Phenol Toxicity

Etiology

Acute phenol toxicity mainly occurs through unintentional exposure in the home or workplace; intentional exposures are much less common.[3] Severe toxicity has occurred from accidental ingestions in healthcare settings.[4] Recurring occupational exposures in the explosives production industry and healthcare settings resulted in a historical syndrome of malaise, fatigue, and hepatitis called “phenol marasmus.”[5] Today, phenol exposures are more likely to result in dermal exposure following laboratory or industrial spills.[6]

Epidemiology

The National Poison Data System receives approximately 1000 calls per year related to phenol exposure; about 90% are unintentional. Most result in minimal or no significant clinical effects, with only 6 to 8% of cases exhibiting moderate to major clinical effects.[7][8]

Pathophysiology

Phenol is a protoplasmic poison with myriad effects. Its dual hydrophilic and lipophilic properties allow it to easily break through cellular membranes, denaturing proteins, ultimately leading to cell death and necrosis. A caustic effect resulting in coagulation necrosis can also occur. Phenol distributes widely and, with severe toxicity, results in pathologic effects involving most organ systems. Substituted phenol derivatives possess an additional mechanism of toxicity by uncoupling oxidative phosphorylation, potentially resulting in severe toxicity manifesting as hyperthermia and acidosis.[9] Examples include 2,4-dinitrophenol (DNP), pentachlorophenol, and dinitro-ortho-cresol (DNOC).

Toxicokinetics

Phenol is readily absorbed through multiple routes of exposure (ingestion, dermal, inhalational) and distributes widely through the body within minutes. It is believed to undergo hepatic metabolism similar to acetaminophen via glucuronidation, sulfonation, and oxidation via CYP2E1.[3] These metabolites get excreted renally.

History and Physical

Efforts to obtain a history should not delay the treatment of life-threatening toxicity. Furthermore, patients with severe phenol toxicity may be unable to provide a history of exposure due to depressed mental status or seizures. When appropriate, a focused history should seek to determine the toxin of concern, including the concentration, dose, route, and time of exposure. Questions regarding using personal protective equipment such as gloves, coveralls, or respirators may help stratify the degree of exposure and possible exposure routes. Following workplace and household exposures, a review of a safety data sheet may help identify active ingredients. 

The clinician might detect phenol's sweet, medicinal odor and provide a clue to the exposure. The onset of clinical effects varies by route of exposure but would be expected to occur within minutes to less than 1 hour. Examination findings may also vary by route of exposure. Central nervous system excitation or depression may occur rapidly, resulting in coma or seizures within minutes. Vomiting or other signs of gastrointestinal irritation may be presenting symptoms. White patches may be present in the oropharynx. Increased work of breathing and/or hypoxia may be a feature secondary to the development of acute respiratory distress syndrome. Severe phenol poisonings may also result in cardiovascular instability, including ventricular arrhythmias and hypotension.[4] Rhythmic perioral movements, the so-called “rabbit syndrome,” may occur after resolving life-threatening toxicity.[10] 

Dermal exposure to small amounts of phenol acutely results in a painless, white skin discoloration at the contact site. Deeper burns may occur if decontamination does not occur promptly. The skin may later progress to erythema blistering and, in some cases, necrosis. Interestingly, phenol burns may also present with initial erythema at the contact site, followed by brown staining of the skin. These lesions are frequently painless due to topical phenol's anesthetic and cooling effect. Skin desquamation may occur over 3 to 5 days following contact before healing begins. Dermatologists historically utilized this progression of phenol chemical burns in facial chemical peels.[2] Repeated dermal exposure to phenol may result in either hyperpigmentation, a blue-black discoloration called ochronosis, or hyperpigmentation, causing chemically induced vitiligo.[11][12]

Evaluation

Laboratory assessment of phenol exposure is not widely available and, in most cases, does not alter initial management. However, if desired, laboratory exposure confirmation can be obtained by obtaining a serum or urine phenol level. Monitoring urine phenol levels is common in workplaces with occupational benzene exposure but has no definitive role in acute phenol poisoning. Phenol-exposed patients should receive regular monitoring of vital signs and mental status. A baseline electrocardiogram and continuous cardiac monitoring should be obtained to evaluate for dysrhythmias. Laboratory evaluation should focus on identifying the presence of acute kidney injury, metabolic acidosis, hepatitis, rhabdomyolysis, or methemoglobinemia. A chest radiograph should be obtained in cases of ingestion or inhalational exposure or in patients with hypoxemia or respiratory complaints. Phenol metabolites may also produce characteristic blue-green urine that may provide a clue to the diagnosis in cases of unknown exposure.[13] 

Treatment / Management

Ingestion or dermal exposure to phenol concentrations greater than 5% should receive a referral to an emergency department for evaluation. Consultation with a regional poison control center in the United States is possible by calling 1-800-222-1222. Managing a phenol-poisoned patient should focus first on primary supportive measures such as ensuring a patent airway, supporting ventilation and oxygenation, and hemodynamic support as needed.

There have been proposals for various decontamination agents for external decontamination of phenol exposure. However, low molecular weight (300-400MW) polyethylene glycol (PEG) is the currently accepted decontamination fluid.[14] Notably, this is not the same as high molecular weight PEG typically used in medical settings as a bowel preparation or osmotic laxative. LMW PEG should be included in phenol exposure first aid kits in labs or worksites, and phenol should be used to provide external decontamination as soon as possible. Decontamination should occur with an LMW PEG-soaked sponge or towel to remove residual phenol. When LMW PEG is unavailable, flushing the exposed area with copious amounts of water for 15 minutes may be effective. Early studies showed potentially increased absorption of phenol when using only small amounts of water.[15] Isopropyl alcohol may also be as effective as LMW PEG for external phenol decontamination.[14] For ocular exposure to phenol, the eyes should be flushed with copious amounts of water or saline for at least 15 minutes after exposure.(B3)

Gastrointestinal decontamination with activated charcoal is generally not recommended following phenol ingestion. The risk of aspiration in the setting of phenol-induced seizures likely outweighs the potential benefit of activated charcoal. Furthermore, activated charcoal may obscure or confuse the visualization of gastrointestinal endoscopic findings. Upper endoscopy should be a consideration for patients following phenol ingestion to grade the degree of esophageal injury. Management of extensive surface area phenol burns should take place in conjunction with a regional burn center. Extra-corporeal removal of phenol by hemodialysis is not recommended. However, hemodialysis may be necessary to manage the complications of phenol toxicity. Patients with systemic manifestations of phenol toxicity should be admitted to a monitored setting for at least 24 hours. Asymptomatic patients with normal vital signs and laboratory findings may be released from emergency care after 6 to 8 hours of monitoring.

Differential Diagnosis

The differential diagnosis of the manifestations of phenol toxicity is broad, given that phenol exerts effects on nearly all organ systems. Dermal exposure may present similar to other potent acid or alkali exposures, but the characteristic brown-stained skin may be a clue to phenol. Hypopigmented skin may also present with hydrofluoric acid dermal exposures. The combination of seizures and cardiovascular collapse is very non-specific and is observable with a broad range of life-threatening toxin exposures. The characteristic blue-green urine is also a possible feature with the therapeutic use of propofol, a phenol-derived pharmaceutical.

Prognosis

Most patients with phenol toxicity are expected to recover, provided they receive prompt decontamination and supportive care. Complications may be extensive, however. Multisystem organ failure requires extensive critical care support until resolution.[16][17][18]

Complications

Untreated dermal exposure to phenol may result in partial or full-thickness chemical burns or necrotic soft tissue damage. The systemic complications of severe phenol toxicity are myriad. Mental status depression or seizures may result in airway compromise and respiratory failure. Acute respiratory distress syndrome may necessitate mechanical ventilation. Ventricular arrhythmias and/or cardiovascular collapse may occur. Acute kidney injury requiring dialysis may result from extensive rhabdomyolysis or hemoglobinuria due to intravascular hemolysis. Reports also exist of acute hepatotoxicity and methemoglobinemia.