Registration Dossier
Registration Dossier
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EC number: 269-044-8 | CAS number: 68186-64-1
- 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:
- 11.1 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 450 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 555.3 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Step 1: PoD: NOAEL = 450 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:
= 450 mg/kg bw/day x 0.5 x 1/0.38 m3/kg bw/day x (6.7 m3/10 m3) x 1.4
= 555.3 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 63 days for females and 29 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:
- DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.
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:
- 3.15 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Dose descriptor starting point:
- NOAEL
- Value:
- 450 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 630 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
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 450 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 = 450 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 identical dermal and oral absorption values even though a low dermal absorption value can be expected due to the physico- chemical properties of the test item.
Corrected NOAEL (dermal) for workers:
450 mg/kg bw/day x 1.4
= 630 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 63 days for females and 29 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 exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 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 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:
- DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.
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)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
Systemic DNEL short-term and long-term:
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 no signs of systemic toxicity up to the highest dose tested i. e. 450 mg/kg bw/d. The NOAEL for systemic toxicity, was therefore considered to be 450 mg/kg bw/day. NOAEL for fertility and developmental toxicity was determined to be 200 and 450 mg/kg bw/d, respectively based on the conditions of this study. The NOAEL of systemic toxicity is applied as Point of Departure for DNEL derivation since it is considered to reflect worst case assumption. Findings observed at the highest dose level were associated with local irritation of the test item at the site of first contact (GIT). Therefore, a NOAEL for local effects was determined to be 200 mg/kg bw/d which corresponds to a concentration of 40 mg/mL. Since the registered substance is classifieed for skin corrosion and eye damage a high hazard is assumed for local effects.
Step 1: PoD: NOAEL = 450 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:
= 450 mg/kg bw/day x 0.5 x 1/0.38 m3/kg bw/day x (6.7 m3/10 m3) x 1.4
= 555.3 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 63 days for females and 29 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.
AF
for remaining uncertainties: 1
DNEL Derivation is considered conservative, reflecting reasonable worst
case assumptions. Therefore, no further AF for remaining uncertainties
is applied.
In conclusion, long term systemic inhalation DNEL, workers = 11.1 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.
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 450 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 = 450 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 identical dermal and oral absorption values even though a low dermal absorption value can be expected due to the physico- chemical properties of the test item.
Corrected NOAEL (dermal) for workers:
= 450 mg/kg bw/day x 1.4
= 630 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 63 days for
females and 29 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 = 3.15 mg/kg bw/day
Acute, systemic DNEL- dermal exposure (workers)
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. Moreover, the test item is classified as skin corrosive cat 1B according to CLP and protection measures to avoid local effects are considered sufficient to protect against systemic effects as well.
Local DNEL for inhalation and dermal route, short-term and long-term:
The test item is classified for skin and eye corrosion according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted. Appropriate qualitative risk managements measures should be implemented to avoid exposure. The substance is assigned to the medium hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.95 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:
- 450 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 195.6 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Step 1: PoD: NOAEL = 450 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:
= 450 mg/kg bw/day x 0.5 x 1/1.15 m3/kg bw/day
= 195.6 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 63 days for females and 29 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 heterogenous group "consumer" 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:
- DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.
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:
- 1.125 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:
- 450 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 450 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
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 450 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 = 450 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- 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 63 days for females and 29 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 exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 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 intraspecies differences:
- 10
- Justification:
- The default value for the heterogenous group "consumer" 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:
- DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.
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)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.125 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:
- 450 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 450 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No modification of PoD needed.
- 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 63 days for females and 29 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 exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 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 intraspecies differences:
- 10
- Justification:
- The default value for the heterogenous group "consumer" 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:
- DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
Systemic DNEL short-term and long-term:
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 (consumer)
Using a conservative approach, a consumer DNEL (long-term inhalation exposure) is calculated. This consumer 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 no signs of systemic toxicity up to the highest dose tested i. e. 450 mg/kg bw/d. The NOAEL for systemic toxicity, was therefore considered to be 450 mg/kg bw/day. NOAEL for fertility and developmental toxicity was determined to be 200 and 450 mg/kg bw/d, respectively based on the conditions of this study. The NOAEL of systemic toxicity is applied as Point of Departure for DNEL derivation since it is considered to reflect worst case assumption. Findings observed at the highest dose level were associated with local irritation of the test item at the site of first contact (GIT). Therefore, a NOAEL for local effects was determined to be 200 mg/kg bw/d which corresponds to a concentration of 40 mg/mL. Since the registered substance is classifieed for skin corrosion and eye damage a high hazard is assumed for local effects.
Step 1: PoD: NOAEL = 450 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:
= 450 mg/kg bw/day x 0.5 x 1/1.15 m3/kg bw/day
= 195.6 mg/m3
Step 3: Overall AF= 100
Intraspecies AF (consumer): 5
The default value for the heterogenous group "consumer" 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 63 days for females and 29 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.
AF
for remaining uncertainties: 1
DNEL Derivation is considered conservative, reflecting reasonable worst
case assumptions. Therefore, no further AF for remaining uncertainties
is applied.
In conclusion,long term systemic inhalation DNEL, workers = 5.55 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.
Dermal
Long term, systemic DNEL- exposure via dermal route (consumer)
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 450 mg/kg bw/day derived from an OECD TG 422 study performed with the test item was used as the Point of Departure.
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 450 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 = 450 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
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 (consumer): 10
The default value for the heterogenous group "consumer" 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 63 days for
females and 29 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, consumers = 1.125 mg/kg bw/day
Acute, systemic DNEL- dermal exposure (consumer)
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. Moreover, the test item is classified as skin corrosive cat 1B according to CLP and protection measures to avoid local effects are considered sufficient to protect against systemic effects as well.
Local DNEL for inhalation and dermal route, short-term and long-term:
The test item is classified for skin and eye corrosion according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted. Appropriate qualitative risk managements measures should be implemented to avoid exposure. The substance is assigned to the medium hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).
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