1,4-Dioxane

Exposure to 1,4-Dioxane may occur through inhalation of vapors, ingestion of contaminated food and water or dermal contact; however, inhalation is the most common route of human exposure, and workers at industrial sites are at greatest risk of repeated inhalation exposure (ATSDR 2012). 1,4-Dioxane is absorbed rapidly following inhalation or ingestion, with much less absorption occurring from the dermal route. 1,4-Dioxane is primarily metabolized to beta-hydroxyethoxy acetic acid (HEAA), which is excreted in urine. Liver, kidney, and nasal toxicity are the primary noncancer health effects associated with exposure to 1,4-Dioxane in humans and laboratory animals (USEPA 2013). Short-term inhalation exposure to 1,4-Dioxane may cause irritation of the eyes, nose, throat, and lungs. Symptoms of acute exposure include coughing, drowsiness, vertigo, headache, nausea, vomiting, stomach pains, coma, and death (HSDB 2015).

Under the Guidelines for Carcinogen Risk Assessment (USEPA 2005), 1,4-Dioxane is "likely to be carcinogenic to humans" based on evidence of multiple tissue carcinogenicity in several 2-year bioassays conducted in three strains of rats, two strains of mice, and in guinea pigs (USEPA 2013). A small prospective study of 165 U.S. workers exposed intermittently to low levels of 1,4-Dioxane found no excess of death from cancer; however, the study was limited by the small number of cancer deaths (3) among the exposed workers (RoC 2016).

The mode of action by which 1,4-Dioxane produces liver, nasal, peritoneal (mesotheliomas) and mammary gland tumors was not conclusive, and the available data did not support any hypothesized carcinogenic mode of action for 1,4-Dioxane (USEPA 2017). USEPA (2013) concluded that overall, the available literature indicates that 1,4-Dioxane is nongenotoxic or weakly genotoxic.

Based on available data, 1,4-Dioxane exhibits low aquatic toxicity. It does not readily bioconcentrate within aquatic organisms (BCF = 0.4; USEPA 2013), and LC₅₀ or EC₅₀ values derived from multiple empirical studies are all well above 100 mg/L (Health Canada 2010).

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Human Health

1,4-Dioxane
California Office of Environmental Health Hazard Assessment. (Accessed 12/5/17)

This page provides links to California's toxicity criteria for 1,4-Dioxane for soil screening, cancer potency, acute air reference exposure levels (RELs), chronic RELs, and water.

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

The studies used in EPA's 2013 Toxicological Review of 1,4-Dioxane (With Inhalation Update) for IRIS are listed in the HERO database. The database also can be searched for references to 1,4-Dioxane studies published after 2013.

1,4-Dioxane, CAS No. 123-91-1
Report on Carcinogens, 14th Ed. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program, 3 pp, 2016

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).

1,4-Dioxane (1,4-Diethyleneoxide): Air Toxics Hazard Fact Sheet
U.S. EPA, Health Effects Notebook for Hazardous Air Pollutants, 4 pp, 2000.

Bioassay 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.

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.

Report on 1,4-Dioxane
Interstate Technology Regulatory Council (ITRC).

ITER compiles human health risk values for chemicals of environmental concern from organizations around the world.

Studies 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
U.S. EPA, Office of Chemical Safety and Pollution Prevention.
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.

Toxicity and Risk Assessment: 1,4-Dioxane
Interstate Technology and Regulatory Council (ITRC), 4 pp, 2020

The Interstate Technology and Regulatory Council (ITRC) has developed a series of six fact sheets to summarize the latest science and emerging technologies regarding 1,4-Dioxane. The purpose of this fact sheet is to: provide a summary of frequently asked questions regarding the potential human and ecological risks related to 1,4-Dioxane environmental contamination; and introduce several potential sources of 1,4-Dioxane exposure (however, potential occupational risks or risks to consumers from use of personal care products that may contain 1,4-Dioxane is not the focus).

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

In addition to the toxicologic properties of 1,4-Dioxane, the profile contains chapters on chemical and physical information; production, import, use, and disposal; potential for human exposure (i.e., occurrence); and analytical methods.

Toxicological Review of 1,4-Dioxane (with Inhalation Update) in Support of Summary Information on the Integrated Risk Information System (IRIS)
EPA 740-R-17-003, 58 pp, 2017

EPA 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.

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Ecological Impacts

1,4-Dioxane: Canadian Water Quality Guidelines for the Protection of Aquatic Life
Canadian Council of Ministers of the Environment, 5 pp, 2008

Toxicity information on 1,4-Dioxane from the literature for fish and invertebrates is summarized.

Assessment for the Challenge: 1,4-Dioxane
Health Canada, Environment Canada. 61 pp, 2010

Based upon a review of the literature, 1,4-Dioxane meets the persistence criteria but not the bioaccumulation criteria set out in the Canada's persistence and bioaccumulation regulations. In addition, empirical aquatic toxicity data indicate that the substance poses a low hazard to aquatic organisms.

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

A searchable database provides a comprehensive set of ecotoxicological screening benchmarks for surface water, sediment, and surface soil applicable to a range of aquatic organisms, soil invertebrates, and terrestrial plants.

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