Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 109-99-9 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • Tetrahydrofuran
  • 1,4-EPOXYBUTANE

Human Toxicity Excerpts

  • ... SEVERE OCCIPITAL HEADACHE REPORTED IN INVESTIGATORS TESTING ITS PHARMACOLOGICAL PROPERTIES. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-408]**PEER REVIEWED**
  • Signs and symptoms accompanied by a marked decrease in the number of white blood cells were observed in researchers engaged in experimental spinning of synthetic fibers. These effects were suspected to be due to poisoning by tetrahydrofuran which was used as a solvent for polyvinyl chloride. ... [Hariguchi S; Sumitomo Bulletin of Industrial Health 17: 69-75 (1981)]**PEER REVIEWED**
  • Tetrahydrofuran can cause dermatitis on prolonged exposure. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1]**PEER REVIEWED**
  • Exposure to THF has been reported to be irritating to the skin, eyes, and mucous membranes; no specific concn for irritation has been described. Individuals exposed to high concn of THF have elevated circulating enzymes and have complained of nausea, tinnitus, and occipital headache. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1518]**PEER REVIEWED**
  • Liver biopsy confirmed fatty degeneration and siderosis along with elevated gamma glutamyl transferase and alanine aminotransferase occurred in one adult male occupationally exposed to THF. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1518]**PEER REVIEWED**
  • Case study:: A polyvinyl chloride pipe insulator ... /was exposed/ to THF ... /for/ 2 wks in a poorly ventilated, confined space. After hospitalization for acute appendicitis with enflurane anesthesia, the patient developed cerebral convulsions. ... /It was/ suggested that the interaction of the anesthetic & occupational exposure to THF may have contributed to the onset of the convulsions. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1518]**PEER REVIEWED**
  • Two cases of occupational exposure to THF were reported ... The symptoms included irritation of mucous membranes, nausea, headache, dizziness, and possible cytolytic hepatitis. The effects on mucous membranes and the central nervous system resolved within a few hours after cessation of exposure. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1518]**PEER REVIEWED**
  • This study /was conducted/ in a video tape manufacturing facility in Singapore where workers were exposed to mixed solvents consisting of methyl ethyl ketone (MEK), cyclohexanone (CHE), tetrahydrofuran (THF), and toluene (TOL). The objectives were to quantify workers' exposure to the various solvents and to evaluate if there were any neurobehavioral changes among workers compared to controls. Nineteen exposed workers out of a workforce of 45 were studied. Twenty six workers (with no exposure) matched for ethnic group, age, years of education served as controls. Eight hr personal environmental samples were analyzed for the 19 workers along with symptom questionnaires, clinical exam, and neurobehavioral tests including the Santa Ana Dexterity, Finger Tapping, Digit Span, and Visual Reproduction tests. The mean TWA concn /for the cmpds/ were all below the threshold limit values (TLVs). However, the total solvents concn index exceeded unity in one of the work areas. Significant differences were /noted/ for prevalence of headache, and eye and nose irritation among the exposed workers. There were also significant differences for the Santa Ana test for both hands, Digit Span test and Visual Reproduction test. ... No dose effect relation between behavioral scores and airborne solvent exposure was noted. ... [Chia Se et al; Neurotoxicol 14 (1): 51-6 (1993)]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • A single 4 hr inhalation of THF in rabbits in the range of 100 to 12,000 ppm resulted in a transient dose related decrease of tracheal ciliary activity. Single or repeated exposures have been associated with cytolytic hepatitis and fatty degeneration of the liver. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1517]**PEER REVIEWED**
  • ... Concentrations of THF >25,000 ppm were required to produce anesthesia. The anesthetic properties were rather poor in that onset was delayed & recovery poor; this was accompanied by pronounced hypotension & marked respiratory hyperpnea. There was a narrow margin of safety between anesthesia & death in dogs & mice. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1517]**PEER REVIEWED**
  • ... When dogs inhaled 200 ppm THF 6 hr/day for 3 to 4 weeks, an observable effect on pulse pressure was recorded; however, no demonstrable histopathologic changes were found despite extended exposure of 9 weeks, followed by an additional 3 week exposure at up to 400 ppm. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1517]**PEER REVIEWED**
  • ACUTE ORAL ADMIN /OF TETRAHYDROFURAN TO CATS/ WAS FOUND ... TO CAUSE INFLAMMATION, NECROSIS & HEMORRHAGE OF GASTROINTESTINAL TRACT. KIDNEYS SHOWED INJURY TO TUBULES. ... INFLAMMATION /OF LIVER/ & CONGESTION & EDEMA /OF LUNGS, WERE OBSERVED/. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 701]**PEER REVIEWED**
  • THF was irritating to rabbits when applied topically in aq soln exceeding 20% concn. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1517]**PEER REVIEWED**
  • Male rats that inhaled more than 5000 ppm THF for 12 weeks at 4 hr/day showed signs of systemic intoxication, skin and respiratory tract irritation, liver function disturbance, and abnormalities in glucose metabolism. Although systemic effects were not observed after similar exposures at lower concn, slight respiratory tract irritation occurred in some rats that inhaled concn less than 200 ppm. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1517]**PEER REVIEWED**
  • CNS DEPRESSANT: ... DOSE /OF TETRAHYDROFURAN/. BY INHALATION, FOR MICE, 6.7 VOL % IN 5 MIN; 1.1 VOL % IN 43 MIN; FOR DOGS, 5.6 VOL % (OXYGEN MIXT) FOR 2 HR. [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 701]**PEER REVIEWED**
  • RABBITS EXPOSED TO TETRAHYDROFURAN (THF) @ 12,000 PPM FOR 4 HR HAD PARALYSIS OF THE NASAL CILIARY FUNCTION DUE TO THE ABSENCE OF CILIARY BEATING, WHILE MORPHOLOGICAL DAMAGE OF CILIATED CELLS WAS NOT SO SEVERE. MODERATE DESTRUCTIVE CASES, PARTIAL DESTRUCTION OF THE OUTER CELLULAR MEMBRANE WAS RECOGNIZED. THE FALLING OFF OR ABSENCE OF CILIATED CELLS WAS NEVER OBSERVED. [OHASHI Y ET AL; SUMITOMO SANGYO EISEI 18: 89-93 (1982)]**PEER REVIEWED**
  • RATS WERE EXPOSED TO TETRAHYDROFURAN AT 200 OR 1000 PPM, 4 HR/WK FROM 12 TO 24 WK OF AGE. THE LOWER CONCN CAUSED SLIGHT DAMAGE WHEREAS THE HIGHER CONCN CAUSED SEVERE DAMAGE TO THE NASAL & TRACHEAL EPITHELIUM. THE DEGREE INCL DECR NUMBER OF CILIA, VACUOLIZATION & INCR DENSE GRANULES OF THE CYTOPLASM. [HORIGUCHI S ET AL; SEIKATSU EISEI 25 (4): 176-7 (1981)]**PEER REVIEWED**
  • 2.2 vol % Tetrahydrofuran killed 50% of exposed mice in less than 2 hr. Anesthesia was marked by prolonged induction, profuse salivation, poor muscular relaxation, fall in blood pressure, respiratory stimulation, and a narrow margin of safety. [Gosselin RE et al; Chemical Hazards of the Workplace p.471 (1978)]**PEER REVIEWED**
  • Tetrahydrofuran tested negative for sex-linked recessive lethal heritable genetic effects in Drosophila in FY 1983. /No additional data given/ [NTP; Fiscal Year 1984 Annual Plan p.82 (1984) NTP-84-023]**PEER REVIEWED**
  • In test results for cytogenetic effects in Chinese hamster ovary cells, tetrahydrofuran tested positive for chromosomal aberrations and negative for sister chromatid exchanges. /No additional data given/ [NTP; Fiscal Year 1984 Annual Plan p.75 (1984) NTP-84-023]**PEER REVIEWED**
  • Oral lethal dose of a 20% solution in rabbits 2.5 g/kg. ... A vapor concn of 2.2 vol % killed 50% of exposed mice in less than 2 hr. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-408]**PEER REVIEWED**
  • Tetrahydrofuran (THF) was tested for mutagenicity in the Salmonella/microsome preincubation assay using the standard protocol approved by the National Toxicology Program. THF was tested at doses of 0.1, 0.33, 1.0, 3.3, and 10 mg/plate in as many as 5 Salmonella typhimurium strains (TA1535, TA1537, TA97, TA98, and TA100) in the presence and absence of rat or hamster liver S-9. Tetrahydrofuran was negative in these tests and the highest ineffective dose tested in any Salmonella typhimurium strain was 10 mg/plate. [Mortelmans K et al; Environ Mutagen 8: 1-119 (1986)]**PEER REVIEWED**
  • Rats were exposed to 100, 200, 1000 or 5000 ppm tetrahydrofuran for 4 hr/day for 12 weeks. 100 and 200 ppm had no significant effects except for slight mucosal irritation. 1000 ppm affected liver function as indicated by serum chemistry tests. 5000 ppm caused marked local irritant symptoms and morphological damage of the respiratory mucosae, and affected white blood cell counts, blood sugar levels and liver functions. [Katahira T et al; Japanese Journal of Industrial Health 24 (4): 379-87 (1982)]**PEER REVIEWED**
  • The LD50 of tetrahydrofuran dissolved in olive oil was approximately 2500 mg/kg in mice and dissolved in saline was 1900 and 2900 mg/kg in mice and rats, respectively. The median lethal concentration was approximately 21000 ppm in rats when tetrahydrofuran was inhaled for 3 hr. Rats exposed to 100-200 ppm of tetrahydrofuran showed no significant effects, except for slight local irritant symptoms such as redness of the nose and eyelids. Almost all rats exposed to > 5000 ppm of tetrahydrofuran displayed marked local irritant symptoms, such as edema or opacity of the cornea, salivation, and discharge or bleeding in nasal mucosa. A cataleptoid posture, coma, and clonic muscle spasms indicating irritant symptoms of the central nervous system were also observed. [Katahira T et al; Sangyo Igaku 24 (4): 373-8 (1982)]**PEER REVIEWED**
  • Muscle acetylcholinesterase activity increased in a concentration dependent manner in male rats that inhaled 200, 1000, or 2000 ppm for 18 weeks at 6 hr/day. THF concentrations in brain and peripheral fat appeared to decrease after 2 weeks. At 200 ppm, hepatic protein and mixed function oxidase activity were increased. At 2000 ppm, liver function was inhibited. Increased skeletal muscle succinate dehydrogenase activity was noted. In a 13 week study inhalation study, ataxia was reported in rats at 5000 ppm and ... /CNS depression/ was reported in mice at 1800 ppm. Hepatocytomegaly developed in mice of both sexes at 5000 ppm; uterine atrophy and degeneration of the adrenal cortex occurred in the female mice. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1517]**PEER REVIEWED**
  • High concn (1x10-2 M) of THF inhibited the in vitro activity of rat hepatic cytochrome p-450 by 80%. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1518]**PEER REVIEWED**
  • Sensory irritation in mice exposed to chemical emissions was investigated using a modification of an ASTM standard protocol. Samples of carpet, ceiling tile, wallcovering, resilient flooring, and veneer were tested as typical indoor products. Sensory irritation during head only animal exposure was assessed by monitoring changes in respiratory frequency and waveform when test products were continuously ventilated at either 23 or 70 deg C. Animals /were exposed/ to 1 hr exposures to product emissions, corresponding to 1, 4, 24 and 27 elapsed hr of product exposure. Sensory irritation was generally not observed when products were tested at 23 deg C, but could be induced during at least one exposure period from all products except the carpet sample at 70 deg C. Although the total volatile organic cmpd emissions from a given product tested at elevated temperature incr between 5 and 30 fold from the emissions at ambient temperature, gas chemicals showed differences in the relative chemical compositions of the test atmospheres. ... Incr the temperature to 70 deg C may incr the total chemical concn of product emissions, it may not produce a chemical exposure comparable to that at ambient conditions. Since most human exposure to product emissions occurs at ambient conditions, the significance of irritation at elevated temperatures is ... questionable. [Muller WJ, Black MS; Amer Indust Hyg Assoc J 56 (8): 794-803 (1995)]**PEER REVIEWED**
  • Sprague-Dawley rats and Swiss CD-1 mice were exposed to 0, 600, 1,800 or 5,000 ppm tetrahydrofuran ... vapors 6 hr/day, 7 days/wk (6-19 days of gestation) for rats; 6-17 days of gestation for mice). Body weights of pregnant rats in the 5,000 ppm group were reduced at /sacrifice/. There were no effects on the percentage of live rat fetuses/litter or on the fetal sex ratio. Fetal body weight was significantly reduced in the 5,000 ppm group, but the incidence of abnormalities was not incr. Mice in the 1,800 ppm and 5,000 ppm group were sedated during exposure; approx 27% of the mice in the 5,000 ppm group died. Mean body and uterine weights of mice were reduced for the 1,800 and 5,000 ppm groups at /sacrifice/ (18 days of gestation), but adjusted maternal weight gain was not affected at 1,800 ppm. There was a reduction in the percentage of live fetuses/litter for the mice in the 1,800 and 5,000 ppm groups (95% resorptions in the 5,000 ppm group). Fetal weight and sex ratio in mice were not affected. An incr in the incidence of reduced sternebral ossifications was correlated to tetrahydrofuran concn, although differences between groups were not statistically significant. There were no incr in the incidences of any other malformations or variations. These results suggest that tetrahydrofuran may be embryotoxic in mice, but if the conceptus survives, development as assessed by this experimental design continues in a normal fashion. The no observable adverse effect level (NOAEL) for maternal toxicity was 1,800 ppm in both rats and mice. The NOAEL for developmental toxicity was 1,800 ppm in rats and 600 ppm in mice. [Mast TJ et al; Fundam Appl Toxicol 18 (2): 255-65 (1992)]**PEER REVIEWED**
  • ... CONCLUSIONS: Under the conditions of these 2 yr inhalation studies, there was some evidence of carcinogenic activity of tetrahydrofuran in male F344/N rats based on incr incidences of renal tubule adenoma or carcinoma (combined). There was no evidence of carcinogenic activity of tetrahydrofuran in female F344/N rats exposed to 200, 600 or 1,800 ppm or male B6C3F1 mice exposed to 200, 600 or 1,800 ppm. There was clear evidence of carcinogenic activity of tetrahydrofuran in female B6C3F1 mice based on incr incidences of hepatocellular neoplasms. [Toxicology & Carcinogenesis Studies of Tetrahydrofuran in F344/N Rats and B6C3F1 Mice p.6 Technical Report Series No. 475 (1998) NIH Publication No. 98-3965 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • Toxicity threshold (cell multiplication inhibition test) Pseudomonas putida (bacteria) 580 mg/l [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 1087]**PEER REVIEWED**
  • LD50 Mouse inhalation 6.7%/30 min [Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 701]**PEER REVIEWED**
  • LC50 Rat inhalation 80,975 ppm/1 hr [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 1088]**PEER REVIEWED**
  • LC50 Rat inhalation 62,000 ppm/2 hr [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 1088]**PEER REVIEWED**
  • LC50 Rat inhalation 18,000-22,000 ppm/4 hr [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 1088]**PEER REVIEWED**
  • LC50 Rat inhalation 21,000 ppm/3 hr [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 3108]**PEER REVIEWED**
  • Growth inhibition Microcystis (blue green algae) 225 mg/l (pH 7.0) [Bringmann G; Vom Wasser 50: 145-60 (1975)]**PEER REVIEWED**
  • Toxicity threshold (cell multiplication inhibition test) Uronema parduczi Chatton-Lwoff (protozoa) 858 mg/l [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 1087]**PEER REVIEWED**
  • Toxicity threshold (cell multiplication inhibition test) Microcystis aeruginosa (algae) 225 mg/l [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 1088]**PEER REVIEWED**
  • LD50 Rat oral 3.2 ml/kg, older rats [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1517]**PEER REVIEWED**
  • LD50 Rat oral 2.3 ml/kg, 14 day old males [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1517]**PEER REVIEWED**
  • LD50 Rat oral 3.6 ml/kg, young adults [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1517]**PEER REVIEWED**
  • LD50 Rat oral 1650 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 3108]**PEER REVIEWED**
  • LD50 Rat ip 2900 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 3108]**PEER REVIEWED**
  • LD50 Mouse ip 1900 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 3108]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • EXCRETION OF TETRAHYDROFURAN IN MOTHER'S MILK REPORTED IN 1 OF 12 SAMPLES COLLECTED IN 4 URBAN AREAS IN NEW JERSEY, PENNSYLVANIA, AND LOUISIANA. [PELLIZZARI ED ET AL; BULL ENVIRONM CONTAM TOXICOL 28: 322-8 (1982)]**PEER REVIEWED**
  • Adult male rats exposed to tetrahydrofuran vapor at 8.2 (200 ppm), 41 (1,000 ppm) or 82 mumol/l (2,000 ppm) for 2 to 18 weeks, five days a week, 6 hrs daily, showed dose-dependent brain and perirenal fat solvent burden linearly correlated to each other. After two weeks of exposure, the body burden of tetrahydrofuran seems to decrease. This might have been caused by increased oxidative metabolism as enhanced 7-ethoxycoumarin-O-deethylase activity was detected in liver and kidneys in the second week and onwards. The exposure also caused inhibition of alcohol and formaldehyde dehydrogenase activities in liver at the highest dose. Biochemical effects in the cerebellum were not detected, while gluteal muscle specimens showed increased succinate dehydrogenase activity in a dose-related manner. This points to effects on the energy metabolism. Muscle acetylcholine esterase activity was also increased showing possible effects on the myoneural junctions. [Elovaara E et al; Acta Pharmacol Toxicol 54 (3): 221-6 (1984)]**PEER REVIEWED**
  • When healthy volunteers were exposed at 100 or 400 ppm THF in air, the percentage of expired THF was 35% in males with normal breathing, 25% in males with deep breathing, and 19% in females with deep breathing. Three hour exposures at 50 ppm THF resulted in 40% expiration of THF in males with normal breathing and 27% in males with deep breathing. The elimination half life of THF was 30 minutes. In subjects exposed at 50 ppm THF in air for 6 hours, traces of THF were present at 3 hours after the end of exposure. In individuals exposed at 200 ppm THF for 3 hours, THF blood concn were higher at 1 hour after the end of exposure than immediately after cessation of exposure. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1518]**PEER REVIEWED**

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Metabolism/Metabolites

  • In vitro studies indicated that THF was first hydroxylated by the microsomal enzymes and further cleaved to the straight chain fatty acid in the presence of cytosol. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1518]**PEER REVIEWED**

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TSCA Test Submissions

  • Tetrahydrofuran (CAS# 109-99-9) was evaluated for the effect on cell proliferation. F344/N rats and B6C3F1 mice were exposed to tetrahydrofuran at concentrations of 0, 200, 600, and 1800 ppm in a 13-week inhalation toxicity study sponsored by NTP (NTP TR475). The kidneys of male rats and the livers of female mice (10/species/exposure group) were embedded in paraplast, then processed and stained for the Proliferating Cell Nuclear Antigen (PCNA). There was a slight increase in PCNA in the liver of mice from the high dose group with a minimal decrease in the other groups. The rat kidneys showed a minimal decrease in all tubular compartments, being most pronounced in the low dose group. Because the study was based on a single time point observation and there was no clear increase in cell proliferation, no conclusions could be drawn concerning the tumorigenicity potential of tetrahydrofuran.[Tetrahydrofuran Task Force; Tetrahydrofuran (THF) Study on Cell Proliferation in F344/N Rats and B6C3F1 Mice; 8/31/98; EPA Doc No. 86-990000001; Fiche No. OTS0573851]**UNREVIEWED**
  • Tetrahydrofuran (CAS# 109-99-9) was evaluated for developmental toxicity. In part I of the experiment the test material was administered to 14, 7, 7, 7, and 7 CD rats by inhalation at exposure levels of 0, 200, 500, 2500, and 5000 ppm, respectively on gestational days 6-15. In part II, 29, 87, and 38 CD rats were administered the test material by inhalation at exposure levels of 0, 1000, and 5000 ppm, respectively from days 6-15 of gestation. In both parts I and II, no maternal deaths occurred but the 5000 ppm exposure induced significant decreases in feed consumption (p<0.05) and body weight gain (p<0.05) along with absence of response to noise stimulus during the exposure period, followed by lethargy and incoordination for 1 hour post-exposure. No toxic responses were observed at 200 or 500 ppm (part I). At 1000 ppm (part II) and 2500 ppm (part I) only a reduced response to a noise stimulus was observed in comparison to controls. The mean number of implantations per dam and the incidence of malformed fetuses were not exposure related (among part I or part II). At 5000 ppm, the fetal variations of reduced weight and less ossified sternae were significantly different (p<0.05) from controls (for both part I and part II). Embryotoxicity expressed as developmental delay occurred at 5000 ppm.[E I DuPont De Nemours & Co; Tetrahydrofuran (THF) Inhalation Effect on the Rat Conceptus; 1982; EPA Doc No. 86-940000744S; Fiche No. OTS0557154]**UNREVIEWED**
  • Tetrahydrofuran (CAS #109-99-9) was evaluated for subchronic toxicity in dogs (breed not specified). Four dogs were exposed (6 hrs./5 days/9 wks.) to the test material at 200 ppm (average weekly concentration) followed by 366 ppm (average weekly exposure) for 3 additional weeks at 6 hrs./5 days/week for a total of 12 weeks. Two of the four dogs were then exposed an additional two successive days to 2,100 ppm (approximate). Blood pressure measurements were taken morning and afternoon four weeks preceding exposure period (control period) and before and after daily exposures. A decrease in pulse pressure was noted in 3 dogs after 3 to 4 weeks' exposure at 200 ppm accompanied by a decrease in systolic pressure in 2 dogs (153-B & 153-C), while the third (153-A) experienced an increase in diastolic pressure. In general, two dogs (153-A & 153-D) showed an increase in diastolic and systolic pressure, dog# 153-B showed an increase in diastolic pressure, and dog# 153-C showed a steady drop in systolic and diastolic pressure. At 366 ppm, blood pressure was decreased in 3 of 4 dogs. When exposed to 2,100 ppm (dogs #153-A & 153-C), the diastolic, systolic, and pulse pressure dropped sharply on the second day. Dog #153-C showed a steady drop in hemoglobin count and a considerably higher than control level white blood count. There were no other significant gross or microscopic effects observed in the heart, lungs, spleen, pancreas, or kidney.[E I DuPont De Nemours & Co; Toxicity of Tetrahydrofuran; 1947; EPA Doc No. 86940000738S; Fiche No. OTS0557148]**UNREVIEWED**

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008