1 FINAL REPORT INCA PROJECT NO. 223 THE BIOLOGICAL IMPORTANCE OF COPPER A Literature Review June, 1989 The contractor who produced this report is an independent contractor and is not an agent of INCA. INCA makes no express or implied warranty with regard to the information contained in this report. INCA PROJECT 223 Preface In 1973 the International Copper Research Association Incorporated initiated a grant to review the literature dealing with the biological importance of copper in marine and estuarine environments. This was followed by a second review in 1978. It was then apparent that the number of publications concerning copper in the marine environment was large and that an annual review was appropriate. Reviews prior to 1984 considered copper only in marine and estuarine environments. However, events occurring on land and in freshwater were often mentioned because chemical and biological factors and processes pertinent to one environment could often be applied to the others. As a result, the review became larger, covering not only freshwater, saltwater and terrestrial environments but also agriculture and medicine. These broad reviews pointed out the broad application of concepts about the biological importance of copper. 2 The present review includes literature for the period 1986-1987 although a number of earlier works are included and, where appropriate, a few appearing early in 1988 have been used. Many of the earlier than 1986 references are from eastern European and Asian workers. This is because this literature takes some time to appear in the North American data review bases. References were obtained in major part, through literature search programs available through the Woodward Biomedical Library at The University of British Columbia. Mr. Brian Moreton, the European INCA Director, has kindly provided the metals section of the Marine Pollution Research Titles as a source of European as well as North American References. It will be apparent to the reader that the background of the reviewer is in marine science. With the reviewer aware of this, special effort has been made to cover all aspects of the biological importance of copper. Because of the problems of obtaining certain references, particularly manuscript reports, this review should be considered as a critical review" of the literature. The cross-referencing scheme used in the preparation and writing of the review provides an integration of concepts from all areas covered by the literature search. It is a review that addresses four basic questions: 1. What does copper do to organisms? 2. What are the sources of environmental copper? 3. What happens to copper once it enters the environment? 4. What are the relationships between the chemistry of copper and its biological importance? These questions translate into a series of topics that form the chapters of this review. Signature of Grant Recipient A.G. Lewis, Professor Department of Oceanography The University of British Columbia 3 Executive Summary The 1986-1987 literature on the biological importance of copper is voluminous and covers a wide array of topics. These include the requirement for copper, exhibited by all organisms, the effects of excess metal, biologically important chemical properties of copper, and the uses of the metal by man. From the estimated 2,940 references that were selected for this review, some of the highlights include: The increasing evidence that, under certain conditions, plants and animals need copper supplementation for normal growth to occur. With plants, this is especially true in organic-rich soils such as peat (Adams et al., 1981) in which the copper that is present is often bound by organics and not available for uptake. In animals, Copper deficiency has been Pinked with swayback in sheep, certain types of haemolytic anaemia, and decreased resistance to infection. Copper supplementation may be essential for the production of normal connective tissue (Strause et al., 1987) as well as normal enzyme and hormone balance (e.g. Recant et al., 1986). Copper has long been used to control the growth of organisms in wood products as well as in aquaculture, agriculture and medicine. Additional references cite the benefits of these uses. As well, a number of copper-containing antiviral, antibacterial and antitumour agents have been tested. Copper in fungicides offers an alternative to a number of organics that promote resistance in fungi (e.g. Olvang, 1987). There is continued use of copper sulfate as a control for noxious weeds and aquatic plants. It also continues to be an economical method of controlling the mollusc hosts of a parasite that causes schistosomiasis in man. Recent references describe the continued beneficial uses of dietary copper in the control of parasites in economically important animals such as pigs and rabbits. The ability of copper to control the growth of noxious organisms is achieved with high levels of metal. Concern has been expressed about the effects of excess copper released into the environment. The use of copper-containing fungicides can, for example, increase soil copper levels enough to cause a some plant damage (e.g. Johnson et al., 1986). Similar concerns have also been expressed about the effects of copper in municipal and industrial effluents and the release of aerosol metal. Long term exposure of plant communities to high concentrations of copper has been reported to affect the types of organisms found in the communities. Certain species of ferns and plants are restricted to localities where copper is abundant (e.g. Tabbada and Tenorio-Borja, 1986). Levels of aerosol copper are often used as an indication of industrial activity. As an example, concentrations in the northern hemisphere are estimated to be approximately 50 times 4 those in the southern hemisphere (Delmas, 1986). However, the biological impact of copper is controlled by the chemistry of the metal, the chemistry of the environment and the amount of metal released. Craig (1986) comments that "... the chemical form of an element is vital in the determination of the actual properties of stability, toxicity, and transport ... in the natural environment." Environmental factors such as pH can affect biological impact which is one of the reasons for the concern about acid rain. Campbell and Tessier (1987), for example, report biologically important changes in the chemistry of copper over the pH range from 7 to 4. It is pleasing to see more and more references pointing out the necessity of understanding metal chemistry to predict biological impact. Bernhard et al. (1986c), for example, comment that "an effort should be made to develop chemical methods suitable for (chemical) species identification and quantification." Geochemical techniques and models are now being proposed that win relate metal speciation to biological effects of copper and other metals (e.g. Cowan et al., 1986). Davies and Wilson (1987) successfully used factor analysis to differentiate anthropogenic metals from naturally occurring metals in soils of a mineralized area. Efforts like this will ultimately allow more realistic environmental standards to be achieved. Metals often interact so that a change in the concentration of one metal can offset the effect of another. With copper, perhaps the best known metal-metal interaction is with molybdenum. The action of one metal tends to offset the action of the other, especially in ruminants. This interaction is frequently considered in fertilizers, to maintain a proper balance within plants (e.g. Coventry et al., 1987). In sheep, the detrimental effects of excess copper can sometimes be offset by increasing the concentration of dietary molybdenum. However excess molybdenum can produce an apparent copper deficiency. Literature used in the present review provides information about the basic processes that allow or prevent an organism from obtaining the copper that is essential for life. It also provides information important to a better understanding of the effects of copper when used to control organisms or when present as metal released from man's activities. 5 TABLE OF CONTENTS Preface .................................................................................................................1 Executive Summary..............................................................................................4 Table of Contents .................................................................................................5 I - The Biological Importance of Copper ..............................................................8 I. 1 Copper as a required trace metal.........................................................8 I.2 Biologically important uses of copper ................................................13 I.3 Copper in organisms..........................................................................22 I.3.1 Metal levels in normal tissues ..............................................22 I.3.2 Levels in abnormal tissues ...................................................29 I.3.3 Copper and the response of the organism.............................35 1.3.4 The use of copper in contraceptive devices.........................42 I.3.5 Physiology and the effects of copper....................................43 I.3.6 The interaction of copper with organics...............................48 I.3.7 The effects of copper on growth..........................................53 1.3.8 The effect of copper on behavior.........................................55 1.3.9 The effects of copper