Cadmium is a contaminant which may enter the food chain from
    a number of natural and industrial sources. Cadmium was last
    reviewed at the sixteenth meeting of the Committee in 1972 (Annex
    1, reference 30) when a provisional tolerable weekly intake of 
    400-500 g per person (6.7-8.3 g/kg bw/week) was allocated.

         Since the previous evaluation, additional information has
    become available and is summarized and discussed in the following


         Cadmium occurs naturally in the environment at low levels
    usually with zinc, lead and copper ore deposits. High cadmium
    concentrations are often associated with industrial emission
    sources, e.g., mining and smelting operations. Major industrial
    uses of cadmium are in electroplating, pigments, particularly in
    plastics, plastic stabilizers (e.g., cadmium stearate), and nickel-
    cadmium rechargeable batteries. Although cadmium is easily
    complexed with some organic compounds (e.g., thiocarbamates), and
    organometallic compounds have been synthesized, these have not been
    found in the general environment since they are rapidly decomposed.
    There is, however, some evidence that in certain foods, such as
    oysters, cadmium is bound to a metallothionein-like protein
    (Friberg et al., 1986; Friberg et al.,  1985).

         Cadmium concentrations in air relate to the degree of
    industrialization and range from less than 1 ng/m3 in remote
    uninhabited areas up to 40 ng/m3 in urban environments. In close
    vicinity to industrial operations (e.g., zinc smelters), air
    concentrations have been found to range as high as 11,000 ng/m3.
    For the general population not living in proximity to industrial
    operations, cadmium intakes from air are unlikely to exceed 0.8 g
    per day (Friberg et al., 1986; Friberg et al., 1985).

         In fresh surface waters and most groundwaters, cadmium levels
    are generally less than 1 g/l. The use of galvanized pipes in
    water distribution systems can result in a 5 to 10-fold increase in
    cadmium levels in drinking water (i.e. up to 10 g/l). Similarly,
    in areas where there are zinc-bearing mineral formations, cadmium
    levels in groundwater may also reach g/l. Thus, for most
    individuals, cadmium intake from drinking water would be less than
    about 2 g/day but for certain persons cadmium intakes from water
    could reach as high as 20 g/day (Friberg et al., 1985; Mranger
    et al., 1981).

         Results from more recent surveys demonstrate that most foods
    contain on average less than 0.02 g/g cadmium. Exceptions include
    certain shellfish (e.g., oysters) and offal. Dietary intake
    estimates range from 13-35 g/day or 0.2 to 0.7 g/kg bw for an
    adult. Some of the variation in reported intakes relates to the use
    of the limit of detection. In one instance, for example, using zero
    concentration versus detection limit value for samples in which
    cadmium could not be detected resulted in estimated intakes of
    20 g/day and 35 g/day, respectively. For infants and children,
    cadmium intakes on a body weight basis are generally higher than
    that estimated for adults and, in some countries, intakes for the
    younger age groups have been reported to exceed 1 g/kg bw (Friberg
    et al., 1986; Friberg et al., 1985; Ministry of Agriculture,
    Fisheries and Food, 1985; Dabeka et al., 1987 & FAO/WHO, 1986).

         In addition to intake from air, water and food, smoking can
    represent a significant source of cadmium exposure. It has been
    estimated that a smoker of 20 cigarettes per day would increase
    his/her daily intake of cadmium by 2 to 4 g (Friberg et al.,
    1986, Friberg et al., 1985).

         In summary, the intake of cadmium from air, excluding
    industrial areas, is a minor portion of the total intake from all
    sources. Although water is not a major contributor of cadmium
    intake for most individuals, elevated cadmium levels in water can
    occur and resultant cadmium intakes can be as high as the dietary
    contribution. Foods represent the major route of cadmium exposure
    by the general public.


    Biochemical aspects

    Absorption, distribution, and excretion

         The retention of ingested cadmium varied between 4.7-7.0% in
    five adult men (Rahola et al., 1971). Cadmium deficiency
    increases the retention of cadmium in rats and this may also be the
    case in man (Larsson & Piscator, 1971).

         In mammals, cadmium is virtually absent at birth but will
    accumulate with time, especially in liver and kidneys. The primary
    period of rapid renal concentration may occur during the early
    years of life (Henke et al., 1970) and 50-75% of the total body
    burden will be found in these two organs.

    In various animal studies involving acute and chronic exposure,
    10-40% of inhaled cadmium was absorbed (Friberg et al., 1974). It
    has been estimated that about 50% of cadmium inhaled in cigarette
    smoke is absorbed (Friberg et al., 1985; 1986).

         Absorption of cadmium from the gastro-intestinal tract depends
    on species, type of cadmium compound, dose size and frequency, age
    and interaction with various dietary components (Nomiyama, 1978).
    When cadmium chloride was given to rats in drinking water over a
    period of 122 months, less than 1% of the total dose ingested was
    retained in liver and kidney (Decker et al., 1958).

         After single oral doses of cadmium chloride or cadmium
    nitrate, absorption varied between 0.5 and 8% in mice, rats and
    monkeys (Friberg et al., 1974; Nordberg et al., 1975) and
    limited human studies indicate a mean absorption of orally
    administered inorganic cadmium of about 5% (Kitamura, 1972; Rahola
    et al., 1972; Yamagata et al., 1974; Flanagan et al., 1978;
    Shaikh & Smith, 1980).

         Metallothionein-bound cadmium in food is absorbed and
    distributed differently from inorganic ionic cadmium compounds.
    Mice given cadmium-metallothionein had lower blood and liver
    cadmium but higher kidney cadmium concentrations than animals given
    a similar dose as cadmium chloride (Cherian et al., 1978;
    Sullivan et al., 1984). Similarly, cadmium bound to protein in
    oysters may be absorbed differently from inorganic cadmium
    (McKenzie et al., 1982).

         The proportion of an orally-administered dose which is
    absorbed varies with age. Young mice retained 10% of an orally
    administered dose of cadmium after two weeks whereas adult mice
    retained only 1% (Matsusaka et al., 1972) and other studies have
    confirmed that neonatal mice and rats absorb cadmium to a greater
    extent than older animals (Kello & Kostial, 1977a, b; Engstrom &
    Nordberg, 1979b).

         Low dietary levels of calcium, iron or protein lead to
    enhanced absorption in experimental animals (Friberg et al.,
    1985, 1986; Nordberg et al., 1983). Iron deficiency leads to a
    higher absorption of cadmium in both animals and humans (Hamilton
    & Valberg, 1974; Flanagan et al., 1978). In the latter case,
    women with low serum ferritin levels absorbed on average four times
    as much (10%) of orally ingested cadmium as a control group, the
    highest individual absorption rate being 20% of the dose.

         After absorption, cadmium is transported in the blood, mainly
    within the erythrocytes. A greater proportion of the blood cadmium
    is found in erythrocytes although the concentration is slightly
    higher in leucocytes (Friberg, 1952; Friberg et al., 1985; Garty
    et al., 1981). Cadmium is intracellularly bound to high molecular
    weight and low molecular weight protein fractions (Nordberg, 1972).
    The low molecular weight fraction is similar to metallothionein,
    which also binds cadmium in plasma.

         Erythrocyte cadmium can be released into plasma following
    haemolysis (a feature of chronic cadmium intoxication) or when the
    erythrocyte lifetime has expired. Plasma metallothionein has an
    important role in the transport of cadmium and similar proteins
    have been found in various tissues including duodenal mucosa
    (Starcher, 1969; Evans et al., 1970). Injected cadmium is
    partially dialyzable during the first few minutes (Friberg et
    al., 1974) but plasma concentrations decrease rapidly during the
    first few hours to less than 1% of the initial value by 24h;
    subsequently clearance is much slower. In the fast elimination
    phase, cadmium is mainly associated with the high molecular weight
    proteins whereas later it is bound also to metallothionein
    (Nordberg, 1978).

         Metallothionein (mw 6000-7000) can consist of up to 11%
    cadmium by weight, bound to sulfhydryl groups (Kagi et al., 1984;
    Elinder & Nordberg, 1985) and occurs in large quantities in the
    liver of animals exposed to cadmium. Metallothionein occurs in
    varying amounts in other tissues, particularly kidney, and its
    concentration correlates with that of cadmium in these tissues.

         The amount of free metallothionein in plasma is small but its
    low molecular weight permits filtration through the glomeruli and
    the subsequent reabsorption of cadmium-metallothionein in the
    proximal tubules explains the selective accumulation of cadmium in
    the renal cortex (Nordberg, 1972). The transport of cadmium bound
    to metallothionein from blood to renal tubular cells is rapid and
    virtually complete (Nordberg & Nordberg, 1975; Johnson & Foulkes,
    1980). Cadmium not bound to metallothionein is not taken up by the
    kidneys to a similar degree.

         Whereas early in gestation cadmium can reach the embryo/fetus
    (Dencker et al., 1983), transfer across the fully developed
    placenta is normally low (Ahokas & Dilts, 1979; Sonawane et al.,
    1975) found that only 0.02% of an injected dose reached the fetus.
    The concentration of cadmium in the organs of an embryo, fetus or
    neonate is three orders of magnitude lower than in the
    corresponding organs of an adult woman (Chaube et al., 1973;
    Henke et al., 1970).

         Numerous studies have shown that chronic exposure leads to a
    selective accumulation of cadmium in the liver and kidneys (renal
    cortex) and in some studies up to 75% of the total body burden was
    found in these organs (Friberg et al., 1985). Distribution to the
    kidneys is particularly important in view of the chronic
    nephrotoxicity of cadmium. However, distribution of cadmium in the
    body varies with the dosing protocol.

         In various species, after administration of a single dose
     per os or parenterally, the highest burden initially occurs in
    the liver but kidney levels may increase over several months to
    exceed liver levels (Gunn & Gould, 1957); pancreas and spleen also
    acquire relatively high concentrations (Nordberg & Nishiyama,
    1972). The accumulation of cadmium in the liver and subsequent
    redistribution to the kidney is probably due to efficient
    metallothionein synthesis in the liver; cadmium-metallothionein may
    be slowly released into the plasma, filtered through the glomeruli
    and reabsorbed in the tubules as previously mentioned. Thus in high
    exposure situations, even after discontinuation of exposure,
    concentrations of cadmium in the renal cortex may be maintained for
    a prolonged period or may even continue to increase if liver stores
    are high.

         The fate of cadmium after chronic exposure by various routes
    has been reviewed by Friberg et al., (1974, 1975, 1986) and
    Nomiyama (1978). Initially, cadmium in liver increases rapidly and
    is redistributed slowly to the kidney so that the higher the
    intensity of exposure, the higher the ratio of liver to kidney
    concentrations. The route of administration can also affect this
    ratio (Nomiyama et al., 1976).

         The concentration of cadmium in liver and renal cortex may
    fall subsequent to renal damage and increased leakage of bound
    cadmium into the urine (Bonnel et al., 1959; Nomiyama et al.,

         In humans, after normal levels of exposure, about 50% of the
    body burden is found in kidneys, about 15% in the liver and about
    20% in the muscles (Kjellstrom, 1979). As in animals, the
    proportion of cadmium in the kidney decreases as liver
    concentration increases (Friberg et al., 1985). The lowest
    concentrations of cadmium are found in brain, bone and fat (Sumino
    et al., 1975; Cherry, 1981). Accumulation in the kidneys
    continues up to 50-60 years of age in humans and falls thereafter,
    possibly due to age-related changes in kidney integrity and function;

    in contrast, cadmium levels in muscle continue to increase throughout
    life (Friberg et al., 1985). Differences in population mean renal
    cortex cadmium levels in different countries have been attributed
    mainly to differences in daily intake via food (Friberg et al.,
    1986) and smoking increases renal cortex cadmium concentration by
    about 10 mg/kg irrespective of differences in the intake in food
    (Vahter, 1982).

         Normal urinary excretion of cadmium is low. In chronic
    injection studies in mice, average daily urinary cadmium excretion
    prior to the onset of tubular proteinuria was about 0.01-0.02% of
    the body burden (Nordberg, 1972) and in a second study (Elinder &
    Pannone, 1979), one month after repeated sub-cutaneous injection,
    daily urinary excretion was only 0.001% of body burden. Similar,
    low urinary excretion rates have been found in rabbits and monkeys
    (Nomiyama, 1973; Nomiyama & Nomiyama, 1976a, b; Nomiyama et al.,
    1979, 1982a). Over a range of doses, there was an increase in
    urinary excretion associated with an increase in cadmium content of
    the renal cortex (Nomiyama & Nomiyama, 1976a; Suzuki, 1980; Bernard
    et al., 1981). Studies in mice, rats and rabbits indicate that
    urinary excretion of cadmium increases slowly with increasing body
    burden but, as renal dysfunction develops, there is a sharp
    increase in excretion and a fall in hepatic and renal cadmium
    concentrations (Friberg, 1952; Axelsson & Piscator, 1966a; Nomiyama
    & Nomiyama, 1976a; Nordberg & Piscator, 1972; Suzuki, 1974).

         In humans not excessively exposed to cadmium, mean urinary
    cadmium concentrations range from < 0.5 = 2.0 g/L, or about 0.01%
    of body burden, and urinary excretion increases with age and
    increasing body burden (Nordberg et al., 1976; Elinder et al.,
    1978; Kowal et al., 1979). Urinary cadmium is mainly bound to
    metallothionein (Tohyama et al., 1981; Roels et al., 1983b).

         It is difficult to estimate the extent of biliary/gastrointestinal
    excretion after oral administration of cadmium since most of the faecal
    cadmium is unabsorbed material (approximately 95% of the dose). Animal
    studies of gastro-intestinal excretion after parenteral administration
    indicate that a few per cent of the dose is excreted in the faeces in
    the first few days after dosing and faecal excretion initially exceeds
    urinary excretion (Nomiyama, 1978; Friberg et al., 1985). The
    mechanism of faecal excretion may involve both sloughed off mucosal
    cells and excretion in bile. Biliary excretion of cadmium within 24
    hours after parenteral administration is dose-dependent (Cirkt &
    Tichy, 1974; Nomiyama, 1974; Klaassen & Kotsonis, 1977) and varies
    between 0.3% and 13% of the dose; after the initial rapid phase,
    excretion is the bile is about 0.02-0,04% of body burden, mostly
    associated with a fraction of molecular weight below 10,000
    (Nordberg et al., 1977; Elinder & Pannone, 1979). At low or
    moderate doses, faecal excretion is quantitatively about the same
    as urinary excretion.

         Minor routes of excretion include hair (Anke et al., 1976),
    breast milk (Schroeder & Balassa, 1961) and pancreatic fluid
    (Friberg et al., 1985) but collectively these make little
    contribution to total excretion or biological half-life.

         The slow excretion results in an extremely long biological
    half-life for cadmium, in mouse and rat, the half-life is about
    200-700 days (Friberg et al., 1985) and in squirrel monkey is
    more than 2 years (Nordberg, 1972). Estimates of biological half-
    lives based on animal experiments in mice, rats, rabbits, dogs and
    monkeys are highly variable and range up to 22 years in some
    primate species (Friberg et al., 1974; Nomiyama et al., 1978,
    1979). The retention functions are multi-phasic and the body
    contains several compartments with different half-lives. The half-
    time of the slowest compartment usually is greater than 20% of the
    lifespan of the animal.

    Toxicological studies

    Special studies on carcinogenicity

         Intramuscular or s.c. injection of cadmium metal of cadmium
    compounds caused injection site sarcomas (Heath et al., 1962;
    Kazantzis, 1963; Kazantzis & Hanbury, 1966; Haddow et al., 1964;
    Gunn et al., 1967; Nazari et al., 1967).

         Regeneration of Leydig cells following testicular necrosis
    induced by a single parenteral dose of cadmium salts has been
    interpreted as Leydig cell tumours (Gunn et al., 1963, 1965;
    Favino et al., 1968, Lucis et al., 1972). Other studies by
    injection or peroral administration have proved negative for
    interstitial testicular tumours (Schroeder et al., 1964, 1965;
    Loser, 1980) but the doses were lower than would cause renal damage
    and which have been encountered in man.

         Rats were exposed to cadmium at a concentration of 5 mg Cd/L
    in drinking water for 2 years. There were a total of 7 malignant
    tumours among 47 cadmium-exposed male animals compared with 2
    tumours in 34 controls but this difference was not statistically
    significant and it was concluded that cadmium was not carcinogenic
    (Kanisawa & Schroeder, 1969). However, the present reviewer
    concludes that this study would not meet modern requirements for an
    adequate carcinogenicity study.

         Three groups of 40 rats were exposed to cadmium chloride
    aerosols continuously for 18 m at concentrations of 12.5, 25 or 
    50 g/m3; a control group of 41 animals was also included. The
    experiment was terminated after 31 m when the incidence of lung
    tumours was 15%, 53% and 71% at the three increasing dose levels
    compared with a zero incidence of lung tumours in controls
    (Takenaka et al., 1983).

         A series of studies were performed to investigate the possible
    role of cadmium in the aetiology of cancer of the prostate. Three
    groups of rats received weekly s.c. injections of 0.022, 0.044 or
    0.087 mg Cd/rat as CdSO4 (average weight 220 g at start and 410 g
    at termination) for 2 years. A control group of rats was similarly
    injected with water. Although high tissue concentrations of cadmium
    were achieved (80 mg Cd/kg in the liver of the high dose group), no
    malignant changes were observed in the prostate and no significant
    differences in tumour incidence at other sites were found between
    exposed and control animals (Levy et al., 1973).

         In studies on the prostate carcinogenicity of cadmium sulfate
    after gavage, rats were given weekly doses of 0.08 to 0.35 mg/kg bw
    and mice received 0.44 - 1.75 mg/kg bw. Due to the low gastro-
    intestinal absorption, tissue levels after two years were low
    and the highest dose group of rats had average kidney cadmium
    concentrations of 5 mg/kg i.e. lower than in normal human adults.
    No differences in tumour incidence were seen between controls and
    treated rats or mice after two years and 18 months respectively
    (Levy et al., 1975; Levy & Clack, 1975).

    Special studies on mutagenicity and clastogenicity

          Drosophila exposed to various cadmium compounds failed to
    display any chromosomal abnormalities (Ramel & Friberg, 1971;
    Vorobjeva & Sabalina, 1975) and  in vitro studies on cultured
    human lymphocytes and fibroblasts were also negative (Paton &
    Alison, 1972; Deknudt & Deminatti, 1978; Kogan et al., 1978).
    Andersen et al., (1983) found that cadmium chloride (1.1 mg Cd/L)
    had a spindle-inhibiting effect on cultured human lymphocytes and
    showed that induction of metallothionein synthesis in these cells
    had a protective effect.

         Cadmium (as sulfate) at a concentration of 62 mg Cd/L in the
    culture medium caused a marked increase in the frequency of
    chromatid breaks, translocations and discentric chromosomes in
    cultured human leucocytes (Shiraishi et al., 1972) and Rohr and
    Bauchinger (1976) observed a reduced mitotic index in cultured
    hamster fibroblasts at 100 g Cd/L, with chromosomal aberrations at
    concentrations above 500 g/L. The effects on cultured hamster
    fibroblasts appeared to depend on the medium used (Deaven &
    Cambell, 1980).

         Watanabe et al., (1979) observed aneuploidy in rat oocytes
    after exposure to cadmium chloride  in vivo. When lambs received
    cadmium in feed (60 g Cd/kg) for 191 days there was a significant
    increase in extreme hypodiploidy which may be related to the
    spindle-inhibiting effect noted above (Doyle et al., 1974).

         After injection of 0.6 - 2.8 mg Cd/kg bw in mice, there was an
    increased frequency of chromatid breaks in bone marrow cells after
    6 h and chromosome gaps and breaks in spermatocytes (Felten, 1979).
    These effects may be associated with the acute effects on
    haemopoiesis and the testes.

         One cytogenetic study on Itai-Itai patients showed some
    chromosomal aberrations (Shiraishi et al., 1972) but another
    study was negative (Bui et al., 1975). Studies on cadmium workers
    have similarly been equivocal as Bui et al., (1975) found no
    chromosomal abnormalities whereas Deknudt & Leonard (1975) reported
    a significant increase in chromosomal anomalies in leucocytes from
    such workers. Mice examined three months after an i.p. dose of
    1.75 mg Cd/kg displayed no chromosomal abnormalities (Gilliavod &
    Leonard, 1975).

    Special studies on teratogenicity and fetotoxicity

         In experiments in a variety of animal species, teratogenic
    effects have been observed after single injections of high doses of
    cadmium (3 mg/kg bw or more). These effects have been demonstrated
    after i.v. injection of cadmium sulfate in hamsters (Ferm &
    Carpenter, 1968; Mulvihill et al., 1970; Ferm, 1971, 1972) and
    after i.p. or subcutaneous administration of cadmium chloride to
    rats or mice (Barr, 1973; Chernoff, 1973; Ishizu et al., 1973).
    The effects included cleft lip and palate and limb and tail

         The above teratogenicity studies all involved high parenteral
    doses but similar teratogenic effects have been seen after dosing
     per os (Scharpf et al., 1972). Pregnant rats were given daily
    doses of 20, 40, 60 or 80 mg CdCl2/kg bw by gavage on days 6 - 19
    of pregnancy, with simultaneous administration of sodium chloride.
    In addition to the skeletal abnormalities, the offspring were
    examined for soft tissue defects. These were found to include heart
    and kidney anomalies which were treatment but not dose related. At
    the lowest dose, heart abnormalities were detected in 19.7% of test
    fetuses, compared with 6.6% of controls; caudal ectopia of the
    kidney occurred in 15.7% of low-dose fetuses with no such
    abnormality in controls (Scharpf et al., 1972).

         In a long-term multigeneration study in mice in which cadmium
    was administered in drinking water at a concentration of 10 mg
    Cd/L, increased fetal mortality and malformations were observed
    (Schroeder & Mitchener, 1971). A high neonatal mortality (30.5%)
    occurred prior to weaning in the F1 and F2a litters.

         The teratogenicity of cadmium has been reviewed by Ferm &
    Layton (1981) and Ferm & Hanlon (1983). It has been reported that
    pretreatment of the dams with low doses of cadmium protects against
    a subsequent dose of cadmium at a level that would normally be
    teratogenic, presumably by inducing synthesis of metallothionein.
    In addition, protection is afforded by co-administration of zinc

    (Ferm & Carpenter, 1968; Daston, 1982) or selenium (Holmberg & Ferm,
    1969). Maternal zinc deficiency alone can produce congenital
    malformations (Hurley et al., 1971) and administration of cadmium
    to zinc-deficient animals further increased the incidence of
    malformations (Parzyck et al., 1978).

         Support of the hypothesis that cadmium induces a fetal zinc
    deficiency was provided by the observation that, after
    administration of cadmium at doses of 0.25-1.25 mg Cd/kg bw to
    pregnant rats on day 12 of gestation, there was a dose-related
    decrease in the fetal uptake of a dose of 65 mg zinc given 4 h
    later, and decreased activity of the fetal zinc-dependent thymidine
    kinase (Samarawickrama & Webb, 1979).

         Interactions with copper have also been observed and when
    pregnant goats were given high oral doses of cadmium in the diet
    (80-500 mg Cd/kg dry matter in a diet containing 10 mg Cu/kg) fetal
    death occurred in half of the offspring with neonatal death of the
    remainder (Anke, 1973). Very low copper concentrations were found
    in fetal liver and other organs and there were typical signs of
    copper deficiency.

         High doses of cadmium by injection caused placental damage and
    fetal deaths in rats and mice (Parizek, 1964; Parizek et al.,
    1986b; Chiquoine, 1965) and fetotoxicity was also seen in rats
    exposed by inhalation (Cvetkova, 1970).

         In most experiments in which adverse effects on the embryo/
    fetus were seen, the doses were very large and administered
    parenterally, conditions which are unlikely to occur in pregnant
    women. In view of the low placental transfer at realistic levels of
    exposure (see metabolic studies above), the protective effect of
    prior low-level exposure, and the nutritional complications of
    induced zinc and/or copper deficiency, the relevance for humans of
    the teratogenicity observed in these studies is doubtful and there
    are no reports of teratogenic effects in occupationally exposed
    women. In some such cases, however, birth weights of offspring of
    exposed mothers were lower than controls and a few cases of rickets
    were observed (Cvetkova, 1970).

    Other effects on reproductive organs and function

         Single injections of cadmium salts, equivalent to 1-3 mg Cd/kg
    bw caused dramatic testicular necrosis (Parizek & Zahor, 1956;
    Parizek, 1957). Within hours the testes undergo selective and
    complete destruction (Gabbiani et al., 1974); at a later stage,
    Leydig cells regenerate (Parizek, 1960; Allanson & Deansley, 1962).
    Similar doses also induce haemorrage and necrosis in ovaries of
    pre-pubertal rats (Parizek et al., 1968a; Kar et al., 1959).

         The cadmium induced testicular necrosis generally results in
    permanent infertility. Ramaya & Pomerantzeva (1977) found markedly
    reduced weights of testes with morphological changes in mice up to
    6 months after dosing; the animals were sterile. Krasovskii et
    al., (1976) reported decreased sperm motility and lowered
    spermatogenic index in rats given cadmium in the diet at doses of
    0.5-5.0 mg Cd/kg bw.

         The extensive literature in this field has been reviewed by
    Barlow & Sullivan (1982). However, the circumstances of
    experimental exposure frequently are unrelated to the human chronic
    low-dose situation. There are no indications of impaired
    reproductive function or testicular atrophy in humans exposed to

    Acute toxicity

         The LD50 after injection of soluble cadmium compounds is in
    the range of 2.5-25 mg/kg bw (Friberg, 1950; Eybl & Sykora, 1966;
    Commission of the European Community, 1978). Shortly after
    injection, severe endothelial damage occurs in the small vessels of
    the peripheral nervous system and testes (Gabbiani, 1966; Parizek,
    1957). After some hours, marked liver changes are seen and liver
    damage may be the cause of death after acute parenteral

         For most compounds, the oral LD50 is 10-20 times that after
    parenteral administration (see Table 3). This is explicable by the
    relatively poor absorption of cadmium compounds from the
    gastro-intestinal tract.

         The acute effects on the gonads have been described above and
    probably result from initial endothelial damage in the vessels,
    oedema, decreased capillary blood flow, ischaemia and cell necrosis
    (Aoki & Hoffer, 1978; Francavilla et al., 1981). After parenteral
    administration of doses near the LD50, pronounced histological
    changes are seen in the small vessels of several organs/tissues.
    Hoffman et al., (1975) observed such changes in the liver of rats
    given 6 mg Cd/kg bw and Dudley et al., (1982) concluded that the
    liver was the major primary target organ for acute cadmium
    toxicity. This conclusion is supported by the fact that cadmium
    initially accumulates in the liver prior to translocation to the
    kidney. Acute changes in blood pressure have also been reported
    (Dalhamn & Friberg, 1954; Perry et al., 1970).

         Oral administration of single high doses of cadmium compounds
    causes desquamation of the epithelium, necrotic changes in the
    gastrointestinal mucosa and dystrophic changes in heart, liver and
    kidneys (Tarasenko et al., 1974; Vorobjeva & Sabalina, 1975).

    Table 3. Acute toxicity of orally-administered cadmium


    Species             Chemical form                LD50 (mg Cd/kg bw)

    Mouse               Cd metal                     890
                        CdO                          63
                        CdSO4                        47
                        CdCl2                        57
                        Cd(NO3)2                     48
                        CdI2                         51
                        CdCO3                        202
                        CdS                          907
                        Cd caprylate                 85
                        Cd stearate                  98
                        Cd sulphoselenide            1623
                        Ba-Cd stearate               258
                        CdTe                         > 7500

    Rat                 Cd caprylate                 270
                        Cd stearate                  203
                        Ba-Cd stearate               161

    (From: Tarasenko et al., 1974; Vorobjevo & Sabalina, 1975;
    Vorobjevo & Bubnova, 1981)

    Short-term studies

         Numerous short-term studies have been performed, mainly aimed at
    investigating the pathogenesis of kidney lesions and the critical levels
    of cadmium associated with adverse effects in the renal cortex. However,
    the results are not always readily interpretable since renal cadmium
    levels fall with the onset of proteinuria.

         Renal lesions consequent on the administration of cadmium were
    first reported in cats by Prodan (1932) and in rats by Wilson
    et al., (1941). In cats, the lesions occurred after oral
    administration of 100 mg Cd/day for one month and were characterized by
    desquamation in proximal tubular epithelium with no changes in the
    glomeruli. Wilson et al., (1941) reported slight renal tubular changes
    after administration of a diet containing 62 mg Cd/kg to rats.

         A summary of subsequent short-term studies in which the levels of
    cadmium in the kidney were determined is given below.


         Mice received daily subcutaneous injections of 0.25 or 0.5 mg Cd/kg
    bw for 6 months. Total kidney cadmium concentrations at termination were
    110-170 mg/kg in the lower dose group and about 170 mg/kg in the high
    dose group. These concentrations correspond to about 138-212 mg Cd/kg in
    the renal cortex (assuming kidney cortex concentrations are about 1.25
    times whole kidney concentrations). No effects were reported at the
    lower dose but tubular proteinuria was observed in the higher dose group
    (Nordberg & Piscator, 1972).


         Groups of 3-5 male Sprague Dawley rats, body weight 240 g, were
    given s.c. injections of 0.5 mg Cd/kg bw daily for 30, 48 or 54 days.
    Urinary protein concentration increased in the 5th week, when the kidney
    cadmium concentration was 100 mg/kg (equivalent to 125 mg/kg in renal
    cortex). Urine volume increased in the eighth week (kidney cadmium 150
    mg/kg) and by the ninth week, urinary protein and urinary cadmium were
    markedly elevated (Suzuki, 1974).

         A group of Wistar rats, initial bw 250 g, were given s.c. doses of
    1 mg Cd/kg bw three times a week; 3-5 animals were sacrificed every four
    weeks to measure cadmium in the kidney, and protein and ribonuclease
    activity were measured in the urine. Urinary cadmium and protein began
    to increase in the eighth week when the kidney cadmium concentration was
    170 mg/kg. By the tenth week, kidney cadmium had increased to 200 mg/kg
    and urinary ribonuclease levels began to rise (Kishino et al., 1975).

         A group of 4 male rats were given i.p. doses of cadmium chloride of
    0.75 mg/kg twice weekly for 10 months. In two animals, the cadmium
    concentration in kidney was 168 mg/kg and the concentration in urine was
    1.58 mg/L; there was marked total proteinuria with histological changes
    both in renal tubules and glomeruli (Murakami et al., 1974).

         Sprague Dawley rats were given cadmium in drinking water at
    concentrations of 10, 50, 100 or 200 mg Cd/L for 8.5 months. No
    significant histological changes were seen in the lowest dose group in
    which the kidney cadmium concentration was 12 mg/kg (15 mg/kg in renal
    cortex). Slight histological changes occurred in the 50 mg/L dose group
    in which the kidney cadmium levels was 38 mg/kg (44 mg/kg in cortex) and
    became progressively more marked at the two highest dose levels when the
    kidney cadmium was 90 and 145 mg/kg (113 and 181 mg/kg in cortex)
    respectively (Kawai et al., 1976). This study provides evidence of
    treatment-related changes in the kidney at renal cortex levels of
    cadmium as low as 44 mg/kg and the no effect level was 15 mg Cd/kg in
    the cortex. Kajikawa et al., (1981) also reported morphological
    changes in the kidneys of rats given drinking water containing 200 mg
    CdCl2/L for 91 weeks. Histologically there were degenerative

    changes in the proximal tubule and, at the electron microscope level,
    proliferation of smooth endoplasmic reticulum and vacuolization and
    coagulative necrosis of the tubular cells. No significant changes were
    seen in glomeruli or interstitial tissue.

         Three pairs of Sprague Dawley rats received drinking water
    containing 0.5, 5 or 50 mg CdCl2/L for 18 m and one animals from each
    group was sacrificed. Slight histological changes were seen in the renal
    tubules of the rats given 50 mg CdCl2/L and the kidney cadmium
    concentration was 100 mg/kg, equivalent to 125 mg/kg in the cortex
    (Murakami et al., 1974).

         When rats were given cadmium in drinking water at a concentration
    of 7.5 mg Cd/L for 12 months, an increase in urinary ribonuclease
    activity was seen; the concentration of cadmium in renal cortex was
    found to be 90 mg/kg (Piscator & Larsson, 1972). In a similar study in
    which female rats were given 200 mg Cd/L in drinking water for 11
    months, the average concentration of cadmium in the cortex was 200 mg/kg
    and this was accompanied by low molecular weight (tubular) and total
    proteinuria (Bernard et al., 1981). Rats given a lower concentration
    of 50 mg Cd/L in water for 3 months were reported to have acquired
    cadmium levels of 100 mg/kg in whole kidney (125 mg/kg cortex) and to
    display functional deficits (decreased inulin clearance and p-amino
    hippuric acid secretory Tm); histological abnormalities were also in
    evidence (Kawamura et al., 1978). Conversely, rats similarly exposed
    for 6 months were reported to have lower renal cortical cadmium levels
    of 50 mg/kg but, again, histological changes were apparent (Aughey
    et al., 1984).


         Groups of rabbits were given sub-cutaneous doses of 0.25 mg Cd/kg
    bw for 2.5 and 4 months by which times the renal cortex cadmium
    concentrations were 235 and 460 mg Cd/kg, respectively. At the lower
    concentration there were slight histological changes in the proximal
    tubules which were more severe at the higher level and accompanied by
    reduced alkaline phosphatase activity in the renal cortex and total
    proteinuria (Axelsson & Piscator, 1966a; Axelsson et al., 1968). In
    similar studies by subcutaneous administration, rabbits received 0.5 mg
    Cd/kg bw for 0.7 and 2.5 months, leading to renal cortical cadmium
    concentrations of 200 and 300 mg/kg, respectively. In both cases,
    proteinuria was observed (Nomiyama et al., 1982b; Nomiyama & Nomiyama,
    1982). After 0.7 months exposure the rabbits displayed glucosuria and
    aminoaciduria, and there was a decrease in inulin clearance and in

         In other studies by subcutaneous administration, rabbits given 0.5
    mg Cd/kg for 1 month displayed beta-2-microglobulinuria at a renal
    cortex concentration of 120 mg/kg (Nomiyama et al., 1982b) and early
    work had revealed decreased tubular reabsorption at 50-200 mg Cd/kg

    renal cortex after s.c. administration of 1.5 mg Cd/kg for one month
    (Nomiyama, 1973; Nomiyama et al., 1978). However, after administering
    cadmium to rabbits s.c. at a dose level of 0.5 mg/kg bw for two months,
    Kawai et al., (1976) reported only slight histological changes when
    the levels of cadmium in the renal cortex were about 200 mg/kg.

         Administration of cadmium to rabbits in drinking water at a
    concentration of 160 mg/l for 6 months resulted in average levels of
    cadmium in the kidney of 170 mg/kg (212 mg Cd/kg renal cortex) and this
    was associated with marked histological changes and extensive fibrosis
    (Stowe et al., 1972).

         When cadmium was administered in drinking water to rabbits at
    concentrations of 50 or 200 mg/L for 10 months, the resultant levels in
    renal cortex were 58 and 200 mg/kg, respectively. At the lower level
    there was slight tubular atrophy but at the higher level severe
    interstitial and tubular fibrosis were in evidence (Kawai et al.,

         Dietary administration of cadmium to rabbits at a level of 300
    mg/kg diet for 4, 10 or 11 months resulted in cadmium levels in the
    renal cortex of 200, 300 and 250 mg/kg; at the lowest level
    aminoaciduria and elevated urinary enzyme levels were recorded, beta-2-
    microglobulinuria was evident at the intermediate level and there was
    proteinuria and glucosuria at the highest level (Nomiyama et al.,
    1975; 1982b).

         Twenty-one male rabbits were divided into three groups; two groups
    received cadmium chloride in the diet at a concentration of 300 mg/kg
    for 19 and 44 weeks respectively while the third group served as
    controls. The treated animals displayed proteinuria and aminoaciduria by
    week 19 and it continued to increase in severity when treatment was
    continued for 44 weeks. After cessation of treatment, animals which had
    received cadmium for 44 weeks showed only slight improvement.
    Proteinuria, aminoaciduria and liver function which had not returned to
    normal after 24 weeks; anaemia also did not readily recover. Conversely,
    animals treated for 19 weeks recovered from the effects of cadmium;
    proteinuria and aminoaciduria in most animals disappeared soon after the
    end of the cadmium exposure, plasma GTP fell after 1 week and
    haemoglobin and haematocrit returned to normal after 6-11 weeks. It was
    concluded that the mild cadmium-induced health effects are reversible in
    the rabbit but more severe injury is not readily reversible (Nomiyama &
    Nomiyama, 1984).

         In a study designed to determine the critical level of unbound
    cadmium in rabbit renal cortex which causes renal injury, 15 male
    rabbits were given single i.v. doses of cadmium chloride of 0, 0.25,
    0.5 or 1.0 mg Cd/kg simultaneously with excess mercaptoethanol to
    prevent binding to plasma proteins. The critical concentration of

    unbound cadmium in the renal cortex at which proteinuria was observed
    was 13 mg/kg and it was suggested that the non-metallothionein bound
    cadmium concentration was a better index of critical concentration than
    total cadmium in the renal cortex (Nomiyama & Nomiyama, 1986).


         Pigs were given cadmium chloride in the diet at concentrations of
    50, 150, 450 and 1350 mg/kg. A decrease in leucine aminopeptidase
    activity was observed at a renal cadmium concentration of 78 mg/kg
    (equivalent to 100 mg/kg in renal cortex). At the lowest cadmium level
    of 12 mg/kg, the only effect was an equimolar increase in zinc in the
    kidney (Cousins et al., 1973).


         Ten male rhesus monkeys were divided into four groups of 2, 2, 3
    and 3 and were fed daily 100 g food containing 0, 3, 30 and 300 mg Cd/kg
    respectively. Urine was collected every 2 weeks and blood samples every
    4 weeks. One monkey from each of the two top treatment groups was
    sacrificed at week 24 for pathological examination and determination of
    tissue cadmium levels.

         The lowest dose group did not show any effect of treatment over a
    period of 55 weeks. The 30 mg/kg group showed no significant changes for
    up to 24 weeks although urine levels were up to 18 g Cd/L and, in the
    animal sacrificed at this time, the renal cortex cadmium concentration
    was 300 mg/kg. In this group plasma urea nitrogen and urine protein
    increased after 30 and 36 weeks. After 55 weeks, qualitative tests were
    negative for low molecular weight proteinuria and glycosuria; blood
    analyses and liver and kidney function tests were essentially normal
    although the cadmium concentrations in the renal cortex of the two
    monkeys were 460 and 730 mg/kg and those in the liver were 110 and 160
    mg/kg, respectively.

         In the highest exposure group, renal dysfunction was observed as
    total proteinuria, increased excretion of beta-2-microglobulin and
    retinol binding protein, glucosuria, aminoaciduria, decreased
    creatinine clearance and decreased tubular reabsorption of phosphate.
    Cadmium concentrations in renal cortex and liver of the two monkeys
    was 350 and 580 mg/kg, and 410 and 630 mg/kg, respectively. The
    critical cadmium concentration in the renal cortex was estimated as
    380 mg/kg for low molecular weight proteinuria and 470 mg/kg for
    proteinuria, glucosuria and aminoaciduria. The apparent biological
    half-life of cadmium at autopsy was calculated to be 22.4, 5.2, 6.4
    and 0.66 years for the 0, 3, 30 and 300 mg/kg groups, respectively
    (Nomiyama et al., 1979).

         In a second experiment, 35 rhesus monkeys were divided into five
    groups and each group were fed pelleted food containing 0, 3, 10, 30 or
    100 mg/g respectively at a daily dose of 100 g for one month, 150 g for
    the next 13 months and 200 g for the following 16 months, urine and
    blood samples were examined every 3rd and 6th week respectively. One
    animal from each group was sacrificed for tissue cadmium determination
    and pathological examination after 60 and 101 weeks; additional animals
    were sacrificed from the top dose group after 39 and 50 weeks, and from
    the 30 mg/kg group after 77 weeks and similarly examined.

         No adverse effects were recorded in the 3 mg/kg group. In the 10
    mg/kg group, slight pathological changes were observed in the tubular
    epithelium during the 101st week but no other adverse effects were
    noted. In the 30 ppm group, slight proteinuria (described as
    "negligible") was detected after 58 weeks but no pathological changes
    were seen and cadmium concentration in the renal cortex after 60 weeks
    was 809 mg/kg. During the 101st, week slight pathological changes were
    observed in the tubular epithelium in this dose group when the renal
    cortex cadmium concentration was 844 mg/kg. It was concluded that the
    critical concentration for proteinuria was 780 mg/kg for proteinuria and
    in excess of 840 mg/kg for histopathological changes.

         In the 100 mg/kg close group, slight proteinuria, aminoaciduria and
    beta-2-microglobulinuria occurred after the 39th-42nd week when the
    cadmium concentration in the renal cortex was 635 mg/kg. Subsequently,
    marked proteinuria, aminoaciduria and decreases in renal function were
    observed during the 48th-54th week when the cadmium concentration in the
    cortex was 612 mg/kg. Renal function further deteriorated with time of
    exposure and, at termination, marked tubular pathology was evident.
    After 101 weeks the cadmium concentration in the renal cortex was 560

         These results were taken to indicate that the critical
    concentration for proteinuria, aminoaciduria, beta-2-microglobulinuria,
    glycosuria, renal dysfunction and pathological changes were all
    approximately 635 mg/kg. However, other changes (elevated plasma enzymes
    and anaemia) were detected after 6 and 54 weeks, respectively, in the
    100 mg/kg dose group (Nomiyama et al., 1982a).

         Forty male and female rhesus monkeys were divided into eight groups
    (4-8 per group). Half were given a diet containing cadmium chloride at
    a level of 3 mg/kg for one year and then at a level of up to 30 mg/kg
    for a further 2 years. The other half were given no additional cadmium
    above normal pelleted food. Some animals received diets low in calcium
    and/or vitamin D. No proteinuria was noted after 3 years and no
    abnormalities in creatinine clearance or phenolsulphophthalein test.
    Cadmium concentrations in the renal cortex of monkeys given cadmium and
    maintained on a low calcium and vitamin D deficient diet were between

    611 and 1017 mg/kg after the third year of the experiment. Biopsy
    specimens of renal cortex form 2 monkeys given cadmium in an adequate
    diet contained 624 and 1255 mg/kg respectively at the 50th month
    (Tertiary Monkey Experiment Team, 1983).

    Long term studies


         In a long-term study thirty seven male rhesus monkeys, age about 3
    years, were divided into five groups and given daily 200 g solid feed
    containing added cadmium chloride at concentrations of 0, 3, 10, 30 or
    100 mg Cd/kg respectively; the basal diet contained the minimum
    requirement of zinc of 6 mg/day (30 mg/kg) in order to avoid the
    protective effect of excess zinc and was found to contain 0.27 mg Cd/kg.
    The exposure was continued for up to 9 years. Urine and blood specimens
    were collected at three and six week intervals respectively and the
    animals were examined for haemopoietic, circulatory, liver and renal
    functions, calcium and phosphate metabolism and blood and urine metal
    levels. Lumbar X-ray examinations were carried out at 12 week intervals
    and animals were sacrificed at regular intervals for histopathological
    examination and determination of organ metal concentrations.

         Dose related decreases in weight and body length were recorded in
    the groups given 10 mg Cd/kg diet or more. Over 50% of the 100 mg/kg
    showed decreased erythrocyte counts after 120 weeks and a similar effect
    occurred after 240 weeks and 360 weeks in the 30 mg/kg group and 10
    mg/kg groups respectively. The anaemia was not accompanied by an
    increase in reticulocytes. The highest dose group had a higher blood
    pressure than other groups during the first 18 months but the age
    related increase in the controls was not seen in the test animals. No
    change was seen in ECG or pulse rate.

         The 100 mg/kg group displayed glucosuria, proteinuria after 48
    weeks and plasma creatinine and phosphorous clearance values were
    elevated. Plasma uric acid was elevated at 84 weeks and the frequency of
    aminoaciduria increased from 91 weeks Urine volume was increased from
    101 weeks and beta-2-microglobulin began to rise from 138 weeks and
    exceeded 2 mg/L at 172 weeks.

         The 30 mg/kg group showed an increase in plasma uric acid at 300
    weeks and from 306 weeks there was an increase in urine amino acids and
    plasma creatinine. Beta-2-microglobulinuria was noted at 311 weeks and
    exceeded 2 mg/L at 426 weeks; total proteinuria was observed at 384

         The onset of beta-2-microglobulinuria was later than other clinical
    indications of renal dysfunction in the 100 mg/kg dose group but these
    indicators coincided in the 30 mg/kg group. Despite the early clinical

    signs at 48 weeks in the top dose group, there was no marked
    aggravation of the condition over the following eight years and no
    case of renal failure developed.

         No abnormality of renal function was seen in the 3 or 10 mg/kg 
    dose groups.

         In the highest dose group, elevated plasma GOT and GPT were
    detected from 6 weeks and increased LDH and decreased plasma A/G ratios
    from 18 weeks. No other indications of liver dysfunction were seen in
    any dose group. No radiological or clinical biochemical changes in bone
    mineral metabolism were seen and serum vitamin D levels and metabolism
    in the kidney appeared normal (see also Short-term Studies, Tertiary
    Monkey Experiment Team, 1983).

         Histologically, dose dependant pathological changes were seen in
    the kidneys of the 10, 30 and 100 mg/kg groups but the lesions were only
    classified as mild to moderate. Even at the top two dose levels, the
    changes were not particularly progressive and only mild renal cortical
    fibrosis was evident at completion of the 9 year experiment. No
    osteomalacia or osteoporosis was observed in the femur.

         Cadmium excretion in the urine showed an exponential relationship
    to dose and duration of exposure and did not increase following signs of
    renal dysfunction Concentrations in the renal cortex increased to a
    maximum of 635 mg/kg at 39 weeks in the 100 mg/kg group, 1170 mg/kg at
    257 weeks in the 30 mg/kg groups and 1070 mg/kg at 216 weeks in the 10
    mg/kg group, after which there was a decrease irrespective of the
    absence or presence of renal dysfunction. Cadmium levels in the liver of
    the top dose group reached a maximum of 1040 mg/kg after 101 weeks but
    in all other groups it continued to rise until completion of the
    experiment when the levels were 106, 430 and 1400 mg/kg in the 3, 10 and
    30 mg/kg groups, respectively.

         Administration of cadmium caused a dose-dependent increase in
    copper and zinc concentrations in blood, plasma, renal cortex and liver.
    Organ levels of copper and zinc fell and urinary excretion of these
    metals increased following the onset of renal dysfunction.

         It was estimated that the critical concentration of cadmium in the
    renal cortex was 635 mg/kg in the 100 mg/kg group and 1170 mg/kg in the
    30 mg/kg group (Nomiyama et al., 1987).

         In a long-term study to investigate whether any difference in
    toxicity could be detected between cadmium in contaminated rice and
    inorganic cadmium, crab-eating monkeys were given diets containing rice
    to a level of 80 g Cd/day, or cadmium chloride to a level of 190 g
    Cd/day. Two animals on standard diets served as controls. The experiment
    was conducted over a period of 6 years. Effects due to treatment
    included high urinary cadmium (occasionally exceeding 10 g/L) but no

    changes could be detected in urinary beta-2-microglobulin, renal or
    hepatic function nor any other haematological or clinical biochemical
    index. Cadmium concentrations in the renal cortex and liver increased
    proportionally to the dose level and duration of exposure and renal
    cortex levels reached a maximal of 570 mg/kg after CdCl2 and 300
    mg/kg after contaminated rice (Nomiyama & Nomiyama, 1988).

         In the absence of significant treatment-related differences in
    organ function and pathology, and in the light of the different doses
    used in rice and as inorganic cadmium, it is not possible to reach
    conclusions about the relative toxicity of inorganic cadmium and that in
    contaminated rice.

    Effects on the liver

         Friberg et al., (1950) observed fibrosis in the liver of rabbits
    given repeated s.c. doses of cadmium and periportal and interlobular
    colgen deposition was found in rabbits after administration of 160 mg
    Cd/L in drinking water (Stowe, et al., 1972). In the latter case,
    liver cadmium concentration was 188 mg,/kg but liver function tests were
    normal. Dystrophic changes were observed after intragastric
    administration of cadmium caprylate at a dose corresponding to 47 mg
    Cd/kg bw and blood lactate was elevated (Tarasenko et al., 1974).
    Decreased glycogen has been recorded in the liver of rats given barium
    cadmium laurate in 8-10 daily doses of 169 mg/kg bw by gavage (Larionova
    et al., 1974) and glycogen depletion and increased levels of
    gluconeogenetic enzymes were reported after cadmium exposure (Merali et
    al., 1974; Chapatwala et al., 1982). In long-term studies in rabbits,
    amyloid deposition in the liver was associated with administration of
    cadmium in the diet at a level of 300 mg/kg diet (Kawai et al., 1976).
    In the studies reported above, changes in hepatic enzyme activities have
    been reported in rats, rabbits and monkeys.

    Effects on calcium metabolism and bone

         In view of the manifestations of Itai-Itai disease, considerable
    attention has been paid to the effects of cadmium on calcium metabolism
    and bone.

         Following pregnancy, female rats exposed to cadmium by inhalation
    showed radiological evidence of osteoporosis (Tarasenko & Vorobjeva,
    1973) and rats exposed subcutaneously showed osteoporosis and
    osteosclerosis. Histopathological examination showed an increase in
    osteoclasts and "mosaic" bone indicative of osteomalacia.

         Rats given 50 mg Cd/L in drinking water showed impaired calcium
    absorption (Sugawara & Sugawara, 1974) and histological changes in
    duodenal mucosa were seen in these rats and in Japanese quail

    (Richardson & Fox, 1974). Dietary cadmium was reported to cause negative
    calcium balance in rats and administration with a low protein, low
    calcium diet led to reduction in bone calcium and zinc levels.

         Impaired calcium absorption may be secondary to effects on the
    kidney and renal hydroxylation of 25-hydroxy-cholecalciferol to 1,
    25-dihydrocholecalciferol, the active form of vitamin D, was shown to be
    inhibited in rats by high dietary cadmium in normal but not in calcium
    deficient diets (Feldman & Cousins, 1973; Lorentzon & Larsson, 1977).
    Further, rats given cadmium by gastric intubation showed impaired
    response to stimulation of calcium absorption by 1-a-hydroxy-vitamin D3
    (Ando et al., 1981) and the concentration of calcium-binding protein
    in intestinal mucosa is reduced after exposure to cadmium (Fullmer et
    al., 1980).

         Numerous other studies have reported skeletal changes including
    decalcification, osteoporosis and osteomalacia after exposure of rats in
    the diet (Kawai et al., 1976; Takashima et al., 1980; Nogawa et
    al., 1981), drinking water (Itokawa et al., 1974; Kawamura et al.,
    1978), or after s.c. injection (Nogawa et al., 1981). Conversely,
    Kajikawa et al., (1981) were unable to detect either osteoporosis or
    osteomalacia in a long-term study in rats at 22 mg/L in drinking water.

         Monkeys receiving cadmium orally with a diet adequate in calcium
    and vitamin D did not develop osteomalacia in the absence of renal
    damage (Nomiyama et al., 19791.

         Most experiments suggest a direct effect of cadmium on bone
    mineralization, causing osteoporosis, and an indirect effect on calcium
    absorption via vitamin D hydroxylation.

    Effects on Haematopoiesis

         Anaemia is a common feature of cadmium intoxication in animals
    exposed orally or parenterally (Wilson et al., 1941; Friberg, 1950;
    Decker et al., 1958; Prigge et al., 1977). This probably results
    from impaired intestinal absorption of iron and may be ameliorated by
    dietary supplementation with iron or ascorbic acid (Fox & Fry, 1970; Fox
    et al., 1971).

         Parenteral cadmium caused destruction of erythrocytes (Berlin &
    Friberg, 1960) but there was no indication of either effects on
    haemoglobin synthesis or haemolytic anaemia having been reported in
    rabbits (Axelsson & Piscator, 1966b).

    Effects on blood pressure and the cardiovascular system

         Chronic exposure of rats to cadmium can induce hypertension
    (Schroeder & Vinton, 1962; Schroeder, 1964; Perry & Erlanger, 1974) but
    the effect appears to depend on the dose. Low doses (1-5 mg Cd/L in
    drinking water) for 1 year caused elevation of blood pressure but at
    higher doses (10-25 mg/L) a transient rise was observed which returned
    to normal by 1 year while at still higher levels of 50 mg Cd/L a
    decrease in blood pressure was observed after 12 months. Generally
    similar results were obtained by Perry et al., (1977) with the
    greatest increases in blood pressure being seen after prolonged exposure
    to low doses of cadmium and hypotension being associated with high

         The mechanisms by which cadmium affects blood pressure have been
    reviewed by Perry & Kopp (1983). At doses causing hypertension,
    increased circulatory renin activity was detected (Perry & Erlanger,
    1973) and both parenteral and chronic oral exposure was reported to
    increase sodium retention (Vander, 1962; Perry et al., 1971; Lener &
    Musil, 1971).

    Effects on the immune system

         Effects on the immune system have been reported after both acute
    and chronic exposure to cadmium. A decrease in antibody production and
    of antibody-forming cells in the spleen was seen in mice given cadmium
    in drinking water (Koller et al., 1975) and an inhibition of the cell-
    mediated immune response was seen in mice after repeated injections i.p,
    (Bozelka & Burkholder, 1982). There is no evidence of increased
    susceptibility to infections or other secondary effects of compromised
    immune surveillance.

    Observations in man

         As indicated above (see metabolic studies), absorption and
    retention of orally ingested cadmium in man typically is about 5% of the
    dose e.g., 4.7-7.0% in five adult men (Rahola et al., 1971) but may be
    influenced by other dietary components, and by iron and cadmium status,
    and there is considerable individual variation. Absorption of inhaled
    cadmium is greater than after oral ingestion.

         The slow excretion of cadmium results in an extremely long
    biological half-life for absorbed cadmium and this has variously been
    estimated at 10-33 years or 15-40% of the lifespan (Nordberg et al.,

         In humans, the longest half-lives are observed in muscle, liver and
    renal cortex (Kjellstrom, 1979; Friberg et al., 1974). Based on an
    eight-comportment model, the half-lives in liver and kidney were
    estimated to be 7.5 and 12 years, respectively (Kjellstrom & Nordberg,

    1978). Estimates based on a single compartment model range from 10 to
    30+ years (Kjellstrom, 1971; Tsuchiya & Sugita, 1971; Nordberg
    et al., 1985). Experimental studies using radioactive cadmium have
    variously shown biological half-lives of 26 years (Shaikh & Smith, 1980)
    and 93-202 days (Rahola et al., 1972; Flanagan et al., 1978;
    McLellan et al., 1978); the confidence limits in the study by Rahola
    et al., (1972) were given as 130 days to infinity.

         The biological half-life is shorter if there is renal tubular
    dysfunction. In three subjects with proteinuria, the average half-life
    in the liver, determined by neutron activation analysis, was 2 years
    whereas in nine other subjects without proteinuria, the half-life was
    13.5 years (Fletcher et al., 1982).

         Because of the long half-life in the kidney and probable continuing
    transfer from other tissues, accumulation will continue in the renal
    cortex. Mean levels of cadmium in renal cortex at mean age 50 found in
    various countries are shown in table 4.

         In summary, the average cadmium concentration in the renal cortex
    of a non-occupationally exposed person aged 50 years varies between
    11 - 100 mg/kg in different regions and the 90th percentile is about
    twice the median value in those groups studied.

         It has been calculated that a daily intake of 62 g would be
    required to reach a concentration of 50 mg/kg in the renal cortex at age
    50, assuming an absorption rate of 5%, that 10% of the absorbed daily
    dose is rapidly excreted and also that 0.005% of the total body burden
    is excreted and also that 0.005% of the total body burden is excreted
    daily. A similar calculation assuming that 0.01% of the total body
    burden is excreted daily showed that the daily intake would have to be
    88 g to reach the same final level in the renal cortex (Kjellstrom,
    1971). Essentially similar conclusions were reached later by Kjellstrom

         Using data gathered from the literature, a statistically
    significant relationship was established between average cadmium intake
    and average kidney cadmium concentration in various countries (Morgan &
    Sherlock, 1984). Using this relationship, it was concluded that a
    regular dietary intake of 175 g Cd/day would cause the concentration of
    cadmium in the renal cortex to reach a level of 200 mg/kg in 50 years.
    Taking the maximum dietary intake recorded in a U.K. one week duplicate
    diet study of 150 g Cd/day (Sherlock et al., 1983), it was
    calculated that levels in the renal cortex would reach 200 mg/kg in 60

    Table 4. mean renal cortex cadmium concentrations at age 50


    Country                      Renal cortex Cd   Reference
                                 (mg/kg wet

    Australia                    40                Miller et al., 1976
    Belgium      (Liege)         46                Vahter, 1982
    Canada                       55                Le Baron et al., 1977
    China                        18                Vahter, 1982
    Denmark                      40                Miljoministeriet, 1980
    Finland                      20 - 25           Vuori et al., 1979
    France                       19                Gretz & Laugel, 1982
    FRG                          10                Fischer & Weigert, 1975
    GDR                          11 - 22           Anke & Schneider, 1974
    India                        24                Vahter, 1982
    Japan        (Akita)         135               Kobayashi, 1983
                 (Kobe)          54                Kitamura et al., 1970
                 (Kanazawa)      95                Ishizaki, 1972
                 (Tokyo)         99                Tsuchiya et al., 1972
                 (Tokyo)         59 (men)
                                 55 (women)
    Norway                       30                Syverson et al., 1976
    Sweden                       11 - 23           Elinder et al., 1976
    U.K.                         21                Curry & Knott, 1970
    U.S.A.       (Dallas)        13 - 29           Kowal et al., 1979
                 (N. Carolina)   14 - 28           Hammer et al., 1973
    Yugoslavia                   38                Vahter, 1982

    Effects of exposure

         Acute intoxication in man has been reported following inhalation or
    oral ingestion. Acute effects after inhalation include chemical
    pneumonitis and sometimes pulmonary oedema (Elinder, 1985) and the onset
    of symptoms may be delayed for up to 24 hr. In severe cases, there may
    be respiratory insufficiency, shock and death.

         Acute oral intoxication has been recorded following the use of
    Cadmium-plated utensils and vessels in contact with acidic foods (U.S.
    Public Health Service, 1942; Cole & Baer, 1944; Lufkin & Hodges, 1944),
    and after consumption of drinks from a vending machine in which cadmium-
    containing solder had been used in construction of the water cooling

    tank (Nordberg et al., 1973). In the latter case the cadmium
    concentration was approximately 16 mg/L. The symptoms were rapid in
    onset and included nausea, vomiting, abdominal cramps and headache; in
    more severe cases diarrhoea and shock ensued.

         There is no evidence of the extreme effects on the gonads which is
    a feature of acute intoxication in animals.

         In relation to general population exposure, the cumulative chronic
    toxicity is more relevant than acute toxicity provided that the use of
    cadmium is food-contact materials is avoided. Much of the information on
    the chronic effects of cadmium in man has come from occupational
    exposure and excessive intake in the diet has been limited to only a few

         After occupational exposure by inhalation, the kidney is most
    frequently the critical organ although, under some conditions, the
    target organ may be the lung (Bonnel, 1955). After chronic oral
    exposure, the kidney is the critical organ. Fully developed intoxication
    among industrial workers may present the major features of emphysema and
    renal dysfunction similar to that described in animals. In addition,
    anaemia, impaired liver function and changes in bone mineralization may
    be seen.

         The metallothionein-bound cadmium is filtered by the glomeruli and
    reabsorbed and selectively concentrated in the proximal tubules. An
    early feature of the renal effects in man is impairment of the
    reabsorption functions of the tubules with an increase in urinary
    excretion of low-molecular weight proteins (tubular proteinuria; beta-2-
    microglobulinuria) (Friberg, 1950; Kazantzis et al., 1963; Piscator,
    1966). Renal injury may progress and, in severe cases, involve
    glomerular damage with proteinuria, aminoaciduria, glucosuria and
    phosphaturia. Deranged mineral metabolism in the kidney may cause
    resorption of calcium and phosphate from bone and signs of kidney stones
    and nephrocalcinosis have been reported in Swedish workers (Axelsson,
    1963) and osteomalacia has been seen in French (Gervais & Delpech, 1963)
    and English (Kazantzis. 1979) workers. Similar signs of renal
    dysfunction have been encountered in cadmium polluted areas in one such
    region. Ishizaki (1969) reported a high incidence of proteinuria and
    glucosuria. Comparisons of the effects of general environmental and
    industrial exposure to cadmium have confirmed that tubular proteinuria,
    aminoaciduria and other signs of tubular damage (Saito et al., 1977)
    occur in both situations.

         It has generally been found that tubular proteinuria, once
    manifest, persists even when exposure ceases (Piscator, 1966; Nogawa et
    al., 1979; Roels et al., 1982) although it has been claimed that mild
    renal effects may be responsible if exposure ceases (Tsuchiya, 1976) and
    this has been supported by animal experiments in rabbits (Nomiyama &
    Nomiyama, 1984) and monkeys (Akahori et al., 1983).

         Anaemia has been a common feature in cadmium-exposed workers
    (Bernard et al., 1979) but this is reversible and independent of renal
    damage. It appears that cadmium impairs absorption of iron (Fox et
    al., 1971) and does not directly affect haemopoiesis; an increased
    destruction of erythrocytes has also been reported in animal experiments
    (Elinder, 1985).

         The hypertension which has been observed in chronic animal studies
    at low doses has not been a consistent feature of human intoxication
    (Elinder, 1986). The prevalence of hypertension in polluted areas of
    Japan has not been found to be noticeably increased (Shigematsu et
    al., 1982) although Nogawa et al., (1975) found an increased
    mortality from cardio- and cerebrovascular disease among Japanese
    farmers with cadmium-induced proteinuria.

         As previously indicated, the renal damage caused by cadmium leads
    to deranged mineral metabolism due to effects on vitamin D hydroxylation
    which impairs absorption of calcium and bone mineralization; in
    addition, increased losses of calcium and phosphate occur in urine.
    Itai-Itai disease is an extreme manifestation of this which was first
    reported in Toyama, Japan (Kohno et al., 1956) and has since been
    reported from three other cadmium contaminated areas (Nogawa et al.,
    1975; Takabayashi, 1980); 132 cases with 94 deaths were officially
    recorded between 1967 and 1982 (Kato, 1983). The pathogenesis of Itai-
    Itai is not totally clear but in a particularly sensitive population of
    mainly post-menopausal, multiparous women, who were deficient in both
    calcium and vitamin D, cadmium appears to have played a role. The
    disease is characterized by severe osteomalacia and sufferers displayed
    tubular proteinuria of a similar type to that seen in workers
    occupationally exposed to cadmium. Cadmium alone may not be sufficient
    cause and a low cadmium and vitamin D intake were accompanying factors
    in both occupational and general environmental cases (Friberg et al.,
    1985; Kjellstrom, 1985).

    Human carcinogenicity

         Some epidemiological studies (Potts, 1965; Kipling & Waterhouse,
    1967; Winkelstein & Kantor, 1969) indicated an increased risk of cancer
    of the prostate in workers exposed to cadmium and an enhanced incidence
    of lung cancer was also indicated (Lemen et al., 1976; Kjellstrom et
    al., 1979). Subsequent studies (Armstrong & Kazantzis, 1983; Sorahan &
    Waterhouse, 1983; Andersson et al., 1984) have not provided good
    evidence for a casual association between industrial cadmium exposure
    and cancer of the prostate or lung and a study of mortality in Japanese
    cadmium-polluted areas revealed no definite increase in prostatic cancer
    (Shigematsu et al., 1982). IARC (1976) considered that "available
    studies indicate that occupational exposure to cadmium in some form
    (possibly the oxide) increases the risk of prostate cancer in man. In
    addition, one of these studies suggests an increased risk of respiratory
    tract cancer". IARC updated this evaluation in 1982 and concluded that

    cadmium and its components should be classified as carcinogenic group
    2B i.e. "probably carcinogenic to humans" with "sufficient evidence in
    animals and inadequate data in humans".


         Since the previous evaluation a large number of reviews have been
    carried out and these have been considered by the present Committee.

         Cadmium is a pollutant which affects many environmental sectors.
    The general population is exposed to cadmium principally from food and
    water. Although water is not a major contributor to cadmium intake for
    most individuals, elevated natural cadmium levels in water can occur and
    resultant cadmium intakes can be as large as the dietary contribution.
    Food normally represents the major source of cadmium exposure and
    available data indicate that the current intake of cadmium from the diet
    is most commonly 10-35 g/day. Non-food sources may also be a source of
    cadmium, e.g., smoking 20 cigarettes per day may contribute a further 
    1-4 g/day.

         Cadmium is a metal with an extremely long biological half-life in
    man. Even low exposure levels may, in time, cause considerable
    accumulation, especially in the kidneys.

         The kidney has been identified as the critical organ in relation to
    chronic exposure to relatively low levels of cadmium (Task Group on
    Metal Toxicity, 1976) and in particular the renal cortex. The critical
    tissue concentration of cadmium at which renal injury occurs is subject
    to inter-individual variation and the Population Critical Concentration
    (PCC) has been applied in relation to a specific response rate (e.g.,
    PCC50 = the concentration at which 50% of the human population studied
    have reached their individual critical concentration). In relation to
    cadmium, the first adverse functional change is usually a low molecular
    weight (LMW) proteinuria, and intakes in the range of 140-255 g/day
    have been associated with increased LMW proteinuria in the elderly. LMW
    proteinuria is not accompanied by any specific histological changes and
    the pathological significance of this finding is unclear. However, it
    can be used as an indicator of the threshold of a possible toxic effect
    and it is appropriate to set the PTWI on the basis of the dose-response
    data for this end-point.

         Using the concept of PCC, there are limited data on which to base
    an evaluation, particularly since the concentrations of cadmium in the
    renal cortex may fall when proteinuria occurs. Evidence of renal
    dysfunction in animal studies generally has been seen at renal cortex
    concentrations of 200-400 mg/kg, but there is evidence of effects at
    even lower concentrations. In humans with no, or only slight, changes in
    renal tubular function, cadmium levels in the renal cortex have varied,
    with few exceptions, between 100 and 450 mg Cd/kg and studies aimed at
    determining critical concentrations in the renal cortex have yielded
    estimates of about 200 mg Cd/kg for the PCC10. This, of course, does not
    represent a no-effect-level.

         Using dose-response analysis for individual critical
    concentrations, a 10% prevalence rate for LMW proteinuria would be
    estimated to occur after 45 years exposure to dietary intakes of 200 g
    Cd/day for a 70 kg person. From regression analysis of cadmium intake
    and mean kidney cadmium concentration in various countries, essentially
    similar estimates result i.e. the PCC10 of 200 mg Cd/kg renal cortex
    would be attained after a dietary intake of 175 g Cd/day for 50 years.
    As LMW proteinuria can be demonstrated among people over 50 at a daily
    intake of 140-255 g/day, this confirms that these estimates are
    reasonable and that there is only a relatively small safety margin
    between exposure in the normal diet and those which produce effects.

         In view of estimates that daily intake of 100 g Cd/day would lead
    to about 2% of the population exceeding their individual critical
    concentration, levels of cadmium in foods and total diet should continue
    to be monitored and should not rise further. The Committee reiterated
    its previously stated position that the use of cadmium-plated utensils
    in food processing or preparation should be discouraged and galvanized
    equipment should be avoided where possible. Likewise, leachable cadmium
    in enamel and pottery glazes may be a source of contamination and
    cadmium-based pigments and stabilizers should not be used in food
    contact plastics. The use of phosphate fertilizers and sewage sludge on
    agricultural land may be a significant source of cadmium and, in some
    circumstances this use could lead to elevated levels in crops. Attempts
    should be made to minimize accumulation in the crops from such
    agricultural sources of cadmium.

         In order that levels of cadmium do not exceed 50 g/g in renal
    cortex, assuming an absorption rate of 5% and a daily excretion of
    0.005% of body burden, total intake should not exceed about 1 g/kg
    bw/day continuously for 50 years. The provisional tolerable weekly
    intake for cadmium was therefore set at 7 g/kg bw.

         Since the PTWI is derived from estimated accumulation of cadmium
    over a period of 50 years at an exposure rate equivalent to 1 /kg
    bw/day for adults, excursions above this figure may be tolerated
    provided that they are not sustained for a long period of time and do
    not produce a significant increase in integrated lifetime dose. In
    particular, it is recognized that this exposure will not be uniform with
    age. The Committee noted that the estimate of the PTWI does, in fact,
    take into account the higher cadmium intake on a body weight basis by
    infants and children.

         It is recommended that biological monitoring of groups exposed to
    relatively high levels of cadmium should be carried out with a view to
    providing supplementary data to that obtained from estimates of dietary


    Ahokas, R.A. & Dilts, P.V. (1979). Cadmium uptake by the rat embryo as
    a function of gestation age.  Am. J. Obstet. Gynecol., 135, 219-222.

    Akahori, F., Nomiyama, K., Masaoka, T., Nomiyama, H., Nomura, Y.,
    Kobayashi, K. & Suzuki, T. (1983). [Effects on monkeys of long-term
    exposure to cadmium chloride,] Japan Public Health Association, Tokyo,
    pp. 1-27 (Kankyo Hoken Report No. 49) (in Japanese).

    Allanson, M. & Deansley, R. (1962). Observations on cadmium damage and
    repair in rat testes and the effects on the pituitary gonads.
     J. Endocr., 24, 453-462.

    Andersen, O., Ronne, M. & Nordberg, G.F. (1983). Effects of inorganic
    metal salts on chromosome length in human lymphocytes.  Hereditas, 98,

    Andersson, K., Elinder, C.-G., Hogstedt, C., Kjellstrom, T. & Spang, G.
    (1984). Mortality among cadmium workers in a swedish battery factory.
    In:  Proceedings of the 4th International Cadmium  Conference. Munich,
     March 1983, Cadmium Association, London, pp. 152-154.

    Ando, M., Shimizu, M., Sayata, Y., Tanimura, A. & Tobe, M. (1981). The
    inhibition of vitamin D-stimulated intestinal calcium transport in rats
    after continuous oral administration of cadmium.  Toxicol. appl.
     Pharmacol., 61, 297-301.

    Anke, M. (1973). [Copper deficiency induced effects in sheep and deer].
     Monatshefte f. Vet. Med., 25, 805-809 (in German).

    Anke, M. & Schneider, H.J. (1974). [The trace element concentration of
    human kidneys as a function of age and sex].  Z Urol., 67, 357-362 (in

    Anke, M., Hennig, A., Schneider, H.J., Groppel, B., Grun, M.,
    Partschefeld, M. & Ludke, H. (1976). [The influence of the toxic element
    cadmium on the metabolism and health of animals and humans]  Math-
     Naturwiss, R., 25, 241-261 (in German).

    Aoki, A. & Hoffer, A.P. (1978). Re-examination of the lesions in rat
    testis caused by cadmium.  Biol. Reprod., 18, 579-591.

    Armstrong, B.G. & Kazantzis, G. (1983). The mortality of cadmium
    workers.  Lancet, 1, 1424-1427.

    Aughey, E., Fell, G.S., Scott, R. & Black, M. (1984). Histopathology of
    early effects of oral cadmium in the rat kidney.  Environ. Health
     Perspect., 54, 153-161.

    Axelsson, B. (1963). Urinary calculus in long-term exposure to cadmium.
    In: Sangro, P., Akoun, G. & Beate, H.L. (eds)  Proc. 14th Int. Congr.
     Occup. Hlth. Madrid, Int. Congr. Ser. 62. Excerpta Medica Foundation,

    Axelsson, B. & Piscator, M. (1966a). Renal damage after prolonged
    exposure to cadmium: an experimental study.  Arch. environ. Health, 12,

    Axelsson, B. & Piscator, M. (1966b). Serum proteins in cadmium-poisoned
    rabbits with special reference to haemolytic anaemia.  Arch. environ.
     Health, 12, 374-381.

    Axelsson, B., Dahlgren, S.E. & Piscator, M. (1968). Renal lesions in the
    rabbit after long-term exposure to cadmium.  Arch. environ. Health,
    17, 24-28.

    Barlow, S.M. (ed.) & Sullivan, F.M. (1982). Cadmium and its compounds.
    In:  Reproductive hazards of industrial chemicals. An evaluation of
     animal and human data, London, Academic press, pp. 137-173.

    Barr., M. (1973). The teratogenicity of cadmium chloride in two stocks
    of Wistar rats.  Teratology, 7, 237-242.

    Berlin, M. & Friberg, L. (1960). Bone marrow activity and erythrocyte
    destruction in chronic cadmium poisoning.  Arch. environ. Health, 1,

    Bernard, A., Buchet, J.P., Roels, H., Masson, P. & Lauwerys, R. (1979).
    Renal excretion of proteins and enzymes in workers exposed to cadmium.
     Eur. J. clin. Invest., 9, 11-22.

    Bernard, A., Lauwerys, R. & Gengoux, P. (1981). Characterization of the
    proteinuria induced by prolonged oral administration of cadmium in
    female rats.  Toxicology, 20, 345-357.

    Bonnel, J.A. (1955). Emphysema and proteinuria in men casting
    copper-cadmium alloys.  Br. J. int. Med., 12, 181-197.

    Bonnel, J.A., Kazantzis, G., & King, E. (1959). A follow-up study of men
    exposed to cadmium oxide fume.  Br. J. int. Med., 16, 135-147.

    Bozelka, B.E. & Burkholder, P.M. (1982). Inhibition of mixed leukocyte
    culture response in cadmium-treated mice.  Environ. Res., 27, 421-432.

    Bui, T.-H., Lindsten, J. & Nordberg, G.F. (1975). Chromosome analysis of
    lymphocytes from cadmium workers and Itai-Itai patients.  Environ.
     Res., 9, 187-195.

    Chapatwala, K.D., Hobson, M., Desaiah, D. & Rajanna. B. (1982). Effect
    of cadmium on hepatic on hepatic and renal gluconeogenic enzymes in
    female rats.  Toxicol. Lett., 12, 27-34.

    Chaube, S., Nishimura, H. & Swinyard, C.A. (1973). Zinc and cadmium in
    normal human embryos and fetuses.  Arch. environ. Health, 26, 237-240.

    Cherian, M.G., Goyer, R.A. & Valberg, L.S. (1978). Gastrointestinal
    absorption and organ distribution of oral cadmium chloride and cadmium
    metallothionein in mice,  J. Toxicol. environ. Health, 4, 861-868.

    Chernoff, M. (1973). Teratogenic effects of cadmium in rats.
     Teratology, 8, 29-32.

    Cherry, W.H. (1981). Distribution of cadmium in human tissues. In:
    Nriagu, J.A. (ed.)  Cadmium in the environment. John Wiley & Sons, New
    York, Vol. II, pp. 69-536.

    Chiquoine, A.D. (1965). Effect of cadmium chloride on the pregnant
    albino mouse. Y.  Reprod. Fert., 10, 263-265.

    Cirkt, M. & Tichy, M. (1974). Excretion of cadmium through bile and
    intestinal wall in rats.  Br. J. int. Med., 31, 134-139.

    Cole, G.M. & Baer, L.S. (1944). Food poisoning from cadmium. US Naval
    Medical Bulletin, 43, 398-399.

    Commission of the European Communities (1978). Criteria (dose-effect
    relationships) for cadmium, Pergamon Press, Oxford, 202 pp (Report of
    the Working Group of Experts prepared for the CEC, Luxembourg,
    Directorate-General for Social Affairs, Health and Safety Directorate).

    Cousins, R.J., Barber, A.K. & Trout, J.R. (1973). Cadmium toxicity in
    growing swine.  J. Nutr., 103, 964-972.

    Curry, A.S. & Knott, A.R. (1970). Normal levels of cadmium in human
    liver and kidney in England.  Clin. Chim. Acta, 30, 115-118.

    Cvetkova, R.P. (1970). [Materials on the study of the influence of
    cadmium compounds on the generative function]  Gig. Tr. Prof. Zabol.,
    14, 31-33 (in Russian with English summary).

    Dabeka, R.W., McKenzie, A.D. & Lacroix, G.M.A. (1987). Dietary intakes
    of lead, cadmium, arsenic and fluoride by Canadian adults: a 24-hour
    duplicate diet study.  Food Additives and Contaminants, 4, 89-102.

    Dalhamn, T. & Friberg, L. (1954). The effect of cadmium on blood
    pressure and respiration and the use of dimercaprol (BAL) as antidote.
     Acta Pharmacol. Toxicol., 10, 199-203.

    Daston, G.P. (1982). Fetal zinc deficiency as a mechanism for
    cadmium-induced toxicity to the developing rat lung and pulmonary
    surfactant.  Toxicology, 24, 55-63.

    Deaven, L.L. & Campbell, E.W. (1980). Factors affecting the induction of
    chromosomal aberrations by cadmium in Chinese hamster cells.  Cytogenet.
     Cell Genet., 26, 251-260.

    Decker, L.E., Byerrum, R.U., Decker, C.F., Heppert, C.A. & Langham, R.F.
    (1958). Chronic toxicity studies. I. Cadmium administered in drinking-
    water to rats.  AMA Arch. Ind. Health., 18, 228-231.

    Deknudt, G. & Leonard, A. (1975). Cytogenetlc investigations on
    leukocytes of workers from a cadmium plant.  Environ, Physiol.
     Biochem., 5, 319-327.

    Deknudt, G. & Deminatti, M.L. (1978). Chromosome studies in human
    lymphocytes after  in vitro exposure to metal salts.  Toxicology, 10,

    Doyle, J.J., Pfander, W.H., Crenshaw, D.B. & Snethen, J.H. (1974).
     Interface. 3, 9.

    Dudley, R.E., Svoboda, D.J. & Klaassen, C.O. (1982). Acute exposure to
    cadmium causes severe liver injury in rats.  Toxicol. appl.
     Pharmacol., 65, 302-313.

    Elinder, C.G., Kjellstrom, T., Linnman, L. & Pershagen, G. (1978).
    Urinary excretion of cadmium and zinc among persons from Sweden.
     Environ. Res., 15, 473-484.

    Elinder, C.G. & Pannone, M. (1979). Biliary excretion of cadmium.
     Envir. Health Perspect., 28, 123-126.

    Elinder, C.G. (1985). In: Friberg, L., Elinder, C.G., Kjellstrom, T. &
    Nordberg, G.F. (eds.)  Cadmium and Health. A Toxicological and
     Epidemiological Appraisal, CRC Press, Boca Raton, Florida, Chapter 8.

    Elinder, C.G. & Nordberg, M. (1985). In: Friberg, L., Elinder, C.G.,
    Kjellstrom, T. & Nordberg, G.F. (eds.)  Cadmium and Health. A
     Toxicological and Epidemiological Appraisal. CRC Press, Boca Raton,
    Florida, Chapter 4.

    Elinder, C.G. (1986). In: Friberg, L., Elinder, C.G., Kjellstrom, T. &
    Nordberg, G.F. (eds.)  Cadmium and Health. A Toxicological and
     Epidemiological Appraisal, CRC Press, Boca Raton, Florida, Chapter 11.

    Engstrom, B. & Nordberg, G.F. (1979). Factors influencing absorption and
    retention of oral 109Cd in mice: age, pretreatment, and subsequent
    pretreatment with non-radioactive cadmium.  Acta Pharmacol. Toxicol.,
    45, 315-324.

    Evans, G.W., Majors, P.F. & Cornatzer, W.E. (1970).  Biochem. biophys.
     Res. Comm., 40, 1142.

    Eybl, V. & Sykora, J. (1966). [The protection by chelating agents in
    acute cadmium poisoning].  Acta Biol. Med. German, 16, 61-64 (in

    FAO/WHO Joint Food Contamination Monitoring Programme (1986). Global
    Environment Monitoring Programme. Report of the Fourth Session of the
    Technical Advisory Committee, Geneva, 9-13 September 1985.

    Favino, A., Cavalleri, A., Nazari, G. & Tilli, M. (1968). Testosterone
    excretion in cadmium chloride-induced testicular tumors in rats.
     Med. Lav., 59, 36-40.

    Feldman, S.L. & Cousins, R.G. (1973). Influence of cadmium on the
    metabolism of 25-hydroxy-cholecalciferol in chicks.  Nutr. Rep. Int.,
    8, 251-259.

    Felten, T.L. (1979). A preliminary report of cadmium-induced chromosomal
    changes in somatic and germinal tissues of C57BI/6J male mice.
     Genetics, 88, 26-27.

    Ferm, V.H. & Carpenter, S.J. (1968). The relationship of cadmium and
    zinc in experimental mammalian teratogenesis.  Lab. Invest., 15,

    Ferm, V.H. (1971). Developmental malformations induced by cadmium.
     Biol. Neonat., 19, 101-107.

    Ferm, V.H. (1972). The teratogenic effects of metals on mammalian
    embryos.  Advan. Teratol., 5, 51-75.

    Ferm, V.H. & Layton, W.M. (1981). In: Nriagu, J.O. (ed.)  Cadmium in
     the Environment Part 2, John Wiley & Sons, New York, pp. 743-756.

    Ferm, V.H. & Hanlon, D.P. (1983). In: Clarkson, T.W., Nordberg, G.F: &
    Sager, P.R. (eds.)  Reproductive and Developmental Toxicity of Metals,
    Plenium Press, New York, pp. 383-398.

    Fischer, H. & Weigert, P. (1975). Investigations on the lead and cadmium
    content on human organs.  Oeff. Gesundheitsw., 37, 732-737.

    Flanagan, P.R., McLellan, J.S., Haist, J., Cherian, M.F., Chamberlain,
    M.J. & Valberg, L.S. (1978). Increased dietary cadmium absorption in
    mice and human subjects with iron deficiency.  Gastroenterology, 74,

    Flanjak, J. & Lee, H.Y. (1979). Trace metal content of livers and
    kidneys of cattle.  J. Sci. Fd. Agric., 30, 503-507.

    Fletcher, J.C., Chettle, D.R. & Al-Haddad, I.K. (1982). Experience with
    the use of cadmium measurements of liver and kidney.  J. Radioanal.
     Chem., 71, 547-560.

    Fox, M.R.S. & Fry Jr., B.E. (1970). Cadmium toxicity decreased by
    dietary ascorbic acid supplements.  Science. 169, 989-991.

    Fox, M.R.S., Fry Jr, B.E., Harland, B.F., Schertal, M.E. & Weeks, C.E.
    (1971). Effect of ascorbic acid on cadmium toxicity in the young
    coturnix.  J. Nutr., 101, 1295-1305.

    Francavilla, S., Moscardelli, S., Francavilla, F., Casasanta, N.,
    Properzi, G., Martini, M. & Santiemma, V. (1981). Acute cadmium
    intoxication: influence of cyproterone acetate in the testis and
    epididymis of the rat.  Arch. Androl., 6, 1-11.

    Friberg, L. (1950). Health hazards in the manufacture of alkaline
    accumulators with special reference to chronic cadmium poisoning.  Acta
     Med. Scand., 138 (suppl.240), 1-124.

    Friberg, L. (1952). Further investigations on chronic cadmium poisoning.
    A study on rabbits with radioactive cadmium.  Arch. ind. occup. Med.,
    5, 30-36.

    Friberg, L., Piscator, M., Nordberg, G.F. & Kjellstrom, T. (1974).
    Cadmium in the environment, 2nd edition, Chemical Rubber Company Press,
    Cleveland, Ohio, 248 pp.

    Friberg, L., Kjellstrom, T., Nordberg, G.F. & Piscator, M. (1975).
    Cadmium in the environment. III. A toxicological and epidemiological
    appraisal, US Environmental Protection Agency, Office of Research and
    Development, Washington, D.C., 217 pp.

    Friberg, L., Elinder, C.G., Kjellstrom, T. & Nordberg, G.F. (1985). In:
    Friberg, L., Elinder, C.G., Kjellstrom, T. & Nordberg, G.F. (eds.)
     Cadmium and health. A toxicological and epidemiological appraisal, CRC
    Press, Boca Raton, Florida, Chapter 14.

    Friberg, L., Kjellstrom, T. & Nordberg, G.F. (1986). Cadmium. In:
    Friberg, L., Nordberg, G.F. & Vouk, V. (eds.)  Handbook on the
     toxicology of metals, 2nd edition, Elsevier Science Publishers,
    Amsterdam, New York.

    Fullmer, C.S., Oku, T. & Wasserman, R.H. (1980). Effect of cadmium
    administration on intestinal calcium absorption and vitamin D-dependent
    calcium-binding protein.  Environ. Res., 22, 386-399.

    Gabbiani, G. (1966). Action of cadmium chloride on sensory ganglia.
     Experientia, 22, 386-399.

    Gabbiani, G., Badonnel, M.-C., Mathewson, S.M. & Ryan, G.G. (1974).
    Acute cadmium intoxication: early selective lesions of endothelial
    clefts.  Lab. Invest., 30, 686-695.

    Garty, M., Wong, K.-L. & Klassen, C.O. (1981). Redistribution of cadmium
    to blood of rats.  Toxicol. appl. Pharmacol., 59, 548-554.

    Gervais, J. & Delpech, P. (1963). Cadmium intoxication.  Arch. Mal.
     prof. Med. Trav. Sec. soc., 24, 803-816 (in French).

    Gilliavod, N. & Leonard, A. (1975). Mutagenicity tests with cadmium in
    the mouse.  Toxicology, 5, 43-47.

    Gretz, M. & Laugel, P. (1982). A study on the level of human
    contamination by cadmium.  Toxicol. Eur. Res. IV, 2, 63-70.

    Gunn, S.A. & Gould, T.C. (1957). Selective accumulation of 115Cd by
    cortex of rat kidney.  Proc. Soc. Exp. Biol. Med., 96, 820-823.

    Gunn, S.A., Gould, T.C. & Anderson, W.A.D. (1963). Cadmium-induced
    interstitial cell tumors in rats and mice and their prevention by zinc.
     J. Natl. Cancer Inst., 31, 745-759.

    Gunn, S.A., Gould, T.C. & Anderson, W.A.D. (1965). Strain differences in
    susceptibility of mice and rats to cadmium-induced testicular damage.
     J. Reprod. Fertil., 10, 273-275.

    Gunn, S.A., Gould, T.C. & Anderson, W.A.D. (1967). Specific response of
    mesenchymal tissue to cancerogenesis by cadmium.  Arch. Pathol., 83,

    Haddow, A., Roe, F.J.C., Dukes, C.E. & Mitcheley, B.C.V. (1964). Cadmium
    neoplasia: sarcomata at the site for injection of cadmium sulfate in
    rats and mice.  Br. J. Cancer, 18, 667-673.

    Hamilton, D.L. & Valberg, L.S. (1974). Relationship between cadmium and
    iron absorption.  Am. J. Physiol., 227, 1033-1037.

    Hammer, D.I., Colucci, A.V., Hasselblad, V., Williams, M.E. & Pinkerton,
    C. (1973). Cadmium and lead in autopsy tissues.  J. occup. Med., 15,

    Heath, J.C., Daniel, M.R., Dingle, J.T. & Webb, M. (1962). Cadmium as a
    carcinogen.  Nature, 193, 592-593.

    Henke, C., Sachs, H.W. & Bohn, G. (1970). [Cadmium determination by
    neutron activation analysis of liver and kidneys from children and young
    people].  Arch. Toxicol., 26, 8-16 (in German).

    Hoffman, E.O., Cook, J.A., Diluzio, N.R. & Coover, J.A. (1975). The
    effects of acute cadmium administration in the liver and kidney of the
    rat.  Lab. Invest., 32, 655-661.

    Holmberg Jr., R.E. & Ferm, V.H. (1969). Interrelationship of selenium,
    cadmium, and arsenic in mammalian teratogenesis.  Arch. environ.
     Health, 18, 873-877.

    Hurley, L.S., Gowan, J. & Swenerton, H. (1971). Teratogenic effects of
    short-term and transitory zinc deficiency in rats.  Teratology, 4,

    IARC (1976). Cadmium, nickel, some epoxides, miscellaneous industrial
    chemicals, and general considerations on volatile anaesthetics,
    International Agency for Research on Cancer, Lyons, 306 pp (Monographs
    on the Evaluation of Carcinogenic Risk of Chemicals to Man, Vol. 11).

    IARC (1982). International Agency for Research on Cancer, Lyons, 292 pp
    (Monographs on the Evaluation of Carcinogenic Risk of Chemicals to
    Humans, Supplement 4).

    Ishizaki, A., Fukushima, M., Sakomoto, M., Kurachi, T. & Hayashi, E.
    (1969). [Cadmium content of rice eaten in the Itai-Itai disease area]
    In:  [Proceedings of the 27th Annual Meeting of the Japan Public
     Health Association.] Japan Public Health Association, Tokyo, pp. 11
    (in Japanese).

    Ishizaki, A. (1972).  [Concentrations of cadmium and zinc in the
     organs of Itai-Itai disease patients and residents in the Hokuriku
     region,] Japan Public Health Association, Tokyo, pp. 154-157 (Kankyo
    Hoken Report No. 11) (in Japanese).

    Ishizu, S., Minami, M., Suzuki, A., Yamada, M., Sato, M. & Yamamura, K.
    (1973). An experimental study of teratogenic effect of cadmium.  Ind.
     Health, 11, 127-139.

    Itokawa, Y., Abe, T., Tabei, R. & Tanaka, S. (1974). Renal and skeletal
    lesions in experimental cadmium poisoning.  Arch. environ. Health.
    28, 149154.

    Johnson, D.R. & Foulkes, E.C. (1980). On the proposed role of
    metallothionein in the transport of cadmium.  Environ. Res., 21,

    Kagi, J.H.R., Vasak, M., Lerch, K., Gilg, D.E.O., Hunziker, P., Bernard,
    W.R. & Good, M. (1984). Structure of mammalian metallothionein.
     Environ. Health Perspect., 54, 93- 103.

    Kajikawa, K., Nakanishi, I. & Kuroda, K. (1981). Morphological changes
    of the kidney and bone of rats in chronic cadmium poisoning.  Exp.
     Mol. Pathol., 34, 9-24.

    Kanisawa, M. & Schroeder, H.A. (1969). Life term studies on the effect
    of trace elements on spontaneous tumours in mice and rats.  Cancer
     Res., 892-895.

    Kar, A.A., Das, R.P. & Karkun, J.N. (1959). Ovarian changes in
    prepubertal rats after treatment with cadmium chloride.  Acta biol.
     med. germ., 3, 372-399.

    Kato, T. (1983). [Overall analysis of the occurrence of Itai-Itai
    disease patients and their mortality] Japan Public Health Association,
    Tokyo, pp. 121-124 (Kankyo Hoken Report No. 49) (In Japanese).

    Kawai, M., Fukuda, K. & Kimura, M. (1976). Morphological alterations in
    experimental cadmium exposure with special reference to the onset of
    renal lesion. In: Nordberg, G.F., ed.  Effects and dose-response
     relationships of toxic metals, Elsevier Scientific Publishing Company,
    Amsterdam, pp. 343-370.

    Kawamura, J., Yoshida, O., Nishino, K. & Itokawa, Y. (1978).
    Disturbances in kidney functions and calcium and phosphate metabolism in
    cadmium-poisoned rats.  Nephrology, 20, 101-110.

    Kazantzis, G. (1963). Induction of sarcoma in the rat by cadmium sulfide
    pigment.  Nature, 198, 1213-1214.

    Kazantzis, G., Flynn, F.V., Spwage, J.S. & Trott, D.G. (1963). Renal
    tubular malfunction and pulmonary emphysema in cadmium pigment workers.
     Q. J. Med., 32, 165-192.

    Kazantzis, G. & Hanbury, W.J. (1966). The induction of sarcoma in the
    rat by cadmium sulfide and by cadmium oxide.  Br. J. Cancer, 20,

    Kazantzis, G. (1979). Renal tubular dysfunction and abnormalities of
    calcium metabolism in cadmium workers.  Environ. Health Perspect., 28,

    Kello, D. & Kostial, K. (1977a). Influence of age on whole-body
    retention and distribution of 115Cd in the rat.  Environ. Res., 14,

    Kello, D. & Kostial, K. (1977b). Influence of age and milk diet on
    cadmium absorption from the gut.  Toxicol. appl. Pharmacol., 40,

    Kimura, M. & Otaki, N. (1972). Percutaneous absorption of cadmium in
    rabbit and hairless mouse,  Ind. Health (Tokyo), 190, 7-10.

    Kipling, M.D. & Waterhouse, J.A.H. (1967). Cadmium and prostatic
    carcinoma.  Lancet, 1, 730-731.

    Kirkpatrick, D.C. & Coffin, D.E. (1973). Cadmium, lead, and mercury
    content of various cured meats.  J. Sci. Food Agric., 24, 1595-1598.

    Kishino, N., Murakami, M., Takeuchi, M. & Suzuki, S. (1975). Proc. 48th
    Annual Meeting, Japan Association of Industrial Health, Sapporo.

    Kitamura, S., Sumino, K. & Kamatani, N. (1970). [Cadmium concentrations
    in liver, kidneys, and bones of human bodies].  Jpn. J. Public Health,
    17, 177 (in Japanese).

    Kitamura, M. (1972).  [Absorption and deposition of cadmium, especially in
     human subjects,] Japan Public Health Association, Tokyo, pp. 420-45
    (Kankyo Hoken Report No. 11) (in Japanese).

    Kjellstrom, T. (1971). A mathematical model for the accumulation of
    cadmium in human kidney cortex.  Nord. Hyg. Tidsk., 53, 111-119.

    Kjellstrom, T., Lind, B., Linnman, L. & Nordberg, G.F. (1974). A
    comparative study on methods for cadmium analysis of grain with an
    application to pollution evaluation.  Environ. Res., 8, 92-106.

    Kjellstrom, T., Lind, B., Linnman, L. & Elinder, C.G. (1975a). Variation
    of cadmium concentration in Swedish wheat.

    Kjellstrom, T., Tsuchiya, K., Tompkins, E., Takabatake, E., Lind, B. &
    Linnman, L. (1975b). A comparison for methods of analysis of cadmium in
    food and biological material. A cooperative study between Sweden, Japan,
    and the USA. In:  Recent advances in the assessment of the health effects
     of environmental pollution, Commission of the European Communities,
    Luxembourg, pp. 2197-2213.

    Kjellstrom, T. (1977). Accumulation and renal effects of cadmium in men.
    A dose-response study, Karolinska Institute, Stockholm, 80 pp (Doctoral

    Kjellstrom, T. & Nordberg, G.F. (1978). A kinetic model of cadmium metal
    metabolism in the human being.  Environ. Res., 16, 248-269.

    Kjellstrom, T., Friberg, L. & Rahnster, D. (1979). Mortality and cancer
    morbidity among cadmium-exposed workers.  Environ. Health Perspect.,
    28, 199-294.

    Kjellstrom, T. (1979). Exposure and accumulation of cadmium in
    populations from Japan, the United States, and Sweden.  Environ.
     Health Perspect., 25, 169-197.

    Kjellstrom, T. (1985). In:  The Fourth Seminar on Itai-Itai Disease,
    Department of Hygiene, Kanasawa Medical University, Japan, pp. 34-46.

    Kjellstrom, T. (1986a). In: Friberg, L., Elinder, C.G., Kjellstrom, T.
    & Nordberg, G.F. (eds.)  Cadmium and health. A toxicological and
     epidemiological appraisal, CRC Press, Boca Raton, Florida, Chapter 9.

    Kjellstrom, T. (1986b). In: Friberg, L., Elinder, C.G., Kjellstrom, T.
    & Nordberg, G.F. (eds.)  Cadmium and health. A toxicological and
     epidemiological appraisal, CRC Press, Boca Raton, Florida, Chapter 10.

    Kjellstrom, T. (1986c). In: Friberg, L., Elinder, C.G., Kjellstrom, T.
    & Nordberg, G.F. (eds.)  Cadmium and health. A toxicological and
     epidemiological appraisal. CRC Press, Boca Raton, Florida, Chapter 13.

    Klaassen, C.D. & Kotsonis, F.N. (1977). Biliary excretion of cadmium in
    the rat, rabbit and dog.  Toxicol. appl. Pharmacol., 41, 101-112.

    Kobayashi, J., Morii, F., Muramoto, S. & Nakashima, S. (1970). [Effects
    of air and water pollution on agricultural products by Cd, Pd, and Zn
    attributed to a mine and refinery in Annaka City, Gunma Prefecture].
     Jpn. J. Hyg., 25, 364-375 (in Japanese).

    Kobayashi, S. (1983). Effect of aging on the concentration of cadmium,
    zinc and copper in human kidney.  Jpn. J. Publ. Hlth., 30, 27-34.

    Kogan, I.G., Grozdova, T.Y.A. & Kholikova, T.A. (1978). [Investigation
    of the mutagenic effect of cadmium chloride on  Drosophila
     melanogaster germ cells].  Genetika, 16, 2136-2140 (in Russian).

    Kohno, M., Yoshida, T., Sugihara, H. & Hagino, N. (1956). [Report on so
    called Itai-Itai disease First Report].  J. Jap. Society Orthopedics,
    30, 100-101.

    Koller, L.D., Exon, J.H. & Roan, J.G. (1975). Antibody suppression by
    cadmium.  Arch. environ. Health. 30, 598-601.

    Kowal, N.E., Johnson, D.E., Kraemer, D.F. & Pahren, H.R. (1979). Normal
    levels of cadmium in diet, urine, blood and tissues of inhabitants of
    the United States.  J. Toxicol. environ. Health, 5, 995-1014.

    Krasovskii, G.N., Varshavskaya, S.P. & Borisov, A.I. (1976). Toxic and
    gonadotropic effects of cadmium and boron relative to standards for
    these substances in drinking water.  Environ. Health Perspect., 13,

    Larionova, T.I., Zille, L.N. & Vorobjeva, R.S. (1974). [The influence of
    barium-cadmium laurate on some fermentative processes in the liver].
     Gig. Tr. Prof. Zabol., 3, 50-52 (in Russian).

    Larsson, S.E. & Piscator, M. (1971). Effect of Cadmium on skeletal
    tissue in normal and calcium-deficient rats.  Israel J. med. Sci., 7,

    LeBaron, G.J., Cherry, W.H. & Forbes, W.F. (1977). In: Hemphill, D.D.
    (ed.)  Trace substances in environmental health - XI, University of
    Missouri, Columbia, pp. 44-54.

    Lemen, R.A., Less, J.S., Wagoner, J.K. & Blejer, H.P. (1976). Cancer
    mortality among cadmium production workers.  Ann. NY Acad. Sci., 271,

    Lener, J. & Bibr, B. (1971). Cadmium and hypertension.  Lancet, 1, 970.

    Lener, J. & Musil, J. (1971). Cadmium influence on the excretion of
    sodium by kidneys.  Experientia. 27, 902.

    Levy, L.S., Roe, F.J.C., Malcolm, D., Kazantis, G., Clack, J. & Platt,
    H.S. (1973). Absence of prostatic changes in rats exposed to cadmium.
     Ann. occup. Hyg., 16, 111-118.

    Levy, L.S. & Clack, J. (1975). Further studies on the effect of cadmium
    on the prostrate gland. II. Absence of prostatic changes in mice given
    oral cadmium sulfate for eighteen months.  Ann. occup. Hyg., 17,

    Lorentzson, R. & Larsson, S.E. (1977). Vitamin D metabolism in adult
    rats at low and normal calcium intake and the effect of cadmium
    exposure.  Clin. Sci. Mol. Med., 53, 439-446.

    Loser, E. (1980). A 2-year oral carcinogenicity study with cadmium on
    rats.  Cancer Lett., 9, 191-198.

    Lucis, O.J., Lucis, R. & Aterman, K. (1972). Tumorigenesis by cadmium.
     Oncology, 26, 53-76.

    Lufkin, N.H. & Hodges, F.T. (1944). Cadmium poisoning. Report of
    out-break.  US Nay. Med. Bull., 43, 1273-1276.

    McKenzie, J., Kjellstrom, T. & Sharma, R.P. (1982). Cadmium intake
    metabolism and effects in people with a high intake of oysters in New
    Zealand, US Environmental Protection Agency, Washington D.C., 210 pp.

    McLellan, J.S., Flanagan, P.R., Chamberlain, M.J. & Valberg, L.S.
    (1978). Measurements of dietary cadmium absorption in humans. J.
     Toxicol. environ. Health, 4, 131-138.

    Matsusaka, N., Tanaka, M., Nishimura, Y., Yuyama, A. & Kobayashi, H.
    (1972). [Whole body retention and intestinal absorption of 115mCd in
    young and adult mice].  Med. Biol., 85, 275-279 (in Japanese).

    Merali, Z., Kacew, S. & Singhal, R.L. (1974). Response of hepatic
    carbohydrate and cyclic AMP metabolism to cadmium treatment in rats.
     Can. J. Physiol. Pharmacol., 53, 174-184.

    Mranger, J.C., Subramanian, K.S. & Chalifoux, C. (1981). Metals and
    other elements. Survey for cadmium, cobalt, chromium, copper, nickel,
    lead, zinc, calcium and magnesium in Canadian drinking-water supplies.
     J. Assoc. Off. Anal. Chem. 64, 44-53.

    Miljoministeriet (1980). Cadmium Forurening. En Redegotelse om und
    Vendelse, Forekomst og Skad Evirkninger at Cadmium im Danmark.
    Miljoministeriet, Miljostyrelsen, Strandgade 29, 1401, Kobenhavn K.,

    Miller, G.J., Wylie, M.J. & McKeown, D. (1976). Cadmium exposure and
    renal accumulation in an Australian urban population.  Med. J. Aust.,
    1, 20-23.

    Ministry of Agriculture, Fisheries and Food. (1985). A Survey of Cadmium
    in Food, 1st Supplementary Report, 12th Report of the Steering Group on
    Food Surveillance, HMSO, London.

    Morgan, H. & Sherlock, J.C. (1984). Cadmium intake and cadmium in the
    human kidney.  Food Additives & Contaminants, 1, 45-51.

    Mulvihill, J.E., Gamm, S.H. & Ferm, V.H. (1970). Facial formation in
    normal and cadmium-treated golden hamsters.  J. Embryol. exp.
     Morphol., 24, 393-403.

    Murakami, M., Shidoshi, Y., Muto, Y. & Suzuki, S. (1974).  Proc. 48th
     Annual Meeting, Japan Association of Industrial Health, Sapporo.

    Nazari, G., Favino, A. & Pozzi, U. (1967). [Effects of a single
    subcutaneous injection of cadmium chloride in male rats].  Riv. Anat.
     Pathol. Oncol., 31, 251-271 (in Italian).

    Nogawa, K., Ishizaki, A., Fukushima, M., Shibata, I. & Hagino, N.
    (1975). Studies on women with acquired Fanconi syndrome observed in the
    Ichi River basin polluted by cadmium.  Environ. Res., 10, 280-307.

    Nogawa, K., Kobayashi, E., Honda, R. & Ishizaki, A. (1979).
    Clinico-chemical studies on chronic cadmium poisoning. I. Results of
    urinary examinations.  Japan. J. Hyg., 34, 407-414.

    Nogawa, K., Kobayashi, E. & Konishi, F. (1981). Comparison of bone
    lesions in chronic cadmium intoxication and vitamin D deficiency.
     Environ. Res., 24, 233-249.

    Nomiyama, K. (1973). [Mechanism and diagnosis of cadmium poisoning,]
    Japan Public Health Association, Tokyo, pp. 11-15 (Kankyo Hoken Report
    No. 24) (in Japanese).

    Nomiyama, K. (1974). [Studies concerning cadmium metabolism and the
    etiology of poisoning] Japan Public Health Association, Tokyo, pp. 53-59
    (Kankyo Hoken Report No. 31) (in Japanese).

    Nomiyama, K. (1975). Toxicity in cadmium: mechanism and diagnosis. In:
    Krenkel, P.A., (ed.)  Progress in water technology, Pergamon Press,
    Oxford, pp. 15-23.

    Nomiyama, K., Sugata, Y., Yamamoto, A. & Nomiyama, H. (1975). Effects of
    dietary cadmium on rabbits. I. Early signs of cadmium intoxication.
     Toxicol. appl. Pharmacol., 31, 4-12.

    Nomiyama, K. & Nomiyama, H. (1976a). Mechanisms of urinary excretion of
    cadmium: experimental studies in rabbits. In: Nordberg, G.F. (ed.)
     Effects and dose-response relationships of toxic metals, Elsevier,
    Amsterdam, pp. 371-379.

    Nomiyama, K. & Nomiyama, H. (1976b). [Long-term experiment with 300 ppm
    oral cadmium exposure to rabbits. Intermediate report after 12 months,]
    Japan Public Health Association, Tokyo, pp. 161-173 (Kankyo Hoken Report
    No. 38) (in Japanese).

    Nomiyama, K., Sugata, Y., Yamamoto, A. & Nomiyama, H. (1976).
    Dose-response relationship for cadmium. In: Nordberg, G.F. (ed.)
     Effects and dose-response relationships of toxic metals, Elsevier,
    Amsterdam, pp. 380-385.

    Nomiyama, K. (1978). Experimental studies on animals:  in vivo
    experiments. In: Tsuchiya, K. (ed.)  Cadmium studies in Japan,
    Elsevier/North Holland, Amsterdam, pp. 47-86.

    Nomiyama, K., Nomiyama, H., Yotoriyama, M. & Taguchi, T. (1978). Some
    recent studies on the renal effects of cadmium. In:  Proceedings of
     the First International Cadmium Conference, San Francisco,
     California, 31 January-2 February, 1977. Cadmium Association, London,
    pp. 186-194.

    Nomiyama, K. & Nomiyama, H. (1979). Factors modifying critical
    concentration and biological half-time of cadmium.  Arh. hig. rada
     toksikol., 30, (suppl.), 191-200.

    Nomiyama, K., Nomiyama, H., Nomura, Y., Taguchi, T., Matsui, K.,
    Yotoriyama, M., Akahori, F., Iwao, S., Koizumi, N., Masaoka, T.,
    Kitamura, S. & Kobayashi, K. (1979). Effects of dietary cadmium on
    rhesus monkeys.  Environmental Health Perspectives. 28, 223-243.

    Nomiyama, K., Nomiyama, H., Akahori, F. & Masaoka, T. (1981). In:
     Recent studies on health effects of cadmium in Japan, Environment
    Agency, Tokyo, pp. 59-104.

    Nomiyama, K. & Nomiyama, H. (1982). Tissue metallothionein in rabbits
    chronically exposed to cadmium, with special reference to the critical
    concentration of cadmium in the renal cortex. In: Foulkes, E.C. (ed.)
     Biological roles of metallothionein, Elsevier/North Holland,
    Amsterdam, pp. 47-67.

    Nomiyama, K., Nomiyama, H., Akahori, F. & Masaoka, T. (1982a). Cadmium
    health effects in monkeys with special reference to the critical
    concentration of cadmium in the renal cortex. In:  Proceedings of the
     3rd International Cadmium Conference, Miami, Florida, 3-5 February.
     1981, Cadmium Association, London, pp. 151-156.

    Nomiyama, K., Nomiyama, H., Yotoriyama, M. & Matsui, K. (1982b). Sodium
    dodecyl sulfate acrylamide gel electrophoretic studies on low molecular
    weight proteinuria, an early sign of cadmium health effects in rabbits.
     Ind. Health, 20, 11-18.

    Nomiyama, K. & Nomiyama, H. (1984). Reversibility of cadmium-induced
    health effects in rabbits.  Environmental Health Perspective, 54,

    Nomiyama, K. & Nomiyama, H. (1986). Critical concentration of "unbound"
    cadmium in the rabbit renal cortex.  Experientia, 42, 149.

    Nomiyama, K., Akahori, F., Nomiyama, H., Masaoka, T., Arai, S., Nomura,
    Y., Yotoriyama, M., Kobayashi, K., Suzuki, T., Kawashima, H. & Onozawa,
    A. (1987). Dose-effect and dose-response relationships in rhesus monkeys
    after administration of cadmium contaminating diet for 9 years,
    Environmental Health, Japan Public Health Association, Tokyo, pp.
    130-134. Report No. 53.

    Nomiyama, K. & Nomiyama, H. (1988). Health effects of 6 years dietary
    cadmium (cadmium-contaminated rice) in monkeys. In: Prassad, A.S. (ed.)
     Elements research in humans, Alan R. Liss, Inc., New York (in press).

    Nordberg, G.F. (1972). Cadmium metabolism and toxicity.  Environ.
     Physiol. Biochem., 2, 7-36.

    Nordberg, G.F. & Nishiyama, K. (1972). Whole-body and hair retention of
    cadmium in mice.  Arch. environ. health, 24, 209-214.

    Nordberg, G.F. & Piscator, M. (1972). Influence of long-term cadmium
    exposure on urinary excretion of protein and cadmium in mice.  Environ.
     Physiol. Biochem., 2, 37-49.

    Nordberg, G.F., Slorach, S. & Stenstrom, T. (1973). [Cadmium poisoning
    caused by a cooled soft drink machine.]  Lakartidn., 70, 601-604 (in
    Swedish with English summary).

    Nordberg, G.F., Kjellstrom, T. & Nordberg, M. (1975). In: Friberg, L.,
    Elinder, C.G., Kjellstrom, T. & Nordberg, G.F. (eds.)  Cadmium and
     health. A toxicological and epidemiological appraisal, Boca Raton,
    Florida, CRC Press.

    Nordberg, G.F., Robert, K.-H. & Pannone, M. (1977). Pancreatic and
    biliary excretion of cadmium in the rat.  Acta pharmacol, toxicol., 41,

    Nordberg, M. & Nordberg, G.F. (1975). Distribution of metallothione in
    bound cadmium and cadmium chloride in mice: Preliminary studies.
     Environ. Health Perspect., 12, 103-108.

    Nordberg, M. (1978). Studies on metallothionein and cadmium.
     Environ. Res., 15, 381-404.

    Nordberg, M., Cherian, G. & Kjellstrom, T. (1983). Defense mechanisms
    against metal toxicity and their potential importance for risk
    assessments with particular reference of the importance of various
    binding forms in foodstuffs, Swedish State Power Board, Vallingby,
    Sweden, 46 pp (KHM Technical report No. 55).

    Parizek, J. & Zahor, Z. (1956). Effects of cadmium salts on testicular
    tissue.  Nature, 177, 1036-1037.

    Parizek, J. (1957). The destructive effect of cadmium ion on testicular
    tissue and its prevention by zinc.  J. Endocrin., 15, 56-63.

    Parizek, J. (1960). Sterilization of the male by cadmium salts. J.
     Reprod. Fertil., 1, 294-309.

    Parizek, J. (1964). Vascular changes at sites of oestrogen biosynthesis
    produced by parenteral injection of cadmium salts: the destruction of
    placenta by cadmium salts.  J. Reprod. Fertil., 7, 263-265.

    Parizek, J., Ostadalova, I., Benes, I. & Pitha, J. (1968a). The effect
    of a subcutaneous injection of cadmium salts on the ovaries of adult
    rats in persistent oestrus.  J. Reprod. Fertil., 17, 559-562.

    Parizek, J., Ostadalova, l., Benes, I. & Babicky, A. (1968b). Pregnancy
    and trace elements: the protective effect of compounds of an essential
    trace element, selenium, against the peculiar toxic effects of cadmium
    during pregnancy.  J. Reprod. Fertil., 16, 507-509.

    Parzyck, D.C., Shaw, S.M., Kessler, W.V., Vetter, R.J., Van Sickle, D.C.
    & Mayes, R.A. (1978). Fetal effects of cadmium in pregnant rats on
    normal and zinc-deficient diets.  Bull. environ. Contam. Toxicol., 19,

    Paton, G.R. & Allison, A.C. (1972). Chromosome damage in human cell
    cultures induced by metal salts.  Mutat. Res., 16, 332-336.

    Perry Jr., H.M., Erlanger, M.W., Yunice, A., Schoepfle, E. & Perry, E.F.
    (1970). Hypertension and tissue metal levels following intravenous
    cadmium, mercury, and zinc.  Am. J. Physiol., 219, 755-761.

    Perry Jr., H.M., Perry, E.F. & Purifoy, J.E. (1971). Antinutriuretic
    effect of intramuscular cadmium in rats.  Proc. Soc. Exp. Biol. Med.,
    136, 1240-1244.

    Perry Jr., H.M. & Erlanger, M.W. (1973). Elevated circulating renin
    activity in rats following doses of cadmium known to induce
    hypertension.  J. Lab. clin. Med., 82, 399-405.

    Perry Jr., H.M. & Erlanger, M.W. (1974). Metal-induced hypertension
    following chronic feeding of low doses of cadmium and mercury.
     J. Lab. clin. Med., 83, 541-547.

    Perry Jr., H.M., Erlanger, M. & Perry, E.F. (1977). Hypertension
    following chronic, very low-dose cadmium feeding.  Proc. Soc. Exp.
     Biol. med., 156, 173-176.

    Perry Jr., H.M. & Kopp, S.J. (1983). Does cadmium contribute to human
    hypertension?  Sci. Total Environ., 26, 223-232.

    Piscator, M. (1966). Proteinuria in chronic cadmium poisoning. III.
    Electrophoretic and immunoelectrophoretic studies on urinary proteins
    from cadmium workers, with special reference to the excretion of low
    molecular weight proteins.  Arch. environ. Health, 12, 335-344.

    Piscator, M. (1972). Cadmium toxicity: industrial and environmental
    experience. Paper presented at the 17th International Congress on
    Occupational Health, Buenos Aires, September 1972.

    Piscator, M. & Larsson, S.-E. (1972). Retention and toxicity of cadmium
    in calcium-deficient rats. In:  Proceedings of the 17th International
     Congress on Occupational Health, Buenos Aires, September 1972
    (Proceedings not yet published).

    Potts, C.L. (1965). Cadmium proteinuria - the health of battery workers
    exposed to cadmium oxide dust.  Ann. Occup. Hyg., 8, 55-61.

    Prigge, E., Baumert, H.P. & Muhle, H. (1977). Effects of dietary and
    inhalative cadmium on haemoglobin and haematocrit in rats.  Bull.
     environ. Contain. Toxicol., 17, 585-590.

    Prodan, L. (1932). Cadmium poisoning. II. Experimental cadmium
    poisoning.  J. ind. Hyg. Toxicol., 14, 174-196.

    Rahola, T., Aran, R.K. & Miettenen, J.K. (1971). IAEA/WHO Symposium on
    the Assessment of Radioactive Organ and Body Burdens, Stockholm, 22-26

    Rahola, T., Aran, R.K. & Miettenen, J.K. (1972). Half-time studies of
    mercury and cadmium by whole-body counting. In:  Assessment of
     radioactive contamination in man, New York.

    Ramaya, L.K. & Pomerantzeva, M.O. (1977). [Investigation of cadmium
    chloride mutagenic effect on germ cells of male mice.]  Genetika, 13,
    59-63 (in Russian).

    Ramel, C. & Friberg, L. (1971). In: Friberg, L., Piscator, M. &
    Nordberg, G.F. (eds.)  Cadmium in the environment, Ohio, Chemical
    Rubber Company Press, Cleveland, pp. 109-110.

    Richardson, M.E. & Fox, M.R.S. (1974). Dietary cadmium and enteropathy
    in the Japanese quail.  Lab. Invest., 31, 722-731.

    Roels, H.A., Djubgang, J., Buchet, J.P., Bernard, A. & Lauwerys, R.R.
    (1982). Evolution of cadmium-induced renal dysfunction in workers
    removed from exposure.  Scand. J. Work environ. Health. 8, 191-200.

    Roels, H.A., Lauwerys, R.R. & Dardenne, A.N. (1983a). The critical level
    of cadmium in human renal cortex: a reevaluation.  Toxicol. Lett.,
    15, 357-360

    Roels, H.A., Lauwerys, R.R., Buchet, J.P., Bernard, A., Garvey, J.S. &
    Linton, H.J. (1983b). Significance of urinary metaliothionein in workers
    exposed to cadmium,  Int. Arch. occup, environ. Health, 52, 159-166.

    Rohr, G. & Bauchinger, M. (1976). Chromosome analyses in cell cultures
    of the Chinese hamster after application of cadmium sulfate.  Mutat.
     Res., 40, 125-130.

    Saito, S.H., Shioji, R., Furukawa, Y., Nagai, K., Arikawa, T., Saito,
    T., Sasaki, Y., Furuyama, T. & Yoshinaga, K. (1977). Cadmium-induced
    proximal tubular dysfunction in a cadmium-polluted area.  Nephrology,
    6, 112.

    Samarawickrama, G.P. & Webb, M. (1979). Acute effects of cadmium on the
    pregnant rat and embryo-fetal development.  Environ. Health Perspect.,
    28, 245-249.

    Scharpf Jr., L.G., Hill, I.D., Wright, P.L., Plank, J.B., Keplinger,
    M.L. & Calandra, J.C. (1972). Effect of sodium nitrilotriacetate on
    toxicity, teratogenicity, and tissue distribution of cadmium.
     Nature, 239, 231-234.

    Schroeder, H.A. & Balassa, J.J. (1961). Abnormal trace metals in man:
    cadmium.  J. chron. Dis., 14, 236-258.

    Schroeder, H.A. & Vinton Jr., W.H. (1962). Hypertension induced in rats
    by small doses of cadmium.  Am. J. Physiol., 202, 515-518.

    Schroeder, H.A. (1964). Cadmium hypertension in rats.  Am. J.
     Physiol., 207, 62-66.

    Schroeder, H.A., Balassa, J.J. & Vinton Jr., W.H. (1964). Chromium,
    lead, cadmium, nickel, and titanium in mice: effect on mortality,
    tumors, and tissue levels.  J. Nutr., 83, 239-250.

    Schroeder, H.A., Balassa, J.J. & Vinton Jr, W.H. (1965). Chromium,
    cadmium, and lead in rats: effects on life span, tumours, and tissue
    levels.  J. Nutr., 86, 51-66.

    Schroeder, H.A. & Mitchener, M. (1971). Toxic effects of trace elements
    on the reproduction of mice and rats.  Arch. environ.  Health., 23,

    Shaikh, Z.A. & Smith, J.C. (1980). Metabolism of orally ingested cadmium
    in humans. In: Holmstedt, B. et al., (eds.)  Mechanisms of toxicity
     and hazard evaluation, Elsevier/North Holland, Amsterdam, pp. 569-574.

    Sherlock, J.C., Smart, G.A. & Walter, B. (1983). Dietary surveys on a
    population at Shipham, Somerset, United Kingdom.  Sci. Total
     Environ., 29, 121-142.

    Shigematsu, I., Mitamura, S., Akeuchi, J., Minowa, M., Nagai, M. &
    Fukushima, M. (1982). A retrospective mortality study on cadmium-exposed
    populations in Japan. In:  Proceedings of the 3rd International
     Cadmium Conference, Miami, Florida, 3-5 February, 1981, Cadmium
    Association, London, pp. 115-118.

    Shiraishi, Y., Kurahashi, H. & Yoshida, T.H. (1972). Chromosomal
    aberrations in cultured human leukocytes induced by cadmium sulfide.
     Proc. Jpn. Acad., 48, 133-137.

    Shiraishi, Y. (1975). Cytogenetic studies in 12 patients with Itai-Itai
    disease.  Humangenetick, 27, 31-44.

    Sonawane, B.R., Nordberg, M., Nordberg, G.F. & Lucier, G.W. (1975).
    Placental transfer of cadmium in rats: influence of dose and gestational
    age.  Environ. Health Perspect., 12, 97-102.

    Sorahan, T. & Waterhouse, J.A.H. (1983). Mortality study of
    nickel-cadmium battery workers by the method of regression models in
    life tables.  Br. J. ind. Med., 40, 293-300.

    Starcher, B.C. (1969).  J. Nutr., 97, 321.

    Stowe, H.D., Wilson, M. & Goyer, R.A. (1972). Clinical and morphological
    effects of oral cadmium toxicity in rabbits.  Arch.  Pathol., 94, 

    Sugawara, C. & Sugawara, N. (1974). Cadmium toxicity for rat intestine,
    especially on the absorption of calcium and phosphorous.  Jpn. J. Hyg.,
    28, 511-516.

    Sullivan, M.F., Hardy, J.T., Miller, B.M., Buschbom, R.L. & Siewicki,
    T.C. (1984). Absorption and distribution of cadmium in mice fed diets
    containing either inorganic or oyster-incorporated cadmium.  Toxicol.
     appl. Pharmacol., 72, 210-217.

    Sumino, K., Hayakawa, K., Shibata, T. & Kitamura, S. (1975). Heavy
    metals in normal Japanese tissues.  Arch. environ. Health, 30, 487-494.

    Syversen, T.L.M., Stray, T.K., Syversen, G.B. & Ofstad, J. (1976).
    Cadmium and zinc in human liver kidney.  Scan. J Clin. Lab. Invest.,
    36, 251-256.

    Takashima, M., Moriwaki, S. & Itokawa, Y. (1980). Osteomalacic change
    induced by long-term administration of cadmium to rats.  Toxicol.
     appl. Pharmacol., 54, 223-228.

    Takebayashi, S. (1980). First autopsy case, suspicious of cadmium
    intoxication from the cadmium-polluted area in Tsushima, Nagasaki
    Prefecture. In:  Shigematsu, I. & Nomiyama, K. (eds.) Cadmium-induced
     osteopathy., Japan Public Health Association, Tokyo, pp. 124-138.

    Takenaka, S., Oldiges, H., Koenig, H., Hochrainer, D. & Oberdoerster, G.
    (1983). Carcinogenicity of cadmium aerosols in  Wistar rats. J.  Natl.
     Cancer. Inst., 70, 367-371.

    Tarasenko, N.Y. & Vorobjeva, R.S. (1973). [Hygienic problems connected
    with the use of cadmium.]  Vestnick. Akad. Med. SSR., 28, 37-43 (in

    Tarasenko, N.Y., Vorobjeva, R.S., Spiridinova, V.S. & Sabalina, L.P.
    (1974). Experimental investigation of toxicity of cadmium and zinc
    caprylates.  J. Hyg. Epden. Microbiol. Immunol., 18, 144-153.

    Task Group on Metal Toxicity (1976). In: Nordberg, G.F. (ed.)
     Effects and dose-response relationships of toxic metals, Elsevier
    Scientific Publishing Company, Amsterdam, pp. 1-111.

    Tertiary Monkey Experiment Team (1983). The influence of nutritional
    factors on cadmium administration in monkeys, Japan Public Health
    Association, Tokyo, 157 pp.

    Tohyama, C., Shaikh, Z.A., Nogawa, K., Kobayashi, E. & Honda, R. (1981).
    Elevated urinary excretion of metallothionein due to environmental
    cadmium exposure.  Toxicology, 22, 289-297.

    Tsuchiya, K. & Sugita, M. (1972). In:  Proceedings of the 17th
     International Congress on Occupational Health, Buenos Aires, 17-23
     September 1972.

    Tsuchiya, K. (1976). Proteinuria of cadmium workers.  J. occup. Med.,
    18, 463-466.

    US Public Health Service (1942). Cadmium poisoning.  Publ. Health
     Rep., 57, 602-612.

    Vahter, M. (ed.) (1982). Assessment of human exposure to lead and
    cadmium through biological monitoring, National Swedish Institute of
    Environmental Medicine and Department of Environmental Hygiene,
    Karoliska Institute, Stockholm, 136 pp Report prepared for the United
    Nations Environment Programme and the World Health Organization.

    Vander, A.J. (1962). Cadmium enhancement of proximal tubular sodium
    reabsorption.  Am. J. Physiol., 203, 1005-1007.

    Vorobjeva, R.S. & Sabalina, L.P. (1975). [Experimental investigations of
    toxic properties of various cadmium compounds.]  Gig.i Sanit., 2,
    102-104 (in Russian).

    Vorobjeva, R.S. & Bubnova, N.I. (1981). [Effects of elemental cadmium
    and telluric cadmium on organisms.]  Gig. Tr. Prof. Zabol., 2, 42-43
    (in Russian).

    Vuori, E., Huunan-Seppala, A., Kilpio, J.O. & Salmela, S.S. (1979).
    Biologically-active metals in human tissues. II. The effect of age on
    the concentration of cadmium in aorta, heart, kidney, liver, lung,
    pancreas, and skeletal muscle.  Scand. J. Work Environ. Health, 5,

    Watanabe, T., Shimada, T. & Endo, A. (1979). Mutagenic effects of
    cadmium on mammalian oocyte chromosomes.  Mutat. Res., 67, 349-356.

    Wilson, R.H., De Eds, F. & Cox Jr., A.J. (1941). Effects of continued
    cadmium feeding.  J. Pharmacol. exp. Ther., 71,222-235.

    Winkelstein Jr., W. & Kantor, S. (1969).  Amer. J. Publ. Health, 59,

    Yamagata, H., Iwashima, K. & Nagai, T. (1974). [Gastro-intestinal
    absorption of cadmium in normal humans,] Japan Public Health
    Association, Tokyo, pp. 84-85 (Kankyo Hoken Report No. 31) (in

    See Also:
       Toxicological Abbreviations
       Cadmium (EHC 134, 1992)
       Cadmium (ICSC)
       Cadmium (WHO Food Additives Series 52)
       Cadmium (WHO Food Additives Series 4)
       Cadmium (WHO Food Additives Series 55)
       CADMIUM (JECFA Evaluation)
       Cadmium (PIM 089)