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Perfluorohexane


Perfluorohexane (C₆F₁₄) is a perfluorinated , a fully fluorinated analog of n-hexane, characterized by its high chemical and thermal stability due to the strong carbon-fluorine bonds. It exists as a clear, colorless, odorless with a of 56.7 °C, a of 1.684 g/mL at 20 °C, and limited in but good solubility in organic solvents. These properties stem from its nonpolar nature and inertness, making it resistant to , oxidation, and biological degradation under normal conditions.
Perfluorohexane has been utilized in medical applications, particularly as a component in contrast agents like perflexane microspheres for echocardiographic , leveraging its ability to carry gases such as oxygen and undergo acoustic droplet vaporization for enhanced visualization. In contexts, it serves as a and in systems requiring high thermal stability, including space applications and flow boiling experiments. It has also been evaluated as a clean fire extinguishing agent, offering effective suppression without residue due to its rapid vaporization and non-conductive properties. Safety data indicate low , with no significant hazards under standard handling, though of vapors may cause temporary effects at high concentrations. Notable research explores perfluorohexane in , such as lipid-shelled nanoemulsions for and high-intensity therapy, capitalizing on its phase-change behavior for controlled release. Environmentally, as a volatile perfluorocarbon, it contributes minimally to compared to functionalized but possesses a high owing to its long atmospheric lifetime, prompting scrutiny in applications phased out under regulations like the for ozone-depleting alternatives.

Chemical Identity and Properties

Molecular Structure and Nomenclature

Perfluorohexane has the molecular C₆F₁₄, consisting of a linear chain of six carbon atoms fully saturated with atoms and devoid of . The structure features two terminal –CF₃ groups connected by four –CF₂– units, forming an unbranched perfluorocarbon analogous to n-hexane but with all C–H bonds replaced by C–F bonds, which imparts high due to the strong carbon- bonds. This configuration results in a with no and is non-polar, consistent with its classification as a perfluoroalkane. The nomenclature of perfluorohexane follows conventions for fluorinated hydrocarbons. The is tetradecafluorohexane, indicating fourteen substituents on a parent . The systematic substitutive name is 1,1,1,2,2,3,3,4,4,5,5,6,6,6-tetradecafluorohexane, specifying the positions of the atoms along the carbon . In technical and commercial contexts, it is commonly designated as perfluorohexane or perfluoro-n-hexane to emphasize its complete fluorination and straight- structure, distinguishing it from branched perfluorohexane isomers. The is 355-42-0.

Physical Properties

Perfluorohexane (C₆F₁₄) is a colorless, odorless liquid at standard ambient temperature and pressure. Its molecular weight is 338.04 g/mol. The compound exhibits low intermolecular forces typical of perfluorocarbons, resulting in a low boiling point relative to its molecular size. Key thermodynamic properties include a solidification point of -90 °C and an initial ranging from 58 °C to 60 °C. The is 1.669 g/cm³ at 25 °C. measures 309 at 20 °C, with a vapor of 11.7 (air = 1) under the same conditions. Optical and surface properties feature a refractive index of 1.252 and surface tension of 11.3 mN/m. Due to its fully fluorinated structure, perfluorohexane displays high hydrophobicity, with solubility limited to 0.01 g/L at 25 °C and a calculated n-octanol/ (log Pₒₓ) of 6.02. It is miscible with non-polar solvents but immiscible with polar ones.
PropertyValueConditions
-82 °C-
57–60 °C1 atm
1.67 g/cm³25 °C
1.2515–1.25220–22 °C, D-line
Vapor pressure309 20 °C
11.3 mN/m-

Chemical Properties

Perfluorohexane exhibits exceptional chemical inertness owing to the robust carbon-fluorine bonds, which provide resistance to , oxidation, and reduction under standard conditions. It does not react with strong acids, bases, or common oxidizing agents, maintaining stability in diverse chemical environments. The compound is non-flammable, with a flammability rating of 0, indicating it will not burn or support even under exposure. Hazardous does not occur, and no significant reactions are observed during normal handling or storage. Under extreme thermal stress, such as temperatures exceeding operational limits in specialized applications, perfluorohexane may decompose to form toxic byproducts including , though it remains stable up to high temperatures in inert atmospheres. Incompatibilities are minimal but include strong oxidizers that could promote at elevated temperatures.

Synthesis and Production

Industrial Synthesis Methods

Perfluorohexane (C6F14) is primarily synthesized industrially via the (ECF) process, also known as the Simons process, in which n-hexane serves as the organic precursor dissolved in anhydrous (HF) as the . is conducted at a anode and cathode, with a cell voltage typically around 5-8 V and current densities of 50-200 mA/cm2, facilitating anodic oxidation that generates fluoronium ions (HF2+) and enables stepwise replacement of all C-H bonds with C-F bonds through radical and cationic intermediates. This method, developed by Joseph H. Simons in the , produces a complex mixture of perfluorinated products including branched and straight-chain isomers of perfluorohexane, necessitating downstream or for purification to achieve >99% purity for applications like biomedical use. The ECF process inherently yields low selectivity for the linear (n-C6F14), with skeletal rearrangements occurring due to carbocation-like intermediates, resulting in approximately 20-30% of the desired product amid homologues (C5F12 to C7F16) and byproducts like . Reaction conditions are maintained at 0-10°C to control exothermicity and minimize decomposition, with recycled after neutralization of fluorinated acids. While effective for bulk production, generates significant waste, including spent and volatile fluorocarbons, prompting environmental considerations in modern facilities. Alternative routes, such as direct gas-phase fluorination with elemental fluorine (F2) over catalysts like trifluoride, are less common industrially due to risks and lower scalability but may supplement ECF for high-purity needs. Patent literature describes optimized variants, such as US Patent 5,387,323 (1995), which involves reforming mixtures of organic substrates with under electrolytic conditions to enhance yields of perfluoroalkanes like C6F14 by minimizing overfluorination. Overall, ECF remains dominant for perfluorohexane owing to its ability to handle straight-chain alkanes directly, though purification costs and byproduct management limit economic viability to specialized markets.

Historical Development

The synthesis of perfluorohexane, a straight-chain perfluoroalkane (C6F14), originated with the (ECF) process developed by Joseph H. Simons during the 1940s at . This method entails the electrolytic oxidation of or related hydrocarbons dissolved in , where anodic reactions progressively substitute all C-H bonds with C-F bonds, yielding perfluorinated products. The process was initially kept classified due to its relevance to wartime efforts, including the , before Simons publicly detailed it in 1949 and secured U.S. Patent 2,519,983 in 1950, assigned to the Minnesota Mining and Manufacturing Company (). Commercial production of perfluorohexane via ECF commenced in the mid-20th century, primarily by and other firms leveraging the Simons to generate perfluorocarbons for industrial solvents, coolants, and precursors to fluorosurfactants. The method's efficiency in handling straight-chain alkanes produced perfluoro-n-hexane alongside branched isomers, necessitating for purification, but it dominated due to scalability despite challenges like and byproduct formation. By the , refined ECF variants supported growing demand for perfluorocarbons in oxygen-carrying emulsions, as explored by researchers like Leland C. Clark for biomedical applications. Subsequent advancements included alternative fluorination routes, such as cobalt trifluoride-mediated direct fluorination in the , which offered higher selectivity for linear isomers but required more hazardous conditions and proved less economical for bulk production. ECF remained the cornerstone historical method, though environmental concerns over prompted shifts toward shorter-chain alternatives and process optimizations by the 2000s.

Applications

Biomedical Applications

Perfluorohexane (PFH), a perfluorocarbon with high oxygen , has been investigated for use in oxygen delivery systems, particularly in nanocapsules and emulsions designed to transport respiratory gases to tissues. These formulations leverage PFH's capacity to dissolve up to 50 times more oxygen than , enabling applications in artificial oxygen carriers as alternatives to transfusions during hemodilution or ischemia. For instance, liposome-encapsulated PFH has demonstrated enhanced radiotherapy efficacy in tumors by alleviating through localized oxygen release, as shown in preclinical models where it improved radiation-induced by 20-30%. In , PFH serves as a core material in phase-change nanodroplets and emulsions that transition from liquid to gas under acoustic activation, producing microbubbles for enhancement. These agents offer advantages over traditional gaseous microbubbles, including greater stability for intravascular delivery and targeted activation via low-intensity , with droplet sizes tunable to 100-500 for tumor-specific . Studies have reported repeated cycles without significant degradation, enabling reliable in high-frequency for molecular targeting, such as EGFR-overexpressing cancers. PFH-based nanoemulsions have also integrated with guidance for high-intensity , where amplifies acoustic energy deposition in tissues. PFH's biocompatibility and inertness extend to pulmonary applications, including intratracheal instillation to mitigate acute lung injury by facilitating and reducing . In burn patients, liquids like PFH have been explored for partial liquid ventilation, improving oxygenation indices by 15-25% in animal models of injury. Additionally, PFH-loaded polymeric nanovesicles supply oxygen to enhance sonodynamic therapy, generating under for tumor cell , with in vitro efficacy boosted by 2-3 fold compared to normoxic controls. These multimodal uses highlight PFH's role in theranostic platforms, though clinical translation remains limited by formulation stability and regulatory hurdles.

Industrial and Technical Applications

Perfluorohexane (C₆F₁₄) is employed in the as a , insulating fluid, and test bath medium, leveraging its chemical inertness, low toxicity, and non-ozone-depleting properties. Its relatively low of approximately 56–57 °C enables use in low-temperature cooling applications, such as in formulations of perfluorocarbon-based liquids like analogs. In high-precision scientific , perfluorohexane functions as a heat-transfer fluid in cooling systems for particle detectors, including those in CERN's ATLAS, CMS, and LHCb experiments, where its thermal stability and dielectric properties are critical for maintaining operational temperatures without electrical conductivity. NASA evaluations have also assessed isomer variants of perfluorohexane for thermal stressing in perfluorocarbon fluids, indicating potential in and thermal management systems due to resistance to degradation under high temperatures. As a and reaction medium, perfluorohexane supports industrial chemical processes, including photooxidation reactions and polymerizations, where its hydrophobicity and high facilitate efficient and byproduct separation. It serves as a in formulations, mold release agents, and protective coatings, enhancing performance in environments requiring non-reactive, high-stability fluids. These applications capitalize on its biological and chemical inertness, minimizing risks in sensitive technical operations.

Biological Interactions

Oxygen Solubility and Gas Transport

Perfluorohexane exhibits substantially higher oxygen than or typical hydrocarbons, a property stemming from the low and weak van der Waals interactions in perfluorocarbons, which permit efficient gas partitioning into the liquid phase. At 25°C and 1 , experimental data report oxygen in perfluorohexane (Flutec PP6) as 24.4 mL of gas () per 100 g of liquid. Accounting for its of approximately 1.68 g/mL, this equates to about 0.41 mL O₂ per mL of perfluorohexane, or roughly 41 vol%. adheres to , scaling linearly with partial pressure of oxygen, while decreasing with rising due to enhanced thermal motion disrupting gas-liquid equilibria—reaching zero at the of 56°C. Comparisons with n-hexane underscore perfluorohexane's superiority for oxygen: experimental Henry's law constants (dimensionless H_{2,1}) for oxygen in n-perfluorohexane are lower, indicating greater solubility, with measurements precise to ±0.8% over 288–313 K near atmospheric pressure. Molecular simulations corroborate these findings, attributing the difference to favorable solute-solvent radial distributions and reduced oxygen-hexane interactions relative to oxygen-perfluorohexane. Perfluorohexane also dissolves carbon dioxide at 93 mL per 100 g and nitrogen at 15.6 mL per 100 g under identical conditions, enabling balanced transport of respiratory gases without preferential binding. In biological systems, this high gas facilitates via gradients, positioning perfluorohexane as a for oxygen delivery in or liquid ventilation. Oxygen equilibrates rapidly into the perfluorocarbon from high-PO₂ environments (e.g., alveoli) and releases to hypoxic tissues, mimicking convective but reliant solely on physical rather than hemoglobin-like coordination. Such mechanisms have been explored in perfluorocarbon-based oxygen carriers, where linear perfluorocarbons like perfluorohexane support in oxygen-deficient states, though their lower capacity relative to branched analogs (e.g., ) influences emulsion efficacy. The inert nature of dissolved gases ensures reversibility, with no metabolic interference, though limits retention at body temperature (37°C), where drops further.

Pharmacokinetics and Biocompatibility

Perfluorohexane (C6F14), a neutral perfluorocarbon, exhibits characterized by minimal through non-intravenous routes due to its and low in aqueous media; intravenous administration in or microbubble forms results in rapid distribution confined largely to the vascular and extravascular spaces without deep tissue penetration. Its chemical inertness, stemming from stable carbon-fluorine bonds, precludes in biological systems, as confirmed in studies where no metabolites were detected following exposure. is primarily pulmonary via of unchanged compound, with intravenous dosing showing 75% recovery in expired air within 3 hours and 87% within 24 hours, indicating half-lives on the order of minutes to hours and negligible long-term retention. Biocompatibility assessments highlight perfluorohexane's low reactivity with biological tissues, enabling its use in contrast agents and oxygen-carrying emulsions with minimal ; preclinical data from nanocapsule formulations report cell viability exceeding 90% in assays against various lines, including fibroblasts and endothelial cells. rodent models demonstrate reduced expression of pro-inflammatory molecules like and upon peritoneal exposure, suggesting potential anti-inflammatory properties without eliciting significant immune activation or organ damage. Unlike charged perfluoroalkyl substances, its neutral structure limits protein binding and , contributing to favorable safety profiles in short-term biomedical applications, though chronic environmental exposure data remain limited.

Safety, Toxicology, and Health Effects

Human and Animal Toxicity Data

Acute oral toxicity studies in rats have established an LD50 greater than 5,000 mg/kg body weight, classifying as having low via this route. Inhalation toxicity assessments for the commercial product FC-72 () indicate very low acute effects, with no significant adverse outcomes in standard tests. Subchronic inhalation exposure in rats over 65 days showed no marked toxicological effects in males or females. Animal immersion studies demonstrate biological inertness; rats submerged in oxygenated perfluorohexane for liquid ventilation purposes survived without or evident systemic beyond mechanical ventilation challenges, due to efficient oxygen transport and rapid pulmonary clearance. No mutagenicity was observed in Ames tests, and perfluorohexane does not act as a cardiac sensitizer in relevant assays. Chronic toxicity data are limited, reflecting the compound's ( 56°C) and lack of , unlike charged perfluoroalkyl sulfonates; prolonged exposure studies report no persistent organ damage in at tested doses. Human toxicity data are sparse, with no reported cases of acute or occupational illness from vapor or dermal in industrial settings. In biomedical contexts, such as perfluorocarbon emulsions for oxygen delivery, animal models (e.g., rabbits, dogs) tolerated intravenous doses without or toxicity, with clearance via ; human trials for similar applications showed no adverse effects at therapeutic levels. Potential irritation from direct ocular exposure in surgical uses has been noted for perfluorocarbons generally, but specific perfluorohexane incidents are undocumented, emphasizing its inert profile when promptly removed. Overall, empirical evidence supports minimal human health risks at ambient or controlled exposures, prioritizing to mitigate vapor .

Exposure Pathways and Risk Assessment

Human exposure to perfluorohexane (C6F14) primarily occurs through occupational pathways during handling, , or use in applications such as electronic cooling fluids (e.g., FC-72) and research settings. Inhalation of vapors is the dominant route due to its volatility ( 56–60°C), with potential dermal from liquid contact during spills or maintenance, though skin penetration is limited by its non-polar nature. Ingestion is unlikely outside accidental scenarios. No established occupational exposure limits (e.g., PEL or TLV) exist from OSHA, NIOSH, or ACGIH, reflecting its classification as having low acute hazard potential under GHS, though like are recommended to prevent vapor accumulation. General population exposure is minimal, as perfluorohexane is not widely present in consumer products, food, or ; its use in contained systems (e.g., ) limits release, and it volatilizes rapidly without due to inertness and pulmonary clearance via . Biomedical research applications, such as emulsions for oxygen transport or imaging, involve controlled intravenous or exposure, but these are experimental and not routine clinical uses, with rapid elimination ( minutes to hours in lungs). Environmental pathways like air or dust contribute negligibly, unlike persistent acids, as perfluoroalkanes degrade minimally and partition to air. Risk assessments indicate low human health hazards, with no reported acute toxicity data in humans and animal studies showing minimal effects even at high doses; for instance, no significant adverse outcomes in preclinical models for related perfluorocarbons used in emulsions. Perfluorohexane poses no known carcinogenic, mutagenic, or reproductive risks per available safety data, lacking listing on IARC, NTP, or OSHA carcinogen rosters. Primary concerns are physical: potential asphyxiation in confined spaces from oxygen displacement by dense vapors (vapor density ~11.7) and mild irritation to eyes, skin, or respiratory tract at high concentrations (>1000 ppm). Chronic exposure risks remain unquantified due to limited long-term studies, but its chemical inertness and rapid clearance suggest negligible bioaccumulation or systemic effects compared to functionalized PFAS. Site-specific assessments for industrial sites emphasize monitoring vapor levels below 100 ppm for comfort.

Environmental Fate and Impact

Persistence, Bioaccumulation, and Mobility

Perfluorohexane (C₆F₁₄) exhibits extreme environmental persistence due to the strength of its carbon-fluorine bonds, rendering it resistant to , photolysis, and microbial degradation. screening tests demonstrate 0% degradation after 28 days under aerobic conditions, classifying it as not readily biodegradable. Atmospheric oxidation estimates exceed 3,000 years, indicating very persistent (vP) behavior across environmental compartments. Bioaccumulation potential is predicted to be significant based on physicochemical properties, with an estimated (log Kₒw) of 4.5–5.0, leading to factors (BCF) of 1,330–3,550 L/kg in aquatic organisms. This suggests perfluorohexane screens as (B) or very (vB), though empirical data from field or laboratory exposures remain limited, potentially due to its low aqueous and inertness limiting uptake studies. No direct evidence of in food webs has been reported, but structural analogies to other perfluorocarbons support caution regarding trophic transfer. Mobility is governed by high volatility (vapor pressure ≈29 kPa at 25°C) and low water solubility (<0.1 mg/L), favoring partitioning to air over aqueous or soil phases. Henry's Law constant (9.8 × 10⁷ Pa m³/mol) indicates rapid volatilization from surface waters, enabling long-range atmospheric transport with a characteristic travel distance exceeding 1,350,000 km. In soils, moderate adsorption (predicted log Kₒc ≈3.7) limits groundwater leaching, but volatility reduces retention; overall, it screens as mobile (M) with potential for widespread dispersal via air.

Ecological Studies and Effects

Ecological studies on perfluorohexane (C₆F₁₄) indicate moderate acute toxicity to aquatic organisms at concentrations in the mg/L range, though its low water solubility (approximately 40-60 mg/L) limits bioavailability and chronic exposure in natural environments. In standardized laboratory tests, the 96-hour LC₅₀ for lethality in rainbow trout (Oncorhynchus mykiss) was 13 mg/L, suggesting potential harm to fish under high-exposure scenarios such as industrial spills. For aquatic invertebrates, the 24-hour EC₅₀ for Daphnia magna immobilization was 62 mg/L, exceeding the compound's solubility limit and implying reduced practical toxicity due to partitioning into air or sediment rather than sustained dissolution. Algal growth inhibition (EC₅₀ >120 mg/L over 72 hours) similarly surpassed solubility, with no observed effects at environmentally plausible dissolved concentrations. These findings classify perfluorohexane as harmful to aquatic life with long-lasting effects (EU H412, Aquatic Chronic 3), but field monitoring data show negligible widespread contamination, as its ( ~200 mmHg at 25°C) favors atmospheric dispersion over aquatic persistence. Beyond direct hazards, perfluorohexane's confers a long atmospheric lifetime, positioning it as a potent through absorption in the (8-12 μm), potentially amplifying and contributing to climate-mediated ecological disruptions such as shifts or species stress. Perfluorocarbons like perfluorohexane exhibit global warming potentials orders of magnitude higher than CO₂ over century scales, though emissions are low relative to major due to specialized uses (e.g., cooling, medical emulsions). No large-scale ecological field studies document population-level impacts, likely reflecting limited release volumes and rapid volatilization; however, modeling suggests that even trace atmospheric releases could enhance , indirectly affecting ecosystems via temperature elevation and . Bioaccumulation in remains unquantified in peer-reviewed , with no reported trophic magnification, contrasting longer-chain ; its inert nature and may enable temporary uptake in fatty tissues, but resistance precludes metabolic breakdown, favoring excretion or off-gassing. Terrestrial effects, including soil microbe or plant interactions, lack dedicated studies, though analogous perfluorocarbons show minimal disruption at low doses. Overall, empirical data underscore low at ambient levels (<μg/L in monitored sites), prioritizing atmospheric impacts over localized in assessments.

Regulatory Status and Controversies

Global Regulations on PFAS and Specifics for Perfluorohexane

The on Persistent Organic Pollutants lists perfluorooctane sulfonic acid (PFOS), its salts, and related compounds since 2009; (PFOA), its salts, and related compounds since 2019; and perfluorohexane sulfonic acid (PFHxS), its salts, and related compounds since 2022, mandating global phase-out except for approved uses due to their persistence, , and toxicity. These listings influence national implementations, such as the EU's Persistent Organic Pollutants Regulation, which bans PFOS since 2008, PFOA since July 4, 2020, and PFHxS since August 28, 2023. In the , REACH Annex XVII further restricts C9-C14 perfluorocarboxylic acids (PFCAs) since February 2023 and perfluorohexanoic acid (PFHxA) from April 2026, alongside a proposed group restriction on over 10,000 submitted in 2023 and updated August 20, 2025, aiming to limit non-essential uses while allowing derogations for critical applications like semiconductors. The EU Directive sets a 0.5 µg/L limit for the sum of 20 since January 12, 2021. In the United States, the EPA finalized National Primary Regulations in April 2024, establishing maximum contaminant levels (MCLs) of 4 ppt for PFOA and PFOS, 10 ppt for PFHxS, (PFNA), and HFPO-DA (), with a index for mixtures including perfluorobutane (PFBS); compliance monitoring begins by 2027. Perfluorohexane (C6F14), a fully fluorinated , is not specifically listed or restricted under Stockholm Convention POPs, EU REACH individual bans, or EPA drinking water MCLs, which target sulfonic and carboxylic acids rather than inert perfluoroalkanes. However, it qualifies as a under the TSCA Section 8(a)(7) reporting rule, requiring manufacturers to report uses since January 1, 2006, as finalized in October 2023. In the , the ongoing broad restriction proposal could potentially encompass perfluoroalkanes absent essential-use exemptions, though perfluorohexane remains unregulated for toxicity-driven reasons and is primarily subject to fluorinated controls under Regulation () No 517/2014 due to its high . variations exist, such as Denmark's planned ban in consumer products like from July 1, 2025, which may indirectly affect perfluorohexane if classified under broad definitions.

Debates on Utility vs. Precautionary Restrictions

Perfluorohexane's primary utilities stem from its exceptional oxygen solubility—up to 50 times greater than —and chemical inertness, enabling applications in biomedical oxygen transport and imaging. In , it serves as a in microsphere form (e.g., Perflexane), enhancing visualization of cardiac structures without significant metabolism or long-term retention, as it is rapidly exhaled via the lungs. Researchers have explored perfluorohexane emulsions for artificial blood substitutes, such as in trauma or , where it dissolves and delivers oxygen to hypoxic tissues, with preclinical studies demonstrating effective and due to its non-reactivity with biological systems. These properties position it as a potential bridge therapy in oxygen-deprived states, outperforming hemoglobin-based alternatives in solubility while avoiding issues observed in earlier synthetic carriers. Proponents of utility emphasize of low human and rapid clearance, with half-lives in under minutes to hours via pulmonary elimination, contrasting with bioaccumulative perfluoroalkyl acids like PFOS. Phase I/II trials of perfluorohexane-based colloids reported transient effects like mild fluorosis at high doses but no persistent organ damage, supporting targeted use over blanket avoidance. In sonodynamic therapy, perfluorohexane-loaded nanovesicles enhance oxygen supply to tumors, improving generation for , with in vitro data showing controlled release without to healthy cells. Advocates argue that restricting such compounds preempts evidence-based , particularly in critical care, where causal links to harm remain unestablished for volatile perfluorocarbons unlike persistent surfactants. Critics invoking the advocate restrictions on perfluorohexane amid broader scrutiny, citing structural similarities to "forever chemicals" and potential for environmental release during manufacturing or disposal. Environmental assessments of fluorinated compounds highlight risks like atmospheric or indirect impacts from related perfluorocarbons, though specific data for perfluorohexane indicate volatility ( 56°C) limits / accumulation, with no demonstrated in ecological studies due to its and lack of protein binding. Regulatory proposals, such as EU REACH expansions targeting groups, risk encompassing inert perfluorocarbons without differentiated risk profiles, potentially driven by aggregated data rather than compound-specific metrics. This approach overlooks causal distinctions: while PFHxS exhibits half-lives exceeding years and endocrine disruption, perfluorohexane's inertness yields negligible metabolites, with models showing dilution in air over short timescales. The debate underscores tensions between proven, niche biomedical efficacy—bolstered by pharmacokinetic data—and precautionary policies extrapolating from high-risk analogs, which may stifle development absent of perfluorohexane's environmental or . analyses call for risk-based exemptions for fluorocarbons, citing their essential roles without the bioaccumulative pathways of degradable , while environmental NGOs prioritize phase-outs to avert uncertainty, even as monitoring data reveal perfluorohexane concentrations below detection in ambient . Empirical prioritization favors continued into its oxygen-delivery potential, given low-dose safety profiles in human applications, over undifferentiated restrictions that conflate causal mechanisms.

Alternatives and Research Directions

Current Alternatives

Perfluorohexane, a perfluorocarbon used primarily as a in cooling and immersion applications due to its low of 56 °C and properties, has prompted the development of non-PFAS alternatives amid regulatory scrutiny of persistent fluorinated compounds. Hydrocarbon-based fluids such as , n-butane, and serve as functional replacements in cooling systems, offering comparable but introducing flammability risks that require enhanced safety measures. has also been identified as a viable option for similar thermal management roles, though it faces regulatory concerns from agencies like the U.S. EPA regarding and handling. In solvent applications for precision cleaning of , where perfluorohexane's inertness prevents , hydrocarbon and alcohol-based formulations provide effective alternatives without perfluoroalkyl chains, though they may demand adjusted process parameters to match power. Commercial products like ProSolv®5408e, a solvent free of , have been adopted for removing fluxes and contaminants from circuit boards, demonstrating high performance in vapor without the environmental persistence of PFCs. For niche uses in applications such as partial or contrast, silicone-based oils or air-oxygen mixtures have emerged as substitutes, reducing bioaccumulation risks associated with fluorocarbons, though clinical efficacy data remain limited to specific trials showing equivalent in animal models. Overall, while feasible non- options exist for approximately 40% of PFAS applications including those of perfluorohexane, many require further validation for scalability and performance equivalence, with 58 identified alternatives carrying their own environmental or safety caveats.

Ongoing Developments and Potential Advances

Recent research has focused on integrating perfluorohexane into formulations to enhance -mediated therapies, particularly for . In a 2022 study, lipid-based perfluorohexane nanoemulsions were developed for MRI-guided high-intensity (HIFU) , demonstrating improved thermal stability and in tumor models, with potential to overcome limitations in acoustic droplet efficiency. Similarly, perfluorohexane-loaded polymeric nanovesicles, reported in 2020, enable oxygen supply to hypoxic tumor environments, boosting sonodynamic therapy efficacy by generating under activation, with in vitro experiments showing up to 80% cell death in treated lines. Advances in targeted agents represent another key development. A 2022 investigation introduced EGFR-targeted perfluorohexane nanodroplets for molecular of tumors, offering higher resolution than traditional microbubbles due to their liquid-to-gas properties, which allow stable circulation and on-demand activation, validated in preclinical models of . These formulations leverage perfluorohexane's high oxygen solubility and inertness, minimizing risks compared to longer-chain , though long-term safety data remains limited to short-term animal studies. Potential future applications include expanded use in liquid ventilation systems for acute respiratory distress, building on perfluorohexane's oxygen-carrying capacity. Emerging prototypes, such as injectable oxygen microbubbles incorporating perfluorohexane, aim to support partial in preterm infants or ARDS patients, with 2025 preclinical trials indicating improved without significant , though scalability and regulatory hurdles persist. In parallel, research into perfluorohexane alternatives for non-medical uses, like cleaning solvents, explores fluorinated ethers with lower persistence, driven by EU REACH restrictions, but perfluorohexane's thermal stability continues to favor its retention in precision applications pending validated substitutes. Overall, these developments prioritize engineered delivery systems to harness perfluorohexane's physicochemical advantages while mitigating environmental release concerns.

References

  1. [1]
    Perfluorohexane | C6F14 | CID 9639 - PubChem - NIH
    ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapors, ...
  2. [2]
  3. [3]
    EGFR-Targeted Perfluorohexane Nanodroplets for Molecular ... - NIH
    Jun 30, 2022 · The perfluorohexane core used in this study allows for repeated vaporization and recondensation after undergoing acoustic droplet vaporization, ...
  4. [4]
    [PDF] Flow Boiling and Condensation Experiment (FBCE)
    The test fluid for FBCE is normal-perfluorohexane (nPFH-C6F14) which is a coolant used in engineering applications. The properties of the fluid are given in the ...
  5. [5]
    (PDF) Thermal Stability Analysis of Perfluorohexane - ResearchGate
    Aug 6, 2025 · The thermal stability analysis of perfluorohexane (C6F14)is presented in this paper as a preliminary evaluation of the potential application of ...
  6. [6]
    [PDF] Perfluorohexane Clean Extinguishing Agent for Streaming and ...
    Perfluorohexane demonstrated the best combination of properties of any of the proposed clean extinguishing agents for the replacement of Halon 121 1 in ...
  7. [7]
    Lipid Perfluorohexane Nanoemulsion Hybrid for MRI-Guided High ...
    Mar 30, 2022 · This agent showed great potential for in vivo image-guided drug delivery and HIFU therapy against tumors. Nevertheless, the poor thermal ...
  8. [8]
    Critical Review of Thermal Decomposition of Per- and ...
    Apr 21, 2022 · Several perfluorohexane C6F14 fluids with different isomer concns. were evaluated for use in an upcoming NASA expt. Two com. high-purity n ...
  9. [9]
    Hexane, tetradecafluoro- - the NIST WebBook
    Hexane, tetradecafluoro- has the formula C6F14, molecular weight of 338.0418, CAS number 355-42-0, and is also known as Perfluoro-n-hexane.
  10. [10]
    None
    ### Summary of Section 9: Physical and Chemical Properties (Tetradecafluorohexane, Aldrich - 281042)
  11. [11]
    [PDF] PERFLUOROHEXANE (PFH) - HaloPolymer
    PERFLUOROHEXANE. (PFH). CHEMICAL NAME: Perfluorohexane. SYNONYMS: Tetradecafluorohexane. CHEMICAL FORMULA: С6F14. CAS: 355-42-0. Transparent, colorless liquid ...
  12. [12]
    Perfluorohexane
    Melting point: mp -82.26 ±0.01°. Boiling point: bp 57.23°. Index of refraction: nD22 1.2515. Density: d0 1.7560; d25 1.66970 (air satd, 1 atm); d25 1.6717 ...
  13. [13]
    [PDF] Perfluorohexane(s) - Synquest Labs
    The product is stable at normal handling and storage conditions. Strong oxidizing agents. Under normal conditions of storage and use, hazardous decomposition ...
  14. [14]
    [PDF] SAFETY DATA SHEET - Airgas
    Jan 30, 2017 · Under normal conditions of storage and use, hazardous decomposition products should not be produced. The product is stable. Chemical stability.
  15. [15]
    [PDF] Chemical Characterization and Thermal Stressing Studies of ...
    Applications of boiling heat transfer in space can be found in the areas of thermal management, fluid handling and control, and power systems. It is of ...
  16. [16]
    Electrochemical Fluorination - an overview | ScienceDirect Topics
    Abstract. Electrochemical fluorination (ECF, Simons process) is one of the favored processes in the production of perfluorinated materials.Missing: perfluorohexane | Show results with:perfluorohexane
  17. [17]
    Overview on the history of organofluorine chemistry from the ...
    An entirely different approach was also carried out: the electrochemical fluorination (ECF) process for producing fluorocarbons. ECF was invented by Simons ...Missing: perfluorohexane | Show results with:perfluorohexane
  18. [18]
    Simons: Joseph Simons - Penn State Materials Research Institute
    It was his development of the electrochemical fluorination (ECF), or Simons Process, that changed industrialization of fluorinated materials and chemistries.
  19. [19]
    Sources, Fate and Transport of Perfluorocarboxylates
    This review describes the sources, fate, and transport of perfluorocarboxylates (PFCAs) in the environment, with a specific focus on perfluorooctanoate (PFO).<|separator|>
  20. [20]
    [PDF] review on recent development in the synthesis of perfluoro organic ...
    The oxidation reactions of high valent nickel fluorides were found to be similar to those of nickel anodes during electrochemical fluorination [43-44]. Sartori ...
  21. [21]
    US5387323A - Process for preparing fluorochemicals
    A process for preparing fluorochemical compounds, eg, perfluoroalkanes, perfluoroethers, and perfluoroalkyl tertiary amines, comprises (a) forming a mixture.
  22. [22]
    Combining Theory and Experiment to Characterize the Voltammetric ...
    Jul 21, 2020 · The Simons process, otherwise known as the electrochemical fluorination ... 1 Ever since its discovery in the 1940s by Joseph H. Simons,12 ...
  23. [23]
    US2519983A - Electrochemical process of making fluorine ...
    Patented ug. 1950 ELECTROCHEMICAL PROCESS OF MAKING FLUORINE-CONTAININ G CARBON POUNDS COM- Joseph H. Simons, State College, Pa., assigner to Minnesota Mining ...
  24. [24]
    Polyfluorinated Compounds: Past, Present, and Future
    The other main process for the production of PFCs is called telomerization. ... The history of PFC production is difficult to accurately portray due to the ...
  25. [25]
    Electrochemical fluorination of organo-element compounds
    Since more than 50 years electrochemical fluorination in anhydrous HF (Simons process) has been used as a versatile method for the synthesis of perfluorinated ...
  26. [26]
    Biomedical perfluorohexane-loaded nanocapsules prepared by low ...
    Mar 12, 2020 · Perfluorohexane-loaded nanocapsules are interesting materials for many biomedical applications such as oxygen delivery systems or contrast
  27. [27]
    Liposome encapsulated perfluorohexane enhances radiotherapy in ...
    Sep 20, 2016 · Due to its ability of carrying oxygen, perfluorochemical emulsions were originally designed as blood substitutes to replace the O2 carrying ...
  28. [28]
    Monodisperse perfluorohexane emulsions for targeted ultrasound ...
    We demonstrate that membrane emulsification is an excellent tool to create strictly monodisperse echogenic perfluorohexane emulsions with a preset droplet size.
  29. [29]
    Repeated Acoustic Vaporization of Perfluorohexane Nanodroplets ...
    Superheated perfluorocarbon nanodroplets are emerging ultrasound imaging contrast agents that boast biocompatible components, unique phase-change dynamics, and ...
  30. [30]
    Intratracheal Instillation of Perfluorohexane Modulates the ... - PubMed
    Perfluorocarbons (PFCs) have a protective effect against acute lung injury. We aimed to assess the therapeutic effects of perfluorohexane on burn patients with ...
  31. [31]
    Application of Perfluorohexanes - ChemicalBook
    Mar 3, 2020 · Perfluorohexane (C6F14), or tetradecafluorohexane, is a fluorocarbon ... In many applications, perfluorohexane is shown to be a good ...Missing: review | Show results with:review<|control11|><|separator|>
  32. [32]
    Perfluorohexane-Loaded Polymeric Nanovesicles with Oxygen ...
    Jul 19, 2025 · Perfluorohexane (PFH, C 6 F 14 ), a heavier fluorocarbon, has long been investigated for its potential oxygen-carrying capacity [2] and as phase ...
  33. [33]
    Phase-transitional Fe 3 O 4 /perfluorohexane Microspheres for ...
    This unique MDV strategy is expected to substantially broaden the biomedical applications of nanotechnology and promote the clinical treatment of tumors that ...
  34. [34]
    Perfluorohexane CAS NO. 355-42-0 Dakenchem
    Aug 9, 2023 · This compound is colorless and odorless. It also has a high density. Another notable feature is its low reactivity, making it resistant to most ...
  35. [35]
    [PDF] Technical Specification for the Supply of Perfluorocarbon fluids ...
    This technical specification concerns the supply of perfluoropropane (C3F8) and perfluorohexane (C6F14) for ATLAS, CMS and LHCb cooling systems. It is also.
  36. [36]
    Chemical Characterization and Thermal Stressing Studies of ...
    Jan 1, 2006 · Perfluorohexane (PFH), C6F14, is a perfluorocarbon fluid. Several PFH fluids with different isomer concentrations were evaluated for use in ...
  37. [37]
    Perfluorohexane, 98% 355-42-0 India - Otto Chemie Pvt. Ltd.
    It is used in the electronic cooling liquid and insulator. It plays a vital role as a reaction medium, especially for photooxidation reactions.
  38. [38]
    None
    ### Summary of Gas Solubility Data for Perfluorohexane (Flutec PP6)
  39. [39]
    Solubility of oxygen in n-hexane and in n-perfluorohexane ...
    Abstract. The solubility of oxygen in n-hexane and in n-perfluorohexane was determined experimentally and calculated by computer simulation. A precision ...
  40. [40]
    Perfluorocarbon-based oxygen carriers: from physics to physiology
    Nov 3, 2020 · Perfluorocarbons (PFC) are fascinating compounds with a huge capacity to dissolve gases, where the respiratory gases are of special interest for current ...Missing: perfluorohexane | Show results with:perfluorohexane
  41. [41]
    [PDF] METABOLISM AND PHARMACOKINETICS OF HALON 1211 AND ...
    This study has investigated the metabolism and pharmacokinetics of HCFC- 123, perfluorohexane, and Halon 121 1 in Fischer 344 and Sprague Dawley rats.
  42. [42]
    [PDF] Division's Revised Proposed Package Insert Imagent - NCBI
    May 31, 2002 · Approximately 75% of the administered dose of perflexane was recovered in expired air within 3 hours, and approximately 87% was recovered in ...
  43. [43]
    Effect of perfluorohexane on the expression of cellular adhesion ...
    To study biocompatibility and potential anti-inflammatory effects of intraperitoneal perfluorocarbons, we evaluated the influence of perfluorohexane and/or ...
  44. [44]
    Perfluorohexane-Loaded Polymeric Nanovesicles with Oxygen ...
    Mar 29, 2020 · These results demonstrated that the nanovesicles possessed decent biocompatibility advantageous for application as a nano-SDT delivery vehicle.
  45. [45]
    [PDF] Fluorinert™ - Iolitec
    The product also demonstrates very low acute and sub-chronic inhalation toxicity. It is not a mutagen (ames) or a cardiac sensitizer.
  46. [46]
    Perfluorohexane - Wikipedia
    It is odorless and colorless. Unlike typical hydrocarbons, the structure features a helical carbon backbone. In medical imaging it is used as a contrast ...Missing: safety | Show results with:safety
  47. [47]
    [PDF] Safety Data Sheet SECTION 1: Identification SECTION 2: Hazard ...
    Aug 8, 2019 · 3M™ Fluorinert™ FC-72 Electronic Liquid ... Information on Toxicological effects. Signs and Symptoms of Exposure. Based on test ...
  48. [48]
    Perfluorocarbon liquids in ophthalmology - PubMed - NIH
    Perfluorocarbon liquids are not tolerated in the anterior chamber, causing corneal edema within 2-3 days at the site of contact.
  49. [49]
    [PDF] Perfluorohexane - Apollo Scientific
    Unstable in the presence of incompatible materials. Product is considered stable. Hazardous polymerisation will not occur. Possibility of hazardous reactions.
  50. [50]
    [PDF] Environmental risk evaluation report: Perfluoroisohexane [PFiHx]
    Figure 1.2 Structural formula of perfluorohexane: Molecular formula: C6F14. Molecular weight: 338 g/mol. SMILES code: C(C(C(C(F)(F)F)(F)F)(F)F)(C(C(F)(F)F)(F ...
  51. [51]
    Environmental hazards and health risk of common liquid perfluoro-n ...
    However, all perfluoro-n-alkanes should be potent greenhouse gases (GHGs) because of their chemical stability and strong absorption in the longer wavelength, ...
  52. [52]
    Overview - Stockholm Convention
    The most-studied PFASs are perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS). PFOS, its salts and ...
  53. [53]
    Per- and polyfluoroalkyl substances (PFAS) - ECHA - European Union
    The majority of PFAS are persistent in the environment. Some PFAS are known to persist in the environment longer than any other synthetic substance. As a ...
  54. [54]
    ECHA publishes updated PFAS restriction proposal - European Union
    Aug 20, 2025 · The European Chemicals Agency (ECHA) has published the updated proposal to restrict per- and polyfluoroalkyl substances (PFAS) under the EU's ...
  55. [55]
    [PDF] and Polyfluoroalkyl Substances Overview: A Quick Reference Guide
    The PFAS Rule regulates levels of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), ...
  56. [56]
    Per- and Polyfluoroalkyl Substances (PFAS) | US EPA
    On May 14, 2025, EPA announced the agency will keep the current National Primary Drinking Water Regulations (NPDWR) for PFOA and PFOS. As part of this action, ...Missing: Perfluorohexane | Show results with:Perfluorohexane
  57. [57]
    Hexane, 1,1,1,2,2,3,3,4,4,5,5,6,6,6-tetradecafluoro- - Substance ...
    The IUPAC name, InChI, and structure SMILES data on this page has its source from the CompTox Chemicals Dashboard. Additional Metadata ...
  58. [58]
    [PDF] Statement on EU 517/2014 on Fluorinated Greenhouse Gases
    Regulation (EU) No 517/2014 aims to reduce fluorinated greenhouse gas emissions by phasing down HFCs, prohibiting use, and expanding regulations on leak tests, ...<|separator|>
  59. [59]
    PFAS Regulations | Anthesis Global
    Expected to enter into force on July 1, 2025, Denmark plans to ban PFAS in clothing, shoes, and waterproofing agents intended for consumers, to be extended to ...<|separator|>
  60. [60]
    [PDF] Therapeutic oxygen delivery by perfluorocarbon-based colloids - HAL
    Nov 26, 2022 · An effective, safe oxygen delivery system is still needed, including as a bridge to blood transfusion in case of emergency, trauma or shock; ...
  61. [61]
    Perfluorocarbon-based Oxygen Delivery - ResearchGate
    Aug 10, 2025 · PFCs have long been used in patients as oxygen carriers because they are biochemically inert and easily expelled through the circulatory system ...
  62. [62]
    Perflexane - an overview | ScienceDirect Topics
    Perflexane is defined as a perfluorocarbon compound, specifically tetradecafluorohexane, with the empirical formula C6F14, notable for its use as a solvent ...
  63. [63]
    [PDF] Perfluorocarbons as Oxygen Dissolving and Delivering Agent
    Feb 16, 2025 · These PFC-based oxygen carriers are known as "blood substitutes" [3]. 3.1.1. Reason for PFCs able to dissolve more amount of oxygen. PFCs are ...<|separator|>
  64. [64]
    Current Approaches in the Classification of PFAS: An Overview - 2025
    Mar 12, 2025 · This “precautionary principle” asserts that short-chain PFAS are not inherently safer than long-chain ones, as they are even more mobile in the ...
  65. [65]
    Perfluorohexane - an overview | ScienceDirect Topics
    Perfluorohexane is defined as a common liquid perfluoro-n-alkane that exhibits hydrophobic properties, low solubility in water, and high vaporization from water ...
  66. [66]
    Fluoropolymers and PFAS: New Study Calls for Science-Based ...
    Sep 15, 2025 · Peer-reviewed research shows fluoropolymers like PFPEs are stable, low-risk, and distinct from other PFAS, supporting science-based ...
  67. [67]
    and Polyfluoroalkyl Substances (PFAS): Harms, Limitations ... - NIH
    The objective of this review is to provide insights into the toxic potential of PFAS, their exposure, and related mechanisms.
  68. [68]
    [PDF] Full-PFAS-Guidance-12.11.2023.pdf
    ... PFAS Technical and Regulatory Guidance Document. The last full update of this ... perfluorocarbons, that contain a perfluoroalkyl moiety with three or ...
  69. [69]
    An Overview of Potential Alternatives for the Multiple Uses of Per
    Jan 24, 2025 · Synopsis. This study provides an overview of the availability of suitable alternatives to PFAS across their multiple uses.
  70. [70]
  71. [71]
    PFAS-Free Precision Solvent Cleaner for Electronics
    Jun 5, 2025 · PFAS-Free ProSolv®5408e is a high performance precision cleaning solvent for electronics and electrical components.
  72. [72]
    Perfluorohexane-Loaded Polymeric Nanovesicles with Oxygen ...
    Mar 29, 2020 · We constructed a highly efficient liquid fluorocarbon-encapsulated polymeric nanovesicle for enhanced sonodynamic efficacy as well as tumor hypoxia relief.
  73. [73]
    EGFR-Targeted Perfluorohexane Nanodroplets for Molecular ... - MDPI
    Perfluorocarbon nanodroplets offer an alternative to gaseous microbubbles as contrast agents for ultrasound imaging.
  74. [74]
    Liquid Breathing with Perfluorohexane for Medical Applications
    Mar 24, 2025 · Therapeutic applications: In medical treatments, perfluorohexane's inertness and ability to provide gas exchange could aid in therapies for ...
  75. [75]
    Emerging PFAS alternatives: Unveiling environmental fates and ...
    They are widely used in industrial and consumer products such as fire-fighting foams, non-adhere coatings, and waterproof fabrics due to their unique C–F bond ...Missing: perfluorohexane | Show results with:perfluorohexane