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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
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 20.1 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Dose descriptor starting point:
- NOAEL
- Value:
- 71.8 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 502.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated exposure by inhalation. For details on calculations please refer to discussion.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- As the NOAEL of a repeated dose toxicity study with an exposure time of 90 days was used as point of departure an AF of 2 is considered as adequate for the exposure duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).
- AF for other interspecies differences:
- 2.5
- Justification:
- Recommended AF for other interspecies differences.
- AF for intraspecies differences:
- 5
- Justification:
- The default value for the relatively homogenous group "worker" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.15 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 175
- Dose descriptor starting point:
- NOAEL
- Value:
- 71.8 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 201 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated exposure by dermal route. For details on calculations please refer to discussion.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- As the NOAEL of a repeated dose toxicity study with an exposure time of 90 days was used as point of departure an AF of 2 is considered as adequate for the exposure duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 7
- Justification:
- The default allometric scaling factor for the differences between mice and humans is used.
- AF for other interspecies differences:
- 2.5
- Justification:
- Recommended AF for other interspecies differences.
- AF for intraspecies differences:
- 5
- Justification:
- The default value for the relatively homogenous group "worker" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
General
DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.
Workers – Hazard via inhalation route
Long term systemic inhalation DNEL, worker
The DNEL long term, systemic (inhalation) is derived by route-to route extrapolation from the repeated dose oral toxicity study with H2O2.
Step 1: Selection of the relevant dose descriptor (starting point):
The repeated dose 90-day oral toxicity study in rodents with the read across substance H2O2 is selected for DNEL derivation as it is the relevant repeated dose study performed similar to OECD guideline 408. Hydrogen peroxide – urea (1:1) dissolves in water and breaks down to hydrogen peroxide and urea. Toxicity is governed by hydrogen peroxide whereas oral or dermal toxicity of urea is negligible. In the repeated dose oral toxicity study with H2O2, the oral systemic NOAEL was determined to be 100 ppm (26 and 37 mg/kg/day for males and females, respectively). The lower NOAEL value for male mice (26 mg/kg bw/day) is taken for the calculation of a NOAEL for the target substance. Taking molecular weights into account, H2O2 corresponds for 36 % of the mass of hydrogen peroxide – urea (1:1). Based on this, the NOAEL of 26 mg/kg bw/day for H2O2 results in a NOAEL of 71.8 mg for hydrogen peroxide – urea (1:1).
Step 2: Modification into a correct starting point:
Using a conservative approach, a worker DNEL (long term inhalation exposure) is derived considering a two times higher absorption via inhalation than oral absorption.
Relevant dose descriptor (NOAEL): 71.8 mg/kg bw/day
Standard respiratory volume of the mouse (sRVmouse) for 8 hours: 0.67 m³/kg bw/d
Oral absorption of the mouse / inhalation absorption of humans (ABSoral-mouse / ABSinh-human): 0.5
Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³
Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³
Frequency of exposure in study: 7 days/week
Frequency of worker exposure: 5 days/week
Corrected inhalatory NOAEC for workers
= 71.8 mg/kg bw/day* 0.5 * (1 / 0.67 m³/kg bw/day) * (6.7 m³/10 m³) * (7/5)
= 502.6 mg/m³
Step 3: Use of assessment factors: 25
Interspecies: no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed.
Interspecies AF, remaining differences: 2.5
Intraspecies AF (worker): 5
Exposure duration AF: 2
Remaining uncertainties AF: 1
In conclusion, long term systemic inhalation DNEL, workers = 20.10 mg/m3
Short term systemic inhalation DNEL, worker
No data for the classification and labelling of the test substance for acute systemic toxicity (inhalation) is available. The substance is not classified for acute oral toxicity and acute dermal toxicity, therefore no adverse result for inhalation toxicity is expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL is required.
Short and long term local inhalation DNEL, worker
No data on local toxicity after inhalation is available. The substance is classified as skin irritant (Cat.2, H315) and eye damaging (Cat. 1, H318) according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted according to "Guidance on information requirements and chemical safety assessment part E: risk characterisation" (Nov. 2012). The substance is therefore allocated to the medium hazard band.
Workers – Hazard via dermal route
Long term systemic dermal DNEL, worker
The DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose oral toxicity study with H2O2.
Step 1: Selection of the relevant dose descriptor (starting point):
The repeated dose 90-day oral toxicity study in rodents with the read across substance H2O2 is selected for DNEL derivation as it is the relevant repeated dose study performed similar to OECD guideline 408. Hydrogen peroxide – urea (1:1) dissolves in water and breaks down to hydrogen peroxide and urea. Toxicity is governed by hydrogen peroxide whereas oral or dermal toxicity of urea is negligible. In the repeated dose oral toxicity study with H2O2, the oral systemic NOAEL was determined to be 100 ppm (26 and 37 mg/kg/day for males and females, respectively). The lower NOAEL value for male mice (26 mg/kg bw/day) is taken for the calculation of a NOAEL for the target substance. Taking molecular weights into account, H2O2 corresponds for 36 % of the mass of hydrogen peroxide – urea (1:1). Based on this, the NOAEL of 26 mg/kg bw/day for H2O2 results in a NOAEL of 71.8 mg for hydrogen peroxide – urea (1:1).
Step 2: Modification of the starting point:
The dermal uptake is considered to be 50 % of the oral uptake. The water solubility of hydrogen peroxide – urea (1:1) and also of the break down products H2O2 and urea is very high (> 10.000 mg/L) and therefore, the substances are expect to pass the lipid rich environment of the stratum corneum only to a minor content.
Factor for dermal NOAEL= 100 % oral / 50 % dermal= 2
Frequency of exposure in study: 7 days/week
Frequency of worker exposure: 5 days/week
oral NOAEL 71.8 mg/kg bw/day * 2 * (7/5) = 201.0 mg/kg bw/day dermal NOAEL
Step 3: Use of assessment factors: 175
Interspecies AF, allometric scaling (mouse to human): 7
Interspecies AF, remaining differences: 2.5
Intraspecies AF (worker): 5
Exposure duration AF: 2
Remaining uncertainties AF: 1
In conclusion, long term systemic dermal DNEL, workers = 1.15 mg/kg bw/day
Short term systemic dermal DNEL, worker
The test material is not classified and labelled for acute dermal toxicity, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.
Long and short term local dermal DNEL, worker
The substance is classified as skin irritant (Cat.2, H315) and eye damaging (Cat. 1, H318) according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted according to "Guidance on information requirements and chemical safety assessment part E: risk characterisation" (Nov. 2012). The substance is therefore allocated to the medium hazard band.
Worker – Hazard for the eyes
The substance is classified as skin irritant (Cat.2, H315) and eye damaging (Cat. 1, H318) according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted according to "Guidance on information requirements and chemical safety assessment part E: risk characterisation" (Nov. 2012). The substance is therefore allocated to the medium hazard band.
References
(not included as endpoint study record)
- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.
- ECHA (2014). Guidance on information requirements and chemical safety assessment. Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2014.
- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.
- ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.36 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 71.8 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 17.77 mg/m³
- Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated exposure by inhalation. For details on calculations please refer to discussion.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- As the NOAEL of a repeated dose toxicity study with an exposure time of 90 days was used as point of departure an AF of 2 is considered as adequate for the exposure duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).
- AF for other interspecies differences:
- 2.5
- Justification:
- Recommended AF for other interspecies differences.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively homogenous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.41 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 350
- Dose descriptor starting point:
- NOAEL
- Value:
- 71.8 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 143.6 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated exposure by dermal route. For details on calculations please refer to discussion.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- As the NOAEL of a repeated dose toxicity study with an exposure time of 90 days was used as point of departure an AF of 2 is considered as adequate for the exposure duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 7
- Justification:
- The default allometric scaling factor for the differences between mice and humans is used.
- AF for other interspecies differences:
- 2.5
- Justification:
- Recommended AF for other interspecies differences.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively homogenous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.21 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 350
- Dose descriptor starting point:
- NOAEL
- Value:
- 71.8 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation was used as one repeated oral exposure study was available. For details on calculations please refer to discussion.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- As the NOAEL of a repeated dose toxicity study with an exposure time of 90 days was used as point of departure an AF of 2 is considered as adequate for the exposure duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 7
- Justification:
- The default allometric scaling factor for the differences between mice and humans is used.
- AF for other interspecies differences:
- 2.5
- Justification:
- Recommended AF for other interspecies differences.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively homogenous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
General
DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.
General population – Hazard via inhalation route
Long term systemic inhalation DNEL, General population
The DNEL long term, systemic (inhalation) is derived by route-to route extrapolation from the repeated dose oral toxicity study with H2O2.
Step 1: Selection of the relevant dose descriptor (starting point):
The repeated dose 90-day oral toxicity study in rodents with the read across substance H2O2 is selected for DNEL derivation as it is the relevant repeated dose study performed similar to OECD guideline 408. Hydrogen peroxide – urea (1:1) dissolves in water and breaks down to hydrogen peroxide and urea. Toxicity is governed by hydrogen peroxide whereas oral or dermal toxicity of urea is negligible. In the repeated dose oral toxicity study with H2O2, the oral systemic NOAEL was determined to be 100 ppm (26 and 37 mg/kg/day for males and females, respectively). The lower NOAEL value for male mice (26 mg/kg bw/day) is taken for the calculation of a NOAEL for the target substance. Taking molecular weights into account, H2O2 corresponds for 36 % of the mass of hydrogen peroxide – urea (1:1). Based on this, the NOAEL of 26 mg/kg bw/day for H2O2 results in a NOAEL of 71.8 mg for hydrogen peroxide – urea (1:1).
Step 2: Modification into a correct starting point:
Using a conservative approach, a general population DNEL (long term inhalation exposure) is derived considering a two times higher absorption via inhalation than oral absorption.
Relevant dose descriptor (NOAEL): 71.8 mg/kg bw/day
Standard respiratory volume of the mouse (sRVmouse) for 24 hours: 2.02 m³/kg bw/d
Oral absorption of the mouse / inhalation absorption of humans (ABSoral-mouse / ABSinh-human): 0.5
Frequency of exposure in study: 7 days/week
Frequency of general population exposure: 7 days/week
Corrected inhalatory NOAEC for general population
= 71.8 mg/kg bw/day * 0.5 * (1 / 2.02 m³/kg bw/day) * (7/7)
= 17.77 mg/m³
Step 3: Use of assessment factors: 50
Interspecies: no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed.
Interspecies AF, remaining differences: 2.5
Intraspecies AF (general population): 10
Exposure duration AF: 2
Remaining uncertainties AF: 1
In conclusion, long term systemic inhalation DNEL, general population = 0.36 mg/m3
Short term systemic inhalation DNEL, General population
No data for the classification and labelling of the test substance for acute systemic toxicity (inhalation) is available. The substance is not classified for acute oral toxicity and acute dermal toxicity, therefore no adverse result for inhalation toxicity is expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL is required.
Short and long term local inhalation DNEL, General population
No data on local toxicity after inhalation is available. The substance is classified as skin irritant (Cat.2, H315) and eye damaging (Cat. 1, H318) according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted according to "Guidance on information requirements and chemical safety assessment part E: risk characterisation" (Nov. 2012). The substance is therefore allocated to the medium hazard band.
General population – Hazard via dermal route
Long term systemic dermal DNEL, General population
The DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose oral toxicity study with H2O2.
Step 1: Selection of the relevant dose descriptor (starting point):
The repeated dose 90-day oral toxicity study in rodents with the read across substance H2O2 is selected for DNEL derivation as it is the relevant repeated dose study performed similar to OECD guideline 408. Hydrogen peroxide – urea (1:1) dissolves in water and breaks down to hydrogen peroxide and urea. Toxicity is governed by hydrogen peroxide whereas oral or dermal toxicity of urea is negligible. In the repeated dose oral toxicity study with H2O2, the oral systemic NOAEL was determined to be 100 ppm (26 and 37 mg/kg/day for males and females, respectively). The lower NOAEL value for male mice (26 mg/kg bw/day) is taken for the calculation of a NOAEL for the target substance. Taking molecular weights into account, H2O2 corresponds for 36 % of the mass of hydrogen peroxide – urea (1:1). Based on this, the NOAEL of 26 mg/kg bw/day for H2O2 results in a NOAEL of 71.8 mg for hydrogen peroxide – urea (1:1).
Step 2: Modification of the starting point:
The dermal uptake is considered to be 50 % of the oral uptake. The water solubility of hydrogen peroxide – urea (1:1) and also of the break down products H2O2 and urea is very high (> 10.000 mg/L) and therefore, the substances are expect to pass the lipid rich environment of the stratum corneum only to a minor content.
Factor for dermal NOAEL= 100 % oral / 50 % dermal= 2
Frequency of exposure in study: 7 days/week
Frequency of general population exposure: 7 days/week
oral NOAEL 71.8 mg/kg bw/day * 2 * (7/7) = 143.6 mg/kg bw/day dermal NOAEL
Step 3: Use of assessment factors: 350
Interspecies AF, allometric scaling (mouse to human): 7
Interspecies AF, remaining differences: 2.5
Intraspecies AF (general population): 10
Exposure duration AF: 2
Remaining uncertainties AF: 1
In conclusion, long term systemic dermal DNEL, general population = 0.41 mg/kg bw/day
Short term systemic dermal DNEL, General population
The test material is not classified and labelled for acute dermal toxicity, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.
Long and short term local dermal DNEL, General population
The substance is classified as skin irritant (Cat. 2, H315) and eye damaging (Cat. 1, H318) according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted according to "Guidance on information requirements and chemical safety assessment part E: risk characterisation" (Nov. 2012). The substance is therefore allocated to the medium hazard band.
General population – Hazard via oral route
Long term systemic oral DNEL, General population
The DNEL long term, systemic (oral) is derived from the combined repeated dose oral toxicity study with H2O2.
Step 1: Selection of the relevant dose descriptor (starting point):
The repeated dose 90-day oral toxicity study in rodents with the read across substance H2O2 is selected for DNEL derivation as it is the relevant repeated dose study performed similar to OECD guideline 408. Hydrogen peroxide – urea (1:1) dissolves in water and breaks down to hydrogen peroxide and urea. Toxicity is governed by hydrogen peroxide whereas oral or dermal toxicity of urea is negligible. In the repeated dose oral toxicity study with H2O2, the oral systemic NOAEL was determined to be 100 ppm (26 and 37 mg/kg/day for males and females, respectively). The lower NOAEL value for male mice (26 mg/kg bw/day) is taken for the calculation of a NOAEL for the target substance. Taking molecular weights into account, H2O2 corresponds for 36 % of the mass of hydrogen peroxide – urea (1:1). Based on this, the NOAEL of 26 mg/kg bw/day for H2O2 results in a NOAEL of 71.8 mg for hydrogen peroxide – urea (1:1).
Step 2: Modification of the starting point:
No modification is used as the same exposure route is considered.
Step 3: Use of assessment factors: 350
Interspecies AF, allometric scaling (mouse to human): 7
Interspecies AF, remaining differences: 2.5
Intraspecies AF (general population): 10
Exposure duration AF: 2
Remaining uncertainties AF: 1
In conclusion, long term systemic oral DNEL, general population = 0.21 mg/kg bw/day
Short term systemic oral DNEL, General population
The test item is not classified for acute oral toxicity according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.
General population – Hazard for the eyes
The substance is classified as skin irritant (Cat.2, H315) and eye damaging (Cat. 1, H318) according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted according to "Guidance on information requirements and chemical safety assessment part E: risk characterisation" (Nov. 2012). The substance is therefore allocated to the medium hazard band.
References
(not included as endpoint study record)
- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.
- ECHA (2014). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2014.
- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.
- ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016.
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