-------
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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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
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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.
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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
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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.
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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
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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
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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
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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
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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:
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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.
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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
-------
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
-------
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
-------
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
-------
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
-------
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.
C-30
-------
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.
C-31
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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.
C-32
-------
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
-------
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.
C-34
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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
-------
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
-------
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
-------
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
-------
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
C-40
-------
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
C-41
-------
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
-------
en
X
en
O
O
O
OQ
O
cc.
O
z
200i
-------
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
-------
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.
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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.
C-81
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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.
C-84
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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
C-85
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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.
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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
C-101
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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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