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EC number: 246-107-8 | CAS number: 24245-27-0
- 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:
- 0.33 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):
- 75
- Dose descriptor starting point:
- NOAEL
- Value:
- 10 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 24.7 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker
Corrected NOAEC (inhalation) for workers:
= 10 mg/kg bw/day x 1/0.38 m3/kg bw/day x (6.7 m3/10 m3) x 1.4
= 24.7 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is applied.
- AF for differences in duration of exposure:
- 6
- Justification:
- Default factor for extrapolation from sub-acute to chronic is applied.
- 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:
- The recommended AF for other interspecies differences is applied.
- 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 applied study is considered as reliable study with a Klimisch code 1. Therefore no additional AF is applied.
- AF for remaining uncertainties:
- 1
- Justification:
- Even though the Point of departure for DNEL Derivation origins from a structural analogue substances, the read-across approach is considered unremarkable and DNEL derivation is considered conservative. Thus, there are no remaining uncertainties on this approach.
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)
Acute/short term exposure
- Hazard assessment conclusion:
- medium 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:
- 0.47 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):
- 300
- Dose descriptor starting point:
- NOAEL
- Value:
- 10 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:
Corrected NOAEL (dermal) for workers
= 10 mg/kg bw/day x 10 x 1.4
= 140 mg/kg bw/day
- 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:
- Default factor for extrapolation from sub-acute to chronic is applied.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is applied.
- AF for other interspecies differences:
- 2.5
- Justification:
- The recommended AF for other interspecies differences is applied.
- 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 applied study is considered as reliable study with a Klimisch code 1. Therefore no additional AF is applied.
- AF for remaining uncertainties:
- 1
- Justification:
- Even though the Point of departure for DNEL Derivation origins from a structural analogue substances, the read-across approach is considered unremarkable and DNEL derivation is considered conservative. Thus, there are no remaining uncertainties on this approach.
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:
- medium hazard (no threshold derived)
Additional information - workers
General
DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).
Inhalation
Long term, systemic DNEL – exposure via inhalation (workers)
Using a conservative approach, a worker DNEL (long-term inhalation exposure) is calculated. This worker long-term DNEL is considered to ensure also an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected). No repeated dose inhalation toxicity study with the test item is available. Therefore, long-term inhalation DNEL was derived by route-to-route extrapolation from an oral repeated dose toxicity study. No repeated dose toxicity study with the test item is available. However, a sub-acute toxicity study with a read-across substance is available and considered suitable. For more details on read-across justification please refer to respective IUDLID Section. Based on an OECD TG 407 study with the read-across substance, daily oral administration to rats revealed signs of toxicity in the high and mid dose tested i. e. 30 and 90 mg/kg bw/d, respectively. The NOAEL for systemic toxicity was therefore considered to be 10 mg/kg bw/day. This NOAEL of systemic toxicity is applied as Point of Departure for DNEL derivation since it is considered to reflect worst case assumption.
Step 1: PoD: NOAEL = 10 mg/kg bw/day
Step 2: Modification of PoD:
Standard respiratory volume, human (sRVhuman) for 8 h per person (70 kg): 6.7 m3
Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m3/kg bw
Worker respiratory volume (wRV) for 8 hours with light physical activity per person: 10 m3
Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 1/1 (no difference is expected, oral absorption is estimated to be 100 % (Ioannou 1984). According to ECHA Guidance – Chapter R8 (p25), the inhalation absorption is 100%: “if data on the starting route (oral) are available these should be used, but for the end route (inhalation), the worst case inhalation absorption should be assumed (i. e. factor 1)
Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker
Corrected NOAEC (inhalation) for workers:
= 10 mg/kg bw/day x 1/0.38 m3/kg bw/day x (6.7 m3/10 m3) x 1.4
= 24.7 mg/m3
Step 3: Overall AF= 75
Dose
response relationship AF: 1
The dose response relationship is considered unremarkable, therefore no
additional factor is applied.
Exposure
duration AF: 6
Default factor for extrapolation from sub-acute to chronic is applied.
Intraspecies
AF (worker): 5
The default value for the relatively homogenous group "worker" is used.
Interspecies
AF, remaining differences: 2.5
The recommended AF for other interspecies differences is applied.
Allometric
scaling AF: 1
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).
Whole
database AF: 1
The applied study is considered as reliable study with a Klimisch code
1. Therefore no additional AF is applied.
AF
for remaining uncertainties: 1
Even though the Point of departure for DNEL Derivation origins from a
structural analogue substances, the read-across approach is considered
unremarkable and DNEL derivation is considered conservative. Thus, there
are no remaining uncertainties on this approach.
In conclusion, long term systemic inhalation DNEL, workers = 0.33 mg/m3
Acute, systemic DNEL- exposure via inhalation (workers)
There is no short-term or long-term toxicity study via inhalation route available for the test item. Due to its very low vapour pressure (< 1 Pa), high peak-inhalation exposure is not considered as relevant. The test item is unlikely to be available as a vapour to a large extent. Thus, the acute inhalation DNEL was not derived. Further, long-term DNELs are considered sufficient to ensure that acute effects do not occur. In addition, the test item is not classified as acutely toxic via inhalation or dermal route.
Long term & acute, local DNEL- exposure via inhalation (workers)
No data on respiratory irritation are available. The test item is classified for eye corrosion (cat. 1) according to Regulation (EC) No 1272/2008 (CLP). Therefore, a qualitative hazard assessment is applied.
Dermal
Long term, systemic DNEL- exposure via dermal route (workers)
No repeated dose dermal toxicity study with the test item is available. Therefore, long-term dermal DNEL was derived by route-to-route extrapolation.
The NOAEL of 10 mg/kg bw/day derived from a sub-chronic toxicity study performed with a structural analogue substance was used as the Point of Departure.
Step 1: PoD: NOAEL = 10 mg/kg bw/day
Step 2: Modification into a correct starting point:
Correction
for difference between human and experimental exposure conditions: 7 d
rat/5 d worker.
There
are no relevant experimental data on repeated dermal exposure. A low
dermal absorption value can be expected due to the physico- chemical
properties of the test item. The oral absorption is estimated to 100%
(Ioannou 1984), and the dermal absorption is estimated to 10% (Shah
1985) in rats. The correction factor is 100 / 10.
Corrected NOAEL (dermal) for workers
= 10 mg/kg bw/day x 10 x 1.4
= 140 mg/kg bw/day
Step 3: Overall AF= 300
Dose-response relationship AF: 1
The dose response relationship is considered unremarkable. Therefore, no additional factor is used.
Exposureduration
AF: 6
Default factor for extrapolation from sub-acute to chronic is applied.
Interspecies AF, allometric scaling (rat to human): 4
The default allometric scaling factor for the differences between rats and humans is applied.
Interspecies AF, remaining differences: 2.5
The recommended AF for other interspecies differences is applied.
Intraspecies AF (worker): 5
The default value for the relatively homogenous group "worker" is used
Whole
database AF: 1
The applied study is considered as reliable study with a Klimisch code
1. Therefore no additional AF is applied.
AF
for remaining uncertainties: 1
Even though the Point of departure for DNEL Derivation origins from a
structural analogue substances, the read-across approach is considered
unremarkable and DNEL derivation is considered conservative. Thus, there
are no remaining uncertainties on this approach.
In conclusion, long term systemic dermal DNEL, workers = 0.47 mg/kg bw/day
Acute, systemic DNEL- dermal exposure (workers)
An acute dermal toxicity study is available for the test item. Based on the results the test item is not classified for acute dermal toxicity according to Regulation (EC) No 1272/2008 (CLP). Thus, the acute systemic dermal DNEL was not derived. Further, long-term DNELs are considered sufficient to ensure that acute effects do not occur.
Long term & acute, local DNEL- dermal exposure (workers)
The test substance is not classified for skin irritation or skin sensitization. Therefore, no DNEL on long-term or short-term local effects was derived.
Hazard to the eye-local effects (worker)
The test item is classified for eye damaging Cat 1 according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is applied and the substance is assigned to the moderate hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).
References
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 (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:
- 0.06 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):
- 150
- Dose descriptor starting point:
- NOAEL
- Value:
- 10 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 8.7 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Corrected NOAEC (inhalation) for general population:
= 10 mg/kg bw/day x 1/1.15 m3/kg bw/day
= 8.7 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:
- 6
- Justification:
- Default factor for extrapolation from sub-acute to chronic is applied.
- 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:
- The recommended AF for other interspecies differences is applied.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively heterogeneous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The applied study is considered as reliable study with a Klimisch code 1. Therefore, no additional AF is applied.
- AF for remaining uncertainties:
- 1
- Justification:
- Even though the Point of departure for DNEL Derivation origins from a structural analogue substances, the read-across approach is considered unremarkable and DNEL derivation is considered conservative. Thus, there are no remaining uncertainties on this approach.
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)
Acute/short term exposure
- Hazard assessment conclusion:
- medium 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:
- 0.17 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):
- 600
- Dose descriptor starting point:
- NOAEL
- Value:
- 10 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:
Corrected NOAEL (dermal) for general population:
= 10 mg/kg bw/day x 10
= 100 mg/kg bw/day
- 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:
- Default factor for extrapolation from sub-acute to chronic is applied.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is applied.
- AF for other interspecies differences:
- 2.5
- Justification:
- The recommended AF for other interspecies differences is applied.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively heterogeneous group "general population" is applied
- AF for the quality of the whole database:
- 1
- Justification:
- The applied study is considered as reliable study with a Klimisch code 1. Therefore no additional AF is applied.
- AF for remaining uncertainties:
- 1
- Justification:
- Even though the Point of departure for DNEL Derivation origins from a structural analogue substances, the read-across approach is considered unremarkable and DNEL derivation is considered conservative. Thus, there are no remaining uncertainties on this approach.
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:
- 0.016 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):
- 600
- Dose descriptor starting point:
- NOAEL
- Value:
- 10 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No modification of PoD necessary.
- 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:
- Default factor for extrapolation from sub-acute to chronic is applied.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is applied.
- AF for other interspecies differences:
- 2.5
- Justification:
- The recommended AF for other interspecies differences is applied.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for the relatively heterogeneous group "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The applied study is considered as reliable study with a Klimisch code 1. Therefore no additional AF is applied.
- AF for remaining uncertainties:
- 1
- Justification:
- Even though the Point of departure for DNEL Derivation origins from a structural analogue substances, the read-across approach is considered unremarkable and DNEL derivation is considered conservative. Thus, there are no remaining uncertainties on this approach.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.05 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):
- 0.33
- DNEL extrapolated from long term DNEL
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
General Population
Inhalation
Long term, systemic DNEL – exposure by inhalation (general population)
Using a conservative approach, a DNEL for general population (long-term inhalation exposure) is calculated. This long-term DNEL is considered to ensure also an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected). No repeated dose inhalation toxicity study with the test item is available. Therefore, long-term inhalation DNEL was derived by route-to-route extrapolation from an oral repeated dose toxicity study. No repeated dose toxicity study with the test item is available. However, a sub-acute toxicity study with a read-across substance is available and considered suitable. For more details on read-across justification please refer to respective IUDLID Section. Based on an OECD TG 407 study with the read-across substance, daily oral administration to rats revealed signs of toxicity in the high and mid dose tested i. e. 30 and 90 mg/kg bw/d, respectively. The NOAEL for systemic toxicity was therefore considered to be 10 mg/kg bw/day. This NOAEL of systemic toxicity is applied as Point of Departure for DNEL derivation since it is considered to reflect worst case assumption.
Step 1: PoD: NOAEL = 10 mg/kg bw/day
Step 2: Modification of PoD:
Standard respiratory volume of the rat (sRVrat) for 24 hours: 1.15 m3/kg bw
Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 1/1 (no difference is expected, oral absorption is estimated to be 100 % (Ioannou 1984). According to ECHA Guidance – Chapter R8 (p25), the inhalation absorption is 100%: “if data on the starting route (oral) are available these should be used, but for the end route (inhalation), the worst case inhalation absorption should be assumed (i. e. factor 1)
Corrected NOAEC (inhalation) for general population:
= 10 mg/kg bw/day x 1/1.15 m3/kg bw/day
= 8.7 mg/m3
Step 3: Overall AF= 150
Dose
response relationship AF: 1
The dose response relationship is considered unremarkable, therefore no
additional factor is used.
Exposureduration
AF: 6
Default factor for extrapolation from sub-acute to chronic is applied.
Intraspecies
AF (General population): 10
The default value for the relatively heterogeneous group "general
population" is used.
Interspecies
AF, remaining differences: 2.5
The recommended AF for other interspecies differences is applied.
Allometric
scaling AF: 1
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).
Whole
database AF: 1
The applied study is considered as reliable study with a Klimisch code
1. Therefore no additional AF is applied.
AF for
remaining uncertainties: 1
Even though the Point of departure for DNEL Derivation origins from a
structural analogue substances, the read-across approach is considered
unremarkable and DNEL derivation is considered conservative. Thus, there
are no remaining uncertainties on this approach.
In conclusion, long term systemic inhalation DNEL, general population = 0.06 mg/m3
Acute, systemic DNEL- exposure via inhalation (general population)
There is no short-term or long-term toxicity study via inhalation route available for the test item. Due to its very low vapour pressure (< 1 Pa), high peak-inhalation exposure is not considered as relevant. The test item is unlikely to be available as a vapour to a large extent. Thus, the acute inhalation DNEL was not derived. Further, long-term DNELs are considered sufficient to ensure that acute effects do not occur. In addition, the test item is not classified as acutely toxic via inhalation or dermal route.
Long-term and short-term, local DNEL- exposure via inhalation (general population)
No data on respiratory irritation are available. The test item is classified for eye corrosion (cat. 1) according to Regulation (EC) No 1272/2008 (CLP). Therefore, a qualitative hazard assessment is applied.
Dermal
Long term, systemic DNEL- exposure via dermal route (general population)
No repeated dose dermal toxicity study with the test item is available. Therefore, long-term dermal DNEL was derived by route-to-route extrapolation.
The NOAEL of 10 mg/kg bw/day derived from a sub-acute toxicity study performed with a structural analogue substance was used as the Point of Departure.
Step 1: PoD: NOAEL= 10 mg/kg bw/day
Step
2: Modification
into a correct starting point:
Correction for difference between human and experimental exposure
conditions: 7 d rat, 24 h/7 d, 24h general population = 1
There are no relevant experimental data on repeated dermal exposure. A low dermal absorption value can be expected due to the physico- chemical properties of the test item. The oral absorption is estimated to 100% (Ioannou 1984), and the dermal absorption is estimated to 10% (Shah 1985) in rats. The correction factor is 100 / 10.
Corrected NOAEL (dermal) for general population:
= 10 mg/kg bw/day x 10
= 100 mg/kg bw/day
Step 3: Overall AF= 600
Dose-response
relationship AF: 1
The dose response relationship is considered unremarkable, therefore no
additional factor is used.
Exposureduration
AF: 6
Default factor for extrapolation from sub-acute to chronic is applied.
Interspecies
AF, allometric scaling (rat to human): 4
The default allometric scaling factor for the differences between rats
and humans is applied.
Interspecies
AF, remaining differences: 2.5
The recommended AF for other interspecies differences is applied.
Intraspecies
AF (general population): 10
The default value for the relatively heterogeneous group "general
population" is applied
Whole
database AF: 1
The applied study is considered as reliable study with a Klimisch code
1. Therefore no additional AF is applied.
AF
for remaining uncertainties: 1
Even though the Point of departure for DNEL Derivation origins from a
structural analogue substances, the read-across approach is considered
unremarkable and DNEL derivation is considered conservative. Thus, there
are no remaining uncertainties on this approach.
In conclusion, long term systemic dermal DNEL, general population = 0.17 mg/kg bw/day
Acute, systemic DNEL- dermal exposure (general population)
An acute dermal toxicity study is available for the test item. Based on the results the test item is not classified for acute dermal toxicity according to Regulation (EC) No 1272/2008 (CLP). Thus, the acute systemic dermal DNEL was not derived. Further, long-term DNELs are considered sufficient to ensure that acute effects do not occur.
Long term & acute, local DNEL- dermal exposure (general population)
The test substance is not classified for skin irritation or skin sensitization. Therefore, no DNEL on long-term or short-term local effects was derived.
Long term, systemic DNEL- exposure by oral route (general population)
An oral repeated dose toxicity study with the structural analogue substance is available. Here, daily oral administration of the test item to rats revealed signs of toxicity in the high and mid dose i. e. 30 and 90 mg/kg bw/d, respectively. The NOAEL for systemic toxicity was therefore considered to be 10 mg/kg bw/day. This NOAEL of systemic toxicity is applied as Point of Departure for DNEL derivation since it is considered to reflect worst case assumption.
Step 1: PoD: NOAEL = 10 mg/kg bw/day
Step 2: Overall AF= 600
Dose-response
relationship AF: 1
The dose response relationship is considered unremarkable, therefore no
additional factor is used.
Exposureduration
AF: 6
Default factor for extrapolation from sub-acute to chronic is applied.
Interspecies
AF, allometric scaling (rat to human): 4
The default allometric scaling factor for the differences between rats
and humans is applied.
Interspecies
AF, remaining differences: 2.5
The recommended AF for other interspecies differences is applied.
Intraspecies
AF (general population): 10
The default value for the relatively heterogeneous group "general
population" is used.
Whole
database AF: 1
The applied study is considered as reliable study with a Klimisch code
1. Therefore no additional AF is applied.
AF
for remaining uncertainties: 1
Even though the Point of departure for DNEL Derivation origins from a
structural analogue substances, the read-across approach is considered
unremarkable and DNEL derivation is considered conservative. Thus, there
are no remaining uncertainties on this approach.
In conclusion, long term systemic oral DNEL, general population= 0.016 mg/kg bw/day
Acute, systemic DNEL- exposure by oral route (general population)
Due to the acute oral toxicity observed with the test item (LD50 >50, <300 mg/kg bw), the substance is considered to be classified for acute oral toxicity Cat.3 under Regulation (EC) No. 1272/2008 (CLP). ECHA Guidance states that “[..],the acute DNEL can by default be set as 1-5 times the long-term DNEL”. Therefore, the DNEL for acute systemic oral, general population was extrapolated according to the ECHA Guidance by applying the AF of 0.33.
DNEL, long-term systemic oral (0.016 mg/kg bw/day)/ AF (0.33)
DNEL, short-term systemic oral = 0.05 mg/kg bw/day
Hazard to the eye-local effects (general population)
The test item is classified for eye damaging Cat 1 according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is applied and the substance is assigned to the moderate hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).
References
ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterization of dose [concentration]-response for human health. Version 2.1, November 2012
ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterization, Version 3.0, May 2016
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