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EC number: 204-701-4 | CAS number: 124-43-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
No information on toxicity for reproduction and development was located for hydrogen peroxide- urea (1:1) but since the substance dissolves upon contact with water and breaks down to hydrogen peroxide and urea, information for these substances may be read across to the target substance. Existing information for hydrogen peroxide and urea indicates that there is no undue hazard for this endpoint for either source substance.
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Hydrogen peroxide- urea (1:1)
No information on toxicity for reproduction and development was located but since the substance dissolves upon contact with water and breaks down to hydrogen peroxide and urea, information for these substances may be read across to the target substance.
Hydrogen peroxide
Regarding hydrogen peroxide it is noted that existing data from old, non-guideline do not indicate undue effects on reproduction and development parameters in mice, rats and rabbits. These studies were summarised in the EU Risk Assessment Report (ECB, 2003) and it is stated in the conclusions that it was consented at the Technical Meeting level to derogate reproduction toxicity screening. “The decision was reached on the presumption that conventional study protocols (e.g. administration in drinking water) were unlikely to show specific embryonal or foetal effects firstly, because it is doubtful whether hydrogen peroxide (as opposed to its degradation products oxygen and water) would reach the foetus and secondly, because local effects in the mother, possibly causing nutritional disturbances and general toxicity, are expected.” (ECB, 2003). Therefore, new animal studies for hydrogen peroxide are not required and technically not feasible.
Urea
According to REACH Annex VIII point 8.7.1 the study does not need to be conducted as pre-natal developmental toxicity studies are available.
Conclusions
Existing information for hydrogen peroxide and urea indicates that there is no undue hazard for this endpoint for either source substance. Hydrogen peroxide is the most relevant breakdown product and a new animal study with hydrogen peroxide –urea (1:1) is not needed. The reason is that hydrogen peroxide would determine the toxicity whereas that of urea is negligible, as evidenced by the results of existing studies for the substance. It was, however, consented in the EU at Technical Meeting level that reproduction toxicity studies for hydrogen peroxide are derogated on two grounds. Firstly, it was doubted that hydrogen peroxide would reach the foetus, and secondly because local effects in the mother, possibly causing nutritional disturbances and general toxicity, were expected. This applies also to hydrogen peroxide –urea (1:1) because this substance liberates hydrogen peroxide upon contact with water.
Effects on developmental toxicity
Description of key information
No information on toxicity for reproduction and development was located for hydrogen peroxide- urea (1:1) but since the substance dissolves upon contact with water and breaks down to hydrogen peroxide and urea, information for these substances may be read across to the target substance. Existing information for hydrogen peroxide and urea indicates that there is no undue hazard for this endpoint for either source substance.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- ANALOGUE APPROACH JUSTIFICATION
Please refer to the attached read across justification in section 13. - Reason / purpose for cross-reference:
- read-across source
- Clinical signs:
- not specified
- Mortality:
- no mortality observed
- Body weight and weight changes:
- not specified
- Gross pathological findings:
- no effects observed
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- no statistically significant difference between vehicle control and urea-treated rats regarding percent fetal resorptions (2.4 vs. 0%)
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- not specified
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- no statistically significant difference between vehicle control and urea-treated rats regarding number of live fetuses (13.3 ± 0.8 vs. 13.8 ± 2.2)
- Changes in pregnancy duration:
- not examined
- Description (incidence and severity):
- dams sacrificed before parturition
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not examined
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.DescriptionIncidenceAndSeverityEffectsOnPregnancyDuration): dams sacrificed before parturition - Changes in number of pregnant:
- not examined
- Description (incidence and severity):
- only pregnant rats (or mice) were used
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 2 000 mg/kg bw (total dose)
- Based on:
- act. ingr.
- Basis for effect level:
- other: no maternal toxicity noted
- Remarks on result:
- other: result ist for urea; one single dose was administered
- Key result
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- no statistically significant difference between fetuses from vehicle control and urea-treated rats: fetal body weight (3,671 ± 197 mg vs. 3,626 ± 104 mg)
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): no statistically significant difference between fetuses from vehicle control and urea-treated rats: fetal body weight (3,671 ± 197 mg vs. 3,626 ± 104 mg) - Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- no statistically significant difference between fetuses from vehicle control and urea-treated rats: number of live fetuses (13.3 ± 0.8 vs. 13.8 ± 2.2),
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Description (incidence and severity):
- no statistically significant difference between fetuses from vehicle control and urea-treated rats: percent fetuses malformed (0 vs. 1.8%)
- Skeletal malformations:
- not specified
- Visceral malformations:
- not specified
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 2 000 mg/kg bw (total dose)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effect noted
- Remarks on result:
- other: result is for urea; one single dose administered
- Key result
- Abnormalities:
- no effects observed
- Key result
- Developmental effects observed:
- no
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- ANALOGUE APPROACH JUSTIFICATION
Please refer to the attached read across justification in section 13. - Reason / purpose for cross-reference:
- read-across source
- Clinical signs:
- not specified
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified - Changes in number of pregnant:
- not specified
- Details on maternal toxic effects:
- no maternal toxicity noted
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 50 000 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Basis for effect level:
- other: no adverse effect noted
- Remarks on result:
- other: no maternal toxicity
- Abnormalities:
- not specified
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not examined - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- not specified
- Other effects:
- no effects observed
- Description (incidence and severity):
- There was no effect on pup kidney weight. Dry weights, reported as a percentage of the fresh weights, were 14.4 ± 2.54% (≈1.12 g) for the test group compared with 14.7 ± 1.96% (≈1.18 g) for the control group.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 50 000 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects noted
- Remarks on result:
- other: no effect on pup weight or kidney development
- Key result
- Abnormalities:
- not specified
- Key result
- Developmental effects observed:
- no
Referenceopen allclose all
Results are for urea, adminstered to rats and mice (data not shown); can be read across to the target substance
Results are for urea (source substance), may be read across to the target substance
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Hydrogen peroxide- urea (1:1)
No information on toxicity for reproduction and development was located but since the substance dissolves upon contact with water and breaks down to hydrogen peroxide and urea, information for these substances may be read across to the target substance.
Hydrogen peroxide
Regarding hydrogen peroxide it is noted that existing data from old, non-guideline do not indicate undue effects on reproduction and development parameters in mice, rats and rabbits. These studies were summarised in the EU Risk Assessment Report (ECB, 2003) and it is stated in the conclusions that it was consented at the Technical Meeting level to derogate reproduction toxicity screening. “The decision was reached on the presumption that conventional study protocols (e.g. administration in drinking water) were unlikely to show specific embryonal or foetal effects firstly, because it is doubtful whether hydrogen peroxide (as opposed to its degradation products oxygen and water) would reach the foetus and secondly, because local effects in the mother, possibly causing nutritional disturbances and general toxicity, are expected.” (ECB, 2003).Therefore, new animal studies for hydrogen peroxide are not required and technically not feasible.
Urea
Two studies on developmental toxicity using rats and mice indicate low toxicity for this endpoint. These studies are not compliant with current test guidelines, but can be used in a weight of evidence approach.
In the first study, Seipelt et al. (1969) examined whether high urea doses during pregnancy had an effect on kidney weight. Pregnant albino Wistar rats were divided into test and vehicle control groups (six/group). No additional information on mating procedure was provided. The test group was dosed by gavage with urea for 14 days starting 6 days after the last oestrus. Urea was dissolved in water and administered in two doses totalling 50 g/kg-day. No maternal toxicity was reported. Within 48 hours of birth, pups were sacrificed by decapitation and kidneys removed and weighed; the right kidney was then dried at 105 ºC and weighed. No maternal toxicity was reported. Dams of the test group delivered 39 pups, compared to 34 pups in the control group. Hence, litter size was comparable across the groups. The pup fresh and dry kidney weight was not affected (Seipelt et al., 1969). It is concluded that even an excessive dose of urea (50,000 mg/kg bw/day), administered to pregnant rats for 14 days by oral gavage, did not cause maternal or foetal toxicity, or affect development of the foetal kidneys. Hence, the administered dose represents the LOAEL in this study (ECB, 2003).
In a second study, Teramoto et al. (1981) examined the developmental toxicity of urea compounds in pregnant Wistar rats (n=4) and pregnant ICR mice (n=10) that received a single oral dose of urea at 2000 mg/kg bw on gestational day 12 (rats) or GD 10 (mice). Rats were sacrificed on GD 20 (mice: GD 18). The number of implants and live and dead foetuses were counted. Living foetuses from each litter were divided into two groups after being weighed individually and examined for gross abnormalities. Foetuses from the right uterine horn were processed for skeletal examination and those from the left horn were processed for visceral examination. For statistical comparisons, the litter was considered the experimental unit. No maternal toxicity was noted in rats or mice. There were no statistical differences between the vehicle control and the urea-treated rats based on the mean ± SD for number of implants (13.7 + 1.0 vs.13.8 ± 2.2), number of live foetuses (13.3 ± 0.8 vs. 13.8 ± 2.2), percent foetal resorptions (2.4 vs. 0%), foetal body weight (3,671 ± 197 mg vs. 3,626 ± 104 mg), or percent foetuses malformed (0 vs. 1.8%). These endpoints also were unaffected in mice treated with urea (data not shown). Thus, no maternal or developmental toxicity was noted in pregnant rats or mice receiving a single oral dose of 2000 mg/kg bw (EPA, 2011).
The two developmental studies above are not equivalent with a GLP guideline study, however, new animal studies are, not deemed to be necessary as justified below. Urea is of low toxicological activity. No evidence of toxicity was seen in any of the tests available up to 2000 mg/kg bw; no developmental toxicity was seen in pregnant rats and mice up to 2000 mg/kg bw (single dose) or pregnant rats at 50,000 mg/kg bw/day (repeat dose, 14 days). Further, no effects on the reproduction organs were noted in cancer bioassays using male and female rats and mice which were treated for 12 months (oral feeding studies; approximate dose levels for the various groups were 0, 379, 757, or 3,786 mg/kg-day for male F344 rats; 0, 419, 838, or 4,191 mg/kg- day for F344 females; 0, 644, 1,288, or 6,442 mg/kg-day for male C57BL/6 mice; and 0, 655, 1,311, or 6,553 mg/kg-day for C57BL/6 females (Fleischmann et al., 1980; summarised In the EPA assessment, EPA, 2011; assessment attached in section 13). Urea is a normal intermediary metabolite that humans produce and excrete in large quantities (25-50 g/day, i.e. approx. 500 mg/kg bw/day) under normal conditions without any adverse effect on fertility or reproduction. Toxicokinetic information indicates that additional exogenous urea is rapidly excreted via urine, i.e. urea plasma levels are constantly controlled. Small amounts of additional exogenous urea is therefore not considered to cause adverse effects on reproduction. On this basis, animal studies are not considered to be justified.
Conclusions
Existing information for hydrogen peroxide and urea indicates that there is no undue hazard for this endpoint for either source substance. Hydrogen peroxide is the most relevant breakdown product and a new animal study with hydrogen peroxide –urea (1:1) is not needed. The reason is that hydrogen peroxide would determine the toxicity whereas that of urea is negligible, as evidenced by the results of existing studies for the substance. It was, however, consented in the EU at Technical Meeting level that reproduction toxicity studies for hydrogen peroxide are derogated on two grounds. Firstly, it was doubted that hydrogen peroxide would reach the foetus, and secondly because local effects in the mother, possibly causing nutritional disturbances and general toxicity, were expected. This applies also to hydrogen peroxide –urea (1:1) because this substance liberates hydrogen peroxide upon contact with water.
Mode of Action Analysis / Human Relevance Framework
Hydrogen peroxide - urea (1:1) dissolves in water and breaks down to hydrogen peroxide and urea. The toxicity of urea is negligible. Hydrogen peroxide is corrosive at high concentrations, irritating at low concentrations. It determines the toxicity of the target substance. The concentration of exogenous hydrogen peroxide is strictly controlled by glutathione peroxidase, catalase, or antioxidants. It is therefore doubted that hydrogen peroxide does reach the foetus. Based on this, and because local maternal effects are expected, it was concluded at Technical Meeting level hat hydrogen peroxide is of low relevance and animal studies are not feasible. This applies also to hydrogen peroxide –urea (1:1) because this substance liberates hydrogen peroxide upon contact with water.
Justification for classification or non-classification
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 toxicity to reproduction under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.
Additional information
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.