Arsenic, Elemental

CAS RN:7440-38-2

Health Effects

0.2.1 SUMMARY OF EXPOSURE
  • 0.2.1.1 ACUTE EXPOSURE
    • A) USES: Arsenic compounds are used as pesticides and in a variety of occupations (eg, glass/ceramic manufacturing, metallurgy, semiconductor manufacture). However, environmental contamination of groundwater accounts for the majority of modern exposures outside the United States. Organic arsenic (melarsoprol) is used to treat the meningoencephalitis stage of African Trypanosomiasis. Arsenic trioxide is used to treat acute promyelocytic leukemia. Please refer to ARSENIC TRIOXIDE document for more information.
    • B) PHARMACOLOGY: Inorganic arsenic reduces cellular apoptosis via damage of mitochondrial membranes and down-regulation of BCL2, a pro-survival protein. Arsenic is actively transported into Trypanosomes by a purine transporter resulting in inhibition of trypanothione production and subsequent parasite lysis.
    • C) TOXICOLOGY: Trivalent arsenic (As3+) disrupts oxidative phosphorylation, leading to free radical formation via inhibition of pyruvate dehydrogenase, which subsequently decreases gluconeogenesis due to lack of acetyl-CoA. Pentavalent arsenic may be transformed to arsenic or substitute for inorganic phosphate in glycolysis, leading to uncoupling of oxidative phosphorylation and loss of ATP formation. Chronically, arsenic may cause DNA damage, mutation in the p-53 suppressor gene, and inhibition of DNA repair mechanisms leading to cancer. Arsenic-containing metals are considered nontoxic due to their low solubility. Organic arsenic has relatively low toxicity when compared to the inorganic trivalent and pentavalent forms.
    • D) EPIDEMIOLOGY: Toxicity from arsenic is uncommon and major effects are rare.
    • E) WITH POISONING/EXPOSURE
      • 1) ACUTE OVERDOSE: Arsenic compounds are mainly absorbed through the gastrointestinal tract, but some absorption may occur through intact skin or inhalation. Acute arsenic ingestion generally produces signs and symptoms within 30 minutes, but symptoms may be delayed for several hours if ingested with food. Many arsenic compounds are severe irritants of the skin, eye, and mucous membranes; some may be corrosive. Contact produces local hyperemia, followed by vesicular or pustular eruptions. Trivalent compounds are particularly caustic. Acute inhalation exposures have resulted in irritation of the upper respiratory tract.
      • 2) MILD TO MODERATE TOXICITY: Gastrointestinal symptoms occur rapidly after acute ingestion. Initial signs and symptoms include burning lips, throat constriction, and dysphagia. Excruciating abdominal pain, severe nausea, vomiting, and profuse "rice water-like" diarrhea that may lead to hypovolemia follows these symptoms. In addition, hypovolemia from capillary leakage (third-spacing of fluids) is a common early effect. QTc prolongation may occur. Muscle cramps, facial edema, bronchitis, dyspnea, chest pain, dehydration, intense thirst, and fluid-electrolyte disturbances are also common following significant exposures. A garlic-like odor of the breath and feces may also develop. Subacute toxicity can produce neuropathies, both motor and sensory, and can progress to a Guillain-Barre-like syndrome.
      • 3) SEVERE TOXICITY: Hypotension and tachycardia are common early signs of severe poisoning. Hypotension may be resistant to fluid resuscitation and multiorgan failure may ensue. Fever and tachypnea may occur. These patients can develop ventricular dysrhythmias, including torsade de pointes. Encephalopathy, seizures, and coma have been reported. Acute renal failure, hemolytic anemia, rhabdomyolysis, and hepatitis may occur several days after ingestion.
      • 4) CHRONIC TOXICITY: Inhalation is the most common route of exposure in people who work in occupations that use arsenic. The sequence of chronic poisoning involves weakness, anorexia, hepatomegaly, jaundice, and gastrointestinal complaints, followed by conjunctivitis, irritation of the upper respiratory tract, hyperpigmentation, and eczematoid and allergic dermatitis. A hoarse voice and chronic upper respiratory septum is a common result after prolonged inhalation of white arsenic dust or fume. Peripheral nervous system symptoms may include numbness, burning, and tingling of the hands and feet; pain; paresthesias; muscle fasciculations; gross tremors; ataxia; discoloration; and mental confusion. Muscular weakness, limb tenderness, and difficulty walking may follow. The final phase consists of peripheral sensory neuropathy of the hands and feet. Associated motor neuropathy may occur as well. Certain arsenic compounds are known human carcinogens. Chronic exposure in either occupational settings or by drinking contaminated groundwater can cause poisoning and carries an increased risk of skin, lung, bladder, and possibly liver cancers.
0.2.3 VITAL SIGNS
  • 0.2.3.1 ACUTE EXPOSURE
    • A) Hypotension and tachycardia are common early signs. Fever and tachypnea may occur. Hypertension has been associated with chronic environmental arsenic exposure.
0.2.20 REPRODUCTIVE HAZARDS
  • A) Inorganic arsenic crosses the placenta and may result in spontaneous abortion or stillbirth with either acute or chronic poisoning.
0.2.21 CARCINOGENICITY
  • 0.2.21.1 IARC CATEGORY
    • A) IARC Carcinogenicity Ratings for CAS7440-38-2 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
      • 1) IARC Classification
        • a) Listed as: Arsenic and inorganic arsenic compounds
        • b) Carcinogen Rating: 1
      • 1) The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.
  • 0.2.21.2 HUMAN OVERVIEW
    • A) Chronic therapeutic, occupational, and environmental arsenic exposure have been associated with lung, bladder, skin, and other cancers in humans.
    • B) Exposures as little as 1 gram per year have been associated with CANCER (HSDB).
0.2.22 GENOTOXICITY
  • A) Arsenic induced DNA damage in human cells.
  • B) Conflicting genetic effects have been found for arsenicals. Chromosome aberrations were elevated in the white blood cells of persons exposed to arsenic and possibly other substances (Nordenson, 197
    • 8) Burgdorf et al, 1977), but sister chromatid exchanges were not (Friberg et al, 1986). Sodium arsenite did induce sister chromatid exchanges in vitro, however (Friberg et al, 1986).
Find more information on this substance at: Hazardous Substances Data Bank , TOXNET , PubMed