|
Items in cart [0] |
Questions? Call 888-624-8373 |
| Copyright © 2009. National Academy of Sciences. All rights reserved. Terms of Use and Privacy Statement |
Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 162
Copper
The attractive, ductile, and conductive metal copper (Cu) has played a
significant role in civilizations since the Stone Age. From the crude
hammered artifacts dating to about 6000 B.C. to the electrical use for
copper by Western man, one appreciates the past and present reliance
upon this metal. Its presence in biological systems was well established
by the nineteenth century, but not until the early twentieth century did
copper become recognized as an essential trace element.
The literature on biological aspects of copper is voluminous. Severe
comprehensive reviews on the subject exist, including those of the
National Research Council (1977), Schroeder et al. (1966), Scheinberg
and Sternlieb (1960), and Underwood (1977~. Specific reviews on the
toxicologic aspects of copper include those of Buck et al. (1973) and
Clarke and Clarke (l975~.
ESSENTIALITY
The essentiality of copper was suggested by McHargue (1925) in the
early 1920's; however, conclusive evidence of the biological require-
ment for copper was actually provided by Hart e! al. (1!728) working
with anemic, milk-fed rats. While their anemia was not corrected by
162
OCR for page 163
Copper
163
either iron supplementation alone or by a liver extract alone, feeding
iron and liver together caused a marked elevation in the hemoglobin
and packed cell volume within approximately 2 weeks. A bluish tinge
of the ashed liver preparation was a clue to its copper content and
prompted simultaneous copper and iron supplementation of the milk-
fed anemic rats. Their dramatic response in hemoglobin formation was
a milestone in the history of nutrition research. Since then the roles of
copper in ovine enzootic ataxia (swayback), bovine falling disease,
aortic rupture in swine and turkeys, woo! and hair depigmentation, and
anemia have been elucidated. Numerous copper dependent enzymes,
including lysy! oxidase, cytochrome C oxidase, ferroxidase, and tyro-
sinase, have been recognized (O Dell, 1976~.
The level of dietary copper required for health is somewhat species-
dependent and is usually positively correlated with dietary levels of
molybdenum (Mo) and inorganic sulfur. Various data suggest that the
copper requirements for specific biological processes increase in the
rat, for instance, in order as follows: hemoglobin formation, growth,
hair pigmentation, and lactation. When dietary conditions are optimal
for utilization of copper, 4 to 5 ppm copper in swine and poultry rations
and 8 to 10 ppm copper in ruminant rations appear adequate (Under-
wood, 1977~.
METABOLISM
Copper absorption for most species appears to take place in the
duodenum and jejunum. Absorption is affected significantly by the
chemical form of the ingested copper. In domestic species, the absorp-
tion rate may be as low as 10 percent (Comer, 1950~. In general, copper
carbonate (CuCC)3~) and the water soluble forms, copper sulfate, nitrate,
and chloride, are absorbed to a greater extent than copper oxide (CuO).
Metallic copper is very poorly absorbed.
Absorbed copper appears first in plasma as cupric ion loosely bound
to albumin. During hepatic synthesis of ceruloplasm~n, copper is tightly
bound to this metalloprotein, which is then released to the general
circulation (Scheinberg and Sternlieb, 1960~. Ultimately cuproprotein is
present in brain, erythrocytes, and liver as cerebrocuprein, erythro-
cuprein, and hepatocuprein, respectively. The biliary system is the
major excretory pathway for absorbed copper in most species studied
(Underwood, 19771. Copper is also excreted during perspiration and
lactation. Large quantities of copper are excreted by the urinary system
in cases of biliary obstruction or Wilson s disease.
OCR for page 164
164 MINERAL TOLERANCE OF DOMESTIC ANIMALS
SOURCES
There is a great geographical vanability in the copper content of soils
as reflected in the natural incidence of copper deficiency in livestock in
venous parts of the world. Essentially all plant matenals contain
copper, which has an affinity for me plant lipids (Schroeder et al.,
1966~. Of the animal products, oysters have the highest concentration
of copper, approximately 137 ppm on a dry weight basis.
Numerous copper-containing compounds used in agriculture and
veterinary medicine such as plant and animal fungicides, mollusca-
cides, and foot baths for the control of foot rot in cattle and sheep have
provided sources of copper in some instances of copper toxicosis. The
copper residues in litter from copper-supplemented swine and poultry
have become a significant dietary copper source when this litter is
recycled in livestock diets (Fontenot, 1972; Davis, 1974~.
Elevations in hepatic, serum, and urine copper levels have occurred
in Australian livestock from the consumption of lupin containing toxic
alkaloids, although dietary levels of copper are in the low to normal
range. Additionally, the p~antHeiiotropium europium contains hepato-
toxic alkaloids (heliotrine and lasiocarpine), the ingestion of which
impairs hepatic capacity to metabolize copper and results in toxic ele-
vations of liver copper in ruminants (Bull et al., 1956; Underwood,
1977).
TOXICOSIS
LOW LEVELS
A significant time period (weeks to months) is usually required for the
development of chronic copper toxicosis signs; however, their ultimate
expression is so rapid that the fatal course appears to be caused by an
acute process. Calves fed copper, as copper sulfate, at 115 ppm (Strand
and Lewis, 1957) and 300 ppm (Weiss and Baur, 1968) for up to 129 days
exhibited thirst, apathy, hemolytic crises, icterus, hepatic necrosis, and
death. Adult cattle are believed to be more resistant to copper toxicosis
than younger cattle. Felsman et al. (1973) found growing calves were
not affected adversely by supplemental copper at levels of up to 900
ppm as cupric sulfate over a 90-day period. Ferguson (1943) and Cun-
ningham e! al. (1959) have fed 1.2 to 5 g copper sulfate (40 to 500 ppm
of copper) daily for up to 16 months to cattle older than 7 months
without apparent ejects, even in pregnant animals. Kidder (1949),
however, observed copper toxicosis in a 227-kg steer fed ~ g of copper
sulfate per day for 122 days.
OCR for page 165
Copper
165
OCR for page 166
166 MINERAL TOLERANCE OF DOMESTIC ANIMALS
weights have all resulted in the induction of hemolytic crises and var'-
able rates of mortality within 45 to 115 days.
Swine appear more tolerant of dietary copper than ruminants. In fact,
250 ppm of copper as CuSO4 have been used routinely for its anti-
microbial effect and growth promotion in swine. This level of copper
fed to pigs 3 to 7 weeks old has been associated with decreased growth,
hemoglobin, and liver iron levels and increased liver copper and zinc
levels (Ritchie et al., 1963; Gipp et al., 1973a,b, 1974~. AlIcroft et al.
(1961) found that 400 ppm copper in swine rations were nontoxic, but
liver copper levels rose sharply under this regimen. Dietary copper at
500 ppm (as CUSO4) caused reduced gains, anemia, and death among
swine despite molybdenum supplementation (Combs et al., 1966;
DeGoey et al., 19711. Suttle and Mills (1966) reported that feeding
swine 425 to 750 ppm dietary copper caused reduced feed intake,
retarded growth, anemia, jaundice, increased liver and serum copper,
and elevated aspartic transaminase levels. The toxic effects of lower
levels of dietary copper in that experiment were eliminated by supple-
menting with 150 ppm zinc and 150 ppm iron. At the highest level of
copper supplementation, the toxicosis was eliminated by 500 ppm zinc
and 750 ppm iron. Rations containing 1,000 ppm copper are reported to
be lethal in pigs (Allcroft et al., 19611.
Copper has been used as an antimicrobial and/or growth-promoting
agent in poultry, i.e., growth rates in young ducks are increased by
feeding 100 ppm oral copper as cupric sulfate during an 8-week period
(King, 1975~. Mehring et al. (1960) reported that 500 ppm copper in
standard diets was the minimal toxic level for copper in growing chick-
ens, although Mayo et al. (1956) found 324 ppm copper caused growth
retardation and muscular dystrophy in growing chickens fed a cor~soy
diet. Dietary copper at I, 176 ppm fed to growing chickens for a 10-week
period resulted in a 51 percent weight loss in these birds (Mehringet al.,
19601. In adult hens, Goldberg et al. (1956) found 800 to 1,600 ppm
copper as copper acetate caused weight loss, anemia, and a 33 percent
mortality. The minimal toxic effect level of copper for young turkeys
appears to be in the range of 300 to 400 ppm (Supplee, 1964; Vohra and
Kratzer, 1968~. Their studies indicated that 800 to 900 ppm copper in
normal turkey rations caused reduced growth, while 3,240 ppm copper
caused death in 21 days. Copper in purified turkey diets appears much
more toxic than in standard diets inasmuch as 100 ppm copper as
CuSO4 or CuCO3 caused decreased growth and mortality in young
turkeys fed a purified diet for a 3-week period (Waibel et al., 1964~.
Horses appear to be more resistant to copper toxicosis than either
cattle, swine, sheep, or poultry. Smith et al. (1975a) fed ponies diets
OCR for page 167
Copper 167
containing 791 ppm of copper as cupric carbonate (CUC03) for a period
of 6 months without ill effects in the experimental animals or their
offspring. This level of copper resulted in liver copper levels between
3,445 and 4,294 ppm, dry basis. Despite high liver copper values, hemo-
lytic crises were not induced, and no copper was present in the
urine, albeit fecal copper increased steadily during the course of the
experiment.
Dietary copper at 200 ppm as cupric sulfate has proven to improve
growth rates in rabbits (King, 19751.
The toxic effects of copper in tank water for gilled fish include con-
gestion of the respiratory lamellae (P'equignot and Moga, 1975) and
gradual reduction leading to total ablation of mucous cells in the res-
piratory lamellae (P'equignot et ai., 1975), inhibition of growth
(Hubschman, 1967), fatty degeneration of liver, renal necrosis, de-
creased hematopoietic centers (Baker, 1969), blockage of spawning
(Mount, 1968), increased mortality (Hazel and Meith, 1970), and
decreased hatchability of eggs (Brungs et ai., 19761. The maximal
acceptable toxicant concentration (MATC) for copper in continuously
flowing water for minnows has been calculated at between 66 and 118
ppb (Brungs et ai., 19761. Mount and Stephan (1969) have shown that
the softer the tank water for the fish, the lower the MATC for copper will
be. Young fish (fry) are inhibited in growth and have an increased
mortality at approximately one-fourth the levels of copper that are
required to reduce hatchability of fish eggs. Crayfish and lobsters seem
to be less tolerant of copper than finned fish, i.e., copper concentra-
tions as low as 15 ppb retard growth in young crayfish (Hubschman,
1967), while 56 ppb is the lethal threshold (LT") for lobsters in 20 to 30
percent saline water (McLeese, 19741.
Laboratory rats appear very resistant to dietary copper, as indicated
by Boyden et al. (1938), who found the minimal toxic effect level for
copper as CuSO4 in ~owing rat diets to be approximately 1,000 ppm;
2,000 ppm (11.8 mg Cu/rat/day) caused weight loss, and 4,000 ppm
caused death within 1 week. Cho (1973) reported copper-toxic rats
developed hyperplasia of adrenal gland and anterior hypophysis.
HIGH LEVELS
Considering the quantities of copper compounds that have been used in
agriculture and veterinary medicine, there are relatively few veterinary
examples of acute copper toxicoses. Cases of acute copper toxicosis
have occurred in accidental overdosing or the accidental consumption
of copper-containing anthelmintics, foot baths, and fungicides. Copper
OCR for page 168
168 MINERAL TOLERANCE OF DOMESTIC ANIMALS
EDTA and copper glycinate are parenteral copper supplements that
could produce copper toxicosis (Buck et al., 1973~. The cellulitis and
abscess formation, which often accompany the subcutaneous injection
of copper glycinate, might be considered an acute local copper toxi-
cosis (Smith et al., 1975b).
Acute copper toxicosis has been studied in sheep by Isae} et al. (1969)
and by Wiener and Macleod (l970~. They reported that 50 mg of copper
subcutaneously administered produced death within 24 to 72 hours in
sheep of various ages. They also found young sheep to be much more
susceptible to acute copper toxicosis than older sheep. The intravenous
administration of 50 me copper as copper EDTA caused death among
sheep within 3 to 7 days (Macleod and Watt, 1970), and a single oral
dose of 0.7 to 1.5 g copper carbonate (estimated to supply 400 to 800 mg
of copper) also caused death in sheep within 3 to 7 days (Sasu et al.,
1970).
The signs of acute oral copper toxicosis include nausea, vom~tion (in
species capable of vomiting), salivation, violent abdominal pain, con-
vulsions, paralysis, collapse, and death. Necropsy reveals marked
gastroenter~tis, necrotic hepatitis, splen~c and renal congestion, and
evidence of antemortem intravascular coagulation. Sheep dying acutely
of subcutaneous injections of copper EDTA exhibit hydrothorax, hydro-
pentoneum, and hemorrhage into the alimentary tract. The toxic level
of oral copper as CuSO4 in sheep is believed to be between 9 and 20
mg/kg of body weight and approximately 200 mg/kg of body weight in
cattle (Buck et al., 1973~.
Canadian geese ingesting pond water containing 100 ppm copper as
CuSO4 developed acute copper toxicosis with necrosis of the pro-
ventnculus and gizzard and a greenish discoloration of the lungs
(Henderson and Winterfield, 1975~.
Acute copper toxicosis in horses was studied by Bauer (1975), who
found 125 mg CuSO4 per kilogram of body weight in a single oral dose
caused hypercuprem~a, hepatic and renal damage, and death within
2 weeks.
Eden and Green (1939) have conducted acute copper toxicity studies
in rabbits. The level between no effect and LD50 in rabbits for a single
intravenous dose of copper is between 2.0 and 2.5 mg/kg of body
weight. Five milligrams of copper per kilogram of body weight admin-
istered intravenously to rabbits was fatal within a few minutes, and 50
mg/kg of body weight administered to rabbits by a single oral drench
was fatal in 6 hours.
Acute canine copper toxicosis has been produced (GubIer e! al.,
OCR for page 169
Copper 169
1953) with 165 mg copper per Program of body weight in a single of
CuSO4 dose. The toxicosis was charactenzed by vocation and death
within 4 hours.
The ~D50 for CuSO4 in rats is approximately 300 mg per kilogram of
body weight (Stecher, 1968~. In acute cases of copper toxicosis, copper
analysis of feces is considered a more satisfactory diagnostic aid than
hepatic or blood copper levels.
The acute toxic effects of intravenously administered copper have
been studied in pregnant hamsters (Ferm and Hanson, 19741. Both
cupric sulfate and copper citrate caused resorption of fetuses and cop-
per citrate at 250 lag per 100 g of body weight, when given on day ~ of
gestation, caused fetal malformation.
FACIORS INFLUENCING TOXICITY
The apparent differences in copper tolerance between ruminants and
nonrum~nants is influenced significantly by concurrent dietary levels of
iron, zinc, molybdenum, selenium, and inorganic sulfur. How each of
these factors influences the toxic effects of dietary or parenteraBy
administered copper is still being researched. The apparent differences
between ruminants and nonrum~nants in their susceptibility to copper
toxicity seems in large part determined by their differences in sulfur
metabolism. Some variation in susceptibility to copper toxicity exists
among venous breeds within a species; for instance, Merino sheep are
more tolerant of dietary copper than other breeds of sheep (Buck et al.,
1973~. Development of an acquired tolerance to copper from previous
exposure to copper, as occurs with cadmium, for instance, is believed
not to occur.
TISSUE LEVELS
Levels of copper in most tissues, except muscle and endocrine organs,
are directly affected by copper intake, tend to decline with age, and are
quite species-dependent (Underwood, 19771. Liver copper concentra-
tions normally range, on a dry matter basis, from 15 to 30 ppm for a
wide variety of monogastnc mammals and domestic fowl (Beck, 1956),
while liver copper levels of sheep, cattle, and ducks can range 10 times
the above levels (Beck, 1961~. Heart, hair, brain, and kidney tissue
copper levels are intermediate in range (9 to 15 ppm dry basis) and also
reflect copperintake rates (Underwood, 1977~. Certain parts of the eye,
OCR for page 170
170 MINERAL TOLERANCE OF DOMESTIC ANIMALS
especially the pigmented areas, contain copper concentrations exceed-
~ng that of the liver (Bowness et al., 19521. In copper toxicosis hepatic
concentrations of copper can be elevated to 2,000 to 3,000 ppm (Dick,
1954), especially in sheep and cattle, and are believed responsible for
the hemolytic crises of copper toxicosis in these species.
Normal blood copper levels range between 50 to 150 ,ug/dl in many
species (Beck, 1961~. Increases in blood copper levels require rather
exaggerated elevations in copper intake, while deficient copper intakes
readily result in lowered plasma values (Underwood, 1977~.
MAXIMUM TOLERABLE LEVELS
The data reviewed suggest that the maximum tolerable levels of dietary
copper during growth of various species approximate the following
under normal levels of molybdenum, sulfate, zinc, and iron: sheep, 25
ppm; cattle, 100 ppm; swine, 250 ppm; horses, 800 ppm; chickens, 300
ppm; turkeys, 300 ppm; rabbits, 200 ppm; rats, 1,000 ppm; minnows,
100 ppb; trout, 100 ppb; lobsters, 15 ppb; crayfish, 15 ppb; and salmon,
20 ppb. In general, the maximum tolerable levels for copper in adults
of the above species are expected to be greater than for the younger
animals. The maximum tolerable level for copper in purified type diets
is usually lower than in standard type diets. In the case of fish, the
harder the tank water, the more tolerant the fish will be of copper.
SUMMARY
Copper is an essential trace element primarily because of several
copper-dependent enzymes involved with iron metabolism, elastin and
collagen formation, melanin production, and integrity of the central
nervous system. Copper toxicosis, for the most part. stems from the
use of the metal as an antimicrobial and/or growth-promoting sub-
stance. Species vary widely in susceptibility to copper toxicity, in part
due to differences in sulfur metabolism as well as differences in concur-
rent dietary levels of sulfur, molybdenum, zinc, iron, and selenium.
Overt manifestations of copper toxicosis in ruminants are secondary to
a hemolytic crisis triggered by severely elevated hepatic copper levels.
The effects of copper toxicosis in other animals are less dramatic and
include growth inhibition, anemia, muscular dystrophy, impaired
reproduction, and decreased longevity. Copper levels below 1 ppm in
waters inhabited by fish are toxic. Chronic dietary copper levels of 26
OCR for page 171
~~, 171
10 38 ppm far sheep can markedly elevate hepadc copper levels,
wbemas levels of 3~ ppm copper in ~ diets me well 1olera1ed.
Molybdenum is the most 1~uend~ element ^chag 1be level
copper tolerance in mommas Id ~ used 1~ul~1y in cases of
copper10~icosis.
OCR for page 172
c
to
-
-
-
~:
-
Ee~
._
it:
a:
._
.o
Ct
_,
Cal
a
.
£
$.4
a
Cal
o
en
-
v
Fee
CUT
.o
al
In
~ —
o ~
,0 ·—
~ 3
_ ~ ~ E
E ~
Em ~ ~ ~ 3
c ~ ~ m ~ ~ ~ ~ ~ ~ ~ - m C E
. 7 E _ , ' 7 c . E
i C ~ i l ~ ~ 2 E E ~ ~ , ~ j ~ "E j ~ E
_ _, _
~ ~ ~ a a a o~
in
o
~ _
C .O
o 3 ~ ,~ = ~ `~ '; o 3 ~ ~ o,
~ - ~ ' ~ ~ ~ ~ ~ ~ x ~ ~ ^_
O ~ O
co O' O O O 0' 0 0^ 0
~o ~ ~ ~ oo ~ ~ ~ ~ ~ ~ s~ E
5 E ~ '' 8 ° ~ ° °. ~ ~ ~ ° ~ ~ o
~ ~ ~ E o. ~ 0~
_ ~ ~ ~ ~ ~ 0
· (~l ~ oo
u u u u ~ u 3 u ~ ~
172
OCR for page 173
E = E ~ ~ ~ §` ~
· ~
·m ~
a, E o o.D
e ~ t .> e c
~ C)
_ _
| ~ D E e ~ 16 ' ~ ~ ° ~ ~ ' ~
~ ~ ~ 1
a cat _ ' ~ ' =~ ' :,' ' ~ ~ 2
O
~ u, In ~ ~ *"
O ~ I~ =0 ~ =° ,~~~ r— h~~ 0 .~d
a a
0 0
o' 0 o' ti ~ a 0 0 0
us oh u' ~ ~ ~ ~ ~ 3
Cal C) ~ ~ ~ ~ ~
E E co Ott ~~ To as To ~ 3 E
X X v. wO, O v. ~ O ~ I_ D v,
3 E ~ ~ £
~ ~ ~ ~ ~ ~ 3
0 ~ — 3 os
~ Q
o7 Y ~ ~ ~ V' Y
173
OCR for page 174
C, C. ~ _- ~ j
C I ,C ~ . ~ .~ ~ ^_ ~ ~ ~ D
-~ e° ~~ E e = ~ - E o 0 c c
~S.-c=O" ~O~e= ° ~S~-~S ~ c=2= =
:, E io x ° c ,~s ~ ~ 3 C =: ~ O ~ =~ ~ =~ 3 ~ ~ ~ =~ ~ ==
pL1 ~ P: Z; Z ~ ~ ~ P: ~
o
·3
-
U,
._
._
m
`: ~
° ~ 3
ct ce 0
a a
0
'l
~ o.
o
— S
·3
~ 43.)
eC
C)
~V — _
a a . a a
o
U.
O Y
cL ~ ~ 3
_ x
ct
a
~4
.
V)
-
o
V-,
0 0 0 0
C~ ~ ~ C~
~ 3
4_ _
._ ._
a a
-
_
~ ~:
e¢ ."
_
o 3
~:
3
_ c~
o
O O
co cn
oo os
E ~ ~ ~ £ ~ ~ £ £
0 0 ~ v, 0 0 0 0 0
v, '. 0 '. '}
_ _ ~ ~ ~, ~ ~
-
~_
0
E° 3 3 ~° 3
~ _ ~o ~ ~ ~ oo ~
O.c 3 c
4,, _ 0 ~
et 3 C: ~
~c c, E 1 ~ ~L e c e e
Z; o ~ cn v, ~ v, ~ u'
174
OCR for page 175
-
~ ~ ~ E ~ o ~ E
A, y ~ . o id, c ~ Y , o ~ ~ ~ S E j ~ · 5 ~ E E E ~ o
~ .~ ~ ~ ~ ~ I:: ~ o ~ en ~ ~ .~ ~ ~ 3 ~ ~ o ~ ~ O ~ ~ ~ ~
_ _ ~ _ ~ _ _
a ~ a ~ fi a
3
~ Y ~ ~
3 3 ~ 3 3 3
a, ~ o
Ct
_ _ _ _
a
o 3
:^ ;^
·Ct ·Ct
O ~ O
O ~ O O O ~ ~ ~ O O
~ ~ U~ U~ 0~ C~ 3 3 !t
~ U V t-) ~ ~ ~ c) ~ V ~ ~
CL & ~ &
& & ~ &
O ~ o C
', ~ V~
e e ~ ~ se ase e es
& ~ & & & ~ &
& ~ & ~ ~ ~ ~ & ~ &
o 8 ~ ~ ° 8 ~ 8 8 8 8 -°
~ ~, _ ~ ~ ~ ~ ~ ~ ~ oo o~
3 3 ~: ~ 3 ~ °0 3
8 0~' 3 c ~ c ~ —
~ ;,,,
0 0
c~ ~ I 0
3 .C e e e ~, Y y =~' =.
175
OCR for page 176
-
-
-
- ~ - '' ~
- ~ ~ ~ - ~ ~
0\ ~ Cl5 Cell V — —4
D ~ TIC ·—~ Cal :~ <,
3 ~ u, ~ ~ ¢4
-
° s._ ~ 8." EE ~ ' s ·. ~ ~ ,. ~ ~
~ ~ ~ =~ 3 ·~c ~ _ c, 4- o o ce c ~ ~ ~ _ E ~ _ E
o {pi C$) ~U}
V
·' ' _ X in, to ~ C ., I, of
o 0 0- o o 0 ~ O O
V' ~ ~ ~ ~ C) ~ ~ ~
o | ~ E E E E E. E, Ei E E' E C. ~ a, E
E I 0' ~ o 0, ~ g g ~ x o ~ x 0 ~ I, 4,
~ ~ ~o
.
OCR for page 177
Y ~ ~ ~ a ~
sugary,= £~ £5 Ares IRE
U.
~ ° c _ ~ 3 3 0 an ~- ~ c 3
Cot ~ —
o o ·—
s
A` ·a ~ ~ _
t4 — ~ ox art — Cot of o~ =~ ~ oN
~ Ce o
._
O
~ 8~
~ , Cot
·- i.C
Cot Cot
t4 os 04 os
E E E E ~ ~ De ~ ~ D it, D o ~ ~
V, to of Go to _ ~ A of of of ~ _
(~' V, 0 = 0` ~ ~ ~ ~ ~ ~ Go O
`0 4~}
~0
e~~~ os e~s e~o '
~1
._
3
o
,5._ ._ 3 0 0
D ~ D .D C ~ C:
,D D D ~ C C ~ o
177
OCR for page 178
-
c~
-
c)
-
E
:'
o
V'
o
.^
_ ~
~0 4,.)
==
:3
·_
-
A
—
o ~
oo
/V ·—
3
t D E
E ~
~— ~
Ce s _
Hi
IS ~ Y
~ I: ~ _
1 2 ~ | a.,
' E I - J ' Y—E I - — I .
t~.Cs~z,~3~.E~!s~ "~cz
to
· - 0
3 ~ ~ cat
o 5: ~ 3
EN
3
O
~ :, 3
o ._
~ o
o
O .
U] Vat
_ :,
D D D D D ~ D
CL ~ ~ ~ me ~
O. S~ ~ ~ ~ S:L
_ o O . - 0 0 g g g
_ r~
-
-
U,
a0 ;^ :^
t0 s
ct
v'
178
.
~o
o
-
OCR for page 179
i:
a:
~ Is
~ oN
~ -
ad 0\
3 —
V
-
a"
O —
-
-
-
~ O
ce ~
j g ~ '3 ~ ' :' cho $~ ci '.- I
.c O .c O , O
rs ~ a ~ ~
S S ~
. ° ~ ~ -a c ~ 7 ° ~= ~ a a
:, ~ ~ a 0
i ~ ~ ~ o.
[A CO CQ Ca)
C
00 00
,~ D ~ ~ ~ ~ ~ 8= ~ ~ == E E
~ ~ - ~ ~ 8 ~ ~ ~ ~
_
s A:
01} t, 3 _
l, c Co ~ ~ C
8
~ , ~
.o ~ ~ ~ ~ ~ ~ E E
179
U.
s~
o
._
3
o
D
o
00
o
-
._
CO
.~
Eib
._
=
._
U.
CtS
o
o
-
.~
_
e~ U~
_ es
& ·a
U.
·~:
O
~ ._
D ~
~:
C\S
~ 3
Z ~
OCR for page 180
180 ~ MINERAL TOLERANCE OF DOMESTIC ANIMALS
REFERENCES
Adamson, A. H., D. A. Valks, M. A. Appleton, and W. B. Shawl Ig69. Copper toxicity
in housed lambs. Vet. Rec. 8S:368.
Allcroft, R., K. N. Burns, and G. Lewis. 1961.The effects of high levels of copper in
rations for pigs. Vet. Rec. 73:714.
Baker, J. T. P. 1969. Histological and electron microscopical observations on copper
poisoning in the winter flounder. J. Fish. Res. I)d. Can. 26:2785.
Bauer, M. 1975. Copper sulfate poisoning in horses. Vet. Arch. 45:257,
Beck, A. B. 1956. The copper content of the liver and blood of some vertebrates. Aust.
J. Zool. 4:1.
Beck, A. B. 1961. Observations on the copper metabolism of the domestic fowl and duck.
Aust. J. Agric. Res. 12:743.
Bowness, J. M., R. A. Morton, M. H. Shaker, and A. L. Stubbs. 1952. Distribution of
copper and zinc in mammalian eyes. Occurrence of metals in melanin fractions of eye
tissues. Biochem. J. 51:521.
Boyden, R., V. R. Potter, and C. A. Elvehiem. 1938. Effect of feeding high levels of
copper to albino rats. J. Nutr. 15:397.
Brungs, W. A., J. R. Geckler, and M. Gast. 1976. Acute and chronic toxicity of copper
to the fathead minnow in a surface water of variable quality. Water Res. 10:37.
Buck, W. B., G. D. Osweiler, and G. A. VanGelder. 1973. Clinical and Diagnostic
Veterinary Toxicology. Kendall/Hunt Publishing Co., Dubuque, Iowa.
Bull, L. B., H. E. Albiston, G. Edgar, and A. T. Dick. 1956. Toxaemic jaundice of sheep:
Phytogenous chronic copper poisoning, heliotrope poisoning and hepatogenous
chronic copper poisoning. Aust. Vet. J. 32:229.
Cho, S. H. 1973. Morphological eject of excess copper sulfate on the adrenal gland and
anterior hypophysis of the rat. Yonsei J. Med. Sci. 6:82.
Clarke, E. G. C., and M. L. Clarke. 1975. Veterinary Toxicology, p. 86. Williams &
Wilkins, Baltimore, Md.
Comar, C. L. l9S0. The use of radioisotopes of copper and molybdenum in nutritional
studies. In W. D. McElroy and B. Glass, eds. Symposium on Copper Metabolism.
Johns Hopkins Press, Baltimore, Md.
Combs, G. E., C. B. Ammerman, R. L. Shirley, and H. D. Wallace. 1966. Effects of
source and level of dietary protein on pigs fed high-copper rations. J. Anim. Sci. 25:618.
Cunningham, I. J. 1946. The toxicity of copper to bovines. N.Z. J. Sci. Technol.
27A:372.
Cunningham, I. J., K. G. Hogan, and B. M. Lawson. 1959. l~e effect of sulfate and
molybdenum on copper metabolism in cattle. N.Z. J. Agric. Res. 2:145.
Cupps, P. T., and C. E. Howell. 1949. The effects of feeding supplemental copper to
growing foals. J. Anim. Sci. 8:286.
Davis, G. K. 1974. Hith-level copper feeding of swine and poultry and the ecology. Fed.
Proc. 33:1 194.
DeGoey, L. W., R. C. Wahlstrom, and R. J. Emenck. 1971. Studies of high levels of
copper supplementation to rations for growing swine. J. Anim. Sci. 33:52.
Dick, A. T. 1954. Studies on the assimilation and storage of copper in crossbred sheep.
Aust. J. Agric. Res. 5:511.
Doherty, P. C., R. M. Barlow, and K. W. Angus. 1969. Spongy changes in the brains of
sheep poisoned by excess dietary copper. Res. Vet. Sci. 10:303.
Eden, A., and H. H. Green. 1939. Ihe fate of copper in the blood stream. J. Comp.
Pathol. Ther. 52:301.
.
OCR for page 181
Copper
181
Felsman, R. J., M. B. Wise, R. W. Harvey, and E. R. Bamck. 1973. Effect of added
dietary levels of copper sulfate and an antibiotic on performance and certain blood
constituents of calves. J. Anim. Sci. 36:157.
Perguson, W. S.; 1943. The tears pastures of Somerset. IV. The effect of continuous
administration of copper sulfate to dairy cows. J. Agnc. Sci. 33:116.
Ferm, V. H., and D. P. Hanlon. 1974. Toxicity of copper salts in hamster embryonic
development. Biol. Reprod. 11:97.
Fontenot, J. P. 1972. Va. Polytec. Inst. State Univ. Res. Dir. Rep. 145:33.
Gipp, W. F., W. G. Pond, J. Tasker, D. VanCampen, L. Krook, and W. J. Visek. 1973a.
Influence of level of dietary copper on weight gain, hematology and liver copper and
iron storage in young pigs. J. Nutr. 103:713.
Gipp, W. F., W. G. Pond, and E. F. Walker. 1973b. Influence of diet, composition and
mode of copper administration on the response of growing-finishing swine to supple-
mental copper. J. Anim. Sci. 36:91.
Gipp, W. F., W. G. Pond, F. A. Kallfelz, J. B. Tasker, D. R. VanCampen, L. Krook, and
W. J. Visek. 1974. Eject of dietary copper, iron and ascorbic acid levels on hematol-
ogy, blood and tissue ~copper, iron and zinc concentrations and 64Cu and 59Fe metabo-
lism in young pigs. J. Nutr. 104:532.
Goldberg, A., C. B. Williams, R. S. Jones, M. Yanagita, G. E. Cartwrilht, and M. M.
Wintrobe. 1956. Studies on copper metabolism. XXII. Hemolytic anemia in chickens
induced by the administration of copper. J. Lab. Clin. Med. 48:442.
Gopinath, C., and J. M. lIowell. 1975. Experimenta1 chronic copper toxicity in sheep.
Changes that follow cessation of dosing at onset of hemolysis. Res. Vet. Sci. 19:35.
Gopinath, C., G. A. Hall, and J. M. Howell. 1974. The effect of copper poisoning on the
kidneys of sheep. Res. Vet. Sci. 16:47.
Gubler, C. J., M. E. Lahey, G. E. Cartwnght, and M. M. Wintrobe. 1953. Studies on
copper metabolism. LX. The transportation of copper in blood. J. Clin. Invest. 32:405.
Hart, E. B., H. Steenbock, J. Waddell, and C. A. Elvehjem. 1928. Iron in nutntion. VII.
Copper as a supplement to iron for hemoglobin building in the rat. J. Biol. Chem.
77:797.
Hazel, C. R., and S. J. Meith. 1970. Bioassay of king salmon eggs and sac fry in copper
solutions. Calif. Fish Game 56:121.
Henderson, B. M., and R. W. Winterfield. 1975. Acute copper toxicosis in the Canadian
goose. Avian Dis. 19:385.
Hill, R., and H. L. Williams. 1965. The effects on intensively reared lambs of diets
containing excess copper. Vet. Rec. 77:1043.
Hubschman, J. H. 1967. E~ects of copper on the crayfish Orconectes rusticus (Girard).
I. Acute toxicity. Crustaceana 12:33.
Isael, J., J. M. Howell, and P. J. Treeby. 1969. Deaths in ewes following the administra-
tion of copper calcium edetate for prevention of swayback. Vet. Rec. 85:20S.
Kidder, R. W. 1949. Symptoms of induced copper toxicity in a steer. J. Anim. Sci. 8:623.
King, J. O. L. 1975. The feeding of copper sulfate to ducklings. Br. Poult. Sci. 16:409.
Luke, V. F., and B. Marquering. 1972. Untersuchungen uber den Minerals~ gehalt in
der Schafleber. I. Futterungsbedingte und genetische Einflusse auf den Cu-gehalt.
Suchtungskunde 44:45.
Macleod, N. S., and J. A. Watt. 1970. Experimental copper poisoning in sheep. Vet. Rec.
86:375.
Mayo, R. J., S. M. Hauge, H. E. Parker, P. N. Andrews, and C. W. Camck. 1956.
Copper tolerance of young chickens. Poult. Sci. 35:11S6.
McCosker, P. J. 1968. Obser`,ations on blood copper in the sheep. II. Chronic copper
poisoning. Res. Vet. Sci. 9:103.
OCR for page 182
182 MINERAL TOLERANCE OF DOMESTIC ANIMALS
McHargue, J. S. 1925. The association of copper with substances containing the fat-
soluble A vitamin. Am. J. Physiol. 72:583.
McLeese, D. W. 1974. Toxicity of copper at two temperatures and three salinities to the
American lobster (Homarus amencanus). J. Fish. Res. Bd. Can. 31:1949.
Mehring, A. L., J. H. Brumbaugh, A. J. Sutherland, and H. W. Titus. 1960. The tolerance
of growing chickens for dietary copper. Poult. Sci. 39:713.
Morgan, K. T. 1973. Chronic copper toxicity of sheep: An ultrastructure study of spongi-
form leucoencephalopathy. Res. Vet. Sci. 15:88.
Mount, D. I., and C. E. Stephan. 1969. Chronic toxicity of copper to the fathead minnow
(Pimephales promelas) in soft water. J. Fish. Res. Bd. Can. 26:2449,
Mount, P. L. 1968. Chronic toxicity of copper to fathead minnows (Pimephales prm
melas, rafinesque). Water Res. 2:215.
National Research Council. 1977. Medical and Biological Effects of Environmental Pol-
lutants. Copper. National Academy of Sciences, Washington, D.C.
O'Dell, B. L. 1976. Biochemistry of copper. In R. E. Burch and J. F. Sullivan, eds.
Symposium on Trace Elements. Med. Clin. North Am. 60:697.
P'equignot, J., and A. Moga. 1975. Effects of different toxic compounds (Pb, Cu. formal,
NH4) on the carp: Histologic changes in excretory and hematopoietic organs. Eur. J.
Toxic. Environ. Hyg. 8:361.
P'equignot, J., R. Labat, A. Chatelet, and A. Moga. 1975. Action of copper sulfate on
mucous epithelium cells in rainbow trout (Salmo indeus ). Eur. J. Toxic. Environ. Hyg.
8:52.
Ritchie, H. D., R. W. Luecke, B. V. Baltzer, E. R. Miller, D. E. Ullrey, and J. A. Hoefer.
1963. Copper and zinc interrelationships in the pig. J. Nutr. 79:117.
Sasu, V., N. Hagiu, S. Tasca, O. Popescu, and E. Sasu. 1970. Clinical, hematologic and
anatomohistopathological modifications in acute experimental intoxication with basic
copper carbonate in the sheep. Inst. Agron. "Ion Ionescu De La Brad," Iasi 50:2S1.
Scheinberg, I. H., and I. Sternlieb. 1960. Copper metabolism. Pharm. Rev. 12:355.
Schroeder, H. A., A. P. Nason, I. H. Tipton, and J. J. Balassa. 1966. Essential trace
metals in man: Copper. J. Chron. Dis. 19:1007.
Shand, A., and G. Lewis. 1957. Chronic copper poisoning in young calves. Vet. Rec.
69:618.
Smith, B., D. A. Woodhouse, and A. J. Frazer. 1975b. The effects of copper supple-
mentation on stock health and production. I. Field investigations. N.Z. Vet. J. 23:73.
Smith, J. P., R. M. Jordan, and M. L. Nelson. 1975a. Tolerance of ponies to high levels
of dietary copper. J. Anim. Sci. 41:1645.
Stecher, P. G. (ed.). 1968. The Merck Index. Merck & Co., Rahway, N.J.
Supplee, VV. C. 1964. Observations on the effect of copper additions to purified turkey
diets. Poult. Sci. 43:1599.
Suttle, N. F., and C. F. Mills. 1966. Studies of the toxicity of copper to pigs. I. Effects
of oral supplements of zinc and iron salts on the development of copper toxicosis. Br.
J. Nutr. 20:135.
Thompson, R. H., and J. R. Todd. 1974. Muscle damage in chronic copper poisoning of
sheep. Res. Vet. Sci. 16:97.
Todd, J. R., J. F. Gracey, and R. H. Thompson. 1962. Studies on chronic copper
poisoning. I. Toxicity of copper sulfate and copper acetate in sheep. Br. Vet. J.
1 18:482.
Underwood, E. J. 1977. Trace Elements in Human and Animal Nutrition, 4th ed. Aca-
demic Press, New York.
Vohra, P., and F. H. Kratzer. 1968. Zinc, copper and manganese toxicities in turkey
poults and their alleviation by EDTA. Poult. Sci. 47:699.
.
OCR for page 183
Ajar
183
We, P. E., D. C. Snetsi~er, R. A. Bag, Id J. H. S-ner. 1~. Version in lo~e~ce
~ Obeys 10 died copper. fault. Sci. 43:~.
miss, E., ~ P. Bear 1~. Ex~d~n~ studies on conic copper Masons in the
~ ~ _ 13: 1~
Clear, O., ~ N. S. baled. i=. Beed, bay weight ~ Me as Mars in Be
sky ~ ~ sheep ~Dowi~ copper beckon. VeL Rec. Add.
Representative terms from entire chapter:
dietary copper
