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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
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EC number: 821-762-8 | CAS number: 4563-56-8
- 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:
- 4.11 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Dose descriptor starting point:
- NOAEL
- Value:
- 125 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 308.55 mg/m³
- Explanation for the modification of the dose descriptor starting point:
DNEL calculation was based on the results of a 28-day repeat dose toxicity study with the source substance in rats, resulting in a NOAEL (oral) = 125 mg/kg bw/day
Corrected Descriptor: The inhalation route was extrapolated by oral route information in the absence of data for this administration route. The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure of workers, see Table R. 8-2 in Section R.8.4.2, REACH guidance, chapter R8). For workers the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor derives from the inhalative volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity).
Corrected starting point for the inhalative route for workers:
= NOAEL(oral) * (1/0.38 m³/kg bw/day) * (ABSoral-rat/ABSinh-human) * 6.7 m³ (8h) /10 m³ (8h) * (days of exposure per week in rats / days of exposure per week worker)
= 125 mg/kg bw/day * (1/0.38 m³/kg) * 6.7/10 m³ * 7/5 = 308.55 m³/kg
- AF for dose response relationship:
- 1
- Justification:
- The dose descriptor starting point is based on a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- The DNEL is based on a subacute study.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for the inhalation route
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value
- AF for intraspecies differences:
- 5
- Justification:
- Default value for workers according to ECHA REACh Guidance
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on a high quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 5.83 mg/kg bw/day
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 300
- Dose descriptor starting point:
- NOAEL
- Value:
- 125 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 750 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
DNEL calculation was based on the results of a 28-day repeat dose toxicity study with the source substance in rats, resulting in a NOAEL (oral) = 125 mg/kg bw/day
Assume ABS rat – oral is 100%. The dermal route was extrapolated from oral route information in the absence of data for this administration route. Basic physicochemical properties of the source substance were taken into consideration when estimating dermal absorption, (e.g. low water solubility, molecular weight and log Kow), and < 10% dermal absorption was predicted (please refer to toxicokinetics, metabolism and distribution). As the physicochemical properties of the target substance are similar to that of the source substance this assumption is also valid for the target substance.
Corrected starting point for the dermal route for workers:
Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) * (days of exposure per week in rats / days of exposure per week worker)
= 125 mg/kg bw/day * (1/0.1) * 7/5 = 1750 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- The dose descriptor starting point is based on a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- The DNEL is based on a subacute study.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default AF for rats
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value
- AF for intraspecies differences:
- 5
- Justification:
- Default value for workers
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on a high quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
1. Relevant Toxicology Data, exposure pattern and route
The oral repeated dose toxicity of the source substance was evaluated in rats at levels up to 500 mg/kg/day according to OECD 407. Treatment-related deaths occurred at 500 mg/kg/day in both sexes. All of these animals had reddened adrenal and pituitary glands and yellow contents in the stomach. Microscopic examinations found edema and inflammation of the stomach in all 500 mg/kg/day group females and thickened mucosa in the nonglandular portion of the stomach in one male. In the 250 mg/kg/day group, one male also had edema and inflammation of the stomach. Clinical signs were toxicologically significant at 250 mg/kg/day and 500 mg/kg/day dose levels. The occurrence of soft stools, diarrhea, mucoid diarrhea, and a decrease in the general condition of the animals was greater than in the controls and lower dose. Significant decreases in body weight gain occurred only in the 500 mg/kg/day group males and females. Food consumption showed a slightly decrease in the 500 mg/kg/day groups although only the food consumption for females was significantly different from the controls. These findings are primary orsecondary effects dueto the local irritation via the experimental route of administration Treatment-related increases in mean absolute and relative adrenal gland weights occurred at the 250 and 500 mg/kg/day dose levels. However, no test article-related histopathological lesions were observed in the adrenal glands to account for the increases. Based on these findings, the No Adverse Effect Level NOAEL was determined to be 125 mg/kg/day.
2. Mode of action
No non-threshold mode of action is associated with the source substance, in particular, the test substance has no genotoxic potential.
3. Correction of dose descriptor
NOAELoral is converted into a NOAELcorrected in accordance to Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose [concentration] - response for human health, ECHA, May 2008.
Corrected starting point for the dermal route for workers:
Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) * (days of exposure per week in rats / days of exposure per week worker)
= 125 mg/kg bw/day * (1/0.1) * 7/5 = 1750 mg/kg bw/day
Corrected starting point for the inhalative route for workers:
= NOAEL(oral) * (1/0.38 m³/kg bw/day) * (ABSoral-rat/ABSinh-human) * 6.7 m³ (8h) /10 m³ (8h) * (days of exposure per week in rats / days of exposure per week worker)
= 125 mg/kg bw/day * (1/0.38 m³/kg) * 6.7/10 m³ * 7/5 = 308.55 m³/kg
4. Application of assessment factors
Dermal route: The following assessment factors were chosen: interspecies difference (4 for allometric scale, 2.5 for remaining difference), intraspecies difference (5 for workers), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).
Inhalation route: The following assessment factors were chosen: interspecies difference (2.5), intraspecies difference (5 for workers), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.72 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 150
- Dose descriptor starting point:
- NOAEL
- Value:
- 125 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 108.69 mg/m³
- Explanation for the modification of the dose descriptor starting point:
DNEL calculation was based on the results of a 28-day repeat dose toxicity study with the source substance in rats, resulting in a NOAEL (oral) = 125 mg/kg bw/day
Corrected Descriptor: The inhalation route was extrapolated by oral route information in the absence of data for this administration route.
Corrected starting point for the inhalative route for workers:
= NOAEL(oral) * (1/1.15 m³/kg bw/day) * (ABSoral-rat/ABSinh-human)
= 125 mg/kg bw/day * (1/1.15 m³/kg) = 108.69 m³/kg
- AF for dose response relationship:
- 1
- Justification:
- The dose descriptor starting point is based on a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- The DNEL is based on a subacute study.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- AF not used for the inhalation route
- AF for other interspecies differences:
- 2.5
- Justification:
- Default AF
- AF for intraspecies differences:
- 10
- Justification:
- Default AF for general population
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on a high quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.08 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 600
- Dose descriptor starting point:
- NOAEL
- Value:
- 125 mg/m³
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 250 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
DNEL calculation was based on the results of a 28-day repeat dose toxicity study with the source substance in rats, resulting in a NOAEL (oral) = 125 mg/kg bw/day
Assume ABS rat – oral is 100%. The dermal route was extrapolated from oral route information in the absence of data for this administration route. Basic physicochemical properties of the source substance were taken into consideration when estimating dermal absorption, (e.g. low water solubility, molecular weight and log Kow), and < 10% dermal absorption was predicted (please refer to toxicokinetics, metabolism and distribution). As the physicochemical properties of the target substance are similar to that of the source substance this assumption is also valid for the target substance.
Corrected starting point for the dermal route for workers:
Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal)
= 125 mg/kg bw/day * (1/0.1) = 1250 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- The dose descriptor starting point is based on a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- The DNEL is based on a subacute study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default AF for rats
- AF for other interspecies differences:
- 2.5
- Justification:
- Default AF
- AF for intraspecies differences:
- 10
- Justification:
- Default AF for general population
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on a high quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
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:
- 0.208 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 600
- Dose descriptor starting point:
- NOAEL
- Value:
- 125 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation necessary.
- AF for dose response relationship:
- 1
- Justification:
- The dose descriptor starting point is based on a NOAEL
- AF for differences in duration of exposure:
- 6
- Justification:
- The DNEL is based on a subacute study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default AF for rats
- AF for other interspecies differences:
- 2.5
- Justification:
- Default AF
- AF for intraspecies differences:
- 10
- Justification:
- Default AF for general population
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on a high quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
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
1. Relevant Toxicology Data, exposure pattern and route
The oral repeated dose toxicity of the source substance was evaluated in rats at levels up to 500 mg/kg/day according to OECD 407. Treatment-related deaths occurred at 500 mg/kg/day in both sexes. All of these animals had reddened adrenal and pituitary glands and yellow contents in the stomach. Microscopic examinations found edema and inflammation of the stomach in all 500 mg/kg/day group females and thickened mucosa in the nonglandular portion of the stomach in one male. In the 250 mg/kg/day group, one male also had edema and inflammation of the stomach. Clinical signs were toxicologically significant at 250 mg/kg/day and 500 mg/kg/day dose levels. The occurrence of soft stools, diarrhea, mucoid diarrhea, and a decrease in the general condition of the animals was greater than in the controls and lower dose. Significant decreases in body weight gain occurred only in the 500 mg/kg/day group males and females. Food consumption showed a slightly decrease in the 500 mg/kg/day groups although only the food consumption for females was significantly different from the controls. These findings are primary orsecondary effects dueto the local irritation via the experimental route of administration Treatment-related increases in mean absolute and relative adrenal gland weights occurred at the 250 and 500 mg/kg/day dose levels. However, no test article-related histopathological lesions were observed in the adrenal glands to account for the increases. Based on these findings, the No Adverse Effect Level NOAEL was determined to be 125 mg/kg/day.
2. Mode of action
No non-threshold mode of action is associated with this substance, in particular, the test substance has no genotoxic potential.
3. Correction of dose descriptor
NOAELoral is converted into a NOAELcorrected in accordance to Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose [concentration] - response for human health, ECHA, May 2008.
Corrected starting point for the inhalative route for workers:
= NOAEL(oral) * (1/1.15 m³/kg bw/day) * (ABSoral-rat/ABSinh-human)
= 125 mg/kg bw/day * (1/1.15 m³/kg) = 108.69 m³/kg
Corrected starting point for the dermal route for workers:
Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal)
= 125 mg/kg bw/day * (1/0.1) = 1250 mg/kg bw/day
4. Application of assessment factors
Dermal route: The following assessment factors were chosen: interspecies difference (4 for allometric scale, 2.5 for remaining difference), intraspecies difference (10 for general population), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).
Inhalation route: The following assessment factors were chosen: interspecies difference (2.5), intraspecies difference (10 for general population), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).
Oral route: The following assessment factors were chosen: interspecies difference (4 for allometric scale, 2.5 for remaining difference), intraspecies difference (10 for general population), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).
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.
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