Phenol is a flammable and highly corrosive organic acid that is readily absorbed and widely distributed through all routes of exposure, including inhalation, cutaneous, and oral exposure. The substance has hydrophilic and lipophilic properties, which facilitate its penetration through cell membranes. Phenols denature and precipitate cell proteins, resulting in coagulation necrosis.17

On the skin, the substance has an immediate caustic effect, promoting the denaturation and coagulation of epidermal keratin proteins and the superficial layers of the dermis, clinically translated as rapid, uniform whitening (Fig. 3). Its caustic effect results in deep dermal remodeling, stimulating the production of collagen and elastin. This mechanism is widely explored in aesthetic procedures, such as facial rejuvenation, due to its ability to promote structural skin renewal with long-lasting results.18

Figure 3.

Uniform frosting that sets in quickly after applying phenol to the skin, resulting from the denaturation and coagulation of the proteins in the epidermal keratin and the superficial layers of the dermis.

Phenol absorption into the bloodstream after cutaneous application is intense and rapid, with urinary recovery of 70% within 30 minutes and 85%–95% within 24 hours.17,19 Even small amounts can reach significant serum levels, making strict dose control and the use of targeted application techniques essential.16

Studies indicate that cutaneous absorption is little influenced by the concentration of the applied solution but depends largely on the area of exposed skin.20 In 1971, Piotrowski studied solutions containing phenol at concentrations of 5, 10, and 25 mg/m3 and found that, regardless of concentration, the compound is rapidly absorbed through both the skin and the lungs.21

When applied to the skin, phenol is rapidly absorbed due to its lipophilic nature and low molecular weight, penetrating the stratum corneum and reaching the systemic circulation. Once absorbed, it undergoes hepatic detoxification, where approximately 75% is metabolized primarily by glucuronidation, sulfonation, and oxidation via CYP2E1. Elimination occurs predominantly through the kidneys, being excreted in the urine mainly in the form of glucuronides and sulfates. Approximately 25% of the phenol undergoes further metabolism, being converted to carbon dioxide (CO2) and water, while a small fraction may be excreted unchanged in the urine. Furthermore, in the first few minutes after absorption, some of the phenol may be eliminated through the lungs, which may be associated with the characteristic odor exhaled by patients. A smaller fraction of the phenol is eliminated in the feces, resulting from the biliary excretion of metabolites, although this pathway plays a secondary role in the total elimination of the compound. The half-life of phenol varies depending on the dose and route of exposure, but its efficient renal elimination generally prevents accumulation in healthy individuals. Therefore, adequate hydration and stimulating diuresis are interesting strategies to optimize its elimination. Furthermore, because respiratory, urinary, and biliary excretion occur relatively quickly, it is essential to maintain adequate intervals between successive applications in cosmetic units, ensuring complete elimination before further exposure.19,20

Studies report the use of 88% phenol for depigmentation of residual skin in advanced cases of vitiligo.4,22 When applied topically in high concentrations, the substance has melanotoxic action, causing chemical necrosis of melanocytes. This toxic action on melanocytes compromises melanin synthesis in the treated areas, leading to permanent depigmentation and color uniformity. This effect is particularly useful in patients with generalized vitiligo, in whom repigmentation is unfeasible or unsatisfactory.4

A study published in the Anais Brasileiros de Dermatologia in 2005 reported the case of a 62-year-old patient with generalized vitiligo and residual normal-colored areas on the neck who was treated with 88% phenol. After two applications, 45 days apart, the pigmented areas were completely eliminated, with no signs of repigmentation after 18 months.22

A study by Ravikiran et al.5 evaluated the use of 88% phenol in the treatment of idiopathic guttate hypomelanosis. The compound promoted controlled chemical necrosis in the hypopigmented areas, triggering a local regenerative response that led to progressive repigmentation of the lesions. Twenty patients with 139 macules were treated with two monthly applications of 88% phenol. After three months, 64% of the macules showed repigmentation, with 45% showing greater than 75% improvement.

A study compared the efficacy of cryotherapy with liquid nitrogen to 80% phenol in the treatment of hand warts. Sixty patients were randomly divided into two groups and treated weekly for up to six weeks. At the end, 70% of the patients treated with cryotherapy and 82.6% of those treated with phenol achieved complete healing, with no statistically significant difference between the methods.6

Another study compared the efficacy of curettage and electrocoagulation with the application of 80% phenol in the treatment of warts. The treatments were performed simultaneously on different lesions of the same patient, in 17 patients. After six weeks, the cure rate was significantly higher in the curettage and electrocoagulation group (100%) compared to the phenol group (65%). The study concluded that curettage and electrocoagulation were more effective, but the application of phenol may be a less invasive alternative for pain-sensitive patients.23

A study evaluated the use of crystallized phenol in the treatment of sacral hidradenitis suppurativa (HS). Twenty-five patients were treated with phenol, with a mean follow-up of 36.8 months. The oozing openings were dilated with forceps after local anesthesia, the hairs were removed, and phenol was applied. The cure rate was achieved in 60% of cases, with recurrence in 40%, most of which resolved with reapplications. The treatment showed a significant reduction in Hurley severity scores and Physician's Global Assessment of HS after therapy, with no reported side effects. Crystallized phenol has proven to be an effective, minimally invasive option with little impact on patients' daily lives.13

A recently published pilot study (2024) evaluated the efficacy and safety of phenolization in the treatment of hidradenitis suppurativa (HS). After local anesthesia and individualization of the fistulas, 88% phenol was applied (three passes with a soaked cotton swab) to 22 fistulas in 12 patients, resulting in significant improvement in more than half of the cases after one month, with healing within two weeks. The technique proved particularly useful in anatomical areas that are difficult to manage surgically and in small, non-draining fistulas. Tolerance was good, with mild and transient side effects.24

Phenol has been used in the treatment of pilonidal cysts due to its sclerotizing and antimicrobial properties. The application aims to destroy the cyst epithelium, promoting obliteration of the tract and reducing disease recurrence. Numerous studies indicate that the use of phenol, in crystallized or 80% liquid form, is an effective alternative for the treatment of pilonidal cysts.25

Dogru et al.25 evaluated the impact of crystallized phenol on the outpatient treatment of pilonidal disease in 41 patients. The substance was applied 107 times, with most patients (70%) requiring two to three applications. The average recovery time was 42.7 days, with a 95% success rate, and only two recurrences were observed after five and eight months.

A literature review on the use of phenol as a minimally invasive method for the treatment of pilonidal disease revealed a mean time to return to work of 2.3 days and a healing time of 20 days. The overall success rate was 87%, with a mean follow-up of two years. The most common complications were abscess and cellulitis, with a mean incidence of 8.9%.26

A meta-analysis published (2024) compared phenolization with surgical excision in the treatment of pilonidal cysts. The analysis included 14 studies, including five randomized controlled trials and nine non-randomized trials. Phenol treatment showed fewer complications, shorter surgical time (mean 22.76 minutes), faster return to daily activities (mean 10.11 days), and shorter healing time (mean 17.11 days) compared to surgical treatment.27

Sacchidanand et al.12 evaluated the use of 88% phenol in the treatment of mucous cysts. Four patients were treated with intralesional phenol injection, without the need for local anesthesia. After application, ulceration of the lesions was observed, followed by complete healing within two weeks. The absence of intraoperative or postoperative bleeding, minimal surgical defects, and discreet healing offered an advantage to phenol over surgery.12

A prospective study evaluated the efficacy and prognostic relevance of 100% phenol peels in patients with actinic keratoses (AK) and Bowen's disease (BD) using clinical, histological, and immunohistochemical criteria. Forty-six patients (32 with AK and 14 with BD), aged 31 to 91 years, were included. Applications were performed monthly for up to eight sessions, and patients were monitored for at least one year after treatment. There was a complete response in 84.8% of cases. Success rates correlated with factors such as tumor thickness and expression of molecular markers (PCNA and cyclin A).9

A recent study (2024) compared the efficacy of phenol-croton peeling (Hetter 35%/1.6%) versus imiquimod 5% in the treatment of actinic cheilitis. Thirty-six patients were randomized into two groups: one received imiquimod 5% three times a week for 30 days, and the other received a single phenol-croton peeling session. At 56 days, 94% of patients treated with phenol-croton showed complete clearing of the lesions, compared to none in the imiquimod group (p < 0.01). Histological and clinical improvements were more significant in the phenol-croton group. Despite more intense initial adverse effects, the peeling proved to be superior in efficacy and recovery.8

A study by Kaminaka et al.28 evaluated the use of 100% phenol in the treatment of cutaneous angiosarcoma (AS) in three cases. After treatment, biopsies revealed severe degeneration of the tumor and endothelial cells in the dermis, with positive staining using the TUNEL (Terminal Deoxynucleotidyl Transferase dUTP Nick-End Labeling) method, a technique that detects DNA fragmentation associated with apoptosis. Phenol peeling demonstrated advantages such as simplicity, speed, low cost, manageable pain, and sustained efficacy, suggesting its use as a complementary therapy for AS.

Studies have explored the use of phenol as a therapeutic option for alopecia areata. The proposed mechanism of action involves stimulating hair follicles through growth factors and cytokines released in response to necrosis and inflammation. Furthermore, it is suggested that phenol may act directly on the germinal centers of follicles, promoting hair growth.29,30

A study evaluated the efficacy of 88% phenol in 50 patients with stable alopecia areata, applying it every three weeks. Approximately 78% of patients showed a good to excellent response. There was a significant improvement in hair texture and pigmentation within nine weeks, with a progressive increase in hair density.29

A report by Kar and Singh30 described a 13-year-old patient with diffuse alopecia areata involving more than 50% of the scalp who was treated with five biweekly sessions of 88% phenol and four biweekly pulses of intravenous dexamethasone. The phenol induced controlled inflammation and hair regeneration, while the dexamethasone modulated immunity. After 4 months, there was significant terminal hair growth, with no recurrence within 6 months.30

Mseddi et al.14 investigated the use of 40% phenol in the treatment of keloids in 25 patients. The mean age of participants was 37.7 years, with a predominance of phototype IV (64%) and lesions located on the trunk (48%). After an average of 14.2 sessions, a 75.5% reduction in lesion size was observed, with 72% of patients reporting satisfaction with the treatment and 81% adhering to the protocol. There were no recurrences during the average follow-up of 12.8 months. The authors highlighted that the induction of controlled tissue necrosis promoted scar remodeling, improving skin texture and color.14

Platsidaki et al.31 evaluated the combination of 10% phenol and 20% trichloroacetic acid in the treatment of dark circles in 31 women. The peeling was applied with a cotton swab in three layers to the upper and lower eyelids until a homogeneous frosting endpoint was reached. The treatment showed significant improvement, especially in younger patients. The authors suggested that the combination of the two substances offers complementary mechanisms of action, providing effective cosmetic benefits without the potential adverse effects associated with the use of higher concentrations of each compound alone.31

A retrospective study analyzed the efficacy and safety of deep chemical peels in the treatment of constitutional dark circles. Fifty-five procedures were performed on 52 patients, mostly women (92%), with a mean age of 46 years and Fitzpatrick phototypes III–IV (89%). In most cases, a phenol formula (60%–65%) combined with croton oil (0.6–0.7%) was used. The results showed that 89% of patients experienced clinical improvement greater than 50%, with an average duration of benefits of 24 months. Furthermore, 69% maintained satisfactory results until the last follow-up. Complications were rare, with only 4% of cases presenting persistent erythema, without the development of scars.32

A recent (2024) retrospective cohort study7 compared phenol peeling with moderate concentrations of Croton Oil (CO; 0.7–0.9%) versus higher concentrations (1.1–1.6%) in the treatment of recalcitrant melasma. Both groups showed significant improvement in mMASI after treatment and high scores on the Global Aesthetic Improvement Scale. However, the reduction was more pronounced in the group with CO < 1% compared to the group with CO > 1%. Remission was maintained for more than a year in 85% of cases, with no relevant differences between concentrations. The sustained improvement in melasma was attributed to the long-lasting treatment of elastosis, considered an important etiopathogenic substrate of melasma (Fig. 4). However, additional studies with larger sample sizes and longer follow-up are needed to confirm the stability of these results across different phototypes and clinical conditions.

Figure 4.

63-year-old patient with refractory melasma, before and after 6 months: A and B (frontal face); C and D (left hemiface), phenol-croton peeling 35%/1.2%.

Originally developed in 1945 by Boll,33 phenolization is one of the best-documented techniques in the medical literature for the treatment of onychocryptosis. Hundreds of studies, including extensive case series, demonstrate its safety and efficacy. Phenol acts as a sclerotizing agent, selectively destroying the nail matrix. Its benefits include a low recurrence rate, its antiseptic and analgesic properties, and the low risk of infection associated with the procedure.

A study published in 2024 analyzed the recurrence rate after partial matricectomy with 88% phenol, using a contact time of 45 seconds. A total of 1,460 surgeries were performed, with 802 patients followed for a six-month period. The recurrence rate was 0.75% at three months and 1.87% at six months.10

A retrospective study by Andreassi et al.34 analyzed 948 phenol cauterizations in 764 patients. There was no significant morbidity, and the procedure was well tolerated by all patients. The overall recurrence rate was 4.3% after 18 months. All recurrences were successfully treated with repeat application of the substance.

Other studies35,36 corroborate these low recurrence rates, indicating consistency in the results. Furthermore, Cochrane reviews37,38 and a recently published meta-analysis by Vinay et al. (2022)39 confirmed the efficacy and safety of phenolization, with minimal side effects.

The efficacy of phenol in the treatment of acne scars, with particularly notable benefits in deeper scars resistant to other procedures (Fig. 5), has been demonstrated in several studies. Mackee and Karp40 pioneered the use of phenol for acne scars, documenting its effectiveness in softening atrophic scars, a finding that supported the use of phenol decades later. Leheta et al.41 conducted a randomized clinical trial comparing a 60% phenol peel with croton (Skintech Inc., Spain) to Percutaneous Collagen Induction (PCI) combined with 20% Trichloroacetic Acid (TCA) treatment for post-acne atrophic scars. Twenty-four patients were divided into two groups, with Group 1 receiving one session of phenol peel and Group 2 four sessions of PCI with TCA. Both treatments resulted in significant improvement in scars, with the phenol peel showing slightly superior results, with an average improvement of 75.12% in Group 1 and 69.43% in Group 2.

Figure 5.

38-year-old patient with acne scars unresponsive to previous treatments (dermabrasion/CO2 laser), before and after 1 year: A and B (left hemiface); C and D (right hemiface), phenol-croton peeling 35%/1.2%.

Recent studies by Rullan and Rullan (2024)3,42 explored the use of phenol in CROSS procedures (a technique of applying acids to individual scars) and in ring paint for boxcar and polymorphic scars. They observed that localized application of 89% phenol was effective, providing satisfactory results in improving scar texture and depth.

Several studies have analyzed the efficacy of phenol peels in the rejuvenation of photoaged skin, especially in combination with croton oil2,43,44 (Fig. 6). Butler et al.45 and Giese et al.46 showed that these peels significantly improve skin quality by stimulating the remodeling of elastic tissue. Hetter47 investigated phenol and croton oil formulas at various concentrations, highlighting the safety and efficacy of the procedure. Han et al.48 confirmed the rejuvenating effects in animal studies, while Kligman et al.18 performed histopathological analysis on skin biopsies from patients who had undergone peeling up to 20 years earlier, revealing the long-lasting effects of the procedure.

Figure 6.

Rejuvenation of the periocular region with phenol-croton peeling 35%/1.2% in a 58-year-old patient. Before (A and B) and after (C and D) 6 months: A and C (right hemiface); B and D (left hemiface).

A recent study by Cardoso et al. (2022)44 evaluated 30 women with Glogau III–IV photoaging, showing that 87% achieved significant rejuvenation (Glogau I–II) three months after the peeling with 35% phenol and 1.2% croton oil. Another split-face study, conducted by Neitzke et al.43 compared the hemifaces of 48 patients. After six months, 79% showed rejuvenation of two or more points on an eight-point photonumeric scale, with a median improvement of three points (p < 0.0001). Another split-face study, which compared the classic Baker-Gordon peel (2.1% croton oil/50% phenol) and a modified Hetter formula (0.7% croton oil/33% phenol), showed similar efficacy, but with fewer side effects in the Hetter formula.49

Other therapeutic proposals include the treatment of oral leukoplakia, in which topical application of phenol prevented progression to malignancy,50 the treatment of hyperhidrosis, in which phenol is used for sympathectomy by chemical neurolysis,51 or as an alternative to the treatment of pyogenic granuloma.52

A literature review demonstrated that, outside the aesthetic context of deep peels, the use of phenol in other dermatological indications did not produce significant systemic adverse events. Reported complications were predominantly local, such as persistent erythema, burning sensation, scarring, and dyschromia. Phenol treatment has emerged as a simple, accessible, safe, and effective approach, with applications in a variety of dermatological conditions. Its use in small quantities reduces the risk of excessive systemic absorption and potential serious adverse effects, reinforcing its viability in well-conducted clinical practices.

Records of phenol toxicity have been reported in the literature since the 19th century. Numerous publications have highlighted the fatal potential of phenol formulations, whether through accidental or therapeutic exposure, via cutaneous, intravenous, oral, or inhalation routes. From the 1940s-61 to the present day, the authors have found publications that address the two antagonistic characteristics of the substance: the excellent effects of cutaneous applications and the serious risks resulting from systemic absorption and toxicity.

Early reports in animal models, such as those by Deichmann et al.63 point to the serious toxic effects of phenol when absorbed in large quantities, including everything from cardiac alterations to multiple organ failure. Historical reports, such as that by Lucas and Lane64 described cases of coma after dermal absorption of phenol. In 1922, Turtle and Dolan65 reported a fatal case in which a bottle containing phenol broke in a young man's pocket on his train ride home. Another case published by Miller in 194266 reported an 18-year-old man with ringworm whose housekeeper applied a mixture of phenol and camphor to his shoulders and trunk, resulting in death within 15 minutes. In 2016, Giri et al.,67 published a report of four cases of acute phenol poisoning in children in India. The cases highlighted the multiple routes of absorption of the substance, as well as its complications in multiple organs. The severity of poisoning was more correlated with dermal exposure than with oral ingestion. The authors concluded that dermal exposure can rapidly progress to multiple organ failure, and that severity appeared to vary according to the degree of dermal exposure and the time interval to intervention.

Cases of dermal exposure to phenol resulting in lethargy and coma, nausea and vomiting, hypotension, cardiac arrhythmias, seizures, intravascular hemolysis, pulmonary edema, tracheal and bronchial inflammation, acidosis, methemoglobinemia, renal dysfunction, and coma have been reported. The reason for the predilection of some organs over others in different patients is unclear.15,68–70

To minimize the risk of arrhythmias and allow monitoring for signs of intoxication, oral analgesia (avoiding medications that prolong the QT interval) and potent topical analgesia or regional blockade are recommended, rather than deep sedation. Sedation can mask important symptoms, such as changes in speech and alertness, that indicate intoxication. It is recommended that the procedure be stopped immediately if there is any evidence of organ toxicity.57,91,92

Breaks of 10–15 minutes should be instituted after each 0.5% of BSA treated, allowing partial elimination of phenol between sessions and the return of the QTc interval to baseline.57,62,90

Multiparametric monitoring (ECG/BP, HR, and O2 saturation) should be performed for early detection of arrhythmias or other adverse cardiac events whenever the treated area is greater than 1.5% of BSA or the procedure time is longer than 30 minutes.58,91,92

Intravenous hydration before and during the procedure helps minimize renal toxicity and facilitates the excretion of phenol through the urinary system, reducing its systemic concentration. This support can be provided in an outpatient setting, provided the office is adequately equipped and complies with current health regulations for intravenous fluid administration and emergency support. It is recommended to administer 500 mL of Ringer's Lactate before the procedure begins, adding 500 mL for each 1.5% of treated BSA, or 30 minutes into the procedure.90,91 Intravenous hydration with Ringer's Lactate is preferred in procedures involving phenol due to its balanced composition, which contributes to electrolyte and acid-base stability during the procedure. Unlike saline solution, which contains only sodium and chloride in high concentrations, Ringer's Lactate contains additional electrolytes such as potassium and calcium—important for cardiac stability—and lactate, which is metabolized to bicarbonate, helping to prevent metabolic acidosis often associated with systemic phenol absorption. Furthermore, it has a lower risk of hypernatremia and hyperchloremic acidosis. Although there are no specific studies directly comparing these solutions to phenol peels, the choice of Ringer's Lactate reflects a well-established and physiologically sound clinical practice for maintaining homeostasis in situations of increased metabolic stress.93

It is essential that the room be well-ventilated to dissipate phenol vapors, reducing the risk of toxic inhalation. Measures such as keeping windows open, keeping fans and/or air conditioning on, and positioning a portable fan near the patient's nostrils to divert vapors from the airway are highly recommended.94

Personal protective equipment is mandatory for all professionals involved, including a waterproof apron, thick nitrile gloves, an N95 mask, and protective eyewear.94

All materials used in the procedure must be disposed of in rigid containers for hazardous waste, ensuring safe collection and minimizing the risks of environmental exposure.90

It is essential that the physician performing deep peels with phenol-croton oil prepare the formulation immediately before use, following scientifically validated formulas, such as those proposed by Hetter or Baker, with a known, standardized, and reproducible composition.19,84 However, it is important to emphasize that the active ingredients are purchased from compounding pharmacies, whose quality certification, traceability, and compliance with current health regulations must be rigorously verified.

The current indiscriminate marketing of phenol and Croton tiglium oil, including online and to non-medical professionals, poses a serious health risk. Phenol must have a pharmaceutical-grade purity certification seal and be diluted in absolute alcohol (100%) in a controlled manner.95 Croton oil, in turn, has high phytochemical variability between different batches and suppliers. Studies using liquid chromatography, mass spectrometry, and HPTLC (High-Performance Thin Layer Chromatography) have shown that many commercial products do not contain the same profile of phorbol esters, compounds directly responsible for the depth of action and the inflammatory pattern of peels.56,96,97

Furthermore, stability analyses have shown that the oil composition changes with storage, resulting in the degradation of fatty acids and the possible loss of expected clinical action.98 Therefore, choosing reliable suppliers with up-to-date analytical reports and rigorous purity control is essential.

The formulation should be prepared in a screw-top glass bottle, mixed continuously to prevent separation of components, and applied immediately after preparation. For staff protection, appropriate PPE is required, including a waterproof apron, thick nitrile gloves, goggles, and an N95 mask. Handling should be done in a well-ventilated environment to minimize the risk of inhalation of toxic vapors.90

Regarding the emulsifier, scientific literature recommends the preferred use of Novisol®, due to its safety, compatibility with phenol, and role in emulsion stability, as demonstrated in stability studies of the Hetter formula.99,100

Finally, to reduce the risk of systemic toxicity, it is recommended that the total volume of phenol used in a single session does not exceed 10 mL, regardless of the concentration used.19,84

The presence of cardiopulmonary resuscitation equipment is mandatory for the management of serious adverse events, such as Acute Respiratory Distress Syndrome (ARDS) or cardiopulmonary arrest. Furthermore, it is essential that physicians performing phenol procedures be highly qualified and have up-to-date training in Advanced Cardiac Life Support (ACLS), ensuring adequate response capacity to critical complications.76,84,90

Cutaneous Risks

In addition to the recognized systemic risks of phenol, the use of this agent in dermatology is also associated with significant local complications. These include infections, permanent scarring (Fig. 9), pigmentary changes, ocular damage, and impaired healing, particularly in patients with frontal fibrosing alopecia (FFA).92,101 (Fig. 10).

Figure 9.

Hypertrophic scars after phenol-croton peeling in the eyelid region (A and B) and preauricular region (C). Photo: Dr. Felipe Ribeiro.

Figure 10.

Abnormal healing one month after phenol-croton 35%/1.2% peeling in a patient with frontal fibrosing alopecia. Photo: Dr. Felipe Ribeiro.

FFA compromises skin regeneration due to the loss of follicular stem cells, which play a fundamental role in healing. Recent studies, such as that by Landau et al. (2024),101 highlight that patients with AFF have a significantly higher risk of scarring complications, making phenol-croton peeling a contraindication in these cases. These findings support the need for phenol procedures to be performed exclusively by trained physicians capable of assessing and managing individual risks. A detailed analysis of local complications would warrant a separate article, given its relevance and complexity.