a) The provisional tolerable weekly intake (PTWI) of cadmium (the dietary exposure level that can be ingested weekly over a lifetime without appreciable health risk) - 7 mcg/kg of body weight. This information has been obtained from the Joint FAO/WHO Expert Committee on Food Additives and Contaminants (JECFA), a scientific advisory body of the Codex Committee on Food Additives and Contaminants (CCFAC). This PTWI was established in the 33rd meeting in 1988 and has been maintained at the 61st meeting in 2003(Horiguchi et al, 2004).
b) In one study, dietary cadmium exposure at close to the current provisional tolerable weekly intake (PTWI) of cadmium, did not affect renal function among female Japanese rice farmers (Horiguchi et al, 2004).
c) Daily cadmium intake from food averages 10 to 25 mcg/day (Friberg et al, 1985).
d) Itai-itai is an endemic disease in Japan, a result of increased dietary intake of cadmium (Murata et al, 1970). These patients experience renal tubular dysfunction, multiple bone fractures due to osteomalacia, and renal anemia (Horiguchi et al, 2004).

1) ACUTE INHALATIONAL: Cadmium fume fever (caused by inhalation of fumes generated with welding, soldering, or brazing), characterized by cough, fever, chills, wheezing, headache, pleuritic chest pain, myalgias, and sore throat, typically develops 4 to 12 hours following an acute inhalational exposure and resolves within 1 to 2 days. In severe cadmium inhalation, pneumonitis or acute lung injury may develop 24 hours or longer after exposure and may progress to respiratory failure.
2) ACUTE INGESTION: Ingestion of large amounts usually produces vomiting, diarrhea (which can be hemorrhagic), and abdominal pain. This can progress to hypotension, renal failure, and death. Large overdoses can result in caustic injury to the gastrointestinal tract. Hepatotoxicity is uncommon.
3) CHRONIC INHALATIONAL: May cause emphysema or pulmonary fibrosis and is associated with lung cancer. Cadmium is considered an IARC class I carcinogen.
4) CHRONIC INGESTION: Primarily causes bone disease (often termed itai-itai disease) and renal injury. Cadmium accumulates in bones leading to osteomalacia, osteoporosis, and pathologic fractures. Kidney disease primarily manifests as proteinuria and Fanconi syndrome and less often as nephrolithiasis. Neurotoxicity, including peripheral neuropathy, parkinsonism, and anosmia, has been described.

1) Fever may be seen.

1) Acute inhalation of fumes can cause cough, dyspnea and chest tightness which is similar to metal fume fever, but which may progress to pneumonitis, pulmonary edema, and death due to respiratory failure in severe cases. Acute exposure can result in residual emphysema and fibrosis.
2) Bronchitis, emphysema, and fibrosis can result from chronic inhalation of cadmium dusts or fumes.

1) Headaches may occur from chronic occupational exposures.
2) CNS effects of acute exposures have included delayed parkinsonism.

1) INGESTION: Nausea, vomiting, abdominal pain and cramping, diarrhea, salivation, dry mouth, and substernal pain occur.
2) INHALATION: Nausea, vomiting, chills, weakness, diarrhea can occur.

1) Anuria was reported following an acute ingestion of 5 g cadmium iodide.
2) Chronic exposure may result in proximal renal tubule damage.

1) Cadmium interferes with zinc and calcium metabolism, resulting in bone resorption and osteoporosis.

1) Skin eruptions and pruritus may occur.

1) Bone fragility and osteomalacia may be a result of chronic cadmium exposure.

1) For respiratory symptoms, administer oxygen. Administer inhaled beta-agonists for bronchospasm or cough. Treat vomiting and diarrhea with intravenous fluids and anti-emetics.

1) Administer supplemental oxygen and bronchodilators for bronchospasm. Patients with severe respiratory distress may require endotracheal intubation and mechanical ventilation. Hypotension should be managed with intravenous fluid support and vasopressors as needed. Patients with acute renal failure may need dialysis. Direct cardiotoxicity is rare. Endoscopy is needed if there is evidence of caustic injury (ie, odynophagia, abdominal pain, drooling). In patients with acute, life-threatening ingestions of cadmium, it is reasonable to consider chelation, although it is not of proven benefit. The use of succimer may be appropriate, but is not well studied for this purpose.

1) PREHOSPITAL: Prehospital decontamination ( activated charcoal) can be considered for large ingestions in which there will be a delay to definitive health care, but the poison center should be consulted first.
2) HOSPITAL: Gastric lavage should be considered in a life-threatening oral ingestion. The efficacy of activated charcoal is not known, but should be considered provided the patient is adequately protecting their airway and there are no other contraindications. Whole bowel irrigation with polyethylene glycol should also be considered after large ingestions, although persistent vomiting may make this difficult.

1) Patients with severe respiratory distress or with altered mental status may need mechanical respiratory support and orotracheal intubation.

1) None

1) In patients with acute, life-threatening oral ingestions of cadmium, it is reasonable to consider chelation. The use of succimer may be appropriate, but is not well studied for this purpose. Dimercaprol (BAL) should be avoided. Consultation with a toxicologist should be obtained prior to chelation therapy.

1) HOME CRITERIA: All symptomatic patients and patients with deliberate ingestions should be evaluated at a health care facility.
2) OBSERVATION CRITERIA: Patients who are asymptomatic 6 hours after an oral ingestion can be discharged home. Patients may become symptomatic up to 12 hours after inhalational exposures, so they should either be observed for this period or there should be an adequate mechanism for them to return should symptoms develop.
3) ADMISSION CRITERIA: Patients with respiratory symptoms after an inhalational exposure should be admitted because of the possibility of progression to more severe lung injury. Symptomatic patients after large, acute oral ingestions should be admitted as well.
4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing severe poisonings and for recommendations on determining the need for chelation.

1) Initial presentation of an inhalational exposure may be mild but may develop into more severe life-threatening acute lung injury.

1) Cadmium salts are poorly adsorbed via the gastrointestinal tract (3% to 7%). Absorption via inhalation is good (50%).

1) Metal fume fever has the same initial presentation but, unlike cadmium, pneumonitis is self-limiting and generally benign. Acute respiratory infections can also present in a similar manner. Oral ingestions of other heavy metals may also present with a similar presentation of hemorrhagic gastroenteritis. Ingestion of any caustic agent may be similar as well.

1) Fever may be seen.

1) HYPERTHERMIA

1) DISCOMFORT: Eye discomfort infrequently follows cadmium oxide fume exposure in humans, generally without eye injury (Grant & Schuman, 1993).
2) CATARACTS: Increased risk of cataracts in smokers has been postulated as due to cadmium which is elevated in the ocular lens and blood of smokers (Ramakrishnan et al, 1995).

1) HYPOSMIA/ANOSMIA: Decreased or loss of sense of smell, nasal inflammation, epistaxis, and breathing difficulties can occur after occupational exposure (Mascagni et al, 2003; Shaham et al, 1993; Rose et al, 1992; Sittig, 1991).

1) HYPERSALIVATION or dry mouth and a metallic taste have been reported.
2) EDEMA: Facial, pharyngeal and neck edema developed rapidly after a large dose oral ingestion that proved fatal (Buckler et al, 1986).
3) TOOTH DISCOLORATION: Yellow discoloration of the teeth may occur with chronic exposure (Sittig, 1991; Hathaway et al, 1996).

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) Acute inhalation of fumes can cause cough, dyspnea and chest tightness which is similar to metal fume fever, but which may progress to pneumonitis, pulmonary edema, and death due to respiratory failure in severe cases. Acute exposure can result in residual emphysema and fibrosis.
2) Bronchitis, emphysema, and fibrosis can result from chronic inhalation of cadmium dusts or fumes.

1) Acute inhalation can cause pneumonitis and pulmonary edema over 1 to 4 days, with death due to respiratory failure possible in severe cases (Tibbits & Milroy, 1980; Barnhart & Rosenstock, 1984; Lewis, 1998) Seidel et al, 1993; (Okuda et al, 1997).
2) CASE REPORT: Hypoxia, pulmonary edema, respiratory failure and death occurred after inhalation of fumes from welding and soldering on cadmium-containing galvanized sheet metal. Abdominal cramps, fever and cough began within 2 to 3 days of exposure, with death occurring within 6 days of exposure. Blood cadmium levels were 280 nanograms/mL; cadmium levels in unexposed persons are usually < 5 nanograms/mL (Fuortes et al, 1991).
3) CASE REPORT: A 78-year-old man died from pneumonitis after brazing with a cadmium-containing silver solder. Cough was the initial symptom 3 hr after brazing. Sore throat, dyspnea, cyanosis developed over several days, progressing to pneumonia and respiratory insufficiency. Cadmium blood levels at post mortem indicated significant exposure (Seidal et al, 1993).
4) CASE REPORT: Four days following acute inhalation of cadmium fumes from a soldering process, a 64-year-old man was admitted to the ED with dyspnea. A chest x-ray revealed pulmonary edema, necessitating artificial respiration (Okuda et al, 1997).
5) Ingestion of 150 g of cadmium chloride in a 17-year-old girl resulted in acute vomiting, facial edema, hypotension, acidosis, respiratory arrest, followed by pulmonary edema and oliguria over 24 hours, and death 30 hours postingestion (Buckler et al, 1986).

1) Acute or chronic exposure can result in fibrosis and persistent restrictive ventilatory defects, with loss of ventilatory capacity and increased residual lung volume (Barnhart & Rosenstock, 1984; Klaassen, 1990).

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) Headaches may occur from chronic occupational exposures.
2) CNS effects of acute exposures have included delayed parkinsonism.

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) INGESTION: Nausea, vomiting, abdominal pain and cramping, diarrhea, salivation, dry mouth, and substernal pain occur.
2) INHALATION: Nausea, vomiting, chills, weakness, diarrhea can occur.

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) ILEUS

1) WITH POISONING/EXPOSURE

1) Anuria was reported following an acute ingestion of 5 g cadmium iodide.
2) Chronic exposure may result in proximal renal tubule damage.

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) WITH POISONING/EXPOSURE

1) Skin eruptions and pruritus may occur.

1) WITH POISONING/EXPOSURE

1) Bone fragility and osteomalacia may be a result of chronic cadmium exposure.

1) BONE DISORDER
2) COLLAGENOSIS

1) WITH POISONING/EXPOSURE

1) IMMUNE SYSTEM DISORDER

1) In mice, developmental effects of a single dose of cadmium included hemorrhagic bullae, limb malformations, exencephaly, cleft palate, open eyelids, and tail deformities (Harbison, 1998).

1) OCCUPATIONAL EXPOSURE - Offspring of women occupationally exposed to 0.16 to 35 mg soluble cadmium salts/m(3) weighed less than controls (AMA, 1985). These effects may be secondary to cadmium placental toxicity (Anon, 1986).
2) SMOKING - Cigarette smoking during pregnancy reportedly causes fetal cadmium accumulation and decreased birth weight (Sikorski et al, 1988).
3) In one study of pregnancies outcomes among women living in the Suwalki area of Eastern Poland (where there are high levels of cadmium and lead in the soil, but little other pollution), exposed women had fewer full-term deliveries, fewer multiple pregnancies (more than three children) and pre-term infants with lower birth weights than did a control group of women living on an uncontaminated area. Blood cadmium levels were higher in the exposed group (0.29 versus 0.25 mcg/dL), but blood lead levels were not significantly different (6.7 versus 6.2 mcg/dL) (Laudanski et al, 1991).
4) The presence of cadmium in newborns, as measured in hair, is inversely related to birthweight; in the absence of calcification of the placenta, lower birthweight was seen when cadmium was at least 0.3 ppm, and in the presence of calcification, birthweight decreased with increasing cadmium hair levels (Frery et al, 1993).

1) PLACENTAL AND FETAL CADMIUM LEVELS - Cigarette smoking during pregnancy reportedly causes fetal cadmium accumulation and decreased birth weight (Sikorski et al, 1988). Other studies have reported placental accumulation of cadmium, with no increased fetal cadmium levels (Barlow & Sullivan, 1982). Studies in isolated human placenta have indicated that placental transfer is slow and incomplete (Harbison, 1998).
2) In one reproductive study of 100 mother-infant pairs, serum cadmium levels were measured at delivery using venous blood from mothers and umbilical cord blood from neonates. The mean serum cadmium levels of mothers and infants were 0.73 mcg/L (ranged from 0.4 to 2.2 mcg/L) and 0.66 mcg/L (ranged from 0.2 to 1.5 mcg/L), respectively. In most mother-infant pairs, infant cadmium concentrations were approximately 70% of maternal concentrations. Mothers and babies who were passively exposed to tobacco smoke had significantly higher serum cadmium levels. A negative correlation was observed between five-minute Apgar scores and cord blood cadmium levels (Mokhtar et al, 2002).
3) ANIMAL STUDIES

1) Poorer performance on tests of intellectual and motor skills was noted among children 6 years of age whose mothers had been exposed to cadmium during pregnancy (Bonithon-Kopp, 1986).

1) Decreases in reduced blood glutathione levels were found in pregnant women exposed to cadmium while living near a copper smelter; these women had an increased incidence of complications of pregnancy, including toxemia, anemia and threatened spontaneous abortion (Tabacova et al, 1994).

1) Human breast milk cadmium averaged less than 0.1 ng/g, although previously reported values were higher (Dabeka et al, 1986). Although breast milk averaged less than 0.1 mcg/kg the range of cadmium in milk and commercial infant formula was up to 1.2 mcg/L.

1) IARC Classification

1) Cadmium workers exposed to 0.3 mg cadmium/m(3) may be at increased risk for lung and prostatic cancer (Elinder, 1986). However, other studies have failed to demonstrate an increase risk of prostatic cancer (Armstrong & Kazantzis, 1985) (Armstrong & Karantzis, 1983) (Sorahan & Waterhouse, 1985).
2) A weak association between the occurrence of bladder cancer and cadmium exposure was noted in a 7 year study of occupational exposure (Siemiatycki et al, 1994).
3) An increased risk of lung and prostatic cancers has beenlinked with cadmium exposure (especially with chronic exposure to high concentrations), but there are conflicting results, particularly with prostatic cancer (Bingham et al, 2001; Goldfrank, 1998; Harbison, 1998).
4) A mortality study of 292 cadmium production workers in the US reported increased deaths from respiratory and prostate cancers. A follow-up study found that all deaths from lung cancer occurred in persons exposed for at least 2 years; there was a significant correlation between cancer mortality and cumulative cadmium exposure.
5) There was no increased risk of hormone-related cancers, including breast, endometrium, and ovarian, reported with dietary cadmium intake (Eriksen et al, 2014).
6) PROSTATE CANCER was reported in four small studies of workers exposed to cadmium dust or fumes; another study reported no significant increase in prostate cancer as a result of cadmium exposure (IRIS, 2001). Overall, early reports linking an increased risk of prostate cancer have not been confirmed by later studies, which had inconsistent results (IARC , 1997).
7) Although there is some evidence linking prostate cancer with cadmium exposure, it would only account for a small fraction of total cases (Giovannucci, 1995).
8) KIDNEY CANCER: Significantly increased deaths from kidney cancer have been noted in cadmium workers (Mandel et al, 1995).
9) Significantly higher cadmium levels were reported in pediatric patients with confirmed malignancies compared with a control group. The most commonly reported malignancy was leukemia (68.3%) followed by lymphoma (18.6%), Wilm tumor (4.6%) and neuroblastoma (4.6%). Rhabdomyosarcoma, brain tumors, and teratomas were reported in 2.3%, 1.1%, and 0.6% of patients, respectively (Sherief et al, 2015).
10) NASAL AND SINUS CANCERS: Significantly increased incidence of nasal and sinus cancers occurred in 869 Swedish battery workers who had been exposed to cadmium oxide and nickel hydroxide. Because of the mixed exposures, these cancers could not be attributed solely to cadmium (Jarup et al, 1998b).
11) PANCREATIC CANCER: A meta-analysis of cadmium studies found that high exposure to cadmium is associated with increased risk of pancreatic cancer. The risk factors for pancreatic cancer (age, cigarette smoking, residence in Louisiana and occupations of metalworking, paint or pigment manufacture, and exposure to pesticides) are also consistent with a cadmium etiology (Schwartz & Reis, 2000).
12) The village of Shipham, England has very high levels of cadmium in the soil. Its residents did not show increased cancer incidence from 1971 to 1992, compared with a nearby village, however (Elliott et al, 2000).
13) MOLECULAR STUDIES: Cadmium can disrupt the active conformation of the p53 tumor suppressor protein, can inhibit its binding to DNA, and can prevent its activity as a transcription factor, in human breast cancer cells in vitro. Cadmium can also prevent the induction of p53 protein in response to DNA damage. These effects on the p53 protein may be involved in the mechanism of cadmium-induced carcinogenesis (Meplan et al, 1999a; Meplan et al, 1999b).
14) Cadmium induced expression of the p53 gene in normal human prostate epithelial cells in culture, along with the c-myc and c-jun oncogenes (Achanzar et al, 2000). In contrast, cadmium had no effect on expression of p53 in cultured human breast cancer cells, where p53 expression was already high (Meplan et al, 1999a).

1) Cadmium metal is listed as a B1 (probable human carcinogen) in the IRIS system, based on a study reporting increased risk of lung cancer in cadmium smelter workers. Several other studies also showed increased risk of lung cancer from cadmium exposure; arsenic exposure and tobacco smoking were confounding variables in some studies, but not in all (Vainio et al, 1993).
2) Both excess mortality from lung cancer and a dose-response relationship with cumulative exposure and lung cancer risk were shown in a study of US workers in a cadmium recovery plant; this risk was considered unlikely to be confounded by cigarette smoking (IARC , 1997).
3) In a study of 590 cadmium production workers, of 179 deaths, 20 were due to 'respiratory cancer' (compared with 12.5 expected); however, exposure to arsenic and other carcinogens were inadequately controlled confounding variables (ACGIH, 1996). Control for arsenic exposure in one study produced results that indicated significant risk of lung cancer was related only to exposure to both cadmium and arsenic (Bingham et al, 2001).
4) A study of workers in the United Kingdom occupationally exposed to cadmium in the manufacture of nickel-cadmium batteries before 1965 demonstrated an increase in mortality rates from lung cancer; however, a case-control study failed to show an association with cadmium exposure (IARC , 1997).
5) There was a negative trend with cumulative exposure to cadmium and mortality from lung cancer in 1,492 cadmium workers followed from 1946 to 1992; cadmium was not a human carcinogen in this large study (Sorahan et al, 1995).

1) ANIMAL STUDIES: Powdered cadmium, when injected twice intramuscularly in rats at a dose of 5 mg/mL, produced fibrosarcomas in 60 to 80 percent. When NICKEL was injected in the opposite leg, 93% of the males and 50% of the females developed tumors in the leg injected with cadmium (Furst & Fan, 1993).
2) Cadmium at a concentration of 1,000 ppm in the drinking water inhibited development of both spontaneous tumors and those induced by N-nitrosodiethylamine in mice (Waalkes et al, 1993).
3) Strain differences were seen in the carcinogenic effects of cadmium at a dose of 40 micromol/kg as a single dose or 16 weekly intraperitoneal doses in mice. DBA mice were susceptible to lymphomas, NFS mice were not, and NFS mice developed sarcomas at the site of injection and were more susceptible to liver and pulmonary tumors than DBA mice (Waalkes & Rehm, 1994).
4) Cadmium has produced tumors of the ventral prostate in rats (Coogan et al, 1994).

1) Blood cadmium concentrations can be obtained from specialty laboratories to confirm exposure, but are not useful to guide treatment in the acute setting.
2) Cadmium levels in normal adults, not exposed to environmental cadmium and who do not smoke average 0.4 to 1 mcg/L. Smokers average 1.4 to 4.5 mcg/L. These values are for whole blood as cadmium is bound to red blood cells (Friberg et al, 1985).
3) Blood cadmium levels are a reflection of acute/recent cadmium exposure. In addition, cadmium blood levels reflect to a considerable degree on cadmium body burden (Mascagni et al, 2003; Kowal et al, 1979). Blood cadmium correlates well with urinary cadmium following chronic exposure (Verschoor et al, 1987)
4) Monitor serum chemistries and renal function in acute oral ingestions.
5) Obtain blood gases in symptomatic acute inhalational exposures.

1) Urine cadmium levels appear to be a better measurement of chronic exposure (Mascagni et al, 2003; Kowal et al, 1979).
2) Urinary cadmium is normally below or around 1 mcg/L. Care must be taken to accurately measure urinary cadmium (Friberg et al, 1985). A 24 hour urine sample is preferable. Urinary cadmium levels reflect cadmium body burden. Irreversible renal damage may occur at urinary cadmium concentrations above 5 mcg/g urinary creatinine (Mascagni et al, 2003; Verschoor et al, 1987). Levels above 10 mcg/g creatinine can be used as a marker to predict overt nephropathy (Bernard A, Roels H & Buchet JP et al, 1992).
3) PROTEINURIA: Evidenced by increased urinary low molecular weight proteins (eg, B2-microglobulin in pH >5.6 urine) results from nephrotoxicity (Ellis et al, 1983; Shaik & Smith, 1984). This is the first evidence of cadmium-induced renal tubular dysfunction. It correlates with duration of exposure, cumulative exposure, and urinary cadmium. The renal damage appears to be largely irreversible (Elinder et al, 1985). Decreased glomerular filtration rate occurs in severe cases.
4) METALLOTHIONEIN: Also correlates with cumulative cadmium exposure and may be more specific than other proteins (Shaikh et al, 1990; Hochi et al, 1995). Elevated urinary metallothionein suggests exposure to cadmium or other metals (eg, Cu or Zn).
5) Urinary N-acetyl-B-D-glucosaminidase (NAG) also correlates to renal tubular damage from heavy metals; both proteinuria and enzymuria are nonspecific indicators of renal injury (Kosnett, 1990).

1) OTHER

A) Patients with respiratory symptoms after an inhalational exposure should be admitted because of the possibility of progression to more severe lung injury. Symptomatic patients after large, acute oral ingestions should be admitted as well.

A) All symptomatic patients and patients with deliberate ingestions should be evaluated at a health care facility.

A) Consult a poison center or medical toxicologist for assistance in managing severe poisonings and for recommendations on determining the need for chelation.

A) Patients who are asymptomatic 6 hours after an oral ingestion can be discharged home. Patients may become symptomatic up to 12 hours after inhalational exposures, so they should either be observed for this period or there should be an adequate mechanism for them to return should symptoms develop.

1) Prehospital decontamination (activated charcoal) can be considered for large ingestions in which there will be a delay to definitive health care, but the poison center should be consulted first.

1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
2) CHARCOAL DOSE

1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
2) PRECAUTIONS:
3) LAVAGE FLUID:
4) COMPLICATIONS:
5) CONTRAINDICATIONS:

1) CHARCOAL ADMINISTRATION
2) CHARCOAL DOSE

1) Blood cadmium concentrations can be obtained from specialty laboratories to confirm exposure, but are not useful to guide treatment in the acute setting.
2) Obtain chest x-ray and blood gases in symptomatic acute inhalational exposures.
3) Monitor serum chemistries and renal function in acute oral ingestions.
4) Urine cadmium and urine proteins (alpha and beta microglobulins) can be measured in chronic exposures.

1) SUMMARY
2) DOPAMINE
3) NOREPINEPHRINE

1) EFFICACY

1) DOSE: Administer CaNa2 EDTA 75 milligrams/kilogram/24 hours deep intramuscular or slow intravenous infusion, given in 3 to 6 divided doses for up to 5 days. May be repeated for a second course after a minimum of 2 days drug holiday; each course should not exceed a total of 500 milligrams/kilogram body weight.
2) CASE REPORT: A 23-year-old man developed renal impairment, hypoproteinemia, hypoalbuminemia, metabolic acidosis, and cardiac dysrhythmias after intentionally ingesting 5 g of cadmium iodide. On hospital day 1, calcium EDTA was administered in order to accelerate cadmium excretion, with an initial dose of 1 gram and subsequent doses of 0.5 g every 24 hours. After the first dose, cadmium's urinary excretion rate was the highest at 1260 mcg/hour. The excretion rate steadily declined each day, reaching 12 mcg/hour on the sixth day of treatment. On day 7, the patient developed hyperthermia, respiratory dysfunction, and ventricular fibrillation progressing to cardiac arrest and death. An autopsy revealed damage to the cardiac muscle, liver, kidneys, and the alimentary tract. The total amount of cadmium excreted over the course of 7 days was 18 mg (Wisniewska-Knypl et al, 1971).

1) DMSA, 150 mg PO three times daily for 5 days, followed by 150 mg DMSA PO twice daily for 14 days, were used to treat a 3-year-old who had ingested 4 ounces of a battery additive containing 2% cadmium sulfate. Whole bowel irrigation with polyethylene glycol was also performed. Urinary cadmium levels were increased (14.6 to 18.6 mcg/g creatinine), blood cadmium levels decreased from 1.2 ng/mL to undetectable, and no adverse effects of either DMSA or cadmium were noted (Britt et al, 1994).
2) One rodent study evaluated the efficiency of individual and combined treatment with two chelators (DMSA and CaDTPA) in acute oral cadmium intoxication. Oral DMSA after acute oral cadmium intoxication efficiently bound cadmium in the intestinal tract. Parenteral CaDTPA enhanced cadmium excretion in urine; however, it was not adequately reflected in lower organ retentions (especially in the kidneys). It was also shown that when the time interval between cadmium exposure and chelating agents administration was longer, the efficiency of cadmium removal from the body was lower. Overall, the combined therapy was more effective than individual chelating agents (Saric et al, 2004).
3) In mice DMSA (dimercaptosuccinic acid/Succimer) has been shown to effectively reduce cadmium mortality after oral exposure (Andersen & Nielson, 1988).
4) SUCCIMER/DOSE/ADMINISTRATION
5) MONITORING PARAMETERS
6) SUCCIMER/ADVERSE REACTIONS

1) All complexing agents may increase the risk of cadmium-induced renal damage. BAL, EDTA, and penicillamine should not be used with cadmium since the complex formed is nephrotoxic (Friberg, 1956; (Klaassen et al, 1984).

1) DTPA (Chel 330) and DTPA Ca (CaNa2 pentetate; calcium Chel 330) seem to be more effective than EDTA. (Andersen, 1984).
2) Pentetate calcium trisodium (Ca-DTPA) is used to treat individuals with known or suspected internal contamination with transuranium ions, specifically plutonium, americium, and/or curium, to increase rates of elimination (Prod Info Pentetate Calcium Trisodium Injection, 2004). Pentetate calcium trisodium (Ca-DTPA), a chelating agent, increases the rates of radiocontaminant elimination by forming stable chelates with metal ions.
3) One rodent study evaluated the efficiency of individual and combined treatment with two chelators (DMSA and CaDTPA) in acute oral cadmium intoxication. Oral DMSA after acute oral cadmium intoxication efficiently bound cadmium in the intestinal tract. Parenteral CaDTPA enhanced cadmium excretion in urine; however, it was not adequately reflected in lower organ retentions (especially in the kidneys). It was also shown that when the time interval between cadmium exposure and chelating agents administration was longer, the efficiency of cadmium removal from the body was lower. Overall, the combined therapy was more effective than individual chelating agents (Saric et al, 2004).

1) Desferroxamine (50 mg IP) treated rats had less hepatic and renal histopathology (Metwalley & Melies, 1995) or less testicular hemorrhage (Fouad et al, 1995) following IP cadmium chloride than rats which did not receive desferroxamine.

1) SUMMARY: Obtain consultation concerning endoscopy as soon as possible and perform endoscopy within the first 24 hours when indicated.
2) INDICATIONS: Most studies associating the presence or absence of gastrointestinal burns with signs and symptoms after caustic ingestion have involved primarily alkaline ingestions. Because acid ingestion may cause severe gastric injury with fewer associated initial signs and symptoms, endoscopic evaluation is recommended in any patient with a definite history of ingestion of a strong acid, even if asymptomatic.
3) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.
4) The risk of perforation during endoscopy is minimized by (Zargar et al, 1991):
5) GRADING
6) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.

1) DITHIOCARBAMATES
2) B COMPLEX VITAMINS
3) GLYCYLRRHIZIN AND ACETAZOLAMIDE
4) VITAMIN D
5) VITAMIN E
6) SELENIUM

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

a) Autopsy results showed congestive cardiomegaly with pulmonary congestion and edema and small bilateral pulmonary effusions. Cardiac blood revealed a markedly increased cadmium level (250 ng/mL). Renal cadmium levels were minimally elevated, indicating an acute exposure (Fuortes et al, 1991).

a) Inhalation of 4 mg of cadmium may be fatal (Baselt & Cravey, 1995).
b) Workers who inhaled an acutely lethal amount of cadmium fume were found to have 1.5 - 4.1 mg/kg of cadmium in their lungs (Baselt & Cravey, 1995).
c) Death may result 7-10 days after exposure to air concentrations of 0.5-2.5 mg/m(3). An average concentration of 40-50 mg/m(3) cadmium fume, inhaled over the course of an hour, resulted in death. Under similar circumstances, 9 mg/m(3) for 5 hours and 5 mg/m(3) for 8 hours also resulted in death (ACGIH, 1991) ACGIH, 1996; Hathaway et al., 1996; (Sittig, 1991).
d) 50-111 lung cancer deaths per 1000 workers are expected to result from lifetime (45 years) work exposures to cadmium fume at levels of 100 mcg/m(3) (Zenz, 1994).
e) Cadmium oxide fume from a furnace cause death when the worker was exposed for 1 hour to an air concentration of 50 mg/m(3). Similarly, a worker died when exposed to 8.6 mg/m(3) for 5 hours. One researcher estimates that exposure to 5 mg/m(3) for 8 hours will result in death (IPCS, 1992).
f) Inhalation of airborne concentrations of 1-5 mg/m(3) could cause death (ATSDR, 1993).
g) The lowest published lethal concentration for a human (inhalation route) is 39 mg/m(3)/20M (RTECS , 1999; Lewis, 1996).
h) Exposure to probably less than 2500 min x mg/m(3) of cadmium oxide fumes or cadmium chloride aerosol is probably fatal (Friberg et al, 1985). 500 min x mg/m(3) is dangerous.
i) A 20 minute exposure to 39 mg/m(3) aerosolized cadmium resulted in death (NIOSH, 1996).

a) Ingestion of more than 100 mg of soluble salt may be lethal (Baselt & Cravey, 1995).
b) Cadmium ingestion of 300 mg, or more, may be fatal (Zenz, 1994).
c) Two cases of suicide by ingestion of cadmium involved 25 mg/kg and 1500 mg/kg body weight (ATSDR, 1993).
d) Lethal oral doses have ranged upwards from 150 grams (Bernard & Lauwerys, 1984; Buckler et al, 1986). Following oral ingestion, death results from shock due to fluid loss or acute renal failure, and cardiopulmonary depression.
e) CASE REPORT: A 23-year-old man intentionally ingested 5 g of cadmium iodide, dissolved in water (approximately 25 mg cadmium/kg of body weight), and, over the next 2 days, developed renal impairment, hypoproteinemia, hypoalbuminemia, metabolic acidosis, and cardiac dysrhythmias. With supportive treatment, including administration of calcium EDTA to increase cadmium excretion, the patient's condition temporarily improved; however, on day 7, he developed hyperthermia, respiratory dysfunction, and ventricular fibrillation progressing to cardiac arrest and death. An autopsy revealed damage to the cardiac muscle, liver, kidneys, and the alimentary tract (Wisniewska-Knypl et al, 1971).

a) Three people, who succumbed to chronic cadmium poisoning, were found to have an average of 128 mg/kg of cadmium in their livers and 180 mg/kg of cadmium in their kidneys (Baselt & Cravey, 1995).
b) Four workers who died within 10 years after long periods of cadmium exposure (18-26 years) had liver concentrations of cadmium of 23-145 mg/kg and kidney concentrations of 13-80 mg/kg (Baselt & Cravey, 1995).
c) The lowest published lethal dose for a man (unknown route) is 15 mg/kg (RTECS , 1999; Lewis, 1996).

a) Permissible exposure limit (PEL) from the occupational Safety and Health Administration (OSHA) standards for cadmium - 5 mcg/m(3) over an 8-hour TWA (Yassin & Martonik, 2004).
b) The OSHA action level for airborne levels of cadmium - 2.5 mcg/m(3) over an 8-hour TWA (Yassin & Martonik, 2004).
c) Lung inflammation has been caused by inhalation of air containing 0.5-2.5 mg/m(3) cadmium dust. Symptoms of this type of exposure occurred within 4-10 hours and included headache, chills, muscle aches, chest pain, diarrhea, nausea, vomiting, difficulty breathing, wheezing, coughing blood, and a dark purple discoloration of the skin (Sittig, 1991).
d) Inhalation of aerosolized cadmium at concentrations of 0.06-0.68 mg/m(3) over a 4-8 year period may cause sore throat, cough, upset stomach, chest pain, and fatigue. Anemia, lung distention, kidney dysfunction, and protein in urine has resulted from 20 year exposures to cadmium dust and fume in concentrations of 3.0-15.0 mg/m(3) (Sittig, 1991).
e) Inhalation of cadmium oxide fume, generated by performing hot work on cadmium and its alloys, may result in cough, dyspnoea, retrosternal pain, pulmonary oedema, and symptoms of metal fume fever about 10 hours after exposure. Symptoms generally resolve within a week (Raffle et al., 1994).
f) A man who worked for 3 days in an environment with 0.5-2.5 mg/m(3) aerosolized cadmium developed pneumonitis. At concentrations below 0.5 mg/m(3), several cases which involved a condition similar to metal fume fever and acute gastroenteritis arose (ACGIH, 1991) ACGIH, 1996).
g) Inhalation exposures of 0.5 mg/m(3) or less, over a long period of time, cause decreased lung function and emphysema (Hathaway, 1996).
h) Proteinuria may develop after a worker is exposed to cadmium for 5-10 years at a level of 100 mcg cadmium/m(3) (Hathaway, 1996).
i) Workers that used cadmium containing solders for 4-24 years were estimated to have been exposed to 0.35-9.9 mg/m(3)year of cadmium. As a result, these workers were found to have slight to pronounced beta-2-microglobulinuria. Workers with an estimated dose of 1 mg/m(3)year rarely developed tubular proteinuria. Workers with an estimated dose >3 mg/m(3)year were more likely to develop slight and pronounced beta-2-microglobulinuria (Clayton & Clayton, 1994).
j) Workers exposed to >300 mg/m(3)days of cadmium, equivalent to 4.3 years at the current PEL, are more likely to develop multiple tubular abnormalities and raised serum creatinine concentrations (Clayton & Clayton, 1994).
k) 27 male workers, exposed to air concentration of cadmium in a battery factory, were found, on average, to have slightly decreased forced expiratory volume (IPCS, 1992).
l) Of 96 workers exposed to cadmium oxide fume for up to 27 years, 12 were found to have emphysema. Average air concentrations of cadmium were 40-50 mcg/m(3) (IPCS, 1992).
m) Seventeen workers exposed for 6 years to cadmium levels commonly near 200 mcg/m(3), were found to have decreased forced vital capacity. Seven, or more, years of exposure to insoluble cadmium compounds at concentrations of 700 mcg/m(3) was associated with emphysema (IPCS, 1992).
n) Workers using solders containing cadmium were exposed for many years to cadmium concentrations of 0.05-0.5 mg/m(3). Twenty-four of the workers had cadmium related renal tubular dysfunction (IPCS, 1992).
o) The lowest published toxic concentration for a woman (inhalation route) is 129 mcg/m(3) for a 20-year, continuous exposure (Lewis, 1996).
p) The lowest published toxic concentration for a man (inhalation route) is 88 mcg/m(3) for an 8.6-year exposure (RTECS , 1999; Lewis, 1996).
q) In a retrospective study, 311 male workers in an alkaline battery factory were evaluated for cadmium exposure. Workers were exposed to greater than 50 mcg/m(3) for 1 to 35 years. Hypertension (defined by average blood pressure greater than 160/95 over a 5 year period) was noted in 23% of workers over 40 (HSDB , 1999).

a) Consumption of foods and beverages stored in cadmium-plated containers has resulted in human poisonings (OHM/TADS , 2000).
b) Ingestion of 15-30 mg of cadmium, or soluble compounds of cadmium, may cause abdominal pain, anemia, choking, diarrhea, increased salivation, vomiting, and constant need to empty the bladder. Symptoms arise 15-30 minutes after exposure and may progress to heart and lung failure (Sittig, 1991).
c) Complete recovery is expected after an oral dose of cadmium that is less than 300 mg (Zenz, 1994).
d) Drinking water from a vending machine cooling tank was found to have a cadmium concentration of 16 mg/L, which caused acute illness in consumers. Solder in the tank contained cadmium (IPCS, 1992).
e) Children who drank soft drinks containing 16 mg/L cadmium, or ate popsicles containing 13 mg/L, developed gastrointestinal symptoms (ATSDR, 1993).
f) Ingestion of 0.0021 mg/kg/day, corresponding to 2,000 mg of cadmium over a 50 year period, will cause renal damage (ATSDR, 1993).
g) Long-term daily oral intake of more than 1 mg of cadmium may result in severe bone disease (Friberg et al, 1985).
h) Cadmium plating of food and beverage containers has resulted in a number of outbreaks of gastroenteritis (food poisoning) (Lewis, 1993).
i) The provisional tolerable weekly intake (PTWI) of cadmium (the dietary exposure level that can be ingested weekly over a lifetime without appreciable health risk) - 7 mcg/kg of body weight. This information has been obtained from the Joint FAO/WHO Expert Committee on Food Additives and Contaminants (JECFA), a scientific advisory body of the Codex Committee on Food Additives and Contaminants (CCFAC). This PTWI was established in the 33rd meeting in 1988 and has been maintained at the 61st meeting held in 2003 (Horiguchi et al, 2004).

a) Battery workers exposed to cadmium at levels of 0.13-1.17 mg/m(3) for 1-12 years were found to have chronic signs of cadmium exposure. Upon radiological examination of the skeletons of 26 battery workers, 7 were found to have proteinuria, 3 had pseudofractures, 13 had sclerotic focii, and 10 had osteoporosis (IPCS, 1992).

1) Blood cadmium above 0.5 microgram/deciliter warrants careful investigation.
2) Blood cadmium levels of 1.49 micrograms/deciliter were reported in a 64-year-old man following a one hour inhalation exposure to cadmium fumes from a soldering process (Okuda et al, 1997).
3) URINE: Following a one hour inhalation exposure to cadmium fumes from a soldering process, urine levels of 47.9 micrograms/liter were reported in a 64-year-old man (Okuda et al, 1997).
4) URINE: Cadmium level of 438 millimoles/liter (normal range 0 to 20) was measured in the urine of a 43-year-old crematorium worker exposed to high levels of cadmium in the workplace (Nicholson et al, 1997).
5) URINE: Chronic toxicity is associated with urinary excretion of 20 micrograms cadmium/gram creatinine.
6) The OSHA action level for airborne levels of cadmium - 2.5 mcg/m(3) over an 8-hour TWA (Yassin & Martonik, 2004).
7) The World Health Organization (WHO) health-based limit for urinary cadmium level - 5 mcg cadmium/ gram creatinine (Yassin & Martonik, 2004).
8) The OSHA action level for urinary cadmium level - 3 mcg cadmium/gram creatinine (Yassin & Martonik, 2004).
9) The Third National Health and Nutrition Examination Survey; NHANES III, 1988-1994; conducted by the National Center for Health Statistics - One study evaluated the urinary cadmium levels in the US workers (n=11,228) aged 18 to 64 years. Overall, the urinary cadmium levels ranged from 0.01 to 15.57 mcg/L and the geometric mean was 0.30 mcg/L [0.28 mcg cadmium/g creatinine]; this level was well below the OSHA action level. In addition, the prevalence of urinary cadmium levels greater than or equal to 15 mcg/L was 2.8 per 100,000 (n=3907 workers) compared with 60 per 100,000 (n=78,471 workers) for levels greater than or equal to 10 mcg/L. Overall, significantly higher urinary cadmium levels were observed in smokers than nonsmokers (Yassin & Martonik, 2004).
10) CASE REPORT: A 23-year-old man died approximately 7 days after intentionally ingesting 5 g cadmium iodide. Post-mortem cadmium concentrations in his fluids and tissues were as follows (Wisniewska-Knypl et al, 1971):

a) Adopted Value

B) NIOSH REL and IDLH Values for CAS7440-43-9 (National Institute for Occupational Safety and Health, 2007):
C) Carcinogenicity Ratings for CAS7440-43-9 :
D) OSHA PEL Values for CAS7440-43-9 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) LD50- (INTRAPERITONEAL)MOUSE:
2) LD50- (ORAL)MOUSE:
3) LD50- (ORAL)RAT:
4) TCLo- (INHALATION)HUMAN:

a) Low levels of metallothionein, excessive accumulation of cadmium in the renal cortex, high concentrations of cadmium-metallothionein complexes which may directly affect the brush border membranes, interference with zinc-containing enzymes, and autoimmunological processes have been proposed as mechanisms involved in nephrotoxicity (Friberg et al, 1986; Vestergaard & Shaikh, 1994; Klaassen, 1990).
b) Cadmium may also impair glucose transport in the kidney (Blumenthal et al, 1994).

a) Metallothionein is considered a protective protein which is induced by cadmium and other metals (Blumenthal et al, 1994) and binds cadmium and other metals (Coogan et al, 1994). Cadmium pre-treatment can induce synthesis of metallothionein and protect from a subsequent lethal dose of cadmium in animals (Gosselin et al, 1984).
b) Once a critical level of cadmium exposure occurs, the protective ability of metallothionein is exceeded (Klaassen, 1990).
c) Paradoxically, the metallothionein-cadmium complex is also implicated in the development of nephrotoxicity through direct effects on the brush border membrane during reabsorption of the complex at the renal tubule, or as a consequence of hepatic releases of cadmium which are then taken up as metallothionein-cadmium complexes in the kidneys (Vestergaard & Shaikh, 1994).
d) In vitro and animal studies have shown that zinc protects against cadmium toxicity, possibly by inducing metallothionein, inducing enzymes involved in detoxification processes, and other mechanisms (Blumenthal et al, 1994).
e) Zinc deficiency enhances the renal toxicity of cadmium in laboratory animals, possibly as a result of decreased metallothionein concentration in the zinc deficient animals (Tanaka et al, 1995).