Enfluran

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.

Rinse mouth. Refer for medical attention .

Excerpt from NIOSH Pocket Guide for Enflurane:

(General first aid procedures)

Store at room controlled room temperature 15 deg to 30 °C (59 deg to 86 °F).

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 °C

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.

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.

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.

... 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.

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.

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).

Neurotoxin - Acute solvent syndrome

Hemodynamic effects. The administration of enflurane has been known to decrease systemic vascular resistance. This effect causes decreased blood pressure. Enflurane is also known to cause a concentration-dependent decrease in the heart and increased left atrial pressure.

The substance can be absorbed into the body by inhalation of its vapour and by ingestion.

inhalation, ingestion, skin and/or eye contact

Rapidly absorbed into the circulation via the lungs.

Like many inhaled anesthetics, enflurane has associated adverse effects. Amongst the effects are hepatotoxicity, nephrotoxicity, and neurotoxicity.

Enflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Enflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It also appears to bind the D subunit of ATP synthase and NADH dehydogenase. Enflurane also binds to and angonizes the GABA receptor, the large conductance Ca²⁺ activated potassium channel, the glycine receptor, and antagonizes the glutamate receptor receptor. These yield a decreased depolarization and therefore, tissue excitability which results in anesthesia.

Cough. Sore throat. Drowsiness. Weakness. Unconsciousness.

Redness. Dry skin.

Redness. Pain.

See Inhalation.

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

Symptoms of acute overdose include nausea, vomiting, irritation to the eyes, skin and nose/throat, headache, dizziness, and drowsiness. Symptoms of chronic overdose include hypotension, cardiac arrhythmias, respiratory depression, and liver/kidney dysfunction.

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.

/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.

Stable inhalation anesthetic; [ChemIDplus]

MEDICATION

Used for the induction and maintenance of general anaesthesia during surgery and cesarean section and also used for analgesia during vaginal delivery.

Enflurane is prepared by dichlorination of the methyl group of 1-chloro-1,2,2-trifluoro-2- methoxyethane and replacement of these two chlorine atoms by fluorine.

... Prepared by successive chlorination and fluorination of the hydrocarbon ether.

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/