Arsenic Poisoning

Diagnosis

Indications for Testing

• Known or suspected exposure to arsenic

Laboratory Testing

• Acute exposure
  • Due to the short half-life of arsenic in the blood, urine is the preferred specimen for detection of exposure
    • Elevated results will be fractionated to differentiate between toxic inorganic forms and relatively nontoxic organic forms
  • Very recent exposure (<24 hours) – serum testing may be helpful
• Chronic or past exposures (>3 weeks) – analysis of hair or nails is most useful in determining time of exposure
• The Biological Exposure Index (BEI) established by the American Conference of Governmental Industrial Hygienists (ACGIH) for the sum of inorganic arsenic and methylated metabolites of arsenic is 35 µg/L
  • Clinical symptoms may not be evident at 35 µg/L; toxic thresholds are not well established
  • For specimens with a total concentration between 35-2,000 µg/L, fractionation is performed to determine proportion of organic, inorganic, and methylated forms
  • If low-level chronic poisoning is suspected, the µg/gCRT ratio may be more sensitive than total arsenic concentration
    • In some situations, it may be appropriate to fractionate specimens with a ratio >30 µg/gCRT despite a total arsenic concentration <35 µg/L

Pharmacogenetics and Therapeutic Drug Monitoring

• Met287Thr polymorphism of AS3MT gene
  • Correlates with arsenic urinary profile
  • Increased MMA excretion, presumed reduced long-term toxicity from arsenic exposure

Clinical Background

Arsenic exposure can lead to acute and chronic intoxication with variable organ dysfunction.

Epidemiology

• Main routes of exposure – ingestion of arsenic-containing foods, water and beverages, or inhalation of contaminated air; therapeutic exposure may also result in toxicity
  • 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
  • Arsenic trioxide (Trisenox^®) is an FDA-approved treatment in acute promyelocytic leukemia (APL) for relapse or for patients not achieving remission with standard chemotherapy

Toxicity

• Arsenic exists in >30 chemical forms or species that can be grouped into inorganic, methylated, and organic fractions
  • Inorganic – occurs naturally in rocks, soil, and groundwater; also found in many synthetic products, poisons, and industrial processes
    • Toxic forms (trivalent and pentavalent) include arsenite or As(III) and arsenate or As(V)
  • Methylated – arises primarily from metabolism of inorganic species, but small amounts may arise directly from food
    • Toxic methylated compounds such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) are formed by hepatic metabolism of As(III) and As(V)
      • Methylated inorganic forms are considered less toxic than As(III) and As(V); however, they are eliminated more slowly (1-3 weeks)
  • Organic – arises primarily from food such as fish, seaweed, and shellfish
    • Relatively nontoxic organic forms (primarily arsenobetaine and arsenocholine) which are cleared rapidly (1-2 days)
      • Arsenobetaine, the most prevalent arsenic species in seafood, is a common cause for increased total arsenic concentration in urine because it is excreted unchanged for 1-2 days

Clinical Presentation

• Relationship of clinical signs and symptoms to arsenic exposure depends on duration and extent of exposure to inorganic or methylated forms of arsenic and to the underlying clinical status of the patient
• Acute exposure
  • May result in death
  • Best detected by urine; however, if exposure occurred within 24 hours or if patient cannot provide a urine specimen (eg, 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 (torsades de pointes)
    • Central nervous system – encephalopathy, polyneuropathy
    • Renal – renal insufficiency, renal failure
    • Hepatic – hepatitis
    • APL differentiation syndrome (APL patients receiving arsenic trioxide treatment)
      • Symptoms include fever, weight gain, pulmonary infiltrates, pleural or pericardial effusions
• Chronic exposure
  • Dermatologic – Mees lines, hyperkeratosis, hyperpigmentation, alopecia
  • Hepatic – cirrhosis, hepatomegaly
  • Cardiovascular – hypertension, peripheral vascular disease
  • Central nervous system – stocking glove neuropathy, tremor
  • Malignancies – skin (squamous cell), hepatocellular, bladder, lung, renal

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Arsenic Analysis, Nails 2007344 Method: Quantitative Inductively Coupled Plasma/Mass Spectrometry	Evaluate chronic or past exposure to arsenic May be useful if suspicion for poisoning is high and urine and serum testing are negative
Arsenic Analysis, Hair 2007342 Method: Quantitative Inductively Coupled Plasma-Mass Spectrometry	Evaluate chronic or past exposure to arsenic May be useful if suspicion for poisoning is high and urine and serum testing are negative
Heavy Metals Panel 3, Blood 0099470 Method: Quantitative Atomic Absorption/Quantitative Inductively Coupled Plasma-Mass Spectrometry	Includes testing for arsenic, mercury, and lead; useful if symptoms and exposure do not clearly implicate arsenic
Heavy Metals Panel 3, Urine with Reflex to Arsenic Fractionated 0099475 Method: Quantitative Inductively Coupled Plasma-Mass Spectrometry	Includes testing for arsenic, mercury, and lead; useful if symptoms and exposure suggest combined poisoning
Heavy Metals Panel 4, Blood 0020584 Method: Quantitative Atomic Absorption/Quantitative Inductively Coupled Plasma-Mass Spectrometry	Includes testing for arsenic, mercury, cadmium, and lead; useful if symptoms and exposure do not clearly implicate arsenic
Heavy Metals Panel 4, Urine with Reflex to Arsenic Fractionated 0020572 Method: Quantitative Inductively Coupled Plasma-Mass Spectrometry	Includes testing for arsenic, mercury, and lead; useful if symptoms and exposure suggest combined poisoning
Heavy Metals Panel 6, Urine with Reflex to Arsenic Fractionated 0025055 Method: Quantitative Inductively Coupled Plasma-Mass Spectrometry	Includes testing for arsenic, cadmium, copper, zinc, mercury, lead, and creatinine; useful if symptoms and exposure suggest combined poisoning