Decafluorbutan

PFAS -> Other/unspecified

PFAS -> OECD Category

PFAS -> Other Nonpolymers

PFAS -> non-polymer

PFAS -> Other/unspecified

Pharmaceuticals -> Various

Pharmaceuticals -> Listed in ZINC15

Warning

H280 (100%): Contains gas under pressure; may explode if heated [Warning Gases under pressure]

P410+P403</a, and a href="https://pubchem.ncbi.nlm.nih.gov/ghs/#P410+P403">P410+P403 (click each P-code to see the statement)

Aggregated GHS information provided per 41 reports by companies from 2 notifications to the ECHA C&L Inventory.

Chemical: Butane, decafluoro-

Decafluorobutane: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

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.

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.

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 ... .

Eye protection: Wear safety glasses with side shields.

Skin protection: Avoid skin contact. Wear appropriate gloves when handling this material.

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).

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.

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.

/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.

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).

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).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Single intravenous administration of three different 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. Strain differences in the incidences of these lesions were found in both rats and mice. HsdHan:NMRI mice were among the most sensitive of the strains of mice studied. Even at the lowest dose of Sonazoid technically possible to inject in HsdHan:NMRI mice, lesions were found and a no-effect dose could not be determined. In a time-course experiment in HsdHan:NMRI mice, it was found that the lesions began to develop in the cecum and colon within 15 to 30 min after dosing. Lesions in the liver were first observed 120-240 min after dosing. Diet played a role in the etiology of the lesions, as HsdHan:NMRI mice given a diet with reduced amounts of cellulose and starch had reduced incidences of lesions, and when glucose was the only carbohydrate source, no lesions were observed. 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. 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.

/OTHER TOXICITY INFORMATION/ The purpose of this study was to observe Sonazoid perfluorobutane microbubbles ... in and their effects on the cremaster capillary microcirculation of rats. Sonazoid (0.3 x 10+9 microbubbles in 0.5 mL) was observed by intravital microscopy in the cremaster muscle after retrograde administration into the femoral artery of 6 animals. Microbubble and microvessel diameters and blood flow velocities and the overall mean and SD of the 1-minute volume flow through the microscopic field were calculated from the 2 to 4 capillaries observed in the field of each animal. Fluorescein isothiocyanate-dextran leakage was used to assess extravasation after microbubble passage seconds, respectively, before they were released and capillary flow normalized. No microbubble size changes, damming, or coalescence of bubbles and no changes in microvessel diameter or microvascular blood flow velocities, volume flow, or perfusion heterogeneity occurred during or after the passage of the Sonazoid suspension or the vehicle. No fluorescein isothiocyanate-dextran leakage was observed. Conclusions. The passage of Sonazoid bubbles at concentrations higher than those expected after intravenous administration of the Sonazoid did not durably impair microvascular perfusion, structural integrity, or macromolecular retention in the rat cremaster muscle. The duration of discrete capillary obstructions was short and in all cases comparable with that of naturally occurring leukocyte plugging.

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).

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)

Perfluorobutane's production and use as a medical imaging contrast agent may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 2010 mm Hg at 25 °C indicates perfluorobutane will exist solely as a gas in the atmosphere. Gas-phase perfluorobutane has an estimated atmospheric life-time of >2600 years. Perfluorobutane does not contain chromophores that absorb at wavelengths >290 nm and, therefore, is not expected to be susceptible to direct photolysis by sunlight. If released to soil, perfluorobutane is expected to have slight mobility based upon an estimated Koc of 3960. Volatilization from moist soil surfaces is expected to be an important fate process based upon an estimated Henry's Law constant of 670 atm-cu m/mole. Perfluorobutane will volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data in soil or water were not available. If released into water, perfluorobutane is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected to be an important fate process based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 4.5 hours and 6 days, respectively. 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. An estimated BCF of 94 suggests the potential for bioconcentration in aquatic organisms is moderate. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). 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)

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.

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.

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.

Component of the echo contrast agent, BR14, which consists of perfluorobutane gas microbubbles. [ChemIDplus]

Currently available microbubbles used for ultrasound imaging and therapeutics are limited to intravascular space due to their size distribution in the micron range. Phase-change contrast agents (PCCAs) have been proposed as a means to overcome this limitation, since droplets formed in the hundred nanometer size range might be able to extravasate through leaky microvasculature, after which they could be activated to form larger highly echogenic microbubbles. Existing PCCAs in the sub-micron size range require substantial acoustic energy to be vaporized, increasing the likelihood of unwanted bioeffects. Thus, there exists a need for PCCAs with reduced acoustic activation energies for use in imaging studies. In this article, it is shown that decafluorobutane, which is normally a gas at room temperature, can be incorporated into metastable liquid sub-micron droplets with appropriate encapsulation methods. The resulting droplets are activatable with substantially less energy than other favored PCCA compounds. Decafluorobutane nanodroplets may present a new means to safely extend ultrasound imaging beyond the vascular space.

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.

Medical research chemical

MEDICATION

non-polymer PFAS -> Refrigerant systems -> Refrigerants

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<or=0.004). Four demonstrated non-inferior sensitivity (68-77%, P<or=0.002), three demonstrated non-inferior specificity (72-88%, P<or=0.013). Three PSE readers (RAMP-2) were superior for sensitivity. Two PSE readers (RAMP-1) were superior for specificity. Area under the multi-reader receiver operating characteristics curve (0.72) was equal for both modalities. Majority of adverse events followed dipyridamole dosing, and were mild, transient, and required no treatment. Imagify PSE was well-tolerated. Its diagnostic performance in chest pain patients is comparable with SPECT perfusion imaging.