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Cadmium

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names/Main trade names
   1.6 Main manufacturers/Main importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure (formula, molecular weight)
   3.3 Physical properties
   3.4 Other characteristics
4. USES/CIRCUMSTANCES OF POISONING
   4.1 Uses
   4.2 High risk circumstances of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF ENTRY
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
7. TOXICOLOGY
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI)
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL AND BIOMEDICAL ANALYSES
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 CNS
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ears, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
10. MANAGEMENT
   10.1 General principles
   10.2 Relevant laboratory analyses and other investigations
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
   10.3 Life support procedures and symptomatic treatment
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote treatment
      10.6.1 Adults
      10.6.2 Children
   10.7 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
   11.2 Internally extracted data on cases
   11.3 Internal cases
12. ADDITIONAL INFORMATION
   12.1 Availability of antidotes and antisera
   12.2 Specific preventive measures
   12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE (INCLUDING EACH UPDATE)
    1.    NAME

      1.1   Substance 

            Cadmium
 
      1.2   Group 
 
            Cadmium (atomic number 48, relative atomic mass 112.40) occurs 
            in the 0 and +2 oxidation states. It forms many divalent 
            compounds, mostly inorganic. 

      1.3   Synonyms

      1.4   Identification numbers 

            1.4.1 CAS number

                  Cadmium                              7440-43-9
                  Cadmium acetate hydrate              89759-80-8
                  Cadmium acetate dihydrate            5743-04-4
                  Cadmium carbonate                    515-78-0
                  Cadmium chloride                     10108-64-2
                  Cadmium chloride hemi-pentahydrate   7790-78-5
                  Cadmium cyclohexane-butyrate         55700-14-6
                  Cadmium fluoborate                   14486-19-2
                  Cadmium fluoride                     7790-79-6
                  Cadmium fluosilicate                 17010-21-8
                  Cadmium iodide                       7790-80-9
                  Cadmium lactate                      16039-55-7
                  Cadmium nitrate                      10325-94-7
                  Cadmium nitrate tetrahydrate         10022-68-1
                  Cadmium oxide                        1306-19-0 
                  Cadmium oxide fume                   1306-19-0
                  Cadmium phosphate                    13477-1-3 
                  Cadmium selenide                     1306-24-7 
                  Cadmium succinate                    141-00-4 
                  Cadmium sulfate                      10124-36-4        
                  Cadmium sulphate hydrate             7790-84-3 
                  Cadmium sulphate monohydrate         13477-20-8 
                  Cadmium sulphate tetrahydrate        13477-21-9 
                  Cadmium sulphide                     1306-23-6 
 
            1.4.2 Other numbers 
 
                  United Nations (UN) Transportation Number Cadmium 
                  compounds 2570 (UN, 1985) 
 
      1.5   Main brand names/Main trade names

            To be completed by the PCC.

      1.6   Main manufacturers/Main importers

            To be completed by the PCC.

    2.    SUMMARY 

      2.1   Main risks and target organs 
 
            The main risks and target organs depend on the form of cadmium 
            and on the route of entry. 
 
            Inhalation of cadmium-containing fumes or dust.

            Acute exposure: effects on the respiratory tract and lungs with 
            bronchitis, pulmonary oedema, interstitial pneumonia. 

            Chronic exposure: effects on the kidneys and lungs with 
            proteinuria, impairment of lung function. 
 
            Ingestion of cadmium salts 

            Acute exposure: effects on the gastrointestinal tract, nervous 
            system, kidneys, liver, cardiovascular system.  

            Chronic exposure: effects on the kidneys and bone with 
            proteinuria, renal stones and Itai-itai disease. 
 
      2.2   Summary of clinical effects  
 
            Acute poisoning

            Inhalation of cadmium fumes or dust 

            There is usually a latent period of 4-12 hours between the 
            exposure and the onset of symptoms. Initial presentation 
            simulates metal fume fever: chills fever, headache, weakness, 
            dryness of the nose and throat, chest pain, dyspnoea, cough, 
            metallic taste, conjunctivitis, rhinitis, bronchitis. Nausea 
            and vomiting may also be observed. In severe intoxication, 
            patients may develop acute pneumonitis and lesional pulmonary 
            oedema with respiratory failure which can progress to death in 
            3 - 7 days (Beton et al., 1966; Townshend, 1968; Winston, 1971; 
            Townshend, 1982; Friberg & Elinder, 1983; Taylor et al., 1984; 
            Sittig, 1985; Barnhart & Rosenstock, 1984; Ellenhorn & 
            Barceloux, 1988; Yates & Goldman, 1990). 

            Ingestion of cadmium salts 

            Symptoms begin almost immediately after ingestion and include 
            vomiting, diarrhoea and abdominal pain. In severe poisoning, 
            facial oedema, hypotension, pulmonary oedema, metabolic 
            acidosis, oliguria and finally death have been reported 
            (Buckler et al., 1986; Bernard & Lauwerys, 1986a; Ellenhorn & 
            Barceloux, 1988). 

            Chronic poisoning

            Inhalation (occupational exposure)

            Chronic poisoning may appear after several years of 
            exposure. 
            The earliest sign of cadmium-induced nephropathy is increased 
            proteinuria, in particular 2-microglobulin. ( Friberg, 1948; 
            Potts, 1965; Tsuchiya, 1967). Increased excretion of calcium 
            and phosphorus may disturb bone metabolism, and kidney stones 
            have been found in exposed workers (Friberg & Elinder, 1983). 
            There may also be a decrease in the ability of the kidneys to 
            concentrate urine (Friberg et al., 1974). The mortality of 
            long-term exposure to cadmium is uncertain ( Andersson et al., 
            1983; Armstrong & Kazantzis, 1983). 
 
            Impairment of lung function has been described in workers 
            subject to cadmium exposure by inhalation. The changes involve 
            bronchitis and a mild form of obstructive lung disease with 
            functional impairment which may progress to emphysema.  
            Interstitial fibrosis may also be observed (Lauwerys et al., 
            1974; Smith et al., 1976; Stanescu et al., 1977; De Silva & 
            Donnan, 1981; Friberg & Elinder, 1983; Armstrong & Kazantzis, 
            1983; Sittig, 1985; Goyer,1986). 

            Ingestion (environmental exposure)

            In cadmium-polluted areas of Japan renal damage has also 
            been observed in the general population (Kjellstrom et al., 
            1977b; Shiroishi et al., 1977; Saito et al., 1977; Kojima et 
            al., 1977). A higher incidence of proteinuria, and  2-
            microglobinuria has been observed in the Jintzu river basin 
            in Toyama Prefecture and in other areas where high 
            concentrations of cadmium have been discovered in rice. The 
            increased urinary excretion of  2-microglobulin was 
            strongly related to the residence time in that area and to 
            the cadmium level in urine and blood of the affected 
            individuals (Kjellstrom et al., 1977b). 
            Bone effects: Bone lesions are usually a late manifestation 
            of severe chronic cadmium poisoning. They are characterized 
            by osteomalacia, osteoporosis and spontaneous fractures. 
            Signs and symptoms include skeletal deformities, decreased 
            height, difficulty in walking, duck-like gait, pain in the 
            back and extremities, and pain resulting from pressure on 
            the bones (Bernard & Lauwerys, 1986b; Hallenbeck, 1986). 

      2.3   Diagnosis 
 
            Although the total body burden of cadmium is difficult to 
            assess without a renal biopsy, the blood cadmium level is the 
            best measure of recent exposure. Levels above 7 g/L indicate 
            significant exposure. In case of acute inhalation of cadmium 
            fumes perform a chest x-ray and monitor arterial blood gases. 

            In chronic poisoning, renal damage may be evaluated by the 
            concentration of urinary proteins such as b-2 microglobulin; 
            the concentration of cadmium in the urine; and/or the 
            concentration of cadmium in the renal cortex. The urinary 
            activity of a-N-acetylglucosaminidase is also a sensitive 

            indicator of excessive absorption of cadmium. In non-
            occupationally exposed individuals the urinary excretion of 
            cadmium is very low (about 2 mg/day or less). 


      2.4   First-aid measures and management principles 
 
            Acute poisoning

            By inhalation:  The patient should be removed from exposure as 
            soon as possible. Because the onset of symptoms is delayed the 
            patient should seek medical attention as soon as possible. 
            Monitor respiratory function: chest x-ray and blood gases. 

            By ingestion:  If the patient has not already vomited, induce 
            vomiting with syrup of ipecac or perform gastric lavage. 

            Local effects from skin exposure:  Wash skin immediately with 
            copious amounts of water for at least 15 minutes. Remove 
            contaminated clothing. Wash eyes with copious amounts of water 
            for at least 15 minutes. 

            The treatment of respiratory or cardiovascular disturbances is 
            supportive. 

            Antidotal treatment with EDTA has been proposed in acute 
            poisoning. 

            Chronic poisoning:  Treatment is supportive.

    3.    PHYSICO-CHEMICAL PROPERTIES 

      3.1   Origin of the substance 
 
            Cadmium metal does not occur naturally. The only cadmium 
            mineral is greenockite (CdS), which exists as a coating on the 
            zinc sulphide ore sphalerite and is very rare. 

            Small amounts of cadmium are found in zinc, copper and lead 
            ores. It is generally produced as a by-product from the 
            smelting of these metals, particularly zinc. 

            It is obtained by precipitation from zinc electrolyte in 
            electrolytic zinc refining; recovery from the fumes of zinc 
            calcine sintering plants; the fumes of lead and copper 
            smelters; and during the distillation and refining of zinc. It 
            may be in the form of a chloride, oxide or sulphate which is 
            then leached, electrolysed, precipitated and cast into bars, 
            balls or anodes for electroplating (Stokinger, 1981; Friberg & 
            Elinder, 1983; Sittig, 1985). 
 
      3.2   Chemical structure (formula, molecular weight) 
 
            The chemical structures and molecular weigths of the main 
            cadmium compounds are as follows: 

            Name                    Structure          Molecular weight 

            Cadmium                 Cd                 112.40 
            Cadmium carbonate       CdCO3              172.41 
            Cadmium chloride        CdCl2              183.32 
            Cadmium fluoride        CdF2               150.40 
            Cadmium iodide          CdI2               366.21 
            Cadmium oxide           CdO                128.40 
            Cadmium selenate        CdSeO4             191.36 
            Cadmium sulphate        CdSO4              208.46 
            Cadmium sulphide        CdS                144.46 

            (Weast, 1976-7)
 
      3.3   Physical properties 
 
            Cadmium is a soft, ductile, bluish-white electropositive metal, 
            which is very resistant to corrosion. It has many chemical and 
            physical similarities to zinc and occurs together with this 
            metal in many natural forms (Stokinger, 1981; Friberg & 
            Elinder, 1983; Sittig, 1985). 

            Cadmium dust includes various cadmium compounds such as cadmium 
            chloride. Cadmium fumes consist of minute particles of cadmium 
            or cadmium oxide formed during combustion (Sittig, 1985). 

            Cadmium loses its lustre in moist air and is rapidly 
            corroded by moist ammonia and sulphur dioxide (Stokinger, 
            1981). The metal is soluble in acids but insoluble in water 
            (Stokinger, 1981; Sittig, 1985). 

            Cadmium ions are precipitated from solution by hydroxide ions, 
            and form insoluble white hydrated compounds with carbonates, 
            phosphates, arsenates, oxalates and ferrocyanides. All of these 
            compounds are soluble in ammonium hydroxide with the formation 
            of complex cations containing cadmium and ammonia. 

            Solubilities of cadmium compounds (Windholtz et al., 1976)
 
      Name              Soluble                        Insoluble 
 
      Cadmium               -                          Water 
      Cadmium acetate   Water, alcohol                   - 
      Cadmium bromide   Water, alcohol,                  - 
                        acetone(mod), ether(sl)          - 
      Cadmium carbonate Dil acids                      Water 
      Cadmium chloride  Water, acetone,                Ether 
                        methanol(sl), ethanol(sl)        - 
      Cadmium fluoride  Water, acids                   Alcohol, NH4OH 

      Name              Soluble                        Insoluble 

      Cadmium hydroxide NaOH (sl), dil acids,          Water 
                        NH4OH, NH4Cl 
      Cadmium iodide    Water, alcohol, ether,          - 
                        acetone 
      Cadmium nitrate   Water, alcohol, acetone,       Conc HNO3 
                        ethyl acetate
      Cadmium oxide     Dil acids, NH4 salts           Water 
      Cadmium selenate  Water                            - 
      Cadmium selenide  -                              Water 
      Cadmium sulphate  Water                          Alcohol, ethyl 
                                                       acetate 
      Cadmium sulphide  Conc or warm dil acids         Water 
      
      conc  = concentrated 
      dil   = dilute 
      mod   = moderately 
      sl    = slightly 
 
      3.4   Other characteristics 
 
            Cadmium dust is reactive with strong oxidizing agents, 
            elemental sulphur, selenium and tellurium (Sittig, 1985). 

            Most cadmium compounds are reactive with oxidizing agents, 
            strong acids and bases, potassium and magnesium (Lenga, 1988). 

     4.   USES/CIRCUMSTANCES OF POISONING

      4.1   Uses 
 
            The main use of cadmium is the electroplating of other metals, 
            mainly steel, iron and copper. Almost 50% of all cadmium is 
            used for this purpose. Cadmium may also be alloyed with copper, 
            nickel, gold, silver, bismuth and aluminium to form easily 
            fusible compounds which can be used as coatings for other 
            materials, and in welding and in soldering processes (Friberg & 
            Elinder, 1983; Sittig, 1985). 

            In addition, cadmium compounds are used in the production of 
            pigments and dyes (cadmium sulphide, cadmium sulphoselenide), 
            as stabilizers in plastics (cadmium stearate), and in the 
            electrodes of nickel-cadmium alkaline batteries. 

            Cadmium compounds are also used in printing, in textiles, in 
            television phosphors, photography, lasers, in semiconductors, 
            pyrotechnics, solar cells, scintillation counters, as a neutron 
            absorber in nuclear reactors, in dental amalgams, in the 
            manufacture of fluorescent lamps, in jewellery, in engraving, 
            in the automobile and aircraft industries, as pesticides, 
            polymerization catalysts and in paints and glass. Cadmium is 
            found in superphosphate fertilizers (Stokinger, 1981; Friberg & 
            Elinder 1983). 

            Guidance on safe disposal:  recover for re-use or recycling, 
            and bury in a landfill according to local regulations. 

      4.2   High risk circumstances of poisoning 
 
            Inhalation of cadmium fumes and dust by persons employed in the 
            smelting and refining of cadmium ores, in the electroplating 
            industry, during heating, grinding, welding and soldering 
            operations involving cadmium-containing metal products, in the 
            production of cadmium pigments and in the plastics industry. 
            (Friberg & Elinder, 1983; Bernard & Lauwerys, 1986a). 

            The ingestion of food and beverages contaminated with cadmium, 
            the use of cadmium-plated cooking utensils, and the storage of 
            acid juice in cadmium-containing earthenware can cause 
            gastrointestinal toxicity. Acute oral intoxication has also 
            been observed in workers exposed to cadmium dust who employ 
            proper hygiene measures (Bernard & Lauwerys, 1986a). 

            Environmental risks 

            Increased emissions of cadmium from the production, use and 
            waste disposal of the metal, combined with its long-term 
            persistence in the environment and its relatively rapid uptake 
            and accumulation by food chain crops, contribute to its 
            potential hazard.  Soils may be contaminated with cadmium from 
            the air, by the application of water, fertilizers or pesticides 
            which contain cadmium, or by the discharge of cadmium-
            containing waste materials. (Page et al., 1986). 

            Excessive cadmium exposure has also occurred in the general 
            population through the ingestion of contaminated food and water 
            (Kjellstrom et al., 1977b; Kojima et al., 1977; Friberg & 
            Elinder, 1983). 

      4.3   Occupationally exposed populations 
 
            Zinc and lead refiners, welders, solder workers, alloy makers, 
            battery makers, engravers, textile workers and various 
            electronics workers (Ellenhorn & Barceloux, 1988). 

    5.    ROUTES OF ENTRY 

      5.1   Oral  
 
            Although cadmium compounds are relatively poorly absorbed from 
            the gastrointestinal tract (McLellan et al., 1978), the 
            occurrence of systemic toxicity following ingestion (Buckler et 
            al., 1986) indicates that the absorption of cadmium from the 
            gastrointestinal tract does occur and therefore that all 
            cadmium compounds should be considered potentially harmful if 
            ingested. 
 
      5.2   Inhalation 
 
            The occurrence of fulminant acute pneumonitis and pulmonary 
            oedema as well as neurotoxic effects following exposure to 
            cadmium-containing dusts and fumes (see e.g. Beton et al., 
            1966; Barnhart & Rosenstock, 1984) indicates that inhalation 
            of cadmium compounds must be considered serious and 
            potentially fatal (Sittig, 1985; Lenga, 1988). 
 
      5.3   Dermal 
 
            Although dermal absorption of cadmium is not likely to be 
            important, skin irritation may be caused by some cadmium 
            compounds (Sittig, 1985; Lenga, 1988). 
 
      5.4   Eye 

            Exposure to many cadmium compounds as well as cadmium dusts and 
            fumes is likely to produce severe corrosive damages to the eye 
            (Lenga, 1988). 

      5.5   Parenteral 
 
            No relevant data available 
 
      5.6   Others 

            No relevant data available. 

    6.    KINETICS 

      6.1   Absorption by route of exposure 
 
            Oral exposure

            During chronic background exposure, gastrointestinal absorption 
            of cadmium is of the order of 2-8% (McLellan et al., 1978; 
            Friberg & Elinder, 1983; Goyer, 1986). It has been estimated 
            that a European adult absorbs 1.4 - 8 g of cadmium per day 
            (Lauwerys, 1982). Physiological and nutritional factors may 
            modify this: in people with low body stores of iron the 
            absorption of cadmium may be significantly higher than in 
            subjects with normal iron stores (Flanagan et al., 1978). 

            Cadmium absorption tends to be higher in females than in males. 
            Animal experiments have shown that a low intake of calcium and 
            protein may considerably increase the intestinal absorption of 
            cadmium (Suzuki et al., 1969). 
 
            Inhalation

            Cadmium concentrations in ambient air are in the order of 
            0.001-0.005 g/m3 in rural areas, 0.003-0.05 g/m3 in urban 
            areas and up to 0.6 g/m3 near cadmium-emitting sources 
            (Bernard & Lauwerys, 1986a). 

            Much higher concentrations may occur in particular occupational 
            environments. The rate of absorption of cadmium through the 
            lungs is a function of the solubility and surface area of the 
            inhaled particles. 20-30% of the inhaled cadmium is probably 
            retained in the lungs. Therefore, the amount of cadmium 
            retained in the respiratory tract would be 0.005-0.025 g in 
            rural areas, 0.015-0.250 g in urban areas and up to about 3 ug 
            per  day in areas near cadmium-emitting sources. On the 
            assumption that up to about 60% of the retained cadmium is 
            absorbed (Lauwerys, 1982) the amount of cadmium effectively 
            absorbed by the lungs is unlikely to be much greater than about 
            0.2 g per day (Bernard  & Lauwerys, 1986a). 

            Cigarette smoking adds considerably to cadmium intake. 
            Friberg et al. (1974) estimated a daily intake of 2-4 g of 
            cadmium from the smoking of one packet of cigarettes per 
            day. 

      6.2   Distribution by route of exposure 

            Ingestion and Inhalation:  Cadmium is transported in the blood 
            bound mainly in red cells (more than 90%) or bound to high 
            molecular weight proteins in the plasma (Bernard & Lauwerys, 
            1986a; Goyer, 1986). 

            Cadmium is distributed particularly in the liver and kidneys, 
            where the production of metallothionein is induced. About 80-
            90% of cadmium in the body is bound to metallothionein (Friberg 
            &  Elinder, 1983). At steady state the kidney and liver have 
            the highest concentrations of cadmium and contain about 30 and 
            20% of the body burden of the metal, respectively. (Friberg et 
            al., 1979; Bernard & Lauwerys, 1986a; Goyer, 1986). 

            The concentration of cadmium in the renal cortex at 40-50 years 
            of age is between 15 and 50 g/g (Piscator & Lind, 1972; 
            Kjellstrom, 1979).  In acute exposure most of the cadmium is 
            distributed to the liver but redistribution to the kidneys 
            occurs following hepatic production of metallothionein. 

            The thyroid, the pancreas and the salivary glands also 
            accumulate significant amounts of cadmium. 

            Placental transfer of cadmium is limited. Cadmium concentration 
            in newborn blood is on average 50% lower than in maternal blood 
            (Lauwerys et al., 1978). 

      6.3   Biological half-life by route of exposure 

            The half-life of cadmium in the body is not known but estimates 
            range from 208 - 14 years (Kjellstrom & Nordberg, 1978) to 20 - 
            40 years (Friberg et al., 1974). 

      6.4   Metabolism 

            There is no evidence that the divalent cadmium cation undergoes 

            biotransformation in man. 

      6.5   Elimination by route of exposure 

            Cadmium is eliminated mainly in urine. The amount excreted 
            daily represents only about 0.005-0.010% of the total body 
            burden (Friberg et al., 1974). Excretion is proportional to the 
            body burden (Lauwerys et al., 1974; Roels et al., 1981a) and 
            increases up to 50-60 years of age (Elinder et al., 1978). 

            In persons not occupationally exposed to cadmium the urinary 
            excretion is normally less than 2 g/day (Bernard & Lauwerys, 
            1986a). 

    7.    TOXICOLOGY 


      7.1   Mode of action 

            The binding of cadmium to metallothionein prevents the free 
            cadmium ions from exerting their toxic effects. Free cadmium 
            ions in the cells as a result of the degradation of 
            metallothionein initiate the synthesis of new metallothionein 
            which then binds the cadmium thereby protecting the cell from 
            the highly toxic free cadmium ions. Toxicity may be considered 
            to occur when the binding capacity of metallothionein is 
            surpassed. 

            Renal toxicity

            Cadmium induces increased excretion of both low and high 
            molecular weight proteins. The following mechanisms have been 
            proposed. 

            (1) Increased urinary concentrations of low molecular weight 
            proteins ( 2-microglobulin) results from a cadmium-induced 
            defect in the reabsorption of proteins by the proximal tubules 
            and/or directly by cadmium-induced synthesis of  2-
            microglobulin. 

            (2) Altered glomerular function is reflected by increased 
            urinary concentrations of high molecular weight proteins but 
            not of low molecular weight proteins. 

            (3) In the case of mixed-type proteinuria, high molecular 
            weight proteins may be filtered at the glomerulus and then 
            incompletely reabsorbed in the proximal tubules. 

            Pulmonary toxicity 

            Experimental studies have shown that cadmium-containing 
            aerosols induce destruction of Type I epithelial cells with 
            pulmonary oedema, followed by a reparative process. 
            Interstitial cellular infiltration involves mainly 
            polymorphonuclear leukocytes and lymphocytes in the initial 

            phase and the release of alveolar macrophages in the later 
            stages of the lesion (Palmer et al., 1975; Hayes et al., 1976; 
            Strauss et al., 1976; Asvardi & Hayes, 1978). Animal studies 
            have also demonstrated a wide variety of effects of inhaled or 
            instilled cadmium on pulmonary responses such as collagen 
            biosynthesis (Chichester et al., 1981; Sampson et al., 1984), 
            surfactant production (Hayes et al., 1976; Amanuma & Suzuki, 
            1987), susceptibility to bacterial infection (Bouley et al., 
            1977), pulmonary antioxidative systems (Cross et al., 1979; 
            Grose et al., 1987), mitochondrial and microsomal enzymes 
            (Fukuhara et al., 1981; Boisset & Boudene, 1981; Palmer et al., 
            1983; Prasada Rao & Gardner, 1986), and carcinogenesis (Sanders 
            & Mahaffey, 1984). 

            Bone toxicity 

            Bernard & Lauwerys (1986a) have summarized the following four 
            possible mechanisms to account for the cadmium-induced 
            demineralization of bone: 

            (1)   Cadmium-induced renal tubular dysfunction leads to 
                  increased urinary excretion of calcium and phosphorus. 

            (2)   Cadmium-induced inhibition of the activation of vitamin D 
                  in the kidney leads to decreased synthesis of calcium-
                  binding protein in the intestinal mucosa and decreased 
                  intestinal absorption of calcium (Feldman & Cousins, 
                  1973). 

            (3)   Inhibition of calcium-dependent ATPase and calcium-
                  binding protein in the intestinal mucosa may lead to 
                  decreased intestinal calcium absorption (Nechay & 
                  Saunders, 1977; Samarawickrama, 1979). 

            (4)   Cadmium may act directly on bone tissue (Kawamura et al., 
                  1978). 

      7.2   Toxicity 

            7.2.1 Human data 
 
                  7.2.1.1   Adults 
 
                        Acute poisoning

                        Inhalation

                        Acute exposure to moderately high concentrations of 
                        freshly generated cadmium oxide fumes (200-500 g 
                        cadmium/m3) may cause symptoms similar to those of 
                        metal fume fever (Bernard & Lauwerys, 1986a). 
                        Concentrations above 1 mg/m3 in air for 8 hours, or 
                        higher concentrations for shorter periods may lead 
                        to acute chemical pneumonitis (Friberg & Elinder, 
                        1983). The lethal concentration of cadmium oxide 

                        fumes for humans has been estimated to be about 5 
                        mg cadmium/m3 for an 8-hour exposure (Friberg et 
                        al., 1974). 

                        Beton et al. (1966) described a case of acute fatal 
                        exposure to cadmium fumes. At autopsy 5 days after 
                        the exposure, tissue cadmium concentrations were: 
                        lungs 2.2 g/g wet weight, kidneys 5.0 g/g and
                        liver 2.8 g/g.

                        Lucas et al. (1980) reported the case of a welder 
                        who worked for about 30 minutes with an 
                        oxyacetylene torch and silver solder. The patient 
                        developed acute pneumonitis and died 5 days after 
                        the exposure. Post-autopsy cadmium concentrations 
                        were: urine 224 g/l, lung 4.7 g/g wet tissue,
                        liver 4.8 g/g and kidney 30.7 g/g.

                        Taylor et al. (1984) reported the case of a 36-
                        year-old man poisoned with cadmium fumes after 
                        smelting lead. The patient developed a pulmonary 
                        oedema and died on the 5th day after exposure. At 
                        48 hours after exposure blood and urine cadmium 
                        concentrations were 3.6 ug/l (normal  1.1 g/l) and
                        11 g/l (normal  1.1 g/l) respectively. At
                        autopsy, tissue cadmium concentrations (g/g) were 
                        considerably elevated, as compared with a control 
                        patient: kidney 67.95 (control, 9.38), liver 1.37 
                        (0.63), lung 0.82 (0.086), skin 0.24 (0.035), 
                        muscle 0.21 (0.058), heart 0.42, brain 0.08 
                        (0.066), stomach 0.43 and small intestine 0.90. 

                        Ingestion 

                        The no-effect level of cadmium administered as a 
                        single oral dose to humans is estimated to be 3 mg 
                        (Bernard & Lauwerys, 1986a). The ingestion of 
                        drinks contaminated with cadmium at concentrations 
                        exceeding 15 mg/l gives rise to gastrointestinal 
                        symptoms (Friberg & Elinder, 1983; Bernard & 
                        Lauwerys, 1986a). The lethal dose has been reported 
                        to range from 350-8,900 mg (Bernard & Lauwerys, 
                        1986a). 

                        Wisniewska-Knypl et al. (1971) reported a case of a 
                        man who ingested 5 g of cadmium iodide and died on 
                        the 7th day. Initial urine cadmium concentration 
                        was 15,600 g/l and declined to 100 ug/l on the 
                        seventh day. At autopsy the following tissue levels 
                        of cadmium were measured: brain 0.5 g/g, liver 80 
                        g/g, kidney 80 g/g (cortex) and 8.9 g/g
                        (medulla), blood 1.1 g/ml (sampled 3 days after
                        ingestion). 

                        Buckler et al. (1986) reported the case of a 17 
                        year-old woman with severe acute cadmium 
                        intoxication following the ingestion of 150 g of 
                        cadmium chloride. The patient developed 
                        hypotension, respiratory arrest, metabolic 
                        acidosis, pulmonary oedema, oliguria. and died 30 
                        hours after admission. At autopsy the following 
                        cadmium concentrations were observed: blood 23,000 
                        g/l, urine 17,000 g/l, liver 0.4 g/kg, lung 0.2 
                        g/kg. 
 
                        Chronic exposure (occupational)

                        Renal effects

                        Several authors have examined the relationship 
                        between the prevalence of kidney dysfunction and 
                        exposure to airborne cadmium. Bernard & Lauwerys 
                        (1986a) concluded that after 10 years of 
                        occupational exposure to 25 ug cadmium/m3, some 
                        workers may have accumulated toxic concentrations 
                        of cadmium in the renal cortex. 

                        Lauwerys et al. (1974) investigated three groups of 
                        workers exposed to cadmium dust together with three 
                        matched control groups. Excessive proteinuria was 
                        found in 15% of workers who had been exposed for 
                        less than 20 years to an average airborne 
                        concentration of cadmium dust of 134 g/m3. In a 
                        group of workers exposed for more than 20 years to 
                        cadmium dust (average total cadmium concentration 
                        66 g/m3) nearly 70% had excessive proteinuria. 

                        Kjellstrom et al. (1977a) studied 240 male and 
                        female workers exposed to cadmium oxide and  nickel 
                        hydroxide dust in a Swedish battery factory. The 
                        exposure level at the time of the study was about 
                        50 ug cadmium/m3 air. In the group continuously 
                        exposed to cadmium dust in the work environment the 
                        prevalence of increased urinary  2-microglobulin 
                        excretion increased with employment time. The 
                        prevalence in smokers was about three times higher 
                        than in nonsmokers. 

                        Thun et al. (1989) have assessed the quantitative 
                        relationship between exposure to airborne cadmium 
                        and various markers of renal tubular and glomerular 
                        function in 45 male workers employed at a cadmium 
                        recovery plant. Increasing cadmium dose was 
                        associated with reduced reabsorption of   2-
                        microglobulin, retinol binding protein, calcium and 
                        phosphate; serum creatinine concentration was also 
                        increased. Multiple renal abnormalities became 
                        apparent in subjects with a cumulative exposure of 
                        300 mg/m3.days, corresponding to working for 4.3
 
                        years at the current permissible United States 
                        exposure limit for cadmium dust (200 g/m3). 
 
                        Respiratory effects 

                        It is not clear whether lung impairment results 
                        from long-term exposure above a critical airborne 
                        cadmium concentration or from several episodes of 
                        exposure leading to permanent changes. Only a  
                        proposal for a long-term no-effect level of cadmium 
                        in air can be formulated. To prevent deleterious 
                        effects on the respiratory system, the time-
                        weighted average exposure to cadmium oxide fumes or 
                        to cadmium dust should not exceed a cadmium 
                        concentration of 20 g/m3 for a 40-hour working 
                        week for the entire working life (World Health 
                        Organization, 1980). 

                        Lauwerys et al. (1974) investigated three groups of 
                        workers exposed to cadmium dust. A slight but 
                        significant reduction in forced vital capacity, 
                        one-second forced expiratory volume and in peak 
                        expiratory flow rate was found only in those 
                        workers who had been exposed to mean total cadmium 
                        dust concentrations of 66 g/m3 for more than 20 
                        years. 

                        Stanescu et al. (1977) studied 18 workers 
                        exposed to elevated concentrations of cadmium 
                        dust and fumes (50 to 356 g of cadmium oxide) 
                        for 22-40 years in a cadmium production factory. 
                        Dyspnoea was found to be more frequent in the 
                        cadmium-exposed group, but there were no 
                        differences in the prevalence of other 
                        respiratory symptoms. 

                        Edling et al. (1986) examined lung function in 57 
                        male workers previously exposed to cadmium-
                        containing solders, together with a reference 
                        group. Exposure had been in the order of 50-500 g 
                        cadmium/m3. Although 42% of the workers had 
                        cadmium-induced renal damage in the form of  2-
                        microglobulinuria, there was no evidence of 
                        pulmonary damage. 

                        Chronic exposure (environmental)

                        Renal effects

                        Kjellstrom et al. (1977b) studied 138 farming women 
                        between 51 and 60 years who lived in a cadmium-
                        exposed area, together with 40 reference women in 
                        the same age group. The average urinary cadmium 
                        concentration was about twice as high in the 
                        exposed group (16.7 g/g creatinine) as in the 

                        reference group (8.8 g/g creatinine). Cadmium 
                        levels in blood among exposed persons (26 ng/g, 
                        range 7-62 ng/g) were also considerably elevated. 

                        Urinary  2-microglobulin excretion was strongly 
                        related to residence times in the exposed area as 
                        well as to the use of contaminated river water in 
                        the household. There was also a correlation between 
                        cadmium levels in the blood and  2-microglobulin 
                        excretion. 

                        Shiroishi et al. (1977) analysed total  protein,  
                        2-microglobulin and cadmium in urine samples 
                        obtained from people with Itai-itai disease and 
                        tubular kidney disease, as well as in samples from 
                        a reference group. On average, urinary  2-
                        microglobulin excretion among patients suffering 
                        from Itai-itai disease was 100-300 times higher 
                        than among the reference group, whereas total 
                        protein excretion was only 7 - 17 times higher.  

                        Kojima et al. (1977) studied 156 farmers living 
                        in a cadmium-exposed area and 93 farmers in a 
                        reference area. Average cadmium intake in the 
                        reference area was about 40 ug/day and in the 
                        exposed area about 150 g/day. Average urinary 
                        cadmium excretion in the reference group was 2 
                        ug/l and in the exposed group 7.5 g/l. The 
                        prevalence rate of tubular proteinuria was 3% in 
                        the reference group and 14% in the exposed 
                        group. Tubular proteinuria increased with age 
                        and with exposure duration. 
 
                  7.2.1.2   Children 

                        No relevant data available. 
 
            7.2.2 Relevant animal data 
 
                  LD50 of different cadmium compounds in various species.

            Species           Cadmium oxide      Cadmium     Cadmium chloride
                              Inhalation         Oral        Oral
                              (mg/m3/min)        mg/kg       mg/kg

            Rats                500              225          88
            Mice              < 700              636         175 
            Rabbits            2500                           63
            Guinea pigs        3500
            Dogs               4000
            Monkeys           15000

            (LD 50 by inhalation of cadmium oxide fume after exposure for 
             10 - 30 min.) 

                  (Barrett, Irvin and Semmons, 1947)

            7.2.3 Relevant in vitro data 
 
                  No relevant information available. 
 
            7.2.4 Workplace standards 

                  Exposure limits.
 
                  Cadmium dust

                  WHO          20 g/m3 40 hr/week for working life.
                  TWA OSHA    200 g/m3 over 8 hr, 600 g/m3 ceil. 
                  TWA NIOSH    40 g/m3 over 10 hr, 200 g/m3 15 min ceil. 
                  TLV ACGIH    50 g/m3 (including salts, as cadmium). 
                  STEL ACGIH  200 g/m3 (including salts, as cadmium). 
                  IDLH         40 g/m3

                  Cadmium oxide fume

                  WHO          20 g/m3 40 hr/week for working life. 
                  TWA OSHA    100 g/m3, 3 mg/m3 ceil. 
                  TWA NIOSH    40 g/m3 over 10 hr, 200 g/m3 15 min ceil. 
                  TLV ACGIH    50 g/m3 ceil. 
                  IDLH         40 g/m3
                  MAC USSR    100 g/m3
 
                  Cadmium oxide production

                  TLV ACGIH   50 g/m3. 

                  Permissible concentration in water 

                  US EPA, WHO                          10 g/l
                  Germany                              6  g/l 
                  South African Bureau of Standards    50 g/l

                  (WHO, 1980; Friberg & Elinder, 1983; ACGIH, 1986; Sittig, 
                  1985). 
 

            7.2.5 Acceptable daily intake (ADI)
 
                  The main source of the human body burden of cadmium is 
                  food. Drinking water and ambient air usually contribute 
                  considerably less to the daily intake. 

                  Total daily intake from food in North America and Europe 
                  varies considerably but is generally less than 100 
                  g/day, whereas in heavily polluted areas,such as parts 
                  of Japan, cadmium intake from food and water has been 
                  reported to be considerably greater (Friberg et al., 
                  1979; Bernard & Lauwerys, 1986a). 

                  Concentrations of cadmium in domestic water supplies 
                  rarely exceed a few g/l (Friberg et al., 1974; Bernard & 
                  Lauwerys, 1986a).  

                  The upper limit of air cadmium concentrations in urban 
                  areas is about 0.05 g/m3 (Bernard & Lauwerys, 1986a). 
                  Assuming a retention rate of 25% and a daily inhalation 
                  of 20 m3 of air, the amount of cadmium retained in the 
                  respiratory tract would not normally exceed 0.25 g per 
                  day. 

                  Cigarette smoking, however, adds considerably to cadmium 
                  input via inhalation. Friberg et al. (1974) estimates a 
                  daily intake of 2-4 g cadmium from smoking one packet of 
                  cigarettes per day.  

                  Kjellstrom & Nordberg (1978) have calculated that a 
                  daily intake of 440 g of cadmium is necessary for a 
                  European or American population to reach the estimated 
                  critical concentration of about 200 g of cadmium/g 
                  renal cortex. 

      7.3   Carcinogenicity 
 
            Although experimental studies support the potential 
            carcinogenicity of cadmium, epidemiological data provide 
            limited evidence that cadmium is carcinogenic in man. The 
            International Agency for Research on Cancer (1976) has 
            classified cadmium as probably carcinogenic in humans. 
            Currently, cadmium is being assessed by an international 
            working party (Sullivan & Waterman, 1988). 

            Human studies

            Although cadmium has been linked to prostatic cancer in workers 
            heavily exposed to cadmium over a number of years, recent 
            epidemiological studies have shown no evidence of an increased 
            risk. 

            Earlier epidemiological studies have shown that workers exposed 
            to cadmium appeared to have increased lung cancer mortality, 
            and there was a suggestion that the risk increased with the 
            length and intensity of occupational exposure. Ades & Kazantzis 
            (1988) have studied lung cancer mortality in a cohort of 4393 
            men employed at a zinc-lead-cadmium smelter. Although there was 
            an excess of lung cancer especially evident in those employed 
            for more than 20 years, the increasing risk of lung cancer 
            associated with increasing duration of employment could not be 
            accounted for by cadmium exposure. 
 
            Animal studies 

            The subcutaneous and intramuscular administration of inorganic 
            cadmium compounds has resulted in the development of local 
            sarcomas in rats as well as interstitial tumours of the testes 

            in rats and mice. There is no definite evidence that cadmium 
            compounds administered orally or by inhalation cause an 
            increase in the incidence of malignancies in laboratory animals 
            (International Agency for Research on Cancer, 1976). 
 
      7.4   Teratogenicity 
 
            Human studies

            Cvetkova (1970) reported that birth weights of newborn infants 
            of cadmium-exposed mothers were lower than those of unexposed 
            mothers but no congenital malformations were found. There is no 
            evidence that cadmium has caused teratogenic effects in humans. 

            Animal studies

            Embryotoxicity and teratogenicity has been demonstrated in 
            experimental animals treated with cadmium compounds. Ferm & 
            Carpenter (1967) have shown that the intravenous administration 
            of cadmium to pregnant golden hamsters during the early stages 
            of gestation resulted in fetal abnormalities and facial and 
            skeletal deformities in surviving animals. Nayak et al. (1989) 
            showed that pregnant mice treated parenterally with cadmium 
            chloride, had increased embryonic resorption and fetal 
            lethality as well as reduced placental weight. Webb et al. 
            (1988) showed that cadmium-metallothionein given to rats on 
            gestation days 8-14 was teratogenic, as well as nephrotoxic in 
            the mothers. 

      7.5   Mutagenicity 
 
            Data on the mutagenic effects of cadmium in humans are 
            conflicting. In one study of Itai-itai patients in Japan, 
            chromosomal aberrations were seen in peripheral blood 
            lymphocytes (Shiraishi, 1975) but this was not confirmed in 
            another study (Bui et al., 1975). A slight increase in 
            chromosomal aberrations in lymphocytes of cadmium-exposed 
            workers has also been reported (Deknudt & Leonard, 1975; 
            Bauchinger et al., 1976) but their observations have not been 
            confirmed by other researchers. 

            Cadmium chloride and cadmium acetate have been shown to alter 
            the fidelity of DNA replication in vitro (Loeb et al., 1974; 
            Sirover & Loeb, 1976; Mizutani & Temin, 1976). Cadmium chloride 
            has been shown to be a weak, direct-acting mutagen in the Ames 
            bacterial mutagenicity assay and a correlation was seen between 
            its toxicity and mutagenicity (Wong, 1988). 

            In animal mutagenicity studies, Epstein et al. (1972) and 
            Gilliavod & Leonard (1975) showed no effect in the dominant 
            lethal mutation test. Watanabe et al. (1977) have provided some 
            evidence of cadmium-induced mutations in chromosomes of mouse 
            ovaries. 

            In conclusion, although cadmium can be shown to cause point 
            mutations in bacterial DNA and induce in vitro chromosomal 
            aberrations in human lymphocytes it has not been shown 
            conclusively to cause the same effects in in-vivo studies. 

      7.6   Interactions 

            Numerous experimental studies have established that cadmium can 
            interact with several other metals such as zinc, copper, 
            selenium, calcium and iron (see reviews by Sandstead, 1976; 
            Foulkes, 1986; Webb, 1986). In most instances however the 
            studies have been carried out using dose levels of cadmium 
            which are considerably greater than those encountered in either 
            occupational or environmental exposures. 

            In people with low body stores of iron, intestinal absorption 
            of cadmium may be significantly higher than in subjects with 
            normal iron stores (Flanagan et al., 1978). Animal experiments 
            have shown that a low intake of calcium and protein may 
            considerably increase intestinal absorption of cadmium (Suzuki 
            et al., 1969). 

    8.    TOXICOLOGICAL AND BIOMEDICAL ANALYSES

    9.    CLINICAL EFFECTS 
 
      9.1   Acute poisoning

            9.1.1 Ingestion 

                  Symptoms begin almost immediately after ingestion and 
                  include vomiting, diarrhoea and abdominal pain. In severe 
                  poisoning, facial oedema, hypotension, pulmonary oedema, 
                  metabolic acidosis, oliguria and finally death have been 
                  reported (Buckler et al., 1986; Bernard & Lauwerys, 
                  1986a; Ellenhorn & Barceloux, 1988). 

            9.1.2 Inhalation 

                  There is usually a latent period of 4-12 hours between 
                  the exposure and the onset of symptoms. Initial 
                  presentation simulates metal fume fever: chills fever, 
                  headache, weakness, dryness of the nose and throat, chest 
                  pain, dyspnoea, cough, metallic taste, conjunctivitis, 
                  rhinitis, bronchitis. Nausea and vomiting may also be 
                  observed. In severe intoxication, patients may develop 
                  acute pneumonitis and lesional pulmonary oedema with 
                  respiratory failure which can progress to death in 3-7 
                  days (Beton et al., 1966; Townshend, 1968; Winston, 1971; 
                  Townshend, 1982; Friberg & Elinder, 1983; Taylor et al., 
                  1984; Sittig, 1985; Barnhart & Rosenstock, 1986; 
                  Ellenhorn & Barceloux, 1988; Yates & Goldman, 1990). 

            9.1.3 Skin exposure 

                  Although dermal absorption of cadmium is not likely to be 
                  important, skin irritation may be caused by some cadmium 
                  compounds (Sittig, 1985; Lenga, 1988). 
 
            9.1.4 Eye contact

                  Exposure to many cadmium compounds as well as cadmium 
                  dusts and fumes is likely to produce corrosive damages of 
                  the eyes (Lenga, 1988). 

            9.1.5 Parenteral exposure 

                  No relevant data available. 

            9.1.6 Other 

                  No relevant data available. 
 
      9.2   Chronic poisoning

            9.2.1 Ingestion 

                  In cadmium-polluted areas of Japan the signs of renal 
                  damage observed in cadmium workers have also been 
                  observed in the general population (Kjellstrom et al., 
                  1977b; Shiroishi et al., 1977; Saito et al., 1977; Kojima 
                  et al., 1977). A higher incidence of proteinuria, 
                  glycosuria and   2-microglobulinuria has been observed 
                  in the Jintzu river basin and in other areas where high 
                  concentrations of cadmium have been discovered in rice. 
                  In the endemic area of Toyama, the increased urinary 
                  excretion of  2-microglobulin was strongly related to 
                  the residence time in that area and to the cadmium level 
                  in urine and blood of the affected individuals 
                  (Kjellstrom et al., 1977b). 

                  Bone effects: Bone lesions are usually a late 
                  manifestation of severe chronic cadmium poisoning. They 
                  are characterized by osteomalacia, osteoporosis and 
                  spontaneous fractures. Signs and symptoms include 
                  skeletal deformities, decreased height, difficulty in 
                  walking, duck-like gait, pain in the back and 
                  extremities, and pain resulting from pressure on the 
                  bones (Bernard & Lauwerys, 1986b; Hallenbeck, 1986). 
 
            9.2.2 Inhalation 

                  Chronic poisoning may appear after several years of 
                  exposure. The earliest sign of cadmium-induced 
                  nephropathy is increased proteinuria. In particular  2-
                  microglobulin urinary excretion is markedly increased 
                  (Friberg, 1948; Potts, 1965; Tsuchiya, 1967). As kidney 
                  dysfunction progresses, minerals such as calcium and 

                  phosphorus may also be lost into the urine. Increased 
                  excretion of calcium and phosphorus may disturb bone 
                  metabolism, and kidney stones have been found in exposed 
                  workers (Friberg & Elinder, 1983). There may also be a 
                  decrease in the ability of the kidneys to concentrate 
                  urine (Friberg et al., 1974). The significance of 
                  proteinuria in relation to long-term renal dysfunction 
                  remains controversial. Roels et al. (1982), for example, 
                  have shown that once increased proteinuria has occurred 
                  it may be irreversible. Tsuchiya (1976), on the other 
                  hand, has suggested that proteinuria may resolve after 
                  removal of the subject from the cadmium exposure. The 
                  effects of long-term exposure to cadmium on mortality are 
                  uncertain ( Andersson et al., 1983; Armstrong & 
                  Kazantzis, 1983. 
 
                  Impairment of lung function has been described in workers 
                  subject to cadmium exposure by inhalation. The changes 
                  normally involve bronchitis which may lead to a mild form 
                  of obstructive lung disease with functional impairment. 
                  In some cases this condition may progress to fibrosis of 
                  the lower airways with alveolar damage and, in severe 
                  cases, emphysema (Lauwerys et al., 1974; Smith et al., 
                  1976; Stanescu et al., 1977; De Silva & Donnan, 1981; 
                  Friberg & Elinder, 1983; Armstrong & Kazantzis, 1983; 
                  Sittig, 1985; Goyer,1986). More recent investigations on 
                  workers currently exposed to cadmium indicate that 
                  because of improved working conditions the pulmonary 
                  changes are mild and occur less frequently and probably 
                  occurs at a later stage than renal damage (Lauwerys et 
                  al., 1974; Stanescu et al., 1977; Edling et al., 1986). 
 
            9.2.3 Skin exposure

                  No relevant data available 

            9.2.4 Eye contact 
 
                  No relevant data available. 

            9.2.5 Parenteral exposure 

                  No relevant data available. 
 
            9.2.6 Other 

                  No relevant data available. 

      9.3   Course, prognosis, cause of death 

            Acute poisoning following inhalation 

            There is generally a latent period of a few hours before the 
            onset of symptoms; warning signs are often absent. 

            Metal fume fever usually last from 1-2 days. Acute pneumonitis, 
            pulmonary oedema and respiratory failure may develop as early 
            as 8 - 12 hours following exposure. 

            The mortality rate is about 15% with death occurring after 4 - 
            7 days. If the patient survives, there may be a persistent 
            restrictive ventilatory defect which may last for several years 
            (Beton et al., 1966; Townshend, 1968; Winston, 1971; Townshend, 
            1982; Friberg & Elinder, 1983; Taylor et al., 1984; Sittig, 
            1985; Barnhart & Rosenstock, 1986; Ellenhorn & Barceloux, 1988; 
            Yates & Goldman, 1990). 

            Histology has shown congestion with intra-alveolar hemorrhage, 
            metaplasia of the alveoli lining cells and fibrinous intra-
            alveolar exudates (Beton et al., 1966; Barnhart & Rosenstock, 
            1984). 
 
            Acute poisoning following ingestion 

            Symptoms (acute gastroenteritis) begin almost immediately 
            following ingestion. In cases of fatal intoxication the initial 
            symptoms have been followed by either shock due to fluid loss 
            and death within 24 hours, or by acute renal failure with 
            cardiopulmonary depression, liver damage and death in 7-14 days 
            (Buckler et al., 1986; Bernard & Lauwerys, 1986a; Ellenhorn & 
            Barceloux, 1988). 

            Necropsy has shown pulmonary oedema, pleural effusions and 
            ascites, haemorrhagic necrosis of the stomach and duodenum, and 
            pancreatic haemorrhage (Buckler et al., 1986). 

            Chronic poisoning following inhalation

            The prominent feature and probably the earliest sign of 
            cadmium-induced nephropathy is increased proteinuria. Although 
            the minimum latent period before the onset of proteinuria is 
            normally at least 1 year (Tsuchiya, 1967) the first sign of 
            disease may not develop until many years later (Bonnell, 1965). 

            The significance of proteinuria in relation to long-term renal 
            dysfunction remains controversial (see section 9.2.2). 

            Pulmonary changes in patients occupationally exposed to 
            cadmium appear after several years (see section 9.2.2). 

            Chronic poisoning following ingestion

            In cadmium-polluted areas of Japan, renal damage has also been 
            observed in the general population. Bone lesions are usually a 
            late manifestation of severe chronic cadmium poisoning. 

      9.4   Systematic description of clinical effects 

            9.4.1 Cardiovascular 

                  Acute:  Hypotension and dysrhythmias have been observed 
                  after inhalation of cadmium fumes.  In one case 
                  inflammatory changes of the myocardium were noted (Taylor 
                  et al., 1984). 

                  Hypotension and shock have also been reported after 
                  ingestion of cadmium chloride (Buckler et al., 1986; 
                  Bernard & Lauwerys, 1986a). 

                  Chronic: No data available

            9.4.2 Respiratory 

                  Acute:  In cases of acute poisoning following inhalation 
                  the earliest symptom is slight irritation of the upper 
                  respiratory tract. This may be followed over the next few 
                  hours by the development of an acute pneumonitis 
                  including cough, chest pain and dyspnoea. After severe 
                  exposure, fulminant pulmonary oedema may occur (Beton et 
                  al., 1966; Townshend, 1968; Taylor et al., 1984; Barnhart 
                  & Rosenstock, 1984; Yates & Goldman, 1990).   Buckler et 
                  al. (1986) reported respiratory effects after acute 
                  ingestion of cadmium but no direct effect has been 
                  documented. 
 
                  Chronic:  Respiratory effects can also occur as a result 
                  of long-term occupational exposure to cadmium dusts and 
                  fumes. These effects do not normally precede renal 
                  tubular dysfunction and appear to involve only mild 
                  obstructive lung disease (dyspnoea, reduced vital 
                  capacity, and increased residual volume). In some cases 
                  fibrosis with alveolar damage may occur, and emphysema 
                  has been attributed to excessive exposure to cadmium 
                  (Lauwerys et al., 1974; Stanescu et al., 1977; Edling et 
                  al., 1986). 

            9.4.3   Neurological 
 
                  9.4.3.1     CNS 

                        Acute:  Insomnia, confusion and restlessness may be 
                        encountered in cases of inhalational poisoning 
                        (Beton et al., 1966; Taylor et al., 1984). Bernard 
                        & Lauwerys (1986a) list headache as one of the main 
                        symptoms associated with the acute ingestion of 
                        toxic doses of cadmium salts.  The mechanism is 
                        unknown but hypoxaemia may be responsible for these 
                        effects. 

                        Chronic:  No data available.

                  9.4.3.2     Peripheral nervous system 

                        Acute:  No data available.

                        Chronic:  No data available.

                  9.4.3.3   Autonomic nervous system 

                        Acute:  No data available.

                        Chronic:  No data available.

                  9.4.3.4     Skeletal and smooth muscle 

                        Aching pains in the back and limbs, chills,myalgia 
                        and generalized weakness may be observed in acute 
                        inhalational poisoning (Beton et al., 1966). 

                        

            9.4.4 Gastrointestinal 

                  Acute:  Following the ingestion of cadmium compounds 
                  gastrointestinal manifestations are the first symptoms to 
                  appear. Nausea and vomiting occur, normally without 
                  delay. There may also be salivation, diarrhoea, abdominal 
                  pain and discomfort (Buckler et al., 1986; Bernard & 
                  Lauwerys, 1986a). In the fatal case reported by Buckler 
                  et al. (1986) necropsy revealed haemorrhagic necrosis of 
                  the stomach, duodenum and jejunum. 

                  Metallic taste, nausea, vomiting, diarrhoea and abdominal 
                  pain have also been reported after the inhalation of 
                  cadmium-containing dusts and fumes (Beton et al., 1966; 
                  Taylor et al., 1984). 

                  Chronic:  No data available.

            9.4.5 Hepatic 

                  Acute:  In the case reported by Buckler et al. (1986) in 
                  which a young woman ingested 150 g of cadmium chloride, 
                  focal hepatic necrosis was observed at autopsy. Taylor et 
                  al. (1984) reported evidence of fatty infiltration and 
                  acute centrilobular necrosis of the liver in a patient 
                  who died following the inhalation of cadmium fumes. 

                  Chronic:  No data available.

            9.4.6 Urinary 

                  9.4.6.1     Renal 

                        Acute:  In cases of acute ingestion oliguria and 
                        acute renal failure may occur (Buckler et al., 

                        1986; Bernard & Lauwerys, 1986a). 

                        Oliguria, anuria and nocturia have been reported 
                        following the inhalation of cadmium fumes (Beton et 
                        al., 1966; Taylor et al., 1984). In the case report 
                        by Beton et al. (1966) the kidneys showed bilateral 
                        cortical necrosis and tubular degeneration on 
                        autopsy. 

                        Chronic:  Many studies have established that the 
                        kidney is the critical organ for long-term, low-
                        level exposure to cadmium from both occupational 
                        (see e.g. Friberg, 1948; Potts, 1965; Tsuchiya, 
                        1967) and environmental sources (Kjellstrom et al., 
                        1977b; Shiroishi et al., 1977; Saito et al., 1977; 
                        Kojima et al., 1977). The prominent feature and 
                        probably the earliest sign of cadmium-induced 
                        nephropathy is proteinuria. Although the minimum 
                        latent period before the onset of proteinuria is 
                        normally at least 1 year (Tsuchiya, 1967), the 
                        first sign of disease may not develop until many 
                        years later (Bonnell, 1965). 

                        Cadmium-induced proteinuria is considered to occur 
                        at concentrations in the range 100-300 g cadmium 
                        per gram wet weight of renal cortex (Friberg et 
                        al., 1974). The critical concentration of cadmium 
                        in the renal cortex has recently been estimated by 
                        neutron activation to be between 215 and 385 g/g. 
                        The critical body burden and urinary cadmium 
                        concentration has been estimated to be about 180 mg 
                        and 10-15 g cadmium/g creatinine respectively 
                        (Roels et al, 1979, 1981b, 1983). 

                        In cadmium-exposed workers the urinary excretion of 
                        low molecular weight proteins is markedly 
                        increased. This is often accompanied by increased 
                        urinary excretion of high molecular weight 
                        proteins. As the kidney dysfunction progresses, 
                        amino acids, glucose and minerals such as calcium 
                        and phosphorus, as well as cadmium itself are also 
                        eliminated in the urine. Increased excretion of 
                        calcium and phosphorus may disturb bone metabolism, 
                        and kidney stones have been found in exposed 
                        workers (Friberg & Elinder, 1983). There may also 
                        be a decrease in the ability of the kidneys to 
                        concentrate urine (Friberg et al., 1974). 

                        The significance of proteinuria in relation to 
                        long-term renal dysfunction is uncertain. Roels et 
                        al. (1982) have shown that once an increased 
                        proteinuria has occurred it may be irreversible, 
                        whereas Tsuchiya (1976) has suggested that the 
                        proteinuria may disappear after removal of the 
                        subject from the cadmium exposure. It is possible 

                        that slight proteinuria, detectable only by the 
                        determination of urinary   2-microglobulin, may be 
                        reversible depending on the past exposure 
                        conditions and on the health status of the worker 
                        (Bernard & Lauwerys, 1986a). 

                        The effects of long-term exposure to cadmium on 
                        mortality are also equivocal. Andersson et al. 
                        (1983), for example, have reported a significant 
                        increase in deaths from nephritis and nephrosis in 
                        a group of 175 workers exposed to cadmium for more 
                        than 15 years, whereas Armstrong & Kazantzis (1983) 
                        found no significant increase in mortality rate 
                        from nephritis and nephrosis in cadmium-exposed 
                        workers. 

                        The signs of renal damage observed in cadmium 
                        workers have also been observed in the general 
                        population living in cadmium-polluted areas of 
                        Japan. A higher incidence of proteinuria, 
                        glycosuria and delta 2-microglobulinuria has been 
                        observed in the Jintzu river basin in Toyama 
                        Prefecture and in other areas where high 
                        concentrations of cadmium have been discovered in 
                        rice. In the endemic area of Toyama the increased 
                        urinary excretion of delta 2-microglobulin was 
                        strongly related to the residence time in that area 
                        and to the cadmium level in urine and blood of the 
                        affected individuals (Kjellstrom et al., 1977b). 

                        Lauwerys et al. (1980), Lauwerys & De Wals (1981) 
                        and Roels et al. (1981a) have studied the effects 
                        of environmental exposure to cadmium on renal 
                        function in elderly subjects living in Belgium. 
                        Renal function of a group of 60 women of 60 years 
                        of age who had spent the major part of their lives 
                        in a cadmium-polluted area was compared with that 
                        of two groups of aged women from areas less 
                        polluted by this heavy metal. The group of women 
                        from the contaminated area had, on average, a 
                        higher cadmium body burden than the groups from the 
                        other areas. The parameters selected for evaluating 
                        renal function (total protein, aminoacids, delta 2-
                        microglobulin and albumin in the urine) followed 
                        the same trend. A retrospective mortality study 
                        revealed that the standardized mortality ratio from 
                        nephritis and nephrosis was significantly higher in 
                        the cadmium-polluted area than in other areas (see 
                        also Bernard & Lauwerys, 1986b). 

                  9.4.6.2     Others 

                        No data available.

            9.4.7 Endocrine and reproductive systems 

                  No data available.

            9.4.8 Dermatological

                  Acute:  Skin irritation may be expected as a result of 
                  contact with some cadmium compounds (Lenga, 1988). 

                  Chronic:  No data available.

            9.4.9 Eye, ears, nose, throat: local effects 

                  Acute:  The earliest symptom of inhalational exposure is 
                  irritation of the upper respiratory tract, including 
                  dryness of the nose and throat (Beton et al., 1966). 
                  Rhinitis and conjuntivitis may be observed.  The severity 
                  and latency of symptoms are a function of dose. 

                  Chronic:  No data available.

            9.4.10 Haematological

                  Acute:  The ingestion of cadmium chloride has been 
                  reported to produce an elevation in serum haemoglobin 
                  concentration, increased haematocrit and altered 
                  coagulation function (Buckler at al., 1986). 

                  Chronic:  No data available.

            9.4.11 Immunological

                  Acute:  No data available.

                  Chronic:  Although the effects of cadmium exposure on 
                  immune responses in experimental animals have been 
                  studied extensively, the relevance of the findings for 
                  humans remains to be elucidated. 

                  Most of these studies have examined immune function in 
                  young immunologically competent animals. The most 
                  predominant effects of cadmium have been associated with 
                  reduced T lymphocyte-dependent antibody production as 
                  well as with lowered natural killer (NK) cell activity 
                  and suppressed macrophage activity (Stelzer & Pazdernik, 
                  1983; Cook et al., 1984; Thomas & Imamura, 1986; Blakley 
                  & Tomar, 1986). These effects were considerably less 
                  marked in mature animals (Blakley, 1988). 

            9.4.12 Metabolic

                  9.4.12.1    Acid base disturbances 

                        Acute:  Buckler et al. (1986) reported a case in 
                        which ingestion of cadmium chloride produced 

                        metabolic acidosis. 

                        Chronic:  No data available.

                  9.4.12.2    Fluid and electrolyte 
                  disturbances 

                        Acute:  Electrolyte and fluid imbalance may occur 
                        following fluid losses due to diarrhoea after 
                        poisoning by ingestion. 

                        Chronic:  An increase in calcium and phosphorus 
                        urinary elimination may be observed when bone 
                        lesions are present. 

                  9.4.12.3    Others 

                        Townshend (1968) reported slight cyanosis in a 
                        patient more than 3 weeks following an acute 
                        inhalation of cadmium fumes. 

                        A suicidal ingestion of 150 g of cadmium chloride 
                        was associated with glucose intolerance (Buckler et 
                        al., 1986). 

            9.4.13 Allergic reactions

                  Acute:  No data available.

                  Chronic:  A total of 6 of 56 workers employed in a glass 
                  manufacturing plant (4/32) or in an electroplating 
                  factory (2/24), and who were in frequent and prolonged 
                  contact with either cadmium sulphide or cadmium cyanide, 
                  showed evidence of allergic contact dermatitis. None of 
                  these six workers was positive in patch tests to 1% 
                  cadmium chloride, although they tested positive to other 
                  chemicals with which they were in contact including epoxy 
                  resin, triethylenetetramine, chromium, cobalt and nickel 
                  (Rudzki et al., 1988). 

            9.4.14 Other clinical effects

                  Acute:  Hypothermia (temperature 30C) was observed in a 
                  patient following the ingestion of 150 g of cadmium 
                  chloride (Buckler et al., 1986). 

                  Chronic: Bone lesions are usually a late manifestation of 
                  severe chronic cadmium poisoning. They are characterized 
                  by osteomalacia, osteoporosis and spontaneous fractures. 
                  Signs and symptoms include skeletal deformities, 
                  decreased height, difficulty in walking, duck-like gait, 
                  pain in the back and extremities, and pain resulting from 
                  pressure on the bones (Bernard & Lauwerys, 1986b; 
                  Hallenbeck, 1986). 

            9.4.15 Special risks 

                  Pregnancy:  Cvetkova (1970) reported that birth weights 
                  of newborn infants of cadmium-exposed mothers were lower 
                  than those of unexposed mothers, but no congenital 
                  malformations were found. 

      9.5   Others 

            No data available.

    10.   MANAGEMENT 

      10.1  General principles 

            The treatment of acute cadmium poisoning should be directed 
            initially towards decontamination (removal of the patient from 
            further exposure, or the induction of vomiting). 

            In cases of inhalation, respiratory symptoms should be 
            carefully monitored and pulmonary oedema treated. 

            In cases of ingestion, ipecac/lavage/catharsis should be used 
            in the usual manner (Ellenhorn & Barceloux, 1988). 

            Antidotal treatment remains controversial.

            For patients with external dust contamination, health care 
            providers should protect themselves from airborne dust during 
            decontamination of the patient. 

      10.2  Relevant laboratory analyses and other investigations

            10.2.1 Sample collection 

                  For recent exposure whole blood cadmium concentration is 
                  the best measure of exposure. Whole blood levels above 10 
                  g/l indicate significant exposure. Blood should be 
                  collected in 10 ml heparinised vacutainers or preferably 
                  in all-plastic syringes, and refrigerated until analysed.  

                  For long-term, low-level exposure, urine cadmium 
                  concentration best reflects the total body burden, 
                  provided renal tubular dysfunction is normal. A 24-hour 
                  urine sample or an early-morning specimen collected into 
                  a clean 120 ml Nalgene bottle should be refrigerated or 
                  frozen until analysed. 
 
            10.2.2 Biomedical analysis 

                  In cases of acute poisoning from the inhalation of 
                  cadmium dusts and fumes, monitor cardio-respiratory 
                  function: chest X-ray, ECG and blood gases.  Diffusing 
                  capacity may be helpful. 

                  In cases involving the ingestion of cadmium, monitor 
                  cardiovascular parameters (heart rate, blood pressure) 
                  and electrolyte balance. 

                  In chronic poisoning by inhalation or ingestion, the 
                  early nephrotoxic effects of cadmium can be detected on 
                  the basis of the measurement of urinary proteins which 
                  reflect the functional integrity of the tubule or the 
                  glomerulus. Low molecular weight proteins such as  2-
                  microglobulin, retinol-binding protein, or a 1-
                  microglobulin are currently used for screening for 
                  proximal tubular injury, whereas the analysis of urinary 
                  high molecular weight proteins such as albumin permits 
                  the assessment of glomerular filtration selectivity. The 
                  urinary activity of  alpha-N-acetylglucosaminidase is 
                  also a sensitive indicator of excessive absorption of 
                  cadmium. 

            10.2.3 Toxicological analysis 

                  Several studies (e.g. Lauwerys et al., 1974; Bernard et 
                  al., 1979; Roels et al., 1981b, 1983) have revealed that 
                  in cadmium-exposed populations renal dysfunction is 
                  present when the concentration of urinary cadmium exceeds 
                  10 g cadmium/g creatinine 

      10.3  Life support procedures and symptomatic treatment 

            In cases of inhalational exposure life support measures should 
            be directed primarily to the treatment of pulmonary oedema. 

            Emergency treatment may include: oxygen given by mask face, 
            intubation and artificial ventilation using intermittent 
            positive-pressure. The efficacy of diuretics and 
            corticosteroids has not been established. 
 
      10.4  Decontamination 

            In case of poisoning by inhalation of cadmium fumes or dust, 
            the patient should be rapidly moved to fresh air protecting 
            health care workers from secondary exposure from dust. 

            If cadmium-containing substances are ingested, the mouth should 
            be washed out with water. If vomiting is not prominent, use 
            ipecac, gastric lavage or catharsis in the usual manner. Oral 
            activated charcoal is not useful (Friberg & Elinder, 1983; 
            Lenga, 1988; Ellenhorn & Barceloux, 1988) 

            In the case of skin exposure, the affected area should be 
            flooded with water for at least 15 min (Lenga, 1988). 

            Eye contamination should be managed by continuous irrigation of 
            the eye with clean water for at least 15 minutes (Lenga, 1988). 
 
      10.5  Elimination 

            The value of forced diuresis or enhanced elimination techniques 
            has not been established. 

      10.6  Antidote treatment 

            10.6.1 Adults 

                  Acute poisoning 

                  The role of EDTA is unclear. Recommendations for its use 
                  are based on the results of many animal studies which 
                  have shown that when administered to cadmium pre-treated 
                  animals, the body burden of cadmium is reduced and the 
                  urinary excretion of cadmium increased. However, thismay 
                  increase the uptake of cadmium by the kidneys and 
                  increase the risk of nephrotoxicity. Friberg & Elinder 
                  (1983) therefore recommend that calcium disodium EDTA is 
                  contraindicated because of its nephrotoxicity when 
                  administered in combination with cadmium. 

                  Conversely, Dreisbach (1983) proposes the following 
                  dosage regimen applicable in cases of acute cadmium 
                  poisoning: 15-25 mg EDTA/kg (0.08-0.125 ml of 20% 
                  solution/kg body weight) in 250-500 ml of 5% dextrose 
                  intravenously over a 1 - 2-hour period twice daily. The 
                  maximum dose should not exceed 50 mg/kg/day. The drug 
                  should be given in 5 day courses with an interval of at 
                  least 2 days between courses. During subsequent courses 
                  urinalysis should be done daily and the dosage reduced if 
                  any unusual urinary findings occur. 

                  Both Friberg & Elinder (1983) and Ellenhorn & Barceloux 
                  (1988) state that dimercaprol (BAL) should not be used in 
                  cases of acute cadmium poisoning. 

                  Cotter (1958) reported the case of three men exposed to 
                  cadmium fumes who were subsequently treated with calcium 
                  disodium EDTA, at a dose of 0.5 g every 2 hours for 1 or 
                  2 weeks. At the end of the treatment period the patients 
                  were either asymptomatic or had made a significant 
                  recovery, as indicated by a reduction in blood urea 
                  nitrogen, blood cadmium and urinary cadmium 
                  concentrations. 

                  Recent studies in rodents have shown that, for acute oral 
                  cadmium intoxication, meso-2,3-dimercaptosuccinic acid 
                  given orally (Basinger et al., 1988; Andersen & Nielsen, 
                  1988; Andersen, 1989) or calcium disodium 
                  diethylenetriaminepentaacetate (DTPA) given parenterally 
                  (Andersen, 1989) are the most effective antidotes, 
                  provided that treatment is started very soon after 
                  cadmium ingestion. 

                  Chronic poisoning 

                  The current consensus appears to be that there is no 
                  recommended chelation treatment for chronic cadmium 
                  exposure (Jones & Cherian, 1990). 

                  Jones & Cherian (1990), in a recent review paper, state 
                  that in recent years considerable progress has been made 
                  in the development of a compound which can be given 
                  serious consideration for use in human cases of chronic 
                  cadmium intoxication. They suggest that the reduction of 
                  whole body, renal and hepatic levels of cadmium in mice 
                  treated with recently developed compounds such as sodium 
                  N-(4-methoxylbenzyl)-D-glucamine dithiocarbamate is 
                  comparable or superior to the results obtained with 
                  compounds used clinically with other toxic metals for 
                  which chronic intoxication is considered treatable. 
 
            10.6.2   Children 

                  No data available. 

      10.7  Management discussion 

            The usefulness of antidotal treatment in cadmium poisoning 
            remains controversial and has to be assessed by further 
            studies. There is insufficient convincing scientific evidence 
            of efficacy for EDTA to recommend its use. 

    11.   ILLUSTRATIVE CASES 

      11.1  Case reports from literature 

            Young adult, acute ingestion (Buckler et al., 1986).

            A 17-year-old woman was admitted to hospital with facial 
            swelling and vomiting. She was too ill to provide any history. 
            She had facial, pharyngeal and neck swelling and was 
            hypotensive. Subsequent gastric washout (roughly three hours 
            after ingestion) produced a white crystalline material 
            confirmed to be cadmium chloride. She suffered a respiratory 
            arrest, becoming hypothermic (temperature 30C), 
            haemoconcentrated (haemoglobin 222 g/l, packed cell volume 
            0.52), glucose intolerant (glucose 55.8 mmol/l) and acidotic 
            (pH 6.9) without ketones. Results of coagulation studies were: 
            prothrombin time 60 sec (control 13 sec) and partial 
            thromboplastin time 180 sec (control 39 sec). Over 24 hours she 
            developed pulmonary and generalized oedema and oliguria. Full 
            supportive measures including chelation treatment, charcoal 
            haemoperfusion and positive end expiratory pressure ventilation 
            were unsuccessful, and she died 30 hours after admission. 
            Necropsy showed pulmonary oedema, pleural effusion and ascites. 
            There was haemorrhagic necrosis of the stomach, duodenum and 
            jejunum, focal hepatic necrosis and slight pancreatic 
            haemorrhage. The kidneys appeared normal. At autopsy the 

            following cadmium concentrations were measured: blood 23 mg/l, 
            urine 17 mg/l, liver 0.4 g/kg wet tissue, lung, 0.2 g/kg. 

            The patient had ingested a massive dose of 150 g of cadmium 
            chloride, and although the initial diagnosis was delayed, it 
            seems unlikely that any treatment would have prevented the 
            membrane dysfunction and destruction of tissue. The case 
            illustrates the catastrophic effects of ingested cadmium on 
            organ function. 
 
            Adult, acute inhalation (Barnhart & Rosenstock, 1984).

            A 34 year-old man had been soldering silver in an enclosed, 
            unventilated small tank with an opening only large enough to 
            admit his upper body. At the time of exposure he noted only 
            diplopia. Later, he developed dyspnoea, cough, abdominal pain 
            and he felt feverish. Because of persistent cough and dyspnoea 
            he was seen about two weeks later and told he had metal fume 
            fever. His cough and dyspnoea resolved in about four weeks. 
            Chest x-ray films obtained two weeks after his acute exposure 
            revealed bilateral infiltrates. Four years later they were 
            normal. Results of pulmonary function tests revealed moderate 
            restrictive impairment and moderately decreased single breath 
            diffusing capacity (Dco). His Dco returned to normal within two 
            months and his total lung capacity had showed continued 
            improvement but remained below normal nearly four years after 
            exposure. 
 
            Adult, acute inhalation (Lucas et al., 1980). 

            A previously healthy 34 year-old welder worked for 
            approximately 30 minutes with an oxyacetylene torch and silver 
            solder. His workbench was in a large airy building with a high 
            ceiling. Large doors were open, but there was no specific 
            ventilation system in operation. He become dyspnoeic with a 
            persistent non-productive cough within hours of completing the 
            job. His symptoms worsened steadily and he died 5 days after 
            exposure. Both lungs showed changes typical of acute 
            pneumonitis. The source of cadmium was the rod of silver solder 
            which contained 20% cadmium. The case illustrates the fact 
            that, unless specific measures are taken, death from cadmium 
            fume inhalation can occur in an apparently well-ventilated 
            environment, particularly if the presence of cadmium is not 
            suspected. 
 
            Adult, acute inhalation (Taylor et al., 1984).

            A fit 36-year-old man was admitted with a 24-hour history of 
            vomiting and profuse watery diarrhoea. He had generalised 
            diffuse, dull, aching abdominal pains, a severe headache and 
            generalised myalgia with tightness of his chest. He was 
            slightly confused, restless, and dehydrated but had no fever, 
            lymphadenopathy, or rash. He had a regular pulse rate of 108 
            beats/min and blood pressure of 80/40 mm Hg. His chest was 
            clear. His abdomen was diffusely tender without peritoneal 

            signs. Severe gastroenteritis was diagnosed, and he was treated 
            symptomatically. 

            A chest radiograph was normal. Blood cultures and viral 
            agglutinin titres yielded negative results. Despite adequate 
            rehydration he produced only 50 ml of urine over the next 18 
            hours. He became increasingly dyspnoeic and developed bilateral 
            fine basal crepitations and radiographic appearances consistent 
            with gross pulmonary oedema. Electrocardiography showed varying 
            rhythms of atrial fibrillation, nodal rhythm and sinus 
            tachycardia. He became feverish and his myalgia worsened. 

            Twenty four hours after admission it was discovered that he had 
            been smelting about 182 kg of lead for about 24 hours in an 
            enclosed environment without wearing adequate protective 
            clothing. He had felt unwell towards the end of that session. 

            As he was anuric, chelating agents were not indicated. Although 
            he was treated with peritoneal dialysis, his condition 
            deteriorated. He remained dyspnoeic and cyanotic and died 72 
            hours later. Postmortem examination revealed that his lungs and 
            gastric mucosa were appreciably congested with moderate 
            hyperemia throughout the large and small intestines and there 
            was slight cerebral congestion. Histological investigations 
            showed mild hepatic fatty infiltration and severe acute 
            centrilobular necrosis of the liver, acute cellular necrosis in 
            the loops of Henle, mild interstitial oedema and infiltration 
            of the myocardium with eosinophils, lymphocytes, and 
            histiocytes, depletion of lipid content and mild focal 
            haemorrhage in the adrenals, and congestion and acute 
            inflammatory cell infiltration of the spleen. 

      11.2  Internally extracted data on cases  

            No data available.

      11.3  Internal cases

            To be completed by the PCC.

    12.   ADDITIONAL INFORMATION 

      12.1  Availability of antidotes and antisera 

            To be completed locally.

      12.2  Specific preventive measures 

            Processes releasing cadmium fumes or dust should be designed to 
            keep concentration levels to a minimum. When adequate 
            engineering control and ventilation cannot ensure constant safe 
            air levels, respiratory protection must be used.  Eye washing 
            equipment should be easily accessible if cadmium chloride is 
            being used. Adequate sanitary facilities should be supplied, 
            and workers should wash before meals and before leaving work. 

            Work clothing should be changed daily and washed thoroughly at 
            work before re-use.  Smoking, eating and drinking in work areas 
            should be prohibited.  Cigarettes and food should not even be 
            stored briefly in cadmium contaminated air. 

            In the pre-employment physical examination, emphasis should be 
            given to a history or presence of significant kidney or 
            respiratory disease. A chest x-ray and baseline pulmonary 
            function study is recommended (Friberg & Elinder, 1983; 
            Sitting, 1985). 

            Medical examination of cadmium-exposed workers should be 
            carried out at least once every year. These examinations should 
            emphasize the respiratory system (including pulmonary function 
            tests) and the kidneys. Cadmium levels in blood and in urine 
            should be checked regularly. Cadmium levels in urine can be 
            used to estimate the cadmium body burden. The concentration 
            should not be allowed to reach 5-10 g cadmium/g urinary 
            creatinine. In workers exposed to cadmium for longer periods 
            quantitative measurements of  2-microglobulin and for retinol 
            binding protein in urine should be made regularly. 
            Concentrations of  2-microglobulin in urine should normally 
            not exceed 0.5 mg/l (Friberg & Elinder, 1983). 

      12.3  Other 

            No data available.

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    14.   AUTHOR(S), REVIEWER(S), DATE (INCLUDING EACH UPDATE) 

      Author(s):  R.W. Mason 
                  National Toxicology Group 
                  University of Otago Medical School, 
                  PO Box 913
                  Dunedin
                  New Zealand

                  Tel:  (64) (03) 4797-254 
                  Fax:  (64) (03) 4770-509 
                  Tlx:  5706 HOSBORD 
 
                  G.S. Elliott(Sections 7.3, 7.4, 7.5, 9.4.11 & 9.4.13)
                  National Toxicology Group 
                  University of Otago Medical School, 
                  PO Box 913
                  Dunedin
                  New Zealand

                  Tel:  (64) (03) 4797-254 
                  Fax:  (64) (03) 4770-509 
                  Tlx:  5706 HOSBORD 

                  S.D. Jones (Co-author) 
                  National Toxicology Group 
                  University of Otago Medical School, 
                  PO Box 913
                  Dunedin
                  New Zealand

                  Tel:  (64) (03) 4797-254 
                  Fax:  (64) (03) 4770-509 
                  Tlx:  5706 HOSBORD 

      Date:       20 October 1990 
 
      Reviewers:  A. Jaeger, J. Kopferschmitt, Ph. Sauder, F. Flesch
                  Service de Ranimation Mdicale et Centre Anti-Poisons
                  Hpitaux Universitaires de Strasbourg
                  Hpital Civil
                  67091 Strasbourg Cedex
                  France

                  Tel:  33 88 16 11 44
                  Fax:  33 88 16 13 30

      Date:       26 Janvier 1992

      Peer review:Newcastle-upon-Tyne, United Kingdom, February 1992
                  (Group members: P. Edelman, A. Jaeger, O. Kasilo,
                  P. Myrenfors, J. Szajewski)




    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 24)
       Cadmium (WHO Food Additives Series 55)
       CADMIUM (JECFA Evaluation)