Chronic arsenic poisoning

Chronic arsenic poisoning

Toxicology Letters 128 (2002) 69 – 72 www.elsevier.com/locate/toxlet Review article Chronic arsenic poisoning Alan H. Hall a,b,*,1 a Department of ...

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Toxicology Letters 128 (2002) 69 – 72 www.elsevier.com/locate/toxlet

Review article

Chronic arsenic poisoning Alan H. Hall a,b,*,1 a

Department of Emergency Medicine, Di6ision of Toxicology, Texas Tech Uni6ersity Health Sciences Center-El Paso, El Paso, TX, USA b Toxicology Consulting and Medical Translating Ser6ices (FACEP), Inc., 3465 Oxcart Run Street, El Paso, TX 79936, USA Dedicated to the late Philip Chambers

Abstract Symptomatic arsenic poisoning is not often seen in occupational exposure settings. Attempted homicide and deliberate long-term poisoning have resulted in chronic toxicity. Skin pigmentation changes, palmar and plantar hyperkeratoses, gastrointestinal symptoms, anemia, and liver disease are common. Noncirrhotic portal hypertension with bleeding esophageal varices, splenomegaly, and hypersplenism may occur. A metallic taste, gastrointestinal disturbances, and Mee’s lines may be seen. Bone marrow depression is common. ‘Blackfoot disease’ has been associated with arsenic-contaminated drinking water in Taiwan; Raynaud’s phenomenon and acrocyanosis also may occur. Large numbers of persons in areas of India, Pakistan, and several other countries have been chronically poisoned from naturally occurring arsenic in ground water. Toxic delirium and encephalopathy can be present. CCA-treated wood (chromated copper arsenate) is not a health risk unless burned in fireplaces or woodstoves. Peripheral neuropathy may also occur. Workplace exposure or chronic ingestion of arsenic-contaminated water or arsenical medications is associated with development of skin, lung, and other cancers. Treatment may incklude the use of chelating agents such as dimercaprol (BAL), dimercaptosuccinic acid (DMSA), and dimercaptopanesulfonic acid (DMPS). © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Arsenic, poisoning; Arsenic, toxicity; Arsenic, chronic exposure

Arsenic is found in the earth’s crust and is a contaminant in a wide variety of metal ores (Gochfeld, 1995). It is extracted in the smelting of copper, gold, lead, and zinc (Gochfeld, 1995; Hathaway et al., 1991). It is used in metallurgy for hardening alloys of copper and lead, as a dopant in semiconductor production, in the man* Tel.: +1-915-856-9396; fax: +1-915-856-9956. E-mail address: [email protected] (A.H. Hall). 1 Cell phone: + 1-915-373-7058.

ufacturing of pigments and glass, and in organic rodenticides, pesticides, and fungicides (Hathaway et al., 1991). Arsenic compounds occur in various chemical states, including tri6alent, penta6alent, and organoarsenical compounds, some of which are commonly called ‘fish arsenic’ found in many seafoods. Organoarsenicals are generally considered to be nontoxic (Gochfeld, 1995). Arsenic compounds were formerly used as medications and arsenic trioxide (Trisenox®) is currently available in the USA for treatment of acute

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myeloid leukemia. It has rarely been associated with QTc prolongation with torsades de points ventricular arrhythmias and sudden death (Medwatch, 2001). Large numbers of persons in Taiwan, Chile, Mexico, India and Pakistan have been chronically poisoned from naturally occurring arsenic in ground water (ATSDR, 1990; Subramanian and Kosnett, 1998; Ahsan et al., 2000). Arsenic-containing coal used for heating homes and drying foodstuffs in China has been a source of chronic exposure. Attempted homicide and deliberate long-term poisoning for maintaining invalidism have resulted in chronic toxicity (Hutton et al., 1982). Recently in the USA there has been considerable concern about chromated copper arsenate (CCA) treated wood used to make children’s playground equipment or decks. Some playground equipment in public areas has been placed ‘off limits’ or dismantled. However, there is currently no e6idence that CCA treated wood represents a health hazard to children (US EPA, 1997), especially when a sealant is periodically applied. Only burning CCA-treated wood in fireplaces or woodstoves has very rarely resulted in chronic arsenic toxicity. Arsenic exposures comprised 956 of the 2 241 082 total human poison exposure cases reported to the American Association of Poison Control Centers Toxic Exposure System in 1998, but were not differentiated into acute versus chronic exposures (Litovitz et al., 1999). Of these, 90 were in children younger than 6 years of age, 79 were in patients aged 6 to 19 years, and 681 were in patients older than 19 years; 724 (76%) exposures were unintentional. Health care facility evaluation was obtained by 546 (57%) of these patients. Amongst the 338 patients with known outcome, there were 4 arsenic-related deaths, 11 patients developed major (life-threatening) symptoms, 179 patients developed any symptoms, and 155 (46%) patients remained asymptomatic. The mechanisms of arsenic toxicity are inhibition of sulfhydryl group-containing cellular enzymes and replacement of phosphate molecules in ‘high-energy’ compounds (‘arsenolysis’) (ATSDR, 1990). Trivalent arsenic compounds are more po-

tent in inhibiting enzymes, whereas pentavalent compounds are more involved in arsenolysis (ATSDR, 1990). Trivalent arsenic compounds are human carcinogens (Gochfeld, 1995; Hathaway et al., 1991), causing tracheal and bronchogenic carcinomas, hepatic angiosarcomas (Bates et al., 1992), and various skin cancers, such as intraepidermal carcinomas (Bowen’s disease), squamous cell carcinomas, basal cell carcinomas, and ‘combined’ forms of skin cancer (ATSDR, 1990). Myelogenous leukemia may also occur (Kjeldsberg and Ward, 1972). An increased risk of Hodgkin’s disease was found in arsenic-exposed French gold miners (Simonato et al., 1994). Internal cancers of the lung, liver, bladder, and kidney have been associated with chronic ingestion of Fowler’s solution or arsenic-contaminated drinking water (Bates et al., 1992; Cuzick et al., 1992; Chiou et al., 1995). About 60 –90% of soluble arsenic compounds are absorbed from the gastrointestinal tract following ingestion; inhalation exposure may be similar (ATSDR, 1990). Absorption through intact skin is usually negligible (ATSDR, 1990). Absorbed pentavalent arsenic is converted to the more toxic and carcinogenic trivalent form in vitro and in experimental animals (Tsukamoto et al., 1983; Bertolero et al., 1987). In humans, absorbed inorganic pentavalent arsenic is biotransformed to trivalent arsenic. Trivalent arsenic undergoes methylation to form less toxic compounds, monomethylarsenate and dimethylarsenate, that are excreted in the urine (Johnson and Farmer, 1991), but some inorganic arsenic is excreted in the urine unchanged (Hopenhayn-Rich et al., 1993). By 2–4 weeks after exposure cessation, the remaining arsenic body burden is found mainly in the skin, hair, and nails; lesser amounts are found in teeth and bone (ATSDR, 1990). Since arsenic is cleared rapidly from the blood, blood levels may become unmeasurable when urine levels remain elevated (ATSDR, 1990). Skin pigmentation changes, palmar and plantar hyperkeratoses, gastrointestinal symptoms, anemia, various skin cancers, and liver disease are common in chronically exposed persons (ATSDR,

A.H. Hall / Toxicology Letters 128 (2002) 69–72

1990; Mazumder et al., 1992; Subramanian and Kosnett, 1998; Ahsan et al., 2000). Noncirrhotic portal hypertension with bleeding esophageal varices, splenomegaly, hypersplenism, and typical skin manifestations have been found in patients treated with Fowler’s solution (Nevens et al., 1990). A metallic taste in the mouth and gastrointestinal disturbances may be present. Mee’s lines (white transverse bands in the nails) may be seen. Bone marrow depression with anemia, leukopenia, or pancytopenia is common (ATSDR, 1990). Gangrene of the feet (‘blackfoot disease’) has been associated with chronic ingestion in Taiwan; Raynaud’s phenomenon and acrocyanosis also may occur (ATSDR, 1990). Toxic delirium and encephalopathy can be present (Morton and Caron, 1989). In Swedish copper smelter workers chronically exposed to arsenic trioxide, sub-clinical nerve injuries were associated with long-term occupational arsenic exposure (Lagerkvist and Zetterlund, 1994). Peripheral neuropathy is common in persons chronically exposed to arseniccontaminated drinking water (ATSDR, 1990; Mazumder et al., 1992). When exposure is not immediately apparent, patients with arsenical peripheral neuropathy have been misdiagnosed as having Guillian–Barre´ syndrome (Goddard et al., 1992). Asymmetric bilateral phrenic neuropathy has been seen in chronic poisoning with arseniccontaminated opium (Bansal et al., 1991). Chelating agents used clinically in arsenic poisoning include D-penicillamine (no longer recommended), dimercaprol (BAL), dimercaptosuccinic acid (DMSA; Chemet®; Succimer), and dimercaptopanesulfonic acid (DMPS; Dimaval®). Chelation is generally ineffective for treating established arsenical peripheral neuropathies and may not prevent their development in all cases. However, in one recent chronic arsenic poisoning case administration of DMPS was temporally associated with a dramatic improvement in peripheral neuropathy (Wax and Thornton, 2000). Preventive measures include adhering to established occupational exposure limits and testing wells in areas known to be at risk for excessive amounts of naturally occurring arsenic in ground-

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water. In the latter case, an alternative supply of safe drinking water must be supplied. In China where naturally occurring arsenic in coal used for heating homes and drying foodstuffs, construction of downdraft chimneys substantially reduced exposure levels. CCA-treated wood treated should not be burned in fireplaces or woodstoves.

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