Toxicity Profiles

Formal Toxicity Summary for CADMIUM

NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.

EXECUTIVE SUMMARY
1. INTRODUCTION
2. METABOLISM AND DISPOSITION
2.1 ABSORPTION 2.2 DISTRIBUTION 2.3 METABOLISM 2.4 EXCRETION
3. NONCARCINOGENIC HEALTH EFFECTS
3.1 ORAL EXPOSURES 3.2 INHALATION EXPOSURES 3.3 OTHER ROUTES OF EXPOSURE 3.4 TARGET ORGANS/CRITICAL EFFECTS
4. CARCINOGENICITY
4.1 ORAL EXPOSURES 4.2 INHALATION EXPOSURES 4.3 OTHER ROUTES OF EXPOSURE 4.4 EPA WEIGHT-OF-EVIDENCE 4.5 CARCINOGENICITY SLOPE FACTORS
5. REFERENCES

November 1991

Prepared by: Robert A. Young, Ph.D., D.A.B.T., Chemical Hazard Evaluation and Communication Group, Biomedical and Environmental Information Analysis Section, Health and Safety Research Division, *.

Prepared for OAK RIDGE RESERVATION ENVIRONMENTAL RESTORATION PROGRAM.

*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.

EXECUTIVE SUMMARY

Cadmium is a naturally occurring metal that is used in various chemical forms in metallurgical and other industrial processes, and in the production of pigments. Environmental exposure can occur via the diet and drinking water (ATSDR, 1989).

Cadmium is absorbed more efficiently by the lungs (30 to 60%) than by the gastrointestinal tract, the latter being a saturable process (Nordberg et al., 1985). Cadmium is transported in the blood and widely distributed in the body but accumulates primarily in the liver and kidneys (Goyer, 1991). Cadmium burden (especially in the kidneys and liver) tends to increase in a linear fashion up to about 50 or 60 years of age after which the body burden remains somewhat constant. Metabolic transformations of cadmium are limited to its binding to protein and nonprotein sulfhydryl groups, and various macromolecules, such as metallothionein, which is especially important in the kidneys and liver (ATSDR, 1989). Cadmium is excreted primarily in the urine.

Acute oral exposure to 20-30 g have caused fatalities in humans. Exposure to lower amounts may cause gastrointestinal irritation, vomiting, abdominal pain, and diarrhea (ATSDR, 1989). An asymptomatic period of one-half to one hour may precede the onset of clinical signs. Oral LD50 values in animals range from 63 to 1125 mg/kg, depending on the cadmium compound (USAF, 1990). Longer term exposure to cadmium primarily affects the kidneys, resulting in tubular proteinosis although other conditions such as "itai-itai" disease may involve the skeletal system. Cadmium involvement in hypertension is not fully understood (Goyer, 1991).

Inhalation exposure to cadmium and cadmium compounds may result in effects including headache, chest pains, muscular weakness, pulmonary edema, and death (USAF, 1990). The 1-minute and 10-minute lethal concentration of cadmium for humans has been estimated to be about 2,500 and 250 mg/m3, respectively (Barrett et al., 1947; Beton et al., 1966). An 8-hour TWA (time-weighted-average) exposure level of 5 mg/m3 has been estimated for lethal effects of inhalation exposure to cadmium, and exposure to 1 mg/m3 is considered to be immediately dangerous to human health (Friberg, 1950). Renal toxicity (tubular proteinosis) may also result from inhalation exposure to cadmium (Goyer, 1991).

Chronic oral RfDs of 5E-4 and 1E-3 mg/kg/day have been established for cadmium exposure via drinking water and food, respectively (U.S. EPA, 1991). Both values reflect incorporation of an uncertainty factor of 10. The RfDs are based on an extensive data base regarding toxicokinetics and toxicity in both human and animals, the critical effect being renal tubular proteinuria. Confidence in the RfD and data base is high.

Inhalation RfC values are currently not available.

The target organ for cadmium toxicity via oral exposure is the kidney (Goyer, 1991). For inhalation exposure, both the lungs and kidneys are target organs for cadmium-induced toxicity (ATSDR, 1989; Goyer, 1991).

There is limited evidence from epidemiologic studies for cadmium-related respiratory tract cancer (ATSDR, 1989). An inhalation unit risk of 1.8E-3 (µg/m3)-1 and an inhalation slope factor of 6.1E+0 (mg/kg/day)-1 are based on respiratory tract cancer associated with occupational exposure (U.S. EPA, 1985). Based on limited evidence from multiple occupational exposure studies and adequate animal data, cadmium is placed in weight-of-evidence group B1 - probable human carcinogen.

1. INTRODUCTION

Cadmium (Cd) is a naturally occurring metallic element that is used for electroplating and galvanization processes, in the production of pigments, in batteries, as a chemical reagent, and in miscellaneous industrial processes (ATSDR, 1989). Cadmium compounds have varying degrees of solubility ranging from very soluble to nearly insoluble. The solubility affects their absorption and toxicity. Exposure to cadmium and cadmium compounds may occur in both occupational and environmental settings, the latter primarily via the diet and drinking water (ATSDR, 1989).

2. METABOLISM AND DISTRIBUTION

2.1. ABSORPTION

Cadmium is more efficiently absorbed from the lungs than from the gastrointestinal tract (ATSDR, 1989). The absorption efficiency is a function of solubility of the specific cadmium compound as well as its exposure concentration and route.

Inhalation absorption usually involves cadmium in a particulate matter form with absorption being a function of deposition, which in turn is dependent upon the particle size (particles >= 10µm diameter tend to be deposited in the upper airways and particles <= 0.1 µm diameter are deposited in the alveolar region). Alveolar deposition efficiency in animal models ranges from 5 to 20% (Barrett et al., 1947; Boisset et al., 1978). Based on physiological modeling, cadmium deposition in the alveolar region of humans was estimated to be up to 50% for small particles (Nordberg et al., 1985). Actual cadmium absorption via inhalation exposure has been estimated to be 30 to 60% in humans (Friberg et al., 1974; Elinder et al., 1976).

Absorption of cadmium from the gastrointestinal tract appears to be a saturable process with the fraction absorbed decreasing at high doses (Nordberg et al., 1985). It is also important to distinguish true absorption from simple retention of cadmium in the microvilli of the small intestine (Foulkes et al., 1986). Shaikh and Smith (1980) reported a mean retention of 2.8% (1.1 to 7.0% range) for 12 human subjects given a single oral dose of radiolabeled cadmium chloride, and McLellan et al. (1978) reported 5.9% retention of cadmium chloride by 14 human subjects.

Also of importance relative to cadmium absorption is that its absorption may be decreased by divalent and trivalent cations (Zn+2, Mg+2, Cr+3), and increased by iron and calcium deficiencies (Flanagan et al., 1978; Foulkes et al., 1986; Goyer, 1991). Dermal absorption is relatively unimportant (ATSDR, 1989).

2.2. DISTRIBUTION

Cadmium is transported in the blood by red blood cells and high-molecular-weight proteins such as albumin (Goyer, 1991). Normal blood cadmium levels in adults are < 1µg/dL. Although cadmium is widely distributed throughout the body, most (50 to 70% of the body burden) accumulates in the kidneys and liver (Goyer, 1991). Cadmium burden, especially in the kidneys, tends to increase in a linear fashion with age up to about 50 or 60 years of age after which the kidney levels remain somewhat constant or slightly decline (Goyer, 1991). There is evidence that the placenta is a partial barrier to cadmium, and that the fetus is exposed to only small amounts of maternal cadmium (ATSDR, 1989).

2.3. METABOLISM

As with most metallic elements, there is little or no direct metabolic conversions of cadmium, but rather binding to various biological components, such as protein and nonprotein sulfhydryl groups and anionic groups of various macromolecules (ATSDR, 1989). Of special importance, is the binding protein, metallothionein which is very effective in binding cadmium and some other metals and is instrumental in determining the disposition of cadmium in the body (e.g. concentration of cadmium in the kidneys).

2.4. EXCRETION

The principal route of excretion is via the urine, with average daily excretion for humans being about 2 to 3 µg (ATSDR, 1989). Daily excretion represents only a small percentage of the total body burden, which accounts for the 17 to >30 years half-life of cadmium in the body (Tsuchiya et al., 1972; Friberg et al., 1974). Unabsorbed cadmium is removed from the gastrointestinal tract by fecal excretion. Typical daily cadmium excretion has been reported to be about 0.01% of the total body burden (ATSDR, 1989). There is some evidence for biliary excretion of cadmium (Klaassen et al., 1978).

3. NONCARCINOGENIC HEALTH EFFECTS

3.1. ORAL EXPOSURES

3.1.1. Acute Toxicity

3.1.1.1. Human

Doses of 1,500 to 8,900 mg (20 to 30 mg/kg) of cadmium have resulted in human fatalities, but generally, fatal poisoning from cadmium is rare (ATSDR, 1989). High doses of cadmium are known to cause gastrointestinal irritation resulting in vomiting, abdominal pain, and diarrhea (ATSDR, 1989). Lauwerys (1979) reported that the emetic threshold for cadmium in drinking water was about 15 mg/L and CEC (1978) reported that 3 mg was an emetic threshold.

Following ingestion of cadmium, an asymptomatic period of 0.5 to 1.0 hour may precede the onset of clinical signs. Depending on the severity of exposure, clinical signs of cadmium poisoning following acute exposure include: nausea, vomiting, abdominal cramps, headache, muscle cramps, exhaustion, shock, and death (USAF, 1990).

3.1.1.2. Animal

Oral LD50 values for animals range from 225 to 890 mg/kg for elemental cadmium, 63 to 88 mg/kg for cadmium chloride, 72 mg/kg for cadmium oxide, and 590 to 1125 mg/kg for cadmium stearate (USAF, 1990).

3.1.2. Subchronic Toxicity

3.1.2.1. Human

Because the toxic effects of cadmium are a function of a critical concentration being attained in a target organ, similar effects will occur following long-term exposure to low cadmium levels and

short-term exposure to high concentrations (Wang and Foulkes, 1984). Consequently, renal and hepatic toxicity may occur if toxic cadmium levels are attained in these organs even during subchronic exposure. A description of cadmium-induced toxicity following oral exposure is presented in Section 3.1.3. Generally, cadmium is not as toxic via oral routes as via inhalation.

3.1.2.2. Animal

Exposure of rabbits to 1.5 mmol cadmium chloride in drinking water (equivalent to 13 µg/kg/day) produced histological alterations in the liver but no clinical signs of toxicity (Stowe et al., 1972). In a study by Kotsonis and Klaassen (1978), rats exhibited proteinuria after receiving cadmium chloride in the drinking water for six weeks at 30 or 100 mg/L (equivalent to 3.1 and 8.0 mg Cd/kg/day).

Although the effects of cadmium on the immune system of humans is unclear, evidence for cadmium-induced immunotoxicity in animals is available. Koller et al. (1975) noted a decrease in the number of spleen placque-forming cells in mice receiving cadmium at 0.6 mg/kg/day for 10 weeks, and Blakley (1985) reported a dose-dependent suppression of the humoral immune system in mice receiving cadmium in drinking water at concentrations of 5 to 50 mg/L for three weeks. These immune system effects occurred at kidney tissue concentrations (0.3 to 6.0 µg/g) lower than those associated with renal toxicity.

3.1.3. Chronic Toxicity

3.1.3.1. Humans

The most serious chronic effect of oral exposure to cadmium is renal toxicity. This critical effect is characterized by tubular proteinuria resulting from renal tubular dysfunction. Friberg et al. (1974) estimated that this critical effect will not occur in humans until the cadmium concentration in the renal cortex exceeds 200 µg/g.

Dietary intake of cadmium has also been implicated in osteomalacia, osteoporosis and spontaneous fractures, conditions collectively termed "itai-itai" (ouch-ouch) disease and originally documented in postmenopausal women in cadmium-contaminated areas of Japan (Friberg et al., 1974).

Cadmium exposure has also been implicated in hypertensive disorders, a situation that is currently not thoroughly understood or verified (ATSDR, 1989).

3.1.3.1. Animals

Rats given cadmium chloride in the drinking water at a concentration of 10 mg/L (1.2 mg Cd/kg/day) exhibited no renal effects even after 24 months, although higher exposure levels induced proteinuria after six weeks exposure (Kotsonis and Klaassen, 1978).

3.1.4. Developmental and Reproductive Toxicity

3.1.4.1. Human

Developmental and reproductive toxicity in humans have not been demonstrated for oral exposure to cadmium (ATSDR, 1989).

3.1.4.1. Animal

Developmental toxicity data for cadmium administered orally to rats are equivocal. Pond and Walker (1975) reported few, if any effects, for rats exposed to cadmium chloride in the drinking water (15 mg/kg/day) during gestation. Baranski et al. (1985) reported teratogenic effects (fused or absent legs) in rats following gavage administration of cadmium chloride (40 mg/kg/day) during gestation. Neurological effects in rat pups were detected following gestational exposure to 0.4 or 4 mg Cd/kg (Baranski et al., 1986).

3.1.5. Reference Dose

3.1.5.1. Subchronic

  • ORAL RfDs: Not available
  • UNCERTAINTY FACTOR: Not available
  • NOAEL: Not available

3.1.5.2. Chronic

  • ORAL RfDc: 5E-4 mg/kg/day (water) (U.S. EPA, 1991) 1E-3 mg/kg/day (food)
  • UNCERTAINTY FACTOR: 10 (for both food and water)
  • MODIFYING FACTOR: 1 (for both food and water)
  • NOAEL: 0.005 mg/kg/day (water) 0.01 mg/kg/day (food)
  • LOAEL: Not available
  • CONFIDENCE: Study: Not applicable Data base: High RfD: High
  • VERIFICATION DATE: 05/25/88
  • PRINCIPAL STUDY:The data supporting the RfD have been derived from many animal and human studies that have provided information on cadmium toxicity (renal toxicity using proteinuria as the critical effect) and the calculation of pharmacokinetic parameters regarding calcium absorption, distribution and excretion.
  • COMMENTS: Due to background cadmium in the diet, no subchronic RfD was calculated.

3.2. INHALATION EXPOSURES

3.2.1. Acute Toxicity

3.2.1.1. Human

Inhalation of cadmium fumes or dust may result in a wide range of effects, including a metallic taste, headache, dyspnea, chest pains, cough with foamy or bloody sputum, and muscular weakness. Severe exposure may result in pulmonary edema and death (USAF, 1990). If the pulmonary edema is resolved, late-occurring kidney and/or liver damage may develop. Peculiar to inhalation exposure to cadmium is an asymptomatic period that may precede clinical illness by four to eight hours (USAF, 1990).

Based on cadmium lung burdens measured during postmortem examinations, Barrett et al. (1947) estimated a 1-minute lethal concentration of 2,500 mg/m3. Beton et al. (1966) conducted similar calculations and reported a 10-minute lethal concentration of 250 mg/m3. This value was further extrapolated to an 8-hour lethal concentration of 5 mg/m3. Friberg et al. (1974) indicated that exposure to 1 mg Cd/m3 for 8 hours is "immediately dangerous to humans" and the World Health Organization (WHO, 1980) identified 0.5 mg Cd/m3 as the threshold for respiratory effects resulting from an 8-hour exposure.

3.2.1.2. Animal

Acute toxicity values (10-min. LC50) for inhalation exposure of animals (monkeys, rats, mice, guinea pigs, dogs) to cadmium oxide range from 340 mg/m3 to 15 g/m3 (USAF, 1990).

3.2.2. Subchronic Toxicity

3.2.2.1. Human

Both pulmonary effects (emphysema, bronchiolitis, alveolitis) and renal effects (proteinuria) may occur following subchronic inhalation exposure to cadmium and cadmium compounds (ATSDR, 1989).

3.2.2.2. Animal

Pulmonary and renal toxicity have been documented for short-term inhalation exposure of animals to cadmium and cadmium compounds (USAF, 1990). Dose-dependent fibrotic lesions were observed in rats exposed to cadmium chloride aerosol at 0.3 to 1.0 mg/m3, 6 hours/day for 12 weeks, but at a concentration of 2.0 mg/m3 most rats died within 45 days (Kutzman et al., 1986). Friberg (1950) reported emphysema in rabbits exposed to cadmium chloride at 5 mg/m3, 3 hours/day, 20 days/month for 8 months.

3.2.3. Chronic Toxicity

3.2.3.1. Human

Several occupational exposure studies have indicated that inhalation to cadmium dust and cadmium compounds may result in renal and pulmonary effects.

Bonnell (1955) reported that occupational exposure to cadmium oxide (1 to 270 µg/m3) resulted in proteinuria in 16% of the workers exposed for five years or more, and an increased incidence of emphysema in those exposed for more than 10 years. The latter group, however, may have received much higher initial exposures. Kidney lesions were also reported for the majority of workers exposed to the compound at a concentration of 20 µg/m3 for 27 years (Materne et al., 1975) and tubular proteinuria detected in workers exposed to cadmium dust (0.05 mg/m3) for 6 to 12 years (Kjellstrom et al. 1977).

Based on occupational exposure studies, an 8-hour TWA (time-weighted-average) concentration of 0.02 mg/m3 was established for a 20-year exposure to cadmium (OSHA, 1989), which is equivalent to continuous exposure to 0.007 mg/m3 over a lifetime (ATSDR, 1989).

3.2.3.2. Animal

Chronic inhalation exposure studies for animals have demonstrated the carcinogenic potential of cadmium chloride and are discussed in Section 4.2.2.

3.2.4. Developmental and Reproductive Toxicity

3.2.4.1. Humans

Definitive data were not available regarding the developmental or reproductive toxicity of cadmium or cadmium compounds in humans.

3.2.4.2. Animal

Decreased fetal weight (with and without decreased maternal body weight) and minor neurobehavioral alterations in pups have been reported for rats exposed to cadmium oxide (0.16 mg/m3) or cadmium sulfate (about 3 mg/m3) during gestation (ATSDR, 1989). No other significant effects have been documented.

3.2.5. Reference Concentration

The RfC for cadmium is currently under review (U.S. EPA, 1991).

3.3. OTHER ROUTES OF EXPOSURE

3.3.1. Acute Toxicity

No data were available regarding the acute toxicity of cadmium by other routes of exposure.

3.3.2. Subchronic Toxicity

No data were available regarding the subchronic toxicity of cadmium by other routes of exposure.

3.3.3. Chronic Toxicity

No data were available regarding the chronic toxicity of cadmium by other routes of exposure.

3.3.4. Developmental Toxicity

No data were available regarding the developmental toxicity of cadmium by other routes of exposure.

3.4. TARGET ORGANS/CRITICAL EFFECTS

3.4.1. Oral Exposures

3.4.1.1. Primary Target(s)

  1. Kidney: Renal tubular proteinuria is the primary toxic effect of long-term cadmium exposure.
  2. Gastrointestinal tract: Acute exposure to high levels of cadmium and cadmium compounds may cause irritation, vomiting, nausea, and diarrhea.

3.4.1.2. Other Target(s)

The liver, bones, testes, and cardiovascular system have been shown to be affected to various degrees by cadmium.

3.4.2. Inhalation Exposures

3.4.2.1. Primary Target(s)

  1. Kidney: Renal tubular proteinuria may result from chronic exposure to cadmium and cadmium compounds.
  2. Lung: Inhalation exposure to cadmium dust, fumes, aerosols, and some cadmium compounds causes irritation of the respiratory tract, emphysema, and death for acute exposure to high cadmium concentrations.

3.4.2.2. Other Target(s)

No data were available indicating additional target organs/tissues for inhalation exposure to cadmium and cadmium compounds.

4. CARCINOGENICITY

4.1. ORAL EXPOSURES

4.1.1. Human

Limited epidemiologic studies have indicated that exposure to cadmium in food or drinking water is not carcinogenic (Bernard and Lauwerys, 1986).

4.1.2. Animal

Chronic exposure studies using animals exposed to cadmium in the diet or drinking water, have all provided negative results (ATSDR, 1989).

4.2. INHALATION EXPOSURES

4.2.1. Human

Limited evidence is available from epidemiologic studies indicating that inhalation exposure to cadmium may be associated with an increased incidence of respiratory tract cancer (ATSDR, 1989). An exposure-related increase in mortality due to lung cancer in workers with cumulative exposures of 585 to >2,920 mg Cd/m3 (equivalent to TWA daily exposures of 168 to 2,522 µg/ Cd/m3) was reported by Thun et al. (1985).

Limited evidence is available showing that inhalation exposure to cadmium dust and fumes may be associated with prostate cancer, but the total number of cases in the various studies is small (ATSDR, 1989).

A unit risk of 1.8 10-3 (µg/m3)-1 based on an increase in respiratory tract tumors in cadmium smelter workers was calculated by the U.S. EPA (1985).

4.2.2. Animal

Chronic exposure of rats to cadmium chloride aerosols (12.5, 25, or 50 µg/m3) produced a dose-related increase in the frequency of primary lung carcinomas (Takenaka et al., 1983).

4.3. OTHER ROUTES OF EXPOSURE

No data were available regarding the carcinogenic potential of cadmium by other routes of exposure.

4.4. EPA WEIGHT-OF-EVIDENCE

4.4.1. Oral

Not assigned.

4.4.2. Inhalation

Classification-B1: Probable human carcinogen

Basis - Limited evidence from multiple occupational exposure studies showing an association between cadmium exposure and increased incidence of lung cancer. Adequate data are available showing a carcinogenic response to cadmium by rats and mice following inhalation exposure and parenteral administration.

4.5. CARCINOGENICITY SLOPE FACTORS

4.5.1. Oral

Not assigned.

4.5.2. Inhalation

  • SLOPE FACTOR: 6.1 (mg/kg/day)-1
  • VERIFICATION DATE: 11/12/86 (U.S. EPA, 1985; 1991)
  • COMMENT: The inhalation unit risk is based on occupational exposure of humans to cadmium fumes (Thun et al., 1985).

5. REFERENCES

ATSDR (Agency for Toxic Substances and Disease Registry). 1989. Toxicological profile for cadmium. ATSDR/U.S. Public Health Service, ATSDR/TP-88/08.

Baranski, B. 1985. Effect of exposure of pregnant rats to cadmium on prenatal and postnatal development of the young. J. Hyg. Epidemiol. Microbiol. Immunol. 29:253-262. (Cited in ATSDR, 1989)

Baranski, B. 1986. Effect of maternal cadmium exposure on postnatal development and tissue cadmium, copper, and zinc concentrations in rats. Arch. Toxicol. 58:255-260. (Cited in ATSDR, 1989)

Barrett, H.M., D.A. Irwin and E. Semmons. 1947. Studies on the toxicity of inhaled cadmium. I. The acute toxicity of cadmium oxide by inhalation. J. Ing. Hyg. Toxicol. 29:279. (Cited in ATSDR, 1989)

Bernard, A. and R. Lauwerys. 1986. Cadmium in human populations. Experimentia 40:143-152. (Cited in ATSDR, 1989)

Beton, D.C., G.S. Andrews, H. J. Davies, L. Howelss and G.F. Smith. 1966. Acute cadmium fume poisoning: Five cases with one death from renal necrosis. Br. J. Ind. Med. 23:292. (Cited in ATSDR, 1989)

Blakley, B.R. 1985. The effects of cadmium chloride on the immune response in mice. Can. J. Comp. Med. 49:104-108. (Cited in ATSDR, 1989)

Boisset, M., F. Girard, J. Godin and C. Boudene. 1978. Cadmium content of lung, liver, and kidney in rats exposed to cadmium oxide fumes. Int. Arch. Occup. Environ. Health 41:41-53. (Cited in ATSDR, 1989)

Bonnell, J.A. 1955. Emphysema and proteinuria in men casting copper-cadmium alloys. Br. J. Ind. Med. 12:181-197. (Cited in ATSDR, 1989)

CEC (Commission of the European Communities). 1978. Criteria (dose/effect relationships) for cadmium. Pergamon Press, Oxford. pp. 1-198.

Elinder, C.G., T. Kjellstrom, L. Friberg, B. Lind and L. Linman. 1976. Cadmium in kidney cortex, liver, and pancreas for Swedish autopsies. Arch. Environ. Health 31:292-302.

Flanagan, P.R., J. McLellan, J. Haist, M.G. Cherian, M.J. Chamberlain and L.S. Valbar. 1978. Increased dietary cadmium absorption in mice and human subjects with iron deficiency. Gastroenterology 72:841-846.

Foulkes, E.C. 1986. Absorption of cadmium. In: Foulkes, E.C., ed. Handbook of Experimental Pharmacology. Vol. 80, Springer-Verlag, Berlin, pp. 75-100. (Cited in ATSDR, 1989)

Friberg, L. 1950. Health hazards in the manufacture of alkaline accumulators with special reference to chronic cadmium poisoning. Acta Med. Scad. (Suppl 240) 138:1-124. (Cited in ATSDR, 1989)

Friberg, L., M. Piscator, G.F. Nordberg and T. Kjellstrom. 1974. Cadmium in environment. 2nd. Ed. CRC Press, Boca Raton, FL.

Goyer. R. 1991. Toxic effects of metals. In: Amdur, M.O., J.D. Doull and C.D. Klaassen, Eds. Casarett and Doull's Toxicology. 4th ed. Pergamon Press, New York. pp.623-680.

Klaassen, C. D. 1978. Effect of metallothionein on hepatic disposition of metals. Am. J. Physiol. 234:E47-E53. (Cited in ATSDR, 1989)

Kjellstrom, T., P.E. Evrin and B. Rahnster. 1977. Dose-response analysis of cadmium-induced tubular proteinuria. A study of urinary ß2-microglobulin excretion among workers in a battery factory. Environ. Res 13:303-317. (Cited in ATSDR, 1989)

Koller, L.D., J. H. Exon and J.G. Roan. 1975. Antibody suppression by cadmium. Arch. Environ. Health 30:598. (Cited in ATSDR, 1989)

Kotsonis, F. N. and C. D. Klaassen. 1978. The relationship of metallothionein to the toxicity of cadmium after prolonged administration to rats. Toxicol. Appl. Pharmacol. 46:39-54.

Kutzman, R.S., R.T. Drew, R.N. Shiotsuka and B. Y. Cockrell. 1986. Pulmonary changes resulting from subchronic exposure to cadmium chloride aerosol. J. Toxicol. Environ. Health 17:175-189. (Cited in ATSDR, 1989)

Lauwerys, R. 1979. Cadmium in man. In: Webb, N. ed. The chemistry, biochemistry, and biology of cadmium. Elsevier/North Holland Biomedical Press, pp. 433-453. (Cited in ATSDR, 1989)

Materne, D. R. Lauwerys, J. P. Buchet, H. Roels, J. Brouwers and D. Stanescu. 1975. Investigations sur le risques resultant de l'exposition au cadmium dans deux enterprises de production et deux entreprises d'utilisation du cadmium. Cahiers de Medecine du Travail XII:1.

McLellan, J.S. P. R. Flanagan, M. J. Chamberlain and L. S. Valberg. 1978. Measurement of dietary cadmium absorption in humans. J. Toxicol. Environ. Health 4:131-138. (Cited in ATSDR, 1989)

Nordberg, G. F., T. Kjellstrom and M. Nordberg. 1985. Kinetics and metabolism . In: Friberg, L., C.G. Elinder, T. Kjellstrom and G.F. Nordberg, eds. Cadmium and Health: A toxicological and epidemiological appraisal. Vol. 1. Exposure, dose, and metabolism. CRC Press, Boca Raton, FL., pp. 103-178. (Cited in ATSDR, 1989)

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Shaikh, Z. A. and J. C. Smith. 1980. Metabolism of orally ingested cadmium in humans. In: Holmstead, B., et al., eds. Mechanisms of toxicity and hazard evaluation. Elsevier/North Holland, Amsterdam. pp. 569-574. (Cited in ATSDR, 1989)

Stowe, H. D., M. Wilsom and R. A. Goyer. 1972. Clinical and morphological effects of oral cadmium toxicity in rabbits. Arch. Pathol. 94:389-405.

Takenaka, S., H. Oldiges, H. Konig, D. Hochrainer and G. Oberdörster. 1983. Carcinogenicity of cadmium chloride aerosols in Wistar rats. J. Natl. Cancer Inst. 70:367-373.

Thun, M. J., T. M. Schnorr, A. Smith, W. E. Halperin and R. A. Lemen. 1985. Mortality among a cohort of U.S. cadmium production workers - an update. J. Natl. Cancer Inst. 74:325-333. (Cited in ATSDR, 1989)

Tsuchiya, K., Y. Seki and M. Sugita. 1972. Organ and tissue cadmium concentration of cadavers from accidental deaths. Proc. 17th Internat. Congress Occup. Health, Buenos Aires. (Cited in ATSDR, 1989)

USAF. 1990. Cadmium. In: Installation Restoration Program Toxicology Guide, Vol. 5. Harry G. Armstrong Aerospace Medical Research Laboratory, Wright Patterson AFB, OH.

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WHO (World Health Organization). 1980. Recommended health-based limits in occupational exposure to heavy metals. Geneva. (Cited ATSDR, 1989) Retrieve Toxicity Profiles Condensed Version

Last Updated 8/29/97