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TETRAHYDROFURAN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Tetrahydrofuran is a solvent for high polymers, especially polyvinyl chloride. It is a colorless, mobile, flammable liquid. Inhalation of high concentrations may cause a general anesthesia effect.

Specific Substances

    1) Tetrahydrofuran
    2) Diethylene oxide
    3) Tetramethylene oxide
    4) Cyclo-tetramethylene oxide
    5) 1,4-epoxy butane
    6) Butylene oxide
    7) Furanidine
    8) Hydrofuran
    9) Oxacyclopentane
    10) Oxolane
    11) THF
    12) CAS 109-99-9
    13) BUTYLENE OXIDE, STABILIZED
    14) OXOLONE
    15) TETRAHYDROFURANO (ITALIAN)
    1.2.1) MOLECULAR FORMULA
    1) C4-H8-O

Available Forms Sources

    A) FORMS
    1) Tetrahydrofuran is a colorless, mobile, flammable liquid with an ether-like odor (HSDB , 2000).
    B) USES
    1) Tetrahydrofuran is used as a solvent for high polymers, such as polyvinyl chloride and in histological techniques. It is a solvent for resins, adhesives and manufacture of lacquers. It may be used in packaging or storage containers for food in concentrations of less than 1.5% (HSDB , 2000).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) INGESTION - Tetrahydrofuran may cause nausea, dizziness, headache, and CNS depression.
    B) INHALATION - Vapors may be a respiratory tract irritant, or produce nausea, dizziness, and CNS depression with general anesthesia.
    C) OCULAR - Tetrahydrofuran is an eye irritant.
    D) DERMAL - Tetrahydrofuran will cause burning and dermatitis on prolonged skin exposure.
    0.2.4) HEENT
    A) Profuse salivation and irritation of eyes and mucous membranes may be noted.
    0.2.5) CARDIOVASCULAR
    A) Hypotension may be noted.
    0.2.6) RESPIRATORY
    A) Upper respiratory irritation or stimulation may be noted.
    0.2.7) NEUROLOGIC
    A) Occipital headache and dizziness are common. Anesthesia lasting 6 to 8 hours may occur with inhalation of high concentrations.
    0.2.8) GASTROINTESTINAL
    A) Nausea and gastrointestinal irritation may be noted.
    0.2.9) HEPATIC
    A) Liver damage may result following tetrahydrofuran exposures.
    0.2.14) DERMATOLOGIC
    A) Tetrahydrofuran is irritating in concentrations of 20% or greater.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no studies were found on the potential reproductive effects of THF in humans.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no studies were found on the carcinogenic potential of THF in humans.

Laboratory Monitoring

    A) Monitor hepatic and renal function.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    B) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    D) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    E) Treatment of CNS depression is symptomatic.
    F) Monitor renal and hepatic function.
    G) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) 25,000 ppm will produce anesthesia in humans.

Clinical Effects

Summary Of Exposure

    A) INGESTION - Tetrahydrofuran may cause nausea, dizziness, headache, and CNS depression.
    B) INHALATION - Vapors may be a respiratory tract irritant, or produce nausea, dizziness, and CNS depression with general anesthesia.
    C) OCULAR - Tetrahydrofuran is an eye irritant.
    D) DERMAL - Tetrahydrofuran will cause burning and dermatitis on prolonged skin exposure.

Heent

    3.4.1) SUMMARY
    A) Profuse salivation and irritation of eyes and mucous membranes may be noted.
    3.4.3) EYES
    A) CONJUNCTIVITIS and irritation of eyes and mucous membranes may occur (NIOSH, 1990; (Hathaway et al, 1996).

Cardiovascular

    3.5.1) SUMMARY
    A) Hypotension may be noted.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) Hypotension may occur in substantial exposures.

Respiratory

    3.6.1) SUMMARY
    A) Upper respiratory irritation or stimulation may be noted.
    3.6.2) CLINICAL EFFECTS
    A) COUGH
    1) Cough and chest pain have been reported after inhalation exposures (Garnier et al, 1989).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPERVENTILATION
    a) Respiratory stimulation was observed in anesthetized animals (Stoughton & Robbins, 1936). Upper respiratory irritation occurred in animals exposed to 3000 ppm/day for 20 days.

Neurologic

    3.7.1) SUMMARY
    A) Occipital headache and dizziness are common. Anesthesia lasting 6 to 8 hours may occur with inhalation of high concentrations.
    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) Severe occipital headache and dizziness have occurred on exposure to vapors (Garnier et al, 1989).
    B) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Inhalation may cause a general systemic anesthesia effect in humans. High concentrations produce narcotic-like effects (Lewis, 1996).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) COMA
    a) High concentrations in animals (25,000 ppm) produced general anesthesia lasting 6 to 8 hours (Stoughton & Robbins, 1936). Onset of symptoms was gradual.

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea and gastrointestinal irritation may be noted.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA
    1) Nausea may occur on exposure to vapors. Gastrointestinal irritation may occur following ingestions (Garnier et al, 1989).
    B) EXCESSIVE SALIVATION
    1) Salivation may be noted.

Hepatic

    3.9.1) SUMMARY
    A) Liver damage may result following tetrahydrofuran exposures.
    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) Transaminase levels are often increased, as demonstrated by high AST, ALT, and GGT. Enzyme levels usually return to normal within 2 to 3 weeks (Garnier et al, 1989).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) Liver damage was observed in experimental animals exposed to 3000 ppm for 20 days (ACGIH, 1986) NIOSH, 1990; (Hathaway et al, 1996). It is believed to be related to impurities.
    b) FURAN TREATED RATS - Fourteen rats were exposed to furan at 60 mg/kg/day for 10 to 14 days by gavage. Only four rats survived the hepatotoxic furan treatment; post mortem examination following lethal injection revealed severe liver lobe atrophy marked by replacement in each case with hyperplastic bile ductular structures supported by fibrotic stroma. Histopathology of sections of the liver lobes revealed cholangiolarlike structures composed of biliary epithelial cells and containing one ductular hepatocytic cell in various stages of maturation (Sirica et al, 1994).

Genitourinary

    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RENAL FUNCTION ABNORMAL
    a) Kidney damage was observed in experimental animals exposed to 3000 ppm for 20 days (ACGIH, 1986) NIOSH, 1990; (Hathaway et al, 1996). It is believed to be related to impurities.

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) LEUKOPENIA
    1) Clinical symptoms were accompanied by a marked decrease in the number of white blood cells in chronic occupational exposures (HSDB , 2000).

Dermatologic

    3.14.1) SUMMARY
    A) Tetrahydrofuran is irritating in concentrations of 20% or greater.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Tetrahydrofuran is an irritant in concentrations greater than 20%.
    B) DERMATITIS
    1) This compound will cause burning and dermatitis on prolonged exposure to the skin (AAR, 1987; (HSDB , 2000).

Musculoskeletal

    3.15.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPERTONIA
    a) Muscle rigidity was noted in anesthetized animals.

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no studies were found on the potential reproductive effects of THF in humans.
    3.20.2) TERATOGENICITY
    A) HUMANS
    1) PLACENTAL BARRIER
    a) Furan congeners have been found to cross the placental barrier and have been measured in the adipose tissue of infants. It is speculated that this is related to the fatty acid transport (Koppe et al, 1992). Long-term effects on the fetus are not known.
    B) ANIMAL STUDIES
    1) THF was considered possibly embryotoxic but NOT teratogenic in a study by Mast et al (1992). The daily inhalational exposure (gestational days 6 to 19) of pregnant mice to 5000 ppm THF resulted in dose-related increase in reduced sternebral ossifications.
    3.20.3) EFFECTS IN PREGNANCY
    A) HUMANS
    1) PLACENTAL BARRIER
    a) In one woman the concentration of furans in the placenta was related to her blood concentrations (Koppe et al, 1992).
    B) ANIMAL STUDIES
    1) Daily inhalational exposure (gestational days 6 to 19) of pregnant mice to 5000 ppm THF resulted in reduced maternal and fetal body weights, but no effects on the percentage of live births. Resorptions occurred to the extent of 95% and there was a nonsignificant but dose-related increase in reduced sternebral ossifications (Mast et al, 1992).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS109-99-9 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no studies were found on the carcinogenic potential of THF in humans.
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) THF was not carcinogenic when applied to the skin of mice (HSDB), but did enhance the tumorigenicity of benzo(a)pyrene metabolites on mouse skin (Slaga, 1978).
    2) Furans may be liver carcinogens in animals (Sirica et al, 1994).

Genotoxicity

    A) THF caused DNA damage in mammalian cells (HSDB , 2000). It was mutagenic in E. coli (RTECS , 2000), but not in the Ames Salmonella/microsome assay (HSDB , 2000). It did not increase DNA repair in human cells and was inactive for producing sex-linked recessive lethal mutations in fruit flies, sperm abnormalities in mice, and dominant lethal mutations in male rats (McGregor, 1981). It strongly enhanced the mutagenicity of pyrolysis products of tryptophane in Salmonella (Arimoto, 1982).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor hepatic and renal function.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor renal and hepatic function, especially AST, ALT, and GGT.
    4.1.3) URINE
    A) URINARY LEVELS
    1) One study found a correlation between uncorrected urinary THF and measured environmental THF to be 0.86. However, when urine values were corrected for creatinine content, the correlation fell to 0.56. This may be a promising method to develop for routine monitoring of THF exposure (Ong et al, 1991).

Methods

    A) CHROMATOGRAPHY
    1) Head space gas chromatography with an FID detector has been used for quantitation of THF in air, urine, and blood (Ong et al, 1991).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor hepatic and renal function.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED
    1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression.
    B) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    C) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    C) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment of CNS depression is symptomatic.
    B) MONITORING OF PATIENT
    1) Monitor renal and hepatic function, especially AST, ALT, and GGT.
    C) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

Summary

    A) 25,000 ppm will produce anesthesia in humans.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) 3000 parts per million - chronic exposure results in respiratory irritation.
    2) 17,000 parts per million - is safe for 3 hours.
    3) 25,000 parts per million - results in anesthesia (TCLo in humans) (RTECS , 2000).

Workplace Standards

    A) ACGIH TLV Values for CAS109-99-9 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Tetrahydrofuran
    a) TLV:
    1) TLV-TWA: 50 ppm
    2) TLV-STEL: 100 ppm
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A3
    2) Codes: Skin
    3) Definitions:
    a) A3: Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    b) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.
    c) TLV Basis - Critical Effect(s): URT irr; CNS impar; kidney dam
    d) Molecular Weight: 72.1
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS109-99-9 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Tetrahydrofuran
    2) REL:
    a) TWA: 200 ppm (590 mg/m(3))
    b) STEL: 250 ppm (735 mg/m(3))
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 2000 ppm
    b) Note(s): [10%LEL]
    1) [10%LEL]: The 10%LEL designation is provided where the IDLH was based on 10% of the lower explosive limit. This is used for safety purposes in some cases even though toxicity is not indicative of irreversible health effects or impairment of escape exists only at higher concentrations.

    C) Carcinogenicity Ratings for CAS109-99-9 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: Tetrahydrofuran
    a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Tetrahydrofuran
    5) MAK (DFG, 2002): Category 3B ; Listed as: Tetrahydrofuran
    a) Category 3B : Substances for which in vitro or animal studies have yielded evidence of carcinogenic effects that is not sufficient for classification of the substance in one of the other categories. Further studies are required before a final decision can be made. A MAK value can be established provided no genotoxic effects have been detected. (Footnote: In the past, when a substance was classified as Category 3 it was given a MAK value provided that it had no detectable genotoxic effects. When all such substances have been examined for whether or not they may be classified in Category 4, this sentence may be omitted.)
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS109-99-9 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Tetrahydrofuran
    2) Table Z-1 for Tetrahydrofuran:
    a) 8-hour TWA:
    1) ppm: 200
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 590
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) Reference: RTECS, 2000
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 1900 mg/kg
    2) LD50- (INTRAPERITONEAL)RAT:
    a) 2900 mg/kg
    3) LD50- (ORAL)RAT:
    a) 1650 mg/kg
    4) TCLo- (INHALATION)HUMAN:
    a) 25,000 ppm

Pharmacology Toxicology

Toxicologic Mechanism

    A) Tetrahydrofuran is a cyclic ether, structurally related to diethyl ether and cyclopropane.

Physicochemical

Physical Characteristics

    A) Tetrahydrofuran is a colorless, mobile liquid with an ether-like or faint odor (Lewis, 1996; ACGIH, 1986) NIOSH, 1985).

Molecular Weight

    A) 72.10 (Budavari, 1996)

Other

    A) ODOR THRESHOLD
    1) 20-50 ppm (CHRIS , 2002)

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