye salmon (adult),
Oncorhynchus nerka
Silver salmon (adult),
Oncorhynchus kisutch
Chinook salmon (adult),
Oncorhynchus tshawytscha
Hod alga (sporting),
I'lumarla elogans
Chealcal        Duration          Effect

                             LC50 after 7 days


                             Trace metal upset


                  24 hrs     EC50 photosynthesis
PhenyImercurlc    18 hrs
chloride

PhenyImercurlc    19 days
ch loride
Result'
(uq/D

   54
   50
PhenyImercurlc
acetate
PhenyImercuric   370 mln
acetate

Phenylmercurlc    18 lirs
Iodide

Dlphenylmercury   24 hrs
                             LC100
                             LC50 after 7 days
  100
                             EC50 photosynthesis    18
Pyrldylmercurlc  12-15 wks,  1.2 mg Hg/kg wet wt  1,000
acetate          1  hr wkly   muscle 12 weeks
                             post-exposure

Pyrldylmercurlc  12-15 wks,  0.24 mg HgAg wet    1,000
acetate          hr wkly as  wt muscle 3 yrs
                 juveniles   post-exposure
Pyrldylmercurlc  12 1-hr
acetate
                             0.04 mg Hg/kg wet    1,000
                 exposures   wt muscle 4  yrs
                 as juven-   post-exposure
                 lies
Pyrldylmercurlc  12-15 wks   0.03 mg Hg/kg wet    1,000
acetate          as juven-   wt muscle 2 yrs
                 lies 1  hr   post-exposure
                 wkly

Pyrldylmercurlc  35 wks  as   up to 0.12 mg Hg/kg  1,000
acetate          juveniles   muscle 4 yrs later
                 I  hr wkly
I soamy (mercuric   18 hrs
chloride
                             LC50 after 7 days
Reference

Boney, et al. 1959
Kopfler, 1974
    1.5    Harrlss, et al. 1970
Boat Ius. 1960
  104      Boney, et al. 1959
           Harrlss, et al. 1970
                                                             Amend,  1970
                                                              Amend,  1970
           Amend, 1970
                                                             Amend,  1970
                                                             Amend,  1970
   19      Boney, et al. 1959
                                                    B-54

-------
Table 6.  (Continued)
Species

Red alga (sporlIng),
Clumarla elegans

Red alga (sporting),
Plumarla elegatis

Red alga (sporting),
Plumarla elegans

Red alga (sporlIng),
Plumarla elegans
 Chemical

 N-AmyImercuric
 chlorlde
Duration
  18 hrs
IsopropyImercurlc  18 hrs
chloride

 N-Propy(mercuric  18 hrs
 ch lorlde

 N-Buty(mercuric   18 hrs
 ch lorlde
     Effect

LC50 after 7 days


LC50 after 7 days
Result*
(|iq/l)     Reference
   13      Boney, et al. 1959


   28      Boney, et al. 1959
             LC50 after 7 days        13      Boney, et al.  1959


             LC50 after 7 days        13      Boney, et al.  1959
*   Results are expressed as mercury, not as the compound.

**  Static, continual  loss over time.

*** Not at steady-state.

*"**BCF Independent of concentration  In water over range tested.
                                                  B-55

-------
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(eds.),  Physiological   Responses  of  Marine  Biota  to Pollutants.   Academic



Press, New York.  p. 185.








Ukeles,  R.   1962.  Growth  of pure  cultures  of  marine phytoplankton  in  the



presence of toxicants.  Appl. Microbiol.  10: 532.







U.S.   EPA.    1980.    Unpublished   laboratory  data.   Environ.   Res.   Lab.,



Narraqansett, Rhode Island







U.S.  Food  and Drug  Administration.   1978.   Administrative Guidelines  Manual,



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Vernberg, W.B.  and  J.  Vernberg.   1972.  The synergistic  effects  of  tempera



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crab, Uca piqilator.  U.S. Dept.  Comm. Fish.  Bull.   70: 415.








Warnick, S.L. and H.L. Bell.  1969.   The acute toxicity of  some heavy metals



to  different  species  of aquatic  insects.   Jour.  Water Pollut.  Control  Fed.



41: 280.







Waterman, A.J.   1937.  Effect of  salts  of  heavy  metals on development of  the



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Weis, J.S.   1976.   Effects  of mercury, cadmium,  and  lead  salts on  regenera



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Matl. Ocean.  Atmos. Admin. Fish.  Bull.  74: 464.
                                     B-76

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Wobeser,  G.A.   1973.  Aquatic  mercury  pollution:  Studies  of  its occurrence
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                                     B 77

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Mammalian Toxicology and Human Health Effects
     Human beings are exposed to a variety of physical  and  chemical  forms  of
mercury.  Since  these  forms  differ in their toxicity and  in  the  hazard  they
present to human health  it will  be  necessary in many parts of this  document
to  treat  these  forms  separately from the  point of  view  of hazard  evalua-
tion.  The situation is  made  even  more complicated  by our  lack of  knowledge
of  the forms  of  mercury  in water.   Thus,  the approach being taken is to  dis-
cuss the  most important forms of  mercury to which  humans  are  exposed, and
from this to evaluate the importance of intake from  the  water supply.
     At this point, it is useful  to give  at  least general  definitions of the
usual forms  that mercury can take.  It is customary  (Maximum Allowable  Con-
centrations Committee, 1969) to consider  three  broad  categories of  the phys-
ical and  chemical  forms  of  mercury.   These  categories  are  selected mainly
because of the difference in  their  toxic  properties and in the hazards  they
present to  human health.  The first  category consists  of  metallic  mercury.
Mercury  in  the  zero  oxidation  state  (Hg°)  is  usually  referred  to as  mer-
cury vapor when  present  in  the  atmosphere or as  metallic  mercury when  pre-
sent in  its  liauid form.  The second  category comprises the inorganic  com-
pounds of mercury,  which include the  salts  of  the two  oxidation states  of
mercury,  Hg^  (mercurous   salts),   and   Hg++   (mercuric   salts).   The
third major  category  contains the  so-called organic mercurials  or  organic
mercury compounds.   These are defined  as  those  compounds of mercury  in which
mercury is attached  to  at  least  one  carbon  atom by a  covalent  bond.   The
toxic properties in this third category,  however, vary enormously.   The most
important subgroup  in  the  organo-mercurials category  is   comprised  of  the
methylmercury  and  related short-chain alkyl  mercurial  compounds.  From the
point of  view of environmental  exposures,  the methylmercury compounds  are
                                     C-l

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the ones of greatest concern.   Th«  other  organo-mercurials  may take the form
of aryl  and  alkoxy-aryl mercurials as  well  as a wide  variety of  other  or-
gano-mercurials used  in medicine and agriculture.  In  general  these organic
forms of mercury are much less toxic than the short-chain alkyl mercurials.
     The main  sources  of human mercury exposure  are  methylmercury compounds
in the food supply and  mercury  vapor  in the  atmosphere  of occupational  sett-
ings.  Exposure to other forms  of mercury result  from occupational, medicin-
al, or accidental circumstances.  As will  be discussed  later,  the water sup-
ply  probably  contains  mercury  mainly  in the form of  Hg++ salts  complexed
with a variety of constituents in water.
     The topics  of mercury  in  the environment,  human  exposure  to mercury,
and an estimate of health effects and  hazards  of  mercury have  been the sub-
ject of  many reviews  by expert committees  and  individual  authors  over  the
past ten years.   Included are  reviews  by the Swedish  Expert  Group (1971);
Norton (1971); World Health  Organization  (WHO, 1971,  1972,  1976); Miller and
Clarkson (1973); Friberg and  Vostal  (1972);  Nordberg  (1976); and  The Nation-
al Academy of  Sciences  (NAS,  1978).   Additional  references are  Hartung  and
Dinman (1972), and Buhler (1973).
     The source  material  for  this  document  comes  primarily  from original
scientific  publications,  but the reviews  mentioned above have also  been  of
inestimable value  in  the preparation of  this  document  and  in developing  an
overall perspective of  the  mercury  problem.   Special  mention  should  be made
of the  review  prepared by the  WHO  (1973) where the  recommended  safe levels
of mercury in water are discussed.
                                      C-2

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                                 INTRODUCTION
     A  variety of  original  articles  and  reviews  have  dealt with  sources,
pathways  and  mechanisms of transport,  and  sinks of mercury  in  the  environ-
ment.   These   include  Wallace,   et  al.  (1971);  D'ltri  (1972);  Friberg  and
Vostal  (1972); Garrels,  et al.  (1973); Kothny (1973);  WHO (1972,  1976);
Heindryckx,  et  al.   (1974);  Korringa  and   Hagel   (1974);  Wollast,  et  al.
(1975); Abramovskig,  et al. (1975);  and  National  Academy of  Sciences  (NAS,
1978).  In view of  the  number of recent reviews, and the fact that  a  review
has  just  been completed by a National  Academy of  Sciences  panel,  no attempt
will be made  in  this section to deal  with  this  subject  in detail except  to
emphasize  those  data that  deal  directly with human uptake of  mercury from
the water supply.
     The dynamics of mercury in  the  environment  may be viewed in the context
of  a global cycle.   This cycle  presents  a  general  perspective  within  which
man's contribution  to  the  environmental mercury  burden may be viewed.   How-
ever, before  Quoting numbers related  to  the  global  turnover of this  element,
several caveats are  in  order.   Many of the  calculations  involve assumptions
for  which  supporting experimental  evidence  is  tenuous,  to  say the  least.
Concentrations of  mercury in certain  environmental samples (e.g.,  in  fresh
water  and  ocean  water)  are  so   low  as to challenge the skill  of  the  best
analyst using the  most sophisticated modern eauipment.   Matsunaga, et  al.
(1979) have recently reviewed the methodological  errors  involved  in  the mea-
surement of mercury  in  seawater.  These  analytical  figures  are multiplied  by
huge numbers, e.g.,  the  area  of  oceans (361 x 1012 m2)  and  the  precipi-
                                17   2
tation  over   oceans  (4.11  x  10  1/m  yr),  to   calculate  the "mercury  bud-
gets" for  the global cycle.  Authorities differ in their  interpretation  of
                                     C-3

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certain environmental samples and the most  recent  data  seem  to conflict with
earlier  data  (NAS,  1978;  Korringa  and   Hagel,   1974).    It   is   likely,
therefore, that the  "up-datinq" of the global  cycle  and other more localized
cycles  will  continue.   Nevertheless,  certain   general  conclusions   have
survived the  test of time  and are useful  in  developing a  perspective with
regard to human exposure to mercury and the possibilities of  control.
     The Global  Cycle  of Mercury:  The  atmosphere is  the major  pathway for
distribution  of  mercury.   Most reviewers  are  in good  agreement that  the
total entry  into  the atmosphere ranges from 40,000  to  50,000 tons*  per year
(Table  1)  on  a worldwide basis.   The main  input  to the atmosphere  is from
natural sources.   Emission  (degassing) from continental land masses  accounts
for  about  66  percent of  the  total  natural  input.   Emission from the  ocean
surface is  next  in importance, whereas emission from land biota  and volcan-
oes seems to be negligible.
     Manmade  (anthropogenic) release,  although  less  than that due to natural
causes, is substantial, accounting for about one-third of total input.
     The  amount  of  mercury contained in  the  atmosphere  is the  subject  of
widely  divergent  figures (Table  2).   The  main point  of  contention is  the
assumption  with  regard  to  the change of  atmospheric  mercury concentration
with height.  The  most  recent  review of the subject (NAS,  1978)  assumed  an
exponential  decline  with increasing  altitude,  whereas others have  assumed
mercury mixes to  a  height  of 1  kilometer  (Heindryckx,  et  al. 1974).   A
Japanese group has calculated  the residence time  of  Hg in the atmosphere to
be 5.7 years  (Katsuniko and Takumi, 1976).
*"Tons" are metric tons, i.e., 1,000 kg, in this text.
                                      C-4

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                                   TABLE 1

                     Entry of Mercury into  the Atmosphere
              Source
 Annual  input (metric tons)

(1)           (2)             (3)
Natural
Continental degassing
Oceanic emission
Coastal emission
Emission from land biota
Volcanic
Total
Anthropogenic
Total
17,800
7,600
1,420
40
20
26,880
10,000
36,880
25,000
16,000
4l,00u
50,000
(1)   National  Academy of Sciences,  1978
(2)   Korringa  and Hagel, 1974
(3)   Heindryckx.  et al,  1974
                                     C-5

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                                   TABLE 2

                The Amount of Mercury  in some Global Reservoirs
          Reservoir                     Mercury Content (metric tons)

                                       (1)                  (2)
          Reservoir
Atmosphere                               850
Freshwater                              2000
Freshwater biota3                        400
Oceanwater                                41 x 106        70 x
Oceanic 8iotab                       200,000
(1) National Academy of Sciences, 1978
(2) WHO, 1976
aOnly 1iving biota
^Living and dead biota
                                     C-6

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     Mercury  is  removed  from  the atmosphere  mainly by precipitation.   The
National  Academy  of  Sciences  (1978) has  calculated that  about 280  metric
tons/year  of  mercury  are deposited  into  fresh water  from the  atmosphere.
Although  this  is  less than  other sources of  input  (730 metric  tons/year),
variations in distribution of  atmospheric  deposition might  lead  to  substant-
ial local pollution.
     Most  of  the  atmospheric transport goes  to the  oceans (Table  3).   Fig-
ures vary widely.   The  most recent estimates  indicate  deposition  from  the
atmosphere to be  about  11,000 metric tons/year.   The entry of  mercury  into
the ocean from all  known sources seems  not  to exceed  about  50,000  metric
tons/year  although  the contribution  from  hydrothermal sources  is unknown  and
may be important (U.K. Dep. Environ., 1976).
     The  amount of  mercury contained in  the  oceans  is extremely large  com-
pared to  the  known  inputs.  Most estimates (see Table  2)  fall in  the  range
of 41 million  to  70  million  tons.   Based on  the  figures  given in Tables  2
and 3,  it  is clear that mercury concentrations  in the open  oceans (as  oppos-
ed to  coastal  and  inland waters) have not  changed  significantly.  Oceanic
fish  levels  most  probably  have  remained unchanged  by  man's  activities,
especially in wide ranging oceanic fish  such  as shark,  swordfish, and tuna.
     Mercury in living biota accounts for about one-half  of  the total  mer-
cury in  freshwater.   The figures in Table 2 are expressed  in  terms of total
mercury.   If expressed in terms  of  methylmercury, the  amount  of mercury  in
biota would considerably exceed that in  freshwater.
     Data  on concentrations of mercury  in  the  lithosphere have been reviewed
by  several expert  groups (World Health  Organization  WHO,  1976;  U.K.  Dep.
Environ.,  1976; NAS,  1978).   Mercury concentrations  in nonmineralized  soils
vary over two orders  of  magnitude,  the   average  concentration  being  about
                                     C-7

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                                    TABLE  3

                        Entry of Mercury into  the  Ocean
    Source                                   Annual input (metric tons)

                                      (1)                 (2)         (3)


Atmospheric deposition                                  41,000      50,000
    Open Ocean and Polar             7,600
    Coastal waters                   3,600               5,000       5,000
Land runoff
    Soluble                          1,600
    Participate                      3,700               5,000       5,000
Hydrothermal                            *                   *           *


(1)  National Academy of Sciences, 1978
(2)  Korringa and Hagel, 1974
(3)  Heindryckx, et al. 1974

*No data available
                                     C-8

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0.07 yg  Hg/g.   Freshwater sediments  in  nonpolluted rivers and  lakes  in  the
United States  usually  contain  less than 0.1 ug/g  (wet  sediment).   Insuffic-
ient data exist to  calculate average  values  and  ranges  of mercury concentra-
tions in oceanic sediments.
     Mercury is strongly  bound  to soil and  is predominantly  attached  to  or-
ganic matter  (Anderson,  1976;  Keckes and  Miettinen,   1970;  Landry,  et  al.
1978).   Kimura  and  Miner (1970)  reported  that  mercury mobility  is minimal
even  in  soils  contaminated by  mercury fungicides.   However, Fuller  (1978)
has reported that  the  mobility of mercury in soils  is  increased  in  the pre-
sence of leachates from municipal landfills.
     Chemical   and  Physical Forms  of  Mercury  in  the  Environment and  Their
Transformation:  Mercury  occurs  in  a  variety of physical  and  chemical  forms
in nature.  Mercury is mined as  cinnabar  (HgS)  but in  some  areas  (Almaden,
Spain) the ore is so rich that  metallic mercury is also  present.
     Human activities have resulted in the release of a wide  variety of both
inorganic and organic forms of mercury (Table 4).   The  electrical  and  chlor-
alkali industries and the  burning  of  fossil  fuels  release  mercury to the  at-
mosphere  mainly as  Hg°.   Release  to water via  direct discharge  involves
Hg++  and Hg°  (e.g., chloralkali).   Methylmercury compounds  have been  re-
leased to fresh and oceanic water in  Japan as a  byproduct  of  the  manufacture
of aceteldehyde  and vinyl  chloride.   Other anthropogenic sources have  re-
sulted in release of aryl and  alkoxy-aryl  compounds as well  as methyl-  and
ethylmercury compounds used as  fungicides.
     The inorganic forms of mercury may undergo oxidation-reduction  reactions
in water as indicated by the eauations:
                                     C-9

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                                   TABLE 4

            Patterns of Mercury Consumption in the United States*
      End use                       Annual  Consumption  (percent  total)

                                 1970                1973            19751
Electric Apparatus
Caustic Chloride
(chloralkali)
Paints
Industrial Instruments
Dental
Catalysts
Agriculture
Laboratories
Pharmaceuticals
Others
26

25
17
7.9
3.7
3.7
3.0
3.0
1.1
9.6
33

24
14
13
4.9
1.2
3.4
1.2
1.1
4.2
32

23
5.1
21
6.2
0.8
1.1
7
6.8
9.8
Total consumption
(metric tons)                  2100                1867              2091
*Source:  NAS, 1978; U.S. EPA, 1975a

iThe percentages were estimated under the assumption that consumption by
 laboratories was negligible.
                                     C-10

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                       2 Hg° = Hg2     * 2  e"	  (1)
                       Hg2  +* = ZHg4"1" + 2  e"	  (2)
Stock  and  Cucuel   (1934)   have  demonstrated  that  Hg°  can  be oxidized  to
Hg++  in  water  in  the  presence  of  oxygen.   The  reaction  probably  takes
place  in  rain  droplets during removal of Hg° from  the atmosphere  by pre-
cipitation.  Wallace,  et al.  (1971)  have noted that mercury concentrations
as high as  40  g/'l can  be attained  when water saturated with oxygen is expos-
ed  to  mercury  vapor.   The  mercurous   form  of  mercury  (Hg- )  undergoes
disproportionation  to  Hg°  and Hg4"*"  in  the  presence  of  sulfur  ligands
(Cotton and Wilkinson,  1966).   Jensen and  Jernelov  (1972)  have  noted that
the presence  of organic  substances  in water facilitates  the transformation
of  Hg°  to  Hg4'*.   The mercuric ion,  Hg4"1", is  the  substrate  for the bio-
methylation reaction that  occurs  in microorganisms present in  aauatic  sedi-
ments (Figure 1).
     In a  recent review by the National  Academy of  Sciences  (1S78),  it was
noted  that  the main  pathway  of   methyl at ion  of  soluble Hg     involved  a
transfer of methyl  groups  from methyl  cobalarnine (methyl-B^-) and that the
rate of formation  of methylmercury  is largely determined by  the  concentra-
tions of soluble Hg   and methyl B,^.
     Both  dimethyl  mercury and monomethyl mercury may be  formed  by bacteria
present in  sediments.   The  formation  of   dimethyl  mercury is  favored   by  a
high pH.   Dimethyl  mercury  is  volatile and may enter the  atmosphere,  where
it may  undergo  decomposition to  yield  Hg° (Wood,  1976).   It  may  also  be
converted  to  monomethyl mercury in  rainfall especially  in  acid  rains con-
taining Hg   .    In  the presence of  Hg  ,  one  molecule  of dimethyl  mercury
is converted  to two molecules  of  monomethyl  mercury (Cotton  and  Wilkinson,
1966).
                                     C-ll

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LM4 ••• v,2n6 -
(CH3)2Hg

Fish
t
CH3Hg+


o° ^ CH Hn* *, rru
Bacteria ^^ Bacteria

$N^
C>^^^
MS^^^w
•d ^v

Shellfish
f
CH3SHgCH3
i
T
3)2Hg CH3S-HgCH3
^
/
//
*
Hg°
IAir



Water



Sediment

                                                             Hg°
                                                 Bacteria
                                   Figure 1.

              The mercury cycle demonstrating the bioaccumulation
                       of mercury in fish and shellfish.
Source:  NAS, 1978
                                     C-12

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     A  variety  of  bacterial  and  funqal  organisms  have  the  capacity  to
methylate  Hg+ .   Jensen  and  Jernelov  (1972)  have  pointed  out that  condi-
tions  which  promote bacterial growth will  enhance  methylation of  mercury.
Thus,  the  highest  rates of methylation  in the aouatic  environment  are  seen
in  the uppermost  part  of the  organic  sediments  and  in suspended  organic
material in water.   Furthermore,  those  microorganisms  able  to methylate  mer-
cury at high rates are also usually resistant to the toxic effect of Hg  .
     Microorganisms  are  also  capable  of  demethylating  methylmercury  com-
pounds and of  splitting the carbon-mercury bond  in a variety of other organ-
ic  mercurials.   This process  involves:  first, the  cleavage  of the  carbon-
mercury  bond  to  release  Hg    and,  second,  the  reduction  of  Hg    to
Hg°.   Both  processes are  enzyme-mediated (MAS,  1978).   Microorganisms  cap-
able of  demethylation  reactions  have  been shown  to  occur  in  aauatic  sedi-
ments, soils,  and  human fecal material.   Microbial  resistance  to  methylmer-
cury  correlates  with the  capacity to  convert methylmercury  to  Hg°.   Both
methylation and  demethylation  rates  have been measured  in  aauatic sediments
in  the  laboratory  (for  review,  see NAS,  1978).   In  general,  methylation and
demethylation  account for  the conversion  of  a small  fraction  of the  total
mercury  in  the  sediment  on  an  annual  basis  (probably  5 percent or  less).
The total  production of methylmercury  in freshwater on  a  global  scale was
estimated to  be  about  10  metric  tons per year and in  the oceans to  be about
480 metric  tons/year.
     Divalent  inorganic   mercury   (Hg   )   may  undergo   reduction  to  Hg°.
Certain widely occurring bacteria  such  as Pseudomonas have been shown to  be
capable  of this  reduction  (Magos,   et  al.  1964;  Furukawa,   et   al.  1969).
Yeast cells also carry out this  reaction  and  the capacity to do this  corre-
lates  with  a  resistance  to  the  toxic  effects of  Hq     (Singh and  Sherman,
1974).
                                     C-13

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     In addition to  being  a  substrate  for both methylation and reduction re-



actions in  microorganisms,  Hg   is  available  to form  a  variety  of precipi-



tates,  complexes,  and  chelates  in  water.   A  stable  precipitate  is  formed



with  the   sulfide   ion,  S=.   The  latter  is  usually  present in  anaerobic



aouatic environments.  The formation of  HgS may limit  the  amount of mercury



available  for  methylation  reactions (Jensen  and  Jernelov  1972).   However,



our  knowledge  of  the chemical  forms  of  mercury  in  natural  waters  is  in-



complete.    For  theoretical  reasons, the  degree of oxygenation,  pH,  and  the



presence  of inorganics  (e.g.,  Cl~),  and organics  (e.g.,  -S~,   COO",  and



N  in  organic matter  in water),  ligands  are  probably important   factors  in



determining  the chemical  species  of  mercury  in  water.   On  thermodynamic



grounds,  one would  expect  inorganic mercury  to  be  present mainly  as  Hg



compounds  in well  oxygenated  water and  an  increasing  fraction  of mercury  as



Hq°  or  HgS  in reducino  conditions  (NAS,  1978).   In   view of  the  high



concentrations  of  chloride  and, to  a  lesser  extent,  bromide anions  in  sea



water,  inorganic  mercury  should  be  present  as   various   halide  complexes



(HgCl4 =,      HgCl38 =,     HqCl",      HqC^Br",     HgClj)     in     marine



water.



     Methylmercury compounds  readily pass across cell  membranes  and  bind  to



tissue ligands.  Thus, methylmercury tends to  be removed from  water  by  liv-



ing  biota.   Fagerstrom and Asell  (1973)  have  concluded  that  the concentra-



tion of methylmercury  in water  is  of major importance  for  the  end  result  in



terms  of  fish  accumulation.   This  conclusion  was based on  a mathematical



model of methylmercury accumulation  in  a  simple food chain.



     Limited information  is  available  on  concentrations  of methylmercury  in



fresh or marine water  (see Table  5).  Chau and Saitoh  (1973)  were  unable  to



detect  methylmercury  (detection   limit  0.24  ng  Hg/1)  in  unfiltered  Great



Lakes water, and measured 0.5  to  0.7 ng  Hg/1  in four  small mercury-polluted
                                     C-14

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                                                 TABLE  5

                           A Survey of Reported Methylmercury Concentrations in
                                              Natural Waters*
CH3Hg CHaHg Cone Total Hg Cone CH3Hg
Location Detection (ppt) (ppt)
Limit Mean/Range Mean/Range Total Hg
ng/1 ng/1 ng/1 %
Canada
Most Lakes <0.25 <0.25
and Rivers
Lake St. Clair)
Clay Lake ) 0.5-1.7
Pinchi Lake )
Sweden
Uncontaminated 0.1 0.1 <10 <1
Lakes
U.S.A.
Mississippi 1.0 1 30-40 1-3
River
N.W. Quebec
Rivers <0.5 <0.5 <0.5 5-50
References
Chow and Saitoh (1973)
Chou and Saitoh (1973)
Jernelov et al. (1975)
Andren and Harris (1975)
McLean, et al. (1980)
*Source:  McLean, et al.  1980.
                                                    015

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lakes.  Andren  and  Harris (1975) could  not  detect methyl mercury  in  samples
of river and coastal waters of the eastern Gulf of Mexico  and  McLean,  et  al.
(1980) could not  detect  methylmercury in rivers in northwestern  Quebec  con-
taining 5 to 50 ng/1 of total mercury.   In all the studies  reported  in Table
5, methylmercury  accounted  for  less than  10 percent  of  the total  mercury
content of ambient water.
     Wood  (1976)  has  pointed  out  that,  as  a  result of  methylation  and
demethylation reactions,  the concentrations of methylmercury will  approach  a
steady state in any given  ecosystem.  The  steady  state  concentration  will  be
affected by  any environmental factors  that  influence  either  or  both  reac-
tions.   Many factors  may be  involved, some  of  which  have  been  mentioned
above.  However,  there  is  a need  for   further  studies on  the  dynamics  of
methylmercury in the environment.
                                   EXPOSURE
Ingestion from Water
     The concentrations  of mercury in  rainwater were  reported by Stock  and
Cucuel (1934) to average  200 ng  Hg/1,  and to range from 50 to  480  ng  Hg/1  in
Germany.  Nearly  40 years  later, Pierson,  et al.  (1973)  reported  that rain-
water samples in  the  U.K.  usually contained  below 200  ng Hg/1.    In  Sweden,
Eriksson (1967)  found  values of up  to  200  ng Hg/1  and  Brune  (1969)  noted
values of approximately 300 ng Hg/1 in  rainwater.  Values  of mercury  concen-
trations in  snow show considerable  variability  and  probably  depend  greatly
upon  collection  conditions  and  upon  how long  the  snow  has lain  on  the
ground.  Straby (1968) noted  values  of  80 ng Hg/kg in  fresh snow  but  400  to
500 ng Hg/kg in snow that may have partly melted or evaporated over the win-
ter.   Analyses of the  Greenland  ice sheet by Weiss, et al.  (1971)  and Weiss
(1975) indicate values in  the range  of  13 to 230 ng  Hg/1  with no definite
trends according to  the age of the ice sample.
                                     C-16

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     The WHO  expert  group (WHO,  1976) concluded that  levels  in noncontamin-
ated freshwater were less than 200 ng  Hg/1.  Stock  and Cucuel  (1934)  report-
ed  values  in the  range of  10 to  50 ng Hg/1  of drinking water  in  Germany.
The CEC  International  Symposium  reviewed data on over  700  samples  collected
from drinking  water  and  found that  out of a  total  of 193 samples where  Hg
was found,  153 had  values  below 0.25  ug/1.   No  value  above  0.8 ug/1 was
detected.   The  U.S. EPA (1975b) established  that only  2.5  percent of  512
drinking water  samples had mercury  levels  which exceeded the  proposed  1975
Federal  standard  for drinking water  of  2,000  ng Hg/1.   A  geological  survey
of  mercury  in U.S.  rivers  and  estuaries  reported by Wershaw (1970)  found
that more  than  half of  the  73 rivers that were sampled  had  mercury  concen-
trations lower than  1,000 ng Hg/lg  and  34  of  the rivers had  concentrations
of  less  than  100  ng  Hg/1.  Windom in  1973, reporting  on  measurements  of the
Savannah estuary found  that concentrations  ranged up to 450  ng Hg/1.
     Fitzgerald  (1979)  has   summarized  data  on mercury concentrations  in
estuarine waters.   Values are reported in the  range 2  to  450  ng/1.   However,
these  values  refer to  total  mercury,  i.e.  both  dissolved and  that found  on
suspended solids.
     Reported mercury  concentration  in  coastal  waters  also  refer to  both
dissolved and particulate mercury  (Fitzgerald, 1979).   The  mean  values  from
8 different studies did not exceed  62 ng/1.   The  median value  was  17 ng/1.
     Levels of mercury  in ocean  waters  are  usually below 300 ng  Hg/1.  Stock
and Cucuel in 1934 reported  a mean value of 30 ng Hg/1.  Hosohara (1961) re-
corded mercury levels at different depths in the Pacific; values  on the  sur-
face were  about 80 to  150 ng Hg/1,  and  values at a depth of  300  meters  were
found  to  range  between  150  and  270  ng  Hg/1.  Further details on the  ocean
mercury  levels have  been given  in  the publication by  the U.K.  Department  of
                                     C-17

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the Environment  (1976).  A  recent  review by Fitzgerald (1979)  indicates that
95 percent of reported mean values are below  126  ng/1  with  a median value of
about 15  ng/1.   Matsunaga,  et al. (1979),  in  the most recent  report on mer-
cury in waters, claim that 5 to 6  ng Hg/1  "may be a  reliable value for base-
line of  mercury  in  unpolluted oceans," which  is  roughly  10  to  100 times
lower than  concentrations reported  above.  The  authors  (Matsunaga,  et  al.
1979) attribute  the  wide scatter  in  previously reported values  to problems
in analytical techniaues, i.e., contamination.
     Most samples of drinking  water  obtained  in the  United  States and Europe
have mercury levels  below  50 ng  Hg/1.   Assuming a  daily  consumption of  2
liters of water  by the 70 kg  standard man, this  would correspond to a daily
intake of 100  ng Hg.  Values  up to  200  ng Hg/1  have  been  reported in water
in areas  with  minerals rich  in  mercury.  This concentration  would indicate
an intake of 400  ng  Hg/day.   Most  mercury in  fresh water is probably in  the
form of  complexes  of Hg   .   Gastrointestinal  absorption  of  this  form  of
mercury  is  less  than  15  percent.   Thus,  an  intake of  400 ng  Hg/day would
correspond  to  a  retained dose  of  less  than  100 ng  Hg/day.   The  current
drinking water  standard  in the United  States  is  200  ng Hg/1.   This corre-
sponds to a  daily intake of  400  ng Hg  or an  estimated retained  dose of 60
ng Hg.
Inqestion from Foods
     The U.K. Department  of  the Environment (1976) and  the National  Academy
of Sciences  (1978) have reviewed the results of a large  number  of surveys of
mercury  concentrations  in  food.   These surveys  uniformly indicate  that  a
distinction  must be made between fish and  nonfish food.   In foodstuffs other
than fish and fish  products,  the concentrations  of mercury are  so low as to
be near or below the limit of  detection  of mercury by  the  analytical  methods
                                     C-18

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used  in  reported  studies.  In  the  United States, figures from  surveys  car-
ried  out  by  the  Food and  Drug  Administration  indicate that most  foodstuffs
have  total  mercury  levels  below  20 ng Hg/g.   Meat  and poultry may  contain
levels up to 200 ng Hg/g  (NAS,  1978).   In view  of the  uncertainties  in these
numbers,  it  is impossible to  calculate  average daily  intakes  for  nonfish
food  in the United States.  A low  intake  of mercury from nonfish  sources  is
consistent  with   the finding  that  nonfish eaters  have  the  lowest blood
concentration of mercury.
     A variety of surveys  have  been  carried  out in  the United  States  of  con-
centrations of mercury and  the  forms  of mercury in fish (NAS, 1978).  These
surveys  indicate  that  the  average concentration  of  mercury in most  fish  is
less  than  200  ng/g,  with  virtually all  the mercury  in fish  muscle in  the
form  of methylmercury compounds.   However,  certain  large carnivorous  oceanic
fish can regularly develop  much higher levels.   In general, over  50  percent
of swordfish tested  had  values  more than 1,000  ng/g.   Observations on 3,000
samples of canned  tuna   indicated  an  average  total  mercury concentration  of
approximately 250 ng/g,  with  4  percent of the  samples  being above 500 ng/g.
Concentrations  much  higher than  these,  ranging  to  over  20,000  ng/g,   have
been  reported in  freshwater fish  caught in heavily polluted areas (Fimreite
and Reynolds,  1973).  The  oceanic  fish  in Minamata  Bay in  Japan also  had
values of this  order  of  magnitude.
     The age or length or  weight of  the fish appears  to be  an  important  fac-
tor in determining the mercury  concentration in fish muscle for both fresh-
water and marine fish; the  older the  fish,  the  higher  the mercury  concentra-
tion.   This is  consistent with the report that  the halftime of methylmercury
in fish  is  of  the order of 1,000 days  (Miettinen,  et al.  1969;  Miettinen,
1972).  Thus,  accumulation might be expected to occur  throughout the  life  of
                                     C-19

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these species.   In  general,  fish  that are carnivorous and are at the  end  of
a food chain tend to have the highest concentrations.  Thus,  freshwater  fish
such  as  the  northern pike and oceanic  fish  such as the shark and  swordfish
have  elevated  mercury levels  compared  to  other fish.  Marine  mammals can
also  accumulate  mercury.   For example,  the livers  of  seal  may attain  very
high concentrations of total mercury  in  the  order of 340,000 ng/g, but  over
90 percent of  this  is  in the form of inorganic  mercury  probably combined  in
an inert form with  selenium  (Koeman,  et  al.  1973).   Nevertheless,  sufficient
amounts of methylmercury  are found  in seal tissue,  including liver,  so  that
individuals  consuming  seal   meat,  such  as  Eskimos,  may develop  high blood
concentrations of methylmercury (Galster,  1976).
     Observations on  museum  specimens  of tuna  fish and  swordfish  suggest
that  the  concentrations   of  mercury  have  not  changed  throughout  this  cen-
tury.  For  example, Miller,  et  al.   (1972)  found mercury  concentrations  in
tuna ranging from 180 to  640 ng/g, which  may be  compared with present values
in tuna ranging  roughly from 200  to  1,000  ng/g wet weight.  The lack  of ob-
servable change  in  mercury  levels in tuna and other oceanic  fish  is  consis-
tent with the large reservoir of  mercury in the oceans.
     The U.S.  Department  of Commerce (1978) has published data relating  to
the intake of mercury from fish in the diet  of the  U.S.  population.   Mercury
analyses were  made on the  edible tissues of  19,000 samples of fish  repre-
senting  all  major  recreational  species of  the   U.S.  collected  in  1971-73.
Information  on  seafood  consumption  was  obtained from  a   survey  of  25,647
panelists who  maintained  a  diary of their fish  consumption.  One-twelfth  of
the  panelists  recorded consumption  each  month  for 1  year  from  September,
1973  to  August  1974.   The  selected  data from  these  studies  are given  in
                                     C-20

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Table  6.   Approximately 95  percent  of the  panelists  reported eating  fish.
Tuna fish was by  far  the most  popular  item with 68 percent of the  fish eat-
ers reporting they ate  tuna  fish.  Since  20 percent  did  not report  the  spec-
ies of  fish  consumed,  and  assuming that  a  high  proportion  of this group  in
fact consumed tuna, the proportion eating  tuna  would be  about three-quarters
of  the  test  population.   By comparison,   the  next most  popular  species  of
fish was flounder, eaten by only 13 percent.
     The average  concentration  of  mercury in tuna is  one  of the highest  in
the group of  fish species  consumed by more  than  5 percent  of the  panelists.
It  is  clear, therefore,  that  the  consumption of  tuna  fish  in  the United
States  accounts  for  most  of  the  dietary  intake  of  methylmercury, as  this
form of  mercury  accounts  for  more than  90  percent of the total  mercury  in
tuna and most other species of fish.
     The data in  Table 6 do not allow an estimate of the  average  daily in-
take.   However,  if we assume (a) FDA figure  of 27 g fish/day  as the upper  95
percent of fish  intake in the  U.S.  population;  (b)  an average value of 220
ng Hg/g for mercury in tuna; and (c) that  75 percent of  the fish consumption
is  tuna,  it follows  that  95  percent  of   the  population  consumes   less  than
4,500 ng Hg/day  as methylmercury from tuna.  Contributions from other  fish
listed  in  Table   5 would  be less  than 1,000  ng  Hg/day  assuming an  average
concentration of  100 ng Hg/g fish.   Thus,   it seems likely that 95 percent  of
the population will  consume less than 5,000 ng Hg as methylmercury per day
from fish.   If  the average  daily  fish consumption in the  United   States  is
taken as 18.7  g  instead of  27  g  (Cordle,  et al. 1978), the  average methyl-
mercury consumption from fish would be  3,000 ng Hg/day/70 kg person.
     The U.S. Department of  Commerce Report  (1978) did not  give estimates  of
daily intakes of  mercury from  fish.  The  report did,  however, calculate the
                                     C-21

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Species3
                                   TABLE 5

            Average  and Maximum Mercury Levels  in Species of Fish
                Eaten  by 2  Percent or More of  24,652 Panelists*
Mercury concentration^
   ug Hg/g fresh weight


Tuna (light)

Shrimp
Flounder
Perch (marine)
Salmon
Clams
Cod
Pollock
Haddock
Herring
Oysters
Panelists
(percent)
68

21
13
10
10
9
6
5.9
5.8
5.1
5.0
Average

0.14 (skipjack)
0.27 (yellow fin)
0.05
0.10
0.13
0.05
0.05
0.13
0.14
0.11
0.02
0.03
NumberC
of
Maximum Fish in

0.39
0.87
0.33
0.88
0.59
0.21
0.26
0.59
0.95
0.37
0.26
0.45
sample
70
115
353
1179
268
806
584
134
227
88
272
260
*Source:  U.S. Dept of Commerce,  1978.

aApproximately 21 percent of the  panelists did not report  the species  of
 fish consumed.  Approximately 6.1 percent of the panelists  consumed other
 species of finfish.
^Numbers are rounded to two decimal places.
CThe fish were sampled at source  and are not samples  of the  fish  consumed
 by the panelists.
                                     C-22

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probability  of  individuals exceeding  an average daily  intake of  30,000  ng

Hg/70 kg  body weight.   It concluded  that,  under the  previous  FDA guideline

of 500 ng  Hg/g  fish, 99.89 percent of the U.S. population would have a daily

intake of  less  than 30,000 ng Hg/70  kg  body weight.  The report  also esti-

mated that 99.87 percent  would be  below  this intake figure under the current

FDA guideline of 1,000 ng Hg/g fish.

     The  National  Academy of Sciences (1978)  criticized  the  U.S.  Department

of Commerce  Report  (1978)  because "consumption  rates  were  figured  at  less

than normal  portions and  at minimum mercury levels."  They noted that Weight
        p
Watchers   diet  portions  of  fish are  larger  than the values of  portions  of

fish used  in  the  U.S.  Department of Commerce  (1978)  study.   McDuffie (1973)

has  reported  intakes   of mercury  by  41  dieters   in  New York   State.   He

reported  that 25  percent  consumed between  9  and  16  gg  Hg/day,  the second

ouartile  between  17 and  26,  the third  quartile  between  27  and 38,  and  the

highest auartile from 40 to 75 ug Hg/day.

     Given the  difficulties in accurately estimating dietary  intakes of mer-

cury, it  is  surprising that no  comprehensive  surveys have been  reported  on

blood concentrations of mercury  in representative  samples of  the  U.S. popu-

lation.    Goldwater (1964) reported on  a study  involving  15  countries  and

1107 samples  and  found that  concentrations of  total  mercury  in  blood  were

below 5 ng Hg/ml  in 77 percent  of  the samples and  below  10  ng Hg/ml  in  89

percent of the samples.   The  Swedish Expert  Group (1971) noted  that blood

concentrations  in  the  general  population  in  Sweden were influenced  by  fish

consumption.   Blood concentrations  were  in the range of <1 to  6  ng Hg/ml  in

people having  low  or zero fish  consumption.   High  fish  consumers,  particu-

larly those  consuming   large  carnivorous oceanic  fish,  develop much higher
                                                                       p
blood concentrations.   In McDuffie's  study  (1973)  on Weight  Watchers ,  two
                                     C-23

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of  the  41 dieters  had maximum  blood  concentrations between  50  and  100  ng
Hg/ml, which is consistent with  a  daily  intake  in  the range 50 to  100  yg  Hg
(using the model  discussed in the next  section).   Gowdy, et  al.  (1977)  re-
ported that 9  of  210 subjects whose blood  was  collected for  health  reasons
showed total  mercury  levels  above  50  ng  Hg/ml,  and  4 were  above  100  ng
Hg/ml.  The form of mercury was  not  identified  so  that  these  high  values  may
not have  been  due to the intake of  methylmercury  in  fish.  However,  the  re-
lationship between  inorganic  and methylmercury  may be more complicated than
previously suspected because  of  a  recent report on dentists  in which methyl-
mercury levels were  found  to  be five times  higher in dentists than  in con-
trols not exposed to inorganic mercury (Cross,  et al. 1978).
     A bioconcentration factor (BCF) relates the concentration  of  a chemical
in  water  to  the  concentration  in  aouatic  organisms.  A number of attempts
have  been  made to determine  the BCF experimentally.  Using  mercuric  chlor-
ide, Pentreath (1976a) found  a BCF of  about 250 for  muscle of plaice (floun-
der).  Kopfler (1974) obtained a value of about  10,000 for oysters.
     The  BCF  has  also been determined experimentally for  methylmercury com-
pounds.    Tests with  freshwater  fish  have obtained BCF  values  for  methylmer-
cury  up to 8,400  for rainbow trout  (Reinert, et al.  1974), 20,000  for brook
trout (McKim,  et  al. 1976),  and 63,000  for fathead  minnows  (Olson,  et  al.
1975) for a  geometric mean  of  22,000.   For saltwater fish,  a steady-state
BCF  of  about   1,200  was  predicted  for the  plaice (Pentreath,  1976a)   and  a
value of  1,100 was found for skate  (Pentreath, 1976b) for a  geometric mean
of  1,150.
     Kopfler (1974)  found  that  oysters achieved BCF  values up  to  30,000  for
methylmercury, although many  of  the  animals  died in  the 60-day exposure.   No
data  are  available  concerning BCF  values for decapods,  but they would prob-
ably have values similar to those of saltwater fishes.
                                     C-24

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     The wide  range  of BCF values obtained experimentally  no  doubt reflects
the many  practical  and  theoretical  difficulties underlying such  determina-
tions.   The factors  governing methylmercury  accumulation  in  fish  are  not
completely understood  but  species,  age  of the fish  (or  length), position  in
the food  chain,  water temperature,  the  chemical form  of mercury,  are  su-
spected  as  being  important   (for   discussion,   see  Ottawa  River  Project,
1976).  The  chemical  and  physical  species of  mercury in  various  bodies  of
water will also vary with  salinity,  pH, etc.  as  discussed  previously in this
text.
     Given the  large  number of variables  involved and the  wide  range of  ex-
perimentally determined  BCFs,  i.e.,  from  250  to 63,000,  it would  seem  un-
realistic  to  attempt  to  apply these values  to  the  real conditions  of fish
exposure to mercury in natural waters.  Instead,  an  attempt has  been made  to
estimate  a practical  approximation  to the  true value  of the  average BCF.
These  practical   approximations  will  be  termed  practical  bioconcentration
factors (PBCF).   These values  will be calculated  as  the  ratio  of the average
concentration  of  mercury  in muscle  in one  species  of  fish  to  the  average
concentration of  mercury  in the body of water  in which  the species normally
lives.  These  values  are  listed  in  Table   7  for  three   bodies  of  water:
freshwater,  estuarine  and  coastal  and open  ocean   waters.   The species  of
fish chosen  are  that which are most freauently  consumed  in the USA,  i.e.,
trout  from  freshwater,   flounder  and  shrimp  from  estuarine  and  coastal
waters, and tuna  from  open  ocean  waters (see  Table  8).  The PBCF are  in  the
range 3,750 to 13,000.
     These calculations depend upon  a number of  assumptions.  The  basic  as-
sumption is that, on the  average, the concentration  of methylmercury in fish
muscle  is  related  to the  concentration  of  total   mercury in water.   This
                                     C-25

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                                   TABLE 7

           Estimate of Practical Bioconcentration Factors (PBCF) for
         the Most Freauently Consumed Fish  Living in Different Bodies
                                   of Water
water Body
Median Mercury
Concentration3
    (ug/g)
 Most frequently consumed fish

Species"    Mean mercury concen-
                 trationC
                   wg/1
PBCF
Freshwater
Estuarine
and
Coastal
Ocean
40
17
15
Trout 0.15d
Flounder 0.08
Shrimp
Tuna 0.20
3,750
4,700
13,000
     details see text

bThe most frequently consumed species in that body of water
 see Table 8 and Cordle, et al.  1978

cValues taken from Table 8.

dStanford Research Institute, 1975.
                                     C-26

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                                    TABLE  8

              Fish  and  Shellfish  Consumption  in  the  United  States
                         (September  1973-August  1974)*
                                        Percent of   Number ofMean Amount
                          Amount, 1C)6  total by   Actual users  per user,
                   Rank       Ib/yr       weight     (millions)    g/day
Total
Tuna (mainly
Canned)
Unclassified
(mainly breaded,
including fish
sticks)
Shrimp
Ocean Percha
Flounder
Clams
Crabs/lobsters
Salmon
Oysters/scallops
Troutb
Coda
Bassb
Catfishb
Haddocka
Pollocka
Herring/smelt
Sardines
Pikeb
Halibuta
Snapper
Whiting
All other
classified


1



2
3
4
5
6
7
8
9
9
11
12
12
12
15

16
17
18
18
20


2957

634



542
301
149
144
113
110
101
88
88
78
73
73
73
60

54
35
32
32
25

152
100.

21.4



18.4
10.2
5.0
4.9
3.8
3.7
3.4
3.0
3.0
2.7
2.5
2.5
2.5
2.0

1.8
1.2
1.1
1.1
0.9

5.1
197

130



68
45
19
31
18
13
19
14
9
12
7.6
7.5
11
11

10
2.5
5.0
4.3
3.2


18.7

6.1



10.0
8.3
9.7
8.6
7.6
10.6
6.7
7.8
12.3
8.1
12.0
12.1
8.6
6.8

6.7
17.4
8.0
9.3
9.7


*Source:  Cordle, 1978.

aMainly imports.
bFresh water.
                                     C-27

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might be true  if  (1)  methyl mercury on the average  is  a  constant  fraction  of
total mercury in water and  (2)  uptake of methylmercury either via the  gills
and from the food chain, depends  ultimately  on  average methylmercury concen-
tration in water.   Studies on uptake  of methylmercury  by perch in the Ottawa
River indicate  that  direct absorption via the  gills  is more  important  than
uptake from the food chain  (Ottawa  River Project,  1976).  The PBCF  given  in
Table 7  will  represent  the  overall  average  resulting from an interplay  of
the factors  operative  in  that  particular body  of water.   If a  systematic
change takes  place  in that  body of  water,  the PBCF  may  also change.  For
example,  acid  rain  may lead  to  acidification of  freshwater.   The  lower  pH
leads to  greater  accumulation of mercury  by fish   (Jernelov,  1980)  and  thus
increases the PBCF.
Inhalation
     In  1934,  Stock  and Cucuel  reported average  air  concentrations in the
general   atmosphere  in  Germany  to  be  20 ng  Hg/m .  Swedish  and  Japanese
findings made  30 years  later were similar (Fujimura,  1964;  Eriksson, 1967).
Sergeev  (1967)  reported  concentrations  averaging  10  ng Hg/m   in the  USSR.
McCarthy, et al. (1970), working  in Denver has  documented  the  lowest report-
ed  findings,  2 to  5  ng Hg/m .   In  the  San Francisco  area,  concentrations
                                      o
were in the range of 0.5 to 50 ng Hg/m ,  according  to Williston (1968).
     Isolated "hot spots" having  unusually high  concentrations of mercury  in
the atmosphere  have  been reported  near  suspected  points of emissions.  For
example,  air  levels  of  up  to 10,000 ng Hg/nr  near  rice  fields  where  mer-
cury fungicides had  been  used  and values of up  to  18,000 ng Hg/m  near  a
busy superhighway  in  Japan have  been reported  by   Fujimura  (1964).   Maximum
air  concentrations  of 600  and 15,000 ng  Hg/m  near  mercury  mines  and re-
                                     C-28

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fineries, respectively, were reported by McCarthy,  et  al.  (1970).   The high-
est reported  levels  of mercury in the  atmosphere is reported  Fernandez,  et
al. (1966)  who found  values of  up to 800,000  ng Hg/m3 in a  village  near a
large mercury  mine  in Spain.   The remarkably  high mercury vapor  levels  re-
ported  by  these  authors  indicate  a need  for  further investigations  into
localized high concentrations of mercury in the atmosphere.
    Many of these authors  have  suggested that  elemental  mercury vapor  is  the
predominant form of  mercury in the atmosphere  (NAS,  1978).   Observations  by
Johnson  and Braman   (1974)  at  a suburban site  in Florida indicate  that  ap-
proximately 60  percent of the mercury  in  the  atmosphere  is  in the form  of
vapor,  19 percent  is inorganic,   and  14.9 percent  occurs as  methylmercury
compounds.  Mercury  present in  a  particulate  form accounted for less  than 1
percent.  The  amount  of mercury bound to particulates  seems  to be  related  to
area of  industrialization  and urbanization.  For  example,  Heindryckx,  et  al.
(1974)  found  that  aerosol  mercury levels corresponding  to  remote  background
levels  in  Norway and Switzerland were as  low  as  0.02 ng Hg/m  .   In a heav-
ily industrialized area of Belgium near  Liege the aerosol  levels  noted were
as  high as 7.9  ng  Hg/m3.  In  New York City  (Goldwater,  1964) and  Chicago
(Brar, et al.  1969),  concentrations of particulate-bound mercury of  up to  41
and 14  ng  Hg/m3, respectively,  were observed.   However,  as pointed  out  by
the National Academy  of Sciences  (1978), considerable  technical  difficulties
present  themselves   in the  attempt  to  measure  particulate-bound  mercury;
methods development  and more reliable data  are needed in this  area.
    The  average  concentration  of  mercury  in  the ambient  atmosphere  appears
to  be  about  20  ng   Hg/m3.   Assuming a daily  ventilation  of  20  nr for  the
"standard 70  kg  man," and  assuming that 80 percent  of  the inhaled  vapor  is
retained,  the  average  daily  retention  should  be  320 ng  Hg/70  kg body
                                     C-29

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weight.   In  urban  and  industrialized areas,  it seems unlikely  that  the  mer-
cury concentration  in  the  atmosphere  will  regularly exceed  50 nq/m  ,  cor-
responding to  800  ng  Hg daily  retention.   The  contribution of  inhalation
where people may  be living  near "hot spots" is impossible  to assess without
further information on  air  concentrations  and  the  time  of residence  of  in-
dividuals in these areas.
     Occupational exposure  to mercury vapor occurs in  this  country (Smith,
et  al.  1970).    The current  threshold  limit  for  occupational  exposures  is
             3                                    3
0.05 mg  Hg/m .   Assuming  a  ventilation  of  10 m  during  the working  day,
a  5-day  per  week  exposure,  and an  average  time-weighted  air  concentration
which does not  exceed  0.05 mg  Hg/m ,  then  the maximum daily retention  from
occupational  sources should  not exceed 2,800  ug/70kg for  a 7-day week.
Dermal
     In general, absorption of mercury through the  skin  is  not  a  significant
route of human exposure.  However,  under certain  circumstances, such as  occ-
upational and medicinal exposure, it may be significant  (see  Absorption  sec-
tion) .

                               PHARMACOKINETICS
     The disposition of mercury  in  the body was reviewed  by  a  Task  Group  on
Metal Accumulation  (1973) and more  recently  by a WHO Expert  Committee (WHO,
1976).   Since the disposition of mercury in the body is highly  dependent  up-
on  the  physical  and chemical  forms of this  metal,  it will  be necessary  in
this section to  consider them separately.  Most  information  with regard  to
disposition  in man  and  animals is  available  for methylmercury  compounds  and
organic complexes of mercury  ingested  in the diet and  for  the  inhalation  of
mercury vapor.
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     In general,  insufficient  information  is  available  on  other  compounds of
mercury, except  for the mercurial diuretics,  to  allow an extensive  discus-
sion.   Because mercurial diuretics are  now virtually  obsolete  for therapeut-
ic use, a complete review of this topic is not called  for.
     Nordberg  (1976)  and the  Task  Group  on  Metal  Accumulation  (1973)  have
reviewed evidence for  suitable indicator media for methylmercury.  The  evi-
dence  reviewed below indicates  that  the blood concentration  of methylmercury
is a measure  of the accumulation  in the  body  and  the concentration in  the
target  organ, the brain.  Urinary excretion  is  a  poor indicator  of body bur-
den as  most of the  mercury  is  excreted  via the feces.  The  hair  is  probably
the  indicator  medium of choice as  not  only  does it  indicate current  blood
concentrations but  also, depending  upon the  length of  the hair  sample,  can
give a  recapitulation of past exposures.
     Caution, however,  should be observed  in  the  proper use  of these  indica-
tor media.  There is still  uncertainty  as  to  whether  the  brain concentration
exactly parallels the  blood concentration  in man.  Secondly,  the  blood  con-
centration could  undergo a  transient  increase in  individuals who have  re-
cently  consumed a large  amount  of methylmercury.   The hair sample has to  be
analyzed in  a  special  way  and  has  to be  collected,  transported,  and stored
under  special  conditions,   as   discussed  by  Giovanoli  and  Berg  (1974),  to
avoid the appearance of artifacts.
     There  is  no  satisfactory  indicator  medium  for  assessment  of  mercury
vapor exposure, body burdens,  and concentration  in  the target organ.  It  is
the practice  in  industry to use urinary concentrations on a  group basis  to
give an indicator  of exposures  and  body  burden.    However,  it seems likely
that urinary concentrations may  reflect  kidney  levels  rather than concentra-
tions in the target  tissue  of the brain.
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     Since  several   exponential  terms  are  required  to  describe the  blood
curve following a brief mercury  vapor,  muHicompartment  pharmacokinetics  are
implied for man.  Thus, an  isolated  blood  sample  will  not provide any infor-
mation regarding exposure or  body burden.   Serial samples, however,  may  in-
dicate the existence of a steady state  or  give limited information about  re-
cent  exposure.   If  individuals   are  in  steady  state,  correlation  between
time-weighted average  air concentrations  and  blood concentration  should  be
expected.  This was confirmed by  Smith,  et  al.  (1970)  in chronically exposed
workers.  The authors  observed  about a 49  yg/100 ml  increase  in  the steady-
state blood  level  for  each 1 mg/m   increase  in  the blood exposure concen-
tration.
     The  same considerations  with regard  to  indicator media apply  to  inor-
ganic mercury as to  inhaled mercury vapor.  It  is  likely that urinary mer-
cury  excretion  primarily reflects the  accumulated  amount in  kidney tissue.
Conclusions about the  role  of blood as  an  indicator medium cannot  be  made,
since little is known  about the  biological  halftimes of  mercury in the  blood
compartment versus other tissues.
Absorption
     Methyl mercury and  Other  Short Chain  Alkyl Mercurials:   No quantitative
information is  available  on the  absorption of the  short-chain  alkyl mercur-
ial  compounds  through  human  skin.   However, cases  of severe  poisoning  have
occurred  following   the  topical   application,  for  medicinal  purposes,   of
methylmercury compounds (Tsuda,  et al.  1963; Ukita,  et  al.  1963;  Okinata,  et
al.  1964;  Suzuki  and  Yoshino,  1969).   Although,  in these  cases,  the main
pathway  of  intake  was  probably  through skin,  the possibility  of some  inha-
lation exposure cannot be excluded.
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     Likewise,  no  specific  data  are  available  on the  inhalation of  alkyl
mercurial compounds.  The  Task  Group on Metal Accumulation  (1973)  suggested
that the  retention  of  the inhaled mercurials would probably  be  on the  order
of 80 percent.  These conclusions were  based  mainly on  the  diffusibility and
the  lipid  solubility of  many of the  compounds  of methylmercury.   Further-
more, no quantitative information  is available  on dusts and  aerosols of the
alkyl mercurial  compounds.  Many of these compounds  have  been used in the
past as  fungicides,  resulting in occupational exposures  of  workers.   Since
some of these occupational exposures  have  led to severe poisoning  and death,
it  seems  likely  that  lung   retention  would  be  high,  although  both   skin
absorption and gastrointestinal  absorption might  also  have played a role.
     Several Quantitative  measurements  have been  made  on  the absorption  of
methylmercury compounds  in the  gastrointestinal   (GI) tract.   Experiments  on
volunteers  by  Aberg, et  al.  (1969)  and  Miettinen (1973)  have  demonstrated
virtually complete  absorption  in the  GI  tract  whether the  methylmercury  is
administered as  a  simple  salt  in solution or  whether it  is bound  to  pro-
tein.  The  findings of  the  tracer  studies  have been confirmed in  observa-
tions of volunteers  who  ingested  tuna fish for several days  (Turner, et al.
1974, 1975).   Shahristani and coworkers  (1976),  in  studies  of the  dietary
intake of methylmercury  in homemade  bread  contaminated with a fungicide, ob-
tained results consistent with a high degree of  absorption from the diet.
     No Quantitative information  is  available on  the  other  short-chain  alkyl
mercurials.  However, the  fact  that several outbreaks of poisoning have oc-
curred due  to  the  consumption of homemade bread  contaminated with ethylmer-
cury fungicides  suggests  that  this  form  of mercury  is  also well  absorbed
from the GI tract.
                                     C-33

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     Age  and  sex  differences  in  GI  absorption  of methylmercury  compounds
have not  been  reported.   However,  the fact  that  very high  blood  concentra-
tions of  methylmercury were attained in infants who had  ingested  methylmer-
cury solely  in  their  mothers'  milk  suggests  that  absorption  in  the  very
young is substantial (Amin-Zaki, et al. 1974b).
     Mercury Vapor and Liouid Metallic Mercury:  About 80 percent  of  inhaled
mercury vapor  is  retained  as evidenced by observations of humans  (Teisinger
and  Fiserova-Bergerova,  1965;  Neilsen-Kudsk,  I965a;  Hurch,  et  al.  1976).
Teisinger and Fiserova-Bergerova (1965) proposed that  the vapor was absorbed
across the walls of the bronchioles and larger  airways of the lung,  but sub-
seauent evidence  points  strongly  to the alveolar regions  as the predominant
site of absorption into the blood stream (Berlin,  et al.  1969).
     The  importance  of  skin  as a  pathway for  transport  of  metallic  mercury
into the  blood stream is debatable.   Juliusberg (1901) and Schamberg,  et al.
(1918)  indicated  that  aporeciable  skin absorption of  metallic mercury takes
place in  animals.  However,  the possibility  cannot  be  excluded that some in-
halation exposure also occurred in these experiments.
     The  gastrointestinal  absorption  of  metallic  mercury  in  the  liauid form
is  believed  to  be  very small.   Bornmann,  et  al.  (1970)  administered gram
ouantities orally to animals,  and  Friberg   and  Nordberg (1973)  calculated
that less than 0.01  percent of  the administered dose of  metallic mercury was
in  fact  absorbed.   Persons  have  accidentally  ingested several  grams  of
metallic  mercury  and  showed some  increase  in  blood   levels  (Suzuki  and
Tonaka,  1971).   However,  there are  many  case  reports  in the  literature  of
individuals consuming, accidentally or otherwise, gram Quantities  of  liauid
metallic  mercury  and the metal  passing through the  GI tract  into  the feces
without any ill effects.
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     Salts  of  Inorganic Mercury:   No  Quantitative information  is  available
on  the  absorption  of  mercury  in the  form  of  inorganic  mercuric  (Hg  )
salts  by human  skin.   However,  solutions of  mercuric  chloride  have  been
shown to be absorbed by guinea  pigs;  5  percent  of the mercury in a  2 percent
solution of mercuric chloride  was absorbed across  the intact skin  of  these
animals  over   a  5-hour  period   (Friberg,  et  al.  1961;  Skog and  Wahlberg,
1964).   If  such  a  rate  of penetration applied  to  human skin, one might  ex-
pect substantial absorption of mercuric  chloride salts in man.
     Information on  the  pulmonary deposition  and absorption  of  inorganic
mercury  aerosols is  lacking except  for the  experimental  work  on  dogs by Mor-
row, et  al.  (1964).  This group  reported that 45  percent  of mercury  adminis-
tered as mercuric  oxide aerosol  having a mean  diameter of 0.16 ym was clear-
ed within 24 hours; the remainder cleared with  a halftime of  33 days.
     Rahola, et  al.  (1971)  reported findings  on the  GI  absorption  of  inor-
ganic mercury given  to  ten  volunteers.   Eight  of the  volunteers, five  males
and three females, received  a  single  dose of mercuric nitrate bound to calf
liver protein,  containing  approximately  6 ug  of inactive mercury per  dose.
The  other  two  volunteers  received  an   acid  solution  of mercuric  nitrate.
During the 4 to  5  days  following treatment, an  average of 85 percent of  the
dose was excreted  in the feces;  urinary excretion was only  0.17 percent  of
the dose.  These findings suggest that GI  absorption  of  inorganic mercury  by
humans is less than  15  percent,  which correlates  with studies on experiment-
al  animals  (Clarkson,   1971).   Experiments  on  animals  indicate  that GI  ab-
sorption is greater  in  suckling  animals  than in  mature ones  (Kostial,  et  al.
1978).
     Other  Compounds  of Mercury:   The  aryl and  alkoxy-aryl  mercurials  are
used as  fungicides  and  slimicides, and  as  such  occupational  exposures  to
                                     C-35

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these compounds probably still occur.  To what extent these mercurials  reach
the water supply is not known.  In general, the aryl mercurials are well  ab-
sorbed  from  the  GI tract,  as evidenced  by  animal  experiments  (Clarkson,
1971).  Most classes of  these organo-mercurial  compounds undergo rapid con-
version to inorganic mercury in body tissues.
Distribution and Metabolism
     Methylmercury  and  Other Short-Chain Alkyl  Mercurials:   Details on  the
distribution and retention of methylmercury in man and animals were  reviewed
by  Friberg  and  Vostal   (1972),   by the  Task  Group  on  Heavy  Metal   Ac-
cumulation (1973),  and by  a WHO Expert  Committee  (1976).   The general pic-
ture  which  emerges  is  that methylmercury compounds,  after absorption from
the GI  tract,  distribute  readily  to all  tissues in  the  body.   Unlike  inor-
ganic mercury,  large concentration  differences  in  various  tissues  are  not
seen.  Methylmercury is characterized by its ability to  cross  diffusion bar-
riers and cell  membranes without difficulty.
     Tracer studies in volunteers  have revealed  that about 5 percent of  the
ingested dose is deposited in the blood compartment  after tissue  distribution
is completed.  About 90 percent of the methylmercury in blood is  associated
with  the  red blood cells.   Thus,  the red cell to plasma ratio is  between 10
to  1  and  20 to  1.   The  mercury in  the  red  blood cells  is almost  entirely
(more than 90  percent)  in the form  of methylmercury compounds.  However,  in
plasma approximately 25 percent can be in the form of inorganic mercury that
has  been  produced  by cleavage  of  the  carbon-mercury  bond  (Bakir,  et  al.
1973).  The  rate of decline in blood concentration  of  methylmercury  after
cessation of exposure can  be well  described by  a single biological  halftime
as evidenced by both tracer  experiments in volunteers and  also in  people  who
had  ingested methylmercury in substantial  amounts from  either fish or con-
taminated food  (see Table  9).  The  tracer experiments  reveal  a halftime  of
                                     C-36

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approximately  50  days.  However,  the range  of halftimes  reported  in  both
tracer experiments  and  in  people having  substantial  exposures covers a  wide
range.  Whether this  range  of values is  due to  individual  differences or  to
experimental or observational inaccuracies  in  the measurements  is  not clear.
     Based  on  observations  in  animals,  the  entry of the  mercury into the
brain is delayed by a few days as compared to entry into other tissues (Nor-
seth  and   Clarkson,  1971).   According  to  observations  on volunteers,  the
amount transferred  to  the  head  region following the  ingestion of a single
dose of radioactive tracer  is about  10 percent  of  the  body  burden after  tis-
sue distribution is complete.  However, only three subjects were  involved  in
this study  (Aberg,  et  al.  1969).  There  is a great need for more data which
would allow  estimation  of  the amount  of  mercury  that enters  this critical
organ (the brain).  In man,  the  brain to blood  ratio  is  in  a range of 5  to 1
or  10 to  1.  The biological  halftime  of  methylmercury in  the  brain  is  not
well described in man, but  the observations by  Aberg,  et al.  (1969) of three
volunteers indicate a halftime in roughly the same range as that  observed  in
blood and  in  the  whole body  (Table 9).   Whether or not  the halftimes  in
brain and blood are  identical  is an  important consideration in the decision
to use blood as an indicator medium for brain  concentrations.
     The concentration  of  methylmercury in other  tissues  such  as  muscle,
liver, and  kidney usually  does  not  vary by  more  than a factor  of  2  or  3,
with the highest concentrations  being  found in  the  kidney  cortex.  In  mus-
cle, the  mercury  is usually almost  entirely in the  form  of methylmercury,
but in liver and kidney a substantial proportion can be present as inorganic
mercury.   Most of this  evidence  is based  on studies using  animals.  Autopsy
data in Irao indicate  a  substantial  proportion  present as  inorganic mercury
in the liver (Magos, et al.  1976).
                                     C-37

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                                            TABLE  9

                            Mercury Intake  and  Biological  Halftimes
No. of
subjects
5
15
5
5
16
48
aMean
bRange
Halftimes (days)
Hg intake
(gg/kg/day) Body Blood Hair
trace 70a
trace 76 50
up to 5 — — (33-120)
up to 5
(58-164)c
up to 50 — 65
(45-105)
up to 50 — — 72d
(35-189)


References
Aberg, et al. (1969)
Miettinen (1973)


Birke, et al. (1967)
Skerfving, et al. (1974)
Bakir, et al. (1973)
Shahristani and Shihab


(1974)


C0ne person had a biological  halftime of  164  days.   The other four were in the range of
 58-87 days.
     data were distributed bimodally.   One  group  accounting for 89 percent of the samples
 had a mean value of 65 days and the other  group  had  a mean value of 119 days.
                                               C-38

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     Methylmercury  is  readily transferred  from mother  to  fetus across  the
placenta.  At birth  the  concentration  in  the umbilical cord or  infant  blood
is usually  slightly  higher  than  that observed  in maternal  blood.   In  obser-
vations of women having normal pregnancies and on a low  to moderate fish  in-
take,  Tejning  (1970) reported that  methylmercury in  the  fetal  blood  cells
was  about  30 percent  higher than  in  the  maternal  cells.  Suzuki,  et  al.
(1971)  confirmed  the  finding of higher  fetal  blood concentrations.   The
studies on  the  outbreak  of  methylmercury  poisoning  in  Iraa  (Bakir,  et  al.
1973;  Amin-Zaki,  et  al. 1974a,  1976) also  showed that  methylmercury  was
readily transferred  across  the placenta,  resulting  in higher  concentrations
in fetal blood  at  the time  of delivery.  Apparently the differences  between
fetal and maternal blood are due  to  differences in  concentration in the  red
blood cells rather than to differences  in  plasma concentrations.
     Methylmercury is  secreted  in mother's milk.  The studies of the  Iraai
outbreak revealed  the close  correlation between maternal milk  and blood con-
centrations, with  the milk  concentration  on the  average being about  5 per-
cent of the simultaneous blood concentration  (Bakir, et  al.  1973).  About 40
percent  of  the  mercury  in  milk  was  found  to be  in  the  inorganic  form.
Skerfving,   et   al.  (1974),   in  a  study of  15  lactating  females  following
intake  of  methylmercury  from fish,  also  noted a  correlation  with  blood
concentrations  but  found a  smaller percentage  (approximately  20 percent)  of
mercury in the form of methylmercury  in the  milk.
     Mercury  is accumulated  in  head  hair  after exposure  to methylmercury
compounds.   A variety of  observations  (Table 10) indicate  that  the hair  to
blood concentration ratio is  about 250 to 1 with  considerable  variation from
one study to another.  Mercury is  accumulated in the hair at the time of  its
formation and  thus,  in  freshly  formed hair,  the concentration  in hair  is
proportional to  that  in  blood.   Once incorporated into  the  hair sample  the
                                     C-39

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                                   TABLE 10

 Relationship between Concentrations of Mercury in Samples of Blood and Hair
        in  People having Long-term Exposure to Methylmercury from Fish*
No. Of
subjects
12
51
50
45
60
Whole blood (x)
(mg/kg)
range
0.004
0.004
0.005
0.002
0.044
- 0.65
- 0.11
- 0.27
- 0.80
- 5.5
Hair (y)
(mg/kg)
range
1
1
1
20
1
- 180
- 30
- 56
- 325
- 142
Linear regression
y =
y =
y -
y =
y -
280x
230x
140x
260x
230x
- 1.3
+ 0.6
+ 1.5
+ 0
- 3.6
*Source:  WHO, 1976
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concentration of mercury  is  stable  and thus,  as the hair  is examined  longi-
tudinally, a history is obtained of previous blood concentrations  (Clarkson,
et  al.  1976).   Hair grows at  approximately  1  cm per month (Shahristani  and
Shihab, 1974) so  that  the measurement of  each  1 cm  segment  corresponds to
the  average  blood  concentration  during  a particular  month.   The  hair is
therefore a very useful medium to recapitulate  past  exposures  as well as to
give  information  on current exposure  to methylmercury.   An  example of  the
close parallel between concentration in  hair and blood  is  shown in  Figure  2
(Amin-Zaki, et al.  1976).
     Methylmercury  is  metabolized  to  inorganic mercury  in  animal   tissues
(Gage,  1961;  Norseth  and  Clarkson,  1970).  In  man,  conversion to inorganic
mercury is an important process in excretion,  as shall be discussed later.
     Mercury Vapor and Liouid  Metallic Mercury:  Approximately 2 percent of
an  inhaled dose of  radioactive mercury vapor  was found to be  deposited  in  1
liter of whole blood  after  tissue  distribution was  complete  (Hurch, et  al.
1976).  The  concentration in  the  red blood  cells of  these  volunteers  was
higher than that seen in plasma.  The  halftime  in  blood was estimated to be
about 4 days, accounting for at least  60 percent of  the mercury deposited in
the blood volume.
     An accidental mercury vapor exposure  of  a  family has supplied  some  ad-
ditional information concerning halftimes  (Figure  3).   The major portion of
the exposure probably occurred within a  half-hour period with  a  smaller  pro-
tracted exposure over the  duration  of an evening.  It appears  that there  was
an  early rapid decline over  the first  few days postexposure,   and by about  5
to  7  days,  the  mercury in blood was  decreasing with an approximate  15-day
halftime which was maintained for the remainder of the  first month's postex-
posure.  Another family's exposure  to  mercury  vapor  involved  a husband  and
daughter who were exposed for  6 to  8 months in  the  home.   The wife had  ex-
perienced a prior  exposure for about 18 months in her workplace.  Samples of
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            I
300CK
2000-

1000-

 500


 200

 100

 50


 20-

 10

  5
                     a BIRTH
                   1
                        MOTH«»MC-UO
                        BA8Y-MC-13?
                                       o MOTHER'S W.OCO
                                       A MOTHER'S HAIR
                                       A MOTHER'S MILK
                                       • BABY'S 81000
3000
2000

1000

 500


 200

 100 ^

 50 |


 20 J

 10 J

  5 5
                   UKMOCM.TMjGSPrott.MXttClAN.ni. MMUM.MM IMU.1 MXiaKQCtMOiotCWHftl MM

                  >•— t?»	•«	1977	f-1973—|
                                       FIGURE 2.

      Concentration  of total  mercury  in  1  cm  segments  of  sample  of  mother's
hair,  whole blood,  and  milk,  and  baby's blood(postnatal  exposure).   Concen-
trations in milk and blood are plotted according to dates of  collection.

Source:  Amin-Zaki,  et al. 1976.
                                         C-42

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             en
             X
             en


             O
             O
             O

             OQ
             O
             cc.
             O
             z
                 200i

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blood were  collected  starting about one month  after cessation of exposure.
Therefore, an early and rapid fall in blood concentration due to short half-
time components was missed.   The  blood  concentration of mercury in the wife
declined, with  a  halftime  of 30  days.   The other  two family  members  had
longer  halftimes,  but their  blood levels  were sufficiently  low  that die-
tary mercury might have influenced the results.
     Evidence from animal experiments and from  isolated suspensions of human
blood indicate  that mercury vapor, once absorbed  into  the bloodstream,  can
undergo  oxidation  to  divalent mercury (Hg  ).  The  red  cells are an  impor-
tant site of this oxidation process,  which is believed to be mediated by the
hydrogen peroxide catalase pathway (WHO, 1976; Clarkson, et al. 1978).  How-
ever, the oxidation in the red blood cells is not sufficiently rapid to pre-
vent some of the  dissolved mercury vapor from persisting in the blood  stream
for sufficient periods of time to reach the blood-brain barrier.  Here it is
believed to cross  rapidly  into  brain  tissues where  it is again subjected to
oxidation processes.   A  scheme  for  the  pathway  of inhaled  mercury vapor
reaching the brain is given  in Figure 4.  Hurch, et  al.  (1976) made regional
body counts  on volunteers who had (Figure 4) inhaled a tracer dose of radio-
active mercury vapor.   They found that approximately 7 percent of the  inhal-
ed  dose  was absorbed  into  the  head  region  following completion  of tissue
distribution.   The halftime  in  the  head  region  was  found  to be  21 days
(Table 11).   This  halftime was considerably  shorter  than  that seen in other
tissues  in the body with the exception of  blood.
     The main site of  accumulation of mercury  in  the  body after inhalation
of  mercury  vapor  is  the kidney.   In  fact,  animal  experiments indicate that
as  much  as   90  percent  of  the  total  body  burden  can be  found  in  kidney
tissues  (Rothstein and Hayes,  1964).
                                     C-44

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           AIR
            Hg°
BLOOD
BRAIN
                                                                    X
                                                                   r
                                                            %  J
                                                            l_l«+ +

                                  FIGURE 4.

     A diagrammatic representation  of  the pathway of  inhaled  mercury vapor
(HgO)  to  the  brain.   The  oxidation  process   (HgO  Hg**)  is  depicted  as
occurring in the red blood cells and brain tissue.  Oxidation also occurs in
other  areas.   The ligands to  which Hg"1"1"  attaches  have  not been  identified
(depicted as S and X)  but  sulfhydryl groups are  suspected to be  involved.

Source:  Clarkson, 1974.
                                     C-45

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     Mercury can penetrate into the fetus after maternal exposure to mercury
vapor.  This rate  of  transfer appears to be  considerably  greater than  that
seen for the inorganic species of mercury (Clarkson, et  al.  1972).  However,
no published  information  is  available with regard  to  human exposures.  Ob-
servations  of  a family  accidentally  exposed  for a  brief  period  of time to
mercury vapor  indicated  that the mercury  concentration at  delivery  of the
baby was the same as that in  the mother.
     A summary of  the estimated biological  halftimes of mercury in the  body
following exposures to mercury  vapor  is  given in Table  11.  Most of the in-
formation  in  this  table comes  from  tracer  experiments  of  Hurch,  et al.
(1976) and  from unpublished observations of people who were  accidentally ex-
posed for brief  periods  of  time.  The whole-body  halftime and the halftime
in kidney tissue  seem to be  approximately the same  as  that  of  methylmercury
in man.
     Salts  of  Inorganic  Mercury:  Studies using  a variety of animal species
have shown that, in general,  the distribution of mercury after  doses of  mer-
curic salts or  inorganic mercury bound to protein  is similar to the distrib-
ution observed  after  exposure to  mercury vapor (Clarkson,  1972a,  b; Friberg
and Vostal, 1972).  However,  there  are important differences.   The red  cell
to plasma ratio  has been reported to  be 0.4 in humans  exposed to a  tracer
dose of  Hg    (Rahola, et al. 1971), whereas  the  amount in the red cells is
considerably higher after exposure to  mercury vapor (Cherian,  et al.  1978).
The most  dramatic  differences  lie  in  the  ability  to  penetrate  across the
blood-brain and placental barriers.   Relatively small amounts of the mercur-
ic  ion penetrate  the brain  or the  fetus  following  exposure  to  inorganic
salts as compared to mercury vapor and alkyl  mercury compounds.  Jogo  (1976)
has reported that  the blood-brain barrier of  suckling  rats is more permeable
to inorganic mercury than that of  adults.
                                     C-46

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                                           TABLE 11

                       Summary of Halftimes of Mercury in Human Tissues
Tissue
Blood*
Bloodb
Bloodb
Lunge
Kidneyc
Headc
Whole Bodyc
Exposure
Cone. Duration
mg/m3
0.1
0.1
0.05
0.1
0.1
0.1
0.1
20 min
few hours
months
20 min
20 min
20 min
20 min
First Component
Percent Deposited
60
90
d
100
100
100
100
t 1/2
days
4.0
2.0
d
1.7
64.0
21.0
58.0
Second Component
Percent Deposited
not detected
10
100
not detected
not detected
not detected
not detected
T 1/2
days

14.9
30




aCherian, et al. 1978
bClarkson, 1978.  For details,  see text.
CHurch, et al. 1976.
dNot measured
                                               C-47

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     Inorganic Mercury Accumulation  in  the  Kidneys:  Animal  experiments  have
shown that  as  much as 90  percent  of the body  burden  can be  found in  this
organ.  Inorganic mercury has the  ability to  induce  the  synthesis  of metal 1-
othionein or metallothioneinlike  proteins   in kidney tissue  (Piotrowski, et
al. 1974a,  1974b).  This ability is  shared  with  inhaled  mercury  vapor  (Cher-
ian and Clarkson, 1976).
     The  retention  of  mercury by  five  human  volunteers  after a single  dose
of inorganic mercury has been reported by Rahola, et al.  (1971).   The  whole-
body biological halftime averaged  45 days and was significantly  greater  than
the biological halftime observed for plasma (24 days) or  for  the red blood
cells (28 days).   Rahola,  et al.   (1971) reported that 0.2 to 0.4  percent of
the ingested dose was found in the  blood volume  1 day after dosing.
     Other  Compounds  of  Mercury:    The  conversion   of  organomercurial  com-
pounds to inorganic mercury  results  eventually  in a pattern of  distribution
that  is  similar  to  that  obtained  after exposure to  inorganic  salts.  The
kidney is the main organ of accumulation in  all  cases.
Excretion
     Methylmercury and Other  Short-Chain Alkyl Mercurials:  The  excretion of
mercury from the body in humans exposed  to  methylmercury occurs  predominate-
ly  by  the  fecal   route.   Less  than  2   percent  of  excretion occurs  in  the
urine.   The form of mercury in feces is  almost completely  the inorganic  form
(Turner,  et al.  1974), and  about  90 percent of the mercury in urine is  also
inorganic (Bakir,  et  al.  1973).    These  observations  indicate  that,  in  man,
an  important  step in the  excretion  process is  the  cleavage  of  the carbon-
mercury bond.
     The site of the cleavage of this carbon-mercury bond  in the body  is not
known.   Animal  experiments indicate there is a substantial biliary secretion
                                     C-48

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of  methyl mercury  raising  the  possibility  that   biotransformation  to  the
inorganic  form might  be  affected  by  microflora   in  the  gut   (Norseth  and
Clarkson, 1971).
     Mercury  Vapor and  Liouid Metallic  Mercury:   UVine  and  feces  are  the
main pathways  of  excretion  after  exposure to mercury vapor, although exhala-
tion of  vapor and excretion in saliva  and  sweat may contribute (Lovejoy,  et
al.  1974;  Joselow,  et  al.  1968).   Animal  data indicate  that,  shortly  after
exposure,  the GI  tract  is  the predominant pathway of excretion,  but as  the
kidney becomes more and  more  the  predominant site  of  storage of  mercury,
urinary  excretion  takes  over  (Rothstein   and  Hayes,   1964).    In  humans,
following  a  brief  exposure,  urine accounted  for   21 percent  of  the  total
urine  and fecal  excretion,  but  after  a  long-term occupational  exposure,
urine  contributed 58  percent  (Table  12).   Tracer  experiments using  human
volunteers  indicated  that  the specific  activity   of mercury  in  urine  was
unrelated to  the  specific activity in  plasma  (Cherian,  et al.  1978).   This
observation suggests  that  urinary  mercury  originates from a  large  pool  of
mercury  in the   kidney  rather than  from  glomerular filtration  of  plasma
mercury.
     Approximately  7 percent  of an inhaled  dose  of  mercury vapor was  shown
to be  excreted in the  expired air  of  humans.   The  majority of this  was  ex-
pired within  seven  days  and comprised  37 percent of  the  first  week's excre-
tion (Table 12).
     Quantitative information  on  the  excretion via  sweat and  saliva  is  not
available.  In workers experiencing profuse  perspiration,  amounts  of  mercury
excreted  in the sweat may exceed those of urine (Lovejoy,  et al. 1974).
     High  individual  variation  and great  day-to-day fluctuation  were  the
principal  features  of  urinary mercury  excretion   by workers  under  similar
exposure  conditions (Jacobs, et  al. 1964).   Copplestone  and McArthur (1967)
                                     C-49

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                                   TABLE 12

                   Parameters of Excretion of Mercury in Man
                      Following Exposure to Mercury Vapor
Excretion
Medium
Urine
Urine
Feces
Feces
Expired air

Cone.
(mg Hg/m3)
0.1
0.05 - 0.2
0.1
0.05 - 0.2
0.1
Exposure
duration
20 minutes
(years)
20 minutes
(years)
20 minutes
Percent of
Total Observed
Excretion
133
58b
49a
42b
3?a
aAveraqe excretion during first week after exposure (Hurch,  et al. 1976;
 Cherian, et al.  1978).

^Combined urine and feces (Tejning and Ohman, 1966).
                                     C-50

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 found  no correlation between urinary excretion and air'Concentrations.   They
 noted  that some  individuals excreted  extremely  large  amounts  of  mercury,
 some  in excess of 1,000 yg/1 without  apparent  ill effects.   Their own  find-
 ings  and their review of the literature  (Jacobs,'
-------
with analytical methodology, volatilization of mercury  from  urine  (Magos,  et
al. 1964), adsorption of  mercury to glassware, the diffusion of mercury out
of  plastic bottles,  and the  entrainment  of  mercury  into  the  participate
fraction of urine, all make  the  analysis  of urinary mercury  extremely diffi-
cult (Greenwood and Clarkson, 1970).
     In  conclusion,   although  correlation  of  urine  mercury  concentrations
with blood or  time-weighted  air concentrations may yield  consistent  results
when the data  from large  groups  of  people are  averaged, there is no explana-
tion is  at hand for  the  large fluctuations in  daily excretion by  individ-
uals.  However,  few   longitudinal studies have been  made,  and  all  measure-
ments to date  on exposed  workers with  one exception have measured  concentra-
tions  of  total  mercury.   Recently,  Henderson   and  coworkers  (1974)  have
pointed  to  the  importance  of  identifying chemical  forms  of  mercury  in
urine.   They  concluded  that dissolved elemental  vapor  in  urine might  be  a
better indicator than total mercury.
     The exhalation of mercury in expired air is a recent finding  in humans
(Hurch, et al. 1976).  The  short halftime reported by  these  workers  follow-
ing brief  exposure  to the vapor  suggests that mercury  in expired  air would
indicate only  recent  exposure.  However,  experiments on animals given  mer-
curic  salts  (Clarkson and  Rothstein,  1964;  Dunn,  et  al.  1978) reported  a
close  correlation  between the rate  of exhalation   and the  body  burden  of
divalent  mercury (Hg++).   During  chronic  exposures to mercury vapor,  the
body  burden  of  Hg++  may reach  levels at  which reduction  of  this  form  of
mercury  can  make a  significant  contribution to  loss by exhalation.   Thus,
sampling of  expired  air   at  appropriate times  after  inhalation  of  vapor may
provide information on both recent and  long-term exposure.
     Salts of  Inorganic Mercury:  Studies by Rahola,  et al.  (1971)  on volun-
teers who  ingested tracer doses of  inorganic mercury  revealed  that  urine and
                                     C-52

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fecal excretion were  approximately  eaual  after  the unabsorbed oral dose was
cleared by  the  GI tract.   The  whole body  halftime  of 45  days  observed in
these volunteers  is consistent  with excretion  in urine and feces, amounting
to a total of 1.5 oercent of the dose per  day.
     It is possible that urinary excretion could be  increased by  kidney dam-
age.  For example, Cember  (1962)  reported that  cytotoxic  doses  of inorganic
mercury could  lead to desauamation  of  renal tubular  cells,  resulting in a
sharp increase  in  mercury  excretion.  Magos  (1973) has reviewed other stud-
ies  where  agents producing  kidney  damage leading to  desauamation of cells
cause an increase in  urinary mercury excretion.
     Other  Compounds   of  Mercury:   Retention  halftimes   of  the aryl  and
alkoxy-aryl mercurials in  man are  generally not known.  Their rapid conver-
sion to  inorganic  mercury would suggest  that  their  halftimes would not ex-
ceed those reported in volunteers  discussed  earlier.  The mercurial  diuret-
ics generally have halftimes considerably shorter  than that reported for in-
organic mercury because of the rapid excretion of the intact mercurial.
     Mathematical Models of  Accumulation  of  Methylmercury in  Man:  The body
will continue to accumulate  methylmercury so long  as intake is  greater than
excretion until  a  steady state   is  obtained  where intake  and  excretion bal-
ance.  A common way to describe  the  progress of accumulation  in  the body is
in terms of  the biological halftime.  This concept  is useful, provided that
the processes of  transport  and  distribution in  the  body  occur  more rapidly
than the  elimination  step.  Thus,  the  single   biological   halftime can then
describe the  decline  in  not only the amount  in  the  body  but  also  in  the
concentration in various tissues.   As pointed  out by the  WHO Expert Commit-
tee  (1976),  if  tissue compartments  retain mercury with widely differing re-
tention halftimes, then the  whole-body biological  halftime would not be use-
ful and could give misleading toxicological  information.
                                     C-53

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     However, this evidence  indicates that  the  rate  of  decline  of mercury in
the whole body  and in  various  tissues  including the target organ can  be  de-
scribed by a single biological halftime.
     The  WHO Expert  Committee has summarized  the mathematical  expressions
relating daily  intake  to  biological halftime  and  accumulation  in  man.   These
derivations are Quoted below.
     In cases where the elimination of  a  metal  such as  methylmercury follows
a single exponential first order  function,  the  concentration in  an  organ  at
any time can be expressed by the following eauation:
               C  = CQe-bt	(1)
where:         C  = concentration in the organ at time t
               C   = concentration in the organ  at time  zero
               b = elimination constant, and
               t  = time.
The relation between the  elimination constant and  the biological  halftime  is
the following:
                     In 2
               T  -  ~
where:         T  = biological halftime, and
               In 2 (natural  logarithm of 2) = 0.693
     If data on  exposure  and absorption of the metal are  known,  then  it  is
possible to  predict  the body  burden  of the metal at constant  exposure over
different time periods.  If a constant fraction of the  intake is  taken  up  by
a certain organ,  the  accumulated  amount in that organ  can  also be  calculat-
ed.  The following expression  gives  the accumulated  amount  of  metal  in  the
total body (or organ):
               A  = (a/b)  (l-e-bt)	(2)
where:         A  = accumulated amount,  and
               a  = amount taken up by the body  (or organ)  daily.
                                     C-54

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At steady-state the following applies:
               A  = a/b	  .  (3)
      In  other words,  the  steady-state amount  in  the body  (or  organ)  A  is
proportional  to  the average daily  intake  and  inversely proportional to the
elimination  rate.   The latter  point will  be discussed  in a  later  section  in
relation  to human  hazards,  as  large individual  variations  in elimination
rates  imply  large  individual variations in  steady-state body burden, even  in
people having the same average daily intake.
     Equations  (1),  (2),  and  (3)  are illustrated  graphically  in  Figure  5.
During the  period  of  steady  daily intake  (assumed  to  be 10  wg/70  kg body
weight),  the amount in the body rises rapidly  at first,  reaching half its
maximum  (steady-state)  value  in a  time eouivalent to one elimination half-
time  (assumed to  be  69 days for methylmercury  in man).   After an  exposure
period equivalent  to five  elimination halftimes (approximately one year for
methylmercury),  the body  is  within   3  percent  of  its  final  steady-state
value.  The  steady-state body  burden  is 100 times the  average daily intake
assuming  an  elimination halftime  of  69 days.   Upon  cessation of exposure,
the  body burden will  immediately  begin  to fall,  following  an exponential
curve  that   is an  inverse  image of the accumulation curve.   Thus the body
burden will  have returned to within three  percent of pre-exposure values  in
five halftimes.
     In this example,  it is assumed that the hair-to-blood ratio is  constant
and eaual to  250 and  that  1 percent of the body burden  is  found in 1 liter
of blood in a 70 kg man.
     Eauation  3  is useful  in that  it predicts a  relationship between long-
term  dietary intake  and  the  concentrations  of  mercury  in  such  indicator
media  as  blood  and hair.    It  is  thus possible to test  the predictive value
                                     C-55

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         1000-1
j	I Exposure oeriod
	  Body burden & blood
	Hair
    -o °   400-
    > CQ
    T3 -o

    " S   200^
                          345     01

                             Number of halftimes
   3   4
                                   FIGURE 5.

     The changes  in the  body burden  and hair  and blood  concentrations of
mercury  during constant  daily  exposure (shaded  area)  and  after exposure.
This calculation was based  on a  daily intake of  10 ug of methylmercury  dur-
ing  the  exposure  period, an  elimination halftime  of  69  days,  and a hair to
blood concentration ratio of  250.

Source:  WHO,  1976.
                                      C-56

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of  equation 3  by carrying  out  dietary studies  on  exposed populations  and
measuring concentrations  of  methylmercury in blood  and  hair.   A  prediction
of  equation 3  is that once  the  individual  has  attained  steady  state,  the
concentration in  blood  should be  directly proportional to the  average  daily
intake.   This  prediction  was  confirmed in  a  study  by  Skerfving,  et  al.
(1974)  in a group of fish eaters in  Sweden.   Results  of  Skerfving1s  study,
along with  studies on other  fish-eating  populations, are summarized  in  Table
13.  In some cases, observations were made on concentrations in hair,  and  in
others, measurements of  blood concentrations  were made.   All have been  con-
verted  into  blood concentrations  for  comparative  purposes.  Furthermore,  it
is  possible  to  predict  the steady-state concentration  in  blood from  a  given
dietary intake with the kinetic parameters given  in the studies by Aberg,  et
al. (1969),  and Miettinen  (1973) on volunteers.   This  estimate  is  also  given
in Table 13.  The calculation involves the assumption  that 95 percent of  the
methylmercury was  absorbed from the  diet,  that  1 percent  was distributed  in
1 liter of blood,  and that the biological halftime in  blood  was approximate-
ly  50 days.   In general,  the factor relating the steady-state  blood  concen-
tration to the  average daily  intake  (the coefficient of  x; Table  13)  varies
from a  value of 0.3 to LO,  The low  values  for  this  coefficient have  been
attributed to the  difficulty  of  an  accurate estimate  of  dietary  intake  and
to  the  possibility that in  some  of  the populations studied the  individuals
had not attained  a true steady state.   Nevertheless, eouation  3 seems to  be
useful in that  it  allows comparison of the results of  various types of  stud-
ies, including  both  exposed  populations and volunteers.   A  recent study  of
five volunteers ingesting contaminated freshwater fish yielded  a coefficient
of about 0.8, close to the tracer prediction of  1.0  (Kershaw,  et  al.  1978).
Quantitative  accuracy   in  relating  dietary  intake  to  steady-state  blood
levels is of considerable  importance to  estimates of hazard to human health
from dietary intake of  methylmercury.
                                    C-57

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                                   TABLE  13
              Relationship of Steady-State Blood Concentrations
                      to Daily Intake of Methylmercurya
No. of Time of
subjects exposure
6+26& years
139+26b years
6+14b years
725C years
22 years
15 single tracer
dose
Avg. Ha intake
(ug/day/70 kg
Body Weight)
(x)
0-800
0-400
0-800
0-800
0-800
Steady blood
concentration
(ng/ml)
(y)
y=0.7x
y=0.3x
y=0.8x
y=0.5x
y=0.5x
y=1.0x
+ 1
+ 5
+ 4
+ 10
Source:  WHO, 1976
aFor details of these ealeulationSj  see text,
^Little or no fish consumption in this group.
cEstimated from  data on hair concentrations and  daily intake.  The hair to
 blood concentration ratio was assumed to be 250 and the average body weight
 of the population under study to be 60 kg.
                                     C-58

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     Thus  far,   the  discussions  have employed  average  values  for  various
parameters used  in mathematical modeling of  accumulation  of  methylmercury  in
man.   In  fact,   there  are  substantial differences.  The  biological  halftime
in man, as indicated  in  Table  11,  actually varies  over a wide range  of  val-
ues.   Shahristani  and  Shihab  (1974) have  published  the  observation  that
there  is  a bimodal distribution of  biological  halftimes as calculated  from
analysis of hair samples in  the  Iraai  outbreak.  As  shown in Figure 6,  these
authors found  that the  majority  of  a population  of 48  people  studied had
halftimes distributed around the  normal  value of about 65 days, but  about  9
percent of the  population  had  a  significantly different  distribution of
halftimes, averaging  about  119 days.   Greenwood,  et  al.  (1978)  have  noted
that the halftime in blood of  lactating females  (average  42  days)  is  signif-
icantly lower  than that  of nonlactating  adult females  (average  74  days).
The excretion of methylmercury in  milk is  not sufficient to explain  the re-
duced biological halftime in blood of lactating  females.
     Experiments on   mice  by  Doherty,  et  al.  (1977)  have  revealed  that
methylmercury is not  eliminated  from mice throughout their  suckling  period.
Observations  by  Landry,  et  al. (1978) revealed   that  changes  in  the  diet of
mice can also lead to  large  changes  in the biological  halftime of  methylmer-
cury.
     There are  important species  differences in the kinetics and  distribu-
tion of methylmercury.   For example,  the  blood to  plasma  ratio,  which is
about  10  to  1  for man  and other primates,  is as  high  as 300 to 1  in  rats.
The blood  to  brain ratios exhibit  substantial  species  differences with man
and other  primates  having  a ratio of  about  1 to 5,  most laboratory  animals
having ratios of 1  to  1,  and the  rat having a ratio of  10 to 1.  The  biolog-
ical halftimes may be  as  short as  seven  days in the mouse or  as high as 700
days or more  in  certain marine  species (Clarkson, 1972a).
                                     C-59

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u
03
8"  10-
                                           80        100
                            Biological Half-Life. Days
                               FIGURE 6
            Population distribution curve of methylmercury
                Source:   Shahristani  and Shihab, 1974
120
                                 C-60

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                                    EFFECTS
     Greatest emphasis will  be  placed  on  those effects occurring at the low-
est  levels  of exposure to mercury  and  to the target systems that suffer ef-
fects most  hazardous  to  the  animal  at the lowest  exposure.   Greater weight
will  be given  to  human  data when  reliable;  otherwise, animal  data  will  be
used.
     This  section  gives  separate  treatment  to the  physical  and  chemical
forms of  mercury that are  toxicologically distinct.   The  short-chain  alkyl
mercurials,  mercury in the  zero oxidation state  (mercury vapor  and  liquid
metallic  mercury)  and  the  compounds  of  divalent  inorganic  mercury  (Hg   )
will receive  the most attention as these  are the  forms of mercury  to  which
man  is most freauently exposed.
Acute, Subacute, and Chronic Toxicity
     Methylmercury  and  Other  Short-Chain Alkyl Mercurials:   The toxic  ef-
fects of methylmercury have been described in  several  recent  reviews (Swed-
ish  Expert  Group,  1971;  Norton, 1971;  WHO, 1972,  1976; Miller and Clarkson,
1973; Friberg and Vostal, 1972;  Nordberg,  1976;  NAS,  1978).   A major conclu-
sion of these reviews is that  prenatal  methylmercury poisoning differs  Qual-
itatively and  probably  quantitatively  from  postnatal   poisoning.  These  two
situations will be treated separately in this section.
     Effects on Adults:  Prior  to  the  major  outbreaks  in Japan  in  the  1950s
and  1960s,  cases  of poisoning due to occupational  and  accidental  methylmer-
cury exposure had already indicated the principal  signs and  symptoms  of sev-
ere  poisoning.   The first  recorded  poisoning took  place  in  1863  (Edwards,
1865).   In  that  year,  three young laboratory workers  developed  neurological
symptoms 3  months  after  they were first exposed;  two  of  them died.   Four
cases of  methylmercury  poisoning were  described by  Hunter,  et al.  (1940).
                                     C-61

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The  patients  had worked  in a  factory  that manufactured  methylmercury com-
pounds for use as a  seed  grain  fungicide.   They were asymptomatic during the
initial  3  to  4  months of  exposure and then  contracted symptoms  that were
confined to the  nervous system.   The presenting symptoms were paresthesia of
the  extremities, impaired  peripheral  field of vision, slurred  speech,  and
unsteadiness  of  gait  and  of limbs.  Examination  showed  that  all  four  had
ataxia,  constriction  of  visual  fields,  and  impaired stereognosis, two-point
discrimination,  and  joint  position sensation in the  fingers.   Three had dy-
sart.hria.  In  all  cases,  the maximum  severity of symptoms  occurred several
weeks  after  exposure to the  poison had ceased.   The degree of  improvement
varied,  and  persisting  neurological signs  were  found  in  all   four  cases.
Twelve coworkers remained  asymptomatic.   One  of  the  patients  died  in 1952
and  the   neuropathological   findings  were  reported  by Hunter   and  Russell
(1954).  These  authors correlated  the  ataxia  with  cerebellar  atrophy that
particularly affected  the  granule  cell   layer,  and related  the visual  signs
to focal  atrophy of the calcarine cortex.
     In 1956, four patients were  admitted  to the  hospital  attached to a fac-
tory in  Minamata, Japan  exhibiting a neurological disorder  of  unknown  etio-
logy.  Within  a  few  weeks  about 30  individuals with  similar complaints were
identified in  the  Minamata area.   Faculty from Kumamoto  University carried
out investigations and by 1959  it  became clear  that  Minamata disease was the
Hunter-Russell syndrome  of  methylmercury  poisoning  (Katsuna,  1968),  which
resulted  from  the  consumption of  fish  from Minamata Bay  that were contami-
nated  by methylmercury.   The  latter was  discharged  into  the bay via  the
local factory effluent, but may also have  been  produced  by biomethylation of
Hg   released  from  the  factory.    The  hair and  brain  of victims  contained
elevated   concentrations  of  methylmercury.   Similar  cases  appeared   in
                                     C-62

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Niigata,  Japan  in 1965  (Tsubaki  and Irukayama, 1977).   The  total  number of
Japanese  case.s  was  recently  reported  to  be  at  least  1,224  (Tsubaki  and
Irukayama,  1977).   A poison that had previously been  recognized as an occu-
pational  hazard had  become identified  as  an  environmental  risk  to  public
health.
      In the  late  1960s  a Swedish  Expert Group (1971) conducted an exhaustive
review  of toxicological  and epidemiological  data related to methylmercury
poisoning  in  man  and animals.   This review was  initiated as  a result  of the
discovery  that  widespread  mercury  pollution  existed   in  Swedish  lakes  and
rivers, that  all  forms  of mercury were  subject to  biomethylation by microor-
ganisms present in  sediments in  both fresh  and oceanic water,  and  that fish
readily accumulated  and concentrated methylmercury  in  their  edible tissues.
The  main  purpose of  the group was  to assess  the margin  of  safety  in  the
Swedish population with  respect to  dietary  intake  and  risk of poisoning from
methylmercury in fish.   Their  strategy  was  to obtain  information on  two re-
lationships:  (1)  the relationship  between  blood  concentrations  and  risk of
poisoning  (freauency  of signs  and  symptoms)  from  methylmercury and  (2)  the
relationship between  long-term dietary  intake and  steady-state blood  concen-
trations.   By combining these  two  relationships they  obtained  estimates of
risks to  various  groups  in  the  Swedish populations classified  according to
their fish consumption.   Ultimately  this  information was  used  by the  Swedish
government  to  set  regulations  on  maximal   permissible  concentration  of
methylmercury in fish.
     For information on  blood concentrations  and health effects,  the  Swedish
group had to rely on  limited data from the Niigata  outbreak.   Blood  samples
had been collected  from only 17 patients (Figure  7);  these data were  insuf-
ficient to establish  a  statistical  relationship between  blood concentration
and freauency of  cases  of  poisoning  (blood concentration-response).   Conse-
auently, they attempted to identify the  lowest blood  concentration  associ-
                                     C-63

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                 _. 100
                  E
                 o

                 g  50
                  en
                  "8
 Onset of symptoms .2
                     20
                  •§  10
                  s

                  I   5
                  8
                  3
                  a
                  o
                                  100
200
300
400
                                 Days after appearance of symptoms
                                   FIGURE  7.


     Concentration of  mercury in  samples of  blood  collected  from patients
suffering  from methylmercury  poisoning  in  the  Niigata outbreak.   Samples
from the same patients are connected  by a straight  line.  The arrow indicat-
es the estimated time  of  onset of  symptoms.   The units of mercury concentra-
tion  in  blood  are  pg Hg/100  ml.   The  numbers  on  the  ordinate  should  be
multiplied by ten to convert to ng Hg/ml.


Source:  Swedish Expert Group, 1971.
                                     C-64

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ated  with  the onset  of signs and  symptoms  of poisoning.   In  patients from
whom  several  blood samples had been collected, the  methylmercury concentra-
tion  fell  exponentially with  time, corresponsing to  a halftime  roughly  in
the  range  of  70  days.  Where sufficient  data points  were available,  the
blood  concentration was  extrapolated back to the  time  of  onset of symptoms.
The  group  concluded that  the  lowest concentration in  blood  associated with
the  onset  of  symptoms  in  the most sensitive  individual  was  200 ng  Hg/ml
whole  blood.  They calculated  the maximum safe blood concentration to  be  20
ng Hg/ml,  using  a  safety factor  of 10.   The safety factor took  into account,
among  other  things,  the   greater  sensitivity of  the   fetus  as  compared  to
adults (see Effects of Prenatal Exposure).
      Information   on  the  relationship  between  average  daily  intake  and
steady-state blood concentration  came from two sources:   radioactive  tracer
experiments using  volunteers  and  dietary studies  on individuals  eating fish
over  long  periods of  time.    Information was  available on  three volunteers
who  received  an  oral  dose  of  radioactive   methylmercury   (Aberg,  et  al.
(1969).  Gastrointestinal  absorption was virtually  complete (about 95 per-
cent of the dose)  and  the  whole  body halftime was about 70  days,  roughly  in
agreement with the halftimes observed in blood in  the Japanese patients.
     Mathematical  models of accumulation of  methylmercury in man  have been
discussed  previously.   The accumulated  amount  in  the  body,  A, would be  re-
lated to the average daily amount taken  up by the  body,  a,  by the expression:
                     A  = (a/b) (1  - e-bt)	(1),
where t is the time of  exposure  and b  is the elimination  constant, which  is
related to the whole body halftime T, by the expression:
                        In 2_	(2).
                    T =  ".
                                     C-65

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     Equation  (1)  is  depicted  diagrammatically  in  Figure  5.  The  steady
state  body  burden,  A   ,  would  be  closely  attained  after  exposure for  a
period of time eauivalent to five halftimes.  AQC would be given by:
                    A = a/b	(3).
     The  tracer  experiments indicated  two  important  criteria  that  might be
applied  to dietary  studies on  steady-state  relationship:   (1)  individuals
should be  receiving  a steady daily  intake  for about 1 year,  and  (2) the ac-
cumulated  amount  in the  body  A  should  be linearly related  to  the average
daily  intake  (eauation  3).   If  the  blood compartment  equilibrates relatively
rapidly  with  other  compartments, steady-state  blood  concentrations  should
also be proportional to daily intake.
     Dietary  studies  were conducted with Swedish  fishermen and their famil-
ies whose  regular diet contained fish.   Blood concentrations  were  compared
to  the average estimated  dietary intake of  methylmercury.   The  latter  was
estimated from measurements of mercury  in the  fish muscle  and the results of
careful Questioning  about  dietary intake of fish.  The  results of  two stud-
ies are  given in Figure  8.  Both studies  appear  to  confirm a  linear  rela-
tionship but  the  slopes  of the lines differ  greatly.  Despite  the  fact  that
the regression  line  of the  Birke,  et al.  (1967)  study  depended heavily on
one high data point, the  authors  rejected  the  other data on  the basis of in-
accurate dietary  information.   They concluded that an  average daily intake
of 300 yg Hg  as methylmercury would  yield  a steady-state blood  concentration
of 200 ng  Hg/ml  and that  the  maximum safe daily  intake would  be  30 ug Hg.
These  conclusions were  endorsed by the  World  Health  Organization  (1972)
which recommended a tolerable weekly intake arithmetically equivalent  to  the
Swedish maximum safe daily intake.
                                     C-66

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           Hg IN BLOOD CELLS
            ng/g
            1200
            1000 -
             800 -
             600 -
             400
            200
                                   0.4        0.5        0.8

                                  MeHg -INTAKE THROUGH FISH
                                                    mg Hg/DAY
                                  FIGURE 8.

     Relation between total mercury concentrations in blood cells  and  expo-
sure to methylmercury through  fish.   The figures in the  ordinate  should  be
divided by two to convert  the concentration units to ng Hg/ml whole blood.

Source:  Swedish  Expert  Group,  1971.
                                    C-67

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     Despite the  excellence of these in-depth reviews,  the  conclusions  were
necessarily limited by  the  Quality of the  data  available at that  time.   In
fact, the  Swedish  Expert Group (1971) pointed to  several  weaknesses  and un-
certainties in  the  data.  (1) No  information  was  available on  the accuracy
of  the  analytical  methods  used to  detect mercury  during the  Niigata  out-
break.  The dithizone procedure  used for the  blood  and hair analyses has  a
low sensitivity.  Large  volumes  of blood (up  to 50  ml)  must  have been  used.
In  several patients,  the hair to blood ratio  departed  from what is  now be-
lieved to  be the  true ratio  (WHO, 1976).   (2) The patients  were admitted to
the hospital after  the  appearance of signs and  symptoms.  It was  necessary
to  extrapolate  the  observed  blood  concentrations  (based on samples  collected
in the hospital) back to the  time  of  onset  of  symptoms.  The  statistical un-
certainty  in the  linear  regression extrapolation was high.   (3)  The  Swedish
data relating  dietary intake  to  blood concentration  are also  fraught  with
uncertainty.
     By the  time more  recent major  reviews  appeared  (Nordberg 1976;  WHO,
1976), several  studies   had  been  published on  fish-eating  populations  and
preliminary  reports had appeared  on the  large  outbreak of  poisoning  in
Iraa.  Miettinen  (1973)  had  completed  his study on  14 volunteers  taking
radioactive  methylmercury.    His  data,  along  with  observations  of  exposed
populations in  Iraq and  elsewhere,  allowed development  of a  compartmental
model for  uptake,  distribution,  and  excretion of  methylmercury  in man  (see
Pharmacokinetics section).   The  World Health  Organization review  adopted  a
similar approach as the  Swedish Expert Group in  defining relationships:   (1)
between symptoms  and  blood  concentration,  and  (2) between daily intake  and
steady-state blood concentrations.
                                     C-68

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     A World  Health  Organization  Committee  examined  the Iraqi  data on adults
 (WHO, 1976).. The outbreak  in  Iraq  occurred in  the winter of 1971-1972 among
 people living in rural  areas.   These  people consumed homemade  bread prepared
 from seed grain that had  been  treated with  a methylmercury fungicide.  There
 were 459 deaths among 6,540 hospitalized  cases;  many others were not admitt-
 ed  to  the  hospitals (Bakir, et  al.  1973).  Cases  of severe  poisoning  and
 fatalities  that occurred  outside  of hospitals may have  been considerably
 greater.  The Iraqi  data  derive  from three studies:   (1)  a  preliminary  re-
 port based  on 120 patients  (Bakir,  et al. 1973); (2) an epidemiological sur-
 vey by a WHO  team  involving 956 persons  in  a heavily  affected  rural village
 and  1,014   persons  in a  control  village  (Mufti,  et  al.  1976); and  (3)  an
 Iraai study by Shahristani,  et  al.  (1976) of 184 persons  in rural  areas,  143
 of whom consumed the contaminated bread.
     Using  the data  of Bakir, et  al.  (1973),  Clarkson,  et al.  (1976) compar-
 ed the frequency of  paresthesia with  mercury concentrations in  blood (Figure
 9).  Frequencies of  paresthesia (5  to 10  percent)  observed  at  low  Hg concen-
 trations were interpreted to be background  values  for  the population and  un-
 related to  methylmercury.   The  point  of intersection of the two lines repre-
 senting paresthesia  frequencies and Hg concentrations  was  taken to indicate
 the blood Hg concentration  at which paresthesias due to methylmercury emerge
 above  the   background  frequency.    This   blood  Hg  concentration  is  290  ng
 Hg/ml.   However,  the  Hg  concentrations  were  those existing  65 days  after
 cessation of exposure to methylmercury and,  in  view  of the  reported blood  Hg
 halftimes of 65 days in these  patients,  the maximum blood  Hg  concentration
was probably about  480 ng  Hg/ml whole  blood  at the  end  of  exposure.
     The Shahristani, et al. (1976) study reported no  cases of  methylmercury
poisoning occurring below a  hair  concentration of  120  yg  Hg/gm  hair, equiva-
 lent to about  480 ng Hg/ml whole  blood.   The  World Health Organization  study
                                     C-69

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          ioo n
       -s  so-
                                                                  O
        0>
        v>
        Jf  60-
        o>
        o.
        
-------
 (Mufti, et  al.  1976)  measured total  dose according to the amount of contami-
 nated bread  consumed.   The  relationship  between  frequency of paresthesia and
 total dose  of methylmercury had the same  general  relationship  as that shown
 in Figure 9.   The  background  parasthesia frequency was  estimated to be about
 four  percent  (WHO,  1976), and the  total  body  burden  of  methylmercury at
 which  paresthesias due to  methylmercury emerged  above  the  background  fre-
 quency was  approximately  37 mg.  Since  the  average body weight in the group
 was  50 kg,  this  dose  would  correspond  to  50  mg in  a 70  kg  human.   The
 equivalent  blood  concentration  would be  approximately  500  ng  Hg/ml  whole
 blood.
     The Iraqi  studies  failed to identify a diagnosed  case  of  methylmercury
 poisoning at  200 ng Hg/ml  whole blood.   If such  cases existed,  they could
 not  be  differentiated  from individuals having  nonspecific  signs  and symp-
 toms.  The Iraqi studies clearly show a  need for  more specific  tests  for ef-
 fects of methylmercury at low doses.
     Several  studies  of fish-eating  populations  were  also  reviewed  by the
 World Health  Organization   (1976).   Findings  in  Peru  (Turner,  et  al.  1974)
 and Samoa (Marsh,  et al. 1977)  agreed with  those from other  fish-eating  pop-
 ulations.  No adverse health  effects  in  adults could be  associated with ex-
 posure to methylmercury from  fish.   However, only  about  15  people had blood
 levels in the range of 200 to 400 ng Hg/ml.
     As noted  previously,  a wide individual  variation exists in  blood half-
 times.  A study by Shahristani  and Shihab  (1974)  indicates a  bimodal  distri-
 bution in 48  Iraqis.   One  group,  accounting  for 89 percent of  the  samples,
 had a mean halftime value of 65 days, while the other group  had  a mean value
 of 119 days.
     The significance of  individual variation  in  halftimes  is  demonstrated
by the report of Nordberg and Strangert  (1976).   The  steady-state blood  con-
centration for any given dietary intake  of methylmercury is  directly  related
                                     C-71

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to the  biological  halftime (see equations 2  and  3).   These authors realized
that  the  bimodai  distribution  of  halftimes  reported   by Shahristani  and
Shihab  (1974)  predicted that  a subgroup  of  the population  (the  group with
the 119-day average halftime)  would  attain steady-state  blood concentrations
almost  double  those  of the  group  having  the 65-day  halftime.   Nordberg and
Strangert  (1976)  went on  to calculate  the  overall  risk  of poisoning from
dietary methylmercury by combining the  relationships  of  the blood concentra-
tion versus frequency  of  paresthesia (reported  by  Bakir, et al.  1973) with
the bimodai  distribution  of halftimes.   A  result of  their calculation  is
given in Figure 10,
     Since the WHO review  (WHO, 1976) some reports had  appeared on Canadian
Indians exposed  to methylmercury in  fish.  Residents of two Ojibway Indian
Reserves in Northwestern Ontario had  blood levels  of  total  mercury from 5  to
330 ng  Hg/ml  most of which  was in the  form  of methylmercury  (Clarkson,  et
al. 1975).  A  Japanese  team conducted clinical  examinations  on  89 residents
of the two reserves out of a total population of  about 1,200 (Harada, et al.
1976).  A  variety of  sensory,  coordination,  and  other neurological  disturb-
ances  were found  (paresthesia,  visual field  constriction,  ataxia,  dysarthr-
ia) similar to those  reported  in cases  of methylmercury  poisoning in Japan.
However, as  the  authors pointed  out, the neurological  symptoms  were  rela-
tively mild and many were thought to  be  due to other causes.
     A Canadian medical team examined 49 Cree Indians living in  northwestern
Quebec and exposed to methylmercury in fish.  They  concluded that at least 6
and possibly 25  had  signs and  symptoms  of methylmercury intoxication  (Bar-
beau et  al.  1976).  The  blood levels of  mercury were elevated,  80  percent
having levels  above 50 ng Hg/ml.
                                     C-72

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          A probability of

            poisoning ,P



               %

              100
               50
           B  2.0r
           eS  1.5 -
           I
           5
           a.
           CO

           .O

           O
                                                      -P(a)
0.5    1.0     1.5     2.0     2.5 mg daily dose


                            P(a)
                 0  .01  .02 .03    .05     .07



                               DOSE (mg/day)

                                    FIGURE 10.


                         , f?r 1oxng-term  exposure  to  methylmercuric  compounds
                         bod^ wt)-   A, whole  dose-response curve;  8,  detailed


                                                                               "

Source:  Nordberg  and  Strangert, 1976.
                                      C-73

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     The  lack  of appropriate controls  for  such confounding factors  as  age,
alcohol intake,  and nutrition, make  it  impossible  to  draw conclusions on the
role of methylmercury  in the  clinical  picture  of both the Harada and Barbeau
investigations.  A  National  Academy of Science Committee  (NAS,  1978)  in re-
viewing  data  available to  the WHO  group  (WHO, 1976)  and the  Canadian re-
ports, concluded that  "Until  more definitive evaluations  of the exposed na-
tive  Canadian  populations  and the  prenatal  and  perinatally exposed  Iraqi
populations have been  completed,  the guidelines  concerning human exposure to
methylmercury suggested in the WHO  document  (WHO,  1976),  ...should be adher-
ed to."
     New  data on   the Niigata  outbreak  was  reported  by Tsubaki,  et  al.
(1978).   He reported  on new  analytical  determinations by  atomic  absorption
method of mercury  in   hair samples  that had been  previously analyzed  by the
dithizone method at the time  of the  Niigata  outbreak  in  1965.   They reported
that  in  one patient  whose  hair  concentration  had been  estimated to be  52
vg/g at the time of the onset of  symptoms,  the  new atomic absorption analys-
es indicated a value of about 82  vg/g.   Other  patients in the  original Niig-
ata group had estimated hair  concentrations  about  100 ug/g at  onset of symp-
toms.  Unfortunately,   blood samples were not available for reanalysis by the
atomic absorption procedure.   In  the original  group  of  patients,  (Figure 7;
Swedish Expert Group,  1971),  one patient had  an  estimated blood  concentra-
tion at the time of onset of symptoms  of approximately  200 ng  Hg/ml.   How-
ever,  the extrapolation had  to  be  made with  only three  data points.   Fur-
thermore,  the  concentration  of mercury in   the  hair  sample  taken from  the
same  patient   indicated  that  the corresponding  blood  concentration  should
have been higher.  All other blood samples in the  original  group in Figure 7
                                     C-74

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when  extrapolated  back to  time of  onset  of symptoms, yielded  values  above
300 ng Hg/ml.  These new  data  would  suggest  that previous evaluations of the
original data  from Niigata  had overestimated the risk  and  that  evidence for
a lowest observable effect  level  (LOEL) of 200  ng Hg/ml blood  had been  weak-
ened.
      In  the  same publication,  Tsubaki reported  on  clinical  foUowup studies
of four  patients who were exposed to methylmercury  in  the  Niigata outbreak.
These  patients developed  symptoms of methylmercury poisoning several  years
after  the  original outbreak.   The maximum  hair concentrations  in  the  four
patients were  between  50  and 300  pg/g  as measured  by  atomic  absorption.
They  were  described as   "methylmercury poisoned patients  with  delayed  on-
set."  The patients had mild nonspecific  symptoms so that methylmercury poi-
soning could not be diagnosed  with certainty.    However,  the Tsubaki, et al.
report on delayed  onset of  symptoms  is  supported by observations on nonhuman
primates.  Evans,  et al.  (1977)  reported  that  the length of the  latent  per-
iod  in  monkeys was inversely  related to  the  steady-state  blood  concentra-
tions.  Latent periods  of up to 1 year were found at the lowest doses.
      In brief, analytical data from  Japan points to an overestimate of  risk
by previous  evaluation (Swedish  Expert  Group,  1971).*   The  clinical  fol-
lowup  indicated  that delayed cases of poisoning may be associated with  hair
concentrations as  low as  50 pg/g.  This evidence as well  as the  animal  data
from  Evans,  et al. (1977), and  the  continuing  studies on  Canadian Indians,
indicate that  it would  be prudent to retain 200 ng Hg/ml as the  lowest  ob-
servable effect level  in nonpregnant  adults.
*Howpver,  it  should  be noted  that dithizone  and  atomic absorption  methods
disagreed  only  in the  one  patient who  had the  lowest hair  concentration.
Agreement  was  excellent between  the two  methods  in  hair  samples from  two
other patients.   Agreement between the two methods was  found  at  mercury con-
centrations below 50
                                     C-75

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     Several  important  conclusions  may be drawn from these  studies  of adult
poisonings.   (1)  More data are  needed on the  prevalence  of effects  at  the
Tower regions of  the  dose-response  relationships.   (2)  More  people should be
studied in fish-eating  populations  to  identify  individuals having  blood con-
centrations in excess  of 200 ng Hg/ml.   Even negative  results  would be most
helpful in  setting the  upper  limits  of  risk,  assuming that selection pro-
cesses  can  be eliminated.   (3)  Objective methods  are  needed  to  detect  the
first effects  of  methylmercury  exposure.   Paresthesia  and  other  subjective
complaints  are  the  first  effects  associated  with methylmercury  poisoning,
but are not good for detecting these first effects  because of the  high back-
ground, i.e., high frequency  in  nonexposed  individuals.  At  present, no bio-
chemical,  neurophysiological,  or other  objective  test  serves   as  an  early
warning sign  (Nordberg,  1976).   (4)   The  bimodal  distribution   of halftimes
reported by Shahristani  and Shihab  (1974)  needs confirmation and further  re-
fining  through  observation of  larger  numbers  of  people.    (5)   Further data
are needed on  the relationship between long-term dietary  intake and steady-
state blood  concentrations in  order   to  test  the  model  for both  long  and
short halftime  groups.   The tentative blood-level  limits  based on  the data
from  Iraq  also need  verification  in   another population  because  dietary or
genetic factors may be important.
     A  statistical  relationship  has   been  suggested  by  Skerfving, et  al.
(1974) between frequency of  chromosomal  aberrations and blood  concentration
of methylmercury.  This  report  was  based on 37  people  exposed  to  methylmer-
cury through intake of  various  amounts of fish.  The highest exposure  group
had blood concentrations  in  the  range  of 14 to  116 ng  Hg/ml, and  the nonex-
posed group showed  concentrations  in   the  range of 3 to  18  ng   Hg/ml.  How-
ever, a  study made  a  few months after  the outbreak in  Iraq could  find  no
correlation between  chromosomal  damage and exposure  to methylmercury  (Far-
man, 1974).

                                    C-76

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      Bakir,  et  al. (1973) found few  clinical  effects associated with damage
 to  nonnervous  tissue in the  victims  of  methylmercury poisoning.  An earlier
 outbreak  of methylmercury poisoning  revealed cardiovascular  effects  due to
 renal  and  cardiac  damage  (Jalili and  Abbasi, 1961).
      The  Swedish  Expert Group (1971)  reviewed case reports of dermatitis due
 to  occupational  skin  contact  with  alkyl  mercurials used as fungicides.  Jal-
 ili  and  Abbasi   (1961)  and  Damluji,  et  al.  (1976) have reported exfoliative
 dermatitis   resulting   from   oral   ingestion  of  methyl-  and  ethylmercury
 compounds.
      Effects of Prenatal Exposure:   The earliest mention  in  the literature
 of  psychomotor  retardation  caused  by fetal  exposure  to methylmercury was by
 Engleson  and Herner (1952).  A  Swedish  family had eaten  porridge  made from
 methylmercury-treated grain.  The  asymptomatic mother gave birth to a daugh-
 ter  who  appeared to be  normal  at  birth  and in  the  first  2  months  of life.
 It  later  became clear that the  child was mentally and physically  retarded.
 Upon  further examination a year or  two later, she continued  to have marked
 psychomotor  retardation,  and  the authors (Engelson and  Herner,  1952)  postu-
 lated  that  "mercury intoxication,  perhaps during  early  fetal  life,  seems to
 us to be a possible cause."   Her father  and  brother were diagnosed  as having
 mercury  poisoning.   Urinary  mercury concentrations  were elevated  in  the
 mother; no blood or hair analyses were performed.
     Harada  (1968)  reported on 22  children from  Minamata,  Japan  who had sev-
 ere  psychomotor  retardation  which  he concluded  was  due to fetal  methylmer-
 cury poisoning.   All children came from  families  in which  at  least  one other
member had been  diagnosed  as  having methylmercury poisoning,  with  fatal  re-
 sults  in  13  families.   Five  of the mothers  had  experienced transient pares-
 thesia during pregnancy but  had been well  otherwise.  The  childrens1  ages
 ranged  from  1   to  6   years  at  the  time  of   initial  examination  and  at
                                     C-77

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those  ages  it was  not possible  to determine  their degree  of  exposure  to
methylmercury JJT_ utero.   Two of  these children  died  and  neuropathological
studies were  reported  by  Takeuchi  (1968).   He concluded that  there  was  evi-
dence of a disturbed brain  development and that the cerebral  and  cerebellar
lesions were  the same  as  those found  in  kittens that  had been  exposed  to
methylmercury _in_ utero.
     In August 1969 a  family  in New  Mexico began  to  eat  pork from a  hog  that
had been fed  methylmercury-treated seed grain  (Snyder  1971; Pierce, et  al.
1972).  At that  time the  mother was 3 months pregnant and  ate the contamin-
ated pork  regularly for the  following 3  months.   She remained  asymtomatic
but delivered  a  severely  brain-damaged infant  who,  at 8 months of  age,  was
blind  and  hypotonic.   Some  other members  of the  family  suffered  severe
methylmercury poisoning.   This  was the first  report of methylmercury toxi-
city from eating contaminated meat and the only published  fetal  case  in  the
United States (Snyder,  1971).
     The Iraqi outbreak offered an excellent opportunity to  develop Quanti-
tative  information  with  regard  to  prenatal  exposures  to  methylmercury.
Large  numbers  of people,  of both  sexes,  were  exposed  to  a  wide  range  of
dietary intake  of methylmercury  within  a  period  of  a  few months.  Thus,
pregnant females  could have been  exposed  to  a pulsed dose  of methylmercury
at any time during  pregnancy,  and might have consumed a very wide  range  of
doses.  Early studies  on  15 mother-infant  pairs identified  infants  who  were
prenatally exposed to  and  severely poisoned by methylmercury  (Amin-Zaki,  et
al. 1974a).   Choi,  et  al.  (1977)  reported abnormal  neuronal migration  in  a
human  infant  prenatally poisoned  with methylmercury  in  Iraq.   A group  of
infants was also  identified that had been  exposed  to methylmercury primarily
by sucking (Amin-Zaki,  et  al.  1974b).
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     Follow-up   neurological   and  pediatric  studies  by  a  University  of
Rochester  team  obtained dose-effect relationships  between  prenatal  exposure
and effects  on  the  infants  (Marsh,  et  al. 1977).  Ten infants of mothers who
had  maximum  hair concentrations  in  the range  of  99  to  384  ppm  (pg/g)
differed from two groups  having  lower  maternal  hair concentrations  (12 to 85
ppm and  0  to 11  ppm,  Figure  11) in the  freauency  of signs  and  symptoms of
psychomotor  retardation.   Statistically  significant  differences were  found
(P <.03) by  the Chi-Sauare  test  in the delayed  achievement in developmental
milestones  (delayed  walking  and  talking)  and  in the histories  of  seizures.
The high mercury  group  also differed from the other two  groups in the number
of infants having multiple  signs and of  poisoning  symptoms (Table  14).   For
example, all the  infants  in the  high  exposure group except  two  had  three or
more adverse health effects  per infant.   In  contrast,  the  two  groups  with
lower  exposures consisted mainly of  infants having  one or no  adverse  ef-
fects.    A  statistical   analysis  revealed  a highly  significant  (P<0.005,  chi
sauare test) difference  in distribution  between the  high  exposure  and  the
two lower exposure groups.
     The small  number of  infant-mother pairs  in  this  study  does not  allow us
to identify  a specific  threshold  maternal  hair  concentration below which ad-
verse  effects do not occur in  both mother and  infant.   A  high  risk  of  ad-
verse  effects appear to exist at maternal hair concentrations in the  range
of 99  to 384 ppm.  However,  in the next  lower  concentration  range (12  to 85
ppm)  the freouencies have fallen  dramatically and do  not differ significant-
ly from  those  seen  in   the lowest range  (0.5  to 11  ppm).   Thus,  the  adverse
effects seen at maternal  hair concentrations up  to  85 ppm may have  been  due
to causes  other than  methylmercury  exposure.    Unfortunately,  only  four
infant-mother pairs  were  available between  25  and 50  ppm  maximum  maternal
hair  concentration.
                                     C-79

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                          Maternal Hair Mercury
                          I—I 0-11 ppm (N=9)
                          ESI 12-85 ppm (N=10)
                          CSS 99-384 (N= 10)

                                 Historical Data
No. of
Infants
                       10-
                        8-
                        6-
                        4.

                        2-
                               J
                             Motor   Speech   Mental  Seizures

                            I	Retardation-
                 No. of
                 Infants
ID-
 S'
 6-
 4-
 2-
 0-
                            Clinical Data
                            Extensor Other CNS Srnajl
                            Planters    Signs    Head
                                      None
                                      Short
                                      Height
                                               	2SD	
                                                below mean
                                   FIGURE 11.

     Signs  (clinical data)  and  symptoms of  psychomotor  retardation  in  29
Iraqi  infants  exposed  prenatally to methylmercury.   The  frequency of abnorm-
alities are compared in groups of  infants according to  the  maximum maternal
hair concentration during  pregnancy.

     The  following  criteria  for  abnormalities  were adopted:  motor retarda-
tion if  the child was  not walking  at 18 months,  speech retardation  if not
talking by 24  months,  mental  retardation or seizures (or convulsive-1ike at-
tacks)  according to  the  history provided  by the  mother,  and  neurological
signs  by  agreement  of  the  two  examiners.   No  standards are  available for
head circumference or  height  of  Iraai  children,  so  these  factors  were eval-
uated  in terms of standard deviations  below  the  mean for  the group.

Source:  Marsh, et al.  1980.
                                      C-80

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                                   Table 14
                   Frequency of Infants  Symptoms and Signs
                Related  to  Maternal  Hair Mercury Concentration*



No.
of Infants
Abnormalities per Infant
Maternal
Hg (ppm)
0-11
12-85
99-384

0
3
4
1

1
5
4
0

?.
0
0
1

3
0
2
2

4
0
0
3

5
1
0
1

6
0
0
2
Total
Infants
9
10
10
*Source:  Marsh, et al. 1980.
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     An epidemiological study of  school  children  living  in  the Minamata area
of Japan has recently  been  reported  (Med.  Tribune,  1978).   Children suspect-
ed of  prenatal  and early postnatal  methylmercury exposures  (age  group  8 to
16) exhibited  a higher incidence  of neurological deficits,  learning  diffi-
culties, and poor  performance on  intelligence  tests  than children  of similar
age in  a  control  area.  These  findings  confirm predictions  from  studies of
animals prenatally  exposed  to  methylmercury (Spyker, et al.  1972),  in  which
a variety  of behavioral  and neurological  tests revealed deficits  only  after
the animals had reached maturity.
     In summary, our knowledge  is  still  limited in  perhaps  the most critical
area of methylmercury  toxicity  in man.  A study  on  a  fish-eating  population
is needed  to complement  the Iraqi program to  test  if  methylmercury ingested
from  contaminated  bread  is  eauivalent  toxicologically  to  methylmercury
chronically  ingested  from  fish.   The ongoing  Iraai study has  demonstrated
the feasibility of  relating the dose of the  mother  during pregnancy to ef-
fects  seen  in  the  infant during  the first 6  years  of  life.   Other effects
may manifest themselves in later years as the child matures.
     Effects on Animals:   Animal studies reveal that  effects on  nonhuman
primates are similar  to  those  on man (Berlin,  et  al.  1973).   Neurological
damage  has also  been reported  in  various  other   species   (Swedish  Expert
Group,  1971;  WHO,  1976).   In  general,  effects  manifest  themselves at  the
same brain  concentrations  but corresponding blood concentrations  may  differ
widely due to species  differences in  blood  to brain  ratios  (Figure  12).
     The rat appears  to  experience  effects  not seen in man.   Kidney  damage
has been reported  by  several  investigators (Klein,  et  al.  1972,  1973;  Fow-
ler, 1972; Magos and Butler, 1972).   Damage to  the  peripheral nervous  system
has  been   reported  in rats  (Somjen,  et  al.   1973a,b;  Chang  and  Hartman,
                                     C-82

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    50-
-.  40-

Q.
__a

z  30-
QC
QQ
    20-
j
0
              10
 1
20
 1
30
_
40
50
-
60
J.
70
_
80
 i
90
100
110
                                       BLOOD (ppm)
                                     FIGURE 12.

         Comprehensive  brain/whole  blood  regression  lines  in four species orally
    dosed with methylmercury.  The  shaded  areas correspond to  the  onset of the
    first detectable  signs and symptoms of poisoning.

    Source:  Weiss, et  al. 1978.
                                        C-83

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1972a,b), whereas neurological  signs  in man appear to  be  due  mainly to dam-
aae to the central nervous system  (Von  Burg  and  Rustam, 1974).  However,  ef-
fects on  the  neuromuscular  junction have been found  in severe cases of poi-
soning in Iraa (Von Burg and Landry, 1976).
     The  first  effects of methylmercury  as  evidenced  by  animal  experiments
are on  protein  synthesis  in neurons  (Yoshino,   et  al.  1966; Cavanagh  and
Chen, 1971;  Chang and  Hartman,  1972a, b;  Syversen,  1977).   The  effects  of
methylmercury on  the neuromuscular junction are due  to a  highly selective
interaction with the acetylcholine receptor (Shamboo,  et al. 1976).
     Ganther, et al. (1972) reported a  sparing effect  of dietary selenium on
methylmercury toxicity  in  rats  and Japanese quail.   Subsequent  animal  stud-
ies have  confirmed Ganther's findings  (WHO,  1976;  Nordberg,  1976).  However,
the concentrations of  methylmercury or selenium  added  to  the  diet have been
higher than those found in human diets.   Following the  observation of Ganth-
er, et al.  (1972)  that selenium salts, added to  the  diet,  delayed the  onset
of toxic  effects due  to  methylmercury in  Japanese  quail,  several  publica-
tions have  appeared  in the literature on  selenium-mercury  interactions (for
review,  see WHO, 1976;  Nordberg, 1976).   However,  in  the most  recent evalua-
tion of experimental data,  it  was concluded that there is insufficient evi-
dence that  selenium  in  the  human  diet  would   protect against  the  toxic
effects  of methylmercury (Permanent Comm.  Int.  Assoc.  Occup. Health, 1977).
     Effects  on  Adults of Mercury Vapor and  Liquid  Metallic Mercury:   The
effects  of  inhaled mercury  vapor  on human health have  been  known  since anc-
ient times.   Recently,  several  reviews have dealt  with this  topic (Friberg
and Vostal,  1972;  NIOSH,  1973;  Friberg  and  Nordberg,  1973; Nordberg,  1976;
WHO,  1976).   However,  health  effects  have not  been  associated  with  oral
ingestion of liquid metallic mercury.
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     Exposure  to  extremely high  concentrations of  mercury  vapor  (greater
than  1  mg Hg/m  )  can  damage lung tissue,  causing  acute mercurial pneumoni-
tis  (Milne,  et  al.  1970).  Exposure  to lower  levels  results in signs  and
symptoms  indicating effects primarily on the central nervous system.
     Most  of  our knowledge  derives  from studies of  occupational  exposures.
These reviews  listed above refer  to  observations of more than 1,000 individ-
uals  and  indicate that  the classical  signs  and  symptoms  of mercury  vapor
poisoning  (mental  disturbances,  objective  tremors,  and  gingivitis)  occur in
workers following  chronic  exposures  to  average  air  concentrations above  0.1
to  0.2  mg Hg/m3  (Neal,  et al. 1937,  1941; Bidstrup, et al.  1951;  Friberg,
1951; Rentes and Seligmann, 1968).
     In a comparative study  of  over 500 workers,  Smith, et  al.  (1970)  re-
ported effects on  the  nervous system that  were  related  to  the time-weighted
average air  concentration  of mercury.   Objective tremors were found  at  air
concentrations  above  0.1  mg Hg/m .    Nonspecific symptoms  such  as  loss  of
appetite, weight loss, and  shyness seem  to  occur at a greater freauency than
in  the  control  group at average  air concentrations in the  range  of 0.06 to
0.1 mg Hq/m .
     Extensive Russian  studies on occupationally exposed workers have been
reported  in a  monograph  by Trachtenberq  (1969)  and reviewed  by  Friberg  and
Nordberg  (1973).  A  syndrome involving insomnia,  sweating,  and  emotional
lability was claimed to occur  at  a higher  freauency  as  compared  to  controls
in workers exposed at high ambient temperatures  (40 to 42°C  in summer  and 28
to 38°C in winter) to mercury concentrations in  the  range of 0.006 to  0.1 mg
Hg/m3.
     Considerable uncertainty  still  exists  with regard to health  effects at
concentrations below  0.1   mg  Hg/m .   Friberg  and  Nordberg  (1973) point  to
the possibility  of "interviewer"  effects  in  occupational  studies in  which
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the  factory physician  is  aware  of  the mercury  concentration  to which  the
workers are exposed.
     In the study of  Trachtenberg (1969), uptake  of iodine by  the  thyroid
was  significantly  greater  in a  mercury-exposed  group of  workers than in  a
control group.   However, Kazantzis  (1973)  has suggested  that  these  studies
should  be  repeated and  should  include measurements  of  serum  thyroxin.   He
pointed out that  increased  uptake of radioactive  iodine  will  occur  if  the
store of iodine  in the  thyroid  gland  is  low and need not  necessarily  be  as-
sociated with increased secretion of thyroxin.
     Four cases  of proteinuria were  reported  in  workmen  exposed  to  mercury
vapor  (Kazantzis,  et  al.   1962).   Exposure  levels  were  probably high,  as
urinary concentration was in excess of 1,000  ug Hg/1.   Increased  urinary  ex-
cretion of  protein  in  exposed  versus nonexposed  workers  was reported  by
Joselow and Goldwater  (1967).   Ashe,  et al.  (1953) found  morphological evi-
dence of kidney damage in rabbits exposed to mercury vapor.
     Few biochemical changes have  been reported due to  inhalation of  mercury
vapor.   Wada, et al,  (1969)  noted  that blood  cholinesterase  activity  was  de-
creased when  urinary  mercury excretion  was   greater  than  200  yg  Hg/g  of
urinary creatinine.   This  rate  of excretion   should  correspond to an  aver-
age air concentration slightly lower than  0.1  mg Hg/m   (Wada, 1969).
     Table  15,  which summarizes  data from animal  and  human studies,  shows
that the earliest  effects  of mercury vapor appear at roughly  similar  brain
concentrations in  a  variety of  species.   Because  of  species differences  in
ventilation rates  and  pharmacokinetics  parameters  of  inhaled  mercury,  the
same brain concentration in  various species would not necessarily correspond
to the  same average air concentration.
                                     C-86

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                                    TABLE 15

              Estimated  Average  Brain  Concentrations  at which  Toxic
                   Effects Appear in Adult Humans and Animals
Species             Brain Cone.       Severity of         Reference
                  pg Hg/g wet wt.      effects


Rabbit                 1.0              mild*        Ashe, et al. (1953)
                     (approx.)

Rat                    2.8              mild3        Rothstein and Hayes (1964)

Rat                    1.9              mild3        Berlin, et al. (1969)
Human                  0.85             mildb        Estimated0 from
                                                     Hurch, et al.  (1976)
                                                     Smith, et al.  (1970)


aThe animals were described as irritable.

^Subjective symptoms such as complaints of loss of appetite.

cThe  steady-state  brain  concentration  was  estimated  from  the  data  of
 Hurch, et  al.  (1976),  which show  that 7  percent of an  inhaled  dose  is
 deposited  in  the  brain, and that the  halftime in brain  is  21 days.   Brain
 weight was assumed to be  1.5  kg,  and the time-weighted  average air  concen-
 tration  associated with  mild  effects  to  be 0.1  ng  Hg/m3,  according  to
 data of  Smith,  et al.  (1970).   Workers were assumed  to inhale  10 m3  air
 during an 8-hour occupational exposure, to  retain  80  percent of the  inhaled
 mercury,  and to work  for 5 days  per  week.
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     Effects of  Prenatal  Exposure:   Little information  is  available  on  bio-
logical effects  in  humans  due to prenatal exposure to  mercury  vapor.  Stud-
ies carried out  early  in  this century suggest that women chronically exposed
to mercury vapor experienced  increased  frequencies  of  menstrual  disturbances
and spontaneous  abortions;  also,  a  high  mortality rate  has been  observed
among  infants  born  to women who  displayed  symptoms  of  mercury  poisoning
(Baranski and Szymczyk, 1973).   However,  the  degree of exposure  of  these wo-
men to mercury  vapor  is  unknown.   In  1967, an  epidemiological  survey  in
Lithuania called attention  to an increased incidence of abortion and masto-
pathy  related to duration  of time on the  job among women  working  in dental
offices where mercury  vapor  concentrations ranged  up  to 0.08 mg/m   (Baran-
ski and  Szymczyk,  1973).   Another  report described  the  case  of   a  woman
chronically intoxicated by mercury vapor  in  whom two pregnancies  ended  un-
favorably.  After  recovering  from overt mercury  poisoning,  this woman  gave
birth  to a healthy child (Derobert and Tara,  1950).
     In summary, little  is known about  the  reproductive effects of  inhaled
mercury vapor.   In  view  of the observed reproductive  effects of other  forms
of mercury, studies are urgently needed in this area.
     Salts of Inorganic  Mercury:  The  lethal  oral  dose in man  of  HgC^  has
been estimated to be between 1 and 4 grams (Gleason, et  al.  1957).   Death  is
due to acute renal  failure.   The  effects  of chronic exposure to  salts of  in-
organic mercury  have not  been described in man.   Long-term  occupational  ex-
posure to  HgfNOj^ must  have occurred  in  the felt hat industry  (Neal,  et
al. 1937).  However, poisoning was  believed to  be due to inhalation  of  mer-
cury  vapor  produced  from  HgfNt^Jg during  the  procedure  of  treating  the
felt.
     Fitzhugh,  et  al.  (1950)  treated rats with  HgClp  added to  the food  for
periods of up  to 2 years.  Morphological changes  were  induced in kidney  tis-
sue at dietary  concentrations of 0.5  yq  Hg/g food.  However, these  studies

                                     C-88

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have been  criticized  by Goldwater  (1973)  who noted that no effects were pro-
duced  in  other groups of rats  receiving  much higher dietary  levels  of mer-
cury  (2.5  to 10 yg Hg/g).
     Compounds  of inorganic mercury have  been  shown to  be  diuretic  in dogs
(Mudge  and Weiner,  1958).   The nature of  the anion  is  important.  Inorganic
mercury complexed with cysteine is a more potent diuretic than HgC^.
     Piotrowski,  et al.  (1973)  have  discussed the role  of metallothionein in
controlling  the  toxic  action  of  Hg   on  the  kidney.    The  authors  pointed
out  that   the  toxic  effects on the  kidney  following a single dose  of Hg
salt appear when  the  metallothionein binding capacity is  exceeded.  Repeated
daily  doses of Hg    cause  induction of  metallothionein  synthesis.   Conseq-
uently, much higher  concentrations of inorganic mercury  may  be tolerated by
the kidney after chronic exposures (Clarkson, 1977).
     Aryl, Alkoxy-aryl,  and Other  Organic  Compounds  of  Mercury:   Despite the
widespread  usage  of  phenyl mercury  compounds,  little  information  is avail-
able  regarding their  effects   on  human  health.    Since  Goldwater's  review
(1973), new information has come  to light.   No  evidence of  adverse health
effects could  be  found  in 67 workers  occupationally exposed to  phenyl  mer-
                                                                           3
cury  compounds.   Air  concentrations  were  generally  below  0.1  mg  Hg/m .
Elemental  vapor was the principal  form of mercury in air.
     A  case  of acrodynia has been reported in  a  child allegedly  exposed to
mercury after the bedroom had been painted  with paint containing  phenyl  mer-
cury compounds.   The  form of mercury in  the air was  not identified but it is
likely that mercury vapor was  a principal  component (Hirschman,  et al. 1963).
     Goldwater   (1973) referred  to  seven  workers  who had  spent  about  6 weeks
working with material  containing  methoxyethyl mercury  chloride.   Remarkably
high blood  levels were reported (range 340  to 1,090,  average  650  ng Hg/ml) 4
weeks after the end of exposure.   No adverse  health  effects could  be  detect-
ed.
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     Rats exposed  for  2  years  to phenyl  mercury acetate in the diet exhibit-
ed morphological changes  in  the  kidneys  (Fitzhugh,  et al.  1950).  As pointed
out  by Goldwater  (1973),  a  dose-response relationship was  not established,
as animals receiving higher doses showed no effect.
Teratogenicity
     Methylmercury  and Other  Short-Chain  Alky! Mercurials:   Although  brain
damage due to prenatal exposure  to  methylmercury has occurred in human popu-
lations, no  anatomical defects have been reported.   However, adequate epide-
miological studies  have  not  been performed and the possibility of teratolog-
ical action  of  methylmercury  in  human  subjects cannot be  dismissed at this
time.
     Embryotoxicity and  teratogenicity of  methylmercury in  animals have been
reported by  several  authors.   Oharazawa  (1968) noted  an  increased frequency
of  cleft  palate  in mice  treated with  an alkyl  mercury phosphate.   Fujita
(1969) treated mice to daily administration  of 0.1  mg Hg/kg of methylmercury
and found that the  offspring had significantly reduced birth weight and pos-
sible neurological  damage.  No gross  teratological  effects  were noted.   His-
tological evidence  of  damage  to  the  brain as  a result of  prenatal  exposure
to methylmercury has been reported on several  animal  species (Matsumoto,  et
al.  1967;  Nonaka,  1969;  Morikawa, 1961).  Non-lethal anatomical  malforma-
tions in animals prenatally exposed to methylmercury have  also been reported
by Spyker and Smithburg  (1972) and  Olson and Massaro (1977).  Effects due to
prenatal exposure in mice were found to  be about twice  as great as those in-
duced by postnatal  exposure  and  were greater  when  the  methylmercury was ad-
ministered late in the period of organogenesis.
     Mercury  Vapor  and  Liquid Metallic  Mercury:   Although the  syndrome  of
mercury vapor poisoning  has  long been known  in adults, practically nothing
is known  about  prenatal  damage.   Rats  exposed  prenatally  to  mercury  vapor
                                     C-90

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 are  reported  to  have died  within  6  days  after birth.   In  one experiment,
 where  exposures were continued  throughout  gestation, all  of  the pups died;
 some  of  the  deaths  could  be attributed  to  a  failure  of  lactation  in  the
 dams.   A second part of the experiment exposed  the dams  only  prior  to  the
 time  of  impregnation.   In  this  case,  during lactation  and  nursing,  viable
 pups  appeared normal, yet  25  percent of these  pups died  before day  6.   No
 teratological  effects were  observed, birth  weights were  reportedly  within
 the  normal  range,  and histopathologic findings  were negative,  although  the
 concentrations  of  vapor  were high  (l^c  for  the   adult  females)  (Baranski
 and Szymczyk,  1973).
     Salts  of Inorganic  Mercury:   Teratological  effects of HgCl^  have been
 reported  in animals  (Gale and  Perm  1971).   However,  no  data are available on
 the teratogenicity of inorganic mercury in human populations.
 Mutagenicity
     Methylmercury and Other Short-Chain Alkyl Mercurials:   No mutagenic  ef-
 fects have been reported in human populations due to exposure to methylmer-
 cury.   However,  a  statistical relationship  was  found between  the  frequency
 of chromosome  breaks  and  blood concentrations of methylmercury in 23  Swedish
 subjects  on  fish  diets.   The mercury  concentration  in  the  blood  of  the
 exposed  group  ranged from  14  to  116  ng Hg/ml,  and  in   the  nonexposed  group
 from 3 to 18 ng/ml  (Skerfving, et al. 1974).
     Khera  (1973)  has reported  that,  in  rats,  alkylmercury  compounds  may
 damage  gametes  prior to  fertilization.  Similar experiments  in  mice  failed
 to demonstrate  statistically significant effects (Suter, 1975).  Studies  by
 Ramel (1972) have revealed  damage to  reproduction resulting from exposure  to
 alkylmercurials during  adult life.   Methylmercury  has   been  shown  to  block
mitosis  in  plant  cells,   human  leukocytes  treated  in vivo, and  human  cells
                                     C-91

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in tissue culture, and to  cause  chromosome  breakage  in  plant cells and point
mutations in Drosophila (Swedish Expert Group, 1971;  Ramel, 1972).
     Mercury  Vapor  and Liouid  Metallic  Mercury:   Nothing has  been  reported
on the  mutagenic  effects  of mercury  vapor  in humans,  animals,  or  ir\_ vitro
tests.
     Salts  of Inorganic  Mercury:   Reversible  inhibition of  spermatogonial
cells has  been observed  in  mice treated with  HgCU (Lee and  Oixon,  1975).
No evidence  has been  published concerning the mutagenicity  of  mercury salts
in humans.
Carcinogenicit^
     When metallic mercury was  injected  intraperitoneally into  rats, sarcom-
as were observed only  at  those  tissues  that had been in  direct  contact  with
the metal (Oruckrey, et al. 1957).
     No other evidence exists that  links exposure to  mercury  with cancer.
                                     C-92

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                             CRITERION FORMULATION

 Existing  Guidelines  and  Standards
      A  World  Health Organization expert  group has  recommended  an interna-
 tional  standard  for  drinking water of 1  ug Hg/1 (WHO, 1971); the U.S. Envir-
 onmental  Protection Agency  has recommended  a standard  of 2  yg  Hg/1   (U.S.
 EPA,  1973).
 Current Levels of  Exposure
      The  median  levels of  total mercury for various bodies of uncontaminated
 water were  summarized  in Table 7.  This  information  is  also presented  later
 in  this document in  Table  18 to allow consideration with the derived criter-
 ia  values.   Reported values  are reviewed in the main  text  of this document.
 In  general,  values  for  uncontaminated  freshwater  do not exceed  200 ng Hg/1
 and for ocean  water 125  ng  Hg/1.   It is  likely  that the wide range  of re-
 ported  individual  values are  a result  of difficulties  in  obtaining precise
 analytical measurements  (McLean, et al. I960).
     Measurements  of different chemical  and  physical species  of  mercury in
 natural waters have  rarely been made.   It  is  suspected  that a wide variety
 of  different chemical  compounds  of  mercury  are  present,  that the relative
 proportions may vary from one  body of water to  another,  and may vary season-
 ally.    Methylmercury compounds  are   below  the limit  of detection by  most
methods and amount to a  small  fraction  (probably  less  than  3  percent)  of the
 total  mercury.   Nevertheless,   this  small amount  of  methylmercury  in  water
 probably determines  uptake by  fish either directly through the gills or in-
directly through  the food chain.
     Methylmercury  in  edible  fish  is   the  predominant,  if not  the  only,
source of  methylmercury exposure to human populations.
                                     C-93

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Special Groups at Risk
     The  evidence  presented  in this  document  indicates  that intake  of  mer-
cury from drinking water  is  negligible.   Human exposure to  the  most  hazard-
ous form  of this metal, methylmercury,  is  almost  exclusively via consumption
of fish.  Thus, the population most  likely to  be at risk  is  heavy consumers
of fish containing the highest mercury concentrations.   The  stage of  the hu-
man life cycle subject to the greatest hazard  from  mercury intake is  probab-
ly prenatal.
     Other forms of mercury  probably do not present a  significant risk,  ex-
cept in the case of mercury  vapor.   The  latter may present a health  risk  if
occupational  exposures  are  not maintained below acceptable  limits.   Unfor-
tunately, the stage of the life  cycle most susceptible to the  toxic  effects
of mercury vapor has not yet been identified.
     An unusual and rare reaction to inorganic  mercury  forms,  called  acrody-
nia or  "Pink's  Disease,"  has been  described.   This disease  has  occurred  in
children  receiving oral  doses of medications  containing  inorganic mercury,
or inhaling mercury vapor.   Only  a   small  number  of  children  develop  acrody-
nia when exposed to mercury.   It is  unlikely that a  small  amount  of inorgan-
ic mercury ingested in drinking water would cause this  disease.
Basis and Derivation of Criterion
     From a health effects perspective and recognition  of  exposure potential
the organo-mercury compounds  are  the most important,  especially  methylmer-
cury.  However, inorganic compounds  of mercury  should also be considered  be-
cause of  their  toxicity potential,   and  perhaps more importantly  because  of
the  ease  with which  inorganic mercury  can be  converted  to  organo-mercury
compounds in biological systems.  Methylation  and demethylation  are discuss-
ed in the text of the  criterion document  (see Exposure  section conclusion).
                                     C-94

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     The  approach  that  has been adopted  in  this  criterion  document involves
the following steps:  (1)  Identify  those  organs or tissues  most sensitive to
damage  by the  different  chemical  and  physical  forms  of  mercury.   Damage
beina  defined  as  an  effect  that  adversely changes  normal  function  or
diminishes an  individual's reserve capacity  to deal with  harmful  agents  or
diseases.  (2) Determine  the  lowest body burden known to be  associated with
functional damage  in man  and,  if  possible,  determine the highest body burden
tolerated  by man.  (3)  Estimate  the  potential  human intake  from ingesting
water and eating contaminated fish products.   (4) Estimate a  criterion for
mercury in ambient water that will provide  adeauate  protection from adverse
effects on human health.
     Table 16, taken from  the  review  by the World Health Organization expert
group (WHO,  1976),  indicates  long-term daily intakes of  mercury which relate
to the  earliest  effect  on  the central nervous system.  This  system is more
sensitive to damage from  mercury  than other functional  systems  in the human
body.  The conclusions represented  in  Table  16 were recently  endorsed by the
National Academy of Sciences (NAS, 1978).
     Evidence reviewed in  the  Effects  section  of  this document is essential-
ly the  same  as  the evidence reviewed  by  the WHO group with regard  to adult
exposures to mercury.   Effects on  the adult nervous system have  been esti-^
mated to  occur at  blood concentrations in the range of 200 to  500 ng Hg/ml,
corresponding to  a long-term  daily intake of  mercury in the  diet of  3  to  7
ug Ha/kg  body weight.  The risk of  effects at this  intake  level  is  probably
less than 8 percent (1 in 12 chances).
     Since the WHO (1976)  criteria document was  written,  new  evidence  has
been documented.   As  reported in  the Effects  section, clinical  follow-up
studies  of  the  Niigata  outbreak  (1978)  point to  delayed  cases  of  mercury
                                     C-95

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                                   TABLE  16*

            The Concentrations of Total Mercury in Indicator Media
             and the Eauivalent Long-Term Daily Intake of Mercury
             as  Methylmercury  Associated  with  the  Earliest  Effects
            in the Most Sensitive Group in the Adult Population^.b
Concentrations in indicator media
 Blood                           Hair       Equivalent long-term daily intake
(ng/ml)                         (u9/g)            (ug/kg body weight)
200-500                         50-125                    3-7
*Source:  WHO, 1976.

aThe risk of the earliest effects can be expected to be between
 3 to 8 percent.

bThe table should not be considered independently of the text.
                                     C-96

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poisoning.  One case had  a  maximum hair  concentration  of 50 ug/g.  Thus, de-
spite conclusions based on  new  analytical  results  indicating that the lowest
observed  effect  level  had  been underestimated, the  new clinical  data  from
Japan are  still  consistent  with a LOEL  of  200 ng  Hg/ml in  blood.   New  data
from  Iraa  indicated females  who experienced maximum hair concentrations  dur-
ing pregnancy  in  the  range  of  99  to 384 ug  Hg/g  had a high  probability of
having  retarded  development in  children (Mufti, et  al.  1976).   Unfortunate-
ly, the population size was  too small  to establish a  lower  limit to effects
of prenatal exposure.  A  hair concentration  of 99  ug Hg/g  is equivalent  to a
blood concentration of about 400 ng Hg/ml.
     The  most  recent  information  on the effect of mercury on  human  health
has come from  the study of  the  Iraa outbreak of 1971-1972.  The followup of
the cases  of  prenatal  exposure  is still in  progress.   As  noted by  the Na-
tional  Academy of Sciences  (1978),  "continued careful evaluation of  this
very  important cohort  of  prenatally  exposed  individuals  will   provide the
most sensitive assessment of human mercury toxicity."
     Thus,  at  this stage of knowledge  of  the dose-effect relationship  of
mercury in man, it appears  that the  earliest detected effects in man  are at
blood  concentrations   between   200  and  500  ng Hg/ml,  for  both  pre-   and
postnatal   exposures.   Blood  concentrations  of mercury correspond  to  body
burdens in  the range of 30  to  50  mg Hg/70  kg body weight,  and  to  long-term
daily intakes  in the range of 200 to 500 ug  Hg/70 kg.
     Mercury intake from  drinking water, according  to data reviewed  in the
Exposure section of this  document, is generally less  than  1 ug  Hg/day,  and
is considerably  less  than  the  diet portion  (Table  17).  Assuming  that the
concentration  of mercury  in all  samples  of  drinking water  is at the current
U.S.  EPA standard of 2  ug Hg/1, the maximum  daily intake would  only be  4 yg
Hg, assuming 2  liters  of drinking  water are consumed  per  person each  day.
This   maximum   intake would   amount  to  only  about   1  to  2  percent  of   the
                                     C-97

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                                   TABLE 17

           Estimate of Average and Maximum Daily Intakes of Mercury
             by  the  "70 kg  Standard Adult"  in  the U.S. Populations


                Mercury intake yg/day/70 kg            Predominate form

Media            Average         Maximumb
Air
Water
Food
0.3
0.1
3.0
0.8
0.4
5.0
HgO
Hg++
CHaHg*
aFor details on the calculation of these numbers,  see the
 Exposure section of this document.

bThese are approximate figures indicating that 95  percent
 of the population have intakes less than these figures.
 Occupational exposures are not included.
                                     C-98

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minimum  toxic  intake  given  in Table 16.  Thus, from the toxicological stand-
point, exposure to mercury, via drinking water only, would be negligible.
      Indirect  transfer  of mercury  from water to man  is  much more important
than  transfer  from direct routes.  This  conclusion is based on  the assump-
tion  that  fish  bioaccumulate  a significant amount of mercury from water.  In
theory,  it  should  be  possible to  calculate the maximum concentration of mer-
cury  in  water  which  would  ensure  that intake from  fish  does not exceed the
lowest observable  effect  level  (LOEL)  in man.  Thus, if the bioconcentration
factor is  known for each  species  of edible fish, it is arithmetically simple
to estimate the maximum concentration of mercury  in water.
Calculation of Criteria for Mercury in Natural Waters
      BCF values  have  been determined  experimentally in a  limited  number of
cases.   Experiments were  made for  both  freshwater and  marine fish.   Inorgan-
ic and methylmercury  compounds were used.  The  range  of values  for  the BCF
was enormous,  from 250  to 60,000.  Estimating a  mean  value  from  such  a wide
range would not be realistic.   Indeed,  there  are both  practical  and theoret-
ical  difficulties  in measuring  an experimental  BCF  that  is applicable  to
mercury  accumulation  by  fish  in  natural  waters.   Instead,  a practical  BCF
has been estimated based on  observed  average concentrations in  fish  and in
the natural bodies of water in which the fish  live  (Table  18).   The practic-
al values  of  the  BCF, referred to as  PBCF, are  average values covering the
whole range  of fish  sizeSj  and water  temperatures* averaging chemical  and
physical  species of  mercury,  and  other  factors  that may be  expected  to af-
fect the fish accumulation of mercury  (Table  18).   The  PBCFs  depend upon the
assumption  that fish  accumulation  of  mercury is  related to  the  average con-
centration  of total mercury in  natural  water,  as discussed in detail  in the
main document.   Specifically,  uptake of mercury by  a  fish  whether  by  direct
                                     C-99

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                               TABLE 18

Data Used in the Estimation of Average Individual  Fish Intake,  Average
 Individual  Mercury  Intake, Average  Practical Bioconcentration Factors
 for Bodies of  Fresh Water, Estuarine-coasta1. Water, and Open Oceans

SPECIES




Trout
Bass
Catfish
Pike
TOTAL
MEDIAN

Shrimp
Flounder
Clams
Crabs/
Lobsters
Oysters/
Scallops
TOTAL
MEDIAN

F R E S
H WATER
FISH INTAKEa
Proportion
by weight


0.030
0.025
0.025
0.012


E S T U A R
0.102
0.049
0.038
0.037

0.030



Amount


q/day
0.561
0.467
0.467
0.224
1.719

I N E -
1.910
0.910
0.711
0.692

0.561

4.78

Concentration
in edible
tissue
wq/q
0.240C
0.200C
0.070C
0.390C


COASTAL w
0.050C
0.100C
0.050C
0.0906

0.030C




TOTAL MERCURYb
Average
intake

ug/day/70kg
0.135
0.093
0.0327
0.0873
0.348

A T E R S
0.0950
0.0910
0.0356
0.0623

0.0168

0.301



PBCF



6000
5000
1750
9750

5500

2941
5882
2941
5294

1765


3765
                                 C-iOO

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                               TABLE 18 (continued)

      Data Used in the Estimation of Average Individual Fish Intake, Average
        Individual Mercury Intake, Average Practical Bioconcentration Factor
        for Bodies of Fresh  Water,  Estuarine-coastal Water,  and Open Oceans

SPECIES

OPEN
OCEANS
FISH INTAKE*
Percent total Amount
by weight

Tuna
Unclassified
Ocean Perch
Salmon
Cod
Haddock
Pollock
Sardines
Halibut
Snapper
Whiting
All Other
TOTAL
MEDIAN

0.214
0.184
0.050
0.034
0.027
0.025
0.020
0.018
0.011
0.011
0.009
0.051

g/day
4.00
3.441
0.935
0.636
0.505
0.467
0.374
0.337
0.206
0.206
0.168
0.954
12.229

Concentration
in edible
tissue
ug/g
0.205C
0.140d
0.130C
0.050C
0.130C
0.110C
0.14C
0.026
0.1976
0.30f
0.12f
0.14d


TOTAL MERCURY
Average
intake
v g/day/ 70kg
0.820
0.4817
0.1216
0.0318
0.0657
0.0514
0.0524
0.0067
0.0406
0.618
0.0202
0.1336
2.4437



PBCF

13,666
9,333
8,666
3,333
8,666
7,333
9,333
1,333
13,133
20,000
8,000
9,333
9,000
aCordle, et al. 1978, Table 8, total fish intake were taken as
 18.7 g/day/70 kg.
^Associated total Hg water concentration were 40 ng/1  for fresh water;
 17 ng/1 for estuarine-coastal waters,  and 15 ng/1  for the open ocean.   For
 details, see chapter on Exposures
CTable 6 of this document
dMean of reported values for oceanic fish in this table
estanford Research Institute, 1975
fFOA, 1978
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 sorption  in  the gills or  via  the food chain  is  proportional  to the average
 mercury  concentration in  natural  water.   It  is further  assumed  that  the
 methylmercury  level  in natural waters,  on  the average,  is  a  constant frac-
 tion of total mercury.
     The  criterion  for   a natural  body of  water  is  the  maximum  average
 mercury concentration  which  shall not result  in  significant risk  of adverse
 effects on  human  health  from  consumption  of  fish and  drinking water. f'The
 calculation of the criterion for  freshwater, shown  in  Table  19, was based on
 the  assumption  that  2 liters of water  are  consumed  daily  while  that  for
 estuarine-coastal  and  open ocean  waters  is  based  on  consumption of marine or
 estuarine  organisms  only.   The   concentration  in  natural  water  C   that
 would  correspond  to  the  lowest  observable effect  level  (LOEL)   for  daily
 human intake of mercury in the 70 kg adult is given by
                    LOEL = c' (2 + d x PBCF)	(4)
 where  d  (g/day/70 kg)  is  the average  intake  of freshwater,   estuarine  and
 ocean species most freauently  consumed;  the PBCF relates  to the appropriate
 body of water in which the fish live.
     The value of  d  (the daily amount of fish  consumed)  in  equation (4)  was
 calculated by  apportioning the  average total  daily  intake of   fish  from  all
 sources—18.7  g/day—according  to  average  individual  consumption  of  fish
 from each body of  natural  water.   Using  data  listed  in Table 18,  it  was  de-
 termined that the  average  individual  fish consumption  from freshwater bodies
 is 1.72 g/day,  from estuarine-coastal waters  is 4.78  g/day,  and  from  open
 oceans is 12.2 g/day.
     Species of fish used  in the  calculation are  those for which information
was available  on  human consumption  and  on  average mercury concentration  in
edible tissue.  The  average  individual  mercury intake shown in  Table  19  was
estimated as 0.348 ug/day/70 kg individual  from freshwater, 0.301  from estu-
 arine and  coastal water,  and 2.44  from open  ocean water.

                                     C-102

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                                    TABLE 19

             Estimation of Criteria Taking  into Account Both Average
      Fish Consumption and Average Mercury Intake from Each Body of  Water3
Average individual
Body daily consumption
of FishD Mercury^
water (g/day) (jig/day)
Freshwater 1.72 0.348
Estuarine 4.78 0.301
Coastal
Open Ocean 12.22 2.4*
Total 18.73
Apportioned Criteria
LOELC
(ug/day/70 kg) PBCF1? (ng/l)
 of water.

^Criteria concentration  eouals C1  from equation  (4)  divided  by  a safety
 factor of 10.
                                    C-103

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     The  LOEL   used   to  calculate  C   was  200   vg   Hg/day/70  kg  (2.86



ua/day/ka) individual.   This  LOEL  was  apportioned to each body  of  water ac-



cording to  the  average  individual  intake  of total  mercury from the  body of



water.  The  average individual daily  intake was calculated from the amount



of each fish species consumed per  day  and  the average concentration of total



mercury in edible  tissue for that species  (see  Table 18 for  details).   Ap-



portioning the  total daily intake  of 200 yg Hg/day/70  kg  according to aver-



age individual  intake  from each body of natural  water, the LOEL for fresh-



water was  calculated  as 22.5, for  estuarine and coastal  as  19.5,  and  for



open oceans as 158 ug/day/70 kg individual.



     The average  practical  bioconcentration factor  (PBCF) was chosen as the



median value  for each  species  in  each body  of  water.   The median PBCF  for



freshwater is 5,500, for estuarine and coastal water is  3,760,  and for  open



ocean it  is  9,000.   Given  the large  values of PBCF,  the contribution  of



drinking water  to  total  daily intake is negligible  so  that  assumptions  con-



cerning the chemical form of mercury in drinking water become less important.



     Substituting  in  eauation  (4)  the apportioned  values of  LOEL,   d,  and



PBCF for each body of  water, and  using a  safety factor of 10 the  following



criteria were  calculated:   freshwater 196  ng/1; estuarine-coastal  waters,



108 ng/1; and open ocean 143  ng/1  (Table  19).   The  safety  factor  of 10 is



intended to take  into  account individual  differences in habits  of  fish  con-



sumption and  in susceptibility to the toxic  effects of methylmercury,  in-



cluding  prenatal exposures.



     In  view  of the assumptions and  approximations  involved in  the  deriva-



tion, the values for the criteria  will  be  rounded to 2  significant figures.



Thus three levels  are  as follows:   freshwater,  0.19  pg/1;  estuarine-coastal,



0.1-1 ug/1;  and open oceans, 0.14 yg/1.
                                    C-104

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     Since  Hg  is extensively  bioaccumulated  in the  tissures of  open  ocean
organisms  and   these  marine  species  constitute  the  major  portion  (i.e.,
approximately  65  percent)  of total  ingested  fish  (Table  19),  the criterion
calculation of primary significance  to  human  health  is  one that incorporates
the  ingestion  of  open  ocean  fish  or  shellfish as well  as freshwater  and
estuarine/coastal  aouatic   organisms.   This  criterion  level  reflects  the
intake  of  2 liters of water  per day and  the daily intake of  0.00172  kg of
freshwater  aouatic  organisms,  0.00478  kg  of  estuarine/coastal  organisms,  as
well as 0.0122 kg of open ocean organisms  (Table 19).   It is calculated as:
r,,  	(LOEL)/uncertainty factor   	  ...5
           2  +  (0.00172  x  PBCFf)+(0.00478  x  PBCFe(J + (0:oi22 x  PCBF^
where:
     LOEL = 200 ug/day
     Uncertainty factor = 10
     PBCFf = Practical BCF (5500) for Hg in freshwater organisms
     PBCFgc = Practical BCF (3760) for Hg in estuarine/coastal organisms
     PBCF  = Practical BCF (9000) for Hg in open ocean (marine) organisms
     2 = daily water consumption in liters
Substituting for eouation (5),

C" =	   200 uq/da.y/10	
      2 + (0.00172 x 5500)+(0.00478 x 2760)+(0.0122  x 9000)
   = 20 uq/day
        139.2"
    = 0.144 ug/1 or 144 nq/1

     This concentration  would be  protective  against the adverse  effects  of
Hg via daily ingestion of  2  liters of water and consumption  of contaminated
anuataic organisms from  all  sources  (freshwater, coastal/estrarine,  and open
ocean).
                                     C-105

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     The  inclusion  of  open  ocean  marine  organisms  in  this  calculation
represents an effort to  consider all  pertinent sources of  human  exposure to
Hg.   However,  the  use  of  ingestion  and  bioconcentration  data  for  marine
species  in  this  criterion derivation  is  an  additional important factor  not
used  in  other documents  of  this series.  Contributions  from  non-fish  food
sources are not considered since  levels of mercury  in  these materials  are so
low as to be undetectable using available analytical techniques (NAS, 1978).
     In  summary,  based  on  the  use of  human  epidemiological data and  an
uncertainty factor of  10, the  criterion  level  of  mercury  corresponding to an
acceptable  daily  intake  of  2,86  vg/kg,  is  144  ng/1.   Drinking   water
contributes  approximately 1  percent   of  the  assumed  exposure while  eating
contaminated fish products accounts for 99 percent.  The  criterion  level  can
similarly be  expressed  as  146 ng/1  if  exposure  is assumed  to be  from  the
consumption of fish and shellfish products alone.
Comment on Criteria
     Experimental   investigation   indicated  that  when  fish  are  exposed  to
methylmercury, a rapid uptake phase is completed  in about  2 to 3  months  (Ot-
tawa River  Project,  1976).   Thereafter,  uptake may continue  but  at  a  slower
pace.  Thus,  it seems  reasonable to regard  the criteria as  a time-weighted
average concentration  covering a period  of 2 months or so.  In other  words,
it should not be regarded as an  instantaneous  value that  should never  be  ex-
ceeded even for brief periods of  time.
     In  this  document  a  total  of four  criteria  have been  calculated  using
various  assumptions  relative to  average daily intakes of  aquatic  organisms
from  fresh,  estuarine/coastal,  and  open  ocean waters.   The  criteria  have
been  calculated   by  an   arithmetical  procedure  using  the  best  available
evidence  for  the   important  parameters,  e.g.,  LOEL,   BCF  and  average  daily
                                    C-106

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intake  of  fish.   It  should be  noted,  however,  that  of  the  four  values
derived, the  recommended  criterion  of 0.14  yg/1  is  based on  a total  daily
consumption of 18.7  g  of  freshwater,  estuarine, and marine  organsims  and  an
intake of 2 liters of water daily.
                                    C-107

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•U.S. OOVEHKBfT PKUTHIK) OmCE:  198O-0-720-O1 a/596%
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