COPPER
Ambient Water Quality Criteria
Criteria and Standards Division
Office of Water Planning and Standards
U.S. Environmental Protection Agency
Washington, D.C.
-------
CRITERION DOCUMENT
COPPER
CRITERIA
Aquatic Life
For copper the criterion to protect freshwater aquatic
life as derived using the Guidelines is "e(0.65'ln(hardness)-
1 94
" as a 24-hour average (see the figure "24-hour average
copper concentration vs. Hardness") and the concentration
should not exceed «e(0.88'(hardness) - 1.03). {see fche figure
"maximum copper concentration vs. hardness") at any time.
For copper the criterion to protect saltwater aquatic
life as derived using the Guidelines is 0.79 ug/1 as a 24-
hour average and the concentration should not exceed 18
ug/1 at any time.
Human Health
To prevent the adverse organoleptic effects of copper
in water, a criterion of 1 mg/1 has been established.
-------
CRITERION DOCUMENT
COPPER
CRITERIA
Aquatic Life
For copper the criterion to protect freshwater aquatic
life as derived using the Guidelines is "e ((K65" ln(hardness)~
1 94
" as a 24-hour average (see the figure "24-hour average
copper concentration vs. Hardness") and the concentration
should not exceed -a'0-88"(hardness) - 1.03). (see fche figure
"maximum copper concentration vs. hardness") at any time.
For copper the criterion to protect saltwater aquatic
life as derived using the Guidelines is 0.79 ug/1 as a 24-
hour average and the concentration should not exceed 18
ug/1 at any time.
Human Health
To prevent the adverse organoleptic effects of copper
in water, a criterion of 1 mg/1 has been established.
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COPPER
Introduction
Copper is a soft heavy metal, atomic number 29, with
an atomic weight of 63.54, a melting point of 1,083°C, a
boiling point of 2,595°C, and a density in elemental form
at 20° of 8.9 g/cc (Stecher, 1968). Elemental copper is
readily attacked by organic and mineral acids that contain
an oxidizing agent and is slowly soluble in ammonia water.
The halogens attack copper slowly at room temperature to
yield the corresponding copper halide. Oxides and sulfides
are also reactive with copper.
Copper has two oxidation states; Cu I (cuprous) and
Cu II (cupric). Cuprous copper is unstable in aerated water
over the pH range of most natural waters (6 to 8) and will
oxidize to the cupric state (Garrels and Christ, 1965).
Bivalent copper chloride, nitrate, and sulfate are highly
soluble in water whereas basic copper carbonate, cupric hydrox-
ide, oxide, and sulfide will precipitate out of solution
or form colloidal suspensions in the presence of excess
cupric ion. Cupric ions are also adsorbed by clays, sediments,
and organic particulates and form complexes with several
inorganic and organic compounds (Riemer and Toth, 1969;
Stiff, 1971). Due to the complex interactions of copper
with numerous other chemical species normally found in natural
waters, the amounts of the various copper compounds and
complexes that actually exist in solution will depend on
the pH, temperature, alkalinity, and the concentrations
of bicarbonate, sulfide, and organic ligands. Based on
equilibrium constants, Stumm and Morgan (1970) calculated
-------
copper solubility in a carbonate bearing water. They found
2 +
that cupric ion (Cu ) would be the dominant copper species
up to pH 6 and from pH 6 to 9.3 the aqueous copper carbonate
complex (CuC03 aq.) would dominate. The presence of organic
ligands such as humic acids, fulvic acids, amino acids,
cyanide, certain polypeptides, and detergents would alter
this equilibrium (Stiff, 1971).
Zirino and Yamamoto (1972) developed a model to predict
the distribution of copper species in seawater. Mixed ligand
complexes and organic chelates were not considered in the
model. They predicted that the distribution of copper species
in seawater would vary significantly with pH and that Cu(OH)2f
2+
CuCOj and Cu would be the dominant species over the entire
ambient pH range. The levels of Cu(OH)2 increase from about
18 percent of the total copper at pH 7 to 90 percent at
pH 8.6. CuCO3 drops from about 30 percent at pH 7 to less
than 0.1 percent at pH 8.6 Field and laboratory studies
by Thomas and Grill (1977) indicate that copper adsorbed
to sediments and particulates in freshwater may be released
as soluble copper when it comes in contact with seawater
in estuarine environments.
Copper is ubiquitous in the rocks and minerals of the
earth's crust. In nature copper occurs usually as sulfides
and oxides and occasionally as metallic copper. Weathering
and solution of these natural copper minerals results in
background levels of copper in natural surface waters at
concentrations generally well below 20 ^ig/1. Higher concen-
trations of copper are usually from anthropogenic sources.
-------
These sources include corrosion of brass and copper pipe
by acidic waters, industrial effluents and fallout, sewage
treatment plant effluents, and the use of copper compounds
as aquatic algicides. Potential industrial copper pollution
sources number in the tens of thousands in the United States.
However, the mdjot industrial sources include the smelting
arid refining industries, copper wire mills, coal burning
industries, and iron and steel producing industries. Copper
may enter natural waters either directly from these sources
or by atmospheric fallout of air pollutants produced by
these industries. Precipitation to atmospheric fallout
may be a significant source of copper to the aquatic environment
in industrial and mining areas.
The levels of copper able to remain in solution are
directly dependent on water chemistry. Generally, ionic
copper is more soluble in low pH, low alkalinity waters
and less soluble in high pH, high alkalinity waters. Copper
is an essential trace element for humans as well as for
many other life forms. In humans most of this copper require-
ment is obtained from food. Although copper poisoning in
humans is rare, ingestion of milligram quantities of ionic
copper (usually from acidic waters or foods exposed to copper)
can cause acute symptoms of nausea, vomiting and diarrhea.
Many aquatic organisms are more sensitive than man to copper
and significant changes in the aquatic community may occur
at copper concentrations significantly lower than those
hazardous to human health. Copper occurs at higher concentra-
tions in freshwater than in seawater and is more toxic to
aquatic life in soft acidic waters than in hard alkaline
waters.
A-3
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REFERENCES
Carrels, R.M./ and C.L. Christ. 1965. Solutions, minerals
and equilibria. Harper and Row, New York.
Riemer, D.N., and S.J. Toth. 1969. Absorption of copper
by clay minerals, humic acid, and bottom muds. Jour. Am.
Water Works Assoc. 62: 195.
Stecher, P.G., ed. 1968. The Merck Index. Merck and Co.,
Inc. Rahway, N.J.
Stiff, M.J. 1971. The chemical states of copper in polluted
fresh water and a scheme of analysis of differentiates them.
Water Res. 5: 585.
Stumm, W., and J.J. Morgan. 1970. Aquatic chemistry - an
introduction emphasizing chemical equilibria in natural
waters. John Wiley and Sons, Inc., New York.
Thomas, D.J., and E.V. Grill. 1977. The effect of exchange
reactions between Fraser River sediment and seawater on
dissolved Cu and Zn concentrations in the Strait of Georgia.
Estuarine Coastal Mar. Sci. 5: 421.
Zirino, A., and S. Yamamoto. 1972. A pH dependent model
for the chemical speciation of copper, zinc, cadmium, and
lead in seawater. Limnol. Oceanogr. 17: 661.
A-4
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AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
Copper, which occurs in natural waters primarily as the diva-
lent cupric ion (free and complexed forms), is a minor nutrient
for both plants and animals at low concentrations but is acutely
toxic to aquatic life at concentrations only slightly higher.
Usual concentrations of 1-10 u.g/1 (total copper) are reported for
a majority of surface waters in the United States. Concentrations
in the vicinity of municipal and industrial outfalls, particularly
smelting, refining, or metal plating industries, may exceed 500
ug/l.
The cupric ion is highly reactive and forms moderate to
strong complexes and precipitates with many inorganic and organic
constitutents of natural waters, e.g. carbonate, phosphate, amino-
acids, and humates, and is readily absorbed on surfaces of
suspended solids. The proportion of total copper present as the
free cupric ion is generally low, and may be less than one percent
*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
following tables contain the appropriate data that were found in
the literature, and at the bottom of each table are the calcula-
tions for deriving various measures of toxicity as described in
the Guidelines.
B-l
-------
in eutrophic waters where complexation predominates. Fortunately,
the various copper complexes and precipitates appear to be largely
non-toxic and tend to mask or remove toxicity attributable to
total copper (Andrew, 1976). This fact greatly complicates the
interpretation and application of available toxicity data, since
the proportion of free cupric ion present is highly variable and
is difficult to measure except under ideal laboratory conditions.
Few toxicity data ,'have been generated using measurements of other
than total or dissolved copper. As evidenced by the criteria
derived herein, concentrations required for survival, growth and
reproduction of the more sensitive aquatic species are at or below
ambient total concentrations in some surface waters of the United
States. This results from a majority of the tests having been
conducted with oligotrophic waters.
Seasonally and locally, toxicity may be mitigated by the pre-
sence of naturally occurring chelating, complexing, and precipi-
tating agents. Removal from the water column may be rapid due to
normal growth of the more resistant species and settling of sol-
ids. The various forms of copper are in dynamic equilibrium and
any change in chemical conditions, e.g. pH, could rapidly alter
the proportion of the various forms present, and therefore, tox-
icity.
Since increasing calcium hardness and associated carbonate
alkalinity are both known to reduce copper toxicity, expression of
the criteria as a function of water hardness (see Figures labeled
"24-hour average copper concentration vs. hardness" and "maximum
copper concentration vs. hardness"), allows adjustment of the
B-2
-------
criteria based on total copper concentration for these water qual-
ity effects. This results in a much better fit with the available
toxicity data. That is, the criteria are higher at high hardness
to reflect calcium antagonism and carbonate complexation in the
receiving waters.
The following data on the effects of copper on aquatic biota
(Tables 1-7) have been summarized from the literature from
1950-1978. Efforts to obtain residue data, or effects data on
algae and other plants were not exhaustive, since earlier reviews
indicated these effects to be of minor importance relative to
toxicity to fish and invertebrate species.
Acute Toxicity
Acute toxicity tests with copper have been conducted on a
total of 29 fish species (Table 1), with nearly 250 values avail-
able for comparison. Most of these tests have been conducted with
four salmonid species, fathead and bluntnose minnows, and blue-
gills .
Unadjusted values range from a low of 10 ug/1 for chinook
salmon in soft water to 10,000 uxj/1 for bluegills tested in hard
water. The majority of tests conducted since about 1970 have been
flow-through tests with measurements of both total and dissolved
copper. Where available, LC50 values based on dissolved copper
have been included and notated in the tables.
Following the Guidelines, an exponential equation describing
the relationship of toxicity to hardness for each species was fit
by least squares regression of the natural logarithms of the LC50
values and hardness.
B-3
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There were sufficient data available for five species to show
correlation of acute toxicity and water hardness. These were the
chinook salmon, cutthroat and rainbow trout, fathead minnows, and
bluegills. The slope of the regression equations ranged from 0.72
for chinnok salmon to 0.84 for bluegills, with a mean of 0.79.
The close agreement of the slopes and the highly significant (p =
0.01) regressions in each case reflect the quality of the toxico-
logical data available, the steepness of the slopes, and the simi-
larity in response of the species tested.
In the absence of contradictory data, it will be assumed that
the hardness relationship holds for all aquatic species. Adjust-
ments for hardness effects on toxicity were made for all species
by fitting the mean slope (0.79) through the geometric mean tox-
icity value and hardness for each species. Logarithmic intercepts
were then used as a measure of relative species sensitivity to
copper. Chinook salmon is the most sensitive fish species. Rain-
bow trout and the other salmonids are somewhat less sensitive.
Fathead minnows and several other cyprinids are approximately 3-11
times more resistant to copper than the salmonids. Bluntnose min-
nows however, are nearly as sensitive as the salmonids. Bluegills
and other centrarchids are approximately 20-110 times more resis-
tant than salmonids. These results indicate that the 1,000 fold-
range in LC50 values observed in Table 1 is largely a function of
water quality, and that the actual range of sensitivity is more n-
arrow.
Following the Guidelines, the mean intercept, adjusted by the
species sensitivity factor, for all 29 fish species is 1.12. Since
results of flow-through tests with measured concentrations for
B-4
-------
both rainbow trout and chinook salmon are lower than this, the
data for chinook salmon are used to derive the final fish acute
equation. Thus the Final Fish Acute Value is e(°-72*ln
(hardness) + 0.83).
The overall variation observed in acute toxicity values for
invertebrate species (Table 2) is nearly the same as that for
fish, with adjusted values ranging from 4.2 ug/1 for Daphnia hyal-
ina to 10,200 ug/1 for eggs of snails (Amnicola sp.) and 9,100
ug/1 for adult stoneflies (Acroneuria lycorias). However, hard-
ness effects are much more difficult to determine with the inver-
tebrate data, since few species have been tested over a range of
water quality (particularly hardness). Sufficient data were
available however, to show a weak dependence on hardness (r =
0.39) for copper toxicity to Daphnia magna, and a somewhat better
relationship (r = 0.51, p = 0.05) for Daphnia pulicaria. The
slopes (0.75 and 1.03) were similar to those for fish. The calcu-
lated mean intercept for the 26 invertebrate species that have
been tested is 2.01, which indicates that the invertebrate species
are acutely more sensitive than fish.
After using the calculated intercepts as a measure of rela-
tive species sensitivities, the range of sensitivity is much grea-
ter than for fish. This wider range may be the result of a grea-
ter taxonomic diversity than exists for fish.
Daphnia hyalina, the most sensitive species (intercept =
-2.25), is approximately 70 times more sensitive to copper than
indicated by the mean sensitivity. At least eight or nine inver-
tebrate species are more sensitive than chinook salmon. The most
resistant adult insects, however, have not been tested in hard-
B-5
-------
nesses higher than 40-50 g/1. Even with adjustment of the data
for hardness effects, the overall range of sensitivities is ap-
proximately 3,000-fold.
Using the Guidelines, the adjusted mean intercept is -1.03,
which is adequate to protect all species except possibly Daphnia
hyalina. Only a single LC50 value, run under static conditions
with unmeasured copper concentrations, is available for this spe-
cies. The adjusted mean intercept thus appears adequate for in-
vertebrate species. The Final Invertebrate Acute Value is
e(0.88-in (hardness) - 1.03). since this value is lower
than that for fish, it becomes the Final Acute Value.
Chronic Toxicity
The fish chronic values (Table 3) range from 1.9 ug/1 for
embryo-larval tests with brook trout in soft water to 75.4 ug/1
for a life cycle test with fathead minnows in very hard water.
Only for fathead minnows are there enough data to indicate the re-
lationship of chronic toxicity to hardness. The slope (0.65) is
similar to that (0.77) for acute toxicity values for the same spe-
cies (Table 1). The correlation (r = 0.82) is nonsignificant pri-
marily because of the small number of chronic test values avail-
able. Using the fathead minnow slope and adjusting for hardness
effects as for the acute values, the relative sensitivity of the
fish appears to be consistent with the acute results. That is,
salmonids are the most sensitive group, blue gills much more re-
sistant, and the minnows intermediate. For chronic tests, north-
ern pike was the most resistant species. There are, however, no
LC50 values for this species for comparison.
B-6
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The mean logarithmic intercept for the 11 species tested is
-0.042. Comparing this intercept with the mean intercept for acute
values for fish (2.48), indicates that fish are approximately 12
times more sensitive when exposed chronically to copper, than
acutely. This is equivalent to an application factor of 0.08,
which agrees closely with the mean application factor (0.067)
derived from the seven values available (Table 3).
The adjusted mean intercept (-1.94) using the species sensi-
tivity factor (6.7) from the Guidelines is adequate to protect
brook trout and bluntnose minnows, the most sensitive species. The
Final Fish Chronic Value is thus e(°*65*ln (hardness) - 1.94).
Seven invertebrate species (four of which were daphnids) have
been tested for chronic effects of copper (Table 4). Chronic
values spanned the range of 6.1 to 49 ug/1. Three other species
were more sensitive than daphnids at equivalent hardnesses.
No hardness relationship could be derived for any inver-
tebrate species. Assuming a similar hardness relationship as with
fish chronic values, the slope (0.65) results in a mean intercept
for the seven invertebrate"species of 0.21. This is not signifi-
cantly different from that for fish. The adjusted mean intercept
(-1.42) is also slightly above that for fish.
The derived equation for fish chronic values: e(0.65*In
(hardness) - 1.94) is therefore used as the Final Chronic
Value.
Plant Effects
Copper has been widely used in the past as an algicide and
herbicide for nuisance aquatic plants. Although copper is known
B-7
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as an inhibitor of photosynthesis and plant growth, toxicity data
on individual species (Table 5) are not numerous. The relation-
ship of toxicity to water chemistry and the importance of the
culture medium has only recently been recognized (Gachter, et al.
1973) .
Copper concentrations from 1 to 8,000 ug/1 have been shown to
inhibit growth of various plant species. Several of the values
are near or below the chronic values for fish and invertebrate
species. Since the values indicated cause lag in growth or. inhib-
it photosynthesis, they should be considered important ecological
effects of copper. Calculations using the equation for Final Fish
Chronic Value indicate that even the most sensitive algal species
would be adequately protected in waters with a hardness greater
than 20 ug/1. In extremely soft water, some growth reduction of
Chlorella sp. might be expected to occur at the Final Chronic
Value. This single result does not seem to warrant lowering the
criteria, however.
Residues
Bioconcentration factors (Table 6) ranged from 203 for stone-
flies (]?. californica) to 2,000 for the alga (Chlorella regularis),
Since copper is a required element for animal nutrition, the im-
portance of copper residues has never been established and few
tests have been run for the purpose of determining bioconcentra-
tion factors.
B-8
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CRITERION FORMULATION
Freshwater-Aquatic Life
Summary of Available Data
All concentrations herein are expressed in terms of copper.
Final Fish Acute Value = e(0.72*ln(hardness) + 0.83)
Final Invertebrate Acute Value = e(°-88'ln(hardness) - 1.03
Final Acute Value = e(°.88«in(hardness) - 1.03)
Final Fish Chronic Value = e<0-65*ln(hardness) - 1.94)
Final Invertebrate Chronic Value = e(°65-ln(hardness)-1.42)
Final Plant Value = 1 v.g/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = e(°*65'In(hardness) - 1.94)
The maximum concentration of copper is the Final Acute Value.
Of e(°«88'ln(hardness) - 1.03) ana t^e 24-hour average
concentration is the Final Chronic Value of e(0.65-In(hardness)
1.94)^ No important adverse effects on freshwater aquatic
organisms have been reported to be caused by concentrations lower
than the 24-hour average concentration.
CRITERION: For copper the criterion to protect freshwater
aquatic life as derived using the Guidelines is "e(0»65*ln
(hardness) - 1.94)« as a 24-hour average (see the figure "24-hour
average copper concentration vs. hardness") and the concentration
should not exceed "e(°*88*ln(hardness) - 1.03)" (see the
figure "maximum copper concentration vs. hardness") at any time.
B-9
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20.0
IO.O
O»
8
(T
4.0
Q_
< c
a:
LJ
§
or
o
2.0
1.0
0.4
0.2
10
24-HOUR AVERAGE
COPPER CONCENTRATION
VS.
HARDNESS
20 40 100
TOTAL HARDNESS (mg/l)
In scale
200
400
B-10
-------
100.0
MAXIMUM COPPER CONCENTRATION
VS.
HARDNESS
4O.O
o>
20.0
h-
LU
O O
^ R
8 8 10.0
LU
0_
Q.
O
O
X
<
4.0
2.0
1.0
10
20 40 100
TOTAL HARDNESS (mg/l)
In scale
200
400
B-ll
-------
Table 1. Freshwater fish acute values for copper
Organism
American eel
Bioassay Test
Method* Cong.**
S
M
Hardness
(mq/1 as
CaC03)_
53
Time
(nra)
96
Anguilla roscrata
American eel
S
M
55
96
LC50
jug/I}
6,400
6,000
Adjusted
LCbO
(uq/lj Reference
4.540
4,260
Anguilla rostrata
CO
1
H
N)
Coho salmon,
Oncorhynchus
Coho salmon,
Oncorhynchus
Coho salmon,
Oncorhynchus
Coho salmon,
Oncorhynchus
Coho salmon,
Oncorhynchus
Coho salmon,
Oncorhynchus
Coho salmon,
Oncorhynchus
Coho salmon,
Oncorhynchus
Coho salmon,
Oncorhynchus
Coho salmon,
Oncorhynchus
Coho salmon,
Oncorhynchus
Coho salmon.
Oncorhynchus
Coho salmon.
kisutch
kisutch
kisutch
kiautch
kiautch
kisutch
kisutch
kisutch
kisutch
kisutch
kisutch
kisutch
FT
S
FT
S
S
S
S
S
S
S
S
S
S
M
U
U
U
U
M
M
M
M
M
M
M
M
20
v-80
x.80
v-80
v,80
v40
v-40
^,55
v.55
v.40
*55
v.55
v-40
96
72
72
72
72
72
72
72
72
72
72
72
72
43
280
370
190
480
440
460
480
560
780
510
520
480
43
141
262
96
241
287
300
314
366
509
333
340
314
Rehwoldt
1971
Rehwoldt
1972
Chapman
In press
Holland,
1960
Holland,
1960
Holland,
1960
Holland,
1960
Holland,
1960
Holland,
1960
Holland,
1960
Holland.
1960
Holland.
1960
Holland,
1960
Holland,
I960.
Holland,
. et
. et
& St
et
et
et
et
et
et
et
et
et
et
et
et
al
al
evei
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
Oncorhynchus kisutch
1960
-------
Table I- (Continued)
I
OJ
Bioassay
Orqar.ism Method*
Coho salmon (yearling) ,
Oncorhynchus kisutch
Coho salmon (yearling) ,
Oncorhynchus kisutch
Coho salmon (smolt) ,
Oncorhynchus kisutch
Chinook salmon (alevin) ,
Oncorhynchus tshawytscha
Chinook salmon (swim-up) ,
Oncorhynchus tshawytscha
Chinook salmon (parr) ,
Oncorhynchus tshawytscha
Chinook salmon (smolt) ,
Oncorhynchus tshawytscha
Chinook salmon,
Oncorhynchus tshawytscha
Chinook salmon,
Oncorhynchus tshawytscha
Chinook salmon,
Oncorhynchus tshawytscha
Chinook salmon,
Oncorhynchus tshawytscha
Chinook salmon,
Oncorhynchus tshawytscha
Cutthroat trout,
Salmo clarki
Cutthroat trout,
Salmo clarki
Cutthroat trout,
S
S
S
FT
FT
FT
FT
FT
FT
FT
FT
S
FT
FT
FT
Test
Cone .**
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
Hardness
(mo,/ 1 as
CaC00)
89-99
89-99
89-99
25
25
25
25
13
46
182
359
x.80
205
70
18
Time
inrs)
96
96
96
96
96
96
96
96
96
96
96
72
96
96
96
Adjusted
LC50 LCbO
Juq/ifr (uq/il
74
70
60
26
19
38
26
10
22
85
130
190
367***
186***
36.8***
53
50
43
26
19
38
26
10
22
85
130
124
367
186
36.8
Retei fence
Lorz &
McPherson, 19
Lorz &
McPherson, 19
Lorz & '
McPherson, 19
Chapman , In
press
Chapman , In
press
Chapman , In
press
Chapman , In
press
Chapman &
McCrady. 1977
Chapman &
McCrady. 1977
Chapman &
McCrady, 1977
Chapman &
McCrady, 1977
Holland, 1960
Chakoumakos , i
al. In press
Chakoumakos , i
al. In press
Chakoumakos , i
Salmo clarki
al. In press
-------
Table 1. (Continued)
Hardness
O3
I
Organism
Cutthroat trout,
S a lino clarki
Cutthroat trout,
Salmo clarki
Cutthroat trout,
Salmo clarki
Cutthroat trout,
Salmo clarki
Cutthroat trout,
Salmo clarki
Cutthroat trout,
Salmo clarki
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gatrdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
issay Test (m
-------
Table 1- (Continued)
Hardness
Dioassay Test (mn/I as Time
. . _ _ .L.I. r*-r>r\ \ ftirQl
LC50
Adjusted
urqanism
Rainbow trout ,
Salmo Eairdneri
Rainbow trout,
Salmo Eairdneri
Rainbow trout ,
Salmo Eairdneri
Rainbow trout,
Salmo Eairdneri
Rainbow trout,
Salmo pairdneri
Rainbow trout,
tfl Salmo Eairdneri
Jt Rainbow trout,
Salmo Eairdneri
Rainbow trout ,
Salmo Eairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout.
Salmo Eairdneri
Rainbow trout.
Salmo Eairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout.
Salmo pjairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout.
FT M
FT M
FT M
FT M
FT M
FT M
FT M
FT M
FT M
FT M
FT M
FT M
FT M
FT M
FT M
101
99
100
100
98
370
366
371
361
371
360
364
194
194
194
96
96
96
96
96
96
96
96
96
96
96
96
96
96
96
Reteifcuce
45.3*** 46 . 3
47.9*** 47.9
48.l*** 48.1
81.1*** 81.1
85.9*** 85.9
232*** 232
70*** 70
82.2*** 82.2
298*** 298
516*** 516
309*** 309
HI*** 111
169*** 169
85.3*** 85.3
83.3*** 83.3
Salmo Eairdneri
Howarth &
Sprague, In press
Howarth &
Sprague, In press
Howarth &
Sprague, In press
Howarth &
Sprague, In press
Howarth &
Sprague, In press
Howarth &
Sprague, In press
Howarth &
Sprague, In press
Howarth &
Sprague, In press
Howarth &
Sprague, In press
Howarth &
Sprague. In press
Howarth &
Sprague, In press
Howarth &
Sprague, In press
Chakoumakos, et
al. In press
Chakoumakos, et
al. In press
Chakoumakos, et
al. In press
-------
Table 1. (Continued)
Organism
Bioassay Test
Method * Cone.**
Hardness
as Time
Rainbow trout ,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout ,
Salmo gairdneri
Rainbow trout ,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout ,
f Salmo gairdneri
a\ Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout ,
Salmo gairdneri
Rainbow trout (alvein) ,
Salmo gairdneri
Rainbow trout (swim-up), -
Salmo gairdneri
Rainbow trout (parr) ,
Salmo gairdneri
Rainbow trout (smolt) ,
Salmo gairdneri
Rainbow trout.
FT .
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
194
194
194
194
194
194
194
194
94
177
25
25
25
25
42
96
96
96
96
96
96
"96
96
96
96
96
96
96
96
96
Adjusted
LC50 LCbO
(uq/ij (uci/ii Peter fence
Salmo gairdneri
103*** 103
274*** 274
128*** 128
221*** 221
165*** 165
197*** 197
514*** 514
243*** 243
62.9*** 62.9
48.9*** 48.9
28 28
17 17
18 18
29 29
57 57
Chakoumakos, et
al. In press
Chakoumakos, et
al. In press
Chakoumakos, et
'al. In press
Chakoumakos, et
al. In press
Chakoumakos, et
al. In press
Chakoumakos, et
al. In press
Chakoumakos, et
al. In press
Chakoumakos, et
al. In press
Chakoumakos, et
al. In press
Chakoumakos, et
al. In press
Chapman, In
press
Chapman, In
press
Chapman, In
press
Chapman, In
"press
Chapman & ..
Stevens, In press
-------
Table 1, (Continued)
W
I
Organism
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo Rairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
oassay
thod*
S
S
S
FT
FT
FT
Field
S
FT
S
S
S
S
R
S
Test
Cone .**
M
M
M
M
M
. U
M
M
M
M
M
U
M
U
Hardness
(mq/ 1 as
CaC03)
36
36
36
350
-
360-369
21-26
290
100
_
250
320
240
"soft-
Time
(His)
24
24
24
96
96
96
48
96
96
24
24
72
48
48
48
LCSO
(uq/il
950
430
150
102
253
250-680
70
890
250
140
130
580
500
750
150
Adjusted
LCbO
(UC|/1)
445
201
70
102
253
193-524
57
632
250
66
61
379
221
431
66
Retei fence
Cairns, et al.
1978
Cairns, et al.
1978
Cairns, et al.
1978
Fogels & .
Sprague, 1977
Hale, 1977
Lett, et al.
1976
Calamari &
Marchetti. 1975
Calamari &
Marchetti, 1973
Goettl, et al.
1972
Shaw & Brown,
1974
Shaw & Brown ,
1974
Brown, et al .
1974
Brown, 1968
Brown &
Dalton, 1970
Cope, 1966
-------
Table 1. (Continued)
Organism
Bioassay Test
Method* Cong,**
Haraness
(mq/1 as Time
CaCOj)
O)
I
I-1
00
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Atlantic salmon,
Salmo salar
Atlantic salmon,
Salmo salar
Atlantic salmon,
Salmo salar
Brook trout,
Salvelinus fontinalis
Stoneroller,
Campostoma anomalum
Stoneroller,
Campostoma anomalum
Goldfish,
Carassius auratus
Goldfish,
Carassius auratus
Goldfish.
Carassius auratus
Goldfish.
Carassius auratus
Carp.
Cyprinus carpio
Carp,
Cyprinus carpio
Golden shiner,
Notemigonius chrysoleucas
FT
FT
FT
FT
FT
M
M
M
M
M
M
U
M
M
M
M
M
M
320
320
20
8-10
14
45
200
318
20
AO
40
40
53
55
36
72
48
96
96
96
96
96
96
96
24
24
24
96
96
24
Adjusted-
LC50 LCbO
(uq/il jaq/i.) fcetei. fence
1,100 720 Lloyd. 1961
270 155 Herbert & .
Vandyke. 1964
i48 i48 Sprague, 1964
125 89 Wilson, 1972
v.32 -v.32 Sprague &
Ramsey, 1965
100 100 McKim &
Benoit. 1971
290 290 Geckler. et
al. 1976
340*** 340
36 20
2.700 1.270
2,900 1.360
Geckler, et
al. 1976
Pickering &
Henderson, 1966
Cairns, et al.
1978
Cairns, et al.
1978
1.510 708 Cairns, et al.
1978
810 575 Rehwoldt. et
al. 1971
800 568 Rehwoldt, et
al. 1972
330 155 Cairns, et al.
1978
-------
Table 1. (Continued)
Organism
Bioassay Test
5l£.tti2S*_ Cone.**
Hardness
(inn/1 as Time
Golden shiner,
Notemigonius chrysoleucas
Golden shiner,
Notemigonius chrysoleucas
Striped shiner,
Notropis chrysocephalus
Striped shiner,
Notropis chrysocephalus
Striped shiner,
Notropis chrysocephalus
Striped shiner,
tp Notropis chrysocephalus
1
(X> Striped shiner,
Notropis chrysocephalus
Striped shiner,
Notropis chrysocephalus
Striped shiner,
Notropis chrysocephalus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow, ~~
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
S
S
FT
FT
FT
FT
FT
FT
FT
S
S
S
S
S
S
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
36
36
200
200
314
303
318
316
274
324
318
318
314
318
324
24
24
96
96
96
96
96
96
96
24
24
24
24
24
24
Adjusted
LC50 LCbO
(ug/l> liJU/i) Reteifence
230 108
270 127
790 790
1,900 1,900
720*** 720
1,100*** 1.100
630*** 630
680*** 680
690*** 690
430*** 201
420*** 197
300*** 141
320*** 150
330*** 155
420*** 197
Cairns, et al.
1978
Cairns, et al.
1978
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
-------
Table 1. (Continued)
Hardness
Adjusted
CD
I
N)
O
Organism
Bluntnose minnow,
Plmephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
UlunLno.se minnow,
Pimephales notatus
assay
ago*
S
s
s
s
s
s
FT
FT
FT
FT
FT
FT
FT
S
S
Test
ConcA**
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
(mo/ 1 as
CaCO-j)
310
296
308
314
315
200
200
200
200
200
200
314
303
303
303
Time
Hill)
24
24
24
24
24
24
96
96
96
96
96
96
96
96
96
LC50 J
Jiia/iL
330***
370***
340***
400***
390***
150***
290
260
260
280
340
390
620***
450***
470***
(uq/ll
145
173
159
187
183
70
290
260
260
280
340
390
620
320
334
Beteifcnce
Geckler,
1976
Geckler,
1976
Geckler,
1976
Geckler,
1976
Geckler,
1976
Geckler,
1976
Geckler,
1976
Geckler .
1976
Geckler,
1976
Geckler,
1976
Geckler,
1976
Geckler,
1976
Geckler,
1976
Geckler,
1976
Geckler,
1976
et al
et al
et al
et al
et al
et al
et al
et al
et al
et al
et al
et al
et al
et al
et al
-------
Table 1. (Continued)
ro
i
to
H
Organism
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow.
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Bluntnose minnow,
Pimephales notatus
Fathead minnow.
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
HiOdssay
Method *
FT
FT
FT
FT
FT
FT
FT
FT
FT
S
S
S
S
S
FT
Test
Cone .**
M
M
M
M
M
M
M
M
M
U
U
U
U
U
M
Hardness
(mq/ 1 as
CaCO-j)
318
316
194
194
194
202
202
200
45
360
20
400
20
200
200
Time
(nrs)
96
96
96
96
96
96
96
96
96
96
96
96
96
96
96
LC50
Juq/1)
480***
570***
210
220
270
460
490
790***
200***
1.450
23
1,400
50
430
470
Adjusted
LCbO
(uq/i)
480
570
210
220
270
460
490
790
200
793
13
765
27
235
470
Pimephales promelas
Ketet fence
Geckler, et al.
1976
Geckler, et al.
1976
Horning &
Neiheisel, In press
Horning &
Neiheisel. In press
Horning &
Neiheisel. In press
Pickering, et al.
1977
Pickering, et al.
1977
Andrew, 1976
Andrew. 1976
Pickering &
Henderson, 1966
Pickering &
Henderson, 1966
Tarzwell &;'.
Henderson, 1960
Tarzwell &
Henderson, 1960
Mount, 1968
Stephan, 1969
-------
Table 1. (Continued)
m
I
to
10
Organism
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
iassay
£00*
S
FT
S
S
S
S
S
S
S
S
S
S
S
S
S
Hardness
Test (mq/ 1 as
Cone. ** CaCO.)
U
M
M
M
M
M
M
M
M
M
M
M
M
M
M
j-
31
31
280
244
212
260
224
228
150
310
294
308
280
280
120
Adjusted
Time
ilii§)
96
96
96
96
96
96
96
96
96
96
96
96
96
96
96
LC50 LCbO
(UQ/11 (uq/J.1
84 46
75
750***
750***
600***
820***
980***
830***
930***
870***
730***
840***
770***
630***
690***
75
533
533
426
582
696
589
660
618
518
596
547
447
490
Keter fence
Mount &
Stephan
Mount &
Stephan
Brungs ,
1976
Brungs ,
1976
Brungs ,
1976
Brungs ,
1976
Brungs ,
1976
Brungs ,
1976
Brungs ,
1976
Brungs ,
1976
Brungs ,
1976
Brungs ,
1976
Brungs ,
1976
Brungs ,
1976
Brungs ,
1976
, 1969
, 1969
et al
et al
et al
et al
et al
et al
et al
et al
et al
et al
et al
et al
et al
-------
Table
(Continued)
03
I
NJ
U)
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Bioassay
Method *_
S
FT
FT
FT
FT
FT
S
FT
S
FT
FT
FT
FT
TtJSt
Cone. **
M
M
M
M
M
M
M
M
M
M
M
M
M
Haianess
(mq/1 as
CaC00)
298
200
200
314
303
318
318
316
316
274
48
45
46
Time
(fas)
96
96
96
96
96
96
96
96
96
96
96
96
96
LCbO
(uq/1)
860***
440
490
540***
1 , 000***
670***
740***
865***
1,300***
610***
114
121
88.5
Adjusted
LC^O
611
440
490
540
1,000
670
525
865
923
610
114
121
88.5
fcetfcreiice
Brungs, et al.
1976
Geckler, et al
1976
Geckler, et al
1976
Geckler, et al
1976
Geckler, et al
1976
Geckler, et al
1976
Geckler, et al
1976
Geckler, et al
1976
Geckler, et al
1976
Geckler, et al
1976
Lind, et al.
Manuscript
Lind, et al.
Manuscript
Lind, et al.
Manuscript
-------
Table 1. (Continued)
Bioassa;
Organism Method*
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
to
1 Fathead minnow,
jy Pimephales promelas
Fathead minnow,
Pimephales promelas
Blacknose dace,
Rhinichthys atratulua
Creek chub ,
Semotilus atromaculatus
Creek chub,
Semotilus atromaculatus
Creek chub,
Semotilus atromaculatus
Brown bullhead,
Ictalurus nebulosus
Brown bullhead,
Ictalurus nebulosus
Brown bullhead,
Ictalurus nebulosus
Channel catfish,
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
S
y Test
Cone.**
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
Hardness
(mq/i as
CaCO,)
J
30
37
87
73
84
66
117
121
200
200
316
274
200
200
303
36
Time
(his)
96
96
96
96
96
96
96
96
96
96
96
96
96
96
96
24
LCSO
436
516
1.586
1.129
550
1,001
2,050
2.336
320
310
1.050***
340***
180
540
570***
3,700
Adjusted
LCbO
(uq/il kete-rence
436 Lind, et al.
Manuscript
516
1.586
1,129
550
1.101
2.050
2,336
320
310
1,050
340
180
540
570
1,730
Lind, et al
Manuscript
Lind, et al
Manuscript
Lind, et al
Manuscript
Lind, et al
Manuscript
Lind, et al
Manuscript
Lind. et al
Manuscript
Lind, et al
Manuscript
Geckler, et
1976
Geckler, et
1976
Geckler, et
1976
Geckler, et
1976
Brungs , et
1973
Geckler, et
1976
Geckler, et
1976
Cairns, et
al
al
al
al
al.
al
al
al.
Ictalurus punctatus
1978
-------
Table 1. (Continued)
tfl
I
to
cn
Organism
Channel catfish,
Ictalurus punctatus
Channel catfish,
Iccalurus punctatus
Banded killifish,
Fundulus diaphanus
Banded killifish,
Fundulus diaphanus
Flagfish,
Jordanella floridae
Guppy,
Poecilia reticulata
Guppy.
Poecilia reticulata
Guppy,
Poecilia reticulata
Guppy,
Poecilia reticulata
White perch,
Morone americanus
White perch,
Morone americanus
Striped bass,
Morone saxatilis
Striped bass,
Morone saxatilis
Striped bass,
Morone saxatilis
Striped bass (larva),
Morone saxatilis
Striped bass (larva),
Morone saxatilis
Hardness
Bioassay Test (mq/l as Time
Methpd*_ Cone.** CaCO.) ihre)
S M 36 24
S
S
S
FT
S
S
FT
FT
S
S
S
S
S
S
M
M
M
M
U
U
M
M
M
M
M
M
U
U
36
53
55
350-375
20
76
87.5
67.2
53
55
53
55
35
68.4
68.4
24
96
96
96
96
24
96
96
96
96
96
96
96
96
96
LC50
juq/i)
2.600
3.100
860
840
1.270
36
1,250
112
138
6.200
6,400
4,300
4,000
620
50
100
Adjusted
LCbO
(uq/il
1.220
1,450
611
596
1.270
20
450
112
138
4.400
4,540
3,050
2,840
339
Reference
Cairns, et al.
1978
Cairns, et al.
1978
Rehwoldt. et
al. 1971
Rehwoldt, et
al. 1972
Fogels &
Sprague. 1977
Pickering &
Henderson, 1966
Minicucci, 1971
Chynoweth, et
al. 1976
Chynoweth, et
al. 1976
Rehwoldt. et
al. 1971
Rehwoldt, et
al. 1972
Rehwoldt. et
al. 1971
Rehwoldt, et
al. 1972
Wellborn, 1969
27 Hughes, 1973
55 Hughes. 1971
-------
Table 1 (Continued)
Bioassay
Organism Method
03
1
ro
ON
Striped bass (f ingerling) ,
Morone saxitilis
Rainbow darter,
Etheostoma caeruleum
Rainbow darter,
Etheostoma caeruleum
Rainbow darter,
Etheostoma caeruleum
Rainbow darter,
Etheostoma caeruleum
Johnny darter,
Etheostoma nigrum
Orangethroat darter.
Etheostoma spectabile
Orangethroat darter,
Etheostoma spectabile
Orangethroat darter,
Etheostoma spectabile
Orangethroat darter,
Etheostoma spectabile
Orangethroat darter,
Etheostoma spectabile
Rock bass,
Ambloplites reipestris
Pumpkinseed.
Lepomis gibbosus
Pumpkinseed,
Lepomis gibbosus
Bluegill,
Lepomis macrochirus
Bluegill.
S
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
S
S
FT
S
Test
Cone.**
U
M
M
M
M
M
M
M
M
M
M
M
_
_
M
M
Hardness
(mq/i aS
CaCO,)
37
68.4
200
318
316
274
316
200
303
318
316
274
24
53
55
45
36
Time
(hrs)
96
96
96
96
96
96
96
96
96
96
96
-
96
96
96
96
24
LC50
juq/il
150
320
630***
610***
500***
610***
850
590***
520***
760***
700***
1.432
2,400
2.700
1.100
2.590
Adjusted
U.-JD
fuq/11 Reference
82
320
630
610
500
610
850
590
620
760
700
1.432
1.700
1.920 .
1,100
1.210
Hughes. 1971
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al .
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Lind, et al.
Manuscript
Rehwoldt, et al
1971
Rehwoldt, et al
1972
Benoit, 1975
Cairns, et al.
Lepomis macrochirus
1978
-------
Table 1. (Continued)
Bioassay Test
Method* Cone**
Hardness
(mq/l as Time
CaCO-j)
Adjusted
LC50 LCbO
(uq/il (aq/il Reretence
03
I
to
Bluegill,
Lepomis macrochirus
Bluegill.
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Bluegill.
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
FT
FT
FT
FT
S
S
S
S
S
FT
M
M
M
M
U
U
U
U
36
36
316
318
200
200
43
20
360
45-47
101
35
24
24
48
96
96
96
96
96
96
96
96
96
96
2,500 1,170
3,820 1.790
2,800 1,610
4.300*** 4.300
4.250*** 4,250
8.300 8.300
10.000 10.000
1,250 890
660 360
10.200 5.580
740
Cairns, et al.
1978
Cairns, et al.
1978
Cope, 1966
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Geckler, et al.
1976
Patrick, et al.
1968
Pickering &
Henderson, 1966
Pickering & -
Henderson, 1966
525 Trama, 1954
Turnbull, et al.
1954
1,800 980
2.400 1,850 O'Hara. 1971
* S = static, FT = flow-through, R = renewal
'"' U = unmeasured, M = measured
***Results are for dissolved copper.
-------
Table 1. (Continued)
Organism
Bioassay
Method
Test
Cone.
Hardness
(mq/l as Time
CaCO,) (hrs)
j ^L""
LC50
Juq/ii
Adjusted
LCbO
fteterence
Adjusted LC50 vs. hardness
Chinook salmon: slope = 0.72, intercept = 0.83. r = 0.88, p = 0.01, N = 9
Cutthroat trout: slope = 0.88, intercept = 0.79, r = 0.78, p = 0.01, N = 9
Rainbow trout: slope = 0.75, intercept - 1.05, r - 0.69, p - 0.01, N = 56
Fathead minnow: slope = 0.77, intercept =2.27, r » 0.66, p - 0.01, N = 46
Bluegill: slope = 0.84, intercept = 3.86, r = 0.83, p = 0.01, N - 14
Geometric mean slope =0.79
Mean intercept for 29 fish species =2.48
to
I Adjusted mean intercept = 2.48 - ln(3.9) = 1.12
" Final Fish Acute Value = e<0-72-In(hardness + 0.83) fr(m chlnook salmon_
-------
Table 2. Freshwater invertebrate acute values for copper
Hardness
Adjusted
Bioassay
Organism Method*
Annelid worm, S
Aeolosoma headleyi
Annelid worm,
Aeolosoma headleyi
Annelid worm,
Aeolosoma headleyi
Annelid worm,
Aeolosoma headleyi
Annelid worm,
Aeolosoma headleyi
Worm,
03 Limnodrilus hoffmeisteri
1
^ Worm.
Nais sp.
Snail (egg) ,
Amnicola sp.
Snail (adult) ,
Amnicola sp.
Snail,
Campeloma decisum
Snail,
Goniobasis livescens
Snail,
Gyraulus circumstriatris
Snail ,
Lymnea emargtnata
Snail,
Nitrocris sp.
Snail,
Nitrocris sp.
S
S
S
S
S
S
S
S
FT
S
S
S
S
S
Test (m
-------
TabJ.e 2. (Continued)
03
1
OJ
Organism
Snail,
Nitrocris sp.
Snail,
Nitrocris sp.
Snail,
Nitrocris so.
Snail,
Physa heterostropha
Snail,
Physa integra
Cladoceran,
Daphnia hyalina
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Bioaesay
Method*
S
S
S
S.
FT
S
S
R
R
S
S
S
S
Test
Cone**
M
M
M
U
M
U
U
U
U
U
U
U
U
Baroness
(mq/1 as
CaCO,)
y
45
45
45
100
35-55
66
226
45.3
45.3
99
99
0.120
_
Time
inrs):
48
48
48
96
96
48
48
48
48
48
48
48-64
48
LCiO
(uq/ll
1,000
300
210
69
39
5
/
200
9.8
60
65
30
12.7
100
Adjusted
LCt>0
(uq/1)
470
142
99
85
39
4.2
169
8.3
51
55
25
10.8
85
fcetereiice
Cairns, et al.
1978
Cairns, et al.
1978
Cairns, et al.
1978
Wurtz &
Bridges, 1961
Arthur &
Leonard, 1970
Baudouin &
Scoppa, 1974
Cabejszek &
Stasiak, 1960
Biesinger &
Christensen, 1972
Biesinger &
Christensen. 1972
Adema &
Degroot-Vaii Zijl,
1972
Adema &
Degroot-Van Zijl,
1972
Anderson, 1948
Bringraann &
Kuhn, 1959
-------
Table 2. (Continued)
W
Ui
H
Organism
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulicarta
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Bioassay
Method*
S
s
S
s
s
s
s
s
s
s
R
R
R
R
R
Test
Cone.**
U
U
U
U
U
U
U
U
U
U
M
M
M
M
M
Haianess
(mq/1 as
CaCO,)
3
45
45
45
45
45
45
45
45
45
45
48
48
48
44
31
Time
li>is)
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
Adjusted
LCbO LCbO
-------
. k
Table 2. (Continued)
BJ
I
to
to
Organism
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicarta
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Hardness
Bioassay Test
Me
Adjusted
assay
hod*_
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
Test
Cone.**
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
(mq/l as
CaCO,)
3
29
28
v-88
100
86
82
84
16
151
96
26
84
92
106
45
95
Time
Jhra)
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
LC50
55.3
53.3
97.2
199
627
213
165
35.5
78.8
113
76.4
84.7
184
240
9.3
17.8
LCbO
luq/1)
60.8
58.6
107
219
690
234
182
39.1
86.7
124
84
93.2
202
294
10.2
19.6
Reference
Lind, et al,
Manuscript
Lind, et al ,
Manuscript
Lind, et al
Manuscript
Lind, et al,
Manuscript
Lind, et al.
Manuscript
Lind, et al.
Manuscript
Lind, et al,
Manuscript
Lind, et al
Manuscript
Lind, et al
Manuscript
Lind, et al
Manuscript
Lind, et al,
Manuscript
Lind, et al,
Manuscript
Lind, et al,
Manuscript
Lind, et al
Manuscript
Lind, et al
Manuscript
Lind, et al,
Manuscript
-------
Tabie 2. (Continued)
Organism
Cladoceran,
Daphnia pulicaria
Cladoceran ,
Daphnia pulicaria
Cladoceran,
Daphnia pulicaria
Cladoceran,
Paphnia pulicaria
Cladoceran,
Daphnia pulicaria
Copepod,
Cyclops abyssorum
CO
1 Copepod,
£j Eudiaptomus padanus
Scud,
Gammarus lacustris
Scud,
Gammarus pseudolimnea
Scud,
Gammarus sp.
Crayfish,
Orconectes rusticus
Mayfly,
Ephemerella subvaria
Stonefly,
Acroneuria lycorias
Damself ly ,
Unidentified
Midge .
Chironomus sp.
Caddisfly,
Unidentified
Bioassay
Method*
R
R
R
R
R
S
S
S
FT
S
FT
S
S
S
S
S
Test
Cone.**
M
M
M
M
M
U
V
U
M
M
M
M
M
M
M
M
Hardness
(mq/i as
CaCO,)
145
245
95
145
245
66
66
35-55
50
100-125
40
40
50
50
50
Time
ihta)
48
48
48
48
48
48
48
96
96
96
96
48
96
96
96
96
LC50
fuq/11
23.7
27.3
25.2
25 . 1
25.1
2.500
500
1.500
20
910
3.000
320
8.300
4,600
30
6,200
Adjusted
LCiO
(ug/1)
26.1
30.0
27.7
27.6
27.6
2.120
424
1,270
20
1,000
3.000
151
9.130
5,060
33
6,820
Reterence
Lind, et al.
Manuscript
Lind, et al .
Manuscript
Lind, et al.
Manuscript
Lind, et al.
Manuscript
Lind, et al.
Manuscript
Baudouin &
Scoppa, 197,4
Baudouin &
Scoppa, 1974
Nebeker &
Gaufin. 1964
F
Arthur &
Leonard, 1970
Rehwoldt, et al
1973
Hubshman 1967
Warnick &
Bell. 1969
Warnick &
Bell, 1969
Rehwoldt, et al
1973
Rehwoldt , et
1973
Rehwoldt, et
1973
al
al
-------
Tatle 2. (Continued)
Bioassay
Organism Method*
Rotifer,
Philodina acuticornis
Rotifer,
Philodina acuticornis
Rotifer,
Philodina acuticornis
Rotifer,
Philodina acuticornis
Rotifer.
Philodina acuticornis
Rotifer,
Philodina acuticornis
W
1 Rotifer,
U) Philodina acuticornis
Rotifer,
Philodina acutitomis
S
S
S
S
S
S
R
R
* S = static, FT = flow- through,
** U = unmeasured, M = measured
Adjusted LC50 vs. hardness
Daphnia magna : slope
Daphnia pulicaria: slope
Hardness
Test (mq/i as Time
Cone.** CaCO,) (hrs)
J
M 45
M 45
M 45
M 45
M 45
M 40
U 25
U 8].
R = renewal
= 0.75, intercept
= 1.03, intercept
48
48
48
48
48
96
96
96
= 0.19, r
= 0.11. r
LCSO
(uq/il
1,300
1.200
1,130
1,000
950
160
700
1.100
= 0.39. not
- 0.51. p =
Adjusted
LCbO
1,430
1.320
1,240
1.100
1,050
176
593
932
Fniterence
Cairns, et al .
1978
Cairns, et al.
1978
Cairns, et al .
1978
Cairns, et al.
1978
Cairns, et al.
1978
Buikema, et al.
1977
Buikema, et al .
1974
Buikema, et al.
1974
significant. N = 11
0.05. N » 19
Geometric mean slope = 0.88
Mean intercept for 26 species =2.01
Adjusted mean intercept = 2.01 - ln(21) = -1.03
Final Invertebrate Acute Value = e(0.88-In(hardness) - 1.03)
-------
Table 3. Freshwater.fish chronic values for copper
03
I
U)
LH
Organism
Rainbow trout:,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Brown trout,
Salmo trutta
Brook trout,
Salvelinus fontinalis
Brook trout,
Salvelinus fontinalis
Brook trout,
Salvelinus fontinalis
Brook trout,
Salvelinus fontinalis
Lake trout,
Salvelinus namaycush
Northern pike,
Esox lucius
Bluntnose minnow.
Pimephales notatus
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pinicphnlcs promelas
Teat*
E-L
E-L
E-L
LC
E-L
E-L
E-L
E-L
E-L
LC
LC
LC
LC
LC
E-L
Limits
fuq/ll
12-19
11.4-31.7
22.0-43.2
9.5-17.4
22.3-43.5
3-5
5-8
22.0-42.3
34.9-104.4
4.3-18
14.5-33.
106-18.4
24-32
57-100
13.1-26.2
Chronic
Value
(uq/11
7.5
9.5
15.4
12.9
15.6
1.9
3.2
15.3
30.2
8.8
21.9
14.0
27.7
75.4 .
9.3
Hardness
(mq/1 as
CaCOJ
45.4
45.4
45
45.4
37.5
187
45.4
45,4
194
198
30
200
274
45
Reference
Goettl, et al. 1974
McKim, et al. In press
McKim, et al; In press
McKim & Benoit, 1971
McKim, et al. In press
Sauter, et al. 1976
Sauter, et al. 1976
McKim, et al. In press
McKim, et al. In press
Horning & Neiheisel. In
press
Mount, 1968
Mount & Stephan, 1969
Pickering, et al. 1977
Brungs, et al. 1976
Lind, et al. Manuscript
-------
Table 3. (Continued)
CO
I
u>
Chronic Hardness
Limits Value (mq/1 as
Organism Teat* (uq/l> (uq/1) CaCO.j)
White sucker, E-L 12.9-33.8 10,4 45.4
Catostomus commersoni
Channel catfish, E-L 12-18 7.3 36
IcCalurus punctatus
Channel catfish, E-L 13-19 7.9 186
Ictalurus punctatus
Bluegill, LC 21-40 29.0 45
Lepomis tnacrochirus
Walleye, E-L 13-21 16.5 35
Scizostedion vitreum
Reference
McKim, et al. In pre
Sauter, et al. 1976
Sauter, et al. 1976
Benoit. 1975
Saucer, et al. 1976
* E-L = embryo-larvaI, LC = life cycle or partial life cycle
Fish chronic value vs. hardness
Fathead minnow: slope = 0.65, intercept = 0.071, r = 0.82, not significant, N = 5
Geometric mean slope =0.65 (only value available)
Mean intercept for 11 fish species » -0.042
Adjusted mean intercept *=-0.042 -ln(6.7) = -1.94
Final Fish Chronic Value = e(0-65-In(hardness) -1.94)
-------
Table 3. (Continued)
Application Factor Values
CO
1
Ul
Species
Brook trout ,
Salvelinus fontinalis
Bluntnose minnow,
Pimephales notatus
Fathead minnow.
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Bluegill,
Lepomis macrochirus
96-hr LC50
(PR/D
100
230
470
75
790
475
1.100
MATC
9.5-17.4
4.3-18
14.5-33
10.6-18.4
57-100
24-32
21-40
AF
0.13
0.038
0.046
0.19
0.096
0.058
0.026
Reference
McKim & Benoit; 1971
Horning & Neiheisel, In press
Mount, 1968
Mount & Stephan, 1969
Brungs, et al. 1976
Pickering, et al. 1977
Benoit, 1975
Geometric mean AF = 0.067
-------
Table 4. Freshwater invertebrate chronic values for copper
03
1
u>
00
Organism
Snail.
Campeloma decisum
Snail,
Physa Integra
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia pulex
Cladoceran,
Daphula parvula
Cladoceran,
Daphnia ambigua
Amphipod ,
Gammarus pseudolimnaeus
Teat*
LC
LC
LC
LC
LC
LC
LC
LC
LC
LC
LC
Limits
(uq/11
8-14,8
8-14.8
22-35
20-40
20-40
20-40
40-60
40-60
40-60
40-60
4.6-8
Chronic
Value
(uq/1)
10.9
10,9
27.7
28.2
28.2
28.2
49.0
49.0
49.0
49.0
6.1
Hardness
(mq/1 as
CaCO,)
45
45
45.3
145
145
145
145
145
145
145
45
Reference
Arthur
Arthur
& Leonard, 1970
& Leonard, 1970
Biesinger & Christensen
1972
Winner
Winner
Winner
Winner
Winner
Winner
Winner
Arthur
, et al. 1977
, et al. 1977
, et al. 1977
& Farrell, 1976
& Farrell, 1976
f, Farrell, 1976
& Farrell, 1976
& Leonard, 1970
* LC = life cycle or partial life cycle
Invertebrate chronic value vs. hardness
No hardness relationship could be derived for any invertebrate species.
Slope = 0.65 from fish chronic values.
Mean intercept for 7 invertebrate species = 0.21
Adjusted mean intercept = 0.21 - ln(5.1) = -1.42
Final Invertebrate Chronic Value = e(0.65-In(hardness) -1.42)
-------
Table 5. Freshwater plant effects for copper
Concentration
Orqanism Effect (uq/1)
03
1
co
ID
Alga, 75% growth
Anabaena flos-aqua inhibition
Alga, Growth
Anabaena variabilis inhibition
Alga, Growth
Anacystis nidulans inhibition
Alga, Growth
Chlamydomonas sp. reduction
Alga, Lag in
Chlorella pyrenoidosa growth
Alga, Growth
Chlorella pyrenoidosa inhibition
Alga, Lag in
Chlorella regularis growth
Alga, Photosynthesis
Chlorella sp. inhibited
Alga, Growth
Chlorella vulgaris inhibition
Alga, EC50 growth,
Chlorella vulgaris 33 days
Alga, 507. growth
Chlorella vulgaris reduction
Alga , Growth
Cyclotella meneghiniana reduction
Alga, Growth
Eudorina californica inhibition
Alga, 407. growth
Scenedesmus acuminatus reduction
Alga, Threshold
Scenedesmus guadricauda toxicity
Alga, Growth
Scenedesmus quadricauda reduction
200
100
100
8,000
1
100
20
6.3
200
180
100-200
8,000
5,000
300
150
8,000
Reference
Young & Lisk, 1972
Young & Lisk, 1972
Young & Lisk. 1972
Cairns, et al. 1978
Steeman-Nielsen & Wium-Andersen ,
1970
Steeman-Nielsen & Kamp-Nielsen, 1970
Sakaguchi, et al. 1977
Gachter, et al. 1973
Young & Lisk, 1972
Rosko & Rachlin, 1977
Stokes & Hutchinson, 1976
Cairns, et al. 1978
Young & Lisk, 1972
Stokes & Hutchinson, 1976
Bringman & Kuhn . 1959
Cairns, et al. 1978
-------
Table 5. (Continued)
w
1
o
Organism
Algae,
Mixed culture
Blue green algae,
Mixed culture
Diatom,
Nitzschia linearis
Diatom,
Nitzschia palea
Duckweed,
Lemna minor
Eurasian watermilfoil,
Myriophyllum spicatum
Green alga,
Selanastrum
capriconutum
Concentration
Effect (uq/i)
Significant 5
reduction in
photosynthesis
50% reduction in 25
phosotynthesis
TLM-120 hr 795-815
Complete growth 5
inhibition
EC50, 7 day 119
50% root weight 250
reduction
Growth 50
reduction
Reference
Elder & Home, 1978
Steeman-Nielsen & Bruun-Laursen,
1976
Patrick, et al. 1968
Steeman-Nielsen & Wium-Anderson,
1970
Walbridge, 1977
Stanley, 1974
Bartlett. et al. , 1974
Final plant value - 1 pg/1
-------
Organism
Table 6. Freshwater residues for copper
Bioconcentration Factor
Alga,
Chlorella regularis
Stonefly.
Pteronarcys californica
Fathead minnow (larva),
Pimephales promelas
2,000
203
290
Time
(days)
rcelerence
20 hrs Sakaguchi, et al. 1977
14 days Nehring, 1976
30 days Lind, et al.,
Manuscript
Geometric mean bioconcentration factor for all species = 490
03
-------
Table ^ ' Other freshwater data for copper
Organism
Test
Duration Effect
Result
(ug/11 Reference
Cladoceran,
Daphnia ambigua
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Q) Cladoceran,
1 Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia parvula
Cladoceran,
Daphnia parvula
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex
72 hrs
life
cycle
life
cycle
life
cycle
72 hrs
72 hrs
72 hrs
72 hrs
72 hrs
72 hrs
29 hrs
24 hrs
72 hrs
72 hrs
72 hrs
72 hrs
LC50
Reduced number of
young produced
Reduced number of
young produced
Reduced number of
young produced
LC50
LC50 .
LC50
LC50
LC50
LC50
Median survival time
LC50
LC50
LC50
LC50
LC50
^^»l^B*M^MB
67.7
10
10
10
86.5
88.8
85
81.5
81.4
85.3
12.7
80
57
72
54
86
Winner
Winner,
Winner ,
Adema £
1972
Winner
'Winner
Winner
. Winner
Winner
Winner
Andrew ,
& Farrell, 1976
et al. 1977
et al. 1977
, DeGroot Van Zijl,
& Farrell, 1976
& Farrell, 1976
& Farrell, 1976
& Farrell, 1976
b Farrell, 1976
& Parrell, 1976
et al. 1977
Bringman & Kuhn, 1977
Winner
Winner
, Winner
, Winner
& Farrell, 1976
6 Farrell, 1976
& Farrell, 1976
6 Farrell, 1976
-------
Table 7. (Continued)
Organism
Mayfly,
Ephemerella grandis
Stonefly,
Pteronarcys califomica
Caddisfly,
Hydropsyche betteni
Crayfish,
Orconectes rusticus
Coho salmon,
Oncorhynchus kisutch.
Coho salmon,
_ Oncorhynchus kisutch
03
4* Sockeye salmon,
U) Oncorhynchus nerka
Chinook salmon,
Oncorhynchus
tshawytscha
Chinook salmon,
Oncorhynchus
Ishawytscha
Chinook salmon
(alevin) ,
Oncorhynchus
tshawytscha
Chinook salmon
(alevin) ,
Oncorhynchus
tshawytscha
Chinook salmon
(swim-up) ,
Oncorhynchus
tshawytscha
Test
Duration
14 days
14 days
14 days
17 days
96 hrs
30 days
24 hrs
5 days
26 days
200 hrs
200 hrs
200 hrs
Effect
LC50
LC50
507. survival
Survival of newly
hatched young
Reduced survival on
transfer to seawater
LC50
Significant change in
corticosteroid (stress)
LC50
Reduced survival and
growth of sac fry
LC50
LC10
LC50
Result
(uq/11
180-200
10.100-
13.900
32,000
125
30
360
64
178
21
20
15
19
Reference
Nehring, 1976
Nehring, 1976
Warnick & Bell. 1969
jllubshman, 1967
_
Lorz & McPherson,
Holland, et al. .
Donaldson & Dye,
Holland, et al.
1976
1960
1975
1960
Hazel & Meith, 1970
Chapman, In press
Chapman, In press
Chapman, In press
-------
Table 7. (Continued)
Organism
Test
Duration Ertect
Resuit
(ug/i) Retereiicfe
Chinook salmon
(swim-up),
Oncorhynchus
200 hrs LC10
14
Chapman, In press
tshawytscha
Chinook salmon (parr) ,
Oncorhynchus
tshawytscha~
Chinook salmon (parr) .
Oncorhynchus
tshawytscha~
Chinook salmon
(smolt) ,
Oncorhynchus
tshawytscha
to *
ji, Chinook salmon
£» (smolt) ,
Oncorhynchus
tshawytscha~
Rainbow trout ,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout (alevin) ,
Salmo gairdneri
Rainbow trout (alevin) ,
Salmo gairdneri
Rainbow trout
> * v
200 hrs
200 hrs
200 hrs
200 hrs
2 hrs
7 days
21 days
10 days
7 days
186 hrs
186 hrs
200 hrs
LC50
LC10
LC50
LC10
Depressed olfactory
response
LC50
Median period of
survival
Depressed feeding
rate and growth
Median period of
survival
LC50
LC10
LC50
30
17
26
18
8
44
40
75
44
26
19
17
Chapman, In press
Chapman, In press
Chapman, In press
Chapman, In press
Kara, et al. 1976
Lloyd. 1961
Grande, 1966
Lett, et al. 1976
Lloyd. 1961
Chapman, In press
Chapman, In press
Chapman, In press
(swim-up),
Salmo gairdneri
-------
Table 7. (Continued)
Organi sm
Rainbow trout
(swim-up) ,
Salmo gairdneri
Rainbow trout (parr) ,
Salmo gairdneri
Rainbow trout (parr) ,
Salmo gairdneri
Rainbow trout (smolt) ,
Salmo gairdneri
Rainbow trout (smolt) ,
Salmo gairdneri
Rainbow trout (smolt) ,
Salmo gairdneri
w
^ Rainbow trout (smolt) ,
m Salmo gairdneri
Rainbow trout (fry) ,
Salmo gairdneri
Atlantic salmon,
Salmo salar
Atlantic salmon,
Salmo salar
Atlantic salmon,
Salmo salar
Atlantic salmon,
Salmo salar
Brown trout ,
Salmo trutta
Brook trout,
Salvelinus fontinalis
Brook trout,
Test
Duration
200 hrs
200 hrs
200 hrs
200 hrs
200 hrs
>10 days
14 days
1 hr
7 days
7 days
21 days
27-38
hrs
21 days
24 hrs
21 days
LC10
LC50
LC10
LC50
LC10
Threshold LC50
LC50
Avoidance behavior
Incipient lethal
level
Incipient lethal
level
Median period of
survival
Median period of
survival
Median period of
survival
Significant change
in. cough rate
Significant changes in
Result
(Uq/lL
9
15
8
21
7
94
870
0.1
48
32
40
50
-v-45
9
23
Reference
Chapman, In press
Chapman, In press
Chapman, In press
Chapman, In press
Chapman, In press
Fogels & Sprague, 1977
Calamari & Marchetti, 1973
Foltnar, 1976
Sprague, 1964
Sprague & Ramsay, 1965
Grande, 1966
Zitko & Carson, 1976
Grande, 1966
Drummond, et al. 1973
McKim, et al . 1970
Salvelinus fontinalis
blood chemistry
-------
Table 7. (Continued)
CO
I
Organism
Test
Duration Effect
Result
(ug/ll
Reference
Brook trout,
Salvelinus fontinalis
Golden shiner.
Notemieonius
chrysoleucas
Channel catfish,
Ictalurus punctatus
Flagfish,
Jordanella floridae
Bluegill,
Lepomis macrochirus
337 days Significant changes in 17.4
blood chemistry
94 hrs Decrease blood 2,500
osmolarity
94 hrs Decreased blood 2,500
osmolarity
10 days LC50 680
24-36 Altered oxygen 300
hrs consumption rate
McKim. et al. 1970
Lewis & Lewis, 1971
Lewis & Lewis, 1971
Fogela & Sprague, 1977
O'Hara, 1971
-------
SALTWATER ORGANISMS
Acute Toxicity
Data for two saltwater fish species and two different life
history stages are available (Table 8). Adjusted 96-hour LC50
values range from 21 ug/1 for summer flounder embryos (Cardin et
al. 1978) to 278 ug/1 for the Florida pompano, (Birdsong, et al.
1971. Studies of the effects of salinity on copper toxicity to
adult Florida pompano indicate copper is more toxic at 10°/oo than
at 30°/oo (Birdsong, et al. 1971).
The species sensitivity factor of 3.7 applied to the geomet-
ric mean LC50 (69 ug/1) yields 19 ug/1 which is sufficient to pro-
tect the species reported in Table 8. This Final Fish Acute Value
is also low enough to encompass the tests of even longer duration.
For example, Cardin, et al. (1978) obtained an LC50 of 23 ug/1 for
summer flounder embryos exposed for 144 hours in a flow-through
system with measured concentrations (Table 13).
Saltwater invertebrate species are more sensitive to acute
copper poisoning than saltwater fishes (Table 9). The inverte-
brate data include investigations on three phyla: Annelida,
Mollusca, and Arthropoda (Crustacea). The adjusted LC50 values
ranged from 5 ug/1 for Acartia tonsa (Sosnowski, et al. 1979) to
407 ug/1 for the polychaete worm, Nereis diversicolor (Jones, et
al. 1976). Pesch and Morgan (1978) determined that the 96-hour
LC50 value for Neanthes arenaceodentata of 77 ug/1 in a flow-
through system increased to 200 ug/1 in the presence of a sandy
sediment. Jones, et al. (1976) indicated that Nereis diversicolor
exhibited a variable response to salinity over a range of 5 to
34°/oo with the greatest toxicity occurring at 5°/oo. The lowest
B-47
-------
reported copper acute toxicity for the bivalve molluscs was 33 '
ug/1 for the soft-shelled clam, Mya arenaria (Eisler, 1977), and
the highest was 108 ug/1 for the embryo of the American oyster
(Calabrese, et al. 1973). Eisler (1977) indicated that the copper
sensitivity of Mya arenaria varied according to the seasonal tem-
perature, with copper toxicity being at least 100 times greater at
summer temperatures (22°C) than at winter temperatures (4°C)
(Table 13). The crustaceans ranged in copper toxicity from the
most sensitive of all the saltwater animals tested, Acartia tonsa
at 5 ug/1 (Sosnowski, et al. 1979) to the least sensitive, larvae
of the shore crab Carcinus maenas (Connors, 1972). Sosnowski, et
al. (1979) showed that the sensitivity of field populations of
Acartia tonsa to copper was strongly correlated with population
density and food ration. Cultured A. tonsa manifested a reproduc-
ible toxicological response to copper through six generations
(Sosnowski and Gentile, 1978). Johnson and Gentile (1979) report-
ed that lobster larvae appear to be twice as sensitive to copper
as the adults.
When the geometric mean of 86 ug/1 is divided by the species
sensitivity factor (49), the result is 1.8 ug/1. The data base
(Table 9), contains a flow-through measured toxicity value of 5
ug/1 for Acartia tonsa. Using the recommended guideline procedure
of selecting the lower of these two values, the Final Invertebrate
Acute Value is 1.8 ug/l« All values reported in Table 9 are grea-
ter than 1.8 ug/1 indicating probable protection of 95 percent of
the invertebrate species.
B-48
-------
Since the Final Invertebrate Acute Value of 1.8 ug/1 is lower
than the Final Fish Acute Value of 19 v-g/1, the Final Acute Value
for saltwater aquatic life is 1.8 ug/1/.
Chronic Toxicity
There were no reported studies on the chronic toxicity of
copper to saltwater fishes.
The chronic toxicity of copper to mysid shrimp,,Mysidopsis
bahia, has been determined from the flow-through, life cycle expo-
sure of this species (Sosnowski and Gentile, 1979). Groups of 20
individuals were reared in each of five copper concentrations for
46 days at 20°C and 30°/oo salinity (Table 10). The biological
responses examined included time of appearance of first brood, the
number of spawns, and mean brood size and growth. The appearance
of eggs in the brood sac was delayed for 6 and 8 days at 77 ug/1
and 140 ug/1 respectively. Broods developing at 135 ug/1 never
matured and no spawns were observed at this concentration. The
number of spawns recorded at 77 ug/1 was significantly (P<0.05)
lower than at 38 ug/1. There were no statistically significant
differences in the number of spawns at control, 24 ug/1/ and 38
ug/1. Brood size was significantly (P<0.05) reduced at 77 ug/1 but
not at lower concentrations. No effects on growth were detected at
the copper concentrations tested. Based on reproductive data the
maximum copper concentration tested resulting in no observable ef-
fects is 38 ug/1. The chronic value, 54 ug/lf is the geometric
mean of the limits (38-77 ug/1). The chronic value, when divided
by the species sensitivity factor (5.1) results in a Final Inver-
tebrate Chronic Value of 11 ug/1. This concentration is higher
than the Final Acute Value (1.8 ug/1) based on the invertebrate
B-49
-------
invertebrate species. Apparently, this is because the chronic
data are for Mysidopsis bahia, one of the more resistant inver-
tebrate species to copper in acute toxicity tests (Table 9).
Plant Effects
The copper EC50 values (Effective Concentration to inhibit 50
percent photosynthesis or growth) are tabulated in Table 11 for
one species of macro-algae and eight species of micro-algae. Cop-
per inhibited the growth rate of Thalassiosiria pseudonana and
Scrippsiella faeroense at 5 ug/1. Therefore, the Final Plant
Value for copper is 5 ug/1 and since this is the lowest of the
chronic values, it becomes the Final Chronic Value.
Bioconcentration
Copper is an essential element in the respiratory pigments of
some saltwater invertebrate species, especially crustaceans.
Saltwater plants have enzymes containing copper which are neces-
sary for photosynthesis. However, copper is also bioconcentrated
in excess of any known needs by several saltwater species (Table
12). The highest bioconcentration for copper was obtained with
the bivalve molluscs. Shuster and Pringle (1969) found that the
American oyster could concentrate copper 28,208 times after a 20-
week continuous exposure to 50 ug/1. Even though the tissue of
the oyster became bluish-green in color, mortalities at this level
were only slightly higher than the controls. The polychaete worm,
Neanthes arenaceodentate, bioconcentrated copper 2,546 times
(Pesch and Morgan, 1978). In a series of measurements with algae
by Riley and Roth (1971), the highest reported concentration fac-
tor was 617 for Heteromastix longifillis.
B-50
-------
There is no Residue Limited Toxicant Concentration (RLTC) for
copper because no maximum permissible tissue concentration is
available. However, there have been instances recorded that oys-
ters have been unmarketable because of their green appearance due
to high copper content.
Miscellaneous
Exposures for longer than the standard 96-hour acute studies
have been recorded in Table 13. Most noteworthy are the mortality
values reported for the bay scallop, Argopecten irradians, by
Zaroogian (1978). At a flow-through exposure of 5 ug/1 or 10 ug/1
all scallops died within 119 or 112 days, respectively. Even
though several studies have been reported on the sub-lethal ef-
fects on survival, growth and reproduction, the signficance of
these effects have yet to be evaluated.
B-51
-------
CRITERION FORMULATION
Saltwater-Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures. All concentrations herein are expressed in terms of
copper.
Final Fish Acute Value = 19 ug/1
Final Invertebrate Acute Value = 1.8 ug/i
Final Acute Value = 1.8 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = 11 ug/1
Final Plant Value = 5.0 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 5.0 ug/1
0.44 x Final Acute Value = 0.79 ug/1
It is recognized that the copper criterion approaches the
concentrations of dissolved copper reported for saltwater. A
concentration of 1 ug/1 is common for copper in saltwater, but
copper can range over more than one order of magnitude. There is
evidence which indicates that, if copper is complexed by organic
compounds in saltwater, the toxicity of the metal can be greatly
reduced. As a consequence, it is not necessarily the total
concentration of copper in saltwater that determines the toxicity
to saltwater organisms but the form of the metal that is the toxic
component. However, it must be emphasized that any addition of
copper to saltwater above the criterion could exceed the chelation
capacity and render saltwater toxic.
B-52
-------
The maximum concentration of copper is the Final Acute Value
of 1.8 ug/1 and the 24-hour average concentration is 0.44 times
the Final Acute Value. No important adverse effects on saltwater
aquatic organisms have been reported to be caused by concentra-
tions lower than the 24-hour average concentration.
CRITERION: For copper the criterion to protect saltwater
aquatic life as derived using the Guidelines is 0.79 ug/1 as a
24-hour average and the concentration should not exceed 1.8 ug/1
at any time.
B-53
-------
Tabled. Marine fish acute values for copper
03
01
Organism
Florida pompano,
Trachinotus carolinus
Florida pompano,
Trachinotus carolinus
Florida pompano
Trachinotus carolinus
Summer flounder (embryo)
Parallchthys dentatus
Bioaseay
Method*
S
S
S
. s
Test
Cone.**
U
U
U
U
Time
(hrs)
96
96
96
96
Adjusted
LC50 LC50
(uq/ll luq/11
360 197
380 207
510 278
38 21
Heference
Birdsong, et al. 1971
Birdsong, et al. 1971
Birdsong, et al. 1971
Cardin, et al. 1978
* S = static
** U = unmeasured
Geometric mean of adjusted values = 69 yg/1
Mg/1
-------
Table 9. Marine invertebrate acute values for copper
CD
I
U1
en
Bioaeeay
Organism Method*
Polychaete worm, FT
Neanthes arenaceodentata
Polychaete worm,
Neanthes arenaceodentata
Polycheate worm,
Nereis diversicolor
Polychaece worm,
Nereis diversicolor
Polychaete worm,
Nereis diveriscolor
Polychaete worm,
Nereis diversicolor
Polychaete worm,
Phyllodoce maculata
American oyster (larva),
Crassostrea virginica
Black abalone,
Haliotis cracherodii
Red abalone,
Haliotis rufescens
Red abalone (larva) ,
Haliotis rufescens
Soft shelled clam,
Mya arenaria
Calanoid copepod,
Acartia tonsa
Calanoid copepod,
Acartia tonsa
Calanoid copepod,
Acartia tonsa
Calanoid copepod,
FT
S
S
S
S
S
S
S
S
S
S
FT
FT
FT
FT
Test
Cone . **
M
M
U
U
U
U
U
U
U
U
U
U
M
M
M
M
Time
(hrs)
96
96
96
96
96
96
96
48
96
96
48
96
72
72
72
72
LC50
(ug/11
77
200
200
445
480
410
120
128
50
65
114
39
26
29
13
45
Adjusted
LC50
(uq/1) keference
77
200
169
377
407
347
102
108
42
55
97
33
16
18
8
27
Pesch & Mi
Pesch & Mi
Jones, et
Jones, et
Jones, et
Jones, et
McLusky &
Calabrese
Martin, e'
Martin, e
Martin, ei
Eisler. . 1'
Sosnowski
Sosnowski
Sosnowski
Sosnowski
Acartia tonsa
-------
Table 9. (Continued)
CO
I
m
0\
Organism
Calanoid copepod,
Acartia tonsa
Calanoid copepod,
Acartia tonsa
Calanoid copepod,
Acartia tonsa
Calanoid copepod,
Acartia tonsa
Calanoid copepod,
Acartia tonsa
Mysid shrimp,
Mysidopsis bahia
Bioassay Test
Method* Cone.**
FT
FT
S
S
S
FT
American lobster (larva), S
Homarus americanus
Brown shrimp (larva), S
Crangon crangon
Shore crab (larva). S
Carcinus maenas
M
M
U
U
U
M
U
U
U
Time
ihrs)
72
72
96
96
96
96
96
48
48
Adjusted
LC50 LC50
lug/A.1 (uq/1) Heterence
73 45 Sosnowski, et al. 1979
9 5 Sosnowski. et al. 1979
17 14 Sosnowski & Gentile, 1978
55 47 Sosnowski & Gentile, 1978
31 26 Sosnowski & Gentile, 1978
195 195 Sosnowski & Gentile. 1979
48 41 Johnson & Gentile, 1979
330 120 Connor. 1972
600 218 Connor, 1972
* S = static, FT = flow-through
** U = unmeasured, M = measured
86
Geometric mean of adjusted values = 86 wg/1 .A = 1.8 yg/1
Lowest values from a flow-through test with measured concentration = 5 wg/1
-------
Table 10. Marine invertebrate chronic values for copper (Sosnowski & Gentile, 1979)
Organism
My aid shrimp,
Mysidopsis bahia
Teat*
LC
Limits
(ug/il
38-77
Chronic
Value
iug/Il
54
to
I
* LC = life cycle or partial life cycle ,,
Geometric mean of chronic values = 54 ug/1 ^ = 11 yg/1
5Tl
Lowest chronic value = 54 yg/1
-------
Table 11. Marine plant effects for copper
Concentration
Reference
CO
I
m
00
Alga, giant kelp,
Macrocystis pyrifera
Alga,
Thalassiosira
pseudonana
Alga.
Amphidinium carteri
Alga,
Olischodiscus luteus
Alga.
Skeletonema costatum
Alga.
Nitschia closterium
Alga.
Scrippsiella faeroense
Alga.
Prorocentrum micans
Alga,
Gymnodinium splendens
96-hr EC-50 100
photosynthesis
inactivation
72-hr EC-50 5
growth rate
14-day~EC-50 <50
growth rate
14- day EC-50 <50
growth rate
96- hr EC-50 10
growth rate
96- hr EC-50 33
growth rate
5-day EC-50 5
growth rate
5- day EC-50 10
growth rate
5-day EC-50 20
growth rate
Clendenning & North. 1959
Erickson. 1972
Erickson. et al. 1970
Erickson, et al. 1970
Jensen, et al. 1970
Rosko & Rachlin. 1975
Saifullah. 1978
Saifullah, 1978
Saifullah, 1978
Lowest plant value » 5 pg/1
-------
Tafcle 12 . Marine
Organism
Polychaete worm,
Cirriformia spirabracha
Polychaete worm,
Neanthes arenaceodentata
Polychaete worm,
Nereis diversicolor
Polychaete wrom,
Phyllodoce maculata
Bay scallop,
Argopecten irradians
Bay scallop,
Argopeccen irradians
American oyster,
Crassostrea virginica
American oyster,
Crassostrea virginica
Northern quahaug,
Mercenaria mercenaria
Soft shelled clam,
Mya arenaria
Mussel,
Mytilus edulis
Mussel ,
Mytilus edulis
Mussel ,
Mytilus edulis
Mussel,
Mytilus galloprovincialis
Alga,
residues for copper
Bioconcentration Factor
250*
2,546*
203*
1,746*
3,310
4,155
28,208
20,688
88
3,300
208
108
90
800
153*
(day;
24
28
24
21
112
112
140
140
70
35
112
112
14
25
25
Dunaliella primolecta
Keterence
Milanovich, et al. 1976
Pesch & Morgan, 1978
Jones, et al. 1976
McLusky & Phillips, 1975
Zaroogian, 1978
Zaroogian, 1978
Shuscer & Pringle, 1969
Shuster & Pringle, 1969
Shuster & Pringle, 1968
Shuster & Pringle, 1968
Zaroogian, 1978
Zaroogian, 1978
Phillips, 1976
Majori & Petronio, 1973
Riley & Roth. 1971
-------
CD
I
Table 12. (Continued)
Organism Bioconcentration Fact
Alga. 168*
Dunaliella tertiolecta
Alga,
Chlamydomonas sp .
Alga,
Chlorella salina
Alga,
Stichococcus bacillaris
Alga,
Hemiselmis virescens
Alga,
Hemiselmis brunescens
Alga,
Olisthodiscus luteus
Alga ,
Asterionella japonica
Alga,
Phaeodactylum tricomutum
Alga,
Monochrysis lutheri
Alga,
Pseudopedinella pyriformis
Alga,
Heteromastix longifillis
Alga,
Micromonas squaraata
Alga,
Tetraselmis tetrathele
135*
74*
156*
273*
553*
182*
309*
323*
138*
85*
617*
279*
265*
Time
or (days)
25
25
25
25
25
25
25
25
25
25
25
25
25
25
«eterence
Riley & Roth,
Riley & Roth,
Riley & Roth,
Riley & Roth,
Riley & Roth,
Riley & Roth,
Riley & Roth,
Riley & Roth,
Riley & Roth,
Riley & Roth,
Riley & Roth,
Riley & Roth,
Riley & Roth,
Riley & Roth,
1971
1971
1971
1971
1971
1971
1971
1971
1971
1971
1971
1971
1971
1971
* Dry weight to wet weight conversion
Geometric mean bioconcentration 'factor for all species - 382.
-------
Table 13. Other marine data for copper
Organism
Test
Duration
Etfect
Result
(uq/M
Retereiicfc
ta
I
(Ti
Colonial hydroid,
Campanularia flexuosa
Colonial hydroid,
Campanularia flexuosa
Colonial hydroid,
Eirene viridula
Polychaete worm,
Cirriformia spirabracha
Polychaete worm,
Phyllodoce maculata
Polychaete worm,
Neanthes arenaceodentata
Polychaete worm,
Neanthes arenaceodentata
Bay scallop,
Argopecten irradians
Bay scallop,
Argopecten irradians
11 days Growth rate inhibition 10-13 Stebbing, 1976
Enzyme inhibition
1.43 Moore & Stebbing, 1976
14-21
days
Growth rate inhibition 30-60 Karbe, 1972
26 days 50% mortality
9 days
28 days
28 days
112 days
119 days
American oyster (larva), 12 days
Crassostrea virginica
Black abalone, 4 days
Haliotis cracherodii
Red abalone, 4 days
Haliotis rufescens
Northern quahaug 8-10
(larva) , days
Mercenaria mercenaria
Northern quahaug, 77 days
Mercenaria mercenaria
Soft; shelled clam, 7 days
Mya arenaria
Soft; shelled clam, 7 days
Mya arenaria
507. mortality
50% mortality
50% mortality
100% mortality
100% mortality
50% mortality
Histopathological gill >32
abnormalities
Histopathological gill >32
abnormalities
50% mortality
53% mortality
50% mortality
(22°C)
50% mortality
(4°)
40 Milanovich. et al. 1976
80 McLusky & Phillips, 1975
44 . Peach & Morgan, 1978
100 Pesch & Morgan, 1978
10 Zaroogian, 1978
5 Zaroogian, 1978
46 Calabrese, et al. 1977
Martin, et al. 1977
Martin, et al. 1977
30 Calabrese, et al. 1977
25 Shuster & Pringle, 1968
35 Eisler, 1977
>3,000 Eisler, 1977
-------
Table 13. (Continued)
Test
Organism Duration
Mussel, 7 days
Mytilus edulis
»
1
a\
to
Channeled whelk,
Busycon canaliculatum
Mud snail,
Nassarius obsoletus
American lobster,
Homarus americanus
Coral-reef echinoid,
Echinometra mathaei
Sea urchin,
Arbacia punctulata
Sea urchin,
Paracentrotus lividus
Mummichog,
Fundulus heteroclitus
Mummichog,
Fundulus heteroclitus
Atlantic silversides,
Menidia menidia
Summer flounder (embryo)
Paralichthys dentatus
Summer flounder (embryo)
Paralichthys dentatus
Plaice,
Pleuronectes platessa
Winter flounder,
Pseudopleuronectes
americanus
77 days
3 days
13 days
4 days
4 days
21 days
4 days
4 days
, 5 days
, 6 days
4 days
14 days
Ettect
507. mortality
50% mortality
Decrease in oxygen
consumption
50% mortality
Suppression of larval
skeletal development
58% decrease in sperm
motility
Retardation of growth
of pluteal larvae
Histopathological
lesions
Enzyme inhibition
Histopathological
lesions
50% mortality
50% mortality
50% mortality
Histopathological
lesions
Result
juq/il
200
470
100
56
a.
20
300
10-20
<500
600
<500
32
23
750
180
Alga,
Laminaria hyperboria
28 days Growth decrease
50
Reterencfc
Scott & Major, 1972
Betzer & Yevich, 1975
Maclnnes & Thurberg, 1973
McLeese. 1974
Heslinga. 1976
Young & Nelson, 1974
Bougis, 1965
Gardner & La Roche, 1973
Jackim. 1973
Gardner & La Roche, 1973
Cardin, et al. 1978
Cardin, et al. 1978
Saward, et al. 1975
Baker, 1969
Hopkins & Kain, 1971
-------
COPPER
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of deleterious concentrations of copper on the growth of
Chlorella pyrenoidosa. Physiol. Plant. 23: 828.
Steemann-Nielsen, E., and S. Wium-Andersen. 1970. Copper
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B-79
-------
Stokes, P., and T.C. Hutchinson. 1976. Copper toxicity
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B-80
-------
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Chemosphere 5: 299. B-81
-------
COPPER
Mammalian Toxicology and Human Health Effects
EXPOSURE
Introduction
Copper is widespread in the earth's crust, and the
extensive use of copper and its compounds by man since prehis-
toric times has added copper to the environment and the
ecosystem in wide ranges of concentration.
From 1955 to 1958 the annual United States production
of recoverable copper was about 900,000 metric tons. By
1975, the production had risen to 1,260,000 metric tons
(D'Amico, 1958; U.S. Bur. Mines, 1976). The world trade
in refined copper amounted to 2,271,150 metric tons in 1973
(World Metal Statistics, 1974).
Human exposure to copper can occur from water, food,
and air, and through direct contact of tissues with items
that contain copper. Copper is essential to animal life;
consequently, abnormal levels of copper intake can range
from levels so low as to induce a nutritional deficiency
to levels so high as to be acutely toxic.
C-l
-------
Ingestion from Water
Water can be a significant source of copper intake
depending upon geographical location, the character of the
water (i.e., whether it is soft or hard), the temperature
of the water, and the degree of exposure to copper-containing
conduits.
Schroeder, et al. (1966) place considerable emphasis
on drinking water as a source of copper. They reported
that the mean values of copper in human livers (56 cases)
from Dallas, Denver, and Chicago varied from 410 to 456
ug/g of ash, and that the mean value from Miami was 578
ug/g of ash . The municipal water supplies of these cities
each provided relatively hard potable waters with measured
hardness ranging from 75 to 125 mg/1. On the other hand,
143 livers from seven cities with relatively soft waters
ranging from 10 to 60 mg/1 had mean levels of copper varying
from 665 to 816 ug/g of ash. Of the cases from softwater
areas, 37.1 percent had hepatic copper of 700 or more jug/g
of ash, compared with only 14.3 percent of the samples from
the hardwater cities. Of the 56 individuals from three
cities with the hardest water, only two showed such high
values. Unfortunately no studies were made of cities with
very hard water.
The values cannot readily be converted to total copper
content present in liver on a wet weight basis since they
were secured at autopsy. Information regarding the indivi-
duals from which samples came was minimal.
C-2
-------
Schroeder, et al. (1966) suggested that the higher
copper levels in residents of cities with soft water might
be due to the ability of soft water to corrode copper pipes
and fittings, thereby increasing the intake of soluble copper,
Another explanation may lie in the ability of calcium or
magnesium ions in hard water to suppress the intestinal
absorption of copper.
Schroeder, et al. (1966) reported on the progressive
increase of copper in water from brook to reservoir to hos-
pital tap, and the considerable copper increment in soft
water, compared with hard water, from private homes (see
Table 1). The authors found that the daily increment of
copper ingested from soft water may amount to 10 to 20 per-
cent of dietary intake.
In contrast to Schroeder,- et al. (1966), Hadjimarkos
(1967) suggested that drinking water may be only a minor
source of copper. He reported that the mean drinking water
concentration of copper is 0.029 mg/1, which could mean
a daily intake of 58 pg of copper in water, or 1 to 8 percent
of total daily intake if food intake is 3,200 yig of copper
per day.
It is probable that the difference in intakes estimated
by Schroeder, et al. and Hadjimarkos reflects location.
However, it is difficult to pinpoint local copper concen-
trations in drinking water sources, since the only readily
available information on concentrations of copper in stream
water is from areas of 10,000 square miles or greater. (Kopp
and Kroner, 1968; Thornton, et al. 1966).
C-3
-------
TABLE 1
Copper in Water Flowing through Copper Pipes
a,b
Item
Spring water, Brattleboro, Vermont, mountain
Municipal water, soft, Brattleboro
Brook, inlet to reservoir
Reservoir, lake
Water, main end
Hospital, at tap
cold, running 30 min
hot, running 30 min
cold, standing 12 hr
cold, standing 24 hr
Spring water, soft, private houses, Brattleboro,
Vermont, at tap
No. 1 from spring, unpiped
running 30 min
cold, standing 24 hr
hot, standing 24 hr
No. 2
No. 3
Well water, private houses, Windham County, at tap
No. 4, hard
No. 5, hard
No. 6, hard
No. 7, hard, at well
at tap
No. 8, soft
1.2'
16
55
150
170
440
550
730
2.8'
190
1400
1460C
1240
75
36 c
4.4C
40
4S
36C
278
aSchroeder, et al. 1966.
Water from the main was taken after it had passed through the
treatment plant at the entrance to hospital supply system,
from whence it ran through copper pipes. This water was
chlorinated. Spring and well waters were untreated.
°By chemical method using diethyldithiocarbamate after
evaporating 1 litre water.
C-4
-------
Robinson, et al. (1973) in New Zealand have suggested
that soft water used exclusively from the coldwater tap
to make up daily beverages may add as much as 0.4 mg of
copper per day per individual, but that if hot water from
the same source is used for the same purposes, it would
add at least 0.8 mg of copper per day to an individual's
intake.
The average concentration of copper in the United States
water systems is approximately 134 jag/1 (U.S. Dep. Health,
Edu. Welfare, 1970). The highest concentration reported
was 8,350 ug/1; a little over 1 percent of the samples exceed-
ed the drinking water standard of 1 mg/1.
The 1 mg/1 copper standard was established not because
of toxicosis but because of the taste which develops with
higher levels of copper in the water. It is most commonly
exceeded in soft water that is acid in nature; however,
it is rare that the concentration of copper in drinking
water is high enough to affect its taste or to produce toxi-
cosis (McCabe, et al. 1970; Fed. Water Quality Adm., 1968).
For this reason, regulatory agencies have not treated copper
in public water supplies as a significant problem. In New
York City, copper is intentionally added to the water supply
to maintain a concentration of 0.059 mg/1 in order to control
algal growth (Klein, et al. 1974).
Prolonged contact of acid beverages with copper con-
duits, such as occurred in earlier drink dispensing machines,
may produce sufficient copper concentration to cause acute
copper toxicosis (see "Acute, Subacute, and Chronic Toxi-
C-5
-------
city" section); however, because of taste problems, modern
equipment does not contain copper conduits.
The national impact of a water-borne contribution of
copper is difficult to detect, predict, or evaluate because
information is either absent or irretrievable. The cur-
rent trend for recycling waste (animal wastes, sewage solids,
and liquids, channel dredging, and industrial waste) to
the land offers very real possibilities that imbalances
in organisms may unwittingly be created, because such wastes
are commonly high in trace element concentration. These
trace elements may directly alter crop production and indi-
rectly affect the consumer (Patterson, 1971).
Another source of copper in water is the use of copper
sulfate to control algae. Some idea of the distribution
of copper sulfate may be gained from the work of Button,
et al. (1977), who applied granular copper sulfate to the
surface of Hoover Reservoir, Franklin County, Ohio. Soluble
and particulate cupric copper concentrations at several
depths were measured by atomic absorption spectrophotometry
for four days after application. The soluble cupric copper
concentration decreased to near baseline values in 2 to
6 hours when 0.2 or 0.4 gms of copper sulfate per square
meter were added to the surface. Most of the copper sulfate
was dissolved in the first 1.75 meters of water column,
and only 2 percent of the total copper sulfate reached the
depth of approximately 4.5 meters. A concentration of 0.4
gms of copper per square meter controlled a diatom bloom.
:c-6
/
-------
Ingestion from Foods
Levels of copper in various foods are given in Table 2.
Some foods, such as crustaceans and shellfish (especially
oysters), organ meats (especially lamb or beef liver), nuts,
dried legumes, dried vine and stone fruits, and cocoa, are
particularly rich in copper. The copper content of these
items can range from 20 ug/g to as high as 400 }ig/g (McCance
and Widdowson, 1947; Schroeder, et al. 1966). On an "as-
cooked and as-served" basis, calves' liver, oysters, and
many species of fish and green vegetables have recently
been classed as unusually good sources of copper, (more
than 100 pg copper/100 kcal).
High levels of copper may also be found in swine because
of the practice, common in the United Kingdom and elsewhere,
of feeding to swine diets that are high (up to 250 jag/g)
in copper in order to increase daily weight gain. Levels
of copper in swine liver vary greatly depending on the copper
content of the feed. A high copper diet fed continuously
until slaughter may produce levels of up to 400 to 600 >ag/g
in the liver. However, swine will rapidly eliminate copper
once it is removed from the diet. Sheep also accumulate
copper in direct proportion to the level of copper in the
diet, but they eliminate excess copper very poorly (NCR-
42, 1974; Barber, et al. 1978). The National Research Council
(1977) noted that the use of sheep or swine livers that
are high in copper could result in excessive levels of copper,
especially in baby foods where the actual amount of copper
might exceed the copper requirements of very young children.
C-7
-------
Copper in Foods (Wet Weight)
Item
Sea food
Clams, raw
Clams, fresh frozen
Oysters
Sardines, canned Portugese
Kipper snacks, Norway, canned
Anchovies, canned Portugese
Pan fish, dried, V.I.
Lobster, frozen
Shrimp, frozen
Mean, excluding oysters
Meat
Beef liver
Beef kidney
Beef fat
Port kidney
Pork loin
Pork liver
Lamb kidney
Lamb chops
Chicken leg and wing
Mean
Dairy products
Egg yolk
Egg white
Dried skimmed milk
Whole milk, dairy 1
Whole milk, dairy 2
Butter, salted
Mean
Vegetables
Peas, green
Peas, split, green dry
Peas, green, V.I.
Peas, split, green, V.I.
Lentils
Yam, white V.I.
Yam, yellow, V.I.
Turnip, white
Turnip greens
w/9
3.33
0.48
137.05
1.12
1.70
0.81
0.58
0.51
3.40
1.49
11.0
0.42
0.83
5.30
3.90
3.72
0.95
7.13
1.99
3.92
2.44
1.70
2.09
0.26
0.12
3.92
1.76
0.45
12.30
1.14
2.25
1.41
0.32
0.41
1.84
0.73
ug/100 ,
calories
694
100
27,410
38
85
27
49
42
297
167
769
34
21
441
130
260
96
381
99
249
70
460
63
40
18
49
117
70
410
181
75
47
37
47
1022
663
f*Schroeder, et al. 1966
Caloric values of foods from McCance, R.A. and, E.M.: Widdowson,
The Chemical Composition of Foods. Chemical Publishing
Co., Brooklyn, New York, 1947. V.I. indicates that the
sample came from St. Thomas, Vir,grn Islands.
-------
TABLE 2 (cont'd)
Copper in Foods
Item
U9/9
pg/100
calories
Vegetables (cont'd)
Beets
Carrots
Tomato, V.I.
Pepper, green, No. 1
Pepper, green, No. 2
Pepper, green, V.I.
Pepper, hot, red, V.I.
Cucumber, No. 1
Cucumber, No. 2
Christofine, V.I.
Egg plant, V.I.
Asparagus
Celery
Cabbage
Parsley
Rhubarb
Mushrooms
Fruits
Banana, V.I.
Papaya, V.I.
Coconut, V.I.
Coconut seed, V.I.
Apple, Macintosh
Mean
Mean, excluding seed
0.15
3.42
0.34
0.68
0.28
0.90
0.56
0.07
0.47
0.18
0.06
0.37
0.31
0.70
0.20
0.34
0.65
TTTT
0.66
1.06
0.19
3.31
1.39
0.82
32
1487
143
453
187
600
70
470
257
40
205
344
350
567
929
"362
86
265
100
278
TF2
C-9
-------
TABLE 2 (cont'd)
Copper in Foods
Item /ig/g pg/100 .
calories
Grains and cereals
Wheat seed 1.09 33
Wheat, whole 2.48 75
Wheat germ . 0.15 -
Wheat head, chaff and stalk 0.14 -
Bread, white 0.19 8
Bread, whole wheat 0.6>3 25
Oats, whole 0.40 10
Corn, No. 1 0.46 13
Corn, No. 2 0.65 19
Rye, No. 1 0.92 27
Rye, No. 2 4.12 123
Rye, dry, flour 4.20 124
Benzene extract 10.82 -
Residue 1.87
Barley 3.83 106
Buckwheat 8.21 227
Rice, brown, U.S. 0.47 13
Rice, Japanese, polished 3.04 84
Bengal gram, India, 1 4.23 120
Bengal gram, India, 2 0.56 16
Grapenuts 14.95 415
Millet 2.34 67
Doughnut, cream filled 2.32 66
Mean, excluding grapenuts and extracts 2.02 58
C-10
-------
TABLE 2 (cont'd)
Copper in Foods
Item
Oils and fats
Lard, canned, 1
Lard, canned, 2
Lard, canned, 3
Lecithin, animal
Lecithin, egg
Cod liver oil, Norway
Castor oil, refined
Corn oil
Corn oil margarine
Cottonseed oil
Olive oil
Sunflower oil
Linseed oil, pressed
Peanut oil, pressed
Lecithin, vegetable, pure
Lecithin, soy, 90 percent pure
Lecithin, soy, refined
Mean, excluding lecithins
Nuts
Hazelnuts
Peanuts
Walnuts
Brazil nut
Pecans
Almonds
Mean
Condiments, spices, etc.
Garlic, fresh
Garlic powder
Mustard, dry
Pepper , black
Paprika
Chili powder
Thyme, ground
Bay leaves (laurel)
Cloves, whole
Ginger, ground
Ginger, root, V.I.
Caraway seeds
Vinegar, cider
Yeast, dry, active
Molasses
Sugar, refined
pg/g
3.06
2.50
2.13
26.38
10.52
6.80
1.70
2.21
24.70
1.26
3.20
5.44
1.75
0.83
5.31
4.37
20.95
4.63
12.80
7.83
12.70
23.82
12.64
14.11
14.82
3.15
0.75
3.04
20.73
8.47
5.98
23.58
3.68
8.67
2.63
1.87
4.31
0.76
17.79
2.21
0.57
pg/100
calories
34
28
24
-
-
-
-
25
274
14
36
60
19
9
.
-
~
58
233
131
231
370
211
234
235
-
.
-
. -
-
-
-
-
-
-
-
-
-
85
14
Mean 6.76
C-ll
-------
TABLE 2 (cont'd)
Copper in Foods
Item pg/g ug/100 .
calories
Beverages
Gin, domestic. 0.03 1
Vermount, French 0.88 102
Vermouth, Italian 0.38 44
Whiskey, Scotch 0.35 14
Whiskey, Broubon 0.18 " 7
Brandy, California . 0.45 . 18
Bitters, Angostura 0.75
Wine, domestic, red 0.28 33
Beer, canned 0.38 76
Cola 0.38 100
Grape juice 0.90 136
Orange drink, carbonated 0.20 43
Orange juice, packaged 0.89 234
Coffee, dry, ground 2.35
Coffee, infusion 0.22
Tea, infusion 0.31 -
Mean, excluding dry coffee 0.44 20
Miscellaneous
Chocolate bar, Hershey 0.70 18
Ice cream, vanilla 0.29 15
Gelatin, Knox 3.87 148
Purina laboratory chow 15.61 -
Aspirin, Squibb 3.12 -
Saccharin 5.43 . :-
C-12
-------
The poorer sources of copper are dairy products, white
sugar, and honey, which rarely contain more than 0.5 pg
copper/g. The non-leafy vegetables and most fresh fruits
and refined cereals generally contain up to 2 ug/g. Cheese
(except Emmental), milk, beef, mutton, and white and brown
oread, and many breakfast cereals (unless they are forti-
fied) are relatively poor sources of copper, i.e., they
have less than 50 pg copper/100 kcal (World Health Organ.
1973).
The refining of cereals for human consumption results
in significant losses of copper, although this loss is not
so severe as it is for iron, manganese, and zinc. Levels
of copper in wheat and wheat products are given in Tables 3
and 4.
Schroeder, et al. (1966) have suggested that since
copper occurs widely in human foods, it is difficult to
prepare a diet of natural foods which provides a daily cop-
per intake of less than 2 mg, the level that is considered
to be adequate for normal copper metabolism (Adelstein,
et al. 1956).
Tompsett (1934) reported that the normal daily intake
of copper from food appeared to be 2 to 2% mg per day for
human subjects. Daniels and Wright (1934) reported an average
intake of 1.48 mg copper per day in young children, with
a requirement of not less than 0.10 ug/kg of body weight
per day.
C-13
-------
TABLE 3
Mineral Content of Known Wheats, the Flours Milled from Them
and the Products Prepared from the Flours
V K
d t O
Sample
Wheat, common hard
Flour, Baker's patent
Bread, sponge-dough
Bread, continuous-mix
Wheat, common soft
Flour, soft patent (cake)
Cake
Flour, straight-grade0
Cracker
Flour, cut-off (cracker)
Cracker
Wheat, Durum
Semolina
Marcaroni
Number
of
Samples Moisture
5
5
5
5
4
6
6
5
5
2
2
2
2
2
11.
13.
36.
35.
10.
11.
22.
11.
4.
12.
4.
10.
14.
9.
0
9
3
3
6
9
8
4
9
6
5
7
7
6
1.
0.
3.
3.
1.
0.
2.
0.
3.
0.
3.
2.
0.
0.
Ash
87
49
39
42
73
42
71
50
42
71
09
03
83
82
+
+
+
+
+
+
+
+
+
+
+
+
+
+
0
0
0
0
0
0
0
0
0
0
0
0
0
0
.10
.03
.19
.30
.17
.03
.11
.05
.50
.04
.34
.01
.01
.01
Copper
ug/g
5.1
1.9
2.3
2.0
4.5
1.6
0.8
1.6
1.6
2.6
2.4
. 4.8
2.2
2.5
+
+
+
+
+
+
+
+
+
+
+
+
+
+
0.5
0.2
0.3
0.2
0.5
0.3
0.1
0.2
0.1
0.1
0.1
0.1
°*i
°-v
j!2ook, et al. 1970.
Mean and standard deviation, dry weight basis.
clncludes two flours prepared by air classification.
C-14
-------
TABLE 4
Mineral Content of Consumer Products Purchased in Ten Cities
a,b
o
1
U)
Product
Cereal- to-be-cooked
Shredded wheat
Wheat flakes
Bread, whole wheat
Bread, white
Conventional dough
Continuous-mix
Rolls, hamburger
Doughnuts, cake
Biscuit mix
Flour, all-purpose
Total
Samples
Collected
No.
24
47
28
38
52
29
52
28
23
31
Producers Sampled
Total
No.
7
6
3
26
37
17
34
20
8
19
Per
City
Range
1-3
4-6
2-3
2-8
3-9
1-4
4-9
1-5
1-4
3-4
Model
City
No.
3
4
3
2
4
2
4
3
2
3
Moisture
%
9.5
8.0
4.8
37.8
35.8
36.7
33.6
21.9
9.8
12.9
Ash
1.85
1.87
3.78
3.87
3.23
3.10
2.85
2.61
4.28
0.56
%
+
+
+
+
+
+
+
+
+
+
0.07
0.12
0.17
0.12
0.12
0.13
0.08
0.20
0.26
0.03
Copper
5.3
6.1
4.7
5.1
2.1
2.3
2.5
1.7
1.6
1.8
JKj/9
+ 0.2
+ 0.4
+ 0.3
+ 0.5
+ 0.2
+ 0.3
+ 0.2
+ 0.2
+ 0.2
+ 0.2
*Zook, et al. 1970.
3Mean and standard deviation, dry weight basis.
-------
Most western style diets supply adults with 2 to 4
ir.g of copper per day. This is evident from studies in Eng-
land, New Zealand, and the United States. Lower estimates
have been made for certain Dutch and poorer Scottish diets,
while Indian adults consuming rice and wheat diets have
been shown to ingest from 4.5 to 5.8 mg of copper per day
(Schroeder, et al. 1966).
Scheinberg (1961) has contended that most adult diets
supply a substantial excess of copper. Klevay, on the other
hand, has suggested on the basis of recent food analyses
that the copper content may be less than earlier analyses
indicated and has cautioned that United States diets may
not be adequate to provide 2 mg of copper per day. (Klevay,
1977; Klevay, et al. 1977).
Dr. Walter Mertz in a personal communication reported
that in 1978 the analysis of diets of more than 20 indivi-
duals employed at the Institute of Nutrition of the U.S.
Department of Agriculture, Beltsville, Md., showed that
only two approached an intake of 2 mg of copper per day.
The diets of these individuals included soft drinks, water,
and snacks, suggesting that food subjected to modern proces-
sing and preparation methods may be much lower in copper
than was supposed based on earlier analyses, and that many
individuals eating these foods may be receiving considerably
less than the 2 mg of copper per day.
C-16
-------
Engel, et al. (1967) conducted studies on young girls
which indicated that 2 ^jg copper/g of diet was adequate
for good nutrition. Petering, et al. (1971) mention that
the copper content of hair appears to be related to the
age of the individual and suggest that the need for copper
may differ between the sexes.
Because of the essentiality of copper, the copper balance
in newborn infants has been examined (Cavell and Widdowson,
r
1964). It was noted that breast milk ranged from 0.051
mg/100 ml and that total copper intakes of the babies ranged
from 0.065 to 0.1 mg/kg per day. In the first week of life,
some infants excreted more copper than was contained in
the milk which they consumed. Of 16 babies, 14 were in
negative balance.
As a general statement it would appear that, at least
in the United States, there is a greater risk of inadequate
copper intake than of an excess above requirements.
A bioconcentration factor (BCF) relates the concentration
of a chemical in water to the concentration in aquatic organisms,
Since BCF's are not available for the edible portions of
all four major groups of aquatic organisms consumed in the
United States, some 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 nineteen major species identified
in the survey, the relative consumption of the four major
groups can be calculated.
c-17
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A bioconcentration factor of zero was reported for
copper in the muscle of bluegill sunfish (Benoit, 1975).
Since no data are available for saltwater fish or decapods,
the same value will be used. Data are available for several
species of saltwater molluscs:
Species BCF
Bay scallop, 3,310
Argopecten irradians
Bay scallop 4,155
Argopecten irradians
American oyster, 28,208
Crassostrea virginica
American oyster, 20,688
Crassostrea virginica
Northern quahaug, 88
Mercenaria mercenaria
Soft shelled clam, 3,300
Mya arenaria
Mussel, 208
Mytilus edulis
Mussel, 108
Mytilus edulis
Mussel, 90
Mytilus edulis
Mussel, 800
Mytilus galloprovincialis
Reference
Zaroogian, 1978
Zaroogian, 1978
Shuster & Pringle,
1969
Shuster & Pringle,
1969
Shuster & Pringle,
1968
Shuster & Pringle,
1968
Zaroogian, 1978
Zaroogian, 1978
Phillips, 1976
Majori & Petronio,
1973
The geometric means for scallops, oysters, clams, and mussels
are 3,708, 24,157, 539, and 200, respectively, and the overall
mean is 290.
C-18
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Consumption Bioconcentration
Group (Percent) factor
Freshwater fishes 12 0
Saltwater fishes 61 0
Saltwater molluscs 9 290
Saltwater decapods 18 0
Using the data for consumption and BCF for each of these
groups, the weighted average BCF is 26 for consumed fish
and shellfish.
Inhalation
The principal source of elevated copper levels in air
is copper dust generated by copper-processing industrial
operations. However, since the economic value of copper
encourages its capture from industrial processes, extraneous
emissions are reduced. Other possible sources of copper
in air may be tobacco smoke and stack emissions of coal-
burning power plants.
Copper has not been considered a particularly hazardous
industrial substance because the conditions that would produce
excessive concentrations of copper dust or mist in a par-
ticle size that could be absorbed and generate toxic effects
are apparently quite rare. Investigations of Chilean copper
miners have shown that liver and serum concentrations of
copper are normal, despite years of exposure to copper sul-
fide and copper oxide dust, both of which are insoluble
(Scheinberg and Sternlieb, 1969). However, workers can
be exposed to excess concentrations of copper in any of
its forms, and when this does occur undesirable health effects
C-19
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can result. Metal fumes, a 24 to 28-hour illness characteriz-
ed by chills, fever, aching muscles, dryness in the mouth
and throat, and headache, has been noted where workers are
exposed within closed areas to the welding of copper structures
(McCord, 1960).
Special care should be taken to avoid conditions where
copper or a copper compound dust is a problem (Cohen, 1974).
The U.S. Occupational Safety and Health Administration (OSHA)
has adopted standards of exposure to air-borne copper at
work. The time-weighted average for 8-hour daily exposure
to copper dust is limited to 1 mg/m of air. The standard
for copper fume was changed in 1975 to 0.2 mg/m (Gleason,
1968; Nat. Res. Counc. 1977).
In 1966, a National Air Sampling Network survey showed
that the airborne copper concentrations were 0.01 and 0.257
jig/m in rural and urban communities respectively (Nat.
Air Pollut. Control Admin. 1968). Even near copper smelters,
where high levels (1 to 2 pg/m ) are reached the dose of
metal that would be acquired through inhalation of ambient
air would comprise only about 1 percent of the total normal
daily intake (Schroeder, 1970).
Generally speaking, inhalation of copper or copper
compounds is of minor significance compared to other sources,
e.g., copper in foods, drinking water, and other fluids,
and application of copper to tissues for medical purposes.
C-20
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Dermal
Copper toxicity has resulted from the application of
copper salts to large areas of burned skin or from introduc-
tion of copper into the circulation during hemodialysis.
The source of the copper in hemodialysis may be the membranes
fabricated with copper, the copper tubing, or heating coils
of the equipment. Copper stopcocks in circuits can also
cause potentially hazardous infusions of copper (Holtzman,
et al. 1966; Lyle, et al. 1976).
Studies with monkeys indicated that copper used as
dental fillings and placed in cavities in the deciduous
teeth of the monkey caused more severe pulp damage than
any of the other materials studied. This is additional
evidence that tissues exposed directly to copper or copper
salts will suffer adverse effects due to the direct absorp-
tion of the copper by the tissues (Mjor, et al. 1977).
Recent papers from Australia (Walker, 1977; Walker,
et al. 1977) suggest the possibility of copper absorption
through the skin as a result of perspiration action on the
copper bracelet, sometimes worn as treatment for arthritis,
although the therapeutic value of this has little support.
Concern has been directed toward the absorption of
copper as a result of the use of the intrauterine device
(IUD) as a contraceptive measure (National Research Council,
1977). Analysis of lUDs that have been in utero for months
to years shows that about 25 to 30 mg of copper are lost
each year. Some of the metal is excreted with endometrial
secretions. Experimental evidence to date does not indicate
C-21 ,
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that use of an IUD results in harmful accumulations of copper.
(See "Absorption" section for additional information.)
PHARMACOKINETICS1
Absorption
Radioactive studies provide the basis for the conclu-
sions that most absorption in man takes place in the stomach
and the duodenum. Copper absorption appears to be regulated
by the intestinal mucosa, and maximum copper levels occur
in the blood serum within one to three hours after oral
intake.
Much of the information on copper absorption in humans
has come from studies of patients with Wilson's disease.
Studies conducted with these patients using radioactive
copper indicate that about one-half of the copper in the
diet is not absorbed but is excreted directly into the feces.
The average absorption in these individuals has been reported
to be.approximately 40 percent (Sternlieb, 1967; Strickland,
et al. 1972a). Investigations by Cartwright and Wintrobe
Acknowledgement is made of the courtesy of the late Dr.
Karl E. Mason and Dr. Walter Mertz who allowed the author
to read their manuscript, Conspectus on Copper, to be published
in the Journal of Nutrition.
C-22
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(1964a) indicated that the daily intake of copper in Wilson's
disease patients was 2 to 5 ing, of which 0.6 to 1.6 mg were
absorbed, 0.5 to 1.2 mg were excreted in the bile, 0.1 to
0.3 mg passed direct.ly into the bowel, and 0.01 to 0.06
mg appeared in the urine.
Information from these studies indicates that absorbed
copper is rapidly transported to blood serum and taken up
by the liver, from which it is released and incorporated
into ceruloplasmin. Any copper remaining in the serum is
attached to albumin or amino acids or is used to maintain
erythrocyte copper levels (Weber, et al. 1969; Beam and
Kunkel, 1954, 1955; Beckner, et al. 1969; Bush, et al. 1955;
Jensen and Kamin, 1957).
Estimates of the amount of the copper that is actually
absorbed by normal individuals vary considerably and must
be considered inconclusive. The values obtained have ranged
from as low as 15 percent to as high as 97 percent (Weber,
et al. 1969), although it seems probable that subjects giving
these extreme values were not in a steady state. These
values are confounded by the lack of accurate information
regarding the excretion of copper in its various forms by
way of the biliary system. Even less information is avail-
able regarding the reabsorption of copper or copper compounds
from the intestine after they have been excreted in the bile.
Most of the values that have been obtained with normal
subjects suggest that 40 to 60 percent of the dietary copper
is absorbed (Van Ravensteyn, 1944; Cartwright and Wintrobe,
C-23
-------
1964a; Bush, et al. 1955; Matthews, 1954; Weber, et al.
1969; Strickland, et al. 1972a; Strickland, et al. 1972b;
Sternlieb, 1967).
Animal studies have shown that copper is absorbed by
at least two mechanisms, an energy-dependent mechanism and
an enzymatic mechanism (Crampton, et al. 1965), and that
many factors may interfere with copper absorption, including
competition for binding sites as with zinc, interactions
with molybdenum and with sulphates, chelation with phytates,
and the influence of ascorbic acid. Ascorbic acid will
aggravate copper deficiency by decreasing copper absorption.
In cases of excess copper intake, ascorbic acid can reduce
the toxic effects (Gipp, et al. 1974; Hunt, et al. 1970;
Voelker and Carlton, 1969).
Studies with laboratory animals have shown that once
copper enters the epithelial cells, it is taken up by a
cellular protein similar to metallothionein which occurs
in liver (Evans, et al. 1973; Evans, 1973; Starcher, 1969).
Absorbed copper is bound to albumin and transported in the
plasma. Approximately 80 percent of the absorbed copper
is bound in the liver to metallothionein. The remaining
copper is incorporated into compounds such as cytochrome-
c-oxidase or is sequestered by lysosomes (Beam and Kunkel,
1954, 1955). Little information is available concerning
absorption of copper into the lymphatics, although in patho-
logical conditions this may be signficiant (Trip, et al.
1969) .
C-24
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Several studies have been conducted on humans and labora-
tory animals concerning absorption of copper as a result
of the use of copper intrauterine devices (lUD's). Studies
with the IUD in rats have suggested that as much as 10 to
20 mg of copper may be absorbed (Oreke, et al. 1972). This
amount, which is small compared to the dietary copper usually
ingested, may or may not be metabolized and excreted by
the same homeostatic mechanisms that operate with ingested
copper. If an IUD were used for many decades and the absorbed
copper were retained, it would result in amounts of copper
similar to those retained from dietary copper by patients
with Wilson's disease. Such levels could result in chronic
toxicosis.
Japanese investigators (Okuyuma, et al. 1977) have
compared effects of using the IUD with copper and the IUD
without copper in two groups of women, using a third group
as controls. Pregnant women with an IUD in place were also
examined. No significant difference was found in the endome-
trial copper levels in the three groups. There was a tendency
toward an increase above controls in the endometrial level
of copper during the secretory phase in those women using
the IUD with or without copper. No significant difference
was found between women who had used an IUD more than 13
months and those who had used it less than 13 months. The
copper content of the chorion and the decidua of the pregnant
women with lUD's in place did not differ from the levels
noted in pregnant women without lUD's. Apparently, the
long-term use of copper-containing lUDs did not lead to
an accumulation of copper in the uterus.
C-25
-------
Tamaya, et al. (1978) have studied the effect of the
copper IUD on the histology of the endometrium in the proiif-
erative and the secretory phases of women. Their results
indicate that the copper IUD affected the secretory endomet-
rium but not the proliferative endometrium.
In another study, Israeli women with the Latex Leaf
IUD which contains both copper and zinc showed increased
levels of both metals if they had had low serum levels of
copper and zinc before insertion. However, their copper
and zinc levels did not exceed the upper limits of normal
values. No significant statistical difference was found
between the serum levels of copper before and after insertion
of the IUD.
It has been suggested that diabetic women may respond
differently from normal healthy women to the use of a copper
IUD. In 11 diabetics, the presence of a copper IUD did
not increase the fibrolytic activity in the endometrium,
although such an effect was observed in non-diabetics.
Since there is evidence that enhancement of the endometrial
fibrolytic activity prevents adhesion and implantation of
ova, the results may explain the report of less reliable
contraceptive effect of the IUD in diabetic women (Larsson,
et al. 1977).
A number of studies of the effect of copper upon fer-
tility in animals have incidentally measured copper in tissues,
Studies of copper beads in rabbits (Quijada, et al. 1978),
copper wires inserted into the vas deferens of male rats
C-26
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(Kartar and Chowdhury, 1977), and copper lUDs in rats have
all suggested that copper does have some influence on hor-
mone secretion and tissue copper levels in the reproductive
tract; however, these experiments do not present any evi-
dence for accumulation of copper as a result of the use
of lUDs (Murakimi, et al. 1978).
Distribution
The amount and distribution of copper in body tissues
varies with sex, age, and the amount of copper in the diet.
Copper content of fat-free tissues of most animals ranges
upward from about 2 )ig/g. The highest concentrations of
copper in both animal and human tissues are found in the
liver and the brain, with lesser amounts in the heart, the
spleen, the kidneys, and blood (Cartwright and Wintrobe,
1964a,b; Smith, 1967; Schroeder, et al. 1966). Some tissues
are very high in copper, e.g., the iris and the choroid
of the eye which may contain as much as 100 ug/gm (Bowness
and Morton, 1952; Bowness, et al. 1952).
Estimates of the total amount of copper in a 70-kilo-
gram man have ranged from 70 to 120 mg. Approximately one-
third of body copper is found in the liver and the brain,
one-third is found in the musculature, and the remaining
one-third is dispersed in other tissues. It has been esti-
mated that, on the average, about 15 percent of the total
body copper is contained in the liver (Tipton and Cook,
1963; Sumino, et al. 1975; Sass-Kortsak and Bern, 1978).
The relatively high percentage of liver copper is related
to the liver's function as a storage organ for copper and
C-27
-------
as the only site for the synthesis and release of cerulo-
plasmin, the most abundant copper protein in the blood.
In the brain, the striatum and both components of the
cortex (gray matter) have the highest copper content, with
the cerebellum (white matter) being the lowest (Hui, et
al. 1977; Cumings, 1948; Earl, 1961). The brain appears
to be the only tissue in which there is a consistent increase
in copper content with age. Other tissues appear to be
under a homeostatic control.
Copper levels in hair vary widely with respect to age,
sex, and other factors, and therefore have little meaning-
fulness in evaluating copper levels in man (Underwood, 1977).
However, Jacob, et al. (1978) have suggested that the copper
in hair may be useful in evaluating the total liver content
of copper. Engel, et al. (1967) surveyed over 180 adoles-
cent girls in the 6th to 8th grades for dietary intake and
nutritional status. They found that the mean concentration
of copper in hair samples was 31 + 23 ug/g. No significant
difference was found between girls who had experienced menarche
and those who had not.
Levels of copper in the blood of normal adults average
103 pg/100 ml of blood. The amount of copper in blood serum
can range widely from 5 ug/100 ml to 130 ug/100 ml. In
practically all species, copper deficiency is first mani-
fested by a slow depletion of body copper stores, including
the blood plasma, eventually resulting in a severe anemia
identical to that caused by iron deficiency (Cartwright,
et al. 1956).
C-28
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Both the plasma and the erythrocyte have two pools
of copper, a labile pool and a stable pool, which contain
approximately 40 and 60 percent respectively, of the copper
in the blood (Bush, et al. 1956). Ceruloplasmin represents
the serum stable pool. There appears to be little or no
interchange between ceruloplasmin copper and other forms
of copper in the blood stream (Sternlieb, et al. 1961).
Mondorf, et al. (1971) indicate that the blood contains
an average of 30 ug of ceruloplasmin/100 ml of blood. This
is in reasonable accord with accepted levels of copper in
the blood of normal adults (approximately 103 pq total cop-
per/100 ml of blood. White blood cells contain a small
amount of copper, about one-fourth the concentration in
erythrocytes (Cartwright, 1950).
The distribution of copper in the fetus and in infants
is quite different from that in the adult. The percentage
of copper in the body increases progressively during fetal
life (Shaw, 1973). Chez, et al. (1978) found that concentra-
tions of copper in amniotic fluid increased between the
26th and 33rd weeks of pregnancy, but that there did not
appear to be a correlation between maternal and fetal copper
concentrations.
At birth, the liver and spleen contain about one-half
the copper of the whole body (Widdowson and Spray, 1951).
A newborn infant contains about 4 mg/kg as compared to approxi-
mately 1.4 mg/kg in the 70-kilogram man (Widdowson and Dick-
er son, 1964). The liver of the newborn has approximately
C-29
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6 to 10 times the amount of copper in the liver of an adult
man on a per gram basis (Bruckmann and Zondek, 1939; Nusbaum
and Zettner, 1973; Widdowson, et al. 1951).
The concentration of copper in the serum of newborn
infants is significantly lower than in 6- to 12-year-old
healthy children, but by 5 months of age the serum concen-
tration of copper is approximately the same as in older
children. There is no difference between copper levels
in male and female infants, although breast-fed infants
seem to have somewhat higher copper levels by 1 month than
bottle-fed infants (Ohtake, 1977). The liver copper content
of the fetus is several times higher than maternal liver
copper (Seeling, et al. 1977).
Metabolism
The copper content of red blood cells remains remark-
edly constant, but the plasma copper is subject to striking
changes associated with the synthesis and release of cerulo-
plasmin, the most abundant copper protein (Gubler, et al.
1953; Lahey, et al. 1953).
Some 20 mammalian copper proteins have been isolated,
but at least three are identical and others have more than
one name. Most of this information has come from animal
studies, and its applicability to humans is uncertain.
Evans (1973) and others have reviewed this subject (Mann
and Keilin, 1938; Osborn, et al. 1963; Morell, et al. 1961;
Sternlieb, et al. 1962).
C-30
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Copper plasma levels during pregnancy may be two to
three times the normal nonpregnant level. This is almost
entirely due to the increased synthesis of ceruloplasmin
(Henkin, et al. 1971; Markowitz, et al. 1955; Scheinberg,
et al. 1954). The source of this copper appears to be the
maternal liver. The increase in maternal plasma copper
levels appears to be associated with estrogen, since either
sex receiving estrogen shows an increase in copper level
of the plasma (Eisner and Hornykiewicz, 1954; Gault, et
al. 1966; Humoller, et al. 1960; Russ and Raymunt, 1956).
The use of oral contraceptives causes a marked increase
in serum copper levels which may be greater than those observed
during pregnancy (Oster and Salgo, 1977; Smith and Brown,
1976; Tatum, 1974).
Infant levels of serum copper are low at birth but
promptly increase due to the synthesis of ceruloplasmin
by the infant's liver (Henkin, et al. 1973; Schorr, et al.
1958).
There are two inherited diseases which represent abnor-
mal copper metabolism, Menkes1 disease and Wilson's disease.
Menkes' disease is a progressive brain disease caused by
an inherited sex-linked recessive trait. It is often referred
to as the "kinky hair" disease or "steely hair" disease
(Danks, et al. 1972). The primary defect of Menkes1 disease
appears to be a diminished ability to transfer copper across
the absorptive cells of the intestinal mucosa (Danks, et
al. 1972, 1973). The general symptoms of the disease are
C-31
-------
similar to those observed in animals suffering from copper
deficiency (Oakes, et al. 1976). The prospects for more
effective therapeutic measures as a result of early diagnosis
appear to be limited.
The second abnormal disease associated with copper,
Wilson's disease, which has also been designated "hepatolen-
ticular degeneration," is caused by an autosomal recessive
trait (Beam, 1953) . The disease is actually a copper toxi-
cosis with abnormally high levels of copper in the liver
and brain (Cumings, 1948). Symptoms include increased uri-
nary excretion of copper (Spillane, et al. 1952; Porter,
1951); low serum copper levels due to low ceruloplasmin
(Scheinberg and Gitlin, 1952); decreased intestinal excre-
tion of copper; and occurrence of Kayser-Fleischer rings
due to excessive accumulation of copper around the cornea.
If therapy with D-penicillamine is instituted during the
early phases of Wilson's disease, it can assure a normal
life expectancy, especially when accompanied by a low-copper
diet (Deiss, et al. 1971; Sternlieb and Scheinberg, 1964,
1968; Walshe, 1956).
Other abnormalities of copper metabolism are primarily
associated with low levels of copper. Hypocupremia, which
is defined as 80 jag or less of copper/100 ml (Cartwright
and wintrobe, 1964a), usually refers to a low ceruloplasmin
level. In most cases it is probably due to a dietary defi-
ciency of copper or to a failure to synthesize the apoenzyme
of ceruloplasmin (Kleinbaum, 1963). Hypocupremia can also
result from malabsorption that occurs during a small bowel
disease (Sternlieb and Janowitz, 1964).
C-32
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Hypercupremia, abnormally high levels of copper, occurs
with a number of neoplasms (Delves, et al. 1973; Herring,
et al. 1960; Goodman, et al. 1967; Janes, et al. 1972).
Elevated serum copper levels occur in psoriasis (Kekki,
et al. 1966; Molokhia and Portnoy, 1970).
It is well recognized that copper is necessary for
the utilization of iron. Much of this work has been done
in animals, and the subject is well covered by Underwood
(1977). It appears that ceruloplasmin is essential for
the movement of iron from cells to plasma (Osaki, et al.
1966). Reticulocytes from copper-deficient animals can
neither pick up iron from transferrin normally nor synthe-
size heme from ferric iron and protoporphyrin at the normal
rate (Williams, et al. 1973).
The ratio of copper to other dietary components, e.g.
zinc and iron, may be almost as important as the actual
level of copper in the diet in influencing the metabolic
response of mammalian species (Smith and Larson, 1946).
The cardiovascular disorder "falling disease", reported
by Bennetts, et al. (1942), is associated with a copper
deficiency in cattle. Similar conditions have been observed
in pigs and chickens (O'Dell, et al. 1961; Shields, et al.
1961). In this disorder the elastic tissue of major blood
vessels is deranged, markedly reducing the tensile strength
of the aorta. This appears to be associated with a biochemical
lesion, the reduced activity of lysyl oxidase, a copper-
requiring enzyme necessary for elastic tissue formation
and maintenance (Hill, et al. 1967).
C-33
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Evans has discussed the metabolic disorders of copper
metabolism including nutritional disorders, inborn order
errors of proper homeostasis, and disorders due to the lack
of copper-requiring enzymes (Evans, 1977).
Particular attention has been given to the role of
copper as associated with cardiovascular diseases (Vallee,
1952; Adelstein, et al. 1956). More recently there has
been considerable interest in the role of copper and its
ratio to zinc as a factor in the level of cholesterol and
cholesterol metabolism as it may relate to ischemic heart
disease (Klevay, 1977). It has been suggested that a low
copper - .high zinc ratio may result in an increased level
of cholesterol, particularly that part of the blood choles-
terol in the serum low density lipoprotein which has been
associated with increased susceptibility to ischemic heart
disease (Allen and Klevay, 1978a,b; Petering, 1974; Lei,
1978; Klevay, et al. 1977). In a different context, Barman
(1970) has suggested that copper in the diet in excess of
needs may result in free radicals that cause adverse effects
in the cardiovascular system.
Excretion
It has been noted that perhaps 40 percent of dietary
copper is actually absorbed (Cartwright and Wintrobe, 1964a) .
These estimates are largely based on the difference between
oral intake and fecal excretion. Urinary excretion of copper
plays a very minor role. The fecal excretion represents
unabsorbed dietary copper and the copper that is excreted
C-34
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by the biliary tract, the salivary glands and the gastric
and intestinal mucosae (Gollan and Deller, 1973). It should
be noted that some of the excreted copper is reabsorbed
in the course of its movement down the intestinal tract.
Some loss of copper may occur by way of sweat and in the
female menses.
One of the principal routes of excretion is by way
of the bile; however, because of the difficulty in studying
biliary excretion in normal subjects, the evidence for quanti-
tative values of copper excretion by this route is fragmen-
tary. Cartwright and Wintrobe (1964a) suggest that 0.5
to 1.2 mg per day is excreted in the bile. This is in reason-
able accord with the report (Frommer, 1974) that excretion
was approximately 1.2 mg per day in ten control subjects.
It is possible that very little of the copper excreted in
the bile is reabsorbed (Lewis, 1973).
Some copper (approximately 0.38 to 0.47 mg per day)
is excreted in the saliva, but there is little evidence
as to whether this copper is or is not absorbed in the intes-
tine (DeJorge, et al. 1964).
It is possible that the gastric secretion of copper
approximates 1 mg of copper per day, but there is very little
published information on this subject (Gollan, 1975) .
The amount of copper excreted in the urine is small.
Estimates range from 10 to 60 ug per day and average 18
ug per day (Cartwright and Wintrobe, 1964a; Zak, 1958).
It is possible, of course, that copper may be reabsorbed
from the kidney tubules (Davidson, et al. 1974).
C-35
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Studies in New Zealand conducted on young women with
a copper intake of 1.8 to 2.09 mg per day showed an excre-
tion in the feces of between 65 and 94 percent of the intake,
The urinary excretion amounted to 1.7 to 2.2 percent of
the intake (Robinson, et al. 1973).
Under some conditions a considerable amount of copper
may be lost through sweat/ perhaps as much as 1.6 mg of
copper per day or about 45 percent of the total dietary
intake (Consolazio, et al. 1964).
There is very little information on the loss of copper
by way of the menstrual flow but an average value of 0.11
+ 0.07 mg per period seems reasonable (Ohlson and Daum,
1935; Leverton and Binkley, 1944).
Sternlieb, et al. (1973) note that 0.5 to 1.0 mg of
copper is catabolized daily by the adult liver and about
30 mg of ceruloplasmin, which contains 0.3 percent copper/
is excreted into the intestine (Waldmann, et al. 1967).
The copper excreted into the intestine in the bile may not
be readily available for reabsorption because it is bound
to protein; the copper found in the feces seems to come
from various secretions, as well as the copper which is
not absorbed from food (Gollan and Deller, 1973).
In summary it may be said that most copper is excreted
by way of the biliary system with additional amounts in
sweat, urine, saliva, 'gastric and intestinal mucosae, and
in women in the menses.
C-36
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Examination of the pharmokinetic data points up the
fact that the biological half-life of copper is very short.
This provides significant protection against accumulations
of copper even with intakes considerably above levels con-
sidered adequate.
EFFECTS
Acute, Sub-Acute, and Chronic Toxicity
Copper toxicity produces a metallic taste in the mouth,
nausea, vomiting, epigastric pain, diarrhea, and, depending
on the severity, jaundice, hemolysis, hemoglobinuria, hema-
turia, and oliguria. The stool and saliva may appear green
or blue. In severe cases anuria, hypotension, and coma
can occur.
Toxic levels of copper ingested are promptly absorbed
from the upper gut and the copper level in the blood is
rapidly increased, primarily because of an accumulation
in the blood cells. Hemolysis occurs at high copper levels.
A high level in the blood can also result from absorption
through the denuded skin, as when applied to burns, because
of dialysis procedures or because of exchange transfusions.
The hemolysis is due to the sudden release of copper into
the blood stream from the liver which has been damaged by
an increasing load of copper and is unable to utilize the
copper in the synthesis of ceruloplasmin, which in turn
can be excreted by way of the biliary system (Chuttani,
et al. 1965; Bremmer, 1974; Cohen, 1974; Deiss, et al. 1970;
Roberts, 1956; Bloomfield, et al. 1971; Ivanovich, et. al.
1969; Bloomfield, 1969).
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Chatterji and Ganguly (1950) describe a non-fatal type
of copper poisoning in which the symptoms are laryngitis,
bronchitis, intestinal colic with catarrh, diarrhea, general
emaciation, and anemia.
Burch, et al. (1975) have estimated that the chronic
toxic intake level of inorganic copper for an adult man
is 10 to 15 mg per dose. The vomiting and diarrhea induced
by ingesting small quantities of ionic copper generally
protect the patient from the serious.systemic toxic effects
which include hemolysis, hepatic necrosis, gastrointestinal
bleeding, oliguria, azotemia, hemoglobinuria, hematuria,
proteinuria, hypotension, tachycardia, convulsions or death
(Chuttani, et al. 1965; Davenport, 1953).
Because most of the information about acute copper
toxicity in humans has come from attempts at suicide or
from the accidental intake of large quantities of copper
salts, the information about the changes occurring with
acute toxicity are meager.
Acute copper poisoning does occur in man when several
grams of copper sulfate are eaten with acidic food or bever-
ages such as vinegar, carbonated beverages, or citrus juices
(Walsh, et al. 1977). Some cases of acute poisoning have
occurred when tablets containing copper sulfate were given
to children (Forbes, 1947).
When carbonated water remains in copper check valves
or drink-dispensing machines overnight, the copper content
of the first drink of the day may be increased enough to
cause a metallic taste, nausea, vomiting, epigastric burning,
C-38
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and diarrhea (Hooper and Adams, 1958) . Drinks that are
stored in copper-lined cocktail shakers or vessels can have
the same effect (Pennsylvania Morbidity and Mortality Weekly
Reports, 1975; McMullen, 1971).
Salmon and Wright' (1971) have reported the possibility
of chronic copper poisoning as a result of water moving
through copper pipes. They document a case in which a family
moved into a house in North London with a hot water system
entirely composed of copper. The water was stored in a
40-gallon copper tank which reached a temperature of 93°
Celsius at night. The family used hot water for all cooking
and beverages. After two months, the electric kettle was
coated inside with a thick green film of the copper complex.
The child in the family was admitted to the hospital after
five weeks of behavior change, diarrhea, and progressive
marasmus. When first seen the clinical picture was that
of "pink" disease with prostration, misery, red extremities,
hypotonia, photophobia, and peripheral edema. The liver
was palpable for 2 cm below the costal margin. The serum
copper level was 286 ug/100 ml, compared to a normal range
of 164 + 70 pg/100 ml. Analysis found 35 ug copper/100
ml of cold water in the home, and 79 pg/100 ml hot water.
Cold and hot water levels in the hospital were 4 and 30
^ug/100 ml respectively, and in North London the values were
8 and 16 pg/100 ml.
C-39
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Walker-Smith and Blomfield (1973) found that a child
showing symptoms of Wilson's disease had in fact drunk water
with a very high copper level (675^/100 ml). Therefore,
they suggest that individuals with suspected cases of Wilson's
disease should have the copper content of their drinking
water investigated.
Eden and Green report oh a male infant who received
high levels of copper, resulting in chronic copper poisoning
from contaminated water ingested over a period of 3 months.
Treated with D-penicilliamine and prednisolone, the infant
made a slow recovery (Eden and Green, 1940).
In general, however, the problems associated with high
levels of copper in drinking water are more of less control-
led because of taste (since high levels of copper in water
produce a metallic taste) or because of cosmetic considera-
tions (since water with high copper content develops a sur-
face scum due to the formation of insoluble copper compounds).
Chronic toxicity has been studied in animals, and there
appears to be a wide variation in the tolerance of different
species for high levels of copper in the diet. Sheep are
very susceptible to high copper intakes, whereas rats have
been shown to be very resistant to the development of copper
toxicity.
Swine will develop copper poisoning at levels of 250
jag of copper/g of diet unless zinc and iron levels are increased.
Suttle and Mills (1966) have studied dietary copper levels
ranging up to 750 ug/g in the diet of swine. Toxicosis
C-40
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does develop with hypochrbmic microcytic anemia, jaundice,
and marked increases in the liver and serum copper levels
as well as serum aspartate amino transferase. These signs
of copper toxicosis in swine can be eliminated by including
an additional 150 pg of zinc and of iron/g of diets containing
up to 450 pg of copper/g; the addition of even more zinc
and iron, 500 to 750 pg/g, will overcome the effects of
750 ^pg of copper/g of diet.
Chronic oral intake of copper acetate in swine and
rats can produce a condition comparable to hepatic hemosi-
derosis in man (Mallory and Parker, 1931a). Some question
exists as to whether hemosiderosis in man is a result of
copper toxicity, because people consuming comparatively
high levels of copper do not develop this condition regularly.
Sheep are quite susceptible to high levels of copper
in the diet. Levels of 35 pg/g of feed have resulted in
toxicity when fed over a period of 9 months to 1 year (Fontenot,
et al. 1972). Cattle are much more resistant to copper
in the diet; 2 grams of copper sulfate given daily did not
produce toxic reactions (Cunningham, 1931).
It is well known that with ruminant animals, molybdenum
and sulfate interact with the copper. Copper toxicity is
counteracted by inclusion of molybdenum and sulfate in the
diet of ruminants (Dick, 1953; Kline, et al. 1971; Wahal,
et al. 1965).
C-41
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Syneigism and Antagonism
There is some evidence that copper may increase the
mutagenic activity of other compounds. Using strain TA-100
of Salmonella typhimurium, Omura, et al. (1978) studied
the mutagenic actions of triose reductone and ascorbic acid.
They found that the addition of the copper to triose reduc-
tone at a ratio of 1:1000 lowered the most active concen-
tration of the triose reductone to 1 mM from 2.5 to 5 mM.
Another enediol reductone, asborbic acid, had no detect-
able mutagenic action by itself, but a freshly mixed solu-
tion of 5 mM of ascorbic acid and 1 or 5 /iM of cupric copper
had an effective mutagenic action. Ascorbyl-3-phosphate
had no mutagenic function even in the presence of cupric
copper. The investigators suggested that it was the enediol
structure in the reductones that was the essential for muta-
genicity.
In the "Acute, Subacute, and Chronic Toxicity" section,
it was pointed out that the dietary levels of zinc and iron
are as important as the level of copper in determining the
toxic level of copper.
Teratogenicity
There is very little evidence in the literature to
suggest that copper has a teratogenic effect in either animals
or humans.
Mutagenici ty
No data were found to suggest that copper itself has
a mutagenic effect in either animals or humans; however,
one report exists suggesting that copper may increase the
mutagenic activity of other compounds (see "Interactions,
Including Synergism and Antagonism" section).
C-42
-------
Carcinogenicity
There is very little evidence in the literature to
suggest that copper has a carcinogenic effect in either
animals or humans. Pimental and Marques (1969) noted that
vineyard workers in France, Portugal, and southern Italy
exposed to copper sulfate sprays mixed with lime to control
mildew developed granulomas and malignant tumors in their
livers and lungs (Pimental and Menezes, 1975; Villar, 1974).
Because of the route of exposure, quantitative estimates
are, at best, speculative.
It has been noted earlier that the conditions in industry
that would produce excessive concentrations of copper as
a dust or a mist with particle sizes that would result in
toxic effects if the copper were absorbed are apparently
quite rare. Some investigators have suggested that lung
cancer, which has been present with increased frequency
in workers, in copper smelters, is actually due to the arsenic
trioxide in the dust and that the copper itself did not
play any etiologic role in the development of the cancer
(Kuratsune, et al. 1974; Lee and Fraumeni, 1969; Milham
and Strong, 1974; Tokudome and Kuratsune, 1976).
Some studies have reported that, with the development
of various tumors, the copper content of both blood and
the tumor tissue is likely to increase, although this is
not always the case (Pedrero, 1951). However, when an increase
occurs, it appears to be more a result of an inflammatory
reponse or stress than any direct causative relationship.
C-43
-------
Czech workers have noted that the high copper content of
melanomas is probably due to the presence of the copper-
containing enzyme tyrosinase.
Polish workers (Legutko, 1977) have suggested that the
copper level of the serum is a particularly sensitive indi-
cator of the clinical condition and effectiveness of treat-
ment of lymphoblastic leukemia in children, but again no
particular relationship to the development of the leukemia
is indicated.
Russian scientists (Bezruchko, 1976) have also studied
the copper and ceruloplasmin in patients with cancer and
noted that the levels of both ceruloplasmin and copper were
increased in metastatic cancer of the mammary gland, in
skin melanoma, and in ovarian cancer. The serum levels
of ceruloplasmin increased 27, 20, and 44 percent, respec-
tively, for those tumors, and the copper increased by 41,
35, and 51 percent respectively, for those same tumors as
compared with normal tissue. Again there was no connec-
tion between the copper and the tumors as a causative agent.
Workers in Hong Kong (Fong, et al. 1977) have been
investigating copper concentrations in cases of esophageal
cancer in both humans and animals. They report that serum
copper is increased slightly and that this is paralleled
by a decrease in zinc content.
In summary, it must be stated that evidence for the
oncological effects of copper, even at high concentrations,
C-44
-------
is essentially nonexistent., With the exception of the refer-
ences cited, there appear to be no reports of copper as
a causative agent in the development of cancer. There is
much more evidence that a deficiency of copper will have
adverse effects both in animals and in humans due to its
essential role in the functioning of many enzyme systems.
C-45
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CRITERION FORMULATION
Existing Guidelines and Standards
Far more attention has been given to the problems of
copper deficiency than to the problems of excess copper
in the environment. The 1 mg/1 standard which has been
established for copper levels in water for human consumption
has been adopted more for organoleptic reasons rather than
because of any evidence of toxic levels (Fed. Water Quality
Admin. 1968).
The U.S. Occupational Safety and Health Administration
has adopted standards for exposure to airborne copper at
work. The time-weighted average for 8-hour daily exposure
to copper dust is limited to 1 mg/m of air. The standard
for copper fume was changed in 1975 to 0.2 mg/m (Gleason,
1968; Cohen, 1974).
There are no standards for copper in medical practice
such as the treatment of burns or dialysis or for parenteral
feeding.
Current Levels of Exposure
As has been mentioned earlier, principal concern has
been for conditions of copper deficiency rather than copper
toxicity. It has been suggested earlier that copper intakes
in food and water may range from 6 to 8 mg per day, and
that the percentage absorbed varies with the nutritional
status. On the other hand, because of changes in food proces-
sing and, perhaps, because of better methods of analysis,
copper intakes may not reach the 2 mg per day considered
C-46
-------
an adequate nutritional intake (Klevay, et al. 1977; Diem
and Lentner, 1970; Robinson, et al. 1973; Schroeder, et
al. 1966; World Health Organization, 1973; Cartwright and
Wintrobe, 1964a).
The average concentration of copper in United States
water systems is approximately 134 jug/1 with a little over
1 percent of the samples taken exceeding the drinking water
standard of 1 mg/1 (McCabe, et al. 1970). When the U.S.
Public Health Service studied urban water supply systems,
they found that only 11 of 969 systems had copper concentra-
tions greater than 1 mg/1 (U.S. Dep. Health Educ. Welfare,
Pub. Health Serv. 1970).
In 1966, the National Air Sampling Network found airborne
copper concentrations ranging from 0.01 to 0.257 /jg/m in
rural and in urban communities, respectively. Levels of
copper as high as 1 to 2 jug/m were found near copper smelters,
but this was not considered hazardous (Natl. Air Pollut.
Control Admin. 1968; Schroeder, 1970).
Special Groups at Risk
Increased copper exposure, with associated health effects,
has occasionally occurred in young children subjected to
unusually high concentrations of copper in soft or treated
water that has been held in copper pipes or stored in copper
vessels. Discarding the first water coming from the tap
can reduce this hazard. Similar problems have developed
in vending machines with copper-containing conduits where
acid materials in contact with the copper for periods of
time have dissolved copper into the vended liquids.
C-47
-------
Other groups that may be at risk are medical patients
suffering from Wilson's disease, and those patients who
are being treated with copper-contaminated fluids in dialysis
or by means of parenteral alimentation. These are medical
instances in which the copper content of the materials used
should be carefully controlled.
A final group that may be subject to risk of copper
toxicity consists of those people occupationally exposed
to copper, e.g., industrial or farm workers.
In reviewing the medical and biologic effects of environ-
mental pollutants, the National Research Council Committee
(Copper, 1977) pointed out that use of livers from animals
fed high levels of copper in the diet could produce a baby
food product that was excessively high in copper. The Com-
mittee also raised the question of exposure to copper from
intrauterine contraceptive devices (lUDs), but subsequent
reports have failed to demonstrate any abnormal accumulation
of copper because of the use of these devices.
Basis and Derivation of Criterion
Copper is an essential dietary element for humans and
animals. A level of 2 mg per day will maintain adults in
balance (Adelstein, 1956) and has been considered adequate,
although because of interactions with other dietary consti-
tuents which limit absorption and utilization, a requirement
level must be considered in conjunction with such constituents
as zinc, iron, fiber, and ascorbic acid. The minimum level
meeting requirements for copper intake in intravenous feeding
was 22 jug copper/kg body weight. (Vitter, et al. 1974).
C-48
-------
The short biological half-life of copper and the homeo-
stasis that exists in humans prevents copper from accumulating,
even with dietary intakes considerably in excess of 2 mg
per day. In the opinion of many investigators, there is
much more likelihood of a copper deficiency occurring than
of a toxicity developing with current dietary and environmental
situations.
Although acute and chronic levels of intake may occur,
there are no good data which define these levels. It has
been suggested that chronic intakes of 15 mg of copper per
day may produce observable effects, but if zinc and iron
intakes are also increased, much higher levels may be consumed
without adverse reactions. The data for acute toxicity
are even more uncertain, since practically all human informa-
tion stems from cases of attempted suicide.
The available literature leads to the conclusion that
copper does not produce teratogenic, mutagenic, or carcinogenic
effects. The limited information available indicates that
where such action has occurred, e.g., with mixtures of copper
sulfate and lime, arsenic, or enediols, the copper should
be considered as interacting with the other materials and
not as the active material.
The current drinking water standard of 1 mg/1 is consi-
dered to be below any minimum hazard level, even for special
groups at risk such as very young children, and therefore
it is recommended that this level be maintained for water
quality purposes.
C-49
-------
Since the recommended criterion of 1.0 mg/1 is based
on organoleptic effects and is not a toxicological assessment,
the consumption of fish and shellfish will not be considered
as a route of exposure.
C-50
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64
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