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EC number: 406-040-9 | CAS number: 125643-61-0
- 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:
- 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):
- 50
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 151.1 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No data by inhalation is available, therefore, a route to route extrapolation was performed
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:
- 8.6 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):
- 17.5
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No data by the dermal route is available, therefore, a route to route extrapolation was performed
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Identification of relevant dose descriptor
The most relevant study for hazard assessment was considered to be the one-generation study in mice. The subacute oral toxicity study in rats was not considered adequate because of the rat-specific effects on the liver-thyroid axis (for more details see also chapter 7.5). Mice proved to be much less sensitive and showed adaptive effects on liver with a NOAEL of 150 mg/kg body weight for exposure for 12-18 weeks. Both liver and thyroid, the target organs identified in the rat study, were investigated in the one-generation study, therefore adequate information for assessment is provided. Consequently, the NOAEL of 150 mg/kg body weight obtained in the one-generation study was used as point of departure for DNEL calculations. This is in line with the results obtained with the structurally related compound CAS 2082-79-3. Here, chronic treatment resulted in increases in liver and thyroid weights in rats but not in mice, with NOAELs of 64 and 54 mg/kg body weight, respectively. These studies do not only confirm the rat specific mode of action of this substance class, they also confirm the level of toxicity with NOAELs in the same range, taking the longer exposure period into account. The NOAEL of 150 mg/kg obtained in the 1-gen study in mice is therefore considered adequate for hazard assessment.
Calculation of DNELs
Systemic, long-term, dermal:
DNEL = NOAEL (oral) / Sum of assessment factors applicable
The dermal route is typically covered by oral route information in the absence of data for this administration route. Based on the available dermal absorption data, only minimal amounts of test substance penetrate the skin (4.42 % after 6 h dermal exposure). For further risk assessment, an additional factor of 0.1 is applied. The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen:Intraspecies differences (worker): 5
Interspecies variations: 2.5
Allometric scaling (mouse to human): 7
Exposure duration: 2 (12 -18 weeks)
Oral to dermal route extrapolation factor: 0.1
Dose-response factor: 1
Overall, an assessment factor of 17.5 was employed for the dermal route.
DNEL= 150 mg/kg body weight / 17.5 = 8.57 mg/kg body weight.
Systemic, long-term, inhalative
According to ECHA guidelines, a route to route extrapolation is performed if no information by inhalation is available. Following ECHA guidance document Chapter R.8 the NOAEL (oral) has to be adjusted for differences in respiratory volume for test animals (mice) and humans and corrected for activity driven differences of respiratory volumes in workers compared to workers in rest, resulting in a corrected starting point of 151.1 mg/m3. The DNEL is calculated as follows:
NOAEL (corrected) / Sum of assessment factors applicable.
The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen:
Intraspecies differences (worker): 5
Interspecies variations: 2.5
Exposure duration: 2 (12 -18 weeks)
Default factor to account for differences in oral and inhalative absorption properties: 2
Dose-response factor: 1
The overall assessment factor employed for the inhalation route is therefore 50.
DNEL = 151.1 mg/m3/ 50 = 3.0 mg/m3
Systemic, short-term, dermal and inhalative
According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified. Therefore, because the substance is not classified for acute toxicity according to Directive 67/548/EEC and Regulation 1272/2008/EC, no systemic DNELs for short-term exposures were calculated.
Local, long-term and short-term, inhalative and dermal
Based on the available key toxicological information, the test item is not subject to classification for skin and eye irritation and skin sensitization (according to 67/548/EEC and EC/1272/2008). Accordingly, no DNELs for local effects following acute/short-term or long-term exposure are derived. This is in line with the ECHA guidance document (Chapter R.8).
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.74 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
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 74.4 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No data by inhalation is available, therefore, a route to route extrapolation was performed
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:
- 4.3 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):
- 35
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No data by the dermal route is available, therefore, a route to route extrapolation was performed
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.43 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):
- 350
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
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
Identification of relevant dose descriptor
The NOAEL of 150 mg/kg obtained in the 1-generation study was used as point of departure for DNEL calculations (see above).
Calculation of DNELs
Systemic, long-term, dermal:
DNEL = NOAEL (oral) / Sum of assessment factors applicable
The dermal route is typically covered by oral route information in the absence of data for this administration route. Based on the available dermal absorption data, only minimal amounts of test substance penetrate the skin (4.42 % after 6 h dermal exposure). For further risk assessment, an additional factor of 0.1 for dermal absorption is applied. The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen:Intraspecies differences (general population): 10
Interspecies variations: 2.5
Allometric scaling (mouse to human): 7
Exposure duration: 2 (12-18 weeks)
Oral to dermal route extrapolation factor: 0.1
Dose-response factor: 1
Overall, an assessment factor of 35 was employed for the dermal route.
DNEL= 150 mg/kg body weight / 35 = 4.3 mg/kg body weight.
Systemic, long-term, inhalative
Because no inhalation study is available, a route to route extrapolation was performed. The NOAEL (oral) has to be adjusted into a NOAEL (corrected) based on differences in respiratory volumes for test animals (mice) and humans in accordance to guidance on information requirements and chemical safety assessment, Chapter R.8, ECHA, May 2008. The corrected starting point here is 74.4 mg/m3 per day. The DNEL is calculated as follows:
NOAEL (corrected) / Sum of assessment factors applicable.
The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen:
Intraspecies differences (general population): 10
Interspecies variations: 2.5
Exposure duration: 2 (12-18 weeks)
Dose-response factor: 1
Default factor to account for differences in oral and inhalative absorption properties: 2
The overall assessment factor employed for the inhalation route is therefore 100.
DNEL = 74.4 mg/m3/ 100 = 0.74 mg/m3
Systemic, long-term, oral:
The NOAEL of 150 mg/kg body weight observed in the 1-gen study in rats was used as starting point for DNEL derivation. The following assessment factors according to "ECHA guidance on information requirements and chemical safety assessment, Chapter R8" were chosen:
Intraspecies differences (general population): 10
Interspecies variations: 2.5
Allometric scaling (mouse to human): 7
Exposure duration: 2 (12-18 weeks)
Dose-response factor: 1
Overall, an assessment factor of 350 was employed for the dermal route.
DNEL= 150 mg/kg body weight / 350 = 0.43 mg/kg body weight.
Systemic, short-term, dermal and inhalative
According to the ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose[concentration]-response for human health", a DNEL for acute systemic toxicity should only be derived if an acute systemic toxicity hazard leading to classification is identified. Therefore, because the substance is not classified for acute toxicity according to Directive 67/548/EEC and Regulation 1272/2008/EC, no systemic DNELs for short-term exposures were calculated.
Local, long-term and short-term, inhalative and dermal
Based on the available key toxicological information, the test item is not subject to classification for skin and eye irritation and skin sensitization (according to 67/548/EEC and EC/1272/2008). Accordingly, no DNELs for local effects following acute/short-term or long-term exposure are derived. This is in line with the ECHA guidance document (Chapter R.8).
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