Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 204-701-4 | CAS number: 124-43-6
Based on a study according to OECD Guideline 423 in rats the oral LD50 of the test item was determined to be > 2000 mg/kg bw.
As hydrogen peroxide determines the toxicity of the target substance, the estimated dermal LD50 for hydrogen peroxide (source substance) is used to derive an estimate of the dermal LD50 value for the target substance. The dermal LD50 of the target substance was derived to be 13800 mg/kg.
The acute oral toxicity of hydrogen peroxide-urea (carbamide peroxide) was determined in the female rat, according to the OECD TG 423 and under GLP conditions. Animals (two groups of 3 rats each) received the test material by oral gavage at 2000 mg/kg bw. Clinical signs were seen during the first 6 hours after dosing. The animals gained body weight after 7 and 14 days post treatment. No mortalities occurred, and there were no necropsy findings at termination on day 14 post treatment. Hence, the oral LD50 is > 2000 mg/kg bw in the rat.
This study is considered to be valid and suitable for assessment.
Number of animals with gastric mucosa lesions (rated as present or not present)
Female rats (Wistar Kyoto, 3 per dose group) received either 0, 5, 15, or 50 mg hydrogen peroxide-urea (1:1)/ kg bw, or a tooth-bleaching agent at 150 and 500 mg/kg bw (which corresponds to 15 and 50 mg hydrogen peroxide-urea (1:1)/kg bw, respectively) in water by oral gavage. The animals were sacrificed at 1 hour and 24 hours after dosing and necropsied. Stomach, liver and kidney specimen were subjected to histopathological examinations.
No effects were seen in the liver and the kidneys. Gastric ulceration was seen in all groups receiving test material at 1 hour after dosing. Healing was seen in groups receiving hydrogen peroxide-urea (1:1) within 24 hours, i.e. the effect was absent in the low dose group at 5 mg/kg bw and was diminished in the animals at 15 and 50 mg hydrogen peroxide-urea (1:1)/kg bw. No healing was seen in animals dosed with the consumer product, most probably because the viscous material prolonged the contact to the mucous membrane.
Overall, reversible local irritation of the gastric mucosa was seen within 1 hour after oral dosing of 15 and 50 mg hydrogen peroxide-urea (1:1)/kg bw whereas no effects were seen in the liver or kidneys (Dahl and Becher, 1995).
The oral LD50 for the source substance urea was 14,300 mg/kg bw in the male and 15,000 mg/kg in the female rat. Taking into account molecular weights, the lower value of 14,300 mg urea/kg bw corresponds to 22,408 mg of the target substance, hydrogen peroxide (1:1) / kg bw.
The oral LD50 for the source substance urea was 11,500 mg/kg bw in the male and 13,000 mg/kg in the female mouse. Taking into account molecular weights, the lower value of 11,500 mg urea/kg bw corresponds to 20,724 mg of the target substance, hydrogen peroxide (1:1) / kg bw.
2000 mg/kg of a 35% solution corresponds to 700 mg H2O2 /kg bw.
Taking the molecular weights of the source substance (H2O2) and of the target substance into consideration, the LD0 for H2O2 (700 mg/kg bw) corresponds to 1935 mg of the target substance/kg bw.
The study is considered to be valid and suitable for assessment. The toxicity of hydrogen peroxide largely depends on its concentration; this is discussed in the endpoint summary. For the read across to hydrogen peroxide - urea (1:1), the result for the 35% solution can be adopted. This is explained in the endpoint summary.
700 mg of the active ingredient/kg bw corresponds to 1935 mg of the target substance, hydrogen peroxide – urea (1:1), per kg bw .
Results most probably refer to the respective hydrogen peroxide solutions, i.e. no deaths were seen at 140 mg/kg bw of the active ingredient, whereas the LD50was >2240 mg active ingredient /kg bw with the 28% hydrogen peroxide solution.
Taking the molecular weights into consideration, 2240 mg of the active ingredient correspond to 6182 mg of the target substance/kg bw in the mouse.
Acute oral toxicity
The acute oral toxicity of hydrogen peroxide-urea (1:1) (carbamide peroxide) was determined in the female rat, according to the OECD TG 423 and under GLP conditions. Animals (two groups of 3 rats each) received the test material by oral gavage at 2000 mg/kg bw. Clinical signs were seen during the first 6 hours after dosing. The animals gained body weight after 7 and 14 days post treatment. No mortalities occurred, and there were no necropsy findings at termination on day 14 post treatment. Hence, the oral LD50 is > 2000 mg/kg bw in the rat.
Acute inhalation toxicity
No study was located. Information is waived because inhalation is not considered to be a likely route of exposure, taking into account the physico-chemical properties (solid crystals; vapour pressure) of hydrogen peroxide - urea (1:1).
Acute dermal toxicity
Hydrogen peroxide - urea (1:1) is present as solid crystals at ambient temperature, and as such it is not dermally absorbed and does not cause systemic effects, and no acute dermal studies have been located. However, it dissolves in water and decomposes to hydrogen peroxide and urea. Under certain use conditions this could lead to absorption of hydrogen peroxide or urea. It is therefore reasonable to use data on these breakdown products for assessment.
Hydrogen peroxide governs the acute toxicity of the target substance, Hydrogen peroxide - urea (1:1). H2O2 is a moderate reactive oxygen species that may react at the point of contact and cause skin irritation or corrosion depending on the concentration, but which is also absorbed through the skin and may distribute with the blood stream to other sites where it is either enzymatically decomposed by catalase and glutathione peroxidase, or it oxidises cellular molecules (e.g. thiol groups), or decomposes to give rise of the highly reactive hydroxyl radical which reacts with any material including DNA at the site of generation. In this context it should also be noted that the degradation by catalase leads to the formation of water and oxygen according to the equation
2 H2O2 → 2 H2O + O2 (enzyme: catalase).
About 100 mL of oxygen are liberated by 1 mL of a 30% solution of H2O2, with bubble formation, local lesions and embolism as one of the acute toxic principles following uptake via either route of exposure.
Only skin reactions (eschar, exfoliation) but no mortality were seen in 10 rabbits receiving 2000 mg/kg bw of a 35% hydrogen peroxide solution under an occlusive dressing for 24 hours, Therefore, the LD0 value was 700 mg hydrogen peroxide/kg bw in this study. The LD50 value for hydrogen peroxide in rats or rabbits was in the range of > 5000 mg/kg bw in modern studies, as can be seen from data in published assessments (see table below). According to the assessments from ECB (2003) and SCCP (2007), the older dermal study results have to be interpreted with caution because the technical conditions are generally poorly described.
Overview and discussion of data contained in assessments
Dermal toxicity data are reported in several assessments. A compilation of the available data on acute dermal toxicity of hydrogen peroxide is presented in the table below.
(LD0or LD50, based on active ingredient, H2O2)
700 – 5000
LD50, rabbit: 700
(mortality: 6/12 animals)
LD50, rat: 5000
Hrubetz et al. (1951)
LD0, rabbit: 6500
LD50, rabbit: 9200
Rabbit: no mortality
Mouse: “some mortality” at > 8000
Liarskii et al. (1983)
Mouse: no mortality
LD50, rabbit: 630
LD50, rat: 700 - 7500
The data from Hrubetz et al. (1951) suggest the rabbit is more sensitive than the rat. However, the LD50value obtained in modern studies with rabbits (9200 mg/kg bw) was comparably high as the values reported for the rat. On the basis of these findings it is concluded that the dermal LD50 is > 5000 mg/kg bw for both the rat and the rabbit, with no need for classification for acute dermal toxicity according to the regulation (EC) 1272/2008.
The acute dermal NOAEL for the target substance was calculated from the subchronic NOAEL value for urea in rats, taking into account the molecular weights of the target substance (mw 94) and of the source substance (mw 60). As no mortality or any other adverse effect was seen at the NOAEL level, 338.4 mg urea/kg bw can be taken as the dermal LD0 value.
As no adverse effects were seen at all it is conceivable that the LD50 value is much higher and in the range of the oral or intravenous LD50value. It is reasonable to assume that the bioavailability, dose rate, target concentrations and, hence, acute toxicity is maximal via the intravenous route of exposure. On the basis of the available data for the rat (cf. table below) the acute dermal LD50value for the rat is estimated to be > 5000 mg/kg bw. Data for the mouse support this.
This data basis shows that urea is of negligible toxicity in the rat or mouse, regardless of the exposure pathway. The toxicity of hydrogen peroxide is more pronounced and, therefore, determines the toxicity of the target substance, hydrogen peroxide – urea (1:1).
[mg urea/kg bw]
14,300 (m)15,000 (f)
Sato et al., 1977
(4 and 25 weeks)
On the basis of the considerations above, the following acute toxicity dose descriptors (LD50 values) are derived and presented for comparison. The dermal LD50 for the target substance depends mainly on hydrogen peroxide because for urea the estimate for this value is very conservative, taking data for the oral and intravenous route into consideration.
LD50values [mg/kg bw]
Source substance 1
Source substance 2
Hydrogen peroxide- urea (1:1)
LD50, rat > 2,000
LD50, rat> 14,000
LD50, mouse> 11,500
No data located
LD50, rat > 13,800
LD50 rat, rabbit > 5,000C
LD50, rat > 5,000
LD50, rat> 5,000
LD50, mouse> 4,600
A data available but not explored because reliable data for the target substance are available B relevant exposure unlikely C derived from published data n.a. not applicable
The estimate for dermal LD50value for the target substance is as follows:
1. Taking molecular weights into account, H2O2corresponds for 36% of the mass of hydrogen peroxide – urea (1:1).
2. Therefore, 13,800 mg hydrogen peroxide - urea (1:1) would liberate 5000 mg of hydrogen peroxide when dissolved in water.
3. The solubility of hydrogen peroxide – urea (1:1) in water is 500 g/L, or 500 mg/mL. Hence, the final volume would be 27.6 mL, and the solution would be a 18% hydrogen peroxide solution.
It is obvious from this calculation that the amount of hydrogen peroxide - urea (1:1), estimated as the dermal LD50 dose, cannot be applied on the skin, and no classification for acute oral or dermal toxicity is required.
Classification, Labeling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on these data the substance is not considered to be classified for acute oral or acute dermal toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again