297 925
MERCURY
Ambient Water Quality Criteria
Criteria and Standards Division
Office of Water Planning and Standards
U.S. Environmental Protection Agency
Washington, D.C.
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CRITERION DOCUMENT
MERCURY
CRITERIA
Aquatic Life
Inorganic Mercury
The data base for freshwater aquatic life and in-
organic mercury is insufficient to allow use of the Guide-
lines. The following recommendation is inferrred from toxic-
ity data for saltwater organisms.
For inorganic mercury the criterion to protect
freshwater aquatic life as derived using procedures other
than the Guidelines is 0.064 ug/1 as a 24-hour average and
the concentration should not exceed 3.2 ug/1 at any time.
For inorganic mercury the criterion to protect
saltwater aquatic life as derived using the Guidelines is
0.19 ug/1 as a 24-hour average and the concentration should
not exceed 1.0 ug/1 at any time.
Methylmercury
For methylmercury the criterion to protect fresh-
water aquatic life as derived using the Guidelines is 0.016
ug/1 as a 24-hour average and the concentration should not
exceed 8.8 ug/1 at any time.
The data base for saltwater aquatic life and
methylmercury is insufficient to allow use of the Guidelines.
The following recommendation is inferred from toxicity data
for freshv/ater organisms.
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For methymercury the criterion to protect saltwater
aquatic life as derived using procedures other than the
Guidelines is 0.025 ug/1 as a 24-hour average and the con-
centration should not exceed 2.6 u9/l at any time.
Human Health
For the protection of human health from the toxic prop-
erties of mercury ingested through water and through contami-
nated aquatic organisms the ambient water criterion is deter-
mined to be 0.2 ug/1.
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Introduction
Mercury, a silver-white metal which is a liquid at
room temperature, can exist in three oxidation states: elemental,
mercurous, and mercuric; it can be part of both inorganic
and organic compounds.
Mercury is a silver-white metal, atomic weight 200.59.
A liquid at room temperature, its melting point is -38.87°C
and its boiling point ranges from 356 to 358°C. The metal
is insoluble and is not attacked by water. At 20°C, the
specific gravity is 13.546 (Stecher, 1968), and the vapor
pressure is 0.0012 mm Hg (Stecher, 1968).
Mercury exists in a number of forms in the environment.
The more commonly found mercuric salts (with their solubili-
ties in water) are HgCl2 (lg/13.5 ml water), Hg(N03) (soluble
in a "small amount" of water), and Hg (CH3COO)250 (lg/2.5
ml water). Mercurous salts are much less soluble in water.
HgNo3 will solubilize only in 13 parts water containing
1 percent HNO^. Rq2^2 *s Practi-caHy insoluble in water.
Because of this, mercurous salts are much less toxic than
the mercuric forms (Stecher, 1968).
The Department of the Interior carried out a nationwide
reconnaissance of mercury in U.S. water in the summer and
fall of 1970 (Jenne, 1972). Of the samples from the indus-
trial wastewater category, 30 percent contained mercury
at greater than 10 jug/1: nearly 0.5 percent of the samples
in this group contained more than 1,000 jug/1. Only 4 percent
of the surfacewater samples contained more than 1,000 jug/1.
The higher mercury concentrations were generally found in
A-l
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small streams. About half the 43 samples from the Mississippi
River contained less than 0.1 jug/1. The mercury content
of lakes and reservoirs was between 0.1 and 1.8 /ag/1. With
few exceptions, the mercury content of groundwater samples
w,as below detection (O.ljug/1).
In a survey by the EPA Division of Water Hygiene, 273
community, .recreations, and federal installation water sup-
plies were examined. Of these, 261 or 95.5 percent, showed
either no detectable mercury or less than 1.0 >ug/l in the
raw and finished water. Eleven of the supplies had mercury
concentrations of 1,0 to 4.8jug/l and one supply exceeded
5,0/jg/l. When this one supply was extensively reexamined,
the mercury concentration was found to be less than 0.8
jug/1 (Hammerstrom, et al. 1972).
Seawater contains 0.03 to 2.0jug/l, depending on the
sampled area, the depth, and the analyst. In a study of
Pacific waters, mercury concentrations were found to increase
from .surface values of near 0.10 jjg/1 to 0.15 to 0.27/ig/l
at greater depths. In an area seriously affected by pollution
(Minamata B.ay, Japan), values ranged from 1.6 to 3.6jjg/l.
The National Research Council (1977) has shown typical oceanic
values for mercury to be .01 to .03/ig/1. Oceanic mercury
is generally present as an anionic complex (HgCo- ), which
does not have as pronounced a tendency to bind to particulate
substances and then settle out as do mercury compounds found
in freshwater (Wallace, et al. 1971).
A major use of mercury has been as a cathode in the
electrolytic preparation of chlorine and caustic soda; this
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accounted for 33 percent of total demand in the United States
in 1968. Electrical apparatus (lamps, arc rectifiers, and
mercury battery cells) accounted for 27 percent, and indus-
trial and control instruments (switches, thermometers, and
barometers), and general laboratory applications accounted
for 14 percent of demand. Use of mercury in antifouling
and mildew proofing paints (12 percent) and mercury formula-
tions used to control fungal diseases of seeds, bulbs, plants,
and vegetation (5 percent) were other major utilizations,
however, mercury is no longer registered by the EPA for
use in antifouling paints or for the control of fungal dis
eases of bulbs. The remainder (9 percent) was for dental
amalgams, catalysts, pulp and paper manufacture, Pharmaceuticals,
and metallurgy and mining.
Several forms of mercury, ranging from elemental to
dissolved inorganic and organic species, are expected to
occur in the environment. The finding that certain micro-
organisms have the ability to convert inorganic and organic
forms of mercury to the highly toxic methyl or dimethyl
mercury has made any form of mercury potentially hazardous
to the environment (Jensen and Jernelov, 1969). In water,
under naturally occurring conditions of pH and temperature,
inorganic mercury can be coverted readily to methyl mercury
(Bisogni and Lawrence, 1973).
Mercury is able to form a series of organometallic
compounds with alkyl, phenyl, and methoxyethyl radicals.
Short-chained alkyl mercurials are toxicologically important
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because the carbon-mercury bond can be broken in vivo, with
the subsequent disappearance of the organic radical. In
humans, mercurials have been associated with neurological
disorders, sensory impairment, tremors, buccal ulceration,
.gastro-intestinal complaints and multisystem involvement
due to general encephalopathy (Matsumoto, et al. 1965; Chang,
et -;al. .1973; Davis, et al. 1974; Rustam, et al. 1975; Weiss
-a'nx3-Doherty, ,1976) . Mercurials will damage the bronchial
epithelium -:and interrupt respiratory function in freshwater
invertebrates. Rainbow trout will suffer loss of equilibrium,
and ;trout fry ate more susceptible to mercury poisoning
-than finger.lings. Mercurial compounds may interfere with
receptor membranes in fish (Kara, et al. 1976).
Mercury can be bioconcentrated many fold in fish and
.other aquatic organisms because of rapid uptake and the
relative inability of fish to excrete methyl mercury from
:their•tissues. Freshwater values of 63,000 have been found
as-well, as :sa'ltwater bioconcentration values of 10,000.
Non-human mammals have been shown to suffer central
nervous system :rdamage as well as teratogenesis and spontaneous
tumorigenesis (Robbins and Chen, 1951; Spann, et al. 1972;
Inamoto, et al. '1976). There is no data available on the
.teratogenicity or mutagenicity of inorganic mercury in human
'. t
populations Furthermore, there is no evidence of mercury
.exposure producing carcinogenicity.
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REFERENCES
Bisogni, J.J., and A.W. Lawrence. 1973. Methylation of mercury
in aerobic and anaerobic environments. Tech. Rep. 63. Cornell
Univer. Resour. Mar. Sci. Center, Ithaca, New York.
Chang, L.W., et al. 1973. Minamata disease. Acta Neuropathol.
26: 275.
Davis, L.E., et al. 1974. Central nervous system intoxication
from mercurous chloride laxatives. Arch. Neurol. 30: 428.
Hammerstrom, R.J., et al. 1972. Mercury in drinking water
supplies. Am. Water Works Assoc. 64: 60.
Kara, T.J., et al. 1976. Effects of mercury and copper on
the olfactory response in rainbow trout, Salmo gairdneri.
Jour. Fish Res. Board Can. 33: 1568.
Jenne, E.A. 1972. Mercury in waters of the United States,
1970-1971. Open file rep. U.S. Dep. Interior Geol. Surv.
Menlo Park, Calif.
Jensen, S., and A. Jernelov. 1969. Biological methylation
of Nature. 223: 753.
A-5
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Hat sumo to/ H. , et al. 1965. Fetal minomata disease. A neuro-
pathological. study of two cases of intrauterine intoxication
by a methyl mercury compound. Jour. Neuropathol. Exp. Neurol.
24: 563..
National Research: Council. 1977. An assessment of mercury
in the environment. National Academy of Sciences, Washington,
D.C..
Robbi.ns,,. E:..B, ,. .and. R'.,K., Chen. 1951. A new mercurial diuretic.
Jo.urf.- Am:*- Pharma. Assoc. 40: 249.
(
i
Rastam, H.:, et al. 1975. Arch. Environ. Health 30: 190.
,, J..W..,, et al.. 1972. Ethyl mercury p-toluene sulfonanilide;
l;e-t-ha«i: and reproductive effects on pheasants. Science 175: 328.
Ste.eh'er, PiG'. ,. ed. 1968. The Merck Index. 8th ed., Merck
and Co..,. Rahway,, New Jersey.
!
Wallace, R.A.., et al. 1.971. Mercury in the environment:
the human element. Oak Ridge, Tenn.
Weiss, B,. , and R..A. Doherty. 1976. Methylmercury poisoning.
i
TJer-atology 12.: 311.
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AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
Mercury has long been recognized as one of the more toxic
metals but only recently was it identified as a serious pollutant
in the aquatic environment. Initially, elemental mercury which is
a liquid at room temperature, was considered a relatively inert
heavy metal. It was thought that it would quickly settle to the
bottom of a body of water and remain there in an innocuous state.
However, both aerobic and anaerobic bacteria in the sediments are
capable of methylating mercury. Largely because of this bacterial
methylation process, which is maximum at a pH of 6, elemental mer-
cury can be a serious threat to the aquatic environment.
The toxicological data base and environmental chemistry of
mercury suggest that monomethyl mercury and divalent inorganic
mercury are the principal environmental concerns for mercury in
aquatic systems. In the following discussion and criteria, the
terms inorganic mercury and methylmercury will be used unless re-
ferring to a specific compound. All data are expressed as mercury,
*The reader is referred to the Guidelines for Deriving Water
Quality Criteria for the Protection of Aquatic Life '[43 FR 21506
(May 18, 1978) and 43 FR 29028 (July 5, 1978)] in order to better
understand the following discussion and recommendation. The fol-
lowing tables contain the appropriate data that were found in the
literature, and at the bottom of each table are the calculations
for deriving various measures of toxicity as described in the
Guidelines.
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The methylated form is more water soluble than the elemental
form and it is also more biologically active. Mercury bioconcen-
trates significantly from water and from food. Depuration is slow
and the biological half-life of mercury in aquatic organisms is
estimated at about two years.
Mercury is one of the few major pollutants that adversely af-
fects the aquatic environment through both direct toxicity and
bioaccumulation. Bioaccumulation has been more thoroughly studied
and has raised more concern. Methylmercuric compounds are more
tox.ic than inorganic mercury to mammals as well as aquatic life
and most of the tissue residue data reported are for the organic
form. There is no known physiological function of mercury and any
mercury added to the aquatic environment may increase tissue resi-
dues. The methylation of mercury in aquatic systems raises a
question as to what basis should be used to develop a criterion
for mercury. Some organic forms are substantially more toxic than
other organic forms and the inorganic forms.
Phenylmercuric acetate (PMA) is variable in formulation, hav-
ing various levels of active ingredients. In adjusting the data
in the tables the percentage of active ingredients given by the
authors was used in converting to metallic mercury concentrations.
When the percentage of active ingredients was not given, 80 per-
cent PMA was assumed (Allison, 1957).
Acute Toxicity
Table 1 contains the acute toxicity data for various mercury
compounds and groups these different types into inorganic mercury
salts, methylmercuric compounds and others, chiefly organic. The
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latter information exists principally because many of these com-
pounds have been used for disease treatment and parasite control
i
in fish cultural practices.
The acute toxicity data for inorganic and methylmercuric com-
pounds are probably biased by the lack of data on other than sal-
monid species. The single value for the nitrate salt is lower
than the values for the chloride salts but no major significance
can be attributed to the difference since the work was done by a
different investigator. Clearly, however, methylmercuric chloride
is more toxic as shown by the rainbow trout data. Brook trout
appear more resistant than rainbow trout to methylmercuric
chloride.
The available data for inorganic mercury do not give any in-
dication of differences in sensitivity among species of fish.
Since only two species have been tested for methylmercuric chlo-
ride there is an inadequate data base to draw inferences. Phenyl-
mercuric acetate (PMA) is variable in mercury content and although
the values have been corrected for mercury content as indicated
earlier, some variability may be due to the compounds used. Ig-
noring any uncorrected differences in PMA formulations tested, the
differences within species are as great as between species. ,
MacLeod and Pessah (1973) reported temperature effects of
mercuric chloride toxicity to rainbow trout. At 5, 10, and 15°C,
the unadjusted LC50 values were 400, 280, and 220 ug/lf respec-
tively. Clemens and Sneed (1958) found that at temperatures of
10, 16.5, and 24°C, the unadjusted LC50 values for channel catfish
and phenylmercuric acetate were 1,154, 863, and 233 ug/1,/ respec-
tively. They also investigated the influence of life stage of
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channel catfish on its sensitivity to pyridylmercuric acetate. At
i
23 to 24°C, they found about the same influence of age between
yolk sac fry (unadjusted 48-hour LC50 value of 374 ug/D and 3-
inch juveniles (unadjusted 24-hour LC50 value of 3,750 ug/D as
they did for temperature between 10 and 24°C.
Table 2 contains acute toxicity data for invertebrate spe-
cies. No data for organic forms of mercury were found, probably
because most of the recent concerns regarding mercury have been
with regard to residues and health effects. The adjusted LC50
values for inorganic mercury range from 0.02 to 2,310 ug/1.
Again, no judgment can be made on the appropriateness of the ad-
justment factors except that the adjustment of 21 is certainly not
excessive for differences between species.
9
In summary, the Final Fish Acute Values are 38.0 and 8.8 ug/1
for inorganic mercury and methylmercury, respectively. No final
values, will be derived for the other mercury compounds because of
the wide range of toxicity of this diverse mixture of compounds.
The Final Invertebrate Acute Value is 3.2 ug/1 for inorganic mer-
cury. Therefore the Final Acute Values are 3.2 and 8.8 ug/1 for
inorganic mercury and methylmercuric compounds, respectively.
Since invertebrate species are approximately 12 times more sensi-
tive than fish to inorganic mercury, the Final Acute Values for
methylmercury would probably be lower if data were available for
invertebrate species.
Chronic Toxicity
Table 3 contains the chronic toxicity data for fish. McKim,
et al. (1976) observed adverse effects of methylmercuric chloride
on brook trout at 0.93 ug/1 but not at 0.29 ug/1. Brook trout
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were approximately three to four times more resistant than rainbow
trout based on acute toxicity. This is not greatly different than
the species sensitivity factor (6.7) from the Guidelines and would
tend to support that factor as a minimum. The geometric mean of
these values divided by the species sensitivity factor (6.7) gives
an estimate of 0.078 ug/1 as the concentration protective of 95
percent of fish species. The estimate of chronic toxicity using
the application factor is 1.8 ug/1. The Final Fish Chronic Value
for methylmercury is the lower, or 0.078 ug/1.
The only chronic data for invertebrate species are for
Daphnia magna. The Final Invertebrate Chronic Values are 0.44 and
0.20 ug/1/ for inorganic mercury and methylmercury, respectively.
However, the source of the Final Invertebrate Chronic Value for
methylmercury (0.20 ug/D is a static test with measured concen-
trations of methylmercuric chloride (Beisinger, et al. manu-
script). A comparable flow-through test with methylmercuric chlo-
ride by the same authors resulted in an observed effect at the
lowest measured exposure concentration of 0.04 ug/1- No chronic
value could be calculated from this latter test since methylmer-
curic chloride could not be detected in the control test water
(Beisinger, et al. manuscript). There was no great difference be-
tween the static and flow-through tests with measured concentra-
tions of mercuric chloride (Beisinger, et al. manuscript) with
chronic values of 1.27 anmd 1.87 ug/1/ respectively.
Plant Effects
A variety of endpoints have been used to measure the effects
of mercury compounds on plants. The respective Final Plant Values
for inorganic mercury and methylmercury are 60.0 ug/1 and between
2.4 and 4.8 ug/1.
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Residues
Table 6 contains bioconcentration factor (BCF) data for in-
organic mercury with an alga and methylmercuric compounds with
fish.
No equilibrium of mercury in the fish tissues could be demon-
strated by Reinert, et al. (1974) after an 84-day exposure of
juvenile rainbow trout and the uptake of methylmercuric chloride
by brook trout had not reached equilibrium after 273 days (McKim,
et al. 1976). In the latter study, there was no detectable loss
of mercury from various tissues after a 16-week exposure in con-
trol water. Since whole fathead minnows were only analyzed once
at the end of a life-cycle exposure (Olson, et al. 1975) no com-
ment can be made with regard to equilibrium in this species.
Data (Reinert, et al. 1974) indicate an influence of tempera-
ture on rate of uptake but was not considered for BCF calculations
since a steady state was not achieved even at the highest tempera-
ture studied. Tissue residue concentrations after 12 weeks of ex-
posure followed temperature directly with the lowest bioconcentra-
tion factor (4,525) occurring at 5°C, and intermediate BCF (6,628)
at 10°C, and the highest BCF (8,376) at 15°C.
The contrast between fathead minnows (Olson, et al. 1975) and
brook trout (McKim, et al. 1976) is one of considerable interest
and potential importance. Of the factors that differ between
these tests, the species and feeding habits, the latter is the
most intriguing to consider. Since the trout were fed on pelleted
trout feed, there was little opportunity for food chain input to
the trout. In contrast, the fathead minnow, a browser, had the
opportunity not only to feed on the introduced food but also on
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the Aufwuchs growing within the mercury-enriched environment of
the exposure chamber. The higher bioconcentration factor for the
fathead minnows, 62,898, may be more representative of field data.
Since the lowest maximum permissible tissue concentration
(1.0 mg/kg) is based on the marketability of fish and shellfish,
only data on the edible portion of these organisms may be used to
calculate a Residue Limited Toxicant Concentration (RLTC). Of the
three tested fish species, the rainbow trout and fathead minnows
were analyzed whole. Muscle data are available for the brook
trout. However, McKim, et al. (1976) concluded that for the brook
trout there was no difference in bioconcentration factors between
residues in muscle and total body. Consequently, the highest geo-
metric mean BCF for a single species will be used to calculate the
RLTC for methylmercury. This bioconcentration factor is 62,898.
The RLTC is, therefore, 0.016 ug/1 to protect the marketability of
fish and shellfish.
There are no bioconcentration factors for inorganic mercury
and freshwater fish and shellfish,. However, there are data for
the American oyster (Kopfler, 1974) that demonstrate the, relation-
ship of uptake between inorganic mercury and methylmercuric com-
pounds. The BCF for inorganic mercury (10,000) is 0.25 of the
comparable value (40,000) for methylmercuric chloride. It seems
reasonable to assume that the freshwater BCF for edible portions
of fish and shellfish and inorganic mercury should be 0.25 times
62,898 or 15,725. This BCF results in a RLTC of 0.064 ug/1 using
the 1.0 mg/kg limit for marketability.
Miscellaneous
Table 7 contains no additional data that would alter the
selection of the RLTCs for the Final Chronic Value.
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CRITERION FORMULATION
Freshwater-Aquatic Life
Summary of Available Data
The concentrations herein are expressed as mercury. The
concentrations below have been rounded to two significant
figures.
Inorganic Mercury
Final Fish Acute Value = 38 ug/1
j
Final Invertebrate Acute Value = 3.2 ug/1
Final Acute Value = 3.2 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = 0.44 ug/1
!
Final Plant Value = 60 ug/1
Residue Limited Toxicant Concentration = 0.064 ug/1
Final Chronic Value = 0.064 ug/1
0.44 x Final Acute Value =1.4 ug/1
The maximum concentration of inorganic mercury is the
Final Acute Value of 3.2 ug/1 which is based on the more acutely
sensitive invertebrate organisms. The 24-hour average concen-
tration is 0.064 ug/1 and is based on an estimated Residue Lim-
ited Toxicant Concentration. No important adverse effects on
freshwater organisms of inorganic mercury have been reported to
be caused by concentrations lower than the 24-hour average con-
centration.
CRITERION: For inorganic mercury the criterion to pro-
tect freshwater aquatic life as derived using procedures other
than the Guidelines is 0.064 ug/1 as a 24-hour average and the
concentration should not exceed 3.2 ug/1 at any time.
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Methylmercury
Final Fish Acute Value =8.8 ug/1
Final Invertebrate Acute Value = not available
Final Acute Value = 8.8 ug/1
Final Fish Chronic Value = 0.078 ug/1
Final Invertebrate Chronic Value = 0.20 ug/1
Final Plant Value = greater than 2.4 ug/1/ less than 4.8 ug/1
Residue Limited Toxicant Concentration = 0.016 ug/1
Final Chronic Value = 0.016 ug/1
0.44 x Final Acute Value =3.9 ug/1
The maximum concentration of methylmercury is the
Final Acute Value of 8.8 ug/1 and the 24-hour average concen-
tration is the Residue Limited Toxicant Concentration of
0.016 ug/1. No important adverse effects on freshwater aqua-
tic life have been reported to be caused by concentrations
lower than the 24-hour average concentration.
CRITERION: For methylmercury the criterion to protect
freshwater aquatic life as derived using the Guidelines is
0.016 ug/1 as a 24-hour average and the concentration should
not exceed 8.8 ug/1 at any time.
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Table I. Freshwater fish acute values for morcury
Organism
Bloassay Test Chemical
Method* Conc.»» Description
Adjusted
Time LC50 LC50
(hrs) (ug/l)"» (ug/1)***
Reference
Rainbow trout (juvenile),
Salmo gairdneri
Rainbow trout (juvenile),
Salmo gairdneri
Rainbow trout (juvenile),
Salmo galrdneri
Rainbow trout (juvcnl le),
Salmo galrdnerl
Rainbow trout (juvenile),
Salmo gulrdnori
Rainbow trout (juvenile),
m Salmo galrdneri
1
o
Rainbow trout (larva),
Salmo gairdnerl
Rainbow trout (juvenile),
Salmo gairdneri
Rainbow trout (juvenile),
Salmo galrdneri
Hrook trout (juvenile),
Salvellnus fontlnalls
Brook trout (yearling),
Salvollnus fontlnalis
Rainbow trout (juvenile),
Salmo galrdnerl
•Rjlnbo* trout (juvenile).
Sol mo rjcilrriner i
Inorganic Mercury
KT U Mercuric %
ch 1 or i de
FT U Mercuric 96
chloride
rT U Mercuric 96
ch 1 or i de
R U Mercuric 96
ch 1 or 1 de
R U Mercuric 24
ct> 1 or 1 de
FT 11 Mercuric 96
nitrato
Methy Imercuric Compounds
R U Methy Imurcuric 96
ch 1 or 1 do
R U Methy Imercuric 96
ch lorlde
R U Mothy Imercuric 96
chloride
FT 11 Methy Imercuric 96
chloride
FT M Methy Imercuric 96
ch lorlde
Other Mercury Compounds
R U Ethyl mercury 4fl
phosphate
R U Pheny Imorcury 96
acetate
400 300 MacLeod &
Pessah, 1973
260 216 MacLeod &
Pessah, 1973
220 169 MacLeod &
Pessah, 1973
155 05 Mat! da, 1971
903 326 Wobesor, 1973
33 33 Hale, 1977
24 1J Wobesor, 1973
42 23 Wobesor, 1973
25 14 Mat Ida, et al
1971
04 04 McKim, et al.
1976
65 65 McKim, et al.
1976
43 19 Mat Ida, et al,
1971
5.1 2.0 Matlda, et al,
1971
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Table I. (Continued)
CD
Organ Ism
Rainbow trout (juvenile),
Salmo galrdnerI
Rainbow trout (juvenile),
Salmo galrdnorl
Rainbow trout (juvenile).
Salmo galrdnerI
Brown trout (juvenile),
Salmo trutta
Brown trou t (j uven iIe),
Salmo trutta
Brook trout (juvenile),
Salvellnus fontlnalls
Brook trout (juvenile),
SaIve11nus font i naI Is
Lake trout (juvenile),
Salvellnus namaycush
Lake trout (juvenile),
Sal veilnus namaycush
Goldfish,
Carassius auratus
Channel catfish (juvenile),
I eta Iurus punctatus
Channel catfish (juvenile),
Ictalurus punctatus
Channel catfish (juvenile),
Ictalurus punctatus
Channel catfish (juvenile),
Ictalurus punctatus
Bloassay Test
Method* Cone."
FT
S
S
S
S
S
S
S
S
S
S
S
U
U
U
U
U
U
U
U
U
U
U
U
Chemical
Description
Phenylmercury
acetate
Phenylmercury
acetate
Merthlolate
Pyr Idy Imercury
acetate-
Merthlolate
Pyr Idy Imercury
acetate
Merthlolate
Pyr Idy Imercury
acetate
Merthlolate
Phenylmercury
lactate
Ethy Imercury
phosphate
Ethy Imercury
p-to 1 uene
sulfonanl 1 Ide
Phenylmercury
acetate
Phenylmercury
acetate
Time
(hrs)
24
48
48
48
48
48
48
48
48
96
96
96
96
96
LC50
25
1,781
10,505
2,954
26,760
5,082
39,910
3,610
1,055
82
50
51
35
1,154
Adjusted
LC50
'•• (ug/l)»»«
12.8
789
4,652
1 ,308
1 1 .850
2,250
16,345
1,599
467
45
27
28
19
635
Reference
MacLeod &
Pessah, 1973
Wlllford,
1967
Wlllford,
1967
Will ford ,
1967
Wlllford,
1967
Wll Iford,
1967
Wlllford,
1967
Wlllford,
1967
Wlllford,
1967
Ellis, 1947
Clemens &
Sneed, 1959
Clemens &
Sneed, 1959
Clemens 4
Sneed, 1959
Clemens &
Sneed, 1958
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Table I. (Continued)
OJ
I
t~-
1-0
Organism
Channel cafflsh (juvenile),
I eta I urus punctatus
Channel" catfish (juvenile),
I eta Iurus punctatus
Channel catfish (yolk sac fry),
I eta Iurus punctatus
Channel catfish (I wk-6ld),
I eta Iurus punctatus
Channel catfish (juvenile 3")
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Channel catfish,
Ictalurus punctatus
Blueglll (Juvenile),
Lepomls macroch I ru's
Blueglll (juvenile),
Lepomls macrochIrus
Bloassay
Method*
Test
0
U
U
U
U
U
U
U
U
Chemical
pfocfjpttdn
PhenyImercufy
acetate
Pheny(mercury
acetate
PhenyImercury
acetate
PhenyImercury
acetate
PhenyImercury
acetate
Pheny Imercury
acetate
Merthlolate
PyrIdyImercury
acetate
Merthlolate
Time
(hrs)
72
48
48
Adjusted
LC50 LC50
(ug/f )'»'•• (ug/l)*«»
863'
233
374
48 1,373
434
103
24 2,180 340
24 3,750 585
608
48 2j800 1,240
48 7,600 3,365
48 31,960 14i152
Reference
Clemens &
Sneed, 1958
Clemens &
Sneed. 1958
Clemens &
Sneed, 1958
Clemens &
Sneed, 1958
Clemens &
Sneed, 1958
Will ford,
1967
Will ford.
1967
Will ford,
1967
Will ford,
1967
* S = static, R = renewal, FT = flow-through
»• 0 = unmeasured, M = measured '
*** Reported as concentration of mercury.
Geometric mean of adjusted LC50: Inorganic mercury = 147 ug/l
= 38 ug/l
Methyl mercuric compounds = 34.5 ug/l
= 8.8 ug/l
Lowest LC50 value with measured Inorganic mercury concentration and flow-through exposures = 33 ug/l
-------
Table 2. Freshwater Invertebrate acute values for norcury
Organ Ism
Adjusted
Bloassay Test Chemical Time LC50 LC50
Method* Cone." Description (hrs) (ug/l)"** (ug/l)*«»
Reference
Rotifer,
Ph 1 1 od 1 na acut i corn 1 s
Kotlfur,
Philodlna acut 1 corn Is
Sludge worm,
Tubifex tub! f ex
Sludge worn,
Tubifex tub! fox
Daphnld,
Oaphn la maqna
Crayfish (nixed agos),
I Faxonella clypcata
U) Crayfish (mixed ages),
Faxonellij clypeata
Crayf isli,
Orconcctcs 1 Imosus
Crayfish (mixed ages),
Procnmbarus cl.irkl
Crayfish (mixed ages),
Proconibrirus clarki
Hay fly,
Ephumcrello subvaria
Stoncf ly,
Acroncuria lycorius
Inorganic Morcury
S U Morcurlc
ch 1 or i do
S U Mercuric
ch 1 or 1 do
R U . Mercuric
chloride
R U Mercuric
ch 1 or 1 do
R U Mercuric
chloride
R U Mercuric
chloride
R U Mercuric
ch 1 or 1 de
S U Mercuric
ch 1 or 1 do
R U Mercuric
ch 1 or i de
R U Mercuric
chloride
S U Mercuric
chloride
S U Mercuric
ch 1 or 1 de
96 518 439 Bulkoma. et
at. 1974
% 1,105 1,004 Hulkoma, ot
al. 1974
48 82 30 Brkovlc-
Popovlc &
Popov ic, 1977*-
48 100 36.4 Drkovlc-
Popovic &
Popov Ic, 19771
48 5 4 Bleslnger &
Christenson,
1972
96 0.02 0.02 Holt &
Finrjorman, 1977
72 10 5 Kelt &
Fingerman, 1977
% 50 42 Boutet 4
Chalsemart In,
1973
72 0.2 0.1 Holt &
Flngorntan, 1977
72 10 5 Holt &
Flngorman, 1977
96 2,000 1,694 Warnick &
Dell, 1969
96 2,000 1,694 Warnick i
fJoll, 1969
-------
Tab 10 2. (Continued)
00
Adjusted
Organism
Caddlsf ly,
Hydropsyche bettenl
Br 1st leworm,
Nals sp.
Snail (egg),
Amnlcola sp.
Snail (adult).
Amnlcola sp.
Scud,
Gammarus sp.
Midge,
Chlronomus sp.
Bloassay
Method**
S
S
S
S
S
S
Test
Cone.**1
U
M
M
M
M
M
Chemical
Description
Mercuric
chloride
Mercuric
nitrate
Mercuric
nitrate
Mercuric
nitrate
Mercuric
nitrate
Mercuric
nitrate
Time
{hrs)
96
96
96
96
96
96
LC50
(ug/l)"»
2,000
1 ,000
2,100
80
10
20
LC30
-------
Table 3. Freshwater fish chronic values for mercury (McKIm, et al. 1976)
Chronic
Limits Value
Organism Test* (up/I)" (ug/l)««
Methylmercuric chloride
Brook trout, LC 0.29-0.93 0.52
Salvellnus fontlnalls
* LC = life cycle or partial life cycle
** Reported as concentration of mercury.
Geometric mean of chronic value = 0.52 ug/l 0.52 _ Q.078 ug/l
6.7
Lowest chronic value = 0.52 ug/l
Application Factor Values
96-hr LC50 MATC
Species (ug/l) (ug/l) AF
Brook trout, 75 0.52 0.007
Salve IInus fontlnalIs
Geometric mean AF = 0.007 Geometric mean LC50 « 75 ug/l
3.007 |/ 75 u
g/l x 8.8 ug/l = 1.8 ug/l
-------
Table 4» :Fr,es:hw.$ter Invertebrate ^chronic values for mercury
03
I
Organ 1 sm
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Chronic
Limits Value
Test? Jug/!)"
-------
Table 5. Freshwater plant effects for mercury
00
I
Organ 1 sra
Alga,
Anklstrodesmus braunll
Alga,
Chlorella pyrenoldosa
Alga,
Chlorella pyrenoldosa
Alga,
Effect
Concentration
(ug/l)
Inorganic Mercury
Mercuric chloride
Enzyme 2,590
Inhibition
Growth 100
Retarded growth 150
(12 hrs)
Inhibited rates 2,006
Reference
Mat son, et al. 1972
Hannan & Patoul 1 let,
Kamp-Nlelsen, 1971
DeFlllppIs & Pallaghy
1972
, 19
Chlorella sp. Emerson strain
Alga,
Chi orel la vulgar Is
Alga,
Summer assemblage
Water milfoil,
MyrIophy11 urn spIcatum
Alga,
Anklstrodesmus braunll
Alga,
Coelastrum mlcroporum
Alga,
Florida Lake assemblage
of chlorophlll
synthesis,
respiration, and
photosynthesis
Growth
Photosynthetlc
activity
1,030
60
Growth Inhibition, 1,200
50 percent
Methylmercuric Compounds
Methylmercuric chloride
Enzyme Inhibition 1,598
Growth Inhibition, >2.4-<4.8
50 percent
Rosko & Rachlln, 1977
Bllnn, et al. 1977
Stanley, 1974
Matson, et al. 1972
Holderness, et al. 1975
Other Mercury Compounds
Methylmercuric dlcyandlamlde
Growth <0.8 Harrlss, et al. 1970
-------
Table 5. (Continued)
00
I
M
00
Organism
Effect
Concentration
(ug/l)
Reference
N-Methylmercurlc-1,2,3,6-tetrahydro-3,6-methano-3,4>5t6,7,7-hexachlorophthalImlde
Alga, Growth
Florida Lake assemblage
A|ga, Nuisance
Cladophoraceao control
Alga, Nuisance
Ulothrlchaceae control
Alga,
Chlorella sp. Emerson strain
Ethylmercuric phosphate
38.6
38.6
PhenyImercuric acetate
Inhibited rates 200.6
of chlorophllI
synthesis, respiration,
and photosynt hesIs
Alga, Growth
Florida Lake assemblage
Alga, Growth
Florida Lake assemblage
<0.6
Diphenyl mercury
<28.3
Harrlss, et al. 1970
Burrows & Combs, 1958
Burrows & Combs, 1958
OeFlllppIs iPallaghy, 1976
Harrlss, et al. 1970
Harrlss, et al. 1970
Final plant value: Inorganic mercury = 60 ug/l
Methylmercuric compounds = >2.4, <4.8 ug/l
-------
Organ Ism
Table 6. Freshwater residues for mercury
Bloconcentratlon Factor
Time
(days) Reference
Inorganic Mercury
Mercuric chlorldo
Alya,
Syncdra ulna
33,800 0.29
Mo thy liner cur ic Compounds
Fujlta 4 Hashlzume. 1972
Kethy Imorcurlc chlorldo
Rainbow trout (juvenile),
Salmo galrdneri
Rainbow trout (juvenile),
Salmo gairdnerl
Rainbow trout (juvenile),
Salmo galrdneri
Brook trout,
Salvelinus fontirialls
03 Brook trout,
1 Salvelinus fontlnalls
Fathead minnow,
Plmophales promelas
Organism
Man
Mink
Mustcla vlson
4,532
6,622
8,049
20,000
12,000
62,890
Maximum Permissible Tissue
Action Level or Effect
edible fish or shot If Ish
hlstological evidence
of Injury
84
84
84
273
756
336
Concentration
Concentration
(mg/kg)
1.0
1.1
Re inert, et al. 1974
Ro Inert, et al . 1974
Ue Inert, et al . 1974
McKim, et al . 1976
McKIm, ot al . 1976
Olson, ot al. 1975
Reference
44 Fl< 4012
Wobosor, 1973
Highest geometric mean edible tissue bloconcentrat Ion factor for methyl mercury and a single spades = 62,898
Lowest miixlrnun permissible tissue concentration = 1.0 mg/kg, ....... = 0.000016 mg/kg = 0.016 ug/l
-------
Organism
Table 7. Other freshwater data for mercury
Effect
Test
Duration
Result
(ug/l)
Inorganic Morcury
Miircur Ic tlilor I do
community
(pr Imnry produi.ur1.,,
horbl vfMjrs ami
carnivorous midges)
Oayflsh (odult),
Orconoctci I Imosus
1 yr
lrjdl mmibors,
!>t), 96 hrs LC50
(blastula embryo), 96 hrs LC'JO
(gastrula embryo), 96 hrs LCbO
(nuurula embryo), 96 hrs LCt>0
(tall bud embryo), 96 hrs LC50
(larva), 5 days LCbO
(adult), 96 hrs LC50
2
<2
>1.0-<10
>l.0r<10
>0.l-<10
1,000
>7,500-
-------
Table 7. (Continued)
Organism
Rainbow trout (juvenile),
Salmo galrdneri
Rainbow trout (juvenile),
Salmo gairdnerl
Brook trout,
Salvelfnus fontlnalls
Carp (embryo),
Cyprlnus carplo
White sucker (adult),
Catostomus commersonl
White sucker (adult),
Gatostomus commerson 1
Threesplne stickleback,
Gasterosteus aculeatus
Threesplne stickleback,
03 Gasterosteus aculeatus
1
Rainbow trout,
Salmo galrdneri
Rainbow trout,
Salmo gairdnerl
Rainbow trout,
Salmo gairdnerl
Test
Duration
2 hrs
>64 days
48 hrs
60-72 hrs
6 mln
16 mln
10 days
110 mln
>64 days
120 days
269 days
Effect
Depressed ol factor
bulbor response
Growth
Increased cough
frequency
Reduced hatching
success
Blood enzyme (LDH)
Inhibition 20*
Blood enzyme (GOT)
Inhibition 20*
LCO
Death
Methyl mercuric Compounds
Methyl mercuric chloride
Growth Inhibition
Loss of appetite (as ug
of Hg In total ration
consumed, 1/3 as CH^ngCI
Loss of nervous control
(as ug/l of Hg In total
Result
(ug/l)
74
>3
>3,000
8,000
10,000
>8
4,018
>0.04
860
1,600
Reference
Mara, et al. 1976
Matlda, et al. 1971
Drummond, et al . 1974
Huckabee & Griffith, 1974
Chrlstensen, 1971/72
Chrlstensen, 1971/72
Jones, 1939
Jones, 1947
Matlda, et al. 1971
Matlda, et al . 1971
Matlda, et al. 1971
Rainbow trout,
Salmo gairdnerl
Brook trout (embryo),
SalvolInus fontlnalls
Brook trout (a lev In),
SalvelInus fontlnalls
30 mln
16-17 days
Incubation period
+ 21 days
ration consumed, 1/3 as
CH3HgCI)
Reduced vlabl I Ity 1,000
of sperm - EC50
Decreased enzyme 0.88
(GOT) activity
Reduced growth 0.79
Mclntyre, 1973
Chrlstensen, 1975
Chrlstensen, 1975
-------
":'.- .' • „•. 41 iC.*t- ij'.v* *
Table 7. (Continued)
CD
1
NJ
to
Organ 1 sm
Brook trout (a lev In),
Sa 1 vo 1 1 nus font 1 na 1 is
Brook trout (juvenile),
Salvellnus tonti nails
Brook ;trout,
Salvellnus (ontlnalls
Newt,.
Triturus vlridoscens
Newt,.
Triturus virldescens
Newt, , . .
Triturus virldescens
Leopard frog (tadpole) '',
Rana plpiens
Leopard frog,
Rana plpiens
>':.,!: . '..'
Leopard frog (blastula embryo),
Rana plpiens
Leopard frog (gastrula embryo),
Rana plpiens
Leopard frog (neural plate
embryo) , .
Rana piplens
Leopard frog (blastula embryo),
Rana plpiens
Leopard frog (gastrula embryo),
Rana plpiens
Leopard frog (neural plate
Test ..
Duration
38 days
14 days
8 days
>2 days
17 days
8 days
48 hrs
<4 mos
5 days
5 days
5 days
96 hrs
96 hrs
96 hrs
Effect
{ •'•>
Increased enzyme
(GOT) activity
Increased blood
plasma chloride
Increased, cough
frequency
Delayed limb
regene'rat ion
Death
Death
Lciod
Fa i 1 ure to
metamorphose
LC50
LC50
LC50
Teratogenesis EC50
Teratogenes 1 s EC50
Teratogenesis EC50
Resui.t
(ug/l)'
0.79
2.93
>3
8
24
8
50
1
12-16
8-12
12-16
4-8
12-16
12-24
Reference
Christonsen, 1975
Christensen; et al. 1977
Drummond,* et al. 1974
Chang, ot al. 1976
Chang, et al . 1976
Chang, et a'l.' 1976
Chang, et al . 1974
Chang, et al . 1974
Dial, 1976
Dial, 1976
Dial, 1976
Dial, J976
Dial, 1976
Dial, 1976
embryo),.
Rana plpiens
-------
Table 7. (Continued)
Organism
Mink (ailult),
Mustola vlscn
Mink (adult),
Mustola vlson
Mallard duck,
Anas platythynclos
Lous 1 ana red crayfish
(juveni le),
Procambarus clarkl
Chinook salmon (finger) Ing),
Oncorhynchus tshawytscha
1 Chinook salmon,
t>o Oncorhynchus tshawytscha
OJ
Sockeye salmon (juvenile),
Oncorhynchus nerka
Sockeye salmon (juvenile),
Oncorhynchus nerka
Sockeye salmon (juvenile),
Oncorhynchus nerka
Rainbow trout (juvenile).
Sal mo galrdnerl
Rainbow trout (juvenile).
Test
Duration
93 days
93 days
2
generations
110 hrs
1 hr
20 hrs
1.5 hrs
1 'hr
1 hr
1 hr
i
l^hr
Effect
Hlsto logic evidence of
Injury
LC50 In brain tissue
Other Mercury Compounds
Methyl mercuric dicyandl amide
Reduced fortuity and
food conversion
off Iclency
LC50
Ethyl mercuric phosphate
Distress
Safe for disease control
Pyr Idyl mercuric acetate
LC50
Safe for disease
control
; Safe for dlsoase
control
j LCI 00
!LCO
Result
(ug/l)
1,100
11,900
0.1
mg/kg
In food
53.6
77
39
10,560-
15,840
<954
<4,752
1,034
967
Reference
Woboser, 1973
Wobeser, 1973
Heinz, 1976
Hendrlck & Everett, 1965
Burrows A Combs, 1958
Burrows & Combs, 1958
Burrows 4 Palmer, 1949
Rucker, 1948
Ruckor 1 Hhlpple, 1951
Allison, 1957
Allison, 1957
Salmo galrdnerl
-------
Table 7. (Continued)
'33
1
M
Organism
Rainbow trout (juvenile),
Salmo galrdnerl
Rainbow trout (juvenile),
Salmo galrdnerl
Rainbow trout (a lev In),
Salmo galrdnerl
Rainbow trout (juvenile),
Salmo galrdnorl
Rainbow trout,
Salmo galrdnerl
Brown trout (juvenile),
Salmo trutta
Brook trout (juvenile),
Salvellnus fontlnalls
Brook trout (juvenile),
Salvellnus fontlnalls
Test
Duration
1 hr
1 hr
1 hr
1 hr
>64 days
1 hr
1 hr
1 hr
Effect
LC50
LC18
Safe for disease
control
LC60
Phenyl mercuric acetate
Growth
Safe for disease control
Safe for disease control
Safe for disease control
Result
(ug/l)
4,752
2,376
<4,752
517
0.11-1.1
4,752
2,067
4,752
Reference
Rodgers, et al. 1951
Rodgers, et al. 1951
Rucker & Whlpple, 1951
Allison, 1957
Matlda, et al.' 1971
Rodgers, et al..-1951
AHUon, .19.57, .
Rodgers, et al . 1951
-------
SALTWATER ORGANISMS
Acute Toxicity
In static tests of 96-hour duration (Table 8), adjusted LC50
values for mercuric chloride and the mummichog are 437 ug/1
(Eisler and Hennekey, 1977) and 1,093 ug/1 (Klaunig, et al. 1975).
Extended exposure for 168 hours did not increase toxicity (Table
13). When the geometric mean of 691 ug/1 is adjusted for species
sensitivity, it results in a Final Fish Acute Value of 190 ug/1
for mercuric chloride.
The data for saltwater invertebrate species are more abundant
(Table 9) and encompass various life stages of annelids, bivalve
and gastropod molluscs, crustaceans, and echinoderms. Early life
stages were more sensitive to mercuric chloride. Embryos of the
clam, Mercenaria mercenaria, and oyster, Crassostrea virginica,
had adjusted LC50 values of 4.1 and 4.7 ug/1/ respectively
(Calabrese, et al. 1977). Among crustaceans, larval stages were
also more sensitive. Larvae of the shrimp, Palaemonetes vulgaris,
had an adjusted LC50 value of 3.6 ug/1 (Shealy and Sandifer,
1975). Similar sensitivity was shown by juvenile mysid shrimps
Mysidopsis bah ia. Under flow-through conditions with measured
concentrations, the 96-hour LC50 values were 3.6 and .3.9 ug/1
(Sosnowski, et al. 1979). The value for larval Carcinus maenas is
5.1 ug/1 (Conner, 1972) while adults of this species were less
sensitive with adjusted LC50 values of 364 ug/1 (Portmann, 1968)
and 437 ug/1 (Connor, 1972).
Among the microcrustaceans tested, the calanoid copepods,
Acartia tonsa and Acartia clausi, were the most sensitive to
mercuric chloride. The adjusted 96-hour LC50 values for these
B-25
-------
species ranged from 8.5 to 17 ug/l« The harpactacoid copepod,
Tigriopus japonicus, was the most resistant with a LC50 of 189
ug/1.
The adjusted LC50 values for polychaete annelids ranged from
12 ug/1 for larval Capitella capitata and 19 ug/1 for adult
Nean.thes arenaceodentata to 85 ug/1 for juvenile N. arenaceo-
dentata (Reisch, et al. 1976). Eisler and Hennekey (1977) ob-
served ah LC50 of 59 ug/1 for adult Nereis virens. Among the
echinoderms tested, the LC50 value for the adult starfish,
Asterias. forbesi, was 51 ug/1 (Eisler and Hennekey, 1977).
Application of the Guidelines to the invertebrate acute data
for mercuric chloride results in a geometric mean of 49 ug/1 and
when adjusted for species sensitivity, produces a Final Inverte-
!»'
brate Acute Value of 1.0 ug/1 for mercuric chloride. Of the re-
ported studies, none had values lower than this, indicating that
guideline procedures are protective of at least 95 percent of the
invertebrate' species.
There was only one study reported on the acute toxicity of
methylmercuric compounds to a saltwater invertebrate species. The
adjusted 96-hour LC50 value was 127 ug/1 for methylmercuric chlo-
ride and the amphipod, Gammarus duebeni (Lockwood and Inman,
1975). This results in a Final Invertebrate Acute Value of 2.6
ug/1 for 'methylmercury.
Chronic
The chronic toxicity of mercuric chloride has been determined
(Table 10) based upon a flow- through, life-cycle exposure of the
mysid shrimp, Mysidopsis bahia (Sosnowski, et al. 1979). In this
experiment, groups of 30 juvenile shrimp were reared in each of
B-26
-------
four concentrations and a control for 36 days at 21°C and a salin-
ity of 30°/oo. Responses examined include time of appearance of
first brood, time of first spawn, productivity, and growth. All
of these responses were significantly (P<0.05) affected at a con-
tinuous mercury concentration of 1.65 ug/1.
The highest concentration of mercuric chloride tested having
no effect on growth and reproductive parameters was 0.82 ug/l«
This no-observed-effect concentration is approximately 0.22 times
the mean 96-hour LC50 (3.75 ug/1) determined for juveniles. The
chronic value, calculated as the geometric mean of the chronic
limits, for Mysidopsis bahia exposed to mercuric chloride is 1.2
ug/1. Because Mysidopsis bahia is among the most sensitive to
mercuric chloride (Table 9) it is not appropriate to correct for
species sensitivity. Therefore, in the absence of any other suit-
able chronic data, the Final Invertebrate Chronic Value becomes
1.2 ug/1.
Plant Effects
Inorganic mercury compounds at concentrations as low as 1.0
ug/1 (Kayser, 1976) have affected several species of saltwater
algae (Table 11). Growth inhibition was observed among 18 species
of saltwater algae between 5 ug/1 (the lowest concentration
tested) and 15 ug/1 (Berland, et al. 1976). Similar results were
observed for various mercury compounds including mercuric acetate,
mercuric cyanide, ethymercuric phosphate, phenylmercuric iodine,
and n-alkyl mercuric chlorides.
The work of Harriss, et al. (1970) convincingly demonstrates
that various organomercurial fungicides at concentrations as low
as 0.1 ug/1 reduced photosynthesis and growth in laboratory cultures
B-27
-------
of the saltwater diatom, Nitzchia delicatissima, and several natu-
i
ral .phytoplankton communities from Florida lakes. The Final Plant.
Values are 1.0 and 100 ug/1 for inorganic mercury and methylmer-
1
cury.
Residues
The rapid accumulation of inorganic and organic mercury com-
pounds by.various species of saltwater biota is summarized in
Table 12.. Inorganic mercury is rapidly accumulated by a variety
of. saltwater phytoplankton (Hannan, et al. 1973a,b; Laumond, et
!
al. 1973; Parrish and Carr, 1976). The lobster, Homarus
americanus, when exposed to 6 ug/1 mercuric chloride for 30 days,
had a bioconcentration factor (BCF) of 129 and mean tissue residue
of 1.00 mg/kg wet weight (Thurberg, et al. 1977) which is the
lower limit of the current FDA guideline.
Cunningham and Tripp (1973) exposed oysters to seawater con-
taining 10 ug Hg/1 (as mercuric acetate). Whole body residues of
2.8 mg/kg were obtained after a 45-day exposure resulting in a BCF
of 2., 800. Kopfler (1974) exposed oysters to 1.0 ug Hg/1 (as mer-
curic chloride) for 74 days. Whole body residues of approximately
10 mg/kg were obtained resulting in a BCF of 10,000. The depura-
tion of inorganic mercury occurred during the first 18 days post
exposure and resulted in a 21 percent decline in tissue residues.
No significant decreases in residue concentrations were recorded
for the remainder of the 160-day depuration period (Cunningham and
Tripp, 1973). These studies indicate that inorganic forms of mer-
cury are rapidly bioaccumulated, result in tissue residues in ex-
cess of regulatory guidelines, and are not rapidly or completely
depurated after several months.
B-28
-------
Kopfler (1974) determined the rate of bioaccumulation and
equilibrium residue concentrations in oysters for both methyl and
phenylmercuric chloride exposed at 1.0 ug Hg/1 for 74 days. There
were no significant differences in the rate of accumulation nor
the final residues (40 mg/kg). This resulted in a BCF of 40,000
compared to the 10,000 value determined for the inorganic form of
mercury (Kopfler, 1974). Therefore, the form of mercury had a
significant effect on bioconcentration.
The Residue Limited Toxicant Concentration (RLTC) for mer-
curic chloride is calculated by dividing the maximum permissible
tissue concentration (1.0 mg/kg) by the highest geometric mean of
the bioconcentration factors for the lobster (129) and for the
oyster (2,800 and 10,000). The oyster geometric mean of 5,291
results in a RLTC for inorganic mercury of 0.19 ug/1.
The RLTC for methylmercuric chloride is calculated by divid-
ing the maximum permissible tissue concentration by the geometric
mean of the oyster BCF of 40/000. Therefore, the RLTC for methyl-
mercury chloride is 0.025 ug/1.
Miscellaneous
For several groups of saltwater organisms, mercury concentra-
tions of 10 ug/1 and lower reportedly interfere with or impair
various metabolic processes considered essential for normal
growth, survival, reproduction, and well-being (Table 13).
Weis and Weis (1977) show that embryonic Fundulus hetero-
clitus exposed to concentrations as low as 10 ug/1 for 3 days ex-
hibit some developmental abnormalities as fish larvae. Winter
flounder adults exhibit decreased respiration and changes in
various blood chemistry values after exposure for 60 days to
B-29
-------
10 ug/1 (Calabrese, et al. 1975). Adult striped bass also exhibit
decreased respiration 30 days after immersion in 5 ug/1 mercury
for 30 days (Dawson, et al. 1977). Protozoans showed reduced
growth during immersion in 2.3 ug/1 for 8 days (Gray and Ventilla,
1973), or 2.5 to 5.0 ug/1 for 12 hours (Gray, 1974). Some deaths
were observed among adult clams exposed to 4.0 ug/1 for 168 hours
(Eisler and Hennekey, 1977) and among oyster embryos subjected to
3.3 ug/1 for 12 days and clam larvae exposed to 4.0 ug/1 for 8 to
10 days (Calabrese, et al. 1977). Inorganic mercury concentra-
tions that did not produce significant mortality include 1.0 ug/1
(43 hours) for oyster embryos (Calabrese, et al. 1973), 2.5 ug/1
(42 to 48 hours) for clam larvae (Calabrese, et al. 1973), and 1.0
ug (168 hours) for adult softshell clams (Eisler and Hennekey,
1977). Exposure to 10 ug for less than 2 hours interferes with
the ability of barnacle cyprids to attach to the substrate
(Pyefinch and Mott, 1948). Copepods show a decrease in egg and
faecal pellet production after exposure to 2.0 ug and higher for
10 days (Reeve, et al. 1977), growth inhibition after exposure for
70 days, to 5 ug (Sonntag and Greve, 1977), and no growth inhibi-
tion during a 70-day period to 1.0 ug (Sonntag and Greve, 1977).
Signigicant mortality was observed among crab larvae in 47 hours
at 10.0 ug (Connor, 1972) and at 1.8 ug for 8 days (DeCoursey and
Vernberg, 1972). Crab larvae also demonstrate increased metabolic
rate after 24 hours in 1.8 ug and increased swimming activity in 5
days, at 1.8 ug (DeCoursey and Vernberg, 1972). Grass shrimp lar-
vae, exhibit abnormal development after exposure for 48 hours to 10
to 18 ug (Shealy and Sandifer, 1975). However, no measurable ef-
fect on respiration, growth or molting of 'Shrimp adults was ob-
B-30
-------
served at 1.0 ug after 60 days (Green, et al. 1976), on mortality
of adult hermit crabs exposed for 168 hours to 10.0 ug/1 (Eisler
and Hennekey, 1977), and on mortality of grass shrimp larvae after
48 hours to concentrations lower than 5.6 ug (Shealy and Sand ifer,
1975). Among echinoderms, adult starfish exhibited no change in
survival patterns after exposure to 10.0 ug for 168 hours (Eisler
and Hennekey, 1977), but mercury did retard growth and development
of larvae after exposure for 40 hours to 3.0 ug (Soyer, 1963).
All of the data listed thus far in this section apply to inorganic
mercury compounds. Within the 10 ug constraint, there is only one
observation with organomercury compounds, that of Cunningham
(1976). She demonstrates that adult oysters held 12 hours daily
for 15 days in 10 ug, as mercuric acetate, showed a reduction in
shell growth.
B-31
-------
CRITERION FORMULATION
Saltwater-Aquatic Life
Summary of Avialable Data
The concentrations herein are expressed as mercury. The
concentrations below have been rounded to two significant
figures.
Inorganic Mercury
Final Fish Acute Value = 190 ug/1
Final Invertebrate Acute Value = 1.0 ug/1
Final Acute Value = 1.0 ug/1
Final Fish Chronic Value = not available
Final 'Invertebrate Chronic Value =1.2 ug/1
Final 'Plant Value = 1.0 ug/1
Residue Limited Toxicant Concentration = 0.19 ug/1 *
Final Chronic Value = 0.19 ug/1
0.44 x Final Acute Value = 0.44 ug/1
.The maximum concentration of inorganic mercury is
•the Fi'na.! -Acute Value of 1.0 ug/1 which is based on the more
acutely sensitive invertebrate species. The 24-hour average
•conj&entration is the Residue Limited Toxicant Concentration
of .0...19 ug/1. No important adverse effects have been re-
ported to be caused by concentrations lower than the 24-hour
-.average .concentration.
CRITERION: For inorganic mercury the criterion to pro-
tect .saltwater aquatic life as derived using the Guidelines
is 0.. 19 .ug/1 as a 24-hour average and the concentration
should not exceed 1.0 ug/1 at any time.
B-32
-------
Methylmercury
Final Fish Acute Value = not available
Final Invertebrate Acute Value = 2.6 ug/1
Final Acute Value =2.6 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value » 100 ug/1
Residue Limited Toxicant Concentration = 0.025 ug/1
Final Chronic Value = 0.025 ug/1
0.44 x Final Acute Value =1.1 ug/1
No saltwater criterion can be derived for methylmercury
using the Guidelines because no Final Chronic Value for
either fish or invertebrate species or a good substitute for
either value is available. However, results obtained with
methylmercury and freshwater organisms indicate how a cri-
terion may be estimated.
For methylmercury and freshwater organisms the Residue
Limited Toxicant Concentration is lower than either the Final
Fish or Final Invertebrate Chronic Value. Therefore, it
seems reasonable to estimate a criterion for methylmercury
and saltwater organisms using the Residue Limited Toxicant
Concentration.
The maximum concentration of methylmercury is the Final
Acute Value of 2.6 ug/1 and the 24-hour average concentration
is the Residue Limited Toxicant Concentration of 0.025 ug/l«
CRITERION: For methylmercury the criterion to protect
saltwater aquatic life as derived using procedures other than
the Guidelines is 0.025 ug/1 as a 24-hour average and the
concentration should not exceed 2.6 ug/1 at any time.
B-33
-------
« S = static
** U = unmeasured
Table 8* Marine fish acute values for mercury
Adjusted
Organ 1 sm
Muntnlchog (adult),
Fundulus heterocl Itus
Mummlchog (adult),
Fundulus heterocl Itus
. .
Blpassay Test
Method*' OpfiCif!1
S U
S U
Chemical
Description
Inorganic Mercury
Morcurlc
ch 1 or 1 do
Mercuric
chloride
Time
(hrs)
96
96
LC50
(ug/l)
aoo
2,000
LC50
(ug/l)
- ^ f- ;-
43?
1.093
Reference
Elsler &
1977
Klaunlg,
Hennekey*
et al. 1975
Geometric mean of adjusted values for mercuric chloride - 691 ug/l -^-~- = 190 ug/l
3 •/
03
I
U)
-------
Table 9. Marine Invertebrate acute values for mercury
03
1
CO
Ul
Organism
Polychaete (larva),
Capital la capltata
Polychaete (adult),
Neanthes arenacoodentata
Polychaete (juvenile),
Noanthes arenaceodentata
Sandworm (adult).
Nereis vlrens .
Bay scallop (Juvenile),
Argopecten Irradlans
Oyster (embryo),
Crassostrea virgin lea
Soft-shell clam (adult),
Mya arenarla
Hard-shell clam (embryo),
Merconarla mercenarla
Mud snal 1 (adult),
Nassarlus obsoletus
Clam (adult),
Rangla cuneata
Mysld shrimp,
Mysldopsls bah la
Mysld shrimp,
Mysldopsls bah la
Copepod,
Acartla tonsa
Copopod,
Acartla tonsa
Copepod ,
Acartla tonsa
Bloassay
Method*
S
S
S
S
S
S
S
S
S
S
FT
FT
S
S
S
Test
Cone.**
U
U
U
U
U
U
U
U
U
U
M
M
U
U
U
Chemical
Description
Inorganic Mercury
Mercuric
ch 1 or 1 de
Mercuric
ch 1 or 1 de
Mercuric
chloride
Mercuric
chloride
Mercuric
ch 1 or 1 de
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
ch 1 or 1 de
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Mercuric
chloride
Time
(hrs)
96
96
96
96
96
48
96
48
96
96
96
96
96
96
96
LC50
(ug/l)
14
22
100
70
89
5.6
400
4.8
32,000
5,100
3.9
3.6
to
14
15
Adjusted
LC50
(ug/l)
12
19
85
59
75
4.7
339
4.1
27,104
4,320
3.9
3.6
8.5
12
13
Reference
Relsh, et al. 1976
Relsh, et al. 1976
Relsh, et al. 1976
Eisler & Hen nek ey,
1977
Nelson, et al . 1976
Calabrese, et al .
1977
Eisler & Hennekey,
1977
Calabrese, et al .
1977
Eisler & Hennekey,
1977
Olson & Harrel, 1973
Sosnowskl, et al .
1979a
Sosnowskl , et al .
1979a
Sosnowskl and
Gentile, 1978
Sosnowskl and
Gentile, 1978
Sosnowskl and
Gentile. 1978
-------
Table 9. (Continued)
Organism
Copepod ,
Acartla tonsa
Copepod ,
Acartla clausl
Copepod ,
PsQudodlaptomus coronatus
Copopod,
Eurytemora af finis
Copopod ,
Tlgrlopus japonlcus
Crab (adult),
Carclnus maenas
Crab (adult),
Carclnus maenas
Crab (larva),
00 Carclnus maenas
1
w Hermit crab (adult),
°^ Pagurus long 1 carpus
Grass shrimp (larva),
Palaemonetes vulgar Is
White shrimp (adult),
Peneus setllerus
Starfish (adult),
Ast.erlas forbesl
Amphlpod (adult),
Gammarus duebenl
Bloassay
Method"
S
S
S
S
S
S
S
S
S
S
S
S
S
Tost
Cone."*
U
U
U
4J
U
:U
U
U
U
U
U
U
U
Chemical
Description
Tlirso
thrs)
Mercuric 96
c.hlorldo
Mercuric 96
chloride
Mercuric 96
chloride
Mercuric 96
chloride
Mercuric 96
chloride
Mercuric 48
chloride
Mer.curl.c 48
chloride
Mercur 1 c 48
chloride
Mercuric 96
chloride
Mercur 1 c 48
chloride
Mercur l.c 96
chl or 1 de
Mercur 1 c 96
ch 1 or 1 de
Methyl mercuric Compounds
Methy (mercuric
ch 1 or 1 do
%
LC50
(ug/l)
20
'0
79
158
223
1,000
1 ,2.00
14
50
10
... - '7
60
150
LC50
-------
tn
I
U)
•-J
Table 10. Marine Invertebrate chronic values for mercury (Sosnowskl, et al. I979a)
Organism
Test*
Limits
(ug/l)
Chronic
Value
(ug/l)
Mercuric chloride
Mysld shrimp,
MysIdopsls bah I a
LC
0.82-1.65
1.2
* LC = life cycle or partial life cycle
Geometric mean of chronic values - 1.2 ug/l, since this species Is among the most sensitive (Table 9) no
species sensitivity factor will be used.
Lowest chronic value- 1.2 ug/l
-------
Table iii Marine plant effects for mercury
Organ 1 sm
Concentration
Effect (iig/l)
Reference
Inorganic Mercury
Mercuric chloride
CO
1
OJ
00
Alga,
Chaetoceros costatum
A 1 ga ,
Chaetoceros galvestonensls
Alga,
Chaetoceros galvestonensls
Alga,
Chi orel la sp.
Alga,
Cyclotel la sp.
Alga,
Dunal lei la sp.
Alga,
Dunal lei la ter.tlolecta
Alga,
Dunal lei la tertlolecta
Alga,
Dunal lei la tertlolecta
Alga,
Isochrysls galbana
Alga,
Isochrysls galbana
Kelp (zoospores, gameto-
phytes; sporophytes),
Laminar la hyperborea
Accumu 1 at 1 on
after death
Reduced growth
No growth
66% reduction
In CC>2
Reduced growth
75? reduction
In C02
Chlorophy 1 l-a
decrease
Decreased growth
No effect on
growth
Accumulation
No growth
Growth Inhibition
10
100
2,500
100
2,500
143
10
2
10
2,000,000
to
Glooschenko, 1969
Hannan, et al . 1973b
Hannan, et al . 1973b
Mills & Col well, 1977
Hannan 1 Patoul 1 let, 1972
Mills & Colwell, 1977
Betz, 1977
Da vies, 1976
Da vies, 1976
Da vies, 1974
Da vies, 1974
Hopkins 4 Kaln, 1971
Kelp (zoospores, gameto-
phytes, sporophytes).
Laminar Ia hyperborea
Lethal
10,000
Hopkins & Kaln, 1971
-------
Table 11. (Continued)
Organ 1 sm
Giant Kelp,
Macrocystls pyrlfera
Alga,
Phaeodacty lum trlcornutum
Alga,
Phaeodacty lum tr icornuluni
Red alga (spore ling),
(' lunar la e logons
Pod a (go (spore ling),
. Plumarla olcgans
Hod alga (spore ling),
Plumarla elegans
Rod alga (spore ling),
6 species
03
I Algae,
W |fl species
Algao,
16 species
Algae,
3 species
Algae,
3 species
Algae,
3 species
Dlnof lagol late,
Gymnodinlum splondcns
Dlnof lagol late,
Scrippslul la fnuroense
Concentration
Effect (ug/l)
Decreased 50
photosynthesis
Reduced growth 50
No growth 120
Growth Inhibition 40-1,000
Abnormal 1,000
development
LC50 13
Lethal 3,000-8,000
Growth inhibition <5-l5
Lethal
Depressed growth
No further
bioaccunu 1 at ion
Changes in eel 1
chemistry
Morcur ic
Reduced growth
Reduced growth,
morphological
_ » _ *•
10-50
30-350
40
30-350
acetate
10
1-10
Reference
Clendennlng & North,
Hannan, et al. I973a
tlannan, ot al. I973a
Boney, 1971
Boney, 1971
Donoy, ct al. 1959
Bonoy & Corner, 1959
Borland, et al. 1976
Borland, ot al. 1976
Sick & Windom, 1975
Sick & Windom, 1975
Sick & Windom. 1975
Kaysor, 1976
Kayser, 1976
-------
Organism
Dlnoflagcllate,
Scrlppsleila faeroense
Alga,
Dunallolja tertjolecta
Alga,
Phaoodactylum trlcornutum
Alga;
Cyclotella sp.
table 1U (Continued)
Effocf
GohcontratIon
jug/I)
Photosy ht hes is >2,000
Dimethyl mercury
Reduced growth
100
Other Mercury Compounds
Roforonco'
No growth 1^000 Kayser^ 1976
Methylmercuric Compounds
MothyImercuric chIor I do
Photosynthesis >2jOOO Overnelj, 1975
Overnell, 1975
Hannan i Patoulilot, 1972
N MethyImercurIc-1,2,3,6-tetrahydro-3,6-methano-3,4,5^6,7,
7-hexachloropFTthai (mine
Diatom,
Nltzchla delIctlsslma
Algae, .
§ species
Algae,
5 species
DI atom,
Nltzchla delicatlsslma
Red alga (sporcllng),
Plumarla elegans
Reduced
photosynthesis
0.1
Ethyl mercuric phosphate
Lethal 60
Growth Inhibition 0.6-60
Reduced
photosynthesis
PhenyImercuric acetate
OJ
LC50
PhenyImercuric Iodine
13
Harrlss, et al. 1970
Ukeles, 1962
Ukeles, 1962
Harrlss, et al. 1970
Boney, et al. 1959
-------
Organ Ism
Diatom,
Nltzchla del I cat IssIma
Red alga (sporolIng),
Plumarla olegans
Red alga (sporellng),
Plumarla elegans
Red alga (sporellng),
Plumarla elegans
Red algae (sporellng),
6 species
Table 11. (Continued)
Effect
Concentration
(ug/l)
PI phony I mercury
0.1
Reduced
photosynthesis
n-Alkyt mercuric chlorides
Growth Inhibition 40-1,000
Abnormal
development
LC50
Lethal
1,000
13
12-80
Reference
Harrlss, et al. 1970
Boney, 1971
Boney, 1971
Boney, et al. 1959
Boney & Corner, 1959
00
I
Lowest plant value: Inorganic morcury = 1.0 ug/l
methy(mercuric compounds = 100 ug/l
-------
Table 12. Marine residues for mercury
DO
Organism
A,l,ga,
Chaetoceros galvestonensls
Alga,
.Croomonas sallna
AJga .(mixed),
Aster .lone 1:1 a' J apon I ca p I us
U;l,P9enos~sp7 "
Alga,
.Phaeodjacty I urn fr I cor nutum
Lobster (adult),
Komarus amerlcanus
Oyster (aduTt),
Crassostrea v.lrglnlca
Oyster (adult),
Q"assQStr,ea virgin lea
Oyster (adult),
Crassostrea virgin lea
Oyster (adult),
Crassostrea virgin lea
B.loconcentratlon factor
•I norga.nj c Mercury
Time
(days) Reference
c ,chlor;lde
, 7,400
853
3,467
7,120
129
2,8.00
10,000
Hannan, et a,l . ,1973J»
Par.rlsh A Carr, J-976
8 Laumond, et at. 1973
4
30
45
74
Methylmercuric Compounds
Methylmercuric chloride
40,000 74
•
Other Mercury Compounds
PhenyImercuric chloride
40,000 74
Han.nan, et al. ,1973 «
Thurberg, et al. 1977
Cunningham & Trlpp, 1973
Kopfler, J974
Kopfler, 1974
Kopfler, 1974
-------
Table 12. (Continued)
Organ ism Bioconcentration Factor (days) Reference
Maximum Permissible Tissue Concentration
Concentration
Organism Action Level or Effect (mg/kg) Reference
Man edible fish and shellfish 1.0 44 FR 4012
Geometric mean edible tissue bioconcentration factor = 5,291 for mercuric chloride and 40,000 for methyl-
mercuric chloride.
Lowest maximum permissible tissue concentration = 1.0 mg/kg
13
I
4-
Ul
1.0
mercuric chloride •= ' = 0.00019 mg/kg = 0.19 ug/1
methylmercuric chloride = 0.000025 mg/kg = 0.025 ug/1
-------
03
I
Organism
Shiner perch,
Cymatogast.er aggregata
Mufnnicftog (adult),
Fundulus heteroclltus
Mummlchog (adult),
Fundulus heteroclltus
Mummlchog (adult),
Fundulus heteroclltus
Mummlchog (adult),
Fundulus heteroclltus
Mummlchog (adult),
FunduI us heteroc11tus
Mummlchog (embryo),
FunduI us heteroc11tus
Mummlchog (ombryo),
Fundulus heteroclltus
Munmlchog (embryo),
Fundulus heteroclltus
Mummlchog (adult),
Fundulus heteroclltus
Mummlchog (adult),
Fundulus heteroclltus
Mummlchog (adult),
Fundulus heteroclltus
Mummlchog (adult),
Fundulus hetoroclltus
Test
Ouretlon
Table 13, ipthpr marine data ;for mercury
Effect
168 hrs
168 hrs
168 hrs
24 hrs
28 days
3 days
3 days
12 hrs
96 hrs
48 hrs
96 hrs
Result
(ug/l)
rlnorganjc Mercury
Mercuric chloride
Brain chplInesterase
Inhibition
LCO
LC50
LCI 00
33,900
100
800
Reference
Abou-Donla & Menzel , 1967
Elsler & Hennekey, 1977
Elsler & Hennekey, 1977
1,000 Elsler & Hennokey, 1977
Disrupted osmoregulatlon 125 Renfro, et al. 1974
Enzyme Inhibition
Many developmental
abnormal Itles
Some developmental
abnormal Itles
Some developmental
abnormal Itles
12
Jacklm, 1973
30-40 Wels & Wels, 19773
10-20 Wols 4 Wels, 1977a
30-40 Wols & Wols, 19773
Mercury redistribution 1,000 ug/Hg Shellne & Schmidt Nielsen,
among organs following kg body wt 1977
Se pretreatment plus 400 ug
Se/kg body wt
Hlstopathology
LCI 00
Aberrant behaviour
250-5,000 Gardner, 1975
2,000 Elsler, et al. 1972
1,150 Klaunlg, et al. 1975
-------
Table 13. (Continued)
Organ 1 sm
Mummlchog (adult),
Fundulus hcteroclltus
Munmlchog (adult),
Fundulus hoterocl Itus
Stickleback (adult),
Gastorosteus aculeatus
W inter flounder (adult),
Pseudoplcuronectes americanus
Winter flounder (adult),
Pseudopleuronectes amerlcanus
Striped bass (adult),
Morono saxat ills
Protozoan,
Crlstlgera sp.
03
1 Protozoan,
•^ Crlstlgera sp.
Protozoan,
Crlstigera sp.
Protozoan,
Euplotes vannus
Protozoan,
Cup lotos vannus
Polyctiacte (adult),
Ctonodilus sorrntus
Polycluiote (adult),
Ctenotlllus r.(;rratus
Polychnoto (ydult),
Ctcnodllus sorratus
Sandworm (adult).
Test
Duration
10.5 days
96 hrs
950 mlns
24 days
60 days
30 days
8 days
12 hrs
7 hrs
48 hrs
48 hrs
96 hrs
96 hrs
21 days
16U hrs
Effect
LCIOO
Reduction In enzyme
activity
LCIOO
Increased enzyme
activity of bladder
and kidney
Decreased respiration,
blood chemistry changes
Decreased respiration
30 days post-exposure
Reduced growth
Reduced growth
Death
Reproduction Inhibition
No effect on reproduction
LC62
LCIOO
Reprodud Ion Inhibited
LCO
Result
(ug/l)
too
170
1,000
Injections
of 1,000 ug
Hg/kg body
10
5
2.3
2.5-5
20
1,000
100
50
100
>50
25
Reference
Weis 4 Wels, 1976
Jackim, ct al. 1970
Boetlus. 1960
Schmidt-Nielsen, et al. 1977
wt
Calabrese, et al. 1975
Dawson, et al. 1977
Gray 4 Vent ilia, 1973
Gray, 1974
Cray 4 Ventilla, 1971
Persoone 4 Uyttersprot, 1975
Persoono 4 Uyttcrsprot, 1975
Relsh I. Carr, 1978
Relsh 4 Carr, 1970
Relsh 4 Carr, 1970
Elsler 4 Hennnkey, 1977
tlerels v I runs
-------
Table 13. (Continued)
Organism
Sand worm (adult).
More is v Irons
Sandworm (adult),
Nereis V irons
Polychaoto (adult),
Ophryotrocha dladena
Polychaete (adult),
Ophryotrocha diadcma
Polychocto (adult),
Ophryotrocha dladema
Polychacto (adult)j
Ophryotrocha diadcma
Polychacte (adult),
Ophryotrocha labronlca
Oyster (larva),
, Crassostroa gigns
•u
Crassostrea virginica
Oyster (embryo),
Crassostroa virginica
Oyster (mlult),
Crassostren virginica
Hard-shell clam (larva),
Mcrccnarla morconnrla
Test
Duration
168 hrs
160 hrs
96 hrs
96 hrs
96 hrs
21 days
0.5 hrs
24 hrs
12 days
12 days
12 days
40 hrs
19 days
8-10 days
E100
1,000
32
3.3
12
20
1
50
4
Reference
Elslcr 4 Honftekey, 1977
Elslor 4 Honnekoy, 1977
Rolsh 4 Carr, 1978
Relsh & Carr, 1978
Rolsh & Carr; 1978
Relsh A Carr, 1978
Brown & Ahsanullah, 1971
Okubo & Okubo, 1962
Calabreso, et al. 1977
Calabrose, et al. 1977
Calabreso, et al. 1977
Calabroso, et al. 1973
Kopfler, 1974
Calabreso, et al. 1977
Hard-she 11 clam (larva), 8-10 days
Mcrconarla mercenarla
LC50
"14 " Calabrese, ot al. 1977
-------
Table 13. (Continued)
Organism
llard-sholl clam (larva),
Morconarl;» mcrcenarla
Hard-sholl clan (larva),
Mcrconaria norcenarla
Soft-she 1 1 clan (adult),
Mya arcnaria
Soft-sholl clan (adult),
Mya arcnaria
Soft-sholl clam (adult),
Mya arenarla
Uluo mussel (larva),
Mytl lus edul Is
riud snal 1 (adult),
Ucissarlus obsoletus
G> Mud snai 1 (adult),
^ Nassarius obsoletus
Mud snal 1 (adu It),
Nassarius obsolotus
Barnacle (cyprid),
Halanus Improvlsus
Fiarnacle (adult),
Ftalanus balanoidcs
(iarnacle (cyprid),
Balanus bctlanoldcs
I'iarnacle (cyprid),
Ralanus balanoidcs
Barnacle (naupllus).
Test
Duration
C-IO days
42-48 hrs
160 hrs
160 hrs
160 hrs
24 hrs
168 hrs
168 hrs
160 hrs
40 hrs
48 hrs
<2 hrs
6 hrs
6 hrs
Effect
LC95
LCO
LCO
LC50
LCI 00
Abnormal development
LCO
LC50
LCI 00
Abnormal development
LC90
Substrate attachment
inhibition
LC50
LC50
Result
(ug/l)
25
2.5
1
4
30
32
100
700
5,000
16,600
1,000
10
90
60
Reference
Calabrose, et al. 1977
Calabroso, et al. 1973
Elslor 4 Honnekey, 1977
Eisler 4 Honnekey, 1977
Elsler 4 Hennekoy, 1!»"
Okubo 4 Okubo, 1962
Elslor 4 Honnekey, 1977
Elsler & Hennekoy, 1977
Eisler 4 Hennokoy, 1977
Clarke, 1947
Clarke, 1947
Pyof inch I Mott, 1948
Pyef inch 4 Mott, 1948
Pyof inch & Mott, 1948
Ralanus cren^itus
-------
Tiibib 13; icbhtliiuoc
Ofcjaffli/ii
Copcpods (adult),
5 fjoridr<»
CbpcpbiJs (adult),
5 rjbhera
Copejibd (adu'ltJ;
Acaftia fclausl
Copcpod (adult),
Pscudbca'tarius nilriutus
fcbpopod (ridult);
Pscudpcaianus nl.hutus
Isopod (adult),
Jacra alb'l.frohs
Isopod (adult);
Jaora nordriiarin I.
ro Isopod (adult);
1 Jacrn alblfrohs sorisu
CO Iscpod (adult);
Idotoa noglbcla
Isopod (adult),
idotea' fcnnrfjiriafa
Crab ( larva);
Care inns nabrias
Crab (larva),
Carclnus maona's
Crab ( larva),
Corclnus mannas
Cral) (larva),
Carclnus irnr-nns
Crali (larva).
JO days
48 hrs
1.9 hrs
70 days
70 days
5 days
57 hrs
<24 hrs
<24 hrs
<24 hrs
47 hirs
20^30 hrs
4i3-J3.5 hrs
2.7 hrs
0.55 Hrs
Decrease In ^tja and ( ,
faecal pel'ibt product Ifari
ii(j-Cu interact Ions oV)
survival
LC50
Growth inhibition
tto growth inhibition
Osradregu'iatldh disruption
LC95
LCI 00
LCI DO
LC90
LWO
LC50
LC50
LC50
IC50
50
5
i
100
100
100
100
100
10
33
100
l;000
3,300
Rbbve> et ai. 1977
Rcbvb,* et ai; 1977
Cbrfler & Sparrow; 1956
Sbnritag £ Grieve, 1977
Sonhtat) 4 Greve; 1977
Jones; 1975
Jones; 1973
Jonos; J973
Jbnbs, 1973
Jones, J973
Connor; 1972
Connor, 1972
Conner, 1972
Conner; 1972
Connor, 1972
-------
Table 13. (Continued)
Organism
Crab (larva),
Carcinus maenas
Whlto shrimp (adult),
Peneus setlferus
Hermit crab (adult),
Pagarus longlcarpus
Hermit crab (adult),
Pagarus longlcarpus
Hermit crab (adult),
Pagarus longicarpus
Grass shrimp (larva).
Pa 1 aemonetes vulgar Is
Grass shrimp (larva),
Palacmonotes vulgar is
W Grass shrimp (larva),
J^ Palaemonotos vulgar is
Fiddler crab (adult),
Uca pugl lator
Fiddler crab (adult).
Oca pugi lator
Fiddler crab (adult),
Uca pugi later
Fiddler crab (zoea),
Uca pugl Ifitor
Fiddler crab (zoea),
Uca pugl lator
Fiddler crab (zoea).
Test
Duration
0.22 hrs
60 days
168 hrs
168 hrs
168 hrs
24 hrs
48 hrs
-18 hrs
28 days
6 days
24 hrs
8 days
24 hrs
5 days
Effect
Result
(ug/l)
LC50 10,000
No effect on respiration, 1
growth, or molting
LCD 10
LC50 50
LC100 125
LCI 00 56
LCD <5.6
Abnormal development 10-18
Low survival, Inhibited 1,000
1 Imb regeneration
Decreased survival 180
Increased oxygen 180
consumption
Decreased survival 1.C
Increased metabolic rate 1.8
Increased swimming activity 1.8
Reference
Conner, 1972
Green, et al . 1976
Elsler 4 Hennekcy, 1977
Eislor 4 Hennekoy, 1977
Elsler 4 Hennekey, 1977
Shealy 4 Sandifer, 1975
Shealy 4 Sandifer, 1975
Shealy 4 Sandifer, 1975
Weis, 1976
Vernberg 4 Vernberg, 1972
Vernberg 4 Vernberg, 1972
DeCoursey 4 Vornberg, 1972
DeCoursoy 4 Vernberg, 1972
DeCoursey 4 Vernborg, 1972
Uca pugllator
-------
Table 13. (Continued)
03
1
cn
0
Organ 1 sm
Sea urchin (spormatazoa),
Arbacla punctulata
Sea urchin {spormatazoa),
Arbacla punctulata
Starfish (adult).
Aster las forbosl
Starfish (adult).
Aster las forbosl
Starfish (adult).
Aster las forbesl
Sea urchin (embryo),
Arbacia punctulata
Echlnoderm (larva),
Paracentrotus llvldus
Oyster (adult),
Crassostrea virgin lea
Oyster (adult),
Crassostrea virgin lea
Copepod (adult),
Acartla clausl
Test
Duration
0 rains
24 mlns
168 hrs
168 hrs
168 hrs
13 hrs
40 hrs
Result
Effect (ug/l)
Increased swimming 20
spood
Decreased swimming 2,000
speed
LCO 10
LC50 20
LC100 125
Abnormal development 92
Retarded growth and 3
development
Mercuric acetate
15 days Reduction In shell growth
12 hrs dally
60 days LC55
1.9 hrs LC50
Methyl- and Ethylmercury Compounds
Methyl mercuric chloride
10
100
50
Reference
Young 4 Nelson, 1974
Young & Nelson, 1974
Elsler & Hennekey, 1977
Elslor & Hennekey, 1977
Elsler & Hennekey, 1977
Waterman, 1937
Soyer, 1963
Cunningham, 1976
Cunningham, 1976
Corner & Sparrow, 1956
Mumrnlchog (adult),
Fundulus heteroclltus
Oyster (adult),
Crassostrea vlrglnlca
24 hrs
Disrupted osmoregulatlon 125 Ronfro, et al. 1974
19 days Trace metal upset
50
Kopfler, 1974
-------
Table 13. (Continued)
Organ Ism
Amphi pod (adult),
Gammarus duebenI
Fiddler crab (adult),
Uca spp.
Fiddler crab (adult),
Uca spp.
Blue mussel (adult),
Mytil us edulls
Test
Duration
3 days
Effect
Diuresis
32 days No limb regeneration
32 days Melanin absent In
regenerated IImbs
Methylmercuric acetate
24 hrs Reduced feeding
Result
(ug/l) Reference
56
100
400
Lockwood & Inman, 1975
300-500 WeIs, 1977
WeIs, 1977
Dorn, 1976
CO
I
Ul
Copopods (adult),
Acartla clausl
Oyster (adult),
Crassostrea virgin lea
Stickleback (adult),
Gasterosteus aculeatus
Sockeye salmon (juvenile),
Oncorhynchus nerka
Sockeye salmon (adult),
Oncorhynchus nerka
Sockeye salmon (adult),
Oncorhynchus nerka
1.9 hrs
19 days
370 mlns
12-15 wks,
1 hr wkly
12-15 wks,
hr wkly as
juvenlles
12 1-hr
exposures
as Juveniles
Ethylmercuric chloride
LC50 50
Other Mercury Compounds
Phenylmercurlc chloride
Trace metal upset 50
Phenylmercurlc acetate
LC100 100
PyrIdylmercuric acetate
1.2 mg Hg/kg wet wt 1,000
muscle 12 weeks post-
exposure
0.24 mg Hg/kg wet muscle 1,000
3 yrs post-exposure
0.04 mg Hg/kg wet muscle 1,000
4 yrs post-exposure
Corner & Sparrow, 1956
Kopfler, 1974
Boetlus, 1960
Amend, 1970
Amend, 1970
Amend, 1970
-------
Table 13, (Continued)
Organism
Silver salmon (adult),
Oncorhynchus klsutch
Chinook salmon (adult),
Oncorhynchus tshawytscha
Test
Duration
12-15 wks
as juventIcs
1 hr wkly
35 wks as
juvaniles
I hr wkly
Effect
0.03 m1t)/kg wet muscle
2 yrs post-exposure
up to 0.12 mg Hg/kg wt
muscle 4 years later
Result
(ug/l)
1,000
1,000
Reference
Amend, 1970
Amend, 1970
08
I
tn
-------
MERCURY
REFERENCES
Abou-Donia, M.B., and D.B. Menzel. 1967. Fish brain cholin-
esterase—Its inhibition by carbamates and automatic assay.
Compar. Biochem. Physiol. 21: 99.
Allison, L.N. 1957. Variation in strength of pyridylmercuric
acetate technical and its effect on rainbow trout. Prog.
Fish-Cult. 19: 108.
Amend, D.F. 1970. Retention of mercury by salmon. Prog.
Fish-Cult. 32: 192.
Berglund, R., and A. Wretling. 1967. Var Foda 19: 9 (as
quoted in Water Quality Criteria 1972. U.S. Environ. Prot.
Agency, R3-73-033).
Berland, B.R., et al. 1976. Action toxique de quatre metaux
lourds sur la croissance d'algues unicellulaires marines.
C.R. Acad. Sci. Paris, t. 282, Ser. D: 633.
Betz, M. 1977. Investigations on the simultaneous uptake
and release of mercury by Dunaliella tertiolecta. Mar.
Biol. 41: 89.
3-53
-------
Biesinger, K.E., and G.M. Christensen. 1972. Effects of
various metals on survival, growth, reproduction, and metabo-
lism of Daphnia magna. Jour. Fish. Res. Board Can. 29: 1691.
Biesinger, K.E. et al. 1979. The chronic toxicity of mercury
to Daphnia magna. Manuscript.
Birge, W.J., and J.J. Just. 1973. Sensitivity of vertebrate
embryos to heavy metals as a criterion of water quality. PB-226 #50
Natl. Tech. Inf - Serv. . Springfield, VA
Blinn, D.W., et al. 1977. Mercury inhibition on primary
productivity using large volume plastic chambers iin situ.
Jour. Phycol. 13: 58.
Boetius, J. 1960. Lethal action of mercuric chloride and
phenylmercuric acetate on fishes. Medd. Komm. Havundersog.,
Kbh. 3(N.S.): 93.
Boney, A.D. 1971. Sub-lethal effects of mercury on marine
algae. Mar. Pollut. Bull. 2: 69.
Boney, A.D., and E.D.S. Corner. 1959. Application of toxic
agents in the study of the ecological resistance of intertidal
red algae. Jour. Mar. Biol. Assn. U.K. 38: 267.
-------
Boney, A.D., et al. 1959. The effects of various poisons
on the growth and viability of sporelings of the red alga
Plumaria elegans (Bonnem.). Schm. Biochem. Pharmac. 2: 37.
Boutet, C., and C. Chaisemartin. 1973. Specific toxic
properties of metallic salts in Austropotamobius pallipes
and Orconectes limosus. C.R. Soc. Biol. 167: 1933.
Brkovic-Popovic, I., and M. Popovic. 1977?^ Effects of
heavy metals on survival and respiration rate of tubificid
worms: Part I—Effects on survival. Environ. Pollut.
13: 65.
A. •'
Brkovic-Popovic, I., and M. Popovic. 1977.'^ Effects of
heavy metals on survival and respiration rate of tubificid
worms: Part II—Effects on respiration rate. Environ.
Pollut. 13: 93.
Brown, B., and M. Ahsanullah. 1971. Effect of heavy metals
on mortality and growth. Mar. Pollut. Bull. 2: 182.
Buikema, A.L., Jr., et al. 1974. Rotifers as monitors
of heavy metal pollution in water. Virginia Polytech. Inst.
and State Univ., Water Resour. Res. Center Bull. 71, 74 p.
Burrows, R.E., and B.D. Combs. 1958. Lignasan as bactericide
and algaecide. Prog. Fish-Cult. 20: 143.
13-55
-------
Burrows, R.E., and D.D. Palmer. 1949. Pyridylmercurie
.acetate: It's toxicity to fish, efficacy in disease control,
and applicability to a simplified treatment technique.
Prog. Fish-Cult. 11: 147.
Calabrese, A., and D.A. Nelson. 1974. Inhibition of embryonic
development of the hard clam, Mercenaria mercenaria, by
heavy metals. Bull. Environ. Contam. Toxicol. 11: 92.
i
Calabrese., A., et al. 1973. The toxicity of heavy metals
to embryos of the American oyster Crassostrea virginica.-
Mar. Biol. 18: 162.
Calabrese, A., et al. 1975. Sublethal physiological stress
induced by cadmium and mercury in winter flounder, Pseudo-
pie uronectes amerjcanus. In Sublethal effects of toxic
chemicals on aquatic animals. Elsevier Sci. Pub. Co. Amster^
dam: 15.
Calabrese, A.., et al. 1977. Survival and growth of bivalve
larvae under heavy-metal stress. Mar. Biol. 41: 179.
i
Chang, L.W., et al. 1974. Effects of methylmercury chloride
on Rarla, pi pi ens tadpoles. Environ. Res. 8: 82.
Chang, L.W., et al.. 1976. Dose-dependent effects of methyl-
mercury on limb regeneration of newts (Triturus viridescens).
Environ. Res. 11: 305.
-------
Christensen, G.M. 1971. Effects of metal cations and other
chemicals upon the in vitro activity of two enzymes in the
blood plasma of the white sucker, Catostomus commersoni
(Lacepede). Chem.-Biol. Inter. 4: 351.
Christensen, G.M. 1975. Biochemical effects of methylmercuric
chloride, cadmium chloride, and lead nitrate on embryos
and alevins of the brook trout, Salvelinus fontinalis.
Toxicol. Appl. Pharmacol. 32: 191.
Christensen, G., et al. 1977. The effect of methylmercuric
chloride, cadmium chloride, and lead nitrate on six biochemi-
cal factors of the brook trout (Salvelinus fontinalis).
Toxicol. Appl. Pharmacol. 42: 523.
Clarke, G.L. 1947. Poisoning and recovery in barnacles'
and mussels. Biol. Bull. 92: 73.
Clendenning, K.A., and W.J. North. 1959. Effects of wastes
on the giant kelp, Macrocystic pyrifera. ^n Proc. 1st Conf.
Waste Disposal Marine Environ., Berkeley, Calif. :82.
Clemens, H.P., and K.E. Sneed. 195#. Effect of temperature
and physiological condition on tolerance of channel catfish
to pyridylmercuric acetate (PMA). Prog. Fish-Cult. 20: 147.
Clemens, H.P., and K.E. Sneed. 1959. Lethal doses of several
commercial chemicals for fingerling channel catfish. Bur.
Sport Fish. Wildl. Serv., Spec. Sci. Kept.—Fish. No. 316.
U.S. Dep. Inter. 10 p.
-------
Connor, P.M. 1972. Acute toxicity of heavy metals to some
marine larvae. Mar. Pollut. Bull. 3: 190.
Corner, E.D;S., and B.W. Sparrow. 1956. The modes of action
I
of toxic agents. I. Observations on the poisoning of cer-
tain crustaceans by copper and mercury. Jour. Mar. .Biol..
Assn. U.K. 35: 531.
iCorner, E.iD.S., and B.W. Sparrow. 1957. The modes of action
io-f toxic agents^ II. Factors influencing "the toxicity
•>o;f mercury compounds to cerain Crustacea.. Jour. Mar. Biol..
.Assn. U.K. 36: 459.
-Cunningham, .P.A. 1976. Inhibition of shell growth in the
presence of mercury and subsequent recovery of juvenile
•oysters. Proc. 'Natl. Shellfish. Assoa. 66: 1.
Cunningham., P.A., and M.R. Tripp. 1973. Accumulation and
depura.tion of mercury in the American oyster Crassostrea
!
'vl.rginic'a.. Mar. Biol. 20: 14.
i
Navies, A.G. 1974. The growth kinetics of Isochrysis galbana
'in cultures containing sublethal concentrations of mercuric
Chloride. -Jour. Mar. Biol. Assn. U.K. 54: 157.
Davies, A.-G. 1976. An assessment of the basis of mercury
tolerance in Dunaliella tertiolecta. Jour. Mar. Biol. Assn.
U.K. 56: 39.
-------
Dawson, M.A., et al. 1977. Physiological response of juvenile
striped bass Morone saxatilis, to low levels of cadmium
and mercury. Chesapeake Sci. 18: 353.
DeCoursey, P.J., and W.B. Vernberg. 1972. Effect of mercury
on survival, metabolism and behaviour of larval Uca pugilator
(Brachyura). Oikos 23: 241.
De Filippis, L.F., and C.K. Pallaghy. 1976. The effect
of sub-lethal concentrations of mercury and zinc on Chlorella.
II. Photosynthesis and pigment composition. Z. Pflanzen-
physiol. Bd. 78: 314.
Dial, N.A. 1976. Methylmercury: Teratogenic and lethal
effects in frog embryos. Teratology 13: 327.
Dorn, P. 1976. The feeding behaviour of Mytilus edulis
in the presence of methylmercury acetate. Bull. Environ.
Contam. Toxicol. 15: 174.
Doyle, M., et al. 1976. Acute toxicological response of
the crayfish (Orconectes limosus) to mercury. Bull. Environ.
Contam. Toxicol. 16: 422.
Drummond, R.A., et al. 1974. Cough response and uptake
of mercury by brook trout, Salvelinus fontinalis, exposed
to mercuric compounds at different hydrogen-ion concentrations.
Trans. Am. Fish. Soc. 103: 244.
-------
Easier, R., et al. 1972. Acute toxicology of sodium nitro-
lotriacetic acid (NTA) and NTA-containing detergents to
marine organisms. Water Res. 6: 1009.
Eisler, R., and R.J. Hennekey. 1977. Acute toxicities
of ed'f2,Cr"l"6,Hg+2,Ni"'"2, and Zn+2 to estuarine macrofauna.
Arch. Environ. Contain. Toxicol. 6: 315.
Ellis, M.M. 1947. Toxicity of phenyl mercuric lactate
for fish. U.S. Fish. Wildl. Serv. Spec. Sci. Rep . 42.
U.S. Dep. Inter.
Fujita, M., and K. Hashizume. 1972. The accumulation of
i
mercury by freshwater planktonic diatom. Chemosphere 5:
.203.
Gardner, G.R. 1975. Chemically induced lesions in estuarine
or marine teleosts. In The pathology of fishes. Univ. .
of Wisconsin Press, Madison, Wis .
Gentile, J.H., et al. 1979. Manuscript.
203
Glooschenko.W.A. 1969. Accumulation of Hg by the marine
diatom Chaetoceros costatum. Jour. Phycol. 5: 224.
Gray, J.S. 1974. Synergistic effects of three heavy metals
on growth rates of a marine ciliate protozoan. Iri Pollution
and ptfysiology of (fyarine /rganisms. Academic Press, New York
fi-60
-------
Gray, J.S., and R.J. Ventilla. 1971. Pollution effects on
micro- and meiofauna of sand. Mar. Pollut. Bull. 2: 39.
Gray, J.S., and R.J. Ventilla. 1973. Growth rates of sedi-
ment-living marine protozoan as a toxicity indicator for
heavy metals. Ambio 2: 118.
Green, F.A., Jr., et al. 1976. Effect of mercury on the
survival, respiration and growth of postlarval white shrimp,
Penaeus setiferus. Mar. Biol. 37: 75.
Hale, J.G. 1977. Toxicity of metal mining wastes. Bull.
Environ. Contam. Toxicol. 17: 66.
Hannan, P.J., and C. Patouillet. 1972. Effect of mercury
on algal rates. Biotech. Bioeng. 14: 93.
Hannan, P.'J. , et al. 1973a. Hg as tracer on pigments
of Phaeodactylum tricornutum. Int.•«••-. Jour. Appl. Radiat
~—-————— »
Isotopes 24: 665.
Hannan, P.J., et al. 1973b. Measurements of mercury sorption
by algae. U.S. Naval Res. Lab.^fashingtonp.C. Rep .
Kara, T.J., et al. 1976. Effects of mercury and copper
on the olfactory response in rainbow trout, Salmo gairdneri.
Jour. Fish. Res. Board Can. 33: 1568.
-------
Harriss, R.C., et al. 1970. Mercury compounds reduce photo-
: : - '. 1
synthesis by plankton. Science 170: 736.
Heinz, G.H» 1976. Methylmercury: Second-generation repro-
ductive and behavioral effects on mallard ducks. Jour.
Wildl. Manage. 40: 710.
Heit, M.,. and M. Fingerman. 1977. The influences of size,
sex and temperature on the toxicity of mercury to two species
of crayfishes. Bull. Environ. Con tarn.. Toxicol. 18: 572.
Hendrick, R.D. , and T.R. Everett. 1965. Toxicity to the
Louisana red crayfish of some pesticides used in rice culture.
Jour.. Econ. Entomol. 5.8: 958.
Holderness,. J., et al. 1975. The effect of methyl mercury
on the growth of the green alga, Coelastrum microporum Naeg.
strain. 280. Bull. Environ. Contain. Toxicol. 13: 348.
-/
Hopkins, R.., and J.M. Kain. 1971. The effect of marine
pollutants on Laminarea hyperboria. Mar. Pollut. Bull.
2: 75.
Huckabee, J..W. , and N.A. Griffith. 1974. Toxicity of mercury
and selenium to the eggs of carp (Cyprinus carpio). Trans.
Am. Fish. Soc. 103: 822.
8-62.
-------
Jackim, E. 1973. Influence of lead and other metals on
fish delta-aminolevulinate dehydrase activity. Jour. Fish.
Res. Board Can. 30:560.
Jackim, E., et al. 1970. Effects of metal poisoning in
five liver enzymes in the killifish (Fundulus heteroclitus).
Jour. Fish. Res. Board Can. 27: 383.
Jones, J.R.E. 1939. The relation between the electrolytic
solution pressures of the metals and their toxicity to the
stickleback (Gasterosteus aculeatus L.). Jour. Exp. Biol.
16: 425.
Jones, J.R.E. 1947. The oxygen consumption of Gasterosteus
aculeatus L. in toxic solutions. Jour. Exp. Biol. 23:
298.
Jones, M..B. 1973. Influence of salinity and temperature
on the toxicity of mercury to marine and brackish water
isopods (Crustacea). Estuarine 5. Coastal Mar. Sci. 1:
425.
Jones, M.B. 1975. Synergistic effects of salinity, tempera-
ture and heavy metals on mortality and osmoregulation in
marine and estuarine isopods (Crustacea). Mar. Biol. 30:
13.
-------
Ramp-Nielsen, L. 1971. The effect of deleterious concentra-
tions of mercury on the photosynthesis and growth of Chlorella
pyrenoidosa. Physiol. Plant 24: 556.
Kayser, H. 1976. Waste-water assay with continous algal
cultures: The effect of mercuric acetate on the growth
of some marine dinoflagellates. Mar. Biol. 36: 61.
Klaunig, J., et al. 1975. Acute toxicity of a native mummig-
hog population (Fundulus heteroclitus) to mercury. Bull.
Environ. Contam. Toxicol. 14: 534.
Kopfler, F.C. 1974. The accumulation of organic and inorganic
mercury compounds by the eastern oyster (Crassostrea virginica),
Bull. Environ. Contam. Toxicol. 11: 275.
Laumond, F., et al. 1973. Experimental investigations,
at laboratory, on the transfer of mercury in marine trophic
chains. Ir\ 6th Int. Symp. Medicale Ocean., Portoroz, Yugo-
slavia, Sept. 26-30, 1973- "~-
Lockwood, A.P.M., and C.B.E. Inman. 1975. Diuresis in
the amphipod, Gammarus duebenj induced by methylmercury,
D.D.T., lindane and fenithrothion. Comp. Biochem. Physiol.
52C: 75.
MacLeod, J.C., and E. Pessah. 1973. Temperature effects
on mercury accumulation, toxicity, and metabolic rate in
rainbow trout (Salmo gairdneri). Jour. Fish. Res. Board
Can. 30: 485.
B-feV
-------
Matida, Y., et al. 1971. Toxicity of mercury compounds
.to aquatic organisms and accumulation of the compounds by
the organisms. Bull. Freshwater Fish. Res. Lab. 21: 197.
Matson, R.S., et al. 1972. Mercury inhibition on lipid
biosynthesis in freshwater algae. Environ. Sci. Technol.
6: 158.
Mclntyre, J.D. 1973. Toxicity of methyl mercury for steel-
head trout sperm. Bull. Environ. Contam. Toxicol. 9: 98.
McKim, J.M., et al. 1976. Long-term effects of methylmercuric.
chloride on three generations of brook trout (Salvelinus
fontinalis): Toxicity, accumulation, distribution, and*
elimination. Jour. Fish. Res. Board Can. 33: 2726.
Middaugh, D.P., and C.L. Rose. 1974. Retention of two
mercuricals by striped mullet, Mugil cephalus. Water Res.
8: 173.
Mills, A.L., and R.R. Colwell. 1977. Microbiological effects
of metal ions in Chesapeake Bay water and sediment. Bull.
Environ. Contam. Toxicol. 18: 99.
Nelson, D.A., et al. 1976. Biologial effects of heavy
metals on juvenile bay scallops, Argopecten irradians, in
short-term exposures. Bull. Environ. Contam. Toxicol.
16: 275.
-------
I
Okubo, K., and T. Okubo. 1962. Study on the bioassay method
for the evaluation of water pollution - II. Use of the
fertilised eggs of sea urchins and bivalves. Bull. Tokai
Reg. Fish. Res. Lab. 32: 131.
Olson, G.F., et al. 1975. Mercury residues in fathead
minnows, Pimephales promelas Rafinesque, chronically exposed
to methylmercury in water. Bull. Environ. Contain. Toxicol.
14: 129.
i •
Olson, K.R., and R.C. Barrel. 1973. Effect of salinity
on acute toxicity of mercury, copper, and chromium for Rangia
cuneata (Pelecypoda, Mactridae). Contrib. Mar. Sci. 17: 9.
Qvernell, J. 1975. The effect of heavy metals on photosysn-
thesis and loss of cell potassium in two species of marine
algae, Dunaliella tertiolecta and Phaeodactylum tricornutum.
Mar. Biol. 29: 99.
Parrish,, K.M., and R.A. Carr. 1976. Transport of mercury
through a laboratory two-level marine food chain. Mar.
Pollut. Bull. 7: 90.
Persoone, G., and G. Uyttersprot. 1975. The influence
of inorganic and organic pollutants on the rate of reproduc-
tion of a marine hypotrichous ciliate: Euplotes vannus
Muller. Rev. Int. Oceanogr. Med. 37-38: 125.
-------
Portmann, J.E. 1968. Progroess report on a programme of
insecticide analysis and toxicity-testing in relation to
the marine environment. Meeresuntersuchungen 17 (1-4):
247.
Pyfinch, K.A., and J.C. Mott. 1948. The sensitivity of
barnacles and their larvae to copper and mercury. Jour.
Exp. Biol. 25: 296.
Reeve, M.R., et al. 1977. Evaluation of potential indicators
of sub-lethal toxic stress on marine zooplankton (feeding,
fecundity, respiration and excretion): controlled ecosystem
pollution experiment. Bull. Mar. Sex. 27: 105.
Rehwoldt, R., et al. 1973. The. acute toxicity of some
heavy metal ions toward benthic organisms. Bull. Environ.
Contain. Toxicol. 10: 291.
Reinert, R.E., et al. 1974. Effect of temperature on accumu-
lation of methylmercuric chloride and p,p'DDT by rainbow
trout (Salmo gairdneri). Jour. Fish Res. Board Can. 31:
649.
Reish, D.J., and R.S. Carr. 1978. The effect of heavy
metals on the survival, reproduction, development, and life
cycles for two species of polychaetous annelids. Mar. Pollut.
Bull. 9: 24.
-------
Re;ishv D.J-. , e.t al.. 1976. The effect of heavy metals on
labor-a^tory populations of two polychaetes with comparisons
to, the' wa-ter quality conditions and standards in southern
Ca*li.for.nia marine waters. Water Res. 10: 299.
rroy ' J . L . , et al. 1.974.. Methyl mercury and inorganic
me/E'cury: uptake:, distribution,^ and effect, on osmoregulatory
mecfran.rsms in fishes,. In' Pollution and physiology of.
jryaiE:i.rte c'rg.artl.sms ,• Academic Press-, New- York-.
i
Ro:d:g;;e'r*s;,/' ELCL, „ et. a-lk., 1951. the' toxicity of pyridylmercuric
a«fe taster 'technical (PMft) ta rairfbow trout ( S almo gairdnerii) .
E.rog,.,. EishVG,ial.t.^ 13;: 71.
-'Giiffitea,,. J.'..Ji. ,. andi >I'...Wv.t Rachlin.- 1977. T.h~e: effect of cadmium,
E,, merr;cuT.'y ,• z.'in'c1 an-d^ lead, on" cell division,, growth,
; C-hlor.ophy.-ll ar cont:era'«fc of, the' chloTop'hyt:e Ch lor el la vulg'aris.
104.: 22:6.
Ruicteer.^- R.R., andf W.J. Wifepple. 195"!.. Effect of bactericides
on: site^lhead tr:ou:t: f;ry. Prog. F'ish-C'ult.. 13: 43.
S:ctimik3;t-N:ielsen-,, B'...r e.t al. 1977'. Effect of methylmercury
ugon'.i osmoreg.u,la:tion,- cel'lUla't volume,, and. ion regulation
i,n winter flounder, Psgudopleuron'ectes ajmerjcanus. In Physio
lb:g-,i'c-ai. Responses: o-fv Ma'r'i-n'e? Hiota1- to' Pollutants-. Academic
E"r:e;:ssv,.;New York-
B-
-------
Shealy, M.H./ and P. A. Sandifer. 1975. Effects of mercury
on survival and development of the larval grass shrimp,
Palaemonetes vulgar is. Mar. Biol. 33: 7.
Sheline, J., and B. Schmidt-Nielsen. 1977. Methylmercury-
selenium: interaction in the killifish, Fundulus heteroclitus,
Ir\ Physiological Responses of Marine Biota to Pollutants.
Academic Press, New York
Sick, L.V. , and H.L. Windom. 1975. Effects of environmental
levels of mercury and cadmium on rates of metal uptake and
growth physiology of selected genera of marine phytoplankton.
Iri Mineral cycling in southeastern ecosystems. U.S. Energy.
Res. Dev. Admin. CONF-740513 from
Natl. Tech. Info. Serv. Springfield,
Sigmon, C.F., et al. 1977. Reductions in biomass and diver-
sity resulting from exposure to mercury in artificial streams
Jour. Fish. Res. Board Can. 34: 493.
Sonntag, N.C., and W. Greve. 1977. Investigation of the
impact of mercury on enclosed water columns using a zooplank-
ton simulation model. Jour. Fish. Res. Board Can. 34: 2295.
Sosnowski, S.L., and J.H. Gentile. 1978. Toxicological com-
parison of natural and cultured populations of Acartia tonsa
to cadmium, copper, and mercury. Jour. Fish. Res. Board
Can. 35: 1366.
-------
Sosnowski, S,L., et al. 1979. The effects of chronic mercury
i
-ex.pos.ure on the mysid .shrimp. Mysidopsis bahia Abs±. N.E.
Fish & Wildlife Conf. April 1-4. Providence R.I.
Soyer, J. 1963. Contribution to the study of the biological
&-££ec,ts o.f mercury and .silver in sea water. Vie et Milieu
Stanley, "R.A. -1974. Toxicity of heavy metals and salts
±o Eurasian watermilfoil ( My r 1 op hy.ll um spicatum L.) . Arch.
?Envi:r,on. Eontam. Toxicol, 2: 331.
a?hux,berg, F^P. , 'et --al.. 1977.. Response of the lobster,
Homarus amer;icanus , to sublethal levels of cadmium and mer-
;;cu-ry. in Physiological Responses of Marine Biota to -Pollut
Academic ;Pr,ess,, New York.
s,f ,R. 19,62. Growth of .pure cultures of marine phyto-
plankton in ±he presence of toxicants. Appl. Microbiol...
:i£)-: '53.2.
Vernberg, W.B. , and .J. Vernberg. 1972. The synergistic
'.effects of :temper.a,turef salinity, and mercury on survival
,and metabolisms of the adult fiddler crab, Uca pug i la tor .
VU,.,S.. Dep . .Comm. Fish. Bull.. 70: 415.
8 -70
-------
Warnick, S.L., and H.L. Bell. 1969. The acute toxicity
of some heavy metals to different species of aquatic insects
Jour. Water Pollut. Control Fed. 41: 280.
Waterman, A.J. 1937. Effect of salts of heavy metals on
development of the sea urchin, Arbacia punctulata. Bioi.
Bull. 73: 401.
Weis, J.S. 1976. Effects of mercury, cadmium, and lead
salts on regeneration and ecdysis in the fiddler crab, Uca
**
pugilator. U.S. Dep .". Comm , Natl. Ocean/ Atmos. Admin.
i
Fish. Bull. 74: 464.
Weis, J.S. 1977. Limb regeneration in fiddler crabs:
species differences and effects of methylmercury. Biol.
Bull. 152: 263.
Weis, P., and J.S. Weis. 1976. Effects of heavy metals
on fin regeneration in killifish, Fundulus heteroclitus.
Bull. Environ. Contam. Toxicol. 16: 197.
Weis, P., and J.S. Weis. 1977d« Effects of heavy metals
on development of the killifish, Fundulus heteroclitus.
Jour. Fish Biol. 11: 49.
Weis, P., and J.S. Weis. 1977fc. Methylmercury teratogenesis
in the killfish, Fundulus heteroclitus. Teratology 16: 317.
-------
Willford, W.A. 1967. Investigations in fish control:
18. Toxicity of 22 therapeutic compounds to six fishes.
Bur. Sport Fish. Wildl. Serv. U.S. Dep. Inter. .
Wobeser, G.A. 1973. Aquatic mercury pollution: Studies
of its occurrence and pathologic effects on fish and mink.
Ph.D. Thesis/ Univ .Saskatchewan (Canada).
Young/ L.G., and L. Nelson. 1974. The effects of heavy
metal ions on the motility of sea urchin spermatozoa. Biol,
Bull. 147: 236.
-------
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
evaluation. 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 discuss the most impor-
tant 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 Concentrations Committee,
t
1969) to consider three broad categories of the physical
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 mercury
vapor when present in the atmosphere or as metallic mercury
when present in its liquid form. The second category compris-
es the inorganic compounds of mercury, which include the
salts of the two oxidation states of mercury, Hg2"l"+ (mercurous
salts), and Hg++ (mercuric salts). The third major category
C-l
-------
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
sub-group in the organo-mercurials category is comprised
of the methyl mercury and related short-chain alkyl mercurial
compounds. From the point of view of environmental exposures,
the methyl mercury compounds are the ones of greatest concern.
The other organo-mercurials may take the form of aryl and
' *,
alkoxy-aryl mercurials as well as a wide variety of other
organo-mercurials used in medicine and agriculture. In
general these organic forms of mercury are much less toxic
I - !
than the short-chain alkyl mercurials.
The main sources of human 'mercury exposure are methyl
mercury compounds in the food supply and mercury vapor in
the atmosphere of occupational settings. Other sources
i
of exposure to a wide variety of mercury forms result from
occupational, medicinal, or accidental circumstances. As
will be discussed later, the water supply probably contains
mercury mainly in the form of Hg salts complexed with
i
a variety of constituents in water.
The topics of mercury in the environment, human expo-
sure to mercury, and an estimate of health effects and hazards
o'fr mercury have been the subject of many reviews by expert
committees and individual authors over the past ten years.
Included are reviews by the Swedish Expert Group (1971);
Study Group on Mercury Hazards (1971); WHO (1972, 1976);
C-2
-------
Miller and Clarkson (1973); Friberg and Vostal (1972); Nordberg
(1976); and The National Academy of Sciences (1978). Addit-
ional references are Hartung and Dinman (1972) , and Buhler
(1973).
The source material for this document comes primarily
from original scientific publications, but the reviews ment-
ioned above have also been of inestimable value in the prepara-
tion of this document and in developing an overall perspec-
tive 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.
EXPOSURE
Introduction
A variety of original articles and reviews have dealt
with sources, pathways and mechanisms of transport and sinks
of mercury in the environment. These include Wallace, et
al. (1971); D'ltri (1972); Friberg and Vostal (1972); Gar-
rels, et al. (1973); Kothny (1973); WHO (1972, 1976); Heindryckx,
et al. (1974); Korringa and Hagel (1974); Wollast, et al.
(1975); Abramovskig, et a.". (1975); and National Academy
of Sciences (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
C-3
-------
environmental mercury burden may be viewed. However, 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 equipment.
Matsunaga, et al. (1979) have recently reviewed the methodo-
logical errors involved in the measurement of mercury in
seawater.. These analytical figures are multiplied by huge
12 2
numbers (e.g. the area of oceans (361 x 10 ) m and the
17 2
precipitation over oceans (4.11 x 10 1/m yr) to calculate
the "mercury budgets" for the global cycle. Authorities
differ in their interpretation of certain environmental
samples and the most recent data seem to conflict with earlier
data (N'atl. Acad. Sci. 1978; Korringa and Hagel, 1974).
It is likely, therefore, that the "up-dating" of the global
cycle and other more localized cycles will continue. Never-
theless, 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
i
*"tons" are metric tons, ie. 1,000 kg, in this text.
C-4
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TABLE 1
Entry of Mercury into the Atmosphere
Source Annual input (metric tons)
Ref. (1) (2) (3)
Natural
Continental degassing 17,800 50,000
Oceanic emission 7,600
Coastal emission 1,420
Emission from land biota 40
Volcanic 20
Total 26,880 25,000
Anthropogenic 10,000 16,000
Total 36,880 41,000
(1) National Academy of Sciences (1978)
(2) Korringa and Hagel (1974)
(3) Heindryckx, et al. (1974)
C-5
-------
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 volcanoes seems to
be negligible.
Manmade (anthropogenic) release, although less than
'tha't due to natural causes, is substantial, accounting for
•about one third of total input.
The amount of mercury contained in the atmosphere .is
tine 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 (Natl. Acad. Sci.
-'1978) assumed an exponential decline with increasing altitude,
i
whereas others have assumed that mercury mixes to a height
i
•'Q'f 1 kilometer (Heindrykx, et al. 1974) . This wide range
-------
TABLE 2
The Amount of Mercury in some Global Reservoirs
Reservoir Mercury Content (metric tons)
(1) (2)
Reservoir
Atmosphere 850
Fresh water 2000
Fresh water biota 400
Ocean Water , 41 x 106 70 x 106
Oceanic Biota 200,000
(1) National Academy of Sciences (1978)
(2) WHO (1976)
a Only living biota
Living and dead biota
C-7
-------
lead to substantial local pollution..
Most of the atmospheric transport goes to the oceans
(Table 3). Figures vary widely. The earlier estimates
gave numbers of about 40,000 to 50,000 metric tons/year.
However, 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. 19-76).
'The amount of mercury contained in the oceans is-extreme-
ly; large compared with 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
•
(a.s- opposed to coastal and inland waters) have not changed
significantly over recorded history. Oceanic fish levels
most probably have remained unchanged by man's activities,
i
especially in wide ranging oceanic, fish such as shark, sword-
fish,, and tuna fish..
The amount of mercury dissolved in ocean water is ex-
tremely large as. compared to the amount in oceanic biota
(Table 2). On the other hand, mercury in living biota ac-
counts for abo.ut one^half of the total mercury in freshwater.
The figures in Table 2 are expressed, in, terms of total mercury.
I
If expressed in terms of methyl mercury, the amount of mercury
i
in biota would considerably exceed that in fresh water.
Data on concentrations of mercury in the- lithos.phere
C-8
-------
TABLE 3
Entry of Mercury into the Ocean
Source
Annual input (metric tons)
(1) (2) (3)
Atmospheric deposition
Open Ocean and Polar
Coastal waters
Land run-off
Soluble
Particulate
Hydrothermal
7,600
3,600
1,600
3,700
?
41,000
5,000
5,000
?
50,000
5,000
5,000
?
(1) National Academy of Sciences, 1978
(2) Korringa and Hagel, 1974
(3) Heindryckx, et al. 1974
C-9
-------
have been reviewed by several expert groups (World Health
.Organ., 1976; U.K. Dep. Environ., 1976; Natl. Acad. Sci.,
.1978). Mercury concentrations in nonmineralized soils vary
.over two. orders of magnitude, the average concentration
.bel'ng .about 0.07 pg Hg/g. Freshwater sediments in non-pollut-
-xed .rivers and lakes in the United States usually contain
."less than 0.1 A9/9 (wet sediment). Insufficient 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 organic matter (Andersson, 1976; Keckes and
Mlet.tinen, 1970.; Landry, et al. 1978) . Kimura and Miller
i
.(.1970) .reported that mercury mobility is minimal even in
soils con.taminated by mercury fungicides. However, Fuller
(-1,977(, 1978) has reported that the mobility of mercury in
i
soils i's increased in the presence of leachates from municipal
i
.lanrTfl.lls.
i
Chemical and 'Physical Forms of Mercury in the Environ-
ment .awd Theix Transformation: Mercury occurs in a variety
i
JQ£ ^physical and chemical forms in nature. Mercury is mined
;;as cinnabar (:Hg,s) but in some areas (Almaden, Spain) the
..ore is BO rich that metallic mercury is also present.
Human activities ;have resulted in the release of a
t
.wide .variety of both inorganic and organic forms of mercury
'(-Table 4).. The electrical and chloralkali industries and
i
'the burning .of fossil fuels ..release mercury to the atmosphere
ma.rn.l-y as Hg°. Release to water via direct discharge involves
rEg and Hg° (e.g. chloralkali). Methyl mercury compounds
have been .released to fresh and oceanic water in Japan as
C-10
-------
Patterns of Mercury Consumption in the United States
End use
Annual Consumption (% total)
1970
1973
1985'
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
0.8
9.8
Total consumption
(metric tons)
2100
1867
2091
This table is adapted from table 1.3 in the report of the
National Academy of Science (1978) and from figures
derived from U.S. EPA. (1975a).
3The percentages were estimated under the assumption that consumption
by laboratories was negligible.
(CH3)2Hg
Fish
Hg°-»
j
Shellfish
\
CH3SHgCH3
• CH.Hg* *-(CH,),Hg CH.S-HgCH,
Bacteria 3 >^ Bacteria 4 •* VJ J
Bacteria
v..
Air
Water
Sediment
Figure 1. The mercury cycle demonstrating the bioaccumulation
of mercury in fish and shellfish.
Taken from Figure 3.1 in the National Academy of Sciences
(1978).
C-ll
-------
a byproduct of the manufacture of aceteldehyde and vinyl
chloride. Other anthropogenic sources have resulted in
i
release of aryl and alkoxy-aryl compounds as well as methyl
and ethyl mercury compounds used as fungicides.
The inorganic forms of mercury may undergo oxidation
—-reduction reactions in water as indicated by the equations:
2 Hg° = Hg+* + 2 i . . ..... (1)
(.2).
;;Stock (193-4) has demonstrated that Hg° can be oxidized to
-Hg r in water in the presence of .oxygen. The reaction prob-
ably "fakes "place in rain droplets during removal of Hg°
•from 'the ratmosphere by precipitation. Wallace, et al. (1971)
i
have noted tha.t mercury concentrations as high as 40 g/1
;can be attained when water .saturated with oxygen is exposed
-.to .mercury vapor. The mercurous form of mercury (Hg7 )
i * •
undergoes .disproportionation to Hg° and Hg in the presence
,:o"f rsulf.ur ligands (Cotton and Wilkinson, 1966) . Jensen
i
:arid 'Jerne.lov (1972) have noted that -the presence of organic
substances in water facilitates .the transformation of Hg°
to Hg . "The mercuric ion, Hg is the substrate for the
"biomethylation reaction that occurs in microorganisms present
..in .aquatic sediments (Figure 1) .
In -a recent review by the National Academy of Sciences
(197.8), it was noted -that the main pathway of methylation
"o;f soluble Hg involved --a transfer of methyl groups from
i
.'methyl cobalamine (methyl-B12) and that the rate of formation
;of methyl mercury is largely determined by the concentra-
tions x>f soluble Hg and methyl B,--
C-12
-------
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 containing Hg . In the presence of Hg , one
molecule of dimethyl mercury is converted to two molecules
of monomethyl mercury (Cotton and Wilkinson, 1966).
A variety of bacterial and fungal organisms have the
capacity to methylate Hg . Jensen and Jernelov (1972) have
pointed out that conditions which promote bacterial growth
will enhance methylation of mercury. Thus, the highest
rates of methylation in the aquatic environment are seen
in the uppermost part of the organic sediments and in suspend-
ed organic material in water. Furthermore, those microorgan-
isms able to methylate mercury at high rates are also, usually
resistant to the toxic effect of Hg
Microorganisms are also capable of demethylating methyl
mercury compounds and of splitting the carbon-mercury bond
in a variety of other organic 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 (Natl. Acad. Sci. 1978).
Microorganisms capable "of demethylation reactions have been
shown to occur in aquatic sediments, soils and human fecal
material. Microbial resistance to methyl mercury correlates
013
-------
with the capacity to convert methyl mercury to Hg • Both
methylation and demethylation rates have been measured in
aquatic sediments in the laboratory (for review, see Natl.
I
Acad. Sci. 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 methyl mercury in fresh
water on a global scale was estimated to be about 10 metric
tons/year per year and in the oceans to be about 480 metric
tons/year.
I ++
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 correlates
with a resistance to the toxic effects of Hg (Singh and
Sherman, 1974).
In addition to being a substrate for both methylation
and reduction reactions in microorganisms, Hg is avail-
able to form a variety of precipitates, complexes, and chelates
in water. A stable precipitate is formed with the sulfide
ion S~. The latter is usually present in anaerobic aquatic
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 incomplete. For theore-
tical reasons, the degree of oxygenation, pH, and the presence
of inorganic (e.g. Cl~) and organic (e.g.-S~f C00~, and
N in organic matter in water) ligands are probably important
C--14
-------
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-oxy-
genated water and an increasing fraction of mercury as Hg°
or HgS in reducing conditions (Natl. Acad. Sci. 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~, HgCl-jBr"
HgCl.,~, HgCl2Br~, HgCl2) in marine water.
Methyl mercury compounds readily pass across cell mem-
branes and bind to tissue ligands. Thus, methyl mercury
tends to be removed from water by living biota. Unfortu-
nately, little information is available on concentrations
of methyl mercury in fresh or marine water. Chau and Saitoh
(1973) were unable to detect methyl mercury (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 lakes.
Andren and Harriss (1975) could not detect methyl mercury
in samples of river and coastal waters of the Eastern Gulf
of Mexico.
Wood (1976) has pointed out that, as a result of meth-
ylation and demethylation reactions, the concentrations
of methyl mercury 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
reactions. Many factors may be involved, some of which
have been mentioned above. However, there is a need for
further studies on the dynamics of methyl mercury in the
environment.
C-15
-------
found that 153 samples out of a total of 193 had values
below 0.25 jug/1. No value above 0.8 jug/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 Wers.haw (1970) found that more
t.han half of the 73 rivers that were sampled had mercury
Concentrations low.er than 1,000 ng Hg/1 and 34 of the rivers
had concentrations of less than 100 ng Hg/1. windom in
1973, reporting on measurements of the Savannah estuary
fo.und. that concentrations ranged up to 450 ng Hg/1.
Levels of- mercury in ocean waters are usually below
3QQ ng Hg/1. Stock and Cucuel in 1934 reported a mean value
of 30 ng Hg/1. Hosohara (1961) recorded mercury levels
a,t different depths in the Pacific; values on the surface
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 o.f the Environment
(•1976,). Matsunaga, et al. (1979), in the most recent report
on mercury in waters, claim that 5 to 6 ng Hg/1 "may be
a reliable value for baseline 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 techniques (i.e. contamination).
C-1.6
-------
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 concen-
tration 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 corresponds to a daily intake
of 400 ng Hg or an estimated retained dose of 600 ng Hg.
Ingestion 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 merury concentrations in
food. These surveys uniformly indicate that a distinction
must be made between fish and non-fish 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 detec-
tion of mercury of the analytical methods used in reported
studies. In the United States, figures from surveys carried
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 (quoted
in Nat. Acad. Sci. 1978). In view of the uncertainties
in these numbers, it is impossible to calculate average
C-17
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daily intakes for non-fish food in the United States. An
extensive study in Sweden noted that dietary mercury from
non-fish sources was about 5,000 ng Hg/day, and that the
methyl mercury content was not known. A low intake of mercury
from non-fish sources is consistent with the finding that
non-fish eaters have the lowest blood concentrations of
mercury.
A variety of surveys have been carried out in the United
States of concentrations of mercury and the forms of mercury
in fish (for review, see Natl. Acad. Sci., 1978). These
surveys indicate that the average concentration of mercury
in most fish is less than 200 ng/g, with virtually all the
i
mercury in fish muscle in the form of methyl mercury 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. Observa-
tions on 3,000 samples of canned tuna indicated an average
total mercury concentration of approximately 250 ng/g, with
.four percent of the samples being above 500 ng/g. Concentra-
tions 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 factor in determining the mercury concen-
tration in fish muscle for both freshwater and marine fish;
C-18
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the older the fish, the higher the mercury concentration.
This is consistent with the report that the half-time of
methyl mercury 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 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 methyl mercury are found in seal tissue,
including liver, so that individuals consuming seal meat,
such as Eskimo, may develop high blood concentrations of
methyl mercury (Galster, 1976).
Observations on museum specimens of tuna fish and sword-
fish suggest that the concentrations of mercury have not
changed throughout this century. 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 observable change in mercury levels
in tuna and other oceanic fish is consistent with the large
reservoir of mercury in the oceans.
C-19
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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 representing
i
all major and 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 one year from September,
1973 to August 1974. The selected data from these studies
are given in Table 5. Approximately 95 percent of the panel-
ists reported eating fish. Tuna fish was by far the most
popular item with 68 percent of the fish eaters reporting
they ate tuna fish. Since 20 percent did not report the
species 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 five percent of the panelists. It is clear, there-
fore, that the consumption of tuna fish in the United States
accounts for most of the dietary intake of methyl mercury,
as this form of mercury accounts for more than 90 percent
of the total mercury in tuna and most other species of fish.
i
The data in Table 5 do not allow an estimate of the
average daily intake. However, if we assume (a) F.D.A.
020
-------
TABLE 5
Average and Maximum Mercury Levels in Species of Fish
Eaten by 2% or More of 24,652 Panelists3.
Species
Tuna (light)
Shrimp
Flounder
Perch (marine)
Salmon
Clams
Cod
Pollock
Haddock
Herring
Oysters
Mercury concentration0
jug Hg/g fresh weight
Panelists
(%)
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
Max imum
0.39
0.87
0.33
0.88
0.59
0.21
0.26
0.59
0.95
0.37
0.26
0.45
Number
of
Fish in
sample
70
115
353
1179
268
806
584
134
227
88
272
260
Data from U.S. Dept of Commerce, 1978.
Approximately 21% of the panelists did not report the
species of fish consumed. Approximately 6.1% of the
panelists consumed other species of finfish.
Numbers are rounded to two decimal places.
The fish were sampled at source and are not samples of
the fish consumed by the panelists.
C-21
-------
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
methyl mercury 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 methyl mercury per day from fish.
If- the averag.e, daily fish consumption in the United States
is taken, as: 17 g instead of 27 g (Food Agric. Organ. 1946-
196,6 quoted in Table 5.2 in the Natl. Acad. Sci. 1978),
the; average methyl mercury consumption from fish would be
i
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 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 estimated that
99.87 percent would be below this intake figure under the
current. F.D.A., guideline of 1,000 ng fish.
The National Academy of Sciences (1978) criticized
the. U.S. Department of Commerce Report (1978) because "consump-
tion rates were figured at less than normal portions and
a.t minimum mercury levels." They noted that Weight WatchersR
C-22
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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 jug Hg/day, the second quartile between
17 and 26, the third quartile between 27 and 38, and the
highest quartile from 40 to 75 /ag Hg/day.
Given the difficulties in accurately estimating dietary
j^ntakes of mercury, it is surprising that no comprehensive
surveys have been reported on blood concentrations of mer-
cury in representative samples of the U.S. population.
In McDuffie's study (1973) on Weight Watchers,R two 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 ug Hg (using the model discussed in
the next section). Gowdy, et al. (1977) reported that 9
of 210 subjects whose blood was collected for health reasons
showed total mercury levels above 50 ng Hg/ml, and four
were above 100 ng Hg/ml. The form of mercury was not identi-
fied so that these high values may not have been due to
the intake of methyl mercury in fish. However, the relation-
ship between inorganic and methyl mercury may be more complica-
ted 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 controls 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 aquatic organ-
C-23
-------
isms. Since bioconcentration tests have not been conducted
to steady-state for all four major groups of aquatic organisms
consumed in the United States, some BCF values have to be
estimated. A recent survey on fish and shellfish consumption
in the United States (Cordle, et al. 1978) found that the
per capita consumption is 18.7 g/day. From the data on
the 19 major species identified in the survey, the relative
consumption of the four major groups can be calculated.
Pentreath (1976a) found a BCF of about 250 for the
muscle of plaice, whereas Kopfler (1974) obtained a value
of about 10,000 for oysters. Since these values are 0.21
ancf 0.33, respectively, of the comparable values for methyl
rneEcury, it seems reasonable to assume that the BCF values
for mercuric chloride should be 0.27 times those for methyl
mercury, on the average.
!
Consumption Bioconcentration
group (Percent) factor
Freshwater fishes 12 6,000
ga.ltw.ater fishes 61 310
Saltwater molluscs 9 8,000
S.altwater decapods 18 310
Using the data for consumption the BCF for mercuric chloride
is 'estimated to be 1,700 for consumed fish and shellfish.
Tests with freshwater fish have obtained BCF values
for methyl mercury 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,
C-24
-------
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 methyl mercury, although many of the animals
died in the 60-day exposure. No data are available concerning
BCF values for decapods, but they would probably have values
similar to those of saltwater fishes.
Consumption Bioconcentration
Group (Percent) factor
Freshwater fishes 12 22,000
Saltwater fishes 61 1,150
Saltwater molluscs 9 30,000
Saltwater decapods 18 1,150
Using the data for consumption and BCF for each of these
groups, the weighted average BCF for methyl mercury is esti-
mated to be 6,200 for consumed fish and shellfish.
Inhalation
In 1934, Stock and Cucuel reported average air concentra-
tions 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
reported findings - 2 to 5 ng Hg/m . In the San Francisco
area, concentrations 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
C-25
-------
ng Hg/m near rice fields where mercury fungicides had been
used and values of up to 18,000 ng Hg/m near a busy super-
I
highway in Japan have been reported by Fujimura (1964).
Maximum air concentrations of 600 and 15,000 ng Hg/m near
mercury mines and refineries, respectively, were reported
by McCarthy, et al. (1970). The highest reported levels
5
of. mercury in the atmosphere come from a study by 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 remark-
ably high mercury vapor levels reported 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 (for review, see Natl. Acad. Sci., 1978). Obser-
vations by Johnson and Braman .(1974) at a suburban site
in Florida indicate that approximately 60 percent of the
mercury in the atmosphere is in the form of vapor, 1.9 percent
is; inorganic', and 14.9 percent occurs as methyl mercury
compounds;. Mercury present in a particulate form accounted
i
for less than one percent. The amount of mercury bound
to. particulate:s s.eems to be related to area of industrializa-
tion; and urbanization. For example, Heindryckx, et al.
(.1.974) found that aerosol mercury levels corresponding to
remote background levels in Norway and Switzerland were
ajs- low as: 0..02 ng Hg/m . In1 a heavily industrialized area
of Belgium near Liege the aerosol levels noted were as high
as; 7.9- ng Hg/m .. In New York City (Goldwater, 1964) and
Chicago. (B-rar, et al. 1969) , concentrations of particulate-
bound; mercury of up to 41 and 14. ng Hg/m , respectively,
C-26
-------
were observed. However, as pointed out by the National
Academy of Sciences (1978), considerable technical difficul-
ties 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/m . Assuming a
daily ventilation of 20 m 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
weight. In urban and industrialized areas, it seems unlikely
that the mercury concentration in the atmosphere will regular-
ly exceed 50 ng/m , corresponding 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 individuals in these areas.
Occupational exposure to mercury vapor occurs in this
country (Smith, et al. 1970). The current threshold limit
for occupational exposures is 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 concentra-
tion which does not exceed 0.05 mg Hg/m , then the maximum
t
daily retention from occupational sources should not exceed
286 ;ug/70 kg for a seven-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 occupational and medici-
nal exposure, it may be significant (see Absorption section).
C-27
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PHARMACOKINETICS
The disposition of mercury in the body was reviewed
•by a Task Group on Metal Accumulation (1973) and more recent-
i '
•ly .by :a -WHO Expert Committee (World Health Organ., 1976).
i'Since the disposition of mercury in the body is highly depen-
.•deht upon the physical and chemical .forms of .this metal,
,-iit-.will .;be necessary in this .section to consider them sepa-
i t
irately. Most information with regard to disposition in
I
:;man ,and ^animals is available for methyl mercury compounds
i + *
.and inorganic (Hg ) .complexes of mercury ingested in the
adiet -and :for ..the inhalation of •••mercury vapor.
•'In general, insufficient information is available on
-oithver compounds of mercury, except for the mercurial diuretics,
»to allow .an extensive discussion. .Because mercurial diuretics
-,;ar-e .now virtually obsolete .for therapeutic use a complete
review of this topic is not called for.
i
•Nordberg (197-6) and the Task Group on Metal Accumulation
.(.Ii973) have reviewed evidence for -suitable indicator media
;:for . me.thyl mercury. The evidence reviewed below indicates
•;t;hat :th.e blood .concentration of methyl mercury is a measure
.-.of -:'the .accumulation in the body and the concentration in
-the tar.get organ, the brain. Urinary excretion is a poor
.indicator o'f body bur,den as -most of the mercury is excreted
.-via .the .feces. The hair is probably the indicator medium
of choice ..as
-------
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 recently consumed a large amount of methyl mercury.
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 indi-
cator of exposures and body burden. However, it seems likely
that urinary concentrations may reflect kidney levels rather
vthan concentrations in the target tissue of the brain.
Since several exponential terms are required to describe
the blood curve following a brief mercury vapor, multi-compart-
ment pharmacokinetics are implied for man. Thus, an isolated
blood sample will not provide any information regarding
exposure or body burden. Serial samples, however, may indi-
cate the existence of a steady state or give limited informa-
tion about recent exposure. If individuals are in steady-
state, correlation between time-weighted average air concen-
trations and blood concentration should be expected. This
was confirmed by Smith, et al. (1970) in chronically exposed
workers. The authors observed about a 49 microgram per
100 ml increase -in the steady-state blood level for each
1 mg/m increase in the blood exposure concentration.
C-29
-------
The same considerations with regard to indicator media
apply to inorganic mercury as to inhaled mercury vapor.
It is. likely that urinary mercury 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 half-times 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 mercurial compounds through human
!
s.kin.- However, cases of severe poisoning have occurred
fol.lowing the topical application, for medicinal purposes,
o,f. methyl mercury compounds (Tsuda, et al. 1963; Ukita,
et al. 1.963; Okinata, et al. 1964; Suzuki and Yoshino, 1969).
__
Although,, in these cases, the main pathway of intake was
pr.ob.ably through skin, the possibility of some inhalation
exposure- cannot be excluded.
Likewise, no specific data are available on the inhala-
tion of alkyl mercurial compounds. The Task Group on Metal
i :
Accumulation (1973) suggested that the retention of the
inhaled mercurials would probably be on the order of 80
percent.. These conclTusions were based mainly on the diffusi-
bility and the lipid solubility of many of the compounds
of methyl mercury. Furthermore,; no quantitative information
Is: available on d.usts and aerosols of the alkyl mercurial
compounds. Many of these compounds have been used in the
past as fungicides, resulting in occupational exposures
o£ workers. Since some of these occupational exposures
C-30
-------
have led to severe poisoning and death?S^!se)eihs" likely
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 methyl mercury compounds in the gastro-
intestinal (G.I.) tract. Experiments on. volun.teers by Aberg,
et al. (1969) and Miettinen (1973). have demonstrated virtually
complete absorption in the G.I. tract whether the methyl
. mercury is administered as a simple salt in solution or
whether it is bound to protein. The findings of: the tracer
studies have been confirmed in observations on.volunteers
who ingested tuna fish for several days .(Turner, et al...
1974, 1975). Shahristani.and cowprkers. (1976)/ in studies
of the dietary intake of methyl mercury in homemade bread
contaminated, with a fungicide, obtained 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 occurred due to the consumption
.of homemade bread contaminated with ethyl mercury fungi-
cides suggests that this form of mercury is also well absorbed
from the G.I. tract. .
.Age and sex differences in G.I., absorption of methyl
mercury compounds have not been reported. However, the
fact that very high blood concentrations of methyl mercury
were attained in infants who had ingested methyl mercury
solely in their mothers' milk suggests that absorption in
the very young is also substantial (Amin-Zaki, et al. 1974b).
C-31
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Mercury Vapor and Liquid Metallic Mercury: About 80
percent of inhaled mercury vapor is retained as evidenced
by observations of humans (Teisinger and Fiserova-Bergerova,
1965; Neilsen-Kudsk/ 1965a; Hursh, 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 subsequent 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. Julius-
berg (1901) and Schamberg, et al, (1918) indicated that
appreciable skin absorption of metallic mercury takes place
in animals. However/ the possibility cannot be excluded
that some inhalation 'exposure also occurred in these experi-
_
ments.
The gastrointestinal absorption of metallic mercury
in the liquid form is believed to be very small. Bornmann,
et al. (1970) administered gram quantities 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 Tanaka, 1971). However, there
are many case reports in the literature of individuals con-
suming, accidentally or otherwise, gram quantities of liquid
metallic mercury and the metal passing through the G.I.
tract into the feces without any ill effects.
C-32
-------
Salts of Inorganic Mercury: No quantitativ'&-'i^ipirm9't'i-.0.n'
is available on the absorption of mercury in the form of
_L 1. .'.-',.,
inorganic mercuric (Hg ) salts by human skin. However,
solutions of mercuric chloride have been shown to be absorbed
by guinea pigs; five percent of the mercury in a two percent
solution of mercuric chloride was absorbed across the intact
skin of these animals over a five-hour period (Friberg,
et al. 1961; Skog and Wahlberg, 1964). If such a rate of
penetration applied to human skin, one might expect substan-
tial 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 Morrow, et al. (1964). This
group reported that 45 percent of mercury administered as
mercuric oxide aerosol having a mean diameter of 0.16 urn
was cleared within 24 hours; the remainder cleared with
a half-time of 33 days.
Rahola, et al. (1971) reported findings on the G.I.
absorption of inorganic 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 four to five 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 G.I. absorption of inorganic
-.-,-,-
mercury by humans is less than 15 percent, which correlates
with studies on experimental animals (Clarkson, 1971).
C-33
-------
Experiments on animals indicate that G.I. absorption is
greater in suckling animals than in mature ones (Kostial,
et al. .1978).
Other Compounds of Mercury: The aryl and alkoxyaryl
mercurials are used as fungicides and slimicides, and as
such occupational exposures to these compounds probably
still occur. To what extent these mercurials reach the
water supply is not known. In general/ the aryl mercurials
are well absorbed from the G.I. tract, as evidenced by animal
experiments (Clarkson, 1971). Most classes of these organo-
mercurial compounds undergo rapid conversion to inorganic
mercury in body tissues.
C-34
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Distribution and Metabolism
•r.
Methyl Mercury and Other Short-Chain Alkyl Mercurials:
Details on the distribution and retention of methyl mercury
in man and animals were reviewed by Friberg and Vostal (1972),
by the Task Group on Heavy Metal Accumulation (1973), and
by a WHO Expert Committee (1976) . The general picture which
emerges is that methyl mercury compounds, after absorption
from the G.I. tract, distribute readily to all tissues in
the body. Unlike inorganic mercury, large concentration
differences in various tissues are not seen. Methyl mercury
is characterized by its ability to cross diffusion barriers
and cell membranes without difficulty.
Tracer studies in volunteers have revealed that about
five percent of the ingested dose is deposited in the blood
compartment after tissue distribution is completed. About
90 percent of the methyl mercury in blood is associated
with the red blood cells. Thus/ the red cell to plasma
ratio is between 10:1 and 20:1. The mercury in the red
blood cells is almost entirely (more than 90 percent) in
the form of methyl mercury 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 methyl mercury after cessation
of exposure can be well described by a single biological
half-time as evidenced by both tracer experiments in volunteers
and also in people who had ingested methyl mercury in substan-
tial amounts from.either fish or contaminated food (see
Table 6). The tracer experiments reveal a half-time of
C-35
-------
approximately 50 days. However, the range of half-times
reported in both tracer experiments and in people having
substantial exposures covers a very wide range. Whether
this range of values is due to individual differences or
to experimental or observational inaccuracies in the measure-
>„
ments 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 (Norseth and Clarkson, 1971).
According to observations on volunteers, the amount trans-
ferred to the head region following the ingestion of a single
dose of radioactive tracer is about 10 percent of the body
burden after tissue distribution is complete. However,
only three subjects were involved in this study (Aberg,
i-
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 5:1 or 10:1. The biological half-
time of methyl mercury in the brain is not well described
in man but the observations by Aberg, et al. (1969) of three
volunteers indicate a half-time in roughly the same range
as that observed in blood and in the whole body (see Table
6). Whether or not the half-times 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 methyl mercury 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 concentra-
tions being found in the kidney cortex. In muscle, the
C-36
-------
TABLE 6
Mercury Intake and Clearance
Clearance half-times (days)
o
i
co
«J
NO. Of
subjects
5
15
5
5
16
48
Hg intake
C/ug/kg/day)
tracer :
tracer
up to 5
up to 5
up to 50
up to 50
Body
70
76
(52-93)
—
— . .
• - . —
—
Blood
_._
50
— .
seea
(58-164)
65
(45-105)
—
Hair References
s -'•
— Aberg, et al. (1969)
• — Miettinen (1973)
••' ' ' • .
(33-120) Birke, et al. (1967)
Skerfving (1974)
' - '-"' • • ' '•.... ::
— . Bakir, et al. (1973)
K
72° Shahristahi & Shihab (1974)
(35-189)
One person had a biological half-time of 164 days. The other four were in the range of
58-87 days.
The data were distributed bimodally. One group accounting for 89% of the samples had
a mean value of 65 days and the other group had a mean value of 119 days.
-------
mercury is usually almost entirely in the form of methyl
mercury 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 Iraq
indicate a substantial proportion present as inorganic mercury
in liver (Magos, et al. 1976).
Methyl mercury 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 observations on
women having normal pregnancies and on a low to moderate
fish intake, Tejning (1970) reported that methyl mercury
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 methyl mercury poisoning in Iraq (Bakir,
et al. 1973; Amin-Zaki, et al. 1974a, 1976) also showed
that methyl mercury was readily transferred across the placen-
ta, 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 concentra-
tion in the red blood cells rather than to differences in
plasma concentrations.
Methyl mercury is secreted in mother's milk. The studies
of the Iraqi outbreak revealed the close correlation between
maternal milk and blood concentrations, with the milk concen-
tration on the average being about 5 percent of the simul-
038
-------
taneous blood concentration (Bakir, et al. 1973). About
40 percent of the mercury in milk was found to be in the
inorganic form. Skerfving (1974), in a study of 15 lactating
females following intake of methyl mercury from fish, also
noted a correlation with blood concentrations but found
a smaller percentage (approximately 20 percent) of mercury
in the form of methyl mercury in the milk.
Mercury is accumulated in head hair after exposure
to methyl mercury compounds. , A variety of observations
(see Table 7) indicate that the hair to blood concentration
ratio is about 250:1 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 concentration
of mercury is stable and thus, as the hair is examined longitu-
dinally, 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 ex-
posures as well as to "give information on current exposure
to methyl mercury. An example of the close parallel between
concentration in hair and blood is shown in Figure 2 (Amin-
Zaki, et al. 1976).
Methyl mercury is metabolized to inorganic mercury
in animal tissues (Gage, 1961; Nors.eth and Clarkson, 1970).
C-39
-------
BOTH
MOTHtt'MC-OO
o MQTHfIfS 81000
4 MOTHERS HAIR
* MOTHEfS MUK
• BAST'S 81000
'3009
2000
1000
200
200
100 "*
50 |
• 20 5
. „ I
• 3 i
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). Concentrations in milk and blood
are plotted according to dates of collection. This figure
is taken from Figure 4 of the report of Amin-Zaki, et al. 1976
TABLE 7
Relationship between Concentrations of Mercury in Samples of Blood and Hai;
in People having Long-term Exposure to Methyl Mercury from Fish
No. Of
subjects
12
51
50
45
60
0
0
0
0
0
Whole blood
(x)
.004
.004
.005
.002
.044
(mg/kg)
- 0.
- 0.
- 0.
- 0.
- 5.
65
11
27
80
5
Hair
(y)
(mg/kg)
1 -
1 -
1 -
20 -
1 -
180
30
56
325.
142
Linear regression
y =
y =
y =
y =
y =
280x-l.
230x+0.
140X+1.
260x+0
230x-3.
3
6
5
6
This Table is adapted from Table 1 in the report
of the WHO, 1976.
C-40
-------
In man, conversion to inorganic mercury is an important
process in excretion, as shall be discussed later:
Mercury Vapor and Liquid 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 (Hursh, et al. 1976).
The concentration in the red blood cells of these volunteers
was higher than that seen in plasma. The half-time 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 additional information concerning half-times
(Figure 3). The major portion of the exposure probably
occurred within a half-hour peri'od with a smaller protracted
exposure over the duration of an evening. It appears that
there was an early rapid decline over the first few days
post exposure, and by about days five to seven, the mercury
in blood was decreasing with an approximate 15-day half-
time which was maintained for the remainder of the first
month's post exposure. Another family's exposure to mercury
vapor involved a husband and daughter who were exposed for
six to eight months in the home. The wife had experienced
a prior exposure for about 18 months in her workplace.
Samples of blood were collected starting about one month
after cessation of exposure. Therefore, an early and rapid
fall in blood conentration due to short half-time components
was missed. The blood concentration of mercury in the wife
declined, with a half-time of 30 days. The other two family
C-41
-------
160-1
120-
80-
n
a
o
o
40-
0-r
200-
ee
ui
z
** 30
C 3°
ce
O
Z
- 20H
25 30
Oct.
9 14 19
November
24
Figure 3. The fall in mercury concentrations in blood in two
adult females following a brief exposure (less than 3 hr) to
mercury vapor. Upper graph has a linear scale on the ordi-
nate. The lower graph has a logarithmic scale and curve
stripping procedures were used to estimate a component with
the different half-time (slow component, 14.9 days; fast com-
ponent, 2.4 days). Data from Clarkson, 1978. (unpublished data)
C-4.2
-------
members had longer half-times but their blood levels were
sufficiently low that dietary 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 important
site of this oxidation process, which is believed to be
mediated by the hydrogen peroxide catalase pathway (for
review, see World Health Organ. 1976; Clarkson, et al. 1978).
However, the oxidation in the red blood cells is not suffic-
iently rapid to prevent 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 rapidly cross into brain tissues where it is again subject-
ed to oxidation processes. A scheme for the pathway of
inhaled mercury vapor reaching the brain is given in Figure
4. Hursh, et al. (1976) made regional body counts on volunte-
ers who had inhaled a tracer dose of radioactive mercury
vapor. They found that approximately seven percent of the
inhaled dose was absorbed into the head region following
completion of tissue distribution. The half-time in the
head region was found to be 21 days (Table 8). This half-
time 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
C-43
-------
Figure 4. A diagrammatic representation of the pathway of in-
halgd mercury vajj>or (Hg ) to the brain. The oxidation process
(Hg — ^ Hg ) is depicted as occurring in the red blood
cells and brain tissue.++0xidation also occurs in other areas.
The ligands to which Hg attaches have not been identified
(depicted as S and X) but sulfhydryl groups are suspected to
be involved. Taken from Clarkson (1974).
.;-44
-------
TABLE 8
Summary of Half-Times'o£ Mercury in Human Tissues
Tissue
Exposure
Conc~
Duration
First Component
% deposited
mg/m
0
i
*>•
tn
Blood3
Bloodb
Bloodb
Lung°
Kidney0
Head0
Whole Body0
0.
0.
0.
0.
o.
0.
0.
1
1
05
1
1
1
1
20
min
few hours
60
90
T 1/2
Second Component
% deposited
days
4
2
.0
.0
months ? ?
20
20
20
20
min
min
min
min
100
100
100
100
1
64
21
58
.7
.0
.0
.0
not
10
100
not
not
not
not
detected
detected
detected
detected
detected
T 1/2
days
20
|0
|* Cherian et al., 1978
D Hursh, et al. (1976).
Observations made at Rochester but not published. For details, see text,
-------
the total body burden can be found in kidney tissues (Rothstein
and Hayes, 1964).
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. Observations on 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 half-times of
mercury in the body following exposures to mercury vapor
is given in Table 8. Most of the information in this table
comes from tracer" experiments of Hursh, et al. (1976) and
from unpublished observations of people who were accidentally
exposed for brief periods of time. The whole body half-
time and the half-time in kidney seem to be approximately
the same as that of methyl mercury in man.
Salts of Inorganic Mercury: Studies using a variety
of animal species have shown that, in general, the distribu-
tion of mercury after doses of mercuric salts or inorganic
mercury bound to protein is similar to the distribution
observed after exposure to mercury vapor (for review, see
Clarkson, 1972a,b; Friberg and Vostal, 1972). However,
there are important differences. The red cell to plasma
ration has been reported to be 0.4 in humans exposed to
a tracer dose of Hg"1"1" (Rahola, et al. 1971) whereas the
amount in the red cells is considerably higher after exposure
C-46 :''. '
-------
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 mercuric ion penetrate the brain or the fetus follow-
ing 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 i.s more permeable
to inorganic mercury than' that of adults.
Inorganic Mercury Accumulates 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 metallothionein
or metallothionein-like proteins in kidney tissue (Piotrowski,
et al. 1974a, 1974b) . This ability is shared with inhaled »
mercury vapor (Cherian 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 half-time
averaged 45 days and was significantly greater than the
biological half-time 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 one day after dosing.
Other Compounds of Mercury: The conversion of organo-
mercurial compounds to inorganic mercury results in a pattern
of distribution that eventually is similar to that obtained
C-47
-------
after exposure to inorganic salts. The kidney is the main
organ of accumulation in all cases.
Excretion
Methyl Mercury and Other Short-Chain Alkyl Mercurials:
The excretion of mercury from the body in humans exposed
to methyl mercury occurs predominately by the fecal route.
Less than ten percent of excretion occurs in the urine.
The form of mercury in feces is almost completely the inorgan-
ic 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 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 of methyl mercury raising
the possibility that biotransformation to the inorganic
form might be affected by micro flora in the gut (Norseth
and Clarkson, 1971).
Mercury Vapor and Liquid Metallic Mercury: Urine and
feces are the main pathways of excretion after exposure
to mercury vapor, although exhalation 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 G.I. 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
i
C-48
-------
total urine and fecal excretion, but after a long term occupa-
tional exposure, urine contributeded 58 percent (Table 9).
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 seven percent of an inhaled dose of mercury
vapor was shown to be excreted in the expired air of humans.
The great majority of this came out within seven days and
comprised 37 percent of the first week's excretion (Table 9).
.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 fluctu-
ation were the principal features of urinary mercury excretion
by workers under similar exposure conditions (Jacobs, et
al. 1964). Copplestone and McArthur (1967) found no cor-
relation between urinary excretion and air concentrations.
They noted that some individuals excreted extremely large
amounts of mercury, some in excess of 1,000 /ig/1 without
apparent ill effects. Their own findings and their review
of the literature (Jacobs, et al. 1964; Neal, et al. 1941)
led Copplestone and McArthur (1967) to propose that "mercu-
C-49
-------
TABLE 9
Parameters of Excretion of Mercury in Man
Following Exposure to Mercury Vapor.
Excretion
Medium
Urine
Urine
Feces
Feces
Expired air
Exposure
Cone. 3 Duration
(rag Hg/m )
0.1 20 minutes
0.05 - 0.2 (years)
0.1 20 minutes
0.05 - 0.2 (years)
0.1 20 minutes
Percent of
Total Observed
Excretion
13a
58b
49a
42b
37a
a
et al. 1976; Cherian, et al. 1978).
Combined urine and 'feces (Tejning and Ohman, 1966).
C-50
-------
rialism might be due to an inability to excrete absorbed
mercury rather than simply to exposure."
Piotrowski, et ail. (1973) observed workers following
exposure to mercury vapor, arid reported that urinary excretion
could be described'by a two-term exponential equation equi-
valent to-half-times at 2 and 70 days. The authors claimed
that individual variations in urinary excretion are minimized
when urine samples are collected at the same time each morning.
Lundgren, et al. (1976), Smith, et al. (1970), and
Hernberg -and Hassanan (1971) have reported generally similar
relationships between steady-state urinary excretion and
blood levels. Averaging their results, one would expect
a 0.06; mg/r "increase in 'the urinary excretion rate for
each .10"0 ug/100 ml change in the blood mercury level. These
results can be combined with the data on blood levels versus
exposure concentration 'reported by Smith, et al. (1970)
to predict a '2.9 mg/1 change in the urinary excretion for
each 1 mg/m change in the time-weighted air concentration.
Tejriing and Ohman (1966) cited steady-state urine and
fecal excretion rates which can be interpreted to mean that
urinary excretion will account for approximately 57 percent
of combined urinary and fecal excretion when the exposure
concentration, is between 0.05 and 0.2 mg/m . When these
excretion rates arer compa'red to those predicted above a
discrepancy of a :factor of two to three is found1; with the
predicted rates being greate'r than those observed by Tejriing
and Ohman (1966).
C-51
-------
Several factors might contribute to the daily vari-
ability of urinary mercury concentrations. Daily changes
in urinary specific gravity, problems with analytical metho-
dology, volatilization of mercury from urine (Magos, et
al. 1964) , absorption of mercury to glassware, the diffusion
of mercury out of plastic bottles, and the entrainment of
mercury into the particulate fraction of urine, all make
the analysis of urinary mercury extremely difficult (Greenwood
and Clarkson, 1970).
In conclusion, although correlation of urine mercury
concentrations with blood or time-weighted air concentration
may yield consistent results when the data are averaged
over large groups of people, no explanation is at hand for
the large fluctuations in daily excretion by individuals.
However, few longitudinal studies have been made, and all
measurements to date on exposed workers with one exception
have measured concentrations of total mercury. Recently,
Henderson and co-workers (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 (Hursh, et al. 1976). The short half-
time reported by these workers following brief exposure
to the vapor suggests that mercury in expired air would
indicate only recent exposure. However, experiments on
animals given mercuric salts (Clarkson and Rothstein, 1964;
Dunn, et al. 1978) reported a close correlation between
C-52
-------
the rate of exhalation and the body burden of divalent mercury
*) . 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 volunteers who ingested tracer doses of inorganic
mercury revealed that urine and fecal excretion were approx-
imately equal .after the unabsorbed oral dose was cleared
by the G.I. tract. The whole body half-time of 45 days
observed in these volunteers is consistent with excretion
in urine and feces, amounting to a total of 1.5 percent
of the dose per. day.
It is possible that urinary excretion could be increased
by kidney damage. For example, Cember (1962) reported that
cytotoxic doses of inorganic mercury could lead to desquamation
of renal tubular cells, resulting in a sharp increase in
mercury excretion. Magos (1973) has reviewed other studies
where agents producing kidney damage leading to desquamation
of cells cause an increase in urinary mercury excretion.
Other Compounds of Mercury: Retention .half-times of
the aryl and alkoxy-aryl mercurials in man are generally
not known. Their rapid conversion to inorganic mercury
would suggest that their half-times would not exceed those
reported in volunteers discussed above. The mercurial diuretics
generally have half-times considerably shorter than that
C-53
-------
reported for inorganic mercury because of the rapid
excretion of the intact mercurial.
Mathematical Models of Accumulation of Methyl Mercury
in Man: The body will continue to accumulate methyl mercury
so long as intake is greater than excretion until a steady-
state is obtained where intake and excretion balance. A
common way to describe the progress of accumulation in the
body is in terms of the biological half-time. This concept
is useful, provided that the processes of transport and
distribution in the body occur more rapidly than the elimina-
tion step. Thus, the single biological half-time 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 Committee (1976), if tissue compartments
retain mercjary with widely differing retention half-times,
then the whole body biological half-time would not be useful
and could give misleading information toxicologically.
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 described by a single biological
half-time.
The WHO Expert Committee has summarized the mathema-
tical expressions relating daily intake to biological half-
time and accumulation in man. These derivations are quoted
below.
In cases where the elimination of a metal such as methyl
mercury follows a single exponential first order function,
the concentration in an organ at any time can be expressed
by the following equation:
' C-54 ' •''.-'• -.
-------
c =C e~b-fc „.,,,:,,,•..,,,.,,...
c *-o*e ........... * * * •••••'--'"• •
. . .(1)
where C =concentration in the organ at time t
C concentration in the organ at time p
b =elimination constant, and
t =time.
The relation between the elimination constant and the biolo-
gical half-time is the following:
T =ln2/b
where: T =biological half-time, and
In2 (natural lo garithm 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
calculated. The following expression gives the accumulated
amount' of metal in the total body (or organ):
A =(a/b) (l-exp(-b.t) ) . . . . . . . . . . . . .
. . . . (2)
where A =accumulated amount, and
A =amount taken up by the body (or organ) daily.
At steady-state the following applies:
A =a/b ............... ......
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 elimi-
nation rates imply large individual variations in steady-
C-55
-------
1000
Exposure pwidd
Body burdtn & blood
KUir
7.0
0
E
•1JJ -
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 /ag of methyl mercury during
the exposure period, an elimination half-time of 69 days,
and a hair to blood concentration ratio of 250. This
figure is taken from Figure 1 of WHO (1976).
056
-------
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 jug/70 kg body weight) , the amount in the body rises
rapidly at first, reaching half its maximum (steady-state)
value in a time equivalent to one elimination half-time
(assumed to be 69 days for methyl mercury in man). After
an exposure period .equivalent to five elimination half-times
(approximately one year for methyl mercury), the body is
within three percent of its final steady state value. The
steady-state body burden is 100 times the average daily
intake assuming an elimination half-time of 69 days. Upon
cessation of exposure, the body burden will immediately
begin to fall, following an exponential^curve that is an
inverse .mage of the accumulation curve. Thus the body
burden will have returned to within three percent of pre-
exposure values in five half-times.
In this example, it is assumed that the hair-to-blood
ratio is constant and equal to 250 and that one percent
of the body burden is found in 1 liter of blood in a 70 kg
man.
Equation 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 of equation
3 by carrying out dietary studies on exposed populations
and measuring concentrations of methyl mercury in blood
C-57
-------
and hair. A prediction of equation 3 is that once the indi-
vidual 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 (1974)
in a group of fish eaters in Sweden. Results of Skerfving's
study, along with studies on other fish eating populations,
are summarized in Table 10. In some cases, observations
were made on concentrations in hair, and in others, measure-
ments of blood concentrations were made. All have been
converted 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 10. The calculation involves the
assumption that 95 percent of the methyl mercury was absorbed
from the diet, that one percent was distributed in 1 liter
of blood, and that the biological half-time in blood was
approximately 50 days. In general, the factor relating
the steady-state blood concentration to the average daily
intake (the coefficient of x; Table 10) varies from a value
of 0.3 to 1.0. 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, equation 3 seems to
be useful in that it allows comparison of the results of
various types of studies, including both exposed populations
and volunteers. A recent study of five volunteers ingesting
C-58
-------
TABLE 10
No. of
subjects
h
6+26°
139+26°
6+14^
725C
22
15
Time of
exposure
years
years
years
years
years
single tracer
dose
Ave. Hg. intake
Oug/day/70 kg B.W.)
(x)
0-800
0-400
0-800
0-800
0-800
Steady blood
concentration
(ng/ml)
(y)
y=0.7x+l
y=0.3x+5
y=0.8x+l
y=0.5x+4
y=0.5x+10
y=1.0x
For details of these calculations, see text.
is adapted from Table 3 of WHO (1976).
This table
None or low fish consumers.
Estimated 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-59
-------
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 methyl mercury, as will be discussed later.
Thus far, the discussions have employed average values
for various parameters used in mathamatical modeling of
accumulation of methyl mercury in man. In fact, there are
substantial differences. The biological half-time in man,
as indicated in Table 6, actually varies over a wide range
of values. Shahristani and Shihab (1974) have published
the observation that there is a bimodal distribution of
biological half-times as calculated from analysis of hair
samples in the Iraqi outbreak. As shown in Figure 6, these
authors found that the majority of a population of 48 people
studied had half-times distributed around the normal value
of about 65 days, but about nine percent of the population
had a significantly different distribution of half-times,
averaging about 119 days. Greenwood, et al. (1978) have
noted that the half-time in blood of lactating females (average
42 days) is significantly lower than that of non-lactating
adult females (average 74 days). The excretion of methyl
mercury in milk is not sufficient to explain the reduced
biological half-time in blood of lactating females.
Experiments on mice by Doherty, et al. (1977) have
revealed that methyl mercury is not eliminated from mice
throughout their suckling period. Observations by Landry,
C-60
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20
40 60 80 100
Biological Half-Life. Days
120
Figure 6. Population distribution curve of methyl mercury
(Shahristani & Shihab, 1974). For details, see text.
C-61
-------
et al. (1978) revealed that changes in the diet of mice
can also lead to large changes in the biological half-time
of methyl mercury.
There are important species differences in the kinetics
and distribution of methyl mercury. For example, the blood
to plasma ratio, which is about ten to one 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 one to five,
most laboratory animals having ratios of one to one, and
the rat having a ratio of ten to one. The biological half-
times may be as short as seven days in the mouse or as high
as 700 days or more in certain marine species (for review,
see Clarkson, 1972a).
EFFECTS
Greatest emphasis will be placed on those effects occur-
ring at the lowest levels of exposure to mercury and to
the target systems that suffer effects 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 dis-
tinct. 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 frequently exposed.
062
-------
Acute, Sub-acute, and Chronic Toxicity
Methyl Mercury and Other Short-Chain Alkyl Mercurials:
The toxic effects of methyl mercury have been described
in several recent reviews (Swedish Expert Group, 1971; Study
Group on Mercury Hazards, 1971; World Health Organ. 1972,
1976; Miller and Clarkson, 1973; Friberg and Vostal, 1972;
Nordberg, 1976; Natl. Acad. Sci., 1978). A major conclusion
of these reviews is that prenatal methyl mercury poisoning
differs qualitatively and probably quantitatively from postna-
tal poisoning. These two situations will be treated separate-
ly in this section.
Effects on Adults: Prior to the major outbreaks in
Japan in the 1950's and 1960's, cases of poisoning due to
occupational and accidental methyl mercury exposure had
already indicated the principal signs and symptoms of severe
poisoning. The first recorded poisoning took place in 1863
(Edwards, 1865). In that year, three young laboratory workers
developed neurological symptoms three months after they
were first exposed; two of them died. Four cases of methyl
mercury poisoning were described by Hunter, et al. (1940).
The patients had worked in a factory that manufactured methyl
mercury compounds for use as a seed grain fungicide. They
were asymptomatic during the initial three to four months
of exposure and then contracted symptoms that were confined
to the nervous system. The presenting symptoms were par-
esthesia of the extremities, impaired peripheral field of
vision, slurred speech, and unsteadiness of gait and of
limbs. Examination showed that all four had ataxia, con-
striction of visual fields, and impaired stereognosis, two-
C-63
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point discrimination and joint position sensation in the
fingers. Three had dysarthria. 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 co-workers 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 parti-
cularly 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 factory in Minamata, Japan exhibiting a neuro-
logical disorder of unknown etiology. Within a few weeks
about 30 individuals with similar complaints were identi-
fied 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 methyl
mercury poisoning (Katsuna, 1968), which resulted from the
consumption of fish from Minamata Bay that were contaminated
by methyl mercury. The latter was discharged into the bay
via the local factory effluent, but may also have been pro-
duced by biomethylation of Hg released from the factory.
Hair and brain of victims contained elevated concentrations
of methyl mercury. Similar cases appeared in.Niigata, Japan
in 1965 (Tsubaki and Irukayama, 1977). The total number
of Japanese cases was recently reported to be at least 1,224
(Tsubaki and Irukayama, 1977). A poison that had previously
C-64
-------
been recognized as an occupational hazard had become identi-
fied as an environmental risk to public health.
In the late 1960's a Swedish Expert Group (1971) con-
ducted an exhaustive review of toxicological and epidemio-
logical data related to methyl mercury 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 microorganisms present in sediments
in both fresh and oceanic water, and that fish readily accumu-
lated and concentrated methyl mercury 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 methyl mercury in fish.
Their st ^tegy was to obtain information on two relationships:
(1) the relationship between blood concentrations and risk
of poisoning (frequency of signs and symptoms) from methyl
mercury and (2) the relationship between long-term dietary
intake and steady-state blood concentrations. 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 infor-
mation was used by the Swedish government to set regulations
on maximal permissible concentration of methyl mercury 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
C-65
-------
from only 17 patients (Figure 7); these data were insufficient
to establish a statistical relationship between blood con-
centration and frequency of cases of poisoning (blood con-
centration-response) . Consequently, they attempted to iden-
tify the lowest blood concentration associated with the
onset of signs and symptoms of poisoning. In patients from
whom several blood samples had been collected, the methyl
mercury concentration fell exponentially with time, corre-
sponding to a half-time roughly in the range of 70 days.
Where sufficient data points were available, the blood concen-
tration 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 methyl mercury
(Aberg/ et al. 1969). Gastrointestinal absorption was
virtually complete (about 95 percent of the dose) and the
C-66
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100
1
3 50
^
1 20
ffl
o
\
100 200 300
Days after appearance of symptoms
400
Figure 7. Concentration of mercury in samples of blood
collected from patients suffering from methyl mercury poison-
ing in the Niigata outbreak. Samples from the same patients
are connected by a straight line. The arrow indicates the
estimated time of onset of symptoms. The units of mercury
concentration in blood are /ag Hg/100 ml. The numbers on
the ordinate should be multiplied by ten to convert to ng
Hg/ml. Data is taken from Swedish Expert Group (1971).
C-67
-------
whole body half-time was about 70 days, roughly in agreement
with the half-times observed in blood in the Japanese patients.
Mathematical models of accumulation of methyl mercury
in man have been discussed previously. The accumulated
amount in the body, A, would be related to the average daily
amount taken up by the body, a, by the expression:
. A= (a/b) (1 - exp(-b.t) (1) ,
where t is the time of exposure and b is the elimination
constant, which is related to the whole body half-time T,
by the expression:
T = In 2/b (2) .
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 equivalent
to five half-times. A 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 one year, and two) the accumulated amount
in the body A should be linearly related to the average
daily intake (equation 3). If the blood compartment equili-
brates 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 families whose.regular diet contained fish. Blood
concentrations were compared to the average estimated dietary
intake of methyl mercury. The latter was estimated from
C-68
-------
measurements of mercury in the fish muscle and the results
of careful questioning about dietary intake of fish. The
results of two studies are given in Figure 8. Both studies
appear to confirm a linear relationship but the slopes of
the lines differ greatly. Despite the fact that the regres-
sion 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 inaccurate dietary information. They conclud-
ed that an average daily intake of 300 ug Hg as methyl mercury
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.
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 uncertainties
in the data: 1) No information was available on the accuracy
of the analytical methods used to detect mercury during
the Niigata outbreak. The dithizone procedure used for
the blood and hair analyses has a low sensitivity and high
background. 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 believed to be the true ratio
(see World Health Organ, 1976). 2) The patients were admitted
to the hospital after the appearance of signs and symptoms.
C-69
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Hg IN BLOOD CELLS
09/9
1200
1000
800
600
400-
200
0.5 0.8
M«Hg-|NTAKE THROUGH FISH
mg HO/DAY
EXTREME
FISH CONSUMERS BIRKE ET AC 1987 n. (I
ONON F.SH CONSUMERS TEJN.NC 1*89 A«0 ,970 n. J.
ABNORMAL SUBJECTS* - 1B87 /a
A FISHERMEN - ,,59 H*"
O FISHERMEN OF LAKE • ' 1M7 „"«,
^w * . n • 9 A
—— y « 1*00 x . 3
••.
y . »oox. 11
Figure 8. Relation between total mercury concentrations
in blood cells and exposure to methyl mercury through fish.
The figures in the ordinate should be divided by two to
convert the concentration units to ng Hg/ml whole blood.
The regression equations of Birke, et al. and of Tejning
quoted above are the same as those quoted in Table 1.2 except
the units of Y and X have been changed. Taken from Figure
11.2 in Swedish Expert Group (1971).
C-70
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It was necessary to extrapolate the observed blood concentra-
tions (based on samples collected in the hospital) back
to the time of onset of symptoms. The statistical uncertainty
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; World Health Organ. 1976), several studies had been
published on fish-eating populations and preliminary reports
had appeared on the large outbreak of poisoning in Iraq.
Miettinen (1973) had completed his study on 14 volunteers
taking radioactive methyl mercury. His data, along with
observations of exposed populations in Iraq and elsewhere,
allowed development of a compartmental model for uptake,
distribution, and excretion of methyl mercury in man. 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.
A World Health Organization Committee examined the
Iraqi data on adults (World Health Organ. 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 methyl
mercury fungicide. There were 459 deaths among 6,540 hospi-
talized cases; many others were not admitted to the hospitals
(Bakir, et al. 1973). Cases of severe poisoning and fatal-
ities that occurred outside of hospitals may have been consider-
C-71
-------
ably greater. The Iraqi data derive from three studies:
1) a preliminary report based on 120 patients (Bakir, et
al. 1973); 2) an epidemiological survey by a WHO team involv-
ing 956 persons in a heavily affected rural village and
1,014 persons in a control village (Mufti, et al. 1976);
and 3) an Iraqi 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) compared the frequency of paresthesia with mercury
concentrations in blood (Figure 9). Frequencies of paresthesia
(five to ten percent) observed at low Hg concentrations
were interpreted to be background values for the population
and unrelated to methyl mercury. The point of intersection
of the two lines representing parasthesia frequencies and
Hg concentrations was taken to indicate the blood Hg con-
centration at which paresthesias due to methyl mercury 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 methyl mercury
and, in view of the reported blood Hg half-times 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 methyl mercury poisoning occurring below a hair concentra-
tion of 120 ug Hg/gm hair, equivalent to about 480 ng Hg/ml
whole blood. The World Health Organization study (Mufti,
et al. 1976) measured total dose according to the amount
C-72
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1001
80-
3 60-
.5
*3»
u
o>
IB
20-
10 30 TOO
Mercury in blood (pg/IOOml)
300
Adapted from Figure 3 of Clarkson, et al. (1976).
C-73
-------
of contaminated bread consumed. The relationship between
frequency of paresthesia and total dose of methyl mercury
had the same general relationship as that shown in Figure
9. The background parasthesia frequency was estimated to
be about four percent (World Health Organ. 1976), and the
total dose at which paresthesias due to methyl mercury emerged
above the background frequency 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 standard man.
The equivalent blood concentration would be approximately
500 ng Hg/ml whole blood.
The Iraqi studies failed to identify a diagnosed case
of methyl mercury poisoning at 200 ng Hg/ml whole blood.
If such cases existed, they could not be differentiated
from individuals having non-specific signs and symptoms.
The Iraqi studies clearly show a need for more specific
tests for effects of methyl mercury 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.
(1978) agreed with those from other fish-eating populations.
No adverse health effects in adults could be associated
with exposure to methyl mercury 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 distribution in 48 Iraqis. One
C-74
-------
group, accounting for 89 percent of the samples, had a mean
half-time value of 65 days, while the other group had a
mean value of 119 days.
The significance of individual variation in half-times
is demonstrated by the report of Nordberg and Strangert
(1976). The steady-state blood concentration for any given
dietary intake of methyl mercury is directly related to
the biological half-time (see equations 2 and 3). These
authors realized that the bimodal distribution of half-times
reported by Shahristani and Shihab (1974) predicted that
a subgroup of the population (the group with the 119-day
average half-time) would attain steady-state blood concentra-
tions almost double those of the group having the 65 day
half-time. Nordberg and Strangert (1976) went on to calculate
the overall risk of poisoning from dietary methyl mercury
by combining the relationships of the blood concentration
versus frequency of paresthesia (reported by Bakir, et al.
1973) with the bimodal distribution of half-times. A result
of their calculation is given in Figure 10, which shows
that, for example, a daily intake of 280 pg Hg/70 kg man
(close to the minimum toxic intake calculated by the Swedish
Expert Group, 1971) would yield a risk of paresthesia of
about eight percent based on the Bakir, et al. (1973) data
and of three to four percent based on data from the WHO
study in Iraq (Mufti, et al. 1976).
Several important conclusions may be drawn from these
studies of adult poisonings: (1) More data are needed on
the prevalence of effects at the lower regions of the dose-
response relationships. (2) More individuals should be identi-
C-75
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A Probability of
poisoning, P
0.5 1.0 1.5 2.0 2.5 mg daily dose
'JO' .01~-02'.T>3- .'OS' ;OX .I'D
DOSE (mg/day)
Figure 10. Dose-response curve for long-term exposure to
methyl mercuric compounds in human beings (50 kg body wt).
A, whole dose-response curve; B, detailed presentation of
the curve representing lower doses. a, daily dose of Hg
in the form of MeHg ; P(a), probability of poisoning calculated
for the total population; P.,(a), probability of poisoning
for the part of the population with biological half-time
of 64 days. Probability P = 1.0 corresponds to 100%. (From
Nordberg and Strangert, 1976).
C-76
-------
fied in fish-eating populations having blood concentrations
in excess of 200 ng Kg/ml. Even negative results would
be most helpful in setting the upper limits of risk, assuming
that selection processes can be eliminated. (3) Objective
methods are needed to detect the first effects of methyl
mercury exposure. Paresthesia and other subjective com-
plaints are the first effects associated with methyl mercury
poisoning, but are not good for detecting these first effects
because of the high background, i.e., high frequency in
non-exposed individuals. At present, no biochemical, neuro-
physiological, or other objective test serves as an early
warning sign (Nordberg, 1976). (4) The bimodal distribu-
tion of half-times reported by Shahristani and Shihab (1974)
needs confirmation and further refining 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 half-time 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 methyl mercury. This report
was based on 37 people exposed to methyl mercury 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 non-exposed group showed concentrations
C-77
-------
in the range of 3 to 18 ng Hg/ml. However, a study made
a few months after the outbreak in Iraq could find no corre-
lation between chromosomal damage and exposure to methyl
mercury (Firman, 1974).
Bakir, et al. (1973) found few clinical effects associated
with damage to non-nervous tissue in the victims of methyl
mercury poisoning. An earlier outbreak of ethyl mercury
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. Jalili and Abbasi (1961)
and Damluji, et al. (1976) have reported exfoliative dermatitis
resulting f ronv oral ingestion of methyl and ethyl mercury
compounds.
Effects of Prenatal Exposure: The earliest mention
in the literature of psychomotor retardation caused by fetal
exposure to methyl mercury was by Engleson and Herner (1952) .
A Swedish family had eaten porridge made from methlymercury
treated grain. The asymptomatic mother gave birth to a
daughter who appeared to be normal at birth and in the first
two months of life. It later became clear that the child
was mentally and physically retarded. Upon further examina-
tion a year or two later, she continued to have marked psycho-
motor retardation and the authors (Engelson and Herner,
1952) postulated 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
posioning. Urinary mercury concentrations were elevated
C-78
-------
in the mother; no blood or hair analyses were performed.
Harada (1968) reported on 22 children from Minamata,
Japan who had severe psychomotor retardation which he conclud-
ed was due to fetal methyl mercury poisoning. All children
came from families in which at least one other member had
been diagnosed as having methyl mercury poisoning, with .
fatal results in 13 families. Five of the mothers had experi-
enced transient paresthesia during pregnancy but had been
well otherwise. The childrens' ages ranged from one to
six years at the time of initial examination and at those
ages it was not possible to determine their degree of exposure
to methyl mercury in utero. Two of these children died
and neuropathological studies were reported by Takeuchi
(1968). He concluded that there was evidence 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 methyl mercury iri utero.
In August 1969 a family in New Mexico began to eat
pork from a hog that had been fed methyl mercury-treated
seed grain (Snyder, 1971; Pierce, et al. 1972). At that
time the mother was three months pregnant and ate the con-
taminated pork regularly for the following three months.
She remained asymtomatic but delivered a severely brain-
damaged infant who, at eight months of age, was blind and
hypo-tonic. Some other members of the family suffered severe
methyl mercury poisoning. This was the first report of
methyl mercury toxicity from eating contaminated meat and
the only published fetal case in the United States (Snyder,
1971).
C-79
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The Iraqi outbreak offered an excellent opportunity
to develop quantitative information with regard to prenatal
exposures to methyl mercury. Large numbers of the popula-
tions, of both sexes, were exposed to a wide range of dietary
intake of methyl mercury within a period of a few months.
Thus, pregnant females could have been exposed to a pulsed
dose of methyl mercury 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 prena-
tally exposed to and severely poisoned by methyl mercury
(Amin-Zaki, et al. 1974a). Choi, et al. (1977) reported
abnormal neuronal migration in a human infant prenatally
poisoned with methyl mercury in Iraq. A group of infants
i
was also identified that had been exposed to methyl mercury
primarily by sucking (Amin-Zaki, et al. 1974b).
Follow-up neurological and pediatric studies by a Univer-
sity of Rochester team obtained dose-effect relationships
between prenatal exposure and effects on the infants (Marsh,
et al. 1978). Ten infants of mothers who had maximum hair
concentrations in the range of 99 to 384 ppm (ug/g) differed
from two groups having lower maternal hair concentrations
(12 to 85 ppm and 2 to 11 ppm, Table 11) in the mean age
of walking and talking and in mean heights. The high mercury
group also differed from the other two groups in the number
of infants having multiple signs and of poisoning symptoms
(Figure 11). For example, all the infants in the high exposure
i
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 effects.
C-80
-------
TABLE 11
Maternal Hair Hg and Symptoms in Children and Mothers
Exposure Groups3
Maternal hair peak Hg
ug Hg/g
29 Children
Walking, mean age (months)
Talking, mean age (months)
height at 54-60 months (cm)
29 Mothers
Asymptomatic in pregnancy
Paresthesias in pregnancy
I
0-11
16.4
20.5
100.5
78%
22%
II
12-85
15.8
21.9
97.8
60%
40%
III
99-384
29.1
33.9
85.5
20%
80%
3 The ranges for hair concentrations were chosen to give
as near as possible the same number of infants in each
group - Group 1,9; Group II, 10 and Group III, 10. The
student "t" test revealed no significant differences in
mean ages of walking and talking and mean heights between
Groups I and II. Group. Ill differed significantly from
Group I and II (walking P < 0.001, talking P< 0.005, height P<
0.05). The chi-square test revealed no difference in
frequency of maternal paresthesia between Groups I and
II. Group III differed significantly from the two lower
groups (P < 0.015) (Marsh, et al. 1978).
C-81
-------
E3 MATER/AL PEAK HAIR
Hg CONCENTRATION
1
m
i?l
no$
II
27?
^
^xl
|i
i&
%
Uj
0.5-
11 ppm
22°-o
§ 1-^
,
',$2'.
10
12- 30c-o
85 ppm
10
99-
334 ppm
80°
NO. OF ABNORMALITIES/INFANT
Figure 11. The number of abnormalities in each infant are
compared in three groups of infants. The infants are grouped
according to peak (maximal) maternal hair concentrations
during pregnancy. The maximum concentration, ppm (jig Hg/g) ,
is given as a number in each shaded square. More abnormalities
were found in infants in the high exposure group (maternal
hair 99^-384 ppm) as compared to the two lower exposure groups
(12-85, 0.5-11 ppm). The frequencies of maternal paresthesia
are also listed (Marsh, et al. 1978).
C-82
-------
A statistical analysis revealed a highly significant (P
005, chi square 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 adverse effects do not occur
in both mother and infant. A high risk of adverse 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 frequencies have fallen dramatically
and do not differ significantly from those seen in the lowest
range (0.5 to 11 ppm). Thus, adverse effects seen in maternal
hair concentrations up to 85 ppm may have been due to causes
other than methyl mercury exposure. Unfortunately, only
four infant-mother pairs were available between 25 and 50
ppm maximum maternal hair concentration.
An epidemiological study of school children living
in the Minamata area of Japan has recently been reported
(Med. Tribune, 1978). Children suspected of prenatal and
early postnatal methyl mercury exposures (age group 8 to
16) exhibited a higher incidence of neurological deficits,
learning difficulties, and poor performance on intelligence
tests than children of similar age in a control area. These
findings confirm predictions from studies of animals prenatal-
ly exposed to methyl mercury (Spyker, et al. 1972), in which
a variety of behavioral and neurological tests revealed
deficits only after the animals had reached maturity.
C-83
-------
In summary/ our knowledge is still limited in perhaps
the most critical area of methyl mercury toxicity in man.
A study on a fish-eating population is needed to complement
the Iraqi program to test if methyl mercury ingested from
contaminated bread is equivalent toxicologically to methyl
mercury chronically ingested from fish. The on-going Iraqi
study has demonstrated the feasibility of relating the dose
of the mother during pregnancy to effects seen in the infant
during the first six years of life. Other effects may mani-
fest themselves in later years as the child matures.
Effects on Animals: Animal studies reveal that effects
on non-human 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; World
Health Organ. 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; Fowler, 1972a; Magos and Butler,
1972). Damage to the peripheral nervous system has been
reported in rats (Somjen, et al. 1973a,b; Chang and Hartman,
1972a,b), whereas neurological signs in man appear to be
due mainly to damage to the central nervous system (Von
Burg and Rustam, 1974). However, effects on the neuromuscular
.. N
junction have been found in severe cases of poisoning in
Iraq (Von Burg and Landry, 1976).
C-84
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0-
10 20 30 40' 50 60 -70 80
SlOOD(ppm)
90 ICO
Figure 12. Comprehensive brain/whole blood regression lines
in four species orally dosed with methyl nercury. The shaded
areas correspond to the onset of the first detectable signs
and symptoms of poisoning.
Figure by courtesy of Weiss, Laties and Wood. Environmental
Health Sciences Center, Univ. of Rochester.
C-35
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The first effects of methyl mercury as evidenced by ani-
mal experiments are on protein synthesis in neurons (Yoshino
et al. 1966; Cavanagh and Chen, 1971; Chang and Hartmari,
1972a,b; Syversen, 1977). The effects of methyl mercury
on the neuromuscular junction are due to a highly selective
interaction with the acetyl choline receptor (Shamoo, et
all. 1976). !
Ganther, et al. (1972) reported a sparing effect of
dietary selenium on methyl mercury toxicity in rats and
Japanese quail. Subsequent animal studies have confirmed
Ganther's findings (World Health Organ. 1976; Nordberg,
1976). However, the concentrations of methyl mercury or
selenium added to the diet have been higher than those found
'"'*•**•„ ' ' • -
in human diets. Following the observation of Garither, et
al. (1972) that selenium salts, added to the diet, delayed
the onset of toxic effects, due to methyl mercury in Japanese
quail, several publications have appeared in the literature
on selenium-mercury interactions (for review, see World
Health Organ. 1976; Nordberg, 1976). However, in the most
recent evaluation of experimental data, it was concluded
that there is insufficient evidence to conclude that selenium
in the human diet would protect against the toxic effects
of methyl mercury (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 ancient times. Recently, several
reviews have dealt with this topic (Friberg and Vostal,
C-86
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1972; Natl. Inst. Occup. Safety Health, 1973; Friberg and
Nordberg, 1973; Nordberg, 1976; World Health Organ. 1976).
Health effects have not been associated with oral ingestion
of liquid metallic mercury.
Exposure to extremely high concentration of mercury
vapor (greater than 1 mg Hg/m ) can damage lung tissue,
causing acute mercurial pneumonitis (Milne, et al. 1970).
Exposure to lower levels results in signs and symptoms indica-
ting effects primarily on the central nervous system.
Most of our knowledge derives from studies of occupa-
tional exposures. These reviews listed above refer to observa-
tions of more than 1,000 individuals 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/m (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) reported effects on the nervous system that
were related to the time-weighted average air concentration
of mercury. Objective tremors were found at air concentra-
tions above 0.1 mg Hg/m . Nonspecific symptoms such as
loss of appetite, weight loss and shyness seem to occur
at a greater frequency than in the control group at average
air concentrations in the range of 0.06 to 0.1 mg Hg/m .
Extensive Russian studies on occupationally exposed
workers have been reported in a monograph by Trachtenberg
C-87
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(1969) and reviewed by Friberg and Nordberg (1973). A syn-
drome involving insomnia, sweat-ing, and emotional lability
was claimed to occur at a higher frequency 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 concen-
trations in the range of 0.006 to Q..1 mg Hg/m .
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 the factory physician
is aware of the mercury concentration to which the workers
are exposed. The Russian "analytical methods seem to be
crude, being based on subjective evaluation of color shades."
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 associated 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 i,000 pg Hg/1. Increased urinary excretion
of protein in exposed versus non-exposed workers was reported
by Joselow and Goldwater (1967). Ashe, et al. (1953) found
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morphological evidence of kidney damage in rabbits exposed
to mercury vapor.
Few biochemical changes have been reported due to inhala-
tion of mercury vapor. Wada, et al. (1969) noted that blood
cholinesterase activity was decreased when urinary mercury
excretion was greater than 200 ug Hg per gram of urinary
creatinine. This rate of excretion should correspond to
an average air concentration (eight hrs/day, five days/week)
in the range of 0.05 to 0.1 mg Hg/m .
Table 12, 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 concentrations in various species would not
i
necessarily correspond to the same average air concentration.
Effects of Prenatal Exposure: Little information is
available on biological effects in humans due to prenatal
exposure to mercury vapor. Studies carried out early in
this century suggest that women chronically exposed to mercury
vapor experienced increased frequencies of menstrual distur-
bances and spontaneous abortions; also, a high mortality
rate has been observed among infants born to women who dis-
played symptoms of mercury poisoning (Baranski and Szymczyk,
1973). However, the degree of exposure of these women to
mercury vapor is unknown. In 1967, an epidemiological survey
in Lithuania called attention to an increased incidence
of abortion and mastopathy related to duration of time on
C-89
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TABLE 12
Estimated Average Brain Concentrations at which Toxic
Effects Appear in Adult Humans and Animals
Species Brain Cone. Severity of
Hg/g wet wt. effects
Reference
Rabbit
Rat
Rat
Human
1.0
(approx. )
2.8
1.9
0.85
mild3
mild3
mild3
mildb
Ashe, et al. (1953)
'
Rothstein & Hayes (1964)
Berlin, et al. (1969)
Estimated0 from
Hursh, et al. (1976)
Smith, et al. (1970)
The animals were described as irritable.
Subjective, symptoms such as complaints of loss of appetite.
The steady-state brain concentration was estimated from
the data of Hursh, et al. (1976), which show that 7% of
an inhaled dose is deposited in the brain, and that the
half-time in brain is 21 days. Brain weight was assumed
to be 1.5 kg, and the time-weighted average air concentration
associated with mild effects to be 0.1 ng Hg/m , according
to data of Smith, et al. (1970). Workers were assumed
to inhale 10 m air during an 8-hour occupational exposure,
to retain 80% of the inhaled mercury, and to work for
5 days per week.
C-90
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the job among women working in dental offices where mercury
vapor concentrations ranged up to 0.08 mg/m (Baranski and
Szymczyk, 1973). Another report described the case of a
woman chronically intoxicated by mercury vapor in whom two
pregnancies ended unfavorably. After recovery from overt
mercury poisoning, this woman gave birth to a healthy child
(Derobert and Tara, 1950).
In summary, little is known about the reproductive
i
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 HgClj 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 inorganic mercury
have not been described in man. Long-term occupational
exposure to HgfNO^)^ must have occurred in the felt hat
industry (Neal, et al. 1937). However, poisoning was believed
to be due to inhalation of mercury vapor produced from HgfNO^
during the procedure of treating the felt.
Fitzhugh, et al. (1950) treated rats with HgCl2 added
to the food for periods of up to two years. Morphological
changes were induced in kidney tissue at dietary concentra-
tions of 0.5 pg Hg/g food. However, these studies have
been criticized by Goldwater (1973) who noted that no effects
I
were produced in other groups of rats receiving much higher
dietary levels of mercury (2.5 to 10 /ag Hg/g).
Compounds of inorganic mercury have been shown to be
diuretic in dogs (Mudge and Weiner, 1958). The nature of
!
C-91
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the anion is important. Inorganic mercury complexed with
cysteine is a more potent diuretic than HgCl2-
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 Kg"1"* cause induction of metallothionein
synthesis. Consequently, 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 available regarding their effects
on human health. Since Goldwater's review (1973), new infor-
mation has come to light. No evidence of adverse health
effects could be found in 67 workers occupatibnally exposed
to phenyl mercury 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 mercury compounds. The form of
mercury in the air was not identified but it is likely that
mercury vapor was the principal component (Hirschman, 1963).
Goldwater (1973) referred to seven workers who had
spent about six weeks working with material containing methoxy-
C-92
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ethyl mercury chloride. Remarkably high blood levels were
reported (range 34 to 109, average 65 jug Hg/100 ml) four
weeks after the end of exposure. No adverse health effects
could be detected.
Rats exposed for two years to phenyl mercury acetate
in the diet exhibited 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
Methyl Mercury and Other Short-Chain Alkyl Mercurials:
Although brain damage due to prenatal exposure to methyl
mercury has occurred in human populations, no anatomical
defects have been reported. However, adequate epidemiological
studies have not been performed and the possibility of terato-
\
logical action of methyl mercury in human subjects cannot
be dismissed at this time.
!
Embryotoxicity and teratogenicity of methyl mercury
in animals have been reported by several authors. Oharazawa
(1968) noted an increased frequency of cleft palate in mice
treated with an alkyl mercury compound. Fujita (1969) treated
mice .to daily administration of 0.1 mg Hg/kg as methyl mercury
and found that the offspring had significantly reduced birth
weight and possible neurological damage. No gross terato-
logical effects were noted. Histological evidence of damage
to the brain as a result of prenatal exposure to methyl
mercury has been reported on several animal species (Matsumoto,
et al. 1967; Nonaka, 1969; Morikawa, 1961). Non-lethal
C-93
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anatomical malformations in animals prenatally exposed to
methyl mercury 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 induced by postnatal exposure and were greater when
the methyl mercury was administered late in the period of
brganogenesis.
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 are reported to
have died within six 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 six. No teratological effects were observed,
birth weights were reportedly within the normal range, and
histopathologic findings were negative, although the concen-
trations of vapor were high (LC25 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.
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Mutagenicity
Methyl Mercury and Other Short-Chain Alkyl Mercurials:
No mutagenic effects have been reported in human populations
due to exposure to methyl mercury. However, a statistical
relationship was found between the frequency of chromosome
breaks and blood concentrations of methyl mercury in 23
Swedish fish eaters. The mercury concentration in the
blood of the exposed group ranged from 14 to 116 ng Hg/ml,
and in the non-exposed group from 3 to 18 ng/ml (Skerfving,
et al. 1974).
Khera (1973) has reported that, in rats, alkyl mercury
compounds may damage gometes prior to fertilization. Similar
experiments in mice failed to demonstrate statistically
significant effects. Studies by Ramel (1972) and Suter
(1975) have revealed damage to reproduction resulting from
exposure to alkyl mercurials during adult life. Methyl
mercury has been shown to block mitosis in plant cells,
human leukocytes treated in vivo, and human cells 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 Liquid Metallic Mercury: Nothing
has been reported on the mutagenic effects of mercury vapor
in humans, animals, or in vitro tests.
Salts of Inorganic Mercury: Reversible inhibition
of spermatogonial cells has been observed in mice treated
with HgCl (Lee and Dixon, 1975). No evidence has been
C-95
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published concerning the rautagenicity of mercury salts in
humans.
Carcinogenicity
When metallic mercury was injected intraperitoneally
into rats, sarcomas were observed only at those tisues that
had been in direct contact with the metal (Druckrey, 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 international standard for drinking water of 1 ug Hg/liter
(World Health 0, 1971); the U.S. Environmental Protection
Agency has recommended a standard of 2 jug Hg/liter (U.S.
EPA, 1973) .
Current Levels, of Exposure
Evidence reviewed in the Exposure section indicates
that the predominant form of mercury in freshwater (and
probably marine water also) is Hg , present as chelates
and complexes with a variety of inorganic and organic ligands.
However, the data are not sufficiently detailed or accurate
to exclude the possibility of the presence of other forms
of mercury, especially in contaminated areas. Methyl mercury
compounds may be present due to biomethylation of inorganic
mercury in sediment, elemental mercury (Hg°) due to discharge
from industry, and aryl and alkoxy mercurials due to their
use in the paint industry. Although it is highly probable
that the proportions of organo-mercurials and elemental
mercury vapor are small compared to inorganic divalent mercury
(Hg ) compounds, it will be assumed that the species most
toxic to man accounts for 100 percent of the total mercury
in water because methyl mercury compounds are the forms
of mercury which are most toxic to man and present the greatest
risk of irreversible functional damage. (See Effects section.)
C-97
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Special Groups at Risk
The evidence presented in this document indicates that
intake of mercury from drinking water is toxicologically
negligible. Human exposure to the most hazardous form of
this metal, methyl mercury, is almost exclusively via consump-
tion 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 human life cycle
subject to the greatest hazard from mercury intake is probably
prenatal.
Other forms of mercury probably do not present a signifi-
cant risk, except in the case of mercury vapor. The latter
may present a health risk if occupational exposures are
not maintained below acceptable limits. Unfortunately,
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 acrodynia 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
acrodynia when exposed to mercury. It is unlikely that
a small amount of inorganic 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 methyl mercury. However, inorganic
compounds of mercury should also be recognized because of
C-98
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their toxicity potential but perhaps more importantly because
with alkylation from environmentally present biological
systems the inorganic mercury can be converted to methyl
and dimethyl mercury.
The approach that has been adopted by 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 being defined
as an effect that adversely changes normal function or dimin-
ishes 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 ingest-
ing water and eating contaminated fish products; and (4)
estimate the effect on body burden of mercury by establishing
a criterion for mercury in ambient water based on human
health effects.
Table 13, taken from the review by the World Health
Organization expert group (1976), indicates long-term daily
intakes of methyl mercury which relates to the earliest
effect on the central nervous system. This system is more
sensitive to damage from methyl mercury than other functional
systems in the human body. The conclusions represented
in Table 13 were recently endorsed by the National Academy
of Sciences (1978).
Evidence reviewed in the Effects section of this document
is essentially the same as the evidence reviewed by the
WHO group with regard to adult exposures to methyl mercury.
C-99
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TABLE 13
The Concentrations of Total Mercury in Indicator Media
and the Equivalent Long-Term Daily Intake of Mercury
as Methyl Mercury Associated with the Earliest Effects
in the Most Sensitive Group in the Adult Population ''
Concentrations in indicator media
BloodHairEquivalent long-term daily intake
(jug/100 ml) (pg/g) (jug/kg body weight)
20-50 50-125 3-7
a The risk of the earliest effects can be expected to be
between 3 to 8%.
The table should not be considered independently of the text,
0 This table is adapted from Table 6 in WHO, 1976.
Effects on the adult nervous system have been estimated
to occur at blood concentrations in the range of 200 to
500 ng Hg/ml, corresponding to a long-term daily intake
of methyl mercury in the diet of 3 to 7 /ag/kg body weight.
^>N
The risk of effects at this intake level is probably less
than eight percent (1 in 12 chances).
Since the WHO (1976) criteria document was written,
new evidence has been documented. As reported in the Effects
C-100
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section, females who had experienced maximum hair concentra-
tions during pregnancy in the range of 99 to 384 jug Hg/g
had a high probability of having children liable to retarded
development. Unfortunately, the population size was too
small to establish a lower limit to effects of prenatal
exposure. A hair concentration of 99 jug/g is equivalent
to a blood concentration of about 400 ng Hg/ml.
The most recent information on effect of mercury on
human health has come from the study of the Iraq outbreak
of 1971-1972. The follow-up of the cases of prenatal ex-
posure is still in progress. As noted by the National Academy
of Sciences (1978), "continued careful evaluation of this
very important cohort of pre-natally exposed individuals
will provide the most sensitive assessment of human methyl-
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 post-natal exposures.
Blood concentrations of methyl 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
jug Hg/70 kg.
Mercury intake from drinking water, according to data
reviewed in the Exposure section of this document, is less
than 1 jug Hg/day, and is considerably less than the diet por-
tion (Table 14). Assuming that the concentration of methyl
mercury in all samples of drinking water is at the current
C-101
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TABLE 14
Estimate of Average and Maximum Daily Intakes of Mercury
by the "70 kg standard Adult" in the U.S. Population3,
Mercury intake pg/day/70kg. Predominate form
Media
Air
Water
Food
Average
0.3
0.1
3.0
Maximum
0.8 Hg°
0.4 Hg
5.0 CH-.Hg"1'
aFor details on the calculation of these numbers, see
the Exposure section of this document.
These are approximate figures indicating that 95%
of the population have intakes less than these figures.
Occupational exposures are not included.
U.S. EPA standard of 2 jug Hg/1, the maximum daily iatake
would only be 4 jug Hg, assuming 2 liters of drinking water
are consumed per person each day. This maximum intake would
amount to only about one to two percent of the minimum toxic
intake given in Table 14. Thus, from the toxicological
standpoint, exposure to mercury via drinking water only
would be negligible.
The ingestion of water has been assumed to be the main
pathway of direct intake of mercury from water. The transport
of mercury through skin is another possible route of intake.
Indirect transfer of mercury from water to man is much more
important than transfer from direct routes. This conclusion
is based on the assumption that fish bioaccumulate a signifi-
cant amount of methyl mercury from water. In theory, it
should be possible to calculate the maximum concentration
C-102
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of methyl mercury in water which would assure that concen-
trations in edible tissues of fish do not exceed the Food
and Drug Administration Guidelines of 1.0 jug Hg/g fresh
tissue. Thus, if the bioaccumulatiori factor is known for
each species of edible fish, it is arithmetically simple
to estimate the maximum concentration of methyl mercury
in water. For example, the U.S. EPA (1978) calculated bio-
concentration factors (concentration in fish/concentration
in water) 'for methyl mercury compounds based on literature
reports. These factors are for edible fish species: 4,525
to 8,376 for rainbow trout Salmo gardineri, 20,000 for
brook trout Salvelinus fontinalis, and 900 to 1,640 for
clams Anodanta grandis, Lampsitis radiata, Lasmigona complanta.
Thus, if the maximum bioaccumulation factor of 20,000 is
adopted, the maximum concentration of methyl mercury in
freshwater that would prevent fish from exceeding the current
FDA guideline would be 0.05 jug/1.
Unfortunately, both practical and theoretical difficul-
ties thwart any accurate calculation. First, quantitative
information is inadequate with regard to the role of direct
uptake from water versus accumulation from food chains as
contributors to the total amount of methyl mercury in fish.
Differences may be expected between fish at lower and upper
ends of the food chain. Second, the accumulation factors
for methyl mercury uptake by fish are only known for few
species. Third, the concentration of methyl mercury in
water is probably a variable fraction of total mercury in
water. The proportion of methyl to total mercury will prob-
ably vary in different bodies of water, being influenced
C-.103
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by such factors as water pH, degree of oxygenation, the
amount of biota and the sedimentary concentrations of mercury.
Fourth, in most cases, the concentration of methyl mercury
in water will be so low as to defy accurate measurement
even by the most modern technology.
When more information is available on the behavior
of mercury in aquatic environments, it might be possible
to calculate a reliable criterion based on acceptable concen-
trations of mercury in fish. In the meantime, a more pragma-
tic approach will have to be used. The discharge of mercury
into bodies of water must be carefully controlled. Those
bodies of freshwater supporting edible fish with mercury
concentrations above the acceptable levels will have to
be identified, and anthropogenic discharge of mercury curtail-
ed. It is also possible that non-anthropogenic sources
are predominant (for example, in ocean waters) so that control
is not possible. This empirical approach, although the
only one available, is unsatisfactory as it allows mainly
after-the-fact corrections. Development of procedures for
estimating maximum safe concentrations of mercury in ambient
water that will prevent unacceptable bioaccumulation of
methyl mercury by fish is clearly desirable.
Methyl Mercury
Two approaches could be used to derive a criterion
for methyl mercury. One approach is to use the existing
U.S. drinking water standard of 2 >ug/l and the typical water
quality exposure assumptions (2 1 water/day, 0.0187 kg fish
products/day) along with an estimated fish/shellfish biocon-
C-104
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centration factor of 6,200 to calculate a potential uptake.
This can then be compared to the lowest Observable Effect
Level (LOEL) to determine the range of safety. A second
approach is to use the LOEL as a basis for establishing
an acceptable daily intake (ADI) and calculate a criterion
level using the typical water quality assumptions.
Given: fish/shellfish consumption = 0.0187 kg fish/person/day
bioconcentration factor for methyl mercury = 6,200 = ^
water consumption = 2 I/person/day
(1) Assume criterion = 2 jug/1
Human exposure = (2 I/day + (6,200 x 0.0187)
= 2 (2 + 115.9)
= 235.8 pg/day
Recognizing that the LOEL range is 200 to 500 ug Hg/day,
we could hypothesize that there is little or no margin of
safety at the 2 jug/1 criterion level especially where realiz-
ing that dietary sources other than fish products may be
contributing to the body burden.
(2) Derive ADI using typical water quality exposure and LOEL
LOEL range = 200-500 pg Hg/day
Use 220 jjg Hg/day to assure marginal safety
ADI = 200 pg/day
= C 2 I/day + (6,200 x 0.0187)
200 = C (2 + 115.9)
200/117.9 = C
1.7 pg/1 = C
According to the National Academy of Science (1977)
an uncertainty factor of ten can be applied to the ADI as
C-105
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the 200 to 500 data results from studies on prolonged inges-
tion by man, with no indication of carcinogenicity.
200/10 = C (2 + 115.9)
0.17 jjg/1 = C
0.2 jjg/1 "-• C
Whereas, approach #1 has an estimated narrow margin
of safety if any and given that LOEL's do exist it is reason-
able to focus on the ADI based criterion with an uncertainty
factor as the preferred basis for establishing a criterion.
C-105a
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REFERENCES
Aberg, B., et al. 1969. Metabolism of methyl mercury (Hg-
203) compounds in man. Arch. Environ. Health 19: 478.
Abramovskig, B.P., et al. 1975. Global balance and maximum
permissible mercury emissions into the atmosphere. Second
joint U.S./U.S.S.R. symposium on the comprehensive analysis
of the environment. Oct. 21-26, 1975. Honolulu. U.S. Environ,
Prot. Agency.
Amin-Zaki, L., et al. 1974a. Intrauterine methyl mercury
poisoning in Iraq. Pediatrics 541: 587.
Amin-Zaki, L., et al. 1974b. Studies on infants postnatally
exposed to methyl mercury. Jour. Pediat. 85: 587.
Amin-Zaki, L., et al. 1976. Perinatal methyl mercury poison-
ing in Iraq. Am. Jour. Dis. Children 130: 1070.
Andersson, A. 1976. Kvicksilvret i marken. Grundforbattring
20: 95.
Andren, A.W., and R.C. Harriss. 1975. Observations on associ-
ation between mercury and organic matter dissolved in natural
waters. Geochimica et Cosmo. Chimica. Acta. 39: 1253.
C-106
-------
Ashe, W., et al. 1953. Behavior of mercury in the animal
organism following inhalation. AMA Arch. Ind. Occup. Med.
7: 19.
Bakir, F., et al. 1973. Methyl mercury poisoning in Iraq.
Science 181: 234.
Baranski, B., and I. Szymczyk. 1973. Effects of mercury
vapor upon reproductive functions of female white rat.
Medycyna. Pracy. 24: 248.
Berlin, M.H., et al. 1969. On the site and mechanism of
mercury vapor resorption in the lung. Arch. Environ. Health
18: 42.
Berlin, M.H., et al. 1973. The uptake and distribution
of methyl mercury in the brain of Saimari siuireus in relation
to behavioral and morphological changes. Page 187 ir\ M.W.
Miller and T.W. Clarkson, eds. Mercury, mercurials and
mercaptans. Charles C. Thomas, Springfield, 111.
Bidstrup, P., et al. 1951. Chronic mercury poisoning in
man repairing direct current meters. Lancet 251: 856.
Birke, G., et al. 1967. Methylkvicksilverforgifring genom
forrating.av fisk? Lakortidningen 64: 3628.
C-J.G7
-------
Bornmann, G., et al. 1970. uber die enterale resorption
von metallischem quicksilber. Arch. Toxicol. 26: 203.
Bouquiaux, J. 1974. Page 23 i_n Proc. International symposium
on the problems of contamination of man and his environment
by mercury and cadmium. Luxembourg 3-5 July 1973. CEC
Luxembourge.
Brar, S.S.,et al. 1969. Thermal neutron activation analysis
of airborne particulate matter in Chicago metropolitan area.
Natl. Bur. Stand., Washington, D.C.
Brune, D. 1969. Aspects of low temperature irradiation
in neutron activation analysis. An. Chem. Acta. 44: 15.
Buhler, D..R. 1973. Mercury in the western environment.
Continuing Education Publications, Corvallis, Ore.
Cavanagh, J.B., and F.C.K. Chen. 1971. The effects of
methyl mercury-dicyandiamide on the peripheral nerves and
spinal cord of rats. Acta Neuropathol. 19: 208.
Camber, H. 1962. A model for the kinetics of mercury elimina-
tion. Am. Ind. Hyg. Assoc. Jour. 23: 204.
Chang, L., and H.A. Hartmann. 1972a. Ultrastructural studies
of the nervous system after mercury intoxication I. Patho-
logical changes in the nerve cell bodies. Acta. Neuropathol.
20: 122.
C-lOb
-------
Chang, L., and H.A. Hartmann. 1972b. Blood-brain dysfunction
in experimental mercury intoxication. Acta. Neuropathol.
21: 179.
Chau, Y.K., and H. Saitoh. 1973. Determination of methyl
mercury in lake water. Int. Jour, Environ. Anal. Chem. 3: 133.
Cherian, M.G., and T.W. Clarkson. 1976. Biochemical changes
in rat kidney on exposure to elemental mercury vapor: Effect
on biosynthesis of metallothionein. Chem. Biol. Interactions
12: 109.
Cherian, M.G., et al. 1978. Radioactive mercury distribution
in biological fluids and excretion in human subjects after
inhalation of mercury vapor. Arch. Environ. Health 33i 109.
Choi, B., et al. 1977. Abnormal neuronal migration in human
fetal brain due to mercury poisoning. Am. Jour. Pathol.
84 (2) 55A.
Clarkson, T.W. 1971. Epidemiological and experimental aspects
of lead and mercury contamination of food. Food Cosmet.
Toxicol. 9: 1.
Clarkson, T.W. 1972a. Recent advances in toxicology of
mercury with emphasis on the alkyl mercurials. Page 203
i_n L. Goldberg, ed. Critical reviews in toxicology. Issue
2. Chemical Rubber Co., Cleveland.
C-109
-------
Clarkson, T.W. 1972b. The pharmacology of mercury compounds.
Ann. Rev. Pharmacol. 12: 375.
Clarkson, T.W. 1974. Quantitative measurement of the toxicity
of mercury in man. Page 453 in A. Prasod, ed. Trace ele-
ments and human disease. Academia, New York.
Clarkson, T.W. 1977. Plenary lecture - mercury poisoning.
Page 189 in S.S. Brown, ed. Clinical chemistry and chemical
toxicology of metals. Elsevier/North Holland, Amsterdam.
Clarkson, T.W. 1978. Unpublished data. Environ. Health Sci.
Center. University of Rochester.
Clarkson, T.W., and A. Rothstein. 1964. The excretion
of volatile mercury by rats injected with mercuric salts.
Health Phys. 10: 1115.
Clarkson, T.W., et al. 1972. The transport of elemental
mercury into fetal tissues. Biol. Neonate. (Basel) 21:
239.
Clarkson, T.W., et al. 1976. An outbreak of methyl mercury
poisoning due to consumption of contaminated grain. Fed.
Proc. 35: 2395.
Clarkson, T.W., et al. 1978. The metabolism of inhaled
mercury vapor in animals and man. Jour. Am. Chem. Soc.
(In press.)
C-110
-------
Copplestone,
-------
Druckrey, H., et al. 1957. Carcinogenic action of metallic
mercury after intraperitoneal administration in rats. z.
Krebsforsch. 61: 511.
Dunn, J., et al. 1978. Ethanol increases exhalation of
mercury in mice injected with HgCl2« Brit. Jour. Ind. Med.
35: 241.
Edwards/ G.N. 1865. Two cases of poisoning by mercuric
methide. St. Bart's Hospital Rep. 1: 141.
Engleson, G., and T. Herner. 1952. Alkyl mercury poisoning.
Acta. Pediat. Scan. 41: 289.
Eriksson. E. 1967. Mercury in nature. Page 13. in The mercury
problem. Oikos, Sullp.
Fernandez, N., et al. 1966. A case of atmospheric contami-
nation with mercury. Rev. de Sanid. Hyg. Publica. Madrid.
40: 325.
Fimreite, N., and L.M. Reynolds. 1973. Mercury contami-
nation of fish in northwestern Ontario. Jour. Wildl. Manage.
37: 62.
Firman, N. 1974. jlri WHO Conference on Intoxication due
to Alkyl Mercury-treated seed. November 9-11. Baghdad.
C-112
-------
Fitzhugh, O.G., et al. 1950. Chronic oral toxicants of
mercuric-phenyl and mercuric salts. Arch. Ind. Occup. Med.
2: 433.
Fowler, B.A. 1972a. Ultrasturctural evidence for neuropathy
induced by long-term exposures to small amounts of methyl
mercury. Science 175: 780.
Friberg, L. 1951. Aspects of chronic poisoning with inorganic
mercury based on observed cases. Nord. Hyg. Tidskr. 32: 240.
Friberg, L., and F. Nordberg. 1973. Inorganic mercury-
A toxicological and epidemiological appraisal. Pages 5-
19 in M.W. Miller, and T.W. Clarkson, eds. Mercury, mercu-
~~~ *
rials and mercaptans. Charles C. Thomas, Springfield, 111.
Friberg, L., and J. Vostal, eds. 1972. Mercury in the
environment. Chemical Rubber Co., Cleveland, Ohio.
Friberg, L., et al. 1961. Resorption of mercuric chloride
and methyl mercury dicyandiamide in guinea-pigs through
normal skin and through skin pre-tested with acetone, alkyl-
arylsulphonate and soap. Acta. Derm. Venerol. 41: 40.
Fujimura, Y. 1964. Concentrations of mercury in the atmo-
sphere. Jap. Jour. Hyg. 18: 10.
C-113
-------
Fujita, E. 1969. Experimental studies on organic mercury
poisoning: the behavior of Minamata disease causal agent
in maternal bodies and its transfer to their infants via
either placenta or breast milk. Jour. Kumamoro Med. Soc.
43: 47.
Fuller, W.H. 1978. Investigation of landfill leachate pollutant
attenuation by soils. Municipal Environ. Res. Lab. U.S.
Environ. Prot. Agency.
Furukawa, K., et al. 1969. Decomposition of organic mercurial
compounds by mercury resistant bacteria. Agric. Biol. Chem.
33: 128.
Gage, J.C. 1961. Distribution and excretion of methyl
and phenyl mercury salts. Br. Jour. Ind. Med. 21: 197.
Gale, T., and V. Farm. 1971. Embryopathic effects of mercuric
salts. Life Sci. 10: 1341.
Galster, W.A. 1976. Mercury in Alaskan -Eskimo mothers and
infants. Environ. Health Perspect. 15: 135.
•s
Ganther, H.E., et al. 1972. Selenium: relation to decreased
toxicity of methyl mercury added to diets containing tuna.
Science 175: 1122.
Garrels, E.M., et al. 1973. Chemical cycles and global
influences. William Kaufman, Inc., Los Altos, Calif.
C-114
-------
Giovanoli, T., and G.G. Berg. 1974. Measurement of mercury
in human hair. Arch. Environ. Health 28: 139.
Gleason, M.N., et al. 1957. Page 154 in Clinical toxicology
of commercial products. Williams and Wilkins Co., Baltimore.
Goldwater, L.J. 1964. Occupational exposure to mercury:
the Harben lectures. Inst. Publ. Health Hyg. 27: 279.
Goldwater, L.J. 1973. Aryl and alkoxymercurials. Pages
56-67 jji M.W. Miller and T.W. Clarkson, eds. Mercury, mercur-
ials and mercaptans. Charles C. Thomas, Springfield, 111.
Gowdy, J.M., et al. 1977. Mercury concentrations in blood
in patients in hospital. Sci. Total Environ. 8: 247.
Greenwood, M.R., and T.W. Clarkson. 1970. Storage of mercury
submolar concentrations. Am. Hyg. Assoc. 31: 250.
Greenwood, M.R., et al. 1978. Blood clearance half-times
in lactating and nonlactating members of a population exposed
to methyl mercury. Environ. Res. 16: 48.
Hammerstrom, R.J., et al. 1972. Mercury in drinking water
supplies. Jour. Am. Water Works Assoc. 64: 60.
C-115
-------
Harada, Y.C. 1968. Clinical investigations on Minamata
disease. C. Congenital (or fetal) Minamata disease. Page
93. in M. Kutsuna, ed. Minamata disease. Study group of
Minamata disease. Kumomoto University, Japan.
Hartung, R., and B.D. Dinman. 1972. in Environmental mercury
contamination. Ann Arbor Science Pub., Inc. Ann Arbor,
Mich.
Heindryckx, R., et al. 1974. in Proc. International symposium
on the problems of contamination of man and his environment
by mercury and cadmium. Comm. Eur. Commun., Luxembourg.
July 3-5, 1973.
Henderson, R., et al. 1974. Analysis for total, inorganic
and elemental mercury as a basis for a biological standard.
Am. Ind. Hyg. Assoc. Jour. 35: 576.
Hernberg, S., and E. Hassanan. 1971. Relationship of inor-
ganic mercury in blood and urine. Work Environ. Health
8: 39.
Hirschman, S.Z., et al. 1963. Mercury in house paint as a
cause of acrodynia. New England Jour. Med. 269: 889.
Hosohara, K. 196.1. Mercury content of deep sea water.
Jour. Chem. Soc. (Japan) 82: 1107.
C-116
-------
Hunter, D., and D.S. Russell. 1954. Focal cerebral and cere-
bellar atrophy in a human subject due to organic mercury
compounds. Jour. Neurol. Neurosurg. Psychiatry 17: 253.
Hunter, D., et al. 1940. Poisoning by methyl mercury com-
pounds. Q. Jour. Med. 33: 193.
Hursh, J.B., et al. 1976. Clearance of mercury (197Hg,
203 g) vapor inhaled by human subjects. Arch. Environ.
Health 4: 302.
Jacobs, M.B., et al. 1964. Absorption and excretions of
mercury in man. VI. Significance of mercury in urine. Arch,
Environ. Health 9: 454.
Jalili, M.A., and A.H. Abbasi. 1961. Poisoning by ethyl
mercury toluene sulphonanilide. Br. Jour. Ind. Med. 18:
303.
Jensen, S., and A. Jernelov. 1972. Behavior of mercury
in the environment. Page 43. In Mercury contamination in
man and his environment. Vienna Int. Atomic Energy Agency.
Tech. Rep. Ser. 137.
203
Jogo, S. 1976. Retention and distribution of
in suckling and adult rats. Health Physics 30: 240.
C-117
-------
Johnson, D.L., and R.S. Braman. 1974. Distribution of
atmospheric mercury species near ground. Environ. Sci.
Technol. 8: 1003.
Joselow, M.M., and L.J. Goldwater. 1967. Absorption and
excretion of mercury in man. XII. Relationship between
urinary mercury and proteinuria. Arch. Environ. Health
15: 155.
Joselow, M.M., et al. 1968. Absorption and excretion of
mercury in man. XI. Mercury content of "normal" human
tissues. Arch. Environ. Health 15: 64.
Juliusberg, F. 1901. Experimentelle untersuchungem uber
quicksilber-resorption bei der schmierkur. Arch. Derm.
Syph. 56: 5.
Katsuhiko, M., and G. Takumi. 1976. Mercury in the air
and precipitation. Geochem. Jour. 10: 107.
Katsuna, M. 1968. in M. Katsuna, ed. Minamata disease.
Kumomota University, Japan.
Kazantzis, G. 1973. Discussion. Page 20 in M.W. Miller
and T.W. Clarkson, eds. Mercury, mercurials and mercaptans.
Charles C. Thomas, Springfield, 111.
C-118
-------
Kazantzis, G., et al. 1962. Albuminuria and the nephrotic
syndrome following exposure to mercury and its compound.
Q. Jour. Med. 31: 403.
Keckes, S., and J.K. Miettinen. 1970. Mercury as a marine
pollutant. Pages 276-289 in M. Ruivo, ed. Marine pollu-
tion and sea life. Fishing News (Books) Ltd., London.
Kershaw, T., et al. 1978. Studies on the relationship
between blood concentrations and doses of methyl mercury
in man. (Submitted for publication.)
Khera, K.S. 1973. Reproductive capability of male rats and
mice treated with methyl mercury. Toxicol. Appl. Pharmacol,
24: 167.
Kimura, Y., and V.L. Miller. 1970. The degradation of
organo-mercury fungicides in soil. Jour. Agric. Food Chem.
12: 253.
Klein, R., et al. 1972. A model of acute methyl mercury
intoxication in rats. Arch. Pathol. 93: 408.
Klein, R., et al, 1973. Methyl mercury intoxication in
rat kidneys; functional and pathological changes. Arch.
Pathol. 96: 83.
Koeman, J.H., et al. 1973. Mercury-selenium correlations
in marine mammals. Nature 245: 385.
C-119
-------
Kopfler, F.C. 1974. The accumulation of organic and inorganic
mercury compounds by the eastern oyster, Crassostrea virginica.
Bull. Environ. Contam. Toxicol. 11: 275.
Korringa, P., and P. Hagel. 1974. ir\ Proc. International
symposium on problems of contamination of man and his environ-
ment by mercury and cadmium. Comm. Eur. Commun., Luxembourg.
July 3-5 1973.
Kostial, K., et al. 1978. Influences of age on metal meta-
bolism and toxicity. Environ. Health Perspect. 25: 81.
Kothny, E.L. 1973. The three stage equilibrium of mercury
in nature. Pages 48-80. In: R.T. Gould, ed. Trace elements
in the environment. Advances in Chemistry Series No. 123.
Amer. Chem. Soc., Washington, D.C.
Landry, T.D., et al. 1978. Dietary effects on mercury
metabolism and excretion after parenteral administration
of methyl mercuric chloride and mercuric chloride. Toxicol.
Appl. Pharmacol. 45: 350.
Lee, I.D., and R.L. Dixon. 1975. Effects of mercury on
spermatogenesis studied by velocity sedimentation, cell
separation and serial mating. Jour. Pharmacol Exp. Ther.
194: 171.
C-120
-------
Lovejoy, H.B., et al. 1974. Mercury exposure evaluations
and their correlation with urine mercury excretion. Jour.
Occup. Med. 15: 590.
Lundgren, K.D., et al. 1976. Studies in humans on the
distribution of mercury in the blood and the excretion in
urine after exposure to different mercury compounds. Scand.
Jour. Clin. Lab. Invest. 20: 164.
Magos, L. 1973. Factors affecting the uptake and retention
of mercury by kidneys in rats, jji M.W. Miller and T.W.
Clarkson, eds. Mercury, mercurials and mercaptans. Charles
C. Thomas, Springfield, 111.
Magos, L., and W.H. Butler. 1972. Cumulative effect of
methyl mercury dicyandiamide given orally to rats. Food.
Cosmet. Toxicol. 10: 513.
Magos, L., et al. 1964. Volatilization of mercury by bacteria,
Br. Jour. Ind. Med. 21: 294.
Magos, L., et al. 1976. Tissue levels of mercury in autopsy
specimens of liver and kidney. Page 93. iin WHO Conf. on
intoxication due to alkyl mercury treated seed. Baghdad
Nov. 9-13, 1974. Geneva, WHO 11 (Suppl. to Bull. WHO 53).
C-121
-------
Marsh, D.O., et al. 1978. Fetal methyl mercury poisoning;
new data on clinical and toxicological aspects. Trans.
Am. Neurol. Assoc. 102: 1.
Matsumoto, H., et al. 1967. Preventative effect of penicil-
lamine on the brain defect of fetal rat poisoned transpla-
centally with methyl mercury. Life Sci. 6: 2221.
Matsunaga, K., et al. 1979. Possible errors caused prior
to measurement of mercury in natural waters with special
reference to seawater. Environ. Sci. Technol. 13: 63.
Maximum Allowable Concentrations Committee. 1969. Maximum
allowable concentration of mercury compounds. Arch. Environ.
Health 19: 891.
McCarthy, J.H., et al. 1970. Mercury in the atmosphere.
Page 37. ir\ Mercury in the environment. U.S. Dep. Interior.
Geolog. Survey, Prof. Pap. No. 713 U.S. Government Printing
Office.
McDuffie, B. 1973. Discussion. Pages 50-53. In: M.W.
Miller and T.W. Clarkson, eds. Mercury, mercurials and mer-
captans. Charles C. Thomas, Springfield, 111.
McKim, J.M., et al. 1976. Long-term effects of methyl-mercuric
chloride on three generations of brook trout, Salvelinus
fontinalis Toxicity, accumulation, distribution, and elimina-
tion. 33: 2726.
C-122
-------
Medical Tribune. 1978. Methyl mercury affects Japanese school-
children. 13 September, 1978.
Miettinen, J.K. 1972. Preliminary study on the distribution
and effects of two chemical forms of methyl mercury in pike
and rainbow trout. Pages 298-303 i.n M. Ruivo, ed. Marine
pollution and sea life. Fishing News, London.
Miettinen, J.K. 1973. Absorption and elimination of dietary
(Hg ) and methyl mercury in man. Page 233. i_n M.W. Miller,
and T.W., Clarkson, eds. Mercury, mercurials and mercaptans.
Charles C. Thomas, Springfield, 111.
Miettinen, J.K. 1974. Mercury pollution of fish in Finland.
i_n Proc. of the international symposium .on problems of con-
tamination of man and his environment by mercury and cadmium.
Commission of the European Community, Luxemburgh. July
3-5 1973.
Miettinen, J.K., et al. 1969. Distribution and excretion
rate of phenyl and methyl mercury nitrate in fish, mussels,
molluscs and crayfish. Pages 473-478 jjrc Proc. 9th Japanese
conference on radiosotopes. Japan Ind. Forum Inc., Tokyo.
Miller, M.W., and T.W. Clarkson, eds. 1973. Mercury, mercur-
ials and mercaptans. Charles C. Thomas, Springfield, 111.
Miller, G.E., et al. 1972. Mercury concentrations in museum
specimens of tuna and swordfish. Science 175: 1121.
C-123
-------
Milne, J., et al. 1970. Acute mercurial pneumonitis. Br.
Jour. Ind. Med. 27: 334.
Morikawa, N. 1961. Pathological studies in organic mercury
poisoning. Kumamota Med. Jour. 14: 71.
Morrow, P.E., et al. 1964. Clearance of insoluble dust
from the lower respiratory tract. Health Phys. 10: 543.
Mudge, G.H., and J.M. Weiner. 1958. The mechanism of action
of mercurial and xanthine diuretics. Ann. N.Y. Acad. Sci.
71: 344.
Mufti, A.W., et al. 1976. Page 23 in WHO Conf. on intoxica-
tion due to alkyl mercury treated seed. Baghdad. Nov.
9-13, 1974. Geneva WHO 53. (Suppl. to Bull. WHO)
National Academy of Sciences. 1978. An assessment of mercury
in the environment. Panel on Mercury. Washington, D.C.
National Institute for Occupational Health and Safety. 1973.
Criterion document. Occupational exposure to inorganic
mercury. U.S. Dep. Health Edu. Welfare.
Neal, P., et al. 1937. A study of chronic mercurialism
in the hatters fur-cutting industry. Pages 1-70. ir\ Pub.
Health Bull. 234. U.S. Publ. Health Serv., U.S. Treasury
Dep.
C-124
-------
Neal, P., et al. 1941. Mercurials and their control in
the felt hat industry. Pages 1-132. In: Public Health
Bull. 234. Fed. Security Agency, U.S. Treasury Dep.
Nielsen-Kudsk, F. 1965a. Absorption of mercury vapor from
the respiratory tract in man. Acta. Pharmacol. 23: 250.
Nonaka, I. 1969. An electron microscopic study of the experi-
mental congenital Minamata Disease in rat. Kumamoto Med.
Jour. 22: 27.
Nordberg, G.F., ed. 1976. Effects and dose-response of
toxic metals. Elsevier-Amsterdam.
Nordberg, G.F., and P. Strangert. 1976. Pages 18-23.
ir\ Effects and dose-response of toxic metals. Rep. Interna-
tional Meet, arranged by the Sub-comm. on the Tox. Metals.
Tokyo.
Norseth, T., and T.W. Clarkson. 1970. Studies on the bio-
203
transformation of Hg-labelled methyl mercury chloride
in rats. Arch. Environ. Health 22: 717.
Norseth, T. and T.W. Clarkson. 1971. Intestinal transport
203
of Hg-labelled methyl mercury chloride; role of biotrans-
formation in rats. Arch. Environ. Health 22: 258.
C-125
-------
Oharazawa. 1968. Chromosomal abnormalities and teratogenesis
induced by ethyl mercuric phosphate in pregnant mice. Nippon
Sanka-Fujinka Gakka: Zasshi 20: 1479.
Okinata, S., et al. 1964. Encephalopathy due to an organic
mercury compound. Neurology 14: 69.
Olson, F.C., and E.J. Massaro. 1977. Pharmacodynamics
of methyl mercury in the marine maternal/embryo fetal unit.
Toxicol. Appl. Pharmacol. 39: 263.
Olson, G.F., et al. 1975. Mercury residues in fathead minnows,
Pimephales promelas Rafinesque, chronically exposed to methyl
mercury in water. Bull. Environ. Contam. Toxicol. 14: 129.
Pentreath, R.J. 1976a. The accumulation of organic mercury
from seawater by the plaice, Pleuronectes platessa L. Jour.
Exp. Mar. Biol. Ecol. 24: 121.
Pentreath, R.J. 1976b. The accumulation of mercury by the
thornback ray, Raja clavata L. Jour. Exp. Mar. Biol. Ecol.
25: 131.
Permanent Commission and International Association on Occupa-
tional Health. 1977. Metal Interactions meeting in Stockholm.
Sub-committee on Toxic Metals.
C-126
-------
Pierce, P.E., et al. 1972. Alkyl mercury poisoning in humans.
Report of an outbreak. Jour. Am. Med. Ass. 220: 1439.
Pierson, D.H., et al. 1973. Trace elements in the atmospheric
environment. Nature 241: 252.
Piotrowski, J., et al. 1973. Page 247 iri M.W. Miller and
T.W. Clarkson, eds. Mercury, mercurials, and mercaptans.
Charles C. Thomas, Springfield, 111.
Piotrowski, J., et al. 1974a. Binding of cadmium and mercury
by metallothionein in the kidneys and liver of rats following
repeated administration. Arch. Toxicol. 32: 351.
Piotrowski, J., et al. 1974b. Mercury binding in the kidney
and liver of rats repeatedly exposed to mercuric chloride;
induction of metallothionein by mercury and cadmium. Toxicol.
Appl. Pharmacol. 27: 1119.
Rahola, T., et al. 1971. The biological half-time of inorgan-
2+
ic mercury (Hg ) in
27: 77 (Suppl. 116).
2+
ic mercury (Hg ) in man. Scand. Jour. Clin. Invest. Abst.
Ramel, C. 1972. Genetic effects. Page 9 jin L. Friberg,
and J. Vostal, eds. Mercury in the environment -a toxico-
logical and epidemiological appraisal. Chemical Rubber
Co., Cleveland.
C-127
-------
Reinert, R.E., et al. 1974. Effect of temperature on accumu-
lation of methylmercuric chloride and p,p'DDT by rainbow
trout, Salmo gairdneri. Jour. Fish. Res. Board Can. 31:
1649.
Rentos, P., and E. Seligman. 1968. Relationship between
environmental exposure to mercury and clinical observations.
Arch. Environ. Health 16: 794.
Rothstein, A., and A.D. Hayes. 1964. The turnover of mercury
in rats exposed repeatedly to inhalation of vapor. Health
Phys. 10: 1099.
Schamberg, J., et al. 1918. Experimental studies of the
mode of absorption of mercury when applied by inunction.
Jour. Am. Med. Assoc. 70: 142.
Sergeev. Ye. A. 1967. Methodology of mercurimetric investi-
gation*. j.n V.I. Kransnikov, ed. Proc. First all-union
conference on geochemical methods of prospecting for ore
deposits. Moscow.
Shahristani, H., and K. Shihab. 1974. Variation of bio-
logical half-time of methyl mercury in man. Arch. Environ.
Health 18: 342.
Shahristani, H. , et al. 1976. _in WHO Conf. intoxication
alkyl mercury treated seed. Baghdad 9013 November 1974.
Geneva, WHO Suppl. to Bull. WHO 53.
C-12B
-------
Shamoo, A.E., et al. 1976. Localization of ionopone activity
in a 20,000 dalton fragment of the adenosine triphosphatase
of sarcoplasmic reticulum. Jour. Biol. Ghem. 251: 4147.
Is
Singh, A., and F. Sherman. 1974. Characteristics and rela-
tion-ships of mercury resistant mutants and methionine auxo-
trophs of yeast. Jour. Bacteriol. 118: 911.
Skerfving, S. 1974. Methyl mercury exposure, mercury levels
in blood, hair and health status in Swedes consuming con-
taminated fish. Toxicology 2: 3.
Skerfving, S., et al. 1974. Methyl mercury-induced chromo-
some damage in man. Environ. Res. 7: 83.
Skog, E. and J.E. Wahlberg. 1964. A comparative investi-
gation of the percutaneous absorption of metal compounds
in the guinea-pig by means of the radioactive isotopes Cr,
58Co, 65Zn, 110Aq, 115mCd, 203Hg. Jour. Invest. Derm. 43:
187.
Smith, R., et al. 1970. Effects of exposure to mercury
in the manufacture of chlorine. Ann. Ind. Hyg. Assoc. Jour.
31: 687.
Snyder, R.D. 1971. Congenital mercury poisoning. New
England Jour. Med. 284: 1014.
C-12y
-------
Somjen, G.G., et al. 1973a. Electrophysiology of methyl
mercury poisoning. Jour. Pharmacol Exp. Ther. 186: 579.
Somjen, G.G., et al. 1973b. The uptake of methyl mercury
203
( Hg) in different tissues related
Jour. Pharmacol Exp. Ther. 187: 602.
203
( Hg) in different tissues related to its neurotoxic effects.
Spyker, J.M., and M. Smithberg. 1972. Effects of methyl
mercury on prenatal development in mice. Teratology 5: 181.
Spyker, J.M., et al. 1972. Subtle consequences of methyl
mercury exposure. Science 177: 621.
Stock, A., and F. Cucuel. 1934. pie Verbreitung des Quick-
silbers. Naturwissenschaften 22: 390.
Straby, A. 1968. Analysis of snow and water, iri T. Wester-
mark and K. Ljunggren, eds. Development of analytical methods
for mercury and studies of its dissemination from industrial
sources. Swedish Tech. Res. Counc. Stockholm. (Mimeographed
document.)
Study Group on Mercury Hazards. 1971. Environ. Res. 4: 1.
Suter, K.E. 1975. Studies on the dominant lethal and fertil-
ity effects of the heavy metal compounds methyl mercuric
hydroxide, mercuric chloride, and cadmium chloride in male
and female mice. Mutat. Res. 30: 365.
C-130
-------
Suzuki, T., and A. Tonaka. 1971. Methyl mercury in maternal
and fetal red blood cells. Ind. Med. 13: 52.
Suzuki, T., and K. Yoshino. 1969. Effects of d-penicillamine
on urinary excretion of mercury in two cases of methyl mercury
poisoning. Ind. Med. 11: 21.
Suzuki, T., et al. 1971. Comparison of mercury contents
in maternal blood, umbilical cord blood and placental tissue.
Bull. Environ. Contain. Toxicol. 5.
Swedish Expert Group. 1971. Methyl mercury in fish - toxi-
cological-epidemiological evaluation of risks. Report from
an expert group. Nordisk. Hyg. Tidsknift. Suppl. 4.
Syversen, T. 1977. Effects of methyl mercury on iin vivo
protein synthesis in isolated cerebral and cerebellar neurons.
Neuropathol. Appl. Neurobiol. 3: 225.
Task Group on Metal Accumulation. 1973. Accumulation of
toxic metals, excretion and biological half-times. Environ.
Phys. Biochem. 3: 65.
Teisinger, J., and V. Fiserova-Bergerova. 1965. Pulmonary
retention and excretion of mercury vapors in man. Ind.
Med. Surg. 34: 580.
C-131
-------
Tejning, S. 1970. Mercury contents in blood corpuscles and
in blood plasma in non-fisheaters. Dep. Occup. Med.f Univer-
sity Hospital, Lund. Rep. No. 700406.
Tejning, S., and H. Ohman. 1966. Uptake, excretion and
retention of metallic mercury in chloralkali workers. Page
239 ir\ Proc. 15th Int. Congr. Occup. Health, Vienna.
Trachtenberg, I. 1969. The chronic action of mercury on
the organism, current aspects of the problem of micro-mercuri-
alism and its prophylaxis. Kiev. Zdorov'ja. 292.
Tsubaki, T., and K. Irukayama. 1977. Minamata disease.
»
Elsevier Publ. Co.
Tsuda, M., et al. 1963. Organic mercury poisoning - a case
*
report. Yokokama Med. Bull. 14: 287.
Turner, M.D., et al. 1974. Methyl mercury (MeHg) in human
population eating large quantities of marine fish in Northern
Peru. Page 229 ir\ Proc. 1st Int. Congr. Mercury. Barcelona,
May 5-10.
Turner, M.D. et al. 1975. Studies on volunteers consuming
methyl mercury in tuna fish. Clin. Res. 23: 2.
Ukita, T., et al. 1963. Determination of mercury in urine,
blood and hair of man in organic mercurial poisoning. Jour.
Hyg. Chem. 9: 138.
C-132
-------
United Kingdom Department of the Environment. 1976. Environ-
mental mercury and man. A report of an inter-departmental
working group on heavy metals. Pollut. Pap. No. 10. Her
Majesty's Stationary Office.
U.S. Department of Commerce. 1978. Report on the chance
of U.S. seafood consumers exceeding the current acceptable
daily intake for mercury and on recommended regulatory con-
trols. Natl. Oceanic Atmos. Admin. Natl. Mar. Fish. Serv.
Off. Fish. Develop.
U.S. EPA. 1973. Water quality criteria, 1972. Ecol. Res.
Ser. Rep. comm. of Water Quality Criteria. Natl. Acad.
Sci. EPA/R3/73/033. U.S. Government Printing Office. Washing-
ton, D.C.
»
U.S. EPA. 1975a. Materials balance and technology assessment
of mercury and its compounds on national and regional bases.
EPA-560/3/75/007. U.S. Environ. Prot. Agency Rep. Washing-
ton, D.C.
U.S. EPA. 1975b. Chemical analysis of interstate carrier
water supply systems. EPA-430/9/75/005. U.S. Environ. Prot.
Agency Rep. Washington, D.C.
U.S. EPA. 1978. Draft document. Derivation of marine criterion
for mercury.
C-133
-------
Von Burg, R., and B.C. Rustam. 1974. Electrophysiological
investigations of methyl mercury intoxication in humans.
Electrpencaphal. Clin. Neurophysiol. 37: 381.
Von Burg, R., and T. Landry. 1976. Methyl mercury and
the skeletal muscle receptor. Jour. Pharm. Pharmacol. 28:
548.
Wada, 0., et al. 1969. Response to a low concentration
of mercury vapor-relation to human porphyrin metabolism.
Arch. Environ. Health 19: 485.
Wallace, R.A., et al. 1971. Mercury in the environment,
the human element. ORNL, NSF-EP-1. Oak Ridge Natl. Lab.,
Oak Ridge, Tenn.
r
Weiss, H.V. 1975. The chemical composition of a Greenland
glacier. Geochimica et Cosmochimica Acta 39: 1.
Weiss, H.V., et al. 1971. Mercury in a Greenland ice sheet;
evidence of recent input by man. Science 174: 692.
Wershaw, R.L. 1970. Page 29 in Mercury in the environment
U.S. Dep. Inter. Geolog. Survey. Prof. Pap. 713.
Williston, S.H. 1968. Mercury in the atmosphere. Jour.
Geophysical Res. 73: 7051.
C-13-.
-------
Windom, H.L. 1973. Mercury concentrations in river water.
Jour. Waterways Harbors Coastal Eng. Div. 99: 257.
Wollast, R., et al. 1975. Behavior of mercury in natural
systems and its global cycle. Ln Ecological toxicology
research. Effects of heavy metal and organo halogen compounds.
Proc. NATO Sci. Comm. Conf.
Wood, J.M. 1976. Les mataux toxiques dans I1environment.
La Recherche 7: 711.
World Health Organization. 1971. International standards
for drinking water. 3rd ed. Geneva.
f
World Health Organization. 1972. Joint expert committee
on food additives. WHO Food Additives Ser. No. 4. April
4-12. Geneva.
World Health Organization. 1973. WHO Regional office for
Europe. The hazards to health of persistent substances
in water. Copenhagen. 147.
World Health Organization. 1976. Environmental health
criteria, Mercury. Geneva.
Yoshino, Y., et al. 1966. Biochemical changes in the brain
in rats poisoned with an alkyl mercury compound, with special
reference to the inhibition of protein synthesis in brain
cartes slices. Jour. Neurochem 13: 1223.
C-135
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