Toxicity Profiles

RAGs A Format for Arsenic, Inorganic - CAS Number 7440382

Arsenic is a naturally occurring element widely distributed in the earth's crust. In the environment, arsenic is combined with oxygen, chlorine, and sulfur to form inorganic arsenic compounds. Arsenic in animals and plants combines with carbon and hydrogen to form organic arsenic compounds. Inorganic arsenic compounds are mainly used to preserve wood. Organic arsenic compounds are used as pesticides, primarily on cotton plants. Arsenic cannot be destroyed in the environment. It can only change its form. Arsenic in air will settle to the ground or is washed out of the air by rain. Many arsenic compounds can dissolve in water. Fish and shellfish can accumulate arsenic, but the arsenic in fish is mostly in a form that is not harmful. The toxicity of inorganic arsenic depends on its valence state and also on the physical and chemical properties of the compound in which it occurs.

Water soluble inorganic arsenic compounds are absorbed through the gastrointestinal tract and lungs; distributed primarily to the liver, kidney, lung, spleen, aorta, and skin; and excreted mainly in the urine at rates as high as 80%. Symptoms of acute inorganic arsenic poisoning in humans are nausea, anorexia, vomiting, epigastric and abdominal pain, and diarrhea. Dermatitis (exfoliative erythroderma), muscle cramps, cardiac abnormalities, hepatotoxicity, bone marrow suppression and hematologic abnormalities (anemia), vascular lesions, and peripheral neuropathy (motor dysfunction, paresthesia) have also been reported. Oral doses as low as 20-60 g/kg/day have been reported to cause toxic effects in some individuals. Severe exposures can result in acute encephalopathy, congestive heart failure, stupor, convulsions, paralysis, coma, and death. The acute lethal dose to humans has been estimated to be about 0.6 mg/kg/day.

General symptoms of chronic arsenic poisoning in humans are weakness, general debility and lassitude, loss of appetite and energy, loss of hair, hoarseness of voice, loss of weight, and mental disorders. Primary target organs are the skin (hyperpigmentation and hyperkeratosis), nervous system (peripheral neuropathy), and vascular system. Anemia, leukopenia, hepatomegaly, and portal hypertension have also been reported. In addition, possible reproductive effects include a high male to female birth ratio.

Epidemiological studies have revealed an association between arsenic concentrations in drinking water and increased incidences of skin cancers, as well as cancers of the liver, bladder, respiratory and gastrointestinal tracts. Occupational exposure studies have shown a clear correlation between exposure to arsenic and lung cancer mortality. Several studies have shown that inorganic arsenic can increase the risk of lung cancer, skin cancer, bladder cancer, liver cancer, kidney cancer, and prostate cancer. The World Health Organization (WHO), the Department of Health and Human Services (DHHS), and the EPA have determined that inorganic arsenic is a human carcinogen and is classified: A; human carcinogen.

The following is a presentation of the toxicity information associated with Arsenic:

• The Oral Chronic Reference Dose is 3.00E-04 (mg/kg-day).
• The Oral Chronic Reference Dose has a modifying factor of 1.
• The Oral Chronic Reference Dose has an uncertainty factor of 3.
• The Oral Chronic Reference Dose is based on the Tseng study from 1977.
• The Oral Chronic Reference Dose study critical effects are hyperpigmentation, keratosis, and possible vascular complications.
• The overall confidence in the Oral Chronic Reference Dose is medium.
• The Dermal Chronic Reference Dose is 1.23E-04 (mg/kg-day).
• The Dermal Chronic Reference Dose is based on a gastrointestinal absorption factor of 0.4100.

• The Oral Subchronic Reference Dose is 5.00E-03 (mg/kg-day).
• The Oral Subchronic Reference Dose has a modifying factor of 1.
• The Oral Subchronic Reference Dose has an uncertainty factor of 10.
• The Oral Subchronic Reference Dose is based on a human study (EPA 2002).
• The Oral Subchronic Reference Dose study critical effects are skin / hyperpigmentation and hyperkeratosis.
• The overall confidence in the Oral Subchronic Reference Dose is not listed.
• The Dermal Subchronic Reference Dose is 1.23E-04 (mg/kg-day).
• The Dermal Subchronic Reference Dose is based on a gastrointestinal absorption factor of 0.4100.

• The Oral Unit Risk is 5.00E-02 (mg/L)^-1.
• The Oral Slope Factor is 1.50E+00 (mg/kg-day)^-1.
• The Oral Slope Factor study target organ is skin.
• The Oral Slope Factor study cancer type is skin cancer.
• The Oral Slope Factor is based on the U.S. EPA study from 1988.
• The Inhalation Slope Factor is 1.51E+01 (mg/kg-day)^-1.
• The Inhalation Unit Risk is 4.3E+00 (mg/m3)^-1.
• The Inhalation Risk study target organ is lung.
• The Inhalation Unit Risk study cancer type of lung cancer.
• The Inhalation Unit Risk is based on the Brown and Chu study from 1983.
• The Dermal Slope Factor is 3.66E+00 (mg/kg-day)^-1.
• The Dermal Slope Factor is based on a gastrointestinal absorption factor of 0.4100.