Enflurane

184.49

184.49

1737129

237-553-4

0887

115944

DTXSID1020562

Clear, colorless liquid|Stable, volatile, non-flammable liquid

N - Nervous system

2909199090

9.2

2.1

1.52 g/cm³

48.5

56.5 °C

56-57°C

1.303

Low

Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Store under inert gas. hygroscopic Recommended storage temperature: -20 deg C

Vapour pressure, kPa at 20°C: 23.3

Relative vapour density (air = 1): 1.9

Noncombustible Liquid

TLVWA 570 mg/m3 (75 ppm) (ACGIH).

Mild, sweet odor

1.19e-14 cm3/molecule*sec

Henry's Law constant = 7.54X10-3 cu m-atm/mol at 25 °C (est)

Conversion: 1 ppm = 7.75 mg/cu m|Hydroxyl radical reaction rate constant = 1.2X10-14 cu cm/molec-sec at 298 K|Oxygen Depletion Potential: 0.0096 (est)|Global Warming Potential: 1791 for a 20 year horizon; 462 for a 100 year horizon (relative to CO2) (est)

No rapid reaction with air No rapid reaction with water

Ethers

The material ENFLURANE is incompatible with the following oxidizing materials, peroxides, combustible materials. Although nonflammable, a fire may cause enflurane to decompose to toxic compounds including phosgene, hydrogen chloride, and hydrogen fluoride. Decomposes slowly in the light.

Noncombustible Liquid

The vapour is heavier than air and may accumulate in lowered spaces causing a deficiency of oxygen.

UN 3334

36

23-26-36-39

KN6800000

F,T,Xi

Keep in a well-ventilated room.

Flammable/Toxic

P305 + P351 + P338

H319

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

Volatile with anesthetic properties, but non-flammable.

Diagnostic Devices. Enflurane gas analyzer. An enflurane gas analyzer is a device intended to measure the concentration of enflurane anesthetic in a gas mixture.

Not combustible. Gives off irritating or toxic fumes (or gases) in a fire.

|Warning|H315 (54.74%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 95 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H316: Causes mild skin irritation [Warning Skin corrosion/irritation]|P201, P202, P260, P261, P264, P270, P271, P280, P281, P304+P340, P305+P351+P338, P308+P313, P309+P311, P312, P314, P332+P313, P337+P313, P403+P233, P405, and P501

Skin: No recommendation is made specifying the need for personal protective equipment for the body. Eyes: Wear appropriate eye protection to prevent eye contact. Wash skin: No recommendation is made specifying the need for washing the substance from the skin (either immediately or at the end of the work shift). Remove: No recommendation is made specifying the need for removing clothing that becomes wet or contaminated. Change: No recommendation is made specifying the need for the worker to change clothing after the work shift. (NIOSH, 2016)|Respiratory protection not required. For nuisance exposures use type OV/AG (US) or type ABEK (EU EN 14387) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|Wear appropriate eye protection to prevent eye contact.|(See protection codes)

Explosive limits , vol% in air: 4.25-?

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special protective equipment for fire-fighters: Wear self contained breathing apparatus for fire fighting if necessary.

Personal precaution:s Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Keep in suitable, closed containers for disposal.

Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

An eye irritant.

Recommended Exposure Limit: 60 Minute Ceiling Value: 2 ppm (15.1 mg/cu m). (REL for exposure to waste anesthetic gas.)

Ventilation. Collect leaking and spilled liquid in sealable containers as far as possible. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations. Personal protection: self-contained breathing apparatus.

Keep in a well-ventilated room.

A harmful contamination of the air can be reached rather quickly on evaporation of this substance at 20 °C.

The substance is irritating to the eyes, skin and respiratory tract. The substance may cause effects on the central nervous system and cardiovascular system. Exposure at high levels could cause unconsciousness.

Use ventilation, local exhaust or breathing protection.

Protective gloves.

Wear safety spectacles or eye protection in combination with breathing protection.

The LD50 of enflurane in rats is 14000 ppm/3 hour(s) when inhaled. There is limited information in the literature about enflurane overdose. Hepatotoxicity, cardiotoxicity, nephrotoxicity, and neurotoxicity are expected. One report in the literature of an enflurane overdose describes an accidental fatal overdose in a 21-year-old male. About 72 hours after death, high amounts of enflurane were found in the brain, blood, and subcutaneous fat. Gas chromatographic studies revealed enflurane concentrations of 350 mg/l-1 in the brain, 130 mg/l-1 in the blood, and 100 mg/l-1 in the subcutaneous fat. In the event of an enflurane overdose, immediately stop the administration of enflurane, establish a patent airway, and administer pure oxygen by assisted or controlled ventilation.

Prospective, serial blood testing often demonstrates minor transient elevations in serum aminotransferase levels in the 1 to 2 weeks after major surgery and anesthesia. Appearance of ALT levels above 10 times the upper limit of normal, however, is distinctly unusual and points to significant hepatotoxicity. Clinically apparent, severe hepatic injury from enflurane has been reported but is very rare. The injury resembles halothane hepatotoxicity and is marked by acute elevations in serum aminotransferase levels (5- to 50-fold) and appearance of jaundice 2 to 21 days after surgery and anesthesia. There are usually minimal increases in alkaline phosphatase and gammaglutamyl transpeptidase levels. The liver injury is often preceded by a day or two of fever and may be accompanied by rash and eosinophilia. The acute liver injury may be self-limited and resolve within 4 to 8 weeks, but can be severe and associated with acute liver failure. A strong risk factor is previous exposure to any of the halogenated anesthetics and particularly a history of halothane hepatitis or unexplained fever and rash after anesthesia with one of these agents.

... Twenty-four, one-year-old male, Fischer 344 rats were assigned randomly to four anesthetic exposure groups. Groups 1 and 2 were controls exposed only to halothane and enflurane, respectively. Group 3 was exposed for 1 hr to 0.3% halothane, followed by 2 hr of 1% enflurane. Group 4 was exposed for 1 hr to 1% halothane and then to 2 hr of 1% enflurane. Blood samples were taken prior to, immediately following, and 1, 24, and 48 hr after anesthetic exposure. Serum was assayed for inorganic fluoride (F-), SGOT and SGPT. Twenty-four-hour urinary collections were assayed for F excretion. Group 1 rats exposed to halothane alone had the lowest peak mean serum F- (5.0 uM). Group 2 rats exposed to enflurane alone had the highest serum F concentration 4 hr after anesthesia (18.7 uM). Peak serum F in Group 3 rats (9.5 uM) was significantly lower than in Group 2 rats (enflurane control). In Group 4 rats, serum F- was not significantly different from Group 1 rats (halothane control) at any time. In the first 24 hr after anesthetic exposure, urinary F- excretion in Groups 2 and 3 was significantly higher than in Groups 1 and 4. This study demonstrated that prior exposure to halothane reduced the metabolism of enflurane; previous work suggested that this was due to an interaction of halothane with hepatic cytochrome P-450.|... The influence of ethanol and ... /6 hours a day, 5 days a week exposure/ to subanesthetic and anesthetic concentrations of enflurane on liver function in BALB/c mice /was examined/. ... Animals were divided in six groups of twenty. The ethanol treated group was injected with ethanol ip (1 g/kg). Two enflurane treated groups were ip injected with a 0.9 % solution of sodium chloride (10 mL/kg) and one /was also/ exposed to subanesthetic (0.5 vol%) and the other one to anesthetic (2.75 vol%) concentrations of enflurane. ... /Two additional/ groups received ethanol (1 g/kg) and each of them inhaled enflurane at previously mentioned doses. The control group was ip injected with a 0.9 % solution of sodium chloride (10 mL/kg) and did not receive any anesthetic. On the day following the last day of exposure half of the animals from each group were sacrificed for determination of glucose levels, erythrocyte glutathion levels, hematocrit, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), liver protein and glutathione levels, and total cytochrome P-450 (CYP P-450). The other half ... from each group were injected ip with caffeine (20 mg/kg). ... Two caffeine metabolic ratios - 1,3-dimethyl uric acid and 3,7-xanthine ... and 3,7-dimethyl xanthine + 7-xanthine and 1-xanthine + 1,7-dimethyl uric acid ... /were measured/. The difference in caffeine metabolite ratios suggests that enflurane changes oxidative metabolism in liver via certain subtypes of mixed function oxidase, probably via CYP-4502E1. This effect is more expressed when ethanol and enflurane are applied together. Ethanol is well known inductor of CYP-4502E1 and the registrated enzyme induction could be explained by both influences - of ethanol and enflurane.|This investigation tested the hypothesis that P450 2E1 is ... the isoform responsible for human enflurane metabolism in vivo. Disulfiram, which is converted in vivo to a selective inhibitor of P450 2E1, was used as a metabolic probe for P450 2E1. ... Twenty patients undergoing elective surgery were randomized to receive disulfiram (500 mg orally; n = 10) or nothing (control subjects; n = 10) the evening before surgery. All patients received a standard anesthetic of enflurane (2.2% end-tidal) in oxygen for 3 hours. Blood enflurane concentrations were measured by gas chromatography. Plasma and urine fluoride concentrations were quantitated by ion-selective electrode. ... Patient groups were similar with respect to age, weight, gender, duration of surgery, and blood loss. Total enflurane dose, measured by cumulative end-tidal enflurane concentrations (3.9 to 4.1 MAC-hr) and by blood enflurane concentrations, was similar in both groups. Plasma fluoride concentrations increased from 3.6 +/- 1.5 umol/L (baseline) to 24.3 +/- 3.8 umol/L (peak) in untreated patients (mean +/- SE). Disulfiram treatment completely abolished the rise in plasma fluoride concentration. Urine fluoride excretion was similarly significantly diminished in disulfiram-treated patients. Fluoride excretion in disulfiram-treated patients was 62 +/- 10 and 61 +/- 12 umol on days 1 and 2, respectively, compared with 1090 +/- 180 and 1200 +/- 220 umol in control subjects (p < 0.05 on each day). CONCLUSIONS: Disulfiram prevented fluoride ion production after enflurane anesthesia. These results suggest that P450 2E1 is the predominant P450 isoform responsible for human clinical enflurane metabolism in vivo.|Halogenated inhalation anesthetics interfere with each other's hepatic microsomal metabolism. The increase in plasma inorganic fluoride concentration, caused by the metabolism of a standardized dose of enflurane, was attenuated by isoflurane given either before or after the enflurane exposure...|For more Interactions (Complete) data for Enflurane (9 total), please visit the HSDB record page.

LD50 Rat oral 5450 mg/kg|LC50 Rat inhalation 14,000 ppm/ 3 hr|LD50 Rat intraperitoneal 6 g/kg|LD50 Rat subcutaneous 19,500 mg/kg|For more Non-Human Toxicity Values (Complete) data for Enflurane (8 total), please visit the HSDB record page.

The plasma protein binding for enflurane is 97%.

Enflurane's production and use as an anesthetic(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 100(SRC), determined from a log Kow of 2.10(2) and a regression-derived equation(3), indicates that enflurane is expected to have high mobility in soil(SRC). Volatilization of enflurane from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.5X10-3 atm-cu m/mole(SRC), derived from its vapor pressure, 174.5 mm Hg(4), and water solubility, 5.62X10+3 mg/L(5). Enflurane is expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Biodegradation data in soil were not available(SRC, 2011).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 100(SRC), determined from a log Kow of 2.10(2) and a regression-derived equation(3), indicates that enflurane is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(4) based upon an estimated Henry's Law constant of 7.5X10-3 atm-cu m/mole(SRC), derived from its vapor pressure, 174.5 mm Hg(5), and water solubility, 5.62X10+3 mg/L(6). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 4.1 hours and 5.4 days, respectively(SRC). According to a classification scheme(7), an estimated BCF of 11(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2011).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), enflurane, which has a vapor pressure of 174.5 mm Hg at 20 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase enflurane is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 3.7 years(SRC), calculated from its rate constant of 1.2X10-14 cu cm/molecule-sec at 25 °C(3). Enflurane's photochemical lifetime was calculated as 5,340 years(3); therefore, it is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of enflurane with photochemically-produced hydroxyl radicals has been measured as 1.2X10-14 cu cm/molecule-sec at 25 °C(1). This corresponds to an atmospheric half-life of about 3.7 years at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(2). Enflurane does not degrade in the presence of alkali or light(3). Enflurane had substantial UV absorption only below 250 nm; its photochemical lifetime (50 deg N latitude, equinox) was calculated as 5,340 years(1). Therefore, enflurane is not expected to be susceptible to direct photolysis by sunlight(SRC). An estimated Oxygen Depletion Potential of 0.0096 and estimated Global Warming Potentials 1791 for a 20 year horizon and 462 for a 100 year horizon (relative to CO2) have been reported(4).

An estimated BCF of 11 was calculated in fish for enflurane(SRC), using a log Kow of 2.10(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of enflurane is estimated as 100(SRC), using a log Kow of 2.10(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that enflurane is expected to have high mobility in soil.

The Henry's Law constant for enflurane is calculated as 7.5X10-3 atm-cu m/mole(SRC) derived from its vapor pressure, 174.5 mm Hg(1), and water solubility, 5.62X10+3 mg/L(2). This Henry's Law constant indicates that enflurane is expected to volatilize rapidly from water surfaces(3). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(3) is estimated as 4.1 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(3) is estimated as 5.4 days(SRC). Enflurane's calculated Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). The potential for volatilization of enflurane from dry soil surfaces may exist(SRC) based upon its vapor pressure(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 86,214 workers (73,440 of these were female) were potentially exposed to enflurane in the US(1). Occupational exposure to enflurane may occur through inhalation. Use data indicate that exposure among the general population may be limited to those administered enflurane as an anesthetic(SRC).

Enflurane may be used for both the induction and maintenance of general anesthesia. It can also be used to induce analgesia for vaginal delivery. Low concentrations of enflurane can also be used as an adjunct to general anesthetic drugs during delivery by Cesarean section.

Enfurane is a volatile anesthetic agent with an excellent safety record which was previously widely used, but has now been replaced by more modern volatile anesthetic agents. Case series and isolated case reports of severe acute liver injury similar to halothane hepatitis attributed to enflurane have been published, but are rare.

Anesthetics, Halogenated

Anesthetics, Inhalation|Enflurane may be used for induction and maintenance of general anesthesia. Enflurane may be used to provide analgesia for vaginal delivery. Low concentrations of enflurane (see DOSAGE AND ADMINISTRATION) may also be used to supplement other general anesthetic agents during delivery by Cesarean section. Higher concentrations of enflurane may produce uterine relaxation and an increase in uterine bleeding. /Included in US product label/

A patient developed fever and acute hepatitis shortly after enflurane anesthesia. Other causes of postoperative hepatitis were excluded. Cross-sensitization with halothane may have occurred, and the enflurane hepatitis may have been aggravated by halothane hepatitis.|A case of mild post operative jaundice and transient renal insufficiency associated with enflurane anesthesia ... was eventually treated vigorously and successfully. ... Although other types of viral hepatitis cannot be completely ruled out, the anesthesiologist should be aware of the potential hazard of hepatic and renal toxicity attributed to enflurane...|A case of succinylcholine and enflurane induced rhabdomyolysis and myoglobinuric acute renal failure in a mentally retarded patient is presented. The report illustrates some principles of management and the correlation of laboratory findings with the syndrome...|Enflurane, as well as other general anesthetics, may cause a slight decrease in intellectual function for 2 or 3 days following anesthesia. As with other anesthetics, small changes in moods and symptoms may persist for several days following administration.|For more Drug Warnings (Complete) data for Enflurane (9 total), please visit the HSDB record page.

Enflurane rapidly induces anesthesia via the stimulation of inhibitory neural channels and the inhibition of excitatory neural channels. Muscle relaxation, obtundation of pharyngeal and laryngeal reflexes, and lowering of blood pressure are some of the main pharmacodynamic effects of this drug. Enflurane also decreases cardiac muscle contractility. High concentrations of enflurane may lead to uterine relaxation and increase the risk of uterine bleeding during delivery. Rare but clinically significant elevations in ALT may indicate hepatoxicity from the use of enflurane. In some susceptible patients, enflurane may cause malignant hyperthermia.

Gases or volatile liquids that vary in the rate at which they induce anesthesia; potency; the degree of circulation, respiratory, or neuromuscular depression they produce; and analgesic effects. Inhalation anesthetics have advantages over intravenous agents in that the depth of anesthesia can be changed rapidly by altering the inhaled concentration. Because of their rapid elimination, any postoperative respiratory depression is of relatively short duration. (From AMA Drug Evaluations Annual, 1994, p173) (See all compounds classified as Anesthetics, Inhalation.)

Enflurane is rapidly absorbed into the circulation through the lungs. The minimum alveolar concentration is oxygen is 1.68%.|Metabolism accounts for 5-9% of enflurane elimination, sometimes causing nephrotoxicity. Excretion through the skin is believed to be minimal.|Enflurane distributes to the brain, blood, and subcutaneous fat.

Enflurane is metabolized by the CYP2E1 enzyme in the liver to produce inorganic fluoride ions, the major metabolite of enflurane metabolism. One reference indicates that enflurane is only 2-5% eliminated after oxidative metabolism in the liver, however more recent evidence suggests that about 9% is eliminated via hepatic oxidation.|The toxicity of the chiral fluorinated volatile anesthetics halothane, enflurane, and isoflurane is closely related to their metabolism by hepatic cytochrome P450. Although individual anesthetic enantiomers have been shown to exhibit a difference in anesthetic efficacy, metabolism of anesthetic enantiomers has not been reported. Human liver enflurane metabolism to difluoromethoxydifluoroacetic acid (DFMDFA) and inorganic fluoride is catalyzed in vivo and in vitro by cytochrome P450 2E1. The purpose of this investigation was to characterize enflurane racemate and enantiomer metabolism to test the hypothesis that fluorinated ether anesthetic metabolism by cytochrome P450 2E1 exhibits substrate stereoselectivity. Enflurane metabolism by microsomes from three human livers and by microsomes containing cDNA-expressed human P450 2E1 was measured at saturating enflurane concentrations. DFMDFA was quantitated with gas chromatography-mass spectrometry by detection of the ethanolamide derivative. In microsomes from all three livers, (R)-enflurane metabolism was significantly greater than that of (S)-enflurane, whereas rates of racemic enflurane metabolism were generally between those seen for the R- and S-enantiomers. The ratio of (R)-enflurane to (S)-enflurane metabolism in the three livers studied was 2.1:1, 1.9:1, and 1.4:1. (R)-, (S)-, and racemic enflurane were all metabolized by expressed P450 2E1. The ratio of (R)-enflurane to (S)-enflurane metabolism was 1.9:1. The metabolic enantiomeric selectivity of human liver P450 2E1 for (R)-enflurane suggests that enflurane metabolism by P450 2E1 occurs by direct substrate oxidation, rather than indirectly through the generation of a P450-dependent reactive oxygen species, and supports the hypothesis that the P450 2E1 active site is somewhat restrictive and capable of stereochemical discrimination.|Difluoromethoxydifluoroacetic acid (CHF2OCF2CO2H) has been identified as a metabolite of enflurane (CHF2OCF2CHCIF) in rat liver microsomes in vitro and in human urine by gas chromatography mass spectrometry. The formation of the metabolite in rat liver microsomes was dependent upon the presence of NADPH and O2, and was inhibited when SKF 525-A or CO/O2 (8:2, v/v) were present in the reaction mixture. When the C-H bonds of the CHCIF group of enflurane or of the CHCI group of isoflurane (CHF2OCHCICF3) were replaced with a C-CI bond, virtually no fluoride ion was produced from either derivative in rat liver microsomes. These results indicate that cytochrome P-450 catalyzes the oxidative dehalogenation of CHF2OCF2CHCIF at its CHCIF group to form CHF2OCF2CO2H and chloride and fluoride ions. In contrast, the CHF2 group does not appear to be appreciably susceptible to metabolic oxidative dehalogenation...|Enflurane is a fluorinated volatile anesthetic, mostly eliminated unchanged in exhaled air. About 10% of inhaled enflurane undergoes oxidative metabolism in liver via mixed function oxidase.|Fluorinated ether anesthetic hepatotoxicity and nephrotoxicity are mediated by cytochrome P450-catalyzed oxidative metabolism. Metabolism of the volatile anesthetic enflurane to inorganic fluoride ion by human liver microsomes in vitro is catalyzed predominantly by the cytochrome P450 isoform CYP2E1.

Rats exposed to enflurane (100 ppm) ... in a closed all glass-system eliminated /enflurane/ from the atmosphere of the system with a half-life of 6.84 hr... . 24 hr-fasting had no influence on /the elimination half-life/. ... Pretreatment with diethyl maleate (1 mL/kg ip), dimethylsulfoxide (DMSO, 1 g/kg ip) or dithiocarb (100 mg/kg ip) prolonged the elimination half-life... . An accelerated metabolic elimination was only observed in DDT-pretreated rats exposed to enflurane; other inducers of the microsomal mixed-function oxidase system like phenobarbital or rifampicine had no significant influence on the in vivo metabolism ...

The mechanism of action of enflurane is not completely established. Studies on rats indicate that enflurane binds to GABAA and glycine receptors, causing depressant effects at the ventral neural horn. It has been reported that 30% of the central nervous system depressant effects on the spinal cord after enflurane is administered are caused by the (GABA-A) receptor while binding to glycine receptors is responsible for about 20 % of the depressant effects. The relevance of these findings to humans is unknown. Other studies have found that enflurane binds to the calcium channels in the cardiac sarcoplasmic reticulum causing cardio depressant effects. Other studies support that this drug potentiates glycine receptors, which results in central nervous system depressant effects.|Renal toxicity has occasionally been observed after enflurane anesthesia. Although originally attributed to its oxidative metabolism to inorganic fluoride, serum levels of inorganic fluoride appear to be small to explain these renal effects. Formation of potentially nephrotoxic halogenated alkenes during alkaline degradation in carbon dioxide absorbers and subsequent bioactivation via the glutathione conjugation pathway may be considered as an alternative mechanism for renal toxicity. ... Alkaline degradation products of enflurane can be conjugated to thiol compounds, forming S-conjugates that could theoretically contribute to adverse renal effects observed occasionally with enflurane anesthesia. The N-acetyl-L-cysteine S-conjugates identified may be biomarkers to assess exposure of humans to alkaline degradation products of enflurane.|Clinical case reports of unexplained hepatic dysfunction following enflurane and isoflurane anesthesia led to the hypothesis that oxidative metabolism of these drugs by cytochromes P-450 produces immunoreactive, covalently bound acylated protein adducts similar to those implicated in the genesis of halothane-induced hepatic necrosis. Microsomal adducts were detected by enzyme-linked immunosorbent assay and immunoblotting techniques utilizing specific anti-trifluoroacetyl (TFA) IgG hapten antibodies in rat liver following enflurane, isoflurane, or halothane administration. Preincubation of the antibodies with microsomes from halothane-pretreated rats or with 500 uM TFA-lysine, markedly inhibited adduct recognition, while preincubation with 500 uM acetyllysine had no effect. The relative amounts of immunoreactive protein adducts formed were halothane much greater than enflurane much greater than isoflurane and correlates directly with the relative extents of metabolism of these agents. These results support the view that acyl metabolites of the volatile anesthetics may become covalently bound to hepatic proteins, thus serving as antigens, and thereby account for the apparent cross-sensitization and idiosyncratic hepatotoxicity reported for these drugs.

Exposure Routes: inhalation, ingestion, skin and/or eye contact Symptoms: Irritation eyes; central nervous system depression, analgesia, anesthesia, convulsions, respiratory depression Target Organs: Eyes, central nervous system (NIOSH, 2016)

Eye: If this chemical contacts the eyes, immediately wash the eyes with large amounts of water, occasionally lifting the lower and upper lids. Get medical attention immediately. Contact lenses should not be worn when working with this chemical. Skin: If this chemical contacts the skin, wash the contaminated skin with soap and water. Breathing: If a person breathes large amounts of this chemical, move the exposed person to fresh air at once. If breathing has stopped, perform mouth-to-mouth resuscitation. Keep the affected person warm and at rest. Get medical attention as soon as possible. Swallow: If this chemical has been swallowed, get medical attention immediately. (NIOSH, 2016)|(See procedures)

Fresh air, rest. Artificial respiration may be needed. Refer for medical attention.

Remove contaminated clothes. Rinse skin with plenty of water or shower.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

In the event of overdosage, or what may appear to be overdosage, the following action should be taken: Stop drug administration, establish a clear airway and initiate assisted or controlled ventilation with pure oxygen.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ Exposure at 15,000 to 20,000 ppm enflurane causes anesthesia.|/HUMAN EXPOSURE STUDIES/ /A study/ tested decision-making behavior in volunteers exposed at 2500 ppm of enflurane and found an increased tendency to adopt more risky strategies in decision-making situations. ... Diminished learning ability of volunteers exposed at the same concentration /was also observed/.|/HUMAN EXPOSURE STUDIES/ /A study/ exposed volunteers at 2000, 4200, and 5300 ppm of enflurane for 0.5 hour and evaluated the changes in behavior by digit span test, choice reaction time, and Purdue Pegboard Assembly test. Exposure at 2000 ppm did not affect the volunteers' performance, but exposure at 4200 and 5300 ppm caused amnesia for word pairs.|/SIGNS AND SYMPTOMS/ Mild, moderate and severe liver injury, including hepatic failure, may rarely follow anesthesia with enflurane Serum transaminases may be increased and histologic evidence of injury may be found. The histologic changes are neither unique nor consistent. In several of these cases, it has not been possible to exclude enflurane as the cause or as a contributing cause to liver injury. The incidence of unexplained hepatotoxicity following the administration of enflurane is unknown, but it appears to be rare and not dose related. Enflurane has also been associated with perioperative hyperkalemia. There have been rare post-marketing reports of hepatic failure and hepatic necrosis associated with the use of potent volatile anesthetic agents, including Enflurane. Due to the spontaneous nature of these reports, the actual incidence and relationship of Enflurane to these events cannot be established with certainty.|For more Human Toxicity Excerpts (Complete) data for Enflurane (8 total), please visit the HSDB record page.

Alyrane

The substance can be absorbed into the body by inhalation of its vapour and by ingestion.|inhalation, ingestion, skin and/or eye contact

irritation eyes; central nervous system depression, analgesia, anesthesia, convulsions, resp depression

Cough. Sore throat. Drowsiness. Weakness. Unconsciousness.

Redness. Dry skin.

Redness. Pain.

Eyes, central nervous system

Enflurane, USP is packaged in 250 mL amber-colored bottles. (Piramal Critical Care Inc.)

Prepn: Terrell, GB patent 1,138,406, US patent 3,469,011, US patent 3527813 (1969, 1969, 1970 all to Air Reduction)|Fluorinated greenhouse gases (fluorinated GHGs) are man-made gases used in several sectors. They include hydrofluorocarbons (HFCs), perfluorocarbons (PFCs), sulfur hexafluoride (SF6), nitrogen trifluoride (NF3), and a number of fluorinated ethers. Fluorinated GHGs also include chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs), but these ozone-depleting substances (ODSs) are currently being phased out and otherwise regulated under the Montreal Protocol and Title VI of the Clean Air Act, and EPA is not proposing requirements for them under the GHG Reporting rule. /Fluorinated greenhouse gases/

Method: OSHA 103; Procedure: gas chromatography using a flame ionization detector; Analyte: enflurane; Matrix: air; Detection Limit: 25.0 ppb (189 ug/cu m) (Anasorb CMS); 40.7 ppb (307 ug/cu m) (Anasorb 747).|Diagnostic Devices. Enflurane gas analyzer. An enflurane gas analyzer is a device intended to measure the concentration of enflurane anesthetic in a gas mixture.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients