Table Of ContentTo my grandchildren in the UK and Australia
Trace elements in health
A review of current issues
Edited by
J. Rose, MSc, PhD, FRSC, C Chem, FI Env Sci, CBIM, FRSA
Honorary Director, Institution of Environmental Sciences, London, UK.
Butterworths
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First published 1983
© Butterworth & Co (Publishers) Ltd. 1983
British Library Cataloguing in Publication Data
Rose, J.
Trace elements in health
1. Trace elements in the body
I. Title
612'.3924 QP531
ISBN 0-407-00255-3
Typeset by Mid-County Press, London SW15
Printed and Bound by Cambridge University Press, Cambridge
Preface
Trace elements play an important part in the vegetable and animal kingdom.
Considerable research has been carried out in the last three decades on the effects of
trace elements on health in human beings and animals, but much remains to be done,
particularly in respect to some metals in the rare earth, transition and transuranic
series. There are still some wide gaps in the areas concerned with the mode of action of
various elements and their effects on health. This book aims to show how some metals
affect health, growth and well-being of man and animals in a variety of ways, when the
amounts involved are excessive or deficient.
Since most of the existing knowledge is relatively recent and has still to be applied in
medical and veterinary practice, as well as in the production of food and dietetic
preparations, this concise and up-to-date book will endeavour to acquaint the relevant
personnel in industry, in particular, and the public, in general, with the modern and
sound advances in this field. Another aim is to spread the awareness of this important
issue among the community at large. Bearing in mind the widespread conviction
among many experts that many diseases, especially those prevalent in the western
world, are due to excesses or deficiencies of trace metals, the application of recent
advances in knowledge in this realm is clearly of considerable importance.
In order to further the above aim, this work tends to condense a great body of
knowledge into an accessible source for direct consultancy, while its bibliography will
serve as a means of finding more detailed information in voluminous textbooks,
physiological treatises and many scientific journals. It is, of course, realized that it is
impossible to encompass the whole corpus of knowledge in the confines of one concise
book; several volumes would do justice to this topic. On the other hand, this
publication will act as an introduction to a number of aspects of this vast area of
knowledge and indicate future developments in a number of vital fields. The book aims
to guide, teach and enlighten experts and non-experts alike in a subject which is
growing at a nearly explosive rate and which is of essential relevance to human and
animal welfare. It is believed that future medical advances will be made on the basis of
research in the problems of trace elements, as well as general nutrition studies.
The various aspects of trace elements are examined from three points of view: firstly,
the toxicological and beneficial properties are described in eleven chapters. The first
chapter deals with general toxicological properties, while the remaining ten cover, in
detail, advances in the field of the following elements: cadmium, copper, indium and
thallium, lead, mercury, molybdenum, selenium, zinc and the transuranic series. This
v
vi Preface
section is followed by one dealing with genetic effects, health among young children
and birth rate problems as related to trace elements. The book concludes with a chapter
that discusses the role of trace elements in agriculture, the requirements of plants and
animals and the consequences of excesses and imbalances of trace elements in soils and
animal diets. It is hoped that this compendium, though not comprehensive as regards
all the elements of the Periodic Table, will not only act as an agent for disseminating
knowledge and spreading awareness of the vital issues involved, but also play the part
of a catalyst in furthering advances in physiology, dietetics and medicine.
J. Rose
Blackburn, UK
List of contributors
Frank W. Bonner, Robens Institute of Industrial and Environmental Health and
Safety, University of Surrey, Guildford, Surrey, UK.
James W. Bridges, Robens Institute of Industrial and Environmental Health and
Safety, University of Surrey, Guildford, Surrey, UK.
D. Bryce-Smith, Department of Chemistry, University of Reading, Whiteknights,
Reading, Berkshire, UK.
Louis W. Chang, Department of Pathology, University of Arkansas for Medical
Sciences, Little Rock, Arkansas, USA.
U. M. Cowgill, Department of Biological Sciences, University of Pittsburgh,
Pittsburgh, Pennsylvania, USA.
Bruce A. Fowler, Laboratory of Pharmacology, National Institute of Environmental
Health Sciences, National Institute of Health, Research Triangle Park, North
Carolina, USA.
James L. Garraway, Department of Biochemistry, Physiology and Soil Science, Wye
College, University of London, Ashford, Kent, UK.
Bryan E. Hainline, Department of Biochemistry, Duke University Medical Center,
Durham, North Carolina, USA.
Edward D. Harris, Department of Biochemistry and Biophysics and the Texas
Agricultural Experiment Station, Texas A & M University, College Station, Texas,
USA.
M.P. Ireland, Department of Zoology, University College of Wales, Aberystwyth,
Dyfed, UK.
Marc Lappe, Department of Social and Administrative Health Sciences, University of
California, Berkeley, California, USA.
W. Jack Miller, Animal and Dairy Science Department, University of Georgia College
of Agriculture, Athens, Georgia, USA.
K. V. Rajagopalan, Department of Biochemistry, Duke University Medical Center,
Durham, North Carolina, USA.
vii
viii List of contributors
Elizabeth Lodge Rees, The Rees Medical Center, Carson City, Nevada, USA.
Kenneth R. Reuhl, Division of Biological Sciences, National Research Council of
Canada, Ottawa, Ontario, Canada.
Gervin Samarawickrama, Department of Community Medicine, Faculty of Medicine,
General Hospital, Galle, Sri Lanka.
Raymond J. Shamberger, Department of Biochemistry, The Cleveland Clinic,
Cleveland, Ohio, USA.
R. Stephens, Department of Chemistry, University of Birmingham, Birmingham, UK.
R. L. Watters, Opce of Health and Environmental Research, US Department of
Energy, Washington DC, USA.
Chapter summaries
Chapter 1 Toxicological properties of trace elements
A wide range of pathological conditions have been described in both humans exposed
to metals either via the general environment or the workplace, and experimental
animals. The toxic effects produced will depend upon the characteristics of the element
and its ability to reach and accumulate in tissues. Targets of toxic metals therefore
include both the sites of contact or uptake into the body (local toxicity) and specific
organs (systemic toxicity). The molecular mechanisms underlying the toxic effects are
not well understood, but can be envisaged as occurring due to the interaction of a metal
with some sensitive structural or functional component of the cell which results in an
adverse or malfunctional response.
Chapter 2 Cadmium in animal and human health
Whilst contamination of food and water, rather than air, by cadmium would seem to
present more of a potential problem for man, present knowledge provides no solid
evidence that these environmental forms of cadmium constitute a hazard to the general
population. This might not be the case for individuals who smoke or are subject to
excessive occupational exposures. Furthermore, the presence of the cation in the
environment may be a greater hazard to the newborn, pregnant and lactating females.
Cadmium has a long biological half-life and thus is cumulative in the organs. When
absorbed, it will accumulate in the liver and the kidneys, about one-third of the total
body burden being retained in the latter. Long-term exposure to fairly small amounts of
cadmium, therefore, may result in kidney values of 200 ppm at which concentration
renal damage occurs. With a higher body burden this value may be reached much
sooner. It is likely that, through changes in absorption and excretion, the body burden,
and thus susceptibility to cadmium toxicity may vary during various phases of life.
Cadmium is teratogenic in animals. Following intravenous administration, the
embryonic RNA and protein synthesis are unaffected, whereas DNA synthesis is
inhibited, which may be related to teratogenic effects of cadmium.
ix
x Chapter summaries
Chapter 3 Copper in human and animal health
Copper in its many forms and complexes is indispensable to the life and health of all
living organisms. Adequate intake of copper is needed to prevent the onset of many
disorders including anaemia, connective tissue disorders and neurological distur-
bances. The function of copper is that of a co-factor for many body enzymes, although
its scope of functions is by no means limited to this role. Disorders of copper metabolism
have alerted us to specific biochemical systems, susceptible to genetic lesions, that are
responsible for the safe utilization of copper. At present we know very little about these
mechanisms. The efficacy of copper medicinals has opened a new chapter in the
treatment of many diseases, some of which appear to have as their base the improper
metabolism of copper.
Chapter 4 Indium and thallium in health
Indium and thallium are relatively rare but highly toxic trace elements whose expanded
use in the electronics industry may increase the possibility of human exposure in future
years. Indium is poorly absorbed following oral or inhalation exposure. Depending
whether it is in the ionic or colloidal form, it concentrates in the kidney or
liver/reticuloendothelial systems, respectively. Cellular toxicity to the kidney and liver
appears to primarily result from disruption of the endoplasmic reticulum and
alteration of haem biosynthesis/degradation following acute exposure. In contrast,
thallium is readily absorbed after inhalation or ingestion, apparently as a result of its
chemical similarity to K + ions. This element is also extensively concentrated by the
liver and kidney but it has been primarily reported as being toxic to the gastrointestinal
and central nervous systems. Mitochondrial damage is the main subcellular manifes-
tation of thallium toxicity apparently due to extensive accumulation by this organelle
of TI+ ions in place of K + ions. Inhibition by thallium of mitochondrial haem
biosynthetic pathway enzymes and stimulation of haem degradation have also been
observed following high dose exposure.
Chapter 5 Sources and effects of environmental lead
Present levels of lead in man and the general environment are reviewed in historical and
evolutionary contexts, and are shown to be grossly elevated above pre-technology
levels, in some cases by several orders of magnitude.
The main sources of environmental lead in air, food, water, soil and urban dust are
discussed: airborne lead, coming largely from the almost worldwide use of lead petrol
additives, and its fall-out, appear to constitute a particularly serious and ubiquitous
source.
The general toxicological and pathological properties of inorganic lead are
discussed, with some emphasis on the neurotoxic effects on mentation and behaviour
since these appear to occur at lead levels that are exceeded in the great majority of
urban children, thereby generating social effects. The ability of lead to generate social
effects at contemporary body burdens appears to place this element in a unique
position among environmental contaminants.
Chapter summaries xi
Chapter 6 Mercury in human and animal health
Mercury, particularly methylmercury, is recognized as a hazardous environmental
pollutant. Because of the episode of methylmercury poisoning in Japan, it is also known
as Minamata disease. The most prominent toxic features of methylmercury in-
toxication are neurological disturbances including ataxia, sensory loss and con-
striction of visual field. Pathologically, neuronal death can be demonstrated in the
cerebellum granule cells, dorsal root ganglia and visual cortex. Cellular damage can
also be observed in the kidney and liver. The impact of methylmercury on the
developing fetus should also be noted. Fetal tissues, particularly fetal brain, tend to
concentrate higher mercury levels than the maternal tissues. Neuronal destruction as
well as migratory abnormality of neurons can be demonstrated. Behavioural studies on
offspring which have been exposed to methylmercury prenatally revealed learning
deficits and behavioural abnormalities in later life. Methylmercury is therefore an
extremely hazardous chemical to both human and animal health.
Chapter 7 Molybdenum in animal and human health
Recent studies concerning the molecular biology of molybdenum are discussed in
relation to the involvement of the element in nutritional and pathological process. The
role of molybdenum and its associated co-factor in known molybdoenzymes is
emphasized. The authors first study the distribution of the metal in tissues and body
fluids, and then consider the biochemistry of this element, stressing the role played by
the molybdenum hydroxylases. Recent advances in the study of the co-factor are
described. This is followed by a section devoted to the pathological states due to
molybdenum excess or deficiency in the diet. The authors conclude by indicating the
areas of interest for the future, e.g. role of co-factor in the assimilation of the element,
control of protein synthesis, possibility of other molybdenum enzymes, requirements of
the metal in patients debilitated by bowel disease or malignancy, etc. The essentiality of
this element for normal human health is underlined.
Chapter 8 Selenium and health
The aim of this chapter is to summarize some of the more important areas of selenium
research in regard to human and animal health. Firstly, the selenium deficiency
disorders in animals are discussed, e.g. dietary liver necrosis in rats, nutritional
muscular dystrophy in sheep, exudative diathesis in chicks, pancreatic degeneration in
chicks, Mulberry heart disease in pigs, myopathy of the gizzard in turkeys and
reproductive and growth difficulties in general. Some of these may be improved by
adding selenium to the diet, or a mixture of selenium and vitamin E. Next, the toxicity
of selenium is treated in detail, including the resulting disorders, such as 'blind staggers',
alkali disease and cases of acute toxicity. This is followed by a study of the relationship
between selenium and human disorders, with particular reference to cancer and heart
disease. The chapter concludes with observations concerning the recommended daily
intake in man. A rigorous clinical trial is advocated to investigate the promising link
between selenium and cancer and heart disease in order to evaluate the therapeutic
actions of the element.
