The Registry of Toxic Effects of Chemical Substances

Furan, tetrahydro -

RTECS #: LU5950000

CAS #: 109-99-9

UPDATE: February 2005 MW: 72.12 MF: C4H8O


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. MUTATION DATA:
  3. REPRODUCTIVE EFFECTS DATA:
  4. TUMORIGENIC DATA:
  5. ACUTE TOXICITY DATA:
  6. OTHER MULTIPLE DOSE DATA:
  7. REVIEWS:
  8. STANDARDS AND REGULATIONS:
  9. NIOSH DOCUMENTATION AND SURVEILLANCE:
  10. STATUS IN FEDERAL AGENCIES:
  11. REFERENCES:

SYNONYMS:

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


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
N/R
 N/R N/R N/R


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
mutation in microorganisms Escherichia coli 1 µmol/L (-enzymatic activation step) GTPZAB 26(1),43,1982


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
mouse 		lowest published toxic concentration: 1,800 ppm/6 hour (6-17 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) FAATDF 18,255,1992
inhalation
rat 		lowest published toxic concentration: 5,000 ppm/6 hour (6-19 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) FAATDF 18,255,1992
oral
mouse 		lowest published toxic dose: 2,592 mg/kg (6-17 day 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 		lowest published toxic dose: 2,592 mg/kg (6-17 day pregnant) Reproductive: Other effects to embryo or fetus

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		NTIS** #DE89-001383/LL
oral
rat 		lowest published toxic dose: 3,500 mg/kg (6-19 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) NTIS** #DE89-001383/LL
oral
rat 		lowest published toxic dose: 153 gm/kg (91 day male/91 day prior to copulation-7 day after birth) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) FCTOD7 40,1515,2002
oral
rat 		lowest published toxic dose: 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/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
mouse 		lowest published toxic concentration: 1,800 ppm/6 hour/2 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors 		NTPTR* NTP-TR-475,1998
inhalation
mouse 		lowest published toxic concentration: 113,400 mg/kg/105 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors 		NTIS** PB98-164544
inhalation
rat 		lowest published toxic concentration: 1,800 ppm/6 hour/2 year- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors 		NTPTR* NTP-TR-475,1998
inhalation
rat 		lowest published toxic concentration: 18,900 mg/kg/105 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

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


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
human 		lowest published toxic concentration: 25,000 ppm Behavioral: General anesthetic 34ZIAG -,580,1969
inhalation
mouse 		lowest published lethal concentration: 24,000 mg/m3/2 hour Behavioral: Somnolence (general depressed activity)

Behavioral: Muscle weakness

Lung, Thorax, or Respiration: Dyspnea 		TPKVAL 5,21,1963
inhalation
rat 		lethal concentration (50 percent kill): 21,000 ppm/3 hour Behavioral: Sleep

Lung, Thorax, or Respiration: Respiratory stimulation

Gastrointestinal: Nausea or vomiting 		SSEIBV 20,141,1984
inhalation
rabbit 		lethal concentration : >1,200 ppm/4 hour Olfaction: Other olfaction effects SSEIBV 18,89,1982
intraperitoneal
guinea pig 		lowest published lethal dose: 500 mg/kg Liver: Fatty liver degeneration AIHAAP 35,21,1974
intraperitoneal
mouse 		lethal dose (50 percent kill): 1,900 mg/kg N/R SAIGBL 24,373,1982
intraperitoneal
rat 		lethal dose (50 percent kill): 2,900 mg/kg N/R SAIGBL 24,373,1982
oral
guinea pig 		lethal dose (50 percent kill): 2,300 mg/kg N/R GISAAA 34(9),114,1969
oral
rat 		lethal dose (50 percent kill): 1,650 mg/kg N/R GAFCC*


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
mouse 		lowest published toxic concentration: 5,000 ppm/6 hour/91 day- intermittent Liver: Changes in liver weight

Endocrine: Adrenal cortex hypoplasia

Endocrine: Changes in thymus weight 		FAATDF 14,338,1990
inhalation
mouse 		lowest published toxic concentration: 8 gm/m3/2 hour/60 day- intermittent Lung, 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: 200 ppm/6 hour/14 week- intermittent Liver: Changes in liver weight NTPTR* NTP-TR-475,1998
inhalation
rat 		lowest published toxic concentration: 1,000 ppm/4 hour/12 week- intermittent Olfaction: Deviated nasal septum SEEIAY 25,176,1981
inhalation
rat 		lowest published toxic concentration: 5,000 ppm/6 hour/91 day- intermittent Endocrine: 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/6 hour/18 week- intermittent Liver: 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: 5,000 ppm/6 hour/14 week- intermittent Cardiac: 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: 4,550 mg/kg/17 week- intermittent Blood: 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: 3,600 mg/kg/6 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field NTIS** #DE89-001383/LL
oral
mouse 		lowest published toxic dose: 2,592 mg/kg/12 day- intermittent Nutritional and Gross Metabolic: Weight loss or decreased weight gain NTIS** #DE89-001383/LL
oral
mouse 		lowest published toxic dose: 2,592 mg/kg/12 day- intermittent Behavioral: General anesthetic NTIS** #DE89-001383/LL
oral
rat 		lowest published toxic dose: 4,550 mg/kg/17 week- intermittent Blood: 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
rat 		lowest published toxic dose: 3,500 mg/kg/14 day- intermittent Nutritional and Gross Metabolic: Weight loss or decreased weight gain NTIS** #DE89-001383/LL
oral
rat 		lowest published toxic dose: 4,900 mg/kg/7 day- continuous Behavioral: Fluid intake

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		FCTOD7 40,1515,2002


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value time-weighted average 200 ppm DTLVS* TLV/BEI,2002
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value time-weighted average 200 ppm;short term exposure limit 250 ppm DTLVS* TLV/BEI,2003
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value short term exposure limit 250 ppm DTLVS* TLV/BEI,2002
TOXICOLOGY REVIEW
MUREAV 543,201,2003


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Mine Safety and Health Administration (MSHA) STANDARD - air time-weighted average 200 ppm (590 mg/m3) DTLVS* 3,252,1971
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry) 8 hour time-weighted average 200 ppm (590 mg/m3) CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction) 8 hour time-weighted average 200 ppm (590 mg/m3) CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards) 8 hour time-weighted average 200 ppm (590 mg/m3) CFRGBR 29,1915.1000,1993
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors) 8 hour time-weighted average 200 ppm (590 mg/m3) CFRGBR 41,50-204.50,1994
Occupational Exposure Limit - AUSTRALIA time-weighted average 200 ppm (590 mg/m3), short term exposure limit 250 ppm, JAN1993
Occupational Exposure Limit - AUSTRIA MAK 200 ppm (590 mg/m3), JAN1999
Occupational Exposure Limit - BELGIUM time-weighted average 200 ppm (590 mg/m3), short term exposure limit 250 ppm (738 mg/m3), JAN1993
Occupational Exposure Limit - DENMARK time-weighted average 100 ppm (295 mg/m3), JAN1999
Occupational Exposure Limit - FINLAND time-weighted average 100 ppm (290 mg/m3), short term exposure limit 150 ppm (440 mg/m3), JAN1999
Occupational Exposure Limit - FRANCE VME 200 ppm (590 mg/m3), JAN1999
Occupational Exposure Limit - GERMANY MAK 200 ppm (590 mg/m3), JAN1993
Occupational Exposure Limit - HUNGARY time-weighted average 200 mg/m3, short term exposure limit 400 mg/m3, JAN1999
Occupational Exposure Limit - JAPAN Occupational Exposure Limit 200 ppm (590 mg/m3), JAN1999
Occupational Exposure Limit - THE NETHERLANDS MAC-TGG 300 mg/m3, Skin, 2003
Occupational Exposure Limit - NORWAY time-weighted average 50 ppm (150 mg/m3), JAN1999
Occupational Exposure Limit - THE PHILIPPINES time-weighted average 200 ppm (590 mg/m3), JAN1993
Occupational Exposure Limit - POLAND MAC(time-weighted average) 600 mg/m3, MAC(short term exposure limit) 750 mg/m3, JAN1999
Occupational Exposure Limit - RUSSIA time-weighted average 200 ppm, short term exposure limit 100 mg/m3, JAN1993
Occupational Exposure Limit - SWEDEN NGV 50 ppm (150 mg/m3), KTV 80 ppm (250 mg/m3), JAN1999
Occupational Exposure Limit - SWITZERLAND MAK- week 200 ppm (590 mg/m3), short term exposure limit 1000 ppm, JAN1999
Occupational Exposure Limit - TURKEY time-weighted average 200 ppm (590 mg/m3), JAN1993
Occupational Exposure Limit - UNITED KINGDOM time-weighted average 100 ppm (300 mg/m3), short term exposure limit 200 ppm, Skin, SEP2000
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN, KOREA American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value;

short term exposure limit 250 ppm
Occupational Exposure Limit IN NEW ZEALAND, SINGAPORE, VIETNAM American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value
short term exposure limit 250 ppm


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO TETRAHYDROFURAN-air 10 hour time-weighted average 200 ppm;
short term exposure limit 250 ppm 		NIOSH* DHHS #92-100,1992
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: 71695;
Number of Industries 72;
Total Number of Facilities 4,141;
Number of Occupations 60;
Total Number of Employees Exposed 95,003
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 71695;
Number of Industries 101;
Total Number of Facilities 17,866;
Number of Occupations 83;
Total Number of Employees Exposed 356,038;
Total Number of Female Employees Exposed 47,382


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as solvent, also used in syntheses
EPA TSCA Section 8(d) unpublished health/safety studies
On EPA IRIS database
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NIOSH Analytical Method, 1994: Tetrahydrofuran, 1609
NCI Carcinogenesis Studies (inhal);clear evidence:mouse
NTP Carcinogenesis Studies (inhalation):some evidence:rat NTPTR* NTP-TR-475,1998
NCI Carcinogenesis Studies (inhal);equivocal evidence:rat


REFERENCES:

CODEN
REFERENCE
34ZIAG "Toxicology of Drugs and Chemicals," Deichmann, W.B., New York, Academic Press, Inc., 1969
AIHAAP American Industrial Hygiene Association Journal. (AIHA, 475 Wolf Ledges Pkwy., Akron, OH 44311) V.19- 1958-
APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH
CFRGBR Code of Federal Regulations. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402)
DTLVS* The Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs) booklet issues by American Conference of Governmental Industrial Hygienists (ACGIH), Cincinnati, OH, 1996
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1-40, 1981-97. For publisher information, see TOSCF2
FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982-
GISAAA Gigiena i Sanitariya. For English translation, see HYSAAV. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1- 1936-
GTPZAB Gigiena Truda i Professional'nye Zabolevaniya. Labor Hygiene and Occupational Diseases. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1-36, 1957-1992. For publisher information, see MTPEEI
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NIOSH* National Institute of Occupational Safety and Health, U.S. Dept. of Health, Education, and Welfare, Reports and Memoranda.
NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information.
NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206-
SAIGBL Sangyo Igaku. Japanese Journal of Industrial Health. (Nippon Sangyo Eisei Igakkai, Kosu Eisei Bldg., 1-29-8, Shinjuku, Shinjuku-ku, Tokyo 160, Japan) V.1- 1959-
SEEIAY Seikatsu Eisei. Living and Health. (Osaka Seikatsu Eisei Kyokai, c/o Osaka-shiritsu Kankyo Kagaku Kenkyusho, 8-34 Tojo-cho, Tennoji-ku, Osaka, 543, Japan) V.1- 1957-
SSEIBV Sumitomo Sangyo Eisei. Sumitomo Industrial Health. (Sumitomo Byoin Sangyo Eisei Kenkyushitsu, 5-2-2, Nakanoshima, Kita-ku, Osaka 530, Japan) No.1- 1965-
TPKVAL Toksikologiya Novykh Promyshlennykh Khimicheskikh Veshchestv. Toxicology of New Industrial Chemical Substances. For English translation, see TNICS*. (Izdatel'stvo Meditsina, Moscow, USSR) No.1- 1961-

Used as solvent, also used in syntheses

NIOSH PROFILE (TETRAHYDROFURAN), SRI, 2/77

RTECS Compound Description:
   Tumorigen
   Mutagen
   Reproductive Effector
   Human Data

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