Perfluorobutane

238.02700

238.03

206-580-3

SE4TWR0K2C

DTXSID5059876

Colorless gas

2903399090

0

3.38160

0.63 g/cm³

-128.2 °C

-1.9 °C

4.2ºC

1.233

Soluble in benzene, chloroform

Store in a cool place. Keep container closed when not in use. Store in explosion-proof containers.

2.01X10+3 mm Hg at 25 deg C

Henry's Law constant = 667 atm-cu m/mol at 25 °C (est)

Global Warming Potential (GWP): Chemical: PFC-3-1-10 (Perfluorobutane); GWP: 8,860 (100-Year Time Horizon)

2.2

3163

S3-S7

Xi: Irritant;

Stable.

P41, P403

H280

SRP: 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 air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|Incinerate at a facility equipped to handle gaseous waste. Facility must be capable of handling aerosol cans. Combustion products will include HF. Dispose of empty cans in a sanitary landfill. Reclaim if feasible.

Materials/conditions to avoid: Finely divided active metals, alkali and alkaline earth metals.

Danish EPA; Survey of selected fluorinated green-house gases (2015)[Available from, as of March 3, 2016: http://eng.mst.dk/]

Eye protection: Wear safety glasses with side shields.|Skin protection: Avoid skin contact. Wear appropriate gloves when handling this material.

Nonflammable.

When fire fighting conditions are severe and total thermal decomposition of the product is possible, wear full protective clothing, including helmet, self-contained, positive pressure or pressure demand breathing apparatus, bunker coat and pants, bands around arms, waist and legs, face mask, and protective covering for exposed areas of the head. No unusual effects are anticipated during fire extinguishing operations. Avoid breathing the products and substances that may result from the thermal decomposition of the product or the other substances in the fire zone. Keep containers cool with water spray when exposed to fire to avoid rupture.

Exposure to extreme heat can give rise to thermal decomposition.

Ventilate area. Close cylinder or if necessary vent in hood or remote area. Place leaking containers in a well-ventilated area, preferrably in an exhaust hood, if available, or outdoors.

Use with adequate dilution ventilation.|Avoid prolonged breathing of vapors.|No smoking: Smoking while using this product can result in contamination of the tobacco and/or smoke and lead to the formation of ... hazardous decomposition products ... .

IDENTIFICATION AND USE: Perfluorobutane is a colorless gas. It is used as a medical research chemical, and as an ultrasound contrast agent. HUMAN EXPOSURE AND TOXICITY: Seventy-one patients undergoing prostate biopsy received intravenous injection of perfluorobutane microbubbles (Sonazoid). The safety observation period was 2 days after contrast administration. The incidence of adverse events was 6.7% and that of adverse reactions was 4%. ANIMAL STUDIES: Single intravenous administration of gas-carrier contrast agents used in ultrasound imaging to mice caused inflammation, necrosis, and ulceration of cecum and proximal colon (cecocolonic area) and focal necrosis in the liver. Similar intestinal lesions were also found in rats after treatment with a single iv administration of a gas-carrier contrast agent. No intestinal or hepatic lesions were found in guinea pigs or rabbits after repeated intravenous administrations of Sonazoid. In dogs, minimal to mild granulocytic inflammation of the cecum and/or colon was found after daily repeated intravenous injections for 28 days, but not after daily repeated administration for 14 days nor after a single administration. It is proposed that the intestinal and hepatic lesions in rats and mice after a single intravenous injection of gas-carrier contrast agents are caused by a common mechanism: intravascular growth of gas-carrier agents in tissues with gas supersaturation, as occurs in the cecal wall of rats and mice. In this particular environment the growing gas bubbles cause ischemia and necrosis in the cecal and colonic wall and liver.

Perfluorobutane's production and use as a medical imaging contrast agent(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 3960(SRC), determined from a structure estimation method(2), indicates that perfluorobutane is expected to have slight mobility in soil(SRC). Volatilization of perfluorobutane from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 670 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Perfluorobutane is expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 2010 mm Hg at 25 °C(3). Biodegradation data in soil were not available(SRC, 2016).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3960(SRC), determined from a structure estimation method(2), indicates that perfluorobutane is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 670 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 4.5 hours and 6 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The volatilization half-life from a model pond is about 32 days when adsorption is considered(4). Perfluorobutane is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). According to a classification scheme(5), an estimated BCF of 94(SRC), from an estimated log Kow of 3.49(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data in water were not available(SRC, 2016).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), perfluorobutane, which has a vapor pressure of 2010 mm Hg at 25 °C(2), is expected to exist solely as a gas in the ambient atmosphere. Perfluorobutane has an estimated atmospheric life-time of >2600 years(3). Perfluorobutane does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

The Ozone Depletion Potential has been reported as zero and perfluorobutane has an estimated atmospheric half-life of >2600 years(1). The Global Warming Potential of perfluorobutane is 8,860 (100-year)(2). Perfluorobutane is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Perfluorobutane does not contain chromophores that absorb at wavelengths >290 nm(3), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 94 was calculated in fish for perfluorobutane(SRC), using an estimated log Kow of 3.49(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of perfluorobutane can be estimated to be 3960(SRC). According to a classification scheme(2), this estimated Koc value suggests that perfluorobutane is expected to have slight mobility in soil.

The Henry's Law constant for perfluorobutane is estimated as 670 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that perfluorobutane is expected to volatilize rapidly from water surfaces(2). 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)(2) is estimated as 4.5 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)(2) is estimated as 6 days(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The volatilization half-life from a model pond is about 32 days when adsorption is considered(3). Perfluorobutane's Henry's Law constant indicates that volatilization from moist soil surfaces will occur(SRC). Perfluorobutane is expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 2010 mm Hg(4).

Occupational exposure to perfluorobutane may occur through inhalation and dermal contact with this compound at workplaces where perfluorobutane is produced or used. Use data indicate that the general population may have limited exposure to perfluorobutane via medical procedures. (SRC)

Visualisation of myocardial perfusion for diagnostic purposes

/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Perfluorobutane is included in the database.|/Experimental Therapy/ Ultrasound contrast agents are known to enhance high intensity focused ultrasound (HIFU) ablation, but these perfluorocarbon microbubbles are limited to the vasculature, have a short half-life in vivo, and may result in unintended heating away from the target site. Herein, a nano-sized (100-300 nm), dual perfluorocarbon (decafluorobutane/dodecafluoropentane) droplet that is stable, is sufficiently small to extravasate, and is convertible to micron-sized bubbles upon acoustic activation was investigated. Microbubbles and nanodroplets were incorporated into tissue-mimicking acrylamide-albumin phantoms. Microbubbles or nanodroplets at 0.1 x 10(6) per cu cm resulted in mean lesion volumes of 80.4 +/- 33.1 cu mm and 52.8 +/- 14.2 cu mm (mean +/- s.e.), respectively, after 20 s of continuous 1 MHz HIFU at a peak negative pressure of 4MPa, compared to a lesion volume of 1.0 +/- 0.8 cu mm in agent-free control phantoms. Magnetic resonance thermometry mapping during HIFU confirmed undesired surface heating in phantoms containing microbubbles, whereas heating occurred at the acoustic focus of phantoms containing the nanodroplets. Maximal change in temperature at the target site was enhanced by 16.9% and 37.0% by microbubbles and nanodroplets, respectively. This perfluorocarbon nanodroplet has the potential to reduce the time to ablate tumors by one-third during focused ultrasound surgery while also safely enhancing thermal deposition at the target site.|To explore the possibility of targeted biopsy (TBx) using transrectal ultrasound (US) with perflubutane microbubbles, we studied the findings of different cancerous tissue imaging modalities and evaluated needle biopsy in prostate cancer (PCa) using contrast-enhanced US (CEUS) in a multicenter clinical trial. Seventy-one patients undergoing prostate biopsy received intravenous injection of perflubutane microbubbles (Sonazoid). We evaluated and compared images obtained by CEUS. The safety observation period was 2 days after contrast administration. Among the 30 patients with cancer, one or more sites with findings suggestive of cancer in CEUS were detected in 23 patients (32.4%) by TBx. Although 22 patients had positive cores of cancer by systematic biopsy (SBx), 8 patients had positive cores of cancer in TBx alone (11.3%). There was a significant difference in cancer detection rate by TBx between two cohorts with PSA < 10 ng/mL (22.9%) and PSA /greater than or equal to/ 10 ng/mL (52.2%) (P < 0.02). Close observation of various CEUS findings with Sonazoid enabled targeting of cancerous areas, and consequently, a significant difference (P < 0.05) in the detection rate of cancer was recognized in the transition zone (TZ): SBx; 21/120 (17.5%) and TBx; 17/55 (30.9%). The incidence of adverse events was 6.7% and that of adverse reactions was 4%. CEUS with Sonazoid improved the detection rate of PCa by visualizing cancerous lesions. More detailed examination of CEUS images provided efficient characterization especially in the TZ area. TBx according to this procedure is expected to enable a lower number of biopsies and more accurate diagnosis of PCa.|Sonazoid is an ultrasound contrast agent (UCA) consisting of stabilized /perfluorobutane/ gas microbubbles in an aqueous suspension. Sonazoid has overcome the stability problems of first generation UCA and can produce myocardial perfusion images. Myocardial imaging using ultrasound contrast agents provides diagnosis of chronic heart disease and assessment of the coronary arteries and of the coronary blood flow reserve.|Sonazoid is taken up by healthy Kupffer cells in the liver and spleen, but break down in high amplitude ultrasound imaging modes such as color Doppler imaging. The bubble rupture produces a transient pressure wave, which results in a characteristic mosaic color pattern from tissues containing the microbubbles (induced acoustic emission). Liver tumors without Kupffer cells will not display the mosaic pattern and can therefore be identified easily.

This study has been performed to examine which cells are responsible for the hepatic clearance of the new ultrasound contrast agent Sonazoid and to study whether uptake of these gas microbubbles disturbs the function of the cells involved. Sonazoid was injected into rats and perfused fixed livers were studied by electron microscopy, which revealed that the Sonazoid microbubbles were exclusively internalized in Kupffer cells, i.e. by the macrophages located in the liver sinusoids, and not by parenchymal, stellate or endothelial cells. This is the first demonstration of intact phagocytosed gas microbubbles within Kupffer cells. Uptake of the Sonazoid perfluorobutane microbubbles by the Kupffer cells following injection of a dose corresponding to 20x the anticipated clinical dose for liver imaging did not result in measurable changes in the uptake and degradation of radioactively labelled albumin microspheres previously shown to be a useful indicator marker for Kupffer cell phagocytosis.|The new ultrasound contrast agent Sonazoid was injected IV in rats at doses of 0.8 and 8 muL perfluorobutane (PFB)-containing microbubbles/kg body weight. Samples were obtained from blood, liver, spleen, fat, kidney, muscle, heart, lung and brain from both males and females and the PFB gas was analyzed using validated gas chromatography mass spectrometry methods. No differences were observed between genders or doses for any of the pharmacokinetic parameters. For all tissues, the highest concentrations were observed at the first time point (i.e., 5 min postinjection) (51% of injected dose in liver; total recovery of 69%). The highest concentrations of PFB in tissue were observed in spleen > liver > lung > kidney >> other tissues. At 24 hr after dosing, the total amount of PFB remaining in the tissues was 1.9%. These data fit well with the finding that after a Sonazoid dose of 8 microL microbubbles/kg to male rats, more than 50% of the injected PFB was recovered in exhaled air by 20 min after dosing. During the first 24 hr after administration, more than 96% of the PFB dose was recovered in exhaled air.|The purpose of these studies was to determine the pharmacokinetics, tissue distribution, and exhaled elimination kinetics in rats for intravenously administered AI-700, which consists of porous microspheres containing decafluorobutane (DFB), for use as an ultrasound contrast agent. [Pd]-AI-700 was administered intravenously to rats (10 mg microspheres/kg). Blood and tissue samples collected at specified times were analyzed for palladium by inductively coupled plasma-mass spectrometry (ICP-MS). AI-700 was also administered intravenously to rats (40 mg microspheres/kg) and expired air was collected over time. Expired air samples were analyzed for DFB by validated adsorbent trapping-thermal desorption-gas chromatography-mass spectrometry methodology. Pd from [Pd]-AI-700 was cleared from blood with a ca. 50-85% decline from peak concentration within 5 min. At 1440 min post-dose, 52-72% of the Pd dose was recovered from organs of the reticuloendothelial system. Approximately 77% of the intravenously injected DFB was found in expired air within 3h after dosing, with most of the DFB dose (61+/-6%) expired within the first 10 min after dosing. As expected, the microspheres were cleared through the reticuloendothelial system, and the DFB was eliminated in expired air, with more than half of the DFB eliminated within the first 10 min after dosing.|The ultrasound contrast agent Sonazoid trademark was administered as an i.v. bolus injection of 0.6 uL microbubbles/kg body weight or as a continuous infusion over 30 min at a rate of 1.2 uL microbubbles/kg body weight to healthy volunteers and patients with reduced pulmonary diffusing capacity. Expired air and blood samples were collected from 32 subjects and perfluorobutane (PFB) gas was analyzed using validated gas chromatography mass spectrometry methods. Blood concentrations of PFB declined biphasicly with a distribution half-life (t(0.5 to 15)) of 2 to 3 min and an elimination half-life (t(15 to 120)) of 30 to 45 min. Area under the curve (AUC) values in patients with impaired gas diffusion were significantly larger than those in healthy volunteers. The exhalation kinetics were somewhat variable with a PFB elimination half-life (t(15 to 120)) of 28 to 111 min. Clearance of PFB was independent of study population and mode of administration. There were no deaths and no serious adverse events that resulted in the withdrawal of a subject from the study. With the exception that arthralgia predominated in healthy volunteers, healthy volunteers and diseased subjects did not show a different adverse event profile whether Sonazoid was administered as a bolus injection or as an infusion. Assessment of laboratory parameters (serum biochemistry, hematology and urinalysis), vital signs, oxygen saturation and electrocardiograms (ECGs) showed no changes which caused safety concern.

The ultrasound contrast agent Sonazoid trademark was administered as an i.v. bolus injection of 0.6 uL microbubbles/kg body weight or as a continuous infusion over 30 min at a rate of 1.2 uL microbubbles/kg body weight to healthy volunteers and patients with reduced pulmonary diffusing capacity. ... Blood concentrations of PFB declined biphasicly with a distribution half-life (t(0.5 to 15)) of 2 to 3 min and an elimination half-life (t(15 to 120)) of 30 to 45 min. ... The exhalation kinetics were somewhat variable with a PFB elimination half-life (t(15 to 120)) of 28 to 111 min.

Perflubutane perfusion echocardiography has the potential to be a cost-effective and convenient alternative to nuclear perfusion imaging. Perflubutane is easy to use and echocardiographers in the clinical trials can be trained to use it after imaging only a few patients. Based on data from previous clinical trials, ultrasound enhanced with Perflubutane was able to image myocardial perfusion and obtain information that appears comparable to nuclear imaging. Acusphere's Phase 3 program is designed with the appropriate comparative standards to determine the value of Perflubutane perfusion echocardiography relative to nuclear perfusion imaging. These standards are coronary angiography, nuclear perfusion imaging, and patient outcome.|Sonazoid is taken up by healthy Kupffer cells in the liver and spleen, but break down in high amplitude ultrasound imaging modes such as color Doppler imaging. The bubble rupture produces a transient pressure wave, which results in a characteristic mosaic color pattern from tissues containing the microbubbles (induced acoustic emission). Liver tumors without Kupffer cells will not display the mosaic pattern and can therefore be identified easily.|...It is proposed that the intestinal and hepatic lesions in rats and mice after a single intravenous injection of gas-carrier contrast agents are caused by a common mechanism: intravascular growth of gas-carrier agents in tissues with gas supersaturation, as occurs in the cecal wall of rats and mice. In this particular environment the growing gas bubbles cause ischemia and necrosis in the cecal and colonic wall and liver. This proposed mechanism of action is consistent with the absence of clinical reports indicative of intestinal and/or hepatic lesions in humans after administration of gas-carrier contrast agents.

/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 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. /Halogenated aliphatic hydrocarbons and related compounds/|/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 necessary. 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. Administer activated charcoal ... . Cover skin burns with sterile dressings after decontamination ... . /Halogenated aliphatic hydrocarbons and related compounds/|/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 ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasosupressors if patient is hypotensive with a normal fluid volume. Watch for signs of cardiac irritability and fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Halogenated aliphatic hydrocarbons and related compounds/

/HUMAN EXPOSURE STUDIES/ The ultrasound contrast agent Sonazoid trademark was administered as an i.v. bolus injection of 0.6 uL microbubbles/kg body weight or as a continuous infusion over 30 min at a rate of 1.2 uL microbubbles/kg body weight to healthy volunteers and patients with reduced pulmonary diffusing capacity. ... There were no deaths and no serious adverse events that resulted in the withdrawal of a subject from the study. With the exception that arthralgia predominated in healthy volunteers, healthy volunteers and diseased subjects did not show a different adverse event profile whether Sonazoid was administered as a bolus injection or as an infusion. Assessment of laboratory parameters (serum biochemistry, hematology and urinalysis), vital signs, oxygen saturation and electrocardiograms (ECGs) showed no changes which caused safety concern.|/HUMAN EXPOSURE STUDIES/ To explore the possibility of targeted biopsy (TBx) using transrectal ultrasound (US) with perflubutane microbubbles, we studied the findings of different cancerous tissue imaging modalities and evaluated needle biopsy in prostate cancer (PCa) using contrast-enhanced US (CEUS) in a multicenter clinical trial. Seventy-one patients undergoing prostate biopsy received intravenous injection of perflubutane microbubbles (Sonazoid). We evaluated and compared images obtained by CEUS. The safety observation period was 2 days after contrast administration. ...The incidence of adverse events was 6.7% and that of adverse reactions was 4%. CEUS with Sonazoid improved the detection rate of PCa by visualizing cancerous lesions.

AI 700

Butane, 1,1,1,2,2,3,3,4,4,4-decafluoro-: ACTIVE|/The goal of the study was/ to determine if perfusion stress echocardiography (PSE) with Imagify (perflubutane polymer microspheres) is comparable to stress perfusion imaging using (99m)Tc single photon emission computed tomography (SPECT) for coronary artery disease (CAD) detection. PSE is a novel technique for evaluating myocardial perfusion. RAMP (real-time assessment of myocardial perfusion)-1 and -2 were international, Phase 3 trials that evaluated the ability of PSE with Imagify, to detect CAD. Chronic, stable, chest pain patients (n=662) underwent Imagify PSE and gated SPECT imaging at rest and during dipyridamole stress. Independent blinded cardiologists [three PSE readers per trial, and four SPECT readers (one for RAMP-1, three for RAMP-2)] interpreted images. CAD was defined by quantitative coronary angiography or 90-day outcome with clinical review. Accuracy, sensitivity, and specificity were evaluated using non-inferiority analysis (one-sided alpha=0.025) compared with SPECT. SPECT results for RAMP-1 and -2 were: accuracy (70%, 67%), sensitivity (78%, 61%), and specificity (64%, 76%). Accuracy of all six PSE readers was non-inferior to SPECT (66-71%, P

Gas chromatographic method for determining fluorocarbons in air is described. Concn in air are determined directly. /Fluorocarbons/|A gas chromatographic procedure for determining atmospheric levels of fluorocarbons is described. Column is temp programmed to separate halogenated components while maintaining short retention times for each component. Freon 113 incl. /Fluorocarbons/

Human Drugs -> EU pediatric investigation plans|PFAS (per- and polyfluoroalkyl substances) -> OECD Category