U.S. EPA Contaminated Site Cleanup Information (CLU-IN)


U.S. Environmental Protection Agency
U.S. EPA Technology Innovation and Field Services Division

For more information on 1,4-Dioxane, please contact:

Linda Fiedler
Technology Assessment Branch

PH: (703) 603-7194 | Email: fiedler.linda@epa.gov



1,4-Dioxane

Toxicology

The greatest human health threat from 1,4-dioxane comes from repeated inhalation exposure to low concentrations of 1,4-dioxane among workers at industrial sites. Systemic effects reported among workers from inhalation exposures involve primarily the liver and kidneys. While evidence of carcinogenicity in laboratory animals is sufficient for EPA to classify 1,4-dioxane as a probable human carcinogen, inadequate evidence exists for the carcinogenicity of 1,4-dioxane in humans. EPA's Office of Air Quality Planning and Standards has placed 1,4-dioxane in the low category for carcinogenic hazard under Superfund's ranking. Acute inhalation of high levels of 1,4-dioxane may cause vertigo and irritation of the eyes, nose, throat, lungs and skin in mammals.

1,4-Dioxane is absorbed by all exposure routes, including lungs, skin and gastrointestinal tract. Distribution is rapid and uniform in lung, liver, kidney, spleen, colon and skeletal muscle tissue of laboratory animals. In rats, the percentage of covalent binding is highest in the liver, spleen and colon. 1,4-Dioxane is excreted mostly in the urine and through the lungs in expired air.

Although 1,4-dioxane has been detected in surface water and groundwater, human risks from lifetime exposures to contaminated water appear low. EPA estimates that, if an individual were to continuously drink water containing 1,4-dioxane at an average of 3.0 µg/L over his or her entire lifetime, that person would theoretically have no more than a one-in-a-million increased chance of developing cancer as a direct result of drinking water containing this chemical. Rats chronically exposed to 1,4-dioxane in drinking water exhibit liver and kidney damage. Limited data suggest that 1,4-dioxane does not bioaccumulate in fish or food chains.

Adapted from:

Adobe PDF Logo 1,4-Dioxane—Emerging Contaminant of Concern: Fact Sheet. Orange County Water District, CA.

Adobe PDF LogoMemorandum: 1,4-Dioxane Action Level
G. Alexeeff, California Office of Environmental Health Hazard Assessment, 1998.


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Human Health

1,4-Dioxane
Re-Evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide.
International Agency for Research on Cancer (IARC) Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Vol 71, p 589-602, 1999.

1,4-Dioxane (1,4-Diethyleneoxide): Air Toxics Hazard Summary
U.S. EPA, Technology Transfer Network, Air Toxics Website.

Adobe PDF Logo1,4-Dioxane, CAS No. 123-91-1
Report on Carcinogens, Twelfth Edition. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program, 3 pp, 2011.

1,4-Dioxane is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity in experimental animals.

1,4-Dioxane (CASRN 123-91-1)
U.S. EPA, Integrated Risk Information System (IRIS).

Adobe PDF Logo1,4-Dioxane—Emerging Contaminant of Concern: Fact Sheet
Orange County Water District, CA.

Adobe PDF Logo 1,4-Dioxane: Hazardous Substance Fact Sheet
New Jersey Dept. of Health and Senior Services, 6 pp, 2002.
Contact: NJ Right-to-Know Program, 609-984-2202

1,4-Dioxane - Inhalation
U.S. EPA, Health & Environmental Research Online (HERO).

The studies used in EPA's draft 2010 Toxicological Review of 1,4-Dioxane (Inhalation) for IRIS are listed in the HERO database. HERO is updated with newly published 1,4-dioxane toxicity studies as they are identified.

Adobe PDF LogoBioassay of 1,4-Dioxane for Possible Carcinogenicity, CAS No. 123-91-1
U.S. Dept. Of Health, Education, and Welfare, National Institutes of Health.
NCI-CG-TR-80, 124 pp, 1978.

Adobe PDF LogoChronic Toxicity Summary: 1,4-Dioxane
California Office of Environmental Health Hazard Assessment, Chronic Reference Exposure Levels Adopted by OEHHA as of August 2003.

Adobe PDF LogoMemorandum: 1,4-Dioxane Action Level
G. Alexeeff.
California Office of Environmental Health Hazard Assessment, 7 pp, 1998.
Contact: Anna Fan, 510-622-3170

Opinion on the Results of the Risk Assessment of 1,4-DIOXANE - CAS No: 123-91-1, EINECS No: 204-661-8. Final Version, 5 November 1999 carried out in the framework of Council Regulation (EEC) 793/93 on the evaluation and control of the risks of existing substances 1. Opinion expressed at the 19th CSTEE plenary meeting, Brussels, 9 November 2000
European Commission on Public Health.

Safety (MSDS) Data for 1,4-Dioxane
Oxford University, Physical and Theoretical Chemistry Laboratory.

Adobe PDF LogoStudies on Metabolism of 1,4-Dioxane
Eck, W.S.
U.S. Army Public Health Command, Toxicology Report No. 87-XE-08WR-09, 61 pp, 2010

Past work has identified two potential metabolites of 1,4-dioxane, but definitive studies on the relationship of these possible metabolites to one another in living systems and their possible relation to carcinogenesis have remained unanswered. This report provides information pointing to 2-hydroxyethoxyacetic acid (HEAA) as the principal metabolite and provides the first quantitative data on the chemical equilibrium between HEAA and the other potential metabolite, dioxanone.

Scope of the Risk Evaluation for 1,4-Dioxane
EPA 740-R-17-003, 58 pp, 2017

EPA presents the occupational scenarios in which workers and occupational non-users might be exposed to 1,4-dioxane during conditions of use, such as manufacturing, processing, repackaging, and recycling. EPA believes that workers and bystanders as well as certain other groups of individuals may experience greater exposures to 1,4-dioxane than the general population. The report is accompanied online by a separate extensive bibliography of literature concerning the chemical's fate, exposure, and environmental and human health hazards.

Table A-3-92: Chemical-Specific Inputs for 1,4-Dioxane (123-91-1)
Human Health Risk Assessment Protocol for Hazardous Waste Combustion Facilities, Volume 2.
Appendix A: Chemical-Specific Data. U.S. EPA, 3 pp, 1998.

Toxicological Profile for 1,4-Dioxane
Agency for Toxic Substances and Disease Registry, 295 pp, 2012

Toxicological Review of 1,4-Dioxane (with Inhalation Update) in Support of Summary Information on the Integrated Risk Information System (IRIS)
Gillespie, P., E.D. McLanahan, R. Sams, J. Stanek, et al.
EPA 635-R-11-003F, 419 pp, 2013

EPA has updated the 2005 toxicological review and IRIS summary for 1,4-dioxane to provide scientific support and rationale for the hazard and dose-response assessment in IRIS pertaining to chronic exposure to the compound. Additional information.

TOXNET
National Library of Medicine Specialized Information Services.

This site contains a cluster of databases on toxicology, hazardous chemicals, and related areas, including the Hazardous Substances Data Bank (HSDB), Integrated Risk Information System (IRIS), and Toxics Release Inventory (TRI). The site supports simultaneous searching in multiple databases.

Ecological Impacts

Adobe PDF LogoChemicals in the Environment: Report on Environmental Survey and Wildlife Monitoring of Chemicals in FY2001
Environmental Health Department, Ministry of the Environment, Government of Japan, 126 pp, 2003.

Ecological Benchmark Tool
U.S. DOE, Oak Ridge National Laboratory.