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EC number: 202-815-9 | CAS number: 100-06-1
- 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:
- 4.937 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:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 123.42 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:
- The adequate time extrapolation factor for the reduced body weight development is considered to be 2 because the study period covered half of the time between birth and adulthood and no body weight effect was seen in the treatment of the adult parental animals.
- 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
- Explanation for the modification of the dose descriptor starting point:
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.
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.4 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:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 140 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:
- The adequate time extrapolation factor for the reduced body weight development is considered to be 2 because the study period covered half of the time between birth and adulthood and no body weight effect was seen in the treatment of the adult parental animals.
- 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:
- 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:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low 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 conducted with the source substance p-methoxybenzyl acetate (CAS 104-21-2).
Step 1: Selection of the relevant dose descriptor (starting point):
The OECD TG and GLP compliant combined repeated dose oral toxicity and reproductive screening study with the read-across substance is selected for DNEL derivation. In this study, the NOAEL for fertility effects and parental toxicity was 400 mg/kg/day, i.e. the highest dose tested. The adequate time extrapolation factor for the parental effects is considered to be 4. As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
Thus the starting points from repeated dose toxicity would be 100 mg/kg/day, including time extrapolation.
The NOAEL for developmental effects was 100 mg/kg bw/day for reduced viability between PND0 and PND4 and reduced body weight gain of pups between PND4 and PND13. The adequate time extrapolation factor for the postnatal mortality is 1 since the window of susceptibility was covered completely. The adequate time extrapolation factor for the reduced body weight development is considered to be 2 because the study period covered half of the time between birth and adulthood and no body weight effect was seen in the treatment of the adult parental animals. Thus the starting points from developmental effects would be 100 and 50 mg/kg/day, respectively, including time extrapolation.
Overall, the starting point of 100 mg/kg/day for F1 body weight effects between PND4 and PND13, together with a time extrapolation factor of 2, is considered the most sensitive endpoint for DNEL derivation.
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): 100 mg/kg bw/day
Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d
Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / 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
= 100 mg/kg bw/day* 0.5 * (1 / 0.38 m³/kg bw/day) * (6.7 m³/10 m³) * (7/5)
= 123.42 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 = 4.937 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 respiratory irritation is available. However, the test substance is classified as eye irritant cat. 2 according to Regulation (EC) No 1272/2008 (CLP). This implies a potential to damage mucosal tissue by inhalation exposure (according to "Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health", November 2012)and therefore the substance is allocated to the low hazard band (according to " Guidance on Information Requirements and Chemical Safety Assessment Part E: Risk Characterisation", May 2016). A qualitative risk assessment is conducted.
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 (OECD 422).
Step 1: Selection of the relevant dose descriptor (starting point):
The OECD TG and GLP compliant combined repeated dose oral toxicity and reproductive screening study with the read-across substance is selected for DNEL derivation. In this study, the NOAEL for fertility effects and parental toxicity was 400 mg/kg/day, i.e. the highest dose tested. The adequate time extrapolation factor for the parental effects is considered to be 4.As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
Thus the starting points from repeated dose toxicity would be 100 mg/kg/day, including time extrapolation.
The NOAEL for developmental effects was 100 mg/kg bw/day for reduced viability between PND0 and PND4 and reduced body weight gain of pups between PND4 and PND13. The adequate time extrapolation factor for the postnatal mortality is 1 since the window of susceptibility was covered completely. The adequate time extrapolation factor for the reduced body weight development is considered to be 2 because the study period covered half of the time between birth and adulthood and no body weight effect was seen in the treatment of the adult parental animals. Thus the starting points from developmental effects would be 100 and 50 mg/kg/day, respectively, including time extrapolation.
Overall, the starting point of 100 mg/kg/day for F1 body weight effects between PND4 and PND13, together with a time extrapolation factor of 2, is considered the most sensitive endpoint for DNEL derivation.
Step 2: Modification of the starting point:
The test substance was determined to have a logPow of 1.9, water solubility of 616 mg/L and a molecular weight above 100 g/mol. Therefore the dermal uptake is considered to be 100 % of the oral uptake in the worst case.
Factor for dermal NOAEL= 100 % oral / 100 % dermal= 1
Frequency of exposure in study: 7 days/week
Frequency of worker exposure: 5 days/week
oral NOAEL 100 mg/kg bw/day * 1 * (7/5) = 140 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: 2.5
Intraspecies AF (worker): 5
Exposure duration AF: 2
Remaining uncertainties AF: 1
In conclusion, long term systemic dermal DNEL, workers = 1.4 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 term local dermal DNEL, worker
The test item is classified as irritating to skin (cat. 2) according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E).
Short term local dermal DNEL, worker
The test item is classified as irritating to skin (cat. 2) according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E).
Worker – Hazard for the eyes
The test item is classified for eye irritation into cat. 2 according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is required.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.741 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:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 37.037 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:
- The adequate time extrapolation factor for the reduced body weight development is considered to be 2 because the study period covered half of the time between birth and adulthood and no body weight effect was seen in the treatment of the adult parental animals.
- 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:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.5 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):
- 200
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 100 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:
- The adequate time extrapolation factor for the reduced body weight development is considered to be 2 because the study period covered half of the time between birth and adulthood and no body weight effect was seen in the treatment of the adult parental animals.
- 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:
- 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:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.5 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):
- 200
- Dose descriptor starting point:
- NOAEL
- Value:
- 100 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:
- The adequate time extrapolation factor for the reduced body weight development is considered to be 2 because the study period covered half of the time between birth and adulthood and no body weight effect was seen in the treatment of the adult parental animals.
- 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:
- 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:
- 1.5 mg/kg bw/day
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
- Dose descriptor starting point:
- other: long-term systemic DNEL
- Value:
- 0.5 mg/kg bw/day
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 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 conducted with the source substance p-methoxybenzyl acetate (CAS 104-21-2).
Step 1: Selection of the relevant dose descriptor (starting point):
The OECD TG and GLP compliant combined repeated dose oral toxicity and reproductive screening study with the read-across substance is selected for DNEL derivation. In this study, the NOAEL for fertility effects and parental toxicity was 400 mg/kg/day, i.e. the highest dose tested. The adequate time extrapolation factor for the parental effects is considered to be 4. As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
Thus the starting points from repeated dose toxicity would be 100 mg/kg/day, including time extrapolation.
The NOAEL for developmental effects was 100 mg/kg bw/day for reduced viability between PND0 and PND4 and reduced body weight gain of pups between PND4 and PND13. The adequate time extrapolation factor for the postnatal mortality is 1 since the window of susceptibility was covered completely. The adequate time extrapolation factor for the reduced body weight development is considered to be 2 because the study period covered half of the time between birth and adulthood and no body weight effect was seen in the treatment of the adult parental animals. Thus the starting points from developmental effects would be 100 and 50 mg/kg/day, respectively, including time extrapolation.
Overall, the starting point of 100 mg/kg/day for F1 body weight effects between PND4 and PND13, together with a time extrapolation factor of 2, is considered the most sensitive endpoint for DNEL derivation.
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): 100 mg/kg bw/day
Standard respiratory volume of the rat (sRVrat) for 24 hours: 1.35 m³/kg bw/d
Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / 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
= 100 mg/kg bw/day * 0.5 * (1 / 1.35 m³/kg bw/day) * (7/7)
= 37.037 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 = 0.741 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 respiratory irritation is available. However, the test substance is classified as eye irritant cat. 2 according to Regulation (EC) No 1272/2008 (CLP). This implies a potential to damage mucosal tissue by inhalation exposure (according to "Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health", November 2012)and therefore the substance is allocated to the low hazard band (according to " Guidance on Information Requirements and Chemical Safety Assessment Part E: Risk Characterisation", May 2016). A qualitative risk assessment is conducted.
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 OECD TG and GLP compliant combined repeated dose oral toxicity and reproductive screening study with the read-across substance is selected for DNEL derivation. In this study, the NOAEL for fertility effects and parental toxicity was 400 mg/kg/day, i.e. the highest dose tested. The adequate time extrapolation factor for the parental effects is considered to be 4. As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
Thus the starting points from repeated dose toxicity would be 100 mg/kg/day, including time extrapolation.
The NOAEL for developmental effects was 100 mg/kg bw/day for reduced viability between PND0 and PND4 and reduced body weight gain of pups between PND4 and PND13. The adequate time extrapolation factor for the postnatal mortality is 1 since the window of susceptibility was covered completely. The adequate time extrapolation factor for the reduced body weight development is considered to be 2 because the study period covered half of the time between birth and adulthood and no body weight effect was seen in the treatment of the adult parental animals. Thus the starting points from developmental effects would be 100 and 50 mg/kg/day, respectively, including time extrapolation.
Overall, the starting point of 100 mg/kg/day for F1 body weight effects between PND4 and PND13, together with a time extrapolation factor of 2, is considered the most sensitive endpoint for DNEL derivation.
Step 2: Modification of the starting point:
The test substance was determined to have a logPow of 1.9, water solubility of 616 mg/L and a molecular weight above 100 g/mol. Therefore the dermal uptake is considered to be 100 % of the oral uptake in the worst case.
Factor for dermal NOAEL= 100 % oral / 100 % dermal= 1
Frequency of exposure in study: 7 days/week
Frequency of general population exposure: 7 days/week
oral NOAEL 100 mg/kg bw/day * 1 * (7/7) = 100 mg/kg bw/day dermal NOAEL
Step 3: Use of assessment factors: 200
Interspecies AF, allometric scaling (rat to human): 4
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 = 0.50 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 term local dermal DNEL, General population
The test item is classified as irritating to skin (cat. 2) according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E).
Short term local dermal DNEL, General population
The test item is classified as irritating to skin (cat. 2) according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E).
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 (OECD 422).
Step 1: Selection of the relevant dose descriptor (starting point):
The OECD TG and GLP compliant combined repeated dose oral toxicity and reproductive screening study with the read-across substance is selected for DNEL derivation. In this study, the NOAEL for fertility effects and parental toxicity was 400 mg/kg/day, i.e. the highest dose tested. The adequate time extrapolation factor for the parental effects is considered to be 4. As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of approx. 50 days (males: 50 days; females: 2 weeks prior to mating until Postpartum Day 13) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.
Thus the starting points from repeated dose toxicity would be 100 mg/kg/day, including time extrapolation.
The NOAEL for developmental effects was 100 mg/kg bw/day for reduced viability between PND0 and PND4 and reduced body weight gain of pups between PND4 and PND13. The adequate time extrapolation factor for the postnatal mortality is 1 since the window of susceptibility was covered completely. The adequate time extrapolation factor for the reduced body weight development is considered to be 2 because the study period covered half of the time between birth and adulthood and no body weight effect was seen in the treatment of the adult parental animals. Thus the starting points from developmental effects would be 100 and 50 mg/kg/day, respectively, including time extrapolation.
Overall, the starting point of 100 mg/kg/day for F1 body weight effects between PND4 and PND13, together with a time extrapolation factor of 2, is considered the most sensitive endpoint for DNEL derivation.
Step 2: Modification of the starting point:
No modification is used as the same exposure route is considered.
Step 3: Use of assessment factors: 200
Interspecies AF, allometric scaling (rat to human): 4
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 = 0.50 mg/kg bw/day
Short term systemic oral DNEL, General population
The substance is classified for acute oral toxicity into cat. 4. The DNEL short-term oral was calculated 3-fold the corresponding DNEL long-term oral (ECHA CSR guidance R.8, 2012). The DNEL short-term oral for acute oral exposure was based on the DNEL long-term oral of 0.5 mg/kg bw/d. DNEL short-term oral = 0.5 mg/kg bw/d * 3 = 1.5 mg/kg bw/d. As the DNEL acute oral is based on DNEL long-term oral, AFs were already considered and therefore no further AFs were applied.
General population – Hazard for the eyes
The test item is classified for eye irritation into cat.2 according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is required.
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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