Ambient Water Quality Criteria
Criteria and Standards Division
Office of Water Planning and Standards
U.S. Environmental Protection Agency
Washinaton, D.C.
-------
CRITERION DOCUMENT
ZINC
CRITERIA
Aquatic Life
For zinc the criterion to protect freshwater aquatic life as
derived using the Guidelines is "e < ° • 67 ' ln ( hardness ) +
0.67)" as a 24-hour average (see the figure "24-hour average
zinc concentration vs. hardness") and the concentration should not
exceed "e(0.64•ln(hardness) + 2.46)» (see the figure
"maximum zinc concentration vs. hardness") at any time.
For saltwater aquatic life no criterion for zinc can be
derived using the Guidelines, and there are insufficient data to
estimate a criterion using other procedures.
Human Health
For the prevention of adverse effects due to the organoleptic
properties of zinc, the current standard for drinking water of 5
nig/I was adopted for ambient water criterion.
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Introduction
Zinc is a bluish-white metal which dissolves readily
in strong acids. Its principal uses include electroplating
and the production of alloys. Zinc is never, found free
in nature, but occurs as the sulfide, oxide, or carbonate
(Lange, 1955).
In the aquatic environment zinc is acutely toxic to
freshwater organisms at concentrations as low as 90 ug/1
(Rabe and Sappington, 1970) and the lowest reported chronic
effects lie between 26 and 51 ug/1 (Spehar, 1976). In marine
waters comparable values are 141 ug/1 in acute tests (Calabrese,
et al. 1977) and 220 ug/1 in chronic tests (Reish, et al.
1976).
Water quality has been shown to affect zinc toxicity.
The best-studied of these is the protective effect exerted
by water hardness, which has been incorporated into the
freshwater criterion for the protection of aquatic life.
Because zinc is an element it can be expected to persist
in the environment indefinitely in some form.
In humans zinc ingestion has produced no clinical symptoms
at daily intakes of 150 mg/day for as long -as six months
(Greaves and Sillen, 1970). Brown, et al. (1964) reported
food poisoning from ingestion of a meal estimated to contain
nearly 1,000 ppm of zinc and another case among people who
had drunk punch containing zinc at a concentration of 2,200
ocm.
A-l
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REFERENCES
Brown, M.A., et al. 1964. Food poisoning involving zinc
contamination. Arch. Environ. Health. 8: 657.
Calabrese, et al. 1977. Survival and growth of bivalve
larvae under heavy-metal stress. Mar. Biol. 41: 179.
Greaves, M.W., and A.W. Sillen. Effects of long-continued
ingestion of zinc sulphate in patients with venous leg ulcera-
tion. Lancet. Oct. 31, 1970.
Lange, N.A. 1956. Handbook of Chemistry. Handbook Publishers,
Inc., Sandusky, Ohio.
Rabe, F.W., and C.W. Sappington. 1970. Biological productivity
of the Couer D'Alene river as related to water quality.
Water Resour. Res. Inst. Univ. Idaho, Moscow, Idaho. Project
A-024-IDA. 15 p.
Reish, D.J., et al. 1976. The effect of heavy metals on
laboratory populations cf two polychaetes with comparisons
to the water quality conditions and standards in southern
California marine waters. Water Res. 10: 299.
Spehar, R.L. 1976. Cadmium and zinc toxicity to flagfish,
Jordanella floridae. Jour. Fish. Res. Board Can. 33: 1939.
A-2
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AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
Zinc is one of the most commonly occurring heavy metals in
natural waters, and is an essential element for most plants and
animals. Zinc is used principally for alloys and galvanizing.
Predicting the toxicity of a .given total zinc concentration
in water is complicated by numerous physical-chemical factors
which alter the form of the zinc and hence change its avail-
ability, rate of uptake, and toxicity. Seasonally and locally,
toxicity may be altered by the presence of naturally occurring
chelating, complexing, and precipitating agents. While there are
many such factors which may alter zinc toxicity, the only factor
for which the effect is well documented is hardness. Therefore
the criterion for zinc is expressed as a function of water hard-
ness. However, as evidenced by the criteria derived herein, con-
centrations required for survival, growth, and reproduction of the
more sensitive aquatic species may at time be below ambient total
zinc concentrations in some surface waters of the United States
*The reader is referredfto 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.
3-1
-------
This results, in large part, from the current inability to corre-
late quantitatively the effects on zinc toxicity of physical-chem-
ical factors other than hardness.
Acute Toxicity
One hundred and thirty 96-hour LC50 values for 21 species of
freshwater fish are listed in Table 1, including 34 for the rain-
bow trout, 31 for the fathead minncw, and 20 for the bluegill.
The 96-hour LC50 values for all species ranged from 90 to 40,900
ug/1. Approximately one-half of the values were based on flow-
through tests with measured zinc concentrations; the range of
values from these tests was 93 to 35,500 ug/1.
Because there are no studies which directly compare static
and flow-through results, the Guideline factors for converting
static to flow-through LC50 values are used. Similarly, the
Guideline factors for adjusting unmeasured to measured values and
less than 96-hour to 96-hour values were used. The resultant ad-
justed acute values ranged from 49 to 48,266 ug/1- The use of the
Guideline factors did not produce an appreciable change in the
range of 96-hour LC50 values.
Data on interspecific variability in zinc sensitivity are
provided by several studies. Holcombe ^and Andrew (1978) found
that rainbow trout are two- to four-times more sensitive to zinc
and six to seven times less sensitive than the fathead minncw.
Following the Guidelines, the mean intercept, adjusted by the
species sensitivity factor, for all 20 fish species is 3.93.
Since results of flow-through tests with measured concentrations
for Chinook salmon are lower than this, the data for chincok
salmon are used to derive the Final Fish Acute Value which is
B-2
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e(0.67-ln(hardness) + 3.63)^
The effect of hardness on zinc toxicity is not as well
documented with invertebrate species as with fish; however, the
data of Cairns and Scheier (1958) and Wurtz and Bridges (1961)
indicate that zinc is more toxic to the snail, Physa
heterostropha, in soft water than in hard water.
Sufficient data are available for Physa heterostropha to fit
a hardness regression equation. The slope (0.64) is similar to
that for fish thus lending additional support to this approach.
The calculated mean intercept for the 16 invertebrate species is
5,50, indicating that invertebrate species are slightly less
sensitive than fish. The range (1,937 times) of adjusted LC50
values for invertebrate species (33 to 63,910 u.g/1) is somewhat
greater than that for fish, with cladocerans being more sensitive
than any fish.
Daphnia hyaline, the most sensitive species' (intercept = +
1.49), is approximately 55 times more sensitive to zinc than
indicated by the mean sensitivity. At least 3 invertebrate
species are more sensitive than Chinook salmon. The most
resistant adult insects, however, have not been tested in
hardnesses higher than 40-50 ug/-l •
Using the Guidelines, the adjusted mean intercept is 2.46,
which is adequate to protect all species except possibly Daphnia
hyalina. Only a single acute value, run under static conditions
with unmeasured zinc concentrations, is available for this
species. The adjusted mean intercept thus appears adequate for
invertebrate species. The Final Invertebrate Acute Value is
e(0.64-ln(hardness) + 2.46). since this value is lower
than that for fish, it becomes the Final Acute Value.
B-3
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Chronic Toxicity
Chronic toxicity values for five fish species ranged from 36
to 852 ug/1 (Table 3). All chronic tests were conducted in soft
water (25-46 mg/1 as CaCC^); no acceptable hard water chronic
tests are found in the literature to compare with the soft water
data. A life-cycle test with the fathead minnow in hardwater
(Brungs, 1969) observed adverse effects at all exposure
concentrations (as low as 180 ug/1) (Table 7). However, it is
felt to be inappropriate to estimate a chronic value using that
concentration and the much lower average control concentration of
30 ug/1.
Since no other appropriate fish data were available to
establish a significant relationship between chronic toxicity
values and hardness, a relationship was estimated by using the
slope (0.67) from fish acute values. Calculated intercepts for
the five species tested ranged from 1.05 for flagfish to 4.20 for
brook trout, with a nean of 2.57. The adjusted mean intercept'
(0.67) is below that for all species. Thus the Final Fish Chronic
Value is obtained from e(° • 67*ln(hardness) + 0.67).
Only one invertebrate chronic test result is available (Table
4). This test with Daphnia magna was conducted in soft water, and
the resulting chronic value is 3.3 tines lower than the acute
value (280 ug/D for the same species in the same water. Daphnids
are the most sensitive invertebrate organisms tested in the acute
exposures; therefore, it seems reasonable to assume that the
chronic zinc value for Daphnia magna would be equal to or lower
than most ether invertebrate chronic values. Thus, it would
appear to be inappropriate to use the species sensitivity factor
B-4
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(5.1) with the chronic data for Daphnia magna, since it is one of
the most sensitive invertebrate species. Consequently the sensi-
tivity factor was not used in the calculations to derive the Final
Invertebrate Chronic Value. It is also interesting to note that
the Daphnia magna chronic value for zinc is relatively close to
the fish chronic value (Table 3). Even though invertebrate
chronic tests have not been conducted in hard water, it again
seems logical to assume that a similar relationship probably
exist^ between chronic zinc toxicity and water hardness for inver-
tebrate species as is demonstrated for acute and chronic exposures
of fish.
Since appropriate invertebrate data are not available to
establish a relationship between chronic toxicity values and
hardness, a relationship i.s estimated by using the slope (0.64)
from invertebrate acute values and the zinc value and water
hardness from the Daphnia magna chronic "test. Thus the Final
Invertebrate Chronic Value is from e(°•64'In(hardness) +
2.00)^
$ince the Final Fish Chronic Value is lower than that for
invertebrate species, it becomes the Final Chronic Value.
Plant Effects
Tests with five species of plants, including four species of
algae, are listed in Table 5. Zinc concentrations from 30 to
21,600 ug/1 have been shown to reduce the growth of various plant
species. .The significance of short-term growth inhibition in
algae has not been established; however, since many algal tests
are conducted in artificial media which may complex zinc more
B-5
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than most natural waters, the existence of low effect levels
should be considered as a potential important ecological effect.
The lowest plant value (30 ug/1) is similar to the chronic
values for fish and invertebrate species, so sensitive algal
species will probably be protected by criteria for the protection
of other sensitive freshwater organisms.
Residues fe
1
Table 6 contains the zinc bioconcentration factors for two
fish species and two invertebrate species. The bioconcentration
»
factors for fish are low (8 and 12.2), whereas the factors for
r
invertebrate species are one or two orders of magnitude greater- <
(106 and 1,130).
Dietary zinc at a level of 2,000 mg/kg has been shown to
produce stillbirths and inhibition of postnatal growth in rats
(Ketcheson, et al. 1969). Assuming a diet of invertebrate
organisms which could bioconcentrate zinc by a factor of l,13o£-*it
would require a zinc water concentration of 1,800 ug/1 (the
Residue Limited Toxicant Concentration) to produce this effect.
This concentration is well above chronically toxic levels for
freshwater fish and invertebrate species; therefore biocon-
centration does not seem to be a critical factor in establishing a
freshwater criterion for zinc.
Miscellaneous
Table 7 contains other data on the effects of zinc on
freshwater organisms. With the exception of the avoidance data of
Sprague (1968), no data are found which would appear to influence
the criterion for zinc. Sprague (1968) found that rainbow trout
B-6
-------
would avoid a zinc concentration of 5.6 ug/1 in a laboratory
behavior test in water with a hardness of 14 mg/1 as CaCO3. The
final chronic value for zinc at a water hardness of 14 mg/1 is 7.6
ug/1 (Figure 1), and may or may not protect against significant
av.oidance behavior.
B-7
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CRITERION FORMULATION
Freshwater-Aquatic Life
Summary of Available Data
All concentrations herein are expressed in terms of zinc.
Final Fish Acute Value = e<°•67*ln(hardness) + 3.63)
Final Invertebrate Acute Value = e(°•64'ln(hardness) + 2.46)
Final Acute Value = e <° • 64 " ln( hardness ) +-2.46)
Final Fish Chronic Value = e°•67*ln(hardness) + 0.67)
Final Invertebrate Chronic Value = e(°•64'ln(hardness) + 2.00)
Final Plant Value = 30 v.g/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = e<°•67'ln
-------
lOO.Op
40.0
O
O 20.0
O
O
N a>
UJ S
§ OT 10.0
o: ^
UJ
24-HOUR AVERAGE
ZINC CONCENTRATION
VS.
HARDNESS
cr
a
4.0
2.0
1.0
10
20 40 ICO
TOTAL HARDNESS (mg/l)
In scale
200
4CO
B-9
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2000
1000
MAXIMUM ZINC CONCENTRATION
VS.
HARDNESS
cc
H-
z: w 200
8 —
o
z;
M
5 ICO
1
X
40
20
10
20
100
TOTAL HARDNESS (mg/l)
In scale
200
400
B-10
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Table 1. Freahwiiter fi:;h acute values for zinc
03
I
u
Orj.ir.ir.ni M
American eel.
An^ui 1 la rosirata
American eel .
Anruilla ro.stratu
Coho salmon,
Oiicorhynclms ki sutch
Coho salmon.
Oncorlivnuhii;; kisutch
Sockeye salmon.
OiK'orhynchui; nerka
Sockeye salmon,
Onrorhynchus norka
Chinook salmon,
Oiicorhynchu:; tnhawy tscha
Chinook salmon,
Oncorhyrichiiii tyhawy_tscha
Chinook salmon.
Oncorliynchus tshawytscha
Cut.lhroat trout.
Sal mo clarki.
Cm throat Trout ,
5i:iliuo el at k i.
Rainbow trout,
Sal mo £,aj rilnori
Ka i nbow trout ,
Sa Inio jj;.ii rdneri
Ka i nbow 1 rout ,
Sal mo «ni r Jneri
itainl.ow trout.
OthOiI'.'--
S
S
FT
FT
FT
FT
1;"l
FT
FT
S
FT
S
FT
S
FT
llct illness
y Tost (in. |/ 1 oS
o>iiO»* CaC()n)
M 53
M 55
M 89-99
M 25
M 34
M 13
M 24
M 2 A
M 24
M 24
M 24
M 320
M 500
II 5
M
Time
Jura)
96
96
96
96
96
96
X
96
96
06
96
24
48
48
96
96
l.t"jO
Jn^/JJ
1.4.600
14.500
4 . 600
905
749
1.000
97
701
463
90
420
3,500
4 , 700
2.80
550
Adjusted
l.i.'.'jO
ili-J/tJ
10.366
10.295
4 , 600
005
740
770
97
701
463
49
277
2.012
3.807
153
550
hi.-l 11 fiicf
Kehwoldt, et al
1971
Rehwoldt, et al
1972
l.o r z & McPheruoi
1976
Chapman & Stevei
197K
Chapman, 197fia
Boyce & Yamada ,
1977
Chapman. 1.978b
Chapman, 19731,
Chapman, 19781)
Rabc k
Sappington, 197i
Rabe f«
Scippington, lOV'i
Brown, 1968
Solbe, 1974
McLcay, 1976
Hale. 1977
en l r (Inert
-------
Table 1 . (Continued)
llarunesu
(m«i/ ! JH Time
Ol'U.lliJ. Hill
Adjunfed
LCSU J.OU
(»>|/1 ) JiiU/il !• ct C-i 0111:1;
CO
1
1 — '
M
Rainbow tr-out,
S a 1 mo j;ai rdner i
Rainbow trout,
S.'i lino j;.ai rdner i.
Rainbow trout ,
Salmo ^ai rdner i
Kainbow trout,
Salmo gairdnei'L
Rainbow trout ,
Salmo gai rdneri.
Rainbow trout ,
Salmo £,ai. rdner i
Ra i nbow trout ,
Salmo jjairdneri.
Rainbow trout,
Sri lino ^a i rdner i
Kainbow trout.
Salmo ^airdneri
Kainbow trout,
Salmo gai.rdneri
Kainbow trout,
SalniO ga.ir drier i
Rai.nbow trout ,
Salmo j'.ai rdnori
Rainbow trout,
Salmo gairdnerl
Rainbow trout ,
Salmo i?.ai rdneri
FT M
FT M
R M
S M
S M
S M
S U
FT M
S II
FT _ M
FT M
FT M
FT M
FT M
333
26
240
36
36
36
320
83
320
47
47
44.4
178
179
96
96
48
24
24
24
48
96
. 72
y«,
96 v
96
96
96
7
4
2
1
2
2
t:
3
2
o
,210
430
,000
,800
.560
,100
,460
.755
,500
370
517
756
,510
,960
7,210
430
2 , 300
1 ,312
731
984
1,089
1,755
1 . 760
370
517
756
2.510
2,960
Sinley , ct al .
1.974
Sinley, et al.
1974
I'rown &
Da It on, 1970
Cai vn s , et a 1 .
1978
Cairns, et al.
1978
Cairns, et al.
1978
Herbert &
Van Dyke, 1964
Cbapman & Stevens
1978 :
Lloyd, 1961
llolcombe £>
Andruw, 1978
llolcombe &
Andrew, 1978
llolcombe &
Andrew, 1978
llolcombe &
Andrew, 1978
llolcombe &
Andruw. 1978
-------
Table 1. (Continued)
09
I
U)
Hardness
Bicassay Test (me,/ 1 as Time
Orqanism Method* Cone.** CaCCK) furs)
— — — — .NT • ••- j ' — -* — T
Rainbow trout, .FT M 170 96
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 (yearling) ,
Salmo gairdneri
Rainbow trout
(fingerling) ,
Salmo gairdneri
Rainbow trout
(fingerling) ,
Salmo gairdneri
Rainbow trout
(fingerling) ,
Salmo gairdneri
Rainbow trout ,
Salmo. gairdneri
FT
FT
FT
FT
FT
FT
FT
FT
FT
S
S
FT
M
M
M
M
M
M
M
M
U
U
U
M
333
333
26
26
26
26
26
365
320
320
44
23
96
96
96
96
96
96
96
96
48
48
48
96
LC50
1,910
4,520
1.190
560
240
810
410
830
5,340 .
3.860
2.400
910
93
Adjusted
LC1>0
iiia/iL_
1,910
4,520
1.190
560
240
810
410
830
5.340
2.407
1.063
403
93
1
FeteLfcii
ice
Hoi combe &
Andrew, 1978
Goettl, et al.
1972
Goettl. et al.
1972
Goettl, et al.
1972
Goettl, et al.
1972
Goettl, et al.
1972
Goettl, et al.
1972
Goettl. et al.
1972
Watson, 1975
Herbert &
Shurben, 1964
Herbert &
Shurben, 1964
Herbert &
Shurben, 1964
Chapman, 1978b
Rainbow trout,
Salmo gatrdneri
FT
M
23
96
136
136 Chapman, 1973b
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Table 1. (Continued)
03
I
Organism
Rainbow trout,
Salmo gairdneri
Atlantic salmon.
Salmo salar
Atlantic salmon.
Salmo salar
Atlantic salmon,
Salmo salar
Atlantic salmon,
Salmo salar
Brook trout,
Salvelinus fontinalis
Brook trout,
Salvelinus fontinalis
Brook trout,
Salvelinus fontinalis
Brook trout,
Salvelinus fontinalis
Brook trout,
Salvelinus fontinalis
Brook trout,
Salvel'inus fontinalis
Goldfish,
Carassius auratus
Goldfish.
Carassius aura'tus
Goldfish.
Carassius auratus
Goldfish,
Carassius auratus
Bioassay Test
Metl)on*_ Cone... **
Hardness
(mo/1 as Tipie LC50
CaCOj)
Adjusted
LOO
.FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
FT
S
S
S
S
M
M
M
M
M
M
M
M
M
M
M
M
M
M
U
23 96
14 96
352 96
20 96
14 96
47 96
47 96
44 96
178 96
179 96
170 96
36 24
36 24
36 24
20 96
815
740
3,130
-v.420
1.550
2,120
2,420
6.140
6,980
4.980
103.000
40.000
24,000
6.440
815 Chapman, 1973b
740 Carson &
Carson, 1972
3,130 Hodson &
Sprague, 1975
•x.600 Sprague, 1964
i420 Sprague &
Ramsey, 1965
1.550 Holcombe &
Andrew. i978i.
2,120 Holcombe &
Andrew. 1978
2.420 Holcombe &
Andrew, 1978
6,140 Holcombe &
Andrew, 1978
6,980 Holcombe &
Andrew, 1978
4,980 Holcombe &
Andrew, 1978
48,266 Cairns, et al.
1978
18.744 Cairns, et al.
1978
11.246 Cairns, et al.
1978
3.521 Pickering &
Henderson, 1966
-------
Table 1 . (Cuiitifiued)
11
ic-abi;ay Test
H jcciness
(tin;/ ! .is
Oi 'Jjiiii sin He tin id '•'•' I'niic:.** CaCO.,)
Goldfish,
Carass lit';; aural. us
Car p.
Cyprinus carpi o
Carp,
Cypri.mis carpio
Golden shiner.
Hoi fini jjonus crysol eucus
Golden shiner.
Hotemi ^onus cr^soleucus
Golden shiner,
tp Nol emi i^onus eryjuil eucus
1 "" ~
I—1 Golden shiner,
01 Notemiftonus crysoleucus
Fathead minnow,
I'imephalcs promelas
Fathead minnow,
1'i nienhjl es prciinel as
Fathead minnow,
IMmephales nromclas
Fathead minnow,
JM.mephal.es promelas
Ful.head minnow,
1'imephalet; nrome las
1'athead minnow,
IMmephales promelas
Fathead minnow,
IMniepha 1 e.s promelas
Katliuad ininnov/,
S U
S M
S M
S H
S M
S M
S IJ
FT M
FT M
FT M
FT M
FT M
FT M
FT M
FT M
50
53
55
36
36
36
50
50
50
100
100
200
200
50
50
Tune
Jt.tij)
96
96
96
24
24
24
96
96
96
96
96
96
96
96
96
I.CSu
Ad i us Led
i.C'jO
Jtii(/i) ('"I/-1) 1- c- 1 --I c.i» :tr
7
7
7
11
7
8
6
12
13
18
25
29
35
13
6
. 500
,800
,800
,400
.760
,330
,000
, 500
.800
,500
,000
.000 .
,500
,700
,200
4. 100
5.538
5.538
5,342
3.636
3,903
3.280
1.2.500
13.800
J8.500
25,000
29,000
35,500
13,700
6,200
Cairns ,
1969
et al .
Rehwoldt, et al
1971
Kehwoldt, et al
1972
Cai rns ,
1978
Cairns ,
1978
Cai rns ,
1978
Cairns ,
1*69
Mount ,
Mount ,
Mount ,
Mount ,
Mount ,
Mount,
Hout t ,
Mount ,
et al.
et al .
e t a 1 .
et al .
1966
1966
1966
1966
1966
1966
1966
1966
''iDii'I'Llril^ii promts las
-------
Tame 1. (continued)
03
CTi
Organism
Fathead minnow,
l'imepj)a les promelas
Fathead minnow,
I'i merlin les promelas
Fathead minnow,
1'i me nil u 1 es jiromelas
Fathead mLnnov;,
Vimojihalos promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimuplial os promelas
Fathead minnow,
I'imepha les promelas
Falhuad minnow,
I'imepha] es promo la. i
Fathead minnow,
I'imepha les promelas
Fathead minnow,
1'imephales promelas
Fathead minnow,
I'inii-pjialcs p_romelas
F;ithu;id minnow,
Hmephales promelas
Fathead minnow,
1'imephales promelas
Fathead minnow,
I'imepha les promelaa
Fathead minnow,
iliCxiSSay
Method*
FT
1'T
FT
1-T
FT
FT
FT
FT
FT
FT
FT
FT
S
S
FT
Test
Cone .**
M
M
M
M
M
M
M
M
M
M
M
M
U
U
M
lUtiiriess
(in«;/l .is
CaCO.j)
100
100
200
200
50
50
100
100
200
200
203
203
203
203
46
Time
96
96
96
96
96
96
96
96
96
96
96
96
96
96
96
LC50
J'w/ijL
12,500
12,500
1 9 , 000
13,600
4 , 700
5,100
8.100
9,900
8,200
15,500
8,400
10.000
12.000
13,000
600
Ad j us red
l'"J/i]
12,500
12,500
19,000
13,600
4 .700
5,100
8 . 100
9 . 900
8,200
15.500
8.400
. 10,000
6,560
7.107
600
hereifc
Mount ,
Mount ,
Mount ,
Mount ,
Mount ,
Mount ,
Mount ,
Mount ,
Mount ,
Mount ,
llrungs
Hrungs
Brunts
Orungs
Benoit
,K:C
1966
1966
1966
1966
1.966
1966
1966
1966
1966
1966
. 196
. 196
. 196'
, 196
& Ho
Lim£Pnilli^ promclag
1978
-------
TaLae I. (Continued)
I
-J
l-'athead minnow (embryo) ,
I'imeplwileu promelas
Tathead minnow (embryo),
Pinivphiilcs promelas
Kalhoiid minnow (Cry),
Pimcplialc£ Iiri2!ni:]jl:i
Fathead minnow,
P i nig 1> h .• 11_ u s prome la a
(•'ill head minnow,
j'iniepluileji premie las
Kathcad miiinou,
PiiiiL'piiales proniolas
I'aLhead iniiinuw.
Piuionluilcs promelas
l-'alheail minnow,
I'inu:p_hal_es pronielas
Handed klllifisli.
I'undidiiu d_iaphanua
Han.led kill il'ish,
Kiiniliil us tliaphanus
Flagfish,
Jiirdanel la I'Loridae
Uuppy,
Poeci^l ia rot iculatus
Southeirn platyfish,
X_i ['^'P.liHHl'l macul atua
White perch,
llurone aiiio
While perch,
Morone americana
Aliiiiay
I:OQ*
Ff
FT
FT
s
S
S
0
s
s
s
FT
S
*
-'>
S
Test
Cone.**
M
M
M
U
U
U
U
U
M
M
M
I)
U
M
M
Hardness
(in.;/ 1 js
CaC03) _
174-198
174-198
174-198
20
20
20
360
166
55
53
44
20
166
53
55
Time
iius)
96
96
96
96
96
96
96
96
96
96
96
96
96
96
96
Juu/iL
1,850
1 ,820
870
960
780
880
33,400
7.630
19,200
19.100
1.500
1.270
1.2,000
14,300
14,400
Adi us ted
l'U/i)
1 .850
1.820
870
525
426
481
18,260
4,171
13.632
13.561
1.500
694
6.560
10.153
10.224
l-.i.-ti-i 4:m:t;
Pickering ft Vi.goi
1965
Pickering & Vigoi
1965
Pickering -It Vigoi
1965
Pickering &
Henderson , 1966
Pickering &
Henderson, 1.966
Pickering &
Henderson , 1966
Pickering 6.
Henderson, 1966
Kach I in 6
Pcrlmutter, 1963
Rehwoldt, et al.
1972
Rehwoldt. et al.
1971
Spehar, 1976
Pickering &
Henderson, 1966
Kachlin ft
Per limit cer, 1968
Rehwoldt, et al.
1971
KehwoLdt, et al.
1972
-------
Table I. (Continued)
UiCviuoay Test
Ot'Hanj :'ifi M Cuiic.**
Si:r ipcd bass , S M
Mornne s.'ixati lis
Striped bans, S M
Mornne saxaL il is
Striped bass (embryo), ;; M
Mortinu sax.aL~i.lis
Siripod bass (fry), i! M
Mortinu .saxat.i J i s
Scriped bass, S 11
Mo rone saxatilis
r~.unpkinsi.~uJ, S M
l.epomis j-.ibbosuu
g-j .._
jL I'uiiipkJn.seeiJ, S M
°° L^L'L-L'L'-i ti-5!.^^!1!!
Ill u eg ill, I-T M
l.eponii s inacrochi rus
Bluegill, S U
I.cpomi s iiiacrochirus
IHuegill, S (I
I.c|>omi s iiiacrochirus
liluogill , S U
I.epomi.s ni.'icrochirus
BUicgilJ, • S U
l.t:~_ioini a mucrorh-i rus
liluugill, S M
l.ojioinis niacrochirus
liluetjill. S M
l.epciin i s iiiacrochirus
lilueKill, .S M
(in.:/! .f.i Tlint.' LCiiU U"<0
CaCOj) (liia) •(••ti/11 (•••J/Jl I't-tt-'i I'lK-
55 96 6,800 4,828 'Kehwoldt:
1972
53 96 6.700 4 757 Keliwoldt
1971
137 96 1.850 1.313 O'Ku.ir.
137 96 1.180 837 O'Kear.
96 100 54 llughus,
53 96 20.000 14,200 Keliwoldt
1971
55 96 20,100 14,271 KcLwoldt
1972
46 96 9,900 9,900 Cairns,
. 1972
10 48 5,200 2,302 Cairns.
1965
96 7.450 4,072 Ca i.rns &
Schcior,
96 7,200 3,936 Cairns &
Scheiur,
96 6,910 1./77 Cairns f<
Schoier ,
36 24 23,000 10.77B Cairns.
1978
36 24 19,100 8,950 Cairns.
1978
36 24 8,850 4.14V .Cairns,
0.
, CL al.
, ci ai
1972
1972
1973
. OL al
, ot a 1
c L a 1. .
e t a 1 .
1959
1959
1959
cl al.
u t a 1 .
,c L a 1 .
l.i.'oini:; macrochi rus
1978
-------
1. (Continued) '
1)1 u.II: 1 Sill
lliG,it;:j;iy Test
Mv thud'" OHIO.
(nui/ 1 .1:; Timo
C.-iCO.) jiu.
... .
LC!»0
Ad jus led
!.<--, 0
-lii'Jil.i.1 __ I- et t-i em ;e
Hiuej'.i 11,. s u
l.i-|n>iiii.s macrochi rus
liluei'.ill . S II
1 .e])i mi i s iiiacroclii.ru:;
Kliu-j'i 11. S U
I.t.-j)onii s macroch i rus
IUuc^il.1. S U
I.ejioni i s macroch i rus
liluc^ii 1 , S U
l.c[ioiiii s iiiacrochirus
m UlucKill, S 1)
1 I.L-jioini u ni.icrochi rus
<^ UlllC|M 11 , S 11
l.«:|iciini s inae.roch i rus
lUuei'i.l 1 . S U
I.L'noini .-> iiiacrochirus
IllllCjM 11, S 11
I.t.-poin i :; mac rochi rus
11 1 in.-,-, i 1 1 , S U
1 .c[x mi i s rn.ic roch i rus
llluec.i 11. , S 'l)
I.c|ioiiii :; macroch i I us
IJIiu:(.,i 11. . .S U
l.r '[111111! s ma croc hi rus
20 96
20 96
20 96
20 9b
360 96
45 96
'.5 96
4/i 96
V, 96
171 96
1 7 1 96
2.860-
3.780
5.460. .
4,8')0
5.820
5,370
40.900
8.020
4 , 900
2 860-
3 , 780
1.930-
3.630
10,130-
12, 500
10,150-
1 2 , 300
2^067
2,985
2,631
3,182
2,936
22.360
4.385
2.679
1 ,560-
2.06/
1 055-
1 /J85
5.538-
6.834
5.549-
6,724
Patrick, OL al .
1968
Picker inj'. iSc
lleiulorson , 1966
lleiulorson , 1966
Pickering, &
Henderson, 1966
Picker in g fir
Hendei son , 1966
Pi eke riii); ft
Henderson , 1966
Cairns ,S,
.Scheier. 1957a
Cairns 6,
Scheier, 1957a
Cairns 6
.Schoier. 1957b
Cairns &
Sc.-hci.er. 19571)
Cairns f,
Scheier. 1957|j
Cairns &
Scheier, 195 7b
S - static, K - renewal, IT = flow-1 hrouf.h
•'.-'• |-| rj inca jurutl. D —• unineasuted
-------
T
-------
2. FreshwuLor invertebrate acute values for zinc
— iil'JLUI;;!!!
Uorm,
Na[s sp.
Snail (egg).
Amnicola sp.
Snail (adult).
Anmir.nl a sp.
Snail .
Coniobasis livescens
Snail,
rymnca emarginata
CO Sna i 1 .
1 1'hysa heterostropha
t-j
1—1 Snail ,
Physu heterostropjia
Snail,
Pbysa heterostropha
Snail,
1'liy s a he t e ros ( ropha
Snail ,
Pliysa heterostropha
Snail ,
1'hysa heterostropha
Snail .
Pliysa herorostropha
Snail.
1'hysa heterostropha
Snail,
I'hvsa hcteroKtroplia
Snail,
H«.'thOd>';
S
S
S
S
S
S
S
S
S
S
S
r>
s
s
s
y Tout
Court ^i
M
M
M
(I
I)
U
U
U
11
U
U
U
U
U
U
( in. i / 1 i\a
CjCO..)
50
50
50
137-171
137-171
4-'.
44
44'
44
171
171
171
171
100
20
Time
llil£)
96
96
96
48
48
96
96
96
96
96
96
96
96
96
96
1-CLiU
(im/n
18,400
20.200
1 4 , 000
13,500
4 , 150
790
1,270
620
780
2,660
5.570
2 . 360
6,360
14 ,000
4,900
Ad jus Led
l.Cb 0
(U'J/l)
20,240
22.220
15.400
4.916
1,511
669
1,075
525
660
2,253
4,717
1 ,998
5.386
11,860
4,150
I'etej frnc
Rehwoldt
1973
Rehwoldt
1973
Kehwoldl
1973
Cairns ,
1976
Cairns ,
1976
Cairns &
1958
Cairns &
1958
Cairns &
1958
Cairns 61
1958
Cairns &
1958
Cairns &
1958
Cairns &
1958
Cairns &
1958
Wurtz &
1961
Uurtz &
:o
, et al.
, et al.
, et al .
et al'.
et al.
Schulcv
Scheier
Scheier
Scheier
Scheier
Scheier
Scheier
Scheier
Bridges ,
Bridges ,
1961
-------
TaLie 2. (Continued)
UicxifcSuy Ti.-iit
Tl
UJ
1
K)
1-0
( >L (] jn i : :in
Snail ,
Hivsa heterostropha
Snail ,
Physa intej^ra
Cladoceran ,
D.'iphnia hyalina
Cladoceran ,
Daphnia niagna
C] adocoran ,
Dapjinia magna
CM adoceran ,
Daphnia niagna
Cladocoi'an,
D.ipjmia magna
Copepod,
?.y£*-9P5. ahyssorum
predpjjius
Copepod,
Fudi apl.omus padainis
p. ida mis
Sowbug ,
Ascllus commnnis
Scud ,
Clanunartis up.
Damsel f ly ,
Unidentified
Miiljie,
Clii ronomus sp.
CaddisCly,
IJniilenti fled
Mi flux:
S
S
S
S
U
R
S
S
S
S
S
S
S
S
I-'-' (..'oiic'-V*
U
U
U
U
M
M
U
U
II
•U
M
M
M
M
-------
TaLle 2. (Continued)
Haroness
Adjusted
CD
I
K>
U)
Bioa'&say Test
Organism Method* •" Cone.**
Rotifer, . SI)
Philodia acucicornus
Rotifer, . S U
Philodi.a acuticornus
Rotifer, S U
Phi.lodla acuticornus
(mq/1 as Time
CaC03) (nrs)
81 24
25 96
25 96
LCbO LCi-0
(uq/1) (uq/1)
4.100 902
1,500 1,270
1,200 1,016
hetcceiice
"
Buikema, et al.
1974
Buikema, et al.
1974
Buikema, ec al.
1974
* S = static, R = renewal
** u = unmeasured, M = measured
Adjusted LC50 vs. hardness:
Snail, Physa heterostropha: slope = 0.64. intercept =• 4.80, r = 0.48, Not significant, N = 11
Geometric mean slope = 0.64 (only value available)
Mean intercept for 16 species =5.50
Adjusted mean intercept = 5.50 - ln(21) = 2.46
Final Invertebrate Acute Value
(0.64'ln(hardness) + 2.46)
-------
Table 3. Freshwater fish chronic values for zinc
CO
to
*>.
Qj.gjni.sm
Chinook salmon,
Oncorhynchus tshawytscha
Rainbow trout,
Snlmo gairdnori
Brook trout ,
Salvelinus fontinalis
Fathead minnow,
Pimephales uromelas
Flagfish,
Jordanella floridae
Limits
Teat* (uq/1)
E-L 280-500
E-L 140-260
LC 534-1,360
LC 78-145
LC 26-51
* LC = life cycle or partial life
Chronic Value vs. hardness:
No hardness relationship could
cycle; E-L -
be derived for
Chronic
Value
187
95
852
106
36
embryo- larval
any fish species
Hardness
( ITUJ / 1 as
CaCO.,)
22
26
45
46
44
Reference
Chapman, Manuscript
Sinley, et al. 1974
Holcombe, et al . 1978
Benoit & Holcombe, 1978
Spehar. 1976
Slope =0.67 from Fish Acute Values
Mean intercept for 5' species = 2.57
Adjusted mean intercept = 2.57 - ln(6.7) = 0.67
Final Fish Chronic Value = e(0.67-ln(hardnesS) + 0.67)
Application Factor Values
Species
Brook trout ,
Salvelinus fontinalis
Fathead minnow,
Pimephales promelas
Flagfish,
Jordanella floridae
96 hr LC50
(v.g/1)
2.000 '
600
1,500
Hardness
(mg/1 as
CaC00)
45
46
44-
MATC
MR/1
534-1.360
78-145
26-51
A.F.
.43
.18
.02
Reference
Holcombe, et al.'
Benoit & Holcombe
Spehar, 1976
1978
. 1978
Geometric mean A.F. = 0.12
Geometric mean LC50 = 1,216 ug/1
-------
Table /i. Freshwater invertebrate chronic vnlues for zinc (Biesinger & Chiri .stensen, 1972)
Chronic
Of Ian ism
Cladoceran,
Daphnia magna
Limit n Value (imj/l as
Teat* (iui/1) I"1!/1! CaCO.,)
l.C 70-102 84.5 45
* ).C = life cycle or partial 1 i.Ce cycle
Chronic Value vs. hardness:
Mo harJneus relationship could he derived for any invertebrate species.
Slope =• 0.64 from invertebrate acute value.
Intercept for Daphntn ma^.na « 2.00 (only upccies tested).
... . , . . „. . „ , (0.64-ln(harduess) + 2.00)
1-inaL InvertebraLe Chronic Value » e •
CO
to
ui
-------
Table 5. Freshwater plant effects for zinc
Concentration
Kttect
Kfetert-nce
Alga.
la. -
CD
I
i-o
cr>
Alga.
Ch 1 oc 1
Alga,
Chlorell a vulgari s
Chloi'el la vulgaris
Alga,
Scenedesnuis
507. inhibition 5,100
of cell division
DxLendecl lag 7,500
Lime to 7 days
Alga,
S\
c.'ipr icornuT uni
A1 ga .
Se K; na s truni
Capricornuturn
Alga,
Selenast ruin
- '21'£ 1 cor ri u f uin
Eurasian waterniilfoil,
Hyri^(.j)hy_l_li.im spica turn
Eurasian waterniilfoil,
Ilyri npliyl 1 um spica i urn
Eurasian watenniIfoil,
i iuin y'™
Decrease
chlorophyll a
507,, reduction
in growth rate
96 hrs
Threshold
toxicity
Alpicldal
Total p.i-owth
inhi hi I:ion
7,500
2,400
1,000-1.400
700
120
Ui. ..I Com,
Ni L:'.'.;{. li i a 1 incur i s
Incipient- growth 30
inhibition
507., root 21,600
weight reduc-.
tion
50% root 21,600
length reduc-
tion
50Z reduction 20,900
in shoot
length
LC50 12.U hrs A, 300
Rosko S, ttachlin. 1977
llosko & Kachlin, 1977
Rcsko & Uachlin. 1977
Rachlin & Farran, 1974
Bringmann & Kuhn, 1959
bartlett, et al. 1974
Ilartlett, ct al. 1974
llartlett. et al. 1974
Stanley, 1974
Stanley, 1974
Stanley, 1974
Patrick, et al. 1968
Lowest plant value - 30 pg/1
-------
TaLle
Freshwater residues for zinc
i)t >jani SHI
Mayfly.
Kpjiemerol la grand i s
SLi>nef ly ,
I'toronarcys cal i forn
Carp,
O/nrinus carpi o
Stickleback,
G.u'.t crosLeiis aculcat
Organ i.sm
W
1 White Kilt
K>
'J'lnie
DiocunceiiC.r ution FdCI 01 (days)
1 . 1 30 1 4
106 I.-'.
. 8 60
12.2 0 . £
Maximum Permissible Tissue Concentration
Concentration
Action Level or ICffect ing/k^
stillbirths and 2,000
postnatal growth
inhibit ion
-t (.-1 er.co
Nelirin;;, 1976
infi. 1976
l.ebedova d Ku^neC.sova, 1969
0.66 Matthieascn f, Hraficld, 1977
Re Corenee
Ketchuson. ot al. 1969
bi.oconccnt ration factor - 1,130
Lowest re:;iiliio concentration = 2,000 mg/lq;
- 1.77 m;./kK = 1.800 ,,g/l
-------
Table
(Continued)
Oruaniii.,,
I.ejiomi :> niacrochi rus
UluiijjiH.
I.epoini s niacrochirus
Bluep/ili ,
I.opornis macrochirus
Pond snail ,
P h v s a 1 1 c; Lc r o s t raplia
Pond snai 1 ,
Physa heterostropha
Pond snail,
DO Pliy.sn heterostropha
1 ~" ~ "
^ Pond snail,
Pliys.-i hetcrost ropjia
Pond snail ,
Physa heterostrogha
Pond snai 1 ,
Physa heterostropha
Eluegi 11 ,
Leponii!) niacroctii rus
I.op'jinis macrochirus
Test
OUI'cl t 1 Oil
20 days
20 days
20 days
96 hrs
96 hrs
96 hrs
96 hrs
96 hrs
96 hrs
96 hrs
96 hrs
LC50
I.C50
1.C50
LC50 ' - ••
soi't water
I.C50
hard water
1.C50
soft water
LC50
hard water
I.C50
soft water
1.C50
hard water
LCO
LCI 00
Hardness
(mj',/1 as
CaCO,
370
370
370
20
100
20
100
20
100
46
A6
KfcSUit.
(UU/U
10,500
12.000
10,700
303
ilV>
1,700
350
1 . , 1 00
13,500 -
32,000
i nsol uble
zj no
18,000 •
soluble
l«jt ei riict.-
Pickering, 1968
Pickering. 1968
Pickering. 1968
Wurt2, 1962
Wurt:'., 1962
Uuruz. 1962
Wurtz, 19b2
Wurt:;:. 1962
Wurc;:, 1962
Cairns, et al. 1971
Cairns, et al . 1971
zinc
-------
SALTWATER ORGANISMS
Acute Toxicity
The mummichog was'the only non-anadromous saltwater teleost
used for acute toxicity tests for zinc (Table 8). The unadjusted
96-hour LC50 value was 60,000 ug/1 (Eisler and Hennekey, 1977).
Longer exposure to zinc (Tables 12) did not significantly change
the result; the 168-hour LC50 was 52,000 ug/1 (Eisler and Hennekey,
1977) and the 192-hour LC50 was 66,000 ug/1 (Eisler, 1967). Smolts
of Atlantic salmon, Salmo salar, acclimatized to 70 percent salt
water, were more sensitive to zinc than yearling rainbow trout, S_.
gairdnerii, at the same salinity under- flow-through conditions,
with unadjusted 48-hour LC50 values of 27,000 ug/1 and 35,000 ug/1/
respectively (Herbert and Wakeford, 1964). Both species were more-
resistant at 30 to 40 percent salt water; LC50 values were 39,000
ug/1 for the salmon and 82,000 ug/1 for the trout.
Application of the adjustment factors to the fish acute toxic-
ity data gives a geometric mean of 33,450 ug/1 which, when adjusted
by the species sensitivity factor (3.7), results in a Final Fish
Acute Value of 9,000 ug/1. No fish acute toxicity data from Table
8 is below 9,000 ug/1/ indicating the procedure allows protection
for at least 95 percent of the species.
Saltwater invertebrate species are more sensitive to acute
zinc toxicity/ as shown by data on various life stages of annelids,
bivalve and gastropod molluscs, arthropod crustaceans, and echinc-
derms (Table 9). Among oolychaete annelids, adults are more toler-
ant than young of the species. Adult Capitella capitata and Neanthes
arenaceodentata had adjusted 96-hour LC50 values of 2,965 and 1,524
ug/1 zinc, respectively (Reish, et al. 1976). While the level for
B-29
-------
larvel C. capitata is 1.440 ug/1 and that for juvenile N. arena-
ceodentata is 762 ug/1 (Reish, et al. 1976). As with fish, salin-
ity affected zinc sensitivity of adult polychaetes. Nereis
diversicolor in 17.5 °/oo had an adjusted 96-hour LC50 value of
46,585 ug/1 while a salinity of 3.5 °/oo, the LC50 was 9,317
(Bryan and Hummerstone, 1973).
Larval bivalve molluscs were the most susceptible invertebrate
species to zinc. Forty-eight-hour LC50 values were 141 ug/1 for
Mercenaria mercenaria larvae (Calabrese, et al. 1977) to 287 ug/1
for Crassostrea virginica (Calabrese, et al. 1973). Acute toxicity
values for adult pelecypods ranged from 2,640 ug/1 for Mytilus
edulis planulatus (Ahsanullah, 1976) to 6,522 ug/1 for Mya arenaria
(Eisler and Hennekey, 1977). Among gastropod molluscs, the ad-
i
justed 96-hour LC50 value for Nassarius obsoletus was 42,350 ug/1
(Eisler and Hennekey, 1977).
Among crustaceans, susceptibility to zinc varied between
species and development stages. The adult crab, Carcinus maenas
was the most resistant of those studied, with adjusted 96-hour LC50
values of 5,281 (Conner, 1972) and 4,370 ug/1 (Portmann, 1968).
Larvae of this species were more sensitive with an adjusted 96-hour
concentrations of 847 ug/1 (Conner, 1972). The copepod, Acartia
tonsa was the most sensitive crustacean species tested, with a
96-hour LC50 value of 246 ug/1 (Sosncwski, et al. 1979). Among
echinoderms, Eisler and Hennekey (1977) showed that the adult
starfish, Asterias forbesi, was rather insensitive to zinc, with an
adjusted LC50 value of 33,033 ug/1.
Toxicity studies of longer duration with invertebrate species
(Table 12) resulted in lower lethal zinc concentrations. Minimum
B-30
-------
LC50 values were 195 ug/1 (12 days) for'larvae of the clam,
Mercenaria mercenaria, (Calabrese, et al. 1977) and 200 ug/1 (168
hours) for adult hermit crab, Pagurus longicarpus, (Eisler and
Hennekey, 1977). The 168-hour LC50 value for adult polychaete,
Nereis virens, was 2,645 ug/1 (Eisler and Hennekey, 1977).
The Final Invertebrate Acute Value of 41 ug/1 was calculated
from the geometric mean of 2,026 ug/1 and a species sensitivity
factor of 49. This value does not exceed the adjusted LC50 value
for any life stage of any invertebrate species (Table 9) thus af-
fording 95 percent protection for invertebrate species. Since this
level is lower than the Final Fish Acute Value (9,000 ug/1), 41
ug/1 is the Final Acute Value.
Chronic Toxicity
No whole or partial life cycle chronic toxicity data are
available for zinc and saltwater fish or invertebrate species.
Plant Effects
The minimum zinc concentration which inhibited growth among
five species of microalgae (Table 10) was 50 ug/1; Skeletonema
costatura was the most sensitive species tested (Bryan, 1964). At
this concentration, zinc also interacted with copper to affect
growth (Braek, et al. 1976). Maximum tolerance to growth inhibi-
tion among algae was 25,000 ug/1/ as' shown by Jensen, et al. (1974)
with Phaeodactylum tricornutum. .The most sensitive kelp species
was La'minaria digitata, with growth inhibition occurring at 100
ug/1 (3ryan, 1964).
The Final Plant Value is 50 ug/1.
Residues
Algal bioconcentration of zinc includes data for both micro-
algae and macroalgae (Table 11). The maximum BCF value for the
B-31
-------
macroalgae, Fucus serratus, was 10,000 after 140 days exposure to
9.5 ug/1 (Young, 1975). Among the microalgal species examined,
Thallossiosira pseudonana, accumulated zinc 12,400 times over
ambient water concentrations of 250 ug/1 in 13 days (Jensen, et al.
1974).
Whole body concentration in adult Crassostrea Virginica was
2,703 mg zinc/kg wet weight after exposure to 0.1 mg/1 for 140-
days, resulting in a BCF of 27,080 (Shuster and Fringle, 1969).
Shuster and Pringle (1968) reported a BCF of 15,240 for C.
virginica exposed to 0.1 mg/1 for 140 days. Among the soft-shell
clams, adult Mya arenaria were poor concentrators of zinc, accumu-
lating only 43 times over a water concentration of 500 ug/1 after
112 days (Eisler, 1977b). Similarly, the hard shelled clam,
Hercenaria mercenaria, had a bioconcentration factor of 85 (Shustjer
and Pringle, 1968) while mussel, Mytilus edulis accumulated zinc up
to 500 times (Pentreath, 1973c).
Bioconcentration factors for crustaceans ranged from 266 in
the mud crab (Duke, et al. 1969) to 9,000 for adult Carcinus maenas
(Bryan, 1971).
Miscellaneous
Various saltwater phyla are well represented in studies of
sublethal effects of zinc (Table 12). After a 14-day exposure to
10,000 ug/lf liver aminolevulinate dehydrase enzyme activity in-
creased in the adult mummichdg, Fundulus heteroclitus, (Jackim,
1973). Although no larvae of oysters, Crassostrea virginica, died
during 48 hours in 75 ug/1 (Calabrese, et al. 1973), C_. gigas
larvae did exhibit abnormal shell development in 70 ug/1 after
immersion for 48 hours (Nelson, 1972). Oyster larvae showed
B-32
-------
reduced development in a slightly higher level of 125 ug/1
(Brereton, et al. 1973). Adult bivalve molluscs were more resis-
tant to zinc toxicity; Crassostrea virginica showed no significant
mortality in 200 ug/1 after 140 days (Shuster and Pringle, 1968;
1969). A small increase in temperature doubled toxicity to adult
Mya arenaria. The 168-hour LC50 value at 20° C was 3,100 ug/1
(Eisler and Hennekey, 1977) while at 22° C it was 1,550 ug/1
(Eisler, 1977a). Larval stages of crustaceans were again the most
sensitive to zinc, as shown by delayed development in crab,
Rhithropanopeus harrisi, during a 16-day exposure to 50 ug/1
(Benijts-Claus and Benijts, 1975). Polychaetes were generally
tolerant of zinc; Reish and Car (1978) reported reduced survival
after 21 days in 1,750 ug/1 for Ophyryotrocha diadema and in 10,000
for Ctenodrilus serratus. Growth of the protozoan, Cristigera sp.,
was reduced in 125 ug/1 after 4 to 5 hours (Gray, 1974).
B-23
-------
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
zinc.
Final Fish Acute Value = 9,000 ug/1
Final Invertebrate Acute Value = 41 ug/1
Final Acute Value = 41 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = 50 ug/1
Final Chronic Value = 50 ug/1
0.44 x Final Acute Value = 18 ug/1
CRITERION: No saltwater criterion can be derived for zinc
using the Guidelines because no Final Chronic Value for either fish
or invertebrate species or a good substitute for either value is
available, and there are insufficient data to estimate a criterion
using other procedures.
B-34
-------
Table 7, Other freshwater data for zinc
CD
I
U)
Ul
Organism
Protozoa,
Chilomonas- sp.
Protozoa,
Chilomonas sp.
Protozoa,
Telrahymena sp.
Protozoa,
Tetrahymena sp.
Protozoa,
Parameclum caudatum
Protozoa,
Paramecium caudatum
Protozoa,
Paramecium multi-
micronucleaturn
Protozoa,
Paramecium multi-
tnicronucTeatum
Protozoa,
Blcphartsma sp.
Protozoa,
Blepharisma sp.
Cladoceran,
Daphnia magna
Mayfly,
Ephemerella grandis
Mayfly,
Ephemerella subvaria
Stonefly,
.Acroneuria lycortas
Stonefly,
Pceronarcys
caTTfornica
Test
3 hrs
10 mint
3 hrs
10 mins
3 hrs
3 hrs
3 hrs
24 hrs
Etfect
LC100
LCO
LCI 00
LCO
LC100
LCO
LC100
LCO
LC100
LCO
LG50
LC50
LC50
LC50
LC50
Hardness
(mg/1 as
CaCO,)
51-68
51-68
51-68
51-68
51-68
51-68
51-68
51-68
51-68
-
-
30-70
44
44
30-70 •
Result
9.200
16,000
32,000
>13,200
Retereiicfc
Ruthven & Cairns. 1973
Ruthven & Cairns, 1973
Ruthven & Cairns. 1973
Ruthven & Cairns, 1973
Ruthven & Cairns. 1973
Ruthven & Cairns. 1973
Ruthven & Cairns. 1973
Ruthven & Cairns, 1973
Ruthven & Cairns, 1973
.Ruthven & Cairns, 1973
Bringmann & Kuhn. 1977
Nehring. 1976
Warnick & Bell, 1969
Warnick & Bell, 1969
Nehring. 1976
-------
Table 7. (Continued)
OJ
Organism
Caddisfly,
Hydropsyche betteni
Coho salmon,
Oncorhynchus kisutch
Sockeye salmon
(embryo- smolt) ,
Oncorhynchus nerka
Cutthroat trout,
Salmo clarkii
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Saimo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout ,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Brown trout,
Salmo trutta
Test
Duration
11 days
96 hrs
18 mos
14 days
7 days
2 hrs
48 hrs
7 days
14 days
20 mins
5 days
7 days
21 days
21 days
Hardness
(mg/1 as
Effect CaCO,
LC50 44
WBC-T 3-10
counts
depressed
No effect 20-90
on survival
or growth
LC50 48
Gill tissue 44-55
damage
Increase in 66
ventilation
rate
Increased 320
swimming
velocity .
increased
toxicity to
Zn
Hyper- -374
glycemia
LC50 48
Threshold 13-15
avoidance
level
LC50
LC50 - 280 '
Median 14
survival
time
Median 14
survival
Result
fuq/1)
32,000
500
242
670
40,000
40,000
1,680
214
410
5.6
4,600
560
500-1.000
-vl.OOO
Reference
Uarnick & Bell, 1969
McLeay, 1975
Chapman, 1978a
Nehring & Goettl. 1974
Skidmore & Tovell. 1972
Hughes & Adeney, 1977
Herbert & Shurben, 1963
Watson & McKeown, 1976
Nehring & Goettl, 1974
Sprague, 1968
Ball, 1967
Lloyd, 1961
Grande, 1967
Grande. 1967
time
-------
Table 7. (Continued)
CD
I
OJ
-J
Organism
Brown trout,
Salmo trutta
Atlantic salmon
Salmo salar
Atlantic salmon,
Salmo salar
Test
Duration Effect
14 days LC50
182 hrs
Incipient
lethal
level
21 days Median
survival
time
Brook trout, 14 days LC50
Salvelinus fontinalis
Golden shiner,
Notemigonus
crysoTeucas
Fathead minnow,
Pimephales promelas
Channel catfish,
Ictalurus nunctatus
Guppy,
Poecilia reticulatus
96 hrs Avoidance
Hardness
(mg/1 as
GaC03
48
14
14
44
51
10 mos
12 hrs
Reproduction 203
reduced
Serum -
osmolarity
decrease .
30 days Growth
inhibition
Stickleback, 3 days Gill damage 282
Gasterosteus aculeatus
Stickleback, 200 hrs
Gasterosteus aculeatus
Increased
oxygen
uptake
Bluegill,
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Bluegill.
Lepomis macrochirus
Bluegill.
Lepomis macrochtrus
Bluegill,
Legomis_ macrochirus
BlueRill.
Lepomis macrochirus
7 days Increased 51
breathing rate
96 hrs
24 hrs
LC50 (swimming 46
stress)
Increased
cough response "
20 days I.C50
20 days LC50
20 days LC50
Result
(uq/i) Reterencfe
640 Nehring & Goettl, 1974
150-1,000 Zitko & Carson. 1977
100-500 Grande, 1967
960 Nehring & Goettl. 1974
3,640 Waller & Cairns. 1972
180 Brungs. 1969
206-236 12.000 Lewis & Lewis. 1971
80 1,150 Crandall & Goodnight, 1962
500-1,000 Matthiessen & Brafield, 1973
282 1.000 Brafield & Mattheissen. 1976
8,700 Cairns & Sparks, 1971
3,200 Burton, et al. 1972
40.000 Sparks, et al. 1972
370 7.200 Pickering, 1968
370 7,500 Pickering. 1968
370 10,700 Pickering, 1968
-------
Table 8. Marine fish acute values for zinc
00
Adjusted
Bioassay Test Time LC50 iXTSO
Orqanism Method- Cone.** (hrs^ (uq/ll (uq/1) Keference
Mummichog (adult) . S U
Fundulus heteroclitus
Rainbow trout (yearling) , FT M
Salmo gairdnerii
Rainbow trout (yearling) , FT M
Salmo gairdnerii
Atlantic salmon (smolt) , FT M
Salmo salar
Atlantic salmon (smolt) , FT M
S.ilmo salar
•
96 60,000 32,802 Eisler & Hennekey, 197.?
48 35,000 28,350 Herbert & Wakeford, 1964
48 82,000 66,420 Herbert & Wakeford, 1964
48 27.000 21,870 Herbert & Wakeford, 1964
48 39,000 31,590 Herbert & Wakeford, 1964
* S = static, FT = flow through
** U = unmeasured, M = measured
Geometric mean of adjusted values = 33,450 33.450 = 9,000ug/l
Lowest value from flow-through test with measured concentrations = 21,870 ug/1
-------
Table 9. Marine invertebrate acute values for zinc
Bioassay Test
Organism MetJiod* Cone.**
Polychaete (adult) , S
Capitclla capitata
Polychaete (larvae). S
Capitella capitata
Polycahete (adult) . S
Neanthes drenaceodentata
to
1
Ul
vo
Polychaete (juvenile),
Neanthes arenaceodentata
Polychaete (adult) ,
Nereis diversicolor
Polychaete (adult),
Nereis diversicolor
Polychaete (adult) .
Nereis diversicolor
Sandworm (adult)
Nereis virens
Oyster (larva) ,
Crassostrea virginica
Oyster (larva),
Crassostrea virginica
Hard-shell clam (larva) ,
Mercenaria mercenaria
Hard-shell clam (larva) ,
Mercenaria mercenaria
Soft-shell clam (adult),
My a arenaria
Soft-shell clam (adult),
S
S
S
S
S
S
S
S
S
S
S
U
U
U
U
U
U
' U
U
U
U
U
U
U
U
Time
(hrs)
96
96
96
96
96
96
96
96
48
48
48
48
96
96
LC50
tug/1)
3,500
1.700
1.800
900
1.500
55.000
11,000
8,100
310
339
166
195
5,200
7,700
Adjusted
LC50
2,965
1.440
1.524
762
1,270
46,585
9,317
6.245
262
287
141 '
165.
4,404
6.522
Reterence
Reish. et al. 1976
Reish. et al. 1976
Reish. et al. 1976
Reish. et al. 1976
Bryan & Hummerstone, 1973
Bryan & Hummerstone, 1973
Bryan & Hummerstone, 1973
Eisler & Hennekey, 1977
Calabrese, et al. 1977
Calabrese, et al. 1973
Calabrese, et al. 1977
Calabrese & Nelson, 1974
Eisler. 1977a
Eisler & Hennekey. 1977
Mya arenaria
-------
Table 9. (Continued)
Organism
Bioassay Test
Method* cone.*"
Time
(hrs)
03
*»
O
Mussel, S
Mytilus edulis planulatus
Mud snail (adult), S
Nassarius obsoletus
Copepod (adult), S
Acartia tonsa
Copepod (adult), S
Apartla claust
Copepod (adult), S
Pseudodiaptomus coronatus
Copepod (adult), S
Eurytemora affinis
Copepod (adult), S
Tigriopus japonicus
Crab (larva). • S
Carcinus maenas
Crab (adult), S
Carcinus maenas
Crab (adult), S
Carcinus maenas
Hermit crab (adult). S
Pagurus longicarpus
Starfish (adult), S
Asterias -forbesi
M
U
U
U
U
U
U
U
96
96
96
96
96
96
96
48
48
48
96
96
Adjusted
LC50 LC50
(uq/l> (ug/1) Reference
2,500 2,640 Ahsanullah, 1976
50,000 42,350 Eisler & Hennekey, 1977
f
290 246 Sosnowski. et al. 1979
950 805 Sosnowski. et al. 1979
1,783 1.510 Sosnowski, et al. 1979
4,090. 3,464 Sosnowski. et al. 1979
2,160 1,830 Sosnowski, et al. 1979
1.000 847 Conner. 1972
14.500 5.281 Conner, 1972
12,000 4,370 Portmann, 1968
400 , 339 Eisler & Hennekey, 1977
39.000 33.033 Eisler & Hennekey. 1977
* S = static, FT = flow- through
** U = unmeasured, M = measured . ,
Geometric mean of adjusted values = 2,026 ug/1
026
— =
41 wg/1
-------
Table 10. Marine plant effects for zinc
Organism
Effect
Concentration
(ug/1)
Reference'
CD
Alga, Growth
Amphldinium carteri inhibition
400
Alga.
Amphidinium carteri
Alga.
Dunaliella tertiolecta
Interaction with 100
copper on growth
Reduction in .gs 6..JOO
potassium content KM
Kelp, Growth
Laminaria hyperiborea inhibition
Kelp, Growth
Laminaria digitata inhibition
Kelp.
Macrocystis pyrifera.
250
100
Photosynthesis 10,000
inhibition
Alga, Growth
Phaeodactylum inhibition
tricornutum
25,000
Braek, et al. 1976
; V Braek. et al. 1976
Overnell, 1975
- Hopkins & Kain. 1971
Bryan, 1964
Clendenning & North, 1959
Jensen, et al. 1974
Alga,
Phaeodactylum
tricornutum
Alga,
Skeletonema costal:urn
Alga,
Skeletonema costatum
Alga,
Skeletonema costatum
Interaction with 1,000
copper on growth.
Growth
inhibition
Growth
inhibition
50
200
Interaction with 50
copper on growth
Braek. et al. 1976
Bryan, 1964
Braek, et al. 1976
Braek, et al. 1976
Alga.
Thalassiosira
pseudonana
Growth
inhibition
500
Alga,
'Thalassiosira pseudonana
Growth inhibition 400
Braek, et al. 1976
Braek. et al. 1976
-------
03
I
•U
to
Table 10. (Continued)
Concentration
organism Etrect (ug/i) Reference
Alga, Interaction with 200 Braek, et al. 1976
Thalassiosira copper on growth
pseudonana
Lowest marine plant value = 50 ug/1
-------
Table
Marine residues for zinc
Organism
Dioconceiitration Factor
rttreience
Alga (live tip) ,
Ascophyllum nodosum
Alga (dead tip),
Ascophyllum nodosum
Alga.
Cladophora sp.
Alga,
Cladophora sp.
Alga.
Fucus serratus
Algae (mixed) ,
Five genera
« Alga.
j^ Laminar ia digitata
OJ
Alga.
Phaeodactylum tricornututn
Alga.
Skeletonema cost a turn
Alga,
Thalassiosira pseudonana
Polychaete (adult) ,
Nereis diversicolor
Scallops (adult) ,
Aequipecten irradians
Oyster (adult)',
Crassostrea virginica
Oyster (adult) ,
Crassostrea virginica
Gastropod (adult) ,
55
950
1.785
4,680
10.000
1.900
3,000
8.100
1
12.400
55
321
27,080
146
670
4
7
12
34
140
90
30
14
13
13
9
15
140
15
50
Skipnes, et al. 1975
Skipnes, et al. 1975
Baudin, 1974
Baudin, 1974
Young. 1975
Cross, et al. 1971
Bryan, 1964
Jensen, et al. 1974
Jensen, et al. 1974
Jensen, et al. 1974
Bryan & Hununerstone, 1973
Duke, et al. 1969
Shuster & Pringle, 1969
Duke, et al. 1969
Young, 1975
Littorina obtusata
-------
Table n> (Continued)
Organism
Hard-shell clams (adult) ,
Mercenaria tnercenaria
Hard-shell clams (adult).
Mercenaria mercenaria
Soft-shell clam (adult),
Mya arenaria
Soft-shell clam (adult).
Mya arenaria
Mussel (adult) ,
Mytilus edulis
Mussel (adult),
Mytilus edulis
Mussel (adult),
y Mytilus edulis
**
•U Mussel (adult),
Mytilus edulis
Amphipod,
Gamma rus locusta
Crab (adult).
Carcinus maenas
Crab (adult) .
Carcinus maenas
Mud crab (adult) .
Bioconcentr ation Factor
22
85
85
43
460
500
105
330
400
9.000
5.400
266
Time
(days)
15
70
50
112
13
21
20
35
27
32
42
15 .
Kfcterence
Duke, et al. 1969
Shuster & Pringle. 1968
Pringle. et al. 1968
Eisler. 1977b
Phillips. 1977
Pentreath. 1973
Van Weers. 1973
Phillips, 1976
Fowler, et al. 1975
Bryan. 1971
Bryan, 1966
Duke, et al. 1969
Panopeus herbstii
-------
Table 12. Other marine data for zinc
Organism
Muuunichog (adult),
Fundulus heteroclitus
Mumiuichog (adu 11) ..
Fundulus heteroclttus
Mumnichog (adult),
Fundulus heteroclitus
Test
Duration Etfect
96 hrs LC28
24 hrs No histological
damage
24 hrs Histological damage
oa
Ul
Mummichog (adult),.
Fundulus heteroclitus
Mummichog (adult).,
Fundulus heteroclitus
Mummichog (adult) ,
Fundulus heteroclitus
Mummichog (adult),
Fundulus heteroclitus
Mummichog (adult) ,
Fundulus heteroclitus
Mummichog (adult),
Fundulus heteroclitus
168 hrs
168 hrs
168 hrs
14 days
48 hrs
48 hrs
LCO
LC50
LC100
lucre*
ALA*D
LCO
LC100
Mummichog (adult)>
Fundulus heteroclitus
Mummichog (adult),
Fundulus heteroclitus
Protozoan,
Cristigera sp.
Protozoan,
Cristinera sp.
Protozoan,
Euplotes vannus
Result
(uq/11 Reterencfc
60,000 Eisler & Gardner, 1973
36,000 Eisler & Gardner, 1973
60,000 Eisler & Gardner, 1973
10,000 Eisler & Hennekey, 1977
52,000 Eisler & Hennekey, 1977
120,000 Eisler & Hennekey, 1977
ALA*D enzyme activity 10,000 Jackim, 1973
10,000 Thomas, 1915
192 hrs LCO
192 hrs LC50
4-5 hrs Reduced, growth
— Growth reduction
48 hrs EC10 (reproduction)
157,000 Eisler. 1967
43,000 Eisler. 1967
66,000 Eisler. 1967
125 Gray. 1974
125 Gray & Ventilla. 1973
10,000 Persoone & Uyttersprot. 1975
-------
Table 12. (Continued)
Organism
Test
Duration Ett'ect
Result
fuq/lL
Reference
Polychaete,
Ctenodrilus serratus
Sandworm (adult),
Nereis virens
Polychaete,
Ophryotrocha diadema
Polychaete,
Ophryotrocha labronica
Oyster (larva),
Crassostrea gigas
Oyster (larva),
Crassostrea gigas
Oyster (larva),
Crassostrea gigas
Oyster (larva),
Crassostrea gigas
Oyster (larva),
Crassostrea virginica
Oyster (larva),
Crassostrea virginica
Oyster (adult),
Crassostrea virginica
Hard-shell clam
(embryo),
Mercenaria mercenaria
Hard-shell clam
(larva),
.Mercenaria mercenaria
21 days
168 hrs
21 days
13 hrs
5 days
48 hrs
' 6 days
48 hrs
48 hrs
48 hrs
140 days
..'•42-48
hrs
Reduced survival 10,000
LC50 2,600
Reduced survival 1,750
LC50 1,000
Substrate attachment 125
inhibition
Reduced development 125
Growth inhibition 125
LCO
LC100
Reish & Carr, 1978
Eisler & Hennekey, 1977
Reish & Carr, 1978
Brown & Ahsanullah, 1971
Boyden, et al. 1975
Brereton, et al. 1973
Brereton, et al. 1973
Abnormal shell development 70 Nelson, 1972
75 Calabrese. et al. 1973
500 Calabrese, et al. 1973
No significant mortality 200 Shuster & Pring'le, 1968, 1969
LCI 00
279 Calabrese & Nelson. 1974
,12 days LC5
50
Calabrese, et al. 1977
-------
Table 12. (Continued)
Organism
Hard-shell clam (larva)
Mercenaria mercenaria
Hard-shell clam (larva)
Mercenaria mercenaria
Soft-shell clam (adult)
Mya arenaria
Soft-shell clam (adult)
Mya arenaria
Mussel (adult) ,
Mytilus edulis
Coot clam (adult) ,
Mulinia lateralis
7 Mud snail (adult).
•*» Nassarius obsoletus
Mud snail (adult),
Nassarius obsoletus
Mud snail (adult) ,
Nassarius obsoletus
Isopod (adult) ,
Idoten baltica
Barnacle (adult) ,
Balanus balanoides
Crab (larva) ,
Carci.nus maenas
Hermit crab (adult) ,
Pagurus longicarpus
Crab (larva),
RhiLhropanopeus harrisi
Test
Duration
, 12 days
. 12 days
, 168 hrs
, 168 hrs
14 days
14 days
72 hrs
72 hrs
168 hrs
120 hrs
5 days
0.22 hrs
168 hrs
16 days
Res
Ettect (u'l
LC50
LC95
LC50 @ 20°C 3
LC50 @ 22°C 1
Decrease in cadmium
uptake
Decrease in cadmium
uptake
No effect on behavior
Decreased oxygen consump-
tion
LC50 7
LC40 @ 34°/oo S 10
],cyo 8
LC50- 33
100
LC50
Delayed
development
ult
/il
195
341
.100
.550
500
500
100
200
,400
,000
,000
.000-
,000
200
50
Ret ereiiCfe
Calabrese, et al. 1977
Calabrese, et al. 1977
Eisler & Hennekey, 1977
Eisler, 1977a
Jackim, et al. 1977
Jackim, et al . 1977
Maclnnes & Thurberg, 1973
Maclnnes & Thurberg, 1979
Eisler & Hennekey, 1977
Jones, 1975
Clarke, 1947
Conner. 1972
Eisler & Hennekey, 1977
Benijts-Claus & Benijts, ]
-------
03
I
Organism
Table 12. (Continued)
Test
Duration Ettec
Result
(uu/ll
Sea urchin (spennatozoa), A mins
Arbacia puctulata
Sea urchin (spermatozoa), A mins
Arbacia puctulata
Sea urchin (spermatozoa), A mins
Arbacia puctulata
Decreased motility
Decreased motility
Decreased motility
163-817 Young & Nelson. 197A
81 Young & Nelson. 197A
1,635 Young & Nelson. 197A
Sea urchin (egg),
Arbacia puctulata
Starfish (adult),
Asterias forbesi
Starfish (adult).
Asterias forbesi
15 hrs Abnormal development 1,250 Waterman, 1937
168 hrs LC50
2A hrs Equilibrium loss
2.300 Eisler & Hennekey. 1977
2.700 Galtsoff & Loosanoff, 1939
00
-------
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variation in the lethality of zinc to juvenile Atlantic
salmon (Salrno salar) . Jour. Fish. Res. Board Can. 34: 139.
B-71
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Mammalian Toxicology and Human Health Effects
Introduction
More than 100 years ago it was shown that zinc was essential for the
growth of Aspergillus niger. It was then shown that it was an essential metal
for plant life. In the 1930's, the essentiality of zinc for the growth of
rats was shown. Zinc has for a long time been regarded as an essential element
for human beings but not until the 1960's was it shown that zinc deficiency
could cause a certain syndrome and that therapy with zinc salts could alleviate
or even cure the symptoms of zinc deficiency. During the recant past some
other disease states including congenital diseases have been related to zinc.
Zinc therapy has attracted the interest of clinicians. The evergrowing interest
in the metabolism of zinc and the relationship between zinc and certain diseases
*
has, during the last decades, been reflected in a large number of reviews and
books (Brewer and Prasad, 1977; Halsted et al., 1974; National Research
Council, 1978; Pories et al., 1974; Prasad, 1966; Prasad, 1976; Prasad, 1978;
Sandstead, 1975; Sandstead 1973; Vallee, 1959; Underwood, 1977). The National
Research Council (NRC) report contains 1,855 references and gives information
not only on metabolism and essentiality of zinc for human beings but also much
information on occurrence of zinc, analytical methods, and human health hazards
form excessive exposure to zinc. Since this chapter to a large extent relies
on the NRC report, reference will be given to chapters or page numbers in that
report whenever it is quoted in this or following sections.
The information given will mainly rely on the above mentioned references
and specific references will only be given when there is information which
might add to the understanding of the metabolism and effects of zinc, esp-
cially in human beings.
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EXPOSURE
Ingestion from Water
The National Research Council (NRC) (1978) (Chapter 2 pp. 25-28 and
Chapter 11 pp. 269-271) summarized available data on zinc in drinking water
and concluded that generally the concentrations were well below 5 mg/1. •, In a
study by the Department of Health, Education and Welfare (HEW) (1970) 2595
water samples were tested and of them 8 had zinc concentrations above the 5
mg/1 level. The highest concentration found was 13 mg/1. The average zinc
concentration was 0.19 mg/1. In water leaving treatment plants, Craun and
McCabe (1975) found that all samples contained less than 5 mg/1 of zinc, but
that in cities with soft acidic water the concentration increased in the
distribution system. Tapwater could thus have concentrations around 5 mg/1.
In a study by EPA (1975) it was found that in 591 water samples all had zinc
concentrations below 4 mg/1.
Uncontaminated fresh water generally contains less than 0.01 mg of zinc/1
(NRC, 1978). Analysis of filtered surface waters in the U.S. revealed that of
714 samples only 7 had concentrations exceeding 1 mg/1 and that 607 (85 percent)
had concentrations below 0.1 mg/1 (Durum et a!., 1971).
The concentration of zinc in both natural waters and in drinking water
are generally low, but may increase due to pollution of water systems or ..,
release of zinc from distribution systems and household plumbing respectively.
Ingestion from Food
In the NRC document the content of zinc in different foodstuffs is listed
in detail (Appendix A-I pp. 313-326). It was noted that meat products contain
relatively high concentrations of zinc, whereas fruits and vegetables have
relatively low concentrations and contribute little to the daily intake. Zinc
C-2
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concentrations in milk are generally low, but at a high intake, milk can make
an important contribution to daily intake of zinc.
Additional data are provided by Mahaffey et al. (1975) who calculated
that meats, fish, and poultry on an average contained 24.5 mg/kg of zinc,
whereas grains (and cereal products) and potatoes only provided 8 and 6 mg/kg,
respectively. These data were obtained from Food and Drug Administration
market basket studies which are based on the diets of teenage males, 15 to 20
years old. In the years 1973 and 1974 it was calculated that the daily intake
in this age group was 18 and 18.6 mg/day of zinc, respectively. Greger (1977)
calculated the daily intake of zinc in subjects living in an institution for
the aged, with an average age of 75 years, and found that on an average the
intake was 18.7 mg/day. In girls 12 to 14 years old, Greger et al. (1978)
found that the average intake of zinc Was 10 mg/day.
In the "recommended dietary allowances" the National Research Council
(National Academy of Sciences, 1974) recommended that adults should have a
zinc intake of 15 mg/day;,but pregnant women should have an intake of 20
/ "* V .
mg/day and lactating women an intake of 25 mg/day. As a requirement of pre-
adolescent children, 10 mg/day was recommended. In infants up to 6 months
old, 3 mg/day was recommended and for children aged 0.5-1 year 5 mg/day was
suggested. Based on body weight the requirement for zinc would be about 0.5
mg/kg for the infant and about 0.2 mg/kg in the adult.
A bioconcentration factor (BCF) relates the concentration of a chemical
in water to the concentration in aquatic organisms. 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.
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At least one BCF from an exposure of 28 days or more is available for
each of the four major groups:
Species
fish
Carp,
Cyprinus carpio
o Saltwater fish
Plaice (adult)
Pleuronectes platessa
o Saltwater molluscs
Hard-shell clams (adult)
Mercenaria mercenaria
Soft-shell clam (adult),
Mya arenaria
Soft-shell clam (adult),
Mya arenaria
Soft-shell clam (adult),
Mya arenaria
Clam (adult),
Tapes jaoonica
Scallops (adult),
Aeouipecten irradians
Oyster (adult),
Crassostrea virginica
Oyster (adult),
Crassostrea virginica
Oyster (adult),
Qstrea edulis
• Mussel (adult),
Myti1 us edulis
o Saltwater decapods
Crab (adult),
Carcinus maenas
Crab (adult),
Carcinus maenas
. Lobster (adult),
Homarus vulaaris
BCF
8
373
85
85
43
52-78 t
500
282-321
15,290-27,080
15,240
450
130-310
8,000-9,000
5,400
142
Reference
Lebedeva &'•' """'
Kuznetsova, 1969
Pentreath, 1973
Shuster & Pn'ngle,
1968
Pringle et al.
1968
Eisler, 1977
Eisler, 1977
Kameda et al. 1970
Duke et al. 1969
Shuster & Pringle,
1S69
Shuster & Pringle,
1968
Romeri1, 1971
Philips, 1976
Bryan, 1971
i
Bryan, 1966
Bryan, 1964
C-4
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From these data the geometric mean bioconcentration factor for each group
can be calculated.
Consumption 8 i concentration
Group (Percent) factor
Freshwater fishes 12 8
Saltwater fishes 61 373
Saltwater molluscs 9 306
Saltwater decapods 18 980
Using the data for consumption and BCF for each of these groups, the
weighted average BCF for zinc is 432 for consumed fish and shellfish.
Inhalation Via Ambient Air
Air quality data compiled in the NRC document (1978) show that zinc
concentrations throughout the U.S.A. generally are less than 1 ug/m (Chapter
3 p. 42-43). In 1975 and 1976, EPA (1979) observed zinc concentrations at
approximately 50 National Air Surveillance Network sites .-throughout the U.S.
Zinc concentrations in most areas were below 1 pg/m , quarterly average.
The air levels of zinc are, in most areas, fairly constant. As an
example, Lioy et al. (1973) presented data on zinc concentrations in New York
City during the years 1972 to 1975 where the annual averages varied from 0.29
to 0.38 pg/m . Much higher concentrations have been reported near smelters.
About 1.5 miles from a smelter in Kellogg, Idaho, Ragaini et al. (1977) found
in ambient air a yearly mean zinc concentration of 5 ug/m . The 24-hour
values ranged from 0.27 to 15.7 ug/m . It should be mentioned that the average
C-5
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lead and cadmium concentrations were 11 and 0.8 ug/m , respectively, indicating
very severe environmental pollution. The U.S. data may be compared to data
from 15 cities in a heavily industrialized European country, Belgium '
(Kretzschmar et a!., 1977). During the period May 1972 to April 1975 the
average concentrations in 15 locations were from 0.22 to 3.05 ug/m . The
highest value recorded during 24 hours was 57 ug/m .
These data from industrialized countries may be compared to background
levels of zinc which have been measured at the South Pole and over the Atlantic
Ocean. At the South Pole an average concentration of 0.03 ng/m was found.
In the air over the Atlantic Ocean concentrations were from 0.3 to 27 hg/m
(Dues, 1975; Maenhaut, 1977; Zoller, 1974).
Exposure Via Smoking
In cigarettes and other tobacco products zinc concentrations have been
reported to vary from 12.5 - 70 ug/g. (Menden et al., 1972; Dermelj et al.,
1973; Franzke et al., 1977). In the studies by Menden et al. and Franzke et
al. the amount of zinc in the mainstream smoke was determined by simulated
smoking in a smoking machine. Menden et al. found in two brands of cigarettes
that 0.06 and 0.36 ug, respectively, was in the mainstream leaving the cigarette,
whereas Franzke et al. found in 16 brands that from 0.12 to 0.92 ug was in the
same fraction. These data indicate that by smoking 20 cigarettes up to 20 ug
of zinc might be inhaled. There might have been some differences in experimental
techniques, since Menden et al. found that about 85 percent of the zinc remained
in the ash, whereas Franzke et al. found that in some cigarettes only about 10
percent remained in the ash.
C-6
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Quantification of Total Intake; Relative Contribution From All Routes of Exposure
The major source of zinc for the general population in the U.S. is food.
The average intake is generally above 10 mg in adults. An individual inhaling
air with an average concentration of 5 ug/m , would have an additional daily
intake of 100 ug, assuming that he inhales 20 m of air per day. Smoking
would contribute even less than that. Compared to the intake via food, airborne
0
exposure is insignificant.
The intake via drinking water might be of more significance. Levels
around 1 mg/1 are not uncommon and levels around 5 mg/1 have been reported.
Assuming a daily intake of 2 liters of water this might result in daily intakes
of 2 and 10 mg, respectively. The latter amount might double the intake for
people on a low dietary intake, but the total intake will still be within
recommended limits. In people with recommended daily intakes of zinc, i.e.,
15-20 mg, the additional intake via water will result in total daily intakes
of 25-30 mg. As discussed later, the homeostatic regulation of zinc ensures
that such amounts and even larger amounts can generally be well tolerated.
C-7
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PHARMACOKINETICS
Metabolism and Homeostatic Regulation
Inhalation
The fate of inhaled particles containing zinc will depend on particle
size and solubility as well as functional state of the lungs. The quanti-
tative features of the deposition patterns of particles have been reviewed by
the Task Group on Lung Dynamics (1966) and the Task Group on Metal Accumulation
(1973). There are no quantitative data on the deposition and absorption of
zinc compounds, but experiments on human beings by Sturgis et al. (1927) and
Drinker et al. (1927) indicated that both zinc oxide fumes and zinc oxide
powder with very small particle size were deposited in the alveoli. That
inhaled zinc is absorbed is shown by the finding of increased serum and plasma
levels of zinc in exposed workers. It should be pointed out, however, that
part of the inhaled material will be transported to the gastrointestinal tract
via ciliary activity and some zinc may also be absorbed that way.
Gastrointestinal Absorption
The absorption of ingested zinc will depend mainly on the zinc status of
the organism. The presence or absence of other nutritional constituents may
also influence absorption.
Spencer et al. (1965) showed in human beings that Zn as the chloride
was rapidly taken up, with plasma peak values within 4 hours. It was calculated^
that about 50 percent was absorbed, but with a wide range (20 to 80 percent).
In that study it was not possible to show that the amount of calcium in the
diet influences the uptake of zinc from the gut. There are difficulties
C-8
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in assessing the absorption of zinc, since there is also considerable excretion
of absorbed zinc via the gastrointestinal tract . There are also several
other earlier studies which show that there are wide variations in the absorp-
tion rates of ingested zinc (NRC Chapter 6 pp. 145-154).
The protein content of the diet has been shown to influence the uptake of
zinc. In studies done on people with zinc deficiency it has been noted that
the effect of zinc therapy is enhanced by a simultaneous administration of
protein. It has also been shown that the absorption of zinc will be reduced
if the diet contains large amounts of phytate .especially in the presence of
large amounts of calcium (NRC Chapter 7 pp. 183-187). S-ince phytates are
found in cereals, zinc in vegetable diets including large amounts of unleavened
bread may be less available for absorption. Arvidsson et al. (1978) found
that the average absorption of Zn added to bread during baking was 25 percent
ranging from 12.2 to 39.1 percent in 11 subjects. The study was repeated
after one month and the same average absorption was found. In this study, the
influence of phytate seems to have been small. The fiber content of the diet
may influence the uptake of zinc (Sandstead et al., 1973). Zinc in anima-1
proteins seems to be easily available and thus meat is a good source of zinc.
The influence of oral contraceptive agents on the absorption of zinc was
studied in 14 women and compared to 8 who did not take contraceptive pills
(King et al., 1978). All were of similar age. Zinc was administered as a
stable isotope, Zn, and the absorption was determined from the difference
between intake and fecal output of the stable isotope which was measured by
neutron activation analysis. Among the women taking the contraceptive agents,
the average absorption was 33 percent and in the control group it was 46
C-9
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percent. The difference, however, was not statistically significant, and the
authors concluded that there was no difference in absorption.
The mechanisms for absorption of zinc are homeostatically controlled, and
data from animal experiments suggest that several proteins and low molecular
weight compounds may be involved in the absorption process. There is evidence
that metallothionein, a low molecular weight, metal-binding protein, in the
intestinal mucosa may bind zinc (Richards and Cousins, 1977). Zinc binding
ligands with molecular weights lower than metallothionein have been found in
animals. Evans et al. (1975) proposed that such a compound .was produced in
the .pancreas and through the pancreatic secretions could bind zinc in the
gastrointestinal tract and enhance absorption.
Of special interest is a zinc binding ligand which occurs in human milk,
but has not been found in bovine milk. In 1976, Eckhert et al. (1976) reported
that gel chromatography of cow's milk and human milk showed that in cow's milk
zinc was associated with high molecular weight fractions, whereas in human
milk it was mainly associated with low molecular weight fractions. This
species difference was taken by these authors as an explanation for the
congenital disease acrodermatitis enteropathica which usually occurred when
infants were weaned from human breast milk. Similar results were reported by
Evans and Johnson (1976) who thought that the low molecular weight zinc binding
ligand in milk was similar to the ligand found in pancreatic secretions from
the rat. During the last years several studies have been performed to isolate
and identify this ligand (Song and Adham, 1977; Evans and Johnson, 1977;
Shricker and Forbes, 1978; Lonnerdal et al., 1979; Evans and Johnson, 1979).
The data are controversial and at present no certain conclusions can be drawn
regarding the nature of the ligand or ligands. It has also been sho.wn by
C-10
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Cousins, et al. (1978) that degradation products of intestinal
proteins including metallothionein r.ay crrur as low molecular
weight zinc binding complexes in rat intestine. The role of.
ligands in zinc absorption has recently been discussed by
Cousins (1979).
Other Absorption Routes
Zinc salts will be absorbed through intact skin of the rat as shown by
Keen and Hurley (1977). According to these authors, the amount of zinc absorbed
was higher in zinc-deficient animals and was of a magnitude which might be
clinically significant.
Hallmans (1978a, 1978b) showed that in rats with excisional wounds there
was a high absorption of zinc from gauzes containing zinc sulfate. At a
concentration of 20 percent there were even systemic effects; Hallmans concluded
that the absorption from zinc sulfate was higher than from zinc oxide. Hallmans
(1977) also showed that in humans treated for burns with gauzes containing
zinc oxide, there was absorption of zinc.
Anteby et al. (1978) reported that in women using an intrauterine device
containing copper and zinc a slight rise in serum zinc could be shown, but no
abnormal values were found.
Transport and Deposition
Zinc is found in erythrocytes mainly due to the presence of the zinc
metallo enzyme carbonic anhydrase and in leucocytes where several zinc metallo
enzymes are present. In plasma, zinc is mainly bound to albumin and it is
thought that the binding is to one of the histidine moieties of the albumin
molecule. About one third of the serum zinc is bound to an a?-macroglobulin
and a few percent to ami no acids. In the albumin and the ami no acids there is
C-ll
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an exchange of zinc, whereas there is no exchange with zinc in the (^-macro-
globulin. The zinc bound to amino acids constitutes the diffusible serum zinc
(Giroux, 1975; Giroux 1976; NRC, 1978).
Of special interest is the relationship between zinc and histidine. It
has been shown in human beings that oral administration of histidine will
cause decreases in serum zinc and an increase in urinary zinc excretion (Henkin
et a!., 1975). This observation has also been made in experiments on rats
(Freeman and Taylor, 1977) and dogs (Yunice et al., 1978). The latter authors
also showed that cysteine caused a considerable increase in excretion of zinc.
This is thought to be one explanation for the losses of zinc seen in patients
given parenterally hyperalimentation, since the fluids given usually contained
large amounts of essential amino acids, without sufficient amounts of essential
metals (Agarwal and Henkin, 1978; Kumar, 1976).
In the tissues, the highest concentrations of zinc are found in the male
reproductive system where the prostate has the highest content. Other organs
with high concentrations of zinc are the muscle, bone, liver, kidney, pancreas,
and some endocrine glands, especially the thyroid. The largest amounts of
zinc are found in the muscles and the bone. Within tissues there may be
variation; in the human prostate gland the highest zinc concentrations are
found in the lateral prostate and the lowest in the interior and inner prostate.
Also significant is the finding that semen has a high zinc content. In most
organs there are relatively small variations in zinc levels during a lifetime
except that in the newborn, zinc concentrations generally are higher than
later in life. It should also be pointed out that the zinc content of the
kidney and liver will, to a large degree, depend on the cadmium concentrations
and renal zinc concentrations will vary with age (Elinder et al., 1978; Piscator
C-12
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and Lind, 1972; Schroeder et al., 1967). Regarding the form in which zinc is
stored in different organs, zinc is generally an essential component of many
enzymes (see section on essentiality). Zinc is also found in metallothionein
(see special section on metallothionein).
Excretion
Zinc is mainly excreted via the gastrointestinal tract but part of that
zinc is reabsorbed. Urinary excretion of zinc is relatively small and during
certain conditions, i.e., extreme heat or exercise, much larger quantities may
be excreted in sweat (Cohn and Emmett, 1978; Kohnadel et al. , 1973). Zinc is
also excreted via hair and milk, and in the female there is a placenta! transfer
to the fetus.
Losses of zinc may also occur via menstrual blood losses and skin. Molin
and Wester (1976) determined by neutron activation the zinc content of epidermis.
They calculated that the daily losses by desquamation would be about 20 to 40
(jg, only about one tenth (1/10) of the urinary excretion.
Biological Half-time
The long-term biological half-time of zinc will depend on the zinc status;
it has been shown that after oral intake or injection of Zn to human beings,
the half-time may vary from about 200 to about 400 days, depending on the zinc
status (NRC Chapter 6 pp. 151-154). Arvidsson et al. (1978) gave eight subjects
single injections of Zn. After the injection, measurements were taken for
84 to 190 days. The slow component for the half-time of the injected zinc for
this group was on an average 247 days. Kennedy et al. (1978) found that the
average half-time was 412 days in 19 female patients undergoing treatment for
rheumatoid and osteoarthritis who were given an oral dose of Zn . In certain
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body compartments, e.g., bone, the half-time may be considerably 1onger'(NRC
Chapter 6 pp. 149-154).
Metal!othionein
Metallothionein was briefly discussed in previous reports and books
concerning zinc, but during the last several years there has been an enormous
increase in the number of papers on this protein. Recently a very comprehen-
sive report on metallothionein has been prepared (Nordberg and Kojima, 1979).
Mammalian metal!cthionein is a protein with a molecular weight of 6,000 to
7,000 which is characterized by a very special amino acid composition, a high
cysteine* content, but lack of aromatic ami no acids and histidine. Metal! othionei'n
was first discovered in equine renal cortex by Margoshes and Vallee (1957) and
has now been shown to occur in most mammalian tissues, and also in lower
organisms. Total metal content of metallothionein can reach 5 to 7 g atoms
per mole. The metals generally found in metallothionein are zinc, copper, and
cadmium. The relative occurrence of these metals will depend on a number of
factors. In fetal liver metallothionein, zinc and copper are the major con-
stituents, whereas in animals exposed to cadmium, cadmium will be the dominat-
ing metal especially in the renal protein. A number of factors can induce the
synthesis of metallothicnein. In addition to administration of the above-
mentioned metals, metallothionein synthesis seems also to be indirectly.induced
by factors that might influence zinc metabolism. Thus, environmental stresses
of different kinds may induce the synthesis.
•
With regard to zinc metabolism, it has been shown that parenteral or
dietary administration of zinc will cause an increase of the synthesis of
matallothionein (Bremner and Davies, 1S75; Richards and Cousins, 1975a;;Richards
and Cousins, 1975b; Richards and Cousins, 1977). Recently, it was shown that
C-14
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hepatic zinc was increased and metallothionein synthesis stimulated in response
to several environmental stresses, such as cool and hot environments, burns,
and exercise (Oh et al., 1978). Food restriction and bacterial infections
have been shown to cause such changes (Bremner and Davies, 1975; Richards and
Cousins, 1976; Sobocinski et al., 1978). Failla and Cousins (1978) demonstrated
that glucocorticoids j_n vitro stimulated the uptake of zinc in liver parenchymal
cells, a process that required synthesis of metallothionein. Such findings
indicate that metallothionein may serve as a regulator of plasma zinc levels
and constitute an easily available pool for acute replacements of zinc in
certain situations. Also of interest is the finding of large amounts of
metallothionein containing zinc and copper in fetal livers reported by several
investigators (Bremner et al., 1977; Hartmann and Weser, 1977; Ryden and
Deutsch, 1978), which gives similar indications. Much is still unknown about
the biological function of metallothionein, but there is no doubt that this
protein must play a very important role in the regulation of zinc in the
mammalian body (Nordberg and Kojima, 1979).
Normal Levels in Tissues and Fluids
In the National Research Council (NRC) report (1978), extensive informa-
tion is given on concentrations of zinc in blood, urine and tissues (Chapter 6
pp. 123-145). The NRC report concluded that the mean serum-zinc concentra-
tion in humans is approximately 1 mg/liter, the same in healthy men and
women. The zinc content of whole blood will be about 5 times higher than the
serum level, since the concentration in the red cells is about 10 times the
amount found in serum. A lowering of the serum concentrations of zinc may be
seen in women who take contraceptive pills, during pregnancy, and as a result
of certain stresses such as infections. In the same individual the zinc
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concentration in serum will be higher than in plasma mainly due to the release
of zinc from platelets (Foley et a!., 1968). In 14 subjects the mean serum
level was 1.15 mg/1 and the mean plasma level 0.98 mg/1, the average difference:
being 16 percent. '
The influence of age and sex on plasma zinc levels was studied by Chooi
et al. (1976). They found that in both males and females there was a'decrease
in plasma zinc from age 20 to age 90. Between men and women below the age of
50 no difference in plasma zinc levels could be noted between the sexes.
However, females using contraceptive agents had lower zinc levels than women
who did not take contraceptive agents. Average plasma levels in the groups
studied were around 0.7 mg/1.
In a recent report, Hartoma (1977) stated that men had higher serum zinc,
levels than women. The average concentration in 154 male blood donors was
1.24 mg/liter (range 0.74 to 2.2 mg/1), and in 95 women it was 1.11 mg/liter
(range 0.64 to 1.82 mg/1). The difference was highly significant according to
the author. It was not stated to what extant the women took contraceptive
pills. Hartoma also found that there was a slight tendency to a lowering of
the serum concentration of zinc in men with increasing age, and that there was
a significant correlation between serum zinc and serum testosterone in, males
aged 36 to 60 years. In men 23 to 35 years of age, there was a negative
correlation, which was not significant. In these two studies plasma and serum
levels,; respectively, were lower and higher than earlier reported data which
indicates -that methodological problems in sampling and analysis may still
exist. In both studies samples were taken in the morning aftar overnight
fasting.
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In the NRC report (Chapter 6 p. 129) it was stated that approximately 0.5
mg of zinc is excreted in the urine every 24 hours by healthy persons. Addi-
tional data have been provided by Elinder et al. (1978) who studied the urinary
excretion of zinc in different age groups. They found that there was a
tendency towards a higher zinc excretion in smokers than in non-smokers.
Among non-smokers there was a tendency to decreased zinc excretion from
about age 20 to higher ages (See Table C-l). The tissue concentrations of
zinc are generally higher in the newborn. After the first year of life there
are fairly small changes in the zinc levels in most organs except the kidney
where the zinc concentrations are dependent on the accumulation of cadmium
(Elinder et al., 1977; Piscator and Lind, 1972; Prasad, 1976). In the liver
the zinc level is constant during a lifetime. In the pancreas there is a
decrease in zinc levels with increasing age on a wet weight basis, whereas if
the pancreas values are calculated on an ash weight basis that decrease is not
seen (Elinder et al., 1977). This is in agreement with Schroeder et al.
(1967). In the study by Elinder et al. (1977), the average concentrations of
zinc in liver and pancreas were 45 and 27 mg/kg wet weight, respectively. The
highest concentrations of zinc are found in the prostate, where the concen-
tration is about 100 mg/kg wet weight. In human semen concentrations of 100
to 350 mg/1 have been reported. The zinc concentrations in hair will vary
depending on age and geographical location (NRC Chapter 6 pp. 140-141).
Sorenscn et al. (1973) found that in 13 communities in the U.S. the average
zinc concentration in hair from adults varied from 148 to 210 mg/kg. The
newborn has zinc levels in hair similar to levels in the adult, but at age 1-4
the levels are lower than in adults (Hambidge et al., 1972; Petering et al.,
1971). Zinc concentrations in hair will decrease during pregnancy (Baumslag
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TABLE C-l. ZINC CONCENTRATIONS IN THE URINE OF SWEDISH PEOPLE
Number of
Group persons
Men, non-smokers
(age in years)
2 to 9
17 to 19
20 to 29
30 to 39
40 to 49
50 to 59
60 to 69
70 to 79
80 to 89
Men, smokers
(age in years)
40 to 49
50 to 59
66
75 .
Women, non-smokers
(age in years)
3
40 to 49
50 to 59
4
10
10
10
16
15
9
11
9
5
5
1
1
4
10
10
Zinc, average (a)a
(mg/g of creatinine)
0.86
0.38
0.32
0.29
0.25
0.32
0.27
0.40
0.35
0.35
0.39
0.32
0.27
1.23
0.23
0.47
Standard Zinc,
Deviation calculated
(a) average (mg/24 hr)
0.23
0.19
0.13
0.10
0.16
0.09
0.17
0.18
0.12
0.19
0.09
.
—
0.21
0.17
0.38
0.33
0.71
0.59
0.49
0.39
0.45
0.35
0.46
0.35
0.55
0.55
0.41
0.31
0.37
0.20
0.34
a, arithmetic averages.
C-18
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et al., 1974; Hambidge and Droegemueller, 1974). The determination of zinc in
hair has been used as a screening tool for zinc deficiency (Hambidge et al.,
1972). The total body store of zinc in adult humans has been estimated to be
2.3 mg for a 70 kg man (NRC Chapter 6 p. 123).
The Homeostatic Regulation of Zinc
The homeostatic regulation of zinc absorption in the rat was studied by
Evans et al. (1973). Rats fed an optimal intake of zinc were compared to rats
which had been on a diet for 7 and 13 days, respectively, containing less than
1 mg/kg of zinc. Whereas, in the controls the absorption was about 15 percent
measured by examining the radioactivity in the carcass 1 hour after a gastric
dose of Zn, it was about 35 and 50 percent, respectively, in the two experi-
mental groups.
Weigand and Kirchgessner (1973) studied the homeostatic mechanisms for
zinc absorption in 36 weanling rats, where in groups of six they were given a
diet with the following zinc contents: 5.6, 10.6, 18.2, 38, 70, and 141
mg/kg. After 6 days the animals had adjusted to the respective intakes and
the absorption of zinc was from 100 to 34 percent in inverse relation to the
intake of zinc. The true zinc absorption and the fecal excretion of endogenous
zinc could be determined by measuring the turnover of radioactive zinc which
had been injected at the start of the experiment. The figure of 100 percent
seems surprisingly high, but these were weanling rats which were growing
rapidly. This may also explain the relatively high absorption figure for the
group receiving 141 mg/kg feed of zinc. The daily zinc retention was the same
in the groups receiving 38, 70, and 141 mg/kg, whereas it was lower in the
groups receiving 5.5, 10.'5, and 18.2, indicating that in this study this
supply was not sufficient. In the three highest exposure groups both total
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absorption and total fecal excretion of endogenous zinc increased in proportion
to the daily intake.
The homeostatic regulation of ingested zinc was also studied by Ansari
et al. (1975). Male rats were given a diet containing 53 ppm zinc, and at
different times groups were given a diet with 600 mg/kg of added zinc
beginning 7, 14, 21, or 42 days before sacrifice. One week before sacrifice
each rat was given, by gavage, an oral dose of Zn as the chloride.: Feces
were collected for 7 days. The elimination of fecal zinc was similar in all
groups except the control group irrespective of length of exposure, 'whereas
the fecal elimination of Zn increased with length of exposure. Also, analysis
of tissues revealed that the longer the exposure to the high zinc.level in the
diet the more rapidly Zn was eliminated. Tissue levels of stable 'zinc were
only slightly influenced by the high zinc content of the diet. Only in the
liver could a significant increase in the zinc level be noted. Levels in
kidney, muscle and heart did not differ from controls. These results also
show the extreme capacity of the organism to handle excess zinc in the diet.
They also show how rapid the exchange will be between absorbed zinc and tissue
stores of zinc.
Ansari et al. (1976) gave male rats dietary zinc at levels of from 1200
to 84QO ppm zinc for 3 weeks. One week before sacrifice each rat was given
Zn as the chloride by gavage and after that feces were collected for one
week. The high zinc content of the diet did not affect weight gains or feed
consumption or produce any obvious signs of toxicity. In controls 65 percent
of the Zn was eliminated in one week in contrast to 86 percent in the rats
given 1200 ppm zinc in the diet. At still higher levels of dietary zinc there
was no further increase of fecal Zn. Rats given 1200 ppm zinc in the diet
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had significantly higher levels of stable zinc in liver, kidney, and tibia
than controls, whereas there was no change in concentrations in heart and
muscle. No further increase was seen at levels of 2400 to 7200 ppm in the
diet, but at 8400 ppm level a new increase was seen, also in heart but not in
muscle. The amount of radioactive zinc was, at all exposure levels, only a
few percent of the amount found in the controls. There were no obvious changes
with increasing dietary zinc, except in tibia where, at the highest levels,
there occurred an increase compared to the previous levels. In heart and
muscle there was a slight but continuous decrease. In liver and kidneys there
was no change. The authors concluded that the data indicated that there was a
good homeostatic control in the range 2400 to 7200 ppm. The authors also
concluded that the homeostatic regulation of zinc was much more effective in
the rat than in calves. Stake et al. (1975) found that calves given a diet
containing 600 mg/kg of zinc after one week had considerably higher zinc
levels in liver, kidney, and pancreas than calves fed a diet containing 34
mg/kg. There was, however, no change in heart or muscle zinc levels.
Essentiality of Zinc. Zinc Metal!oenzymes and Zinc Deficiency
The topics of zinc essentiality and zinc deficiency have been extensively
treated in the National Research Council (NRC) report (1978) and also in a
recent review by Prasad (1973). In 1934, it was shown by Todd et al. (1924)
that zinc was necessary for the growth of rats and since then many studies
have been made on the essentiality of zinc, including studies of human beings.
In human beings zinc is necessary for normal growth and for normal
development of the gonads. Prasad et al. (1963) found that in certain villages
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in Egypt many subjects exhibited a syndrome characterized by dwarfism and
anemia, hypogonadism, hepatosplenomegaly, rough and dry skin, and mental
lethargy. These young persons had a very low intake of animal proteins with
bread as their main food. Zinc deficiency was demonstrated by the finding
that zinc concentrations in plasma, red cells, and hair were decreased; that
subjects had a higher turnover of radioactive zinc than normal, and that the
excretion of zinc in feces and urine was less than in controls. Improvements
were seen after oral administration of zinc with a still greater effect observed
upon additional protein supplementation.
Similar syndromes have been reported in other parts of the world. There
are, however, studies that show that zinc deficiency with less pronounced
symptoms may be more common than thought earlier. In the U.S., evidence of
symptomatic zinc deficiency has been found in Colorado by Hambidge et al.
(1972). Zinc concentrations in hair were used as an index of the zinc status.
Hambidge et al. found that in 132 children ages 4 to 15, 10 children had hair
zinc concentrations below 70 rag/kg, whereas most children had concentrations
above 125 mg/kg. Eight out of 10 of these children were found to have heights
at the lower range for their age group. Poor appetite and a low intake of
meat was thought to be one reason for trie zinc deficiency. In these children
hypogeusia (impaired taste acuity) was also found. After zinc supplementation,
this condition was normalized. An increase in hair zinc could be shown
parallelling the supplementation with zinc. In five children with hair zinc
levels of 10 to 63 mg/kg before therapy, the levels were 67-170 mg/kg after 4
months of therapy. There are studies in other parts of the U.S. showing that
low zinc levels in children's hair is not an uncommon finding (Prasad, 197S).
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The reason for the signs and symptoms caused by the zinc deficiency is
not clear, but it is known from a number of studies in a variety of organisms
including human beings (NRC Chapter 8) that zinc is an essential constituent
of many metal!oenzymes. Typical examples of such metalloenzymes are alcohol
dehydrogenase, carboxypeptidase, leucine aminopeptidase, alkaline phosphatase,
carbonic anhydrase, RNA polymerase and DNA polymerase. Also, thymidinekinase
is thought to be a zinc dependent enzyme. Zinc may be involved in the synthesis
and catabolism of RNA and DNA.
In addition to nutritional zinc deficiency, which is caused solely by a
low dietary zinc intake, there are instances of zinc deficiency which are
thought to have other causes. These are:
(1) zinc deficiency in dialysis patients, which has been attributed tc
depletion of bcdy zinc stores (Atkin-Thor et al., 1978);
(2) zinc deficiency after intravenous hyperalimentation, which might
lead to increased excretion of zinc because of the large amounts of ami no
acids in the infusion fluids (Bernstein and Leyder, 1978; Freeman et al.,
1975);
(3) zinc deficiency after excessive alcohol ingestion (Ecker and Schroeter,
1978; Weismann et al., 1978); and
(4) zinc deficiency after operations such as intestinal bypass surgery
(Atkinson et al., 1973; Weismann et al., 1978). The signs noted are generally
changes in the skin and hypogeusia.
There is also a rare congenital disease called acrodermatitis enteropathica
which generally occurs in children after weaning. As has been discussed
earlier, human milk seems to contain a factor or factors necessary for the
absorption of zinc. Signs in this disease may come from many organs, among
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them the skin, central nervous system, and the gastrointestinal tract. As in
other zinc deficiencies in children, there will be retarded growth and
hypogonadism. Large oral doses of zinc will correct the condition.
Prasad et al. (1978) have recently reported on experimental zinc deficiency
in humans. They studied four male volunteers who were hospital patients with
various diseases. They were given a diet containing about 3 mg Zn/day for
several weeks. In order to decrease the zinc intake it was necessary to give
subjects cereal protein instead of animal protein during the study. In all
subjects considerable weight losses occurred during the zinc depletion period.
The plasma zinc level decreased significantly in all subjects and in three of
four subjects there was a decrease in zinc excretion. Connective tissue was
analyzed in two patients; during the period of low zinc intake thymidinekinase
activity could not be detected, whereas after zinc supplementation it became '
close to the normal values. Also, plasma alkaline phosphatase activity
decreased along with a decrease in plasma lactic dehydrogenase activity during
the zinc depletion. In the connective tissue the RNA and DNA ratio showed
changes during the restriction period.
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EFFECTS
Zinc deficiency will not be covered in this section since it has been
discussed in a previous section; the emphasis will be on the effects caused by
excessive exposure to zinc via inhalation or via ingestion. The literature on
such adverse health effects is limited. One probable reason for the limited
information is that zinc has generally been accepted as a beneficial substance
and adverse effects have neither been expected nor looked for.
Inhalation of Excessive Amounts of Zinc
Effects on the lungs and systemic effects after inhalation of zinc compounds
have only been reported from occupational settings. A special case is the
lung damage seen after inhalation of zinc chloride from smoke bombs. As will
be discussed later, not only zinc chloride but also the hydrochloric acid
formed are of importance for the development of such effects. Health effects
observed in workers exposed to zinc and the results of some studies on animals
will be discussed. Information on the health hazards of zinc will also be
found in most textbooks on occupational hygiene and in the recent National
Institute on Occupational Safety and Health (NIOSH) criteria document on zinc
oxide (NIOSH, 1975).
Acute Effects
Most of our knowledge about metal fume fever and its relationship to
exposure to zinc oxide fumes comes from the beginning of the century when
there was extensive research on this acute type of poisoning (Drinker et a!.,
1927; Drinker et al., 1928; Sturgis, et al., 1927). Reviews on metal fume
fever, often also containing case reports, have been published in large numbers
(Anseline, 1972; Hegsted et al., 1945; Kehoe, 1948; Rohrs, 1957). Metal fume
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fever is described in all textbooks on occupational hygiene. It should also
be mentioned that metal fume fever has not only been associated with inhalation
of zinc oxide fumes, but with many other metal fumes which may produce similar
symptoms.
Metal fume fever only appears after exposure to freshly produced metal
fumes (McCord, I960; Rohrs, 1957) which can penetrate deep into the alveoli.
Zinc oxide dust or other metal dusts are not capable of producing the disease.
Typical for metal fume fever is symptom occurrence within a few hours after
exposure. The symptoms may persist for 1 to 2 days and are characterized by
influenza-like symptoms such as headache, fever, hyperpnea, sweating, and
%
muscle pains. Among the laboratory findings leukocytosis is the most prominent.
There have never been any fatalities from metal fume fever. Metal fume fever
generally occurs at the beginning of the working week when the worker has not
been exposed for a couple of days and further exposure will not cause new
symptoms, indicating a type of immunity. This disease has also been given the
name "Monday fever." It has been suggested by McCord (1960) that there is an
allergic basis for the mechanism of metal fume fever. Several theories have
been put forward, but there is no definite evidence for any of the proposed
different mechanisms for this reaction. One reasonable theory is that the
metal fume penetrates deep into the alveoli, and combines with proteins which
might act as sensitizing agents. There is a lack of data on the levels of
zinc oxide fumes in air that might cause the disease.• The only available
information is from experiments on human beings in 1927 by Sturgis et al.
(1927), who exposed 2 subjects to zinc oxide fumes at a level of 600 mg zinc/m .
It was calculated that the subjects inhaled 48 and 74 mg zinc, respectively.
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There was a report on acute emphysema in cattle reported to have been
exposed to zinc oxide fumes (Hilderman and Taylor, 1974). This episode occurred
in a barn where oxy-acetylene cutting and arc welding of galvanized pipe were
done during remodelling of the barn. Three heifers were severely affected.
Within a short time all three died. Autopsy showed severe changes in the
lungs with edema, emphysema, and hemorrhages. Zinc concentrations in liver,
kidney, and lungs were not above normal values in two animals examined. In
this case, a galvanized material was suspected but the extremely severe condi-
tion caused by the fumes showed either that cattle are extremely sensitive to
zinc oxide fumes or that other metals (such as cadmium) might have been respon-
sible.
Acute pulmonary damage and even death may occur after the inhalation of
zinc chloride which is the major component in smoke coming from so-called
"smoke bombs" which are often used in military exercises. Accidental inhala-
tion of such smoke in confined spaces may rapidly lead to severe disease, but
it should be pointed out that the toxic action may not only be due to the
zinc. The hydrochloric acid component in the smoke may contribute. Further
details on exposure to zinc chloride are provided by Mil liken et al. (1963).
The effects of inhalation of zinc chloride in smcke from smoke bombs have
also been described by Schmal (1974) who reported on 11 cases, of which two
had very severe reactions including edema of the lungs. However, no severe
sequelae were seen. In one case, however, it was almost 2 years before the
lung function was normalized.
Chronic Effects
Batchelor et al. (1925) made an extensive investigation of workers exposed
to zinc in a smelter in New Jersey. The authors pointed out that this smelter
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was «ell suited for studies on chronic effects of zinc since the aaounts of
lead-/ cad»iia», and arsenic in the ore were very low ccsg>ar*d with other types
«•
of zinc ores processed in other parts of the U.S. Of a total work fores of
1,520 aen, a nuaber of workers w*re selected fro*s different work areas for the
special studies. Twelve »en *ere selected from bag rccas where zinc oxide was
tetiKHed. Fro» a zinc oxide packing house five i»en were selected; four of thea
never wore respirators. Fro* another zinc oxide plant t*o sen were selected
arsd two asen were selected frc* a plant handling setallic 2lnc. Finally, three
workers fro* a Hlhopone packing house were selected, A m»ber of deterarina-
tio*>s of zinc concentrations in air were sade. Jn the bzg house an
concentration of 14 JKJ/SI was observed. In other workplaces ^e«an
were generally be'lcw 35 jag/ai. In the zinc dust plant a maxi#i*i concentration
of 130 ss/» was measured. The 24 subjects underwent a tmfcber of
•tefhich included .x-rays, physical exa»inat1ons, Interviews, blood pressure
E»asur*»ents, and *»easuresients of zinc in blood, urine and feces. Regarding
the laboratory findings, It »sy b* noted that 14 Of the 24 wen shov&d a slight
leijkocytosis; hewc^lobin was reported to range between 72 and 97 percent with
an average of 81 percent (100 percent is assi»ed to be ISO §/l). Twenty-four
ho«r zinc elimination via feces in controls was reported to vary froa about 4
to 20 sag, with an average of 9.32 ag, which is in good agreement with present
daily values. In the exposed subjects, 24-hour excretion of zinc via feces
averaged 46,8 wg which indicates an exposure via the $a$lroiniesUr»al tract or
esassive excretion into the Intestine. The conclusion of the euthors was that
the workmen could be exposed to zinc compounds in a spelter for ttecades without
any syfcptods or chronic disease.
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Chmielewski et al. (1974a, 19745) reported on the examination of 60
shipyard workers who were exposed to zinc oxide in different operations. As a
control group, 10 healthy subjects who did not work in the shipyard and 10
shipyard workers not exposed to zinc oxide were used. Interviews showed that
most of the workmen had experienced metal fume fever several times. Exposure
levels varied between 1.7 and 18 mg/m of zinc oxide, but a maximum value of
58 mg/m was found during welding on one occasion. Laboratory investigations
showed a tendency to leukocytes is, but other laboratory investigations gave no
conclusive results. Some enzyme activities were determined before work and
after work. Also in control groups changes were noted during the workday. It
is obvious that in this study many of the workers must have been exposed to
substances other than zinc oxide. For example, levels of nitrogen oxides were
high in some workshops, the highest being 120 mg/m , with mean concentrations
varying from 2-20 mg/m . Also, the total dust was high in some workplaces
with levels around 100 mg/m in several places.
Pistorius (1976) studied the effect of zinc oxide on rat lungs in an
34-day study. The rats were divided into groups so that they were exposed for
1, 4, or 8 hours a day to a concentration of 15 mg/m of zinc oxide, at
particle size less than 1 micron. A number of lung function tests were performed
after 2, 4, and 7 weeks and at the end of the experiment. For most parameters
there was no difference between controls and exposed animals, but in specific
conductance and difference volume there was a significant decrease after two
weeks. Further exposure resulted in all three exposure groups getting closer
to the control values. Paradoxically the animals with the 1-hour exposure per
day had the lowest values and the 8-hour exposure animals the highest values.
The results were interpreted as a bronchial constriction. The author also
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explained the improvement in lung function with extension of exposure as a
result of an increased elimination from the lung due to an increase in
macrophages.
Pistorius et al. (1976) exposed male and female rats for 1, 14, 28, and
56 days to zinc oxide dust at a concentration of 15 mg/m 4 hours a day, 5
days a week. Animals were killed 24 hours after the last exposure and the
zinc content of lungs, liver, kidney, tibia, and femur was measured. After a
single exposure the total zinc content of the lung in males and females was
about 46 and 49 ug, respectively. In the male rats similar amounts were found
after the longest exposure, whereas in female rats the zinc content after
repeated exposure was lower in all groups than at the first exposure. Zinc
concentrations were highest in the lung after 1 and 14 days of exposure. In
liver and kidney there were no major changes during the experiment, but it .
should be pointed out that a non-exposed control group was not followed. No
differences could be noted in bone. Histclogical examination of the lungs
showed infiltration of leukocytes and inflammatory changes; after 28 and 55
days of exposure, an increase in macrophages could be shown. These studies
indicate that there is a rapid elimination of inhaled zinc from the lungs, and
that the absorbed zinc is rapidly eliminated from the body through the hcmeostatic
mechanism.
Zinc stearate is a compound other than zinc oxide which is often encountered
in the plastic industry and is suspected of causing lung disease. "Vctila and
Noro (1957) reported on a fatal case involving a worker employed for 29 years
in a rubber plant. The autopsy showed the cause of death was a diffuse fibrosis
of the lungs with histochemical examination of the lungs showing increased
deposits of zinc. However, no quantitative determinations of the zinc content
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of the lung were made. The role of zinc stearate as a cause of chronic lung
disease has since then been discussed by Harding (1958) and by Weber et al.
(1976). Harding gave rats intratracheal instillations of 50 mg of zinc stearate
which caused about half of the animals' deaths. In the survivors (living up
to 259 days after instillation of the compound) fibrosis could not be detected.
Harding also found that the zinc stearate had disappeared from the lungs
within 14 days. Weber et al. described autopsy findings in a man who was
employed for the last 8 years of his life in a plastics industry and who was
exposed to zinc stearate. Fibrosis was found in the lungs with the zinc
content of 62 mg/kg of lungs on a dry weight basis (Weber et al., 1976). The
same authors found that thirty persons from the same area had concentrations
between 3.3 to 69.3 mg/kg of zinc in lungs. The man had also had other occupa-
tions, but his exposure to silica quartz in another occupation could not
explain the fibrosis. The authors concluded that zinc stearate could not have
caused the fibrosis, one reason being that the zinc content of lungs was
within the normal limits. However, as pointed out by Harding (1958), zinc
stearate is relatively rapidly cleared from the lungs, so a normal content of
zinc in the lungs does not exclude the possibility that zinc stearate might
have contributed to this disease.
Tarasenko et al. (1976) exposed rats to a single intratracheal administra-
tion, of zinc stearate in a dose of 50 mg, and found, like Harding, that 50
percent of the animals died after that dose. In animals that survived,
pathological changes were seen in the lungs 2 months later. Still later a
picture of chronic alveolar emphysema and bronchitis was seen. According to
the report, doses of 10 mg and 5 mg were also given but the results were not
presented.
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Ingestion of Excessive Amounts of Zinc
The hazards of keeping food or liquids in galvanized containers are
illustrated by a report by Brown et al. (1964) on two outbreaks of food poison-
ing assumed to be caused by zinc in California in 1961. In one instance the
food poisoning was caused by keeping chicken with tomato sauce and spinach in
galvanized tubs. In the other instance a punch drink had been kept in galvanized
containers. Zinc content of the food was estimated by repeating the preparation
of the meal. After 24 hours of storage the mixture of chicken and tomato
sauce contained close to 1000 ppm of zinc. The other poisoning was caused by
punch containing 2200 mg/1 of zinc. It was calculated that the doses of zinc
would be 325-650 mg. In the first instance symptoms occurred 3 to 10 hours
after ingestion. Severe diarrhea with abdominal cramping was the main symptom.
Vomiting was not common, whereas after drinking the punch the first symptoms
were nausea and vomiting which occurred within 20 minutes after ingestion.
Diarrhea was also noted in the latter instance. No after effects were observed.
It may be noted that in the first instance zinc was ingested with food and the
delay in symptoms may have been caused by a simultaneous occurrence of vegetables
and meat, whereas in the second instance a more acute effect occurred, since
only drinks were served. Cadmium was not determined in either of these studies.
Galvanized materials often contain relatively large amounts of cadmium.
Murphy (1970) reported on a 16-year-old boy who tried to promote wound
healing by ingesting a large amount of zinc, 12 g of elemental zinc mixed with
peanut butter. The zinc was ingested over a two-day period in doses of 4 and
8 g per day. He became lethargic, had difficulties in staying awake, experi-
enced a slight staggering of gait, and noted problems in writing legibly.
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Nine days after the irigestion of the first dose of zinc, he was admitted to a
hospital. Neurological and laboratory examinations did not reveal anything
abnormal, except a slight rise in serum-amylase and lipase. Zinc in whole
blood was slightly elevated whereas serum zinc was within the normal range.
There was no increase in the zinc level of cerebrospinal fluid. He was treated
with dimercaprol and there was a rapid decrease of whole blood levels of zinc
to subnormal values. This treatment removed his lethargy. The author's
conclusion was that this case showed symptoms indicating an influence of zinc
on the pancreas and the cerebellum, but that these effects were easily reversible
and no sequelae were seen.
Chunn (1973) studied a group of hospitalized children with anemia. There
were 3 children who had levels of zinc in urine above 1 mg/1, but it was not
stated by which method the zinc concentrations were determined. The author
attributed the common factor for anemia and high zinc excretion in these
children to the fact that all 3 children played with metal cars made from an
alloy containing zinc. The author also suggested that the zinc could have
been ingested by the children imbibing water when they were in the bath tub
playing with toys. In a test it was found that placing a toy car in warm
water resulted in zinc levels of 1.8 mg/1 in water. However, it does not seem
likely that significant amounts of zinc could have been taken up by exposure
via that route.
Greaves and Skillen (1970) reported on 18 patients who were given daily
doses of zinc sulfate corresponding to 150 mg zinc per day for between 16 and
26 weeks as treatment for venous leg ulcerations. Before treatment the plasma
zinc levels varied between 0.68 and 1.2 mg/1, and after completion of treatment
the levels were between 0.84 and 1.92 ;ng/l. During the study a number of
laboratory investigations were undertaken on several occasions, but copper
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levels were not determined. No ill effects could be noted from the treatment
with zinc and there were no changes in hemoglobin or serum enzymes. •
In animal experiments it has been shown that zinc may interfere with
copper metabolism and that when the intake of copper is low, excessive zinc
may induce a copper deficiency and anemia (NRC Chapter 9 pp. 256-257; Underwood,
1977; Hamilton et a!., 1979; Murthy and Petering, 1976). The animal data
indicate that prolonged excessive intakes of zinc may constitute a hazard in
patients treated with oral zinc supplements.
During the last years there have been some reports on copper deficiency
in human beings after treatment with zinc. Prasad et al. (1978) and Porter et
al. (1977) have reported hypocupremia after a long-term treatment with zinc
sulfata in doses of 660 mg/day, i.e., 150 mg zinc per day. In both cases it
was easy to correct the hypocupremia. No chronic effects of the treatment
were seen, but Porter et al. pointed out that the daily doses of 650 mg zinc
sulfate may be toe high for long treatment. It should be noted that in both
studies patients with severe diseases were treated (sickle-cell anemia and
coeliac disease).
Zinc poisoning has occurred in cattle. In the outbreak described by
Allen (1968), the zinc poisoning of cattle was caused by dairy nuts which had
been contaminated by error with zinc so that the zinc concentration was- 20
g/kg. ' It was stated that the cows had an intaKe of about 7 kg/day of these
dairy nuts, which would correspond tc an intake of 140 g of zinc per cow per . .
day. Exposure was only for a couple of days but it resulted in severe enteritis.
On one farm 7 out of 40 cows were so severely affected that they died or had
to be slaughtered. The post-mortem findings showed severe pulmonary emphysema
with changes in both myocardium, kidneys, and liver. There were also some
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indications that copper levels were lower than normal. Zinc concentrations in
li'ver were extremely high, measured on a dry matter basis, 1,430 and 2,040
mg/kg in two analyzed livers.
Lead poisoning has occurred in horses living near lead-zinc smelters. In
foals, some symptoms, lameness and joint afflictions especially, have been
described and related to exposure to zinc in areas near smelters. Willoughby
et al. (1972) gave foals a diet containing 5,400 mg/kg of zinc and another
group received, in addition, lead in the amount of 800 mg/kg. The groups were
compared with a control group and a group given only the excessive amount of
lead. It should be mentioned that the groups consisted of only two or three
animals each. In three animals given excessive amounts of zinc, bone changes,
especially in the epiphyseal areas of the long bones, were noted as a first
sign; later the animals had difficulties in standing and walking. In animals
given lead and zinc the symptoms associated with exposure to zinc dominated.
There were less effects from the exposure to lead and zinc than in animals
given only lead. It should be noted that in this experiment exposure to zinc
was extremely high but taken together with the above-mentioned reports on
actual findings in animals living near smelters it is obvious that exposure to
zinc in high amounts may constitute a hazard to horses.
Aughey et al. (1977) gave zinc (as the sulfate) to mice for up to 14
months in drinking water at a concentration of 500 mg/1. The concentrations
of zinc in feed for controls and exposed animals were not stated. That zinc
is readily absorbed was seen by a rapid rise in plasma concentrations of zinc
during the first days of exposure. During 6 months no difference between
controls and exposed animals could be shown regarding zinc concentrations in
liver, spleen, and skin nor was there any difference between the sexes.
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Histological examination showed that several endocrine glands were affected by
the administration of zinc. Hypertrophy was found in the adrenal cortex; in
the pancreatic islets and in the pituitary gland changes consistent with
hyperactivity were noted.
Kang et al. (1977) gave rats, by pair-feeding, diets containing 1.3, 55,
and 550 mg zinc/kg of feed for 4 weeks. The animals were killed after that
time and tissue concentrations of zinc and a number of other metals were
determined. The low zinc diet gave typical signs of zinc deficiency, whereas
there was no difference in weight gains and food efficiency ratios in the two
groups given higher amounts of zinc; this fact, according to the authors,
suggested that the highest level (550 mg/kg) was not toxic. Liver and kidney
concentrations of zinc were slightly higher in the group given the largest
amount of zinc, but no difference was noted in the heart. Iron concentrations
in liver were inversely related to the intake of zinc,-whereas no difference
in copper concentrations or magnesium concentrations in the liver could be
seen between the two highest zinc levels. In the kidney there was also a
tendency for decreasing iron concentrations with increasing zinc intakes as
well as for copper, but there was practically no difference between the two
highest dose levels, nor was there a difference in magnesium.
In pigs given zinc in the diet in concentrations ranging from 500 to 8000
mg/kg, Brink et al. (1959) found that signs of toxicity in the form of weight
gain and feed intake were seen at levels above 1000 ppm. In pigs, given from
2000 ppm and higher, deaths occurred as soon as 2 weeks after exposure and
severe gastrointestinal changes were seen with hemorrhages. There were also
signs of brain damage due to hemorrhages. Changes in the joints were also
seen, mainly in the form of swollen joints. In liver samples from these pigs
levels of zinc above 1000 mg/kg wet weight were found.
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Effects Caused by Exposure Via Other Routes
In a woman given total parenteral nutrition after an operation, acute
zinc poisoning occurred due to an error in prescription. During a period of
60 hours she received 7.4 g of zinc sulfate. She became acutely ill with
pulmonary edema, jaundice, and oliguria, among other symptoms. The serum zinc
concentration was 42 mg/1. In spite of treatment she remained oliguric and
hemodialysis did not improve renal function. She died after 47 days of illness
(Brocks et al., 1977).
It has been reported that zinc and copper could be introduced in excessive
amounts into the blood during hemodialysis (Blomfield et al., 1969). Petrie
and Row (1977) described nine cases of anemia in dialysis patients due to the
release of zinc from a galvanized iron tubing in the dialysis system. Copper
levels were not measured in these cases but there was a rise in hemoglobin
concentrations after removal of the source of the zinc.
Acute effects of hemodialysis have been described by Gallery at al.
(1972). A woman on home dialysis used water stored in a galvanized tank and
two hours after the first dialysis at home she had symptoms including nausea,
vomiting and fever. Similar severe symptoms were experienced by her at two
subsequent dialyses, but subsided between dialyses. Dialyses at the hospital
were then done without any symptoms, but she had symptoms again when she
started dialysis at home. At new admission to the hospital she was found to
be severely anemic. It was then found that the zinc concentration in the tank
water was 6.25 mg/1. The patient's zinc concentration in red cells was 35
mg/1 and after 6 weeks dialysis in the hospital it was reduced to 12 mg/1.
During the same period plasma levels decreased from 7 mg to 1.58 mg/1. Slood
copper was not decreased.
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Carcinogenesis, Mutagenesis,'and Teratogenesis
The relationship between zinc and cancer has been reviewed earlier by the
NRC (1978) (Chapter 7 pp. 208-209, Chapter 9 pp. 231-234 and Chapter 10 pp.
258-261) and by Sunderman (1971). It was concluded that during certain experi-
mental conditions, injections of zinc- salt into the testes could induce testicular
tumors. There was no evidence that zinc given via the oral route or parenterally
could cause tumors. However, zinc is of interest with regard to cancer since
zinc seems to be indirectly involved by being of importance for the growth of
tumors. As discussed earlier zinc is necessary for DNA and RNA synthesis. *It
has been shown that in zinc-deficient rats tumor growth was reduced (Petering
et al.-, 1967; DeWys et a!., 1970). These earlier findings have recently been
confirmed in other studies.
The effect of different levels of dietary zinc on the development of
chemically-induced oral cancer in rats has recently been studied by Wallenius
et al. (1978) and Mathur et al. (1978). In the study by Wallenius et al.
(1978), three groups of female rats were fed diets for 3 weeks which contained
15 mg/kg, 50 mg/kg, and 200 mg/kg of zinc, respectively. The palatal mucosa
was then painted with the carcinogen 4-nitro-quinoline-n-oxide three times a
week. The animals were killed after cancer could be observed macroscppically
in the oral cavity. It was found that in animals given the diet with the
highest level of zinc, the macroscopical signs of cancer appeared earlier, as
compared with animals given lower amounts of zinc. In the study by Mathur et
al. (1978),a similar design was used but the levels of zinc in that experiment
were 5.9, 50, and 250 mg zinc/kg diet. Three, 9, 13, and 23 weeks after the
beginning of exposure the groups of animals were sacrificed and blood, liver,
and palatal mucosa were sampled. Control animals were killed at the same
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time. The carcinogen had been applied 3 times a week. It was found that
after 3 weeks the animals with the lowest zinc intake, which was regarded as
producing zinc deficiency, showed more advanced histological changes than
animals given 50 or 260 mg/kg diet of zinc. After 20 weeks' application of
the carcinogen, there was no difference in the development of tumor between
zinc deficient and zinc supplemented groups. It may be noted that both in the
low and high level zinc groups, carcinoma i_n situ and fully developed carcinomas
were found, whereas in the group given 50 mg zinc/kg diet, regarded as an
adequate level, even after 20 weeks only moderate dysplasia was seen. The
groups studied were quite small and thus did not allow any detailed statistical
analysis. The results were interpreted to mean that zinc deficiency made the
animals more susceptible to the induction of cancer but at the same time
caused a slower growth rate of tumors and that a high zinc intake initially
gave some protection against the development of tumors but that later excessive
zinc intake promoted tumor growth.
Another example of the importance of zinc deficiency for the development
of cancer is the study by Fong et al. (1978). One group of rats was fad a
diet containing 60 mg/kg of zinc and one group of rats was fed a diet contain-
ing 7 mg/kg of zinc. After 12 weeks on these diets the carcinogen methylbenzyl-
nitrosamine was administered by intragastric intubations twice weekly in doses
of 2 mg/kg body weight for 12 weeks. In another experiment the design was
similar but the carcinogen was administered after 4 weeks with the length of
exposure of 9 weeks. Some animals were killed at the end of exposure and some
animals were killed 5 weeks later. In a third experiment the carcinogen was
given for 4 weeks and animals were sacrificed 63 days after the start of
exposure. Finally, there was one experiment where the exposure was only for 2
C-39
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weeks for a total of four doses of the carcinogen. As expected, zinc levels
in the esophagus were lower in zinc deficient animals than in controls, but
they were also lower in animals on an adequate intake of zinc, but which were
given the carcinogen. A general finding was also that in zinc-deficient
animals more carcinomas of the esophagus were found than in animals fed an
adequate intake of zinc. It was also noted that in the groups given the
lowest doses of the carcinogen, the difference between groups was most
significant; a total of eight doses gave figures of 79 and 29 percent,
respectively, for tumor incidence and at a total of four doses the correspond-
ing figures were 21 percent and zero (0) percent. '
Regarding human beings, there is no definite evidence that zinc deficiency
in itself has any etiological role in human cancer. However, many studies
have been performed on the levels of zinc in both malignant and non-malignant
tissues in human beings. The zinc concentrations have been found to be both
lew and high and no definite pattern has occurred (NRC (1978) Chapter 9 pp.
231-234 and Chapter 10 pp. 259-251). As an example it has been shown that in
cancer of the esophagus in human beings zinc concentrations were lower than
normal which is in accordance with the above mentioned experiments on rats
(Lin et a!., 1977). However, there is one organ in the human being where
there seems to be a more consistent pattern, the prostate gland. It has been
discussed earlier that zinc concentrations in the prostate normally are very
high; there has been a consistent finding that in cancer of the prostate there
is a decrease in zinc in the carcinomatus tissue of the prostate.
In the study by Habib et al. (1976), zinc concentrations in the neoplastic
tissue were less than half of the concentrations in normal tissue or in hyper-
trophic prostates. These authors also reported that the cadmium levels were
C-40
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higher in the carcinomatous tissues than in the normal or hypertrophic tissue.
High industrial exposure to cadmium has been implicated as a possible cause of
prostatic cancer and since there are interactions between cadmium and zinc,
this might have some bearing on the problem of the relationship between zinc
and cancer of the prostate. Habib (1978) has reviewed the role of zinc in the
normal and pathological prostate.
Regarding hyperplastic prostatic tissue, it may be noted that most reports
have stated that there are the same concentrations of zinc in the hyperplastic
tissues as in normal tissue. There is one exception; the study by Gyorkey et
al. (1967) found considerable increases in zinc levels in hyperplastic tissue—
more than three times the normal.
The mutagenic effects of zinc have been discussed by the National Research
Council (Chapter 10 p. 261) which could not find literature that suggested
that zinc is mutagenic in animals and human beings nor have any new data
appeared on this subject. The same conclusions are made with regard to
teratogenesis. The greatest risk is related to zinc deficiency which might
cause malformations. However, it is reasonable to assume that indirectly zinc
might have an effect since long-term supplements with large amounts of zinc
will cause disturbances in copper metabolism.
In a study by Cox et al. (1969), it was shown that if rats were fed a
diet containing 4,000 ppm of zinc during gestation, copper levels were reduced
in the fetal body and liver whereas zinc concentrations increased. Ketchescn
et al. (1969) fed rats diets containing up to 5,000 mg of zinc/kg during
gestation. Even at that level malformations were not observed, but there was
a reduction in the copper concentrations of the fatal liver.
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A brief statement in a report by Kumar (1976) states that in a small
group of women supplements of zinc administered during the third trimester of
pregnancy in a dose of 100 mg of zinc sulfate per day (23 mg zinc per day)
caused premature births and one still-birth in four consecutive subjects.
Kumar then made studies in rats and gave them a daily supplement of 100 ppm
zinc orally (it is not quite clear hew the dose was calculated, but it is
stated in the report "received additionally 150 ppm zinc as a 2% zinc sulphate
solution"). The concentration of copper and other nutrients in the diet was
not stated. In the zinc-supplemented animals there was a significant increase
in the number of resorptions of the inplantations. Supplementation for pregnant
women has been recommended, but due to the known interaction between zinc and
copper, excessive zinc intakes during prolonged times could have an adverse
effect on the fetus. It is well documented in animal experiments that zinc
deficiency during pregnancy might have an adverse effect on the fetus (NRC
Chapter 7 pp. 179-180).
C-42
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INTERACTIONS OF ZINC WITH OTHER METALS
As has already been discussed in the section concerning effects of excessive
intakes of zinc, interactions between zinc and other metals may occur. It was
demonstrated that excessive intakes of zinc could influence the metabolism of
iron and copper, but it is also possible that excessive intakes of other
metals may also have an influence on the metabolism of zinc. Such metal-metal
interactions have recently been discussed at an international meeting and
reported (Nordberg, 1978). Interactions between zinc and other metals have
also been reviewed by Underwood (1977) and NRC (Chapter 7 pp. 186-187).
Cadmium
Interactions between cadmium and zinc we-.'e extensively discussed in the.
NRC report (Chapter 10 pp. 251-268) and the literature up to 1974 was reviewed
and discussed. It was concluded that exposure to cadmium would cause changes
in the distribution of zinc with increases in liver and kidney where cadmium
also, accumulates. In animals on marginal zinc intakes there could be a zinc.
deficiency in certain organs parallel with the increase in liver and kidney.
It has also been shown that in both human beings and horses the increase in
renal concentrations of zinc is parallel to the increases in cadmium and that
this increase is nearly equimolar up to cadmium concentrations of about 60
mg/kg wet weight. These earlier findings have recently been confirmed in new
studies both in human beings and in horses (Elinder and Piscator, 1977; Elinder
and Piscator, 1978). The increase in renal zinc is also related to the occurrence
of cadmium in metallothionein. It has recently been shown that whereas at low
levels of cadmium in the kidney there are about equimolar amounts of zinc and
cadmium in metallothionein, with increasing cadmium concentrations the ratio
C-43
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of cadmium to zinc will increase. It was also shown that at a level of about
200 mg/kg wet weight of cadmium the amount of zinc in metal!othionein would be
close to zero (Nordberg et al., In Press 1979) and that corresponds to the
critical level which has been estimated for renal cadmium related to the
occurrence of renal tubular dysfunction (Friberg et al., 1974).
X
Although a large number of animal studies have been performed, there
might be some difficulties in drawing conclusions with regard to the human
situation. A review of the literature by Elinder and Piscator (1978) showed
that there are clear differences between some large mammals (e.g., man, horse)
compared to small laboratory animals. In the rat especially (the most commonly
used laboratory animal), exposure to cadmium will result mainly in an increase
in hepatic zinc, whereas the increase in renal zinc is rather small. On the
other hand, exposure to cadmium causes increases in renal copper concentrations.
Such differences make it reasonable to conclude that one must be cautious when
drawing conclusions from experiments done with rats. The differences between
species are illustrated in Figure C-l. Zinc deficiency a-lone is known to
cause effects on the fetus. If animals are exposed to cadmium during the
gestation period, this may also influence the mineral distribution in'the
fetus. Pond and Walker (1975) showed that both low zinc concentrations and
copper concentrations and decreases in birth weight were found in rat pups
that had been given cadmium orally. Since cadmium does not pass the placenta!
barrier to any significant extent, this is thought to be due to retention of
zinc in the dam parallelling the accumulation of cadmium as mentioned above.
Data by Choudhury et al. (1978) indicate that in the rat fetus a decrease of
copper and iron occurs before the zinc levels are affected.
C-44
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HUMAN
LAMB
PIG
HORSE
BOVINE
GOAT
RAT
RABBIT
GUINEA PIG
MOUSE
CHICKEN
Cd LEVEL,
Figure C-1. Increase of zinc as a function of increasing cadmium
concentration in kidney of 11 different species. (Courtesy Elinder
and Piscator, 1978.)
C-45
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Lai (1976) found that oral exposure to cadmium could cause testicular and
pulmonary lesions in rats en a marginal intake of zinc, 5 mg/kg feed, whereas
such lesions were not seen when the diet contained 40 mg zinc/kg. The exposure
to cadmium in that experiment was 17.2 mg/1 of drinking water. Zinc concentra-
tions in the testes of zinc-deficient animals were 104 mg/kg, compared to 143
mg/kg in the animals at the higher level of exposure.
Copper
It has been mentioned earlier that excessive intakes of zinc may cause
copper deficiencies in human beings and result in anemia, which can be easily
corrected by decreasing the intake of zinc and giving copper supplementation.
It has also been suggested by Klevay (1975) and Klevay and Forbush (1976) that
the ratio between copper and zinc in the American diet contributes to coronary
heart disease. The main reason for this may be that the copper content of the
typical American diet is less than the requirement. These theories have not
been substantiated, even though Klevay (1973) found that in rats hypercholes-
terolemia occurred with an increasing zinc-copper ratio in the diet. It has
since been shown that it is the copper status tnat is the main factor with
regard to cholesterol' levels (Petering et al., 1977; Murthy and Petering,
1976; Allen and Klevay, 1978)
Evans et al. (1974) found that in zinc deficient rats excessive amounts
of copper did not influence the uptake of Zn from the gut, but in zinc-
supplemented rats excess copper had an influence on the uptake of Zn. The
authors tried to explain the findings by suggesting that in the zinc deficient
rats a larger number of zinc binding sites on plasma albumin would be available
and that at such sites there would be no competition with copper.
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Kinamon and Bunce (1965) fed groups of rats a basic diet containing 18
mg/kg of copper, 70 mg/kg of zinc and less than 1 mg/kg of molybdenum. To
these diets zinc, copper, or molybdenum and combinations of these metals were
added in amounts of 100 mg/kg of copper, 1,800 mg/kg of molybdenum, and 5,000
mg per kg of zinc. The length of the experiment was 7 weeks. At the and of
the experiment all animals were given an injection of radioactive zinc. After
4 days the animals were killed. As in other studies, it was found that an
increase in dietary zinc resulted in a decreased retention of the isotope, but
that even the very high level of copper or molybdenum did not influence the
retention of the isotope. These data indicate that the influence of zinc on
copper metabolism is probably of greater importance than the opposite, i.e.,
influence of copper on zinc metabolism.
Calcium
The influence of calcium on absorption of zinc from the gut was discussed
by NRC (1978) (Chapter 7 pp. 184-185). It was concluded that calcium levels
in the diet do not influence zinc absorption except for some indications that
calcium could have an influence when zinc intake is marginal. Also Underwood
(1977) has reviewed the relationships between zinc and calcium. The study by
Hurley and Tao (1972) shows an interesting example of interaction between :inc
and calcium. Beginning on the first day of gestation, female rats were given
either a zinc-deficient diet containing 0.4 mg zinc per kg or a zinc-deficient
and calcium-deficient diet which contained the same amount of zinc but 15
mg/kg feed of calcium. The animals were killed on the 21st day of gestation,
and the fetuses were removed and examined. The results showed that in females
deficient in both calcium and zinc the resorption rate in the uterus was lower
C-47
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and there was a larger number of live births per litter than among the rats
given only the zinc-deficient diet. Eighty-three percent of the fetuses from
females on the zinc-deficient diet showed malformations whereas the corresponding
figure for zinc-deficient and calcium-deficient group was 57 percent. Analysis
of maternal bone showed that there was a reduction in both ash weight and
total calcium content of the femur in the females given the zinc-deficient and
calcium-deficient diet. This was interpreted as calcium being withdrawn from
the bone during pregnancy to provide calcium to the fetus. There was also
lower zinc content in the bones of rats on the calcium-deficient diet. This
suggested that zinc was released from bone during the release of calcium.
This zinc could then be available and transported to the fetus, whereas in
animals on a zinc-deficient diet and high calcium intake there would be no
release of zinc from bone and thus the large amount of zinc stored in bone
would net be available to the fetus. This study shows how two essential
metals can interact with each other.
Iron
As mentioned earlier, high intake of zinc may affect iron metabolism, but
much less is known about the effects of iron on zinc. Sherman et al. (1977)
gave pregnant rats diets containing 5, 29, and 307 mg/kg of iron. Eighteen
days after parturition both the dams and pups were killed and examined. It
was found that the zinc to copper ratio in spleen increased in dams but tended
to decrease in the pups as a result of iron restriction. In the pups the zinc
to copper ratio was considerably lower in the liver of iron-deficient animals
but in the dams no differences were seen between groups with high and low iron
intake. In the iron-deficient pups increased levels of serum lipids were
associated with decreased ratio of zinc to copper in the tissues.
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Hamilton et al. (1978) studied the intestinal absorption of zinc in
iron-deficient mice and found that zinc uptake from the gut was inhibited by
adding iron to the duodenal loop system used. It was concluded that there
were some common mucosal binding sites for both iron and zinc.
Lead
It was mentioned earlier that in horses there can be simultaneous
exposure to lead and zinc and there seem to be some interactions; there was a
lower uptake of lead in animals with high intake of zinc. Cerklewski and
Forbes (1976) studied the influence of three dietary levels of zinc (8, 35,
and 200 mg/kg) on rats given 50 and 200 mg lead per kg feed. They found that
with higher dietary zinc concentrations the symptoms of lead toxicity decreased.
The lead concentrations in tissues were lower in animals with high zinc intake,
but also the hematological changes were less. It was concluded that the main
interaction was in the gut.
Lead will also have an influence on the zinc concentrations in tissues as
was shown by El-Gazzar et al. (1977) in rats given drink-ing water containing 5
and 50 mg/1 of zinc and 100 mg/1 of lead. Lead exposure decreased the plasma
zinc in the low level zinc group but increased erythrocyte zinc. Further
exposure caused reduced plasma zinc levels also in the high zinc level group.
There were also reductions in the zinc levels in liver and tibia of both
groups. There was no change in the brain concentration of zinc.
An effect which has attracted great interest the last years is the effect
of zinc on the activity of ALA dehydratase, a zinc dependent enzyme, in blood.
In a number of studies both ij} vivo and j_n vitro it has been shown that zinc
is antagonistic to lead regarding the ALA dehydratase activity, and that zinc
decreases the excretion of ALA seen in lead-intoxicated rats (Abdulla et al.,
C-49
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1976; Border et al. , .976; Finelli et al., 1975; Thawley et al., 1978; Thomasino
et al., 1977).
Thawley et al. (1977) gave rats a basic diet containing 30 mg/kg of zinc
and 7 mg/kg of lead and then groups were given additions of 5,000 mg/kg of
lead or 6,300 mg/kg of zinc and combinations thereof. These diets were also
combined with two levels of calcium in the diet, 0.9 and 0.1 percent respectively.
The findings indicate that the increase in ALA excretion caused by lead was
reduced by the additional exposure to the high level of zinc. The exposure to
zinc'caused larger reductions in serum iron than lead exposure. The most
severe anemia was seen in animals on a high lead and a high zinc intake together.
Interactions Between Zin.c and Drugs
In the previous chapters it has been mentioned several times that contra-
ceptive pills have an influence on zinc metabolism. The influence of oral
contraceptives on the excretion of zinc in women on a low intake of zinc,
copper, and iron was studied by Hess et al. (1977). Urinary zinc excretion
decreased in women both on contraceptives and not on contraceptives. The
greatest decrease was in the contraceptive group with a decrease of^3 percent
and a 62 percent decrease for those not on contraceptives.
The usual intake of zinc in these women before the study started was
estimated to be about 10 mg/day. During the study the intake averaged only
0.17 mg/day. At the beginning of the study, before the zinc intake'was lowered,
the average excretion of zinc in urine was 0.36 and 0.4 mg, respectively, for
the group on contraceptives and for the control group. These data indicate
that whereas contraceptives will have relatively little influence on zinc
metabolism during normal zinc intake, they may have a more profound influence
when the zinc intake is low. In this study the zinc intake was extremely low.
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Many other drugs, especially drugs with chelating properties, may
influence zinc metabolism. Thiazids and penicillamine can increase the
excretion of zinc. Substances in food such as phytate can influence the
absorption. Also, alcohol will have an influence on zinc metabolism
especially if a state of chronic alcoholism has been reached with cirrhotic
changes in the liver. Such cases often have low serum levels of zinc and an
increased excretion.
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CRITERION FORMULATION
Existing Guidelines and Standards
The National Institute of Occupational Safety and Health
(NIOSH, 1975) has recently reviewed the occupational hazards
of exposure to zinc oxide and no changes were suggested
regarding the existing standard for zinc oxide of 5 mg/m .
The American Conference of Government Industrial Hygienists
(ACGTH, 1976) has an adopted threshold limit value (TLV)
for zinc oxide of 5 mg/m and the Occupational Safety and
Health Administration (OSHA, 1978) has a workplace standard
for zinc oxide of 5 mg/m , eight-hour time-weighted average.
The TLV value has also been adopted in other countries. :
For zinc chloride a limit of 1 mg/m has been adopted by
ACGIK and OSHA also adopted a standard of 1 mg/m for zi'nc
chloride.
The present standard for drinking water, 5 mg/1, is
based on organoleptic effects, i.e.., some people will recog-
o
nize the bitter taste caused by zinc present at such levels.
The World Health Organization (WHO) has also proposed that
the level should be 5 mg/1; however, the USSR has established
a limit for zinc at i mg/1 for other than health reasons
(National Academy of Sciences (NAS), 1977).
There is no acceptable daily intake for zinc in food.
As mentioned earlier zinc is an essential nutrient and there
i
has been no reason to restrict the zinc levels in food. .
In 1974, the National Academy of Sciences recommended
that adults should have an intake of 15 mg of zinc per day,
that pregnant women should have an intake of 20 mg/day and
r-52
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that pre-adolescent children should have 10 mg/day of zinc
(National Academy of Sciences, 1974).
Current Levels of Exposure
It has been well established in several studies that
the present intake of zinc via food for the adult U.S. popula-
tion is from 10 to 20 mg. For the majority of the population
the intake of zinc via drinking water will be only a few
percent of the intake via food, but for some individuals
the zinc concentration in tap wat-er may cause an additional
daily intake of 2 to 10 mg of zinc. The average exposure
to zinc via ambient air will, even in the vicinity of zinc
emitting industries, be in the order of only a few tenths
of a milligram. Smoking will contribute even less.
Special Groups at Risk
Since zinc may interfere with copper and other minerals,
excessive intakes of zinc by people with a tendency to copper
deficiency might cause reversible health effects. Patients
treated for months or years with large oral doses of zinc
salts, about ten times the intake via food, for curing of
r
various diseases caused by zinc deficiency or to promote
wound healing may constitute a group at special risk. Infants
with copper deficiency or low intakes of copper may constitute
another risk group. Occupational exposure to zinc oxide
fumes may cause acute reversible reactions which may put
persons subjected-to such exposure at special risk.
Basis and Derivation of Criterion
Zinc is an essential element and is not a carcinogenic
agent. Studies on experimental animals and on human beings
C-53
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given zinc for therapeutic purposes together with observations
of occupationally exposed persons show that large doses
of zinc can be tolerated for long periods, provided that
the copper status is normal.
Daily ingesticn of about 150 mg of zinc as the sulphate
has not resulted in adverse effects in most patients even
after several months of treatment. A reduction of copper
levels has been reported in patients with diseases such
as sickle cell anemia and coeliac disease. A reduction'
of the dose of zinc and copper supplementation corrected
the copper deficiency.
Laboratory animals have been shown to tolerate zinc
concentration in the range of 100 to 300 rug/kg food and
even higher for long periods when the intake of copper has
been adequate. Copper deficient animals have been shown
to be more susceptible. In many animal experiments zinc
concentration in the diet of 1000 'to 2000 mg/kg have been
reported to be without effect. These concentrations should
be compared to the average zinc content of human food, which
is about 10 mg/kg.
The water•quality criterion for zinc in water based
on available data on effects of ingested zinc would be about
10 mg/1 for the adult U.S. population. Assuming a water
intake of 2 liters per day, this exposure would not cause
more than an additional intake of 20 mg which can be well
tolerated. This concentration is above the present standard
for drinking water which is 5 mg/1 based on organoleptic
effects.
C-T.4
-------
There.are some indications that infants and small children
may have a high intake of water and an additional intake
of 10 to 20 mg might have an influence on copper metabolism
in children with low copper intakes or with copper deficiency
due to, e«g. intestinal diseases. However, due to insuf-
ficient amount of information available for this special
groups at risk, derivation of criterion lower than the current
standard would be difficult to justify. Therefore, it is
recommended that the current level be maintained for water
quality criteria purposes (5 mg/1). As additional information
becomes available reconsiderations of appropriateness of
the current standard should be performed.
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Allen, G. S. An outbreak of zinc poisoning in cattle. Vet. Record. July
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•
Atkinson, R. L., W. T. Dahms, G. A. Bray, R. Jacob, and H. H. Sandstead.
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Baumslag, N., 0. Yeager, L. Lvein.'and H. G. Petering. Trace metal content of
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