An Expert Monograph on Phenol (Carbolic Acid)

Executive Summary

Phenol (CAS: 108-95-2; DrugBank ID: DB03255), also known historically as carbolic acid, is an aromatic organic compound of profound significance in the annals of medicine and modern industry. This report provides a comprehensive, multi-disciplinary analysis of phenol, synthesizing data on its chemical properties, historical context, industrial production, pharmacology, clinical applications, toxicology, and global regulatory status. The central theme that emerges is the compound's pronounced duality: at low, controlled concentrations, it functions as a valuable antiseptic and local anesthetic, yet at higher concentrations, it is a potent, non-specific protoplasmic poison capable of causing severe corrosive injury and systemic toxicity.

Historically, phenol's application by Joseph Lister in the 1860s as an antiseptic agent revolutionized surgery, providing the first practical validation of germ theory and dramatically reducing post-operative mortality. This foundational role contrasts with its modern utility, which is confined to highly specialized and niche applications. Industrially, phenol is a critical chemical precursor, produced predominantly via the Cumene (Hock) process, a method that intrinsically links its supply and cost to the co-production of acetone, creating a notable economic interdependence with diverse industrial sectors.

Pharmacologically, phenol's mechanism of action is rooted in its ability to penetrate cell membranes and denature proteins. This non-specific cytotoxicity underlies its efficacy as a broad-spectrum antiseptic, a local anesthetic via nerve conduction blockade, and a neurolytic agent through targeted chemical destruction of nerve tissue. Its pharmacokinetic profile—characterized by rapid absorption from all routes, wide systemic distribution, and a short half-life—is the primary driver of its acute toxicity, which can manifest as severe cardiovascular, central nervous system, and respiratory effects.

Clinically, phenol is most widely recognized as the active ingredient in over-the-counter oromucosal sprays for the symptomatic relief of sore throat. Its more specialized, professionally administered uses leverage its destructive capabilities, including chemical neurolysis for managing intractable spasticity and chronic pain, and chemical matrixectomy in podiatry for treating ingrown nails. These applications underscore a therapeutic paradigm shift from preservation to controlled tissue ablation.

The toxicology of phenol is well-documented. It is highly corrosive to tissues, and its local anesthetic properties can dangerously mask the severity of a chemical burn, leading to prolonged exposure and increased risk of systemic absorption. While not classified as a human carcinogen by major international agencies, it has demonstrated tumor-promoting activity in animal models.

The global regulatory landscape for phenol is fragmented and highly context-dependent. Agencies such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Australian Therapeutic Goods Administration (TGA) have established distinct regulations based on concentration, formulation, and intended use. Phenol is approved for specific OTC and prescription medical uses but has been restricted or prohibited in other applications, such as consumer antiseptic washes and cosmetics, reflecting a nuanced, ongoing assessment of its risk-benefit profile. This monograph consolidates these disparate data points into a single, authoritative reference for researchers, clinicians, and regulatory professionals.

Compound Identification and Physicochemical Properties

Nomenclature, Synonyms, and Key Identifiers

The compound is officially designated by the International Union of Pure and Applied Chemistry (IUPAC) as Phenol.[1] However, its long history and widespread use have led to a variety of synonyms that are crucial for navigating historical, medical, and chemical literature. The most prominent of these is Carbolic Acid, a name intrinsically linked to its pioneering use as a surgical antiseptic.[2] Other common chemical and trivial names include Benzenol, Hydroxybenzene, Monohydroxybenzene, Oxybenzene, Phenyl alcohol, Phenyl hydroxide, Phenic Acid, and Phenylic Acid.[1]

To ensure unambiguous identification in scientific and regulatory databases, phenol is assigned a series of unique identifiers:

• DrugBank ID: DB03255 [3]
• CAS (Chemical Abstracts Service) Registry Number: 108-95-2 [1]
• PubChem Compound ID (CID): 996 [1]
• ChEBI (Chemical Entities of Biological Interest) ID: CHEBI:15882 [1]

These identifiers serve as a stable reference across different scientific disciplines and international databases, linking the compound to a wealth of experimental and regulatory data.

Chemical Structure and Molecular Characteristics

Phenol is the simplest member of the phenol family of organic compounds, characterized by a hydroxyl group () bonded directly to a carbon atom that is part of an aromatic ring.[4] Its structure consists of a phenyl group () attached to a hydroxyl group, giving it the molecular formula .[1] The molecular weight of phenol is consistently reported as 94.11 g/mol, with more precise measurements at 94.1112 g/mol.[1]

The direct attachment of the hydroxyl group to the aromatic ring confers unique chemical properties upon the molecule, distinguishing it significantly from aliphatic alcohols. The oxygen atom's lone pair of electrons delocalizes into the benzene ring's pi system, which increases the polarity of the O-H bond and stabilizes the corresponding conjugate base (the phenoxide ion) through resonance. This electronic effect is responsible for phenol's notable acidity compared to alcohols.[4]

For computational chemistry and database interoperability, the structure is represented by standardized line notations:

• SMILES (Simplified Molecular-Input Line-Entry System): OC1=CC=CC=C1 [1]
• InChIKey (International Chemical Identifier Key): ISWSIDIOOBJBQZ-UHFFFAOYSA-N [1]

Physicochemical Properties and Analytical Profile

The physical and chemical properties of phenol are critical determinants of its industrial handling, pharmaceutical formulation, biological activity, and toxicity.

Physical State, Appearance, and Odor

Phenol's physical state is highly dependent on purity and temperature. In its pure form, it is a colorless-to-white, crystalline solid.4 However, upon exposure to air and light, it undergoes oxidation, leading to a characteristic change in color to light-pink, red, or eventually yellowish-brown.5 This color change is a direct visual indicator of degradation and impurity. The commercial product is often supplied as a liquid, which may be an aqueous solution or the molten solid.4 Notably, the solid liquefies when mixed with about 8% water.11

The compound has a distinct and easily recognizable odor, described as sickeningly sweet, tarry, medicinal, and acrid.[4] The odor threshold is very low, with detection reported at concentrations well below those associated with harmful effects, serving as an important sensory warning of its presence.[5] It also possesses a sharp, burning taste.[11]

The variation in physical appearance from colorless to pink or red is more than a simple descriptive characteristic; it serves as a crucial first-pass indicator of the compound's purity, age, and storage conditions. Pure phenol is colorless.[11] The observed reddening upon exposure to air and light is a result of oxidation, which can form quinones and other colored polymeric degradation products.[5] These impurities may possess different toxicological profiles and chemical reactivities compared to pure phenol. Therefore, for both laboratory and clinical applications, the color of a phenol sample provides vital information about its chemical integrity and potential for altered behavior or increased hazard.

Solubility, Acidity, and Reactivity

Phenol is moderately soluble in water, with approximately 8.4 g dissolving in 100 mL.4 It is very soluble in a range of organic solvents, including ethanol, ether, chloroform, and glycerol, as well as in aqueous alkali hydroxide solutions.5

As an aromatic alcohol, phenol is a weak acid. Its aqueous solutions are acidic, with a pH of approximately 6.0.[1] It is significantly more acidic than aliphatic alcohols due to the resonance stabilization of the phenoxide anion formed upon deprotonation.[4] This enhanced acidity allows it to react with strong bases like sodium hydroxide.[4]

Phenol is a highly reactive compound, particularly susceptible to electrophilic aromatic substitution. The hydroxyl group is a strongly activating, ortho/para-directing substituent, making the benzene ring highly nucleophilic.[4] This allows it to readily undergo reactions such as halogenation, nitration, and sulfonation.[4] It is corrosive to certain materials, including lead, aluminum, some plastics, and rubber.[11]

A particularly noteworthy and hazardous property of phenol is the paradoxical combination of its corrosivity and its local anesthetic effect. Corrosive substances typically elicit an immediate and intense pain response, which acts as a critical biological warning signal, prompting the individual to terminate the exposure. However, phenol's inherent local anesthetic properties numb the site of contact, masking this initial pain signal.[11] This neutralization of the body's primary defense mechanism can lead to dangerously prolonged contact time, as the individual may not be immediately aware of the ongoing tissue damage. Given that phenol is also rapidly absorbed through the skin, this unique combination of properties creates a significantly elevated risk profile, facilitating the potential for both severe chemical burns and acute systemic toxicity before the extent of the exposure is fully realized.[13] This characteristic has profound implications for emergency response protocols, mandating rapid and thorough decontamination regardless of the presence or absence of pain.

Table 1: Physicochemical Properties of Phenol

Property	Value	Source(s)
Molecular Formula		1
Molecular Weight	94.11 g/mol	1
Physical Form	Colorless-to-pink crystalline solid; Liquid (commercial)	4
Odor	Sweet, tarry, acrid, medicinal	8
Melting Point	40.5 – 43 °C (104.9 – 110 °F)	4
Boiling Point	181 – 182 °C	1
Water Solubility	~8.4 g / 100 mL	4
Density (Solid)	~1.07 g/cm³ (9.9 lb/gal)	4
pH (Aqueous Solution)	~6.0	1
Vapor Pressure	0.357 mm Hg at 20°C	5
Flash Point	~80 °C (175 °F)	5

Analytical Profile

The definitive identification of phenol in laboratory settings relies on modern analytical techniques. Spectrometric data provides a unique chemical "fingerprint." For DrugBank entry DB03255, specific analytical spectra are available for reference, including:

• Gas Chromatography-Mass Spectrometry (GC-MS): The spectrum is identified by the Splash Key splash10-006w-9000000000-c8b41f2899ca8cc9d4bc.[17]
• Mass Spectrum (Electron Ionization): The spectrum from the National Institute of Standards and Technology (NIST) database is identified by the Splash Key splash10-00kf-9000000000-40b376f4e58c23369a01.18 These data are essential for quality control, forensic analysis, and metabolic studies.

Historical Context and Industrial Synthesis

The Advent of Antiseptic Surgery: Lister's Carbolic Acid

The history of phenol is inextricably linked to one of the most significant advancements in modern medicine: the development of antiseptic surgery. Prior to the mid-19th century, surgical outcomes were grim, with postoperative mortality rates from infections like sepsis and gangrene being exceptionally high.[19] The prevailing miasma theory, which attributed disease to "bad air," offered no effective means of prevention.

This paradigm began to shift with the work of French chemist Louis Pasteur, who demonstrated that microscopic organisms, or "germs," were responsible for fermentation and putrefaction.[20] Joseph Lister, a British surgeon, was profoundly influenced by Pasteur's germ theory and hypothesized that these same airborne microbes were the cause of rampant wound infections in surgical wards.[20] Lister reasoned that if germs could be prevented from entering a wound, infection could be avoided.

While German physician Friedrich Küchenmeister is credited with the first use of phenol as a wound dressing in 1860, it was Lister who systemized its application into a coherent surgical methodology.[22] On August 12, 1865, Lister conducted his landmark first antiseptic surgery. He treated a seven-year-old boy with a compound leg fracture by applying a dressing soaked in carbolic acid (the common name for phenol at the time) directly to the wound. The wound healed successfully without any signs of suppuration or gangrene.[19]

Lister's method evolved to include the sterilization of surgical instruments, sutures, the patient's skin, and the surgeon's own hands with carbolic acid solutions.[20] The impact was immediate and dramatic. In his surgical ward, the mortality rate from amputations plummeted from 45% to just 15%.[19] This work, published in The Lancet in 1867, provided the first practical and life-saving application of germ theory, establishing the foundational principles of antisepsis and transforming surgery into a far safer discipline. For this contribution, Lister is widely regarded as the "father of modern surgery".[20]

The history of phenol's medical use provides a compelling case study in the evolution of risk-benefit analysis. In the 1860s, the risk of death from postoperative infection was so high that the benefits of using a known caustic agent like carbolic acid to prevent it were overwhelmingly positive. As scientific knowledge advanced and safer, more effective antiseptics were developed (such as less-toxic phenol derivatives like n-hexylresorcinol), the risk-benefit calculation for phenol shifted dramatically.[19] Its inherent toxicity, once an acceptable trade-off, became a prohibitive liability for general antiseptic use. Consequently, its modern applications are restricted to highly specific scenarios where its potent, destructive properties are precisely the desired therapeutic effect, such as in neurolysis—a stark contrast to its original preservative role.[26]

Modern Industrial Production: The Cumene Process and its Economic Drivers

While phenol was first extracted from coal tar, today's global demand is met through large-scale industrial synthesis from petroleum-derived feedstocks.[4] The predominant method, accounting for the vast majority of worldwide production, is the three-stage Cumene process, also known as the Hock process.[27] This method, developed independently in the 1940s, is valued for its efficiency in converting two inexpensive starting materials, benzene and propylene, into two more valuable products: phenol and acetone.[29]

The chemistry of the Cumene process involves three main steps:

1. Alkylation: Benzene is reacted with propylene in a Friedel–Crafts alkylation reaction to produce cumene (isopropylbenzene). This step is typically carried out at high temperature and pressure in the presence of an acid catalyst, such as phosphoric acid.[29]
2. Oxidation: The cumene is then oxidized using oxygen from the air. This reaction, an autoxidation, selectively forms cumene hydroperoxide.[29]
3. Cleavage: In the final step, the cumene hydroperoxide is treated with an acid (e.g., sulfuric acid), which catalyzes a rearrangement and cleavage reaction (the Hock rearrangement). This reaction yields the two final products, phenol and acetone.[29]

Phenol is a vital industrial commodity, serving as a precursor in the synthesis of a vast array of materials. Its largest applications are in the production of phenolic resins (such as Bakelite), bisphenol A (a key monomer for polycarbonate plastics and epoxy resins), and caprolactam (a precursor to nylon 6).[11] It is also used to manufacture numerous other chemicals, including herbicides and pharmaceuticals like aspirin.[12] In 2022, global production of phenol via the Cumene process reached nearly 10.8 million tonnes.[29]

A critical aspect of this production method is its inherent economic interdependence. The Cumene process produces phenol and acetone in a fixed stoichiometric ratio. As a result, the process is only economically sustainable when there is robust market demand for both chemicals.[29] Acetone is a major industrial solvent and a precursor for products like methyl methacrylate, which is used in acrylic plastics.[30] This co-production model creates a potential supply chain vulnerability. A significant downturn in industries that consume large quantities of acetone, such as the automotive, construction, or electronics sectors, could depress acetone prices and lead producers to scale back overall production. This, in turn, would constrict the supply and potentially increase the cost of phenol, with downstream effects on all dependent industries, including the niche pharmaceutical sector that relies on phenol for specific applications. This reveals a complex dependency where the availability of a medical compound is linked to the economic health of seemingly unrelated industrial markets.

Comprehensive Pharmacological Profile

Mechanism of Action: A Multi-faceted Analysis

The pharmacological and toxicological actions of phenol are all derived from its fundamental property as a non-specific protoplasmic poison.[13] Its chemical structure, featuring both a hydrophilic hydroxyl group and a lipophilic benzene ring, allows it to readily partition into and disrupt cellular membranes. This leads to the denaturation of essential proteins and enzymes, ultimately causing cell dysfunction and death.[25] This core mechanism manifests in distinct ways depending on the concentration and context of its application, primarily as an antiseptic/disinfectant and as a neurolytic/local anesthetic agent.

Antiseptic and Disinfectant Properties

Phenol's historical reputation is built on its efficacy as a broad-spectrum antimicrobial agent, active against a wide range of bacteria (both Gram-positive and Gram-negative), fungi, and some viruses.[7] Its antiseptic action is multifaceted:

• Membrane Damage: At bactericidal concentrations, phenol's primary target is the cytoplasmic membrane. It intercalates into the lipid bilayer, disrupting its structure and increasing its permeability. This leads to a progressive leakage of vital intracellular components, such as potassium ions () and nucleic acids (identified by their 260 nm UV absorbance), which is a key indicator of irreversible membrane damage.[33]
• Protein Denaturation: Phenol denatures and coagulates cellular proteins, including essential enzymes required for metabolism and cell wall synthesis.[16] This inactivation of enzyme systems disrupts critical biological processes, contributing to cell death. At higher concentrations, this effect becomes more pronounced, leading to the gross coagulation of all cytoplasmic constituents.[34]

The antimicrobial activity of phenol is highly dependent on its concentration. It is generally considered bacteriostatic (inhibiting growth) at concentrations between 0.1% and 1%, and bactericidal and fungicidal at concentrations between 1% and 2%. It is only slowly effective against highly resistant bacterial spores, requiring a 5% solution and prolonged contact time (e.g., 48 hours for anthrax spores).[7]

Neurolytic and Local Anesthetic Effects

When used in a clinical setting for nerve blocks, phenol's mechanism shifts from antimicrobial to neurotoxic.

• Chemical Neurolysis: When injected in high concentrations (typically 3% to 7%) in close proximity to a nerve, phenol acts as a neurolytic agent, causing non-selective chemical destruction of nerve tissue.[7] This process is a form of controlled chemical ablation. The mechanism involves potent proteolysis, where the phenol dissolves the nerve tissue on contact.[7] Histologically, this manifests as the denaturation of axonal and blood vessel proteins, loss of cellular fatty content, separation of the protective myelin sheath from the axon, and axonal swelling (edema).[15] The overall effect, which may be compounded by localized ischemia, is a complete and often permanent blockade of nerve conduction.[36]
• Local Anesthesia: Paradoxically, phenol also possesses a rapid-onset local anesthetic effect.[7] This action is believed to result from an immediate, selective effect on smaller, unmyelinated nerve fibers (such as C-fibers that transmit pain signals), blocking their ability to conduct impulses before the slower, more destructive neurolytic process affects larger motor fibers.[36] This anesthetic effect occurs within minutes of application and is responsible for the initially painless nature of phenol burns and injections.[14]

The pharmacology of phenol is not static but exists on a spectrum fundamentally defined by its concentration at the site of action. At very low concentrations (<1%), it is primarily bacteriostatic.[32] In the range used for OTC oromucosal products (~1.4%), it functions as a topical local anesthetic and mild antiseptic.[38] At the higher concentrations employed for neurolysis (>5%), it transforms into a potent proteolytic and neurolytic agent, causing irreversible tissue destruction.[7] This demonstrates that phenol's pharmacological classification—from anesthetic to antiseptic to chemical ablative—is a direct function of its concentration, a principle that governs its entire therapeutic and toxicological profile.

Pharmacodynamics

The pharmacodynamic profile of phenol is characterized by direct, non-receptor-mediated chemical actions on biological tissues rather than interactions with specific molecular targets like receptors or channels.[40] Its effects are a direct consequence of its physicochemical properties.

As an anesthetic, its pharmacodynamic effect is the blockade of nerve conduction through direct interaction with and disruption of nerve fiber membranes, with a rapid onset of 5 to 10 minutes.[7] As an antiseptic, the effect is the physical disruption of microbial cell membrane integrity and the denaturation of intracellular proteins.[34] As a neurolytic agent, the primary pharmacodynamic outcome is localized tissue necrosis via proteolysis and protein coagulation.[7]

The time course of these effects varies. The local anesthetic action is immediate and transient, providing initial numbness. In contrast, the full therapeutic effect from neurolysis is delayed; it cannot be properly evaluated until 24 to 48 hours after the procedure, once the initial anesthetic effect has resolved, and may not become clinically maximal for 3 to 7 days as the process of nerve degeneration completes.[36]

Pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion (ADME)

The pharmacokinetic properties of phenol are central to understanding its potential for systemic toxicity.

• Absorption: Phenol is rapidly and efficiently absorbed into the systemic circulation following all routes of exposure—inhalation, ingestion, and dermal contact.[13] Dermal absorption is particularly efficient, even through intact skin, making it a primary route of concern in occupational settings and accidental exposures.[14]
• Distribution: Following absorption, phenol distributes widely and rapidly throughout the body, typically within minutes.[25] Initial distribution favors highly perfused organs. Studies show that 15 minutes after exposure, the liver contains the highest concentration. By approximately 80 minutes post-administration, it is found to be uniformly distributed in the liver, blood, kidneys, and lungs, as well as in the heart, spleen, and other tissues.[7] In cases of fatal poisoning, significant concentrations have been detected in the brain, muscle, and bile, confirming its ability to cross the blood-brain barrier and distribute into deep tissues.[43]
• Metabolism: Phenol undergoes extensive first-pass metabolism in the liver, with additional metabolic activity occurring in the gut and kidney.[25] The metabolic pathways are similar to those of acetaminophen. The two primary routes are Phase II conjugation reactions:

1. Sulfonation: Conjugation with sulfate to form phenyl sulfate.
2. Glucuronidation: Conjugation with glucuronic acid to form phenyl glucuronide. A minor pathway involves Phase I oxidation via the cytochrome P450 system (specifically CYP2E1) to form reactive metabolites like hydroquinone and catechol, which are then also conjugated.7 The metabolic pathway is saturable; at lower doses, sulfation is the predominant route, but as the dose increases, this pathway becomes saturated, and metabolism shifts increasingly toward glucuronidation and oxidation.43

• Excretion: The water-soluble conjugated metabolites are primarily eliminated from the body via the kidneys in the urine.[7] The elimination half-life is short, reported to be in the range of 0.5 to 4.5 hours, indicating that the compound is cleared from the body relatively quickly.[16] In some cases of poisoning, phenol metabolites can impart a characteristic dark or blue-green color to the urine, which can be a diagnostic clue.[25]

The combination of phenol's pharmacokinetic properties is the key driver of its acute systemic toxicity. The rapid absorption from all routes, coupled with its wide and rapid distribution to critical organs like the heart and central nervous system, allows a large toxic burden to reach target sites almost immediately after exposure.[7] While the metabolic clearance is also rapid, a significant exposure can deliver an initial peak plasma concentration that overwhelms the body's primary metabolic pathway (sulfation).[43] It is this high initial peak concentration, preceding effective clearance, that precipitates the most dangerous acute systemic effects, such as cardiac arrhythmias, seizures, and respiratory arrest.[13] The primary danger of phenol, therefore, lies not in chronic accumulation, but in the rapid, high-magnitude systemic shock it can deliver.

Clinical Applications and Therapeutic Uses

The clinical utility of phenol has evolved significantly from its origins as a general antiseptic. Modern applications are highly specialized, leveraging its distinct properties at different concentrations for specific therapeutic goals.

Oromucosal Formulations for Symptomatic Relief

The most widespread and publicly recognized medical use of phenol is as an active ingredient in over-the-counter (OTC) oromucosal products.[11]

• Indications: These products are indicated for the temporary, symptomatic relief of minor pain and irritation associated with sore throat, sore mouth, and canker sores.[7]
• Mechanism and Products: In these formulations, which typically contain a low concentration of phenol (e.g., 1.4% to 1.5%), the compound functions primarily as a topical oral anesthetic or analgesic, numbing the affected tissues to provide pain relief.[7] It also provides mild antiseptic action. Prominent brands include Chloraseptic, Ulcerease, and Castellani Paint, which are available in various dosage forms such as sprays, gargles, oral rinses, and lozenges.[12]

Chemical Neurolysis in Spasticity and Chronic Pain Management

A highly specialized application of phenol involves the injection of concentrated solutions to perform chemical neurolysis. This leverages its potent neurotoxic properties for therapeutic benefit.

• Indications: Phenol injections are used to treat focal muscle spasticity, a condition of muscle tightness and stiffness resulting from neurological disorders like spinal cord injury, stroke, or cerebral palsy.[7] It is also employed in the management of severe, intractable chronic pain, particularly pain of cancer origin, where conventional analgesics have failed.[26]
• Procedure: The procedure involves the precise injection of a sterile phenol solution (e.g., a 6% solution) directly onto or around a target peripheral nerve. For spasticity, the target is a motor nerve innervating a hypertonic muscle. For pain, the target is a sensory nerve transmitting the pain signals.[26] The phenol then causes localized, non-selective destruction of the nerve tissue, interrupting the pathological signals and providing long-term relief.[26]

This application represents a fundamental shift in the therapeutic paradigm for phenol. Its historical use as carbolic acid was preservative—to prevent infection and preserve tissue integrity.[19] In contrast, its modern neurolytic use is inherently destructive. The goal is the targeted, permanent ablation of problematic nerve tissue where such destruction provides the desired clinical outcome. This places phenol in a "last resort" therapeutic niche. Because nerve destruction is irreversible and carries significant risks, including the potential for worsening pain (deafferentation pain) or unintended motor paralysis, it is reserved for severe conditions that are refractory to safer, conventional treatments.[26]

Dermatological and Podiatric Applications

Phenol's caustic properties are also utilized in dermatology and podiatry for tissue ablation.

• Chemical Matrixectomy: Concentrated liquid phenol is a standard agent used by podiatrists to perform a chemical matrixectomy for the permanent treatment of recurrent or severe ingrown toenails.[12] After partial or total removal of the nail plate, phenol is carefully applied to the nail matrix (the tissue from which the nail grows). This chemically destroys the matrix cells, preventing that portion of the nail from regrowing.[12]
• Chemical Peels: In cosmetic and dermatological surgery, phenol is used as a deep chemical peeling agent.[4] It penetrates through the epidermis and into the dermis to remove layers of aged or damaged skin, promoting regeneration and improving the appearance of deep wrinkles or scars. This is a highly aggressive procedure associated with significant risks, including cardiac toxicity from systemic absorption, and is performed under strict medical supervision.

Miscellaneous Medical and Pharmaceutical Uses

Phenol has several other niche applications in medicine and pharmaceutics:

• Urology: Intraprostatic phenol injection has been described as a treatment for benign prostate hyperplasia (BPH). The injection induces chemical necrosis and subsequent shrinkage of the obstructive prostate tissue.[50] It has also been used for other urologic conditions like hemorrhagic cystitis.[50]
• Sclerosant: It can be used as a sclerosing agent to treat conditions like hydroceles by inducing inflammation and scarring that closes off the fluid-filled sac.[50] Its use as a sclerosant in medical imaging settings is now discouraged in some regions due to safety concerns.[51]
• Vaccine Preservative: In very small quantities, phenol serves as a preservative in several vaccines, including Pneumovax 23 (pneumonia), Typhim Vi (typhoid fever), and ACAM2000 (smallpox). Its role is to prevent bacterial growth and contamination within the multi-dose vials.[47] This is one of its few remaining "preservative" medical uses, where it protects the integrity of the pharmaceutical formulation itself.
• Disinfectant: While its use as a general medical antiseptic has been largely superseded by safer agents, it is still used to disinfect non-critical equipment and contaminated materials that are intended for disposal.[11]

Formulations, Dosage, and Administration

The formulation, dosage, and route of administration for phenol are critically important, as they directly determine its therapeutic effect and safety profile. The concentration of phenol can vary by more than an order of magnitude between different products, reflecting its diverse applications from a mild topical anesthetic to a potent chemical ablative agent.

Survey of Available Pharmaceutical Formulations

Phenol is available in a variety of pharmaceutical forms tailored to specific clinical needs:

• Oromucosal Sprays and Rinses: These are the most common over-the-counter (OTC) formulations. They are aqueous solutions containing low concentrations of phenol, typically 1.4% or 1.5%, intended for topical application to the mucous membranes of the throat and mouth.[38]
• Injectable Solutions: For medical procedures like neurolysis, phenol is prepared as a sterile solution for injection. A common concentration is 6% phenol in water.[40] An oily phenol injection, containing 250 mg in 5 mL, is also available for specific applications like sclerotherapy.[56] The choice of vehicle (e.g., water vs. glycerin vs. oil) is a critical aspect of the formulation. For neurolysis, mixing phenol with glycerin creates a viscous, hyperbaric solution that diffuses slowly and remains localized at the injection site.[36] This is a crucial formulation strategy that acts as an engineering control to minimize the primary risk of the procedure—the unintended spread of the neurolytic agent to adjacent, non-target nerves.
• Topical Solutions: Various topical solutions exist for external use. Castellani Paint Modified is a prescription product containing 1.5% phenol along with other agents like resorcinol and basic fuchsin for antiseptic and antifungal use.[46] Highly concentrated 80% phenol solutions are used by specialists for podiatric procedures but are classified as Schedule 6 poisons in jurisdictions like Australia, with highly restricted storage and handling requirements.[51]
• Lozenges: Some OTC throat lozenges have historically contained phenol or related compounds, although many modern formulations now utilize other local anesthetics such as benzocaine.[53]

Clinical Dosing Regimens by Indication and Patient Population

Dosing regimens for phenol are highly specific to the product, indication, and patient age.

Table 2: Summary of Phenol Formulations and Dosages by Indication

Indication	Formulation	Patient Population	Dosage and Administration	Key Warnings / Max Dose	Source(s)
Sore Throat / Mouth Pain	Oromucosal Spray (e.g., 1.4% Chloraseptic)	Adults & Children ≥ 3 yrs	Apply 1 spray to affected area; hold for 15 sec, then spit out. Repeat every 2 hours as needed.	Do not use for >2 days without medical advice. Supervise children <12 yrs.	38
Sore Throat / Mouth Pain	Oromucosal Spray (e.g., Chloraseptic)	Adults & Children > 12 yrs	Apply 5 sprays to affected area. Repeat every 2 hours as needed.	Do not exceed recommended dosage.	53
Sore Throat / Mouth Pain	Oromucosal Spray (e.g., Chloraseptic)	Children 2-12 yrs	Apply 3 sprays to affected area. Repeat every 2 hours as needed.	Supervise use.	53
Sore Throat / Mouth Pain	Oral Rinse / Gargle (e.g., Ulcerease)	Adults & Children > 3 yrs	Gargle or swish for 15 sec, then spit out. Repeat every 2 hours as needed.	Do not use more than 12 times per day (adults).	45
Sore Throat / Mouth Pain	Lozenge (e.g., Cepastat)	Adults & Children > 12 yrs	Dissolve up to 2 lozenges slowly in mouth every 2 hours as needed.	N/A	53
Sore Throat / Mouth Pain	Lozenge (e.g., Cepastat)	Children 6-12 yrs	Dissolve 1 lozenge slowly in mouth every 2 hours as needed.	Do not exceed 18 lozenges / 24 hours.	53
Focal Spasticity / Chronic Pain	Injection (e.g., 6% Phenol in Water)	Adults	Dose is specific to target nerve (e.g., 100-500 mg per nerve).	Total dose should not exceed 1200 mg per session. Administer with cardiovascular monitoring.	37

Toxicology and Safety Profile

The potent biological activity of phenol makes it a significant toxicological hazard. A thorough understanding of its safety profile is essential for its handling in industrial, laboratory, and clinical settings. It is classified as a protoplasmic poison, capable of causing severe local and systemic effects through all routes of exposure.[13]

Systemic and Local Toxicity: Acute and Chronic Exposure

Phenol's toxicity is well-documented from case reports of accidental and occupational exposures, as well as animal studies. Lethal outcomes have been reported from the ingestion of as little as 1 gram in an adult and from repeated dermal applications of small doses in infants.[14]

Local and Dermal Effects

Direct contact with phenol, even in dilute solutions (1-2%), can cause severe irritation and chemical burns if contact is prolonged.13 A characteristic feature of dermal exposure is the initial formation of a white, precipitated protein patch on the skin, which soon turns red and eventually sloughs off, leaving a brown stain.13 A critical and dangerous aspect of these burns is that they are often initially painless due to phenol's local anesthetic properties, which can delay recognition of the injury and lead to more extensive damage and systemic absorption.14 If left on the skin, phenol penetrates rapidly, leading to deep tissue necrosis and potentially gangrene.13

Systemic Effects of Acute Exposure

Systemic poisoning can occur rapidly following significant exposure by any route and is a medical emergency. The clinical presentation often involves a biphasic central nervous system (CNS) response, with initial, transient stimulation (e.g., muscle tremors, seizures) followed rapidly by profound CNS depression, leading to loss of consciousness, coma, and respiratory arrest.13 Other major systemic effects include:

• Cardiovascular: Severe cardiac arrhythmias, including ventricular tachycardia and bradycardia, as well as hypotension and cardiovascular collapse, are well-documented and often a primary cause of death.[16]
• Respiratory: Inhalation of vapors causes irritation of the respiratory tract. Severe exposure can result in laryngeal edema, chemical pneumonitis, and acute pulmonary edema.[13]
• Gastrointestinal: Ingestion causes severe corrosive injury to the mouth, esophagus, and stomach, along with symptoms of nausea, vomiting, and diarrhea.[16]
• Renal and Hematologic: Acute renal failure can occur. Methemoglobinemia (a condition where hemoglobin cannot effectively release oxygen) and hemolytic anemia have also been reported.[13]

Effects of Chronic Exposure

Long-term, lower-level exposure, typically in occupational settings, has been associated with a different constellation of systemic effects. Reported symptoms in chronically exposed humans include anorexia, progressive weight loss, diarrhea, vertigo, excessive salivation, and a dark coloration of the urine.59 Evidence also points to chronic damage to the liver and kidneys.43

Genotoxicity, Carcinogenicity, and Reproductive Effects

The long-term risks of phenol exposure, particularly its potential to cause cancer, have been extensively studied, though some questions remain.

• Carcinogenicity: Based on the available human and animal data, major international health agencies have concluded that there is inadequate evidence to classify phenol as a human carcinogen. The International Agency for Research on Cancer (IARC) places phenol in Group 3: Not classifiable as to its carcinogenicity to humans.[43] Similarly, the U.S. Environmental Protection Agency (EPA) classifies it as Group D: Not classifiable as to human carcinogenicity.[59] This classification does not affirm safety but rather reflects a lack of conclusive evidence from human epidemiological studies.
• Tumor Promotion: Despite the lack of evidence as a primary carcinogen, several animal studies have demonstrated that phenol applied to the skin can act as a tumor promoter, meaning it can enhance the development of tumors initiated by another carcinogenic substance.[5] This finding suggests a potential hazard that warrants caution.
• Reproductive and Developmental Effects: There are no definitive studies on the reproductive or developmental effects of phenol in humans. Some research has suggested a positive association between parental exposure to phenol and its related compounds and the risk of spontaneous abortion.[7] Animal studies have shown adverse developmental effects, such as reduced fetal body weight and growth retardation, but typically only at exposure levels that also produced signs of toxicity in the mother. It is not generally considered to be a primary teratogen.[59]

Occupational Health, Exposure Limits, and Management of Poisoning

Protecting workers and managing accidental exposures are critical components of phenol's safety profile.

Occupational Exposure Limits

To minimize the risk of adverse health effects in the workplace, regulatory agencies have established occupational exposure limits (OELs). These limits consistently include a "skin" designation, highlighting that dermal absorption is a significant route of exposure that must be prevented through appropriate personal protective equipment (PPE).

Table 3: International Occupational Exposure Limits for Phenol

Agency	Limit Type	Value (ppm)	Value (mg/m³)	Notation(s)	Source(s)
OSHA (USA)	PEL (8-hr TWA)	5 ppm	19 mg/m³	Skin	8
NIOSH (USA)	REL (10-hr TWA)	5 ppm	19 mg/m³	Skin	8
NIOSH (USA)	Ceiling (15-min)	15.6 ppm	60 mg/m³	Skin	8
NIOSH (USA)	IDLH	250 ppm	-	-	8
ACGIH (USA)	TLV (8-hr TWA)	5 ppm	19 mg/m³	Skin	8
Safe Work Australia	TWA	1 ppm	4 mg/m³	Skin absorption	5

Abbreviations: OSHA (Occupational Safety and Health Administration); NIOSH (National Institute for Occupational Safety and Health); ACGIH (American Conference of Governmental Industrial Hygienists); PEL (Permissible Exposure Limit); TWA (Time-Weighted Average); REL (Recommended Exposure Limit); TLV (Threshold Limit Value); IDLH (Immediately Dangerous to Life or Health).

Management of Exposure and Poisoning

There is no specific antidote for phenol poisoning; treatment is focused on rapid decontamination and supportive care of cardiovascular and respiratory functions.13

• Decontamination: Rapid and thorough decontamination is the single most critical intervention. For dermal exposure, the preferred method is to immediately wipe the affected area with a sponge or towel soaked in a low-molecular-weight polyethylene glycol (LMW PEG), which can effectively solubilize and remove the phenol from the skin.[25] This approach is based on a sophisticated understanding of phenol's physicochemical properties; LMW PEG is a more effective solvent than water for this lipophilic compound and can better prevent its further partitioning into the skin. If LMW PEG is unavailable, the alternative is to flush the area with copious amounts of water for at least 15 minutes.[14] It is important to note that using only small amounts of water is discouraged, as it may paradoxically increase absorption by acting as a vehicle before sufficient dilution is achieved.[25]
• First Aid: For eye contact, immediate and continuous flushing with an emergency eyewash for at least 15 minutes is required. For ingestion, vomiting should not be induced; if the victim is conscious, they may be given 4-8 ounces of milk or water. For inhalation, the victim should be moved to fresh air. In all cases of significant exposure, immediate emergency medical attention is imperative.[14]

Global Regulatory Landscape

The regulation of phenol as a pharmaceutical ingredient, food additive, and industrial chemical is complex and varies significantly across different international jurisdictions. Regulatory decisions are not based on the substance in isolation but are highly dependent on the context of its use, including its concentration, formulation, route of administration, and the target population.

United States Food and Drug Administration (FDA)

In the United States, the FDA's regulation of phenol is multifaceted:

• Over-the-Counter (OTC) Drugs: The FDA permits the use of phenol as an active ingredient in OTC oral healthcare products, specifically as an oral anesthetic/analgesic for the temporary relief of sore throat and mouth pain. Products like Chloraseptic sore throat spray, containing approximately 1.4% phenol, are marketed under the OTC drug monograph system.[39] This system allows products to be marketed without a specific New Drug Application (NDA) as long as they comply with established standards for ingredients, doses, and labeling.[39]
• Prohibited Uses: A significant regulatory action occurred in 2016 when the FDA issued a final rule that prohibited the marketing of consumer antiseptic washes (e.g., antibacterial hand soaps and body washes) containing phenol and 18 other active ingredients. The agency concluded that manufacturers had not provided sufficient data to demonstrate that these products were both safe for long-term daily use and more effective than plain soap and water.[49]
• Prescription Drugs and Medical Devices: Phenol is used as an active ingredient in sterile injectable products, such as 6% solutions prepared by FDA-registered compounding facilities for neurolysis.[55] It is also a component of FDA-cleared medical devices, such as the Apdyne Phenol Applicator Kit, which is classified as a Class I device for ear, nose, and throat procedures.[64]
• Food and Water Regulation: The FDA includes phenol on its list of indirect food additives, permitting its use in adhesives and coatings that may come into contact with food.[49] The agency has also established a maximum allowable concentration of 0.001 mg/L for phenol in bottled drinking water.[61]
• Classification Systems: Within the FDA's Global Substance Registration System (GSRS), phenol is assigned the Unique Ingredient Identifier (UNII) 339NCG44TV. It is cross-referenced with multiple Anatomical Therapeutic Chemical (ATC) classification codes, reflecting its diverse roles as a Local Anesthetic (N01BX03), an Antiseptic and Disinfectant (D08AE03), and a Sclerosing Agent (C05BB05).[6]

European Medicines Agency (EMA)

The regulatory framework for phenol in the European Union differs from that in the US.

• National Authorizations: Marketing authorizations for medicinal products containing phenol are not granted centrally by the EMA but are handled at the national level by the competent authorities of individual EU Member States.[66]
• Harmonized Safety Monitoring: Despite national authorizations, the EMA provides centralized pharmacovigilance oversight through the Periodic Safety Update Report Single Assessment (PSUSA) procedure. Phenol is subject to this process (Procedure: PSUSA/00009256/202004), which involves a single, harmonized assessment of safety data from all nationally authorized products containing the substance across the EU.[67] The existence of a PSUSA for a compound as old as phenol is significant; it demonstrates that regulatory agencies are applying modern, data-driven safety monitoring standards to all authorized substances, regardless of their age, ensuring that the regulatory status of even the oldest drugs remains dynamic and responsive to new evidence. The most recent published outcome for the phenol PSUSA was "Maintenance," indicating that no major changes to the marketing authorizations were deemed necessary at the time of the review.[67] The EMA has published a comprehensive list of all nationally authorized medicinal products containing phenol as part of this procedure.[67]
• Cosmetics Regulation: The EU Cosmetics Directive prohibits the inclusion of phenol as an ingredient in cosmetic products sold within the EU.[49]

Australian Therapeutic Goods Administration (TGA)

In Australia, phenol is regulated by the TGA through a combination of product registration and substance scheduling.

• Scheduling: Phenol is listed in the Poisons Standard, also known as the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP). The schedule assigned depends on the concentration and intended use. Highly concentrated phenol (e.g., 80% solutions used for podiatric surgery) is classified as a Schedule 6 Poison, indicating a substance with a moderate potential for causing harm, the availability of which should be distinct from commercial poisons.[51] The scheduling of related compounds, such as aminophenols, is also carefully regulated, often with exemptions for low-concentration use in products like hair dyes.[68]
• Approved Products: Products containing phenol must be registered on the Australian Register of Therapeutic Goods (ARTG). Examples of registered products include "HAEMOROL oily phenol 250mg/5ml injection vial" (ARTG ID 161711), intended for medical procedures, and "NORMAL SALINE/PHENOL Diluent" (ARTG ID 32490).[56]
• Clinical Use Restrictions: Reflecting safety concerns, Australian health authorities have issued strong advisories to remove concentrated 80% phenol from general clinical settings, such as medical imaging departments, to mitigate the risk of accidental injection. Its storage is recommended to be restricted to hospital pharmacy services where appropriate and safe dilutions can be prepared for specific, intended uses.[51]

The global regulatory approach to phenol clearly illustrates the principle of context-dependent regulation. The substance is not uniformly approved or banned. Instead, regulatory bodies conduct a detailed risk-benefit analysis for each specific use case. The FDA's approval of a 1.4% throat spray alongside its ban on phenol in consumer hand soap, and the TGA's registration of a prescription injection while classifying the concentrated form as a Schedule 6 Poison, highlight this nuanced approach. Regulators are assessing the complete picture—concentration, route of administration, duration of use, and user population—to create a mosaic of decisions rather than a single, monolithic verdict on the substance itself.

Synthesis and Expert Recommendations

This comprehensive analysis of phenol reveals a compound of stark contrasts. It is a molecule with a storied past that revolutionized medicine, yet its present-day utility is confined to highly specialized niches defined by its potent and hazardous properties. It is both a therapeutic agent and a formidable toxin, with the line between these two roles being determined almost exclusively by concentration and control.

The overarching risk-benefit profile of phenol is exceptionally steep. At the low concentrations found in OTC oromucosal products (~1.4%), the benefit of temporary symptomatic pain relief is achieved with a relatively low risk of systemic toxicity when used as directed. However, as the concentration increases for applications like neurolysis (e.g., 6%) or chemical matrixectomy (e.g., 80%), the potential for severe local tissue damage and life-threatening systemic effects rises dramatically. The clinical justification for these high-concentration uses rests on the principle of controlled destruction, where the therapeutic goal is the targeted ablation of pathological tissue (e.g., hyperactive nerves, nail matrix) that is refractory to safer interventions.

Based on this integrated analysis, the following recommendations are put forth for clinical practice and future research:

Considerations for Clinical Practice:

1. Strict Adherence to Protocols for High-Concentration Use: The administration of phenol for neurolysis, chemical peels, or podiatric procedures must be performed only by trained specialists in a controlled environment with appropriate cardiovascular monitoring and resuscitation capabilities. Strict adherence to established protocols regarding dose, concentration, and injection technique is paramount to minimize the risk of systemic toxicity and off-target tissue damage.
2. Enhanced Institutional Controls on Concentrated Phenol: Health service organizations should heed advisories to remove highly concentrated (e.g., 80%) phenol from general clinical areas. Its storage should be centralized within pharmacy services, where it can be securely managed and used to prepare specific, ready-to-use dilutions for approved indications. This measure is a critical safeguard against accidental administration, which has been associated with patient deaths.
3. Patient Education for OTC Products: While low-risk, users of OTC phenol-containing throat sprays should be counseled on the importance of adhering to the recommended dosage and duration of use (typically not to exceed 2 days without medical advice). They should be advised that these products provide only symptomatic relief and that persistent or worsening symptoms, especially when accompanied by fever or other systemic signs, warrant prompt medical evaluation.
4. Awareness of the "Painless Burn" Phenomenon: All healthcare and laboratory personnel handling phenol must be educated about its unique ability to cause severe corrosive burns that may not be immediately painful due to its local anesthetic effect. This underscores the absolute necessity of using appropriate personal protective equipment (PPE), including butyl rubber gloves and eye protection, and the critical importance of immediate, thorough decontamination after any suspected skin contact, regardless of the presence or absence of pain.

Directions for Future Research:

1. Development of Safer Neurolytic Alternatives: While effective, phenol's non-selectivity as a neurolytic agent is a significant drawback. Research should continue to focus on developing more targeted neurolytic or neuromodulatory agents that can achieve long-term relief from spasticity and chronic pain with a higher degree of safety and fewer off-target effects.
2. Elucidation of Tumor-Promoting Mechanisms: The classification of phenol as "not classifiable" regarding human carcinogenicity, combined with positive animal data for tumor promotion, represents a significant data gap. Further mechanistic studies are warranted to understand the molecular pathways through which phenol may promote tumorigenesis. This research would help to refine risk assessments for chronic, low-level occupational or environmental exposures.
3. Long-Term Outcomes of Clinical Applications: While the acute efficacy of phenol in neurolysis and matrixectomy is established, more robust, long-term data on patient outcomes are needed. This includes studies on the incidence and management of post-neurolysis deafferentation pain and the long-term success rates of chemical matrixectomy compared to other surgical techniques.

In conclusion, phenol remains a relevant, albeit highly specialized, tool in the modern medical armamentarium. Its continued use is a testament to its potent biological activity, but this same potency demands the utmost respect, caution, and control from all who handle and administer it.

Works cited

1. CAS RN 108-95-2 - Fisher Scientific, accessed October 13, 2025, https://www.fishersci.com/us/en/browse/cas/108-95-2
2. Phenol - the NIST WebBook - National Institute of Standards and Technology, accessed October 13, 2025, https://webbook.nist.gov/cgi/cbook.cgi?ID=108-95-2
3. SID 46508193 - PubChem, accessed October 13, 2025, https://pubchem.ncbi.nlm.nih.gov/substance/46508193
4. Phenol (C6H5OH) - GeeksforGeeks, accessed October 13, 2025, https://www.geeksforgeeks.org/chemistry/phenol/
5. Phenol - Exposure Standard Documentation - Safe Work Australia, accessed October 13, 2025, https://hcis.safeworkaustralia.gov.au/ExposureStandards/Document?exposureStandardID=479
6. PHENOL - precisionFDA, accessed October 13, 2025, https://precision.fda.gov/ginas/app/ui/substances/339NCG44TV
7. Phenol: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed October 13, 2025, https://go.drugbank.com/drugs/DB03255
8. Immediately Dangerous to Life or Health Concentrations (IDLH): Phenol - NIOSH Publications and Products - CDC, accessed October 13, 2025, https://www.cdc.gov/niosh/idlh/108952.html
9. CAS No. 108-95-2 - Phenol - AccuStandard, accessed October 13, 2025, https://www.accustandard.com/prod0000286.html
10. Chemical Properties of Phenol - Unacademy, accessed October 13, 2025, https://unacademy.com/content/neet-ug/study-material/chemistry/chemical-properties-of-phenol/
11. Phenol | C6H5OH | CID 996 - PubChem, accessed October 13, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Phenol
12. PHENOL | - atamankimya.com, accessed October 13, 2025, https://atamankimya.com/sayfalar.asp?LanguageID=2&cid=3&id=11&id2=10594
13. Phenol | Medical Management Guidelines | Toxic Substance Portal ..., accessed October 13, 2025, https://wwwn.cdc.gov/TSP/MMG/MMGDetails.aspx?mmgid=144&toxid=27
14. Appendix P - Phenol First Aid Guide and PPE | Environment, Health and Safety, accessed October 13, 2025, https://ehs.cornell.edu/research-safety/chemical-safety/laboratory-safety-manual/appendix-p-phenol-first-aid-guide-and-ppe
15. Phenol Nerve Block - MD Searchlight, accessed October 13, 2025, https://mdsearchlight.com/therapeutics/phenol-nerve-block/
16. PHENOL AND RELATED COMPOUNDS | Poisoning & Drug Overdose, 8e | AccessMedicine, accessed October 13, 2025, https://accessmedicine.mhmedical.com/content.aspx?legacysectionid=olson8_ch2lev1sec124
17. GC-MS Spectrum - EI-B (DB03255) | DrugBank Online, accessed October 13, 2025, https://go.drugbank.com/spectra/c_ms/29293
18. Mass Spectrum (Electron Ionization) (DB03255) | DrugBank Online, accessed October 13, 2025, https://go.drugbank.com/spectra/ei_ms/1214
19. Phenol | Definition, Structure, Uses, & Facts - Britannica, accessed October 13, 2025, https://www.britannica.com/science/phenol
20. Joseph Lister (1827-1912): A Pioneer of Antiseptic Surgery - PMC, accessed October 13, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9854334/
21. Joseph Lister - Wikipedia, accessed October 13, 2025, https://en.wikipedia.org/wiki/Joseph_Lister
22. pubmed.ncbi.nlm.nih.gov, accessed October 13, 2025, https://pubmed.ncbi.nlm.nih.gov/390320/#:~:text=Phenols%20were%20first%20isolated%20in,classical%20experiments%20in%20antiseptic%20surgery.
23. Phenols: a review of their history and development as antimicrobial ..., accessed October 13, 2025, https://pubmed.ncbi.nlm.nih.gov/390320/
24. 12th August 1865: Joseph Lister conducts the world's first antiseptic surgery using phenol, also known as carbolic acid | HistoryPod, accessed October 13, 2025, https://www.historypod.net/08/12/12th-august-1865-joseph-lister-conducts-the-worlds-first-antiseptic-surgery-using-phenol-also-known-as-carbolic-acid/
25. Phenol Toxicity - StatPearls - NCBI Bookshelf, accessed October 13, 2025, https://www.ncbi.nlm.nih.gov/books/NBK542311/
26. Phenol injections to treat pain - Overview | Guy's and St Thomas' NHS Foundation Trust, accessed October 13, 2025, https://www.guysandstthomas.nhs.uk/health-information/phenol-injections-treat-pain
27. Phenol production in the organic chemical process - Krohne, accessed October 13, 2025, https://www.krohne.com/en-in/industries/chemical-industry/organic-chemicals-in-the-chemical-industry/phenol-production
28. www.krohne.com, accessed October 13, 2025, https://www.krohne.com/en-us/industries/chemical-industry/organic-chemicals-in-the-chemical-industry/phenol-production#:~:text=Today's%20preferred%20industrial%20method%20of,formed%20from%20benzene%20and%20propene.
29. Cumene process - Wikipedia, accessed October 13, 2025, https://en.wikipedia.org/wiki/Cumene_process
30. Phenol - Chemicals - INEOS Group, accessed October 13, 2025, https://www.ineos.com/industry/products/chemicals/phenol/
31. Phenol - DCCEEW, accessed October 13, 2025, https://www.dcceew.gov.au/environment/protection/npi/substances/fact-sheets/phenol
32. Phenols and Related Compounds as Antiseptics and Disinfectants for Use With Animals, accessed October 13, 2025, https://www.merckvetmanual.com/pharmacology/antiseptics-and-disinfectants/phenols-and-related-compounds-as-antiseptics-and-disinfectants-for-use-with-animals
33. Phenol-An effective antibacterial Agent - Research and Reviews, accessed October 13, 2025, https://www.rroij.com/open-access/phenol-an-effective-antibacterial-agent-.pdf
34. Antiseptics and Disinfectants: Activity, Action, and Resistance - PMC, accessed October 13, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC88911/
35. Phenolic Acid Disinfectant | Definition, Toxicity & Usage - Lesson - Study.com, accessed October 13, 2025, https://study.com/academy/lesson/what-are-phenol-disinfectants-definition-advantages-disadvantages.html
36. Phenol Nerve Block - StatPearls - NCBI Bookshelf, accessed October 13, 2025, https://www.ncbi.nlm.nih.gov/books/NBK525978/
37. Phenol nerve block for the management of lower limb spasticity | ACNR, accessed October 13, 2025, https://acnr.co.uk/articles/phenol-nerve-block-for-the-management-of-lower-limb-spasticity/
38. Chloraseptic® MAX Wild Berry Sore Throat Spray, accessed October 13, 2025, https://www.chloraseptic.com/sore-throat-medicine/sore-throat-spray/max-wild-berry
39. PHENOL- sore throat spray spray - DailyMed, accessed October 13, 2025, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5b36529b-628d-4eb6-858e-634e632a9787
40. Clinical Profile: Phenol 6% Solution for Injection - GlobalRx, accessed October 13, 2025, https://www.globalrx.com/articles?article=phenol-6-injection-clinical-profile&product_id=120559
41. Phenolic Compounds and their Biological and Pharmaceutical Activities - ResearchGate, accessed October 13, 2025, https://www.researchgate.net/publication/359391512_Phenolic_Compounds_and_their_Biological_and_Pharmaceutical_Activities
42. Phenols in Pharmaceuticals: Analysis of a Recurring Motif - NSF Public Access Repository, accessed October 13, 2025, https://par.nsf.gov/servlets/purl/10332412
43. Phenol: toxicological overview - GOV.UK, accessed October 13, 2025, https://www.gov.uk/government/publications/phenol-properties-incident-management-and-toxicology/phenol-toxicological-overview
44. www.mayoclinic.org, accessed October 13, 2025, https://www.mayoclinic.org/drugs-supplements/phenol-oromucosal-route/description/drg-20072736#:~:text=Phenol%20is%20used%20to%20relieve,Spray
45. Phenol (oromucosal route) - Side effects & dosage - Mayo Clinic, accessed October 13, 2025, https://www.mayoclinic.org/drugs-supplements/phenol-oromucosal-route/description/drg-20072736
46. Phenol topical solution - Cleveland Clinic, accessed October 13, 2025, https://my.clevelandclinic.org/health/drugs/23878-phenol-topical-solution
47. What is Phenol? Medical Uses, Health Benefits, and Risks - Healthline, accessed October 13, 2025, https://www.healthline.com/health/what-is-phenol
48. Penol Therapy - Nerve Block - ICD DELHI, accessed October 13, 2025, https://www.icddelhi.org/Phenol_Therapy.html
49. Phenol - Cosmetics Info, accessed October 13, 2025, https://www.cosmeticsinfo.org/ingredient/phenol/
50. Medical uses for phenol in the urinary tract: A possible forgotten treatment (Review) - PMC, accessed October 13, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9829081/
51. Preventing harm from phenol in medical imaging - Australian ..., accessed October 13, 2025, https://www.safetyandquality.gov.au/sites/default/files/2025-03/preventing_harm_from_phenol_in_medical_imaging_0.pdf
52. The Physical and Chemical Properties of Phenol - Capital Resin Corporation, accessed October 13, 2025, https://capitalresin.com/the-physical-and-chemical-properties-of-phenol/
53. Indication-specific dosing for Cepastat, Ulcerease, Chloraseptic ..., accessed October 13, 2025, https://reference.medscape.com/drug/ulcerease-cepastat-chloraseptic-phenol-999660
54. Chloraseptic® Cherry Sore Throat Spray, accessed October 13, 2025, https://www.chloraseptic.com/sore-throat-medicine/sore-throat-spray/cherry
55. phenol 6% in Water Injection, 6% (60 mg/mL) (600mg/10mL), in a 10 mL Vial, accessed October 13, 2025, https://www.fagronsterile.com/products/phenol-6-in-water-injection-6-60-mg-ml-600mg-10ml
56. HAEMOROL oily phenol 250mg/5ml injection vial (161711), accessed October 13, 2025, https://www.tga.gov.au/resources/artg/161711
57. Chloraseptic® Cherry Sore Throat Lozenges, accessed October 13, 2025, https://www.chloraseptic.com/sore-throat-medicine/sore-throat-lozenges/cherry
58. Chloraseptic Cough And Throat 10 Mg Lozenges - Uses, Side Effects, and More - WebMD, accessed October 13, 2025, https://www.webmd.com/drugs/2/drug-160880/chloraseptic-cough-and-throat-mucous-membrane/details
59. Phenol - Environmental Protection Agency, accessed October 13, 2025, https://www.epa.gov/sites/default/files/2016-09/documents/phenol.pdf
60. Phenol: general information - GOV.UK, accessed October 13, 2025, https://www.gov.uk/government/publications/phenol-properties-incident-management-and-toxicology/phenol-general-information
61. Phenol | Public Health Statement | ATSDR - CDC, accessed October 13, 2025, https://wwwn.cdc.gov/TSP/PHS/PHS.aspx?phsid=146&toxid=27
62. Table 8-1, Regulations and Guidelines Applicable to Phenol - NCBI, accessed October 13, 2025, https://www.ncbi.nlm.nih.gov/books/NBK599457/table/ch8.tab1/
63. ATSDR Phenol Tox Profile - Agency for Toxic Substances and ..., accessed October 13, 2025, https://www.atsdr.cdc.gov/toxprofiles/tp115.pdf
64. 510(k) Premarket Notification - FDA, accessed October 13, 2025, https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm?ID=K894369
65. MAUDE Adverse Event Report: SUMMIT MEDICAL LLC PHENOL PRO AMPULE; APPLICATOR, ENT - accessdata.fda.gov, accessed October 13, 2025, https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/detail.cfm?mdrfoi__id=19127998&pc=KCJ
66. European Medicines Agency - Europa.eu, accessed October 13, 2025, https://www.ema.europa.eu/en
67. PSUSA/00009256/202004 - periodic safety update report single assessment | European Medicines Agency (EMA), accessed October 13, 2025, https://www.ema.europa.eu/en/medicines/psusa/psusa-00009256-202004
68. 1.1 m-Aminophenol | Therapeutic Goods Administration (TGA), accessed October 13, 2025, https://www.tga.gov.au/resources/publication/scheduling-decisions-final/scheduling-delegates-final-decisions-january-2017/11-m-aminophenol
69. NORMAL SALINE/PHENOL Diluent (32490) | Therapeutic Goods Administration (TGA), accessed October 13, 2025, https://www.tga.gov.au/resources/artg/32490
70. phenol - Healthdirect, accessed October 13, 2025, https://www.healthdirect.gov.au/medicines/medicinal-product/aht,20918/phenol