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EC number: 233-279-4 | CAS number: 10102-90-6
- 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:
- 0.044 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Dose descriptor starting point:
- NOAEC
- Value:
- 6.63 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 3.33 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The NOAEC for CuPP is derived from the NOAEC of Cu2O, determined in a 4-week inhalation study carried out according to OECD Test Guideline 412 in rats (Kirkpatrick, 2010), assuming that toxicity is triggered by the concentration of Cu. Within this study animals were exposed to a dust aerosol atmosphere of the test substance for 6 hours per day for 5 days per week.
- 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:
- 6
- Justification:
- The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point)
- 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:
- DNEL (Derived No Effect Level)
- Value:
- 0.132 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 0.33
- DNEL extrapolated from long term DNEL
- Explanation for the modification of the dose descriptor starting point:
The test material is classified for acute inhalation toxicity cat. 4, according to Regulation (EC) No 1272/2008 (CLP). The acute systemic DNEL (inhalation) is extrapolated from the long term DNEL with multiplication by factor of 3 (assessment factor=1/3=0.33) (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). The long term systemic DNEL (inhalation) is derived from the repeated dose inhalation toxicity study.
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.267 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 12.5
- Dose descriptor:
- NOAEC
- Value:
- 6.63 mg/m³
- 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:
- 1
- Justification:
- No time extrapolation is conducted for local DNEL derivation.
- 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
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.82 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):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 63 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 441 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the 90-day repeated dose oral toxicity study (Hebert, 1993) is identified as the relevant dose descriptor. Assuming that dermal absorption is 10 % of the applied test substance (EFSA Scientific Report (2008)) and the oral absorption in rats is 50 % (EFSA Scientific Report (2008)) as a worst case, and considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated..
- 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:
- The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is used.
- AF for other interspecies differences:
- 1.25
- Justification:
- Reduced from the default value of 2.5 based on similarities observed between rat and human toxicokinetic mechanisms for the uptake of copper following oral administration.
- 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:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
WORKER
General
DNEL derivation for the test substance Copper (II) pyrophosphate (CuPP) 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
Step 1: Selection of the relevant dose descriptor (starting point):
The NOAEC for CuPP is derived from the NOAEC of Cu2O, determined in a 4-week inhalation study carried out according to OECD Test Guideline 412 in rats (Kirkpatrick, 2010), assuming that toxicity is triggered by the concentration of Cu. Within this study animals were exposed to a dust aerosol atmosphere of the test substance for 6 hours per day for 5 days per week.
Step 2: Modification of the starting point:
NOAEC (Cu2O): 2 mg/m^3
As toxicity is triggered by the concentration of Cu, the NOAEC based on Cu is calculated:
M (Cu2O): 143.1 g/mol
M (Cu): 63.5 g/mol
M (Cu) is multiplied with a factor of 2 due to 2 Cu atoms in Cu2O.
Percentage of Cu in Cu2O: 127/143.1 = 0.88 * 100 % = 88 %
NOAEC (Cu): 2 mg/m^3 * 88 % /100 = 1.76 mg/m^3
The NOAEC for CuPP is calculated:
The molecular weight for CuPP is 239.5 g/mol.
The atomic weight for Cu is ca. 63.5 g/mol, and should be multiplied where > 1 Cu molecule is present, which is not necessary for CuPP.
NOAEC (CuPP): 1.76 mg/m^3 * (239.5 g/mol/63.5 g/mol))
= 6.63 mg/m^3(starting point for DNEL derivation)
No modification for absorption is used as the same exposure route is considered. Following corrections were performed:
Relevant dose descriptor (NOAEC): 6.63 mg/m^3
Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m^3
Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m^3
Frequency of exposure in study: 5 days/week, 6 hours/day
Frequency of worker exposure: 5 days/week, 8 hours/day
Corrected inhalatory NOAEC for workers
= 6.63 mg/m^3 * (6.7 m^3/10 m^3) * (5/5) * (6/8)
= 3.33 mg/m^3
Step 3: Use of assessment factors: 75
Interspecies AF, allometric scaling (rat to human): 1
Interspecies AF, remaining differences: 2.5
Intraspecies AF (worker): 5
Exposure duration AF: 6
Remaining uncertainties AF: 1
In conclusion, long term systemic inhalation DNEL, worker = 0.044 mg/m^3
Short term systemic inhalation DNEL, worker
The test material is classified for acute inhalation toxicity cat. 4, according to Regulation (EC) No 1272/2008 (CLP). The acute systemic DNEL (inhalation) is extrapolated from the long term DNEL with multiplication by factor of 3 (assessment factor=1/3=0.33) (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). The long term systemic DNEL (inhalation) is derived from the repeated dose inhalation toxicity study.
For Steps 1-3 please refer to “Long term systemic inhalation DNEL, Worker”
Step 4: extrapolation from the long term DNEL
A factor of 3 is used: long term DNEL*3= short term DNEL
0.044 mg/m^3 *3=0.132 mg/m^3
In conclusion, short term systemic inhalation DNEL, workers = 0.132 mg/m^3
Long term local inhalation DNEL, worker
The DNEL long term, local (inhalation) is derived from the repeated dose inhalation toxicity study.
Step 1: Selection of the relevant dose descriptor (starting point):
The local NOAEC for CuPP is derived from the NOAEC of Cu2O, determined in a 4-week inhalation study carried out according to OECD Test Guideline 412 in rats (Kirkpatrick, 2010), assuming that toxicity is triggered by the concentration of Cu. Within this study animals were exposed to a dust aerosol atmosphere of the test substance for 6 hours per day for 5 days per week.
Step 2: Modification of the starting point:
NOAEC (Cu2O): 2 mg/m^3
As toxicity is triggered by the concentration of Cu, the NOAEC based on Cu is calculated:
M (Cu2O): 143.1 g/mol
M (Cu): 63.5 g/mol
M (Cu) is multiplied with a factor of 2 due to 2 Cu atoms in Cu2O.
Percentage of Cu in Cu2O: 127/143.1 = 0.88 * 100 % = 88 %
NOAEC (Cu): 2 mg/m^3 * 88 % /100 = 1.76 mg/m^3
The NOAEC for CuPP is calculated:
The molecular weight for CuPP is 239.5 g/mol.
The atomic weight for Cu is ca. 63.5 g/mol, and should be multiplied where > 1 Cu molecule is present, which is not necessary for CuPP.
NOAEC (CuPP):1.76 mg/m^3 * (239.5 g/mol/63.5 g/mol))
= 6.63 mg/m^3(starting point for DNEL derivation)
No modification for absorption is used as the same exposure route is considered. Following corrections were performed:
Relevant dose descriptor (NOAEC): 6.63 mg/m^3
Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m^3
Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m^3
Frequency of exposure in study: 5 days/week, 6 hours/day
Frequency of worker exposure: 5 days/week, 8 hours/day
Corrected inhalatory NOAEC for workers
= 6.63 mg/m^3 * (6.7 m³/10 m³) * (5/5) * (6/8)
= 3.33 mg/m^3
Step 3: Use of assessment factors: 12.5
Interspecies AF, allometric scaling (rat to human): 1
Interspecies AF, remaining differences: 2.5
Intraspecies AF (worker): 5
Exposure duration AF: 1 (No time extrapolation is conducted for local DNEL derivation.)
Remaining uncertainties AF: 1
In conclusion, long term local inhalation DNEL, worker = 0.267 mg/m^3
Short term local inhalation DNEL, worker
For short term local inhalation all possible hazards are sufficiently covered by derivation of the long term inhalation DNEL as no time difference is considered for local effects.
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.
Step 1: Selection of the relevant dose descriptor (starting point):
The NOAEL of CuPP is derived from NOAEL of Cu, calculated in an oral repeated dose toxicity study with CuSO4 on rats (Hebert, 1993), assuming that toxicity is triggered by the concentration of Cu. The oral NOAEL is 16.7 mg/kg bw/day for Copper. To adjust the NOAEL for CuPP as follows:
The molecular weight for CuPP is 239.5 g/mol.
The atomic weight for Cu is ca. 63.5 g/mol, and should be multiplied where > 1 Cu molecule is present, which is not necessary for CuPP.
NOAEL (CuPP): 16.7 mg/kg bw/day * (239.5 g/mol/63.5 g/mol)
= 63 mg/kg bw/day(starting point for DNEL derivation)
Step 2: Modification of the starting point:
In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the 90-day repeated dose oral toxicity study (Hebert, 1993) is identified as the relevant dose descriptor. Assuming that dermal absorption is 10 % of the applied test substance (EFSA Scientific Report (2008)) and the oral absorption in rats is 50 % (EFSA Scientific Report (2008)) as a worst case, and considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated.
Factor for dermal NOAEL= 50 % oral / 10 % dermal= 5
Frequency of exposure in study: 7 days/week
Frequency of worker exposure: 5 days/week
oral NOAEL 63 mg/kg bw/day * 5 * (7/5) =441 mg/kg bw/day dermal NOAEL
Step 3: Use of assessment factors: 50
Interspecies AF, allometric scaling (rat to human): 4
Interspecies AF, remaining differences: 1.25 (Reduced from the default value of 2.5 based on similarities observed between rat and human toxicokinetic mechanisms for the uptake of copper following oral administration.)
Intraspecies AF (worker): 5
Exposure duration AF: 2
Remaining uncertainties AF: 1
In conclusion, long term systemic dermal DNEL, workers = 8.82 mg/kg bw/day
Short term systemic dermal DNEL, worker
No data for the classification and labelling of the test substance for acute dermal toxicity is available. The substance is not classified for acute oral toxicity, therefore no adverse result for dermal toxicity is expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL is required.
Short term and long term local dermal DNEL, worker
The test material is not classified and labelled for skin sensitization or skin irritation, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.
Worker – Hazard for the eyes
For exposure to the eyes a low hazard was identified, as the test substance is classified for eye irritation Cat.2 according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E). Therefore goggles and further appropriate RMMs are carried into execution.
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.
- EFSA Scientific Report (2008) 187, 1-101 Conclusion on the peer review of copper compounds.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.008 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 150
- Dose descriptor starting point:
- NOAEC
- Value:
- 6.63 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 1.18 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The NOAEC for CuPP is derived from the NOAEC of Cu2O, determined in a 4-week inhalation study carried out according to OECD Test Guideline 412 in rats (Kirkpatrick, 2010), assuming that toxicity is triggered by the concentration of Cu. Within this study animals were exposed to a dust aerosol atmosphere of the test substance for 6 hours per day for 5 days per week.
- 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:
- 6
- Justification:
- The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
- 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:
- DNEL (Derived No Effect Level)
- Value:
- 0.024 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 0.33
- DNEL extrapolated from long term DNEL
- Explanation for the modification of the dose descriptor starting point:
The test material is classified for acute inhalation toxicity cat. 4, according to Regulation (EC) No 1272/2008 (CLP). The acute systemic DNEL (inhalation) is extrapolated from the long term DNEL with multiplication by factor of 3 (assessment factor=1/3=0.33) (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). The long term systemic DNEL (inhalation) is derived from the repeated dose inhalation toxicity study.
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.047 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Dose descriptor:
- NOAEC
- Value:
- 6.63 mg/m³
- 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:
- 1
- Justification:
- No time extrapolation is conducted for local DNEL derivation.
- 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
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3.15 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):
- 100
- Dose descriptor starting point:
- NOAEL
- Value:
- 63 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 315 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
In order to derive the general population DNEL (long-term dermal exposure), the NOAEL assessed in the 90-day repeated dose oral toxicity study (Hebert, 1993) is identified as the relevant dose descriptor. Assuming that dermal absorption is 10 % of the applied test substance (EFSA Scientific Report (2008)) and the oral absorption in rats is 50 % (EFSA Scientific Report (2008)) as a worst case, and considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated.
- 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:
- The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is used.
- AF for other interspecies differences:
- 1.25
- Justification:
- Reduced from the default value of 2.5 based on similarities observed between rat and human toxicokinetic mechanisms for the uptake of copper following oral administration.
- 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:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.57 mg/kg bw/day
DNEL related information
- DNEL derivation method:
- other: The long term oral DNEL for the general population is derived based on the acceptable daily intake (ADI) published by the WHO (EFSA Scientific Report (2008).
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
General
DNEL derivation for the test substance Copper (II) pyrophosphate (CuPP) 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 NOAEC for CuPP is derived from the NOAEC of Cu2O, determined in a 4-week inhalation study carried out according to OECD Test Guideline 412 in rats (Kirkpatrick, 2010), assuming that toxicity is triggered by the concentration of Cu. Within this study animals were exposed to a dust aerosol atmosphere of the test substance for 6 hours per day for 5 days per week.
Step 2: Modification of the starting point:
NOAEC (Cu2O): 2 mg/m^3
As toxicity is triggered by the concentration of Cu, the NOAEC based on Cu is calculated:
M (Cu2O): 143.1 g/mol
M (Cu): 63.5 g/mol
M (Cu) is multiplied with a factor of 2 due to 2 Cu atoms in Cu2O.
Percentage of Cu in Cu2O: 127/143.1 = 0.88 * 100 % = 88 %
NOAEC (Cu): 2 mg/m^3 * 88 % /100 = 1.76 mg/m^3
The NOAEC for CuPP is calculated:
The molecular weight for CuPP is 239.5 g/mol.
The atomic weight for Cu is ca. 63.5 g/mol, and should be multiplied where > 1 Cu molecule is present, which is not necessary for CuPP.
NOAEC (CuPP): 1.76 mg/m^3 * (239.5 g/mol/63.5 g/mol))
= 6.63 mg/m^3 (starting point for DNEL derivation)
No modification for absorption is used as the same exposure route is considered. Following corrections were performed:
Relevant dose descriptor (NOAEC): 6.63 mg/m^3
Frequency of exposure in study: 5 days/week, 6 hours/day
Frequency of general population exposure: 7 days/week, 24 hours/day
Corrected inhalatory NOAEC for general population
= 6.63 mg/m^3 * (5/7) * (6/24)
= 1.18 mg/m^3
Step 3: Use of assessment factors: 150
Interspecies AF, allometric scaling (rat to human): 1
Interspecies AF, remaining differences: 2.5
Intraspecies AF (general population): 10
Exposure duration AF: 6
Remaining uncertainties AF: 1
In conclusion, long term systemic inhalation DNEL, general population = 0.008 mg/m^3
Short term systemic inhalation DNEL, worker
The test material is classified for acute inhalation toxicity cat. 4, according to Regulation (EC) No 1272/2008 (CLP). The acute systemic DNEL (inhalation) is extrapolated from the long term DNEL with multiplication by factor of 3 (assessment factor=1/3=0.33) (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). The long term systemic DNEL (inhalation) is derived from the repeated dose inhalation toxicity study.
For Steps 1-3 please refer to “Long term systemic inhalation DNEL, general population”
Step 4: extrapolation from the long term DNEL
A factor of 3 is used: long term DNEL*3= short term DNEL
0.008 mg/m^3 *3=0.024 mg/m^3
In conclusion, short term systemic inhalation DNEL, general population = 0.024 mg/m^3
Long term local inhalation DNEL, general population
The DNEL long term, local (inhalation) is derived from the repeated dose inhalation toxicity study.
Step 1: Selection of the relevant dose descriptor (starting point):
The local NOAEC for CuPP is derived from the NOAEC of Cu2O, determined in a 4-week inhalation study carried out according to OECD Test Guideline 412 in rats (Kirkpatrick, 2010), assuming that toxicity is triggered by the concentration of Cu. Within this study animals were exposed to a dust aerosol atmosphere of the test substance for 6 hours per day for 5 days per week.
Step 2: Modification of the starting point:
NOAEC (Cu2O): 2 mg/m^3
As toxicity is triggered by the concentration of Cu, the NOAEC based on Cu is calculated:
M (Cu2O): 143.1 g/mol
M (Cu): 63.5 g/mol
M (Cu) is multiplied with a factor of 2 due to 2 Cu atoms in Cu2O.
Percentage of Cu in Cu2O: 127/143.1 = 0.88 * 100 % = 88 %
NOAEC (Cu): 2 mg/m^3 * 88 % /100 = 1.76 mg/m^3
The NOAEC for CuPP is calculated:
The molecular weight for CuPP is 239.5 g/mol.
The atomic weight for Cu is ca. 63.5 g/mol, and should be multiplied where > 1 Cu molecule is present, which is not necessary for CuPP.
NOAEC (CuPP):1.76 mg/m^3 * (239.5 g/mol/63.5 g/mol))
= 6.63 mg/m^3(starting point for DNEL derivation)
No modification for absorption is used as the same exposure route is considered. Following corrections were performed:
Relevant dose descriptor (NOAEC): 6.63 mg/m^3
Frequency of exposure in study: 5 days/week, 6 hours/day
Frequency of general population exposure: 7 days/week, 24 hours/day
Corrected inhalatory NOAEC for general population
= 6.63 mg/m^3 * (5/7) * (6/24)
= 1.18 mg/m^3
Step 3: Use of assessment factors: 25
Interspecies AF, allometric scaling (rat to human): 1
Interspecies AF, remaining differences: 2.5
Intraspecies AF (general population): 10
Exposure duration AF: 1 (No time extrapolation is conducted for local DNEL derivation.)
Remaining uncertainties AF: 1
In conclusion, long term local inhalation DNEL, general population = 0.0471 mg/m^3
Short term local inhalation DNEL, General population
For short term local inhalation all possible hazards are sufficiently covered by derivation of the long term inhalation DNEL as no time difference is considered for local effects.
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.
Step 1: Selection of the relevant dose descriptor (starting point):
The NOAEL of CuPP is derived from NOAEL of Cu, calculated in an oral repeated dose toxicity study with CuSO4 on rats (Hebert, 1993), assuming that toxicity is triggered by the concentration of Cu. The oral NOAEL is 16.7 mg/kg bw/day for Copper. To adjust the NOAEL for CuPP as follows:
The molecular weight for CuPP is 239.5 g/mol.
The atomic weight for Cu is ca. 63.5 g/mol, and should be multiplied where > 1 Cu molecule is present, which is not necessary for CuPP.
NOAEL (CuPP): 16.7 mg/kg bw/day * (239.5 g/mol/63.5 g/mol)
= 63 mg/kg bw/day(starting point for DNEL derivation)
Step 2: Modification of the starting point:
In order to derive the general population DNEL (long-term dermal exposure), the NOAEL assessed in the 90-day repeated dose oral toxicity study (Hebert, 1993) is identified as the relevant dose descriptor. Assuming that dermal absorption is 10 % of the applied test substance (EFSA Scientific Report (2008)) and the oral absorption in rats is 50 % (EFSA Scientific Report (2008)) as a worst case, and considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated.
Factor for dermal NOAEL= 50 % oral / 10 % dermal= 5
Frequency of exposure in study: 7 days/week
Frequency of general population exposure: 7 days/week
oral NOAEL 63 mg/kg bw/day * 5 * (7/7) =315 mg/kg bw/day dermal NOAEL
Step 3: Use of assessment factors: 100
Interspecies AF, allometric scaling (rat to human): 4
Interspecies AF, remaining differences: 1.25 (Reduced from the default value of 2.5 based on similarities observed between rat and human toxicokinetic mechanisms for the uptake of copper following oral administration.)
Intraspecies AF (general population): 10
Exposure duration AF: 2
Remaining uncertainties AF: 1
In conclusion, long term systemic dermal DNEL, general population = 3.15 mg/kg bw/day
Short term systemic dermal DNEL, General population
No data for the classification and labelling of the test substance for acute dermal toxicity is available. The substance is not classified for acute inhalation and oral toxicity, therefore no adverse result for dermal toxicity is expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL is required.
Short term and long term local dermal DNEL, General population
The test material is not classified and labelled for skin sensitization or skin irritation, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.
General population – Hazard via oral route
Long term systemic oral DNEL, General population
In order to derive the general population DNEL the acceptable daily intake (ADI) for copper was used (EFSA Scientific Report (2008)). This value ensures an appropriate level of protection also with regard to children.
The ADI value = 0.15 mg Cu/kg bw/day
DNEL (CuPP) = 0.15 mg/kg bw/day x (239.5 g/mol/63.5 g/mol)
= 0.57 mg/kg bw/day
In conclusion, long term systemic oral DNEL, general population = 0.57 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
For exposure to the eyes a low hazard was identified, as the test substance is classified for eye irritation Cat.2 according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E). Therefore goggles and further appropriate RMMs are carried into execution.
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.
- EFSA Scientific Report (2008) 187, 1-101 Conclusion on the peer review of copper compounds.
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