ATSDR Public Health Statement, March 1989

What is arsenic?
Arsenic is a naturally occurring element in the earth's crust. Pure arsenic is a gray-colored metal, but this form is not common in the environment. Rather, arsenic is usually found combined with one or more other elements such as oxygen, chlorine, and sulfur. Arsenic combined with these elements is referred to as inorganic arsenic, whereas arsenic combined with carbon and hydrogen is referred to as organic arsenic. Many arsenic-containing substances, both inorganic and organic, are naturally occurring, while others are man-made. It is important to maintain a distinction between inorganic and organic arsenic, since the organic forms are usually less toxic than the inorganic forms.

How might I be exposed to arsenic?
Arsenic is very widely distributed in the environment, and all humans are exposed to low levels of this element. For most people, food constitutes the largest source of arsenic intake (about 25 to 50 micrograms per day--a microgram is one millionth of a gram), with lower amounts coming from drinking water and air. Some edible fish and shellfish contain
elevated levels of arsenic, but this is predominantly in an organic form ("fish arsenic") that has low toxicity. Above-average levels of exposure are usually associated with one or more of the following situations:

· Natural mineral deposits in some geographic areas contain large quantities of arsenic, and this may result in elevated levels of inorganic arsenic in water. If this water is used for drinking, high exposures may result.

· Some waste-chemical disposal sites contain large quantities of arsenic, although the chemical form (inorganic or organic) is often unknown. If the material is not properly stored or contained at the site, arsenic may escape into the water, increasing the chances that nearby residents might be exposed.

· Elevated levels of arsenic in soil (due either to natural mineral deposits or to contamination from human activities) may lead to exposure from ingesting soil. This is of particular concern for small children who swallow small amounts of soil while playing.

· Manufacturing (smelting) of copper and other metals often releases inorganic arsenic into the air. Thus, workers in metal smelters and nearby residents are exposed to elevated arsenic levels.

· Low levels of arsenic are found in most fossil fuels (oil, coal, gasoline, and wood), so burning of these materials (in power stations, furnaces, stoves, automobiles, etc.) results in low levels of inorganic arsenic emissions into the air. There are also low levels of arsenic in cigarette smoke.

· The main use of arsenic in this country is for pesticides. Some products, mostly weed killers, use organic arsenic as the active ingredient. Other pesticides use inorganic forms of arsenic to kill plants, insects, or rodents, or to preserve wood. Persons who manufacture or use these pesticides or who handle treated wood may be exposed to arsenic if adequate safety procedures are not followed. Widespread application of pesticides (e.g., in orchards and fields and along roadways) may lead to water or soil contamination, creating the possibility for more widespread exposure of residents in the area.

· In the past, inorganic arsenic was contained in household products such as paints, dyes, and rat poisons, and in medicines for diseases such as asthma and psoriasis. However, these products are no longer in general use; therefore, exposure from these sources is now unlikely.

How does arsenic get into my body?
Arsenic enters the body principally through the mouth, either in food or in water. Most ingested arsenic is quickly absorbed through the stomach and intestines and enters the bloodstream, although this varies somewhat for different chemical forms of arsenic. Arsenic which is inhaled is also well-absorbed through the lungs into the blood stream. Small amounts of arsenic may enter the body through the skin, but this is not usually an important consideration.

Most arsenic that is absorbed into the body is converted by the liver to a less-toxic form that is efficiently excreted in the urine. Consequently, arsenic does not have a strong tendency to accumulate in the body except at high exposure levels.

How can arsenic affect my health?
Inorganic arsenic has been recognized as a human poison since ancient times, and large doses can produce death. Lower levels of exposure may produce injury in a number of different body tissues or systems: these are called "systemic" effects. When taken by mouth, a common effect is irritation of the digestive tract, leading to pain, nausea, vomiting, and diarrhea. Other effects typical of exposure by mouth include decreased production of red and white blood cells, abnormal heart function, blood vessel damage, liver and/or kidney injury, and impaired nerve function causing a "pins-and-needles" feeling in the feet and hands. There is evidence from animal studies that high oral doses during pregnancy may be damaging to the
fetus, but this has not been well studied in humans.

Perhaps the single most characteristic systemic effect of oral exposure to inorganic arsenic is a pattern of skin abnormalities including the appearance of dark and light spots on the skin, and small "corns" on the palms, soles, and trunk. While these skin changes are not considered to be a health concern in their own right, some of the corns may ultimately progress to skin cancer. In addition, arsenic ingestion has been reported to increase the risk of cancer inside the body, especially in the liver, bladder, kidney, and lung.

Inhalation exposure to inorganic arsenic dusts or fumes sometimes produces the same types of systemic health effects produced by oral exposure. However, this is not common, and the effects are usually mild. Of much greater concern is the ability of inhaled arsenic to increase the risk of lung cancer. This has been observed mostly in humans exposed to high levels of airborne arsenic in or around smelters, but lower levels may increase lung cancer risk as well.

Direct dermal contact with arsenic compounds, frequently from inorganic arsenic dusts in air, may result in mild to severe irritation of the skin, eyes, or throat.

Despite all the adverse health effects associated with arsenic exposure, there is some evidence that low levels of exposure may be beneficial to good health. Animals maintained on a diet with unusually low concentrations of arsenic did not gain weight normally, and they became pregnant less frequently than animals maintained on a diet containing a more normal (but low) concentration of arsenic. Also, the offspring from these animals tended to be smaller than normal, and some died at an early age. The estimated daily dose of arsenic that is beneficial is quite small (about the same as normally supplied in the diet), and no cases of arsenic deficiency in humans have been found.

Is there a medical test to determine if I have been exposed to arsenic?
Several different ways exist for testing people for arsenic exposure. Measuring the levels of arsenic in urine is the best way to determine exposures that occurred within the last 1 to 2 days. However, some common tests do not distinguish nontoxic forms such as fish arsenic from other forms, so a high concentration of arsenic in urine may not necessarily indicate that a health problem exists. Measurement of arsenic in hair or fingernails is sometimes used to detect chronic exposures, but this method is not very reliable for detecting low levels of arsenic exposure.

What levels of exposure have resulted in harmful health effects?
The U.S. Department of Health and Human Services has determined that arsenic and certain arsenic compounds are known carcinogens. The amount of arsenic intake that is required to cause a harmful effect depends on the chemical and physical form of the arsenic. In general, inorganic forms of arsenic are more toxic than organic forms, and forms that dissolve easily in water (soluble forms of arsenic) tend to be more toxic than those that dissolve poorly in water. Also, toxicity depends somewhat on the electric charge (the oxidation state or valence) of the arsenic.

The graphs on the following pages (Figs. 1.1 and 1.2) show the relationship between exposure to soluble forms of inorganic arsenic and known health effects. In the first set of graphs, labeled "Health effects from breathing inorganic arsenic," exposure is measured in micrograms of arsenic per cubic meter of air. In all graphs, effects in animals are shown
on the left side, effects in humans on the right.

In the second set of graphs, the same relationship is represented for the known "Health effects from ingesting inorganic arsenic." Exposures are measured in micrograms of arsenic per kilogram of body weight per day (ug/kg/day).

As shown in the figures, most studies indicate that humans are more sensitive to arsenic than animals, which means that studies in animals are of limited utility in predicting exposure levels affecting humans.

Studies in humans indicate that there is considerable variation among different individuals, and it is difficult to identify with certainty the exposure ranges of concern. For example, some humans can ingest over 150 ug/kg/day without any apparent ill-effects, while more sensitive individuals in exposed populations often begin to display one or more of the characteristic signs of arsenic toxicity at oral doses of around 20 ug/kg/day (about 1000 to 1500 ug/day for an adult). Effects are usually mild at this exposure level, becoming more severe as doses become higher. Doses of 600 to 700 ug/kg/day (around 50,000 ug/day in an adult or 3,000 ug/day in an infant) have caused death in some cases. When exposure is from contaminated water, concentrations of around 100 to 200 micrograms per liter (ug/L) do not seem to produce significant noncancer health risks, while typical signs of arsenic toxicity have been reported in several populations drinking water with 400 ug/L of arsenic or more. The levels of arsenic that most people ingest in food or water (around 50 ug/day) are not usually considered to be of health concern.

For inhalation exposure, air concentrations of around 200 ug/m3 are associated with irritation to nose, throat and exposed skin, and higher levels may occasionally lead to mild signs of systemic toxicity similar to that seen with oral exposure.

Direct skin contact with arsenic compounds can cause mild to severe skin irritation, but no reliable dose estimates are available on the exposure levels at which these effects begin to appear.

Because it is believed that cancer-causing agents can increase risk even at very low exposures, Figs. 1.1 and 1.2 do not identify dose ranges for skin cancer or lung cancer. From available data in humans, the Environmental Protection Agency (EPA) has calculated that lifelong ingestion of 1 ug/kg/day (around 50 to 100 ug/day in an adult) is associated with a risk
of skin cancer of about 0.1% (1/1000). This dose level is comparable to drinking water containing 25 to 50 ug/L for a lifetime. Lifelong inhalation of air containing 1 ug/m3 is estimated by EPA to cause a lung cancer risk of about 0.4% (4/1,000). Since there is considerable uncertainty in the cancer risk assessment process, quantitative estimates of cancer risk such as these are intentionally conservative. That is, the actual risks of cancer could be lower, but are unlikely to be higher.

What recommendations has the federal government made to protect human health?
The federal government has taken a number of steps to protect humans from arsenic. EPA has established limits on the amount of arsenic that can be released into the environment from factories which manufacture or use arsenic. EPA has also restricted or cancelled many of the uses of arsenic in pesticides and is considering further restrictions. EPA has established a Maximum Contaminant Level (MCL) of 50 ug/L for arsenic in drinking water; this value is presently undergoing review by the Agency as part of a rulemaking to establish a new MCL for arsenic. The Occupational Safety and Health Administration (OSHA) has established a maximum permissible airborne exposure limit of 10 ug/m3 for inorganic arsenic and 500 ug/m3 for organic arsenic in various workplaces where arsenic is used.

Where can I get more information?
If you have more questions or concerns, please contact your state health or environmental department or:

Agency for Toxic Substances and Disease Registry
Division of Toxicology
1600 Clifton Road, E-29
Atlanta, Georgia 30333