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1,4-Dioxane Quickview (CASRN 123-91-1)

Health assessment information on a chemical substance is included in IRIS only after a comprehensive review of toxicity data by U.S. EPA health scientists from several Program Offices, Regional Offices, and the Office of Research and Development.

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Status of Data for 1,4-Dioxane

File First On-Line: 08/22/1988; Last Significant Revision: 09/20/2013

Category (section)
Status
Last Revised
Oral RfD Assessment On-line 08/11/2010
Inhalation RfC Assessment On-line 09/20/2013
Carcinogenicity Assessment On-line 09/20/2013
Synonyms
  • 123-91-1
  • diethylene oxide
  • 1,4-dioxane
  • dioxane, 1,4-
  • diethylene dioxide
  • p-dioxane
  • dioxane
  • dioxyethylene ether
  • diethylene ether
  • 1,4-diethylene dioxide
1,4-Dioxane Source Documents
Revision History
Date Section Description
09/21/2013 NA Archived review drafts and comments from the development of this assessment are available. Archived version of the 2010 final oral assessment is available (U.S. EPA, 2010).
Chronic Health Hazard Assessments for Noncarcinogenic Effects

Reference Dose for Chronic Oral Exposure (RfD)

Critical Effect
Point of Departure*
UF RfD
Liver and kidney toxicity NOAEL : 9.6 mg/kg-day 300 0.03 mg/kg-day

* The Point of Departure listed serves as a basis from which the Oral RfD was derived. See Discussion of Conversion Factors and Assumptions for more details.

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Reference Concentration for Chronic Inhalation Exposure (RfC)

Critical Effect
Point of Departure*
UF RfC
Atrophy and respiratory metaplasia of the olfactory epithelium LOAEL (HEC): 32.2 mg/m3 1000 3x10-2 mg/m3

* The Point of Departure listed serves as a basis from which the Inhalation RfC was derived. See Discussion of Conversion Factors and Assumptions for more details.

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Carcinogenicity Assessment for Lifetime Exposure
  • Weight-of-Evidence Characterization
    • Likely to be carcinogenic to humans
  • Weight-of-Evidence Narrative:
    • In accordance with the Guidelines for Carcinogen Risk Assessment (U.S. EPA, 2005a), 1,4-dioxane is characterized as "likely to be carcinogenic to humans." This characterization is based on the following findings: (1) inadequate evidence of carcinogenicity in humans, and (2) sufficient evidence in animals (i.e., hepatic tumors in multiple species [three strains of rats, two strains of mouse, and in guinea pigs] mesotheliomas of the peritoneum, mammary, and nasal tumors have also been observed in rats following 2 years of oral exposure to 1,4- dioxane).
    • This may be a synopsis of the full weight-of-evidence narrative. See IRIS Summary.

Quantitative Estimate of Carcinogenic Risk from Oral Exposure

Oral Slope Factor(s)
Extrapolation Method
1 x10-1 per mg/kg-day Log-logistic model with linear extrapolation from the POD (BMDL50HED) associated with 50% extra cancer risk.
Drinking Water Unit Risks
2.9x10-6 per µg/L
Risk Level
Concentration
E-4 (1 in 10,000) 35 µg/L
E-5 (1 in 100,000) 3.5 µg/L
E-6 (1 in 1,000,000) 0.35 µg/L

Quantitative Estimate of Carcinogenic Risk from Inhalation Exposure

Inhalation Unit Risk(s)
Extrapolation Method
5 x10-6 per µg/m3 Multi-tumor dose-response model with linear extrapolation from the POD (BMDL10HED) associated with 10% extra cancer risk.

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