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Registry of Toxic Effects of Chemical Substances (RTECS)

p-Dioxane

RTECS #

JG8225000

CAS #

123-91-1

Updated

June 2017

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 REVIEWBNYMAM 54,413,1978
TOXICOLOGY REVIEWECIET* (2),-,1983
TOXICOLOGY REVIEWTOLED5 127,111,2002
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
TOXICOLOGY REVIEWFCTOD7 55,596,2013
TOXICOLOGY REVIEWFCTOD7 84,133,2015

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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