Hydrogen peroxide-urea

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

summary of available ADME studies on hydrogen peroxide

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen peroxide

EC Number:

231-765-0

EC Name:

Hydrogen peroxide

Cas Number:

7722-84-1

Molecular formula:

H2O2

IUPAC Name:

hydrogen peroxide

Test material form:

liquid

Test animals

Species:

other: data from several specie have been summarised

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

other: oral, dermal, inhalation

Results and discussion

Main ADME results

Type:

absorption

Results:

biological membranes are highly permeable to H2O2: 0.2 cm/min (peroxisomal mebranes) and 0.04 cm/min (erythrocyte plasma mebrane). Results in rapid absorption from mucuos membranes, skin, and lungs.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Toxicokinetic data are scarce, because it seems impossible to measure the fate of exogenous H2O2
as any measurement would interfere with the physiological equilibria. Available qualitative information: rapid absorption leads to increased levels of H2O2
and O2 in adjacent blood vessels, or even bubble formation.
Mucous membranes, small and large bowel, in vivo: bubble formation in draining vessels at concentrations > 1%
rat skin in vivo: elevated levels of H2O2
in excised epidermis within few minutes following application of 5-30% solutions of H2O2
Skin, mucous membranes: bubble formation in blood of patients undergoing irrigation of surgical wounds within minutes (solutions of 30% H2O2 , 5-20 ml).

Details on distribution in tissues:

H2O2 is sufficiently stable to diffuse longer distances and distribute systemically as evidenced by cerebral oxygen embolism following accidental ingestion of 35% hydrogen peroxide. In another case, a child died after ingestion of 230 of 3% hydrogen peroxide solution. Gas emboli in the intestinal lymphatics and pulmonary vasculature, vacuoles inn spleen, kidney, and myocardium were found.

Transfer into organs

Transfer into organs 1

Key result

Test no.:

#1

Transfer type:

blood/brain barrier

Observation:

slight transfer

Remarks:

in humans, accidental ingestion

Transfer into organs 2

Key result

Test no.:

#2

Transfer type:

other: across blood vessels into organs

Remarks:

e.g. spleen, kidney, heart

Observation:

distinct transfer

Remarks:

case of fatal accidental ingestion

Details on excretion:

H2O2 is a normal metabolite in aerobic cells. In the rat, the total estimated production is 1.45 µmol/min per 100 rat, with approx. 75% produced in the liver. Most H2O2 is degraded by catalase or glutathione peroxidase, a minor fraction may undergo the Fenton reaction. Only small quantities were found in human exhaled air (0.5 E -08 to 0.5 E -06 M).

H2O2 is sufficiently stable to diffuse longer distances and distribute systemically as evidenced by cerebral oxygen embolism following accidental ingestion of 35% hydrogen peroxide. In another case, a child died after ingestion of 230 of 3% hydrogen peroxide solution. Gas emboli in the intestinal lymphatics and pulmonary vasculature, vacuoles inn spleen, kidney, and myocardium were found.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

H2O2 may be reduced to water by Glutathione peroxidase, or water and oxygen by catalase.
In the Fentron reaction, it may also react with free metal ions to give the hydroxyl radical and hydroxal anion.

Applicant's summary and conclusion

Conclusions:

H2O2 is readily absorbed via all routes of exposure and degraded to water and oxygen. It is sufficiently stable to be systemically distributed via draining blood vessels.

Executive summary:

The EU Risk assessment for Hydrogen Peroxide summarises available ADME studies. H₂O₂ is a small, unloaded molecule that can easily cross biological membranes; the permeability of membranes for hydrogen peroxide is comparable to that for water. As a consequence, hydrogen peroxide is readily absorbed via all routes of exposure. As an oxidant. It may react with organic molecules, but is sufficiently stable to diffuse, enter adjacent blood vessels, and distribute throughout the body. Terminally, most of hydrogen peroxide is degraded at low levels by glutathione peroxidase [1] or by catalase [2].

H₂O₂+ 2 GSH  > 2 H₂O                                            [1]

2 H₂O₂               > 2H₂O + O₂                                   [2]

Further, hydrogen peroxide may react with free metal ions like iron or copper in the Fenton reaction [3] to give the highly reactive hydroxyl radical that reacts with organic molecules in the nearest proximity.

H₂O₂+ Fe²⁺/ Cu⁺  >  OH^.+ OH^-+ Fe³⁺/ Cu²⁺ [3]

As a consequence, only trace amounts are found in human exhaled air.

 

The toxicity of hydrogen peroxide is associated with the oxidation of organic molecules at the point of contact (e.g. skin corrosion) and, after absorption and distribution, at distant locations, the generation of the highly reactive hydroxyl radical, and embolism due to the formation of large amounts of oxygen. One mL of 30% H₂O₂ yield approximately 100 mL of oxygen, and oxygen bubbles in blood vessels and organs (brain, spleen, kidneys, hart muscle) were found in animals and humans after accidental ingestion.

Though absorption and degradation are known to occur within few minutes, no precise toxicokinetic data are known to exist, primarily due to analytical difficulties, e.g. to discriminate between endogenous and external hydrogen peroxide (ECB, 2003).

 

This information is considered to be suitable for assessment and can be used in a read across approach for hydrogen peroxide – urea (1:1) because the latter breaks down to the two components with water.