p-Dioxane
RTECS #
JG8225000
CAS #
Updated
December 2018
Molecular Weight
88.12
Molecular Formula
C4H8O2
Synonyms
1,4-Diethylene dioxide
1,4-Dioxacyclohexane
1,4-Dioxane
Di(ethylene oxide)
Diethylene dioxide
Diethylene dioxide (OSHA)
Diethylene ether
Diokan
Dioksan (Polish)
Diossano-1,4 (Italian)
Dioxaan-1,4 (Dutch)
Dioxan
Dioxan-1,4 (German)
Dioxane
Dioxane (ACGIH:OSHA)
Dioxane-1,4
Dioxanne (French)
Dioxyethylene ether
Glycol ethylene ether
NCI-C03689
p-Dioxan (Czech)
p-Dioxin, tetrahydro-
RCRA waste number U108
Tetrahydro-1,4-dioxin
Tetrahydro-p-dioxin
1,4-Dioxacyclohexane
1,4-Dioxane
Di(ethylene oxide)
Diethylene dioxide
Diethylene dioxide (OSHA)
Diethylene ether
Diokan
Dioksan (Polish)
Diossano-1,4 (Italian)
Dioxaan-1,4 (Dutch)
Dioxan
Dioxan-1,4 (German)
Dioxane
Dioxane (ACGIH:OSHA)
Dioxane-1,4
Dioxanne (French)
Dioxyethylene ether
Glycol ethylene ether
NCI-C03689
p-Dioxan (Czech)
p-Dioxin, tetrahydro-
RCRA waste number U108
Tetrahydro-1,4-dioxin
Tetrahydro-p-dioxin
Skin and Eye Irritation and References
| Route/Organism | Dose | Effect | Reference |
|---|---|---|---|
| eye /guinea pig | 10 µg | moderate | JPPMAB 11,150,1959 |
| eye /human | 300 ppm/15M | JIHTAB 28,262,1946 | |
| eye /rabbit | 100 mg | severe | AJOPAA 29,1363,1946 |
| eye /rabbit | 100 mg/24H | moderate | 85JCAE -,810,1986 |
| skin /rabbit | 515 mg open irritation test | mild | UCDS** 12/17/1971 |
Mutation Data and Reference
| System Test | Route/Organism/Tissue | Dose | Reference |
|---|---|---|---|
| Cytogenetic Analysis | subcutaneous/mouse | 7500 mg/kg/5D- intermittent | MUREAV 586,28,2005 |
| DNA Damage | oral/rat | 2550 mg/kg | CALEDQ 53,67,1990 |
| DNA Damage | liver/rat | 300 µmol/L | SinJF# 26OCT1982 |
| DNA inhibition | HeLa cell/human | 400 mmol/L | CRNGDP 13,2389,1992 |
| micronucleus test | subcutaneous/mouse | 7500 mg/kg/5D- intermittent | MUREAV 586,28,2005 |
| micronucleus test | oral/mouse | 900 mg/kg | MUREAV 322,142,1994 |
| micronucleus test | oral/mouse | 3 gm/kg | MUREAV 322,145,1994 |
| morphological transform | fibroblast/mouse | 1 gm/L | EMMUEG 11,41,1988 |
| other mutation test systems | intravenous/rat | 50 mg/kg | ARTODN 49,29,1981 |
| other mutation test systems | oral/rat | 0.5 gm/kg/4W- intermittent | MUREAV 834,51,2018 |
| sister chromatid exchange | ovary/hamster | 10500 mg/L | EMMUEG 10(Suppl 10),1,1987 |
| Unscheduled DNA Synthesis | oral/rat | 20 mg/kg | TXAPA9 60,287,1981 |
Reproductive Effects Data and References
| Route/Organism | Dose | Effect | Reference |
|---|---|---|---|
| oral/rat | 10 gm/kg (6-15D pregnant) | Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) Reproductive: Specific developmental abnormalities: Musculoskeletal system | TOLED5 26,85,1985 |
Tumorigenic Data and References
| Route/Organism | Dose | Effect | Reference |
|---|---|---|---|
| inhalation/rat | lowest published toxic concentration: 111 ppm/7H/2Y- intermittent | Tumorigenic: Equivocal tumorigenic agent by RTECS criteria Blood: Tumors Blood: Lymphoma including Hodgkin's disease | TXAPA9 30,287,1974 |
| intraperitoneal/mouse | lowest published toxic dose: 12 gm/kg/8W- intermittent | Tumorigenic: Neoplastic by RTECS criteria Lung, Thorax, or Respiration: Tumors | TXAPA9 82,19,1986 |
| oral/mouse | lowest published toxic dose: 239 gm/kg/90W- continuous | Tumorigenic: Carcinogenic by RTECS criteria Liver: Tumors | NCITR* NCI-TR-80,1978 |
| oral/mouse | toxic dose: 523 gm/kg/90W- continuous | Tumorigenic: Carcinogenic by RTECS criteria Liver: Tumors | NCITR* NCI-TR-80,1978 |
| oral/mouse | lowest published toxic dose: 292000 mg/kg/2Y- intermittent | Tumorigenic: Carcinogenic by RTECS criteria Liver: Tumors Tumorigenic: Increased incidence of tumors in susceptible strains | FCTOD7 47,2776,2009 |
| oral/rat | lowest published toxic dose: 185 gm/kg/2Y- continuous | Tumorigenic: Carcinogenic by RTECS criteria Olfaction: Tumors Liver: Tumors | NCITR* NCI-TR-80,1978 |
| oral/rat | toxic dose: 416 gm/kg/57W- continuous | Tumorigenic: Carcinogenic by RTECS criteria Olfaction: Tumors Liver: Tumors | BJCAAI 24,164,1970 |
| oral/rat | toxic dose: 528 gm/kg/63W- intermittent | Tumorigenic: Equivocal tumorigenic agent by RTECS criteria Liver: Tumors Kidney, Ureter, and Bladder: Kidney tumors | JNCIAM 35,949,1965 |
| oral/rat | lowest published toxic dose: 365000 mg/kg/2Y- intermittent | Tumorigenic: Carcinogenic by RTECS criteria Liver: Tumors Tumorigenic: Increased incidence of tumors in susceptible strains | FCTOD7 47,2776,2009 |
| oral/rat | toxic dose: 416 gm/kg/57W- continuous | Tumorigenic: Equivocal tumorigenic agent by RTECS criteria Olfaction: Tumors Liver: Tumors | BJCAAI 24,164,1970 |
| oral/rat | toxic dose: 408 gm/kg/2Y- continuous | Tumorigenic: Carcinogenic by RTECS criteria Olfaction: Tumors Liver: Tumors | NCITR* NCI-TR-80,1978 |
| skin/mouse | lowest published toxic dose: 14 gm/kg/60W- intermittent | Tumorigenic: Equivocal tumorigenic agent by RTECS criteria Skin and Appendages: Tumors | EVHPAZ 5,163,1973 |
Acute Toxicity Data and References
| Route/Organism | Dose | Effect | Reference |
|---|---|---|---|
| In Vitro/Human, liver tumor | Inhibitor Concentration (50 percent kill): 45 mmol/L/24H | In Vitro Toxicity Studies: Cell protein synthesis | TIVIEQ 3,189,1989 |
| inhalation/cat | Lowest published lethal concentration: 44 gm/m3/7H | Behavioral: Excitement Lung, Thorax, or Respiration: Dyspnea | KDPU** -,-,1937 |
| inhalation/human | lowest published toxic concentration: 470 ppm | Behavioral: Convulsions or effect on seizure threshold Vascular: BP elevation not characterized in autonomic section Gastrointestinal: Other changes | AMIHAB 20,445,1959 |
| inhalation/human | lowest published toxic concentration: 5500 ppm/1M | Eye: Lacrimation Eye: Conjunctiva irritation Lung, Thorax, or Respiration: Other changes | PHRPA6 45,2023,1930 |
| inhalation/human | Lowest published lethal concentration: 470 ppm/3D | Brain and Coverings: Other degenerative changes Lung, Thorax, or Respiration: Other changes Liver: Other changes | PLENBW 7(9),22,1975 |
| inhalation/mammal (species unspecified) | lethal concentration (50 percent kill): 20500 mg/m3 | GISAAA 51(5),61,1986 | |
| inhalation/mouse | lethal concentration (50 percent kill): 37 gm/m3/2H | 85GMAT -,63,1982 | |
| inhalation/rat | lethal concentration (50 percent kill): 46 gm/m3/2H | Eye: Other eye effects | KBAMAJ 11(6),53,1977 |
| intraperitoneal/mouse | lethal dose (50 percent kill): 790 mg/kg | Lung, Thorax, or Respiration: Other changes Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis) | FEPRA7 6,342,1947 |
| intraperitoneal/rat | lethal dose (50 percent kill): 799 mg/kg | ENVRAL 40,411,1986 | |
| intravenous/cat | lowest published lethal dose: 1500 mg/kg | Behavioral: Altered sleep time (including change in righting reflex) Behavioral: Irritability | JOHYAY 35,540,1935 |
| intravenous/rabbit | lowest published lethal dose: 1500 mg/kg | Kidney, Ureter, and Bladder: Urine volume increased Kidney, Ureter, and Bladder: Urine volume decreased or anuria Nutritional and Gross Metabolic: Weight loss or decreased weight gain | JOHYAY 35,540,1935 |
| oral/cat | lethal dose (50 percent kill): 2 gm/kg | JIHTAB 21,173,1939 | |
| oral/guinea pig | lethal dose (50 percent kill): 3150 mg/kg | Behavioral: General anesthetic Gastrointestinal: Other changes Kidney, Ureter, and Bladder: Other changes | JIHTAB 23,259,1941 |
| oral/mouse | lethal dose (50 percent kill): 5300 mg/kg | IJEBA6 16,54,1978 | |
| oral/rabbit | lethal dose (50 percent kill): 2 gm/kg | JIHTAB 21,173,1939 | |
| oral/rat | lethal dose (50 percent kill): 4200 mg/kg | INHEAO 32,145,1994 | |
| skin/rabbit | lethal dose (50 percent kill): 7600 µL/kg | UCDS** 12/17/1971 |
Other Multiple Dose Data and References
| Route/Organism | Dose | Effect | Reference |
|---|---|---|---|
| inhalation/rat | lowest published toxic concentration: 6000 ppm/4H/2W- intermittent | Behavioral: Change in psychophysiological tests | AIHAAP 25,369,1964 |
| inhalation/rat | lowest published toxic concentration: 20500 µg/m3/13W- intermittent | Kidney, Ureter, and Bladder: Proteinuria Nutritional and Gross Metabolic: Changes in: Cl Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases | KBAMAJ 11(6),53,1977 |
| oral/mouse | lowest published toxic dose: 142870 mg/kg/13W- continuous | Lung, Thorax, or Respiration: Changes in lung weight Liver: Changes in liver weight Nutritional and Gross Metabolic: Weight loss or decreased weight gain | JTSCDR 33,141,2008 |
| oral/mouse | lowest published toxic dose: 35217 mg/kg/13W- continuous | Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi | JTSCDR 33,141,2008 |
| oral/mouse | lowest published toxic dose: 147420 mg/kg/13W- continuous | Lung, Thorax, or Respiration: Changes in lung weight Endocrine: Hypoglycemia Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases | JTSCDR 33,141,2008 |
| oral/mouse | lowest published toxic dose: 242879 mg/kg/13W- continuous | Lung, Thorax, or Respiration: Changes in lung weight Liver: Changes in liver weight Kidney, Ureter, and Bladder: Changes in kidney weight | JTSCDR 33,141,2008 |
| oral/mouse | lowest published toxic dose: 192874.5 mg/kg/13W- continuous | Olfaction: Change in olfactory nerve Endocrine: Hypoglycemia Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases | JTSCDR 33,141,2008 |
| oral/mouse | lowest published toxic dose: 67476.5 mg/kg/13W- continuous | Olfaction: Other olfaction effects Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi Liver: Other changes | JTSCDR 33,141,2008 |
| oral/rat | lowest published toxic dose: 4 gm/kg/2D- intermittent | Liver: Other changes Kidney, Ureter, and Bladder: Other changes Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects | ARTODN 79,74,2005 |
| oral/rat | lowest published toxic dose: 11466 mg/kg/13W- continuous | Liver: Other changes | JTSCDR 33,141,2008 |
| oral/rat | lowest published toxic dose: 24934 mg/kg/13W- continuous | Olfaction: Other olfaction effects Liver: Other changes Kidney, Ureter, and Bladder: Changes in kidney weight | JTSCDR 33,141,2008 |
| oral/rat | lowest published toxic dose: 16835 mg/kg/13W- continuous | Liver: Changes in liver weight Kidney, Ureter, and Bladder: Changes in kidney weight | JTSCDR 33,141,2008 |
| oral/rat | lowest published toxic dose: 38857 mg/kg/13W- continuous | Liver: Changes in liver weight Kidney, Ureter, and Bladder: Changes in kidney weight Nutritional and Gross Metabolic: Weight loss or decreased weight gain | JTSCDR 33,141,2008 |
| oral/rat | lowest published toxic dose: 68796 mg/kg/13W- continuous | Lung, Thorax, or Respiration: Changes in lung weight Liver: Changes in liver weight Kidney, Ureter, and Bladder: Changes in kidney weight | JTSCDR 33,141,2008 |
| oral/rat | lowest published toxic dose: 144144 mg/kg/13W- continuous | Brain and Coverings: Other degenerative changes Endocrine: Hypoglycemia Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases | JTSCDR 33,141,2008 |
Reviews
| Organization | Standard | Reference |
|---|---|---|
| American Conference of Governmental Industrial Hygienists (ACGIH) | Threshold Limit Value-time-weighted average 20 ppm (skin) | DTLVS* TLV/BEI,2013 |
| American Conference of Governmental Industrial Hygienists (ACGIH) | Threshold Limit Value-Confirmed animal carcinogen | DTLVS* TLV/BEI,2013 |
| International Agency for Research on Cancer (IARC) | Cancer Review:Animal Sufficient Evidence | IMEMDT 11,247,1976 |
| International Agency for Research on Cancer (IARC) | Cancer Review:Animal Sufficient Evidence | IMEMDT 71,589,1999 |
| International Agency for Research on Cancer (IARC) | Cancer Review:Human Inadequate Evidence | IMSUDL 7,201,1987 |
| International Agency for Research on Cancer (IARC) | Cancer Review:Human Inadequate Evidence | IMEMDT 71,589,1999 |
| International Agency for Research on Cancer (IARC) | Cancer Review:Group 2B | IMEMDT 71,589,1999 |
| TOXICOLOGY REVIEW | BNYMAM 54,413,1978 | |
| TOXICOLOGY REVIEW | ECIET* (2),-,1983 | |
| TOXICOLOGY REVIEW | TOLED5 127,111,2002 | |
| TOXICOLOGY REVIEW | MUREAV 543,201,2003 | |
| TOXICOLOGY REVIEW | MUREAV 567,227,2004 | |
| TOXICOLOGY REVIEW | MUREAV 567,109,2004 | |
| TOXICOLOGY REVIEW | MUREAV 567,151,2004 | |
| TOXICOLOGY REVIEW | MUREAV 627,10,2007 | |
| TOXICOLOGY REVIEW | ENTOX* -,67,2005 | |
| TOXICOLOGY REVIEW | MUREAV 584,1,2005 | |
| TOXICOLOGY REVIEW | BCLPT* 96,131,2005 | |
| TOXICOLOGY REVIEW | MUREAV 654,114,2008 | |
| TOXICOLOGY REVIEW | HUTOX* -,577,1996 | |
| TOXICOLOGY REVIEW | MUREAV 672,10,2009 | |
| TOXICOLOGY REVIEW | MUREAV 682,94,2009 | |
| TOXICOLOGY REVIEW | MUREAV 705,184,2010 | |
| TOXICOLOGY REVIEW | MUTAEX 26,223,2011 | |
| TOXICOLOGY REVIEW | MUREAV 751,49,2012 | |
| TOXICOLOGY REVIEW | FCTOD7 55,596,2013 | |
| TOXICOLOGY REVIEW | FCTOD7 84,133,2015 | |
| TOXICOLOGY REVIEW | RTOPDW 68,387,2014 | |
| TOXICOLOGY REVIEW | RTOPDW 55,43,2009 | |
| TOXICOLOGY REVIEW | RTOPDW 55,52,2009 |
Standards and Regulations
| Organization | Standard | Reference |
|---|---|---|
| Mine Safety and Health Administration (MSHA) STANDARD-air | time-weighted average 100 ppm (360 mg/m3) (skin) | DTLVS* 3,94,1971 |
| Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN check ACGIH TLV; | ||
| Occupational Exposure Limit IN SINGAPORE, VIETNAM check ACGIH TLV | ||
| Occupational Exposure Limit-AUSTRALIA | time-weighted average 10 ppm (36 mg/m3), JUL2008 | |
| Occupational Exposure Limit-AUSTRIA | MAK-TMW 20 ppm (73 mg/m3);KZW 40 ppm (146 mg/m3), skin, 2007 | |
| Occupational Exposure Limit-BELGIUM | time-weighted average 25 ppm (91 mg/m3), Skin, MAR2002 | |
| Occupational Exposure Limit-DENMARK | time-weighted average 10 ppm (36 mg/m3), skin, carc, MAY2011 | |
| Occupational Exposure Limit-FINLAND | time-weighted average 10 ppm (36 mg/m3), short term exposure limit 40 ppm (150 mg/m3), skin, NOV2011 | |
| Occupational Exposure Limit-FRANCE | VME 10 ppm (35 mg/m3), VLE 40 ppm (140 mg/m3), C3 Carcinogen, FEB2006 | |
| Occupational Exposure Limit-GERMANY | MAK 20 ppm (73 mg/m3), 2011 | |
| Occupational Exposure Limit-HUNGARY | time-weighted average 10 mg/m3, short term exposure limit 10 mg/m3, Skin, SEP2000 | |
| Occupational Exposure Limit-ICELAND | time-weighted average 10 ppm (36 mg/m3), carc, skin, NOV2011 | |
| Occupational Exposure Limit-JAPAN | Occupational Exposure Limit 10 ppm (36 mg/m3), skin, 2B carc, MAY2012 | |
| Occupational Exposure Limit-KOREA | time-weighted average 25 ppm (90 mg/m3), skin, 2006 | |
| Occupational Exposure Limit-MEXICO | time-weighted average 25 ppm (90 mg/m3);short term exposure limit 100 ppm (skin), 2004 | |
| Occupational Exposure Limit-NEW ZEALAND | time-weighted average 25 ppm (90 mg/m3), skin, JAN2002 | |
| Occupational Exposure Limit-PERU | time-weighted average 20 ppm (72 mg/m3), JUL2005 | |
| Occupational Exposure Limit-POLAND | MAC(time-weighted average) 10 mg/m3, MAC(short term exposure limit) 80 mg/me, JAN1999 | |
| Occupational Exposure Limit-RUSSIA | short term exposure limit 10 mg/m3, Skin, JUN2003 | |
| Occupational Exposure Limit-SWEDEN | time-weighted average 10 ppm (35 mg/m3);short term exposure limit 25 ppm (90 mg/m3), Carcinogen, Skin, JUN2005 | |
| Occupational Exposure Limit-SWITZERLAND | MAK-week 20 ppm (72 mg/m3), KZG-week 40 ppm (144 mg/m3), carc 3, skin, JAN2011 | |
| Occupational Exposure Limit-THE NETHERLANDS | MAC-TGG 40 mg/m3, Skin, 2003 | |
| Occupational Exposure Limit-THE PHILIPPINES | time-weighted average 100 ppm (360 mg/m3), Skin, JAN1993 | |
| Occupational Exposure Limit-TURKEY | time-weighted average 100 ppm (360 mg/m3), Skin, JAN1993 | |
| Occupational Exposure Limit-UNITED KINGDOM | time-weighted average 25 ppm (91 mg/m3);short term exposure limit 100 ppm (366 mg/m3), skin, OCT2007 | |
| Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction) | 8H time-weighted average 100 ppm (360 mg/m3) (skin) | CFRGBR 29,1926.55,1994 |
| Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors) | 8H time-weighted average 100 ppm (360 mg/m3) (skin) | CFRGBR 41,50-204.50,1994 |
| Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry) | 8H time-weighted average 100 ppm (360 mg/m3) (skin) | CFRGBR 29,1910.1000,1994 |
| Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards) | 8H time-weighted average 100 ppm (360 mg/m3) (skin) | CFRGBR 29,1915.1000,1993 |
NIOSH Documentation and Surveillance
| Organization | Standard | Reference |
|---|---|---|
| National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO DIOXANE-air | Carcinogen ceiling concentration 1 ppm/30M | NIOSH* DHHS #92-100,1992 |
| National Occupational Exposure Survey 1983 | Hazard Code 25145; Number of Industries 181; Total Number of Facilities 20994; Number of Occupations 137; Total Number of Employees Exposed 429330; Total Number of Female Employees Exposed 149697 | |
| National Occupational Hazard Survey 1974 | Hazard Code 25145; Number of Industries 135; Total Number of Facilities 12911; Number of Occupations 101; Total Number of Employees Exposed 147783 |
Status in Federal Agencies
| Organization | Reference |
|---|---|
| EPA GENETOX PROGRAM 1988, Negative: Cell transform.-SA7/SHE | |
| EPA GENETOX PROGRAM 1988, Positive: Carcinogenicity-mouse/rat | |
| EPA TSCA Section 8(b) CHEMICAL INVENTORY | |
| EPA TSCA Section 8(d) unpublished health/safety studies | |
| EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001 | |
| NCI Carcinogenesis Bioassay (oral);clear evidence:mouse,rat | NCITR* NCI-TR-80,1978 |
| NIOSH Analytical Method, 1994: Dioxane, 1602 | |
| NTP 14th Report on Carcinogens,2016:Reasonably anticipated to be human carcinogen | |
| On EPA IRIS database |
Page last reviewed: November 16, 2018
Content
source: National Institute for Occupational Safety and Health