Camphor (2-bormanone, 2-camphonone), a cyclic ketone of the terpene group, is an essential oil distilled from the bark of the camphor tree, Cinnamomum camphora. Today, most camphor is synthesized from the hydrocarbon pinene, a derivative of turpentine oil. Camphor has been used as an aphrodisiac, contraceptive, abortifacient, suppressor of lactation, analeptic, cardiac stimulant, antiseptic, cold remedy, muscle liniment, and drug of abuse.27,34,40,45,50,60,71,72
Camphorated oil and camphorated spirits contain varying concentrations of camphor. Historically, most camphorated oil was 20% weight (of solute) per weight (of solvent) (w/w) camphor with cottonseed oil, and most camphorated spirits contained 10% w/w camphor with isopropyl alcohol. Toxicity and death following ingestion of camphorated oil, which was confused with castor oil and cod liver oil, prompted the FDA to ban the nonprescription sale of camphorated oil in the United States in 1983.3,21,40,64,81 Today, based on the 1983 FDA ruling, nonprescription camphor-containing products may not have greater than an 11% concentration of camphor. Camphorated oil is still used as an herbal remedy and muscle liniment, and products containing greater than 11% camphor can still be purchased outside of the United States.78
Common camphor-containing products include cold sore ointments (usually <1% camphor), muscle liniments, rubefacients (usually 4%–7% camphor), and camphor spirits (usually 10% camphor). Paregoric, camphorated tincture of opium, contains a combination of anhydrous morphine (0.4 mg/mL), alcohol (46%), and benzoic acid (4 mg/mL) but only a small amount of camphor.43 Camphor for industrial use can be purchased legally in the United States and contains up to 100% camphor. Occupational exposures to camphor occur during the manufacture of plastic, celluloid, lacquer, varnish, explosives, embalming fluids, and numerous pharmaceuticals and cosmetics.35
Although products containing lower concentrations of camphor are implicitly safer, life-threatening toxicity and death may still result, usually from misuse or intentional overdose. Most reported cases of acute camphor poisoning are unintentional ingestions of camphor-containing liquids mistaken for other medications.3,40,63,79 According to data obtained by the American Association of Poison Control Centers (AAPCC), each year there are approximately 10,000 exposures to camphor with very few reports of "major" toxicity. Over the past 20 years, according to the AAPCC, only six reported deaths were attributable to camphor, all in adults, at least two of which occurred in the setting of an intentional suicidal overdose. Chapter 135 contains complete references and discussion of the AAPCC data.
Camphor is a colorless glassy solid. Camphor's pharmacologic activity is not well studied and its mechanism of action remains unclear. It is unlikely that camphor has therapeutic benefit as an expectorant or an antiinfective. Camphor may provide some local analgesic and antipruritic effects, but much safer xenobiotics are available for these indications. No therapeutic benefit of camphor has been proven in any well-controlled clinical trials.
Pharmacokinetics and Toxicokinetics
There are limited data on the pharmacokinetics and toxicokinetics of camphor. Toxicity is reported following ingestion, inhalation, intranasal instillation, intraperitoneal administration, and transplacental transfer.15,65,69,75,76,86 Dermal exposures have been reported to cause systemic toxicity.30,61 Camphor from liquid preparations is rapidly absorbed from the gastrointestinal tract and camphor can be detected in the blood within 15–20 minutes postingestion.65 Camphor is highly lipid soluble and is predominantly metabolized in the liver where it undergoes hydroxylation followed by conjugation with glucuronic acid. Inactive metabolites, including campherol, borneol, hydroxy-camphor, and camphoglycuronic acid, are excreted by the kidneys.66
As with many xenobiotics, the toxic dose of camphor reported in the medical literature is highly variable.31,40,74 As little as 1 teaspoon (approximately 5 gms) of 20% camphorated oil reportedly caused death in an infant.74 Workplace standards include the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL), which is 2 mg/m3, the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV), which is 12 mg/m3 (2 ppm), and the ACGIH short-term exposure limit (STEL), which is 19 mg/m3 (3 ppm); NIOSH Immediately Dangerous To Life or Health Concentration (IDLH) is 200 mg/m3.83
The mechanism of toxicity of camphor is unknown. Camphor is an irritant. Pathologic changes following ingestion include cerebral edema, neuronal degeneration, fatty changes, centrilobular congestion of the liver, and hemorrhagic lesions in the skin, gastrointestinal tract, and kidneys.19,41,74,86
Exposure to camphor can often be detected by its characteristic aromatic odor (Chap. 20). Ingestion of camphor typically produces oropharyngeal irritation, nausea, vomiting, and abdominal pain. Generalized tonic–clonic seizures may be the first sign of camphor toxicity, usually occurring within 1–2 hours postingestion.5,8 Most seizures are brief and self-limited, although some patients may have a more protracted course.5,26,47,75 Delayed seizures, up to 9 hours following ingestion and up to 72 hours following dermal exposure, have been reported.30,67 Central nervous system (CNS) depression is common, but rarely compromises respiratory function.15,46 Other neurologic effects include headache, lightheadedness, transient visual changes, confusion, myoclonus, and hyperreflexia.44,65,69 Psychiatric effects include agitation, anxiety, and hallucinations.31,44,46 Dermal effects include flushing and petechial hemorrhages.15,34,76 Camphor does not typically cause life-threatening cardiovascular effects although a case of myocarditis is reported.9,34 Death is reported secondary to respiratory failure or seizures.15
Case reports suggest that acute ingestion of camphor can cause transient elevations of the hepatic aminotransferases.3,41,65,69,74 Chronic administration of camphor to a child caused altered mental status and elevated hepatic aminotransferases concentrations suggestive of Reye syndrome.41 When hepatotoxicity occurs, however, camphor does not typically produce morphologic changes of the liver characteristic of Reye syndrome. Albuminuria can also occur.74
Camphor crosses the placenta. Both fetal demise and delivery of healthy neonates are reported in mothers who develop camphor toxicity within 24 hours of term delivery.10,65,86 Specific dose-related toxicity could not be determined from these case reports.
Inhalational and dermal exposure from camphor usually produces only mucous membrane and dermal irritation, respectively.29
When managing most patients with camphor toxicity, no specific toxicologic diagnostic testing is indicated. Although camphor and its metabolites can be identified in blood and urine, concentrations are not useful in most cases of acute toxicity because they are not readily available and have not been proven to correlate with clinical toxicity.34,45,66
The patients who should be evaluated in a healthcare facility after an acute ingestion include those who have signs or symptoms consistent with camphor toxicity, those who have ingested more than 1 g of camphor (1 teaspoon of 20% camphorated oil or approximately 2 teaspoons of 11% camphorated oil), suicidal patients, and any patient with a significant occupational exposure.
Gastric decontamination is not well studied in patients who have ingested camphor. If lavage is deemed necessary following recent ingestion of a camphor-containing solution, nasogastric suctioning and lavage are preferable to orogastric lavage. Because camphor-containing solutions are so rapidly absorbed, the benefit of gastrointestinal decontamination is expected to rapidly diminish as the time following ingestion increases. Emetics should not be administered because camphor-induced seizures can occur rapidly prior to the onset of emesis, raising the risk of pulmonary aspiration. There is no human evidence in support for or against the use of activated charcoal in camphor ingestions. A consensus panel has recommended against the use of activated charcoal in isolated camphor ingestions.52 There is no antidote for camphor. Most patients survive with supportive care. Although the management of camphor-induced seizures is not well studied, patients should be treated with benzodiazepines. Repeat doses of benzodiazepines may be needed to control seizures. If benzodiazepines fail to control seizures, other sedative-hypnotic agents, including phenobarbital, pentobarbital, and propofol, should be administered. Case reports suggest that most patients who develop life-threatening camphor toxicity develop symptoms within a few hours postexposure. Based on this, an observation period of at least 2–4 hours following a potentially toxic ingestion of camphor is reasonable. Delayed seizures, up to 9 hours following ingestion and up to 72 hours following dermal exposure, have been reported.30,67 In case reports, hemodialysis with a lipid dialysate and either hemoperfusion using an Amberlite resin or charcoal hemoperfusion successfully removed camphor.3,25,46,47,53 Neither isolated lipid hemodialysis nor lipid dialysis in combination with hemoperfusion is routinely recommended or widely available.