Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

1) Albone
2) Carbamide peroxide
3) Hydrogen dioxide
4) Hydroperite
5) Hydroperoxide
6) Inhibine
7) Perhydrol
8) Perossido di idrogeno (Italian)
9) Peroxan
10) Peroxyde D'hydrogene (French)
11) Eau oxygenee (French)
12) Urea hydrogen peroxide
13) Urea peroxide
14) Wasserstoffperoxid (German)
15) Waterstoffperoxyde (Dutch)
16) CAS 7722-84-1
17) HYDROGEN PEROXIDE (OVER 52%)
18) HYDROGEN PEROXIDE SOLUTION, WITH NOT LESS THAN 20% BUT NOT MORE THAN 52% PEROXIDE
19) HYDROGEN PEROXIDE SOLUTION, WITH NOT LESS THEN 8% BUT LESS THAN 20% PEROXIDE
20) HYDROGEN PEROXIDE, 20 TO 60%
21) HYDROGEN PEROXIDE, 8% TO 20%
22) HYDROGEN PEROXIDE, SOLUTION, 8% TO 20%
23) HYDROGEN PEROXIDE, STABILIZED
24) HYDROGEN PEROXIDE, STABILIZED WITH MORE THAN 60% PEROXIDE

1.2.1) MOLECULAR FORMULA
1) H2-O2

Available Forms Sources

A)

1) Hydrogen peroxide is marketed as a solution in water in concentrations of 3% to 90% by weight (Budavari, 1989).
2) Hydrogen Peroxide USP is 3%.
3) Three percent hydrogen peroxide contains 2.5% to 3.5% of hydrogen peroxide by weight (Budavari, 1989).
4) Common commercial strengths of hydrogen peroxide are 27.5%, 35%, 50%, and 70% (Lewis, 1993).
5) Most industrial applications utilize hydrogen peroxide in concentrations of 35% to 70% by weight (Freeman, 1989).
6) "High-strength" hydrogen peroxide is that which contains greater than 52% peroxide (CHRIS, 1996).

B)

1) Hydrogen peroxide can be prepared by treating barium peroxide with acid (Budavari, 1989).
2) Continuous fractional crystallization will produce anhydrous hydrogen peroxide (Budavari, 1989).
3) The most widely used production method is autoxidizing an alkyl anthrahydroquinone in a continuous, cyclic process so that the quinone formed during oxidation is reduced by hydrogen to the starting material in the presence of a supported palladium catalyst (Lewis, 1993).
4) Another production method involves electrolytic processes which convert aqueous sulfuric acid or acidic ammonium bisulfate to the peroxydisulfate, which then forms hydrogen peroxide by way of hydrolyzation (Lewis, 1993).
5) Hydrogen peroxide also can be manufactured by autoxidation of isopropyl alcohol (Lewis, 1993).

C)

1) The 3% solution is used in plastics manufacturing; in white discharge printing on indigo-dyed wool; in bleaching hair, feathers, silk, straw, ivory, flour, bone, gelatin, and textile fabrics; in renovating paintings and engravings; as an oxidizer in the manufacture of dyes; in disinfecting water and hides; in artificially aging wines, liquors, etc; in refining oils and fats; as antichlor; with paraphenylenediamine as a dye for furs, dead hair, etc; in photography as hypo eliminant; with NaOH for cleaning metal surfaces; for gilding, silvering, etc; and in pharmaceutical preparations, mouthwashes, dentifrices, and sanitary lotions. It is also used as a topical antiseptic and cleansing agent in veterinary medicine (Budavari, 1989).
2) Hydrogen peroxide also is used as a source of organic and inorganic peroxides, in foam rubber, in glycerol manufacturing, in electroplating, as a laboratory reagent, in epoxidation, hydroxylation, oxidation, and reduction, as viscosity control for starch and cellulose derivatives, as an oxidizing and bleaching agent in foods, as a seed disinfectant, and as a substitute for chlorine in water and wastewater treatment (Lewis, 1993).
3) Hydrogen peroxide and peracetic acid act synergistically as a sporicide. When tested against Bacillus spore isolates, the minimal sporicidal concentration (MSC) was peracetic acid 168 to 336 parts per million (ppm) (1 to 2 hours contact time), hydrogen peroxide 5625 to 11,250 ppm (5 to 7 hours contact time) (Alasri et al, 1993).
4) Thirty-five percent "food grade" hydrogen peroxide solutions have recently been marketed in health-food stores, to be diluted and used in "hyper-oxygenation therapy" to treat conditions ranging from arthritis to cancer to AIDS. This has resulted in an increased number of adverse outcomes from exposures to these products (Thompson, 1989).
5) A 90% solution is used in rocket propulsion. Hydrogen peroxide is also used as a dough conditioner, and as a maturing and bleaching agent in food (Budavari, 1989).
6) Concentrated hydrogen peroxide is an oxidizer used in bleaching textiles and paper, and in the production of rocket fuel and foam rubber in industry (Humberston et al, 1990).
7) It is effective in loosening cerumen that occludes the auditory canal, and can clear blocked ventilation tubes used in the treatment of conductive hearing loss caused by otitis media with effusion (Brenman et al, 1986).
8) In the past, hydrogen peroxide was used with enemas to relieve meconium ileus in infants and fecal impaction in adults. However, these practices have been abandoned because of the risk of colonic injury and reports of death (Sheehan & Brynjolfsson, 1960; Olim & Ciuti, 1954; Sheibani & Gerson, 2008).
9) Dental bleaching agents containing hydrogen peroxide are thought to be potentially carcinogenic. There is a lack of strong evidence to support such a risk (Collet et al, 2001; Mahony et al, 2006; Tredwin et al, 2006; Naik et al, 2006). There is evidence to support the risk of demineralization of tooth enamel when a high concentration of hydrogen peroxide is used (Efeoglu et al, 2007; Cavalli et al, 2004; Oltu & Gurgan, 2000).
10) METHOD OF ACTION

a) Hydrogen peroxide is an oxidizing agent that rapidly decomposes into water and oxygen through an exothermic reaction in the presence of alkali, metals, and the enzyme catalase found in tissues. Its action is due to the release of oxygen when applied to tissues. The effect lasts only as long as the oxygen is being released. For each volume of 3% hydrogen peroxide solution, 10 volumes of oxygen may be produced (Gosselin et al, 1984).
b) Acidification enhances the antibacterial properties of hydrogen peroxide, but acidic pH alone is also effective (Tanner & James, 1992).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) USES: Hydrogen peroxide is a colorless, odorless liquid at room temperature, with a bitter taste. It is found in many household products at low concentrations (3% to 5%) for medicinal applications as skin disinfectant and antiseptic, and as a clothes and hair bleach. In industry, hydrogen peroxide in higher concentrations (10% to 35%) is used as bleach for textiles and paper, as a component of rocket fuels, and for producing foam rubber and organic chemicals (up to 70% concentration).
B) PHARMACOLOGY: Hydrogen peroxide is an oxidizing agent. The strength of the oxidizing reaction is determined by the concentration.
C) TOXICOLOGY: The primary effect is tissue injury due to oxidation of proteins. Hydrogen peroxide can be toxic if ingested, inhaled, or contacts the skin or eyes. Occasionally, the release of oxygen may cause distension, gastric or intestinal perforation, as well as venous or arterial gas embolization. One mL of 3% hydrogen peroxide produces 10 mL of oxygen at standard temperature and pressure, while 60 mL of 35% of hydrogen peroxide solution has the potential to produce 6.1 L of oxygen.
D) EPIDEMIOLOGY: Ingestions are relatively common, but serious toxicity is rare with ingestion of household products.
E) WITH THERAPEUTIC USE

1) Hydrogen peroxide may cause burning when applied to wounds as a disinfectant. Systemic embolization has occurred when used for irrigation of surgical wounds resulting in ECG changes and, rarely, cardiac arrest and death. Risk increases when used under high pressure, in closed tissue spaces and a highly concentrated hydrogen peroxide solution is applied.

F) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: The severity of injury depends on the concentration and amount of the ingested hydrogen peroxide. Ingestion of dilute solutions of hydrogen peroxide may result in vomiting, mild gastrointestinal (GI) irritation, gastric distension, and, on rare occasions, gastrointestinal erosions or gas embolism. Inhalation and ocular exposure of household strength hydrogen peroxide (3%) can cause respiratory irritation and mild ocular irritation, respectively.
2) SEVERE TOXICITY: INGESTION: Severe toxicity generally only occurs with ingestion of higher (greater than 10%) concentration products. Ingestions may cause caustic injuries to the gastrointestinal tract, leading to hemorrhagic gastritis, burns in the mouth, throat, esophagus, and stomach, ulcerating colitis, intestinal gangrene, and gas embolization. Systemic gas embolization can involve any organ, resulting in seizure, cerebral infarction, cerebral edema, spinal cord infarction, acute myocardial infarction, hypotension, cardiac arrest, and death. INHALATION: Inhalation of vapors from concentrated (greater than 10%) solutions may result in severe pulmonary irritation. Acute lung injury and respiratory arrest have also been reported following massive exposures. OCULAR: Eye exposure to high concentrations can cause corneal ulceration and perforation. DERMAL: Dermal exposure to concentrated solutions has resulted in burns and gangrene.

0.2.3)

A) WITH POISONING/EXPOSURE

1) Hypotension and apnea have been reported with severe poisonings.

0.2.20)

A) At the time of this review, no reproductive studies were found for hydrogen peroxide in humans. Hydrogen peroxide was not embryotoxic or teratogenic in a single study in rats and mice (when tested in hair dyes). It was weakly embryotoxic and teratogenic to chick embryos exposed in an air chamber. The implications of the latter study for human occupational exposure are unclear.

0.2.21)

A) A study of hairdressers found an increased incidence of leukemias, but this conclusion was based on a fairly small number, has not been independently confirmed, and the increased prevalence of leukemia could not be attributed to hydrogen peroxide because of chronic exposures to multiple substances with carcinogenic potential.
B) There is lack of strong evidence to support that hydrogen peroxide containing tooth whitening products have a tumor-promotion risk.

Laboratory Monitoring

A)

B)

C)

D)

E)

F)

G)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment is symptomatic and supportive. Water can be administered to dilute the solution in the case of ingestion. Gastric distention may be relieved by insertion of a nasogastric tube and suction. A careful examination should be done to detect any gas formation. Ocular exposure to 3% solution usually requires only thorough irrigation.

B) MANAGEMENT OF SEVERE TOXICITY

1) Upper airway injury may require intubation. Patients may require resuscitation for burns. Endoscopy should be performed to assess gastrointestinal tract injury if the patient is symptomatic or if higher concentration ingestion is suspected. Obtain surgical consult for patients with evidence of gastrointestinal tract perforation. If the patient has significant symptoms of oxygen embolism (such as CNS effects), place the patient in Trendelenburg position and consider treatment with hyperbaric oxygen. Treat seizures with IV benzodiazepines or barbiturates. Ocular exposure to high concentrations warrants slit lamp examination and ophthalmologic consultation.

C) DECONTAMINATION

1) PREHOSPITAL: Do not induce vomiting or administer activated charcoal. Irrigate any dermal or ocular exposures with large volumes of water.
2) HOSPITAL: Because hydrogen peroxide causes tissue injury rather than systemic toxicity, there is no role for activated charcoal. Insertion of a nasogastric tube to remove gastric contents and to decompress the stomach may be attempted following large ingestions.

D) AIRWAY MANAGEMENT

1) Endotracheal intubation should be considered early for patients who have symptoms of upper airway obstruction.

E) ANTIDOTE

1) None.

F) ENHANCED ELIMINATION

1) Hemoperfusion, hemodialysis, and peritoneal dialysis are not effective and not recommended.

G) PATIENT DISPOSITION

1) OBSERVATION CRITERIA: Most patients who have inadvertently ingested 3% hydrogen peroxide can be observed safely at home if not symptomatic.
2) ADMISSION CRITERIA: Patients who may have ingested a large amount of lower concentration solution, or any amount of high concentration solution, or who are symptomatic should be evaluated with endoscopy and treated for significant gastrointestinal burns. Patients with evidence of oxygen emboli should be admitted to an intensive care setting.
3) CONSULT CRITERIA: Consult a Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear. Obtain surgical consult as needed for patients with evidence of gastrointestinal tract perforation.

H) PITFALLS

1) Failure to recognize that oxygen embolism may cause symptoms in many organ systems.

I) PHARMACOKINETICS

1) Hydrogen peroxide is absorbed rapidly by the gastrointestinal tract.

J) DIFFERENTIAL DIAGNOSIS

1) Caustic injury may occur from ingestion of acid or alkaline products.

0.4.3)

A) Monitor for respiratory tract irritation and hypoxia after severe inhalation exposure.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
B) Ocular exposure to HOUSEHOLD STRENGTH (3%) solutions usually requires little more than thorough irrigation, since serious complications are rare. However, ocular exposure to INDUSTRIAL STRENGTH (greater than 10%) solutions not only requires thorough irrigation, but given the possibility of corneal ulceration or perforation, evaluation in a healthcare facility is recommended.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

A)

B)

C)

D)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

E)

1) Hydrogen peroxide may cause burning when applied to wounds as a disinfectant. Systemic embolization has occurred when used for irrigation of surgical wounds resulting in ECG changes and, rarely, cardiac arrest and death. Risk increases when used under high pressure, in closed tissue spaces and a highly concentrated hydrogen peroxide solution is applied.

F)

1) MILD TO MODERATE TOXICITY: The severity of injury depends on the concentration and amount of the ingested hydrogen peroxide. Ingestion of dilute solutions of hydrogen peroxide may result in vomiting, mild gastrointestinal (GI) irritation, gastric distension, and, on rare occasions, gastrointestinal erosions or gas embolism. Inhalation and ocular exposure of household strength hydrogen peroxide (3%) can cause respiratory irritation and mild ocular irritation, respectively.
2) SEVERE TOXICITY: INGESTION: Severe toxicity generally only occurs with ingestion of higher (greater than 10%) concentration products. Ingestions may cause caustic injuries to the gastrointestinal tract, leading to hemorrhagic gastritis, burns in the mouth, throat, esophagus, and stomach, ulcerating colitis, intestinal gangrene, and gas embolization. Systemic gas embolization can involve any organ, resulting in seizure, cerebral infarction, cerebral edema, spinal cord infarction, acute myocardial infarction, hypotension, cardiac arrest, and death. INHALATION: Inhalation of vapors from concentrated (greater than 10%) solutions may result in severe pulmonary irritation. Acute lung injury and respiratory arrest have also been reported following massive exposures. OCULAR: Eye exposure to high concentrations can cause corneal ulceration and perforation. DERMAL: Dermal exposure to concentrated solutions has resulted in burns and gangrene.

Vital Signs

3.3.1)

A) WITH POISONING/EXPOSURE

1) Hypotension and apnea have been reported with severe poisonings.

3.3.2)

A) WITH POISONING/EXPOSURE

1) Apnea has been reported after ingestion of concentrated (35% to 50%) solutions (Humberston et al, 1990; Giberson et al, 1989; Zecevic & Gasparec, 1979; Giusti, 1973).
2) Tachypnea and desaturation have been described in patients who develop gas emboli when hydrogen peroxide is used intraoperatively for wound irrigation (Vidil et al, 2008; Shida et al, 2002; Morikawa et al, 1995; Saissy et al, 1994).

3.3.4)

A) WITH THERAPEUTIC USE

1) Shock has been reported in severe cases, probably resulting from systemic embolization (Morikawa et al, 1995; Bassan et al, 1982).

Heent

3.4.3)

A) WITH THERAPEUTIC USE

1) CORNEAL OPACITY

a) CONTACT LENS DISINFECTION: Topical application of solutions containing 50 and 500 ppm H2O2 did not cause significant changes in corneal permeability (McNally, 1990).

B) WITH POISONING/EXPOSURE

1) SUMMARY: Eye exposure to 3% hydrogen peroxide (household strength) may result in immediate pain and irritation, lacrimation, and corneal opacity; however, severe eye injury is rare.

a) Eye exposure to industrial strength solutions (greater than 10%) may result in ulceration or perforation of the cornea. Corneal ulceration may be delayed.

2) IRRITATION: Eye exposure to 3% hydrogen peroxide (household strength) may result in immediate pain and irritation; however, severe eye injury is rare (Dickson & Caravati, 1994; Grant, 1986).
3) ULCERATION: Ocular exposure to industrial strength hydrogen peroxide solutions (greater than 10%) may result in ulceration or perforation of the cornea (Grant, 1986).

a) ONSET of corneal ulceration may be delayed (Proctor & Hughes, 1978).

4) LACRIMATION: Lacrimation may occur from exposure to mist or spray for short periods of time (Proctor & Hughes, 1978).
5) CORNEAL EPITHELIAL DEFECT has been reported in some cases:

a) CASE REPORT: In 2 case reports, ocular exposure to a solution containing 4.5% hydrogen peroxide and 75% denatured ethanol resulted in corneal epithelial defects.
b) CASE REPORT: A 24-year-old woman and an 82-year-old woman developed 90% and 30% corneal epithelial defects, respectively, resulting from inadvertent administration of Hemoccult(R) developer (4.5% hydrogen peroxide, 75% denatured ethyl alcohol) into the eye instead of ophthalmic drops. Both the 4.5% hydrogen peroxide and 75% denatured ethyl alcohol components of the solution may have contributed to the effects observed. Severe pain, tearing, and photophobia were experienced immediately by the 82-year-old patient (Tak Kam Ling et al, 1988).
c) CASE REPORT: An applanation tonometer, left soaking in a cup containing 3% H2O2 solution, evaporated overnight and was not rinsed prior to use. Immediately following tonometry, a circular corneal epithelial defect with adjacent small stromal bubbles was observed. The patient recovered in 2 days (Pogrebniak & Sugar, 1988).
d) CORNEAL CELL CULTURE DAMAGE: Hydrogen peroxide at concentrations ranging from 30 to 100 ppm produced dose-related cytotoxic effects on primary cell cultures of human corneal epithelium (Tripathi & Tripathi, 1989).

6) CORNEAL OPACITY has occurred in several cases following exposure.

a) CASE REPORT: In 2 case reports, ocular exposure to 3% hydrogen peroxide resulted in corneal opacities.
b) CASE REPORT: When 3% hydrogen peroxide was applied to a tonometer tip 30 minutes before use and not irrigated prior to use, blurred vision and pain were noted and an O-shaped opacity developed in the anterior stroma (Levenson, 1989).
c) CASE REPORT: Reversible corneal opacity was seen after insertion of a soft contact lens (without rinsing) that had been soaked in a 3% H2O2 solution for a week (Lavery et al, 1991).

3.4.5)

A) WITH POISONING/EXPOSURE

1) Exposure to hydrogen peroxide vapors or mist may result in irritation and inflammation of the nose.
2) IRRITATION: Exposure to high concentrations of hydrogen peroxide vapor or mist may cause extreme irritation and inflammation of the nose and throat (Proctor & Hughes, 1978).

3.4.6)

A) WITH POISONING/EXPOSURE

1) Exposure to hydrogen peroxide may result in irritation and inflammation, papillae hypertrophy, gingival ulceration, gaseous distention of soft tissue, and burns, depending on the concentration and extent of exposure.

a) IRRITATION/BURNS: Exposure to high concentrations of hydrogen peroxide vapor or mist may cause extreme irritation and inflammation of the nose and throat, or burns (Proctor & Hughes, 1978).
b) CASE REPORT: Oropharyngeal burns were reported in a 4-year-old girl who ingested a refrigerated 35% solution of hydrogen peroxide, mistaking it for chilled water (Thompson, 1989).

2) GASEOUS DISTENTION may occur following toxic exposures.

a) CASE REPORT: Gaseous distention of the soft tissues was reported following irrigation of a root canal during endodontic treatment (Walker, 1975; Bhat, 1974).

3) GINGIVAL ULCERATION: Dilute (3%) solutions may induce oral gingival ulceration or enhance prior injuries of the mucous membranes of the mouth (Rees & Orth, 1986).
4) Dental bleaching agents containing hydrogen peroxide are thought to be potentially carcinogenic. There is a lack of strong evidence to support such a risk (Mahony et al, 2006; Naik et al, 2006; Tredwin et al, 2006; Collet et al, 2001). Demineralization of tooth enamel may occur when a high-concentration hydrogen peroxide solution is used (Efeoglu et al, 2007; Cavalli et al, 2004; Oltu & Gurgan, 2000).
5) PAPILLAE HYPERTROPHY: Hypertrophy of the papillae of the tongue may occur from chronic use of hydrogen peroxide mouthwash (Wade & Reynolds, 1977).

Cardiovascular

3.5.2)

A) AIR EMBOLISM

1) WITH THERAPEUTIC USE

a) CASE REPORT: Marked ST elevation, shock, and coma were reported in 1 patient following irrigation of an infected and fistulous herniorrhaphy wound with 3% hydrogen peroxide (Bassan et al, 1982). The most probable explanation is widespread oxygen embolization. The patient's ECG and clinical status returned to normal within 1 hour.
b) CASE REPORT: Cardiac arrest immediately followed use of hydrogen peroxide during preparation of the femoral canal for a hip arthroplasty (Timperley & Bracey, 1989).
c) CASE REPORT: An 11-month-old developed gas emboli after incision and drainage of an abscess and wound irrigation with 15 mL of 3% hydrogen peroxide (Schwab & Dilworth, 1999). Within 30 seconds, the infant became apneic, and end-tidal CO(2) abruptly fell along with the absence of cardiac output. Radiological gas was confirmed in the abdominal wall along with acute lung injury.

1) The infant recovered without sequelae following supportive care that included cardiac massage, hydrocortisone, and sodium bicarbonate.
2) Extrapolation from animal data suggests that 2 mL of 3% hydrogen peroxide could release 20 mL of oxygen microbubbles, and that a 10 kg infant may only require 2 mL/kg of gas (20 mL) to sustain a cardiac arrest.

d) CASE REPORT: A 66-year-old man developed a venous oxygen embolism after 60 mL of 3% hydrogen peroxide was injected into a perianal fistula during surgery to locate the internal opening. Within 30 seconds, the patient developed a decrease in end-tidal carbon dioxide tension from 32 to 13 mmHg, a drop in blood pressure from 140/65 to 80/50 mmHg, a decrease in oxygen saturation from 100% to 92%, an increase in central venous pressure from 8 to 22 mmHg, and a heart murmur signaling venous oxygen embolism. The authors stated that at standard temperature and pressure, each mL of 3% hydrogen peroxide generates approximately 10 mL of oxygen. The patient was immediately tilted 20 degrees to the left, placed on 100% oxygen, and the central venous line aspirated with no gas return. No resuscitative drugs were required. The symptoms resolved within 32 minutes (Jones et al, 2004).
e) CASE REPORT: A 54-year-old man developed hypotension, oxygen desaturation intraoperatively during cervical spinal surgery when 30 mL of 3% hydrogen peroxide was used for wound irrigation. Symptoms resolved with placing the patient in trendelenburg, aspirating the hydrogen peroxide from the surgical wound, and fluid resuscitation. The event was thought to be the result of an acute oxygen embolus. The patient had a full recovery with no neurologic sequelae (Morikawa et al, 1995).
f) CASE REPORT: A 54-year-old woman developed hypoxia and dysrhythmias after irrigation of a pelvis wound with 250 mL of 3% hydrogen peroxide. After hyperbaric oxygen therapy, the patient recovered without cardiac or neurologic sequelae. Irrigation of the wound under high pressure in a partially closed cavity were thought to have been risk factors for the embolus (Vidil et al, 2008).
g) CASE REPORT: A patient in a military surgery case developed tachypnea, arterial desaturation, and "mill-wheel" murmur after having hydrogen peroxide injected under pressure into a partially closed muscle wound. Arterial gas embolus was confirmed by CT, and the patient recovered with hyperbaric oxygen (Saissy et al, 1994).

2) WITH POISONING/EXPOSURE

a) One study reviewed poison center records of 11 patients (age range, 4 to 89 years) with portal gas embolism after inadvertent exposure to hydrogen peroxide; 10 patients ingested 35% hydrogen peroxide and 1 patient ingested 12% hydrogen peroxide. Abdominal CT scans of all patients showed portal venous gas embolism. All patients were successfully treated with hyperbaric oxygen treatment (French et al, 2010).
b) CASE REPORT: A 32-year-old woman developed severe abdominal pain, nausea, and vomiting after an inadvertent ingestion of about 20 mL of 35% hydrogen peroxide. All laboratory results were normal, except for elevated liver enzymes (serum glutamic-oxalocetic transaminase of 71 Units/L and serum glutamic-pyruvic transaminase of 85 Units/L). A CT scan of the abdomen and pelvis showed air in the portal venous system. She received hyperbaric oxygen (at 3 atmospheres absolute compression) for 3 hours about 5 hours after the ingestion of hydrogen peroxide. A complete resolution of the portal venous air was observed on a repeat CT scan the next day (Papafragkou et al, 2012).
c) CASE REPORT: Ingestion of 2 to 6 ounces (oz) of 35% hydrogen peroxide has resulted in oxygen embolization in the portal venous system and heart, causing ischemic ECG changes and death in 1 case (Christensen et al, 1992; Luu et al, 1992).
d) CASE REPORT: There have been at least 6 fatalities in children from ingestion of hydrogen peroxide. Emboli have been seen in the portal, gastric, superior mesenteric venous systems, as well as in multiple organs (Cina et al, 1994).
e) CASE REPORT: An 11-year-old boy inadvertently received 100 mL of 3% hydrogen peroxide intravenously instead of fluid replacement with isotonic saline, developed ventricular fibrillation, and ultimately died. Autopsy revealed generalized gas embolism upon opening great vessels, heart, and lung under water. Brain biopsy demonstrated evidence of lipid peroxidation (Lubec et al, 1996).

B) MYOCARDIAL INFARCTION

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 60-year-old woman with a history of hypertension presented with a 2-hour history of nausea, vomiting, and chest discomfort after ingesting a mouthful of a 35% hydrogen peroxide solution. She had a blood pressure of 150/90 mm Hg and a heart rate of 100 beats/min. An ECG showed sinus rhythm and ST elevation at inferolateral leads with reciprocal ST segment depression in V1, V2, aVR and aVL. An emergency cardiac catheterization showed normal epicardial coronary arteries and an echocardiogram showed inferior hypokinesia. In the ICU, an ECG revealed ST segment resolution and negative T wave. Her troponin-I value was 7.3 ng/mL (normal limits, less than 0.1 ng/mL) 7 hours after presentation. Following supportive care, she recovered and was discharged after 3 days (Islamoglu et al, 2012).

Respiratory

3.6.2)

A) INJURY OF UPPER RESPIRATORY TRACT

1) WITH POISONING/EXPOSURE

a) IRRITATION: Inhalation of peroxide vapors of high concentration formulations may cause extreme irritation and inflammation in the nose, throat, and tracheobronchial tree.

B) INTERSTITIAL PNEUMONIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 41-year-old worker had transbronchial biopsy-proven interstitial lung disease that was associated with chronic exposure to aerosol hydrogen peroxide concentrations of 41/mg/m(3) (upper legal limit: 1.5 mg/m(3)) in the workplace.

1) Gas exchange impairment improved upon removal from exposure. The patient also had a history of smoking 40 cigarettes a day (Kaelin et al, 1988).

C) APNEA

1) WITH POISONING/EXPOSURE

a) CASE REPORTS: Apnea developed in a patient shortly after ingestion of an unknown amount of concentrated hydrogen peroxide (35% to 50%) (Vander Heide & Seamon, 2003; Giberson et al, 1989). Apnea has been the cause of death in similar fatal cases (Zecevic & Gasparec, 1979; Giusti, 1973).

D) PULMONARY EMBOLISM

1) WITH THERAPEUTIC USE

a) CASE REPORT

1) ADULT: A 53-year-old woman underwent bilateral pulmonary lobectomy with open hemithoracic cavity irrigation (with 300 mL of hydrogen peroxide) at the end of the procedure. The patient had an immediate drop in end-tidal CO2 concentration along with hemodynamic instability (decreased oxygen saturation, ST segment change on the ECG) almost immediately following irrigation. Hypotension and ventricular tachycardia were successfully treated; no permanent sequelae were reported (Konrad et al, 1997).
2) PEDIATRIC: An 11-year-old boy developed a "tonic convulsion" and showed clinical signs of pulmonary embolism after 12 mL of 3% hydrogen peroxide was used to irrigate a relatively closed left femur wound. The patient recovered with symptomatic treatment (Shida et al, 2002).

E) RESPIRATORY DISTRESS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 2-year-old girl developed foaming at the mouth, hematemesis, and epigastric pain right after inadvertently ingesting 2 sips of 35% hydrogen peroxide instead of water. She presented to the ED 45 minutes postingestion with confusion, stridor, apnea, cyanosis, and cardiorespiratory arrest. She died despite cardiopulmonary resuscitation. An autopsy results revealed congestion with thickened white areas of the GI, necrotic areas and erosions, gaseous distension of intestinal mucosal surfaces, congestion of the visceral pleura in the lungs, diffuse alveolar damage with necrosis, and heavy inflammation of the bronchial basal lamina. Respiratory distress syndrome was determined to be the cause of death (Indorato et al, 2014).
b) CASE REPORT: A 3-year-old girl presented with vomiting, lethargy, and respiratory distress after ingesting 10 mL of 20% hydrogen peroxide solution. She also developed generalized tonic-clonic seizures in the ED. Both brain computed tomography and magnetic resonance imaging revealed diffuse cerebral edema. She was transferred to the pediatric intensive care unit with a Glasgow coma score of 3. Despite aggressive supportive care, including IV midazolam and phenytoin for seizures, dexamethasone and mannitol for cerebral edema, vasopressors for hypotension, and 3 sessions of hyperbaric oxygen, her condition did not improve and she died on day 6 (Ikiz et al, 2013).

Neurologic

3.7.2)

A) NEUROPATHY

1) WITH POISONING/EXPOSURE

a) CASE SERIES: In a retrospective chart review of 670 exposures of 3% hydrogen peroxide, 85.6% of cases were asymptomatic (Mofenson et al, 1995). Of those symptomatic patients, neurological effects (confusion, drowsiness, muscle weakness) were reported in only 0.4% of exposures.

B) CEREBRAL EDEMA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Intermittent recurrent tonic-clonic seizures were described within minutes after ingestion of an unknown amount of 35% hydrogen peroxide. Cerebral edema was noted. Residual neurologic sequelae included extremity weakness and truncal ataxia (Giberson et al, 1989).
b) CASE REPORT: Ingestion of 4 to 6 oz of 35% hydrogen peroxide resulted in decorticate posturing, right focal seizures, and eventually death from hypoxic encephalopathy in a 2-year-old boy. Postmortem examination revealed diffuse cerebral edema with cerebellar and uncal tonsillar notching (Christensen et al, 1992).
c) CASE REPORT: A 3-year-old girl presented with vomiting, lethargy, and respiratory distress after ingesting 10 mL of 20% hydrogen peroxide solution. She also developed generalized tonic-clonic seizures in the ED. Both brain computed tomography and magnetic resonance imaging revealed diffuse cerebral edema. She was transferred to the pediatric intensive care unit with a Glasgow coma score of 3. Despite aggressive supportive care, including IV midazolam and phenytoin for seizures, dexamethasone and mannitol for cerebral edema, vasopressors for hypotension, and 3 sessions of hyperbaric oxygen, her condition did not improve and she died on day 6 (Ikiz et al, 2013).

C) HEMIPLEGIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 63-year-old man unintentionally ingested 120 mL of 35% hydrogen peroxide, developed general malaise, and had an initial Glasgow Coma Scale score of 5 on admission (Ijichi et al, 1997). Over a period of 5 days, the patient's neurological status improved, but he began to complain of numbness of the extremities. MRI results showed multiple brain infarction and neurologic examination revealed left hemiparesis (primarily the lower limb).
b) CASE REPORT: Three stockbreeders (aged 30, 45, and 62 years) unintentionally drank from a container of 60% hydrogen peroxide solution. All developed GI tract lesions. One patient developed altered mental status requiring intubation, migratory paresis of the right limbs, cranial nerve VI paresis (reversed in 10 days), and left hemiparesis, which reversed in 2 months (BreaHernando & MartinBurcio, 1991).

D) CEREBRAL EMBOLISM

1) WITH POISONING/EXPOSURE

a) CASE SERIES: Arterial gas embolization with brain infarct was confirmed by MRI and CT scan in 3 patients following exposure of small amounts (30 mL or less) of concentrated hydrogen peroxide (35%) (Ashdown et al, 1998) , resulting in death and permanent CNS damage.

1) The patients included a 4-year-old child who developed permanent spastic quadriplegia and an 84-year-old with persistent hemiparesis; the third patient was a 44-year-old man who initially complained of the inability to move his arms or legs and died 2 days after exposure, without regaining consciousness.

b) CASE REPORT: A 56-year-old woman developed cerebral gas embolism after ingesting hydrogen peroxide, but was successfully treated with delayed hyperbaric oxygen therapy. She developed reduced level of consciousness and vomiting (foamy liquid) within 15 minutes of inadvertently ingesting 30 mL of 3% hydrogen peroxide. A brain MRI 2 days postingestion revealed several non-enhancing intra-axial lesions in both cerebral and cerebellar hemispheres involving anterior and posterior vascular territories. There were lesions with restricted diffusion. About 80 hours postingestion, she received hyperbaric oxygen therapy (HBOT) for 60 minutes, resulting in a dramatic improvement of her symptoms. At this time, she was mildly dysarthric. A week later, she had only mild right arm ataxia. A hypermobile inter-arterial septum was observed on a transthoracic echocardiogram which suggested small patent foramen ovale. On a follow-up visit 4 months postingestion, a repeat MRI revealed scattered white matter T2 hyperintensities within the bilateral centrum semiovale. Most of the lesions observed on the initial MRI had completely resolved (Baharnoori & Lazarou, 2012).
c) CASE REPORT: An 82-year-old woman developed ataxia, diplopia, and confusion immediately after an unintentional ingestion of approximately 3 oz of 35% hydrogen peroxide ("food grade"). Approximately 12 minutes after ingestion, she presented to the emergency department asymptomatic with a normal neurologic examination. Approximately 4 hours and 42 minutes after ingestion, she had a brief grand mal seizure, followed by a deterioration in her mental status (Glasgow Coma Scale score of 6) and a brief episode of apnea. An arterial gas embolism was suspected; the patient received hyperbaric therapy approximately 11 hours postingestion. Because of a dramatic improvement in neurologic status, the second scheduled hyperbaric therapy was cancelled. MRI of brain showed a small area of acute cortical and subcortical ischemia in the left frontal parietal region and extensive chronic small vessel ischemia in the deep white matter of both hemispheres and the pons. She was released from the hospital the next day with no further symptoms or neurologic effects (Vander Heide & Seamon, 2003).
d) CASE REPORT: A 54-year-old woman developed brain gas emboli after an unintentional ingestion of concentrated hydrogen peroxide (Ciechanowicz et al, 2007).

E) CEREBRAL ARTERY OCCLUSION

1) WITH POISONING/EXPOSURE

a) CASE REPORT: An 84-year-old man developed focal neurologic deficits after ingesting 30 mL of 35% hydrogen peroxide solution (Sherman et al, 1994). MRI revealed multiple cerebral and cerebellar infarcts.
b) CASE REPORT: A 48-year-old man unintentionally drank 2 "sips" of an unlabeled container of 33% hydrogen peroxide and developed hematemesis, headache, confusion, left-sided facial droop, motor weakness, and left-sided hemiparesis. CT and MRI revealed findings consistent with multiple areas of cerebral ischemia. The patient was treated with hyperbaric oxygen therapy and recovered with mild residual deficit (Rider et al, 2008).

F) PARAPLEGIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 47-year-old man experienced acute paraplegia after ingesting a reported amount of 100 mL of 50% hydrogen peroxide. The patient was found soon after the time of ingestion with foam around his mouth and weakness in both legs. Upon arrival to the hospital, his neurological exam revealed a grade 0 out of 5 for muscle power in the lower limbs. Symptoms continued to progress over the next 3 hours. The patient became increasingly drowsy and developed muscle weakness in the upper extremities (grade 2/5). Multiple embolic infarcts over the supratentorial and infratentorial regions as well as on the cervical spine were found on MRI. The patient underwent hyperbaric oxygen treatment. Symptoms gradually improved over 6 days, and muscle strength returned to the upper limbs. He was discharged with paraparesis (Liu et al, 2007).
b) CASE REPORT: A 48-year-old man unintentionally drank 2 "sips" of an unlabeled container of 33% hydrogen peroxide and developed hematemesis, headache, confusion, left-sided facial droop, motor weakness, and left-sided hemiparesis. CT and MRI revealed findings consistent with multiple areas of cerebral ischemia. The patient was treated with hyperbaric oxygen therapy and recovered with mild residual deficit (Rider et al, 2008).

G) CENTRAL NERVOUS SYSTEM FINDING

1) WITH POISONING/EXPOSURE

a) BRAIN LIPID PEROXIDATION

1) CASE REPORT: An 11-year-old boy inadvertently received 100 mL of 3% hydrogen peroxide intravenously instead of fluid replacement with isotonic saline, developed ventricular fibrillation, and ultimately died. Autopsy revealed generalized gas embolism upon opening great vessels, heart, and lung under water. Brain biopsy demonstrated evidence of lipid peroxidation (Lubec et al, 1996).

Gastrointestinal

3.8.2)

A) GASTRITIS

1) WITH POISONING/EXPOSURE

a) Spontaneous vomiting may occur (Baharnoori & Lazarou, 2012; Horowitz, 2004).
b) CASE SERIES: In a retrospective chart review of 670 exposures of 3% hydrogen peroxide, 85.6% of cases were asymptomatic. Of those with symptoms, 6.1% developed gastrointestinal symptoms, which included vomiting, nausea, abdominal pain, and throat irritation (Mofenson et al, 1995).
c) INFLAMMATION: In high concentrations, H2O2 may cause extreme irritation and inflammation in the mouth, throat, esophagus, and stomach (Proctor & Hughes, 1978).
d) CASE REPORT: Esophagogastroduodenoscopy performed on an 82-year-old woman who unintentionally ingested approximately 3 oz of 35% hydrogen peroxide ("food grade") revealed grade I gastric damage secondary to caustic ingestion (Vander Heide & Seamon, 2003).
e) HYPERTROPHIED PAPILLAE: Chronic use of H2O2 as a mouthwash may be associated with hypertrophied papillae of the tongue (Wade & Reynolds, 1977).
f) ENTERITIS: Enteritis developed in 7 patients from endoscopes that were recently sterilized with 3% H2O2 (Bilotta & Waye, 1989).
g) HEMORRHAGIC GASTRITIS: Ingestion of 2 to 6 oz of 35% H2O2 has resulted in hemorrhagic gastritis without perforation, as revealed by endoscopic exam or laparotomy (Christensen et al, 1992; Luu et al, 1992; Ijichi et al, 1997).
h) CASE REPORT: After unintentionally ingesting an unknown quantity of 60% hydrogen peroxide, a 6-year-old boy presented with abdominal pain, "white foam" in his mouth, sialorrhea, loss of consciousness, stupor, and edema of the lips. Approximately 2.5 hours postingestion, his vital signs were temperature 36 degrees C, pulse 124 beats per minute (bpm), respiratory rate 48 breaths/min, and blood pressure 88/67 mmHg. His tongue was white and the epiglottis was edematous with local hyperemia (Sansone et al, 2004).

1) Abdominal and chest x-rays revealed gastric dilatation and bilateral diffuse reticulonodular perihilar infiltrates. Upper gastrointestinal endoscopy revealed edema in the middle and inferior esophagus with confluent erythema, involving the entire circumference of the esophagus; there was active bleeding from the mucosa. Twenty-four hours after admission, laparoscopy showed edema of the posterior gastric wall, moderate liquid in Douglas's pouch, and dilatation of transverse colon but no intraabdominal gas. Following supportive care, he recovered fully and was discharged on day 18. A follow-up abdominal ultrasound on day 12 was normal (Sansone et al, 2004).

i) CASE REPORT: A 25-year-old woman presented to the emergency department (ED) with epigastric pain and persistent vomiting, accompanied with a small amount of blood, after ingesting "one mouthful" (approximately 40 mL) of 3% hydrogen peroxide. Lab results revealed a hemoglobin concentration of 12.3 g/dL and an elevated amylase concentration (137 units/L {normal range of 20 to 100 units/L}); however, all other lab values were within normal limits. A CT scan demonstrated the presence of portal venous gas emboli and an upper GI endoscopy, performed 2 hours postingestion, revealed several large, round mucosal erosions in the distal esophagus and diffuse hemorrhagic gastritis of the entire gastric mucosa. Following supportive care, the patient gradually recovered and was discharged approximately 14 days postingestion (Moon et al, 2006).
j) CASE SERIES: A report of 4 cases of unintentional hydrogen peroxide exposure noted gastrointestinal caustic injury in all cases. Two patients were exposed orally and 2 patients were exposed via enemas. All patients had good clinical and endoscopic recovery with conservative treatment (Asanza et al, 1995).
k) CASE REPORT: A 3-year-old girl presented with vomiting, lethargy, and respiratory distress after ingesting 10 mL of 20% hydrogen peroxide solution. She also developed generalized tonic-clonic seizures in the ED. Both brain computed tomography and magnetic resonance imaging revealed diffuse cerebral edema. She was transferred to the pediatric intensive care unit with a Glasgow coma score of 3. Despite aggressive supportive care, including IV midazolam and phenytoin for seizures, dexamethasone and mannitol for cerebral edema, vasopressors for hypotension, and 3 sessions of hyperbaric oxygen, her condition did not improve and she died on day 6 (Ikiz et al, 2013).
l) CASE REPORT: A 2-year-old girl developed foaming at the mouth, hematemesis, and epigastric pain right after inadvertently ingesting 2 sips of 35% hydrogen peroxide instead of water. She presented to the ED 45 minutes postingestion with confusion, stridor, apnea, cyanosis, and cardiorespiratory arrest. She died despite cardiopulmonary resuscitation. An autopsy results revealed congestion with thickened white areas of the GI, necrotic areas and erosions, gaseous distension of intestinal mucosal surfaces, congestion of the visceral pleura in the lungs, diffuse alveolar damage with necrosis, and heavy inflammation of the bronchial basal lamina. Respiratory distress syndrome was determined to be the cause of death (Indorato et al, 2014).

B) COLITIS

1) WITH POISONING/EXPOSURE

a) Administration of H2O2 enemas, as 3% or more diluted solutions, have caused colitis, and in some cases ulcerative colitis (Meyer et al, 1981; Wade & Reynolds, 1977; Sheehan & Brunjolfsson, 1960).
b) CASE REPORT: A 59-year-old man developed rectal bleeding, urgency, and fecal incontinence within 12 hours of self-administering 120 mL of hydrogen solution (60 mL of 3% hydrogen peroxide diluted with 60 mL of tap water) enema. Presacral thickening and diminished anal tone were observed during rectal examination. A flexible sigmoidoscopy revealed superficial necrosis, submucosal hemorrhage, and marked edema without friability. Biopsies showed erosion of the surface, sloughing, decreased number of glands, and edema and hemorrhage within lamina propria with a bubbly appearance of the goblet cells. Following supportive care, including antibiotics and mesalamine enemas, his symptoms resolved within 2 days (Love et al, 2012).
c) PLAQUES: Irrigation of endoscopes prior to sigmoidoscopy or colonoscopy was associated with the development of discrete or confluent white plaques adherent to the colonic mucosa. The plaques were associated with occasional rectal bleeding, tenesmus, or increased frequency of stools (Jones et al, 1988).

C) PROCTITIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 27-year-old woman presented to the hospital with abdominal pain, diarrhea, and rectal bleeding 2 hours after administering 200 mL of 3% hydrogen peroxide as an enema in an attempt to relieve constipation. Physical exam of the distal rectum revealed friable, granular, and ulcerated mucosa. Histological studies of rectal biopsies revealed mucosal congestion, lymphatic ductus ektazi, bleeding, and necrosis. The patient was given budesonide 2 mg and her condition improved. A repeat sigmoidoscopic exam revealed normal tissue at the third day of treatment, and the patient was discharged without further sequelae(Tas et al, 2011).

D) GASTRIC ULCER

1) WITH POISONING/EXPOSURE

a) LACK OF EFFECT: In a retrospective chart review of hydrogen peroxide 3% exposures, 85.6% of cases were asymptomatic with all cases but one resulting in a benign outcome (Henry et al, 1996).
b) CASE REPORT: A 3-year-old ingested 2 to 4 oz of hydrogen peroxide 3% and developed blood-streaked emesis. An upper GI endoscopy was performed for persistent emesis, and multiple gastric ulcers and duodenal erosions were found. Therapy included intravenous cimetidine and sucralfate. Follow-up was negative (Henry et al, 1996).
c) CASE REPORT: A 39-year-old man unintentionally drank 250 mL from a container of 35% hydrogen peroxide. The patient developed hematemesis and evidence of diffuse caustic mucosal injury of the entire stomach on esophagogastroduodenoscopy (Pritchett et al, 2007).

E) CHEMICAL BURN

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Oropharyngeal burns were reported following ingestion of a 35% solution of H2O2 (Thompson, 1989).

F) SWOLLEN ABDOMEN

1) WITH POISONING/EXPOSURE

a) EFFECTS OF GAS PRODUCTION: Frequently, the stomach becomes distended from the rapid liberation of oxygen, which could result in perforation (Proctor & Hughes, 1978).

G) PERFORATION OF INTESTINE

1) WITH THERAPEUTIC USE

a) Cases of ruptured colon and intestinal gangrene with gas embolization have been reported following H2O2 enemas, particularly in the newborn (Bilotta & Waye, 1989; Ellis & Clatworthy, 1966; Sheehan & Brunjolfsson, 1960; Pumphrey, 1951).

H) TENESMUS

1) WITH THERAPEUTIC USE

a) Severe lower abdominal pain and tenesmus were reported following H2O2 enemas (Meyer et al, 1981).

3.8.3)

A) ANIMAL STUDIES

1) GI HEMORRHAGE

a) TOOTH WHITENERS: Rats who were exposed to tooth whiteners containing 10% to 35% carbamide peroxide developed acute toxicity and even death in several cases (Cherry et al, 1993). Rats were given a dose of tooth whitener (5 g/kg fasting body weight) by stomach gavage. Those receiving the 35% product all developed signs of acute distress within 15 minutes of exposure, and 3 died of gastric hemorrhaging and bloating. Rats given the lesser strength products (10% or 15%) developed similar effects, only milder.

Hepatic

3.9.2)

A) AIR EMBOLISM

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 32-year-old woman developed severe abdominal pain, nausea, and vomiting after an inadvertent ingestion of about 20 mL of 35% hydrogen peroxide. All laboratory results were normal, except for elevated liver enzymes (serum glutamic-oxalocetic transaminase of 71 Units/L and serum glutamic-pyruvic transaminase of 85 Units/L). A CT scan of the abdomen and pelvis showed air in the portal venous system. She received hyperbaric oxygen (at 3 atmospheres absolute compression) for 3 hours about 5 hours after the ingestion of hydrogen peroxide. A complete resolution of the portal venous air was observed on a repeat CT scan the next day (Papafragkou et al, 2012).
b) CASE REPORT: A 6-year-old boy developed massive gas emboli throughout the hepatic portal system after he unintentionally drank a glass full of 35% hydrogen peroxide (sold as a health food additive). Following hyperbaric treatment, he recovered without sequelae. The authors calculated that each mL of 35% hydrogen peroxide will release 115 mL of oxygen in the stomach when it reacts with hydrochloric acid. Approximately 7 L of oxygen is released from a 60 mL glass of hydrogen peroxide. Hepatic gas embolism may occur after this large release of oxygen is forced through the gastric mucosa into the portal circulation (Horowitz, 2004).
c) There have been at least 6 fatalities in children from ingestion of hydrogen peroxide. Emboli have been seen in the portal, gastric, and superior mesenteric venous systems, as well as in multiple organs (Cina et al, 1994; Christensen et al, 1992; Luu et al, 1992).
d) CASE REPORT: A 25-year-old woman presented to the ED with epigastric pain and persistent vomiting after ingesting "one mouthful" (approximately 40 mL) of 3% hydrogen peroxide. Chest and abdominal x-rays showed a linear air density at the right upper quadrant of the abdomen, and an abdominal CT scan revealed a peripheral pattern of gas distribution in the liver, indicative of portal venous gas emboli. Resolution of the portal venous gas occurred 48 hours after the patient began high-oxygen therapy (Moon et al, 2006).

Dermatologic

3.14.2)

A) VITILIGO

1) WITH POISONING/EXPOSURE

a) If contact with the skin is relatively short, no damage will occur beyond whitening or bleaching, accompanied by a tingling sensation.

1) MECHANISM: The whitening of the skin is caused by fusion of hydrogen peroxide into the skin and decomposition, forming oxygen bubbles that appear white due to refraction.
2) DURATION: The skin returns to normal within 2 to 3 hours if it has been washed promptly after contact. However, hair may remain permanently bleached.

B) CHEMICAL BURN

1) WITH POISONING/EXPOSURE

a) If spills on the skin are not promptly removed, a chemical burn may occur (Wade & Reynolds, 1977).
b) CASE REPORT: A 15-year-old girl suffered severe scalp injury with necrosis of the galea aponeurotica when a 35% hydrogen peroxide solution was used to highlight her hair. Reconstructive plastic surgery was required (Schroder et al, 2008).

C) GANGRENE

1) WITH POISONING/EXPOSURE

a) Strong hydrogen peroxide solution may produce gangrene of the scalp if the solution is not diluted prior to the hair bleaching process (Wade & Reynolds, 1977).

3.14.3)

A) ANIMAL STUDIES

a) ANIMAL STUDIES: Repeated exposure of 7 ppm for 6 months in dogs caused bleaching of the hair, lacrimation, and sneezing. There was local atelectasis on autopsy (Proctor & Hughes, 1978).

Reproductive

3.20.1)

A) At the time of this review, no reproductive studies were found for hydrogen peroxide in humans. Hydrogen peroxide was not embryotoxic or teratogenic in a single study in rats and mice (when tested in hair dyes). It was weakly embryotoxic and teratogenic to chick embryos exposed in an air chamber. The implications of the latter study for human occupational exposure are unclear.

3.20.2)

A) HUMANS

1) At the time of this review, no reproductive studies were found for hydrogen peroxide in humans.

B) ANIMAL STUDIES

1) Hydrogen peroxide was not embryotoxic or teratogenic in a single study in rats and mice (when tested in hair dyes) (Burnett, 1976).
2) Hydrogen peroxide was weakly embryotoxic and teratogenic to chick embryos exposed in an air chamber, with an ED50 of 2.7 micromoles per egg (Korhonen, 1984). The implications of this study for human occupational exposure are unclear.
3) In a Japanese study, 10% hydrogen peroxide in the diet was associated with some malformations of the bone and viscera in rats, but this was attributed to maternal malnutrition (Moriyama, 1982).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS7722-84-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) IARC Classification

a) Listed as: Hydrogen peroxide
b) Carcinogen Rating: 3

1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.

3.21.2)

A) A study of hairdressers found an increased incidence of leukemias, but this conclusion was based on a fairly small number, has not been independently confirmed, and the increased prevalence of leukemia could not be attributed to hydrogen peroxide because of chronic exposures to multiple substances with carcinogenic potential.
B) There is lack of strong evidence to support that hydrogen peroxide containing tooth whitening products have a tumor-promotion risk.

3.21.3)

A) LEUKEMIA

1) A study of hairdressers found an increased incidence of leukemias, but this conclusion was based on a fairly small number, has not been independently confirmed, and the increased prevalence of leukemia could not be attributed to hydrogen peroxide because of mixed exposures (Walrath, 1978). At the time of this review, chronic exposure to hydrogen peroxide is not known to cause cancer in humans.

3.21.4)

A) ORAL CANCER

1) The concern for oral cancer came about with the popularity of tooth whitening products containing hydrogen peroxide. Animal studies assessing hyperplasia in hamster cheek and in mice demonstrate a weak tumor-promoting activity. However, there is no evidence to support that appropriately used low concentration hydrogen peroxide containing tooth bleaching products are carcinogenic in humans. Further research is indicated (Naik et al, 2006; Tredwin et al, 2006; Collet et al, 2001).

B) GASTRIC CARCINOMA

1) Hydrogen peroxide 30% was found to induce gastrointestinal tumors and was given a rating of Carcinogenic by RTECS criteria in mouse studies (RTECS , 1991).
2) Hydrogen peroxide 90% was found to induce gastrointestinal tumors and was given a rating of Equivocal Tumorigenic Agent by RTECS criteria in mouse studies (RTECS , 1991).

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) No routine laboratory tests are needed when a small amount of 3% hydrogen peroxide is ingested.
B) After a high-volume or high-concentration ingestion, patients should be evaluated for caustic injury and for oxygen embolism.
C) Patients with any symptoms of oral or gastrointestinal tract injury should undergo endoscopy.
D) Any patient with symptoms of cerebral oxygen embolism should have a head CT.
E) Echocardiography or chest CT with contrast may demonstrate oxygen in the right ventricle.
F) Abdominal and upright chest radiograph may reveal radiolucent gas in the gastrointestinal tract, right ventricle, mediastinum, or the portal venous system.
G) An ECG and continuous cardiac monitoring may reveal signs of gas embolization. Desaturation on pulse oximetry, hemodynamic instability, and neurologic deficit may be indicative of gas embolus, and at that time an arterial blood gas would be indicated.

Radiographic Studies

A)

1) If respiratory tract irritation is present, monitor chest x-ray.

B)

1) CT or MRI may reveal evidence of an infarction in patients with neurologic abnormalities after ingestion of concentrated hydrogen peroxide solution (Sherman et al, 1994; Ashdown et al, 1998).
2) CT scan may demonstrate portal venous emboli (Pritchett et al, 2007).

Methods

A)

1) Analysis of body fluids, particularly gastric aspirates, if done immediately, will reveal the presence of peroxides using the titanium chloride reaction.

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients who may have ingested a large amount of lower concentration solution, or any amount of high-concentration solution, or who are symptomatic should be evaluated with endoscopy and treated for significant gastrointestinal burns. Patients with evidence of oxygen emboli should be admitted to an intensive care setting.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear. Obtain surgical consult as needed for patients with evidence of gastrointestinal tract perforation.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Most patients who have inadvertently ingested 3% hydrogen peroxide can be observed safely at home if not symptomatic.

Monitoring

A)

B)

C)

D)

E)

F)

G)

Oral Exposure

6.5.1)

A) Do not induce vomiting or administer activated charcoal. Irrigate any dermal or ocular exposures with large volumes of water.

6.5.2)

A) Because hydrogen peroxide causes tissue injury rather than systemic toxicity, there is no role for activated charcoal. Insertion of a nasogastric tube to remove gastric contents and to decompress the stomach may be attempted following large ingestions.

6.5.3)

A) MONITORING OF PATIENT

1) No routine laboratory tests are needed when a small amount of 3% hydrogen peroxide is ingested.
2) After a high-volume or high-concentration ingestion, patients should be evaluated for caustic injury and for oxygen embolism.
3) Patients with any symptoms of oral or gastrointestinal tract injury should undergo endoscopy.
4) Any patient with symptoms of cerebral oxygen embolism should have a head CT.
5) Echocardiography or chest CT with contrast may demonstrate oxygen in the right ventricle.
6) Abdominal and upright chest radiograph may reveal radiolucent gas in the gastrointestinal tract, right ventricle, mediastinum, or the portal venous system.
7) An ECG and continuous cardiac monitoring may reveal signs of gas embolization. Desaturation on pulse oximetry, hemodynamic instability, and neurologic deficit may be indicative of gas embolus, and at that time an arterial blood gas would be indicated.

B) IRRITATION SYMPTOM

1) Many chemicals cause irritation of the eyes, skin, and respiratory tract. In severe cases respiratory tract irritation can progress to ARDS/acute lung injury, which may be delayed in onset for up to 24 to 72 hours in some cases.
2) Irritation or burns of the esophagus or gastrointestinal tract are also possible if caustic or irritant chemicals are ingested.

C) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

D) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

E) HYPERBARIC OXYGEN THERAPY

1) The use of hyperbaric oxygen has been suggested in cases of severe gas emboli (ie, patients with respiratory compromise or CNS symptoms). Theoretically, hyperbaric therapy should reduce the size of the emboli (Liu et al, 2007; Luu et al, 1992; Mullins & Beltran, 1998).
2) CASE SERIES: One study reviewed poison center records of 11 patients (age range, 4 to 89 years) with portal gas embolism after inadvertent exposure to hydrogen peroxide; 10 patients ingested 35% hydrogen peroxide and 1 patient ingested 12% hydrogen peroxide. Abdominal CT scans of all patients showed portal venous gas embolism. All patients were successfully treated with hyperbaric oxygen, with resolution of all portal venous gas bubbles in 9 patients and resolution of most bubbles in the remaining 2 patients (French et al, 2010).
3) CASE REPORT: A 56-year-old woman developed cerebral gas embolism after ingesting hydrogen peroxide, but was successfully treated with delayed hyperbaric oxygen therapy. She developed reduced level of consciousness and vomiting (foamy liquid) within 15 minutes of inadvertently ingesting 30 mL of 3% hydrogen peroxide. A brain MRI 2 days postingestion revealed several non-enhancing intra-axial lesions in both cerebral and cerebellar hemispheres involving anterior and posterior vascular territories. There were lesions with restricted diffusion. About 80 hours postingestion, she received hyperbaric oxygen therapy (HBOT) for 60 minutes, resulting in a dramatic improvement of her symptoms. At this time, she was mildly dysarthric. A week later, she had only mild right arm ataxia. A hypermobile inter-arterial septum was observed on a transthoracic echocardiogram which suggested small patent foramen ovale. On a follow-up visit 4 months postingestion, a repeat MRI revealed scattered white matter T2 hyperintensities within the bilateral centrum semiovale. Most of the lesions observed on the initial MRI had completely resolved (Baharnoori & Lazarou, 2012).
4) CASE REPORT: A 32-year-old woman developed severe abdominal pain, nausea, and vomiting after an inadvertent ingestion of about 20 mL of 35% hydrogen peroxide. All laboratory results were normal, except for elevated liver enzymes. A CT scan of the abdomen and pelvis showed air in the portal venous system. She received hyperbaric oxygen (at 3 atmospheres absolute compression) for 3 hours about 5 hours after the ingestion of hydrogen peroxide and her symptoms rapidly resolved. A complete resolution of the portal venous air was observed on a repeat CT scan the next day (Papafragkou et al, 2012).
5) CASE REPORT: A military surgery patient developed tachypnea, arterial desaturation, and "mill-wheel" murmur after having hydrogen peroxide injected under pressure into a partially closed muscle wound. Arterial gas embolus was confirmed by CT and the patient recovered with hyperbaric oxygen therapy (Saissy et al, 1994).
6) CASE REPORT: An 82-year-old woman developed ataxia, diplopia, and confusion immediately after an unintentional ingestion of approximately 3 ounces (oz) of 35% hydrogen peroxide ("food grade"). Approximately 12 minutes after ingestion, she presented to the Emergency Department (ED) asymptomatic, with a normal neurologic examination. Approximately 4 hours and 42 minutes after ingestion, she had a brief grand mal seizure, followed by a deterioration in her mental status (Glascow Coma Scale Score of 6) and a brief episode of apnea. An arterial gas embolism was suspected; the patient received hyperbaric therapy (at 3 atmospheres absolute (ATA) compression for 30 minutes, followed by 2 ATA for 60 minutes) approximately 11 hours postingestion. Because of a dramatic improvement in neurologic status, the second scheduled hyperbaric therapy was cancelled. MRI of brain showed a small area of acute cortical and subcortical ischemia in the left frontal parietal region and extensive chronic small vessel ischemia in the deep white matter of both hemispheres and the pons. She was released from the hospital the next day with no further symptoms or neurologic effects (Vander Heide & Seamon, 2003).
7) CASE REPORT: A 47-year-old man was emergently treated with hyperbaric oxygen to prevent further damage from gas emboli after ingesting a reported amount of 100 mL of 50% hydrogen peroxide. The patient was found soon after the time of ingestion with foam around his mouth and weakness in both legs. Upon arrival to the hospital, his neurological exam revealed a grade 0 out of 5 for muscle power in the lower limbs, and his abdomen was distended. Symptoms continued to progress. The patient became increasingly drowsy and developed muscle weakness in the upper extremities (grade 2/5). Multiple embolic infarcts over the supratentorial and infratentorial regions as well as on the cervical spine were found on MRI. The patient underwent hyperbaric oxygen treatment. Symptoms gradually improved over 6 days, and muscle strength returned to the upper limbs. He was discharged with paraparesis. The authors believe the spinal infarctions resulting in permanent damage had occurred prior to hyperbaric treatment and could not be prevented (Liu et al, 2007).
8) CASE REPORT: A 48-year-old man unintentionally drank 2 "sips" of an unlabeled container of 33% hydrogen peroxide and developed hematemesis, headache, confusion, left-sided facial droop, motor weakness, and left-sided hemiparesis. CT and MRI revealed findings consistent with multiple areas of cerebral ischemia. The patient was treated with hyperbaric oxygen therapy and recovered with mild residual deficit (Rider et al, 2008).
9) CASE REPORT: A 54-year-old woman developed hypoxia and dysrhythmias after irrigation of a pelvis wound with 250 mL of 3% hydrogen peroxide. After hyperbaric oxygen therapy, the patient recovered without cardiac or neurologic sequelae. Irrigation of the wound under high pressure in a partially closed cavity were thought to have been risk factors for the embolus (Vidil et al, 2008).

F) INSERTION OF NASOGASTRIC TUBE

1) Gastric distention may require decompression via a nasogastric tube.

G) BURN

1) There is little information specifically about the treatment of caustic injury from concentrated hydrogen peroxide ingestion. The following recommendations are based on information about alkaline corrosive ingestion.
2) DILUTION

a) Do not exceed 8 oz in adults and 4 oz in children (Consensus, 1988), as vomiting may occur with excessive fluid. Contraindications include perforations and patients at risk of vomiting. Give nothing by mouth following initial dilution until after medical/surgical evaluation.
b) Immediate dilution with milk or water decreased the extent of tissue injury induced by 50% sodium hydroxide in isolated rat esophagi (Homan et al, 1994).

3) ENDOSCOPY

a) Severe gastrointestinal burns are possible after ingestion of concentrated hydrogen peroxide solutions. Endoscopy should be reserved for patients with signs and symptoms such as drooling, stridor, pain, or vomiting, and for large, deliberate ingestions.
b) SUMMARY: Obtain consultation concerning endoscopy as soon as possible, and perform endoscopy within the first 24 hours when indicated.
c) INDICATIONS: Endoscopy should be performed in adults with a history of deliberate ingestion, adults with any signs or symptoms attributable to inadvertent ingestion, and in children with stridor, vomiting, or drooling after unintentional ingestion (Crain et al, 1984). Endoscopy should also be performed in children with dysphagia or refusal to swallow, significant oral burns, or abdominal pain after unintentional ingestion (Gaudreault et al, 1983; Nuutinen et al, 1994). Children and adults who are asymptomatic after accidental ingestion do not require endoscopy (Gupta et al, 2001; Lamireau et al, 2001; Gorman et al, 1992).
d) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.

1) REFERENCES: (Dogan et al, 2006; Symbas et al, 1983; Crain et al, 1984a; Gaudreault et al, 1983a; Schild, 1985; Moazam et al, 1987; Sugawa & Lucas, 1989; Previtera et al, 1990; Zargar et al, 1991; Vergauwen et al, 1991; Gorman et al, 1992)

e) The risk of perforation during endoscopy is minimized by (Zargar et al, 1991):

1) Advancing across the cricopharynx under direct vision
2) Gently advancing with minimal air insufflation
3) Never retroverting or retroflexing the endoscope
4) Using a pediatric flexible endoscope
5) Using extreme caution in advancing beyond burn lesion areas
6) Most authors recommend endoscopy within the first 24 hours of injury, not advancing the endoscope beyond areas of severe esophageal burns, and avoiding endoscopy during the subacute phase of healing when tissue slough increases the risk of perforation (5 to 15 days after ingestion) (Zargar et al, 1991).

f) GRADING

1) Several scales for grading caustic injury exist. The likelihood of complications such as strictures, obstruction, bleeding, and perforation is related to the severity of the initial burn (Zargar et al, 1991):
2) Grade 0 - Normal examination
3) Grade 1 - Edema and hyperemia of the mucosa; strictures unlikely.
4) Grade 2A - Friability, hemorrhages, erosions, blisters, whitish membranes, exudates and superficial ulcerations; strictures unlikely.
5) Grade 2B - Grade 2A plus deep discreet or circumferential ulceration; strictures may develop.
6) Grade 3A - Multiple ulcerations and small scattered areas of necrosis; strictures are common, complications such as perforation, fistula formation or gastrointestinal bleeding may occur.
7) Grade 3B - Extensive necrosis through visceral wall; strictures are common, complications such as perforation, fistula formation, or gastrointestinal bleeding are more likely than with 3A.

g) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.
h) SCINTIGRAPHY - Scans utilizing radioisotope labelled sucralfate (technetium 99m) were performed in 22 patients with caustic ingestion and compared with endoscopy for the detection of esophageal burns. Two patients had minimal residual isotope activity on scanning but normal endoscopy and two patients had normal activity on scan but very mild erythema on endoscopy. Overall the radiolabeled sucralfate scan had a sensitivity of 100%, specificity of 81%, positive predictive value of 84% and negative predictive value of 100% for detecting clinically significant burns in this population (Millar et al, 2001). This may represent an alternative to endoscopy, particularly in young children, as no sedation is required for this procedure. Further study is required.
i) MINIPROBE ULTRASONOGRAPHY - was performed in 11 patients with corrosive ingestion . Findings were categorized as grade 0 (distinct muscular layers without thickening, grade I (distinct muscular layers with thickening), grade II (obscured muscular layers with indistinct margins) and grade III (muscular layers that could not be differentiated). Findings were further categorized as to whether the worst appearing image involved part of the circumference (type a) or the whole circumference (type b). Strictures did not develop in patients with grade 0 (5 patients) or grade I (4 patients) lesions. Transient stricture formation developed in the only patient with grade IIa lesions, and stricture requiring repeated dilatation developed in the only patient with grade IIIb lesions (Kamijo et al, 2004).

4) CORTICOSTEROIDS

a) Not only has the use of steroids for the treatment of burns after ingestion of hydrogen peroxide not been studied, but the use of corticosteroids for the treatment of caustic ingestion in general is controversial (Haller & Bachman, 1964; Saedi et al, 1973). Recommendations regarding the use of steroids for the treatment of burns after ingestion of hydrogen peroxide cannot be made based on present evidence.
b) CORROSIVE INGESTION/SUMMARY: The use of corticosteroids for the treatment of caustic ingestion is controversial. Most animal studies have involved alkali-induced injury (Haller & Bachman, 1964; Saedi et al, 1973a). Most human studies have been retrospective and generally involve more alkali than acid-induced injury and small numbers of patients with documented second or third degree mucosal injury.
c) FIRST DEGREE BURNS: These burns generally heal well and rarely result in stricture formation (Zargar et al, 1989; Howell et al, 1992). Corticosteroids are generally not beneficial in these patients (Howell et al, 1992).
d) SECOND DEGREE BURNS: Some authors recommend corticosteroid treatment to prevent stricture formation in patients with a second degree, deep-partial thickness burn (Howell et al, 1992). However, no well controlled human study has documented efficacy. Corticosteroids are generally not beneficial in patients with a second degree, superficial-partial thickness burn (Caravati, 2004; Howell et al, 1992).
e) THIRD DEGREE BURNS: Some authors have recommended steroids in this group as well (Howell et al, 1992). A high percentage of patients with third degree burns go on to develop strictures with or without corticosteroid therapy and the risk of infection and perforation may be increased by corticosteroid use. Most authors feel that the risk outweighs any potential benefit and routine use is not recommended (Boukthir et al, 2004; Oakes et al, 1982; Pelclova & Navratil, 2005).
f) CONTRAINDICATIONS: Include active gastrointestinal bleeding and evidence of gastric or esophageal perforation. Corticosteroids are thought to be ineffective if initiated more than 48 hours after a burn (Howell, 1987).
g) DOSE: Administer daily oral doses of 0.1 milligram/kilogram of dexamethasone or 1 to 2 milligrams/kilogram of prednisone. Continue therapy for a total of 3 weeks and then taper (Haller et al, 1971; Marshall, 1979). An alternative regimen in children is intravenous prednisolone 2 milligrams/kilogram/day followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks then tapered (Anderson et al, 1990).
h) ANTIBIOTICS: Animal studies suggest that the addition of antibiotics can prevent the infectious complications associated with corticosteroid use in the setting of caustic burns. Antibiotics are recommended if corticosteroids are used or if perforation or infection is suspected. Agents that cover anaerobes and oral flora such as penicillin, ampicillin, or clindamycin are appropriate (Rosenberg et al, 1953).
i) STUDIES

1) ANIMAL

a) Some animal studies have suggested that corticosteroid therapy may reduce the incidence of stricture formation after severe alkaline corrosive injury (Haller & Bachman, 1964; Saedi et al, 1973).
b) Animals treated with steroids and antibiotics appear to do better than animals treated with steroids alone (Haller & Bachman, 1964).
c) Other studies have shown no evidence of reduced stricture formation in steroid treated animals (Reyes et al, 1974). An increased rate of esophageal perforation related to steroid treatment has been found in animal studies (Knox et al, 1967).

2) HUMAN

a) Most human studies have been retrospective and/or uncontrolled and generally involve small numbers of patients with documented second or third degree mucosal injury. No study has proven a reduced incidence of stricture formation from steroid use in human caustic ingestions (Haller et al, 1971; Hawkins et al, 1980; Yarington & Heatly, 1963; Adam & Brick, 1982).
b) META ANALYSIS

1) Howell et al (1992), analyzed reports concerning 361 patients with corrosive esophageal injury published in the English language literature since 1956 (10 retrospective and 3 prospective studies). No patients with first degree burns developed strictures. Of 228 patients with second or third degree burns treated with corticosteroids and antibiotics, 54 (24%) developed strictures. Of 25 patients with similar burn severity treated without steroids or antibiotics, 13 (52%) developed strictures (Howell et al, 1992).
2) Another meta-analysis of 10 studies found that in patients with second degree esophageal burns from caustics, the overall rate of stricture formation was 14.8% in patients who received corticosteroids compared with 36% in patients who did not receive corticosteroids (LoVecchio et al, 1996).
3) Another study combined results of 10 papers evaluating therapy for corrosive esophageal injury in humans published between January 1991 and June 2004. There were a total of 572 patients, all patients received corticosteroids in 6 studies, in 2 studies no patients received steroids, and in 2 studies, treatment with and without corticosteroids was compared. Of 109 patients with grade 2 esophageal burns who were treated with corticosteroids, 15 (13.8%) developed strictures, compared with 2 of 32 (6.3%) patients with second degree burns who did not receive steroids (Pelclova & Navratil, 2005).

c) Smaller studies have questioned the value of steroids (Ferguson et al, 1989; Anderson et al, 1990), thus they should be used with caution.
d) Ferguson et al (1989) retrospectively compared 10 patients who did not receive antibiotics or steroids with 31 patients who received both antibiotics and steroids in a study of caustic ingestion and found no difference in the incidence of esophageal stricture between the two groups (Ferguson et al, 1989).
e) A randomized, controlled, prospective clinical trial involving 60 children with lye or acid induced esophageal injury did not find an effect of corticosteroids on the incidence of stricture formation (Anderson et al, 1990).

1) These 60 children were among 131 patients who were managed and followed-up for ingestion of caustic material from 1971 through 1988; 88% of them were between 1 and 3 years old (Anderson et al, 1990).
2) All patients underwent rigid esophagoscopy after being randomized to receive either no steroids or a course consisting initially of intravenous prednisolone (2 milligrams/kilogram per day) followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks prior to tapering and discontinuation (Anderson et al, 1990).
3) Six (19%), 15 (48%), and 10 (32%) of those in the treatment group had first, second and third degree esophageal burns, respectively. In contrast, 13 (45%), 5 (17%), and 11 (38%) of the control group had the same levels of injury (Anderson et al, 1990).
4) Ten (32%) of those receiving steroids and 11 (38%) of the control group developed strictures. Four (13%) of those receiving steroids and 7 (24%) of the control group required esophageal replacement. All but 1 of the 21 children who developed strictures had severe circumferential burns on initial esophagoscopy (Anderson et al, 1990).
5) Because of the small numbers of patients in this study, it lacked the power to reliably detect meaningful differences in outcome between the treatment groups (Anderson et al, 1990).

f) ADVERSE EFFECTS

1) The use of corticosteroids in the treatment of caustic ingestion in humans has been associated with gastric perforation (Cleveland et al, 1963) and fatal pulmonary embolism (Aceto et al, 1970).

5) ANTIBIOTIC THERAPY

a) Antibiotics should be used only for specific indications of infection or if corticosteroids are used. Intravenous antibiotics should be considered in patients with evidence of infection and esophageal or gastric perforation (Howell, 1987).

6) SURGICAL THERAPY

a) SUMMARY: Initially if severe esophageal burns are found a string may be placed in the stomach to facilitate later dilation. Insertion of a specialized nasogastric tube after confirmation of a circumferential burn may prevent strictures. Dilation is indicated after 2 to 4 weeks if strictures are confirmed. If dilation is unsuccessful colonic intraposition or gastric tube placement may be needed. Early laparotomy should be considered in patients with evidence of severe esophageal or gastric burns on endoscopy.
b) STRING - If a second degree or circumferential burn of the esophagus is found a string may be placed in the stomach to avoid false channel and to provide a guide for later dilation procedures (Gandhi et al, 1989).
c) STENT - The insertion of a specialized nasogastric tube or stent immediately after endoscopically proven deep circumferential burns is preferred by some surgeons to prevent stricture formation (Mills et al, 1978; (Wijburg et al, 1985; Coln & Chang, 1986).

1) STUDY - In a study of 11 children with deep circumferential esophageal burns after caustic ingestion, insertion of a silicone rubber nasogastric tube for 5 to 6 weeks without steroids or antibiotics was associated with stricture formation in only one case (Wijburg et al, 1989).

d) DILATION - Dilation should be performed at 1 to 4 week intervals when stricture is present(Gundogdu et al, 1992). Repeated dilation may be required over many months to years in some patients. Successful dilation of gastric antral strictures has also been reported (Hogan & Polter, 1986; Treem et al, 1987).
e) COLONIC REPLACEMENT - Intraposition of colon may be necessary if dilation fails to provide an adequate sized esophagus (Chiene et al, 1974; Little et al, 1988; Huy & Celerier, 1988).
f) LAPAROTOMY/LAPAROSCOPY - Several authors advocate laparotomy or laparoscopy in patients with endoscopic evidence of severe esophageal or gastric burns to evaluate for the presence of transmural gastric or esophageal necrosis (Cattan et al, 2000; Estrera et al, 1986; Meredith et al, 1988; Wu & Lai, 1993).

1) STUDY - In a retrospective study of patients with extensive transmural esophageal necrosis after caustic ingestion, all 4 patients treated in the conventional manner (esophagoscopy, steroids, antibiotics, and repeated evaluation for the occurrence of esophagogastric necrosis and perforation) died while all 3 patients treated with early laparotomy and immediate esophagogastric resection survived (Estrera et al, 1986).

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) Remove contaminated clothing and wash exposed area thoroughly with soap and water.
2) Clinical examination is warranted, if irritation or pain persists after washing.

Abstracts

Case Reports

A)

1) SPECIFIC AGENT

a) CONCENTRATE

1) A 33-year-old woman ingested an unknown amount of 35% hydrogen peroxide and developed vomiting, collapse, and tonic-clonic seizures within minutes.

a) Upon arrival to the ED, she was seizing and cyanotic. Apnea occurred 30 seconds after intubation, and mechanical ventilation was required. The chest x-ray showed evidence of aspiration pneumonitis.
b) The esophagus showed mild erythema, and the gastric mucosa showed diffuse hemorrhages and edema. A subsequent CT scan showed cerebral edema.
c) Neurologic deficits found on discharge on the ninth day included extremity weakness, and truncal ataxia with inability to maintain a sitting position (Giberson et al, 1989).

2) Three stockbreeders (aged 30, 45, and 62 years) unintentionally drank from a container of 60% hydrogen peroxide solution. All developed GI tract lesions. One patient developed altered mental status requiring intubation, migratory paresis of the right limbs, cranial nerve VI paresis (reversed in 10 days), and left hemiparesis, which reversed in 2 months (BreaHernando & MartinBurcio, 1991).
3) CASE REPORT: A patient in a military surgery case developed tachypnea, arterial desaturation, and "mill-wheel" murmur after having hydrogen peroxide injected under pressure into a partially closed muscle wound. Arterial gas embolus was confirmed by CT, and the patient recovered with hyperbaric oxygen (Saissy et al, 1994).
4) CASE REPORT: A 54-year-old man developed hypotension, oxygen desaturation intraoperatively during cervical spinal surgery when 30 mL of 3% hydrogen peroxide was used for wound irrigation. Symptoms resolved with placing the patient in trendelenburg, aspirating the hydrogen peroxide from the surgical wound, and fluid resuscitation. The event was thought to be the result of an acute oxygen embolus. The patient had a full recovery with no neurologic sequelae (Morikawa et al, 1995).
5) CASE REPORT: A 39-year-old man unintentionally drank 250 mL from a container containing 35% hydrogen peroxide. The patient developed hematemesis and evidence of diffuse caustic mucosal injury of the entire stomach on esophagogastroduodenoscopy (Pritchett et al, 2007).
6) CASE REPORT: A 48-year-old man unintentionally drank 2 "sips" of an unlabeled container of 33% hydrogen peroxide and developed hematemesis, headache, confusion, left-sided facial droop, motor weakness, and left-sided hemiparesis. CT and MRI revealed findings consistent with multiple areas of cerebral ischemia. The patient was treated with hyperbaric oxygen therapy and recovered with mild residual deficit (Rider et al, 2008).
7) CASE REPORT: A 54-year-old woman developed hypoxia and dysrhythmias after irrigation of a pelvis wound with 250 mL of 3% hydrogen peroxide. After hyperbaric oxygen therapy, the patient recovered without cardiac or neurologic sequelae. Irrigation of the wound under high pressure in a partially closed cavity were thought to have been risk factors for the embolus (Vidil et al, 2008).

B)

1) Unintentional ingestion of a 35% hydrogen peroxide solution, stored in a refrigerator and confused for chilled water, resulted in oropharyngeal burns in a 4-year-old female child, and death in a 6-year-old female child.

a) 35% hydrogen peroxide solutions have recently been marketed in health-food stores for "hyper-oxygenation therapy" and have resulted in an increase in exposures of this nature (Thompson, 1989).

2) Ingestion of 4 to 6 oz of 35% hydrogen peroxide in a 2-year-old resulted in oxygen embolization to the portal venous system and heart.

a) This caused ischemic ECG changes, severe hemorrhagic gastritis, gastric distention, decorticate posturing, seizures, and eventually death from hypoxic encephalopathy.
b) Postmortem examination revealed diffuse cerebral edema with cerebellar and uncal tonsillar notching (Christensen et al, 1992).

3) A 26-month-old child ingested one mouthful of a 35% hydrogen peroxide solution and vomited spontaneously. Lethargy and hematemesis were noted 30 minutes postingestion.

a) A syncopal episode and periodic apnea developed within 2 hours. Endoscopy at 16 hours postingestion showed stomach cardia erosion, lower esophageal erythema, and a gastric burn. She was treated with sucralfate 500 mg orally.
b) Follow-up at 12 days postingestion showed normal esophageal and duodenal mucosa, and no gastric mucosal ulceration (Humberston et al, 1990).

4) A 3-year-old child ingested a 40% solution of hydrogen peroxide that was stored in a mineral water bottle. Shortly after ingestion, foam appeared on her lips and she lost consciousness.

a) On presentation at an ear, nose, and throat clinic, she was unconscious, cyanotic with blue lips, and with no pulse. Resuscitation was unsuccessful. An autopsy did not reveal the mechanism of death induced by hydrogen peroxide.
b) The stomach mucosa contained about 10 small erosions but no visible bleeding. The authors suggest death was the result of mechanic asphyxia; the foam produced caused obstruction of the distal respiratory tract (Zecevic & Gasparec, 1979).

5) An 11-year-old boy inadvertently received 100 mL of 3% hydrogen peroxide intravenously instead of fluid replacement with isotonic saline, developed ventricular fibrillation, and ultimately died. Autopsy revealed generalized gas embolism upon opening great vessels, heart, and lung under water. Brain biopsy demonstrated evidence of lipid peroxidation (Lubec et al, 1996).
6) An 11-year-old boy developed a "tonic convulsion" and showed clinical signs of pulmonary embolism after 12 mL of 3% hydrogen peroxide was used to irrigate a relatively closed left femur wound. The patient recovered with symptomatic treatment (Shida et al, 2002).
7) A 15-year-old girl suffered severe scalp injury with necrosis of the galea aponeurotica when a 35% hydrogen peroxide solution was used to highlight her hair. Reconstructive plastic surgery was required (Schroder et al, 2008).

Range Of Toxicity

Therapeutic Dose

7.2.1)

A) GENERAL

1) A 1.5% solution of hydrogen peroxide has been used as a mouthwash in the treatment of acute stomatitis and as a gargle solution (S Sweetman , 2002).
2) Hydrogen peroxide 3% is used for disinfecting soft contact lenses (S Sweetman , 2002).
3) Hydrogen peroxide ear drops have been used for the removal of wax. The drops can be prepared by diluting a 6% solution of hydrogen peroxide with 3 parts of water, preferably just before use (S Sweetman , 2002).

Minimum Lethal Exposure

A)

1) The lowest published lethal dose of hydrogen peroxide (30% solution) via the oral route is 1429 mg/kg for a man and 2626 mcg/kg for a woman (RTECS, 1996).

B)

1) Ingestion of small amounts of highly concentrated solution (30% to 40%) has resulted in deaths due to respiratory failure (Giusti, 1973; Zecevic & Gasparec, 1979) and brain infarct secondary to cerebral embolism (Ashdown et al, 1998).

C)

1) PEDIATRIC

a) Ingestion of 4 to 6 ounces of 35% hydrogen peroxide in a 2-year-old child resulted in oxygen embolization to the portal venous system and heart, hemorrhagic gastritis, seizures, and death from hypoxic encephalopathy (Christensen et al, 1992).
b) Ingestion of 2 sips of 35% hydrogen peroxide resulted in foaming at the mouth, hematemesis, epigastric pain, confusion, stridor, apnea, cyanosis, and cardiorespiratory arrest. She died despite cardiopulmonary resuscitation (Indorato et al, 2014).
c) An 11-year-old boy inadvertently received 100 mL of 3% hydrogen peroxide intravenously instead of fluid replacement with isotonic saline, developed ventricular fibrillation, and ultimately died. Autopsy revealed generalized gas embolism upon opening great vessels, heart, and lung under water. Brain biopsy demonstrated evidence of lipid peroxidation (Lubec et al, 1996).
d) A 3-year-old girl presented with vomiting, lethargy, and respiratory distress after ingesting 10 mL of 20% hydrogen peroxide solution. She also developed generalized tonic-clonic seizures in the ED. Both brain computed tomography and magnetic resonance imaging revealed diffuse cerebral edema. She was transferred to the pediatric intensive care unit with a Glasgow coma score of 3. Despite aggressive supportive care, including IV midazolam and phenytoin for seizures, dexamethasone and mannitol for cerebral edema, vasopressors for hypotension, and 3 sessions of hyperbaric oxygen, her condition did not improve and she died on day 6 (Ikiz et al, 2013).

2) ADULT

a) A 63-year-old man ingested 120 mL of 35% hydrogen peroxide and developed left hemiparesis; MRI results confirmed multiple brain infarcts (Ijichi et al, 1997).
b) An 84-year-old man ingested 30 mL of 35% hydrogen peroxide and developed multiple cerebral infarcts (Sherman et al, 1994).

Maximum Tolerated Exposure

A)

1) Concentrations greater than 10% should be considered potentially very toxic.
2) ACUTE EXPOSURE: In one study, 11 healthy volunteers were exposed to hydrogen peroxide vapors (0 [clean air], 0.5 and 2.2 ppm) for 2 hours. Acute exposure to hydrogen peroxide vapors was mildly irritating to upper respiratory airways at 2.2 ppm, but not at 0.5 ppm. In addition, no exposure-related effects on pulmonary function, nasal swelling, breathing frequency and blinking frequency were observed. There were also no clear effects on markers of inflammation and coagulation (interleukin-6, C-reactive protein, serum amyloid A, fibrinogen, factor VIII, von Willebrand factor and Clara cell protein in plasma) (Ernstgard et al, 2012).
3) Although most patients ingesting concentrated solutions (30% to 40%) have succumbed from respiratory arrest (Giusti, 1973; Zecevic & Gasparec, 1979), 1 case of survival has been reported after prompt intubation and respiratory support (Giberson et al, 1989).

B)

1) PEDIATRIC

a) A 3-year-old boy ingested 2 to 4 ounces of 3% hydrogen peroxide and developed blood-streaked emesis (Henry et al, 1996). An upper gastrointestinal endoscopy was performed for persistent emesis with multiple gastric ulcers and duodenal erosions found.
b) SURGICAL IRRIGATION: An 11-month-old developed a gas emboli resulting in cardiac arrest after incision and drainage of an abscess that was irrigated with 15 mL of 3% hydrogen peroxide (Schwab & Dilworth, 1999).

1) Extrapolation from animal data suggests that 2 mL of 3% hydrogen peroxide could release 20 mL of oxygen microbubbles, and that a 10 kg infant may only require 2 mL/kg of gas (20 mL) to sustain a cardiac arrest.

c) SURGICAL IRRIGATION: An 11-year-old boy developed a "tonic convulsion" and showed clinical signs of pulmonary embolism after 12 mL of 3% hydrogen peroxide was used to irrigate a relatively closed left femur wound. The patient recovered with symptomatic treatment (Shida et al, 2002).

2) ADULT

a) A 39-year-old man unintentionally drank 250 mL from a container containing 35% hydrogen peroxide. The patient developed hematemesis and evidence of diffuse caustic mucosal injury of the entire stomach on esophagogastroduodenoscopy. The patient made a complete recovery (Pritchett et al, 2007).
b) SURGICAL IRRIGATION: A 54-year-old woman developed hypoxia and dysrhythmias after irrigation of a pelvis wound with 250 mL of 3% hydrogen peroxide. After hyperbaric oxygen therapy, the patient recovered without cardiac or neurologic sequelae. Irrigation of the wound under high pressure in a partially closed cavity were thought to have been risk factors for the embolus (Vidil et al, 2008).
c) A 32-year-old woman developed severe abdominal pain, nausea, and vomiting after an inadvertent ingestion of about 20 mL of 35% hydrogen peroxide. All laboratory results were normal, except for elevated liver enzymes. A CT scan of the abdomen and pelvis showed air in the portal venous system. She received hyperbaric oxygen (at 3 atmospheres absolute compression) for 3 hours about 5 hours after the ingestion of hydrogen peroxide. A complete resolution of the portal venous air was observed on a repeat CT scan the next day (Papafragkou et al, 2012).
d) A 56-year-old woman developed cerebral gas embolism after ingesting 30 mL of 3% hydrogen peroxide, but was successfully treated with hyperbaric oxygen therapy (Baharnoori & Lazarou, 2012).

C)

1) Dogs exposed 6 hours per day, 5 days per week for 6 months at an average vapor concentration of 7 parts per million (ppm) of 90% hydrogen peroxide developed external body irritation, sneezing, lacrimation, bleaching of the hair, thickened skin, and irritation of the lungs (ACGIH, 1986).
2) Rabbits exposed daily for 3 months at 22 ppm developed bleached hair and irritation around the nose (ACGIH, 1986).
3) A 5% solution applied to the eyes of rabbits has caused severe corneal edema, flare in aqueous, vascularization of the cornea, and significant congestion in the iris (HSDB, 1996).
4) Rats given tooth whiteners containing 10% to 35% carbamide peroxide by gastric lavage developed acute toxicity and even death in several cases (Cherry et al, 1993). Those exposed to the 35% product developed signs of acute distress (shallow respirations) within 15 minutes of receiving the agent. Gastric hemorrhaging and bloating were found at necropsy in the 3 rats that died following lavage with the 35% product.

Workplace Standards

A)

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Hydrogen peroxide

a) TLV:

1) TLV-TWA: 1 ppm
2) TLV-STEL:
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: A3
2) Codes: Not Listed
3) Definitions:

a) A3: Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.

c) TLV Basis - Critical Effect(s): Eye, URT and skin irr
d) Molecular Weight: 34.02

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS7722-84-1 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Hydrogen peroxide
2) REL:

a) TWA: 1 ppm (1.4 mg/m(3))
b) STEL:
c) Ceiling:
d) Carcinogen Listing: (Not Listed) Not Listed
e) Skin Designation: Not Listed
f) Note(s):

3) IDLH:

a) IDLH: 75 ppm
b) Note(s): Not Listed

C) Carcinogenicity Ratings for CAS7722-84-1 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: Hydrogen peroxide

a) A3 :Confirmed Animal Carcinogen with Unknown Relevance to Humans: The agent is carcinogenic in experimental animals at a relatively high dose, by route(s) of administration, at site(s), of histologic type(s), or by mechanism(s) that may not be relevant to worker exposure. Available epidemiologic studies do not confirm an increased risk of cancer in exposed humans. Available evidence does not suggest that the agent is likely to cause cancer in humans except under uncommon or unlikely routes or levels of exposure.

2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Hydrogen peroxide

a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.

4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Hydrogen peroxide
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS7722-84-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Hydrogen peroxide
2) Table Z-1 for Hydrogen peroxide:

a) 8-hour TWA:

1) ppm: 1

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3: 1.4

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value:
4) Skin Designation: No
5) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) References: Lewis, 1996 RTECS, 1996) Note: All values are from RTECS 1996, unless otherwise noted.

1) LD50- (ORAL)MOUSE:

a) 2 g/kg -- 90% concentration

2) LD50- (ORAL)RAT:

a) 1518 mg/kg -- 8%-20% concentration

3) LD50- (SKIN)RAT:

a) 4060 mg/kg -- 90% concentration

Summary

A)

B)

C)

D)

Pharmacology Toxicology

Pharmacologic Mechanism

A)

1) For each volume of 3% hydrogen peroxide solution, 10 volumes of oxygen may be produced (Gosselin et al, 1984).

B)

1) These may potentially lead to gene mutation, cell transformation, and cell death (Blakely et al, 1990).

Physicochemical

Other

A)

1) Currently not available (CHRIS , 2002)

Physical Characteristics

A)

B)

Ph

A)

Molecular Weight

A)

Animal Toxicology

References

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FeedBack

HYDROGEN PEROXIDE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

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Carcinogenicity

Monitoring Parameters Levels

Radiographic Studies

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

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Case Reports

Therapeutic Dose

Minimum Lethal Exposure

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Summary

Pharmacologic Mechanism

Other

Physical Characteristics

Ph

Molecular Weight

General Bibliography