Arsenic

Arsenic

 

Arsenic exposure can lead to acute and chronic intoxication.

Epidemiology

  • Main routes of exposure –  ingestion of arsenic-containing foods, water and beverages or inhalation of contaminated air
    • Arsenic is commonly found in fish and seafood and may also come from dietary supplements and well water
    • Several industries continue to use arsenic in the production of pesticides, preservatives, metal alloys, glasses, enamels, semiconductors and other items
    • Exposure controls are required for workers at risk; arsenic intoxication is rare, except in suicides or accidents

Toxicity

  • Arsenic exists in more than 30 chemical forms or species that can be grouped into inorganic (e.g., arsenite, As+3; arsenate, As+5), methylated (e.g., monomethylarsonic acid, MMA; dimethylarsinic acid, DMA), and organic (e.g., arsenobetaine; arsenocholine) fractions. 
    • Inorganic species of arsenic occur naturally in rocks, soil, and groundwater, and are also found in many synthetic products, poisons, and industrial processes. 
    • Methylated species arise primarily from metabolism of inorganic species, but small amounts may arise directly from food. 
    • Organic species arise primarily from food such as fish, seaweed and shellfish.
  • Nontoxic, organic forms, primarily arsenobetaine and arsenocholine, are cleared rapidly (1-2 days)
  • The nontoxic arsenobetaine, the main arsenic species in seafood, is a common cause for increased total arsenic concentration in urine since it is excreted unchanged for 1-2 days
  • Toxic inorganic forms include pentavalent (AsV), trivalent (AsIII) and methylated forms
  • Methylated arsenic compounds such as monomethyl arsine (MMA) and dimethylarsine (DMA) are formed by hepatic metabolism of AsIII and AsV
    • The methylated inorganic forms are considered less toxic than AsIII and AsV; however they are eliminated slowly (1-3 weeks)
  • The Biological Exposure Index established by the American Conference of Governmental Industrial Hygienists (ACGIH) for the sum of inorganic and methylated metabolites of arsenic is 35 µg/L.  However, clinical symptoms may not be evident at 35 µg/L.  Toxic thresholds are not well established.

Clinical presentation

  • The relation of clinical signs and symptoms to arsenic exposure depends on the duration and extent of the exposure to inorganic and methylated species of arsenic, as well as underlying clinical status of the patient. 
  • Acute exposure
    • Can result in death
    • Best detected by urine
    • If exposure occurred within 24 hours, or for patients who cannot provide a urine specimen (e.g., dialysis patient), arsenic can be detected in blood  
    • Symptoms
      • Gastrointestinal – nausea, emesis, abdominal pain, rice water diarrhea
      • Bone marrow – pancytopenia, anemia, basophilic stippling
      • Cardiovascular – EKG changes
      • Central nervous system – encephalopathy, polyneuropathy
      • Renal – renal insufficiency, renal failure
      • Hepatic – hepatitis
  • Chronic exposure
    • Dermatologic – Mees lines, hyperkeratosis, hyperpigmentation, alopecia
    • Hepatic – cirrhosis, hepatomegaly
    • Cardiovascular – hypertension, peripheral vascular disease
    • Central nervous system – socking glove neuropathy, tremor
    • Malignancies – squamous cell skin, hepatocellular, bladder, lung, renal

Diagnosis

  • Laboratory testing
    • Acute exposure
      • Due to the short half-life of arsenic in the blood, urine is the preferred specimen for detection of arsenic exposure
      • Very recent exposure (<24 hrs) – serum arsenic testing may be helpful
    • Chronic or past exposures (>3 weeks)
      • Analysis of hair or nails may be useful.
  • The Biological Exposure Index established by the American Conference of Governmental Industrial Hygienists (ACGIH) for the sum of inorganic and methylated metabolites of arsenic is 35 µg/L. 
    • However, clinical symptoms may not be evident at 35 µg/L.  Toxic thresholds are not well established.