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Registry of Toxic Effects of Chemical Substances (RTECS)

Furan, tetrahydro-

RTECS #

LU5950000

CAS #

109-99-9

Updated

December 2013

Molecular Weight

72.12

Molecular Formula

C4H8O

Synonyms

1,4-Epoxybutane
Agrisynth THF
Butane, 1,4-epoxy-
Butane, alpha,delta-oxide
Cyclotetramethylene oxide
Diethylene oxide
Furanidine
NCI-C60560
Oxacyclopentane
Oxolane
RCRA waste number U213
Tetrahydrofuraan (Dutch)
Tetrahydrofuran
Tetrahydrofuran (ACGIH:OSHA)
Tetrahydrofuranne (French)
Tetraidrofurano (Italian)
Tetramethylene oxide

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
mutation in microorganisms/Escherichia coli1 µmol/L (-enzymatic activation step)GTPZAB 26(1),43,1982

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
inhalation/rat 5000 ppm/6H (6-19D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)FAATDF 18,255,1992
inhalation/mouse 1800 ppm/6H (6-17D pregnant)Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)FAATDF 18,255,1992
oral/rat 3500 mg/kg (6-19D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)NTIS** #DE89-001383/LL
oral/mouse 2592 mg/kg (6-17D pregnant)Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)		NTIS** #DE89-001383/LL
oral/mouse 2592 mg/kg (6-17D pregnant)Reproductive: Other effects to embryo or fetus

Reproductive: Specific developmental abnormalities: Musculoskeletal system		NTIS** #DE89-001383/LL
oral/rat 153 gm/kg (91D male/91D pre-7D after birth)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)FCTOD7 40,1515,2002
oral/rat 1.125 mg/kg (multigeneration)Reproductive: Effects on newborn: Behavioral

Reproductive: Effects on newborn: Physical

Reproductive: Effects on newborn: Delayed effects		FCTOD7 40,1515,2002

Tumorigenic Data and References

Route/OrganismDoseEffectReference
inhalation/mouse lowest published toxic concentration: 1800 ppm/6H/2Y- intermittentTumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors		NTPTR* NTP-TR-475,1998
inhalation/mouse lowest published toxic concentration: 113400 mg/kg/105W- intermittentTumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors		NTIS** PB98-164544
inhalation/rat lowest published toxic concentration: 1800 ppm/6H/2Y- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors		NTPTR* NTP-TR-475,1998
inhalation/rat lowest published toxic concentration: 18900 mg/kg/105W- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors		NTIS** PB98-164544

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Human, liver tumor Inhibitor Concentration (50 percent kill): 372 mmol/L/24HIn Vitro Toxicity Studies: Cell protein synthesisTIVIEQ 3,189,1989
inhalation/human lowest published toxic concentration: 25000 ppmBehavioral: General anesthetic34ZIAG -,580,1969
inhalation/mouse Lowest published lethal concentration: 24000 mg/m3/2HBehavioral: Somnolence (general depressed activity)

Behavioral: Muscle weakness

Lung, Thorax, or Respiration: Dyspnea		TPKVAL 5,21,1963
inhalation/mouse Lowest published lethal concentration: 19 gm/m3/2HKidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Blood: Hemorrhage

Blood: Changes in spleen		TPKVAL 5,21,1963
inhalation/rabbit Lethal concentration: >1200 ppm/4HOlfaction: Other olfaction effectsSSEIBV 18,89,1982
inhalation/rat lethal concentration (50 percent kill): 21000 ppm/3HBehavioral: Sleep

Lung, Thorax, or Respiration: Respiratory stimulation

Gastrointestinal: Nausea or vomiting		SSEIBV 20,141,1984
inhalation/rat lethal concentration (50 percent kill): 72 gm/m3/2HTPKVAL 10,35,1968
inhalation/rat lowest published toxic concentration: 8 gm/m3/2HPeripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Peripheral Nerve and Sensation: Recording from peripheral motor nerve

Behavioral: Convulsions or effect on seizure threshold		TPKVAL 5,21,1963
inhalation/rat Lowest published lethal concentration: 41 gm/m3/2HBehavioral: Muscle weakness

Lung, Thorax, or Respiration: Respiratory depression

Gastrointestinal: Necrotic changes		TPKVAL 5,21,1963
inhalation/rat Lowest published lethal concentration: 106 gm/m3Behavioral: Alteration of classical conditioningTPKVAL 10,35,1968
inhalation/rat Lowest published lethal concentration: 48 gm/m3Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)TPKVAL 10,35,1968
intraperitoneal/guinea pig lowest published lethal dose: 500 mg/kgLiver: Fatty liver degenerationAIHAAP 35,21,1974
intraperitoneal/mouse lowest published toxic dose: 691.7 mg/kgBehavioral: AtaxiaJTCTDW 41,692,2003
intraperitoneal/mouse lowest published toxic dose: 487.8 mg/kgBehavioral: Muscle weaknessJTCTDW 41,692,2003
intraperitoneal/mouse lethal dose (50 percent kill): 1900 mg/kgSAIGBL 24,373,1982
intraperitoneal/rat lethal dose (50 percent kill): 2900 mg/kgSAIGBL 24,373,1982
ocular/rabbit lowest published toxic dose: 100 pphEye: Conjunctiva irritation

Eye: Corneal damage

Eye: Other eye effects		TPKVAL 5,21,1963
oral/guinea pig lethal dose (50 percent kill): 2300 mg/kgGISAAA 34(9),114,1969
oral/rat lethal dose (50 percent kill): 2.3 mL/kgENTOX* -,155,2005
oral/rat lethal dose (50 percent kill): 1650 mg/kgGAFCC*
oral/rat lethal dose (20 percent kill): 3000 mg/kgLung, Thorax, or Respiration: Respiratory depressionTPKVAL 5,21,1963
oral/rat lowest published toxic dose: 1000 mg/kgBrain and Coverings: Changes in circulation

Cardiac: Other changes

Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi		TPKVAL 5,21,1963
oral/rat lowest published lethal dose: 4000 mg/kgTPKVAL 5,21,1963

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
inhalation/mouse lowest published toxic concentration: 5000 ppm/6H/91D- intermittentLiver: Changes in liver weight

Endocrine: Adrenal cortex hypoplasia

Endocrine: Changes in thymus weight		FAATDF 14,338,1990
inhalation/mouse lowest published toxic concentration: 200 ppm/6H/14W- intermittentLiver: Changes in liver weightNTPTR* NTP-TR-475,1998
inhalation/mouse lowest published toxic concentration: 15000 mg/m3/5D- intermittentLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)		ARTODN 77,459,2003
inhalation/mouse lowest published toxic concentration: 8 gm/m3/2H/60D- intermittentLung, Thorax, or Respiration: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field		TPKVAL 5,21,1963
inhalation/mouse lowest published toxic concentration: 7 gm/m3/20D- intermittentPeripheral Nerve and Sensation: Recording from peripheral motor nerve

Eye: Conjunctiva irritation

Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi		TPKVAL 5,21,1963
inhalation/mouse lowest published toxic concentration: 7 gm/m3/30D- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldTPKVAL 5,21,1963
inhalation/mouse lowest published toxic concentration: 7 gm/m3/61D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gainTPKVAL 5,21,1963
inhalation/rat lowest published toxic concentration: 1.5 gm/m3/61D- intermittentBlood: Changes in leukocyte (WBC) countTPKVAL 5,21,1963
inhalation/rat lowest published toxic concentration: 1.5 gm/m3/91D- intermittentVascular: BP lowering not characterized in autonomic sectionTPKVAL 5,21,1963
inhalation/rat lowest published toxic concentration: 1.5 gm/m3/0.5Y- intermittentVascular: Structural changes in vessels

Lung, Thorax, or Respiration: Changes in pulmonary vascular resistance

Blood: Changes in spleen		TPKVAL 5,21,1963
inhalation/rat lowest published toxic concentration: 6 gm/m3/61D- intermittentPeripheral Nerve and Sensation: Recording from peripheral motor nerve

Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Nutritional and Gross Metabolic: Weight loss or decreased weight gain		TPKVAL 10,35,1968
inhalation/rat lowest published toxic concentration: 8 gm/m3/61D- intermittentPeripheral Nerve and Sensation: Recording from peripheral motor nerve

Cardiac: Changes in coronary arteries

Vascular: Structural changes in vessels		TPKVAL 5,21,1963
inhalation/rat lowest published toxic concentration: 1000 ppm/4H/12W- intermittentOlfaction: Deviated nasal septumSEEIAY 25,176,1981
inhalation/rat lowest published toxic concentration: 5000 ppm/6H/91D- intermittentEndocrine: Changes in spleen weight

Endocrine: Changes in thymus weight

Blood: Changes in erythrocyte (RBC) count		FAATDF 14,338,1990
inhalation/rat lowest published toxic concentration: 200 ppm/6H/18W- intermittentLiver: Other changes

Musculoskeletal: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects		APTOA6 54,221,1984
inhalation/rat lowest published toxic dose: 5000 ppm/6H/14W- intermittentCardiac: Changes in heart weight

Lung, Thorax, or Respiration: Changes in lung weight

Liver: Changes in liver weight		NTPTR* NTP-TR-475,1998
oral/mouse lowest published toxic dose: 4550 mg/kg/17W- intermittentBlood: Change in clotting factors

Blood: Changes in leukocyte (WBC) count

Nutritional and Gross Metabolic: Weight loss or decreased weight gain		GISAAA 32(2),99,1967
oral/mouse lowest published toxic dose: 3600 mg/kg/6D- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldNTIS** #DE89-001383/LL
oral/mouse lowest published toxic dose: 2592 mg/kg/12D- intermittentBehavioral: General anesthetic

Nutritional and Gross Metabolic: Weight loss or decreased weight gain		NTIS** #DE89-001383/LL
oral/rat lowest published toxic dose: 4900 mg/kg/7D- continuousBehavioral: Fluid intake

Nutritional and Gross Metabolic: Weight loss or decreased weight gain		FCTOD7 40,1515,2002
oral/rat lowest published toxic dose: 3500 mg/kg/14D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gainNTIS** #DE89-001383/LL
oral/rat lowest published toxic dose: 26280 mg/kg/2Y- continuousLiver: Tumors

Kidney, Ureter, and Bladder: Kidney tumors		TOXID9 60,286,2001
oral/rat lowest published toxic dose: 4550 mg/kg/17W- intermittentBlood: Change in clotting factors

Blood: Changes in leukocyte (WBC) count

Nutritional and Gross Metabolic: Weight loss or decreased weight gain		GISAAA 32(2),99,1967

Reviews

OrganizationStandardReference
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-time-weighted average 50 ppm;short term exposure limit 100 ppm (skin)DTLVS* TLV/BEI,2013
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-Confirmed animal carcinogenDTLVS* TLV/BEI,2013
TOXICOLOGY REVIEWMUREAV 543,201,2003
TOXICOLOGY REVIEWENTOX* -,155,2005
TOXICOLOGY REVIEWMUREAV 584,1,2005
TOXICOLOGY REVIEWREPTED 25,192,2008
TOXICOLOGY REVIEWMUREAV 566,49,2004
TOXICOLOGY REVIEWHUTOX* -,649,1996
TOXICOLOGY REVIEWTXCYAC 286,1,2011
TOXICOLOGY REVIEWFCTOD7 49,1877,2011
TOXICOLOGY REVIEWMUTAEX 25,335,2010

Standards and Regulations

OrganizationStandardReference
Mine Safety and Health Administration (MSHA) STANDARD-airtime-weighted average 200 ppm (590 mg/m3)DTLVS* 3,252,1971
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 100 ppm (295 mg/m3), JUL2008
Occupational Exposure Limit-AUSTRIAMAK-TMW 50 ppm (150 mg/m3);KZW 100 ppm (300 mg/m3), skin, 2007
Occupational Exposure Limit-BELGIUMtime-weighted average 50 ppm (150 mg/m3), MAR2002
Occupational Exposure Limit-BELGIUMshort term exposure limit 100 ppm (300 mg/m3), Skin, MAR2002
Occupational Exposure Limit-DENMARKtime-weighted average 50 ppm (148 mg/m3), skin, MAY2011
Occupational Exposure Limit-ECtime-weighted average 150 mg/m3 (50 ppm);short term exposure limit 300 mg/m3 (100 ppm), skin, JUN2000
Occupational Exposure Limit-FINLANDtime-weighted average 50 ppm (150 mg/m3), short term exposure limit 100 ppm (300 mg/m3), skin, NOV2011
Occupational Exposure Limit-FRANCEVME 50 ppm (150 mg/m3), VLE 100 ppm (300 mg/m3), Skin, FEB2006
Occupational Exposure Limit-GERMANYMAK 50 ppm (150 mg/m3), skin, 2011
Occupational Exposure Limit-HUNGARYtime-weighted average 150 mg/m3, short term exposure limit 300 mg/m3, Skin, SEP2000
Occupational Exposure Limit-ICELANDtime-weighted average 50 ppm (150 mg/m3), short term exposure limit 100 ppm (300 mg/m3), skin, NOV2011
Occupational Exposure Limit-JAPANOccupational Exposure Limit 200 ppm (590 mg/m3), MAY2012
Occupational Exposure Limit-KOREAtime-weighted average 200 ppm (590 mg/m3), short term exposure limit 250 ppm (735 mg/m3), 2006
Occupational Exposure Limit-MEXICOtime-weighted average 200 ppm (590 mg/m3);short term exposure limit 250 ppm (735 mg/m3), 2004
Occupational Exposure Limit-NEW ZEALANDtime-weighted average 100 ppm (295 mg/m3), skin, JAN2002
Occupational Exposure Limit-NORWAYtime-weighted average 50 ppm (150 mg/m3), JAN1999
Occupational Exposure Limit-PERUtime-weighted average 200 ppm (590 mg/m3); short term exposure limit 250 ppm (737 mg/m3), JUL2005
Occupational Exposure Limit-POLANDMAC(time-weighted average) 600 mg/m3, MAC(short term exposure limit) 750 mg/m3, JAN1999
Occupational Exposure Limit-RUSSIAshort term exposure limit 100 mg/m3, JUN2003
Occupational Exposure Limit-SWEDENtime-weighted average 50 ppm (150 mg/m3);short term exposure limit 80 ppm (250 mg/m3), JUN2005
Occupational Exposure Limit-SWITZERLANDMAK-week 50 ppm (150 mg/m3), KZG-week 100 ppm (300 mg/m3), skin, JAN2011
Occupational Exposure Limit-THE NETHERLANDSMAC-TGG 300 mg/m3, Skin, 2003
Occupational Exposure Limit-THE PHILIPPINEStime-weighted average 200 ppm (590 mg/m3), JAN1993
Occupational Exposure Limit-TURKEYtime-weighted average 200 ppm (590 mg/m3), JAN1993
Occupational Exposure Limit-UNITED KINGDOMtime-weighted average 50 ppm (150 mg/m3);short term exposure limit 100 ppm (300 mg/m3), skin, OCT2007
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction)8H time-weighted average 200 ppm (590 mg/m3)CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors)8H time-weighted average 200 ppm (590 mg/m3)CFRGBR 41,50-204.50,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry)8H time-weighted average 200 ppm (590 mg/m3)CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards)8H time-weighted average 200 ppm (590 mg/m3)CFRGBR 29,1915.1000,1993

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO TETRAHYDROFURAN-air10H time-weighted average 200 ppm;short term exposure limit 250 ppmNIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983Hazard Code 71695; Number of Industries 101; Total Number of Facilities 17866; Number of Occupations 83; Total Number of Employees Exposed 356038; Total Number of Female Employees Exposed 47382
National Occupational Hazard Survey 1974Hazard Code 71695; Number of Industries 72; Total Number of Facilities 4141; Number of Occupations 60; Total Number of Employees Exposed 95003

Status in Federal Agencies

OrganizationReference
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 Studies (inhal);clear evidence:mouse
NCI Carcinogenesis Studies (inhal);equivocal evidence:rat
NIOSH Analytical Method, 1994: Tetrahydrofuran, 1609
NTP Carcinogenesis Studies (inhalation):some evidence:rat NTPTR* NTP-TR-475,1998
On EPA IRIS database

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