United States Office of Water EPA 440/5-80-079
Environmental Protection Regulations and Standards October 1980
Agency Criteria and Standards Division _
Washington DC 20460 C«^"
&EPA Ambient
Water Quality
Criteria for
Zinc
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AMBIENT WATER QUALITY CRITERIA FOR
ZINC
Prepared By
U.S. ENVIRONMENTAL PROTECTION AGENCY
Office of Water Regulations and Standards
Criteria and Standards Division
Washington, D.C.
Office of Research and Development
Environmental Criteria and Assessment Office
Cincinnati, Ohio
Carcinogen Assessment Group
Washington, D.C.
Environmental Research Laboratories
Corvalis, Oregon
Duluth, Minnesota
Gulf Breeze, Florida
Narragansett, Rhode Island
&;j;j"
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DISCLAIMER
This report has been reviewed by the Environmental Criteria and
Assessment Office, U.S. Environmental Protection Agency, and approved
for publication. Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
AVAILABILITY NOTICE
This document is available to the public through the National
Technical Information Service, (NTIS), Springfield, Virginia 22161.
ii
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FOREWORD
Section 304 (a)(l) of the Clean Water Act of 1977 (P.L. 95-217),
requires the Administrator of the Environmental Protection Agency to
publish criteria for water quality accurately reflecting the latest
scientific knowledge on the kind and extent of all identifiable effects
on health and welfare which may be expected from the presence of
pollutants in any body of water, including ground water. Proposed water
quality criteria for the 65 toxic pollutants listed under section 307
(a)(l) of the Clean Water Act were developed and a notice of their
availability was published for public comment on March 15, 1979 (44 FR
15926), July 25, 1979 (44 FR 43660), and October 1, 1979 (44 FR 56628).
This document is a'revision of those proposed criteria based upon a
consideration of comments received from other Federal Agencies, State
agencies, special interest groups, and individual scientists. The
criteria contained in this document replace any previously published EPA
criteria for the 65 pollutants. This criterion document is also
published in satisifaction of paragraph 11 of the Settlement Agreement
in Natural Resources Defense Council, et. al. vs. Train, 8 ERC 2120
(O.D.C. 1976), modified, 12 ERC 1833 (D.D.C. 1979).
The term "water quality criteria" is used in two sections of the
Clean Water Act, section 304 (a)(l) and section 303 (c)(2). The term has
a different program impact in each section. In section 304, the term
represents a non-regulatory, scientific assessment of ecological ef-
fects. The criteria presented in this publication are such scientific
assessments. Such water quality criteria associated with specific
stream uses when adopted as State water quality standards under section
303 become enforceable maximum acceptable levels of a pollutant in
ambient waters. The water quality criteria adopted in the State water
quality standards could have the same numerical limits as the criteria
developed under section 304. However, in many situations States may want
to adjust water quality criteria developed under section 304 to reflect
local environmental conditions and human exposure patterns before
incorporation into water quality standards. It is not until their
adoption as part of the State water quality standards that the criteria
become regulatory.
Guidelines to assist the States in the modification of criteria
presented in this document, in the development of water quality
standards, and in other water-related programs of this Agency, are being
developed by EPA.
STEVEN SCHATZOW
Deputy Assistant Administrator
Office of Water Regulations and Standards
111
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ACKNOWLEDGEMENTS
Aquatic Life Toxicology
Gary A. Chapman, EP.L-Corvall ia Jonn H. Gentile, ERL-Narragansett
U.S. Environmental Protection Agency U.S, Environmental Protection Agency
Mammalian Toxicity and Human Health Effects
Harold Petering (author) Edward Calabrose
University of Cincinnati University of Massachusetts
Christopher T. DeRosa (doc. mgr.) Annerrarie F. Crocetti
ECAO-Cin Johns Hopkins University
U.S. Environmental Protection Agency
Jerry F. Stara (doc. mgr.) ECAO-Cin Patrick Durkin
U.S. Environmental Protection Agency Syracuse Research Corporation
Si Duk Lee, ECAO-Cin Steven D. Lutkenhoff, ECAO-Cin
U.S. Environmental Protection Agency U.S. Environmental Protection Agency
Paul Mushak Magnus Piscator
University of North Carolina Karolinska Institute,
Stockholm, Sweden
Tern' Laird, ECAO-Cin William Sunderman
U.S. Environmental Protection Agency University of Connecticut
Technical Support Services Staff: D.J. Reisman, M.A. Garlouqh, B.L. Zwayer,
P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A/Cooper,
M.M. Denessen.
Clerical Staff: C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks,
B.J. Quesnell, T. Highland, B. Gardiner.
IV
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TABLE OF CONTENTS
Page
Criteria Summary
Introduction A-l
Aquatic Life Toxicology B-l
Introduction B-l
Effects B-5
Acute Toxicity B-5
Chronic Toxicity B-7
Plant Effects B-9
Residues B-10
Miscellaneous B-ll
Summary B-12
Criteria B-14
References B-51
Mammalian Toxicology and Human Health Effects C-l
Introduction C-l
Exposure C-2
Ingestion from Water C-2
Ingestion from Food C-3
Pharmacokinetics C-8
Absorption C-8
Distribution C-12
Excretion C-14
Effects C-26
Acute, Subacute and Chronic Toxicity C-26
Teratogenicity, Mutagenicity and Carcinogenicity C-42
Interactions of Zinc with Other Metals C-47
Cadmium C-47
Copper C-51
Lead C-54
Interactions Between Zinc and Drugs C-55
Criterion Formulation C-57
Existing Guidelines and Standards C-57
Current Levels of Exposure C-58
Special Groups at Risk C-58
Basis and Derivation of Criterion C-58
References C-62
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CRITERIA DOCUMENT
ZINC
CRITERIA
Aquatic Life
For total recoverable zinc the criterion to protect freshwater aquatic
life as derived using the Guidelines is 47 yg/l as a 24-hour average and the
concentration (in yg/1) should not exceed the numerical value given by
e(0.83[ln(hardness)]+1.95) at any time> For example, at hardnesses of 50,
100, and 200 mg/1 as CaC03 the concentration of total recoverable zinc
should not exceed 180, 320, and 570 yg/l at any time.
For total recoverable zinc the criterion to protect saltwater aquatic
life as derived using the Guidelines is 58 ug/1 as a 24-hour average and the
concentration should not exceed 170 yg/l at any time.
Human Health
Sufficient data are not available for zinc to derive a level which would
protect against the potential toxicity of this compound. Using available
organoleptic data, for controlling undesirable taste and odor quality of
ambient water, the estimated level is 5 mg/1. It should be recognized that
organoleptic data as a basis for establishing a water quality criteria have
limitations and have no demonstrated relationship to potential adverse human
health effects.
VI
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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, 1956).
Zinc has an atomic number of 30 and its atomic weight is 65.38 (Weast,
1977). The chemistry of zinc is similar to that of cadmium, which is di-
rectly below it in the periodic table (Cotton and Wilkinson, 1972). In
aqueous solution, zinc always has a valence of +2, and it exhibits amphoter-
ic propertiers, dissolving in acids to form hydrated Zn(II) cations and in
p
strong bases to form zincate anions [probably Zn(OH)^ ]. Compounds of
zinc with the common ligands of surface waters are soluble in neutral and
acidic solutions, so that zinc is readily transported in most natural waters
and is one of the most mobile of the heavy metals. The geochemistry of zinc
in surface water has been extensively reviewed by Hem (1972). Since the
divalent zinc ion does substitute to some extent for magnesium in the sili-
cate minerals of igneous rocks, weathering of this zinc-containing bedrock
gives rise to Zn+^ in solution whereupon the hydrated cation remains domi-
nant to pH values of about 9. Zinc forms complexes with a variety of organ-
ic and inorganic ligands, but these compounds are sufficiently soluble to
prevent their becoming a limiting factor for the solubility of the small
concentrations of zinc found in most aquatic environments. Adsorption on
clay minerals, hydrous oxides, ana organic matter is a more probable limit-
ing mechanism.
Most of the zinc introduced into the aquatic environment is partitioned
into the sediments by sorption onto hydrous iron and manganese oxides, clay
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minerals, and organic materials. Precipitation of the sulfide is an impor-
tant control on the mobility of zinc in reducing environments, and precipi-
tation of the hydroxide, carbonate, or basic sulfate can occur where zinc is
present in high concentrations. Formation of complexes with organic and
inorganic ligands can increase the solubility of zinc and probably increases
the tendency for zinc to be adsorbed.
Sorption of zinc by hydrous metal oxides, clay minerals, and organic
materials is probably the dominant fate of zinc in the aquatic environment.
The tendency of zinc to be sorbed is affected not only by the nature and
concentration of the sorbent but by pH and salinity as well. In a study of
heavy metal adsorption by two oxides and two soils, zinc was completely re-
moved from solution when pH exceeded 7; below pH 6, little or no zinc was
adsorbed. Addition of inorganic complexing ligands enhanced the affinity
for adsorption (Huang, et al. 1977).
Helz, et al. (1975) found that zinc is desorbed from sediments as salin-
ity increases. This phenomenon, which is exhibited by many of the other
metals as well, is apparently due to displacement of the adsorbed zinc ions
by alkali and alkaline earth cations which are abundant in brackish and
saline waters. In summary, sorption is the dominant fate process affecting
zinc, and it results in enrichment of suspended and bed sediments relative
to the water column. Variables affecting the mobility of zinc include the
concentration and composition of suspended and bed sediments, dissolved and
particulate iron and manganese concentrations, pH, salinity, concentration
of complexing ligands, and the concentration of zinc.
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REFERENCES
Cotton, F.A. and A. Wilkinson. 1972. Advanced Inorganic Chemistry. Inter-
science Publishers, New York. p. 600.
Helz, G.R., et al. 1975. Behavior of Mn, Fe, Cu, Zn, Cd, and Pb discharged
from a wastewater treatment plant into an estuarine environment. Water Res.
9: 631.
Hem, J.D. 1972. Chemistry and occurrence of cadmium and zinc in surface
water and groundwater. Water Resource Res. 8: 661.
Huang, C.P., et al. 1977. Interfacial reaction and the fate of heavy
metals in soil-water systems. Jour. Water Pollut. Control Fed. 49: 745.
Lange, N.A. 1956. Handbook of Chemistry. Handbook Publishers, Inc., San-
dusky, Ohio.
Weast, R.E. (ed.) 1977. CRC Handbook of Chemistry and Physics. 58th ed.
CRC Press, Cleveland, Ohio.
A-3
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Aquatic Life Toxicology*
INTRODUCTION
Acute toxicity tests have been conducted with thirty species of fresh-
water animals, and the median toxicity values range from 90 to 58,100 ug/1.
Chronic tests with six species have resulted in chronic values from 47 to
852 ug/1. With nine different plant species the results ranged from 30 to
67,700 ug/1-
The zinc data base for saltwater organisms includes the results of acute
toxicity tests with twenty-one species of invertebrates and three species of
fishes. Zinc was acutely toxic to the mummichog at 83,000 wg/1 and at 166
ug/1 to the hard-shelled clam. A chronic value of 166 ug/1 is available
from a life-cycle test with a mysid shrimp, and residue data are reported
for five species of algae and nine species of invertebrates. Decreased
growth of various plants was reported at concentrations ranging from 50 to
25,000 wg/l.
Zinc is a common trace constituent of natural waters and is a required
trace element in the metabolism of most organisms. The uptake of zinc from
the environment, either via ingestion or absorption, must exceed some mini-
mum rate in order for an organism to function properly. Whether any waters
are deficient in zinc content from the standpoint of the existing biota is
not clear, but the question is probably moot with regard to water quality
criteria for zinc.
Above some theoretical minimum concentration of zinc in water, there
exists a range of zinc concentrations which is readily tolerated through
*The reader is referred to the Guidelines for Deriving Water Quality Crite-
ria for the Protection of Aquatic Life and Its Uses in order to better un-
derstand 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 calculations for deriving various measures of tox-
icity as described in the Guidelines.
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each organism's capacity to regulate the uptake, internal distribution, and
excretion of zinc. This range undoubtedly varies among individuals, spe-
cies, and larger phylogenetic groups. In addition, this ability, and hence
the tolerated range, probably varies with the range of zinc concentrations
to which the various populations have been historically exposed and acclim-
ated. Thus, biological variability in zinc tolerance should be expected to
occur based on phylogenetic differences and historic exposure patterns, both
short-term and geologic in scale.
Compounding the problem of defining biologically safe zinc concentra-
tions is the occurrence of many different forms of zinc in surface waters.
Zinc can occur in both suspended and dissolved forms. Dissolved zinc may
occur as the free (hydrated) zinc ion or as dissolved complexes and com-
pounds with varying degrees of stability and toxicity. Some forms of sus-
pended (undissolved) zinc may be readily dissolved following minor changes
in water chemistry. Other suspended zinc may be reversibly sorbed onto sus-
pended solids or, conversely, almost irreversibly included in suspended
mineral particles.
Paramount to the question of zinc toxicity are the physical and chemical
state of the zinc, the toxicity of each form of the zinc, and the degree of
interconversion to be expected among the various forms. All zinc forms are
presumably nontoxic unless they can be sorbed or bound by biological mate-
rials. Conversely, all zinc forms are potentially toxic if they can be
sorbed or bound by biological tissues. Most likely, zinc will not be sorbed
or bound unless it is dissolved, but some solution of the zinc may reason-
ably be expected to occur in the alimentary canal following ingestion of
particulates containing undissolved zinc. Thus, the toxicity of undissolved
zinc to any organism probably depends on feeding habits, with the result
8-2
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that plants and most fish would presumably be relatively unaffected by sus-
pended zinc, but many invertebrates could be adversely affected by ingestion
of sufficient quantities of particulates containing zinc.
A complex array of data concerning an assortment of toxic responses to
zinc is one result of the physical, chemical, and biological variability de-
scribed. However, by evaluating the toxicity on a species-by-species basis
and by considering several water chemistry parameters, the information can
be simplified.
The toxicity of zinc, as well as other heavy metals, is reported to be
influenced by a number of chemical factors including calcium, magnesium,
hardness, pH, and ionic strength. These factors appear to affect the toxic-
ity of zinc either by influencing the proportion of available zinc or by in-
hibiting the sorption or binding of available zinc by biological tissues.
In freshwater, zinc appears to be less toxic at high hardness levels for a
variety of reasons, such as:
1) The ions contributing to hardness, primarily calcium and magnesium,
are divalent and compete with zinc, which is also divalent for sites of up-
take and binding in biological tissues;
2) Harder waters have higher ionic strengths due to the greater quanti-
ty of charged ions (primarily mono- and divalent cations and anions) in
solution, and these ions electrostatically inhibit the ability of other ions
(including zinc) to approach the absorption or binding sites of the organ-
isms. Basically, zinc ions have lower activity in harder waters; and
3) Generally, harder waters have higher alkalinities and higher pH
values. Insoluble, and possibly soluble, zinc carbonate and hydroxide com-
pounds can form which are not sorbed by many organisms. Changes in
B-3
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hardness, pH, and alkalinity will cause corresponding changes in the
toxicity of the zinc in the water.
Hardness, on the other hand, may have scant relationship to the amount
of zinc sorbed to or included in particulate material or bound to organic
chemicals. Nevertheless, hardness appears to be the single best chemical
parameter to reflect the variation in zinc toxicity induced by differences
in general water chemistry.
However, water quality criteria for freshwater developed with hardness
as the sole physical-chemical variable may be lower than ambient total zinc
levels in some surface waters of the United States. This may result, in
part, from the current inability to correlate quantitatively the effects on
zinc toxicity of physical-chemical factors other than hardness and those
factors such as ionic strength, pH, and alkalinity which are qualitatively
related to hardness. Alternatively, where zinc levels exceed criteria, the
zinc may be harming the biota, or the biota may have evolved as a zinc-re-
sistant population. The actual situation must be evaluated based on the
biological, chemical, and physical factors just discussed.
Of the analytical measurements currently available, a water quality cri-
terion for zinc is probably best stated in terms of total recoverable zinc,
because of the variety of forms of zinc that can exist in bodies of water
and the various chemical and toxicological properties of these forms. The
forms of zinc that are commonly found in bodies of water and are not meas-
ured by the total recoverable procedure, such as the zinc that is a part of
minerals, clays, and sand, probably are forms that are less toxic to aquatic
life and probably will not be converted to the more toxic forms very readily
under natural conditions. On the other hand, forms of zinc that are common-
ly found in bodies of water and are measured by the total recoverable pro-
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cedure, such as the free ion, and the hydroxide, carbonate, and sulfate
salts, probably are forms that are more toxic to aquatic life or can be con-
verted to the more toxic forms under natural conditions.
Because the criteria are derived on the basis of tests conducted on sol-
uble inorganic salts of zinc, the total zinc and total recoverable zinc con-
centrations in the tests would probably be about the same and a variety of
analytical procedures would produce about the same results. Except as
noted, all concentrations reported herein are expected to be essentially
equivalent to total recoverable zinc concentrations. All concentrations are
expressed as zinc, not as the compound.
EFFECTS
Acute Toxicity
Zinc produces acute toxicity to freshwater organisms over a range of
concentrations from 90 to 58,100 pg/1 (Table 1). The range of acute median
effect concentrations is similar for freshwater fish and invertebrates, with
ranges of 90 to 40,900 and 100 to 58,100 yg/1, respectively. A portion of
this range is due to hardness related factors, and the remainder is due to
species differences and other biological and physical-chemical factors.
Within the larger data sets for individual fish species, especially
those for rainbow trout and fathead minnow, the lower IC™ values at a
given hardness were obtained using younger, smaller fish. Also, acute tox-
icity tests conducted by Cairns, et al. (1978) with both Daphnia magna and
Daphnia pulex at 5, 10, 15, 20 and 25°C (Tables 1 and 6) showed that acute
toxicity increased as temperature increased. The value at 20°C in Table 1
was used in the calculation of the species mean acute intercept because
acute and chronic tests with daphnids are usually conducted at this
temperature.
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An exponential equation was used to describe the observed relationship
of the acute toxicity of zinc to hardness in freshwater. Least squares re-
gression of the natural logarithms of the acute values on the natural loga-
rithms of hardness was used to calculate slopes for 10 species (Table 1).
Five of the slopes were significant, two were not significant, and the other
three could not be tested because only two values were available. The a-
rithmetic mean (0.83) of the five significant slopes was used with the geo-
metric mean toxicity value and hardness for each species to obtain a loga-
rithmic intercept for each of the 29 freshwater species for which acute val-
ues are available for zinc. The species mean acute intercept, calculated as
the exponential of the logarithmic intercept, was used to compare the rela-
tive acute sensitivities (Table 3).
Interestingly, all tests with 10 of the 12 species reported to be more
resistant than bluegill (Table 3) were tested in several series of experi-
ments reported by Rehwoldt, et al. (1971, 1972, 1973) conducted in Hudson
River water. Whether the water reduced the toxicity of the zinc or whether
the species tested were really more resistant cannot be determined. Many of
the invertebrates tested by Rehwoldt and his co-workers are known to be gen-
erally resistant to heavy metals, so species resistance is a likely explana-
tion. One species tested by Rehwoldt, et al. (1971, 1972), the striped
bass, was rather sensitive to zinc, but other investigators obtained acute
values which were quite a bit lower for this species.
A freshwater Final Species Acute Intercept of 7.02 pg/1 was obtained for
zinc using the species mean acute intercepts listed in Table 3 and the cal-
culation procedures described in the Guidelines. Thus the Final Acute Equa-
tion is e(0.83[ln(hardness)] + 1.95).
Acute toxicity data for zinc are available for 21 species of saltwater
invertebrates (Table 1) and represent more than two orders of magnitude dif-
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ference in sensitivity. Larval molluscs were the most sensitive inverte-
brates with acute values for an oyster of 310 wg/l and for the hard shelled
clam of 166 wg/l. Acute values for adult molluscs ranged from 2,500 for the
blue mussel to 7,700 for the soft-shelled clam. Zinc was acutely toxic to
saltwater polychaetes over the range from 900 yg/1 for Neanthes arenaceoden-
tata to 55,000 for Nereis diversicolor. The decapod crustaceans had 96-hour
LC5Q values of 175 and 1,000 ug/1 for the lobster and crab, respectively.
The reported acute values for copepods ranged from 290 yg/1 for Acartia
tonsa to 4,090 ug/1 for Eurytemora affinis. Results from tests with two my-
sid shrimp showed similar values; 498 ug/1 for Mysidopsis bahia and 591 ug/1
for Mysidopsis bigelowi.
The data base for saltwater fishes contains nine values for three spec-
ies of fish and three taxonomic families (Table 1). The acute values range
from 2,730 for larval Atlantic silversides to 83,000 for larval mummichog.
Saltwater fish were generally more resistant to acute zinc poisoning than
saltwater invertebrates, although there were cases of individual overlap.
The saltwater Final Acute Value for zinc, derived from the Species Mean
Acute Values listed in Table 3 using the calculations procedures described
in the Guidelines, is 173 ug/1.
Chronic Toxicity
Chronic toxicity tests have been conducted with six species of fresh-
water organisms (Table 2). Chronic values for five species of fish ranged
from 47 ug/1 for flagfish (Jordanella floridae) to 852 ug/1 for brook trout
(Salvelinus fontinalis). No tests of the chronic toxicity of zinc to fish
have been conducted in hard water. Four chronic toxicity tests are reported
for Daphnia magna, with chronic values ranging from 47 to 136 u9/l- Sur-
prisingly, the chronic toxicity of zinc to this daphnid appears to increase
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with increasing hardness, a phenomenon which may be attributable to inges-
tion of precipitated zinc by Daphnia magna in hard water tests.
The 10-month chronic toxicity test conducted by Brungs (1969) provided
evidence that the chronic value for the fathead minnow in hard water would
be below 180 ug/1 (Table 6). In light of the 106 ug/l chronic value ob-
tained by Benoit and Holcombe (1978) in soft water, this strongly suggests
that the chronic toxicity of zinc to fish may also be relatively unaffected
by hardness. Thus, the available toxicity data indicate that hardness ef-
fects are much less dramatic for the chronic toxicity of zinc than for acute
toxicity, and that the slope of the hardness-toxicity regression may be near
zero or even negative for some species.
The only chronic data reported (Table 2) for a saltwater species exposed
to zinc are those for the mysid shrimp, Mysidopsis bahia (U.S. EPA, 1980).
In this flow-through life cycle test the number of spawns recorded at 231
ug/1 was significantly (p<0.05) fewer than at 120 ug/1, but the number of
spawns at 59 and 120 ug/1 were not statistically significantly different
from those in the control. Brood size was significantly (p<0.05) reduced at
231 ug/1 but not at lower concentrations. Based upon reproductive data, the
lower and upper chronic endpoints were 120 amd 231 ug/1, respectively, which
results in a chronic value of 166 ug/1 (Table 3).
The acute-chronic ratios derived from the nine chronic tests with zinc
in freshwater show a rather wide range (Table 2). Some of the range is due
to the differing acute values for different life stages of the same spe-
cies. Additional variation is due to differences in water quality, but in
soft water the values range from less than 1 to 32. It appears that 3 would
be a reasonable estimate of an acute-chronic ratio for zinc in freshwater,
and this agrees with the only value available in saltwater.
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An acute-chronic ratio of 3 used with the freshwater Final Acute Equa-
tion (Table 3) would result in a freshwater Final Chronic Equation of
e(0.83[ln(harness)] + 0.85)^ However, this would result in a Final
Chronic Value of 55 Pg/l at a hardness of 45 and in higher values at higher
hardnesses. Because 47 yg/1 is the chronic value for both a sensitive in-
vertebrate in hard water and a medium sensitive fish in soft water, it would
appear reasonable to set the freshwater Final Chronic Value at 47 Pg/l for
all hardnesses. This is also supported by the data suggesting that in-
creasing hardness does not decrease the chronic toxicity of zinc like it
decreases the acute toxicity of zinc.
The saltwater Final Acute Value of 173 pg/1 divided by an acute-chronic
ratio of 3 results in a saltwater Final Chronic Value of 57.7 ug/l (Table 3).
Plant Effects
Results of zinc toxicity tests with nine species of freshwater plants
are listed in Table 4. Zinc concentrations from 30 to 21,600 ug/l have been
shown to reduce the growth of various plant species. Algae appear to be
more sensitive to zinc than macrophytes, with Selenastrum capricornutum the
most sensitive of the tested algal species. Selenastrum sensitivity to zinc
is greater in softer waters (Greene, et al. 1975), but the range of hardness
values tested was limited (4 to 15 mg/1 as CaC03). The significance of
short-term growth inhibition in algae has not been established; however, the
existence of growth inhibition at low zinc levels should be considered of
potential ecological importance.
Data for the toxic effects of zinc to 13 species of saltwater plants are
also listed in Table 4. The growth of kelp was inhibited at 100 pg/1 for
Laminaria digitata (Bryan, 1969) and 250 ug/l for Laminaria hyperiborea
B-9
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(Hopkins and Kain, 1971). The giant kelp, Macrocystis pyrifera, was rela-
tively insensitive to the effects of zinc on photosynthesis with an EC5Q
of 10,000 ug/1.
Microalgae had a wide range of sensitivities to zinc. Growth inhibition
was reported at 25,000 ug/l for the diatom, Phaeodactylum tricornutum (Jen-
sen, et al. 1974), for Skeletonema costatum and Thalassiosira pseudonana at
200 ug/l (Braek, et al. 1976), at 100 vgf\ for Gymnodinium splendens and
Thalassiosira rotula (Kayser, 1977), and at 50 pg/1 for Schroederella
schroederi (Kayser, 1977).
No freshwater or saltwater Final Plant Value is possible because zinc
concentrations were not measured in any of the toxicity tests with plants.
Residues
Table 5 contains bioconcentration factors for zinc determined with two
freshwater fish species and two freshwater invertebrate species. The fac-
tors for fish were 51 and 432, and those for invertebrate species were 107
and 1,130.
Bioconcentration factors also have been determined for three species of
macroalgae and six species of saltwater invertebrates (Table 5), but no data
are available for saltwater fishes. The accumulation of zinc by macroalgae
varied from a high of 16,600 times ambient for Fucus serratus (Young, 1975)
to 1,530 times above ambient for Enteromorpha pro!ifera (Munda, 1979).
Among invertebrate species bioconcentration factors ranged from 20 for the
polychaete Nereis diversi col or (Bryan and Hummerstone, 1973) to 16,700 for
the oyster Crassostrea virginica (Shuster and Pringle, 1969).
Bioconcentration factors varied considerably among the different species
of bivalve molluscs; 43 was obtained with the soft-shell clam (Eisler,
1976b), 500 with the mussel (Pentreath, 1973) and 16,700 with the oyster
(Shuster and Pringle, 1969). Bryan (1966) reported zinc accumulation in
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crab muscle resulting in a bioconcentration factor of 8,800. Because of the
variation between species and phyla it is difficult to identify specific
trends between bioconcentration and phylogenetic position. Bioconcentration
factors for invertebrate species are generally 500 or less except for the
crab and oyster.
A Final Residue Value cannot be calculated for either fresh or saltwater
because no maximum permissible tissue concentration is available.
Miscellaneous
Table 6 contains other data concerning the effects of zinc on freshwater
organisms. Sprague (1968) found that rainbow trout would avoid a zinc con-
centration of 5.6 pg/1 in a laboratory behavior test in water with a hard-
ness of 14 mg/1 as CaCO^, but the ecological significance of laboratory
avoidance behavior is not known. Sprague (1964b) and Sprague, et al. (1965)
emphasized that laboratory avoidance thresholds are probably low estimates,
because territorial or migrational motivations would be expected to cause
higher thresholds for avoidance in nature. In addition, acclimation to zinc
could substantially alter avoidance behavior.
Significant avoidance behavior probably will not occur in nature at zinc
concentrations below those required for acute and chronic protection for the
most sensitive freshwater organisms. Acclimation and territorial and migra-
tory urges would probably counteract mild aversion to waters containing low
zinc concentrations. However, the possibility that a sensitive, nonaccli-
mated species would at least temporarily avoid a body of water with an ap-
parently acceptable zinc concentration cannot be ruled out on the basis of
existing data.
Anderson, et al. (1980) reported an average LC5Q value of 37 pg/l
(range 26 to 54 ug/1) for the chironomid Tanytarsus dissimilis following
10-day exposure of the embryonic, hatching, and molting stages. Growth of
B-ll
-------
surviving larvae was not significantly affected. Because of the duration
and nature of the test and the short life-span of the chironomid tested,
this test should probably be considered equivalent to the early life stage
test with fish. The sensitivity of this species is further support for a
freshwater Final Chronic Value of 47 yg/1.
The data for saltwater aquatic life in Tables 1 and 6 indicate that zinc
causes increasing cumulative mortality with increasing time of exposure past
96 hours. Eisler and Hennekey (1977) reported a significant increase in
zinc mortality to the mummichog, sandworm, soft-shell clam, and mudsnail
when exposures were extended from 4 to 7 days. Benijts-Claus and Benijts
(1975) reported delayed development of crab larvae after 16 days exposure at
50 pg/1, indicating cumulative mortality to macrocrustaceans.
Data in Table 6 also indicate a relationship between salinity and acute
toxicity. Herbert and Wakeford (1964) reported a decrease in the sensitivi-
ty of Atlantic salmon (smolt) and yearling rainbow trout to the acute tox-
icity of zinc at salinities of 3, 7, and 14 g/kg but an increase in sensi-
tivity at 26 g/kg salinity. The relationship therefore was not linear over
the range of salinities tested. Jones (1975) reported a linear increase in
mortality with decreasing salinities for both the marine isopod, Idotea
baltica and the euryhaline isopod, Jaera albifrons.
Molluscan larvae as a taxa are generally more sensitive than the inver-
tebrates to zinc toxicity. Brereton, et al. (1973) reported that reduced
development and inhibition of substrate attachment occurred at 125 ug/1 with
the Pacific oyster, and Nelson (1972) reported that abnormal shell
development occurred at 70 ug/1.
Summary
Zinc is an essential trace element which can be toxic at higher concen-
trations. The acute toxicity of zinc to aquatic organisms is affected by
B-12
-------
hardness, but the chronic toxicity apparently is not. The range of acute
values for freshwater organisms is from 90 to 38,100 yg/1 and is similar for
fish and invertebrates. Results from chronic toxicity tests indicate a
range of chronic values from 47 to 852 Pg/l. Of the nine reported chronic
toxicity tests, five are tests with fish in soft water and four are tests
with Daphnia magna at hardnesses from 45 to 211 mg/1 as CaCO-j. Chronic
zinc toxicity is relatively unaffected by hardness, with zinc possibly
becoming more toxic in harder waters. Data from two tests with fathead min-
nows confirm the apparent inability of hardness to reduce the chronic tox-
icity of zinc. A chronic value of 47 yg/1 was obtained with both a sensi-
tive invertebrate (Daphnia magna) in hard water and a medium sensitive fish
(flagfish) in soft water. In addition, a 10-day LC5Q of 37 yg/1 was
obtained with a midge.
Although most plants appear to be insensitive to zinc, some values with
one species were below 47 yg/1, but other values for the same species were
much higher. Data on bioconcentration indicates that concentrations of zinc
which do not harm sensitive freshwater organisms will not harm consumers of
aquatic organisms. The possibility of avoidance of zinc at low concentra-
tions is suggested by laboratory behavior tests with fish, but the quaniti-
tative extrapolation of these results to field situation is apparently not
justified.
The saltwater acute values for zinc and fishes ranged from 2,730 yg/l
for larval Atlantic silversides to 83,000 for larval mummichog. Acute va-
lues for the invertebrate species ranged from 166 for clam larvae to 55,000
for adult polychaetes. The one chronic study conducted with the mysid
shrimp produced a chronic value of 166 yg/1 resulting in an acutechronic
ratio of 3.0. Plant studies with macroalgae reported growth inhibition at
100 yg/1 for Laminaria digitata. Microalgae had a wide range of sensitivi-
B-13
-------
ties to zinc with the lowest value being 50 ug/1 for Schroederella
schroederi. Bioconcentration factors were generally less than 500 for the
commercially important species of invertebrates except for the factors of
16,700 and 8,800 for an oyster and crab, respectively. Zinc mortality is
cumulative for exposures beyond four days. The effect of salinity on zinc
toxicity appears to be non-linear with fishes and linear with invertebrate
species.
CRITERIA
For total recoverable zinc the criterion to protect freshwater
aquatic life as derived using the Guidelines is 47 wg/l as a 24-hour
average, and the concentration (in ug/l) should not exceed the numerical
value given by .(0.83Cl«(h.r*«,)M.9S) ^ Jny t1-- Fop e^^ ^
hardnesses of 50, 100, and 200 mg/1 as CaCOo the concentration of total
O
recoverable zinc should not exceed 180, 320, and 570 ug/1 at any time.
For total recoverable zinc the cirterion to protect saltwater aquatic
life as derived using the Guidelines is 58 ug/1 as a 24-hour average, and
the concentration should not exceed 170 ug/1 at any time.
B-14
-------
Table 1. Acute values for zinc
Species
Worm,
Mais sp.
Sna I 1 ,
Physa heterostropha
Snai 1,
Physa heterostropha
Snail,
Physa heterostropha
Sna i 1 ,
Physa heterostropha
Cladoceran,
Daphnla magna
Cd
I Cladoceran,
01 Daphnla magna
Cladoceran,
Daphnia magna
C 1 adoceran ,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla pulex
Scud,
Gamma r us sp.
Damsel f ly.
Unidentified sp.
Midge,
Chlronomus sp.
Method*
Chemical
Hardness
(•g/l as
CaCO,)
LC50/EC50**
(ug/l)
Species Mean
Acute Value**
(ug/ 1 ) Reference
FRESHWATER SPECIES
S, M
S,U
S, U
S, U
S, U
S, M
S, M
S, M
S, M
S, M
S, M
S, M
S, M
S, M
_
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Z i nc su 1 fate
Zinc chloride
Zinc chloride
Zinc chloride
Zinc sulfate
-
_
-
50
43
41
165
178
45
45
54
105
196
45
50
50
50
18,400
900***
600***
3,300***
4,400***
100
280
334
525
655
500
8,100
26,200
18,200
Rehwoldt, et al. 1973
Cairns i Scheier,
1958
Cairns & Scheier,
1958
Cairns i Scheier,
1958
Cairns & Scheier
1958
Bleslnger &
Chrlstensen, 1972
Cairns, et al. 1978
Chapman, et al.
Manuscript
Chapman, et al.
Manuscript
- Chapman, et al.
Manuscript
Cairns, et al. 1978
Rehwoldt, et al. 1973
Rehwoldt, et al. 1973
Rehwoldt, et al. 1973
-------
Table 1. (Continued)
Hardness
Species Mean
Acute Values'1*
Species
Caddlsf ly.
Unidentified sp.
Rotifer,
Ph i 1 od 1 a acut I corn 1 s
Rotifer,
Ph 1 1 od 1 a acut 1 corn 1 s
American eel,
Anguilla rostrata
American eel,
Angui 1 la rostrata
Coho salmon,
Oncorhynchus klsutch
Coho salmon,
i Oncorhynchus klsutch
I--
Sockeye sa Imon
Oncorhynchus nerka
Chinook salmon (swlmup),
Oncorhynchus tshawytscha
Chinook salmon (parr),
Oncorhynchus tshawytscha
Chinook salmon (smolt),
Oncorhynchus tshawytscha
Cutthroat trout.
Sal mo clarki
Rainbow trout (alevln),
Sal mo galrdnerl
Rainbow trout (swimup)
Method*
S, M
S, U
S, U
S, m
S, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
R, M
FT, M
FT, M
Chemical
-
Zinc chloride
Zinc sulfate
Zinc nitrate
-
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc sulfate
Zinc chloride
Zinc chloride
CaC03)
50
25
25
53
55
25
94
22
24
22
24
-
22
22
58,100
1,500
1,200
14,600
14,500
905
4,600
749
97
463
701
90
815
93
nuiiv iatwx>--
(ug/l) Reference
Rehwoldt, et al. 1973
Bulkema, et al. 1974
Bulkema, et al. 1974
Rehwoldt, et al. 1971
Rehwoldt, et al. 1972
Chapman & Stevens,
1978
Lor 2 4 McPherson,
1976
Chapman, 1978a
Chapman, 1978b
Chapman, 1978b
Chapman, 1978b
Rabe 4 Sapplngton,
l<37fl
Chapman, I978b
Chaoman. 1978H
Salmo galrdnerl
-------
CD
I
Table 1. (Continued)
Spec Ies
Rainbow trout (parr),
Salmo galrdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
jalmo galrdnerl
Rainbow trout,
Salmo qalrdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Salmo qalrdnerl
Rainbow trout,
Salmo gairdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Sa|mo galrdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Salmo galrdnerl
Method*
FT, M
FT, M
R, U
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
Hardness
(mg/l as
Chemical CaCO^)
Zinc ch lorlde
Zinc chlori de
Zinc phosphate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
24
83
20
350
350
30
30
30
30
30
47
47
44
178
LC50/EC50»«
136
1,760
90
4,520
1,190
560
240
810
410
830
370
517
756
2,510
Specues Mean
Acute Value**
(ug/l) Reference
Chapman, 1978b
Chapman & Stevens,
1978
Garton, 1972
Goettl, et
Goettl, et
Goettl, et
Goettl, et
Goettl, et
Goettl, et
Goettl, et
Hoi combe &
1978
Hoi combe &
1978
Hoi combe &
1978
Hoi combe &
1Q7B
at. 1972
al. 1972
al. 1972
al. 1972
al. 1972
al. 1972
al. 1972
Andrew,
Andrew,
Andrew,
Andrew,
-------
Table I. (Continued)
Spec 1 es
Rainbow trout,
Salmo galrdneri
Rainbow trout,
Salmo gairdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Salmo galrdnerl
Rainbow trout,
Salmo gairdnerl
Atlantic salmon,
to Salmo sa lar
OD Atlantic salmon,
Salmo salar
Atlantic salmon,
Salmo salar
Brook trout ,
Salvelinus fontinal is
Brook 1rout,
Salvellnus fontinal Is
Brook trout,
Sa I ve I I nus font I na I Is
Brook trout,
Salvellnus font! nails
Brook trout,
Salvellnus fontinal Is
Method*
FT, M
FT, M
R, U
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
FT, M
Hardness
(«g/l as LC50/EC50**
Chemical CaCO*) (tig/ 1)
Zinc sulfate 179 2,960
Zinc sulfate 170 1,910
Zinc sulfate 5 280
Zinc sulfate 333 7,210
Zinc sulfate 26 430
Zinc sulfate 500 4,700
Zinc sulfate 14 740
Zinc sulfate 20 600
14 420
Zinc sulfate 47 1,550
Zinc sulfate 47 2,120
Zinc sul fate 44 2,420
Zinc sulfate 178 6,140
Zinc sulfate 179 6,980
Species Mean
Acute Value"
(uq/l) Reference
Hoi combe & Andrew,
1978
Hoi combe & Andrew,
1978
McLeay, 1976
Slnley, et al. 1974
Slnley, et al. 1974
Solbe, 1974
Carson i Carson, 1972
Sprague, 1964a
Sprague i Ramsey,
1965
Hoi combe i Andrew,
1978
Hoi combe 4 Andrew,
1978
Hoi combe & Andrew,
1978
Hoi combe & Andrew,
1978
Hoi combe i Andrew,
1978
-------
Table 1. (Continued)
tfl
c „«_!«,. Method*
Brook trout, FT, M
Salvel inus fontlnal Is
Longfin dace, R» M
Agosla chrysogaster
Goldfish, s. u
Carasslus auratus
Goldfish, s» u
Carasslus auratus
Carp, s» M
Cyprlnus carplo
Carp, •>, M
Cyprlnus carplo
Golden shiner, SF u
Noterolgonus crysoleucus
Fathead minnow, FT, M
Plmephales promelas
Fathead minnow, FT, M
Plmephales promelas
Fathead minnow, FT, M
Plmephales promelas
Fathead minnow, FT, M
Plmephales promelas
Fathead minnow, S, U
Plmephales promelas
Fathead minnow, s» U
Plmephales promelas
Fathead minnow, S, M
Plmephales promelas
Chemical
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc nitrate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Hardness
(ng/l as
CaCOj)
170
217
20
45
53
55
45
46
200
203
203
203
203
45
Species Mean
LC50/EC50»" Acute Value"
(uq/l) (jig/1)
4,980
790
6,440
7,500
7,800
7,800
6,000
600
2,610
8,400
10,000
12,000
13,000
3,100
Reference
Ho I combe i Andrew,
1978
Lewis, 1978
Pickering &
Henderson, 1966
Cairns, et al. 1969
Rehwoldt, et al. 1971
Rehwoldt, et al. 1972
Cairns, et al. 1969
Benolt i Ho I combe,
1978
Broderlus & Smith,
1979
Brungs, 1969
Brungs, 1969
Brungs, 1969
Brungs, 1969
Judy & Oavies, 1979
-------
Table I. (Continued)
w
tO
O
Species
Fathead minnow.
Plmep hales promelas
Fathead minnow.
Plmephales promelas
Fathead minnow.
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow.
Plmephales promelas
Fathead minnow.
Plmephales promelas
Fathead minnow.
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow.
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow.
Plmephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow.
Plmephales promelas
Fathead minnow.
Method*
FT,
FT,
FT,
FT,
FT,
FT.
FT,
FT,
FT,
FT,
FT,
FT,
FT,
FT,
M
M
M
M
M
M
M
M
M
M
M
M
M
M
Chemical
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
su 1 fate
su 1 fate
su 1 fate
su 1 fate
su 1 fate
su 1 fate
su 1 fate
su 1 fate
su 1 fate
sulfate
su 1 fate
su 1 fate
su 1 fate
su 1 fate
Hardness
(mg/l as
CaC03)
50
50
100
100
200
200
50
50
100
100
200
200
50
50
LC50/EC50**
12,
13,
18,
25,
29,
35,
13,
6,
12,
12.
19.
13,
4.
5,
(ug/l)
500
800
500
000
000
500
700
200
500
500
000
600
700
100
Species Mean
Acute Value**
(yg/l) Reference
Mount,
Mount ,
Mount ,
Mount,
Mount ,
Mount,
Mount,
Mount,
Mount,
Mount,
Mount,
Mount,
Mount,
Mount,
1966
1966
1966
1966
1966
1966
1966
1966
1966
1966
1966
1966
1966
1966
Pimephales promelas
-------
Table 1. (Continued)
Species
Fathead minnow,
Plmephales promeias
Fathead minnow.
Pimephales promeias
Fathead minnow.
Pimephales promeias
Fathead minnow.
Plmephales promeias
Fathead minnow,
Plmephales promeias
Fathead minnow,
Plmephales promeias
Fathead minnow,
Pimephales promeias
Fathead minnow,
Pimephales promeias
Fathead minnow,
Plmephales promeias
Fathead minnow (fry).
Plmephales promeias
Fathead minnow,
Plmephales promeias
Banded kill if Ish,
Fundulus diaphanus
Banded ki 1 lif ish.
Fundulus diaphanus
Method*
FT, M
FT, M
FT, M
FT, M
S, U
S, U
S, U
S, U
S, U
FT, M
S, U
S, M
S, M
Hardness
(«w/l as
Chemical CaCO,)
Zinc sulfate 100
Zinc sulfate 100
Zinc sulfate 200
Zinc sulfate 200
Zinc sulfate 20
Zinc sulfate 20
Zinc sulfate 360
20
20
Zinc sulfate 186
Zinc sulfate 166
55
53
LC50/EC50**
(IKI/I)
8,100
9,900
8,200
15,500
960
780
33,400
2,550
2,330
870
7,630
19,200
19,100
Species Mean
Acute Value**
(yg/l) Reference
Mount, 1966
Mount, 1966
Mount, 1966
Mount, 1966
Pickering &
Henderson, 1966
Pickering &
Henderson, 1966
Pickering &
Henderson, 1966
Pickering &
Henderson, 1966
Pickering &
Henderson, 1966
Pickering and Vigor,
1965
Rachlln & Perl mutter,
1968
Rehwoldt, et al. 1972
Rehwoldt, et al. 1971
-------
Table 1. (Continued)
Species
Flagflsh,
Jordanel la floridae
Guppy,
Poecllla retlculata
Guppy ,
Poecllla reticulata
Southern platyflsh,
Xiphophorus maculatus
White perch,
Morone amerlcana
White perch,
Morone amerlcana
Striped bass,
W Morone saxatl 1 Is
M Striped bass,
Morone saxatl Ms
Striped bass (fry),
Morone saxatl 1 Is
Striped bass (larvae),
Morone saxat ills
Pumpkin seed,
Lepomis glbbosus
Pumpkin seed,
Lepomis glbbosus
Bluegill,
Lepomis macrochlrus
Bluegill,
Method*
FT, M
S. U
S, U
S, U
S, M
S, M
S, M
S, M
S, M
S, U
S, M
S, M
FT, M
FT, M
Chemical
Z 1 nc su 1 fate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc nitrate
Zinc nitrate
Zinc chloride
Zinc nitrate
Zinc sulfate
Zinc sulfate
Hardness
(m/l as
CaC05)
44
45
20
166
53
55
55
53
137
38
53
55
46
46
LC50/EC50**
(Mfl/l)
1,500
30,000
1,270
12,000
14,300
14,400
6,800
6,700
1,180
too
20,000
20,100
9,900
12, 100
Species Mean
Acute Value**
(ng/l) Reference
Spehar, 1976
Cairns, et al. 1969
Pickering &
Henderson, 1966
Rachlin 4 Perlmutter,
1968
Rehwoldt, et al. 1971
Rehwoldt, et al. 1972
Rehwoldt, et al. 1972
Rehwoldt, et al. 1971
O'Rear, 1972
Hughes, 1973
Rehwoldt, et al. 1971
Rehwoldt, et al. 1972
Cairns, et al. 1971
Cairns, et al. 1971
Lepomis macrochlrus
-------
Table t. (Continued)
Species
Bluegi 1 1,
Lepomis macrochlrus
Bluegi 1 1,
Lepomis macrochlrus
Bluegl 1 1,
Lepomis macrochlrus
Bluegi 1 1,
Lepomis macrochirus
Bluegl 1 1,
Lepomis macrochlrus
Bluegl 1 1,
Lepomis macrochirus
Bluegi 1 1,
tp Lepomis macrochirus
w Bluegi 1 1,
Lepomis macrochirus
Bluegl 1 1,
Lepomis macrochlrus
Bluegi 1 1,
Lepomis macrochlrus
Bluegi 1 1,
Lepomis macrochirus
Bluegi 1 1,
Lepomis macrochlrus
Bluegi 1 1,
Method*
S, U
S, U
s, u
s, u
s, u
s, u
s, u
s, u
s, u
s, u
S, M
S, M
S, M
Hardness
(mg/l as
Chemical CaCO?)
Zinc chloride 52
Zinc ch loride 52
Zinc chloride 52
Zinc sulfate 20
Zinc sulfate 20
Zinc sulfate 20
Zinc chloride 20
Zinc sulfate 360
20
Zinc chloride 45
Zinc chloride 45
Zinc chloride 45
Zinc chloride 174
Species Mean
LC50/EC50** Acute Value**
(ug/l) (ug/l) Reference
7,450
7,200
6,910
5,460
4,850
5,820
5,370
40,900
6,440
3,840
3,750***
3,430***
12,390***
Cairns 4 Scheier,
1959
Cairns and Scheler,
1959
Cairns 4 Scheier,
1959
Pickering 4
Henderson, 1966
Pickering &
Henderson, 1966
Pickering 4
Henderson, 1966
Pickering 4
Henderson, 1966
Pickering &
Henderson, 1966
Pickering 4
Henderson, 1966
Cairns 4 Scheler,
1957a
Ca Irns 4 Scheier,
I957b
Ca Irns 4 Scheler,
1957b
Cairns 4 Scheier,
!Qti7h
Lepomis macrochlrus
-------
Table 1. (Continued)
Species Method* Chemical
Blueglll, S,M Zinc chloride
Lepomls macrochlrus
Hardness
(mg/l as
CaCOxI
174
LC50/EC50**
(ug/l)
12,120***
Species Mean
Acute Value**
(ug/l)
Reference
Cairns & Scheler,
I957b
SALTWATER SPECIES
w
I
to
Polychaete (adult), S, U Zinc sulfate
Capltella capltata
Polychaete (larvae), S, U Zinc sulfate
Cap Ite11a cap Itata
Polychaete (adult), S, U Zinc sulfate
Neanthes arenaceodentata
Polychaete (juveniles), S, U Zinc sulfate
Neanthes arenaceodentata
Polychaete (adult), S, U Zinc sulfate
Nereis divers I color
Polychaete (adult), S, U Zinc sulfate
Nereis diversicolor
Sandworm (adult), ' S, U Zinc chloride
Nereis vlrens
t
Oyster, S, U Zinc chloride
Crassostrea virgin lea
Hard shelled clam, S, U Zinc chloride
Mercenarla mercenarla
Soft shelled clam, S, U Zinc chloride
Mya arenaria
Soft shelled clam, S, U Zinc chloride
Mya arenaria
3,500
1,700
1,800
900
55,000
11,000
8,100
310
166
5,200
7,700
Reish, et al. 1976
2,440 Relsh, et al. 1976
Relsh, et al. 1976
1,270 Reish, et al. 1976
- Bryan 4 Hummer stone,
1973
24,600 Bryan 4 Hummerstone,
1973
8,100 Elsler 4 Hennekey,
1977
310 Calabrese, et al.
1973
166 Calabrese 4 Nelson,
1974
Elsler, 1977a
6,330 Elsler 4 Hennekey,
1977
-------
Table I. (Continued)
O1
Species Method* Chemical
Mussel, F, M Zinc chloride
Mytl I us edulls planulatus
Mussel, F, M Zinc chloride
Mytllus edulls planulatus
Mussel, S, M Zinc chloride
Mytllus edulls planulatus
Mud snail (adult), S, U Zinc chloride
Nassarius obsoletus
Copepod (adult) S, U Zinc chloride
Acartla clausl
Copepod (adult), S, U Zinc chloride
Acartla tonsa
Copepod (adult), S, U Zinc chloride
Eurytemora afflnls
Copepod (adult), S, U Zinc chloride
Nltocra splnlpes
Copepod (adult), S, U Zinc chloride
Pseudod laptofnus coronatus
Copepod (adult), S, U Zinc chloride
Tlgrlopus japonlcus
Mysld shrimp, S, M Zinc chloride
Mysldopsls bah I a
Mysfd shrimp, S, M Zinc chloride
Mysldopsls blgelowl
Lobster (larvae), S, U Zinc chloride
Homarus americanus
Lobster (larvae), S, U Zinc chloride
Homarus americanus
Hardness
lmg/1 as
CaCOx)
LC50/EC50
Species Mean
Acute Value**
(ug/l)
4,300
3,600
2,500
50,000
950
290
4,090
1,450
1,783
2,160
498
591
575
375
3,380
50,000
950
290
4,090
1,450
1,780
2,160
498
591
Reference
Ahsanul I ah, 1976
AhsanulIan, 1976
Ahsanul Iah, 1976
Eisler & Hennekey,
1977
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
Bengtsson, 1978
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1980
-------
Table 1. (Continued)
Species
Lobster (larvae),
Homarus amer i canus
Lobster (larvae),
Homarus amer i canus
Crab (larvae),
Carclnus maenas
Hermit crab (adult),
Pagurus lonql carpus
Starfish (adult),
Aster las forbesl
Munrnlchog (adult),
Fundulus heteroci Itus
Mummichog (larvae),
i Fundulus heteroci Itus
^ Atlantic si Iverside
( larvae),
Men i d 1 a men i d i a
Atlantic si Iverside
(larvae),
Menidia men Id la
Atlantic si Iverside
(larvae),
Menidia men Id la
Atlantic si Iverside
(larvae),
Menidia men id la
Atlantic si Iverside
(larvae),
Men i d i a men i d i a
Winter flounder (larvae),
Pseudop 1 euronectes
Method*
S, U
S, U
s, u
s, u
s, u
s, u
s, u
s, u
s, u
s, u
s, u
s, u
s, u
Hardness
(mg/l as
Chemical CaCO,)
Zinc ch lorlde
Zinc chloride
Zinc sulfate -
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
LC50/EC50
-------
Table I. (Continued)
w
Species Method*
Winter flounder (larvae), S, U
Pseudop 1 euronectes
amer 1 canus
« S = static; FT = flow-through; R =
•* Results are expressed as zinc, not
•••Calculated by loglt analysis of the
Species
Snail,
Physa heterostropha
Cladoceran,
Daphnla magna
Coho salmon,
Oncorhynchus klsutch
Rainbow trout.
Sal mo galrdneri
Brook trout,
Sa 1 ve 1 1 nus font I na 1 1 s
Goldfish,
Carasslus auratus
Fathead minnow,
Plmephales promelas
Guppy,
Poec ilia ret 1 cu 1 ata
Striped bass,
Chemical
Zinc chloride
Hardness Species Mean
(mg/l as LC50/EC50 Acute Value**
CaCO}) (jig/I)** (ng/l) Reference
4,920 9,460 U.S. EPA, 1980
renewal; M = measured; U = unmeasured
as the compound.
authors' data.
N Slope Intercept R Significance
4 1.18
5 0.90
2 1.23
22 0. 85
6 0.82
2 0.19
32 0. 78
2 3.90
4 0.79
2.19 0.99 «
1.87 0.80 N.S.
2. 86 -
3.18 0.83 **
4.48 0.% *•
8.20
5.35 0.60 *»
-4.53
4.05 0.22 N.S.
Morone saxatIlls
-------
Table 1. (Continued)
Species
Bluegl 1 1,
Lepomls macrochlrus
N
16
Slope
0.54
1 ntercept
6.80
R
0.76
S 1 qn 1 f 1 cance
*»
* = significant at p = 0.05
** = significant at p = 0.01
Arithmetic mean acute slope = 0.83 (n = 5, see text)
NJ
oo
-------
Table 2. Chronic values for zinc
Species
Cladoceran
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Chinook salmon,
Oncorhynchus tshawytscha
Rainbow trout,
^ Sal mo galrdnerl
to
^ Brook trout,
Salvellnus font! nails
Fathead minnow,
Pimephales promeias
Flagf ish,
Jordanella floridae
Mysid shrimp,
Mysidopsis bahia
Test*
LC
LC
LC
LC
ELS
ELS
LC
LC
LC
LC
Hardness
(mg/l as LI aits" Chronic Value**
Chemical CaCO?)
-------
Table 2. (Continued)
Acute-Chronic Ratio
Species
Cladoceran,
Daphnla magna
Cladoceran,
Oaphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Paphnla magna
Chinook salmon,
Oncorhynchus
tshawytscha
W Rainbow trout,
u Sal mo galrdnerl
o
Brook trout,
Salvellnus fontlnalls
Fathead minnow,
Pimephales promelas
Flagfish,
Jordanella floridae
Mysld shrimp,
Mysldopsls bah la
Hardness
(mg/l as
45
52-54
104-105
196-211
22-25
26-30
45
46
44
Acute
Value
(ug/l)
100
334
525
655
97-701
240-830*
2,000
600
1,500
498
Chronic
Value
(ug/l) Ratio
85 1.2
136 2.4
47 11
47 14
371 0.26-1.89
277 0.87-3.0
852 2.3
106 5. 7
47 32
166 3.0
* Acute values from Goettl et al. 1972.
Final Acute-Chronic Ratio =3.0 (see text)
-------
Table 3. Species mean acute Intercepts and values and acute-chronic ratos for zinc
Rank"
Species Mean Species Mean
Acute Intercept Acute-Chronic
(ug/l) Ratio
FRESHWATER SPECIES
29
28
27
26
25
24
23
22
21
20
19
18
17
16
Caddlsf ly.
Unidentified sp.
Damsel fly,
unidentified sp.
Pumpkinseed,
Leporels glbbosus
Worm,
Nals sp.
Midge,
Chironontus sp.
Banded kllllfish,
Fundulus dlaphanus
American eel,
Angullla rostrata
White perch,
Morone amerlcana
Goldfish,
Carasslus auratus
Guppy,
Poec Ilia ret 1 cu 1 ata
Scud,
Ganvnarus sp.
Blueglll,
Lepomls macroch 1 r us
Carp,
Cyprlnus carplo
Golden shiner,
2,260
1,019
732
716
708
699
531
524
413
367
315
293
285
255
-
NotemIgonus crysoleucus
-------
Table 3. (Continued)
Cd
Rank*
SpecIes
Species Mean Species Mean
Acute Intercept Acute-Chronic
(ug/l)
Ratio
15
14
13
12
11
10
9
8
7
6
5
4
3
2
r,~
Southern platyflsh,
Xiphophorus maculatus
Fathead minnow,
Plmephales promelas
Rotifer,
Phllodla acutlcornis
Brook trout,
Salvellnus fontlnalls
Coho salmon,
Oncorhynchus klsutch
Flagflsh,
Jordanella florldae
Atlantic salmon.
Sal mo salar
Sockeye salmon,
Oncorhynchus nerka
Striped bass,
Morone saxatl 1 Is
Snail,
Physa heterostropha
Rainbow trout.
Sal mo galrdnerl
Chinook salmon,
Oncorhynchus tshawytscha
Cladoceran,
Daphn la pu 1 ex
Longfln dace,
Agosla chrysogaster
172
169 5.7
92.8
82.6 2.3
81.4
64.9 32
57.9
57.6
49.3
42.0
26.2 0.87-3.0
23.1 0.26-1.89
21.2
9.09
-------
Table 3. (Continued)
W
co
CO
Rank*
1
Rank*
24
23
22
21
20
19
18
17
16
15
14
Species
Cladoceran,
Daphnla magna
Spec 1 es
Mummichog,
Fundulus heterocl Itus
Mud snal 1,
Nassarlus obsoletus
Starfish,
Aster las forbesl
Polychaete,
Nereis dlverscolor
Species Mean
Acute Intercept
(M9/I)
8.89
Species Mean
Acute Value
(ug/l)
SALTWATER SPECIES
70,600
50,000
39,000
24,600
Species Mean
Acute-Chronic
Ratio
1.2-14
Species Mean
Acute-Chronic
Ratio
-
Winter flounder, 9,460
Pseudop 1 euronectes amer 1 canus
Sandworm,
Nereis vlrens
Soft she! led clam,
Mya arenarla
Copepod,
Eurytemora af finis
Atlantic si Iverslde
Men Id la men Id la
Mussel ,
Mytllus edulls planulatus
Polychaete,
Capltel la capltata
8,100
6,330
4,090
3,640
3,380
2,440
-
-------
Table 3. (continued)
Rank*
13
12
11
10
9
8
7
6
5
4
3
2
1
Species
Copepod,
Tlgrlopus Japonlcus
Copepod,
Pseudodlaptomus coronatus
Copepod,
Nitocra splnlpes
Polychaete,
Neanthes arenaceodentata
Crab,
Carcinus naenas
Copepod,
Acartia clausl
Mysid shrimp
Mysldopsls bl gel owl
Mysid shrimp,
Mysldopsls bah la
Hermit crab,
Pagurus long 1 carpus
Lobster,
Homarus amer 1 canus
Oyster ,
Crassostrea virgin lea
Copepod,
Acartia tonsa
Hard she! led clam,
Mercenarla mercenarla
Species Mean
Acute Value
(ug/l)
2,160
1,780
1,450
1,270
1,000
950
591
498
400
321
310
290
166
Species Mean
Acute-Chronic
Ratio
3.0
* Ranked from least sensitive to most sensitive based on species mean
acute Intercept or value.
-------
Table 3. (continued)
Freshwater:
Final Acute Intercept = 7.02 ug/l
Natural logarithm of 7.02 = 1.95
Acute slope = 0.83
Final Acute Equation = e<0.83( In(hardness) 1+1.95)
Final Acute-Chronic Ratio =3.0 (Table 2)
Final Chronic Intercept = (7.02 ug/l)/3.0 = 2.34 ug/l
Natural logarithm of 2.34 = 0.85
Chronic slope = 0.83
Final Chronic Equation = e(0-831In(hardness)1+0.85)
Final Chronic Value = 47 ug/l (see text)
Saltwater:
Final Acute Value = 173 ug/l
Final Acute-Chronic Ratio =3.0 (Table 2)
Final Chronic Value = (173 ug/l)/3.0 = 57.7 ug/l
-------
Table 4. Plant values for zinc
Species
Alga,
Chorel la vulgaris
Alga,
Chorel la vulgaris
Alga,
Selenastrum caprlcornutum
Alga,
Selenastrum caprlcornutum
Alga,
Se 1 enastrum caprlcornutum
Alga,
Selenastrum caprlcornutum
Alga,
Selenastrum caprlcornutum
Alga,
Chlamydomonas sp.
Alga,
Scenedesmus quadricauda
Alga,
Cyclotella meneghlnlana
Diatom,
Nltzschia II near is
Eurasian waterml 1 fol 1 ,
Myrlophyllum splcatum
Eurasian waterml 1 fol 1 ,
Myrlophyllum splcatum
Eurasian waterml 1 fol 1 ,
Myriophyllum spicatum
Hardness
(mg/l as
Chemical CaCO,)
Result*
Effect (ug/D
Reference
FRESHWATER SPECIES
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc chloride
33-day EC 50
eel 1 number
96-hour EC50
growth
7-day LC100
7-day EC 1 00
growth
7-day Incipient
growth 1 nh 1 bi t Ion
14-day EC95
growth
14-day EC95
growth
5-day EC65
mean growth rate
5-day EC25
mean growth rate
5-day EC65
mean growth rate
12-hr LC50
32-day EC 50
root weight
32-day EC 50
root length
32-day EC 50
shoot length
5,100
2,400
700
120
30
40
68
15,000
20,000
20,000
4,300
21,600
21,600
20, 900
Rosko 4 Rachlin, 1977
Rachl In i Far ran,
1974
Bartlett, et al. 1974
Bartlett, et al
Bartlett, et al
Greene, et al.
Greene, et al.
Cairns, et al.
Cairns, et al.
Cairns, et al .
Patrick, et al.
Stanley, 1974
Stanley, 1974
Stanley, 1974
. 1974
. 1974
1975
1975
1978
1978
1978
1968
-------
Table 4. (continued)
to
OJ
-J
Species
Duckweed,
Lemna minor
Macrophyte,
El odea canadensis
Macrophyte,
El odea canadensis
Alga,,
Amph 1 d 1 n 1 um carter!
Alga,,
Amph Id 1 ilium carter!
Alga,
Dunallella tertlolecta
Kelp,
Laminar! a hyperiborea
Kelp,
Laminar la digltata
Giant kelp,
Macrocystls pyrlfera
Alga,
Phaeodacty 1 um tr 1 cor nu turn
Alga,
Phaeodacty lum trlcornutum
Alga,
Skeletonema costatum
Alga,
Skeletonema costatum
Chemical
Zinc sulfate
Z I nc su 1 fate
Z 1 nc su 1 fate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc chloride
Zinc sulfate
Zinc sulfate
Zinc sulfate
Hardness
(«g/l as
CaC03) Effect
28-day LC50
28-day LC50
28-day EC50
photosynthes I s
SALTWATER SPECIES
Growth Inhibition
Interaction with
copper on growth
Reduction in
potassium content
Growth inhibition
Growth Inhibition
50* inhibition
of photosy nt hes 1 s
Growth inhibition
Interaction with
copper on growth
Growth inhibition
Interaction with
copper on growth
Result*
(ug/l)
67, 700
22,500
8, tOO
400
100
6,500
250
100
10,000
25,000
1,000
200
50
Reference
Brown & Rattlgan,
1979
Brown & Rattigan,
1979
Brown & Rattlgan,
1979
Braek, et al. 1976
Braek, et al. 1976
Overnell, 1975
Hopkins & Kaln, 1971
Bryan, 1969
Clendenning & North,
1959
Jensen, et al. 1974
Braek, et al. 1976
Braek, et al. 1976
Braek, et al. 1976
-------
Table 4. (continued)
Ed
u>
oo
Hardness
(mo/I as
Chemical CaCO
Effect
Result*
(ug/l) Reference
Algae, Zinc sulfate
Thalassiosira pseudonana
Alga, Zinc sulfate
Thalassiosira pseudonana
Alga, Zinc sulfate
Scrlppslel la faeroense
Alga, Zinc sulfate
Procentlum ml cans
Alga, Zinc sulfate
Gymnodlnlum splendens
Alga, Zinc sulfate
Schroederel la schroederl
Alga, Zinc sulfate
Thalassiosira rotula
Growth Inhibition
Interaction with
copper on growth
Decrease 1 n ce 1 1
numbers
Decrease In eel 1
numbers
Decrease In eel 1
numbers
Decrease 1 n ce 1 1
numbers
Decrease In eel 1
numbers
400 Braek, et al., 1976
200 Braek, et al. 1976
1,000 Kayser, 1977
500 Kayser, 1977
100 Kayser, 1977
50 Kayser, 1977
100 Kayser, 1977
* Results are expressed as zinc, not as the compound.
-------
Table 5. Residues for zinc
w
1
10
lO
Species
Mayfly,
Ephemeral la grand is
Stonef ly,
Pteronarcys ca 1 1 f orn 1 ca
Atlantic salmon.
Sal mo salar
Flagflsh,
Jordanella florldae
Alga,
Cladophora sp.
Alga,
Fucus serratus
Alga,
Enteromorpha prolifera
Polychaete (adult),
Nereis dlversl color
Oyster (adult).
Crassest rea virgin lea
Gastropod (adult),
Llttorlna obtusata
Soft-shell clam (adult).
My a arenarla
Soft-shell clam (adult),
Mya arenarla
Mussel (adult),
Tissue
Whole body
Whole body
Whole body
Whole body
Soft parts
Soft parts
•Soft parts
Hardness
(mg/l as
Chemical CaCO,)
FRESHWATER SPECIES
Zinc sulfate 30-70
Zinc sulfate 30-70
Zinc sulfate 12-24
Zinc sulfate 44
SALTWATER SPECIES
Zinc ch lorlde
Zinc chloride
Z 1 nc su 1 fate
Zinc sulfate
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Blocon centra t ion
factor
1,130
107
51
432
4,680
16,600
1,530
20
16,700
670
85
43
225
Duration
(days)
14
14
80
100
34
140
12
34
140
50
50
112
13
Reference
Nehrlng, 1976
Nehrlng, 1976
Farmer, et al. 1979
Spehar, et al . 1978
Baud in, 1974
Young, 1975
Munda, 1979
Bryan & Hummers tone,
1973
Shuster & Pr ingle,
1969
Young, 1975
Prlngle, et al. 1968
Eisler, 1977b
Phil lips, 1977
Mytllus edulls
-------
Table 5. (Continued)
Species
Mussel (adult),
Mytl lus edulls
Mussel (adult),
Mytl lus edul Is
Crab (adult),
Carclnus roaenas
T 1 ssue
Soft parts
Soft parts
Muscle
Hardness
(mg/l as
Chemical CaCO^)
Zinc chloride
Zinc chloride
Zinc chloride
B 1 oconcentrat 1 on
factor
500
282
8,800
Duration
(days) Reference
21
Pentreath, 1973
35 Phillips, 1976
22 Bryan, 1966
W
-------
Table 6. Other data for zinc
Species
Chemical
Hardness
(nxj/1 as
CaCOx)
Duration
Effect
Result*
(U9/I)
Reference
FRESHWATER SPECIES
Algae,
Selenastrum caprlcornutum
Cladoceran,
Daphnia magna
Snal 1,
Gonobas Is II vescens
Snal 1,
Lymnaea emarglnata
Snal 1,
Physa Integra
Cladoceran,
Daphnia magna
to
£>. Cladoceran,
1-1 Daphnia maqna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex
Mayfly,
Fnh £*mf*r~a I la nr-aoHfc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
Zinc
phosphate
ch 1 or 1 de
sulfate
su 1 fate
su 1 fate
su 1 fate
su 1 fate
su Ifate
su 1 fate
su 1 fate
su 1 fate
su 1 fate
su 1 fate
su 1 fate
15
-
154
154
154
45
45
45
45
45
45
45
45
30-70
14
64
48
48
48
48
48
48
48
48
48
48
48
14
days
hrs
hrs
hrs
hrs
hrs
hrs
hrs
hrs
hrs
hrs
hrs
hrs
days
Growth
Inhibit ion
LC50
LC50
LC50
LC50
LC50
(5 C)
LC50
(10 C)
LC50
(15 C)
LC50
(25 C)
LC50
(5 C)
LC50
(10 C)
LC50
(15 C)
LC50
(25 C)
LC50
64
72
13,500
4,150
4,400
2,300
1,700
1,100
560
1,600
1,200
940
280
>9,200
Garton,
1972
Anderson,
Cairns,
Cairns,
Cairns,
Cairns,
Cairns,
Cairns,
Cairns,
Cairns,
Cairns,
Cairns,
Cairns,
Nehring,
et
et
et
et
et
et
et
et
et
et
et
1948
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
al.
1976
1976
1976
1978
1978
1978
1978
1978
1978
1978
1978
1976
-------
Table 6. (Continued)
Mayfly,
Ephemerella subvarla
Stonef ly,
Acroneuria ly cor las
Stonef ly,
Pteronarcys callfornlca
Midge,
Tanytarsus disslmllis
Caddlsfly,
Hydropsyche bettenl
Coho salmon,
Oncorhynchus kisutch
W Sockeye salmon,
.c, Oncorhynchus nerka
N)
Sockeye salmon,
Oncorhynchus nerka
Sockeye sa Imon,
(Zn accl 1 ma ted)
Oncorhynchus nerka
Sockeye salmon,
(Zn accl I ma ted)
Oncorhynchus nerka
Cutthroat trout.
Sal mo clark I
Rainbow trout.
Sal mo qalrdneri
R a i n Knw tr r»i it _
Chemical
Z 1 nc su 1 fate
Zinc sulfate
Zinc sulfate
Zinc chloride
Zinc sulfate
Zinc sulfate
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Z I nc ch 1 or I de
Zinc sulfate
Zinc sulfate
Hardness
(mg/l as
CaCO^) Duration
54 10 days
50 14 days
30-70 14 days
47 10 days
52 11 days
3-10 96 hrs
20-90 18 mos
53 115 hrs
53 115 hrs
22 96 hrs
34-47 14 days
5 days
240 48 hrs
Effect
Result*
(ug/l)
LC50 16,000
LC50 32,000
LC50 > 13, 900
LC50 37
LC50 32,000
WBC-T counts 500
depressed at
1/2 96-hr LC50
None 242
(embryo to
smolt)
LC50 447
LC50 >630
LC50 1,660
LC50 670
LC50 4,600
LC50 4,000
Reference
Warnick 4 Bel 1, 1969
Warnlck 4 Bel 1, 1969
Nehrlng, 1976
Anderson, et al. 1980
Warnick 4 Bell, 1969
McLeay, 1975
Chapman, 1978a
Chapman, 1978a
Chapman, 1978a
Chapman, 1978a
Nehrlng 4 Goettl, 1974
Ball, 1967
Brown 4 Dalton, 1970
Sal mo galrdnerl
-------
Table 6. (Continued)
U)
Species
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo alrdneri
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Chemical
Zinc sulfate
Zinc sulfate
Z 1 nc su 1 fate
Z 1 nc su 1 fate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc acetate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Hardness
(mg/l as
CaCOx)
40
40
40
14
320
320
320
15-20
320
38-54
25
333
13-15
Duration
24 hrs
24 hrs
24 hrs
21 days
48 hrs
48 hrs
48 hrs
96 hrs
7 days
3 days
14 days
5 days
22 mos
20 min
Effect
LC50
(5 C)
LC50
(15 C)
LC50
(30 C)
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC10
threshold
avoidance
level
Result*
((jg/l)
2,800
1,560
2,100
500-1,000
3,860
2,460
5,000
550
560
3,500
410
135
1,055
5.6
Reference
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Grande, 1967
Herbert & Shurben, 1964
Herbert & Van Dyke,
1964
Herbert 4 Wakeford,
1964
Hale, 1977
Lloyd, 1961
Lloyd, 1961
Nehrlng 4 Goettl, 1974
Sinley, et al. 1974
Sinley, et al. 1974
Sprague, 1968
-------
Table 6. (Continued)
Species
Rainbow trout,
Salmo galrdnerl
Brown trout,
Salmo trutta
Brown trout,
Salmo trutta
Atlantic salmon,
Salmo salar
Atlantic salmon,
Salmo salar
Atlantic salmon,
Salmo salar
Atlantic salmon,
Salmo salar
Atlantic salmon,
Salmo salar
Atlantic salmon
Salmo salar
Atlantic salmon
Salmo salar
Atlantic salmon,
Salmo salar
Brook trout,
Salvelinus font 1 nails
Goldfish,
Carasslus auratus
Goldfish,
Carasslus auratus
Goldfish,
Para«;«;lii«; auratus
Chemical
Z I nc su 1 fate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Zinc sulfate
Hardness
(mg/l as
CaCOjL
374
14
22-35
12-24
12-24
12-24
12-24
12-24
12-24
14
14
12-24
40
40
40
Duration
85 days
21 days
14 days
21 days
21 days
21 days
21 days
21 days
21 days
21 days
96-182 hrs
14 days
24 hrs
24 hrs
24 hrs
Effect
EC25 growth
Inhibition
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
LC50
Incipient
lethal level
LC50
LC50
(5 C)
LC50
(15 C)
LC50
(30 C)
Result*
(ug/l )
1,120
500-1,000
640
1,450
1,600
510
1,460
340
350
100-500
150-1,000
960
103,000
40,000
24,000
Reference
Watson & McKeown, 1976
Grande, 1967
Nehrlng & Goettl, 1974
Farmer, et al. 1979
Farmer, et al. 1979
Farmer, et al. 1979
Farmer, et al. 1979
Farmer, et al. 1979
Farmer, et al. 1979
Grande, 1967
Zitko & Carson, 1977
Nehrlng & Geottl, 1974
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
-------
Table 6. (Continued)
Spec 1 es
Golden shiner,
Notemlgonlus crysoleucus
Golden shiner,
Notemlgonlus crysoleucus
Golden shiner,
Notemlgonlus crysoleucus
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Guppy,
Poecllia ret 1 culatus
Striped bass (embryo),
tp Morone saxatllis
ui Bluegill,
Lepomis macroch 1 rus
Bluegl 1 1,
Lepomis macroch 1 rus
Bluegi II,
Lepomis macroch i rus
Bluegl 1 1,
Lepomis macroch i rus
Bluegi II,
Lepomls macroch 1 rus
Bluegi 1 1,
Lepomis macroch i rus
Bluegill,
Lepomls macroch i rus
Chemical
Z 1 nc su 1 fate
Z i nc su 1 fate
Z 1 nc su 1 fate
Z 1 nc su 1 fate
Z 1 nc acetate
Zinc sulfate
Zinc sulfate
Z i nc su 1 fate
Z 1 nc su 1 fate
Zinc chloride
Z 1 nc su 1 fate
Z 1 nc su 1 fate
Zinc sulfate
Hardness
(mg/l as
CaCOO
40
40
40
203
20
80
137
40
40
40
45
370
370
370
Durat 1 on
24 hrs
24 hrs
24 hrs
10 mos
96 h
90 days
96 hrs
24 hrs
24 hrs
24 hrs
96 hrs
20 days
20 days
20 days
Effect
LC50
(5 C)
LC50
(15 C)
LC50
(30 C)
EC65
fecundity
LC50
EC60
growth
LC50
(5 C)
LC50
(5 C)
LC50
(15 C)
LC50
(30 C)
LC50
periodic
low DO
LC50
(DO 1.7)
LC50
(DO 1.9)
LC50
(DO 3.2)
Result*
1 1 ,400
7,760
8,330
180
880
1,150
1,850
23,000
19,100
8,850
2,350
7,200
7,500
10,700
Reference
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Brungs, 1969
Pickering & Henderson,
1966
Crandal 1 & Goodnight,
1962
O'Rear, 1972
Cairns, et al. 1978
Cairns, et al. 1978
Cairns, et al. 1978
Cairns i Scheier, 1 957a
Pickering, 1968
Pickering, 1968
Pickering, 1968
-------
Table 6. (Continued)
Spec 1 es
Bluegi 1 1,
Lepomls macroch 1 rus
Bluegi 1 1,
Lepomls macroch 1 rus
Bluegi 1 1,
Lepomls macroch I rus
Bluegi 1 1,
Lepomis macroch 1 rus
Bluegi 1 1,
Lepomis macroch 1 rus
Bluegi 1 1,
Lepomis macroch I rus
W
1
cri Marine isopod,
Idotea baltica
Marine isopod,
Idotea baltica
Marine isopod,
Idotea baltica
Marine isopod,
Idotea baltica
Marine Isopod,
Jaera a Ibifrons
Marine isopod,
Jaera a Ibifrons
Marine Isoood.
Hardness
(mg/l as
Chemical CaCO,) Duration
Zinc sulfate 370 20 days
Zinc sulfate 370 20 days
Zinc sulfate 370 20 days
Zinc sulfate - 1-24 hrs
Zinc sulfate 51 3 days
Zinc phosphate 46 96 hrs
SALTWATER SPECIES
Zinc sulfate - 96 hrs
Zinc sulfate - 78 hrs
Zinc sulfate - 72 hrs
Zinc sulfate - 48 hrs
Zinc sulfate - 72 hrs
Zinc sulfate - 67 hrs
Zinc sulfate - 52 hrs
Result*
Effect tyig/L)
LC50 10,500
(DO 3.2)
LC50 12,000
(DO 5.4)
LC50 10, 700
(DO 5.3)
Increased 3,000
cough response
Lethal to fry 235
No death 32,000
40* mortality 10,000
(35 g/kg sal.)
60? mortality 10,000
(28 g/kg sal.)
75$ mortality 10,000
(2 1 g/kg sa 1 . )
100? mortality 10,000
{14 g/kg sal.)
10? mortality 10,000
(35 g/kg sal.)
30? mortllty 10,000
(3 g/kg sal.)
80? mortality 10,000
Reference
Pickering, 1968
Pickering, 1968
Pickering, 1968
Sparks, et al. 1972a
Sparks, et al. 1972b
Cairns, et al. 1971
Jones, 1975
Jones, 1975
Jones, 1975
Jones, 1975
Jones, 1975
Jones, 1975
Jones, 1975
Jaera albifrons
(0.4 g/kg sal.)
-------
Table 6. (Continued)
Spec 1 es
Hermit crab (adult),
Pagurus lonqicarpus
Crab ( larvae),
Khlthropanopeus harrlsi
Mummlchog (adult),
Fundulus heteroclltus
Mummlchog (adult),
Fundulus heteroclltus
Mummichog (adult),
Fundulus heteroclltus
Mummlchog (adult),
Fundulus heteroclitus
Mummlchog (adult),
I Fundulus heteroclltus
Mummlchog (adult),
Fundulus heteroclitus
Mummichog (adult),
Fundulus heteroclltus
Mummichog (adult),
Fundulus heteroclitus
Mummlchog (adult),
Fundulus heteroclltus
Atlantic salmon (smolt),
Salmo salar
Atlantic salmon (smolt),
Salmo salar
Atlantic salmon (smolt),
Salmo salar
Chemical
Zinc ch loride
Zinc ch loride
Zinc ch loride
Z Inc ch lorlde
Zinc ch loride
Zinc ch lorlde
Zinc chloride
Zinc ch lorlde
Zinc chloride
Zinc chloride
Zinc ch loride
Zinc sulfate
Zinc sulfate
Zinc sulfate
Hardness
(mg/l as
CaC03) Duration
168 hrs
- 16 days
96 hrs
24 hrs
168 hrs
168 hrs
168 hrs
14 days
48 hrs
192 hrs
192 hrs
48 hrs
48 hrs
48 hrs
Effect
LC50
Delayed
development
LC28
Hlstologlcal
damage
LCO
LC50
LC100
Increase in
liver ALA-D
enzyme activity
LCIOO
LCO
LC50
50$ survival
(3 gAg sa 1. )
50$ survival
(7 g/kg sal.)
50$ survival
(14 q/kq sal. )
Result*
(ug/l)
200
50
60,000
60,000
10,000
52,000
120,000
10,000
157,000
43,000
66,000
6,000
15,000
35,000
Reference
Eisler 4 Hennekey,
1977
Benijts-Claus 4
Benljts, 1975
Els ler 4 Gardner,
1973
Eis ler 4 Gardner,
1973
Eisler 4 Hennekey,
1977
Eisler 4 Hennekey,
1977
Eisler 4 Hennekey,
1977
Jackim, 1973
Eisler, 1967
Eisler, 1967
Eisler, 1967
Herbert 4 Wakeford,
1964
Herbert 4 Wakeford,
1964
Herbert 4 Wakeford,
1964
-------
Table 6. (Continued)
Hardness
(mg/l as Result*
Species Chemical CeCOO Duration Effect (fig/I) Reference
Atlantic salmon (smolt), Zinc sulfate
Sal mo sa lar
Rainbow trout (yearling). Zinc sulfate
Sal mo gairdneri
Rainbow trout (yearling). Zinc sulfate
Sal mo gairdneri
Rainbow trout (yearling), Zinc sulfate
Sal mo gairdneri
Rainbow trout (yearling). Zinc sulfate
Sal mo gairdneri
Protozoan, Zinc sulfate
Crlstlgera sp.
Protozoan, Zinc sulfate
i Crlstlgera sp.
^
00 Polychaete, Zinc sulfate
Ctenodrllus serratus
Sandworm (adult). Zinc sulfate
Nereis virens
Polychaete, Zinc sulfate
Ophryotrocna dladema
Polychaete, Zinc sulfate
Ophryotrocha labronica
Hard-shell clam (larva). Zinc chloride
Mercenar la mercenar la
Hard-shell clam (larva), Zinc chloride
Mercenar la mercenar la
Soft-shell clam (adult), Zinc chloride
Mya arenaria
48 hrs 50$ survival 28,000 Herbert 4 Wakeford,
(26 g/kg sal.) 1964
48 hrs 50$ survival 15,000 Herbert 4 Wakeford,
(3 g/kg sal.) 1964
48 hrs 50$ survival 25,000 Herbert & Wakeford,
(7 g/kg sal.) 1964
48 hrs 50$ survival 85,000 Herbert 4 Wakeford,
( 1 4 g/kg sa 1 . ) 1964
48 hrs 50$ survival 35,000 Herbert 4 Wakeford,
(26 g/kg sal.) 1964
4-5 hrs Reduced growth 125 Gray, 1974
Growth reduction 125 Gray 4 Ventilla, 1973
21 days Reduced survival 10,000 Relsh 4 Carr, 1978
168 hrs LC50 2,600 Eisler 4 Hennekey,
1977
21 days Reduced survival 1,750 Relsh 4 Carr, 1978
13 hrs LC50 1,000 Brown 4 Ahsanullah,
1971
10 days LC50 195 Calabrese, et al.
1977
12 days LC95 341 Calabrese, et al.
1977
168 hrs LC50 3,100 Eisler 4 Hennekey,
(20 C) 1977
-------
Table 6. (Continued)
Spec 1 es
Soft-shell clam (adult).
Mya arenarla
Mud snal 1 (adult),
Nassarlus obsoletus
Mud snal 1 (adult).
Nassarlus obsoletus
Hard-shell clam (embryo).
Mercenarla mercenarla
Hard-shell clam (larva).
Mercenarla mercenarla
Oyster (larva).
Crassostrea glgas
f Oyster (larva).
^ Crassostrea glgas
if) -, - — - - - — J< MP
\±s
Oyster ( larva).
Crassostrea glgas
Oyster ( larva),
Crassostrea glgas
Oyster ( larva).
Crassostrea vlrglnlca
Oyster (larva),
Crassostrea virgin lea
Sea urchin (spermatozoa).
Arbacla puctulata
Sea urchin (embryo),
Arbacia puctulata
C+=.-«l<:K farful-M
Hardness
(mg/l as
Chemical CaCOO
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
Zinc sulfate
Z 1 nc su 1 fate
Zinc sulfate
Zinc chloride
Zinc chloride
Zinc chloride
Zinc chloride
-
Zinc chloride
Ourat 1 on
168 hrs
72 hrs
168 hrs
42-48 hrs
12 days
5 days
48 hrs
6 days
48 hrs
48 hrs
48 hrs
4 mins
15 hrs
168 hrs
Result"
Effect Cfig/|)
LC50 1
(22 C)
Decreased oxygen
consumption
LC50 7
LC100
LC5
Substrate
attachment
inhibition
Reduced development
Growth inhibition
Abnormal she 1 1
development
LCO
LC100
Decreased
mot i 1 1 tv
IIH^I 1 1 1 i Jr
Abnorma 1
development
LC50
,550
200
,400
279
50
125
125
125
70
75
500
1,635
1,250
2,300
Reference
Elsler, I977a
Maclnnes i Thurberg,
1973
Elsler 4 Hennekey,
1977
Calabrese & Nelson,
1974
Calabrese, et al.
1977
Boyden, et al. 1975
Brereton, et al. 1973
Brereton, et al. 1973
Nelson, 1972
Calabrese, et al .
1973
Calabrese, et al.
1973
Young 4 Nelson, 1974
Waterman, 1937
Els ler 4 Hennekey,
Aster I as forbesl
1977
-------
w
i
Ul
o
Table 6. (Continued)
Species
Starfish (adult).
Aster I as forbesi
Chemical
Zinc chloride
Hardness
(mg/l as
CaCOy)
DuratIon
24 hrs
Effect
Result*
(pg/l)
Equilibrium loss 2,700
Reference
Galtsoff & Loosanoff,
1939
* Results are expressed as zinc, not as the compound.
-------
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Judy, R.D., Jr. and P.H. Davies. 1979. Effects of calcium addition as
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65 SQ
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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 essen-
tiality 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 recent 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, 1976, 1978; Sandstead, 1973, 1975; Vallee, 1959;
Underwood, 1977). The National Research Council (NRC) report con-
tains 1,855 references and gives information not only on metabo-
lism and essentiality of zinc for human beings but also much in-
formation on occurrence of zinc, analytical methods, and human
health hazards from excessive exposure to zinc. Since this docu-
ment relies to a large extent 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.
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The information given will rely mainly on the previously men-
tioned references and specific references will only be given when
there is information which might add to the understanding of the
metabolism and health effects of zinc, especially in humans.
EXPOSURE
Ingestion from Water
The National Research Council (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 U.S. Department of
Health, Education and Welfare (U.S. DHEW, 1970) 2,595 water sam-
ples were tested and of them eight 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 concentrations increased in the distribution
system. Tapwater could thus have concentrations around 5 mg/1.
In a study by U.S. EPA (1975) it was found that in 591 water sam-
ples all had zinc concentrations below 4 mg/1.
Uncontaminated fresh water generally contains zinc at less
than 0.01 mg/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 be-
low 0.1 mg/1 (Durum, et al. 1971).
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The concentration of zinc in both natural waters and in
drinking water is 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 food-
stuffs 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 concentra-
tions and contribute little to the daily intake. Zinc concentra-
tions in milk are generally low, but a high intake of 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 pota-
toes only provided 8 and 6 mg/kg, respectively. These data were
obtained from Food and Drug Administration (FDA) market basket
studies which are based on the diets of 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 liv-
ing 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 (NAS), 1974] recommended
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that adults should have a zinc intake of 15 mg/day, but pregnant
women should have an intake of 20 mg/day and lactating women an
intake of 25 mg/day. As a requirement of preadolescent children,
10 mg/day was recommended. In infants up to six months old, 3
mg/day was recommended and for children aged 0.5 to 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. These recommended doses take individual variations
into account. An intake less than the recommended intake does not
necessarily mean that zinc deficiency will occur.
A bioconcentration factor (BCF) relates the concentration of
a chemical in aquatic animals to the concentration in the water in
which they live. An appropriate BCF can be used with data con-
cerning food intake to calculate the amount of zinc which might be
ingested from the consumption of fish and shellfish. Residue data
for a variety of inorganic compounds indicate that bioconcentra-
tion factors for the edible portion of most aquatic animals are
similar, except that for some compounds bivalve molluscs (clams,
oysters, scallops, and mussels) should be considered a separate
group. An analysis (U.S. EPA, 1980) of data from a food survey
was used to estimate that the per capita consumption of freshwater
and estuarine fish and shellfish is 6.5 g/day (Stephan, 1980).
The per capita consumption of bivalve molluscs is 0.8 g/day and
that of all other freshwater and estuarine fish and shellfish is
5.7 g/day.
Bioconcentration factors are available for the edible por-
tions of several aquatic species (Table 1).
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TABLE 1
Bioconcentration Factors of Edible Portions of Aquatic Organisms
Species
BCF
Reference
Oyster (adult),
Grassestrea virginica
Soft-shell clam,
Mya arenaria
Soft-shell clam,
Mya arenaria
Mussel,
Mytilus edulis
Mussel,
Mytilus edulis
Mussel,
Mytilus edulis
Crab,
Carcinus maenas
16,700
85
43
225
500
282
8,800
Shuster and Pringle,
1969
Pringle, et al. 1968
Eisler, 1977
Phillips, 1977
Pentreath, 1973
Phillips, 1976
Bryan, 1966
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The geometric mean of the values for bivalve molluscs is 353,
but the value for the crab seems too high, considering that values
for the whole body of two species of fish were 51 (Farmer, et al.
1979) and 432 (Spehar, et al. 1978). Based on the available data
for copper and cadmium, the mean BCF value for other species is
probably about 1 percent of that for bivalve molluscs. If the
values of 353 and 3.5 are used with the consumption data, the
weighted average bioconcentration factor for zinc and the edible
portion of all freshwater and estuarine aquatic organisms consumed
by Americans is calculated to be 47.
Air quality data compiled in the NRC document (1978) show
that zinc concentrations throughout the U.S. generally are less
than 1 ug/m3 (Chapter 3 p. 42-43). In 1975 and 1976, U.S. EPA
(1979) observed zinc concentrations at approximately 50 National
Air Surveillance Network sites throughout the U.S. Zinc concen-
trations is most areas were below 1 ug/m3, quarterly average.
The air levels of zinc are, in most areas, fairly constant.
As an example, Lioy, et al. (1978) presented data on zinc concen-
trations in New York City during the years 1972 to 1975 where the
annual averages varied from 0.29 to 0.38 ug/m3. 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/m3. The
24-hour values ranged from 0.27 to 15.7 ug/m3. It should be
mentioned that the average lead and cadmium concentrations were 11
and 0.8 ug/m3, respectively, indicating very severe environ-
mental pollution. The U.S. data may be compared to data from 15
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cities in a heavily industrialized European country, Belgium
(Kretzschmar, et al. 1977). During the period May 1972 to April
1975 the average concentrations in 15 locations were from 0.22 to
3.05 ug/m3. The highest value recorded during 24 hours was 57
ug/m3.
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/m3 was found. In the air over the
Atlantic Ocean concentrations were from 0.3 to 27 ng/m3 (Duce,
et al. 1975; Maenhaut and Zoller, 1977; Zoiler, et al. 1974).
In cigarettes and other tobacco products zinc concentrations
have been reported to vary from 12.5 to 70 ug/g (Menden, et al.
1972; Dermelj, et al. 1978; 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 in-
haled. 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.
The major source of zinc for the general population in the
U.S. is food. The average intake is generally above 10 mg in
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adults. An individual inhaling air with an average concentration
of 5 ug/m3, would have an additional daily intake of 100 ug /
assuming that he inhales 20 m3 of air per day. Smoking would
contribute even less than that. Compared to the intake via food,
airborne 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 recom-
mended limits. In people with recommended daily intakes of zinc,
i.e., 15 to 20 mg, the additional intake via water will result in
total daily intakes of 25 to 30 mg. As discussed later, the
homeostatic regulation of zinc ensures that such amounts and even
larger amounts can generally be well tolerated.
PHARMACOKINETICS
Absorption
The fate of inhaled particles containing zinc will depend on
particle size and solubility as well as functional state of the
lungs. The quantitative 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 com-
pounds, 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
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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 in-
haled material will be transported to the gastrointestinal tract
via ciliary activity and some zinc may also be absorbed that way.
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 65zn
as the chloride was rapidly taken up, with plasma peak values
within four 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 difficul-
ties in assessing the absorption of zinc, since there is also con-
siderable excretion of absorbed zinc via the gastrointestinal
tract. There are also several other earlier studies which show
that there are wide variations in the absorption 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 defi-
ciency it has been noted that the effect of zinc therapy is en-
hanced 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). Since
phytates are found in cereals, zinc in vegetable diets that
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include large amounts of unleavened bread may be less available
for absorption. Arvidsson, et al. (1978) found that the average
absorption of 55Zn 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. 1978). Zinc in animal 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. They were compared with eight
women who did not take contraceptive pills (King, et al. 1978) .
All were of similar age. Zinc was administered as a stable iso-
tope, 70Zn, and the absorption was determined from the differ-
ence between intake and fecal output of the stable isotope which
was measured by neutron activation analysis. Among the women tak-
ing the contraceptive agents, the average absorption was 33 per-
cent and in the control group it was 46 percent. The difference,
however, was not statistically significant, and the authors con-
cluded 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
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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 absorp-
tion.
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. (1977) 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; Schricker and Forbes, 1978; Lonnerdal, et al. 1979;
Evans and Johnson, 1979). The data are controversial and at pres-
ent no certain conclusions can be drawn regarding the nature of
the ligand or ligands. It has also been shown by Cousins, et al.
(1978) that degradation products of intestinal proteins including
metallothionein may occur as low molecular weight zinc binding
complexes in rat intestine. The role of ligands in zinc absorp-
tion has recently been discussed by Cousins (1979).
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Keen and Hurley (1977) have shown that zinc salts will be
absorbed through intact skin of the rat. According to these
authors the amount of zinc absorbed was higher in zinc-deficient
animals and was of a magnitude which might be clinically signifi-
cant.
Hallmans (1978a,b) 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 sys-
temic 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 intra-
uterine device containing copper and zinc, a slight rise in serum
zinc could be shown, but no abnormal values were found.
Distribution
Zinc is found in erythrocytes mainly due to the presence of
the zinc metalloenzyme carbonic anhydrase and in leucocytes where
several zinc metalloenzymes 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 at 2-macroglobulin and a
few percent to amino acids. In the albumin and the amino acids
there is an exchange of zinc, whereas there is no exchange with
zinc in the cX2-macroglobulin. The zinc bound to amino acids
constitutes the diffusible serum zinc (Giroux, 1975; Giroux, et
al. 1976; NRC, 1978).
C-12
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Of special interest is the relationship between zinc and his-
tidine. It has been shown in human beings that oral administra-
tion of histidine will cause decreases in serum zinc and an in-
crease in urinary zinc excretion (Henkin, et al. 1975). This ob-
servation 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 excre-
tion of zinc. This is thought to be one explanation for the
losses of zinc seen in patients given parenteral hyperalimenta-
tion, 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. High concentrations of zinc also occur in the muscle,
bone, liver, kidney, pancreas, and some endocrine glands, especi-
ally 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 varia-
tions 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 concentra-
tions, and renal zinc concentrations will vary with age (Elinder,
C-13
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et al. 1978; Piscator 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. Zinc is
also found in metallothionein.
Excretion
Zinc is mainly excreted via the gastrointestinal tract but
part of that zinc is reabsorbed. Urinary excretion of zinc is
relatively small but with certain conditions, i.e., extreme heat
or exercise, much larger quantities may be excreted in sweat (Conn
and Emmett, 1978; Hohnadel, et al. 1973). Zinc is also excreted
via hair and milk, and in the female there is a placental transfer
to the fetus.
Losses of zinc may also occur via the skin and menstrual
blood losses. Molin and Wester (1976) determined by neutron acti-
vation the zinc content of epidermis. They calculated that the
daily losses by desquamation would be about 20 to 40 ug, only
about one-tenth (1/10) of the urinary excretion.
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 65Zn to human beings, the half-time may vary from about 200
to about 400 days, depending on the zinc status (NRG Chapter 6 pp.
151-154). Arvidsson, et al. (1978) gave eight subjects single
injections of 65Zn. 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
C-14
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osteoarthritis. They were given an oral dose of 65Zn. In
certain body compartments, e.g., bone, the half-time may be con-
siderably longer (NRC Chapter 6 pp. 149-154).
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 comprehensive report on metallothionein has been
prepared (Nordberg and Kojima, 1979). Mammalian metallothionein
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 amino acids and histidine.
Metallothionein 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 6 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 cop-
per are the major constituents, whereas in animals exposed to cad-
mium, cadmium will be the dominating metal especially in the renal
protein. A number of factors can induce the synthesis of metallo-
thionein. in addition to administration of the above-mentioned
metals, metallothionein synthesis seems also to be indirectly in-
duced by factors that might influence zinc metabolism. Thus, en-
vironmental stresses of different kinds may induce the synthesis.
With regard to zinc metabolism, it has been shown that paren-
teral or dietary administration of zinc will cause an increase of
C-15
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the synthesis of metallothionein (Bremner and Davies, 1975;
Richards and Cousins, 1975a,b, 1977). Recently, it was shown that
hepatic zinc was increased and metallothionein synthesis stimu-
lated 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 in 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. Similar indications are given by reports from several
investigators of finding large amounts of metallothionein contain-
ing zinc and copper in fetal livers (Bremner, et al. 1977; Hartman
and Weser, 1977; Ryden and Deutsch, 1978). 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).
In the National Research Council report (1978), extensive
information 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 concentration in humans is approximately 1
mg/1, the same in healthy men and women. The zinc content of
whole blood will be about five times higher than the serum level,
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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 taking contraceptive pills, during preg-
nancy, and as a result of certain stresses such as infections. In
the same individual the zinc concentration in serum will be higher
than in plasma mainly due to the release of zinc from platelets
(Foley, et al. 1968). In 14 subjects the mean serum level was
1.15 mg/1 and the mean plasma level 0.98 mg/1, the average differ-
ence 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/1 (range 0.74 to 2.2 mgl), and in 95
women it was 1.11 mg/1 (range 0.64 to 1.82 mg/1). The difference
was highly significant according to the author. It was not stated
to what extent 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 testo-
sterone in males aged 36 to 60 years. In men 28 to 35 years of
C-17
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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 after overnight
fasting.
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. Additional data have been provided by
Blinder, 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 nonsmokers.
Among nonsmokers there was a tendency to decreased zinc excretion
from about age 20 to higher ages (Table 2).
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 cad-
mium (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 cal-
culated 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, the average concentrations of zinc in
liver and pancreas were 45 (s.d. = 13.6) and 27 (s.d. = 7.2) mg/kg
wet weight, respectively. In these organs the concentrations of
C-18
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O
TABLE 2
Zinc Concentrations in the Urine of Swedish Peoplet
Group
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
~f" *-! rui v oo • Pi i »~i/-l^iv- *-> 4-
N umber of
Persons
4
10
10
10
16
15
9
11
9
5
5
1
1
4
10
10
ri 1 1 n *7 O
Zinc, Average (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
Dev iation
(a)*
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
Zinc,
Calculated
Average (mg/24 hr)
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
• I
*a, arithmetic averages.
-------
zinc were normally distributed, whereas zinc concentrations in
renal cortex had a log-normal distribution. When the renal zinc
bound to metallothionein (assuming a cadmium-zinc ratio of 1.0 in
metallothionein) was subtracted from total zinc, the basal zinc
concentrations thus obtained had a normal distribution (Blinder,
et al. 1977). The highest concentrations of zinc are found in
the prostata, where the concentration 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 depend-
ing on age and geographical location (MRC Chapter 6 pp. 140-141).
Sorenson, 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 to 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,
et al. 1974; Hambidge and Droegemueller, 1974). The determination
of zinc in hair has been used as a screening tool for zinc defi-
ciency (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 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. Where-
as, in the controls the absorption was about 15 percent, measured
by examining the radioactivity in the carcass one hour after a
C-20
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gastric dose of 65Zn/ j_t was about 35 and 50 percent, respec-
tively, in the two experimental groups.
Weigland and Kirchgessner (1978) studied the homeostatic mech-
anisms 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 six 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 rela-
tively 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 5.6, 10.6, and 18.2, indicating that in this study this
supply was not sufficient. In the three highest exposure groups
both total 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 gav-
age, an oral dose of 65Zn as the chloride. Feces were col-
lected for seven days. The elimination of fecal zinc was similar
C-21
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in all groups except the control group irrespective of length of
exposure, whereas the fecal elimination of 65Zn 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 65Zn 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 the kidneys, muscle tissue, and the
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 1,200 to 8,400 ppm zinc for three weeks. One week before
sacrifice each rat was given 65zn 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, feed consumption,
or produce any obvious signs of toxicity. In controls 65 percent
of the 65Zn was eliminated in one week in contrast to 86 per-
cent in the rats given 1,200 ppm zinc in the diet. At still
higher levels of dietary zinc there was no further increase of
fecal 65Zn. Rats given 1,200 ppm zinc in the diet had sig-
nificantly higher levels of stable zinc in the liver, kidney, and
tibia than controls, whereas there was no change in concentrations
in the heart and muscle tissue. No further increase was seen at
levels of 2,400 to 7,200 ppm in the diet, but at 8,400 ppm level a
new increase was seen, also in the heart but not in muscle tissue.
C-22
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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 the tibia
where, at the highest levels, there occurred an increase compared
to the previous levels. In the heart and muscle tissue there was
a slight but continuous decrease. In the liver and kidneys there
was no change. The authors concluded that the data indicated that
there was a good homeostatic control in the range 2,400 to 7,200
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 the
liver, kidneys, and pancreas than calves fed a diet containing 34
mg/kg. There was, however, no change in heart or muscle zinc
levels.
The topics of zinc essentiality and zinc deficiency have been
extensively treated in the National Research Council report (1978)
and also in a recent review by Prasad (1978). In 1934, it was
shown by Todd, et al. (1934) 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 humans.
In humans, zinc is necessary for normal growth and for normal
development of the gonads. Prasad, et al. (1963) found that in
certain villages in Egypt many subjects exhibited a syndrome char-
acterized by dwarfism and anemia, hypogonadism, hepatosplenome-
galy, rough and dry skin, and mental lethargy. There, young per-
sons had a very low intake of animal proteins with bread as their
C-23
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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 nor-
mal; and that the excretion of zinc in feces and urine was less
than in controls. Improvements were seen after oral administra-
tion 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 concen-
trations in hair were used as an index of the zinc status. Ham-
bidge, et al. found that in 132 children ages 4 to 16, 10 children
had hair zinc concentrations below 70 mg/kg, whereas most children
had concentrations above 125 mg/kg. Eight out of ten 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 the zinc deficiency. In these children hypo-
geusia (impaired taste acuity) was also found. After zinc supple-
mentation, 1-2 mg zinc sulfate/kg body weight/day for 1-3 months,
this condition was normalized. An increase in hair zinc could be
shown parallelling the supplementation with zinc. In five chil-
dren with hair zinc levels of 10 to 63 mg/kg before therapy, the
levels were 67 to 170 mg/kg after four months of therapy. There
are studies in other parts of the U.S. showing that low zinc
C-24
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levels in children's hair are not an uncommon finding (Prasad,
1978).
The reason for the signs and symptoms caused by the zinc de-
ficiency 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 metalloenzymes. Typical
examples of such metalloenzymes are alcohol dehydrogenase, car-
boxypeptidase, leucine aminopeptidase, alkaline phosphatase, car-
bonic anhydrase, RNA-polymerase, and DNA-polymerase. Also, thymi-
dinekinase 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 to depletion of body zinc stores
(Atkin-Thor, et al. 1978);
(2) Zinc deficiency after intravenous hyperalimenta-
tion, which might lead to increased excretion of
zinc because of the large amounts of amino acids in
the infusion fluids (Bernstein and Leyden, 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. 1978; 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
C-25
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factor or factors necessary for the absorption of zinc. Signs in
this disease may come from many organs, among them the skin, cen-
tral 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 con-
dition.
Prasad, et al. (1978b) 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 Zn at a level of about 3 mg/day for several weeks.
In order to decrease the zinc intake it was necessary to give sub-
jects 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 signifi-
cantly in all subjects and in 3 of 4 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 phos-
phatase activity decreased along with a decrease in plasma lactic
dehydrogenase activity during the zinc depletion. In the connec-
tive tissue the RNA and DNA ratio showed changes during the re-
striction period.
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
C-26
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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.
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 impor-
tance for the development of such effects. Health effects ob-
served 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 hy-
giene and in the recent National Institute on Occupational Safety
and Health (NIOSH) criteria document on zinc oxide (NIOSH, 1975).
Acute, Subacute, and Chronic Toxicity
Most of our knowledge about metal fume fever and its rela-
tionship 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 al. 1927, 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 fever
is described in all textbooks on occupational hygiene. In sum-
marys 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.
C-27
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Metal fume fever only appears after exposure to freshly pro-
duced metal fumes (McCord, 1960; Rohrs, 1957) which can penetrate
deep into the alveoli. Zinc oxide dust or other metal dusts are
not capable of producing the disorder. 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, sweat-
ing, and muscle pains. Among the laboratory findings leukocytosis
is the most prominent. There have never been any fatalities from
metal fume fever, nor does it cause long-term sequelae. 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. 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. In a study by Sturgis, et al. (1927) two subjects
were exposed to zinc oxide fumes at a level of 600 mg zinc/m3.
It was calculated that the subjects inhaled 48 and 74 mg zinc,
respectively.
There was a report on acute emphysema in cattle reported to
have been exposed to zinc oxide fumes (Hilderman and Taylor,
C-28
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1974). This episode occurred in a barn where oxyacetylene cutting
and arc welding of galvanized pipe were done during remodeling of
the barn. Three heifers were severely affected and 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 ani-
mals examined. In this case, a galvanized material was suspected
but the extremely severe condition 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 responsible.
Acute pulmonary damage and even death may occur after the in-
halation of zinc chloride which is the major component in smoke
coming from so-called "smoke bombs" which are often used in mili-
tary exercises. Accidental inhalation 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
Milliken, et al. (1963).
The effects of inhaltion of zinc chloride in smoke from smoke
bombs have also been described by Schmal (1974) who reported on 11
cases, of which 2 had very severe reactions including edema of the
lungs. However, no severe sequelae were seen. In one case, how-
ever, it was almost two years before the lung function was nor-
malized .
Batchelor, et al. (1926) made an extensive investigation of
workers exposed to zinc in a smelter in New Jersey. The authors
C-29
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pointed out that this smelter was well suited for studies on
chronic effects of zinc since the amounts of lead, cadmium, and
arsenic in the ore were very low compared with other types of zinc
ores processed in other parts of the U.S. Of a total work force
of 1,620 men, a number of workers were selected from different
work areas for the special studies. Twelve men were selected from
bag rooms where zinc oxide was handled. From a zinc oxide packing
house five men were selected; four of them never wore respirators.
From another zinc oxide plant two men were selected and two men
were selected from a plant handling metallic zinc. Finally, three
workers from a lithopone packing house were selected. A number of
determinations of zinc concentrations in air were made. In the
bag house an average concentration of 14 mg/m3 was observed. In
other workplaces mean concentrations were generally below 35
mg/m3. In the zinc dust plant a maximum concentration of 130
mg/m3 was measured. The 24 subjects underwent a number of ex-
aminations which included x-rays, physical examinations, inter-
views, blood pressure measurements, and measurements of zinc in
blood, urine, and feces. Regarding the laboratory findings, it
may be noted that 14 of the 24 men showed a slight leukocytosis;
hemoglobin was reported to range between 72 and 97 percent with an
average of 81 percent (100 percent is assumed to be 160 ug/D •
Twenty-four-hour zinc elimination via feces in controls was re-
ported to vary from about 4 to 20 mg, with an average of 9.32 mg,
which is in good agreement with present daily values. In the ex-
posed subjects, 24-hour excretion of zinc via feces averaged 46.8
mg which indicates an exposure via the gastrointestinal tract or
C-30
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massive excretion into the intestine. The conclusion of the
authors was that the workmen could be exposed to zinc compounds in
a smelter for decades without any symptoms or chronic disease.
Chmielewski, et al. (1974a,b) 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/m3 of zinc oxide, but a maximum
value of 58 mg/m3 was found during welding on one occasion.
Laboratory investigations showed a tendency to leukocytosis, 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/m3, with mean concentrations varying from 2 to 20
mg/m3. Also, the total dust was high in some workplaces with
levels around 100 mg/m3 in several places.
Pistorius (1976) studied the effect of zinc oxide on rat
lungs in an 84-day study. The rats were divided into groups so
that they were exposed for 1, 4, or 8 hours a day to a concentra-
tion of 15 mg/m3 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 para-
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meters there was no difference between controls and exposed ani-
mals, 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 attributed to bronchial constriction. The author
also 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/m3, 4 hours/day, 5 days/wk. Animals were killed 24 hours
after the last exposure and the zinc content of the lungs, liver,
kidneys, 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 after
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 nonexposed control group was not followed. No differ-
ences could be noted in bone. Histological examination of the
lungs showed infiltration of leukocytes and inflammatory changes;
after 28 and 56 days of exposure, an increase in macrophages could
be shown. These studies indicate that there is a rapid elimina-
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tion of inhaled zinc from the lungs, and that the absorbed zinc is
rapidly eliminated from the body through the homeostatic mech-
anism .
Zinc stearate is a compound other than zinc oxide which is
often encountered in the plastic industry and is suspected of
causing lung disease. Votila 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 determina-
tions of the zinc content 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 the deaths of about half of the animals. In the sur-
vivors (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 eight 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 30 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 occupations, but his expo-
sure to silica quartz in another occupation could not explain the
fibrosis. The authors concluded that zinc stearate could not have
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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 cleared relatively rapidly from
the lungs, so a normal content of zinc in the lungs does not ex-
clude the possibility that zinc stearate might have contributed to
this disease.
Tarasenko, et al. (1976) exposed rats to a single intratra-
cheal administration 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 two 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 re-
sults were not presented.
The hazards of keeping food or liquids in galvanized con-
tainers were illustrated in a report by Brown, et al. (1964) on
two outbreaks of food poisoning, 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 galva-
nized containers. Zinc content of the food was estimated by re-
peating the preparation of the meal. After 24 hours of storage
the mixture of chicken and tomato sauce contained close to 1,000
ppm of zinc. The other poisoning was caused by punch containing
2,200 mg/1 of zinc. It was calculated that the doses of zinc
would be 325 to 650 mg. In the first instance symptoms occurred 3
to 10 hours after ingestion. Severe diarrhea with abdominal
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cramping was the main symptom. Vomiting was not common, whereas
after drinking the punch the first symptoms were nausea and vomit-
ing 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 pro-
mote wound healing by ingesting a large amount of zinc, 12 g of
elemental zinc mixed with peanut butter. The zinc was ingested
over a 2-day period in doses of 4 and 8 g per day. He became let-
hargic, had difficulties in staying awake, experienced a slight
staggering of gait, and noted problems in writing legibly. Nine
days after the ingestion of the first dose of zinc, he was ad-
mitted 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 in-
crease 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 symp-
toms indicating an influence of zinc on the pancreas and the cere-
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bellum, but that these effects were easily reversible and no
sequelae were seen.
Chunn (1973) studied a group of hospitalized children with
anemia. There were three children who had levels of zinc in urine
above 1 mg/1, but it was not stated by which method the zinc con-
centrations were determined. The author attributed the common
factor for anemia and high zinc excretion in these children to the
fact that all three children played with metal cars made from an
alloy containing zinc. 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.
The author suggested that the zinc could have been ingested by the
children imbibing water when they were in the bath tub playing
with toys.
Pories, et al. (1967) gave 10 young men with wounds after
removal of pilonidal sinuses, daily doses of 150 mg of zinc as the
sulfate for 43 to 61 days. Compared to 10 men not being supple-
mented by zinc, wound healing was accelerated among the men given
zinc. Except for some gastric discomfort, no ill effects were
noted. However, the authors did not present any results of
laboratory examinations. In the same report, it is mentioned that
in other studies zinc sulfate was given orally in the same dose
for more than 22 months.
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 be-
tween 0.68 and 1.2 mg/1, and after completion of treatment the
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levels were between 0.84 and 1.92 mg/1. During the study a number
of laboratory investigations were undertaken on several occasions,
but copper 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 inter-
fere 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 al. 1979;
Murthy and Petering, 1976). The animal data indicate that pro-
longed excessive intakes of zinc may constitute a hazard in
patients treated with oral zinc supplements.
Hallbook and Lanner (1972) gave 13 patients with leg ulcers
zinc sulfate in oral daily doses of 600 mg, corresponding to 135
mg of zinc per day. Treatment lasted for 18 weeks. Fourteen
patients were given a placebo. Blood counts, liver function
tests, and urine analysis did not show any significant differences
between patients given zinc and the placebo. Serum levels of zinc
rose among patients with an initial level of 1.1 mg/1 no increase in zinc levels was noted during
the 18 weeks of treatment. Copper concentrations were not mea-
sured.
During the last years there have been some reports on copper
deficiency in human beings after treatment with zinc. Prasad, et
al. (1978a) and Porter, et al. (1977) have reported hypocupremia
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after a long-term treatment with zinc sulfate 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
660 mg zinc sulfate may be too 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 to 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. One one farm, 7 out of 40 cows were so severely af-
fected 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 indications
that copper levels were lower than normal. Zinc concentrations in
liver 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 com-
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pared with a control group and a group given only the excessive
amount of lead. It should be mentioned that the groups consisted
of only 2 or 3 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 fewer effects from the exposure to lead and zinc than
in animals given only lead. It should be noted that in this ex-
periment, exposure to zinc was extremely high, but taken together
with the other 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 ani-
mals 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 six months no difference between controls and
exposed animals could be shown regarding zinc concentrations in
the liver, spleen, and skin nor was there any difference between
the sexes. 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.
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Rang, et al. (1977) gave rats, by pair-feeding, diets con-
taining 1.3, 55, and 550 mg zinc/kg of feed for four 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 dif-
ference 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 8,000 mg/kg, Brink, et al. (1959) found that signs of toxi-
city in the form of weight gain and feed intake were seen at
levels above 1,000 ppm. In pigs, given from 2,000 ppm and higher,
deaths occurred as soon as two 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
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liver samples from these pigs, levels of zinc above 1,000 mg/kg
wet weight were found.
In a woman given total parenteral nutrition after an opera-
tion, acute zinc poisoning occurred due to an error in prescrip-
tion. During a period of 60 hours she received 7.4 g of zinc sul-
fate. She became acutely ill with pulmonary edema, jaundice, and
oliguria, among other symptoms. The serum zinc concentration was
42 rag/1. in spite of treatment she remained oliguric and hemodi-
alysis 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 (Blom-
field, 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 zinc.
Acute effects of hemodialysis have been described by Gallery,
et 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 patients's
C-41
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zinc concentration in red cells was 35 mg/1 and after six 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. Blood
copper was not decreased.
Teratogenicity, Mutagenicity, and Carcinogenicity
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 experimental conditions, injec-
tions of zinc salt into the testes could induce testicular tumors.
There was no evidence that zinc given via the oral route or paren-
terally could cause tumors. However, zinc is of interest with re-
gard 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 al. 1970). These earlier findings have recently
been confirmed in other studies.
The effect of different levels of dietary zinc on the de-
velopment of chemically-induced oral cancer in rats has recently
been studied by Wallenius, et al. (1979) and Mathur, et al.
(1979). In the study by Wallenius, et al. (1979), three groups of
female rats were fed diets for three weeks which contained 15
rug/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 macroscopically in the oral cavity. It was
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found that in animals given the diet with the highest level of
zinc, the macroscopical signs of cancer appeared earlier, as com-
pared with animals given lower amounts of zinc. in the study by
Mathur, et al. (1979), a similar design was used but the levels of
zinc in that experiment were 5.9, 50, and 260 mg zinc/kg diet.
The groups of animals were sacrificed and blood, liver, and pala-
tal mucosa were sampled 3, 9, 13, and 23 weeks after the beginning
of exposure. Control animals were killed at the same time. The
carcinogen had been applied three times a week. It was found that
after three 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 _in 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.
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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 fed a diet containing 60 mg/kg of zinc and one
group of rats was fed a diet containing 7 mg/kg of zinc. After 12
weeks on these diets the carcinogen methylbenzylnitrosamine 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 four
weeks with the length of exposure of nine weeks. Some animals
were killed at the end of exposure and some animals were killed
five weeks later. In a third experiment the carcinogen was given
for four weeks and animals were sacrificed 63 days after the start
of exposure. Finally, there was one experiment where the exposure
was only for two weeks for a total of four doses of the carcino-
gen. 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 ani-
mals fed an adequate intake of zinc. It was also noted that in
the groups given the lowest doses of the carcinogen, the differ-
ence between groups was most significant; a total of eight doses
gave figures of 79 and 29 percent, respectively, for tumor inci-
dence and at a total of four doses the corresponding figures were
21 percent and zero (0) percent.
Regarding human beings, there in no evidence that zinc defi-
ciency in itself has any etiological role in human cancer. How-
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ever, many studies have been performed on the levels of zinc in
both malignant and nonmalignant tissues in human beings. The zinc
concentrations have been found to be both low and high and no
definite pattern has occurred (NRC [1978J Chapter 9 pp. 231-234
and Chapter 10 pp. 259-261). 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 men-
tioned experiments on rats (Lin, et al. 1977). However, there is
one organ in the human being where there seems to be a more con-
sistent 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 hypertrophic prostates. These authors also
reported that the cadmium levels were higher in the carcinomatous
tissues than in the normal or hypertrophic tissue. High indus-
trial exposure to cadmium has been implicated as a possible cause
of prostatic cancer and since there are interactions between cad-
mium 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 pathologi-
cal prostate.
Regarding hyperplastic prostatic tissue, it may be noted that
most reports have stated that there are the same concentrations of
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zinc in the hyperplastic tissues as in normal tissue. There is
one exception; the study by Gyorkey, et al. (1967) found consider-
able 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 mal-
formations. 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. Ketcheson, 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 fetal liver.
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 how the dose was calculated, but it is
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stated in the report "received additionally 150 ppm zinc as a 2
percent zinc sulfate solution"). The concentration of copper and
other nutrients in the diet was not stated. In the zinc-supple-
mented animals there was a significant increase in the number of
resorptions of the implantations. Supplementation for pregnant
women has been recommended, but due to the known interaction be-
tween zinc and copper, excessive zinc intakes during prolonged
times could have an adverse effect on the fetus. It is well docu-
mented in animal experiments that zinc deficiency during pregnancy
might have an adverse effect on the fetus (NRC Chapter 7 pp. 179-
180) .
INTERACTIONS OF ZINC WITH OTHER METALS
As has already been discussed in the section concerning ef-
fects of excessive intakes of zinc, interactions between zinc and
other metals may occur. It was demonstrated that excessive in-
takes 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 interna-
tional meeting and reported (Nordberg, 1978). Interactions be-
tween zinc and other metals have also been reviewed by Underwood
(1977) and NRC (Chapter 7 pp. 186-187).
Cadmium
Interactions between cadmium and zinc were extensively dis-
cussed in the NRC report (Chapter 10 pp. 261-268) and the litera-
ture up to 1974 was reviewed and discussed. It was concluded that
exposure to cadmium would cause changes in the distribution of
C-47
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zinc with increases in liver and kidney where cadmium also accumu-
lates. 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 equimo-
lar 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,
1978). The increase in renal zinc is also related to the occurr-
ence 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 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 metallo-
thionein would be close to zero (Nordberg, et al. 1979) and that
corresponds to the critical level which has been estimated for
renal cadmium related to the occurrence of renal tubular dysfunc-
tion (Friberg, et al. 1974).
Although a large number of animal studies have been per-
formed, 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 differ-
ences between some large mammals (e.g., man, horse) compared to
small laboratory animals. In the rat especially (the most common-
ly used laboratory animal), exposure to cadmium will result mainly
C-48
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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 be-
tween species are illustrated in Figure 1. Zinc deficiency alone
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 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 placental barrier to any
significant extent, this is thought to be due to retention of zinc
in the dam parallelling the accumulation of cadmium as previously
mentioned. 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.
Lai (1976) found that oral exposure to cadmium could cause
testicular and pulmonary lesions in rats on 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 in that experiment was
17.2 mg/1 of cadmium in drinking water. Zinc concentrations 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.
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0.6
a
S
ai
UJ
-1
3
4
5
S
7
34.11
10,13
12
13
U
HUMAN
LAMB
PIG
HORSE
BOVINE
GOAT
RAT
RAS81T
GUINEA PIG
MOUSE
CHICKEN
(X
u.
U
O
ut
Ul
e
u
50.3
0.3
Cd LEVEL, jimol/g
FIGURE 1
Increase of zinc as a function of increasing cadmium concen-
tration in kidney of 11 different species. The data are taken
from nine publications. The references are in the paper by Elin-
der and Piscator (1978).
C-50
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Copper
It has been mentioned earlier that excessive intakes of zinc
may cause copper deficiencies in human beings and result in ane-
mia, which can be easily corrected by decreasing the intake of
zinc and giving copper supplementation. It has also been sug-
gested 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 re-
quirement. These theories have not been substantiated, even
though Klevay (1973) found that in rats hypercholesterolemia oc-
curred with an increasing zinc-copper ratio in the diet. It has
since been shown that it is the copper status that 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 exces-
sive amounts of copper did not influence the uptake of 65Zn
from the gut, but in zinc-supplemented rats excess copper had an
influence on the uptake of 65zn. 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.
Kinnamon 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
C-51
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mg/kg of copper, 1,800 mg/kg of molybdenum, and 5,000 mg per kg of
zinc. The length of the experiment was seven weeks. At the end
of the experiment all animals were given an injection of radio-
active zinc. After four days the animals were killed. It was
found that an increase in dietary zinc resulted in an increased
bone retention and decreased urinary excretion of the isotope but
that even the very high level of copper or molybdenum did not
influence the retention or tissue distribution of the isotope.
These data indicate that the levels of zinc retained and excreted
are affected only by zinc dietary levels and not by levels of cop-
per or molybdenum ingested at the same time as zinc.
Calcium
The influence of calcium on absorption of zinc from the gut
was discussed by NRC (1978) (Chapter 7 pp. 184-185). It was con-
cluded that calcium levels in the diet do not influence zinc ab-
sorption 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 zinc 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
of calcium per kg of feed. 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 and there was a larger
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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 there was
a reduction in both ash weight and total calcium content of the
femur in the females given the zinc-deficient and calcium-defi-
cient 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-defi-
cient and high calcium intake there would be no release of zinc
from bone and thus the large amount of zinc stored in bone would
not 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
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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 asso-
ciated with decreased ratio of zinc to copper in the tissues.
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 simul-
taneous exposure to lead and zinc and there seem to be some inter-
actions; there was a lower uptake of lead in animals with high in-
take 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 de-
creased. 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). Rats were
given drinking 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
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tibia of both groups. There was no change in the brain concentra-
tion 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 _in vivo
and in 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. 1976; Border, et al. 1976; 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 addi-
tions of 5,000 mg/kg of lead or 6,300 mg/kg of zinc and combina-
tions thereof. These diets were also combined with two levels of
calcium in the diet, 0.9 and 0.1 percent, respectively. The find-
ings 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 high zinc intake together.
Interactions Between Zinc and Drugs
In the previous chapters it has been mentioned several times
that contraceptive 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
C-55
-------
change was in the contraceptive group with a decrease of 83 per-
cent; a 62 percent decrease was seen for those not on contracep-
tives.
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 con-
traceptives 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.
Many other drugs, especially drugs with chelating properties,
may influence zinc metabolism. Thiazides 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 Confer-
ence of Government Industrial Hygienists (ACGIH, 1976) has an
adopted threshold limit value (TLV) for zinc oxide of 5 mg/m and
the Occupational Safety and Health Administration (OSHA) (29 FR
1910.1000) has a workplace standard for zinc oxide of 5 mg/m3,
8-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 ACGIH and OSHA also adopted a standard of 1 mg/m3 for
zinc chloride.
The present standard for drinking water, 5 mg/1, is based on
organoleptic effects, i.e., some people will recognize 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 1 mg/1
for other than health reasons (NAS, 1977).
There is no acceptable daily intake for zinc in food. As men-
tioned earlier, zinc is an essential nutrient and there 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
C-57
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women should have an intake of 20 mg/day, lactating women should
have 25 mg/day, and that pre-adolescent children should have 10
mg/day of zinc (Table 3) (NAS, 1974).
Current Levels of Exposure
It has been well established in several studies that the pres-
ent intake of zinc via food for the adult U.S. population is from 10
to 20 mg/day. 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 water
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 defi-
ciency might cause reversible health effects. Patients treated for
months or years with large oral doses of zinc salts, about 10 times
the intake via food, for curing of 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 given zinc for
C-58
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TABLE 3
Recommended Allowances (RDA) for Zinc*
Age (Yrs.)
0
0
.0 - 0.5
.5
1-3
mg/day
3
5
10
.0
.0
.0
Age (Yrs.)
4
7
11
- 6
- 10
- Adults
mg/day
10
10
15
.0
.0
.0
*Source: NAS (1980)
C-59
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therapeutic purposes, together with observations of occupationally
exposed persons, indicate that large doses of zinc can be tolerated
for long periods if the copper status is adequate.
The toxicological data base for evaluating water quality cri-
teria for zinc is inadequate. While there is no evidence that zinc
is carcinogenic, there is a lack of usable data on chronic effects.
Most animal studies reported in the literature fail to include
specific exposure data, while studies with humans are generally
either case reports of accidental high exposure or based on data
from special groups (e.g., patients receiving high-dose zinc ther-
apy for certain ailments).
The most common reported effect of high-level exposure to zinc
is copper deficiency, which is readily reversible. The effect
occurs at exposure levels at least an order of magnitude above the
RDA for zinc. The data on special groups at risk for zinc-related
copper deficiency are too sparse to include in criteria evaluation
at the present time.
The presence of zinc in drinking water contributes to the RDA
for this essential metal. Zinc is naturally present in water at
concentrations generally well below the current drinking water
standard of 5 mg/1, based on organoleptic effects. There are no
known instances of adverse effects occurring at current standard.
Therefore, it is reasonable that the current level of 5 mg/1 be
maintained for water quality criterion. As additional data become
available, the current criterion will be reconsidered.
Long-term oral administration of zinc sulphate in daily doses
of 135 to 150 mg of zinc has been well tolerated by patients given
C-60
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the compound to promote wound healing. In patients with metabolic
diseases such treatment might cause reductions in serum copper
levels. Using a safety factor as high as 10, this means that an
additional intake of 15 mg of zinc does not constitute any health
hazard. This corresponds to an intake of 2 liters of water con-
taining 7.5 mg Zn/1. This concentration is above the present stan-
dard for drinking water which is 5 mg/1 based on organoleptic
effects.
C-61
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