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In laboratory tests, animals were fed a single dose of hydrogen peroxide. Those tests determined doses at which hydrogen peroxide would cause the death of half of the animals (oral LD50). This occurred in rats with a single dose ranging between 600 -1617 mg/kg body weight. For tooth whiteners containing 10 to 22% carbamide peroxide, the values of oral LD50 for mice vary between 87.2 - 143.8 mg/kg body weight.
Individual human poisoning cases also provide information on the toxicity of hydrogen peroxide. A 16-month-old boy died after accidentally swallowing a single dose of 600 mg/kg body weight hydrogen peroxide. A man briefly fell into a coma after absorbing an estimated dose of 15 mg/kg body weight before quickly recovering. Discontinued oxygen circulation in the veins and arteries was reported in several infants following exposure to hydrogen peroxide as a result of a medical procedure for cleansing the inner wall of the intestine. More...
Diluted hydrogen peroxide solutions are non-irritant or mildly irritant. However, animal tests have shown that hydrogen peroxide above certain concentrations can cause irritation of the eyes, the skin, and the inside of the mouth, stomach, and intestine.
Skin irritation test on rabbits found no sign that tooth whiteners containing 10-22% carbamide peroxide could irritate the skin. Solutions containing up to 8% hydrogen peroxide were shown to be non-irritant when kept on the skin for 24 hours. Solutions containing 10% and 35% hydrogen peroxide respectively caused a slight and a mild irritation of the skin. In two rabbits out of six, a longer continuous exposure of 14 days caused their skin to peel off.
Skin sensitization tests on guinea pigs did not indicate that solutions containing 3 or 6 % hydrogen peroxide induce skin sensitization when applied on the skin or when injected in the skin. In general, data from studies involvingwomen using or working with hair dyes containing hydrogen peroxide does not provide evidence that hydrogen peroxide is a skin sensitiser in humans.
The dose at which half of the animals tested died following application of hydrogen peroxide on the skin was 700 to 7500 mg/kg body weight for rats and 630 mg/kg body weight for rabbits.
Eye irritation studies on human volunteers show that eye drops containing as little as 0.1% hydrogen peroxide, and contact lenses soaked in solutions containing less than 0.03% hydrogen peroxide, can cause eye irritation. Studies on rabbits indicate that a solution containing 5% hydrogen peroxide is non-irritant to mild-irritant. The larger the amount of hydrogen peroxide in a solution, the more irritation it causes, and solutions with more than 10% hydrogen peroxide present a risk of serious damage to eyes. Moreover, a different type of test has shown that several drops of a 2 to 5% solution or repeated application of a 1% solution can induce clouding of the cornea and inflammation of the conjunctiva of rabbit eyes.
Tests to assess the effect of hydrogen peroxide on mucous membranes in the mouth revealed that solutions containing about 1% hydrogen peroxide dripped continuously onto the gums and tongue of anaesthetised dogs caused the gums to swell and the outer layer of the gums to thicken and come off. As far as tooth whiteners are concerned, those containing 10-22% carbamide peroxide do not appear to irritate the mouth or gums of rats, mice or rabbits.
Solutions of 15 mg/kg body weigth carbamide peroxide given to rats directly into their stomachs caused ulceration, but these appeared to be healing after 24 hours. Hamsters given doses up to 2 000 mg/kg body weight of tooth whiteners containing 10% carbamide peroxide or 70 mg hydrogen peroxide showed no changes in the lining of the stomach or first part of the small intestine.
Biological membranes are highly permeable to hydrogen peroxide, thus hydrogen peroxide could readily enter cells. However, hydrogen peroxide is also effectively transformed by the body, and it is uncertain to what extent the unchanged substance may enter into blood circulation. Moreover, red blood cells are very effective in breaking down hydrogen peroxide and will remove it if it enters the blood stream. More...
To test whether repeated exposure to hydrogen peroxide can harm health, mice and rats were given hydrogen peroxide solutions either with their drinking water, directly into their stomachs through a tube, or through inhalation of hydrogen peroxide vapours.
Mice that were given about 150 mg/kg body weight through their drinking water every day during a 35-week test period grew normally and developed no visible abnormalities, but an examination of these mice after they died showed changes in the liver, kidney, stomach and small intestine. At doses larger than 1000 mg/kg body weight per day of hydrogen peroxide, they lost a lot of weight and died within 2 weeks. The dose below which no harmful effects were observed in mice that are genetically more vulnerable to hydrogen peroxide was 26 and 37 mg/kg body weight per day for males and females respectively.
Rats that were given 506 mg/kg body weight per day of hydrogen peroxide through a tube (directly into the stomach) 6 days a week for 90 days had less appetite, stopped putting on weight and showed changes in their blood and in some organs, particularly the stomach lining. The level of hydrogen peroxide exposure at which no harmful health effect has been observed (No Observed Adverse Effect Level or NOAEL) was 56.2 mg/kg body weight per day. In a similar study where rats were given hydrogen peroxide daily through a tube (directly into the stomach) for 100 days, the NOAEL was 20 mg/kg body weight per day. In another study, rats were exposed to hydrogen peroxide vapors 5 days per week, for a period of 28 days. Cases of irritation and inflamation of the repiratory tract were observed at exposure levels of 14.6 mg/m3 and more, but not at 2.9 mg/m3 (NOAEL).
Based on the various available studies, a lowest observed adverse effect level (LOAEL) of 75 and 86 mg/kg per day was determined for female and male rats respectively. Risks to humans can be assessed by comparing human exposures to the highest exposure at which no harmful effects were observed in any animal studies: 20 mg/kg body weight per day (NOAEL). The ratio between the two is the margin of safety (see question 6.2). More...
2.4.1 In in vitro studies (studies performed on cell cultures grown in laboratory), there is some evidence that hydrogen peroxide may hinder the natural repair of DNA if the DNA has previously been damaged by other reactive chemicals. In other in vitro studies, it was shown that hydrogen peroxide can change and damage the DNA. However, available in vivo studies (studies performed on living animals) do not suggest that it can cause significant changes to the DNA in the examined tissues of test animals such as rats and mice. In similar tests focusing on a limited number of target cells, tooth whiteners containing 10% carbamide peroxide did not seem to change or damage DNA, even in long-term studies on animals. Data on the possible DNA damaging effects of hydrogen peroxide on relevant animal tissues should be gathered.
Regarding cancer, a study on mice, which were given hydrogen peroxide in their drinking water, showed that this can cause an abnormal increase in the number of cells that form the first part of the small intestine, and in a few cases caused localised tumours.
In another study, rats that were given water to drink containing 1% hydrogen peroxide showed benign tumours in their forestomachs more frequently than rats that were not. Even though humans do not have a forestomach, these studies are, in principle, relevant to them since they have comparable tissues in the mouth and the upper part of the oesophagus. Moreover, a substance that causes cancer in the forestomach of rats may cause such effects in other tissues in humans.
Hydrogen peroxide has a weak potential to cause or promote cancers. The way it acts is unclear, but could involve direct damage to DNA, impairment of DNA repair, or chronic inflammation.
For instance, in a study on 19 patients with cancers that had begun in the oral cavity, the 3 patients who had used tooth whiteners in the past were more likely to have diseased lymph nodes than those who did not. This does not necessarily mean that tooth whiteners cause cancer. However, free radicals released by the whitening process have the potential to cause cancer, and therefore the use of these products in this patient population should be studied further. More...
2.4.2 Studies available do not allow a complete evaluation of the potential impact of hydrogen peroxide on reproduction and development.
Limited studies with mice, rats and rabbits which were given hydrogen peroxide in their drinking water suggest that this does not seriously disturb the male or female reproductive functions.
One study on rats showed that powdered feed mixed with hydrogen peroxide was toxic to the foetus. However, this study has major uncertainties and, although it raises some further questions, cannot be used for an assessment. More...
In cells of the body, hydrogen peroxide can be present at very low concentrations as a result of normal biological processes. It passes easily across biological membranes.
Hydrogen peroxide can lead to the production of hydroxyl radicals (OH.), which are highly reactive and attack most molecules in living cells. However, the body has enzymes that limit the amount of hydrogen peroxide by speeding up the break-down of hydrogen peroxide into water and oxygen. In mammals, these enzymes are present in nearly all cells. For instance, enzymes in the saliva process hydrogen peroxide very efficiently and are the primary defences against peroxide produced by bacteria in the mouth.
Individuals with certain inherited genetic disorder, such as acatalasemia, G6PD deficiency, and xerostomia, are more vulnerable to hydrogen peroxide than others.
Acatalasemia is a genetic disorder in which the activity of the enzymes responsible for the break down of hydrogen peroxide is lower than normal.
G6PD deficiency is a genetic disorder in which red blood cells lack an enzyme - G6PD - which causes them to be destroyed prematurely. People with such disorder cannot break down hydrogen peroxide adequately.
Xerostomia, or dry mouth, is a genetic disorder in which the salivary glands are less active than normal. This may affect the break down of hydrogen peroxide in the mouth. However, some studies do not support this theory and suggest that these individuals could still use tooth whiteners without ill effects. More...
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