# Click here for DISCLAIMER Document starts on next pageEPA UnitedStates EPA440/5-80-036 EnvironmentalProtection October1980 Agency OfficeofWater RegulationsandStandards CriteriaandStandardsDivision WashingtonDC20460 Ambient Water Quality Criteria for CopperAMBIENT WATERQUALITY CRITERIA FOR COPPER

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

iDISCLAIMER 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.

iiFOREWORD Section 304 (a)(1) 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)(1) 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 FR43660), and October 1, 1979 (44 FR56628). 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 satisfaction of paragraph 11 of the Settlement Agreement in Natural Resources Defense Council, et. al. vs. Train, 8 ERC2120 (D.D.C. 1976), modified, 12 ERC1833 (D.D.C. 1979). The term "water quality criteria" is used in two sections of the Clean Water Act, section 304 (a)(1) and section 303 (c)(2). The term has adifferent program impact in each section. In section 304, the term represents a non-regulatory, scientific assessment of ecological effects. 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 maywant 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. Guide lines 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

iiiACKNOWLEDGEMENTS

Aquatic Life Toxicology: Charles E. Stephan, ERL-Duluth U.S. Environmental Protection Agency John H. Gentile, ERL-Narragansett U.S. Environmental Protection Agency Mammalian Toxicology and Human Health Effects: George Davis (author) University of Florida Christopher T. DeRosa (doc. mgr.) ECAO-Cin U.S. Environmental Protection Agency Jerry F. Stara (doc. mgr.) ECAO-Cin U.S. Environmental Protection Agency Minka Fugus Yugoslav Academy of Science and Arts for Medical Research and Occupational Health Paul B. Hammond University of Cincinnati Dinko Kello Yugoslav Academy of Sciences and Arts for Medical Research and Occupational Health Si Duk Lee, ECAO-Cin U.S. Environmental Protection Agency David J. McKee, ECAO-RTP U.S. Environmental Protection Agency Magnus Piscator Karolinska Institute Technical Support Services Staff: D.J. William B. Buck University of Illinois Edward Calabrese University of Massachusetts Sylvia M. Charbonneau Health and Welfare, Canada Patrick Durkin Syracuse Research Corp. Earl Frieden Florida State University Norman E. Kowal, HERL-Cin U.S. Environmental Protection Agency Terri Laird, ECAO-Cin U.S. Environmental Protection Agency Steven D. Lutkenhoff, ECAO-Cin U.S. Environmental Protection Agency Harold Petering University of Cincinnati Marc Saric Yugoslav Academy of Sciences and Arts for Medical Research and Occupational Health Reisman, M.A. Garlough, B.L. Zwayer, P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper, M.M. Denessen. ClericalStaff: C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks, B.J. Quesnell, C. Russom, B. Gardiner.

ivTABLE OFCONTENTS Page

Criteria Summary Introduction A-l Aquatic Life Toxicology Introduction EffectsAcute Toxicity Chronic Toxicity Plant Effects Residues Miscellaneous Summary Criteria References Mammalian Toxicology and Human Health Effects Introduct ion Exposure Ingestion from Water Ingestion from Foods Inhalation Dermal Pharmacokinetics Absorption Distribution Metabolism Excretion EffectsAcute, Subacute and Chronic Toxicity Synergism and Antagonism Teratogenicity Mutagenicity Carcinogenicity Criteria Formulation Existing Guidelines and Standards Current levels of Exposure Special Groups at Risk Basis and Derivation of Criterion References B-1 B-1 B-4 B-4 B-8 B-11 B-11 B-12 B-13 B-15 B-67 C-1 C-1 C-1 C-1 C-6 C-18 C-19 C-20 C-20 C-25 C-28 C-31 C-34 C-34 C-38 C-39 C-39 C-39 C-42 C-42 C-43 C-44 C-45 C-47

vCRITERIA DOCUMENT COPPER CRITERIA Aquatic Life For total recoverable cooper the criterion to protect freshwater aquatic life as derived using the Guidelines is 5.4 μg/l as a 24-hour average and the concentration (in μg/l) should not exceed the numerical value given by e(0.94[ln(hardness)]-1.23) at any time. For example, at hardnesses of 50, 100, and 200 mg/l as CaCO3 the concentration of total recoverable copper should not exceed 12, 22, and 43 μg/l at any time. For total recoverable copper the criterion to protect saltwater aquatic life as derived using the Guidelines is 4.0 μg/l as a 24-hour average and the concentration should not exceed 23 μg/l at any time.

Human Health Sufficient data are not available for copper 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 1mg/l. It should be recognized that organoleptic data as a basis for establishing awater quality criteria have limitations and have no demonstrated relationship to potential adverse human health effects.

viCopper is asoft heavy metal, atomic number 29, with an atomic weight of

63.54, amelting point of 1,083°C, a boiling point of 2,595°C, and adensity in elemental form at 20°C of 8.9 g/cc (Stecher, 1968). Elemental copper is readily attacked by organic and mineral acids that contain an oxidizing agent and is slowly soluble in dilute ammonia. The halogens attack copper slowly at room temperature to yield the corresponding copper halide. Oxides and sulfides are also reactive with copper. Copper has two oxidation states: Cu I (cuprous) and Cu II (cupric). Cuprous copper is unstable in aerated water over the pH range of most natural waters (6 to 8) and will oxidize to the cupric state (Garrels and Christ, 1965). Bivalent copper chloride, nitrate, and sulfate are highly soluble in water, whereas basic copper carbonate, cupric hydroxide, oxide, and sulfide will precipitate out of solution or form colloidal suspensions in the presence of excess cupric ion. Cupric ions are also adsorbed by clays, sediments, and organic particulates and form complexes with several inorganic and organic compounds (Riemer and Toth, 1969; Stiff, 1971). Due to the complex interactions of copper with numerous other chemical species normally found in natural waters, the amounts of the various copper compounds and complexes that actually exist in solution will depend on the pH, temperature, alkalinity, and the concentrations of bicarbonate, sulfide, and organic ligands. Based on equilibrium constants, Stumm and Morgan (1970) calculated copper solubility in a carbonate-bearing water. They found that cupric ion (Cu2+) would be the dominant copper species up to pH 6, and from pH 6 to 9.3 the aqueous copper carbonate complex (CuCO3 aq) would dominate. The presence of organic ligands such as humic acids, fulvic acids, amino acids, cyanide, certain polypeptides, and detergents would alter this equilibrium (Stiff, 1971). A-1Zirino and Yamamoto (1972) developed amodel to predict the distribution

of copper species in seawater. Mixed ligand complexes and organic chelates were not considered in the model. They predicted that the distribution of copper species in seawater would vary significantly with pH and that Cu(OH)2, CuCO3, and Cu2+ would be the dominant species over the entire ambient pH range. The levels of CU(OH)2 increase from about 18 percent of the total copper at pH 7 to 90 percent at pH 8.6. CuC03 drops from about 30 percent at pH7to less than 0.1 percent at pH8.6. Field and laboratory studies by Thomas and Grill (1977) indicate that copper adsorbed to sediments and particulates in freshwater may be released as soluble copper when it comes in contact with seawater in estuarine environments. Copper is ubiquitous in the rocks and minerals of the earth's crust. In nature, copper occurs usually as sulfides and oxides and occasionally as metallic copper. Weathering and solution of these natural copper minerals results in background levels of copper in natural surface waters at concentrations generally well below 20 μg/l. Higher concentrations of copper are usually from anthropogenic sources. These sources include corrosion of brass and copper pipe by acidic waters, industrial effluents and fallout, sewage treatment plant effluents, and the use of copper compounds as aquatic algicides. Potential industrial copper pollution sources number in the tens of thousands in the United States. However, the major industrial sources include the smelting and refining industries, copper wire mills, coal burning industries, and iron and steel producing industries. Copper may enter natural waters either directly from these sources or by atmospheric fallout of air pollutants produced by these industries. Precipitation of atmospheric fallout may be a significant source of copper to the aquatic environment in industrial and mining areas.

A-2

### Thelevels of 

### copper able to remain in solution are airectly depenaent

on water chemistry. 

### Generally, ionic copper is more soluble in low pH, acidfc 

### wdters and less soluble in high pH,

### alkaline raters.

A-3RE FERENCES 

### Carrels, R.M. and C.L. Christ. 1965. Solutions, Minerals and Equilibria. Har?er and Row,YewYork. Riemer, O.N. 3r.d 5.:. Tzth. 1363. A2sstp:ion of 

### copperbyclay minerals, humicdcid, and

### bottomvwcis. iuur. Am.

### kiter WorksAssoc. 62: 195. Stecher, P.G. (ed.) 1968. The Merck 

### Index. Merck and Co., Inc., Rahway, NewJersey, Stiff, 

### M.J. 1971. The chemical states of copper In polluted fresh water andaschemeof analysis of differentiating them. Water Res. 5: 585. Stumn, W.and

### J.J. Morgan. 1970. Aquatic Chemistry - An Introduction Emphasizing Chemical Equilibria 

### in Natural Waters. 

### JohnWiley and Sons, Inc., NewYork. 

### Thomas,O.J. and E.V. Grill. 1977. The effect of exchange reactions 

### between Fraser River 

### sediment and seawater on dissolved Cuand

### Znconcentrations in the Strait of Georgia. Estuarine Coastal Mar. Sci. 5: 421. Zirino, A,. and 5. Yamamoto. :9?2. APHdependent model for the chemical speciation of copper, zinc, 

### cadmium,and lead in seawater. Limno. 

### Oceanogr. 17: 661.



### A-4AquaticLifeToxicology* INTRODUCTION

concentrations of copper. Chronic data are available for only one species, Acute toxicity tests on cooper have been conducted with 45 freshwater species and chronic tests with 15 species. Although the acute toxicity of copper seems to be related to water hardness, chronic toxicity apparently is not. Freshwater plants show a wide range of sensitivities to copper, but few data are available concerning bioconcentration by freshwater organisms. Four fish and eighteen saltwater invertebrate species have been acutely exposed to copper. Results of these tests indicate arange of acute sensitivities from 28 μg/l for the summer flounder to 600 μg/l for the shore crab. Most of these tests were conducted using static procedures; however, seven species were exposed in flow-through tests with measurements of the

but bioconcentration tests have been conducted with a wide variety of species.

ion in free and complex forms, is aminor nutrient for both plants and aniCopper, which occurs in natural waters primarily as the divalent cupric

mals at low concentrations but is toxic to aquatic life at concentrations not too much higher. Concentrations of 1 to 10 μg/l are usually reported for unpolluted surface waters in the United States, but concentrations in the vicinity of municipal and industrial outfalls, particularly from smelting, refining, or metal plating industries, may be much higher.

*The reader is referred to the Guidelines for Deriving Water Quality Criteria for the Protection of Aquatic Life and Its Uses in order to better understand the following discussion and recommendation. The following tables contain the appropriate data that were found in the literature, and at the bottom of each table are calculations for deriving various measures of toxicity as described in the Guidelines.

B-1The cupric ion is highly reactive and forms moderate to strong complexes

and precipitates with many inorganic and organic constituents of natural waters, e.g., carbonate, phosphate, amino acids and humates, and is readily absorbed on surfaces of suspended solids. The proportion of copper present as the free cupric ion is generally low and may be less than 1 percent in eutrophic waters where complexation predominates. Various copper complexes and precipitates appear to be largely nontoxic and tend to mask and remove toxicity attributable to copper (Andrew, 1976). This fact greatly complicates the interpretation and application of available toxicity data, because the proportion of free cupric ion present is highly variable and is difficult to measure except under special laboratory conditions. Few toxicity data have been reported using measurements other than total or dissolved copper. Of the analytical measurements currently available, awater quality criterion for copper is probably best stated in terms of total recoverable copper, because of the variety of forms that can exist in natural waters and the various chemical and toxicological properties of these forms. The commonly occurring forms not measured by the total recoverable procedure, e.g., copper occluded in suspended mineral particulates, are farms that are less available to aquatic life and probably will not be converted to the more toxic forms readily under various natural conditions. The procedure for total recoverable copper, however, does measure those forms directly toxic to aquatic life, e.g., the free ion, and those labile forms (hydroxide, carbonate, and some phosphate precipitates) readily converted to more toxic forms under various natural conditions. Since the criteria are derived on the

B-23asis 3L tests conducted lising solubye inorganic c3Doer ja:tS, tots; Jo,:

total recoverable cooper concentrations 

### in the tests should be nearly equivalent, andthe results are used interchangeably. Because amajority of the reported 

### test results (Tables 1 and 2j nave been conducted with oligotrophic 

### raters having relatively low complexing capacities, 

### the criteria derived 

### herein maybe at or below ambient total copper concentrations in somesurface waters of the United States. Season- ally and locally, toxicity in these waters maybemitigated by the presence of naturally occurring chelating, complexing, and precipitating agents. In addition, removal from

### thewater column may

### berapid due to normal growth of the more resistant 

### aquatic organisms and settling of solids. The various forms of copper 

### are in dynamic equilibrium and any change in chemical conditions, e.g., pH, could rapidly alter the proportion of the various forms present and, therefore, toxicity. Since increasing calcium hardness and associated carbonate alkalinity are both known to reduce the acute toxicity of copper, expression of the upper limit as a function of water hardness allows adjustment for these water quality effects, This results in 

### amuchbetter fit with the available acute toxicity data, because the upper limit is higher at high hardness to reflect calcium antagonism and

### carbonate complexation. Somedata onthe relationship of toxicfty to other factors, i.e., temperature, alkalinity, size of organism, and total organic carbon, are available for alimited number of soecies andwfll 

### bedfscussed later. The follouing data on the effects of copper on aquatic biota (Tables I through 6) 

### havebeen summarized front the literature from 

### 1950to 1980. Effqrts to.obtain residue data, or effects data on algae and other plants, were not exhaustive, since previous reviews have indicated. that these

S-3effects are of nrinor impot:ance relative to toxicity of copper to fish and

jnvertebrate species. 11: concentrations are reoorted ascooper, not asthe compound. EFFECTS &cute Toxicity Acute toxicity tests with czpper have been conducted on 18 invertebrate and27fish species (Table l), with approximately 

### 175acutevalues available for comparison. Most of these tests have been conducted with four salmonid species, fathead and bluntnose minnows, and bluegills. The acute values range from a low of 7.24 ug/l for Oaphnia pulicaria in soft water to 10,200 ;rg/l for bluegills tested in hard water. The majority of tests conducted since about 1970 have been flow-through tests with measurements of both total and dissolved copper. For comparative purposes, only values expected to beequivalent to total recoverable copper were included in the tables. ?esults of Cairns, et al. (1978) (Table 6) indicate that daphnids are more resistant to copper at low temperatures in acute tests. Since such data were not available for other species or for longer tests, no generalizations could be made.fot criteria derivation, Chakoumakos, et al. (1979) and Howarth and Sprague (1978) (Tables 1 and 6) have reported that larger (10 to 30 g) rainbow trout are approximately 2.5 to 3.0 times moreresistant to copper than juveniles. This factor is obviously asource of variation in Table 1. However, insufffcient data are available for other species to allow adjustment of *test results or on which to base criteria recomendations. An additional complicating factor is the general lack of knowledge of the range of sensitivity of various life stages of most invertebrate species, or the effects on susceptibility, of starvation and other stress factors under natural conditions.Lind, 

### et al. 

### (Yanuscrigt) (Table 1) and Brown et al, (Table 6)(1974)

have shown quantitative relationships between the acute toxicity of copper and naturally occurring organic chelating agents. Although these relationships have been 

### demonstrated for only afew species (Daphnia magna, fathead minnow, and rainbow trout), the effects shown should be generalizable through chemicai effects on cupric ion activity and bioavailability. Lind et al. (Yanuscript) measured the toxicity of copper in avariety of surface waters and found that 

### total organic carbon (T.O.C.) is a more important variable than hardness, with Daphnia magna acute values varying approximate1.y 30-fold over the range of T.O.C. covered. Similar 

### results were obtained with fathead minnows. This would indicate that the criteria should be adjusted upward for surface waters with T.O.C. significantly above the 2to 3mg/l usually found fn the waters used for toxicity tests. An exponential equatfon was used to describe the observed relationship of toxicity to hardness by performing a least squares regression of the natural logarithms of the acute values on the natural logarithms of hardness. Sufficient data were available for Daphnia maqna, Daphnia pulicaria, chinook salmon, cutthroat and rainbow trout, fathead minnows, and bluegills to show acorrelation of acute toxicity and hardness. Theslope of the regression equations ranged from 0.67 for chinook salmon to 1.34 for Daphnia magna with an arlthrnetlc meanof 0.94. The close agreement of the slopes and the hig)rly sfgnlffcant (p =0.01) regressions In each case reflect the quality of tht toxicological data available andconfirm the premise that the effect of hardness on the acute toxicity of copper is simflar for various aquatic animals. In the absence of the contradictory data, it is assumed that the hardness relationship holds for the acute toxicity of copper t0 all freshwater

B-5aquatic animals. The mean slope (0.94) was fitted throl;gh the geomevic

rrean toxicity value 

### andhardness for each species to obtain a lcgarithmic intercept for each soecies. The species mean intercept, calculated as tne exponential of the logarithmic intercept, was used as ameasure of rel'ative soecies sensitivlty to copper (Table 3). Daphnia pulicaria wasfound to bethe most sensitive species. Two other daphnid soecies and the scud Gammaruspseudolimnaeus were only slightly less sensitive. Salmonids and the bluntnose minnows were nearly as sensitive as the daphnids, but fathead minnows and several other cyprinids were approximately 3to 11 times more resistant. Bluegi 11s and other centrarchids are approximately 

### 10to100times more

### resistant thansalmonids. Afreshwater Final Acute Intercept of 0.29 ug/l was obtained for copper using the species mean acute intercepts listed in Table 3and the calculation procedures described in the Guidelines. Thus the Final Acute Equation is ,(0.94[ln(hardness)]-1.23). The saltwater invertebrate data (Table 1) include investigations on three phyla: annelids, molluscs, and arthropods (crustaceans). The acute sensitivities of 

### crustaceans ranged from 31 pg/l for Acartia tonsa (Sosnowski and Gentile, 1978) to 600 ug/l for shore crab, Carcinus maenus (Connors, 1972). Adult polychaete worm +cute 

### values ranged from 77 ug/l (Pesch and Morgan, 1978) to 480 *g/l 

### (Jones, et al. 1976). Pesch and Morgan (1978) determined that the 96-hour KS0 for Yeanthes arenaceodentata increased from 77 Ug/l in a flowing water system to 200 Ug/l in the presence of a sandy sediment. Jones, et al. (1976) irdicated that Nereis diversicolor exhibited a variable 

### response to salinity ever a range of 5 to 34 g/kg with the greatest toxicity occurring at 5gikg. The lowest reported acute value fcr the bivalve molluscs was 39 gg/l fzr the soft-shelled clam, +& arenaria

3-6'Eisier, !977), ard the highest 

### was560 ug/l for the adult ?acific oyster,

Grassostrea gigas (Okazaki, 1976). Eisler (1977) indicated that the sensitivity of Mya arenaria to coouer varied 

### according tothe seasonal tempera- 'tJ?e-, with copper being at least 100 times more toxic at 22.C than at 4'C. The arthropods (crustaceans) were both the most sensitive invertebrate species 

### tested, with anacute value of 31 Ug,'\ for Acartia tonsa (Sosnowski and Gentile, 1978), and the least sensitive of ali animals tested, with anacute value of 600 ug/l for larvae of the shore crab, Carcinus maenus (Connor, 1972). Sosnowski, et al. (1979) showed that the sensitivity of field populations of Acartia tonsa to copper was strongly correlated with population density and food ration (Table 6), whereas cultured A. tonsa manifested a -- reproducible toxicalogical response to copper (Table 

### 1) through six generations (Sosnowski and Gentile, 1978). Johnson and Gentile 

### (1979) reported that lobster larvae appear to betwice assensitive to copper asthe adults. The acute values for saltwater fishes include data for four species and two different life hfstory stages (Table 

### 1). Acute toxicity ranged from 28 ,,g/l for summerflounder embryos, Paralichthys dentatus (U.S. EPA, 1980) to 510 Dg/l for the Florida pompano, Trachinotus carol inus (Birdsong and Avavit, 1971). The results of the acute tests on the embryos of summer and winter flounder were used in Table 1because embryos of these species apparently are 

### not resistant to copper and because other 

### acutevalues are not available for these specfes. 

### Studies err-the effect of salinity on the toxicity of copper indicate that it is more toxic to adult pomoano at 10g/kg than at 

### 30g/kg (Birdsong aodAvavit 1971). Other species of saltwater fish were tested for sensitivity to 

### copper, but the experimental conditions were not suitable for inclu8-7sion in either 

### theacuteor chronic tables; consequently, these data ;Irere

placed in Table 6. 

### Also, a

### numberof scientists exposed anadromous species such as Atlantic 

### andcoho salmon to copper in freshwater. These 

### datawere utilized in deriving the freshwater criterion, but not the saltwater criterion. ASaltwater Final Acute Value of 22.9 ug/l wasobtained for copper using the species mean acute values in Table 3 and the calculation procedures described in the Guidelines. Chronfc Toxicity The data base for chronic toxic'ty of copper to freshwater aquatic animals (Table 2) includes chronic values for four invertebrate and eleven fish specfes. Life cycle test results are available for two snails, Daphnia magna at three hardnesses, an amphipod, brook trout, bluntnose minnow, fathead - minnow at 

### four hardnesses, and the bluegill. Early life stage tests have been conducted with several additional fish species, including channel catffsh at two hardnesses. Thechronic values range from alowof 3.9 ug/l for early lffe stage tests wfth brook trout in soft water to 60.4 ug/l for a similar test with northern pike. Values for invertebrate species nearly overlap those for fish with arange of 6.1 to 29.0 ug/l. Aseries of tests wfth Oaphnfa magna in 

### a hard pond water (Table 6) wfth unmeasured copper concentrations resulted in chronic values of about 49ug/l. Thedata available concerning the effect of hardness onthe chronic toxicfty of 

### COQQWis somewhat nebulous. The total range of chronic values is 3.9 to 60.4 ug/l (Table 2). which is 

### muchless than the range of 0.23 to 260 *g/l 'for species mean acute intercepts (Table 3). This may be due to differences in the kinds and numbers of species andwaters used in the two kfnds of tests, but it mayalso indicate that hardness affects chronic tox8-8iCity crf copper differently t?an it affects acute tOXic'ty. Indeed, ii

chronic tests with Daphnia magna, Chapman, et al. (Manuscript) found that copper was less toxic at amedium hardness than at a low hardness but was most toxic at a high hardness (Table 2). They indicated that 

### in the nigh 

### hardness tests the daphnids probably ingested some precipitated copper. Also, some copper probably sorbed onto suspended food particles. These factors were not expected to ;aqait chronic toxicity to species whicn are not filter feeders, however. Sauter, et al. (1975) found that hardness affected the chronic toxicity of copper to channel catfish very little, if at all, and the four results available for brook trout donot showany consistent relationship. Thefour chronic tests with the fathead minnow also showed aconsistent but small effect of hardness on chronic toxicity. The slope of 0.26 is not statistically significant and is 

### muchless than the acute mean slope of 0.94. A chronic value (Table 6) from atest conducted with the fathead minnow in a hard stream water contaminated with sewage effluent (8rungs, et al. 1976) wasmore than twice other values for this species. This probably indicates that the high levels of hardness, phosphate, and organic material reduced the chronic toxicity of*copper in this stream. Onthe other hand, afactor of two reduction in toxicity is rather small considering the much greater reductions that occur in acute toxicity of copper. Acute-chronic ratios for copper (Table 3) vary widely, even for 

### tests with the Sam-species. The highest,.ratios (38 and'156) are for two of the more acutely resistant species, bluegills and Campeloma decisum (a snail). Ratios for three tests with 0. magna ranged from 1.2 to 7.3, and for four - tests with fathead minnows from 5.4 to 20. The more sensitive species have ratios below 4, whereas the less sens!tive species have ratios above 4. Also, the ratio seemsto increase with hardness.



### B-9The available evidence seems to indicate that hardness affects the

acute-chronic ratio but not the chronic toxicity of coooer. Chronic tests have been Conducted with quite avariety of aquatic animals and Dresent a good indication of the range of chronic sensitivity to copper. The Freshwater final Chronic Value for copper, derived from the species mean chronic values llsted in Table 2using the calculatjon 

### procedures described in the Guidelines, is 5.6 ug/l. The only chronic value reported (Table 2) for asaltwater species was that for the mysid shrimp, Mysidoosis bahia (U.S. EPA, 1980). The chronic toxicity of copper to this saltwater invertebrate wasdetermined in 

### aflowthrough life cycle 

### exposure in which the concentrations of 

### copper were measured by atomic absorption spectroscopy. Groups of 20 individuals were reared in each of ffve copper concentrations (control - 2.9 f 0.5 ug/l, 24.2 27.0 ug/l, 38.5 26.3 ug/l, 77.4 f, 7.4 ugll, 140.2 2 11.8 ugll) for 46days at 20'C and 30 g/kg salinjty. The biological responses examined included time of appearance of first brood, 

### the number of spawns, meanbrood size, and growth. The appearance of embryos in the brood sac was delayed for 6 and 8days at 77 ug/l and 140ugil, respectively. The number of spawns recorded at 77~g/l wassignificantly (p <0.05) fewer than at 38.5 ug/l. The number of 

### spawnsat 24 and 38 ug/l wasnot signiffcantly different from the control. Brood size was sfgnificantly (p <0.05) reduced at 77ugll but not at lower=concentratlons, and no effects on growth were detected at any of 

### the coopw concentrations. Based 

### uponreproductive data, adverse effects were observed at 38 ugll, but not at 77ug/l, resulting in achronic value of 54.ug/l. Using the acute value of 181 ugll, the acute-chronic ratio for this species is 3.4. The species mean acute-chronic ratios of 38 and 156 appear to be high (Table 3), 

### but the other seven are al! ,dithin afactor af 10. The geometric 3-10mean of :.+ese seven is 5.73. 1' the Saltwater Final acute Val3e 3; 22.3

ug/7 is divided by the acute-chronic ratio of 5.78, a Saltwater Final Chronic 'Value of 4.0 ug/l is obtained, Dlant Effects Copper has been widely used as an algicide and herbicide for nuisance aquatic olants. Although it is known as an inhibitor of photosynthesis and plant growth, toxicity data on individual species (Table 4) are not numerous. The relationship of toxicity to water chemistry and the importance of the culttire medium on toxicity has only recently been recognized (Gachter, et al. 1973). Copper concentrations from 1 to 8,000 ug/l have been shown to inhibit growth of various plant species. Several of the values are near or below the chronic values for fish and invertebrate species, but most are much higher. NoFinal Plant Value can beobtained because none of the plant values were based onmeasured concentrations. For saltwater algae the concentrations cent reduction in photosynthesis or growth species of macro-algae and eight species ofof copper which cause a50 perare tabulated in Table 4for one micro-algae. The most sensitive species were Thalassiosira pseudonana and Scrippsiella faeroense which were inhibited by5ug/l. Residues Bioconcentration factors 

### 2,000 for the alga 

### Chlorella (Table 5) ranged from zero for the bluegill to regularis. Because copper is a required element for animal nutrition, the significance of copper residues has never been established, and few tests have been run for the purpose of determining bioconceotration factors.

3-11Cspoer is 3~ essential eiefrent in the respiratory pi;merlts 2i sxe sa::-

water invertebrates, especially Crustaceans, and plants have enzymes which csntain copper and are recessary for ohotosynthesis. However, copper is also Sioconcentrated in excess of any known needs by several saltwater soecjes (Table 5). The polychaete worm, Neanthes arenaceodentata, bioconcentrated copper 2,550 times (Pesch and Morgan, 1978), whereas in aseries of measurements witn algae by Riley and Roth (1571) the highest reported concentration factor was617 for Heterunastix Longifillis. The highest bioconcentration factors for copper are those for the bivalve molluscs. Shuster and Pringle (1969) found that the American oyster could concentrate copper 28,200 times after a140day continuous exposure to 50ug/l. Even though the tissue of the oyster becamebluish-green in color, mortalities at this level were only slightly higher than the controls. This amount of copper is not known to be harmful to man, but there have been instances recorded that oysters have been unmarketable because of their green appearance due 

### Becauseno freshwater nor to high copper content.

maximum permissible tissue concentration exists, neither a asaltwater Final Residue Value can becalculated. Miscellaneous The results of manyadditional tests of the effects of copper onfreshwater aquatic organisms are listed in Table 6. Many of these are acute tests with non-standard durations for the organisms used. Manyof the other acute tests-in Table 6were conducted in dilution waters which were known to contain matvials which would significantly reduce the toxicity of copper. These reductfons were different from those caused by hardness, and not enough data exist to account for these in the derivation of the criteria. For example, Lind, et al. (Manuscript) conducted tests with Daphnia 

### Pulicar3-12ia and fathead minnow in waters with concentrations of T.O.C. ranging upto

34mgll. Similarly, Geckler, et al. (1976) and Brungs, et al. (1976) conducted tests with many species in stream water which contained a iarge amount of effluent from a sewage treatment plant. Also, Wallen, et al. (1957) tested mosquitofish in aturbid pond water. Until chemical measurements which correlate well vrith the toxfcity 0.fcopper in awide variety of waters 

### are identified and widely used, results of tests in unusual dilution waters, such asthose in Table 6, will not bevery useful for deriving water quality criteria. Longer exposures than the standard acute studies have been recorded in Table 6. Most noteworthy are the values reported for the bay scallop &- 

### Jopecten irradfens (U.S. EPA, 1980). which suffered mortality and reduced growth at concentrations of S and 5.8 ug/l, respectively. Even though several studies have been reported on the sublethal effects on survival, growth, and reproductfon, the significance of these effects has yet to be evaluated. However, these studies do indicate existence of demonstrable lethal effects dueto chronic exposure at very low concentrations of copper. Sumnary Acute toxicity data are available for 45 species of freshwater animals. Theapproximatqly 175 acute values range from 7.2 ug/l for Daphnia pulicaria in soft water to 10,200 vg/l for the bluegill in hard water. Statistically significant regressions of 

### acute toxicity on water hardness are available for seven spccIcs, with toxicity decreasing as hardness increases. Additfonal 

### data for several species indicate that toxicity also decreases with increases in alkalinity andtotal organic carbon. Therange of acute values indicates that someof the more resistant species could survive in copper concentrations over 100 times that which would

8-13

### bereadily lethal to the more sensitive species. Amongthe more sensitive

species are daphnids, scuds, midges, and snails which form the major focdwebsfor both narm- and cold-water fishes. Concentrations of copper lethal to these sensitive organisms in soft water are only slightly above those chronically toxic to most fish and fnvertebrate species. Chronic values are available for I5 freshwater species, ranging from a low 

### of 3.9 ug/l for brook trout to 

### 60.4 ug/l for northern pike. Hardness does 

### notappearto affect the chronic toxicity of 

### copper. Fish and invertebrate species seem

### to be about eoually sensitfve to the chronic toxicity of copper. The two most sensitive species, bluntnose minnow and 5. 

### pseudolimnea, are both important food organisms. Copper toxicity has been tested on awide range of 

### plant species, with results 

### aoproximatfng those for animals. Complexing effects of the test media and alack of good analytical data makeinterpretation and aoplication of these results dlfffcult. 

### Protection of animal 

### species, hawever, 

### appears to offer adequate protection of plants as well, Coooer does not appear to bioconcentrate very much in

### theedible portion of freshwater aouatic soecies. The acute toxicity of copper to saltwater animals ranges from 17 ug/l for acalonoid 

### cupepodto 600 ugll for the shore crab. Achronic lifecycle test has beer? conducted with the mysid' shrimp, and adverse 

### effects were observed at 77 ug/1 but not at 38 ~g/l which resulted in an acute-chronic 

### ratjo of 3.4. Several saltwater algal species have been tested, andeffects were obsewcd between 5 and 100 ug/l. Oysters can bioaccumulate copper UP to 28,200 times, and become blu'sh-green, 

### apparently without significant mortdlity. In long-term exposures, the bay scallop waskflled at 5ug/?. CY?!WIA For total recoverable 

### copper the criterion to protect freshwater aauatic life 

### asderived using the Guidelines is 

### 5.6 ugll as a24-hour average, and 3-14the concentration (in Vgll) should not exceed the numerical value given ?y

e~0~g4~'n~hardness~~~1.23~ at any time. For example, at hardnesses of 50, 

### 100, and 200 mg/l as CaC03 the concentration of total recoverable 

### copper should not exceed 

### 12,22, and43ugll at any

### time. For total recoverable cooper the criterion to protect saltwater aauatic life as derived using the Guidelines is 4.0 ug/l as a 24-hour average, and the concentration should not exceed 

### 23pg/l at any time.

B-15Spmcios Method.



### worm, Limodriiur hoft~irtwi 

### s,u

Snai i Iadult), Amicoia rp. s, hi Snai I, Csrpoim deciur Slldli, Gyraulus clrcurstrlatus s, u 3n.311, lnteyra Physd cIadocer an,

s Daphla CIiWtOCW~n,

maqna Oaphnla Ciadoceran,magna Daphnla CIadocaran, Oaphnis magna Cladoceran,magna qnphnis Ciadoceran, Daphnla maqna FT, M
s, IJ R* u s, u s, u s, tJ s, u CIatieran,rayna DdphnIa s, M rabio 1. Acute vaius la- coppu tiUclrWS bg/l u Lc50~50 ChriUi C&O,) tJIQ/i 1.8

FREWATER SPECIES

Copper WItat4 Copper sultate Wwr wIfate Copper WI tat8 CopPer suIfateG=vPchloride Copper chiorida c0Pl-r chioride Copper suItate Wvr suitate Qvper chloride tipper y1itato loo 54) 50 35-55 100 100 35-55 226 45.3 99 99 la0

52 102

PO 900 1,700 IO8 69 39 200 9.8 65 30 12.7 100 26 Nurtr 6Llridges, 1961 f-&h*oldt, et al. 19711 Fbhroldt, et al. 1973 kthur 1.Leonsd, 1970 Wurtz 4Bridges, I961 wurtr atifidy3,s, I%61

CabeJsrek &stosiolt, 1960 Ulesingef 6 Christensen, 1972 Mema I LLeyoot-Van ZIJI, I972 Adean Lbyoot-Van ZIJI, 1972 Anderson, I946 kb-ingaann AKuhn, 1959 chapcan, at al. Hanuscr IptTabi. 1. iccet lauui) Specla Mean i.CW/ECM Acut Value

(w/l 1’. (i&J/i I*’ 30 MetiKlli~ s,J4 s.Jd s,M

R,M ChviCal

Wwr chloride Species Ciadocei~n,magna Daphnia Ciadoceran, Daphnia maqno Ciadoceran,w3gna Daphnia Ciadocoran,lrsgna Daphnio Cidocwm, Dapbnia puiox CiSdDCUSn,

pullcarla Dephnla CIadocuan, Daphnia puilcaria Cidoceran, Daphnis pullcarla Ciadoceran, Daphnia pullcario Ciadoceran, Daphnia pi icaria Ciadoceran, Daphnia pui lcaria Ciadocefan,

puilcaria Daphnla Cladocaran, Oaphnla pul Icarla Scud, Carrarus pseudollmaeulr Reterence Chapmm, et al. lbnuscr Ipt Chawan, et al. kuruscr lpi Chapman, et al. WMuscript Calms, et al. 1978 hPPN ctriorlbe I06 207 69 cAiorlde co9w suifate tipper uIIfat0 45 IO 45 IO alms, et al. 1978 48 il.4 Llnd, et al. Mmuscr ipt Lind, et 41. Manuscript L:nd, et al. Honuscr Ipt Lind. et al. kmuscr lp? llnd, et al. Uanuscr Ipt Llrld, et a\. kmuscr Ipt Llnd, et al. Wanuscr Ipt IIlId, ot aI. Wanuscr Ipt 9.06 R,M R,M R,M R,M R,M R,.M 18 7.24 44 IO.8 45 9.3 95 17.8 - I45 23.7 245 27.3 f-r, n @rwr

sulfate 35-55 20

B-L?Tsblo 1. uhntIau84) specIss SCUd, Gamerus sp. Crayflsh, Orconectes rustlcur SiOflef If, Acrctneurls Iycwlss Oi¶Wt3lfly, lJnldantlfled

Caddlsf ly, Unldentltled

HotIter, Phi lodlna acut lcornls RotIt=, Phl lodlna acutlcornls AmerlCM eel, Angullla rostrata American eel, Angul Ila rostrats Cub salr*n (adult), Oncmhynchus kIsutch c&o salron lycwllng), Oncorhynchus hlrutch coho 56lmcm (ywrllngl, Oncorhynchus klsutch Method’ s,M

s,M

S,M R,U R,U

S,M FT,M 5. n

s. M Cherlcal

CoPPer suIfate Ww suIfate

f%vr sultate

wwr chloride CoPPer chlor Ide Copper ChlorIde loo- I25 40 50 50 SO 40 25 81 53 55 xl 89-99 89-99 3,ooo

0,31yJ 4,600 30 6,200 I60 700 I,loo 6,400 6,‘300 46 74 70 tlubsctlludn, I967 Wlrnlck 4BelI, I969 Huhuoldt, et al. I973 Retrroldt, et al. 1973

Elulkemd, or al. I977 tlutkena, et al. 1974 tluIkemd, et at. I974 Rehrol(jt, tit dl. I971 Rehroldt, tit al. 1972 Chdpman 4Steven5, I978 Lorz 4WcPhersoc1, I976 LorzaW&hwson, 1976Table I. (comtlwadl tbr&as tdlu spoclmsmeam hart* Value u34vEc50 hu/l)‘~60 zi 19 38

IO 22 85 IXI x7 Spwlos 

### C&X) 89-99 Rotumcs Laz 4McPherson, 1976 Coho saimon (seolt), Oncorhynchus klsutch Chlnook SUI~XI (elovln), Oncorhynchus tshmViscM Chlnoak salmon (swlrrup), Oncorhynchus tshmytscho ChInook salon (parr), Oncarhnychus tshwytscha Chlnook salmm (smelt), Oncorhynchus tshwytscha Chlnook salmm, Oncorhynchus tshauytscha Chlnook sabon, Oncorhynchus tshawytscha Chlnook zdlmon, Oncorhynchus tshawytscha Chlnook salmon, ticarhynchus tsharytscha Cutthroat trout, Salao clarkl -- Cutthroat trout, Salao clarkl -- Cutthroat trout, Salno clarkl -- Cutthraat trout, Sala clarkl -- Cutthroat trout, Salvo clarkl -- 25 Chap-, 1978 25 Chapran, 1978 25 xhdpman, 1978 25 

### abapman, 1978 I3 Chapman 4MaCrady, i977 Chapman hWrcldy, i977 Chapman Atirady, i977 46 I82 Chapran 6Wrady, 1977 chdkouMk6s, tit al. 1979 Chakouraakos. et al. 1979 

## .ZL

Wper chloride CQpper chlorlda Ww chloride FI, M 186 

### xi.8 I8 ChakcMlmdkc6, et el. 1979
ChakourdtG5. et di. 1979 232 204 83 162 Cbkourdws, et dl. 1979

B-19lablm I. Kclntlaued) Hsrdnur hlglr u Cdx,)31 SPecler Dl+a

LC50m Acut0 Valu

fPg/l)‘~ (Pa/l )‘a 73.6 Mathod* FT, M Cherlcal Refwence Ct~kouwkos, et al. IYIY C.lokouwkos, ot dl . 1379 Chakowdko5, et al. I’)79 SPecIes Cutthroat trout, Salvo clarkl -- Cutthrmt trout, Salmo clerk1 -- Cutthroat trout, Sala clsrkl -- Cutthroat trout, Sala clarkl .-- RaIntau trout. Salu, galrdnerl HaInba* trout, Salmo galrdnerl Hdtnti trout, Sslmo qdtrdncrrt RdInbo* trout, SdlW CJdIrdnw 1 Rdlnbow trout, Salmo gslrdnerl HaInbou trout, Salw gulrdnerl RaInban trout, Salmo galrdnerl RaInbam trout, Salmo gelrdnerl Ralnbou trout, Salmo galrdner I Ralnba trout, Salmo galrdnerl Wwer chloride Copw ChlOrlde CQPPer drlorlde Wwr dblorlde FT, M I60 74 91 FT, M 44.4 FT, M FT. M FT, M FT, W 13.7 Cnakourakm, et dt. IV19 CopPer suIfate 30 19.9 22.4 tiwar-th bSprague, 1378 Wv*r 5uIfat8 32 bdrth 4Sprague, I’)ltl %wr bulfate Capper suIfate 31 28.9 tkwdri h6Sprague, I978 FT, M 31 ttrarth ASprague, 1978 Copper suIfdte 30 Wwarth hSprague, 197&i 176 tT, M hPP8f

suIfate Wwr sultate Wwr sulfate IO1 tioudrih &Sprayue, 1978 il, n 40 tiuwdr.th ASprdgu8, 1918 FT, M 99 33.1 tkmarlh 6Sprdyw, I978 30.1 tl, M t-T, W Copper

sulfate Qwper sulfate 102 IO1 tkwdrth ASprdguo, 1970 46.3 tkudr-th 6Sprdgue, l97tJ

9-20Table I, EantIwoll) Specl~s Ralnbmf trout, Salao galrdnerl RaInbomtrout, SaIm 9alrQnwl RaInbar trout, Salm galrdnul Rnlnb0m trout, Salm galrdnsrl Ralnbcu trout, Salm galrdnul Ralnbw trout, Salm gslrdnerl Ralnbw trout, Sdlm gd1rdoer I Halntu trout, Salu qalrdn8rl Ra1nbu trout, Lalm galrdnerl RaInbow trout, Salm qalrdnerl Ralnbcu trout, Salm galrdnerl Ralnbcu trout, Salm galrdnerl Ralnba trout, Salm galrdnerl RaInbar trout, Salm galrdnerl Chadcal

Wper YIfate CoPper wIfate CopPer suIfate QPPW sulfateCopw544 Ifate Copper sulfate bPP@r SUItat Copper chloride Copper &llorldI3 Copper chloride

CoPPer CiIlorlde Hardfmsr @l/l as C8&)99 loo loo 90 370 3.6 371 3661 298 194 169 194 85.3 I94 83.3 I94 194 274 194 48.1

tit.1 85.9 232 70 82.2

103

I28 Spocla Weon

Acat* Valu ROfYWI

Houarth 4Sprague, 1978

bdfth i Sprague, I970 tiwarth ASprague, 197l3 IClwarth &Sprague, 1978 Harorth 4.Sprague, 1978 kmarth ASprague, I978 tkmarth 6Sprague, 1970 tkwarth 6Sprague, 1978 Chakowkos, et al. 1979 ChakOllMkos, et al. 1979 Chakooaakcs, et dt

. 1979 Chakaurakos, at al. 1979 CbkOumkOS, Lit dt

. 1979 Chakouankos, et al. 1979

B-ZiTable I. UhdlWOd) Sp0CI.S Ralntlal trout, salm galrdnul Ralnbcu trout, Salm Qalrdnorl RaInbau trout, Salm galrdnerl Ralnbo* traut, Selm galrdnwl Ralnbcv trout, Sslm galrdntwl Ralnhn trout (alevln)~, Salmo galrdnerl Ralnbou trout (sulrup), Salro galrdnerl RaInbow trout (parr), Sola galrdnorl Halnbon trout (molt), Solr, galrdnerl RaInbow lruut (adult), Sala galrdnerl Ralnboa trout, Salm galrdneri Aalnbou trout, Sale galrdnerl Ralnbcw trout, Salma galrdnerl Ralnbw trout, Salm gdlrdnerl MethlxP FT. W FT, n FT, n FT, II

f-f, M

tl, M t4udnoss a!$-194 221 I94 165 194 197 194 514 194 243 25 25 25 25 42 350 I25 125 I25 28

17 18 29 57 I02 200 IW 210 R.1Y@#BcI Chak~kos, st al. 1979 Ch&omakas, et al. 1979 Chakowlakos, et al. 1979 ~hakoumekos, et al. 1979 Chdtoumakos, et al. 1979 Chspan, 1970 Chapman, 1978 chapran, 1978 Chapman, 1978 Chapman I Stuvons, 1978 Fogels a Spr.+yue, 1911 spear, 1971 Sped, 1977 Spew, 1977

9-22Table 1. Koatlnud) SpOClOS Ralntxm irout, Sala galrdnerl Atlant Ic saIllon, Salao salar -- Atlant Ic welm, Salm salar -- Atfantlc Sal-, Sala salsr -- Brook trout, SalvelInus fontlnafls Stoner01 ler, Caqnntora an- lur Goldflsh, Carasslus suratus Goldflsh, Carasslus auratus Carp. Cyprlnus carplo Carp. Cyprlnus carplo LongfIn &ce,

chry sogast-r AQOSla Strlped shiner. Notrapls chrysocephalus Strlped shInor,

drry+ocephalus Notrdpls bluntnose rlnnou, Plwphafes notatus %wsulfate Copper sulfate

COPPer sulfate CoPper a.11fateQVPnltrata

Wvr su1tate Ww wItat0

Copper suIfate tkudness

(&I as !z?!aL 290 20 e-10 I4

200 290 Gwkler, et al. 197b 20 52 53 55 LC5O/ECSJ

bls/l)~~ 890 48 125 32 100

36 300 810 000 fJ60 7po Speck Mean

Aalto volw (m/l I- R0fWUM.X

Calwiarl 6Marchettl, 1973 Sprague, IW4 Yllson. 1972 Sprague 6Ramsey, I%3 McKlr I fienolt, I971

Plcheflng &HBndersw, I%6 Tsal 6McKee, 1980 Rehwoldt, et al. 1971 Rchroldt, et al. 1972 Leuls, 1978 Geckler, et al. 1976 Geckler, et al. 1976 Geckler, et al. 1976

B-23Tabfo 1. Kant Iwed) Species bluntnose mlnncu, Plmepha les notatur Bluntnose minnow, Plmephales notatus Bluntnose mlnnau, Plmephales notatus flIuntnose mInnou, Plaephales notatus Bluntnose llnnou, Plmnphafes notatus Uluntnose mlnnou, Plmaphales notatus bIuntnosu l lnncu, Plwphales notstus fafhadd alnnou, Plmephales promelas Fathead llnnou, Plmephales prcnelas Fathead olnnow. PImphalos prwelas Fathead mlnaou. Plmephales prmlas Fathead llnnou, Plmephales prowl45 Fathead llnnou, Ploephales prmelas Fathead llnna, Plmephales promnlas ChOdclrl Wvr sulfate Wper suf fate Copper suIfate Copper suIfate Copper suIfate Copper SuIfateCwpefsuIfate 

### 54iate copper suIfate

Wwr 5uIfate CoPper sul fate f%per suIfate HUdmS

k!!&-200 200 a00 200 194 194 194 202 M2 200 45 X0 20 200 260 Geckler. ut al. 1976

200 Heckler. et al. 1974 340 210 220 270 460 490 790 200 1,450 (2)“. 23 f4).*’ 430 - Retuonce Gecklor, et al. 1976

Gecklur, et dl. I976 ttornlng dNelhn 1979 Isel,

llbrtl, llornlng 6Nelhn 1979 Hurnlng &t&lhelsel, 1979 Plckerlng, et al. 1917 Plckerlng, et al. 1977 Andrew, 1976 Andre*, I976 Plckerlng AMndorson, 1966 Plckerlng 4Rendarson, I%6 b&Int, 1966

B-24Tobla I. KwtImu4d) SpeclOS fatha+d rlnncn, PImeph8les prcmelas Fatheaa ~lnnoa, Plmeplmles pr”l+s fathead llnncu, PImphalos prcnelar Fathead lfnncq Plmeph4les promelas Fathead llnna, Plaephales pr-las fathead llnaow, Plmephales promalas Fathead rlnnow, Plm@4les prowalas fathead minnow, Pleeph4les prorelas Blacknose date. Rhlnlchthya atratuluS Creek chub, Seaotllus 4trcwaculatus Brown hrl Ihesd, lctalurus nobulosus Bran bulIhrad, lctalurus nebulosus Banded kllllflsh, fundulus dlaphsnus banded kIIIIfIsh, Fundulus dlaphanus ctmm1cu1 CaQwr sulfate Copper sulfate Wper suItote CoPper suIfate c0pP.r sulfate UUCIWSS ( IU c%, ) 200 31 31 200 200 40 45 46 Copper suIfate CQPper sulfate Copper sulfate CoPPer suIfate Copper nltrate 200 202 200 53 55 

# ZsO

470 Ii4 75 440 490 I14 121 08.5 320 310 spoclu MEan

Acut Valw

I80 (2)*‘* 540 860 wit Refernce Mount 6Stephan, I%9 Mount bstsphan, I%9 Mount &Stephan, I%9 Geckler, et al. 1976 Geckler. et al. I916 llnd, et al. Manuscr Ipi Llnd, et al. Manuscr Ipt Llnd, et al. Manuscr Ipt Geckler, et al. I976 Geckler, at al. 1976 Brungs, et al. 1975 Geckler, at al. 1976 Rehwoldt. et al. 1971 Rehwoldt, et al. IYR

B-25labI* 1. mantIrwl) spec1rs flagflsh, .lofdaneI la fIcvldae W=PY, Pueclll4 retlculata GUPPY, r0diia retlculata GUPPY, Poocllla rotlculata Yhlto perch, Morone amrlcanus YhIte parch, MUonrcOIldclcanus -- 511lyad tuss, k4ono saxatllls Strlped bass, -one saxatllls Sfrlped fass, Worow saxat IIIs Strlped bass flsrva), Morone ssxst 1IIs Strlped bass flarva), Mwcme saxat IIs Strlped bass fflngerllng), )(aonla saxat Ifs Ralnbcu darter, Etheostm caeruleum Ordngethroat darter, ftheostm spectsblle s. M

S,JJ

s. u s, u
s. u s, u cbomlcal

coppsul fata

Qwper nltrste Copper nltrste Copper suIfate

Wwer suIfate Copper suIfate llU&US

(q/las se%L 350-375 20 87.5 67.2 53 55 53 55 35 68.4 68.4 68.4 SpeclwnMn Aane V@hm h/l)- RdY0aco

FogsIs ASprague. 1977 36 PIckwIng 1thnderson, I%6 112 Chynoueth, et al. 1976 138 Chynoueth, et al. 1976 6,200 Rehroldt, ot 41. 1911 6,400 4,3@ 4.000 620 Yol Iham. I%9 50 Hugl~s, 1973 100 lkIghes. 1971 150 liughes, 1971 3m Heckler, et al. l97b 850 Gackler, ot al. 19/b Rehwoldt, et al. 1972 Rehroldt, et 41. 1971 fkhroldt, et al. l9?2

3-26Tsbia 1. mmt iawd) LCMIECSO 1.’ l&I2,400 2,700 1,240 I,= Sp8ci.s PUrpkin~ed,

gIbbsus L+omi s Pwpk inseed,

gibtxms le@mis Plqk inseed, i.oixmis gibiWur Puqkinswd,gibbosus L-is Puqkinsesd,

gibhosus Lapais Purpk Inreod,

gibbosus Lefmais PurQk inseed,

gibtMAsus Lepomis Puapk inseed, Lepmis gibbosus Pumpkinseed. lepamis 9ibhosus Blwgiii, mcrochirus Cepomis EiiU~iii, Lspomis macrochirus Biwgiii, aacmchirus le~omis BlUegill, Lepais wcrochirus fiiwgii I, ~epoais macrochirus ChricSi CoPPer nitrate Henwoidt, et ai. 1972 Wpsr &IIfate CQPper suItate bpprr suIfate Wvr suIfate Cw-- suIfate Wvr sulfate WPW 8411 fate Copw suIfate 125 Spear, 1971

I25 spear. 1977 125 1,670 Spear, 1977 125 I.940 125 1,240 125 I25 45 1.w

1,740 1,100

a.- 10,900 spear, 1977 spear, 1977 5pear, 1977 3pear, 1977 Benoit, 1915

CoPper suIfete Wper chloride copper suIfate Geckier, et al. 1976 Geckier, st al. 1976 1,250 660 Patrick, et al. 1968 20 Pickering I tkmderson, I%6

B-27labi. 1. ckmtIwui)



### BiwgiII, Lepomir wcrochirus Biwgii I, leponis acrochirur Largmnouth tars, Microptams salmolder

Poiychaete uorm, Neanthes srenaceodentata Polychaete worm, Neanthes aronaceodentats Polychaete worm, Nereis diversicolor Polychaete wora, Nereis diversicoior Poiycheeto voca, He-is divarsicoior Poiychaete mm, kareis dlverrlcoior Polychaets wa, Phyi la&co macuiata Pacific oyster, Crassoslrea gigas Awri can oyster, Crassostrea virginica black &lone, tbllotls cracharodll Mmaod’ s,u FT, W

FT, M fl, M 5, u s, u

5. u s* u

s. u 5, ” s, u Copper

nitrots copper nitrato

coppw atIfate Copper SuItsto CoPper rullate Ww suIfate Copper wIfate tipper chloride ~iwr suIfate HuheM spoclrb8m

( IW c%. J g$F ( 23” R*tuwca 360 10,200 Pickering I tbnQrsoe, 1966 35 2,400 O’htra, 1971 IO0 6,9’Eo Bir’ge 1Black, 1919 SALTWATERSPECIES 77 200 200 445 480 410 120 560 I28 30 63 I24

364 I20 560 I28 50 Pesch ACbrgan, 1978

Pesth &Wocgan, 1978 Jonti, et si. 1976 Jones, et al. 1916 Jones, et al. 1976 Jwgi, et al. 1916 KLusky &Phliilps, 1975 (Irazaki, 1976 Calabrese, et al. 1913 Martin, et al. 1971 HartIn, et dl. IYll

B-28Tablr 1. 1Gmt Inuedd)
ifWdWSS bg/lu Li3fvEc50 Caco~l 1”

(us/l II4 Species Wean

krta Valw (~Q,/i~”86 Mdhod~ s,u 5,u 5,u s,u %u s,u s,u species Red abalone (IarvaJ, Hallotis rulescens Soft shelled cl-, & areaaria Calanoid copepod, Acwtia ciausi -- Calanoid copepod, Acartia tonsa -- Caian0ld copepod. Acart la tonsa -- CalMbold copepod, Acartia tonaa -- Cwmod, Luryttmora dffinis COpeP~, Psovdodlaptcws corooatus Copepod l Tlyriopus Japonicus Mysid shriq~, Wysidopsis bahia Mysid shrimp, Hysidopsls bigelwi American lobster fiafva), Homarus aaer icanus fmericau lobster (adult), Humiwus americanus Urorn sbrtrl, (larva), Crangon crsngorr ChwiCai Retwence Martin, et al. 1977 CoPper suIfate Cwper chloride hwr chloride 59 52 I7 55 31 526 I58 39 Cisler, 1971

52 U.S. EPA, 19&l 

## Copper chlor Ide %-wr chlorlde Scsnowskl 4Gentlla, i9!8 So:,nouski 6CentIla, l9?8 51 So2nousk I6(;ent LIu,

19tt.J 526 u.-A.EPA, 19LUI Wwr chloride s, u

s. u t1, M .tT, f4
s, u s, u s, u Cwper Chioricb @pm chloride Copper nitrate Qvw-r niirate Ww nitrate %wr suIfate tipper wIfate I38 U.j. EPA, l9w1 481 487 U.S. CPA, 1960 I81 181 U.S. Lt’A, TYtKI I41 141 U.S. WA, 1980 48 Johnson dCentlIe, 1979 100 330 69 NcLetr5tl, I914

350 Connor, I912

B-29T4bio I. lcodi~~ speciw Shore crab Ilarva), Carcinus menus fiorida pqm.no, Trachinotus caroiiaus Fiwida -0, lrachieotus caroiinus Florida -no, Trachinotus caroiinus Atiant ic siivwsida 1larva), Menidia wnidia -- Surer tlounder ferbcyo), Para Ilchthys dent&us Ylnter llounder (odryo). P’srudop ieuronectes aver icanus Mmthod. cbamicai s,u 3z* s,u WIsuifat. s. u COPPWIfate copper suIfate %-v-r nitrate Copper chloride Copper nitrato IfUdRWS

(m&urn fXXJ,J lbg/iJe’ 600 600 360 380 510 412 I36 17Jkfi’ I36 

### 28131*** 28 129 f9J*** 129 Aafwwa connor, 19n Ulrdsong s,Avavit, I971 8irdsaq I Avsvlt, 1971 Ulrdsong I Avavlt, I971 U.S. EPA, l9Mt

U.S. WA, 1980 U.S. tPA, l9MU

” s= static, R =tla-through, R- reneuai, U=unneasured, M- lleasured .* Results LUOexpressed as copper, not as tha co+xmd. “akArith4tic w of (NJ rosuits. Frashrater; kute toxicity vb. hardness Ciadoceran, Daphnia mqna: slope = 1.34, intercept =-2.64, r - 0.80, p=0.01, N= IO Ciadoceran, Uaphnia put Icarla: slope - 0.70, intercept - 4.40, r =0.94, p=0.01, N=8 Chinook salmon, Uncwhynchus tsharytscha: slop a0.67, intercept =0.93, r - 0.93, p=0.01, N=8 Cutthrmt trout, Salao clarkl:

-_I_ slope =0.88, Intercept =0.79, r =0.78, p=C.01. Na9



### B-20RaInbat trou$, tilr, galrdnerli shpe - 0.87, Intercept - 0.33, r =0.78, p- 0.01, N- 39 fath3ad llnlyI*, Plmphales prmolas: sbpe * 1.12. lntercapt - O.)e, r =O.%, p=0.01, N= 15 Filuegl Il. LefK.dr rscrochIl-us: slope = 1.00, Intercept - 3.40, r =0.95, p- 0.01, N- 7 AfltImotlc Dem sutm slop. * 0.94

B-315pUI.S

Snal I, c8apf3lour declslm Snal I,lntegra Physa CIa-an, magna Daphnla Cladoceran, Odphnla raqna Cl4&K4rdn, Daphnla mqnrl Scud, Gdlmdr-uspQwdollrnaeus -- Halnbw trout, 5sImoqalrdner I l3roun h-out, Sdlmo trutta -- Isrook trout, Salvellnus tontlnalls crook trout, Salve1 lnus fontlnal Is Brook trout, SalvelInus fontlnalls Urcwk trout, SalvelInus tontlnalls Lake trout, S~~lval lnus ntiycush T-t’

LC Lc Lc LC LC LC ELS ELS LC ELS tLS LLS CLS Chadcal

CopQer wIfate &PW chIwIde hw-- chloride Wwer chloride CoPper 5uIfate Wper 5ultat4 Cwper SkIItste CoPper wItate Copper 5uIfait4 Qvper 514 Ifate

copper wIfate FIUWATLH SPECItS 45 45 51 I04 211 45 45.4 45.4 45 45.4 37.5 187 45.4 8-14.8 10.9

8-14.8 IO-9 11.4-16.3 13.6 20-43 29.0 7.2-12.6 9.5 4.6-8 6.I 11.4-31.7 I9 Arthur hLeonard, I970 Arthur hLeonard, 1970 ctmpran, et al. Mmuscr Ipt chapmm, et 01. Hanuscr Iyt Chapran, et al. Mdnuscr Ipt Arthur 4Leoncud, IY70 McKlm, et al. 1976 22.0-43.2 xl.0 McKlm, et al. 1978 9.5-17.4 12.9 WcKlr &Uenolt, 1971 22.3-43.5 31.I McKlm, et al. IYM 3-5 3.9 Sauter, et al. 1YIb 5-8 6.3 Saute, et dl. 1916 22.0-42.3 30.5 MLKlm, et al. 1978

Chrmlc V.lw Cm/l 14. ftofwanco

9-32Iable 2. 4coatIumd~

Species Rorthern pike, Esox luclus -- Bluntnose llnncu, PImphales notatus Fathead mlnnom, Plaeplmlu promlu Fathead llnncm, ~hOQtUbh6 WOrtAO Fathead llnnou, PInphale5 prcnelas Fathead rlnncu, Plaephaies promlas Yhlle suchef, Catostaus C’Suel Channel catf Ish, lctalwus puactatus Chanhel atf Ish, IctalWbls punctatus BluegIll, macrochlrur Lefmmls Hal leye, Stlzostedlon vltreua TasP ELS Lc u Lc lc ElS ELS ELS ELS LC ElS Chemlcsl

copw sulfate CoPper ullfate copprr WItat4

COPF 5uIfat0

c0pp.c sul fat. Copper suIfate coQp-- sultat0 CePpv 5ulfate nBr&mss

(m&l m CdBq)45.4 I91 I98 30 200 45 45.4 36 I86 45 35

SALTWATERSPECIES Mysld shriw, Mysldi~psls lmhla LC Copw nltrate 54 LIDIts (Irg/l* 34.9- 104.4 clwoalc V~luo

(QQjl)- 60.4 4.3-M 8.8 14.5-33 21.9 IO.6 18.4 14.0 24-32 27.1 13.t-26.2 12.9-33.8 12-M u-19 2140 13-21

38-J7 18.5

20.9 II. 1 Sauter, et al. 1976 15.7 Sauter, et al. 1916 29.0 16.5 Sauter. et al. 1976

54 Reterence

McKin~, et al. 1978 Horning I Nelheisei, 1979 Mount, 1960 Mount 4Stephbn, 1909 f’lckerlng, et al. 1977 Lind, et al. M4muscr Ipt FkKlr, et al. 1978

BermIt. 1975

U.S. EPA, 1980

l LC= tlfe cycle or partial llte cycle; ELS- early life stage lHesui ts we expressed a5 copper, not 05 the oolpcund.

B-33Tablo 2. GMtInuul)

w Snal I, declsw ~lcmo Small, Intwa PhVu cladocuan, Oaphnla rgM Cledocoran,mgna Oaphnle CIsdocrran, Daphnla magna Scud, Gaw8ru5 pseudol Inaous Brook trout, SalvelInus focrtlnalls 8Iuntnoso llnna, Plmphalos fbotatus Fathead rlnacw, PlmQha1.S prarrlas Fatlmad rlnnor, elnphalos promoIas Fathead olnnou, PIurhales pcalas fdlmad mlnmou, PlPphnI.8 pramlss t3lu+Jlll, mcrochlrus Lepomls Wysld shrlq, f4Vsldopsis bahla AcuteChronIc Rat lo6 iiardnoas (q/i - kutr Value Cd;ol) QbQ/I) 45 I,Mo 45 39 57 ifI I04 34 211 69 45 20 45 100 I94 233 I98 430 30 75 200 415 45 lo6 45 1,100

I61 Chrallc Value

fpQ/l) 10.9 Ratlo

156 IO.9 3.6 13.6 I.9 29.0 1.2 9.5 I.3 &I 3.3 12.9 1.0 8.8 26 21.9 14.0 21.1 18.5 29.0 54 20

5.4 I7 5.8 36 3.4

--- -

B-34labI* 2. &ontlamd)

Rmk* I5 I4 13 12 II IO 9 8 7 6 5 4 3 Freshwater Species Mean Chronic Valuqs

SQOCll3S W-them plko, Esox luclus -- Speck WBsn Chonlc Valus (w/l, 60.4 tkwn trout, klmo trutta -- Lske trout klvellnus naaaycush 30.8 30.5 Blurglll, Lappals mcrochlrus Whlto sucker, Catostaws C’SM I 29.0 20.9 Fathead alnncw, Plrepbles proretas 19.9 Fblnbom trout, Salvo galrdnerl 19.0 YalIaye, Stlzostedlm vltreu 16.5 clsdocwan, Oaphnla magna 15.5 Channel catt Iah, Ictalurus punctatus 15.2 ball, Physa lntegra Snail, Carpelm declsur 10.9 IO.9 k3ok trout, Saiveilnus fmtlnal Is 10.0

9-35Tablo 2. mlatIund)

R&l&. SpbCl9S 2 Bluntnose llnnou.

Plmophaler not&r Speclas Mean ChroaIIc Value Crs/l) 8.8

l Ranked frcr load sansltlvo to wart sewltlw hosed an spocles mean cRonlc vslw. FreshwOw Flnal Chronic Value - 5.56 &I

8-36Table 3. CamtIau4)

Rank’ 31 30 29 28 27 26 25 24 23 22 21 20 I9 I8 SPuler

Hotlfer, Philodlne mxtlcornls StrIped tass, l&n-on. saxstl IIs Strlpcd shiner, Motropls chrysocephalus orangethrvmt darter, Etheostora spectabl le Laogf In date,

chryscgaster Agosls flagtlsh, Jordanel la flw Ida4 Atlantic salmon, Salvo salar -- GOldtlSh, carssslu5 aufstus Fathead rlnnor, Pimphales pramlas Brook trout, Salvellnus fontlnalls Yom, Nals sp. Ralnbor darter, Etheostm cawuleum Blacknose Qce, Hhlnlchthys atratulus tifan bulIhecld, Ici.3lurus nobuIcEiu5 Sprlw mean speclos llwn Acute lntr4mpt kutdhfOrlC (Vg/l) Ratlo 14.4 IO.I a.41 5.61 5.37 5.00 4.fJ5 3.91 3.29 2.80 2.28 2.20 2.20 2.I3 IO.I 7.8

3-38Tablm 3. Spades mom acute Intercepts 8nd values wt4f auto-clwonlc ratios fw COQPW

45 44 43 42 41 40 39 38 37 34 35 34 33 32 Sprclw Mean Spmcla ban kut* Iaterapt Acuta-Chalc spacl# lr!dl) a&lo

fRESHWATEl? SPECIES stonet Iy, Acrabeurla lycwlas 260 Caddlrf ly, Unldentifled I50 White porch, fkuae amurlcmus I48 Amulcan eel, A0qul Ila rostrata ckmxlfly, Unldmtlfled 145 II7 Largemouth bass, Wlcropterus salaldes 91.8 BluegIll, &xmls mcrochlrus hat I, caqnblaml docI5ur lhyt Ish, Orconectes rustlcus 35.2 Scud, Garsrus sp. 23.I

soal I, lrrnlcols sp. 22.9 Purpk Inseed,

glbbosus Laporls Banded kll Ilflsh, fundulus dlaphanus 21.8 20.1 carp, 18.9 Cyprlnus carplo

a-3718bh3 3. (Cod Inuedk

Rimk~ 17 14 15 14 13 I2 II IO 9 8 7 6 Speclor

Crrtek chub. SemtIlus atromculatus WJPY# Pcecl fla retlculata Stoner01 ler, Campostcem anamafua Bluntnose IpJnnou, Plmaphales notatus Cutthroat trout, Salm clarkl -- Snail. Gyraulus clrcumstrl~tus Worm, Clnmdrl Ius hoffmlsterl Coho salmon, Oncorhynchus kfsutch Snal I,Inteqro Physa Halnbau trout, Salm qalrdnerl ChInook SalDon, Oncorhynchus t-shswytscha Snail, Physa heterostropha Wldge, Unldent Ifled scud, Gamarus pstludollamaeus Species Mean specl.5 tin Acute Intercept ACUiO-CkrOllIC cps/r, Ratlo 2.13 2.12 1.99 I.83 1.68 26

I.42 I.34 I.23 I.01 3.6 1.02 0.91 Cl.91 CL76 0.55 3.3

B-39Rank’ Smcla 3 Clsdocoran,ragns

oaphrls 2 Clatiran,

Oaphnls pulex I Cladoceran,

Oaphnla JBJIIlcarla

22 21 20 I9 18 I7 I6 15 I4 spalr NnM spulr wwr Aato Irhrapt &UtcckOrlC (I&I J adlo 0.43 2.6 0.28 0.23 Spelw hea Spula m Acute Value Acvh-CLrorlc SJUIM (p&l) R8t10

SALTWATERSPECIES Shore carb, Carolnus hiwmus 600 Pacl fIc.oyster, Crsssostraa glws N-pod, Eurytemra aff lnlo 560 526 ~pep~, 407 1lQrlopus Japu4Ilcus Florlda pcqmno, Trschlnotus carol lnus 412 Polychaeto ucwm, Merols dlverslcolor 344 Bran shlq, Cranqon crangon 330 Mysld shrlq, Mysldop sls balIIs Mysld shrlrp, ~ysldopsls blqelarl I81 I4I

B-GOTablo 3.

Rbrlkfi I3 I2 II

IO 9 8 7 6 IContInued)

Species CopePod, Pseudodlaptwius cwonatus Atlant Ic sllversl df3, wklaia lenldla -- Winter flounder, Pseudoplwrww3ctes tWWICi3nUS Am8rlcan oyster, Crassostrea vlrglnlca Polychaete uorm, Neanthes arenaceoduntat~ Polychaete worm, PhyIlodoce mcu latd Red abalone, fiallotls rutescens Amerlcsn lobster, fkmarus amirlcanus Calanold aopepod, Acartla clausl -- Black &~lone, Hsllotls cracherodll Soft shelled clam, w artbnar la Calmold copepod, Acsrt la toasa -I_ Summer flounder, Paral lchthys dcrntatus Speclms Mean Speclar MOM Acute Valtbe AcMm-chronlc (p&l/l 1 Ratio - 138 I36 IB

I28 I24 I20 86 69 52 50 39 31 28

B-41Tablo 1, (Cont1nu.d)

l Ranked trcm least sensltlve to mxt senrltlve based on species mean acuto value or Intercept. Freshrater Flnal Acute lntercspt =0.29 rg/l ktural logarithm of 0.29 a-1.23 Acute slope - 0.94 (see Table I) FI,-,~, Acute Equation I e(0.9411n(hardness) I-I.231 SalWater Flnal Acute Value =22.9 us/l Acute-mrfmlc Rotlo - 5.7% Flnal Chronic Value - (22.9 ug/ (see hurt) 1)/5.78 - 4.0 rg/l

B-42Table 4. Plant vdur tar cqlpu Speclu Alga, fla-aqua Aaabnona Alga, Anabaena varlabl IIs Ahw, Aaacystls nldulsns Alga, Chlemydomnas sp. Alga. Chlorel la pyrenoldosa Alga, Chloreffa pyrenoldosa Alga, Chlorel la reqularls Ww. Chlorel la sp. Ah% Cfilorel la vulgar Is Alga. Chlorof la vulqarls Alga. Chiofella vufgurls Alga, Cyclotef la mmeghlnlsna Alga, Eudorlna callfornlca Alga, Scenedesmus acwlnatus RmUIt Etfut hi/l 1 WfkSffUATER SPtCIES 751 growth InhIbItIon Growth lnhlblt Ion Grouth InhIbIton Growth recluct Ion Lag In gath Grouth InhIbItIon Lag In south Photosynthesis InhIbIted Growth lnhlblt Ion EC50 wowth, 33 days %$ growth reduct Ion Growth reduct lw Grouth lnhlblt Ion 40s grouth reduct luff zoo 100 100 8,0@ I 100 20 6.3 200 WI 100-200 &oofJ 5,0(10 300 R*tYe#blX

Young 4 Llsk, 1972 Young i Llsfc, I972 Young I Llsk, 1972 Calms, et al. 1978 Steeran+ elsen 6 Hlum-Andersen, 1970 Steemawf4Irlsell 4 Kaq-NI elsun, I970 Sakaguchl, et al. 1977 Gachter, et al. 1973 Young &Llsk, 1972 Rosko ARachlln, 1977 Stokes a HutchInson, I916 blrns, et al. 1978 Young 6LIti, 1972 Stokes d HutchInson, 1976

B-43Table 4. Icoetlnuoa) “pecles Alga, Sceeedesaus quadr tcauda Ihreshoid torIcIty Alga, Growth Scanedesus quadr lcauda reduct Ion Algae, Mlxed culture Blue green algae, Wlxed culture Dlatom, Nltzschfa llnaarls Dlatwn, NJtzschla palea OUCkuWd, Lemna minor -- Wirrophyte, Elodea canadensls Eurasian uattumllfoll, Myrlophyl I- splcatua Green alga, Selenastrum capr lcornutun

Alga, glant kelp, Macrocyst Is pyr Itera Alga, jhalassloslra psoudon~n~ Effect

Slgnlf lcant reductlar, In photosynt hesIs 50s reduct Ion In photosynthesls I20 lK Hi50 Coclplrte growth lnhlbltlon EC50, 7day 50# reduction In photosynthetlc 02 product Ion 509 root relght reduct Ion Grouth reduct Ion Result1 (WI150 8.ooO 5

25 7958 I5 5 II9 I50

250 50

SALlWAlER SPECIES 96 fu EC50 photosynthrrsls lnact Ivat Ion loo

I2 hr EC50 yrouth rate 5 Referewe Brlnwan &Kuhn, 1959 Calms, et al. 1978 Elder Afkrne, I978

Strwoti-Nlel sen A Bruun-Laursen, IS76 Patrlck, et df. 1968 Steeran-Ml elstw b Wlum-Anderson, 1970 Yalbridge, 1977 Brown 6Ratt Igdn, 1979 Stanley, 1974 Bartlett, et al. 1974

Clendennlng & Mar-th, I959 trlckson, 1972

B-44Table 4. Kaatlnued) Spacler Alga, hphldlnlur, carter1 Al a, 7 01 sthodlscus luleus Alaa, Skeletonem costatum Alga, ytschla closterlua Alga. Scrlppslells feeroense Akm Proiocentrur deans Alga, Gymodlnlu splendons tttut I4 day EC50 grcmth rote I4 day EC50 grath rate I4 day EC50 gradh rate %hrECw growth rate 5day EC50 gr”rth rate 5day EC50 grath rate 5day EC50 grcuth rate Result tJlg/l,C50

33 5 IO 20 Reference

trIckson, et al. ;970 trlckson, et al. 1910 trIckSon, et al. 1970 Rosko &Ruchlln, 1975 Salful lah, 1978 Salfullah, 1978 Selfullah, 1978

a-15Sped= Akm Chlorella rwulerlr Sionof ly, Pteronarcys callfornlca fatbed rlnnou (larva) , Plnphales praaelas BluegIll, mcrochlrus Lepods

Polychcmta YOTII, Clrr ItorrId splrabracha Polychaete worm, Neanthes arenacfmcbntata Polychaete worm, Nerels dlverslcolor Polychaete worm, Phyllcdoce raculata Bay scallop, Argapecten lrradlans Bay scallop, Argopacten lrradlans Aatvlcm oyster, Crassostrtm vlrglnlca American oyster, Crassostrsa vlrqlnlca Northern quahaug, wtwcwmr la ow-cenar la Tablo 5. fhsldum tar aqlpu Bl-lrmtla huat loa TIS*w fbdor (days) Hofwma

fRESHHATER !iPECIES

2,~ 20 hrs Sskeguchl , et al. 1977 203 I4 NehrIng. 1976

msc le 290 0 30 Llnd, et al. ebnuscr lpi 660 Benol t, 1975

SALTWATERSPECIES

250. 24 2,550. 203. 1,750* 3,310 4,I60 28,200 20,100 88 26

24 21 II2 II2 140 140 70 Mllanavlch, et al.

1976 Pesch &kwgm, 1978 Jones, et al. 1976 ClcLusky APhi IIIps, 1975 ikrooglan, 1918 Zwocglan, 1978 Shuster 6Prlngle, I%9 Shuster- 6PIInyle, I%9 Shuster &PrInyle, I%8

3-46Table 5. uhnt bwu) 6l-tratl0- factor 3,JO0 Ourat loa

(ueya) 35 SPOCI*S Sott shelled cla=, w aremarLa Wurs.1, mm ti*lrul, WI lus euu!ls MUSSII, Byl luc edul Is wUSS61, Wvtl lus ~lcwx3vlnclol Is Alga, Dunsllella prlolects Aha, Dunallella tectlolecta Alw, ChIamydomonss spc Alw. Chlorella ssllns Alga. Stlchococcus baclllarls Rduence Shuster I Prlngle, I%8 lJ,s, fPb, 19fMJ 2(r, 1I2

we 112 U.S. EPA, l9aD 90 I4 Phllllps, l97f 800 25 WaJoorl &?etrmlo. 1973 Riley Sfilth, 1971 153* 25 IMP 25 Hliey &kth, 1971 135* 25 Riley aRoth, I971 74* 25

25 Riley 6Kuth, f9?1

Riley &Roth, 1971 273’ 25 Riley aRoth, 1971 Alga. tiemlselmls vlrescens Alga. Hemlselmls brunescens Alga, 0llsthodlscus luteus Alga. Aster lone1 laJqmnlca Akm. Phaeodactylw t!lcwnutum 553= 25 Hlley aRoth, 1971 25 Riley &Roth, 1971 309’ 25 RIley I Hoth, 1971 323’ 25 Hlley &bth, I971

5-47Table 5. uhnt1lw.d) Spules Al!% Akvr Pseudopedlnella pyrlforals Akw, Hetoromastlx longltlllls TIssuo Bl-centrotlan Ourat Ion factor hAays) IXIB’ 25 B5’ 25 617” 25 Reference Riley ARoth, I971 Hlley bRoth, 1971 Hlley bRoth, 1971 Alga. MIcronnms rquawta Alga, Totraselrls tetrathele 279’ 25 Hlley 6fblh, 1971 265a 25 RIley Alath, 1971
llJry relght to wet uelght converslon

3-18SpUlOS

Aacul Id ua-a, kolo+ay hmdlwl Amal Id warm, Aaotoscma hmadleyl Amnalld rora, Amol- tmadloyl AnnalId worm, Amolosors hmadloyl Annel Id YWD, Aooloscra hrsdleyl Snal I (erbryo), Avrlcol* rp. Snal I, GonIobnsls llvescens Snsl I, Lyme8 emarqlnata Smll, Nltrocrlr sp. Snsl I, Wltrocrlo rp. Snsl I, Wltrocrls sp. Snal I, Nltrocrls sp. Snsll, Nltrocr Is sp. Claboceran, Daphnla amblgua l&bl* 6. Mhu dmta for alppar Result Dwatloa Ettut wa/l)

40 lws ul IUYE

a h-s 4a hrs 4Blwr 96 hrs 18 lur 18 hrs 48 hrs 48 hrs 48 hrs 40 h-s 111hrs 72hs fRESHMATER SPECIES

Llxo

LCM Lcm LC50 LC50 LCM Lao lx50 LCM LCM l.c.50 LC50 h-3 2,m 2,oofJ 1,650 Calms, lt al. 1978

Colrns, et al. 1978 Calms, et al. 1978 Calms, lt al. 1978 blrnc, et al. 1978 9,300 Rehuoldt, ut al. 1973 &xl Calms, et al. 1976

m Calms, at al. 1976 3,m 2,400 1,000 300 210 Calms, et al. 1978

Calms, et al. 1978 Calrn.5, et al. 1978 Calms, ot al. i978 Calrnr, et al. 1978 Ratwro

u30 67.7 Ylnner 4Farrell, 1976

B-49Table 6. Kant Inud) spmclas cw=.-fb Osp(nIa * CllMlO#rWl,magna Daphnla Cladoceran,mgna DophnIs Cladoceron, Daphnlo ragna Ctadocsran. Daphnla raqna cIbldwardll,mgnd OaphnIa CIadocoran, Daphnla aagoa Cladoceran, _Ddpha IQmdgna Cladoceran, OaphnIas Cladoceran,magna L)a_yhnto Cladoceran,magna Daphnta CladO4MNI. Daphnla magna cIadoceran l Oaphnla s CIadoceran,mdqna Oaphnla IhNatlocr 48 hrs 48 tus 40 hl-s 48 hrs 48 trs 1116, cyclb, Llte cycle Lit8 cycle Llf6 cycle life cycle Life cyclu Llfu cycle Lltu cycle l-2 IYS Ettect

LC50 LC50 15C) lmo (IO C) LC50 (I5 C) LC50 (23 Cl Huauced numbr ot young praluced fbduced mmbur of young prcxiuced Reduced producf lvlty Reduced productlvlty Reduoed product IVIty Reduced producf Ivlty Raduced product IvIty Reduced number ot young pratuced Lcm Result OrQto60 90 70 40 I IO IO 21.1 26.2 a.2 lat.2 49 10 80.5 Retwonca

Bleslnger 4 ChrIstensen. I972 Cdlrns, u,t 01. 197tl Gilrns, ut al. 1978

~IIrllL, et 41. 19118 Ulnnor, et dl. 1977 Wlnrier, ot ~1. l-)77 Btualnyor A Chrlstmwn, 1972 bflnrwr, et ‘11. 1377 Wlmar , tit 01. I977 Winner, et IAl. 1977 Winner &tcw-rol I, 1976 Adeuti 6lkkirout Vdn ZIJI, 1972 Wlnnur 6Ior r-4 I, 1976Table 6. Kant Inued~ Species CIadocer dn,

magna DaphnIa CIaWan, l%e!!!alwgns Chkceran, Oophla mugno CIadwxran ,

maqns Daphnlo CIatieran, Oophnlo mqno CIadoceran,

lsqna Oophnla Cladoceran, Oaphnla magna CIado-ran,garvulo Osphnlo CIadocwm, Oaphnla parvula CIadoceran, Daphnla porvulo CIodaceran,pulex Oaphnla CIotieron. Daphnla pulex Cladoceran,pulex Oaphnlo Durst Ion 72 hrs 72hrs 72 tars 72 b-s 72 hrs 29 hrs 24 hrr 72 hrvs R tYs Llte cycle 72 hs 72 hrs life cycle Result Ettect &I/l) LC50 LCSO LC50 lC50 LC50 Mudlan survival tlm LC50 LC50 LC50 Reduced productlvlty LC50 LC50 Reduced product Ivlty 00.8 85 81.5 01.4 85.3 12.7 BQ 57 72 49 54 86 49 Referewe

Winner 6Farrul I, 1976 Wlnnw &Farrel 1976 Winner 4F&rut 1976 Winner 4Farrel 1976 Ylnner AFcurel 1976 Andrew, et al. 1917 BrIngnan 4Kuhn, 1917 Ylnner 6Farrel I, 1976 Wlnnw &Farret I, 1976 Winner 4Farrel I, 1976 Wlnnw- 6Farrel I, 1976 Winner 6Farrel I, I916 Winner 6Farrell, 1976Cl-M, oaklIly. pub* Cl&&CUM,pulu Daphnlm Cl-M, 04phl4 pulrx Cladmoran,Pulex Dsphnlo cIadocrran ,

Jwllcsrls Daphnla CIadoceran,

$ullcarls Uaphnla CIsdoceren, Daphnla pullcarla Clsdocnran, Daphnls pullcarla Cladacoran,pullcarla Daphnle CIadocersn , oaphnla pul Icarlo CIa&wan,pullcarla Osphnla CIabcersn, Oaphnis pul lcarla Cladoceren, Oaphnla pullcarla Clsdoceran, Oaphnla ~llcarla oumtlon 48 hr I hrs 48 h-s 48 hrs 40 IN-S 48 hrs 43 hrs 40 hs 40 lus 48 hs 4a hrs 40 hs 40 hrs 18 hs Elfed

Lc50 (5 Cl Rrullt hwl, Rmtwencm 70 Calms, et al. 1978 Lcw (IO C) 60 Calrnr, at al. 1978 Lc50 (I5 C) 20 Calms, et 41. 1978 Lc50 (25 C) 5.6 Calms, et aI. 1978 LC50 (Tot I4 q/l) 55.5 Llnd, et al. Manuscr Ipt LC50 (1cx.zI3 mg/l) 53.3 Llad, et al. Manuscrlpt Lc50 (Taz I3 q/l) 53.3 Llnd, ut al. Martuscr Ipt LC50 (Ta: 28 q/l) 97.2 Llnd, et al. Mamscr Iyt LC50 (TOC 34 mg/l) I99 Llnd, et al. Manurer Ipt LC50 (TCC 34 19/l, 627 Llnd, et al. Manuscr Ipt LC50 (TOC 32 ag/l, 213 Llnd, et al. Manuscr Ipt Lc50 (TOC 32 q/l, I65 Llnd, et al. Manuscr Ipt Ii30 (Ta: 12mg/l) 35.5 Llnd, ut al. Manuscr Ipt LC50 (TOC I3 q/l) 78.8 Llnd, et al. Cbnuscrlpt

B-52Table 6. Llhntlnwdl

Swles Cladoceran. Dspbel~~f lcar la ClrOourw. Oa+bl~~l lcarla Clwlocmran, Daphnla pl lcarla CIbdocfu-an, Daphnla pl Icarla CIadocaran,

pullcarla Dsphnla Cladoceran,iublqua Uaphnla Scud, Gmw-~s lacustr Is MaYi IY. Lphtmerulla subvarla Wf IY. tpharerel la sand16 stonet ly. Pteronarcys callfornlca Caddlsf ly, Hydropsyche bettenl Mldye, Tanytarsus dlsslmllls Crayf Ish, Orconectes rustlcus RotIfer, Phi lodIm acutlcwnls Duratlan 4fl kc 40 tus 48 hrs 48 hrs 40fKs Life cycle % hrs 48 hrs I4 days I4 days 14days IOdays I7 days 48 hrs Result EfforA wf/l) LC50 (TOC 28 mgg/l) II3 LC50 (TOC25 mg/l) 76.4 LC50 (TCC I3 q/l) 04.7 LC50 (TCC 21 y/l) I84 LC50 (TOC 34 mg/l) 240 Reduced productlvlty 49 LC50 J,!@fJ LC50 320 LC50 kwmo LC50 IO,IOO13,900 501 survival 32,000 LC50 16.3 Survival of 125 newly hdtched young LC50 1,m Rdweace Llnd, et al. Mamscr Ipt Llnd, et al. f4anuscr Ipt Llnd, et al. Manuscr Ipt Llnd, et al. Manuscr Ipt Llnd, et al. Manuscr Ipt Winner &Fsrrel I, 1976 kbf3ker &Laufln, 1964 Warnlck bt&II, I%9 tihr Ing, 1976 Mhr Ing, 1976 Ywnlck 4tioll, 1969 Andeison, et al. 19Ml tfubshmn, I%1 Calms, et al. 1918

B-53Table 6. GoatInud) SpUl~ fwlfw, Phi lodlns acut lcornls Rotltu, Phllodlna acutluwnls Rotlfer, Phflodlna acutlcornlr Rotlfer, Phi lodlna acutlcwnls coho 5alIyy1, Oncorhynchus hlsutch Coho salmon, Oncorhynchur klsutch coho salmon, Oncorhynchus klsutch coho SalmxI. Oncorhynchus klsutch Coho saIlon, Oncorhynchus kfsutch coho salmm, Oncorhynchus klrutch coho salmon, Oncorhynchus klsutch cdl0 Mlmon, Oncorhynchus klsutch coho =I-, Oncorhynchus kIrutch coho salmon, Oncorhynchus klsutch Duretlon 48 hrs JB hrs 43 lus 40 hrs 46 lx-s

30 days n hf-s 72hrs Rfrs 72hrr 72hrs 72hrs 72hs 72bra Efhct

LC50 LC50 LC50 Lcw Reduced surv Ival on transfer to seawater LC50 LC50 LC50 LC50 LC50 LC50 LCM LC50 LCbO RemIt QNl/l) 1,200 1,130 l,oo(-J 950 30

280 370 I90 480 440 460 480 560 Refereeu

Calms, et al. 1918 Calms, et sl. 1978 Calms, et al. I978 Calms, et al. I918 Lorz 4WPherson, 1976 Holland, et al. IWO tblland, et al. I960 HOIland, et al. I%0 Hollsnd, et al. I%0 fblland, et al. I%0 HOIland, et al. I%0 HOIland, et al. I%0 Holland, et al. 1960 tbl land, et al. 1%0

B-54Table 6. Kaatleumd) Sprlu cob0 safm, Oncwhyncbus klsutch colbo YlIp*, Ontxrw klsutch cd0 ~lrn, oacuhyndrus klrutch cdm salam, Chcorhyncfwr klsutch soclmym salnm, Oncorhynchus aerke Chfnook salUn, Oncorhynchus tshawytscha Chfnook salon, Oncwhynchus tshawytscha ChinOoft salwa~ fslsvlnJ, Oncorhynchus tshamytscha Chlnook salrwr (sfevln), Oncorhynchus tshawytscha ChInook salm IsrfrupJ, Ollcorhynchur tshauytrcha Chlnooh salvn fsrlrup), Oncorhynchus tshaaytscha ChInooh ralun Iparr), Oncahynchus tshaytscha Chfnooft saIlron tparr), Oncwhynchus tshawytscha Chfnodc salvwr fsmolt), Oncorhynchus tshauytscha Dwatlon 72 IKS 72 hr 72fur 72fur 24 h-s

5days ia days 200 h-5 2Dofus

zoo hrs 200 MS 200 frs MO hrs 200 ffrs Ettmct

LC50 LC50 LCSO LCM Slgrlf lcant cfban94 in uxtlcostmrlod fstr4ssJ LCSO Reduced urvlval and grouth of sac fry LCM LCIO LCM LCIO LC50 LCIO LC50 Result cl&r I 780 5to 520 480 64

I78 21 20 I5 I9 J4 30 I7 26 Ratwwcw

tilland. et al. 1960 HOIland, et al. I960 Holland, et al. I%0 Holland, et al. I960 Donaldson &Dye, 1975 Holland, et al. I%0 Hazel &Melth, l9Xl Chapman, 1978 Chapron, 1978 -pun, I978 Chapran, 1978 chapMn, 1978 Chaplkm, 1978 Chapman, 1978

B-55Table 6. UkmtIru*d)

N chinook vlwn (molt), Oncorhynchus tshimytscha ChInook salmon, Omxuhynchus tshsrytscha Ralnbou trout, Salm qalrdnerl Halnbou trout, Salvo qalrdnerl RaInhow trout, Salr, Qalrdnerl Halnbw trout, Salm qalrdnerl Halnbou trout, &3lao y~lrdnerl Ralnbow trout, Salm q~lrdnerl Ralnbou trout, Sala qalrdnerl Ralnbow trcwt, Salmo galrdner I Ralnboa trout falevln), Salvo qalrdnerl ftalnbou trout falevln), Salm qalrdnerl RaInbow trout (swlaruy), Salem qdlrdner I Ralnbw trout fswlm-up), SdIre ydII-Jner I ouratlon mo hrs 72fus 96 hrs % hrs % hrs
2 hrs
7 days
21 days IOdays

7 days I86 hrs I66 hrs 200 b-s

mo lus Result Effwt crqI1, LCIO LC50 LC50 LC50 LCSO Oeprtrssed 01factory response LC50 &dlan perfod of survival Depressed feed Ing rate snd grouth kdlan period of wrvl val LC50 LCIO LC50 LCIO I0 I90 516# 309’ Ill’

a
44 40
75
44 26 I9 I7 9 ReferChapMn, 1978 HOIland, I960 tkmuth b Sprague, 1970 tiorwth 4 Sproyue, 1978 tiouarth 6Sprayuu, 1970 tkua, et al. 1976 Lloyd, I%1 Graode, 1966 Lett, et al. 1916 Lloyd, l%l Chap-, In press Chapaan, In press Chapakin, In putis Chapniul, In prt&Ll

3-36Table 6. collt lewd) Species RaInbo* trout (Parr), Salm galrdner I Ralnbou trout (parr), Slrlgpr(rdnwl RaInbaa trout (molt). Salt aslrdnerk RaInbar trout (molt), Salm galrdnerl RaInbar trout (molt), Sala galrdnerl Ralnbou trout (smelt), Salm qalrdner I Ralnbou troui (fry), Salvo qalrdnerl Rainbow trout (fry), SaIw, galrdner t RaInbow trout (fry), Salvo galrdnerl Ralnbou trout (fry), Sala qalrdwl Rain& trout (fry), Sallo qalrdnerl RaInboa trout (fry), Saluo qalrdner I Ralnbou trout (fry), Salr, qalrdnerl RaInbar trout (fry), Salr, qalrdnerl lhwatlon 200 hrs 200 hrs

mo hrs

mo hrs >I0 days I4 days LC50 lhr Avol dance behavlor 24 fws IL50 24 hi-s LC50 24 frs Lcm 96 hrs % hrs 40 hrs % hrs Effect

LC50 cc10 Lc50 LCIO Threshold lE50

LC50 (tIeId) LC50 LC50 IfIeld) LC50 Result kI/IJ 15 Reference

Chapman, In press 8 Chapatn, In pruss 21 Chapman, In press 7 Chapran, In press 94 Fcgels ASprague,

1977 870 Calamarl 4Marchettl,

1973 0.1 folur, 1976 9SO Calms, et al. I978 430 Calms, et al. 1973 I50 Calms, et al. 1978 253 hle, 1977 2s*680 Lett, et al. 1976 70 Cala*arl aMarchettl,

1975 250 Goett1, et al. I972

a-57Tabla 6. (COdIMd)

SIWCIW Ralabcu trout (try), Salc ~lrdnwl Rslnbor trout (fry), salrp g8lcdnwI Ralnba tfft:fry), Salmo ga RaInbar trout, Salmo galrdnerl Rslnbom trout, Sala galrdnerl Ralnbou trout, Salm galrdnwl Rslnbou trout, Sallo galrdnerl Ralnbw trout. Salmo galrdnerl Ralntw trout, Salmo galrdnerl Aslnbw trout, Salr, qalrdnerlRalnbw trout, Salrr, galrdner I Ralnbw trout, Salao galrdfhwl Ralnbw trout, Salr*, galrdnerl Halntmu trout, Salru gnlr4nurl Durrt Ion 24 hr 24 brs
72 trs ,I5 days >I5 cbys ,I5 days >I5 days >I5 days >I5 Qays 40 hrs
48 hrs 40 hrs
72 hrs 4a nrs Effect

lc50

LC50 Threshold iE50 Threshold LC50 Threshold Lc50 Threshold LC50 Threshold LC50 Threshold LIZ50 Lc50 LCSO LC50 Lcxl LC!m ROSUH !rp/l 140 I30 500 I9 54 48 78 I8 %

750 I50 \,I00 270 RdUUU4

shau 6flroun, 1974 Sbau &Brorn, l9?4 Brown, et al. 1974 MlIler 4McKay, 1380 Mll ler &McKay, I980 MlIler 4McKay, 1380 Mll ler I ClcK~y, I380 WI ler &McKisy, 1980 Mll ler 6McKay, 1980 &own, I%8 Eroun &Dslton, 1970 Cope, 1966 Lloyd, \%\ tiurlluI~t 6 Varulyku, I%4

B-Si3Table 6. uhntlnuui) Spuler Atlantic salmon, Salmo salar -- Atlantlc 5almo0, J?J=-= AiIaMlc salroo, salr, salsr -- Atlant Ic LoImoa, Salm salsr -- Brwn trout, Sallo trutta -- Brook trout, SalvelInus fontlnalls crook trout, Salve1 lnus tontlnal I5 tkook trout, SalvelInus tontlnalls Stonerol ler, Carpostonla ancmalw Goldtlsh, Carass lus auratus Coldfls), Carasslus auratus GoldfIsh, Carars Ius W&U5 Golden 5hlner. Noiemlgonlus cry5oleucas Golden shiner. Notmlgonlu5 crysolatcas Golden shiner, Notmlgonlus crysoleucas ourstIoa 7days 7days 21 days 21-30 tu-s 21 days 24 Ius 21 days 33? days % hrs LCSO 24 lrs LC50 24 hrs LC50 2,900 Calms, ut al. 1978 24 hrs LC!xJ 24tars LC50 24 bus 24 b-5 RuU1t Etlect (W/l) RetuUWX lnclplent lethal 48 level Sprague, 1964 Inclplent lethal 32 Sprague &&msay, level I%5 MadIan period ot 40 Grande, I%6 5urvIval Medlan perlod ot 5urvlval 50 Zltko 6Carson, 19/b Medlan period ot wrvlval 45 Grade, l96h SIgnIt Icant change In cough rate 9 Drumond, et al. 1973 Slgnlf lcant change5 In blood chmlstry 23 MLKIR, st al. 1970 Slgnlflcmt changes In blood chumlstry 17.4 McKlr, et al. 1970 1,400 Gerklar, et til. 1976 2,700 CaIrna, et al. 1978

1,510 Calms, et al. 1978 330 Calrn5, et al. 1918 LC50 230 Calrns, et al. 1978 LC50 270 Cdlrns, et al. I978

B-59Table 6. K-oat Inued) Result (W/l) t1,400 brat Ion 96 hrs Effect

LC50 Reference Geckler, at Gil. I916 Species Sir lped shiner. Hotrop chrysocepha 1~5 Strlpmd Miner, No)rop chryrocepha les Strlped shiner, Roiropls chrysocephales Strlped shInor, Motropls chrysocephales Str lped shlnmr, Notropls chrysocephales Strlped shiner,

chyysocephales Notr opls % hrs LC50 16,ooO Geckler, et al. I976 % hrs LCSO 3,400 Geckler, et al. l97b % hrs Lcx 4,m Geckler, ut al. 1976 96hrs LC50 5.ooo Gckler, et al. I916 96hrs DecrtMbrt blood

osmolarlty 2,5oQ 48hs LC50 (21 tests) 750- 21,ooo Gxklrr, al al. 1976 96 hrs LC50 (6 tests) l,laoM,W Ceckler, el dl. 1976 96 hrs LC50 (21 tests) l,600- 21,000 8rungs, et al. 1976 (650 23,600 740- 13,ooo 4x8 BIuntnose minnow, Plwphales notatus bluntnose llnnw, Plrephales notatus fathead rlnnw, Plmephaltrs prorelas 96hrs %.hrs LC50 (36 test;s, Geckler, el al. 1976 Fathead minnow, Plmephales JJrmel~5 Lc50 (7 tests) Geckler, et dl. 1976 Fathead llmww, Plmephales prcmelas Fathead rlnnor, Plmephales prorelas fathead rlnnou, Plmephaler prorelas % hrs LC50 (T(r: - I2 edI) LC50 (TOC = I3 WI) Llnd, et al. Manuscr Ipt Llnd, et ai. Manuscr Ipt 96hrs 516

B-68Tab10 6. soatlw8d) Spulms Fathead llnnw, Plaephales prcmelar Fathoad &mor, w8w F-las fmw ‘&au, ~prcmelas Fathad llnmw, Plmmphslor fbroular fathead llnaw, PIm@ubl~s prKcrrlas FatMad llnnou, Ptmephales prmlas fathead rlnnca, PI*ephales prcuelas Creek chub, Semtl lus atrmculatus Creek chub, Seatllus atrmculatus Bran bulIhead, lctalurus nobulosus Channrl catt Irh, lctalurus punctatus Chsnnel ottIs>, Ictalwus punctatus Channel catt Ish, lctalurus punctatus Channel catflsh, Ictalurus pwrctatus Durat Ian % b-5 % hrs 96 hrs % IN-S 96hrr 96 hrs Llte cycle 96 IKS 96hrs % hrs 94 tars 24 hrs 24 hrs 24 lrs Effect

lC50 (TOC - 36 *4/l) LC50 (TOC - 28 Is/l) LC50 (TOC - I5 *g/l) LC%l (TOC - 34 41) LC50 (TCC - 30 WI) LCBO(TW - 30 WI) aNonlc Ilalts Lcm LC!jo LCW Decrmsd blocd osaolwlty L&m Lcm Lcm Rwult (Pa/l, 1.586 1,129 550 I.001 2,050 2.336 66I20 ll,mo 1.100 ll,Wo 2,5M 1,730 2,a 3,100 Refwuwm

Llnd, et dl. Manuscr Ipt Llnd, et al. Mbnuscr Ipt Llnd, r? ~1. Manuscr Ip: Llnd, at al. Manuscr Ipr Llnd, et al. M8nuscrIpt Llnd, et al. Manuscript fkungs, et al. 1976 ekler, et al. 1976 Geckler. et al. 1976 l%ckler, et al. 1976 LOUIS ALwIs, 1971 Calms, et al. IY?B Calms, et al. 1978 Calms, et al. 1978

B-61Table 6. Kontlrued) Result (p!J/l) 680 E,ttect lC50 uetarence Uurat Ion IOcbys % hrs SlMlClU Fl*#lJ. rarkw) tlorldatl Wosqultot Irh, Gemburls attlnls WJPY, Pcacl II4 retlcula?a Ralnbom darter, Eiheosi4ma caeruleur Aslnbou darter, Eiheosttma cserulew RaInbow dzutor, tthwslw caerutauur Johnny dater, Ltheostema nlgrunl Orangethroat barter, Etheostoma spactabl le Orangethrclat darta-, 6theostoma spectabl le Orangethroat darter, Etheostora spectabl le Orangethroat dafter, Etheostcma spactabl le Rock bass. Adlopl Ites relpastr Is Elluegll I.

wxrochlrus Lepollls Mluaglll, aacrochlrus Lepculs t7els &Spraguu, I9 7 LC50 1750 ag/l turbldlty) LC50 75,ooo Yal len, et til. 1957 1,250 Mlnlcuccl , 1971 24 hr* LCM Geckler, et al. 1976 96 hrs 96 hrs LC50 bckler, et CII. 1976 % hrs 96 hrr 96 hrs LC50 Geckler, ul dl. I976 Gackler, et dl. 1916’ LC50 6,000 LCM 9.800 Geckler, ut ~81. I916 96 lws Lc50 7.900 Geckler, al di. 1976 96hrs LCQ >,400 (;trckltW, tit d,1. lYl6 % tus LCSO 5,mo Guckler, et dl. lg?b % hrs 24-36 hrs LC50 1,432 Llnd, et dl. Mmuscr Ipi OViara, 1971 Altertd oxygen consuqt Ion rates LC50 300 411Iv5 2,800 uq-m, I%6

3-62Table 6. mMbtlnuod) SpecIes Bluegill, macrochlrus Lepomis 8lWBlU l~~ochlrus BlWl~ I,

mcrochlrur Lepo~lr Bluaglll, L-1 5macro& Irus
Colonial hydrold, Clllpanularla tloxuosa Colonial hydrold, ~ampaaularle tlexuosa Colonial hydrold, EIrene vlrldula Polychaete wora, Clrrlforrla splrabrtia Polychaete worm, Phyllodoce naculsta Polychaoto uora, fleanthes armaceodentata Polycheete WI, Neanthes arenaceodntata Bay seal lop, Argopecten lrradians say scallop, Argopacten lrradlans kerlcan oyster (larva), Crassostrea vlrglnlca Duration 96 hrs 96 hrs % hrs % hrs

11days

14-21 days 26days 9days 28 days 20 days 42 days I19 days I2 days Etfect

LCSO LC50 LC50 LCSO SALTWATERWECIES Growth rate lnhlbltlon Enzyme InhIbItIon Growth rate lnhlbltlon 50%mortal Ity 50%aorta1 Iiy 50%mortality 501 moriallty EC%, growth loo% mortality MS rortallty Result crdl) 16,000 17,ooo 740 1,800

lo-131.43 30-60 40 80 44 100 5.8 5 46 Reterence

Geckler, et al. 1976 Geckler, et al. 1976 Tram, 1956 Turnbull. et al. 1954

Stebblng, 1976 Mcwe AStebblng, 1976 Karbe, 1972 Wllanovlch, tit al, 1976 McLusky 1PhiIIIps, 1975 Pesch 4Worgan, 1978 Pusch 6Morgan, 1978 U.S. EPA, 1980 U.S. WA, 1980 Calabrase, et al. 1977

B-63Table 4. aontlnued) -It !yp/l)a32 ournt loa 4days Black Zion*,

ueckodl I Red ahIp% HDllotls rutescubr hrthur quahaug (Iwva) blucmarIn aoqenarla

s&t slml Iod clam, 5 afmnarla MusseI, Mytl lus edul Is Channeled whelk, Fiusycon canallculatum kid snail, Nasser lus cbsoletus Calanold ccbpepad, Acart la clausl -- Calanold copepod, Acartla tonsa -- QWW. Metrldla pacltlcs -popDd, Phlalldaum sp. Calanold copepod, Acartle tonsa -- CopePod, Euchaeta aar lna Erred llIrtopathologlcal glll lbwulltlms Hlrtopatholaglcal gIlI lbMwulltl~ 50%w-tallty Reteruce Mwtln, at al. 1971 4lklys ,32 Wtln, at al. 1977 a-10 days 71 days 30 Calebre6e, lt al. I977 Shuster 4Prlngle, I%6 Elrlar, 1977 53s un-tal Ity 25 7days 50$ oortallty 35 1days 77 days sol mortality Scott 4Ma&r, 1972

50s mortal lty 470 Better &Yevlch, 1915 3days Decrease In oxygen

consumpt ICNI 50%mortality IO0 Maclnnes 6Ttburberg, I973 2days 34-82 Mwa Itaw AposlololKlu IOU, 1978 Sosnouskl, et sl. 1979 Raave, et al. 1976 6days 50s mortallty 9-73 24 h-s 24 hrs 24 Ius 24 lus lc50 I76

Lao 34 Reeve, et al. 1976 lx50 104-31 I fbeve, et sl. 1976 IX50 I88 Reeve, et al. 1976

B-64Tablw 6. woatlaud~ Speclos W-pod, Undlnula vulqarls gep&y’~ Rot1fu, &acblonus pllcatllls ctenophore, Wnerlopsls ucrodyl Ctenophore, Pleurobrachla pl leus Larval annol Ids, Mlxed speclaa Chaetognat h, Sayltta hlsplda Shrlep, Euphausla pacltlca CopePod. Labldocera scott I Aaerlcan lobster, -us amm-lcMus Coral-met achlnold, Echlnorretra mtbael Sea urchin, Arbacla punctulata Sea urchin, Paracentrotus IIvl bus -1cw, Fundulus hetamclltus ouratlon 24 lus 24 h-s 24 hrs 24 lu-s 24 lrs 24 h-s 24 hs 24 hs 24 lus I3 days 4days

4days

21 days Rmsult

litted 1

h/l LC50 192 LC50 40 LC50 100 LCM 17-29 Ia0 33 LC50 89 LC50 43-460 Ueuve, et al. I916 ImQ 14-30 Lc50 I32 50%mortal Ity 56 Supprerslon ot larval skeletal dav*loprent 20

56Y docrease In spera mtlllty 300 Retardat Ion ot gouth ot pluteal larvae IQ-20 tllstopathologlcaI IesIons 600 Rotwonce Reeve, et al. I976 Reeve, et al. 1976 f&eve, et al. 1976 Reeve. et al. 1976 f&eve, et al. 1976 Reeve, et al. 1976

Uewe, et al. 1916 Reeve, et al. 1976 McLeese, 1974 lies IInga, 1976

young &Nelscm, 1974 aougls, 1965

Gardner Ala Hoche, I973

B-65spadu -b=hog, PfldJgu~ betuocl Itus Mloatlc rl Iverslda, baldlo mmldls -- Paclflc herrIng (fwryo), Clupea harwqus pllssl Pacltlc brrlng (Iuva), Clupea harengur pallasl Atlmtlc aeflhaden, Brevooftls tyrannus Spot, 1elostmus x.anlhuc us AtIant Ii croaker, MIcropagan undulate Pint Ish, Laqodon rhcnboldoa Plslce, Pleuronectes platessa YInter tlounder. PS8Udopl8UWW3Ci8S amerICMU5 Alga, Lamlnerls hyperborla Durst loa 4days 4days 6hays 2days 14days I4 dqa I4 days 14days 4days I4 days

28 days 50s lortal

50s -till 50s llKu-talliyIQ

IQ 50s lnortallty 501 mtallty HlstopaiholoyIc~l lesIons Result tPQ/l, 600 Gardner bLoHocht,,

1973

610 Engel, et al. 1976 160 Engel. et al. 1916 210 Qel, et al. 1916 I50 Lngol, et ,al. 1976 750 Wmard, et al. 1975 I60 Baker, 1963 tttwt Enzyme InhIbItIon HlstopatholoyICaI IOSlOWi InCIplent LC50 lnClpl8nt LC50

Grath decrease 50 Hopkins dKrtln, 1971

l Olssolv8d Copper; no other medsuremfmt reported

3-66REFERENCES

Adema, D.Y.M. and A.M. Degroot-Van Zijl. 1972. The influence of copper on the water flea Daphnia 

### magna. TN0Nieuws. 27: 474.
Anderson, 3.G. 1343. The apparent thresholds of toxicity to Oaphnia magna for chlorides of various metals when added to Lake Erie water. Trans. Am. Fish. Sot. 78: 96. Anderson, R.L, et al. 1980. Survival and growth of 

### Tanytarsus dfssimilis (Chironomidae) exposed to copper, cadmium, zinc, and lead. Arch. Environ. Contam. Toxicol. 9: 329. Andrew, R.W. 1976. Toxfcity Relationships Waters. &: Toxicity to 6fota of Metal Forms Cormr.Windsor, Ontario, Canada. p.127. to 

### Copper Forms in Natural in Natural Water. Int. Joint

Andrew, R.W., 

### et al. 1977. Effects of inorganic complexing ontoxicity of copper to Daphnia magna. Water Res. 11: 309. Arthur, 

### J.W.and E.H. Leonard. 1970. Effects of

### copperonGamnaruspseudolinnaeous, Physa Integra, and Campeloma decisum in soft water. 

### Jour. Fish. Res. Board Can. 27: 1277. 8aker, 

### J.T.P. 1969. Histological and electron microscoofcai observations on copper poisoning in the winter flounder (Pseudopleuronectes americanus). Jour. Fish. Res. 8oard. Can. 26: 2785.

B-673drtlett, L., et al. 1974. Effects of cxoer, .zjflc, and :aCm~.m ;n

Selanastrgm caoricornutum. Water Res. 8: 179.
3enoit, D.A. 1975. Chronic effects of copper on survival, growth, and reproduction of the bluegill (Lepomis macrochirus). Trans. Am. Fish Sot. 104: 353. Betxer, 5.8. and P.P. Yevich. 1975. Copper toxicity in Busycon canaliculatun l.. 8101. Bull. 148: 16. -- Bfesfnger, K.E. and G.M. Christensen. 1972. Effects of various fletals on survival, growth, reproduction, andmetabolism of Oaphnia magna. Jour. Fish Res. Board Can. 29: 1691. Birdsong, C.L. andJ.W. Avavit, Jr. 1971. Toxicity of certain chemicals to juvenile pompano. Prog. Fish. Cult. 33: 76. Birge, 

### W.J. and J.A. Black. 1979. Effects of Copper on Embryonic and Juvenile Stages of Aquatics Animals. &: J.O. Nriagu (ed.), Copper in the Environment. J. Wiley andSons, NewYork. Eougis, P. 1965. Effect of copper on growth of the pluteus of the sea urchin (Paracentrotus lividus). C.r. hebd. Seanc. Acad. Sci., Paris. 260: 2929. Bringmann, G. and R. Kuhn. 1959. Comparative water-toxicology tlons onbacteria, algae, and Daphnids. Ges. Ind. 80: 115. invest iga-Srjqgmann, C. and ?. Kuhn. 1377. Conditions of tCXiCity #Jf dater-s3\>bie

substances against 3aphnia magna. Z.f, WasseT und Abwasseriorschung. 10: 151. Brown, B.T. and B.M. Rattigan. 1979. Toxicity of soluble copper and other metal ions to Elodea canadensis. Environ. Pollut. 19: 303.
Brown, V.B. 1968. The calculations of the acute toxicity of mixtures of ooisons to rainbow trout. Water Res. 2: 723. Brown, V.M. and R.A. Oalton. 1970. The acute toxicity to rainbow trout of mixtures of copper, phenol, zinc, andnickel. Jour. Fish. Biol. 2: 211. born, V.M., et al. 1974. Aspects of water quality- andtoxicity of copper to rainbow trout. Water Res. 8: 797. 8rungs, W.A., et al. 1973. Acute and long-term accumulation of copper by the brown bullhead (tctalurus nebulosus). Jour. Fish Res. 8oard Can. 30: 583. 

### bungs, W.A., et al. 1976. Acute and chronic toxicity of copper to the fathead minnow in asurface water of variable quality. Water Res. 10: 37. Buikema, A.L., et al. 1974. Evaluation of Philodina acutacornis (rotifera) asabioassay organism for heavy metals. Water Res. Bull. 10: 648.

B-69Buikema, A.L., et al. 1977. Rot'fer sensitivity '0 combinations of inorganic water PO1

lutants. Bull. 92 - Virginia Mater Resour. ?es. Center, Blacksburg, Virginia. Cabejszek, I. and M. Stasiak. 1960. Studies on the influences of some metals on water biocenosis employing Oaphnia magna. Rozniki Panst. Zakl. Hig, ilarsar. 11: 303‘ Cairns, J., et al. 1978. Effects of 

### temperature onaquatic organism sensitivity to selected chemicals. 3~11. 106 - Virginia Water Resour. Res. Center, Blacksburg, Virginia. Cairns, J., 

### et al. 1979. Invertebrate response to 

### thermal shock following exposure to acutely sub-lethal concentrations of chemicals. Arch. Hydriobiol. 77: 162. Calabarese, A., et al. 1973. The toxicity of heavy metals to embryos of the American oyster Crassostrea virginica. Mar. 8iol. 18: 162. Calabrese, A., et al. 1977. Survival and growth of bivalve 1arvae under heavymetal stress. Mar. 6iol. 41: 179 Calamari, 0. and R. Marchetti. 1973. The toxicity of mixtures of metals and surfactants to rainbow trout (Salmo gairdneri Rich.), Water Res. 7: 1453.

s-70Calanari, 0. and q. Marchetti. 2975. Predicted and observed 

### acute toxicity

of copper-and ammonia to 

### rainbowtrout (Salma gairdneri i7icfr.). Prog. Water Tech. 

### 7:569. Chakoumakos, C., et a?. 1979. The toxicity of copper to rainbow and

### cutthroat trouts under different conditions of alkalinity, pH and hardness. Env. Sci. Tech. 13: 213. Chapman, G.A. 1978. Toxicities of cadmium, copper and zinc to four juvenile stages of chinook salmon andsteelhead. Trans. Am.Fish Sot. 

### 107:841. Chapman, G.A. and J.K. McCrady. 1977. Copper Toxicity: A Question of Form. 2: Recent Advances in Fish Toxicology, a Symposium. EPA 

### 600/3-77-085. U.S. Environ. Prot. Agency, p. 132. Chapman, G.A. and D.G. Stevens. 1978. Acute lethal levels of cadmium, copper and zinc to adult male coho salmon and steelhead. Trans. Am.Fish Sot. 

### 107:837. Chapman, G.A., et al. Effects of water hardness on the toxicity of metals to Daphnta mapna. (Manuscript). Chynoweth, D.P., et al. 1976. Effect of Organic Pollutants onCopper Toxicity to Fish. & foxlc4ty to Biota of Metal Forms in Natural Water. Int. 

### Joint Corm.,Windsor, Ontario, Canada. p. 145.



### 8-71Clendenning, K.A. and 

### W.J. North. 1959. Effects of ilastes on the Giant



### kelp, Macrocystis pyrifer. In: E.A. Pearson, (ed.), Proc. 1st Int. Conf. WasteOisposal in the Yarine Environment. Berkeley, California. Connor, P.M. 1972. Acute toxicity of heavy metals to somemarine larvae. Mar. Pollut. Bull. 3: 190. Cope, 0.8. 1966. Contamination of the freshwater ecosystems by pesticides. dour. Aopl. Ecol. 3(Suppl.): 33. Donaldson, E.M. and H.M. Oye. 1975. Cortfcosteriod concentrations in sockeye salmon (Oncorhynchus nerka) exposed to law concentrations of capper. Jour. Fish Res. Board Can. 32: 533. Drumnond, R.A., Ct al, 1973. Someshort-tam jndfcatots of sublethal effects of copper on brook trout, Salvelinus fontlnalis. Jour. Fish Res. Board Can. 30: 698. Eisler, R. 

### 1977. Acute toxicities of selected 

### heavymetals to the soft

### shell clam, Myaarenaria. Bull. Environ. Contam. Toxicol. 

### 17:137. Elder, J.F.. and A.J. Horne. 1973. 

### Copper cycles and CuSo4 algjcidal capacity in twu California 

### lakes. Environ. Manage. 2: 17. Engel, O.'r(., et al. 1976. 

### Effects of 

### copper on marine eggs and larvae. Environ. Health Perspect. 17: 287.

0-72Erickson, s.;. 1972. Toxicity of coo[;er to Thallassiosira pseudofiana 'I0

unenriched inshore seawater. Jour. Phycology. 34: 318.
Erickson, S.J., et al. 1970. Ascreening technique for estimating 

### copper toxicity to estuarine 

### phytoplankton. Jour. 'dater Pollut. Control Fed. 42, R 270. Fogels, A. and 

### J.3. Sprague. 197?. Comparative short-term zebrafish, flagfish, and rainbow trout to five poisons includ reference toxfcants. Water Res. (GA.) 11: 811. tolerance of ing potential

Folmer, L.C. 1976. 

### Overtavofdance reaction of rainbow trout fry to nine herbicfdes. Bull. Environ. Cont. Toxicol. 15: 509. Gachter, R., et al. 1973. Complexing capacity of the nutrient medium and its relation to inhibition of algal photosynthesis by copper. Schweit. Zeits. fur Hydra?. 35: 252. Gardner, G.R. and G. LaRoche. 

### 1973. Copper induced lesfons in estuarine teleosts. 

### Jour. Fish. Res. Board Can. 30: 363. Geckler, J.R., et al. 

### 1976. Validity of laboratory tests for predicting copper toxicftj in streams. EPA600/3-76416. U.S. Environ. Prot. Agency. Goettl, J.P., et 

### al. 1972. Water pollution studies. Colorado Fish. Res. Rev. No. 7, 

### 36, Dir. Game,Fish. Parks, Fort Collins, Colorado.

B-73Grande, M. 1966. Effect of cooper and zinc on salmonid fishes. Adv. 'AatetPollut. Res. 1: 97. 3rd Conf. 

### yunich. Hale, J.G. 1977. Toxicity of metal mining wastes. Bull. Environ. Contam. Toxicol. 17: 66, Hara, T., et al. 1976. Effects of mercury and copper on the olfactory response in rainbow trout, Salmo qairdneri. Jour. Fish. Res. Board Can, 33: 1568. Hazel, C.R. and S.J. Meith. 1970. Bioassay of king salmon eggs andsac fry in copper solutions. Calif. Fish Game.36: 121. Herbert, D.W.M. and

### J.M. Vandyke. 1964. The toxicity to fish of mixtures of poisons. II. copper - amnonia and zinc - phenol mixtures. Ann. Appl. 8101. 53: 415. Heslinga, G.A. 

### 1976. Effects of copper on the coral-reef echinoid Echinometra mathael. Mar. Biol. 35: 155. Holland, G.A., et al. 

### 1960. Toxic effects of organfc and inorganic pollutants on young salmon and trout. State of Washington - Dep. Fish. Res. Bull. 5: 223. Hopkins,. R. and J.M. Kain. 1971. The effect of marine pollutants on Lamfnarea hyperboria. Mar. Pollut. Bull. 2: 75.

3-74doming, Y.3. 3nd T.J. Neiqeisel. 1979.

bluntnose minnow (Pimephaies notatus Raf Toxicol. 8: 545. Chrcfli inesoue)

Howarth, R.S. and J.8. Sprague. 1978. Cooper lethality to rainbow trout in waters of various hardness and pH. Water Res. 12: 455.
HuSshnan, J.9. 1967. Effects of copper onthe crayfish Crconectes 

### rusticus (Girard): I. Acute toxicity. Crustaceana. 12: 33. Hughes, J.S. 1971. Tolerance of Strfped Bass, Motone saxitalis (Walbaum) Larvae and Fingerlings to Nine Chemicals Used in Pond Cultures. In: Proc. 24th Ann. Conf. S.E. Assoc. GameFish. Comn. p.431. Hughes, 3.5. 1973. Acute toxicity of thirty chemicals to striped bass (Morone saxitalis). Presented at Western Assoc. State GameFish. Comm., Salt Lake City, Utah. Jackim, E. 1973. Influence of lead and other metals on aaminolevulinate dehydrase activity. Jour. Ffsh. Res. Board Can. 30: 560. Johnson, M. andJ.H. Gentile. 1979. The acute toxicity of copper, cadmium, and mercury to larval American lobster Homarus americanus. Environ. Contam. Toxicol. 22: 258.

G-75Jones, L.H., 

### et al. 1976. Someeffects of Salinity on the toxicity of copper to the polychaete Nereis diveriscolor. Estuarine Coastal Mar. Sci. 4: 107.
Karbe, L. 1972. Marine hydroiden als testorganismen zur prufung der toxizitat von abwasserstoffen. Dfewfrkung van schwemetallen auf 'kolonien von Eirene viridula. Mar. Biol. 

### 12:315. Lett, P.F., et al. 1976. Effect of copper onsomeaspects of the bioenergenetics of rainbow trout. Jour. Fish. Res. Board Can. 33: 1335. Lewis, M. 1978. Acute toxicity of copper, zinc, and manganese in single and mixed salt solutions to juvenile longfin date, Agosia. chrysogaster. 

### Jour. Fish Bfol. 13: 695. Lewis, 5.0. andW.M.Lewis. 1971. The effect of zinc and copper onthe osmolarity of blood serum of channel catfish, Ictalurus punctatus Raf., and golden shiner, Noternfgonius crysoleucas Mitchell. Trans. Pm. Fish. Sot. 100: 639. Lind, O., et al. Regional copper-nickel study. Aquatic toxicology progress report. (Manuscript). Lloyd, R. 

### 1961. The toxicity of mixtures of zinc and copper sulphates to rainbow trout (Salmo qafrdntrl R.). Ann. Appl. Biol. 49: 535.

9-76Lam, H.Y. and 8.P. McPherson. 1976. Effects of copper 

### or zinc in fresh

water or the adaptation to seawater and ATPase activity and the effects 

### of copper onmiqatoty disposition of coho salmon. Jour. Fish. Res. Board Can. 33: 2023.
MacInnes, J.R.. and F.P. Thurberg. 1973. Effects of metals onthe behavior andoxygen consumotdon of the mudsnail. Mar. Poll&. Bull. 4: 1895. Majori, L. and F. Petronfo. 1973. Marine pollution 

### bymetals andtheir accumulation by biological indicators (accumulation factor). Rev. 

### Int. Oceanogr. Med.TomesXXXI. Martin, M., et al. 1977. Copper toxicity experjments in relation to abalone deaths observed In apower plant's cooling waters. Calif. Fish. Game. 

### 63:95. McKim, J.M. and O.A. Benott. 1971. Effects of long-term exposures to copper on survival, growth, and 

### reproduction of brook trout (Salvelinus fontinalis). Jour. Fish. Res. Board Can. 38: 655.
McKim, 

### J.M., et al. 1970. Changes in the blood on brook trout (Salvelinus fontfnalis) after short-term and long-term exposure to copper. Jour. Fish. Res. Board Can. 27: 1883. McKIm, 

### J.M., et al. 1978. Metal toxicity to embryos and larvae of eight species of freshwater fish. - 

### II. Copper. Bull, Environ. Contam. Toxicol. 19: 608.

e-77UcLeese, 3.i. 1374. Tzxicjty Of scooper at two temperatures 3r.d :nree

salinities to the American lobster (IJomarus americanus), dour. Fish. ?es. 

### goardCan. 31: 1949. McLusky, O.S. andC.N.K. Phillips. 1975. Someeffects of copper onthe polychaete Phyl:odoce maculata. Estuarine Coastal Mar. Sci. 3: 103. 

### MI!accv:c,.,

.h CO t.,., et al. 1976. Uptake of cupper by the polychaete Cirrifornria spirabranchia in the presence of dissolved yellow organic matter of natural origin. Estuarine Coastal Mar. Sci. 4: 585.
Miller, T.G. andW.C. McKay. 1980. The effects of hardness, alkalinity and pH of test water on the toxicity of copper to rainbow trout (SdlmO qairdneri). Water Res. 14: 129. Fcinicucci, 0.0. 1971. Flow effects in aquatic bioassays the toxicity of copper at various flow rates to the guppy, Lebistes reticulatus. Ph.D. Thesis. Univ. of Michigan.

Moore, M.N. and A.R.O. Stebbing. 1976. The quantitative cytochemical effects of three metal ions on the lysosomal hydrolase of a hydroid. Jour. Var. Viol. Assoc. 56: 995. Moraitou4postolopoulou. 1978. Acute toxicity of copper to a copepod. Yar. Poll. Sull. 9: 278.

B-78Fount, 0.1. 1968. Chronic toxicity of cooper to fathead nrinnows (?i;reohales Dromelas Rafinesquej. Water Res. 2: 215.
Mount, 0.1. andC.E. Steohan. 1969. Chronic toxicity of copper to tne fathead .Tinnow (Pimephales promelas) in soft water. Jour. Fish. Res. Board Can. 26: 2449. Nebeker, A.V. andA.R. Gaufin. 1964. Bioassays to determine pesticide toxicity to the amphipod crustacean (Gamnarus lacustrfs). Proc. Utah Acad. Sci. 41: 64. Nehring, R.B. 1976. Aquatic insects as biotogical mon pollution. Bull. Environ. Contam. Toxicol. 15: 147. itors of heavy 

### meta

O'Hara, J. 1971. Alterations in oxygen consumption by bluegills exposed to sublethal treatment with copper. 

### WaterRes. 5: 321. Okazaki, R.K. 1976. Copper toxicity in the Pacific oyster Ctassostrea gigas. Bull. Envir. Contam. Toxicol. 16: 658* 

### Patrick, R., et al. 1968. The relatfve sensitivity of diatoms, snails, and fish to twenty 

### CORW~ constituents of industrial wastes. Prog. Fish,-Cult. 30: 137. Pesch, C.E. and 0. Morgan. 1978. Influence of sediment in copper toxicity tests with polycfraete Neanthes arenaceodentata. Water Res. 12: 747.

B-79?hil?ips, 

### O.J.H. 1375. The common nussel Yytilus edulis asan indicator of

pollution by zinc, cadmium, lead and copper. I. Effects of environmental variables onuptake of metals. "ar. Viol. 38: 59. Pickering, Q.H. and C. Henderson. L966. The 

### acute toxicity of someheavy metals to different species of warmwater fishes. 

### A+ Water Pollut. Int. 

### Jour. 10:453. Pickering, Q.H., et al. 

### 1977. Effect of exposure time and copper concentration on reproduction of the fathead minnow (Pimephales promelas). Water Res. 11: 1079. Reeve, W.R., et al. 1976. AControlled Environmental Pollution Experiment (CEPEX) and Its Usefulness in the Study of Larger Marine Zooplankton under Toxic Stress. In: P.M. Lockwood fed.), Effects of Pollutants on Aquatic Organisms. Cambridge, Univ. Press, NewYork. p. 145. Rehwoldt, R., et al. 

### 1971. Acute toxicity of copper, nickel, andzinc ions to someHudson River fish species. 8~11. Environ. Contam. Toxicol. 6: 445. Rehwoldt, R., et al. 1972. The effect of increased temperature upon the acute toxicity of sane heavy metal ions. Bull. Environ. Contam. Toxicol. 

### 8:91. Rehwoldt, R., et al. 

### 1973. The

### acutetoxicity of someheavy metal ions toward benthic organisms. Bull. Environ. Contam. Toxical.. 

### 10:291.

B-80?ice, DA,, Lr. and F.L. Yarrison. 1977I Copper sensitiviry of S3~;~i::

herring, C!upca 

### harmgus pallasi, during its early life 

### .history. Fish. 2es. Bull. 76:347. Riley, 

### J.?. and I. Roth. 

### 1971. Thedistribution of 

### trace elementsinsome species of phytoplankton grown in culture. Jour. Yar. Biol. Assoc. 51: 53. Rosko, 

### J.J. andJ.W. Rachlin. 

### 1975. The effect of copper, zinc, cobalt and manganese on the 

### growthof the marine diatom Nitzschia closterium. 8~11. Torrey Bot. Club. 102: 100. Rosko, 

### J.J. and J.iJ. Rachlin. 1977. The effect of cadmium, copper, mercury 9zinc and lead on cell division, growth and chlorophyll d content of the chlorophyte Chlorella vulgaris. Bull. Torrey Bat. Club. 104: 226. Saifullah, S.M. 1978. Inhibitory effects of copper on marine dinoflagellates. Mar. Viol. 44: 299. Sakaguchi, T., et al. 

### 1972. Uptake of copper by Chlorella 

### regularis. Nippon Nog. Kag. Kaishi. 51: 497. Sauter, S., et al. 1976. Effects of exposure to heavy metals in selected freshwater fish, toxfcity of copper, cadmium, chromium and lead to eggs and fry of seven fish species. EPA600/3-76-105. U.S. Environ. Prot. Agency.Saward, a., et 31. :975. ExQer'Rental stlldies on tye effects of copoer on 3narine food chain, Mar. 8iol. 29: 351. Scott, D.M. and C.!4. Major. 1972. The efcect of copper (II) on survival, pespiration, and heart rate in the comnon blue mussel, Mytilus edulis. Eiol. 81~11. 143: 679.
Shaw, T.L. and V.H. Grown. 1374. The toxicity of some forms of copper to rainbow trout. Water Res. 8: 377.
Shuster, C.N., 

### Jr. and 8.H. Pringle. 

### 1968. Effects of trace metals on estuarine molluscs. Proc. 1st MidAtlantic Ind. Waste Conf., Nov. 

### 13-15, 1967.
Shuster, C,N., 

### Jr. and 0.H. Pringle. 1969. Trace metal accumulation by the American eastern oyster, Crassostrea virginica. Proc. Natl. Shellfish. Assoc. 

### 59:91.

Sosnowski, S.L. and J.H. Gentile. 1978. Toxicological comparison of natural and 

### cultured populations of Acartia tonsa to cadmium, copper and mercury. 

### Jour. Ffsh. Res. Board Can. 35: 1366.
Sosnowski, S.L., 

### et al. 1979. The effect of nutrition on the response of field 

### populations of the calanoid copepod Acartia tonsa to COQQer. Water Res. 

### 13:44% Soear, p. 

### 1977. Cooper accumulation kinetics and lethal tolerance in relation to fish size. Y.S. Thesis. Concordia Univ., Montreal, Canada.

### Sorsgue, d.3. 1964. Lethal :oncevtra:ions of cooDer 3~d zirc for jo~,ng Itlantjc salmon. dour. Fish, Res. Soard Can. 31: 17. Sprague, 

### J.B. and B.A. Ramsay. 1965. Lethal levels of mixed copper-tire solutions for juvenile salmon, Jour. Fish. Res. Board Can. 22: 425. Stanley, 8.A. 19?4. Toxicity #2f be3aiy metals and salts to euras ;nilfoil (Myriophyllm spicatus L.). Ai-ch. Environ. Contan. Toxic01 an water2: 33i. Stebbing, A.R.D. 

### 1976. The effects of low metal levels on a clonal hydroid. 

### Jour. Mar. Biol. Assoc. 56: 977.
Steemann-Melsen, E. and H. Bruun-Laursen. 1976. Effect of CuC04 on the photosynthesis rate of 

### phytoplankton in four Danish lakes. 

### Oikos. 27:239.
Steemann-Nielsen, E. and L. Kemp-Nielsen. 1970. Influence of de concentrations of copper on the growth of Chlorella pyrenoidosa. Plant. 23: 828. leter Physious iol.

Steemann-Nielsen, E. and 5. tlium4ndersen. 1970. Copper ions as poison in sea and in freshwater. Mar. 8iol. 6: 93.
Stokes, P. andT.C. Hutchinson. 1976. Cooper Toxicity to Phytoplankton, as Affected 

### by Organic Ligands, Other Cations and Inherent Tolerance of Algae to Copper. &: Toxicity to Biota of Vet31 Furms in Natural Water. Int. 

### Joint Corm.,Windsar, Ontario, Canada. 3. 1591c3r~uell, S.V. 3rd C. qenderson. :960. Toxicity of :ess common -et-Z:s '3

fjshes. !nd. 'rlastes. 5: 12.

-rama, E.8. 1954. The toxicity of copter to the common bluegill (Lepomis machrocnirus Rafinesaue). Notulae Natur. No. 257. p. 1.
'sai, C. and J.A. McKee. 138C. Acute toxicity to goldfish of mjxtures of chloramines, copper, and linear a:%ylate sulfonate. Trans. Am. Fish. Sot. lC9: 132.
Turnbull, Ii., et al. 1954. Toxicity of various refinery materials to freshwater fish. Ind. Eng. Chem. 46: 324.

U.S. E?A. 1980. Unpublished Laboratory data. Environ. Res. Lab.-Narragansett, Rhode Island. Ualbridge, C.T. 1977. A flow-through testing procedure with duckweed, ILemna minor L.). EPA60013-77-108. U.S. Environ. Prot. Agency. -- Wallen, I.E., et al. 1957. Toxicity to Gambusia affinis of certain pure chemicals in turbid waters. Sew. Ind. Wastes. 29: 695.
Warnick, S.L. and H.L. Bell, 1969. The acute toxicity of some heavy metals to different species of aauatic insects. Jour. Water Poll. Control Fed. 41: 280.Mammalian Toxicology and Human Health Effects INTRODUCTION Copper is widespread in the earth’s crust, and the extensive use of copper and its compounds by man since prehistoric times has added copper to the environment and the ecosystem in highly variable concentrations. From 1955 to 1958 the annual United States production of recoverable copper was about 900,000 metric tons. By 1975, the production had risen to 1,260,000 metric tons (D'Amico, 1959; U.S. Bur. Mines, 1976). The world trade in refined copper amounted to 2,271,150 metric tons in 1973 (World Metal Statistics, 1974). Human exposure to copper can occur from water, food, and air, and through direct contact of tissues with items that contain copper. Copper is essential to animal life; consequently, abnormal levels of copper intake can range from levels so low as to induce a nutritional deficiency to levels so high as to be acutely toxic. EXPOSURE Ingestion from Water Water can be a significant source of copper intake depending upon geographical location, the character of the water (i.e., whether it is soft or hard), the temperature of the water, and the degree of exposure to copper-containing conduits. Schroeder, et al. (1966) place considerable emphasis on drinking water as a source of copper. They reported that the mean values of copper in human livers (56 cases) from Dallas, Denver, and Chicago varied from 410 to 456 μg/g of ash, and that the mean value

C-1from Miami was 578 μg/g of ash1. The municipal water supplies of

these cities each provided relatively hard potable waters with measured hardness ranging from 75 to 125 mg/l. On the other hand, 143 human livers from seven cities with relatively soft waters ranging from 10 to 60 mg/l had mean levels of copper varying from 665 to 816 μg/g of ash. Of the cases from soft water areas, 37.1 percent had hepatic copper of 700 or more μg/g of ash, compared with only 14.3 percent of the samples from the hard water cities. Of the 56 individuals from three cities with the hardest water, only two showed such high values. Unfortunately no studies were made of cities with very hard water.

lie in the ability of calcium or magnesium ions in hard water to Schroeder, et al. (1966) suggested that the higher copper levels in residents of cities with soft water might be due to the ability of soft water to corrode copper pipes and fittings, thereby increasing the intake of soluble copper. Another explanation may

suppress the intestinal absorption of copper. Schroeder, et al. (1966) reported on the progressive increase of copper in water from brook to reservoir to hospital tap, and the considerable copper increment in soft water, compared with hard water, from private homes (Table 1). The authors found that the daily increment of copper ingested from soft water may amount to 10 to 20 percent of dietary intake. 1The values cannot readily be converted to total copper content present in liver on a wet weight basis since they were secured at autopsy. Information regarding the individuals from which samples came was minimal.

C-2

### TABLE 1 Copper 

## in Water Flowing 

## through Copper Pipesah 

## Item w/1 Spring water, 

## Brattleboro, Vermont, mountain Municipal water, 

## soft, Brattleboro Brook, 

## inlet to reservoir Reservoir, lake 

### water, main end 

## Hospital, at tap cold, 

## running 30min hot, running 30min cold, 

### standing 12hr cold, 

## standing 24hr Spring water, 

## soft, private houses, Brattleboro, Vermont, at tap 

## No. 1from spring, unpiped running 30mfn cold, standing 24hr hot, standing 24hr 

## No. 2 No. 3 Well water, private houses, Windham County, at tap No. 4, hard No. 5, hard No. 6, hard No. 7, hard, at well

at tap No. 

## 8, soft 1.2= 

## 16 55 150 170 440 550 730 2.8' 190 1,400 1,460' 1,240 75 36 4.4c 40 4= 36' 278 'Source: Schroeder, et al. 1966. b

### Water from the main wastaken after it had passed through 

## the treatment plant at the entrance to hospital supply system, 

## from whence it ran 

## through copper pipes. This water ‘was chlorinated, Spring and

## well waters were 

### untreated. 

## 'By chemical method using diethyldithiocarbamate after evaporating Lliter water.



## c-3

### Zadjiznarkos (:367), on the csntrary, sugqested c,hat drinking 

## water maybeonly 

## aminor source of copper. Hereported that the 

## meandrinking 

## water concentration 

## of copper is 0.029 mg/l, which 

## could nean adaily intake of 58pgof copper in water, or 1to 8 percent 

## of total daily intake if food intake is 

## 3,200 ugof copper per day. It is probable 

## that the difference in intakes estimated by 

## Schroeder, et al. (1966) andHadjimarkos (1967) is duetoadiffer

## ence in location. However, it 

## is difficult to pinpoint local CODperconcentrations indrinking water sources, since the only readily 

## available information 

## on concentrations of copper in stream water is from areas of 

## 10,000 square miles or greater (Kopp and Kroner, 

## 1968; Thornton, et al. 1966). Robinson, et al. (1973) in New

## Zealand have suggested that soft 

## water usedexclusively from the 

## coldwater tap tomakeupdaily beverages mayaddasmuchas0.4 mgof copper per day per 

## individual, but 

## that if hot water from the 

## samesource is used for the 

## samepurposes, it would add

## at least 0.8 mgof copper per day to 

## an individual's intake. Theaverage concentration of copper in the 

## United States water systems is approximately 

## 134ug/l [U.S. 

## Department of Health, Education andWelfare (U.S. HEW), 19701. The highest concentration reported was

## 8,350 ug/l; alittle over 1percent of the samples exceeded the 

## drinking water standard of 1mg/l. The 

## 1mg/l copper 

## standard wasestablished not because of toxicosis but because of the taste which 

## develops with higher levels of copper 

## in the water (U.S. HEW,L970). It is most commonly exc-4

### ceeded in soft water that is acidic in nature; however, it is rare

that the concentration of 

## copper in drinking water is 

## high enough 

## to affect its taste or 

## to produce toxicosis (McCabe, et al. 1970; Fed.water Quality Adm., 1968) l 

### For this reason, regulatory aqenties have not 

## treated copper in public 

## water supplies asasiqnificant problem. In NewYork City, 

## Copper is intentionally added to the water suPPlY to maintain 

## aconcentration of 0.059 mq/l inorder tocontrol algal growth (Klein, 

## et al. 1974). prolonged contact of acidic beverages with copper conduits, 

## suchasoccurred in earlier models of drink dispensing machines, 

## mayproduce sufficient COppet concentration to 

## cause acute copper toxicosis (seeAcuter Subacute, and

## Chronic Toxicity section); however, because 

## of taste 

## problems, modern equipment does not contain 

## copper conduits. Thenational impact of awater-borne contribution of copper is df

## ff

## icult to detect, predict, or evaluate because 

## information is either absent or irretrievable. The 

## current trend for recycling warta 

## (animal wastes, sewage 

## solids and liquids, channel dredging, 

## and indurtrial warts) 

## to the land offers very real possibilities 

## that inbrlancw in organisms mayunwittingly becreated, because 

## muchwastes are comaonly high in trace element concentration0 T)Ieu trace l

## Lraents my directly alter crop production and indirwtly 

## affmt theconrumer (Patterson, 1971). 

## Anotbaesource of copper in water is the use 

## of copper sulfate to

## control alga.. Someidea of the distribution of copper sulfate WYbeWind fra th 

### work of Button, et 

## al. (1977), who applied 9rrnufar CoPPersulfate to the surface of 

## Koover Reservoir, Frank

## C-S

### lin County, Ohio. Soluble andparticulate cupric copper concentrations 

## at several depths weremeasured byatomic absorption spectrophotometry 

## for four days after 

## application. The soluble 

### cupric copper concentration decreased to near baseline values in 2to 6 

## hours when0.2 or 0.4 qmsof copper 

## sulfate per 

## square meter were added to the surface. Most 

## of the 

## copper sulfate 

## wasdissolved in tke first 1.7s meters of 

## water column, 

## andonly 2percent of the total 

## copper sulfate reached the depth of approximately 4.5 meters. 

## Aconcentration of 0.4 qmsof copper per square meter controlled a 

## diatom bloom. Ingestion from 

## Food Levels Of

## copper in 

## various foods are given in Table 2. Some 

### foods, 

## such as crustaceans and shellfish 

## (especially oysters), organ meats (especially lamb or beef liver), nuts, dried legumes, dried vine 

## andstone fruits, andcocoa, are particularly rich in copper. 

## Thecopper content of these items canrange from 20vq/q to 

## ashigh as400pg/q 

## (McCanceandWiddowson, 1947; Schroeder, et 

## al. 1966). flnan"as-cooked andas-served" basis, calves' liver, oysters, 

## andmany species of fish 

## and green 

## vegetables have recently 

## beenclassed asunusually good source3 of copper (more 

## than 100~q copper/100 kcal). High levels 

## of copper mayalso be 

## found in swine because of the 

## practice, commonin the United Kingdom 

## andelsewhere, of feeding to 

## swine diets that are high (upto

## 250pq/q) in 

## copper inorder to increase daily weiqht 

## gain. Levels of copper in swine liver 

## vary greatly depending on the copper 

## content of the 

## feed. Ahigh 

## copper diet fed continuously until 

## sLaughter mayproduce levels of

C-6

## TABLE2 Copper in 

## Foods (Wet

## Weight)'

Item 

# ugnoob calories 

## Seafood Clams, 

## raw Clams, fresh frozen Oysters Sardines, canned Portugese Kipper snacks, Norway, 

## canned Anchovies, canned Portugese Panfish, dried, V.I. Lobster, frozen Shrimp, frozen

Mean, excluding oysters Meat Beef liver Beef kidney Beef 

## fat Pork kidney Pork loin Pork liver Lamb kidney 

## Lambchops Chicken leg andwing



## Mean Dairy products =39Yolk Eggwhite Dried skimmedmilk Wholemilk, dairy 1 Wholemilk, dairy 2 

## Butter, salted

Mean 

## 3.33 0.48 137.05 1.12 1.70 0.81 0.58 0.51 3.40 694

100 27,410 38 85 4'1 42 297 1.49 167 

## 11.00 0.42 0.83 5.30 3.90 3.72 0.95 7.13 1.99 3.92 2.44 1.70 2.39 0.26 0.12 3.92 L.76 769



## 34 21 441 130 260 384; 99 249 70 460 63 cii 49

‘Source: Schroeder, et al. 1966 bdaloric values of foods from R.A. McCanceandE.M.Widdowson, 1947 V.I. - indicates that the sample came 

### from St. 

## Thomas, Virgin Islands. 

## c-7

## TABLE2(cont.) Copper in Foods

Item 

# w/g ug/loo b calories 

## Vegetables Peas, green Peas, split, green dry Peas, green, V.I. Peas, split, green, V.I. Lentils Yam,white, V.I. Yam, 

## yellow, V.I. Turnip, white Turnip greens Beets Carrots Tomato, V.I. Pepper, green, No. 1 Pepper, green, No. 

## 2 Pepper, green, V.I. 

## Pepper, hot, red, V.I. Cucumber, No. 

## 1 Cucumber, No. 2 Christofine, V.I. Eggplant, V.I. Asparagus Celery Cabbage Parsley Rhubarb Mushrooms Mean Fruits Banana, V.I. Papaya, V.I. Coconut, V.I. Coconut seed, V.I. Apple, Macfntosh Mean, excluding coconut seed 0.82 0.45 12.30 1.14 2.25 1.41 0.32 0.41 1.84 

## 0.73 0.15 3.42 0.34 0.68 0.28 0.90 0.56 0.07 0.47 0.18 0.06 0.37 0..31 0.70 0.20 0.34 0.65 1.17 0.66 1.06 0.19 3.31 1.39 70

410 181 75 i:: 1.0:: 663 32 1,487 143 453 187 600 70 470 257 40 205 344 350 567 929 362 86 265 100 278 182

c-a

### TABLE2 (cont.) Copper in 

### Foods 

## Item u9/9 ug/loo b calories 

## Grains andcereals Wheatseed Wheat, whole Wheat germ 

## Wheathead, chaff and stalk 

## Bread, white Bread, whole wheat Oats, whole Corn, No. 

## 1 

## Corn, No.2 Rye,No.1 Rye, No. 

## 2 Rye, dry, flour Benzene extract Residue Barley Buckwheat Rice, brown, U.S. 

## Rice, Japanese, polished 

## Bengal gram, India, 1 Bengal gramr fndia, 2 Grapenuts Millet 

## Doughnut, creamfilled Mean, excluding grapenuts andextracts 1.09 

## 2.48 0.1s 0.14 0.19 0.63 0.40 0.46 0.65 0.92 4.12 4.20 10.82 1.87 3.83 8.21 0.47 3.04 4.23 0.56 14.95 

## 2.34 2.32 2.02 33

75 2: ii 19 27 123 124 106 227 13 1:: 16 415 

## 67 66 58

C-9

## TXBLE2(car.:. Copper in Foods 

## Item ug/lOO b calories Oils 

## andfats Lard, canned, 1 Lard, canned, 2 Lard, canned, 3 Lecithin, animal Lecithin, egg Codliver oil, Norway Castor oil, refined Cornoil Corn oil margarine Cottonseed oil Olive oil 

## Sunflower oil Linseed oil, pressed Peanut oil, pressed Lecithin, vegetable, pure Lecithin, soy, 90percent pure Lecithin, soy, refined

Mean, excluding lecithins Nuts Hazelnuts Peanuts Walnuts Brazil nut Pecans Almonds Mean Condiments, spices, etc. Garlic, fresh Garlic powder Mustard, dry Pepper, black Paprika Chili powder Thyme, ground Bayleaves (laurel) Cloveu, whole Ginger, ground Ginger, 

## root, V.I. Carawayseeds Vinegar, cider Yeast, 

## dry, active Molasses Sugar, refined



## Yean 3.06 2.50 2.13 26.38 10.52 6.80 1.70 2.21 24.70 1.26 3.20 5.44 1.75 0.83 5.31 4.37 20.95 4.63 12.80 7.83 12.70 23.82 12.64 14.11 14.82 3.15 0.75 3.04 20.73 8.47 5.98 23.58 3.68 8.67 2.63 1.87 4.31 0.76 17.79 2.21 0.57 6.76 34

28 24

25 274 14 36 60 19 9
58 233 131 231 370 211 234 235

a5 14

c-10

## TABLE2(cont.) Copper in Foods Item u9/9 ,&loo b 

## calories Beverages Gin, domestic 

## Vermouth, French Vermouth, Italian Whiskey, 

## Scotch whiskey, Bourbon Brandy, California Bitters, Angocltura 

## Wine, domestic, red Beer, canned Cola Grape juice Orange drink, carbonated Orange juice, packaged Coffee, dry, ground Coffee, infusion Tea, infusion

Mean, excluding dry 

## coffee Miscellaneous Chocolate bar, 

## Hershey Ice cream, vanilla Gelatin, Knox Purina laboratory chow Aspirin, 

## Squibb Saccbarin 0.03 0.88 0.38 0.35 0.18 0.45 0.75 0.28 0.38 0.38 0.90 0.20 0.89 2.35 0.22 0.31 0.44 0.70 0.29 3.87 15.61 3.12 5.43 

# E

148

c-11

## upto 400 to 600 

### ug/g in the liver. However, Swine will raGidly

eliminate 

## copper once it is removed from the diet. Sheep 

## also acdumulate copper in direct proportion to the level 

## of copper in the 

## diet, but they 

## eliminate excess copper very poorly [NRC-42, 1974; National Academy 

## of Science (NAS), 1977: Barber, et al. 19781. Animal andindustrial wastes 

## (including sewagesolids) commonly yield high concentrations of copper andother trace elements. The 

## current emphasis onrecycling these wastes mayunintentionally supply excessive amounts of copper andthese other elements to the soil. 

## Such recycling could indirectly affect consumers Lf the yield of 

## crops were reduced or if 

## copper 

## were increased in feed products 

## (NILS,1977). The

## National Academyof Science (1977) noted that theconsumption of sheepor swine livers that are high in 

## copper could result in excessive levels of copper, especially in baby foods where the actual 

## amount of copper might exceed the copper requirements of very young children. Dairy products, white sugarr and honey rarely contain more than 0.5 pg copper/g. 

## The nonleafy vegetables and most fresh fruits and refined cereals generally contain upto 2ug/g. Cheese (except mental), milk, beef, mutton, white andbrown bread, and manybreakfast cereals (unless they are 

## fortified) are 

## relatively poor sources of.copper, i.e., 

## they have less than 50ugcopper/100 kcal [World Health Organization (WHO),19731. Therefining of cereals 

## for humanconsumption results in significant losses of copper, although this loss is 

## not sosevere 

## as it is for iron, manganeser andzinc. 

## Levels of copper inwheat and wheat products are given in 

## Tables 3and4. c-12

### TABLE

## 3 Mineral Content of KnownWheats, the Flours Milled fromthem

andthe Products Prepared from the Floursa&

Number Of 

## Samples Moisture 

## Ash

Q 0 (Wper PS/S Wheat, common 

## hard Flour, Baker's patent Bread, sponge-dough Bread, continuous-mix Wheat, commonsoft Flour, soft patent (cake)= Cake 

## Flour, straight-gradec Cracker Flour, cut-off (cracker) Cracker Wheat, Durum 2 10.7 2.03 +0.01 Semolina 2 14.7 0.83 T0.01 Warcaroni 2 9.6 0.82 z0.01 5 z S 

## 11.0 1.87 +0.10

13.9 0.49Ti0.03 36.3 3.39T0.19 35.3 3.42 z0.30 10.6 11.9 22.8 11.4 1::: 4.5 1.73 +0.17

0.42 T0.03 2.71 70.11 0.50 T0.05 3.42T:0.50 0.71.T 0.04 3.09 z0.34 5.1 + 0.5



## 1.970.2 2.3'i0.3 2.0z0.2 4.5 -t0.5 1.670.3 0.8T0.1 1.6T0.2 1.6T0.1 2.6+0.1 2.4z0.1 4.8 +0.1 2.2T0.1 2.550.1 %ource: Zook, et al. 1970 bMean 

## andstandard deviation, dry weight basis. 'Includes twoflours prepared by 

## air classification.

C-13

## TABLE4 Mineral Content of ConsumerProducts Purchased inTenCities a&

Product Total Producers Sampled

Sample8 Per Model Collected Total city city Hoisture 

## Ash Copper No. No. 

## Range No. 

## 0 0 P9/9 Cereal-to-be-cooked Shredded wheat 

## Wheatflakes Bread, whole wheat Bread, white Conventional dough Continuous-mix 

## Rolls, hamburger Doughnuts, cake 

## Biscuit mix Flour, all-purpose 

# I’$ 28 38 7 

## l-3

6 

## 4-6 3 

## 2-3 26 

## 2-8 9.5 l.as + 0.07 

## 8.0 1.87 T 0.12 

## 4.8 3.78 + 0.17 

## 37.8 3.87 i 0.12 37 17 34 20 8 

## 19 

## 3-9 ;I; 1-s l-4 3-4 35.8

36.7 33.6 21.9 9.8 12.9 3.23 t 0.12 

## 2.1 t 0.2

3.10 T 0.13 2.3 + 0.3 2.85 ri 0.08 2.5 + 0.2 2.61 i 0.20 1.7 T 0.2 4.28 T 0.26 1.6 T 0.2 0.56 ‘i: 0.03 1.8 + 0.2 5.3 + 0.2 6.1 T 0.4 4.7 7 0.3 

## 5.1T0.5 -

“Source: Zook, 

## et al. 1970 b

## Meanandstandard deviation, dry weight basis.

c-14

## Schroeder, et al. (1966) have 

## suggested that since copper DC

## curs widely in human foods, it is difficult to prepare adiet of 

## natural foods that provides adaily copper intake of less than 2 mg, 

### the level that is considered to be adequate for normal copper 

## metabolism (Adelstein, et al. 1956). Tompsett 

## (1934) reported 

## that the normal daily intake of copper 

## from food appeared tobe2to 2.5 my

## per dayfor human

## subjects. Daniels and Wright (1934) reported an average intake of 1.48 mg copper per day in young children, with arequirement of not less than 0.10 pg/kg of bodyweight per day. Most 

## American andwestern European diets supply adults with 2 to 4mgof copper per day. 

## This is evident from studies inEngland, NewZealand, andthe United States. Lowerestimates havebeen 

## made for certain Dutch and poorer Scottish diets, while Indian adults consuming rice andwheat diets have been shownto ingest from 4.5 to 5.8 mgof copper per day (Schroeder, et al. 

## 1966). Scheinberg (1961) hascontended that mostadult diets supply a substantial excess of copper. Klevay, onthe other hand, hassuggested onthe basis of recent food analyses that the copper content maybeless than earlier analyses indicated andhascautioned that United States diets maynot beadequdte to provide 2mgof copper per day (Klevay, 1977; Klebay, et al. 1977). Dr. Walter Mertz in apersonal communication reported that in 1978the analysis of diets of morethan 20individuals employed at the Institute of Nutrition of the U.S. Department of Agriculture, Beltsville, Md., 

## showedthat only twoapproached anintake of 2mg of copper per day. The 

## diets of these 

## individuals included soft

c-15

### drinks, water, andsnacks, suggesting that food subjected to modern

processing 

## andpreparation methods maybeznuchlower in copper than was 

### supposed 

## based onearlier analyses, andthat many individuals 

## eating these 

## foods maybereceiving considerably less than the 2mq of 

## copper per 

## day. Engel, et al. (1967) conducted studies onyoung girls which indicated that 2P’;coppet/ cf die

## t wasadequate for good nutrition. Petering, et al. il971) mention that the copper content of hair appears to berelated to the ageof the 

## individual andsuggest that the 

## need for copper maydiffer between the sexes. Because of the essentiality of copper, the copper balance in newborn infants hasbeenexamined (Cave11andWiddowson, 1964). It wasnoted that breast milk ranged from 0.051 to 0.077 mg/lOOmland that total copper intakes of the 

## babies ranqed from 0.065 to 0.1

w/Wday l 

## In the first week 

## of life, someinfants excreted more copper than wascontained in the milk that they consumed. 

## of 16 

## babies, 14were in negative balance. Asageneral statement it would appear that, at least in the United States, there is agreater risk 

## of inadequate copper intake than of anexcess above requirements. Abioconcentrationlfactor (BCF)relates the concentration of 

## a chemical in aquatic animals to the 

## concentration in the water in which they live. 

## Anappropriate BCFcanbeusedwith data concerning 

## food intake to calculate the amount of 

## cooper which might be ingested from the consumption of fish andshellfish. Residue data for 

## avariety of 

## inorganic compounds indicate that bioconcentration factors for the 

## edible portion of most 

## aquatic animals is similar,

c-16

## except that for somecompounds, bivalve molluscs 

## (clams, oysters,



## scallops, andmussels) should beconsidered 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 andshellfish is 6.5 g/day (Stephan, 1980). Theper capita consumption of bivalve molluscs is 0.8 g/day and that of all other freshwater andestuarine fish andshellfish is 5.7 g/day. Abioconcentration factor of zero wasreported for copper in the muscle of bluegill sunfish (Benoit, 

## 1975). Data are available for several species of saltwater molluscs:

Species BCF Reference Bayscallop, Argopecten irradianr 3,310 Bayscallop Argopecten irradians 4,160 American oyster, Crassoetrea virginica 28,200 American oylter, 20,700 Crassostrea virginica Northern quahaug, Mercenaria mercenaria Soft shelled clafll, Myaarenaria

MusselF Mytilus edulis Mussel, Mytilus edulfs Mussel, Mytilus galloprovincialis 88 3,300 208 Shuster and

Wingle, 1969 Shuster and Pringle, 1969 Shuster and Pringle, 1968 Shuster and Pringle, 1968 Zaroogian, 1978 108 Zaroogian, 1978 90 Phillips, 1976 800 MajOri and

Petronio, 1973 Zaroogian, 1978 Zaroogian, 1978



## c-17

### If the values of zero 

### and 290 are used with the consumption



## data, the 

## weighted average bioconcentration 

## factor for copper and 

## the edible portion of all freshwater andestuarine aquatic organisms consumedbyAmericans is calculated to be36. The

## geometric meansfor scallops, oysters, clams, andmussels 

## are 3,708, 24,157, 539, and200, respectively, andthe overall meanis 290. Inhalation The 

## principal sourca 

## of elevated copper levels in air is copper dust generated bycopper-processing operations. However, since the economic value of copper encourages its capture from industrial processes, extraneous emissions are reduced. Other possible 

## sources of copper in air maybetobacco smokeandstack emissions of coal-burning Copper has trial substance power plants.

not beenconsidered aparticularly hazardous indusbecause the conditions that would produce excessive concentrations of copper dust or mist in aparticle size that could be

## absorbed andgenerate toxic effects are apparently quite rare. Investigations of Chilean copper miners have shownthat liver and serum concentrations of copper are normal, despite years of exposure to 

## copper sulfide andcopper oxide dust, both of 

## which are in

## soluble (Scheinberg andSternlieb, 1969). However, workers can be 

## exposed to excess concentrations of copper in anyof 

## its forms, and whenthis 

## occurs, undesirable health effects can result. A 240 

### to 

## 28-hour illness characterized by chills, fever, 

## aching muscles, dryness in the mouthandthroat, andheadache, hasbeennoted where workers are exposed to metal fumeswithin closed areas zisa

## result of the welding of copper structures (McCord, 1960).

C-18

### The U.S. 

## Occupational Safety andHealth Administration 

## (OSHA)

hasadopted standards of exposure to airborne copper at work. The time-weighted 

## average for 8-hour daily exposure to 

## copper dust is limited 

## to 1mg/m3of air. Thestandard for copper fumewaschanged in 1975to 0.2 mg/m3(Gleason, 1968; NAS, 

## 1977). In 1966, aNational Air Sampling Network survey showed that the 

## airborne copper concentrations were 0.01 and 0.257 pg/m3 

## in rural andurban communities, respectively (Natl. Air Pollut. Control Admin., 1968). Evennear copper smelters, where high levels (1to 2

## ug/m3) are reached, thedoseof metal that would beacquired through inhalation of ambient air would comprise only about I per

## cent of the 

## total normal daily intake (Schroeder, 1970). Generally speaking, inhalation 

## of copper 

## or copper compounds is of minor significance compared toother sources, e.g., copper in foods, drinking water, andother fluids, anduseof copper for medical purposes. Dermal

## Copper toxicity has resulted from 

## the application of copper salts to large areas of burned skin or from introduction of copper into the 

## circulation during hemodialysis. Thesource of the copper in hemodialysis maybe the 

## membranes fabricated with copper* the copper tubing, or the heating 

## coils of the equipment. Copper stopcocks in circuits 

## canalso cause potentially hazardous infusions of copper (Holtzman, et al. 1966; Lyle, et 

## al. 1976). Studies with monkeys indicated that copper used as dental fillings andplaced in cavities in the 

## deciduous teeth of the 

## monkeycaused moresevere pulp damagethan 

## anyof the other materials

c-19

### studied. This is additional evidence that tissues exposed directly

to copper or copper salts will suffer adverse effects due to the direct absorption of the copper bythe tissues (Yjor, et al. 1977). Recent papers from Australia (Walker, 1977: Walker, et al. 1977) suggest the possibility of copper absorption through the skin 

## asa result of perspiration action on the copper bracelet, some

### times worn 

## as treatment for arthritis, although the therapeutic value 

### of this has little support. Concern 

## hasbeen directed toward the absorption of copper as

## a result of the use of the intrauterine device (IUD) as acontraceptive measure 

## (NAS, 1977). Analysis 

## of IUDs that have 

## been in utero_Ifor months to 

## years shows that about 25to 30mqof copper 

## are lost each year. Someof the metal is excreted with endometrial secretions. Experimental evidence to 

## date doesnot indicate that 

## useof an IUD results in harmful accumulations of copper (see Absorption section for additional information). PHARMACOKINETICS2 Absorption Tracer studies provide the basis for the conclusions that most 

## absorption in man 

## takes place in the stomach 

## and the 

## duodenum. Copper absorption appears to be regulated bythe intestinal mucosa, and maximum copper levels occur in the blood serum within one to three hours 

## after oral intake.

2Acknowledgement is made of the courtesy of the late Dr. Far1 E. Mason 

## and Dr. Walter Mertz 

### who allowed the author to read their manuscript, Conspectus onCopper, to bepublished in the Journal of Nutrition. c-20

## Muchof the 

## information on 

## copper absorption in humans has

come 

## from studies of patients with Wilson’s disease. studies conducted with these patients using radioactive copper indicate that 

## about one-half of the copper in the 

## diet is not absorbed but is excreted directly into the feces. Theaverage absorption in these 

## individuals has been reported to be approximately 40 percent (Sternlieb, 1967; Strickland, et al. i972a). Investigations by Cartwright andWintrobe (1964a) indicated that the daily intake of copper inWilson’s disease patients was2to 5mq,of which 0.6 to 1.6 mqwere absorbed, 0.5 to 1.2 mqwere 

## excreted in the bile, 0.1 to 0.3 mgpassed directly into the bowel, and0.01 to 0.06 mgappeared in the urine. Information from these studies indicates that absorbed copper is rapidly transported to blood serum and taken 

## upby the liver, from which it is released andincorporated into ceruloplasmin. Any copper remaining in the 

## serumis attached to albumin or aminoacids or is used to maintain erythrocyte copper levels (Weber, et al. 1969; Bearn andRunktl, 1954, 1955; Beckner, et al. 1969; Bush, et al. 1955; Jensen andRamin, 1957). Estimates of the amount of the copper that is actually absorbed bynormal individuals vary considerably andmust be 

## considered inconclusive. Thevalues obtained have ranged from aslow as 15percent 

## taashigh as97percent (weber, et al. 1969), although it seemsprobable that subjects having these extreme values were not in asteady state. The uncertainty of these values is confounded bythe lack of accurate information regarding the excretion of 

## copper in its 

## various forms bywayof the biliary system. Even

c-21

### less information is available 

### regarding the reabsorption of copper

or copper compounds from the intestine after they have been excreted in the bile. Most of the values 

### that have been obtained with normal subjeats lsuqqest that 40to 60percent of the dietary copper is 

## absorbed (VanRavenstcyn, 1944: Cartwright andWintrobe, 1964a; Bush, et al. 1955; Matthews, 

## 1954: Weber, et al. 1969: Strickland, et al. 1972a,b; Sternlieb, 1967). 

## Animal studies haveshownthat copper is 

## absorbed byat least two 

## mechanisms, an energy-dependent mechanism 

## and an enzymatic mechanism 

## (Crampton, et al. 1965), andthat manyfactors mayinterfere with copper absorption, 

## including competition for 

## binding sites 

## aswith zinc, interactions 

## with molybdenum andwith sulphates, chelation with phytates, 

## andthe influence of ascorbic acid. Ascorbic acid will aggravate copper deficiency by 

## decreasing copper absorption. In cases of excess copper intake, ascorbic acid can reduce the toxic effects (Gipp, et al. 1974: Hunt, et al. 1970: Voelker 

## andCarlton, 1969). Studies with laboratory animals have shownthat once copper enters 

## the epithelial cells, it 

## is taken 

## up by 

## a cellular 

## protein similar to liver metallothionein (Evans, et al. 1973; Evans, 1973; Starcher, 1969). 

## Absorbed copper is bound to albumin and transported in 

## the plasma. Approximately 80percent of the absorbed 

### copper is 

## bound in the liver to metallothionein. 

## The remaining copper is 

## incorporated into compounds suchascytochrome-c-oxidase or is sequestered by lysosomes (Bearn and Kunkel, 1954, 1955) l 

## Little information is available concerning absorption of 

## copper into the 

## lymphatics, although in 

## pathological conditions this may be significant (Trip, et al. 19691. c-22

## Several studies 

## have been 

## conducted on humans 

## and laboratory

animals concerning 

## absorption of copper asaresult of the use of 

## copper IUDs. Studies with the IUDin rats have 

## suggested that as much

## as10

## to 20mgof copper maybeabsorbed (Oreke, et al. 1972). This 

## amount, which is small compared to 

## the dietary copper usually ingested, mayor maynot bemetabolized andexcreted by the same 

## homeostatic mechanisms that operate with ingested copper. If 

## an IUDwere used 

## for manydecades and the absorbed copper were retained, it would result in amounts of copper similar to those retained fromdietary copper bypatients with Wilson's disease. Such 

## levels could result in chronic toxicosis. 

## Japanese investigators (Okuyama, et al. 1977) have compared effects of using the IUDwith copper andthe IUDwithout copper in two 

## groups of 

## womenr using athird group as controls. Pregnant womenwith anIUDin 

## place werealso examined. Nosignificant dif& 

## ference wasfound in the endometrial copper levels in 

## the three 

## groups. There wasatendency toward anincrease abovecontrols in the 

## endometrial level of copper during the secretory phase in those womenusing the IUDwfth orwithout copper. Nosignificant differ

## encewasfound between 

## womenwhohadusedanIUDmorethan 13months andthose whohadused it less than 13months. Thecopper content of the 

## chotion andthe decidua of the pregnant womenwith IUDs in 

## place did notdiffer from the levels noted in pregnant womenwithout 

## IUDs. Apparently, the long-term useof copper-containing IUD3 

## did not lead to anaccumulation of copper in the uterus. Tamaya, et al. (1978) have studied the effect of the copper IUDon the 

## histology of the endometrium in the proliferative and
C-23

### the 

## secretory phases of women- Thefcresult8 [ndfatr ~

copper l[uDaffect&! the Sectetory @*domettfuptbutnot:- Q-wllc ative endometrLun. In another study, fstaclf contains both copper andzinc, als if they had had low strmn 

## section. Rowewes, uppeg limits 

### of normal values. 

## *t3sig*~ffWR 

## statfrtfat, fl* encewad;found between the IerM level* Ofcapprn bfar, r) N tnsettion ot the IU& It has been 

## sugg+atsd that diaktic ra+a w tw ar)lllr,

of th. 

### r?IWttirt ffbrolytic 

## ACttVttp QtWWkt.8JLlllm r) m

### Distribution

The 

## amount and distribution of 

## copper in body tissues 

## varies with sexr ager andtheamountof copper in the 

## diet. Copper content of fat-free tissues of most animals ranges upward from 

## about 2

w/g l 

## The highest 

## concentrations of copper in 

## both animal and human 

## tissues are found in the liver and the brain, with lesser amounts in the heart, the spleen, the kidneys, and blood (Cartwright andWintrobe, 1964a,b: Smith, 1967; Schroeder, etal. 1966). Sometissues are very high in copper, 

## e.g., the iris andthe choroid of the eye

## ,which maycontain asmuchas100~g/gm (Bownessand Morton, 1952; Bowness, et al. 1952). Estimates of the total amount of copper in a70kgmanhave ranged from 70to 120mg. Approximately one-third 

## of body copper is found in the liver andthe brain, one-third is found in the musculature, and the remaining one-third is dispersed in other tissues. It hasbeenestimated that, onthe average, about 15percent of the total body 

## copper is contained in the 

## liver (Tipton and Cook, 1963: Sumino, et al. 1975; Sass-Kortsak and Bearn, 1978). The relatively high percentage of liver copper is related to the liver’s function 

## asa

## storage organ for conper anda8 

### the only site 

## for the synthesis and release of ceruloplasmin, the most abundant copper protein in the 

## blood. In the brain, the striatum andboth components of the cortex (gray matter) have the highest copper content, with the cerebellum (white matter) being the lowest (Hui, et al. 1977; Cumings, 1948: Earl, 1961). Thebrain appears to bethe 

## only tissue inwhich there is aconsistent increase in copper 

## content with age. clther tissues appear to be 

## under ahomeostatic control. c-25

### Copper levels 

### in hair vary widely with respect to age, sex,

and other factors, and therefore have little meaningfulness in evaluating copper levels in man (Underwood, 1977). Rowever, Jacob, et al. (1978) have suggested that the copper in hair maybeuseful in evaluating the total liver content of copper. Engel, et al. (1967) surveyed over 180 adolescent girls in the 6th to 8th grades for dietary intake 

## and nut:iticnal status. They found that the 

## meanconcentration of 

## copper in hair 

## samples was31223vg/g. No 

### significant difference was 

### found between girls whohad experienced menarche 

## andthose 

## whohadnot. Levels of copper in the blood 

### of normal adults average 103 ug/lOO ml of blood. The amount of copper in blood serum 

## can range widely from Sug/lOO ml to 130 pg/lOO ml. In practically all species, copper deficiency is first 

## manifested by

## aslow depletion of body copper stores, including the blood 

## plasma, eventually resulting in 

## asevere 

## anemia identical to that 

## caused by iron deficiency (Cartwright, et al. 1956). Both the plasma 

## andthe erythrocytes have two pools of copperr 

## alabile pool 

## andastable 

### pool, which contain approximately 40and 60 percent respectively, 

## of the 

## copper in the blood 

### (Bush, et al. 195s). 

## Ceruloplasmin represents the predominant portion of cooper in the serum pool. There 

## appears to be little or no interchange between 

## ceruloplasmin copper andother forms of copper in the blood stream (Sternlieb, 

## et al. 1961). Mondorf, et 

## al. (1971) indicate that the blood 

## contains anaverage of 30ugof ceruloplasmin/lOO ml of blood. This is in reasonable 

## accord with accepted levels of 

## copper in the blood of normal adults (approximately 103 ug total

C-26

### copper/100 ml of blood). White blood cells contain asmall arr.cunt

of copper f about 

### one-fourth the concentration in erythrocytes (Cartwright, 1950). The distribution of copper in the fetus and in infants is quite different from that in the adult. The percentage of copper in the body increases progressively during 

## fetal life (Shaw, 1973). Chex, a%al. (1978) found that concentrations of copper in amniotic fluid increased between the 26th 

## and 33rd weeks 

### of 

### pregnancy, but that there did not 

## appear to be

## acorrelation between maternal and fetal copper 

## Concentrations. At 

### birth, the 

## liver andspleen contain about one-half the copper of the whole body (Widdowson and Spray, 1951). Anewborn infant 

## contains about 4mg/kg ascompared to approximately 1.4 mg/kg 

## in the 70

## kgman(Widdowson andDickerson, 1964). The liver of the newborn 

## hasapproximately 6to 10times the amount of copper in the liver of an adult 

## manonaper grambasis (Bruckmann andZondek, 1939; 

## Nusbaumand Zettner, 1973; 

## Widdowson, et al. 1951). The

## concentration of copper in the serum 

## of newborn infants is significantly 

## lower than in 6- to 

## 120year-old healthy children, but byfive months 

## of agethe 

## serumconcentration of copper is approximately the 

## sameas in 

## older children. Ther.e is nodifference between copper 

## levels in maleandfemale infants, although breast-fed infants see, to have somewhat 

## higher copper levels by 

## one month than bottle-fed infants (Ohtake, 1977). 

## The liver copper content of the fetus is several times higher than maternal liver copper (Seeling, et al. 1977).

C-27

## Hetabolism

Thecopper content of red blood cells remains remarkedly constant, but the plasma copper is subject to striking changes 

## asgociated with 

## the synthesis and release of ceruloplasmin, which fs the most 

## abundant copper protein that responds to deficiencies or excesses (Gubler, et al. 1953: Lahey, et al. 1953). Some20mammalian copPer proteins have been isolated, but at least three are identical andothers havemorethan onename. Most of this information hascomefrom animal studies, and its applicability to 

## humans is uncertain. Evans (1973) andothers have re

## viewed this subject (Mannand Keilin, 1938t Osborn, et al. 1963; Morell, et al. 1961; Sternlieb, et al. 1962). Copper plasma levels during pregnancy may 

## be two to three times the normal nonpregnant level. This is almo8t entirely dueto the increased synthesis of ceruloplasmin (Henkin, et al. 1972; Markowitz, et al. 

## 1955; Scheinberg, et al. 1954). Thesource of this copper appears to be the maternal liver. The increase in maternal plasma copper levels appears to beassooiated with estrogen, since either sex receiving estrogen 

## showsanincrease in copper 

## level of the plasma (Elsner andHornykiewicz, 1954: Gault, et 

## al. 1966: Humoller, et al. 1960: RussandRaymunt, 1956). The use 

## of oral contraceptives causes amarked increase in serumcopper lavels that maybegreater than those observed during pregnancy (Oster and Salgo, 1977; Smith and Brown, 1976; Tatum, 1974).Infant levels of serum copper are low at birth but promptly increase due to the 

## synthesis of ceruloplasmin by 

## the infant’s liver (Henkin, et al. 1973; Schorr, et al. 1958). 

## C-28

### There are 

### two inherited 

## diseases that represent abnormal cop

## per metabolism, Menkes' disease andWilson’s 

## disease. Yenkes' disease is aprogressive brain disease caused by an inherited sex

## linked recessive trait. It is often referred to 

## as the “kinky 

## hair” disease or "steely hair" disease (Danks, et al. 1972). The 

## primary characteristic of Menkes' disease appears to beadiminished ability 

## to transfer copper across the absorptive cells of the 

## intcstinalmucosa (Danks, et al. 1972, 1973). Thegeneral symptoms 

## of the disease are similar to those observed in animals suffering 

## from copper deficiency (Oakes, et al. 1976). The 

## prospects for moreeffective therapeutic measures as a result of 

## early diagnosis 

## appear to belimited. Wilson*s 

## disease, which has also been designated “hepatolent

## fcular degeneration, a is caused by an autosomal recessive trait (Beam, 1953). 

## The disease is actually acopper toxicosis with 

## abnormally high levels of copper in the liver and brain (Cumings, 1948). Symptoms include increased urinary excretion of copper 

## (Spillane, et al. 1952: Porter, 1951), low serum copper 

## levels due to low ceruloplasmin (Scheinberg andGitlin, 1952), decreased in

## testinal excretion of 

## copper, and occurrence of Kayser-Fleischer rings due to excessive accumulation of copper around the cornea. 

## If therapy witb d-penicillamine is instituted during the early phases ofWflronls disease, it 

## canassure anormal life expectancy, especially when accompanied by 

## a low-copper diet (Deias, et 31. 1971: Sternlieb andScheinberq, 1964, 1968; WaSshe, 1956). Other abnormalities of copper 

## metabolism are primarily associated with low levels of 

## copper. Ayoocupremia, which is defined as



## c-2980 'Jg or 

### less of copper/100 ml (Cartwright and Wintrobe, 1964a),

usually 

### refers to 

## alow ceruloplasmin level. In most 

## cases it 

## is probably due to 

## adietary deficiency of copper or to 

## afailure to synthesize the apoenzyme of ceruloplasmin 

## (Kleinbaum, 1963). HYPOcupremia 

## can also result from malabsorption that occurs during 

## a small bowel 

## disease (Sternlieb andJanowitz, 1964). Hypercupremia, abnormally hiqh levels of copper, occurs with a 

## number of neoplasms (Delves, et 

## al. 1973; Herring, et al. 1960; 

## Goodman, et al. 1967; Janes, et al. 1972). Elevated 

## serumcopper levels occur in psoriasis (Kekki, et al. 1966; 

## Molokhia and Portnoy, 1970). It is well recognized that copper is 

## necessary for the utili

## zation of iron. 

## Muchof this work 

## hasbeendone in 

## animals, andthe 

## subject is well covered byUnderwood (1977). It appears that ceruloplasmin is essential for the movementof iron from cells to plasma (Osaki, et 

## al. 1966). Reticulocytes from copper-deficient animalscanneither pick upiron from transferrin normally nor synthesize heme from 

## ferric iron andprotoporphyrin at the 

## normal rate 

## (Williams, et al. 1973). The 

## ratio of copper to other dietary components, e.q.# zinc, iron, 

## sulfate, andmolybdenum, maybealmost as important a3 the actual level 

## of copper in the diet 

## in influencing the metabolic response of mammalian species (Smith 

## andLargon, 1946). The 

## cardiovascular disorder "falling disease", reported by Bennetts, et al. (1942), is 

## associated with acopper deficiency incattle. Sim

## ilar conditions havebeenobserved in pigs 

## andchicken3 (O'Dell, et al. 1961; 

## Shields, et al. 1961). In this 

## disorder the 

## elastic tisc-30

### sue of major blood vessels Is deranged, markedly reducing zhe tensile strength of the aorta. This appears to be associated with a biochemical lesion, the reduced activity of lysyl oxidase, acopper-requiring enzyme necessary for elastic tissue formation and maintenance (Hill, et al. 1967). Evans has discussed the metabolic disorders of copper metabolism including nutriticnal disorders, inborn order errors of proper homeostasis, and disorders due to the lack of copper-requiring enzymes (Evans, 1977). Particular attention has been given to the role of copper 

## as associated with cardiovascular diseases (Vallee, 1952; Adelstein, et al. 1956). More recently there has been considerable interest in the role 

## of copper 

## andits ratio to zinc asafactor in the level of cholesterol 

## andcholesterol metabolism as it nay 

### relate to ischemic heart 

## disease (Klevay, 1977). It has been suggested that a low 

### copper-high zinc ratio may result in an increased level of cholesterol, particularly that part of the blood cholesterol in the serum low density lipoprotein whic.h 

## has been 

## associated with in

## creased susceptibility to ischemic heart disease (Allen and Klevay, 1978a,b; Petering, 1974; Lei, 1978; Klevay, et al. 1977). In 

## a different context, Barman (1970) has suggested that copper in the diet in excess of needs may result in free radicals that cause adverse effects fn the cardiovascular system. Excretion It has been noted that perhaps 40percent of dietary copper is actually absorbed (Cartwright and Wintrobe, 

## 1964a). These estimates are largely based on the difference between oral intake and

c-31

### fecal excretion. S’rinary excretion of copper 

## ?Lays avery minor

role. Thefecal excretion represents unabsorbed dietary copper and the copper that is excreted 

## by the 

## biliary tract, the salivary 

## glands, and the gastric 

## and intestinal 

## mucosae (Gollan andDeller, 1973). It should benoted that someof the excreted copper is re

## absorbed in the course of its movement down the intestinal tract. Some loss of copper may 

### occur by way of sweat and in the female menses. One of the principal routes of 

## excretion is by way of 

### the 

## bile; however, because of the difficulty in studying biliary excretion in normal subjects, the 

## evidence for quantitative 

## values of 

## copper excretion bythis route is fragmentary. Cartwright andWintrobe (1964a) suqqest 

## that 0.5 to 1.2 mqper day is excreted in the bile. 

### This is in 

## reasonable accord with the report (Frommer, 1974) that excretion was approximately 1.2 mq/day in ten control subjects. 

## It is possible that very little of the copper excreted in the bile 

## is reabsorbed (Lewis, 1973). Somecopper 

## (approximately 0.38 to 0.47 mq/day) is excreted in the saliva, 

## but there is little evidence as 

### to 

## whether this copper is 

## or is not absorbed in the intestine (DeJorge, et al. 1964). It is possible 

## that the gastric secretion of copper approximates 1mq

## of copper per 

## day, but there is very little published information on this 

## subject (Gollan, 1975). The 

## amount of copper excreted in the urine is small. Estimates range from 10 to 

### 60 

## ug/day andaverage 18 ug/day (Cartwright 

## andWintrobe, 1964a; Zak, 1958). It 

### is possible, of courser that copper maybe reabsorbed from the kidney tubules (Davidson, et al. 1974). 

## C-32

### Studies in New

## Zealand conducted onyoung womenwith acopper

intake of 1.8 to 2.09 mg/day showed an excretion in the feces of between 65 and 

### 94 percent of the intake. The urinary excretion amounted to 1.7 to 2.2 percent of the intake (Robinson, et al. 1973).Under some conditions aconsiderable 

## amount of copper maybe lost through sweat, perhaps as much as 1.6 mg

### of copper per day or about 

### 45 percent of the total dietary 

## intake (Consolazio, et al. 1964).

### There is very little information on the loss of copper byway of the menstrual flow, but an average value 

### of 0.11 f 0.07 mgper period seems reasonable (Ohlson and 

## Daum, 1935; 

## Leverton and

## Binkley, 1944). Sternlieb, et al. 

### (1973) note that 0.5 to 1.0 mgof copper is catabolized daily by 

### the adult liver, and about 

### 30 mgof ceruloplasmfn, which contains 0.3 percent copper, is excreted into the intestine (Waldmann, et al. 

### 1967). The copper excreted into the intestine in the bile 

### maynot be 

### readily 

## available for reabsorption because it is 

## bound to protein: the copper found in the feces seems to come from various secretions, aswell as the copper that is not absorbed from food (Gollan and Deller, 1973). In summary it may be 

### said that most copper is excreted byway 

## of the Uliary system 

## with additional amounts in sweat, urine, saliva, gastric 

### and intestinal mucosae, and menstrual discharge. Examination of the pharmokinetic data points upthe fact that the biological half-life of copper is very short. 

## This provides significant protection against accumulations of copper even with intakes considerably above levels considered adequate. c-33

### EFFECTS

Acute, 

## Subacute, andChronic Toxicity Copper toxicity produces ametallic taste in the mouth, nau

## sea, vomiting, epigastric pain, diarrhea, 

## and depending on the severity, jaundice, 

## hemolysis, hemoglobinuria, hematuria, and oli

## guria. Thestool and saliva 

### mayappear green or blue. In severe 

## cases anuria, hypotension, andcomacanoccur. Toxic levels of copper ingested are promptly absorbed from the upper gut, 

## andthe copper level in the blood is rapidly increased, primarily 

## because of its accumulation in the 

## blood cells. Hemolysis occurs at 

## high copper levels. A

## high level in the blood can also result from 

## absorption through the denuded skin, aswhenapplied to burns, because 

## of dialysis 

## procedures, or because 

### of exchange transfusions. 

## Thehemolysis is 

## dueto the sudden release of copper into 

## the blood 

## stream from the liver that has been 

## damaged by

## anincreasing load 

## of copper andis unable to utilize the 

## copper in the 

## synthesis of ceruloplasmin, which in turn canbeexcreted by 

## wayof the 

## biliary system (Chuttani, et al. 1965; 

## Bremner, 1974: Cohen, 1974; Deiss, et al. 1970; Roberts, 1956; Bloomfield, et al. 1971; 

## Ivanovich, et. al. 1969; Bloomfield, 1969). 

## Chatterji andGanguly (1950) describe a

## nonfatal type of copper poisoning in which the symptoms are laryngitis, bronchitis, intestinal 

## colic with 

## catarrh, diarrhea, general emaciation, and anemia. 

## Burch,. et 

## al. (1975) have estimated 

## that the toxic 

## intake level of 

## inorganic copper for anadult manis greater than 15mgper dose. The

## vomiting anddiarrhea induced by ingesting small quanti

## c-34

### ties 

## of ionic copper 

## generally protect the patient from the serious



## systemic toxic effects which include hemolysis, hepatic necrosis, 

## gastrointedtinal bleeding, oliguria, azotemia, hemoglobinuria, 

## hematuria, proteinuria, hypotension, tachycardia, convulsions, or death (Chuttani, et al. 1965; Davenport, 1953). Because mostof the information about acute copper toxicity in humans has comefrom 

## attempts at suicide or from the accidental intake of large quantities of copper salts, the information about 

## the changes occurring with acute toxicity are meager. 

## Acute copper poisoning doesoccur in manwhenseveral gramsof copper sulfate are eaten with acidic food or beverages 

## suchasvinegah carbonated beverages, or citrus juices 

## (Walsh, et al. 1977). Somecases of acute poisoning haveoccurred whentablets 

### containing 

## copper sulfate were given to children (Forbes, 1947). Whencarbonated water remains in copper check valves ordrinkdispensing machines overnight, the copper content of the first 

## drink of the 

## daymaybeincreased enough to cause 

## ametallic 

## taste, nausear vomiting, epigastric burning, and diarrhea (Hooper and Adams, 1958). Drinks that are stored in copper-lined cocktail 

## shakers orvessels canhavethe sameeffect (Pennsylvania Morbidity andMortality Weekly Reports, 1975: McMullen, 1971). Salmon and Wright (1971) have reported the possibility of chronic comr poisoning asa-result of water moving through copper 

## pipes. They-document acase inwhich afamily movedinto ahouse in North London with ahot water system entirely composedof copper. Thewater wasstored in a40-gallon copper tank which 

## reached a temperature of 93OCat night. The 

## family used hot water for 

## all

c-35

### cooking and beverages. After two rr,ontfis, the electric kettle was

coated inside with athick green film 

## of the copper complex. The child in the family 

## wasadmitted to the 

## hospital after five weeks 

### of behavior 

## change, diarrhea, and progressive marasmus. Whenit 

## was first 

## seen, the clinical picture wasthat of "pink" disease with prostration, misery, 

## red extremities, hypotonia, photophobia, andperipheral edema. The liver 

## waspalpable 2cmbelow the costal margin. 

## Theserum copper level was286 pg/lOO ml, compared to a normal range of 164270ug/lOO ml. 

## Analysis of water in the home 

## found 350pg/l of copper in 

## the cold water and790ug/l of copper in the hot 

## water. Cold andhot water levels in the 

## hospital were40 and300ug/l, respectively, and in North London the values were 80 and 160ug/l. Walker-Smith 

## andBlomfield (1973) 

## treated the 

## male infant de

## scribed in the preceeding paragraph, who

## had received high levels of copper from contaminated water over aperiod of three months, with d-penicillamine andprednisolone. Theinfant madeaslow recovery. Themethod of EdenandGreen (1940) wasusedto determine copper levels. It is possible that 

## the infant wasexhibiting Wil

## son's disease andresponded to the appropriate treatment. Edenand Green 

## (1940) reported on a 

### male 

## infant 'whoreceived high levels 

## of copper frosncontaminated water ingested over aperiod of three months. The result was 

## chronic copper poisoning. Treated 

## with d-penicilliamine and prednisolone, 

## the infant madea slow recovery. In 

## general, however, the problems associated with high levels 

## of copper in drinking water are more 

## or Lesscontrolled because of

C-36

### (1) taste (since high levels of copper in water produce ametallic

taste), and (2) cosmetic considerations (since water with high copper content develops a

## surface scumdue to the 

## formation of insoluble copper 

## compounds). Chronic 

## toxicity has been studied in animals, andthere appears to be

## awide variation in 

## the tolerance of different species for high levels of 

## copper in the diet. Sheep are 

### very susceptible to high 

## copper intakes, whereas rats have been shown to be very 

## resistant to the development of copper toxicity. Swine will develop copper poisoning at levels of 250 pg of 

## copper/g of 

## diet unless zinc and iron 

## levels are increased. Suttle 

## and Mills (1966) 

## have studied dietary copper levels ranging up to 

## 750 pg/g in the diet of swine. Toxicosis does develop with hypochromic 

## microcytic anemia, jaundice, and marked increases in the liver and serum copper levels as well as serum aspartate amino transferase. 

## Thesesigns of copper toxicosis in swine 

## canbeelim

## inated by 

## including an additional 150 pgof zinc and iron/g in diets containing up to 450 ug 

## of copper/g; the addition of even more zinc 

## and iron, 500to 750pg/g, will overcome the effects of 750ugof 

## copper/g 

## of diet. 

## Chronic oral intake of copper acetate in swine and rats can produce a condition comparable to hepatic hemosiderosis in man (Mallory an& Parker, 1931). 

## Somequestion exists as to whether hemosiderosis in 

## manis a

### result 

## of copper toxicity, because people consuming 

## comparatively high levels of copper do not 

## develop this 

## condition regularly.

c-37

### Sheep are quite susceptible to high levels of copper in the

diet. Copper levels of 35 ug/g of feed have resulted in 

## toxicity when fed over aperiod of nine months to one

## year (Fontenot, et al. 

### 1972). Cattle 

### are muchmore resistant to copper in the diet; 2gof copper sulfate given daily did not produce 

## toxic reactions (Gunningham, 1931). It is well known that with ruminant animals, molybdenum and 

## sulfate interact with the copper. Cooper toxicity is counteracted by inclusion of 

## molybdenum and sulfate in the diet of ruminants (Dick, 1953: Kline, 

## et al. 1971; wahal, et 

## al. 1965). Synergism and Antagonism There 

## is some 

## evidence that copper may increase the mutagenic activity of other compounds. Using strain TAlOO of Salmonella typhimurium, 

## Omura, et al. (1978) studied the mutagenic actions of triose reductone 

## and ascorbic 

## acid. They found that the addition of the 

## copper to triose reductone at aratio of l:l,OOO lowered 

### the most 

## active concentration of the triose reductone to 1mMfrom 

## 2.5 to 5ref. Another enediol reductone, 

## asborbic acid, had no detectable mutagenic action by 

### itself, but a

### freshly mixed 

## solution of 5mMof 

## ascorbic acid and 1or 5 UM

### of cupric copper had aneffective mutagenic action. Ascorbyl-3-phosphate had nomutagenic function even in the presence 

## of cupric copper. The investigators suggested that it 

## wasthe 

## enediol structure in the 

### reductones that was the essential for mutagenicity. In the Acute, Subacute, and Chronic Toxicity section, it was 

### pointed out that the dietary levels of zinc and iron are as imporC-38

### tant as the level of copper in determining the toxic level of

copper . Teratoqenfcfty There is very little evidence in the literature to suggest that copper has

## ateratoqenic effect in either animals or humans. Mutagenicity Nodata were found to suggest that copper itself has a muta

### genic effect in either animals or humans: however, one report exists suggesting that copper may increase the mutagenic activity of 

## other compounds (see Synergism 

## andAntagonism section). Carcinoqeniclty There is very little 

## evidence in the literature to suggest 

## that copper hasacarcinogenic effect in either animals or humans. Pimental 

## andMarques (1969) noted that vineyard 

## workers in France, 

## Portugal, and southern Italyr exposed to copper sulfate sprays mixed with lime to control mildew, developed qranulomas in the 

## liver andmalignant tumors in the lung (Pimental and Menezes, 

## 1975; Villar, 1974). 

## Because of the 

## route of expoaure, quantitative estimates are, at best, 

### speculative. 

## It hasbeennoted earlier that the conditions in industry that would produce excessive concentrations of copper 

## as adust or a mist with 

## particle sizes that would result in toxic effects if the 

## copper were absorbed, 

### are apparently quite rare. Some investigators 

## havesuggested that lung cancer, which is 

## prevalent in copper smelter workers, is 

## actually due to the 

## arsenic trioxide in the dust and that the 

## copper itself did not 

## play any etiologic role in the development of the cancer (Xuratsune, et al. 1974; Lee and



## c-39

### Fraumeni, 1969; Yilham 

## and Strong, 1974; Tokudome and Kuratsune,

1976).Some 

### studies have reported that, with the development of various tumors, the copper content in both blood 

## andthe 

## tumor tissue 

### is likely to increase, although this is not 

## always the case (Pedrero 

## andKozelka, 1951; Dick, 1953; Kline, et 

## al. 1971: 

## Wahal, et al. 1965). Kowever, when an increase occurs, 

### it appears to be 

## a result of 

## aninflammatory response or stress rather than anydirect causative relationship. Polish 

## workers (Legutko, 

## 1977) havesuggested that the copper level of the serum is a particularly sensitive 

## indicator 

## of the clinical condition 

## andeffectiveness of treatment of lymphoblastic 

### leukemia in children, but 

## again noparticular relationship to 

## the development of the leukemia 

## is indicated. Russian scientists (Bezruchko, 1976) 

## have also studied the 

### copper 

## andceruloplasmin in 

## patients with cancer andnoted that the levels 

## of both ceruloplasmin 

## and

## copperwere increased in 

## metastatic 

## cancer of the 

## mammarygland, in skin 

## melanoma, and in ovarian cancer. The serum 

## levels of ceruloplasmin increased 27, 20, and 44 

## percent, respectively, for those tumors, andthe copper increased by41, 35, and51percent, respectively, 

## for those sametumors as compared with 

## normal tissue. Again, nocorrelation wasfound be

### tween the tumor 

## and

## copper asacausative agent. Workers in 

## HongKong (Fang, et 

## al. 1977) have 

## been investigating copper concentrations in cases 

## of esophageal cancer in both humans and animals. They report 

## that serum copper is increased slightly andthat this 

## is paralleled by

## adecrease inzinc content.

c-40

## In 3ummaryl 

### it must 

## bestated that evidence for the oncolcgi

## cal effects of copper, evenat high concentrations, is essentially nonexistent. With the exception of the references cited, there 

## appear to be 

## nodefinitive reports of copper asacausative agent in the development of cancer. There is muchmore evidence 

## that a deficiency of copper will haveadverse effects 

## both in animals and in humansdueto .Its ewen,tial 

## role in 

## the functioning of manyenzymesystems.

c-41

### CRITERION FORMULATION

Existing Guidelines 

## andStandards Far more 

## attention has been given to the problems of copper deficiency 

## than to 

## the problems of excess copper in the 

## environment. The 

## 1mg/l standard that has been established for copper levels in water for humanconsumption has been 

## adopted more for 

## organoleptic reasons rather than because of any evidence of toxic levels 

## (Fed. Water Quality 

## Admin., 1968). Cohen, et al. (1960) noted that 

## various investigators 

## have reported adverse taste of water containing 3to 5mg/l, 2mg/l 

## and 1.5 mg/l of copper. The

## choice of 1ppmasalevel that wasorganoleptically 

## satisfactory and below 

## anyvalues of health concern for humanswastherefore considered reasonable. This 

## study wasusedas abasis for the 

## current drinking water standard. The U.S. 

## Occupational Safety and Health Administration has 

## adopted standards for exposure to airborne 

## copoer at work. The time-weighted 

## average for 8-hour daily 

## exposure to copper dust is 

## limited to 

## 1mg/m3of air. Thestandard for 

## copper fumewaschanged in 1975to 0.2 mg/m3(Gleason, 1968: Cohen, 1974). 

## As indicated below, 

## the FoodandNutrition Board 

## of the National Academy

## of Sciences (1980) recommendsadaily allowance of 0.5 to 1.0 

## mg/day for infants, 1.0 to 2.0 mg/day for pre-schoolers, 2.0 

## to 2.5 

## mg/day for older 

## children, and 2.0 to 3.0 mg/day for teenagers and adults. Age.

## (yrs) RDA(mq/day) Age (yrs) RDA(mq/day) 0.0-0.5 0.5-0.7 4- 6 1.5-2.0 0.5-1.0 0.7-1.0 7-10 2.0-2.5 l-3 1.0-1.5 ll-Adult 2.0-3.0 C-42

### There are nostandards for copper in medical practice such as

the treatment of burns or dialysis or for parenteral feeding. Current Levels of Exposure Ashas been mentioned earlier, principal concern has been 

### for conditions of copper deficiency rather than copper toxicity. It has been suggested earlier that copper intakes in food and water may ranqa from 6to 8mgper 

## day, and that the percentage absorbed varies with the 

## nutritional status. Onthe other hand, because of 

## changes in 

## food processing and, perhaps, 

## because of better methods of analysis, 

## copper intakes may

## not reach the 2mgper 

## dayconsidered 

## anadequate nutritional intake (Klevay, et al. 1977; Diem 

### and 

## Lentner, 1970; Robinson, et 

## al. 1973; 

## Schroeder, et 

## al. 1966; WHO, 1973; Cartwright 

## andWfntrobc, 1964a). The average concentration of copper in United States water systems is approximately 134 &l with alittle 

## over 1percent bf the samples 

## taken exceeding the drinking water standard of 1mg/l (McCabe, et al. 1970). 

## Whenthe 

## U.S. Public Health Service studied urban water supply systems, they found 

## that only 11

## of 969 systems 

## had copper 

## concentrations greater than 1mq/l (W.S. HEM,1970). In 1966, 

## the National Air Sampling Network 

### found 

## airborne copper concentrations 

## ranging from 0.01 to 0.257 ug/m3 in rural and in 

## urban communities, respectively. Levels of copper ashigh as 

### 1to 2yg/m3 

## wermfound near copper smelters, 

## but this 

## wasnot considered hazardous 

## (Natl. Air Pollut. Control Admin., 1968; Schroeder, 1970).

c-43

### Special Groups 

## at Risk

Increased 

## copper exposure, with associated health effects, has 

## occasionally occurred inyoungchildren subjected to unusually high concentrations of copper in 

## soft or treated water that has been 

## held in copper pipes or stored in copper vessels. Discarding the first water coming from the 

## tap can reduce this hazard. Similar problems havedeveloped in 

## vending machines with copper-containing conduits where acid materials in contact 

## with the copper for periods of tine have dissolved 

## copper into the vended liquids. Other groups that maybeat risk are medical patients suffering fromWilson's disease 

## andthose patients who are 

### being 

## treated with copper-contaminated fluids in dialysis or bymeansof paren

## teral alimentation. These 

## are medical instances 

## in which the cop

## per content of 

## the materials used should 

## becarefully controlled. There is also a reasonable likelihood that exposure to elevated levels of copper (ca. 1.0 ppm) from 

## community drinking water maybeacontributory factor in the 

## precipitation 

## of acute hemolysis in 

## individuals with a glucose-6-phosphate dehydroqenase (G-6-PD) deficiency. Approximately 13 

## percent of the American black 

## male population has a 

## G-6-PD deficiency 

## (Beutler, 1972). G-6-PDdeficient humane

## werefound to be.markedly more 

## sensitive to several 

## indicators of oxidant stress as measured 

## by increases in methemoglobin. levels and 

## decreases in the activity of red cell acetylcholineeteraea indicating that 

## susceptibility to copperinduced oxidative stress is associated with 

## the presence of low red cell G-6-PD activity (Calabrese 

## and?4oore, 1979; Calabrese, et al. 

## 1980).

c-44

### Afinal group that maybe subject to risk of copper toxicity

consists of those 

## people occupationally exposed to copper, e.g., industrial 

## or farm 

## workers. In reviewing the 

## medical andbiologic effects of environmental 

## pollutants, the National Academyof Science (1977) pointed out,that 

## use of livers from animals fed high levels of copper in the diet could 

## produce a baby 

## focd prcduct that wasexcessively high in 

## copper. The Committee 

## also raised the question of exposure to copper from intrauterine contraceptive devices 

## (IlJDs), but subsequent reports have failed to demonstrate anyabnormal accumulation of copper because of the 

## useof these 

## devices. Basis andDerivation of Criterion Copper is anessential dietary element for humaneandanimals. 

## Alevel of 2mgper daywill maintain adults in balance (Adelstein, et al. 1956) 

## andhasbeenconsidered adequate, although because of interactions with other dietary constituents that limit absorption and 

## utilization, arequirement level mustbeconsidered in conjunction with such constituents aszinc, iron, andascorbic acid. The 

## minimumlevel meeting requirements for copper 

## intake in intravenous feeding is 22vgcopper/kg bodyweight (Vilter, et al. 1974). The 

## short biological half-life of copper and the 

## homeostasis that exists in humaneprevents copper from accumulating, 

## evenwith 

## dietary intakes considerably in excess of 2mg

## per day. In the 

## opinion of manyinvestigators, there is much more likelihood of a 

## copper deficiency occurring than of atoxicity developing with cur

## rent dietary andenvironmental situations.



## c-45

### Although acute 

### and chronic levels Of intake mayoccur, there

are 

## nodata that adequately define these Levels. It 

## has been suggested that 

## intakes above 

## 15mg

## of copper per day mayproduce observable effects, but if 

## zinc and iron intakes are also increased, 

## muchhigher levels maybeconsumedwithout 

## adverse reactions. The 

## data for acute toxicity are evenmoreuncertain, since practically all humaninformation stems 

## from cases of attempted suicide. Theavailable literature leads to the conclusion that copper does not produce teratogenic, mutagenic, or carcinogenic effects. The 

## limited information available indicates that where suchaction hasoccurred, e.g., with mixtures 

## of copper sulfate andlime, 

## arsenic, or enediols, the copper should beconsidered as interacting 

## with the other materials andnot asthe active material. The

## current drinking water standard of 1mg/l is considered to be 

## below anyminimumhazard level, even 

## for special groups at risk 

## such asvery young children, and therefore it is reasonable that this 

## level be 

## maintained asawater quality criterion. Since the 

## current standard andhence the water quality criterion 

## of 1.0 mg/l 

## are basedonorganoleptic effects (U.S. LlEW,1970) andare not toxicological assessments, the 

## consumption 

## of fish and shellfish 

## is not considered asaroute of 

## exposure.

C-46

## REFERENCES

Adelstein, S.J., et 

## al. 1956. Metalloenzymes and myocardial infarction. 1. The 

### relation between serum copper and ceruloplasmin 

## and its 

## catalytic activity. NewEngland Jour. 

## Med. 255: 105. Allen, K.G.D. 

## and L.M. 

## Klevay. 1978a. Cholesterol metabolism in copper-deficient rats. Life 

## Sci. 22: 1691. 

## Allen, K.G.D. andL.M. Rlevay. 1978b. 

## Chalesterolemfa andcardiovascular abnormalities in rats caused by

## copper deficiency. Atherosclerosis. 29: 81. 

## Barber, R.S., et al. 1978. The 

## value of virginiamycin (eskalfn) 

## asa

## feed additive for growing pigs in 

## diets with or without ahigh copper supplement. Jour. Anim. 

## Prod. 26: 151. Bearn, A.G. 1953. 

## Genetic and biochemical aspects of Wilson's disease. Am. Jour. Med. 15: 442. 

## Bearn, A.G. 

## andH.G. Kunkel. 1954. Localization of Cu64 in serum fractions following oral 

### administration: 

## analteration in Wilson's disease. Proc. Sot. Exp. Biol. 

## Med. 85: 44. 

## Bearn, A.G. 

## andH.G. Runkel. 1955. Metabolism studies in Wilson's disease using Cu64

. 

## Jour. Lab. Clin. Med. 45: 623.

c-47

### Beckner, W.M., et al. 1969. External gammascintillation counting



### of 67

## Cuover the liver 

## andother sites in patients with Wilson's disease, 

## family membersandcontrols. Jour. Yucl. Med. 10: 320. 

## Bennetts, H.W., et 

## al. 1942. Studies oncopper deficiency of 

## cattle: The fatal termination ('falling disease’). Aust. Vet. Jour. 

## 18: 50. Benoit, D.A. 1975. 

## Chronic effects of copper onsurvival, growth, 

## andreproduction of the bluegill (Lepomis macrochirus). 

## Trans. Am. Fish. Sot. 104: 353. Beutler, E. 1972. Glucose-6-phosphate 

## Dehydrogenase Deficiency. 

## 2: J.B. Stanbury, et al. teds.), TheMetabolic Basis of Inherited Disease. McGraw-Hill, NewYork. p. 1358. Bezruchko, V.I. 1976. Copper content and ceruloplasmin activity in 

## the blood serumof oncological patients. Aktual. Probl. Onkol. Med. Radiol. 6: 149. Chem.Abstr. 89: 4261~. (Rus.) 

## Bloomfield, J. 1969, Copper contamination in 

## exchange transfusions. Lancet- 1: 731. Bloomfield, J., 

## et al. 1971. Potential 

## hepatotoxicity of copper in recurrent 

## hemodialysis. Arch. Intern. 

## Med. 128: 555.

C-48

### Bowness, 

## J.M. and R.A. Yorton. 1952. Distribution of 

## copper and

zinc in the eyes of fresh water fishes and frogs. Occurrence of metals in melanin fractions from eye tissues. Biochem. Jour. 51: 530. Bowness, J.M., 

### et al. 1952. Distribution of copper and zinc in mammalian eyes. Occurrence of metals in melanin fractions from eye tissues. Biochem. Jour. 51: 521. Bremner, I. 1974. Heavy metal toxicities. Q. Rev. Biophys. 7: 75. Bruckmann, G. and S.G. Zondek. 1939. Iron, copper and manganese in humanorgans at various ages. Biochem. Jour. 33: 1845. Burch, R.E., et al. 1975. Newer aspects of the roles of zinc, manganese and copper in human nutrition. Clin. Chem. 21: 501. Bush, J.A., et al. 1955. Studies on copper metabolism. XVI. Radioactive copper studies in normal subjects and in patients with hepatolenticular degeneration. Jour. Clin. Invest. 34: 1766. Button, R.S., et al. 1977. Copper dispersal in awater supply reservoir. Water Res. 11: 539. Calabrese, E.J. andG.S. Moore. 1979. Canelevated levels of copper in drinking water precipitate acute hemolysis in G-6-PD deficient individuals? Med. Hypotheses. 5: 493. c-49

### Calabrese, E.J., et al. 1980. 

## LOWglucose-G-phosphate dehydrogenase (G-6-PD) activity in red blood cells and susceptibility to cop

### per-induced oxidative damage. Environ. Res. 21. Cartwright, G.E. 1950. Copper Metabolism in KumanSubjects. &: W.D. McElroy and B. Glass (eds.), ASymposium onCopper Metabolism. Johns Hopkins Press. Saltimore. p. 274. Cartwright, G.E. and H.M. Wintrobe. 1964a. Copper metabolism in normal subjects. Am.Jour. Clin. Nutr. 14: 224. Cartwright, G.E. and M.M. Wintrobe. 1964b. Thequestion of copper deficiency in man. Am.Jour. Clin. Nutr. 15: 94. Cartwright, G.E., et al. 1956. Studies on copper metabolism. XVII. Further observations on the anemia of copper deficiency in swine. Blood. II: 143. Cavell, P.A. and E.M. Widdowson. 1964. Intakes and excretions of iron, copper and zinc in the neonatal period. Arch. Dis. Child. 39: 496. Chatterji, S.K. and H.D. Ganguly. 1950. Copper in humanurine and feces. Ind. Jour. Med. Res. 38: 303. Chez, R.A., et al. 1978. Amniotic fluic, copper and zinc concentrations in human pregnancy. Obstetrics Gyn. 52: 125.

c-50

### Chuttani, A.K., et al. 1965. Acute copper sulphate poisoning.

Am.Jour. Med. 39: 849. Cohen, 

## J.M., et al. 1960. Taste threshold concentrations of met

### als in drinking water. 

### Jour. Amer. Water Works Assoc. 52: 660. Cohen, S.R. 1974. 

## Areview of the health hazards of copper exposure. Jour. Occup. Med. 16: 621. Consolazio, C.F., et al. 1964. The trace mineral losses in sweat. U.S. Army Med. Reg. Nutr. Lab. Rep. No. 284: 1. Crampton, R.F., et al. 1965. Observations on the mechanism of absorption of copper by the small intestine. Jour. Physiol. 178: 111. Cumings, J.N. 1948. Thecopper and iron content of brain and liver in the normal and in hepato-lenticular degeneration. Brain. 71: 410. Cunningham, I.J. 1931. Somebiochemical andphysiological aspects of copper in animal nutrition. Biochem. Jour. 25: 1267. D'Amico, R.J. 1959. Mineral Production in the United States. g: Minerals Yearbooks for 1958. U.S. Dep. Interior. Bur. Mines.

c-51

### Daniels, A.L. and 0.9. Wright. 1934. Iron and copper retentions

in young children. Jour. Nutr. 8: 125. Danks, D.M., et al. 1972. Menkes' kinky hair syndrome. Aninherited defect in copper absorption with widespread effects. Pediatrics. 50: 188. Danks, D.M., et al. 1973. Menkes' kinky hair disease: further definition of the defect in copper transport. Science. 179: 1140. Davenport, S.J. 1953. Review of 

### literature on health hazards of metals. I. Copper. U.S. But. Mines Inf. Circ. No. 7666. U.S. Government Printing Office, Washington, D.C. Davidson, I.W.F., et al. 1974. Renal excretion of trace elements: chromium and copper. Proc. Exp. Biol. Med. 147: 720. Deiss, A., et al. 1970. Hemolytic anemia in Wilson's disease. Ann. Intern. Med. 73: 413. Deiss, A., et al. 1971. Long term therapy of Wilson's disease. Ann. Intern. Med. 75: 57. DeJorge, F.B., et al. 1964. Studies on

## copper metabolism. III. Copper contents of saliva of normal subjects 

### andof salivary glands and pancreas of autopsy 

### material. Clin. Chim. Acta. 9: 148.

C-52

## Delves, H-T., et al. 

### 1973. Copper and zinc concentration in the

plasma 

### of leukaemic children. Br. 

## Jour. Haematol. 

## 24: 525. Dick, A.T. 1953. The contro1 of 

## copper storage in the liver of 

## sheep by inorganic sulfate and molybdenum. 

## Austr. Vet. Jour. 29: 233. Diem, K.andC.Lentner, feds.1 1970. Composition of Foods. Cocumentia Geigy. Scientific Tables. 7th ed. Geigy Pharmaceuticals, 

## Division of Ciba-Geigy 

## Corp., Ardsley, N.Y. Earl, C.J. 1961. Anatomical Distribution 

## of Copper in 

## Human Brain. In: J.M. Walshe andJ.N. Cumings (eds.), Wilson's Disease. SomeCurrent Concepts. Blackwell, Oxford. p. 18. Eden, A.A. andH.H. Green. 1940. Micro-determination of copper in 

## biological material. Biochem. Jour. 34: 1202. Elsner, P.and0. Hornykiewicza. 1954. Die beeinflussbarkeit der p-polyphenoloxydase-aktivitat des menschliehen blutserums durch sexualhormone. Arch. Gynakol. 185: 251. Engel, R.W., 

## et al. 1967. CopperImanganese, cobalt, 

## andmolybdenumbalance in pre-adolescent girls. 

## Jour. Nutr. 92: 197. Evans, G.W. 1973. Copper homeostasis in the mammalian system. 

## Physiol. Rev. 53: 535.

C-53

### Evans, G.W. 1977. Yetabolic disorder sof copper ?tetabolism. Tidv.

Nutr. Res. 1: 167. Evans, 

## G.W., et al. 1973. Copper and zinc binding components in rat intestine. Clin. Res. 21: 867. Federal Water Quality Administration. 1968. Water quality criter ia. Rep. Natl. Tech. Adv. Comm.to the Secretary of the Interior, Washington, D.C. Fong, L.Y.Y., et al. 1977. Zinc and copper concentrations in tissues from esophageal cancer patients and animals. Trace Subs. Environ. Health. 11: 184. Fontenot, J.P., et al. 1972. Effects of feeding different levels of broiler litter to ewes for long periods of time on performance and health. Virginia Polytechnic Inst. State Univ. Res. Div. Rep. No. 145: 33. Forbes, G. 1947. Poisoning with apreparation of iron, copper and manganese. Br. Med. Jour. 1: 367. Frommer, D.J. 1974, Defective biliary excretion of copper in Wilson’s disease. Gut. 15: 125. Gault,: M.H.; et al. 1966. Serum ceruloplasmin in hepatobiliary and other disorders: significance of abnormal values. Gastroenterology. 50: 8. c-54

## Gipp, W.F., et al. 1974. Effect of dietary copper, iron andascorbic acid levels onhematology, blood andtissue copper, iron and zinc concentrations and 64Cuand "Femetabolism in young pigs. Jour. Nutr. 104: 532, Gleason, R.P. 1968. Exposure to copper dust. Am. Ind. Hyg. Assoc. Jour. 29: 461. Gollan, J.L. 1975. Studies onthe nature of complexes formed by copper with humanalimentary secretions andtheir influence oncopper absorption in the rat. Clin. Sci. Molec. 

## Med. 49: 237. Gollan, J.L. andD.J. Deller. 1973. Studies onthe nature andexcretion of biliary copper in man. Clin. Sci. 44; 9. Goodman,S.I., et al. 1967. Bypercupremia in apatient with multiple myeloma. Jour. Lab. Clin. Med. 70: 57. Gubler, C.J., et al. 

## 1953. Studies of 

## copper metabolism. IX. The transportation of copper in blood. Jour. Clin. Invest. 32: 405. Hadjimarkos, D.M. 1967. Effect of trace elements on dental caries. Jour- Fed. 70: 967. Harman, D. 1970. Atherogenisis in Minipigs: Effect of Dietary Fat Unsaturation and Copper. z: R.J. Jones ted.), Athersclerosis. Proc. 2ndInt. Symp. Springer-Verlag, NewYork.

c-55

## Henkin, R.I., et al. 1971. Maternal-fetal 

## metabolism of copper

andzinc at term. Am.Jour. Obst. 

## Gynecol. 110: 131. Henkin, R.I., et al. 

## 1973. Changes in total, nondiffusible and diffusible plasma zinc and copper during infancy. Jour. Ped. 82: 831. 

## Herring, W.B., et al. 1960. Trace metals in human plasma and red 

## blood cells. A 

### study of 

## magnesium, chromium, nickel, copper and zinc. II. Observations of patients with somehematologic diseases. Am.Jour. 

## Clfn. Nutr. 8: 855. 

## Hill, C.H., 

## et al. 1967. Role of 

## copper in the formation 

## of elastin. Fed. Proc. 26: 

## 129. Ffoltzman, N.A., 

## et al. 

## 1966. Copper intoxication. 

## Report of a case 

## with observations on ceruloplasmin. New England 

## Jour. Med. 275: 347. 

## Hooper, S.B. and B.S. Adams. 1958. Copper 

## poisoning from vending machines. Pub. Health 

## Rep. 73: 

## 910. Hui, K., et aI, 1977. Analysis of copper in brain 

## bythe mass

## spectrometric integrated-ion-current 

## procedure. Neuro Chem. 

## Res. 2: 495. Chem. Abstr. 88: 3409OM.

C-56

## Humoller, F.Lor et al. 1960. Enzymatic properties of ceruloplasmin. Jour. Lab. 

## Clin. Med. 56: 222. Hunt, C.E., et al. 

## 1970. Copper deficiency in chicks: Effects of ascorbic acid on iron, copper, cytochrome oxidase 

## activity, and aortic mucopolysacchar ides. Br. Jour. Nutr. 

## 24: 607. Ivanovich, P., et al. 1969. Acute hemolysis following hemodialysis. Trans. Am.Sot. Artif. Intern. Organs. IS: 316. Jacob, R.A., 

## et al. 

## 1978. Hair as a

## biopsy material. V. Hair metal asanindex of hepatic metal 

## in rats: copper and 

## zinc. Am. Jour. Clin. Nutr. 31: 477. Janes, H.M., et al. 1972. 

## Trace metals in human osteogenic 

## sarcoma. MayoClin. Proc. 47: 476. Jensen, W.N. and 8. 

## Xamin. 1957. Copper transport andexcretion in normal subjects 

### and 

## in patients with Laennec’s 

## cirrhosis and Wilson's disease: A study with Cu 64

. Jour. Lab. Clin. Med. 

## 49: 200. Kartar, S.anaA.R. Chowdhury. 1977. Release 

## of copper ions 

## from an

## intra vascopper-wire contraceptive device. Ind. Jour. 

## Physiol. Pharmacol. 21: 387.

C-57

## Kekki, M., 

## et al. 1966. Serumceruplasmin-bound copper andnoncetuloplasmin-bound copper in uncomplicated psoriasis. Jour. Invest. Dermatol. 47: 159. Klein, L.A., et al. 1974. Sources of metals inNewYorkCity waste water. Intern. Water Pollut. Control Fed. 46: 2653. Kleinbaum, 8. 

## 1963. Votubergehendt hypoproteinamine mit hypocupramie und eisenmangclanemie bei dystrophen sauglingen. Ztschr. Kinderheilk. 88: 29. Klevay, L.M. 1977. The role of copper and zinc in cholesterol metabolism. Adv. Nutr. Res. 1: 227. Klevay, L.M., et al. 1977. United States diets andthe copper requirement. Fed. Proc. 36: 1175. Kline, R.D., et al. 1971. Effects of copper, molybdenum andsulfate on performance, hematology and copper stores of pigs and lambs. Jour. Anim. Sci. 

## 33: 771.
KoPPI

## J.F. andR.C. Kroner. 1968. Trace metals in waters of the United States: =five-year summaryof trace metals in rivers and lakes of the United States, October 1, 19620September 30, 1967. U.S. Dept. Inter., Fed. Water 

## Pollut. Cmtrol Admin., Cincinnati, Ohio.

C-58

## Kuratsune, Maret al. 1974. Occupational lung cancer amongccpper

smelters. Int. Jour. Cancer. 13: 552. Lahey, M.E., et al. 1953. Studies oncopper metabolism. VII. Blood copper in pregnancy and various pathologic states, Jour. Clin. Invest. 32: 329. Larsson, B., et al. trium in diabetic 15: 711. 1977. women Fibrinolytic activity of the endomeusing copper IUDs. Contraception.

Lee, A.M. and J.F. 

## Fraumeni, Jr. 1969. Arsenic and respiratory cancer in man. Anoccupational study. Jour. Natl. Cancer Inst. 42: 1045. Legutko, L. 1977. Serum iron andcopper levels in acute lymphoblastic leukemia in children. Polish Tyg. Led. 32: 225. Chem. Abstr. 88: 168175b. (Pal.) Lei, K.Y. 1978. Oxidation, excretion andtissue distribution of 260~~C cholesterol in copper-deficient rats. Jour. Nutr. 108: 232. Leverton, R.M. andE.S. Binkley. 1944. Thecopper metabolism and requirement of youngwomen. Jour. Nutr. 27: 43.

c-59

## Lewis, K.O. 1973. Thenature of the copper 

## complexes in bile and their relationship to the absorption and excretion of copper in normal subjects 

## and inWilson's disease. Gut. 14: 221. Lyle, W.H., et al. 1976. Haemodialysis and

## copper fever. Lancet. 2: 1324. Majori, L. and 

## F. Petronio. 1973. Marine pollution bymetals and their accumulation bybiological indicators (accumulation factor). Rev. Intern. Oceanoqr. Med.TomesXxX1. Mallory, F.B. and F. Parker, 

## Jr. 1931. Experimental copper poisoning. Am. Jour. 

## Pathol. 7: 351. Mann, P. and D. Keilln. 1938. Haemocuprein and hepatocouperin, copper protein compounds of 

## blood and 

## liver in mammals. Proc. R. sot. London B-126: 303. Markowitz, H., et al. 1955. Studies oncopper metabolism. XIV. CopperIceruloplasmin and

## oxidase acitivity in Sara of 

## normal human subjects, pregnant women,and patients with infection, hepatolentitular degeneration andthe nephrotic syndrome. Jour. Clin. Invest. 34: 1498. Hatthews, W.B. 1954. Theabsorption andexcretion of radiocopper in hepatolenticular degeneration (Wilson's disease). Jour. Neurol. Neurosurg. Psychiat. 17: 242.

C-60

## McCabe, L-J-I et 

## al. 1970. Survey of community water Supply systems. Jour. em.Waterworks Assoc. 62: 670. 

## McCance, R.A. andE.M.Widdowson. 1947. TheChemical Composition of Foods. Chem.Pub. Co., NewYork. McCord, C.P. 1960. Metal fumefever as

## animmunological disease. Ind. Med. Surg. 29: 101. McMullen, W. 1971. Copper contamination of soft drinks from bottle pourers. Health Bull. (Edinburgh) 29: 94. Mertz, W. Institute of Nutrition. U.S. Dept. of Agric., Beltsville, Md. 

## (personal communication). Milham, S., Jr. andT. Strong. 1974. Humanarsenic exposure in relation to acopper smelter. Environ. Res. 7: 176. 

## Mjor, I.A., et al. 1977. Biologic assessment ofcopper-containing amalgams. Int. Dental Jour. 27: 333. 

## Molokhia, M.M. 

## andB. Portnoy. 1970. Neutron activation analysis of trace elements 

## in skin. V. Copper andzinc in psoriasis. Br. Jour. Dermatol. 83: 376. 

## Mondorf; A.W., et al. 

## 1971. Coeruloplasmin. Teil I: Die Biochemie des 

## Coeruloplasmins. Teil 11: Der Einfluss vonOstroqenen auf dencoeruloplasminqehalt desSerums. Klin Wochnschr. 49: 61. C-61

### Morell, A.G., 

## et al. 1961. Copper Binding Protein of HumanLiver.

z: J.M. Walsh andJ.N. Cumings feds.), Wilson's Disease. Some Current Concepts. Blackwell 

## Sci. Publ. Ltd., Oxford. p. 36. 

## Murakimi, A., et al. 1978. Afundamental study of copper-T (intrauterine device). Nippon 

## Funin Gakkai and Zasski. 23: 28. 

## Chem.Abstr. 88: 1647752. (Gap.) National Academy of Science. 1977. Copper. Nedfcal and 

## biologic effect3 of environmental pollutants. National Research 

## Council, Washington, 

## D.C. National Academy of Science. 

## 1980. Foodand 

## Nutrition Board. National Air Pollution Control Administration. 1968. Air 

## quality data 

## from the National Air Surveillance Networks and 

## contribution of State and local 

## networks, 1966 ed. NAPCA 

## Publ., APTD-68-9. U.S. Government Printing Office, Washington, D.C. NRC-42Committee onSwineNutrition. 1974. Cooperative regional studies with growing swine: the effects of vitamin Eandlevels of supplementary copper during the growing finishing period ongain, feed conversion, and tissue 

## copper storage in swine. Jour. Anim. sci. 39: 512.

C-62

## NusSaum,M.J. andA. Zettner. 1973. Thecontent of calcium, magnesium, copperr iron, sodium, andpotassium in amniotic fluid from eleven to nineteen weeks' gestation. Am.Jour. Obstet. Gynecol. 115: 219. Oakes, 

## B.W., et al. 1976. Humancopper deficiency: ultrastructural studies of the aorta and skin in achild with Menkes' syndrome. Exp. Mol. Pathol. 25: 82. 

## O'Dell, B.L., et al. 1961. Connective tissue 

## defect Fnchicks resulting from copper deficiency. Proc. Sot. Exper. Biol. Med. 108: 402. Ohlson, M.A. andK.Daum. 1935. Astudy of the iron metabolism of normal women. Jour. 

## Nutr. 9: 75. 

## Ohtake, M. 

## 1977. Serum, zinc, andcopper levels in healthy Japa

## nese infants. Tokyo Jour. Exp. Med. 123: 265. 

## Chem. Abstr. 88: 350243. 

## Okuyama, M., et al. 1977. Study oncopper level in endometrium of womenusing copper IUDs. Osaka-Shiritsu Diagaku Xgaku Zasshi. 26: 53. 

## Chem.Abstr. 89: 85133F. (Jap.1 Omura, 

## H., et al. 1978. 

## Mutagenic action of triose reductone and ascorbic acid onSalmonella typhimurium strain TAlOO. Jour. Nutr. Sci. Vitaminol. 24: 185.

C-63

## Oreke, T., et al. 1972. Systemic absorption of intrauterine CODper. Science. 177: 358. Osaki, S., et al. 1966. Thepossible significance of the ferrous oxidase activity of ceruloplasmin in normal humanserum. Jour. Biol. Chem. 241: 2746. Osborn, S.B., et al. 1963. Uptake of radioactive copper bythe liver. A

## study of patients with Wilson's disease andvarious control groups. Clin. Sci. 24: 13. 

## Oster, G.andM.P. Salgo. 1977. 

## Copper in mammalian reproduction. Adv. Pharmacol. Chemother. 14: 327. Patterson, J.B.E. 1971. Metal 

## toxicities arising from industry. Trace elements in soils and crops. ?IMSOMinistry Agrfc. Fish. Food, London Tech. Bull. 21: 190. Pedrero, E.andF.L. Rozelka. 1951. Effect of various pathological conditions on Cu content of human tissues. 

## A.M.A. Arch. Pathol. 52: 447. 

## Pennsylvania Morbidity andMortality Weekly Reports. 1975. Acute copper poisoning, Drinks that are stored in copper-lined cocktail 

## shakers or vessels canhave the sameeffect. 24: 99.



## C-64

## Petering, H.G. 1974. TheEffect of CadmiumandLeadonCopperand

Zinc Metabolism. In: W.G.Hoekshra, et al. (eds.), Trace Element

- Metabolism in Animals-2. University Park Press, 

## Baltimore. p. 311. Petering, H.G., 

## et al. 1971. 

## Trace metal content of hair. 

## I. Zinc and copper 

## content of humanhair 

## in relation to ageandsex. Arch. Environ. Health. 

## 23: 202. Phillips, D.J.H. 1976. The common mussel 

## Mvtilus edulis as an 

## indicator of pollution 

## byzinc, cadmium, lead and copper. I. 

## Effects of environmental variables on uptake of metals. Mar. Biol. 

## 38: 59. Pimental, J.C. and F. Marques. 1969. 'Vineyard sprayer's 

## lung': A newoccupational disease. 

## Thoras. 24: 670. Pimental, J.C. andA.P. Menezes. 1975. 

## Liver granulomas 

## containing copper in vineyards sprayer’s 

## lung. Anew

## etiology of hepatic granulomatosis. Am. Rev. Respir:. 

## Dis. 111: 189. Porter, 

## H. 1951. 

### Copper 

## excretion in the urine of normal individuals and of 

### patients 

## with hepatolenticular degeneration (Wilson's 

## disease). Arch. Biochem. Biophys. 31: 262. Quijada, S., et 

## al. 1978. Fertility inhibition byintra-oviductal insertion of copper beads 

## in rabbits. Contraception. 17: 553.

C-65

## Roberts, R.R. 1956. 

## Hemolytic anemia associated with 

## copper sul

### fate poisoning. Miss. Doctor. 33: 292. 

### Robinson, M.F., et al. 1973. Metabolic 

## balance of zinc, copper, cadmium, iron, 

## molybdenum and

## selenium in young New 

### Zealand 

## women. Br. Jour. Nutr. 30: 195. 

## Russ, E.M. andJ. Raymunt. 1956. 

### serum copper and ceruloplasmfn. 92: 465. 

### Influence of estrogens ontotal Proc. Sot. Exp. Biol. Med.



## Salmon, M.A. 

### and T. Wright. 1971. 

## Chronic copper poisoning presenting as 'pink' disease. Arch. Dis. Child. 46: 108. Sass-Kortsak, A. and A.G. Beatn. 1978. 

### Hereditary Disorders 

## of Copper Metabolism [Wilsonls disease (hepatolenticular degenetation) and Menkes' disease (kinky-hair or steely-hair syndromejl. In: 

## J.B. Stanbury, et al. (eds.), Metabolic 

## Basis of Inherited Disease, 4th ed. McGraw-Eill, New York. 

## p. 1098. Scheinberg, I.B. 1961. Proc. Fed. 

### Am. Sot. Exp. Biol. 20: 10: 179. 

### Scheinberg, I.K. and D.Gitlin. 1952. Deficiency of 

## ceruloplasmin in patients 

## with hepatolenticular degeneration (Wilson's disease) l 

## Science. 116: 484.

C-66

## Scheinberg, I.H. and 

## I. Sternlieb. 1969. Metabolism of Trace Yet

## als. In: B.R. Bondy (ea.), Duncan's Diseases 

## of Metabolism, 

### Vol. 

## 2, Endocrinology andNutrition. 6th ed. W.D.Saunders Co., Phila

## delphia. Scheinberg, I.R., et al. 1954. Theconcentration of copper and ceruloplasmin in maternal and infant plasma at delivery. Jour. Clin. Invest. 33: 963. Schorr, J.B., et al. 1958. Studies of serumceruloplasmin during early infancy. Am.Jour. Dfs. Child. 96: 541. Schroeder, H.A. 1970. Asensible look 

## at air pollution by 

## metals. Arch. Environ. Health. 21: 798. Schroeder, H.A., 

## etal. 1966. Essential trace metals inman. Copper. Jour. Chronic Dis. 19: 1007. Seeling, W., 

## et al. 1977. The trace elements, chromium, manganese, copper andzinc in fetal liver tissue, Jour. Perinatal Med. 38: 55. Shaw,J.C.L. 1973.. Parenteral nutrition in the managementof sick low birth rate infants. Pediatric Clin. N.

## Am. 20: 333. Shields, G.S., et al. 1961. Studies oncooper metabolism. XXXI. Erythrocyte copper. Jour. Clin. Invest. 40: 2007.

C-67

### Shuster, 

## C.N., Jr. andB.H. Pringle. 1968. Zffects of trace netals on estuarine molluscs. Proc. First 

## Mid-Atl. Indus. Waste Conf., NOV. 

## 13-15, 1967. p. 285. Shuster, C.N., Jr. andB.H. Pringle. 1969. Trace metal accumulation bytheAmerican eastern oyster, Crassosstrea virginica. PKOC. Natl. Shellfish. Assoc. 59: 91. Smith, 8. 1967. Thedistribution of antimony, arsenic, copper and zinc in humantissue. Jour. Forensic Sci. Sot. 7: 97. Smith, J.C., Jr. andE.D. Brown. 1976. Effects of Oral Contraceptive 

## Agents onTrace Element Metabolism: AReview. G: A.S. 

### Prasad 

## andD.Oberleas teds.), Trace Elements in HumanHealth andDisease. Academic Press, New

### York. 

## 2: 315. Smith, S.E. andE.J. Larson. 1946. Zinc toxicity in rats: antagonistic effects of copper andliver. Jour. Biol. Chem. 

## 163: 29. Spillane, J.D., et al. 1952. 

## Amino-aciduria and

## copper metabolism in hepatolenticular degeneration. Jour. Clin. Pathol. 5: 16. Starcher, B.C. 1969. Studies onthe mechanism of 

## copper absorption in the chfck, 

## Jour. Nutr. 

## 97: 321. Stephan, C.E. 1980. MemorandumtoJ. Stara. U.S. EPA. July 3.

C-68

## Sternlieb, I. 1967. Gastrointestinal copper absorption in Tan.



## Gastroenterology. 52: 1038. Sternlieb, 

## I. and H.D. 

## Janowitz. 1964. Absorption of copper in malabsorption syndromes. Jour. Clin. Invest. 43: 1049. Sternlieb, I. and 1-H. Scheinberg. 1964. Penicillamine therapy for hepatolenticular degeneration. Jour. Am. Med. Assoc. 189: 748. Sternlfeb, I. and I.H. Scheinberg. 1968. Prevention of Wilson's disease in asymptomatic 

## patients. New England Jour. Med. 278: 352. Sternlfeb, I., et al. 1961. The incorporation of copper 

## into ceruloplasmin in viva: Studies with copper64

-- and 

## copper67

. Jour. Clin. Invest. 40: 1834. Sternlieb, I., et al. 

## 1962. The,unfqueness of ceruloplasmin in the study of plasma plaamin 

## proteinsynthesis. Trans. Assoc. Am. Physicians. 75: 228. Sternlieb, I.# et al. 

## 1973. Lysosomal defect of hepatic copper excretion in Wilson's disease (hepatolenticular 

## degeneration) l 

## Gastroenterology. 64: 99.

C-69

## Strickland, G.T., et al. 1972a. Absorbtion of copper in homozygotes andheterozygotes for Wilson's disease andcontrols: Isotope tracer studies with 67Cuand64cu. Clin. Sci. 43: 617. Strickland, G.T., et al. 1972b. Turnover studies of copper in homozygotes and 

## heterozygotes for Wilson’s disease andcontrols: Isotope tracer studies with 67cu

. Clin. Sci. 43: 605. Sumino, R., et al. 1975. Heavymetals in normal Japanese tissues. Amounts of 15heavy metals in 30subjects. Arch. Environ. Health. 30: 487. Suttle, 

## N.F. andC.F. Mills. 1966. Studies of the toxicity ofcopper to pigs. 2. Effect of protein source andother dietary components onthe response to high andmoderate intakes of copper. Br. Jour. Nutr. 20: 149. Tamaya, 

## T., et al. 1978. Effect of copper IUDonthe humanendometrium. Nippon Funin Gakkai and Zasski. 23: 24. Chem.Abstr. 88: 164776A. (Jap.1 Tatum, H.J. 1974. Copper-bearing intrauterine devices. Clin. Obst. 

## Gynecol.. 17: 93. Thornton, I., et al. 1966. 

## Geochemical reconnaissance andbovine hypocuprosis in County Limerick, Ireland. Irish Jour. Agric. Res. 5: 280.

c-70

## Tipton, I.H. andM.J. 

## Cook. 1963. Trace elements in humantissue.

II. Adult States. Health Phys. 9: 103. Tokudome, S. and M. 

## Kuratsune. 1976. Acohort study onmortality from cancer andother causes among 

## workers at a

## metal refinery. Int. Jour. Cancer. 17: 310. Tompsett, S.L. 1934. The 

## excretion of copper in urine andfaeces andits relation to the copper content of the diet. Biochem. Jour. 28: 2088. Trip, J.A., et al. 1969. The 

## state of copper in humanlymph. Clin. Chim. Acta. 26: 371. Underwood, E.J. 1977, Trace Elements in BumanandAnimal Nutrition, 4th ed. 

## Academic Press, NewYork. U.S. Bureau of 

## Mines. 1976. Copper. Commodity data summaries. 1976. An up-to-date summary of 95 mineral commodities. U.S. Dept. Inter., Washington, D.C. U.S. Department of Health, 

## Education andWelfare. 1970. Significance of 

### national 

## findings. Publ. Health Serv. Environ. Health Serv. Bull. Water Hyg. 

## Community Water Supply Study. Washington, D.C.

c-71

## U.S. EPA. 1980. Seafood consumption data analysis. Stanford Research Institute International, Menlo Park, Calif., Final Report, Task 11. Contract No. 68-01-3887. Vallee, B.L. 1952. Thetime course of serumcopper concentrations of patients with myocardial infarctions. Metabolism. 1: 420. VanRavensteyn, A.H. 1944. Metabolism ofcopper inman. Acta Med. Stand. 118: 163. Villar, T.G. 1974. Vineyard sprayer's lung: Clinical aspects. Am.Rev. Respir. Dis. 110: 545. Vilter, R.W., et al. 1974. Manifestation of copper deficiency in apatient with systemic sclerosis onintravenous hyperalimentation. NewEngland Jour. Med. 291: 188. Voelker, R.W., Jr. andW.W.Carlton. 1969. acid oncopper deficiency in miniature swine. 30: 1825. Effect of ascorbic Am.Jour. Vet. Res.

Wahal, P.K., et al. 1965. Renal complications in acute copper sulphate poisoning. Ind. Pratt. 18: 807. Waldmann, T.A., et al. 1967. Measurement ofgastrointestinalprotein loss using ceruloplasmin labeled with 67copper. Jour. Clin. Invest. 46: 10.

C-72

## Walker, W.R. 1977I Thecouper bracelet story: Someaspects of the

role of copper in the inflammatory disease. Chem.Austr. 44: 247. Walker, W.R., et al. 1977. 

## Profusion of intact skin byasaline solution of bfs (glycinato) copper (II). Bioinorganic Chem. 7: 271. Walker-Smith, J. 

## and J. Bloomfield. 1973. Wilson's disease or chronic copper poisoning? Arch. Dis. Child. 48: 476. Walsh, F.M., 

### et al. 1977. 

## Acute copper intoxication. Pithophysiology and therapy with a case report. Am. Jour. Dis. Child. 131: 149. Walshe, J.M. 

## 1956, Penicillamine, aneworal. 

## therapy for 

## Wilson’s disease. Am.Jour. Med. 21: 487. Weber, P.M., et 

## al. 1969. Gastrointestinal absorption of copper: Studies with 64cu, g5Zr, a

## whole bodycounter andthe scintillation camera. Jour. Nucl. Med. 

## 10: 591. Widdowson, E.M. andJ.W.T. Dickerson. 1964. Chemical Composition of 

## the Body. Et 

## C.L. Comar

## andF.Bronner teds.), Mineral Metabolism: AnAdvanced Treatise. Academic 

## Press, NewYork. p. 1. Widdowson; E.M. 

### and C.M. Spray. 

## 1951. Chemical 

## development & utero. Arch. Dis. Child. 26: 205.

c-73

## Widdowson, E.M., et al. 1951. Thechemical ccmpasitiDn of the

humanbody. Clin. Sci. 10: 113. Williams, D.M., et al. 1973. Mitochondrial iron metabolism. 

## Fed. Proc. 32: 924. 

## World Health Organization. 1973. Trace elements in humannutrition. Tech. Rep.Ser. No. 532. 

## Rep.WHOExpert Comm.World Health Organ., Geneva. World Metal 

## Statistics. 1974. Copper. 27: 33. 

## Zak, B. 1958. Simple procedure for 

## the single sample 

## determination of serumcopper andiron. Clin. Chim. Acta. 3: 328. 

## Zarooqian, G. 1978. EPAEnvironmental Research Lab, Narragansett, RhodeIsland. (In preparation). Zook, E.G., et al. 

## 1970. Nutrient composition of selected wheats andwheat products. VT. Distribution of manganese, copper, nickel, zinc, magnesium, lead, cadmium, chromium andselenium asdetermined by 

## atomic abaorbtion spectroscopy and calorimetry. Cereal Chem. 47: 720.



## c-74