|Smelting and microelectronics industries; wood preservatives, pesticides, herbicides, fungicides; contaminant of deep-water wells; folk remedies; and coal; incineration of these products. ||Organic arsenic (arsenobetaine, arsenocholine) is ingested in seafood and fish, but is nontoxic; inorganic arsenic is readily absorbed (lung and GI); sequesters in liver, spleen, kidneys, lungs, and GI tract; residues persist in skin, hair, and nails; biomethylation results in detoxification, but this process saturates. || |
Acute arsenic poisoning results in necrosis of intestinal mucosa with hemorrhagic gastroenteritis, fluid loss, hypotension, delayed cardiomyopathy, acute tubular necrosis, and hemolysis.
Chronic arsenic exposure causes diabetes, vasospasm, peripheral vascular insufficiency and gangrene, peripheral neuropathy, and cancer of skin, lung, liver (angiosarcoma), bladder, and kidney.
Lethal dose: 120–200 mg (adults); 2 mg/kg (children).
|Nausea, vomiting, diarrhea, abdominal pain, delirium, coma, seizures; garlicky odor on breath; hyperkeratosis, hyperpigmentation, exfoliative dermatitis, and Mees’ lines (transverse white striae of the fingernails); sensory and motor polyneuritis, distal weakness. Radiopaque sign on abdominal x-ray; ECG–QRS broadening, QT prolongation, ST depression, T-wave flattening; 24-h urinary arsenic >67 μmol/d or 50 μg/d; (no seafood × 24 h); if recent exposure, serum arsenic >0.9 μmol/L (7 μg/dL). High arsenic in hair or nails. || |
If acute ingestion, ipecac to induce vomiting, gastric lavage, activated charcoal with a cathartic. Supportive care in ICU.
Dimercaprol 3–5 mg/kg IM q4h × 2 days; q6h × 1 day, then q12h × 10 days; alternative: oral succimer.
|Metal-plating, pigment, smelting, battery, and plastics industries; tobacco; incineration of these products; ingestion of food that concentrates cadmium (grains, cereals). ||Absorbed through ingestion or inhalation; bound by metallothionein, filtered at the glomerulus, but reabsorbed by proximal tubules (thus, poorly excreted). Biologic half-life: 10–30 y. Binds cellular sulfhydryl groups, competes with zinc, calcium for binding sites. Concentrates in liver and kidneys. || |
Acute cadmium inhalation causes pneumonitis after 4–24 h; acute ingestion causes gastroenteritis.
Chronic exposure causes anosmia, yellowing of teeth, emphysema, minor LFT elevations, microcytic hypochromic anemia unresponsive to iron therapy, proteinuria, increased urinary β2- microglobulin, calciuria, leading to chronic renal failure, osteomalacia, and fractures. Possible risks of cardiovascular disease and cancer.
|With inhalation: pleuritic chest pain, dyspnea, cyanosis, fever, tachycardia, nausea, noncardiogenic pulmonary edema. With ingestion: nausea, vomiting, cramps, diarrhea. Bone pain, fractures with osteomalacia. If recent exposure, serum cadmium >500 nmol/L (5 μg/dL). Urinary cadmium >100 nmol/L (10 μg/g creatinine) and/or urinary β2-microglobulin >750 μg/g creatinine (but urinary β2-microglobulin also increased in other renal diseases such as pyelonephritis). || |
There is no effective treatment for cadmium poisoning (chelation not useful; dimercaprol can exacerbate nephrotoxicity).
Avoidance of further exposure, supportive therapy, vitamin D for osteomalacia.
|Manufacturing of auto batteries, lead crystal, ceramics, fishing weights, etc.; demolition or sanding of lead-painted houses, bridges; stained glass–making, plumbing, soldering; environmental exposure to paint chips, house dust (in homes built <1975), firing ranges (from bullet dust), food or water from improperly glazed ceramics, lead pipes; contaminated herbal remedies, candies; exposure to the combustion of leaded fuels. ||Absorbed through ingestion or inhalation; organic lead (e.g., tetraethyl lead) absorbed dermally. In blood, 95–99% sequestered in RBCs—thus, must measure lead in whole blood (not serum). Distributed widely in soft tissue, with half-life ~30 days; 15% of dose sequestered in bone with half-life of >20 years. Excreted mostly in urine, but also appears in other fluids including breast milk. Interferes with mitochondrial oxidative phosphorylation, ATPases, calcium-dependent messengers; enhances oxidation and cell apoptosis. || |
Acute exposure with blood lead levels (BPb) of >60–80 μg/dL can cause impaired neurotransmission and neuronal cell death (with central and peripheral nervous system effects); impaired hematopoiesis and renal tubular dysfunction. At higher levels of exposure (e.g., BPb >80–120 μg/dL), acute encephalopathy with convulsions, coma, and death may occur. Subclinical exposures in children (BPb 25–60 μg/dL) are associated with anemia; mental retardation; and deficits in language, motor function, balance, hearing, behavior, and school performance. Impairment of IQ appears to occur at even lower levels of exposure with no measurable threshold above the limit of detection in most assays of 1 μg/dL.
In adults, chronic subclinical exposures (BPb >40 μg/dL) are associated with an increased risk of anemia, demyelinating peripheral neuropathy (mainly motor), impairments of reaction time and hearing, accelerated declines in cognition, hypertension, ECG conduction delays, higher risk of cardiovascular disease and death, interstitial nephritis and chronic renal failure, diminished sperm counts, and spontaneous abortions.
|Abdominal pain, irritability, lethargy, anorexia, anemia, Fanconi’s syndrome, pyuria, azotemia in children with blood lead level (BPb) >80 μg/dL; may also see epiphyseal plate “lead lines” on long bone x-rays. Convulsions, coma at BPb >120 μg/dL. Noticeable neurodevelopmental delays at BPb of 40–80 μg/dL; may also see symptoms associated with higher BPb levels. Screening of all U.S. children when they begin to crawl (~6 months) is recommended by the CDC; source identification and intervention is begun if the BPb >10 μg/dL. In adults, acute exposure causes similar symptoms as in children as well as headaches, arthralgias, myalgias, depression, impaired short-term memory, loss of libido. Physical exam may reveal a “lead line” at the gingiva-tooth border, pallor, wrist drop, and cognitive dysfunction (e.g., declines on the mini-mental state exam); lab tests may reveal a normocytic, normochromic anemia, basophilic stippling, an elevated blood protoporphyrin level (free erythrocyte or zinc), and motor delays on nerve conduction. U.S. OSHA requires regular testing of lead-exposed workers with removal if BPb >40 μg/dL. New guidelines have been proposed recommending that BPb be maintained at <10 μg/dL, removal of workers if BPb >20 μg/dL, and monitoring of cumulative exposure parameters. ||Identification and correction of exposure sources is critical. In some U.S. states, screening and reporting to local health boards of children with BPb >10 μg/dL and workers with BPb >40 μg/dL is required. In the highly exposed individual with symptoms, chelation is recommended with oral DMSA (succimer); if acutely toxic, hospitalization and IV or IM chelation with ethylenediamine tetraacetic acid calcium disodium (CaEDTA) may be required, with the addition of dimercaprol to prevent worsening of encephalopathy. It is uncertain whether children with asymptomatic lead exposure (e.g., BPb 20–40 μg/dL) benefit from chelation; a recent randomized trial showed no benefit. Correction of dietary deficiencies in iron, calcium, magnesium, and zinc will lower lead absorption and may also improve toxicity. Vitamin C is a weak but natural chelating agent. Calcium supplements (1200 mg at bedtime) have been shown to lower blood lead levels in pregnant women. |
Metallic, mercurous, and mercuric mercury (Hg, Hg+, Hg2+) exposures occur in some chemical, metal-processing, electrical-equipment, automotive industries; they are also in thermometers, dental amalgams, batteries.
Mercury is dispersed by waste incineration. Environmental bacteria convert inorganic to organic mercury, which then bioconcentrates up the aquatic food chain to contaminate tuna, swordfish, and other pelagic fish.
|Elemental mercury (Hg) is not well absorbed; however, it will volatilize into highly absorbable vapor. Inorganic mercury is absorbed through the gut and skin. Organic mercury is well absorbed through inhalation and ingestion. Elemental and organic mercury cross the blood-brain barrier and placenta. Mercury is excreted in urine and feces and has a half-life in blood of ~60 days; however, deposits will remain in the kidney and brain for years. Exposure to mercury stimulates the kidney to produce metallothionein, which provides some detoxification benefit. Mercury binds sulfhydryl groups and interferes with a wide variety of critical enzymatic processes. || |
Acute inhalation of Hg vapor causes pneumonitis and noncardiogenic pulmonary edema leading to death, CNS symptoms, and polyneuropathy.
Chronic high exposure causes CNS toxicity (mercurial erethism; see Diagnosis); lower exposures impair renal function, motor speed, memory, coordination.
Acute ingestion of inorganic mercury causes gastroenteritis, the nephritic syndrome, or acute renal failure, hypertension, tachycardia, and cardiovascular collapse, with death at a dose of 10–42 mg/kg.
Ingestion of organic mercury causes gastroenteritis, arrhythmias, and lesions in the basal ganglia, gray matter, and cerebellum at doses >1.7 mg/kg.
High exposure during pregnancy causes derangement of fetal neuronal migration resulting in severe mental retardation.
Mild exposures during pregnancy (from fish consumption) are associated with declines in neurobehavioral performance in offspring.
Dimethylmercury, a compound only found in research labs, is “supertoxic”—a few drops of exposure via skin absorption or inhaled vapor can cause severe cerebellar degeneration and death.
Chronic exposure to metallic mercury vapor produces a characteristic intention tremor and mercurial erethism: excitability, memory loss, insomnia, timidity, and delirium (“mad as a hatter”). On neurobehavioral tests: decreased motor speed, visual scanning, verbal and visual memory, visuomotor coordination.
Children exposed to mercury in any form may develop acrodynia (“pink disease”): flushing, itching, swelling, tachycardia, hypertension, excessive salivation or perspiration, irritability, weakness, morbilliform rashes, desquamation of palms and soles.
Toxicity from elemental or inorganic mercury exposure begins when blood levels >180 nmol/L (3.6 μg/dL) and urine levels >0.7 μmol/L (15 μg/dL). Exposures that ended years ago may result in a >20-μg increase in 24-h urine after a 2-g dose of succimer.
Organic mercury exposure is best measured by levels in blood (if recent) or hair (if chronic); CNS toxicity in children may derive from fetal exposures associated with maternal hair Hg >30 nmol/g (6 μg/g).
Treat acute ingestion of mercuric salts with induced emesis or gastric lavage and polythiol resins (to bind mercury in the GI tract). Chelate with dimercaprol (up to 24 mg/kg per day IM in divided doses), DMSA (succimer), or penicillamine, with 5-day courses separated by several days of rest. If renal failure occurs, treat with peritoneal dialysis, hemodialysis, or extracorporeal regional complexing hemodialysis and succimer.
Chronic inorganic mercury poisoning is best treated with N-acetyl penicillamine.