Phenol Toxicity


Article Author:
John Downs


Article Editor:
Brandon Wills


Editors In Chief:
Ishwarlal Jialal


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
6/14/2019 5:54:58 PM

Introduction

Phenol is a disinfectant and chemical precursor with a variety of uses and indications.  Joseph Lister introduced the concept of antiseptic surgery using phenol, then known as carbolic acid.  Reports of toxicity were not far behind.[1]  Phenol remained a healthcare disinfectant through much of the 20th century, but its use in healthcare settings is now uncommon.  Phenol has a long history of use in dermatology as a chemical peel and skin rejuvenator, but recently, laser treatments have surpassed it.[2]  Podiatrists use phenol for nailbed matrix ablation following ingrown toenail removal.

Phenol is still occasionally a component in some household disinfectants and a variety of gargles and ointments.  Phenol-containing solutions are also home remedies for head lice.[3]   Methylated phenols, called cresols, are also found in home disinfectant products and may produce clinical toxicity similar to phenol.

Phenol is a common laboratory chemical used in the extraction of nucleic acid material from biological specimens.  It also serves as a chemical precursor to many pharmaceuticals and chemicals including acetaminophen, aspirin, levodopa, propofol, and some herbicides. 

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 exposures following spills in the laboratory or industrial settings.[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 along the way, 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 that of acetaminophen via glucuronidation, sulfonation, and oxidation via CYP2E1.[3]  These metabolites get excreted renally.  

History and Physical

Efforts to obtain history should not delay 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, which includes the concentration, dose, route, and time of exposure.  Questions regarding the wear of personal protective equipment (PPE) such as gloves, coveralls, or respirators may help to stratify degree of exposure and possible routes of exposure. Following workplace and household exposures, safety data sheet (SDS) review may be helpful to identify active ingredients. 

The clinician might detect the sweet, medicinal odor of phenol and provide a clue to the exposure.  The onset of clinical effects vary by route of exposure but would be expected to occur within minutes to less than one 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 (ARDS).  Severe phenol poisonings may also result in cardiovascular instability to include ventricular arrhythmias and hypotension.[4] Rhythmic perioral movements, the so-called “rabbit syndrome,” may occur after resolution of life-threatening toxicity.[10]  

Dermal exposure to small amounts of phenol will acutely result in a painless, white discoloration of the skin at the site of contact.  Deeper burns may occur if decontamination does not occur promptly.  The skin may later progress to erythema and blistering and in some cases necrosis.  Interestingly, phenol burns may also present with initial erythema at the site of contact followed by brown staining of the skin.  Of note, these lesions are frequently painless due to the anesthetic, cooling effect of topical phenol.  Desquamation of skin 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,[11] or hypopigmentation causing chemically-induced vitiligo.[12] 

Evaluation

Laboratory assessment of phenol exposure is not widely available, and in most cases will not alter initial management. However, if desired, laboratory confirmation of exposure can be performed by obtaining a serum or urine phenol level.  Monitoring of urine phenol levels is a common practice 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 should be obtained as well as continuous cardiac monitoring to evaluate for dysrhythmias.  Laboratory evaluation should focus on identifying the presence of acute kidney injury, metabolic acidosis, hepatitis, rhabdomyolysis, or methemoglobinemia. In cases of ingestion or inhalational exposure, or patients with hypoxemia or respiratory complaints, a chest radiograph should be obtained.  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.

The clinical evaluation of 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 a variety of decontamination agents have for external decontamination of phenol exposure.  However, low molecular weight (300-400MW) polyethylene glycol (PEG) is the currently accepted decontamination fluid.[14]  It is critical to note that 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 using phenol to provide external decontamination as soon as possible.  Decontamination should take place with an LMW PEG soaked sponge or towel to wipe away residual phenol.  When LMW PEG is not available, 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.

Gastrointestinal decontamination with activated charcoal is generally not recommended following phenol ingestion.  The risk of aspiration in the setting of phenol induced seizures likely outweigh 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 obtain release 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 that of 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 will be expected to recover provided they receive prompt decontamination and supportive care.  Complications may be extensive, however.  Multisystem organ failure will require 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 (ARDS) 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. 

Enhancing Healthcare Team Outcomes

Patients with severe phenol poisoning will require a multi-disciplinary approach.  Depending on presentation and complications, this may include team members from nursing, critical care medicine, burn surgery, gastroenterology, hepatology, nephrology, medical toxicology, or cardiology.  These patients may require extensive nursing support for a prolonged period in the hospital, and will likely require additional periods of rehabilitation following hospitalization. A close interprofessional dialogue will be necessary to ensure all team members understand treatment goals.  With this team approach, most patients should be expected to make a near full recovery. [Level V]


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Phenol Toxicity - Questions

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A 27-year-old female has been applying a liquid to her hands because she read that it could lead to softer skin. However, after nine months, she noticed that her skin has darkened to a blue-black hue. Despite washing with detergent, she is unable to remove the stain. Which of the following chemicals may be responsible for her skin discoloration?



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A 70-year-old lady presents to a dermatologist for a skin rejuvenation procedure. Which of the following procedural complications is most often associated with the use of phenol-based deep chemical peels in dermatology?



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A lab assistant uses phenol to extract nucleic acid from biological specimens. She has been warned phenol will burn her skin upon contact. An accidental spill of phenol occurs to her ungloved hand. Contact with her skin is not initially painful, but soon a whitish discoloration of the skin develops. Her co-worker reaches for a decontamination fluid to assist her. What decontamination fluid has been recommended for chemical burns by this substance?



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A 12-year-old girl is brought to the emergency department after she accidentally ingested an unknown substance at home. Within minutes, she exhibits central nervous system depression, and over the next several hours develops seizures and ventricular arrhythmias. During her ICU admission, she produces dark blue-green urine. Which of the following chemicals did she most likely ingest?



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A 45-year-old male presents to the clinic for routine medical surveillance. He works in a chemical plant that generates styrene for processing into polystyrene products, and reports increasing fatigue at work recently. A complete blood count is remarkable for hemoglobin of 6.9 g/dL, and a urinary phenol level is elevated. Which of the following chemicals is most likely to be responsible for this patient’s presentation?



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Phenol Toxicity - References

References

Machin ES, Fatal Cases of Poisoning by the Absorption of Carbolic Acid. British medical journal. 1868 Mar 7;     [PubMed]
Bensimon RH, Croton oil peels. Aesthetic surgery journal. 2008 Jan-Feb;     [PubMed]
Vearrier D,Jacobs D,Greenberg MI, Phenol Toxicity Following Cutaneous Exposure to Creolin®: A Case Report. Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2015 Jun;     [PubMed]
Haddad LM,Dimond KA,Schweistris JE, Phenol poisoning. JACEP. 1979 Jul;     [PubMed]
Merliss RR, Phenol marasmus. Journal of occupational medicine. : official publication of the Industrial Medical Association. 1972 Jan;     [PubMed]
Horch R,Spilker G,Stark GB, Phenol burns and intoxications. Burns : journal of the International Society for Burn Injuries. 1994 Feb;     [PubMed]
Gummin DD,Mowry JB,Spyker DA,Brooks DE,Osterthaler KM,Banner W, 2017 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 35th Annual Report. Clinical toxicology (Philadelphia, Pa.). 2018 Dec;     [PubMed]
Gummin DD,Mowry JB,Spyker DA,Brooks DE,Fraser MO,Banner W, 2016 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 34th Annual Report. Clinical toxicology (Philadelphia, Pa.). 2017 Dec;     [PubMed]
Wallace KB,Starkov AA, Mitochondrial targets of drug toxicity. Annual review of pharmacology and toxicology. 2000;     [PubMed]
Kamijo Y,Soma K,Fukuda M,Asari Y,Ohwada T, Rabbit syndrome following phenol ingestion. Journal of toxicology. Clinical toxicology. 1999;     [PubMed]
Bhattar PA,Zawar VP,Godse KV,Patil SP,Nadkarni NJ,Gautam MM, Exogenous Ochronosis. Indian journal of dermatology. 2015 Nov-Dec;     [PubMed]
Harris JE, Chemical-Induced Vitiligo. Dermatologic clinics. 2017 Apr;     [PubMed]
Seak CK,Lin CC,Seak CJ,Hsu TY,Chang CC, A case of black urine and dark skin - cresol poisoning. Clinical toxicology (Philadelphia, Pa.). 2010 Nov;     [PubMed]
Hunter DM,Timerding BL,Leonard RB,McCalmont TH,Schwartz E, Effects of isopropyl alcohol, ethanol, and polyethylene glycol/industrial methylated spirits in the treatment of acute phenol burns. Annals of emergency medicine. 1992 Nov;     [PubMed]
Conning DM,Hayes MJ, The dermal toxicity of phenol: an investigation of the most effective first-aid measures. British journal of industrial medicine. 1970 Apr;     [PubMed]
Ghosh S, Self-injection of intravenous carbolic acid and multiorgan failure. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2014 Jan;     [PubMed]
Giri PP,Sinha R,Sikka S,Meur S, Acute carbolic acid poisoning: A report of four cases. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2016 Nov;     [PubMed]
Gupta S,Ashrith G,Chandra D,Gupta AK,Finkel KW,Guntupalli JS, Acute phenol poisoning: a life-threatening hazard of chronic pain relief. Clinical toxicology (Philadelphia, Pa.). 2008 Mar;     [PubMed]

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