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Registry of Toxic Effects of Chemical Substances (RTECS)

p-Dioxane

RTECS #

JG8225000

CAS #

123-91-1

Updated

September 201

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

Skin and Eye Irritation and References

Route/OrganismDoseEffectReference
eye /guinea pig 10 µg moderateJPPMAB 11,150,1959
eye /human 300 ppm/15MJIHTAB 28,262,1946
eye /rabbit 100 mg severeAJOPAA 29,1363,1946
eye /rabbit 100 mg/24H moderate85JCAE -,810,1986
skin /rabbit 515 mg open irritation test mildUCDS** 12/17/1971

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
Cytogenetic Analysissubcutaneous/mouse7500 mg/kg/5D- intermittentMUREAV 586,28,2005
DNA Damageoral/rat2550 mg/kgCALEDQ 53,67,1990
DNA Damageliver/rat300 µmol/LSinJF# 26OCT1982
DNA inhibitionHeLa cell/human400 mmol/LCRNGDP 13,2389,1992
micronucleus testsubcutaneous/mouse7500 mg/kg/5D- intermittentMUREAV 586,28,2005
micronucleus testoral/mouse900 mg/kgMUREAV 322,142,1994
micronucleus testoral/mouse3 gm/kgMUREAV 322,145,1994
morphological transformfibroblast/mouse1 gm/LEMMUEG 11,41,1988
other mutation test systemsintravenous/rat50 mg/kgARTODN 49,29,1981
sister chromatid exchangeovary/hamster10500 mg/LEMMUEG 10(Suppl 10),1,1987
Unscheduled DNA Synthesisoral/rat20 mg/kgTXAPA9 60,287,1981

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
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/OrganismDoseEffectReference
inhalation/rat lowest published toxic concentration: 111 ppm/7H/2Y- intermittentTumorigenic: 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- intermittentTumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors		TXAPA9 82,19,1986
oral/mouse lowest published toxic dose: 239 gm/kg/90W- continuousTumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors		NCITR* NCI-TR-80,1978
oral/mouse toxic dose: 523 gm/kg/90W- continuousTumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors		NCITR* NCI-TR-80,1978
oral/mouse lowest published toxic dose: 292000 mg/kg/2Y- intermittentTumorigenic: 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- continuousTumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors

Liver: Tumors		NCITR* NCI-TR-80,1978
oral/rat toxic dose: 416 gm/kg/57W- continuousTumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors

Liver: Tumors		BJCAAI 24,164,1970
oral/rat toxic dose: 528 gm/kg/63W- intermittentTumorigenic: 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- intermittentTumorigenic: 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- continuousTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Olfaction: Tumors

Liver: Tumors		BJCAAI 24,164,1970
oral/rat toxic dose: 408 gm/kg/2Y- continuousTumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors

Liver: Tumors		NCITR* NCI-TR-80,1978
skin/mouse lowest published toxic dose: 14 gm/kg/60W- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Skin and Appendages: Tumors		EVHPAZ 5,163,1973

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Human, liver tumor Inhibitor Concentration (50 percent kill): 45 mmol/L/24HIn Vitro Toxicity Studies: Cell protein synthesisTIVIEQ 3,189,1989
inhalation/cat Lowest published lethal concentration: 44 gm/m3/7HBehavioral: Excitement

Lung, Thorax, or Respiration: Dyspnea		KDPU** -,-,1937
inhalation/human lowest published toxic concentration: 470 ppmBehavioral: 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/1MEye: Lacrimation

Eye: Conjunctiva irritation

Lung, Thorax, or Respiration: Other changes		PHRPA6 45,2023,1930
inhalation/human Lowest published lethal concentration: 470 ppm/3DBrain 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/m3GISAAA 51(5),61,1986
inhalation/mouse lethal concentration (50 percent kill): 37 gm/m3/2H85GMAT -,63,1982
inhalation/rat lethal concentration (50 percent kill): 46 gm/m3/2HEye: Other eye effectsKBAMAJ 11(6),53,1977
intraperitoneal/mouse lethal dose (50 percent kill): 790 mg/kgLung, 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/kgENVRAL 40,411,1986
intravenous/cat lowest published lethal dose: 1500 mg/kgBehavioral: Altered sleep time (including change in righting reflex)

Behavioral: Irritability		JOHYAY 35,540,1935
intravenous/rabbit lowest published lethal dose: 1500 mg/kgKidney, 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/kgJIHTAB 21,173,1939
oral/guinea pig lethal dose (50 percent kill): 3150 mg/kgBehavioral: General anesthetic

Gastrointestinal: Other changes

Kidney, Ureter, and Bladder: Other changes		JIHTAB 23,259,1941
oral/mouse lethal dose (50 percent kill): 5300 mg/kgIJEBA6 16,54,1978
oral/rabbit lethal dose (50 percent kill): 2 gm/kgJIHTAB 21,173,1939
oral/rat lethal dose (50 percent kill): 4200 mg/kgINHEAO 32,145,1994
skin/rabbit lethal dose (50 percent kill): 7600 µL/kgUCDS** 12/17/1971

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
inhalation/rat lowest published toxic concentration: 6000 ppm/4H/2W- intermittentBehavioral: Change in psychophysiological testsAIHAAP 25,369,1964
inhalation/rat lowest published toxic concentration: 20500 µg/m3/13W- intermittentKidney, 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- continuousLung, 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- continuousLung, Thorax, or Respiration: Structural or functional change in trachea or bronchiJTSCDR 33,141,2008
oral/mouse lowest published toxic dose: 147420 mg/kg/13W- continuousLung, 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- continuousLung, 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- continuousOlfaction: 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- continuousOlfaction: 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- intermittentLiver: 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- continuousLiver: Other changesJTSCDR 33,141,2008
oral/rat lowest published toxic dose: 24934 mg/kg/13W- continuousOlfaction: 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- continuousLiver: 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- continuousLiver: 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- continuousLung, 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- continuousBrain and Coverings: Other degenerative changes

Endocrine: Hypoglycemia

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases		JTSCDR 33,141,2008

Reviews

OrganizationStandardReference
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 carcinogenDTLVS* TLV/BEI,2013
International Agency for Research on Cancer (IARC)Cancer Review:Animal Sufficient EvidenceIMEMDT 11,247,1976
International Agency for Research on Cancer (IARC)Cancer Review:Animal Sufficient EvidenceIMEMDT 71,589,1999
International Agency for Research on Cancer (IARC)Cancer Review:Human Inadequate EvidenceIMSUDL 7,201,1987
International Agency for Research on Cancer (IARC)Cancer Review:Human Inadequate EvidenceIMEMDT 71,589,1999
International Agency for Research on Cancer (IARC)Cancer Review:Group 2BIMEMDT 71,589,1999
TOXICOLOGY REVIEWTOLED5 127,111,2002
TOXICOLOGY REVIEWECIET* (2),-,1983
TOXICOLOGY REVIEWMUREAV 543,201,2003
TOXICOLOGY REVIEWMUREAV 567,227,2004
TOXICOLOGY REVIEWMUREAV 567,109,2004
TOXICOLOGY REVIEWMUREAV 567,151,2004
TOXICOLOGY REVIEWMUREAV 627,10,2007
TOXICOLOGY REVIEWENTOX* -,67,2005
TOXICOLOGY REVIEWMUREAV 584,1,2005
TOXICOLOGY REVIEWBCLPT* 96,131,2005
TOXICOLOGY REVIEWMUREAV 654,114,2008
TOXICOLOGY REVIEWHUTOX* -,577,1996
TOXICOLOGY REVIEWMUREAV 672,10,2009
TOXICOLOGY REVIEWMUREAV 682,94,2009
TOXICOLOGY REVIEWMUREAV 705,184,2010
TOXICOLOGY REVIEWMUTAEX 26,223,2011
TOXICOLOGY REVIEWMUREAV 751,49,2012

Standards and Regulations

OrganizationStandardReference
Mine Safety and Health Administration (MSHA) STANDARD-airtime-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-AUSTRALIAtime-weighted average 10 ppm (36 mg/m3), JUL2008
Occupational Exposure Limit-AUSTRIAMAK-TMW 20 ppm (73 mg/m3);KZW 40 ppm (146 mg/m3), skin, 2007
Occupational Exposure Limit-BELGIUMtime-weighted average 25 ppm (91 mg/m3), Skin, MAR2002
Occupational Exposure Limit-DENMARKtime-weighted average 10 ppm (36 mg/m3), skin, carc, MAY2011
Occupational Exposure Limit-FINLANDtime-weighted average 10 ppm (36 mg/m3), short term exposure limit 40 ppm (150 mg/m3), skin, NOV2011
Occupational Exposure Limit-FRANCEVME 10 ppm (35 mg/m3), VLE 40 ppm (140 mg/m3), C3 Carcinogen, FEB2006
Occupational Exposure Limit-GERMANYMAK 20 ppm (73 mg/m3), 2011
Occupational Exposure Limit-HUNGARYtime-weighted average 10 mg/m3, short term exposure limit 10 mg/m3, Skin, SEP2000
Occupational Exposure Limit-ICELANDtime-weighted average 10 ppm (36 mg/m3), carc, skin, NOV2011
Occupational Exposure Limit-JAPANOccupational Exposure Limit 10 ppm (36 mg/m3), skin, 2B carc, MAY2012
Occupational Exposure Limit-KOREAtime-weighted average 25 ppm (90 mg/m3), skin, 2006
Occupational Exposure Limit-MEXICOtime-weighted average 25 ppm (90 mg/m3);short term exposure limit 100 ppm (skin), 2004
Occupational Exposure Limit-NEW ZEALANDtime-weighted average 25 ppm (90 mg/m3), skin, JAN2002
Occupational Exposure Limit-PERUtime-weighted average 20 ppm (72 mg/m3), JUL2005
Occupational Exposure Limit-POLANDMAC(time-weighted average) 10 mg/m3, MAC(short term exposure limit) 80 mg/me, JAN1999
Occupational Exposure Limit-RUSSIAshort term exposure limit 10 mg/m3, Skin, JUN2003
Occupational Exposure Limit-SWEDENtime-weighted average 10 ppm (35 mg/m3);short term exposure limit 25 ppm (90 mg/m3), Carcinogen, Skin, JUN2005
Occupational Exposure Limit-SWITZERLANDMAK-week 20 ppm (72 mg/m3), KZG-week 40 ppm (144 mg/m3), carc 3, skin, JAN2011
Occupational Exposure Limit-THE NETHERLANDSMAC-TGG 40 mg/m3, Skin, 2003
Occupational Exposure Limit-THE PHILIPPINEStime-weighted average 100 ppm (360 mg/m3), Skin, JAN1993
Occupational Exposure Limit-TURKEYtime-weighted average 100 ppm (360 mg/m3), Skin, JAN1993
Occupational Exposure Limit-UNITED KINGDOMtime-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

OrganizationStandardReference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO DIOXANE-airCarcinogen ceiling concentration 1 ppm/30MNIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983Hazard 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 1974Hazard 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

OrganizationReference
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,ratNCITR* NCI-TR-80,1978
NIOSH Analytical Method, 1994: Dioxane, 1602
NTP 11th Report on Carcinogens,2004:Reasonably anticipated to be a human carcinogen
On EPA IRIS database

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