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U.S. EPA Technology Innovation and Field Services Division

Arsenic

Toxicology

Human Health

Large oral doses of inorganic arsenic (above 60 ppm in food or water) can produce death. Non-lethal doses may cause irritation of the stomach and intestines, with symptoms such as stomach ache, nausea, vomiting, and diarrhea. Other effects might include decreased production of red and white blood cells, which can lead to fatigue, abnormal heart rhythm, blood-vessel damage resulting in bruising, and impaired nerve function causing a "pins and needles" sensation in the hands and feet.

Long-term oral exposure to inorganic arsenic can cause a pattern of skin changes. These include a darkening of the skin and the appearance of small "corns" or "warts" on the palms, soles, and torso. A small number of the corns may ultimately develop into skin cancer. Swallowing arsenic has also been reported to increase the risk of cancer in the liver, bladder, kidneys, prostate, and lungs. The International Agency for Research on Cancer has determined that inorganic arsenic is carcinogenic to humans. Both EPA and the National Toxicology Program have classified inorganic arsenic as a known human carcinogen.

Breathing high levels of inorganic arsenic may result in sore throat and irritated lungs, as well as the development of some of the skin effects mentioned above. The exposure level that produces these effects is uncertain. Longer exposure at lower concentrations can lead to skin effects and circulatory and peripheral nervous disorders. Some data suggest that inhalation of inorganic arsenic may also interfere with normal fetal development. An important concern is the ability of inhaled inorganic arsenic to increase the risk of lung cancer. This effect has been seen mostly in workers exposed to arsenic at smelters, mines, and chemical factories, but also in residents living near smelters and arsenical chemical factories. People who live near waste sites with arsenic may have an increased risk of lung cancer as well.

Almost no information is available on the effects of organic arsenic compounds in humans. Studies in animals show that most simple organic arsenic compounds (such as methyl and dimethyl compounds) are less toxic than the inorganic forms and that some complex organic arsenic compounds are virtually non-toxic; however, high doses can produce some of the same effects. Thus, exposure to high doses of an organic arsenic compound might result in nerve injury, stomach irritation, or other effects, but this is not known for certain.

Adapted from:

ATSDR Toxicological Profile for Arsenic, Agency for Toxic Substances and Disease Registry, Aug 2007.

For Further Information

Arsenic
U.S. EPA, Health & Environmental Research Online (HERO).

The studies used in EPA's health assessment for arsenic are listed in the HERO database. HERO is updated with newly published arsenic toxicity studies as they are identified.

Arsenic in Drinking Water
National Research Council, Subcommittee on Arsenic in Drinking Water.
National Academy Press, Washington, DC. 332 pp, 1999

Arsenic in Drinking Water: 2001 Update
National Research Council, Board on Environmental Studies and Toxicology, Subcommittee on Arsenic in Drinking Water.
National Academy Press, Washington, DC. 225 pp, 2001

The report can be read online for free, though printing can be accomplished only one page at a time. Contains information on human health effects, experimental studies, variability and uncertainty, quantitative assessment of risks using modeling approaches, and hazard assessment.

Arsenic, inorganic (CASRN 7440-38-2)
U.S. EPA Integrated Risk Information System (IRIS)

Arsenic: Medical and Biological Effects of Environmental Pollutants
National Research Council, National Academy of Sciences Press, 1977

ATSDR ToxFAQsTM for Arsenic

ATSDR Toxicological Profile for Arsenic
Agency for Toxic Substances and Disease Registry, Aug 2007

Cellular Responses to Arsenic: DNA Damage and Defense Mechanisms
X. Lee and M. Weinfeld.
IWA Pub., London. AwwaRF Report 90976F, ISBN: 184339880X, 166 pp, May 2005

Adobe PDF LogoChronic Toxicity Summary: Arsenic and Arsenic Compounds
California Environmental Protection Agency, Office of Environmental Health Hazard Assessment, 21 pp, 2000

Critical Aspects of EPA's IRIS Assessment of Inorganic Arsenic: Interim Report
National Research Council.
National Academies Press, Washington, DC. ISBN: 978-0-309-29706-6, 128 pp, 2013

In response to a congressional mandate for an independent review of the IRIS assessment of inorganic arsenic, EPA asked the National Research Council to convene a committee to conduct a two-phase study. This report, the first phase of that study, evaluates critical scientific issues in assessing cancer and noncancer effects of oral exposure to inorganic arsenic and offers recommendations on how the issues could be addressed in EPA's IRIS assessment. The report can be read on line or downloaded as a PDF file at the National Academies Press website.

Adobe PDF LogoExamination of Risk-Based Screening Values and Approaches of Selected States
Interstate Technology and Regulatory Council (ITRC). RISK-1, 115 pp, 2005.

Screening values for a specific chemical may vary among states and even among different regions of EPA. The ITRC Risk Team examined and documented the screening values for five specific contaminants—arsenic, benzo(a)pyrene, lead, polychlorinated biphenyls, and trichloroethene—that are often identified as drivers for management actions at contaminated sites.

Adobe PDF LogoA Probabilistic Risk Assessment for Children Who Contact CCA-Treated Playsets and Decks
Chen, J., N. Mottl, T. Lindheimer, and N. Cook.
U.S. EPA, Office of Pesticide Programs, 266 pp, 2008

See also additional resources

Adobe PDF LogoA Review of Human Carcinogens: Arsenic and Arsenic Compounds
A Review of Human Carcinogens. Part C: Arsenic, Metals, Fibres, and Dusts
World Health Organization, International Agency for Research on Cancer (IARC) Monographs, Vol 100C, p 41-93, 2012

Adobe PDF LogoA Review of the Toxicity of Arsenic in Air: Science Report SC020104/SR4
J. Maud and P. Rumsby.
Environment Agency, Almondsbury, Bristol, UK. Product SCHO0508BODR-E-P, ISBN: 978-1-84432-912-0, 29 pp, 2008

A search of the primary literature from 2002 to 2008 indicates that most of the toxicological literature on arsenic is based on oral exposure via drinking water, with few studies using inhalation as the route of exposure. Food and drinking water are the principal routes of exposure, with the exception of some industrial workers; however, although air is not an important route of exposure in quantitative terms, it may be significant toxicologically since a principal site for carcinogenicity is the lung. Furthermore, ambient air levels of arsenic may affect concentrations of arsenic in food.

Ecological Impacts

Arsenic's toxicity and bioavailability varies significantly depending upon its chemical form and route of exposure. The effect of arsenic on flora and fauna is also species specific.

Terrestrial Plants. In the past, arsenicals have been used as herbicides and defoliants. While very low concentrations of arsenicals can induce growth, increasing concentrations of water-soluble arsenic in soil generally result in stunted growth, if not outright death. Brake ferns, on the other hand, are hyperaccumulators of arsenic and have been proposed for use in the phytoremediation of arsenic-contaminated soil.

Mammals. Arsenic metabolism and toxicity varies greatly among mammals. Ingestion of large amounts of arsenic will cause death. Mammals generally are able to detoxify and excrete arsenic compounds at environmental levels; however, arsenic is a teratogen for many mammals and can pass through the placenta to cause deformations and sometimes death of a fetus. Carcinogenic effects are generally not observed except for humans.

Birds. Arsenic effects on birds varies widely. In mallards it has been shown to reduce the growth rate of ducklings, reduce liver weight and egg weight, and delay egg laying. On the other hand, arsenic in the feed of chickens stimulates growth and increases egg production. It does not appear to have the same teratogenic effects in birds that it has in mammals. At high doses, some arsenicals act as poisons that result in death, though the dosage required is species and compound specific.

Aquatic Plants and Animals. Depending upon the compound and concentration, arsenicals can inhibit or prevent aquatic plant growth. One case study showed marine algae being inhibited at concentrations as low as 19 to 22 µg As+3/L. In another study, 50% of developing embryos of the narrow-mouthed toad were dead or malformed in 7 days at 40 µg As+3/L. In general, inorganic arsenicals are more toxic than organoarsenicals to aquatic biota, and trivalent species are more toxic than pentavalent species. Early life stages are most sensitive, and large interspecies differences are recorded, even among those closely related taxonomically. Arsenic is accumulated from the water by a variety of organisms; however, there is no evidence of magnification along the aquatic food chain.

Adapted from:

Adobe PDF LogoArsenic Hazards to Fish, Wildlife, and Invertebrates: a Synoptic Review
Eisler, Ronald, U.S. Fish and Wildlife Service, Patuxent Wildlife Research Center, Laurel, MD. U.S. Fish and Wildlife Service, Biological Report 85(1.12), Contaminant Hazard Reviews #12, Jan 1988.

For Further Information

Adobe PDF LogoArsenic (As, CAS number 7440-38-2)
In Environmental Contaminants Encyclopedia, R.J. Irwin, M. VanMouwerik, L. Stevens, M.D.
Seese, and W. Basham (compilers).
National Park Service, Water Resources Division, Fort Collins, CO. 114 pp, 1997
Contact: Roy J Irwin, roy_irwin@nps.gov

Adobe PDF LogoArsenic Hazards to Fish, Wildlife, and Invertebrates: a Synoptic Review
Ronald Eisler, U.S. Fish and Wildlife Service, Patuxent Wildlife Research Center, Laurel, MD. U.S. Fish and Wildlife Service, Biological Report 85(1.12), Contaminant Hazard Reviews #12, Jan 1988
Contact: Ronald Eisler, Ronald_Eisler@usgs.gov

Ecological Soil Screening Levels for Arsenic, Interim Final
U.S. EPA, Office of Emergency and Remedial Response.
OSWER Directive 9285.7-62, 128 pp, 2005.
Contact: Stephen J. Ells, ells.steve@epa.gov

Adobe PDF LogoGuidelines for Interpretation of the Biological Effects of Selected Constituents in Biota, Water, and Sediment
U.S. Department of Interior.
National Irrigation Water Quality Program Information Report No. 3, p 9-24,1998.

This report contains a chapter on arsenic that provides a discussion of arsenic effects on ecological receptors and an extensive table with dose-response data.

Adobe PDF LogoGuidance for Developing Ecological Soil Screening Levels
U.S. EPA, Office of Emergency and Remedial Response
OSWER Directive 9285.7-55, 87 pp, 2003.
Contact: Stephen J. Ells, ells.steve@epa.gov

Methods/Indicators for Determining When Metals Are the Cause of Biological Impairments of Rivers and Streams: Species Sensitivity Distributions and Chronic Exposure-Response Relationships from Laboratory Data
P. Shaw-Allen and G.W. Suter II, U.S. EPA, Cincinnati, OH.
Report No: EPA 600-X-05-027, pp, July 2005

Provides information on the effects of the common aquatic metal contaminants (cadmium, chromium, copper, lead, mercury, nickel, and zinc, plus arsenic and selenium) on laboratory animals for use in the strength-of-evidence step of the stressor identification process to help determine whether metals contribute to biological impairments.

Adobe PDF LogoToxicological Benchmarks for Contaminants of Potential Concern for Effects on Soil and Litter Invertebrates and Heterotrophic Process
U.S. Department of Energy. ES/ER/TM-126/R2, 151 pp, 1997.
Contact: Dan Jones, jonesds@ornl.gov

Adobe PDF LogoToxicological Benchmarks for Screening Contaminants of Potential Concern for Effects on Sediment-Associated Biota
U.S. Department of Energy. ES/ER/TM-95/R4, 44 pp, 1997.
Contact: Dan Jones, jonesds@ornl.gov

Adobe PDF LogoToxicological Benchmarks for Screening Contaminants of Potential Concern for Effects on Terrestrial Plants
U.S. Department of Energy. ES/ER/TM-85/R3, 123 pp, 1997.
Contact: Dan Jones, jonesds@ornl.gov

Adobe PDF LogoToxicological Benchmarks for Screening Potential Contaminants of Concern for Effects on Aquatic Biota
U.S. Department of Energy. ES/ER/TM-96/R2, 151 pp, 1996.
Contact: Dan Jones, jonesds@ornl.gov

Adobe PDF LogoToxicological Benchmarks for Wildlife
U.S. Department of Energy. ES/ER/TM-86/R3, 217 pp, 1996.
Contact: Dan Jones, jonesds@ornl.gov