Substance-Specific Issues

Hydrogen peroxide (35% or greater); classification with respect to acute toxicity

Substance:

Hydrogen peroxide, CAS No. 7722-84-1: classification with respect to acute toxicity following ingestion.

Issue:

Does hydrogen peroxide at a concentration of 35% or greater fall within the Controlled Products Regulations (CPR) criteria of Division 1 of WHMIS Class D for acute toxicity based on human evidence?

Background:

Hydrogen peroxide is a colorless liquid with a slightly sharp, irritating odour and bitter taste. It is currently classified as Class C-Oxidizing, Class E-Corrosive and Class F-Dangerously Reactive material under WHMIS. It is an oxidizing agent which, in the presence of organic matter or if permitted to become alkaline, vigorously decomposes to oxygen and water [1]. The strength of a solution may be described as a percentage or volume. Industrial strengths of hydrogen peroxide are manufactured up to 90%. They are used mainly as bleaching and oxidizing agents. Solutions of 35% are also used in health aid as hyperoxygenation therapy, whereas hydrogen peroxide at a concentration 90% can be used as rocket fuel.

The dissociation of hydrogen peroxide is a violent and exothermic reaction. Ingestion of hydrogen peroxide (>35%) has been associated with irritation of the upper gastrointestinal tract. The rapid liberation of oxygen following decomposition may lead to the distension of the esophagus or stomach, and possibly severe damage and internal bleeding [2]. Large doses may produce gastritis and esophagitis, and cases of rupture of the colon, proctitis and ulcerative colitis have also been reported [3]. Ingestions of industrial strength peroxides can result in severe burns of the oropharynx and gastrointestinal tract, with the possibility of rupture of the hollow viscous secondary to the liberation of oxygen. The foam may cause obstruction of the respiratory tract and may result in mechanical asphyxia. Men accidentally exposed to 90% H2O2 vapor experienced an increased flow of saliva, scratchy feeling of the throat, and respiratory passage inflammation [4]. Respiratory failure has been the alleged cause of death in fatalities reported after oral ingestion of industrial strength (over 10%) hydrogen peroxide [5]. Seventy-five ppm is considered immediately dangerous to life and health [6].

The general EU classification for concentrated hydrogen peroxide is: O; R5 - Oxidizing. Heating may cause an explosion, C; R8 - Corrosive. Contact with combustible material may cause fire, and Xn; R20/22 - Harmful. Harmful by inhalation and if swallowed [7].

The EU also has different classifications for varying concentrations [7]:

a) 35 % = C < 50 %: Xn; R22-37/38-41
b) 50 % = C < 70 %: C; R20/22-34
c) C = 70 %: C; R20/22-35

Considerations:

A 33 year old woman unintentionally ingested a 1 pint bottle of 35% hydrogen peroxide. She vomited, collapsed, and experienced a brief tonic-clonic seizure within minutes. On examination, the patient was intermittently seizing and markedly cyanotic and had copious white foam emanating from her mouth. Vital signs were blood pressure 156/118 mm Hg; pulse, 126; respirations, 32; and temp, 38.2 deg C. Pupils were 6 mm and weakly reactive to light. The heart was rapid and regular, and no SC emphysema was noted. Deep tendon reflexes were 2/4, and plantar responses were flexor. The patient was given 5 mg diazepam, 4 mg naloxone hydrochloride, 100 mg thiamine, and 50 ml of 50% dextrose iv. Within 30 sec after nasotracheal intubation, the patient became apneic and dependent on mechanical ventilation. Gastric lavage was performed. Preoperative esophagogastroduodenoscopy showed mild erythema of the distal esophagus and diffuse hemorrhages and edema of the gastric mucosa. Recurrent postoperative seizures were well controlled with phenytoin therapy. Bilateral cerebral hemisphere swelling was determined; intracranial pressure of 30 cm H2O responded to hyperventilation. Later neurologic examination demonstrated patchy areas of weakness in the upper and lower extremities and truncal ataxia with inability to maintain a sitting position. After 9 days, the patient was transferred to a rehabilitation facility [8].

In another case, a 40-year-old woman mistakenly ingested about 60 mL of 35% hydrogen peroxide solution. She had a burning sensation in the throat and chest and vomited. Radiography of the abdomen showed a large amount of gas in the stomach and gas in the venous system throughout the liver including the left lobe [9]. The calculated intake of hydrogen peroxide was 21 grams, or about 350 mg/kg (based on a 60 kg woman).

Five non-fatal poisonings were reported following consumption of 25-100 mL of an unknown concentration of hydrogen peroxide. Symptoms included sharp pains in the abdomen, foaming at the mouth, vomiting, transitory loss of consciousness, sensory and motor impairment and elevated temperature. Microhemorrhages of the skin and eyes and moderate leukocytosis were also noted. One person exhibited marked visual and neurological symptoms after swallowing 100 mL of hydrogen peroxide. Symptoms were considered to be due to microemboli of generated oxygen. Recovery occurred in 2-3 weeks [10].

A 33-year-old woman ingested less than 500 mL of 35% hydrogen peroxide. She was cyanotic and experienced seizures and foaming at the mouth. The abdomen was slightly distended. Neurological signs included lack of spontaneous eye movement, no verbal responses and withdrawal from noxious stimuli. Laparotomy revealed air bubbles in the stomach, but no perforations. Recovery was complete following treatment [11]. The calculated intake of hydrogen peroxide was 175 grams, or about 2900 mg/kg (based on a 60 kg woman).

A 63-year-old man developed a multiple brain infarction after ingesting a 35% hydrogen peroxide solution. Neurologic examination revealed left hemiparesis, primarily affecting the lower limb and mild weakness of the right lower limb. Patchy bilateral brain lesions were observed upon MRI. Oxygen gas embolism was the likely cause of the brain infarctions. Recovery was only partial. The amount was described as "3 cups of 35% hydrogen peroxide (approximately 120 mL)". The patient vomited soon after the ingestion, which would have reduced the total dose [12]. If the amount ingested was 120 mL, the calculated intake of hydrogen peroxide was 0.6 grams, or about 600 mg/kg (based on a 70 kg man).

A 44-year-old man ingested a small volume (unspecified) of 35% hydrogen peroxide. He collapsed and became unresponsive and comatose, and he died 2 days after admission [13].

A case was reported of a 25-year-old woman who ingested one mouthful of 3% hydrogen peroxide and presented to the Emergency Department with persistent vomiting and epigastric pain. The radiographic evaluation found portal venous gas emboli. In addition, upper gastrointestinal endoscopy performed 2 h after ingestion revealed diffuse hemorrhagic gastritis. She showed a decrease of hemoglobin concentration and a positive test result for occult blood in stool. She was observed for 14 days and discharged. Follow-up endoscopy showed erythematous gastritis. This case illustrates that a low concentration of hydrogen peroxide can cause portal venous gas embolism and severe gastrointestinal injuries even if only a small amount is ingested [14].

The criteria for acute toxicity set out in sections 46 and 49 of the CPR deal only with lethality in animals. However, specific chemicals may cause greater toxicity in humans than animals due to differences in the mechanism of toxicity between species. Although not explicit, subsection 33(2) indirectly supports the use of human data as evidence for classification in Class D - Poisonous and infectious material. The Reference Manual for the WHMIS Requirements of the Hazardous Products Act and Controlled Products Regulations states: In the case of a material (pure substance or tested mixture) which does not meet any of the criteria for Very Toxic Material or Toxic Material, but for which there is valid documented evidence based on established scientific principles that the material causes an adverse effect in humans following occupational exposure, this fact, by itself, is sufficient to include that material within Class D1. The WHMIS Information Bulletin Issue No. 8 indicates that suppliers may classify controlled products in Class D1 based on their professional judgement, if acute toxicity in humans is sufficiently documented.

Conclusion:

Acute toxicity in human has been sufficiently documented to conclude that hydrogen peroxide (>35%) falls within the CPR criteria for acute toxicity, i.e., Class D1B.

References:

1. IPCS. "Hydrogen Peroxide". IPCS Inchem, International programme on chemical safety. 1998.
2. International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 1089.
3. Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-107.
4. Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1222.
5. Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1223.
6. Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1221.
7. Regulation (EC) No 1272/2008 of the European parliament and of the council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing, Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006, Official Journal of the European Union.
8. Giberson TP, Kern JD, Pettigrew DW 3rd, Eaves CCJr, Haynes JF Jr: Near-Fatal hydrogen peroxide ingestion Ann Emerg Med. 1989 18(7):778-9.
9. Luu, T,A., et al. Portal vein gas embolism from hydrogen peroxide ingestion. Annals of Emergency Medicine. Vol. 21, no. 11 (Nov. 1992). p. 1391-1393.
10. ECETOC. Hydrogen peroxide CAS No. 7722-84-1. Joint assessment of commodity chemicals no. 22. European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), Sept. 1992 (in Russian).
11. Giberson, T., et al. Near-fatal hydrogen peroxide ingestion. Annals of Emergency Medicine. Vol. 18 (1989). p. 778-779.
12. Ijichi, T., et al. Multiple brain gas embolism after ingestion of concentrated hydrogen peroxide. Neurology. Vol. 48 (Jan. 1997). p. 277-279.
13. Ashdown, B.C., et al. Hydrogen peroxide poisoning causing brain infarction: Neuroimaging findings. American Journal of Radiology. Vol. 170 (June 1998). p. 1653-1655.
14. Moon JM, Chun BJ, Min YI. : Hemorrhagic gastiritis and gas emboli after ingesting 3% hydrogen peroxide J Emerg Med. 2006 30(4):403-6.