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EC number: 805-722-7 | CAS number: 1064082-81-0
- 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:
- 7.4 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:
- 300 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 370.2 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Corrected NOAEC (inhalation) for workers:
= 300 mg/kg bw/day x 0.5 x 1/0.38 m3/kg bw/day x (6.7 m3/10 m3) x 1.4
= 370.2 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:
- 4
- Justification:
- The exposure duration of the OECD TG 422 study performed with the test item was up to 71 days for females and 51 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.
- 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 OECD TG 422 toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- 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
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.2 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:
- 300 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 840 mg/kg bw/day
- 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.
There are no relevant experimental data on repeated dermal exposure. A conservative approach is used assuming dermal absorption factor of 0.5 compared to oral absorption. Even though very low dermal absorption value can be expected due to the physico- chemical properties of the test item.
Corrected NOAEL (dermal) for workers:
= 300 mg/kg bw/day x 7/5 * 2
= 840 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:
- 4
- Justification:
- The exposure duration of the OECD TG 422 study was up to 71 days for females and 51 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.
- 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 OECD TG 422 toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- 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:
- high hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
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:
Based on an OECD TG 422 study with the test item, daily oral administration to Wistar rats revealed signs of toxicity in the highest dose tested i. e. 1000 mg/kg bw/d. The NOAEL for systemic toxicity, was therefore considered to be 300 mg/kg bw/day. NOAEL for fertility and developmental toxicity was determined to be 300 mg/kg bw/d, as well, under the conditions of this study. Therefore, the NOAEL of 300 mg/kg bw/d is used as Point of Departure for DNEL derivation.
Step 1: PoD: NOAEL = 300 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): 1/2 (default)
Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker
Corrected NOAEC (inhalation) for workers:
= 300 mg/kg bw/day x 0.5 x 1/0.38 m3/kg bw/day x (6.7 m3/10 m3) x 1.4
= 370.2 mg/m3
Step 3: Overall AF= 50
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).
Dose
response relationship AF: 1
The dose response relationship is considered unremarkable, therefore no
additional factor is used.
Exposure
duration AF: 4
The exposure duration of the OECD TG 422 study performed with the test
item was up to 71 days for females and 51 days for males. In comparison
to a subacute 28-day study the OECD TG 422 study provides additional
information on fertility and developmental toxicity, which justifies the
assessment factor of 4.
Whole
database AF: 1
The
OECD TG 422 toxicity study was conducted according to regulatory
standards and was adequately reported. On this basis the quality of the
database is not considered to contribute uncertainty and it is therefore
not necessary to apply an additional factor.
Remaining
uncertainties AF: 1
The
approach used for DNEL derivation is conservative. No further assessment
factors are required.
In conclusion,long term systemic inhalation DNEL, workers = 7.4 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 not classified for skin or eye irritation according to Regulation (EC) No 1272/2008 (CLP). Therefore, it is not considered to pose a hazard for local effects on the mucous membranes of respiratory tract when inhaled. Further, the test item is not expected to be available as a vapour due to its very low vapour pressure. Thus, the inhalation route is not considered relevant for humans
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 300 mg/kg bw/day derived from an OECD TG 422 study performed with the test item was applied as the Point of Departure.
Step 1:PoD: NOAEL = 300 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 conservative approach is used assuming dermal absorption factor of 0.5 compared to oral absorption. Even though very low dermal absorption value can be expected due to the physico- chemical properties of the test item.
Corrected NOAEL (dermal) for workers:
= 300 mg/kg bw/day x 7/5 * 2
= 840 mg/kg bw/day
Step 3:Overall AF= 200
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
Dose-response relationship AF: 1
The dose response relationship is considered unremarkable, therefore no additional factor is used.
Exposureduration
AF: 4
The exposure duration of the OECD TG 422 study was up to 71 days for
females and 51 days for males. In comparison to a subacute 28-day study
the OECD TG 422 study provides additional information on fertility and
developmental toxicity, which justifies the assessment factor of 4.
In conclusion, long term systemic dermal DNEL, workers = 4.2 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 classified as skin sensitizer according to CLP. Therefore, appropriate qualitative risk managements measures should be implemented to avoid exposure. Thus, a qualitative risk assessment is applied and the substance is assigned to the high hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).
Hazard to the eye-local effects (worker)
The test item is not classified for eye irritation according to Regulation (EC) No 1272/2008 (CLP).
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:
- 1.3 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):
- 100
- Dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 130.44 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Corrected NOAEC (inhalation) for general population:
= 300 mg/kg bw/day x 0.5 x 1/1.15 m3/kg bw/day
= 130.44 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:
- 4
- Justification:
- The exposure duration of the OECD TG 422 study was up to 71 days for females and 51 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.
- 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 OECD TG 422 toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- 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
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.5 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):
- 400
- Dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 600 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Correction for difference between human and experimental exposure conditions and correction for dermal absorption as 50 % of oral absorption: 7 d rat, 24 h/7 d, 24h general population = 1 * 2.
- 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:
- 4
- Justification:
- The exposure duration of the OECD TG 422 study was up to 71 days for females and 51 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.
- 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 OECD TG 422 toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- 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:
- high hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.75 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):
- 400
- Dose descriptor starting point:
- NOAEL
- Value:
- 300 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:
- 4
- Justification:
- The exposure duration of the OECD TG 422 study performed with the test item was up to 71 days for females and 51 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.
- 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 OECD TG 422 toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - 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:
Based on an OECD TG 422 study with the test item, daily oral administration to Wistar rats revealed signs of toxicity in the highest dose tested i. e. 1000 mg/kg bw/d. The NOAEL for systemic toxicity, was therefore considered to be 300 mg/kg bw/day. NOAEL for fertility and developmental toxicity was determined to be 300, as well, under the conditions of this study. This NOAEL is used as Point of Departure for DNEL derivation.
Step 1:PoD: NOAEL = 300 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): 1/2 (default)
Corrected NOAEC (inhalation) for general population:
= 300 mg/kg bw/day x 0.5 x 1/1.15 m3/kg bw/day
= 130.44 mg/m3
Step 3: Overall AF= 100
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).
Dose
response relationship AF: 1
The dose response relationship is considered unremarkable, therefore no
additional factor is used.
Exposure
duration AF: 4
The exposure duration of the OECD TG 422 study was up to 71 days for
females and 51 days for males. In comparison to a subacute 28-day study
the OECD TG 422 study provides additional information on fertility and
developmental toxicity, which justifies the assessment factor of 4.
Whole
database AF: 1
The
OECD TG 422 toxicity study was conducted according to regulatory
standards and was adequately reported. On this basis the quality of the
database is not considered to contribute uncertainty and it is therefore
not necessary to apply an additional factor.
In conclusion, long term systemic inhalation DNEL, general population = 1.3 mg/m3
Acute, systemic DNEL- exposure via inhalation (general population)
The test material is not classified and labelled for acute systemic toxicity, according to Regulation (EC) No 1272/2008 (CLP). 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.
The test item is not classified for acute systemic oral or dermal toxicity according to CLP.
Long-term and short-term, local DNEL- exposure via inhalation (general population)
No data on respiratory irritation are available. The test item is not classified for eye irritation according to Regulation (EC) No 1272/2008 (CLP). Therefore, it is not considered to pose a hazard for local effects on the mucous membranes of respiratory tract when inhaled. Further, the test item is not expected to be available as a vapour due to its very low vapour pressure. Thus, the inhalation route is not considered relevant for humans.
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 300 mg/kg bw/day derived from an OECD TG 422 study performed with the test item was used as the Point of Departure.
Step 1: PoD: NOAEL= 300 mg/kg bw/day
Step
2: Modification
into a correct starting point:
Correction for difference between human and experimental exposure
conditions and correction for dermal to oral absorption (1:2): 7 d rat,
24 h/7 d, 24h general population = 1*2
Step 3: Overall AF= 400
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
Dose-response
relationship AF: 1
The dose response relationship is considered unremarkable, therefore no
additional factor is used.
Exposure
duration AF: 4
The exposure duration of the OECD TG 422 study was up to 71 days for
females and 51 days for males. In comparison to a subacute 28-day study
the OECD TG 422 study provides additional information on fertility and
developmental toxicity, which justifies the assessment factor of 4.
In conclusion, long term systemic dermal DNEL, general population = 1.5 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 item is classified as a skin sensitizer, cat. 1A according to Regulation (EC) No 1272/2008 (CLP). Therefore, appropriate qualitative risk managements measures should be implemented to avoid exposure. Thus, a qualitative risk assessment is applied and the substance is assigned to the high hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).
Long term, systemic DNEL- exposure by oral route (general population)
An oral repeated dose toxicity study with the test item is available. Here, daily oral administration of the test item to Wistar rats revealed signs of toxicity in the highest dose tested i. e. 1000 mg/kg bw/d. The NOAEL for systemic toxicity was therefore considered to be 300 mg/kg bw/day. NOAEL for fertility and developmental toxicity was determined to be 300 mg/kg bw/d, as well, under the conditions of this study. This NOAEL is applied as Point of Departure for DNEL derivation.
Step 1: PoD: NOAEL = 300 mg/kg bw/day
Step 2: Overall AF= 400
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.
Dose-response
relationship AF: 1
The dose response relationship is considered unremarkable, therefore no
additional factor is used.
Exposure
duration AF: 4
The exposure duration of the OECD TG 422 study performed with the test
item was up to 71 days for females and 51 days for males. In comparison
to a subacute 28-day study the OECD TG 422 study provides additional
information on fertility and developmental toxicity, which justifies the
assessment factor of 4.
Quality
of whole database AF:
1
The OECD TG 422 toxicity study was conducted according to regulatory
standards and was adequately reported. On this basis the quality of the
database is not considered to contribute uncertainty and it is therefore
not necessary to apply an additional factor.
Remaining
uncertainties AF: 1
The approach used for DNEL derivation is conservative. No further
assessment factors are required.
In conclusion, long term systemic oral DNEL, general population= 0.75 mg/kg bw/day
Acute, systemic DNEL- exposure by oral route (general population)
An acute oral toxicity study is available for the test item. Based on the results the test item is not classified for acute oral toxicity according to Regulation (EC) No 1272/2008 (CLP). Thus, the acute systemic oral DNEL was not derived. Further, long-term DNELs are considered sufficient to ensure that acute effects do not occur.
Hazard to the eye-local effects (general population)
The test item is not classified for eye irritation according to Regulation (EC) No 1272/2008 (CLP).
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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