INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
ENVIRONMENTAL HEALTH CRITERIA 134
CADMIUM
This report contains the collective views of an international group of
experts and does not necessarily represent the decisions or the stated
policy of the United Nations Environment Programme, the International
Labour Organisation, or the World Health Organization.
Published under the joint sponsorship of
the United Nations Environment Programme,
the International Labour Organisation,
and the World Health Organization
First draft prepared by Dr. L. Friberg and Dr C.G. Elinder
(Karolinska Institute, Sweden) and Dr. T. Kjellstr÷m
(University of Auckland, New Zealand)
World Health Organization
Geneva, 1992
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WHO Library Cataloguing in Publication Data
Cadmium.
(Environmental health criteria ; 134)
1.Cadmium - adverse effects 2.Cadmium-toxicity
3.Environmental exposure 4.Environmental pollutants
I.Series
ISBN 92 4 157134 9 (NLM Classification: QV 290)
ISSN 0250-863X
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CONTENTS
ENVIRONMENTAL HEALTH CRITERIA FOR CADMIUM
1. SUMMARY AND CONCLUSIONS
1.1 Identity, physical and chemical properties,
and analytical methods
1.2 Sources of human and environmental exposure
1.3 Environmental levels and human exposure
1.4 Kinetics and metabolism in laboratory animals
and humans
1.5 Effects on laboratory mammals
1.6 Effects on humans
1.7 Evaluation of human health risks
1.7.1 Conclusions
1.7.1.1 General population
1.7.1.2 Occupationally exposed population
2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND ANALYTICAL
METHODS
2.1 Physical and chemical properties
2.2 Analytical methods
2.2.1 Collection and preparation of samples
2.2.2 Separation and concentration
2.2.3 Methods for quantitative determination
2.2.3.1 Atomic absorption spectrometry
2.2.3.2 Electrochemical methods
2.2.3.3 Activation analysis
2.2.3.4 In vivo methods
2.3 Quality control and quality assurance
2.3.1 Principles and need for quality control
2.3.2 Comparison of methods and laboratories
2.3.3 Quality assurance
2.4 Conclusions
3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE
3.1 Natural occurrence and cycling
3.2 Production
3.3 Uses
3.4 Sources of environmental exposure
3.4.1 Sources of atmospheric cadmium
3.4.2 Sources of aquatic cadmium
3.4.3 Sources of terrestrial cadmium
3.5 Conclusions
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION
4.1 Atmospheric deposition
4.2 Transport from water to soil
4.3 Uptake from soil by plants
4.4 Transfer to aquatic and terrestrial organisms
4.5 Conclusions
5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE
5.1 Inhalation route of exposure
5.1.1 Ambient air
5.1.2 Air in the working environment
5.1.3 The smoking of tobacco
5.2 Ingestion routes of exposure
5.2.1 Levels in drinking-water
5.2.2 Levels in food
5.2.3 Other sources of exposure
5.2.4 Daily intake of cadmium from food
5.3 Total intake and uptake of cadmium from all
environmental pathways
5.3.1 General population, uncontaminated areas
5.3.2 General population, contaminated areas
5.3.3 Occupational exposure to cadmium
5.4 Conclusions
6. KINETICS AND METABOLISM IN LABORATORY MAMMALS AND HUMANS
6.1 Uptake
6.1.1 Absorption by inhalation
6.1.2 Absorption via the intestinal tract
6.1.3 Absorption via skin
6.1.4 Transplacental transfer
6.2 Transport
6.3 Distribution
6.3.1 In animals
6.3.1.1 Single exposure
6.3.1.2 Repeated exposure
6.3.2 In humans
6.4 Body burden and kidney burden in humans
6.5 Elimination and excretion
6.5.1 Urinary excretion
6.5.1.1 In animals
6.5.1.2 In humans
6.5.2 Gastrointestinal and other routes of
excretion
6.6 Biological half-time and metabolic models
6.6.1 In animals
6.6.2 In humans
6.7 Biological indices of cadmium exposure, body
burden, and concentrations in kidneys
6.7.1 Urine
6.7.2 Blood
6.7.3 Faeces
6.7.4 Hair
6.8 Metallothionein
6.8.1 Nature and production
6.8.2 The role of metallothionein in transport,
metabolism, and toxicity of cadmium
6.9 Conclusions
7. EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS
7.1 Single exposure
7.1.1 Lethal dose and lethal effects
7.1.2 Pathological changes affecting specific
systems in the body
7.1.2.1 Acute effects on testes and ovaries
7.1.2.2 Acute effects on other organs
7.2 Repeated and/or long-term exposure
7.2.1 Effects on the kidneys
7.2.1.1 Oral route
7.2.1.2 Respiratory route
7.2.1.3 Injection route
7.2.1.4 Pathogenesis of cadmium
nephrotoxicity
7.2.1.5 General features of renal effects;
dose-effect and dose-response
relationships
7.2.2 Effects on the liver
7.2.3 Effects on the respiratory system
7.2.4 Effects on bones and calcium metabolism
7.2.5 Effects on haematopoiesis
7.2.6 Effects on blood pressure and the cardio-
vascular system
7.2.7 Effects on reproductive organs
7.2.8 Other effects
7.3 Fetal toxicity and teratogenicity
7.4 Mutagenicity
7.5 Carcinogenicity
7.6 Host and dietary factors; interactions with other
trace elements
7.7 Conclusions
8. EFFECTS ON HUMANS
8.1 Acute effects
8.1.1 Inhalation
8.1.2 Ingestion
8.2 Chronic effects
8.2.1 Renal effects and low molecular weight
proteinuria
8.2.1.1 In industry
8.2.1.2 In the general environment
8.2.1.3 Methods for detection of tubular
proteinuria
8.2.1.4 Significance of cadmium-induced
proteinuria
8.2.1.5 Glomerular effects
8.2.1.6 Relationship between renal cadmium
levels and the occurrence of effects
8.2.1.7 Reversibility of renal effects
8.2.2 Disorders of calcium metabolism and bone
effects
8.2.2.1 In industry
8.2.2.2 In the general environment
8.2.2.3 Mechanism of cadmium-induced bone
effects
8.2.3 Respiratory system effects
8.2.3.1 Upper respiratory system
8.2.3.2 Lower respiratory system
8.2.4 Hypertension and cardiovascular disease
8.2.5 Cancer
8.2.5.1 In industry
8.2.5.2 In the general environment
8.2.6 Mutagenic effects in human cells
8.2.7 Transplacental transport and fetal effects
8.2.8 Other effects
8.3 Clinical and epidemiological studies with data
on both exposure and effects
8.3.1 Studies on respiratory disorders
8.3.2 Studies on renal disorders in industry
8.3.3 Studies on renal disorders in the general
environment
8.3.3.1 Health surveys in Japan
8.3.3.2 Toyama prefecture (Fuchu area)
8.3.3.3 Hyogo prefecture (Ikuno area)
8.3.3.4 Ishikawa prefecture (Kakehashi area)
8.3.3.5 Akita prefecture (Kosaka area)
8.3.3.6 Nagasaki prefecture (Tsushima area)
8.3.3.7 Other Japanese areas
8.3.3.8 Belgium
8.3.3.9 Shipham area in the United Kingdom
8.3.3.10 USSR
8.4 Conclusions
9. EVALUATION OF HUMAN HEALTH RISKS
9.1 Exposure assessment
9.1.1 General population exposure
9.1.2 Occupational exposure
9.1.3 Amounts absorbed from air, food, and water
9.2 Dose-effect relationships
9.2.1. Renal effects
9.2.2 Bone effects
9.2.3 Pulmonary effects
9.2.4 Cardiovascular effects
9.2.5 Cancer
9.2.6 Critical organ and critical effect
9.3 Critical concentration in the kidneys
9.3.1 In animals
9.3.2 In humans
9.4 Dose-response relationships for renal effects
9.4.1 Evaluation based on data on industrial
workers
9.4.2 Evaluation based on data on the general
population
9.4.3 Evaluation based on a metabolic model and
critical concentrations
10. CONCLUSIONS AND RECOMMENDATIONS FOR PROTECTION OF HUMAN HEALTH
10.1 Conclusions
10.1.1 General population
10.1.2 Occupationally exposed population
10.2 Recommendations for protection of human health
11. FURTHER RESEARCH
12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES
REFERENCES
RESUME ET CONCLUSIONS
RESUMEN Y CONCLUSIONES
WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR CADMIUM
Members
Professor K.A. Bustueva, Communal Hygiene, Central Institute
for Advanced Medical Training, Moscow, USSR
Dr S.V. Chandra, Industrial Toxicology Research Centre, Mahatma
Gandhi Marg, Lucknow, India
Dr M.G. Cherian, Department of Pathology, University of Western
Ontario, London, Ontario, Canada (Joint Rapporteur)
Dr B.A. Fowler, School of Medicine, University of Maryland,
Baltimore, Maryland, USA (Joint Rapporteur)
Dr R.A. Goyer, Department of Pathology, University of Western
Ontario, London, Ontario, Canada (Chairman)
Professor G. Kazantzis, London School of Hygiene and Tropical
Medicine, University of London, London, United Kingdom
Professor G. Nordberg, Department of Environmental
Medicine, University of Umea, Umea, Sweden
Dr J. Parizek, Czechoslovak Academy of Sciences, Institute of
Physiology, Videnska, Prague, Czechoslovakia
Dr I. Shigematsu, Radiation Effects Research Foundation, Hijiyama
Park, Minami-Ku, Hiroshima, Japan (Vice-Chairman)
Dr M.J. Thun, Division of Epidemiology and Statistics, American
Cancer Society, Atlanta, Georgia, USA
Observers
Professor K. Nogawa, Department of Hygiene, Chiba University
School of Medicine, Chiba, Japan
Dr K. Nomiyama, Department of Environmental Health, Jichi Medical
School, Minamikawachi-Machi Kawachi-Gun, Tochigi-Ken, Japan
Secretariat
Dr G.C. Becking, International Programme on Chemical Safety,
Interregional Research Unit, World Health Organization,
Research Triangle Park, North Carolina, USA (Secretary)
Dr L. Friberg, Karolinska Institute, Department of Environmental
Hygiene, Stockholm, Sweden
Dr C.G. Elinder, Section for Renal Medicine, Department of
Internal Medicine, Karolinska Hospital, Stockholm, Sweden
NOTE TO READERS OF THE CRITERIA MONOGRAPHS
Every effort has been made to present information in the
criteria monographs as accurately as possible without unduly
delaying their publication. In the interest of all users of the
environmental health criteria monographs, readers are kindly
requested to communicate any errors that may have occurred to the
Manager of the International Programme on Chemical Safety, World
Health Organization, Geneva, Switzerland, in order that they may be
included in corrigenda.
* * *
A detailed data profile and a legal file can be obtained from
the International Register of Potentially Toxic Chemicals, Palais
des Nations, 1211 Geneva 10, Switzerland (Telephone No. 7988400 or
7985850).
ENVIRONMENTAL HEALTH CRITERIA FOR CADMIUM
A WHO Task Group on Environmental Health Criteria for Cadmium
met in Geneva from 27 November to 1 December 1989. Dr M. Mercier,
Manager, IPCS, opened the meeting on behalf of the heads of the
three IPCS cooperating organizations (UNEP/ILO/WHO). The Task Group
reviewed and revised the draft criteria document and made an
evaluation of the risks to human health from exposure to cadmium.
The first draft of this monograph, which was reviewed by a
Working Group in January 1984, was prepared by Dr L. Friberg and
Dr C.G. Elinder (Karolinska Institute, Stockholm, Sweden), and Dr T.
Kjellström (University of Auckland, New Zealand)1. Based on the
discussions of the Working Group, recent scientific data, and
comments from the IPCS Contact Points, a Task Group draft was
prepared by Dr R. Goyer (University of Western Ontario, Canada).
The Secretariat wishes to acknowledge the contributions made by
Professor K. Tsuchiya (Keio University, Tokyo, Japan), Dr M.
Piscator (Karolinska Institute), Dr G.F. Nordberg (University of
Umea, Sweden), and Professor R. Lauwerys (University of Louvain,
Brussels, Belgium) for their preparation and review of earlier draft
document on cadmium, which assisted greatly in the preparation of
this monograph.
Dr G.C. Becking (Interregional Research Unit) and Dr P.G.
Jenkins (IPCS Central Unit) were responsible for the overall
scientific content and technical editing, respectively, of this
monograph. The efforts of all who helped in the preparation and
finalization of the document are gratefully acknowledged.
1 Present affiliation: Division of Environmental Health, World
Health Organization
ABBREVIATIONS
AAS atomic absorption spectrometry
CC critical concentration
CI confidence interval
EEC European Economic Community
ETA electrothermal atomization
GESAMP Group of Experts on the Scientific Aspects of Marine
Pollution
GFR glomerular filtration rate
GOT glutamic-oxaloacetic transaminase
GPT glutamic-pyruvic transaminase
ICD International Classification of Diseases
IDMS isotope dilution mass spectrometry
IU international units
LDH lactate dehydrogenase
LMW low molecular weight
MMAD mass median aerodynamic diameter
PCV packed-cell volume
PMR proportional mortality rate
PMSG pregnant mare serum gonadotrophin
RBP retinal binding protein
RIA radio-immuno assay
SMR standard mortality ratio
TRP tubular reabsorption of phosphate
XRF X-ray-generated atomic fluorescence
PREFACE
The definitions of terms used in this monograph were derived
from the meeting of the Scientific Committee on the Toxicology of
Metals, Permanent Commission and International Association on
Occupational Health, in Tokyo in 1974 (Task Group on Metal Toxicity,
1976). The term "critical concentration" in an organ was defined as
"the concentration of a metal in an organ at the time any of its
cells reaches a concentration at which adverse functional changes,
reversible or irreversible, occur in the cell". These first adverse
changes would be the "critical effect". The critical concentration
is thus established on an individual level and varies between
individuals. The term "critical organ" was defined as "that
particular organ which first attains the critical concentration of a
metal under specified circumstances of exposure and for a given
population".
The dose-response relationship expressing the occurrence rate
(response) of the particular effect as a function of metal
concentration in the critical organ, displays the frequency
distribution of individual critical concentrations. In risk
estimations it is thus essential to define the variability of the
critical concentration among a population or specific group of
people.
The term that was chosen to predict the variability of the
critical concentration of cadmium occurring in a particular group of
people is the predicted prevalence of the critical concentration.
For example, the critical concentration 5 (CC5) would be the
concentration at which 5% of the population had reached their
individual critical concentrations, and the CC50 would be the
critical concentration occurring in 50% of a defined group of
people. The term "critical concentration" is synonymous with the
term "population critical concentration" used in the WHO publication
on Evaluation of Certain Food Additives and Contaminants (1989).
The critical concentrations and the dose-response relationships
are very much dependent on the definition of critical effect. The
early effects of cadmium on the kidney can be measured as an
increased urinary excretion of low molecular weight (LMW) proteins.
An operational definition is needed to create a cut-off point above
which the proteinuria indicates an "adverse functional change".
Different studies of cadmium effects have used different operational
definitions, which has made it difficult to merge the data into a
dose-response relationship. Examples of these problems are given in
section 8.3.2. The relationship between dose and different types of
effect or different severities of the same effect is called the
dose-effect relationship.
In animal studies, the individual critical concentrations have
not been calculated. Both dose and effect data are based on groups
of animals, and these groups are usually rather small (section 7).
Few animal studies attempt to quantitatively measure the
dose-response relationships within the group (section 7.2.1.4). The
reports of effects occurring at a certain concentration of cadmium
in the kidney cortex may therefore best be interpreted as the
concentration at which 50% or more of the animals suffered the
effect. A 5-10% response will occur at lower cadmium concentrations.
The effects of cadmium on the environment are discussed in
Environmental Health Criteria 135: Cadmium - Environmental Aspects
(WHO, in press).
1. SUMMARY AND CONCLUSIONS
1.1 Identity, physical and chemical properties, and analytical
methods
Several methods are available for the determination of cadmium
in biological materials. Atomic absorption spectrometry is the most
widely used, but careful treatment of samples and correction for
interference is needed for the analysis of samples with low cadmium
concentrations. It is strongly recommended that analysis be
accompanied by a quality assurance programme. At present, it is
possible under ideal circumstances to determine concentrations of
about 0.1 µg/litre in urine and blood and 1-10 µg/kg in food and
tissue samples.
1.2 Sources of human and environmental exposure
Cadmium is a relatively rare element and current analytical
procedures indicate much lower concentrations of the metal in
environmental media than did previous measurements. At present, it
is not possible to determine whether human activities have caused a
historic increase in cadmium levels in the polar ice caps.
Commercial cadmium production started at the beginning of this
century. The pattern of cadmium consumption has changed in recent
years with significant decreases in electroplating and increases in
batteries and specialized electronic uses. Most of the major uses of
cadmium employ cadmium in the form of com- pounds that are present
at low concentration; these features constrain the recycling of
cadmium. Restrictions on certain uses of cadmium imposed by a few
countries may have widespread impact on these applications.
Cadmium is released to the air, land, and water by human
activities. In general, the two major sources of contamination are
the production and consumption of cadmium and other non-ferrous
metals and the disposal of wastes containing cadmium. Areas in the
vicinity of non-ferrous mines and smelters often show pronounced
cadmium contamination.
Increases in soil cadmium content result in an increase in the
uptake of cadmium by plants; the pathway of human exposure from
agricultural crops is thus susceptible to increases in soil cadmium.
The uptake by plants from soil is greater at low soil pH. Processes
that acidify soil (e.g., acid rain) may therefore increase the
average cadmium concentrations in foodstuffs. The application of
phosphate fertilizers and atmospheric deposition are significant
sources of cadmium input to arable soils in some parts of the world;
sewage sludge can also be an important source at the local level.
These sources may, in the future, cause enhanced soil and hence crop
cadmium levels, which in turn may lead to increases in dietary
cadmium exposure. In certain areas, there is evidence of increasing
cadmium content in food.
Edible free-living food organisms such as shellfish,
crustaceans, and fungi are natural accumulators of cadmium. As in
the case of humans, there are increased levels of cadmium in the
liver and kidney of horses and some feral terrestrial animals.
Regular consumption of these items can result in increased exposure.
Certain marine vertebrates contain markedly elevated renal cadmium
concentrations, which, although considered to be of natural origin,
have been linked to signs of kidney damage in the organisms
concerned.
1.3 Environmental levels and human exposure
The major route of exposure to cadmium for the non-smoking
general population is via food; the contribution from other pathways
to total uptake is small. Tobacco is an important source of cadmium
uptake in smokers. In contaminated areas, cadmium exposure via food
may be up to several hundred µg/day. In exposed workers, lung
absorption of cadmium following inhalation of workplace air is the
major route of exposure. Increased uptake can also occur as a
consequence of contamination of food and tobacco.
1.4 Kinetics and metabolism in laboratory animals and humans
Data from experimental animals and humans have shown that
pulmonary absorption is higher than gastrointestinal absorption.
Depending on chemical speciation, particle size, and solubility in
biological fluids, up to 50% of the inhaled cadmium compound may be
absorbed. The gastrointestinal absorption of cadmium is influenced
by the type of diet and nutritional status. The nutritional iron
status appears to be of particular importance. On average, 5% of the
total oral intake of cadmium is absorbed, but individual values
range from less than 1% to more than 20%. There is a maternal-fetal
gradient of cadmium. Although cadmium accumulates in the placenta,
transfer to the fetus is low. Cadmium absorbed from the lungs or the
gastrointestinal tract is mainly stored in the liver and kidneys,
where more than half of the body burden will be deposited. With
increasing exposure intensity, an increasing proportion of the
absorbed cadmium is stored in the liver. Excretion is normally slow,
and the biological half-time is very long (decades) in the muscles,
kidneys, liver, and whole body of humans. The cadmium concentrations
in most tissues increase with age. Highest concentrations are
generally found in the renal cortex, but excessive exposures may
lead to higher concentrations in the liver. In exposed people with
renal damage, urinary excretion of cadmium increases and so the
whole body half-time is shortened. The renal damage leads to losses
of cadmium from the kidney, and the renal concentrations of cadmium
will eventually be lower than in people with similar exposure but
without renal damage.
Metallothionein is an important transport and storage protein
for cadmium and other metals. Cadmium can induce metallothionein
synthesis in many organs including the liver and kidney. The binding
of intracellular cadmium to metallothionein in tissues protects
against the toxicity of cadmium. Cadmium not bound to
metallothionein may therefore play a role in the pathogenesis of
cadmium-related tissue injury. The speciation of other cadmium
complexes in tissues or biological fluids is unknown.
Urinary excretion of cadmium is related to body burden, recent
exposure, and renal damage. In people with low exposure, the urine
cadmium level is mainly related to the body burden. When
cadmium-induced renal damage has occurred, or even without renal
damage if exposure is excessive, urinary excretion increases.
Cadmium-exposed people with proteinuria generally have higher
cadmium excretion than such people without proteinuria. After high
exposure ceases, the urine cadmium level will decrease even though
renal damage persists. The interpretation of urinary cadmium is thus
dependent on a number of factors. Gastrointestinal excretion is
approximately equal to urinary excretion but cannot be easily
measured. Other excretory routes such as lactation, sweating or
placental transfer are insignificant.
The level of cadmium in faeces is a good indicator of recent
daily intake from food in the absence of inhalation exposure.
Cadmium in blood occurs mainly in the red blood cells, and the
plasma concentrations are very low. There are at least two
compartments in blood, one related to recent exposure with a
half-time of about 2-3 months, and one which is probably related to
body burden with a half-time of several years.
1.5 Effects on laboratory mammals
High inhalation exposures cause lethal pulmonary oedema. Single
high-dose injection gives rise to testicular and non-ovulating
ovarian necrosis, liver damage, and small vessel injury. Large oral
doses damage the gastric and intestinal mucosa.
Long-term inhalation exposure and intratracheal administration
give rise to chronic inflammatory changes in the lungs, fibrosis,
and appearances suggestive of emphysema. Long-term parenteral or
oral administration produces effects primarily on the kidneys, but
also on the liver and the haematopoietic, immune, skeletal, and
cardiovascular systems. Skeletal effects and hypertension have been
induced in certain species under defined conditions. The occurrence
of teratogenic effects and placental damage depends on the stage of
gestation at which exposure occurs, and may involve interactive
effects with zinc.
Of greatest relevance to human exposure are the acute
inhalation effects on the lung and the chronic effects on the
kidney. Following long-term exposure, the kidney is the critical
organ. The effects on the kidney are characterized by tubular
dysfunction and tubular cell damage, although glomerular dysfunction
may also occur. A consequence of renal tubular dysfunction is a
disturbance of calcium and vitamin D metabolism. According to some
studies, this has led to osteomalacia and/or osteoporosis, but these
effects have not been confirmed by other studies. A direct effect of
cadmium on bone mineralization cannot be excluded. The toxic effects
of cadmium in experimental animals are influenced by genetic and
nutritional factors, interactions with other metals, particularly
zinc, and pretreatment with cadmium, which may be related to the
induction of metallothionein.
In 1976 and 1987, the International Agency for Research on
Cancer accepted as sufficient the evidence that cadmium chloride,
sulfate, sulfide, and oxide can give rise to injection site sarcomas
in the rat and, for the first two compounds, induce interstitial
cell tumours of the testis in rats and mice, but found oral studies
inadequate for evaluation. Long-term inhalation studies in rats
exposed to aerosols of cadmium sulfate, cadmium oxide fumes and
cadmium sulfate dust demonstrated a high incidence of primary lung
cancer with evidence of a dose-response relationship. However, this
has not so far been demonstrated in other species. Studies on the
genotoxic effects of cadmium have given discordant results.
1.6 Effects on humans
High inhalation exposure to cadmium oxide fume results in acute
pneumonitis with pulmonary oedema, which may be lethal. High
ingestion exposure of soluble cadmium salts causes acute
gastroenteritis.
Long-term occupational exposure to cadmium has caused severe
chronic effects, predominantly in the lungs and kidneys. Chronic
renal effects have also been seen among the general population.
Following high occupational exposure, lung changes are
primarily characterized by chronic obstructive airway disease. Early
minor changes in ventilatory function tests may progress, with
continued cadmium exposure, to respiratory insufficiency. An
increased mortality rate from obstructive lung disease has been seen
in workers with high exposure, as has occurred in the past.
The accumulation of cadmium in the renal cortex leads to renal
tubular dysfunction with impaired reabsorption of, for instance,
proteins, glucose, and amino acids. A characteristic sign of tubular
dysfunction is an increased excretion of low molecular weight
proteins in urine. In some cases, the glomerular filtration rate
decreases. Increase in urine cadmium correlates with low molecular
weight proteinuria and in the absence of acute exposure to cadmium
may serve as an indicator of renal effect. In more severe cases
there is a combination of tubular and glomerular effects, with an
increase in blood creatinine in some cases. For most workers and
people in the general environment, cadmium-induced proteinuria is
irreversible.
Among other effects are disturbances in calcium metabolism,
hypercalciuria, and formation of renal stones. High exposure to
cadmium, most probably in combination with other factors such as
nutritional deficiencies, may lead to the development of
osteoporosis and/or osteomalacia.
There is evidence that long-term occupational exposure to
cadmium may contribute to the development of cancer of the lung but
observations from exposed workers have been difficult to interpret
because of confounding factors. For prostatic cancer, evidence to
date is inconclusive but does not support the suggestion from
earlier studies of a causal relationship.
At present, there is no convincing evidence for cadmium being
an etiological agent of essential hypertension. Most data speak
against a blood pressure increase due to cadmium and there is no
evidence of an increased mortality due to cardiovascular or
cerebrovascular disease.
Data from studies on groups of occupationally exposed workers
and on groups exposed in the general environment show that there is
a relationship between exposure levels, exposure durations, and the
prevalence of renal effects.
An increased prevalence of low molecular weight proteinuria in
cadmium workers after 10-20 years of exposure to cadmium levels of
about 20-50 µg/m3 has been reported.
In polluted areas of the general environment, where the
estimated cadmium intake has been 140-260 µg/day, effects in the
form of increased low molecular weight proteinuria have been seen in
some individuals following long-term exposure. More precise
dose-response estimates are given in section 8.
1.7 Evaluation of human health risks
1.7.1 Conclusions
The kidney is considered the critical target organ for the
general population as well as for occupationally exposed
populations. Chronic obstructive airway disease is associated with
long-term high-level occupational exposure by inhalation. There is
some evidence that such exposure to cadmium may contribute to the
development of cancer of the lung but observations from exposed
workers have been difficult to interpret because of confounding
factors.
1.7.1.1 General population
Food-borne cadmium is the major source of exposure for most
people. Average daily intakes from food in most areas not polluted
with cadmium are between 10-40 µg. In polluted areas it has been
found to be several hundred µg per day. In non-polluted areas,
uptake from heavy smoking may equal cadmium intake from food.
Based on a biological model, an association between cadmium
exposure and increased urinary excretion of low molecular weight
proteins has been estimated to occur in humans with a life-long
daily intake of about 140-260 µg cadmium, or a cumulative intake of
about 2000 mg or more.
1.7.1.2 Occupationally exposed population
Occupational exposure to cadmium is mainly by inhalation but
includes additional intakes through food and tobacco. The total
cadmium level in air varies according to industrial hygiene
practices and type of workplace. There is an exposure-response
relationship between airborne cadmium levels and proteinuria. An
increase in the prevalence of low molecular weight proteinuria may
occur in workers after 10-20 years of exposure to cadmium levels of
about 20-50 µg/m3. In vivo measurement of cadmium in the liver
and kidneys of people with different levels of cadmium exposure have
shown that about 10% of workers with a kidney cortex level of
200 mg/kg and about 50% of people with a kidney cortex level of
300 mg/kg would have renal tubular proteinuria.
2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, AND
ANALYTICAL METHODS
This monograph covers cadmium and its inorganic compounds
alone, since there is no evidence that organocadmium compounds
(where the metal is bound covalently to carbon) occur in nature.
Although cadmium may bind to proteins and other organic molecules
and form salts with organic acids (e.g., cadmium stearate), in these
forms it is regarded as inorganic.
The mobility of cadmium in the environment and the effects on
the ecosystem depend to a large extent on the nature of its
compounds.
Since this monograph evaluates only the health hazards for
humans (and not those for the environment), only chemical data on
cadmium compounds relevant for such an evaluation are included. Data
on cadmium compounds occurring in or toxic to lower animals and
plants are reviewed in Environmental Health Criteria 135:
Cadmium - Environmental Aspects (WHO, in press).
2.1 Physical and chemical properties
Cadmium (atomic number 48; relative atomic mass 112.40) is a
metal that belongs, together with zinc and mercury, to group IIb in
the Periodic Table. Naturally-occurring isotopes are 106 (1.22%),
108 (0.88%), 110 (12.39%), 111 (12.75%), 112 (24.07%), 113 (12.26%),
114 (28.86%), and 116 (7.50%) (Weast, 1974).
Cadmium has a relatively high vapour pressure. Its vapour is
oxidized rapidly in air to produce cadmium oxide. When reactive
gases or vapour, such as carbon dioxide, water vapour, sulfur
dioxide, sulfur trioxide or hydrogen chloride are present, cadmium
vapour reacts to produce cadmium carbonate, hydroxide, sulfite,
sulfate or chloride, respectively. These compounds may be formed in
stacks and emitted to the environment. An example of these reactions
during cadmium emissions from coal-fired power plants is described
by Kirsch et al. (1982).
Some cadmium compounds, such as cadmium sulfide, carbonate, and
oxide, are practically insoluble in water. There is, however, a lack
of data on the solubility of these compounds in biological fluids,
e.g., in the gastrointestinal tract and lung. These water-insoluble
compounds can be changed to water-soluble salts in nature under the
influence of oxygen and acids; cadmium sulfate, nitrate, and halides
are water-soluble. Most of the cadmium found in mammals, birds, and
fish is probably bound to protein molecules.
The speciation of cadmium in soil, plants, animal tissues, and
foodstuffs may be of importance for the evaluation of the health
hazards associated with areas of cadmium contamination or high
cadmium intake. For example, although soil cadmium levels in
Shipham, United Kingdom, were found to be very much higher than in
Toyama, Japan, cadmium uptake by edible plants in Shipham was only a
small fraction of that in Toyama (Tsuchiya, 1978; Sherlock et al.,
1983). Very few data on the occurrence and speciation of cadmium
compounds in nature are available.
2.2 Analytical methods
Only a few nanograms (or even less) of cadmium may be present
in collected samples of air and water, whereas hundreds of
micrograms may be present in small samples of kidney, sewage sludge,
and plastics. Different techniques are therefore required for the
collection, preparation, and analysis of the samples.
In general, the technique available for measuring cadmium in
the environment and in biological materials cannot differentiate
between the different compounds. With special separation techniques,
cadmium-containing proteins can be isolated and identified. In most
studies to date, the concentration or amount of cadmium in water,
air, soil, plants, and other environmental or biological materials
has been determined as the element.
2.2.1 Collection and preparation of samples
The degree of uncertainty in any health risk assessment of
cadmium based on the analysis of environmental or biological samples
depends on how representative the samples are. Each type of material
has specific problems in this respect, and each study should include
an evaluation of the sampling procedures utilized. For example, the
measurement of cadmium in workplace air can be made with "static"
samples or "personal" samples. The latter supposedly gives a better
estimate of true exposure levels. When both are measured, personal
samples usually give higher results, indicating that static samples
may underestimate the exposure.
For the collection of samples, standard trace element methods
can generally be used (LaFleur, 1976; Behne, 1980). The amount of
material needed for analysis varies according to the sensitivity of
the analytical methods and the cadmium concentration in the
material. During recent years, methods have improved and usually
smaller amounts (ml or g) of biological materials are now needed
than those required previously.
In the handling and storage of samples, particularly liquid
samples, special care must be taken to avoid contamination. Coloured
materials in containers, especially plastics and rubber, should be
avoided. Contamination of blood samples has been reported when blood
was collected in certain types of evacuated blood collection tubes
(Nackowski et al., 1977; Nise & Vesterberg, 1978). Disposable
coloured micropipette tips have been found to contaminate acid
solutions with cadmium (Salmela & Vuori, 1979).
Glass and transparent cadmium-free polyethylene, polypropylene
or teflon containers are usually considered as suitable for storing
samples. All containers and glassware should be pre-cleaned in
dilute nitric acid and deionized water. Water samples or standards
with low cadmium concentrations should be stored for only a short
period of time in order to avoid possible adsorption of cadmium on
the container wall. However, experiments carried out within the
UNEP/WHO programme (Vahter, 1982; Friberg & Vahter, 1983) using
haemolysed blood samples spiked with 109Cd showed that, if
properly handled, blood can be stored at room temperature for
several months without any change in the cadmium concentration. Some
solutions, such as urine, should be acidified to prevent
precipitation of salts, thus ensuring that the cadmium remains in
solution.
To prepare samples for analysis, inorganic solid samples (such
as soil or dust samples) are usually dissolved in nitric acid or
other acids. Organic samples need to be subjected to wet ashing
(digestion) or dry ashing. Wet ashing, i.e. heating under reflux
with nitric acid followed by the addition of sulfuric or perchloric
acid, is an adequate method for the digestion of most organic and
biological samples. Heating with perchloric acid is usually avoided
in modern methods because of the explosive nature of the fumes.
Biological samples may also be dissolved using tetramethylammonium
hydroxide (Kaplan et al., 1973).
Dry ashing can also be used without significant losses of
cadmium, provided that the temperature is kept at or below 450 °C
(Kjellström et al., 1974; Koirtyohann & Hopkins, 1976).
Low-temperature (about 100 °C) dry ashing at a high oxygen
concentration has also been used successfully (Gleit, 1965).
2.2.2 Separation and concentration
Some biological samples such as kidneys contain relatively high
concentrations of cadmium; this makes it possible to analyse without
significant interference from other compounds. Dry ashing, followed
by dissolving the ash in acid, is sometimes sufficient for analysis
by atomic absorption spectrometry and other modern methods. When the
cadmium concentration is low, special treatment is sometimes needed.
The procedures for separating cadmium from interfering compounds and
concentrating the samples are very important steps in obtaining
adequate results.
One technique for the solvent extraction of cadmium, which has
been widely used, is based on the APDC/MIBK system, where ammonium
pyrrolidine dithiocarbamate chelate (APDC) is extracted into methyl
isobutyl ketone (MIBK) (Mulford, 1966; Lehnert et al., 1968). Other
chelating agents that can be used to extract cadmium into an organic
solvent are dithiozone (Saltzman, 1953) and sodium diethyl
dithiocarbamate (Berman, 1967).
Ion exchange resins have also been applied for separating and
concentrating cadmium from digested food samples (Baetz & Kenner,
1974) and from urine and blood samples acidified with hydrochloric
acid (Lauwerys et al., 1974c; Vens & Lauwerys, 1982).
2.2.3 Methods for quantitative determination
A number of methods have been developed for cadmium analysis,
but none of them are known to produce absolutely "true"
concentrations of cadmium in any material. The accuracy of a method
also depends on how high the concentration is.
The nearest approximation to the "true" value when analysing
complex organic materials with low cadmium concentration is probably
attained with the isotope dilution mass spectrometry (IDMS) method
carried out in "ultraclean" facilities. However, IDMS is extremely
expensive compared with other methods, and has been used mainly for
quality control of other methods and for certified reference
materials.
The most commonly used methods, at present, are atomic
absorption spectrometry, electrochemical methods, and neutron
activation analysis. These three methods will be discussed in detail
below. Other methods are colorimetry with dithiozone, atomic
emission spectrometry, atomic fluorescence spectrometry, and
proton-induced X-ray emissions (PIXE) analysis. Analytical methods
for cadmium have been reviewed by Friberg et al. (1986).
In addition, in vivo analysis of cadmium in kidney and liver
has been carried out by certain investigators (Ellis et al. 1981a;
Roels et al. 1981b; Roels et al. 1983a, 1983b). The method uses the
principles of neutron activation and is discussed in section 8.2.1.6
of this monograph.
The validity and accuracy of any method should ideally be
ascertained by adequate quality assurance data (section 2.3). In the
absence of such data, the results should at least be accompanied by
intra-laboratory quality control data, results of analysis of
certified standard materials, or inter-laboratory comparison data
(section 2.3). Older basic chemical analysis methods may be as
accurate as newer more complex and expensive methods, at least in
the higher concentration range, and no analytical results should be
dismissed or accepted until the method used has been carefully
evaluated.
2.2.3.1 Atomic absorption spectrometry
The basic principle is to pass the sample into a
high-temperature flame (burner) or furnace and measure the
absorption from the atoms in the ground state. A lamp with a cathode
made up from the pure metal or an alloy of the desired element,
emitting the narrow line spectrum of this element, is used as an
external light source. Atomic absorption spectrometry (AAS) is the
method most commonly used at present for cadmium determination,
because the procedure is relatively simple and fast, and its
detection limit is sufficient for most environmental and biological
materials. The absorption is measured at the cadmium line
(228.8 nm).
There are two main methods for atomization of a sample, the
flame method and electrothermal atomization (ETA). The latter is
also called the heated graphite atomization, graphite furnace or
flameless method. Flame methods are generally used for liquid
samples that can be aspirated into a flame, usually an air-acetylene
flame. The detection limit for cadmium in pure water is of the order
of 1-5 mg/litre and, in biological materials, it is about 0.1 mg/kg.
At lower levels, it is usually necessary to increase the sensitivity
by some accessory or by preconcentration during sample treatment.
One important modification of the flame technique is the use of a
micro-crucible or cup made of nickel (Delves, 1970; Fernandez &
Kahn, 1971; Ediger & Coleman, 1973). The atoms are held much longer
in the light beam that passes through the tube, and this increases
the sensitivity considerably.
ETA methods have undergone rapid development in recent years.
The sample, usually in solution (1-100 ml), is first inserted into a
graphite furnace, which is surrounded by a constant flow of inert
gas, such as argon or nitrogen. The temperature is then increased in
order to dry, ash, and atomize the sample. During atomizing, the
specific absorption from cadmium is deduced from the light beams
passing through or just above the furnace. The detection limit is
extremely low (of the order of a few pg). There have been several
detailed reports describing the analysis, using ETA, of cadmium in
biological samples such as blood and urine (Lundgren, 1976; Castilho
& Herber, 1977; Stoeppler & Brandt, 1978, 1980; Vesterberg &
Wrangskogh, 1978; Gardiner et al., 1979; Delves & Woodward, 1981;
Subramanian & Meranger, 1981; Jawaid et al., 1983). The lowest
detectable concentration of cadmium in blood and urine using ETA is
of the order of 0.1-0.3 mg/litre (Delves, 1982).
Although the atomic absorption spectrometry for cadmium is
specific, the method is not free from problems when applied to
measurements in biological samples. Several important sources of
interference exist, especially light scattering from particles and
nonspecific absorption from the broad molecular absorption band
formed by, for instance, sodium chloride and phosphate ions.
Piscator (1971) showed that sodium chloride, at a concentration of
0.5 mol/litre, gave a signal corresponding to a concentration of
0.1 mg cadmium/litre when using ordinary air-acetylene flame atomic
absorption equipment without background correction. The actual
concentration was less than 0.4 mg cadmium/litre. Many problems
related to interfering salts may be compensated by the use of a
background correction system. A deuterium or hydrogen lamp is
usually used. The nonspecific absorption can thus be measured and
the signal, measured as the difference between the specific and
nonspecific absorption, is proportional to the actual cadmium
concentration (Kahn & Manning, 1972). Background correction for fine
structure nonspecific absorption can also be made by utilizing the
Zeeman effect on incoming light when it is modulated by strong
magnetic fields (Koizumi et al., 1977; Alt, 1981; Pleban et al.,
1981). Some kind of background correction is necessary when the
microcrucible or electrothermal atomization techniques are used for
cadmium analysis, since the nonspecific absorption increases as the
atoms are kept in the light for a relatively long period of time.
2.2.3.2 Electrochemical methods
Cadmium can be determined by different types of
electro-chemical methods such as classic polarographic methods or
the more recently developed anodic stripping voltammetry and
cadmium-selective electrodes. The basic principle behind the
electrochemical methods is the change in the electrochemical
potentials formed when electrons are transferred from one metal to
another. A dropping mercury electrode is placed in a solution where
the metal concentration is to be determined. By changing the charge
of the electrode, different metals will be reduced and form an
amalgam (a solid solution of metal atoms and mercury) with the
mercury electrode. Polarographic waves can thus be recorded.
Different metals can be determined simultaneously in a liquid
sample, since they form amalgams at different charges.
Anodic stripping voltammetry is based on the reverse process,
i.e. the release of metals that have already been reduced and are
bound to the mercury electrode. During oxidation and release from
the amalgam, a peak current can be recorded at a potential that is
characteristic for the particular metal. Anodic stripping
voltammetry is one of the most sensitive methods for cadmium
determination available. The most crucial aspects are complete
destruction of all organic materials and the transfer of cadmium
ions from the sample into a non-contaminated electrolyte. The method
is especially suitable for water analysis, where no sample treatment
is necessary (Piscator & Vouk, 1979), but has also been used for the
measurement of cadmium in various biological materials such as urine
(Jagner et al., 1981), foodstuffs, and tissues (Danielsson et al.,
1981). In urine, a detection limit of about 0.1 mg/litre was
obtained when using a computerized potentiometric stripping analysis
(Jagner et al., 1981).
Specific cadmium-selective electrodes are commercially
available, but their sensitivity is insufficient for cadmium
measurement in most biological materials. Furthermore, the
electrodes are not ion specific, and problems can easily arise from
various contaminants in the solution used (Hislop, 1980).
2.2.3.3 Activation analysis
Cadmium has a number of stable isotopes. Irradiation with
neutrons yields new radioactive cadmium isotopes, which can be
quantitatively measured on the basis of their specific energy and
half-life. A procedure for determining cadmium in human liver
samples by neutron activation analysis has been reported by
Halvorsen & Steinnes (1975). The irradiated sample is usually
digested before the radioactivity is measured. Sometimes, it may be
necessary to concentrate cadmium by chemical methods and to separate
the cadmium ions from other isotopes that have an energy spectrum
overlapping the one for cadmium before measurement can be carried
out. Non-radioactive cadmium can also be added after irradiation to
enable measurement of the recovery after digestion and various
concentration steps. The detection limit for neutron activation
analysis is low, of the order of 0.1-1 mg cadmium/kg or
0.1-1 mg/litre, in most biological materials. However, the method is
expensive since the samples have to be irradiated in a reactor, and
so it is not normally used for screening programmes. Neutron
activation analysis has been used as a reference method for accuracy
tests of other methods (Kjellström et al., 1975b; Kjellström, 1979;
Jawaid et al., 1983).
Neutron activation analysis is not ideal for liquid samples
such as blood and urine, where the detection limit of the method is
very close to the normal values. Furthermore, ampoules filled with
liquid samples sometimes explode as gases are formed when the sample
is irradiated in the reactor.
Irradiation with protons, proton-induced X-ray emission (PIXE),
can also be used for activation analysis of cadmium. Several
elements are measured at the same time. The main advantage of the
method is its ability to detect and quantify cadmium in very small
samples such as thin slices of tissues weighing less than 1 mg
(Hasselmann et al., 1977; Mangelson et al., 1979).
2.2.3.4 In vivo methods
A non-invasive technique for in vivo determination of liver
and kidney cadmium has been developed (Biggin et al., 1974; Harvey
et al., 1975; McLellan et al., 1975) using the principle of neutron
activation analysis and taking advantage of the very large capture
cross-section area for thermal neutrons of one of the
naturally-occurring stable isotopes of cadmium (113Cd; natural
abundance, 12.26%). A portable system using a 238Pu-Be source of
neutrons (instead of the original, which was cyclotron dependent)
has made this technique more easily available (Thomas et al., 1976).
The lowest detection limit for "field-work" techniques
currently in use for this method is about 1.5 mg/kg in liver and
15 mg/kg in whole kidney (Ellis et al., 1981a). These limits are too
high to measure accurately tissue levels in people with "normal"
environmental exposure (section 6.4). In people with occupational
exposure, cadmium levels of up to 100 mg/kg in liver and 400 mg/kg
in whole kidney have been reported (Ellis et al., 1981a; Roels et
al., 1981b). The method is still not developed to its full capacity,
and the results are greatly affected by, for instance, the
variability in the location of the kidney (Al-Haddad et al., 1981).
An alternative method for in vivo determination of cadmium
concentration in kidney cortex using X-ray-generated atomic
fluorescence (XRF method) has been reported (Ahlgren & Mattson,
1981; Christofferson & Mattson, 1983). Skerfving et al. (1987) found
the limit of detection to be 17 µg/g kidney cortex (three standard
deviations above the background). The precision is 23%.
The validity and accuracy of these in vivo neutron activation
and XRF methods have not been studied sufficiently. A comparison of
the results obtained by in situ determination of liver and kidney
cadmium in deceased people with those found by chemical analysis of
the same tissues is needed.
2.3 Quality control and quality assurance
2.3.1 Principles and need for quality control
There is a great need for strict quality control procedures in
the monitoring of trace elements in biological materials. The
purpose of these is to ensure that published data are as accurate as
possible. Quality control involves intra-laboratory or
inter-laboratory procedures that check whether the method gives
acceptable results on samples with known concentrations. Quality
assurance is usually given a broader meaning to cover the whole
system of activities that are carried out to increase the quality of
the operation. Thus, quality assurance includes not only the
chemical analysis, but also the whole pre-analytical chain, data,
handling, reporting, etc.
A review of published data (Vahter, 1982) showed that mean
blood cadmium concentrations in the general population as high as
20-50 mg/litre have been reported. Such values are definitely
unrealistic (section 6.2). Furthermore, most published reports lack
quality control or quality assurance data. Valid comparisons of
cadmium exposure based on blood cadmium levels can, therefore,
seldom be made. Results from interlaboratory comparisons amplify the
need for quality control (section 2.3.3).
2.3.2 Comparison of methods and laboratories
As indicated above, AAS (direct or combined with a separation
procedure by organic solvent extraction or ion exchange) is the
common method and can be applied to ordinary environmental or
biological samples. Each of the other methods has its particular
characteristics and can be used effectively according to the need
for sensitivity and to the type of sample. Of special concern are
methods used for the determination of cadmium in, for instance,
food, blood, and urine, where cadmium concentrations are generally
low and the matrices are complicated. Attempts to evaluate the
accuracy by comparing the proposed method with another method have
seldom been made. When testing a new method for the determination of
cadmium or a new application of a method to a different type of
sample, it is advisable to compare it with another method based on
quite different principles.
Since the principle of neutron activation analysis is quite
different from that of other methods, it is a good method for
comparison. Thus, Linnman et al. (1973) and Kjellström et al. (1974,
1975b) found good agreement between a flameless atomic absorption
method and destructive neutron activation analysis (the sample is
irradiated and then treated chemically so the original material is
"destroyed") for cadmium in wheat at concentrations down to around
20 mg/kg wheat. In the latter study (Kjellström et al., 1975b), good
agreement was also found between cadmium concentrations in urine
(above 5 µg/litre), determined by AAS after extraction into organic
solvent, and cadmium concentrations determined by neutron
activation. Because of technical problems of neutron activation
analysis of liquid samples, Kjellström et al. (1975b) could not
evaluate the accuracy at urine concentrations of around 1 µg/litre.
However, Jawaid et al. (1983) have used neutron activation to
confirm the accuracy of atomic absorption analyses of urine in the
range of 0.2-4 µg/litre.
Further comparisons of destructive neutron activation analysis
and different AAS methods conducted in different laboratories have
been carried out for faeces, rice, wheat, liver, and muscle
(Kjellström, 1979). The best agreement was found for liver, in which
the cadmium concentrations were the highest, but, there was also
reasonable agreement between most of the methods in the case of
other materials.
Another possibility for testing a method is to add radioactive
cadmium to the samples (Kjellström et al., 1974) or to inject
radioactive cadmium into animals and then compare results of
radioactive measurements with those obtained by chemical analysis.
Since there has been a need for comparing cadmium levels in
different areas of the world, studies among laboratories in
different countries have been undertaken to ensure that the
analytical methods give comparable results.
An intercomparison programme involving several European
laboratories, which used flame atomic absorption, flameless atomic
absorption, colorimetry, polarography, and anodic stripping
voltammetry, indicated great variability in results (Lauwerys et
al., 1975). Thus, reported concentrations in the same sample of
blood were from 1 to 92 µg/litre in one case, from 0 to 73 µg/litre
in another, and from 0 to 110 mg/litre in a third. A wide range of
values was also reported in the case of aqueous solutions. Only 29%
of participating laboratories measured cadmium in blood with
sufficient precision. The conclusion from this study was that
several participating laboratories had not yet adequately developed
the technique required for precisely measuring cadmium in blood,
urine, and water.
2.3.3 Quality assurance
An extensive quality assurance programme of cadmium analysis
involving laboratories in nine different countries has been carried
out (Vahter, 1982). This was a part of the UNEP/WHO Global
Environmental Monitoring Programme and involved the analysis of
cadmium in blood and kidney tissue as well as of lead in blood. A
series of quality control samples (spiked specimens), the
concentrations being known or unknown to the participating
laboratories, was used to check the accuracy of the methods before
the population samples were analysed. This procedure was repeated up
to 12 times, development work on the methods being carried out in
between, in order to improve the accuracy of the methods. After
improvement of the techniques and practice, the agreement became
excellent. An overview of various aspects of quality assurance has
been presented by Friberg (1988).
2.4 Conclusions
There are several methods available for the determination of
cadmium in biological materials. Atomic absorption spectrometry
(AAS) is the most widely used, but careful treatment of samples and
correction for interference is needed for the analysis of samples
with low cadmium concentrations. It is strongly recommended to
accompany analysis with a quality assurance programme. At present,
it is possible under ideal circumstances to determine concentrations
of about 0.1 µg/litre in urine and blood and 1-10 µg/kg in food and
tissue samples.
3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE
The metal cadmium belongs, together with copper and zinc, to
group IIb of the Periodic Table. It is a relatively rare element and
is not found in the pure state in nature. Cadmium is mainly
associated with the sulfide ores of zinc, lead, and copper, although
purification first took place in 1817 from zinc carbonate.
Commercial production only became significant at the beginning of
this century. Cadmium is often considered as a metal of the 20th
century; indeed, over 65% of the cumulative world production has
taken place in the last two decades (Wilson, 1988).
Cadmium is commonly regarded as a pollutant of worldwide
concern. The metal has been reviewed by the International Register
of Potentially Toxic Chemicals of the United Nations Environment
Programme. As a result, it has been included on the list of chemical
substances and processes considered to be potentially dangerous at
the global level (IRPTC, 1987).
3.1 Natural occurrence and cycling
Cadmium is widely distributed in the earth's crust at an
average concentration of about 0.1 mg/kg. However, higher levels may
accumulate in sedimentary rocks, and marine phosphates often contain
about 15 mg cadmium/kg (GESAMP, 1984). Weathering also results in
the riverine transport of large quantities of cadmium to the world's
oceans and this represents a major flux of the global cadmium cycle;
an annual gross input of 15 000 tonnes has recently been estimated
(GESAMP, 1987).
Some black shale deposits in parts of the United Kingdom and
USA contain elevated cadmium levels, thus leading to high soil
concentrations in these areas (Lund et al., 1981). High soil
concentrations are more commonly found in areas containing deposits
of zinc, lead, and copper ores. Indeed, such areas are often
characterized by both soil and aquatic contamination at the local
level. The mining of these ore bodies has further increased the
extent of such contamination. In background areas away from such
deposits, surface soil concentrations of cadmium typically range
between 0.1 and 0.4 mg/kg (Page et al., 1981) while fresh water
contains < 0.01-0.06 ng/litre (Shiller & Boyle, 1987).
Volcanic activity is a major natural source of cadmium release
to the atmosphere. Emissions of cadmium take place both during
episodic eruptions and continuous low-level activity. Difficulties
exist in quantifying the global flux from this source but an
estimate of 100-500 tonnes (Nriagu, 1979) has been made. Deep sea
volcanism is also a source of environmental cadmium release, but the
role of this process in the global cadmium cycle remains to be
quantified.
Older measurements of cadmium in the atmosphere and marine
waters from background areas generally yielded much higher values
than those obtained by more recent studies. Improved sampling and
analytical techniques are considered to be responsible for these
changes. Recent measurements of atmospheric concentrations in remote
areas are typically in the range of 0.01-0.04 ng/m3 (GESAMP,
1985). Airborne cadmium concentrations around volcanoes can be
markedly elevated; for example, the plume of Mount Etna, Sicily,
contains about 90 ng/m3 (Buatmenard & Arnold, 1978).
Current measurements of dissolved cadmium in surface waters of
the open oceans give values of < 5 ng/litre. The vertical
distribution of dissolved cadmium in ocean waters is characterized
by a surface depletion and deep water enrichment, which corresponds
to the pattern of nutrient concentrations in these areas (Boyle et
al., 1976). This distribution is considered to result from the
absorption of cadmium by phytoplankton in surface waters, its
transport to the depths incorporated in biological debris, and its
subsequent release. In contrast, cadmium is enriched in the surface
waters of areas of upwelling, and this leads to elevated levels in
plankton unconnected with human activity (Martin & Broenkow, 1975;
Boyle et al., 1976). Oceanic sediments under-lying these areas of
high productivity can contain markedly elevated cadmium levels as a
result of inputs associated with biological debris (Simpson, 1981).
Ice and snow deposits from the polar regions represent a unique
historical record of pollutants in atmospheric precipitation.
However, the problems of contamination are great and no reliable
data are at present available from historic samples; this prevents
an insight into temporal changes in the cycling of cadmium.
Nevertheless, current ice samples have been analysed; those from the
Arctic contain on average 5 pg/g, while corresponding values from
the Antarctic (0.3 pg/g) are much lower (Wolff & Peel, 1985).
3.2 Production
Cadmium is a by-product of zinc production. As a result, the
level of cadmium output has closely followed the pattern of zinc
production, little being produced prior to the early 1920s. The
subsequent rapid increase corresponded to the commercial development
of cadmium electroplating. Worldwide production reached a plateau in
the 1970s but in the 1980s output appeared to be increasing again
(Wilson, 1988b). The worldwide production of cadmium in 1987 was
18 566 metric tonnes (Wilson, 1988b).
3.3 Uses
Cadmium has a limited number of applications but within this
range the metal is used in a large variety of consumer and
industrial materials. The principal applications of cadmium fall
into five categories: protective plating on steel; stabilizers for
poly-vinyl chloride (PVC); pigments in plastics and glasses;
electrode material in nickel-cadmium batteries; and as a component
of various alloys. Detailed consumption statistics are only
available for a limited number of countries but from these it is
apparent that the pattern of use can vary considerably from country
to country (Wilson, 1988b).
Examination of the reported trends in cadmium consumption over
the last 25 years reveals considerable changes in the relative
importance of the major applications. The use of cadmium for
electroplating represents the most striking decrease; in 1960 this
sector accounted for over half the cadmium consumed worldwide, but
in 1985 its share was less than 25% (Wilson, 1988b). This decline is
usually linked to the widespread introduction of progressively
stringent effluent limits from plating works and, more recently, to
the introduction of general restrictions on cadmium consumption in
certain countries. In contrast, the use of cadmium in batteries has
shown considerable growth in recent years from only 8% of the total
market in 1970 to 37% by 1985. The use of cadmium in batteries is
particularly important in Japan and represented over 75% of the
total consumption in l985 (Wilson, 1988b).
Of the remaining applications of cadmium, pigments and
stabilizers are the most important, accounting for 22% and 12%,
respectively, of the world total in 1985. The share of the market by
cadmium pigments remained relatively stable between 1970 and l985
but the use of the metal in stabilizers during this period showed a
considerable decline, largely as a result of economic factors. The
use of cadmium as a constituent of alloys is relatively small and
has also declined in importance in recent years, accounting for
about 4% of total cadmium use in l985 (Wilson, 1988b).
3.4 Sources of environmental exposure
Numerous human activities result in the release of significant
quantities of cadmium to the environment. The relative importance of
individual sources varies considerably from country to country. The
major sources of anthropogenic cadmium release can be divided into
three categories. The first is made up of those activities involved
in the mining, production, and consumption of cadmium and other
non-ferrous metals. The second category consists of inadvertent
sources where the metal is a natural constituent of the material
being processed or consumed. Sources associated with the disposal of
materials that had earlier received cadmium discharges or discarded
cadmium products make up the third category.
Table 1. Estimates of atmospheric cadmium emissions (tonnes/year) from human
activities on a national, regional and worldwide basis
Source United EECb Worldwidec
Kingdoma
Natural sources ND 20 800d
Non-ferrous metal
production
mining ND ND 0.6-3
zinc and cadmium 20 920-4600
copper 3.7 6 1700-3400
lead 7 39-195
Secondary production ND 2.3-3.6
Production of cadmium-containing
substances ND 3 ND
Iron and steel production 2.3 34 28-284
Fossil fuel combustion
coal 1.9 6 176-882
oil 0.5 41-246
Refuse incineration 5 31 56-1400
Sewage sludge incineration 0.2 2 3-36
Phosphate fertilizer manufacture ND ND 68-274
Cement manufacture 1 ND 8.9-534
Wood combustion ND ND 60-180
TOTAL EMISSIONS 14 130 3900-12800
a From: Hutton & Symon (1986); data apply to 1982-1983
b From: Hutton (1983); data apply to 1979-1980 (the EEC consisted, at
that time, of Belgium, Denmark, Federal Republic of Germany, Italy,
Luxembourg, The Netherlands, Republic of Ireland, and
the United Kingdom)
c From: Nriagu & Pacyna (1988); data apply to 1983
d From: Nriagu (1979)
ND Not determined
3.4.1 Sources of atmospheric cadmium
Estimates of cadmium emissions to the atmosphere from human and
natural sources have been carried out at the world-wide, regional,
and national levels; examples of such inventories are shown in
Table 1.
The median global total emission of the metal from human
sources in 1983 was 7570 tonnes (Nriagu & Pacyna, 1988) and
represented about half the total quantity of cadmium produced in
that year. In comparison, the worldwide emission of lead from human
activities was about 10% of the total lead produced in 1983 (Nriagu
& Pacyna 1988). In both the European Economic Community (EEC) and on
a worldwide scale (Nriagu, 1979), about 10-15% of total airborne
cadmium emissions arise from natural processes, the major source
being volcanic action.
Considerable differences exist in the relative importance of
different sources of atmospheric cadmium between the worldwide
situation and that in the United Kingdom and the EEC as a whole.
This is particularly marked for non-ferrous metal production, which
accounts for about 75% of the total anthropogenic emissions
worldwide but only 25% in the EEC. This partly reflects the
extensive emission controls operated by these industries in Europe
compared with many parts of the world. In addition, of the two basic
methods of zinc production, thermal smelting and electrolyte
refining, only the former releases significant atmospheric cadmium
emissions. In recent years, electrolytic refining has assumed the
major share of the world's production of zinc and cadmium and has
largely replaced thermal processes in Europe. The once important
vertical and horizontal retort smelters, which emit large quantities
of atmospheric cadmium, have been phased out in most developed
countries, but are still in operation in several developing
countries (ILZSG, 1988).
Other industries that employ thermal processes, e.g., iron
production, fossil fuel combustion, and cement manufacture, all
release airborne cadmium, the metal being a natural constituent of
the raw materials. The cadmium content of these materials is
generally relatively low but this is offset by the vast quantities
consumed. Furthermore, in common with other thermal processes, the
elevated temperatures employed result in the volatilization of
cadmium. It subsequently condenses in a preferential manner on the
smallest particles in the stack gases, the size range least
efficiently retained by conventional particulate control measures
(Smith, 1982). Despite mechanisms that enhance the release of
cadmium, the quantities emitted from the three processes are now
considered to be smaller than they were in the past, particularly in
the case of fossil fuel combustion (Rauhut, 1980). Municipal refuse
is a waste-related source, the cadmium being derived from discarded
nickel-cadmium batteries and plastics that contain cadmium pigments
and stabilizers. The incineration of refuse, a practice generally
restricted to developed countries, is a major source of atmospheric
cadmium release at the national, regional, and worldwide levels
(Table 1). Indeed, this activity accounts for about one third of the
total cadmium emissions in the United Kingdom and the EEC as a
whole. Cadmium release from this sector originates from a large
number of plants, while the emissions from the non-ferrous metal
industry are derived from relatively few facilities.
Sewage sludge receives cadmium from industrial sources,
particularly from the discharges of plating operations and pigment
works. One disposal option, the incineration of sewage sludge, is a
relatively minor source of airborne cadmium, reflecting the small
quantities of sludge disposed of in this manner (Table 1).
Steel production can also be considered as a waste-related
source, as large quantities of cadmium-plated steel scrap are
recycled by this industry, at least in developed countries. As a
result, steel production is responsible for considerable emissions
of atmospheric cadmium.
3.4.2 Sources of aquatic cadmium
Non-ferrous metal mines represent a major source of cadmium
release to the aquatic environment. Contamination can arise from
mine drainage water, waste water from the processing of ores,
overflow from the tailings pond, and rainwater run-off from the
general mine area. The release of these effluents to local
water-courses can lead to extensive contamination downstream of the
mining operation. The cadmium content of the ore body and mine
management policies, as well as climatic and geographical
conditions, all influence the quantities of cadmium released from
individual sites. Flood and storm conditions, for example, will
enhance the mobilization of cadmium contained in particulate
material. Aquatic inputs of cadmium are not restricted to active
mine sites, and mines disused for many years can still be
responsible for the continuing contamination of adjacent
watercourses (Johnson & Eaton, 1980).
At the global level, the smelting of non-ferrous metal ores has
been estimated to be the largest human source of cadmium release to
the aquatic environment (Nriagu & Pacyna, 1988). Discharges to fresh
and coastal waters arise from liquid effluents produced by gas
scrubbing together with the site drainage waters.
Concerning the locations where environmental health effects of
cadmium have been reported, the water and air contamination from
non-ferrous metal mining and production are the predominant sources
of cadmium. All the major areas of Japan with elevated cadmium
levels have been affected by these sources (Tsuchiya, 1978),
although contamination through the natural mobilization of cadmium
from ore bodies may also have been involved.
Cadmium is a natural constituent of rock phosphates and
deposits from some regions of the world contain markedly elevated
levels of the metal. The manufacture of phosphate fertilizer results
in a redistribution of the cadmium in the rock phosphate between the
phosphoric acid product and the gypsum waste. In many cases, the
gypsum is disposed of by dumping in coastal waters, which leads to
considerable cadmium inputs. Some countries, however, recover the
gypsum for use as a construction material and thus have negligible
cadmium discharges (Hutton, 1982).
The atmospheric fall-out of cadmium to fresh and marine waters
represents a major input of cadmium at the global level (Nriagu &
Pacyna, 1988). Indeed, a GESAMP study of the Mediterranean Sea
indicated that this source is comparable in magnitude to the total
river inputs of cadmium to the region (GESAMP, 1985). Similarly,
large cadmium inputs to the North Sea (110-430 tonnes/year) have
been estimated, based on the extrapolation from measurements of
cadmium deposition along the coast (van Aalst et al., 1983a,b).
However, another approach based on model simulation yielded a modest
annual input of 14 tonnes (Krell & Roeckner, 1988).
Acidification of soils and lakes may result in enhanced
mobilization of cadmium from soils and sediments and lead to
increased levels in surface and ground waters (WHO, 1986). The
corrosion of soldered joints or zinc galvanized plumbing by acidic
waters can dissolve cadmium and produce increased levels of the
metal in drinking-water. In one study from Sweden, cadmium levels in
tap water from areas susceptible to acidic deposition were double
those from a control area (Svensson et al., 1987).
3.4.3 Sources of terrestrial cadmium
Solid wastes from a variety of human activities are disposed of
in landfill sites, resulting in large cadmium inputs at the national
and regional levels when expressed as a total tonnage (Hutton, 1982;
Hutton & Symon, 1986). However, this simple approach exaggerates the
significance of landfilled cadmium in certain high volume wastes
with relatively low concentrations of cadmium. Examples include the
ashes from fossil fuel combustion, waste from cement manufacture,
and the disposal of municipal refuse and sewage sludge. Of greater
potential environmental significance are the solid wastes from both
non-ferrous metal production and from the manufacture of
cadmium-containing articles, as well as the ash residues from refuse
incineration. All three waste materials are characterized by
elevated cadmium levels and as such require disposal to controlled
sites to prevent the mobilization of the cadmium in ground water.
Soil cadmium contamination is a characteristic feature around
non-ferrous metal mines and smelters, particularly in the case of
those handling zinc ores. Contamination from mining is generally
local but may be widespread in areas of high mineral content
(Tsuchiya, 1978). Soil contamination from smelters is generally
greatest next to the source and decreases exponentially with
distance, although cadmium concentrations can still be above the
background level 20 km from the source (Buchauer, 1972). Shipham,
United Kingdom, is a site of extreme soil cadmium contamination.
Between 1650 and 1850 the village of Shipham was the site of a major
zinc mine. Once the mining stopped the area was flattened and
developed for agriculture and housing. Cadmium levels in
agricultural and garden soils are some of the highest ever reported
worldwide (Thornton, 1988).
The agricultural application of phosphate fertilizers
represents a direct input of cadmium to arable soils. The cadmium
content of phosphate fertilizers varies widely and depends on the
origin of the rock phosphate. It has been estimated that fertilizers
of West African origin contain 160-255 g cadmium/tonne of phosphorus
pentoxide, while those derived from the southeastern USA contain
only 35 g/tonne (Hutton, 1982).
The annual rate of cadmium input to arable land from phosphate
fertilizers had been estimated for the countries of the EEC, taking
into account differences in application rates and the cadmium
contents of the fertilizers used (Hutton, 1982). The average cadmium
input (5 g/ha) only represents about 1% of the surface soil cadmium
burden. Despite the relatively small size of this input, long-term
continuous application of phosphate fertilizers has been shown to
cause increased soil cadmium concentrations (Williams & David, 1973,
1976; Andersson & Hahlin, 1981).
The application of municipal sewage sludge to agricultural soil
as a fertilizer can also be a significant source of cadmium. In many
industrialized countries, control measures have reduced the cadmium
content of sewage sludge and at the same time national and regional
regulations have limited the input of cadmium from agricultural
sludge applications (Davis, 1984). Nevertheless, large increases in
soil cadmium concentration have resulted in the past from the
application of contaminated sludge in both North America and Europe
(Davis, 1984). Even today, the high application rates used for
sewage sludge result in relatively large cadmium inputs, a value of
80 g/ha having been estimated for the United Kingdom (Hutton &
Symon, l986). On a national or regional basis, however, these inputs
are much smaller than those from either phosphate fertilizers or
atmospheric deposition (see section 4.2).
3.5 Conclusions
Cadmium is a relatively rare element and current analytical
procedures indicate much lower concentrations of the metal in
environmental media than do older measurements. At present, it is
not possible to determine whether human activities have caused a
historic increase in cadmium levels in the polar ice caps.
Commercial cadmium production started at the beginning of this
century. The pattern of cadmium consumption has changed in recent
years with significant decreases in electroplating and increases in
batteries and specialized electronic uses. Most of the major uses of
cadmium employ it in the form of compounds that are present at low
concentration. This makes it difficult to recycle cadmium in order
to decrease the potential for environmental contamination.
Restrictions on certain uses of cadmium imposed by a few countries
may have widespread impact on the applications of cadmium.
Cadmium is released to the air, land, and water by human
activities. In general, the two major sources of contamination are
the production and consumption of cadmium and other non-ferrous
metals and the disposal of wastes containing cadmium. Areas in the
vicinity of non-ferrous mines and smelters often show pronounced
cadmium contamination.
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND
TRANSFORMATION
4.1 Atmospheric deposition
Cadmium is removed from the atmosphere by dry deposition and by
precipitation. Total deposition rates have been measured at numerous
localities worldwide and values have generally been found to
increase in the order: background < rural < urban < industrial.
In rural areas of Scandinavia, annual deposition rates ranged from
0.4 to 0.9 g/ha (Laamanen, 1972; Andersson, 1977). Similarly, in a
rural region of Tennessee, USA, a deposition rate of 0.9 g/ha was
observed (Lindberg et al., 1982). Hutton (1982) concluded that
3 g/ha per year is a representative value for the atmospheric
deposition of cadmium to agricultural soils in rural areas of the
EEC. This may be compared with a corresponding input of 5 g/ha per
year for these areas from the application of phosphate fertilizers
(see 3.4).
Many industrial sources of cadmium possess tall stacks, which
bring about the wide dispersion and dilution of particulate
emissions. Indeed, it is often assumed that < 10% of such emissions
are deposited locally, the remainder being available for long-range
transport (Krell & Roeckner, 1988). Nevertheless, cadmium deposition
rates around smelter facilities are often markedly elevated nearest
the source and generally decrease rapidly with distance (Hirata,
1981). This pattern of contamination can be reflected in surface
soils and vegetation, and in the former case, contamination will
reflect the long-term history of metal inputs from the atmosphere.
As a result, soil cadmium concentrations in excess of 100 mg/kg are
commonly encountered close to long-established smelters (Buchauer,
1972). In some urban areas, the high density of non-ferrous metal
works results in a city-wide elevation of cadmium deposition (Roels
et al., 1981a).
The possibility that cadmium deposition is enhanced around
atmospheric sources of cadmium other than smelters has been
investigated on a number of occasions. One assessment of studies
conducted around coal-fired power stations concluded that this
source was unlikely to cause any marked local accumulation of
cadmium (Chadwick & Lindman, 1982). In contrast, significant cadmium
contamination was found in surface soil downwind of a phosphate
fertilizer processing plant in the USA, the levels being up to
40 mg/kg (Hutchison et al., 1979). Little attention has been paid to
the pattern of cadmium deposition around refuse incinerators; one
study of a large facility in the United Kingdom observed moderately
elevated deposition rates downwind of the plant (Hutton et al.,
1988).
Crop plants growing near to atmospheric sources of cadmium may
contain elevated cadmium levels (Carvalho et al., 1986). However, it
is not always possible to distinguish whether the cadmium is derived
directly from surface deposition or originates from root uptake,
since soil levels in such areas are generally higher than normal.
One study in Denmark has suggested that atmospheric deposition can
also be an important direct source of cadmium in crop plants even in
background areas (Hovmand et al., 1983).
4.2 Transport from water to soil
Rivers contaminated with cadmium can contaminate surrounding
land, either through irrigation for agricultural purposes, by the
dumping of dredged sediments, or through flooding (Forstner, 1980;
Sangster et al., 1984). For example, agricultural land adjacent to
the Neckar River, Germany, received dredged sediments to improve the
soil, a practice that produced soil cadmium concentrations in excess
of 70 mg/kg (Forstner, 1980).
Much of the cadmium entering fresh waters from industrial
sources is rapidly absorbed by particulate matter, where it may
settle out or remain suspended, depending on local conditions. This
can result in low concentrations of dissolved cadmium even in rivers
that receive and transport large quantities of the metal (Yamagata &
Shigematsu, 1970). Rivers can transport cadmium considerable
distances from the source of the input. In Japan, there are several
areas where soils have been contaminated with irrigation water up to
50 km from the source (Tsuchiya, 1978).
4.3 Uptake from soil by plants
It has been shown repeatedly that an increase in soil cadmium
content results in an increased plant uptake of the metal. This has
been demonstrated for soils with naturally elevated cadmium levels
(Lund et al., 1981), those contaminated by non-ferrous metal mining
(Alloway et al., 1988), and those that have received cadmium via
sewage sludge applications (Davis & Coker, 1980). It is this basic
relationship that makes the soil-crop pathway of human exposure
susceptible to increased levels of soil cadmium. Indeed, since the
major sources of cadmium exposure for the general population are
food and tobacco (see section 5), it is important to assess those
soil and plant factors that influence cadmium uptake by crop plants.
The most important soil factors influencing plant cadmium
accumulation are soil pH and cadmium concentration (Davis & Coker,
1980; Page et al., 1981). Soil cadmium is distributed between a
number of pools or fractions, of which only the cadmium in soil
solution is thought to be directly available for uptake by plants.
Soil pH is the principal factor governing the concentration of
cadmium in the soil solution. Cadmium absorption to soil particles
is greater in neutral or alkaline soils than in acidic ones and this
leads to increased cadmium levels in the soil solution. As a
consequence, plant uptake of cadmium decreases as soil pH increases.
Other soil factors that influence the distribution of cadmium
between the soil and soil solution include cation exchange capacity
and the contents of the hydrous oxides of manganese and iron,
organic matter, and calcium carbonate. Increases in these parameters
result in decreased availability of cadmium to plants owing to a
reduction of the level of cadmium in the soil solution.
A comparative study of cadmium-contaminated soils from
different sources illustrates the importance of the above soil
factors (Alloway et al., 1988). Soils from Shipham, United Kingdom,
contained the highest total cadmium levels but the soil solution
concentrations were lower than in other soils. The small proportion
of soluble cadmium in Shipham soils (0.04%) was related to the high
pH (7.7) and high calcium carbonate and hydrous oxide content of
these soils. In contrast, a paddy soil from the Junzu Valley, Japan,
contained 4% soluble cadmium and possessed a low pH (5), low calcium
carbonate content, and very low hydrous oxide concentration (Alloway
et al., 1988).
Much attention has been paid to the plant availability of
cadmium in agricultural soils to which sewage sludge has been
applied. It has been observed that the repeated application of
sludge to soils can alter the availability of cadmium, and although
soil cadmium levels may increase, crop levels do not always reflect
this increase (Page et al., l981). The long-term availability of
cadmium to plants is uncertain, availability having been reported to
remain constant, decrease, or even increase with time (Tjell et al.,
l983). In another study there were no clear changes in the plant
availability of cadmium over a period of five years after sewage
sludge was applied to the soil (Carlton-Smith, l987).
Concern over the long-term implications of present-day cadmium
inputs to European arable soils has led to modelling studies of the
future cadmium exposure for the general population (Tjell et al.,
1981; Hutton, 1982). It was estimated by Tjell et al. (1981) that
cadmium inputs from phosphate fertilizers and atmospheric deposition
will cause an annual increase of 0.6% in Danish soil cadmium levels.
The corresponding increases in crop cadmium concentrations would
lead to a predicted 70% increase in dietary cadmium intake 100 years
hence. Similar soil and dietary cadmium increases have been
predicted for the EEC as a whole, although the precise values varied
according to the soil properties and crop consumption patterns
employed (Hutton, 1982).
Indirect support for these forecasts was provided by an
investigation of the time trends in soil and crop cadmium levels
using archived samples. Jones et al. (1987) found that the cadmium
content of agricultural soils from a site in the United Kingdom had
increased by 27-55% since the 1850s. Trends in the cadmium
concentrations of wheat grain were less clear, possibly due to
confounding factors such as changes in varieties grown and altered
soil properties.
4.4 Transfer to aquatic and terrestrial organisms
In general, cadmium concentrations in terrestrial and aquatic
biota from uncontaminated localities are low, corresponding to the
geochemical abundance of this metal. However, in certain situations,
cadmium displays a propensity for marked bioaccumulation, a feature
that has implications for human dietary exposure and may be of
toxicological significance for the organisms concerned.
It appears that cadmium shows greatest mobility in certain
marine ecosystems. Phytoplankton in areas of oceanic upwelling
contain raised cadmium levels (Martin & Broenkow, 1975), and
filter-feeding molluscs can accumulate significant concentrations of
cadmium even in coastal localities that are only moderately
contaminated (Bryan et al., 1980). Oysters, in particular, are
well-known cadmium accumulators, levels of up to 8 mg/kg wet weight
having been recorded in New Zealand (Nielsen, 1975). Certain edible
crustaceans such as crab and lobster also contain relatively high
cadmium concentrations, the metal being localized in the
hepatopancreas or "brown meat" (Buchet et al., l983).
Some marine birds and mammals contain remarkably elevated
cadmium burdens in the kidney and liver (Martin et al., 1976;
Stoneburner, 1978; Nicholson & Osborn, 1983). In the case of oceanic
species, this accumulation is probably a natural process associated
with the feeding habits and longevity of the organism in question.
Even so, the high cadmium levels in pelagic sea-birds have been
linked in one study to morphological signs of kidney damage
(Nicholson & Osborn, 1983).
Terrestrial mosses and lichens display a high capacity for
retention of metals deposited from the atmosphere and these plants
have been used to map both local contamination from point sources
and regional patterns of cadmium deposition (MARC, 1986). The
fruiting bodies of some macrofungi contain remarkably high cadmium
concentrations even in areas uncontaminated with cadmium (MARC,
1986). This phenomenon has implications for human dietary exposure
as some accumulator species are edible.
In addition to humans, certain long-lived terrestrial mammals
such as the horse and moose may possess considerable cadmium burdens
in the kidney and liver (Elinder & Piscator, 1978; Frank et al.,
1981; Jeffery et al., 1989). It has been shown that cadmium
accumulates with age in horse kidney.
4.5 Conclusions
Increases in soil cadmium content result in an increase in the
uptake of cadmium by plants; the pathway of human exposure from
agricultural crops is thus susceptible to increases in soil cadmium.
The uptake by plants from soil is greater at low soil pH. Processes
that acidify soil (e.g., acid rain) may therefore increase the
average cadmium concentrations in foodstuffs. The application of
phosphate fertilizers and atmospheric deposition are significant
sources of cadmium input to arable soils in some parts of the world;
sewage sludge can also be an important source at the local level.
These sources may, in the future, cause enhanced soil and hence crop
cadmium levels, which in turn may lead to increases in dietary
cadmium exposure. In certain areas, there is evidence of increasing
cadmium content in food.
Edible free-living food organisms such as shellfish,
crustaceans, and fungi are natural accumulators of cadmium. Regular
consumption of these items can result in elevated human exposure.
Certain marine vertebrates contain markedly elevated renal cadmium
concentrations, which, although considered to be of natural origin,
have been linked to signs of kidney damage in the organisms
concerned.
5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE
Human uptake of cadmium occurs via the inhalation of air and
the ingestion of food and drinking-water. Accidental ingestion of
cadmium through the contamination of foods in contact with
cadmium-containing materials has occurred in the past. Accidental
high-level inhalation exposure during welding operations and cadmium
smelting is still a considerable hazard.
Chronic exposure to cadmium via food or workplace air is the
main concern in assessing the health risks of cadmium.
5.1 Inhalation route of exposure
5.1.1 Ambient air
Many countries carry out regular monitoring programmes for
cadmium in the air. An assessment of the available data from various
European countries showed that average values range from 1 to
5 ng/m3 in rural areas, 5 to 15 ng/m3 in urban areas, and 15 to
50 ng/m3 in industrialized areas (WHO, 1987). Examination of some
individual national data (Table 2) suggests that urban values are
likely to occupy the lower end of the range indicated above
(McInnes, 1979; RIVM, 1988).
Much higher air cadmium concentrations are found in areas close
to major atmospheric sources of the metal. However, these values can
fluctuate widely as a result of changing emission characteristics
and weather conditions (Muskett et al., 1979).
Studies of the particle size distributions of cadmium in urban
aerosols generally show that the metal is associated with
particulate matter in the respirable range (Greenberg et al., 1978).
The enrichment of cadmium on these smaller particles can be linked
to the behaviour of the metal in thermal facilities that are sources
of airborne cadmium (see section 3.4.1).
An air quality study revealed no differences between indoor and
outdoor air cadmium levels when the dwellings of non-smokers were
examined (Moschandreas, 1981). However, significantly higher indoor
air cadmium levels were observed in those houses where smoking took
place.
Table 2. Typical levels of cadmium in ambient air
Type of area Cadmium concentration Sampling Reference
range (ng/m3) periodb
Remote rural
Pacific atoll 0.0025-0.0046 NR Duce et al. (1983)
Europe 0.1-0.3 NR Heindryckx et al. (1974)
Atlantic 3 x 10-6-6.2 x 10-4 NR Duce et al. (1975)
Rural
Belgium 1a 24 h Janssens & Dams (1974)
Federal Republic
of Germany 0.1-1 < 24 h Neeb & Wahdat (1974)
Japan 1-4 24 h Japanese Environment
Agency (1974)
Urban
Belgium 50a 24 h Janssens & Dams (1974)
Federal Republic
of Germany 10-150 < 24 h Neeb & Wahdat (1974)
Japan 3-6.3 1 year Japanese Environment
Agency (1974)
Poland 2-51 1 year Just & Kelus (1971)
USA (New York) 3-23 1 year Kneip et al. (1970)
a Mean value b NR = not reported
5.1.2 Air in the working environment
Elevated air cadmium levels arise in the smelting of
non-ferrous metals and in the production and processing of
cadmium-containing articles. The thermal operations associated with
these processes are mainly responsible for producing cadmium dusts
and, if temperatures are sufficiently high, cadmium fume.
Airborne cadmium concentrations found in the occupational
setting vary considerably according to the type of industry and the
specific working conditions in each plant. Markedly elevated values,
in the mg/m3 range, were prevalent in the 1940s to 1960s (Friberg,
1950; Adams et al., 1969; Tarasenko & Vorobjeva, 1973). Considerable
improvements in occupational hygiene have taken place in developed
countries since then and these have led to progressive reductions in
ambient levels in the workplace. Table 3 illustrates the temporal
decline in air cadmium levels in a Swedish battery factory
(Adamsson, 1979). The lowest values shown in Table 3 may not be
typical for all occupational facilities; levels of 1-5 mg/m3 were
reported for one pigment plant in the mid 1970s (De Silva & Donnan,
1981).
Table 3. Average air cadmium concentrations in a Swedish cadmium
battery planta
Time period Number of Cadmium concentration
observations (µg/m3)
1946 10 5000
1947-1949 16 750
1950-1960 94 650
1965-1973 393 70
1973-1975 373 40
1975-1976 573 15
a From: Adamsson (1979)
In general, only total air cadmium concentrations are monitored
in the working environment; factors influencing respiratory
absorption, such as the speciation of cadmium and the size
distribution of the collected particles, are not taken into account.
In one study of workplaces with high total airborne cadmium levels,
Lauwerys et al. (1974b) found, in general, that less than 25% of the
total cadmium in air was in the respirable range and that this
percentage decreased as the total value increased.
Cadmium-containing dust particles that are too large to be delivered
to the pulmonary region of the lung can enter the gastrointestinal
tract by mucociliary transfer.
5.1.3 The smoking of tobacco
The tobacco plant naturally accumulates relatively high cadmium
concentrations in its leaves. As a result, this material represents
an important source of exposure for smokers. It has been reported
that one cigarette contains about 1-2 µg cadmium (Friberg et al.,
1974) and that about 10% of the cadmium content is inhaled when the
cigarette is smoked (Elinder et al., 1983). One study has suggested
that modifications in cigarette construction and the increasing
popularity of filter cigarettes have reduced cadmium exposure from
this source in recent years (Scherer & Barkemeyer, 1983). Regional
differences exist in the cadmium concentration of cigarettes, and
lower values (0.1-0.5 µg) have been found in samples from Argentina,
India, and Zambia (Nwankwo et al., 1977; Elinder et al., 1983).
Biological monitoring surveys of the general population have
shown that cigarette smoking can cause significant increases in the
concentration of cadmium in the kidney (Lewis et al., 1972; Vahter,
1982).
Occupationally exposed workers who smoke tobacco may be subject
to higher exposure levels than their non-smoking colleagues. This
may be because the original content of tobacco can be considerably
increased when handled during work (Piscator et al., 1976). In
addition, the hand-to-mouth route of exposure may be more important
in workers who are tobacco smokers (Adamsson, 1979).
5.2 Ingestion routes of exposure
5.2.1 Levels in drinking-water
Drinking-water generally contains low cadmium levels and a
value of 1 µg/litre or less is often assumed to be a representative
value in most situations (Meranger et al., 1981). Thus, cadmium
exposure from drinking-water and water-based beverages is relatively
unimportant compared with the dietary contribution.
In a study of drinking-water in Seattle, USA, Sharrett et al.
(1982) reported a median cadmium level of 0.01 µg/litre in tap water
delivered by copper pipes; the corresponding value from homes with
galvanized piping was 0.25 µg/litre. Water samples left to stand in
both types of piping showed increases in cadmium levels with median
values of 0.06 and 0.63 µg/litre in copper and galvanized supplies,
respectively. In a survey from the Netherlands, about 99% of
drinking-water samples in 1982 contained less than 0.1 µg/litre
(RIVM, 1988).
5.2.2 Levels in food
The cadmium content of agricultural crops varies according to
species, variety cultivated and season (Davis & Coker, 1980). The
results of an extensive nationwide survey of cadmium in different
classes of raw agricultural crops from uncontaminated localities
illustrate the range of values encountered within and between crop
classes (Wolnik et al., 1983, 1985). It is evident that cadmium is a
normal constituent of most foodstuffs (Tables 4 and 5).
Table 4. Cadmium concentrations in the major types of crop from
various regions of the USAa
Cadmium concentration (mg/kg wet weight)
Crop Sample size Median Minimum Maximum
Rice 166 0.0045 < 0.001 0.23
Peanuts 320 0.060 0.010 0.59
Soybeans 322 0.041 0.002 1.11
Wheat 288 0.030 < 0.0017 0.207
Potatoes 297 0.028 0.002 0.18
Carrots 207 0.017 0.002 0.13
Onions 230 0.009 0.001 0.054
Lettuce 150 0.017 0.001 0.160
Spinach 104 0.061 0.012 0.20
Tomatoes 231 0.014 0.002 0.048
a From: Wolnik et al. (1983, 1985).
Meat, fish, and fruit generally contain similar cadmium levels
and values of 5-10 µg/kg fresh weight are representative for these
food classes. Most plant-based foodstuffs contain higher cadmium
concentrations and a value of 25 µg/kg fresh weight is considered
representative for the staple items, cereals and root vegetables.
Offal from adult animals and certain shellfish contain even higher
concentrations (see section 4.4); values in excess of 50-100 µg/kg
fresh weight are considered normal. Food preparation can result in
cadmium losses from plant-based items. The milling of wheat grain
results in a reduction of about 50% in the cadmium content of the
white flour produced (Linnman et al., 1973). The washing, peeling,
and cooking of vegetables can also lead to reductions in the
concentrations of cadmium but, in general, these are relatively
small.
The use of glazed ceramic containers to store foodstuffs can
lead to significant cadmium contamination, particularly in the case
of foods that are acidic liquids (Beckman et al., 1979).
Table 5. Cadmium concentrations in different food items from various European
countries (values in µg/kg fresh weight)
Food Group United Finlandb Swedenc Denmarkd The
Kingdoma Netherlandse
Bread and cereals 20-30 20-40 31-32 30 25-35
Meat < 20-30 < 5-5 2-3 6-30 10-40
Offal
pork kidney 450 180 190 1000
pork liver 130 70 50 100
Fish < 15 < 5-20 1-20 14 15
Eggs < 30 4 1 < 10 2
Oils and dairy
products < 20-30 3-20 1-23 < 30 10-30
Sugars and preserves < 10 < 10 3 30 5
Fresh fruit < 10 < 2 1-2 11 5
Vegetables
cabbage < 10 5 4 10
cauliflower < 20 10 10
spinach 120 150 43
broccoli 10 10
legumes < 10-30 < 2-30 1-4 15
lettuce < 60 50 29 43
potatoes < 30 30 16 30 30
carrots < 50 30 41
a From: Bucke et al. (1983)
b From: Koivistoinen (1980)
c From: Jorhem et al. (1984)
d From: Andersen (1979)
e From: RIVM (1988)
Crops grown in cadmium-contaminated localities have been shown
to contain elevated levels of the metal compared with normal values.
The extent of enrichment depends on several factors (see section
4.3). The cadmium concentrations in selected vegetable crops grown
at three contaminated sites in the United Kingdom are shown in Table
6. Highest levels were generally found at Shipham, where soil
cadmium concentrations are markedly elevated, and the greatest
increase was noted in leafy vegetables. Potato, a staple food item,
showed similar values at the three locations and these were about
five times greater than background.
Large scale surveys of cadmium in rice have been carried out in
areas of Japan where environmental contamination was suspected
(Japanese Environment Agency, 1972, 1982). The results of the
earlier survey revealed that large numbers of rice samples contained
elevated cadmium levels; the corresponding data from the later study
indicated that decreases had occurred over the intervening ten
years. More detailed investigations at specific localities have also
been carried out in Japan, often as part of studies on health
effects of the general population (Table 7).
5.2.3 Other sources of exposure
Young children may ingest household dust or garden soil. This
habit may be a source of cadmium exposure, as has been identified
for lead (Duggan et al., 1985). The representative daily intake of
dust via the hands in young children is considered to be 100 mg
(Lepow et al., 1974). In an extensive survey of metals in household
dusts in the United Kingdom, an average cadmium level of 6.9 mg/kg
was obtained from over 4500 samples (Culbard et al., 1988). These
data suggest that the hand-to-mouth route is a minor source of
cadmium intake (about 0.7 µg daily).
The hand-to-mouth exposure pathway may be a significant source
of cadmium in areas around point sources of the metal. In the
vicinity of a small lead refinery in the United Kingdom, cadmium
levels in household dust were reported to be 193 mg/kg (Muskett et
al., 1979). The daily ingestion of 100 mg of this dust would result
in the intake of about 20 ßg cadmium. Buchet et al. (1983) observed
a correlation between cadmium intake from dust and the levels of
blood and urinary cadmium in children from areas of Belgium
subjected to air contamination. Despite markedly elevated soil
cadmium levels in the gardens of Shipham, United Kingdom, Thornton
(1988) found that household dust concentrations were only four times
greater (at an average of 27 mg/kg) than background.
Table 6. Mean cadmium concentrations (µg/kg fresh weight) in selected vegetable crops grown at three contaminated sites
in the United Kingdom
Location Source of cadmium Cabbage Leafy Potato Carrot Reference
contamination salad
Shipham zinc mine 250a 680 130 340 Sherlock et al. (1983)
Walsall atmospheric inputs 73 190 103 120 Tennant (1984)
from a copper
refinery
Heathrow sewage sludge 24 180 150 150 Chumbley & Unwin (1982)
applications
a Median value
5.2.4 Daily intake of cadmium from food
Three approaches are used for estimating the daily intake of
cadmium in food. The first is the total-diet collection method in
which the foods are prepared for consumption and are analysed either
individually or combined in one or more food group composites in
proportions based on available food consumption data. The total
cadmium intake is calculated as the product of the concentration and
the estimated amount of food eaten. In the second approach, a market
basket study, representative samples of individual foodstuffs are
collected from retail outlets and analysed. The cadmium
concentrations are then multiplied by the average amount of intake
of each foodstuff to give the cadmium intakes for each food item.
The sum gives the total dietary intake. The third way of estimating
cadmium intake is the collection of a duplicate sample of the meals
consumed. The combined food sample is homogenized and the cadmium
analysed. Table 8 presents