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EC number: 405-520-5 | CAS number: 95235-30-6 D-8; DD-8
- 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:
- 2.47 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 25
- Dose descriptor starting point:
- NOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 61.7 mg/m³
- Explanation for the modification of the dose descriptor starting point:
For more information please refer to "Additional information".
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (endpoint).
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
- AF for other interspecies differences:
- 2.5
- Justification:
- The default value for interspecies differences is used.
- 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 repeated dose 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
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.7 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Dose descriptor starting point:
- NOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 70 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
see "Additional Information"
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (endpoint).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is used.
- AF for other interspecies differences:
- 2.5
- Justification:
- The default value for interspecies differences is used.
- 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 repeated dose 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
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- sensitisation (skin)
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).
1. Inhalation
Long term, systemic DNEL – exposure via inhalation (workers)
Using a conservative approach, a worker DNEL (long-term inhalation exposure) is derived. This worker long-term DNEL is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected).
No studies have been undertaken by the inhalatory route to characterize the dose-response relationship for systemic effects. Therefore, it will be necessary to obtain a long-term inhalatory DNEL by route-to route extrapolation. Human data are not available.
Step 1: PoD and most sensitive endpoint: repeated dose toxicity (oral)
A 90-day oral toxicity study according OECD TG 408 was performed with D-8 in male and female CRL:(WI) BR Wistar rats.D-8 caused no mortality at up to and including 50 mg/kg bw/day in CRL:(WI)BR rats. There were no test-item related clinical signs following administration of D-8 by oral gavage, daily for 90 days. The behaviour and the general condition of the test animals were normal during the study. There was no treatment-related effect on motor activity or in the functional observation battery tests across groups of treated male or female animals and no findings indicative for neurotoxicity were observed. No effects were noted during the ophthalmoscopy evaluation performed on completion of treatment. There were no toxicologically significant changes in body weight, body weight gain or animal feed intake between the control and test item treated groups. Differences were noted in the test item treated groups compared to controls in a few clinical pathology parameters evaluated prior to necropsy (haematology, coagulation, clinical chemistry and/or urinalysis). Although occasionally these changes were statistically significant, no dose related response was observed, the differences were minor and/or there was no consistent reaction in the male and female groups. These changes were not considered toxicologically significant, nor indicated a test item related etiology. There were no macroscopic or microscopic adverse findings, no statistically or toxicologically significant changes in organ weight values or any pathology changes that could be ascribed to test item administration. In conclusion, D-8 administered daily by oral gavage for 90 days in Wistar rats did not lead to any toxicologically adverse effects at dose levels of 5, 10 or 50 mg/kg bw/day. Under the conditions of this study, the no observed effect level (NOEL) for D-8 is 50 mg/kg bw/day. This systemic NOEL of 50 mg/kg bw/day was used for risk assessment purposes (= used as NOAEL).
Step 2: Modification into a correct starting point:
Relevant dose descriptor (NOAEL): 50 mg/kg bw/day
Oral absorption of the rat / inhalation absorption of humans (ABS oral-rat / ABS inh-human): 50/100
Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/day
Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³
Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³
Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker=1.4
Corrected NOAEC (inhalation) for workers:
= 50 mg/kg bw/day× 0.5 × (1 / 0.38 m³/kg bw/day) × (6.7 m³/10 m³) × 1.4
= 61.7 mg/m³
Step 3: Overall AF= 25
Interspecies: According to Table R.8.4 in chapter R.8 of the ECHA Guidance Document no AF is needed when route (oral)-to route (inhalation) is applied.
Interspecies AF, remaining differences: no evidence for species differences in the general mode of Action
Intraspecies AF (worker): 5
Interspecies AF, remaining differences: 2.5
Dose response relationship AF: 1
Exposure duration AF (subchronic to chronic): 2
Whole database AF: 1
The repeated dose oral toxicity study was conducted according to modern 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, workers = 2.47 mg/m3
Acute, systemic DNEL- exposure via inhalation (workers)
According to ECHA Guidance on information requirements and chemical safety, Chapter R.8, Appendix R. 8-8, "a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. The substance has low acute inhalation toxicity. Therefore, a DNEL is not required.
Long term & acute, local DNEL- exposure via inhalation (workers)
A DNEL acute - local effect is not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitization according to Regulation (EC) No 1272/2008.
2. Dermal
No studies have been undertaken by the dermal route to characterize the dose-response relationship for systemic effects therefore it will be necessary to obtain a long-term dermal DNEL by route-to-route extrapolation.
Long term, systemic DNEL- exposure via dermal route (workers)
Step 1: PoD and most sensitive endpoint: repeated dose toxicity (oral)
A 90-day oral toxicity study according OECD TG 408 was performed with D-8 in male and female CRL:(WI) BR Wistar rats.
Step 2: Modification into a correct starting point:
Relevant dose descriptor (NOAEL): 50 mg/kg bw/day
Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker = 1.4
Oral absorption of the rat/ dermal absorption of humans (ABS oral-rat / ABS derm-human): 100%/100 % (default)
Corrected NOAEL (dermal) for workers:
= 50 mg/kg bw/day x 1 x 1.4
= 70 mg/kg bw/day
Step 3: Overall AF= 100
Interspecies AF, allometric scaling (rat to human): 4
Interspecies AF, remaining differences: 2.5
Interspecies AF, remaining differences: Interspecies differences are fully covered by the allometric
scaling
Intraspecies AF (worker): 5
Dose-response relationship AF: 1
Exposure duration AF (subchromic to chronic): 2
In conclusion, long term systemic dermal DNEL, workers = 0.7 mg/kg bw/day
Acute, systemic DNEL- dermal exposure (workers)
According to ECHA Guidance on information requirements and chemical safety, Chapter R.8, Appendix R. 8-8, „a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. The substance has low acute dermal toxicity with the LD50 of >2000 mg/kg. Therefore, the DNEL is not required.
Long term & acute, local DNEL- dermal exposure (workers)
A DNEL long term/acute - local effects is not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitization according to Regulation (EC) No 1272/2008.
Hazard to the eye-local effects (worker)
The substance is not classified for eye irritation under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.
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:
- 0.37 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:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 18.5 mg/m³
- Explanation for the modification of the dose descriptor starting point:
see "Additional Information"
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (endpoint).
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
- AF for other interspecies differences:
- 2.5
- Justification:
- The default value for interspecies differences is used.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The repeated dose 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
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.25 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:
- 50 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
see "Additional Information"
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (endpoint).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is used.
- AF for other interspecies differences:
- 2.5
- Justification:
- The default value for interspecies differences is used.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The repeated dose 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
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- sensitisation (skin)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.25 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:
- 50 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:
- 2
- Justification:
- The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (endpoint).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- The default allometric scaling factor for the differences between rats and humans is used.
- AF for other interspecies differences:
- 2.5
- Justification:
- The default value for interspecies differences is used.
- AF for intraspecies differences:
- 10
- Justification:
- The default value for "general population" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The repeated dose 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
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).
1. Inhalation
Long term, systemic DNEL – exposure by inhalation (general population)
Using a conservative approach, a DNEL (long-term inhalation exposure) is derived. This long-term DNEL for the general population is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected).
Step 1: PoD and most sensitive endpoint: repeated dose toxicity (oral)
A 90-day oral toxicity study according OECD TG 408 was performed with D-8 in male and female CRL:(WI) BR Wistar rats. D-8 caused no mortality at up to and including 50 mg/kg bw/day in CRL:(WI)BR rats. There were no test-item related clinical signs following administration of D-8 by oral gavage, daily for 90 days. The behaviour and the general condition of the test animals were normal during the study. There was no treatment-related effect on motor activity or in the functional observation battery tests across groups of treated male or female animals and no findings indicative for neurotoxicity were observed. No effects were noted during the ophthalmoscopy evaluation performed on completion of treatment. There were no toxicologically significant changes in body weight, body weight gain or animal feed intake between the control and test item treated groups. Differences were noted in the test item treated groups compared to controls in a few clinical pathology parameters evaluated prior to necropsy (haematology, coagulation, clinical chemistry and/or urinalysis). Although occasionally these changes were statistically significant, no dose related response was observed, the differences were minor and/or there was no consistent reaction in the male and female groups. These changes were not considered toxicologically significant, nor indicated a test item related etiology. There were no macroscopic or microscopic adverse findings, no statistically or toxicologically significant changes in organ weight values or any pathology changes that could be ascribed to test item administration. In conclusion, D-8 administered daily by oral gavage for 90 days in Wistar rats did not lead to any toxicologically adverse effects at dose levels of 5, 10 or 50 mg/kg bw/day. Under the conditions of this study, the no observed effect level (NOEL) for D-8 is 50 mg/kg bw/day. This systemic NOEL of 50 mg/kg bw/day was used for risk assessment purposes (= used as NOAEL).
Step 2: Modification into a correct starting point:
Relevant dose descriptor (NOAEL): 50 mg/kg bw/day
Standard respiratory volume of the rat (sRVrat) for 24 hours: 1.35 m³/kg bw
Oral absorption of the rat / inhalation absorption of humans (ABS oral-rat / ABS inh-human): 50/100 (default)
Differences experimental/human exposure conditions: 7d/24h rat vs.7d/24h (general population)
Corrected NOAEC (inhalation) for general population:
= 50 mg/kg bw/day× 0.5 × (1 / 1.35 m³/kg bw/24h) x 1
= 18.5 mg/m³
Step 3: Overall AF= 50
Interspecies: According to Table R.8.4 in chapter R.8 of the ECHA Guidance Document no AF is needed when route (oral)-to route (inhalation) is applied.
Interspecies AF, remaining differences: no evidence for species differences in the general mode of
Action
Intraspecies AF (general population): 10
Interspecies AF, remaining differences: 2.5
Dose response relationship AF: 1
Exposure duration AF (subchronic to chronic): 2
In conclusion, long term systemic inhalation DNEL, general population= 0.37 mg/m3
Acute, systemic DNEL- exposure via inhalation (general population)
According to ECHA Guidance on information requirements and chemical safety, Chapter R.8, Appendix R. 8-8, " a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. The substance has low acute inhalation toxicity with the LC50 >5000 mg/m3. Therefore, a DNEL is not required.
Long term & acute, local DNEL- exposure via inhalation (general population)
A DNEL acute/long term - local effect is not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitisation according to Regulation (EC) No 1272/2008.
2. Dermal
Long term, systemic DNEL- exposure via dermal route (general population)
Step 1: PoD and most sensitive endpoint: repeated dose toxicity (oral)
A 90-day oral toxicity study according OECD TG 408 was performed with D-8 in male and female CRL:(WI) BR Wistar rats.
Step 2: Modification into a correct starting point:
Relevant dose descriptor (NOAEL): 50 mg/kg bw/day
Oral absorption of the rat / dermal absorption of humans (ABS oral-rat / ABS derm-human): 100/100 (default)
Correction for difference between human and experimental exposure conditions: 7d animal/7d general population
Corrected NOAEL (dermal) for general population:
= 50 mg/kg bw/day
Step 3: Overall AF= 200
Interspecies AF, allometric scaling (rat to human): 4
Interspecies AF, remaining differences: 2.5
Interspecies AF, remaining differences: Interspecies differences are fully covered by the allometric scaling
Intraspecies AF (general population): 10
Dose-response relationship AF: 1
Exposure duration AF (subchronic to chronic): 2
In conclusion, long term systemic dermal DNEL, general population = 0.25 mg/kg bw/day
Acute, systemic DNEL- dermal exposure (general population)
According to ECHA Guidance on information requirements and chemical safety, Chapter R.8, Appendix R. 8-8, „a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. The substance has low acute dermal toxicity with the LD50 of >2000 mg/kg bw. Therefore, the DNEL is not required.
Long term & acute, local DNEL- dermal exposure (general population)
A DNEL acute/long term - local effects is not established because the substance is not classified dangerous for skin/eye irritation/corrosion and skin sensitisation according to Regulation (EC) No 1272/2008.
Long term, systemic DNEL – exposure by oral route (general population)
Step 1: PoD and most sensitive endpoint: repeated dose toxicity (oral)
A 90-day oral toxicity study according OECD TG 408 was performed with D-8 in male and female CRL:(WI) BR Wistar rats.
Step 2: Relevant dose descriptor (NOAEL): 50 mg/kg bw/day
Step 3: Overall AF= 200
Interspecies AF, allometric scaling (rat to human): 4
Interspecies AF, remaining differences: 2.5
Interspecies AF, remaining differences: Interspecies differences are fully covered by the allometric scaling
Intraspecies AF (general population): 10
Dose-response relationship AF: 1
Exposure duration AF (subchronic to chronic): 2
In conclusion, long term systemic oral DNEL, general population= 0.25 mg/kg bw/day
Acute, systemic DNEL- exposure by oral route (general population)
According to ECHA Guidance on information requirements and chemical safety, Chapter R.8, Appendix R. 8-8, "a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. The substance has low acute oral toxicity with the LD50 >5000 mg/kg bw. Therefore, a DNEL is not required.
Hazard to the eye-local effects (general population)
The substance is not classified for eye irritation under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) No 2019/521.
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
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.