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Diss Factsheets
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EC number: 278-859-8 | CAS number: 78181-99-4
- 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:
- 29 mg/m³
DNEL related information
- DNEL derivation method:
- other: ECHA REACH Guidance and ECETOC Technical Report No. 110
- Overall assessment factor (AF):
- 18
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 529 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- There are no experimental data available on repeated exposure by the inhalatory route.
- 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:
- 6
- Justification:
- The default value for extrapolation from subacute to chronic exposure is used.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate.
- AF for other interspecies differences:
- 1
- Justification:
- Interspecies differences are fully covered by the allometric scaling. There is no additional evidence for species differences including toxicodynamics (ECETOC). Therefore, no additional factor is used.
- AF for intraspecies differences:
- 3
- Justification:
- The study used as point of departure for DNEL derivation indicates the kidney and the liver as slightly affected target organs at the limit dose level of 1000 mg/kg bw/day. For the observed minimal effects a low intraspecies variability for humans has to be expected.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 20.8 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH Guidance and ECETOC Technical Report No. 110
- Overall assessment factor (AF):
- 72
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 500 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- There are no relevant experimental data on repeated exposure by the dermal route.
- 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:
- 6
- Justification:
- The default value for extrapolation from subacute to chronic exposure is used in order to cover the min. exposure duration for male animals.
- 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:
- 1
- Justification:
- Interspecies differences are fully covered by the allometric scaling. There is no additional evidence for species differences including toxicodynamics (ECETOC). Therefore, no additional factor is used.
- AF for intraspecies differences:
- 3
- Justification:
- The study used as point of departure for DNEL derivation indicates the kidney and the liver as slightly affected target organs at the limit dose level of 1000 mg/kg bw/day. For the observed minimal effects a low intraspecies variability for humans has to be expected. Therefore, an assessment factor of 3 is proposed to be sufficient to ensure the safety of human workers.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Long-term exposure - systemic effects
Inhalation exposure
In the absence of an inhalation toxicity study with repeated exposure, the worker-DNEL long-term for inhalation route - systemic was derived from the NOAEL obtained in the key subacute oral repeated dose study in Wistar rats. A corrected inhalatory NOAEC (NOAECcorr) was calculated using a default respiratory volume for the rat and a correction for the difference between human respiratory rats under standard conditions and under conditions of light activity (under the assumption of no difference in absorption between rat and human, and between routes). Using this NOAECcorr and considering the appropriate modification and assessment factors, the worker-DNEL (long-term for inhalation route-systemic) was calculated to be 29 mg/m³.
Calculation of the NOAECcorr
- Standard dose descriptor (NOAEL): 300 mg/kg bw/d
- Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d
- Oral absorption of the rat/inhalation absorption of humans (ABSoral-rat)/ABSinhal-human): 1/1
- 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
Corrected inhalatory NOAEC for workers:
= NOAEL * (1/sRVrat) * (ABSoral-rat/ABSinhal-human) *(sRVhuman/wRV)
= 300 mg/kg bw/d * (1/0.38 m³/kg bw/d)* (1/1) * (6.7m³/10 m³)
= 529 mg/m³
Dermal exposure
In the absence of a repeated dose toxicity study with dermal test substance application, the worker-DNEL long-term for dermal route - systemic was derived from the NOAEL obtained in the key subacute oral repeated dose study in Wistar rats. A corrected dermal NOAEL (NOAELcorr) was calculated under the assumption of a 5-times lower dermal absorption compared to oral absorption. Using this NOAELcorr and considering the appropriate modification and assessment factors, the worker-DNEL (long-term for dermal route-systemic) was calculated to be 20.8 mg/kg bw/d.
Calculation of the NOAELcorr
- Standard dose descriptor (NOAEL): 300 mg/kg bw/d
- Oral absorption of the rat/dermal absorption of humans (ABSoral-rat)/ABSdermal-human): 5/1
Corrected dermal NOAEL for workers:
= NOAEL * (ABSoral-rat/ABSdermal-human)
= 300 mg/kg bw/d * (5/1)
= 1500 mg/kg bw/d
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, ECHA-2012 -G-19 -EN.
ECETOC (2010). Guidance on assessment factors to derive a DNEL. ECETOC TR No. 110.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.7 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH Guidance and ECETOC Technical Report No. 110
- Overall assessment factor (AF):
- 30
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 261 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- There are no experimental data available on repeated exposure by the inhalatory route.
- 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:
- 6
- Justification:
- The default value for extrapolation from subacute to chronic exposure is used.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate.
- AF for other interspecies differences:
- 1
- Justification:
- Interspecies differences are fully covered by the allometric scaling. There is no additional evidence for species differences including toxicodynamics (ECETOC). Therefore, no additional factor is used.
- AF for intraspecies differences:
- 5
- Justification:
- The study used as point of departure for DNEL derivation indicates the kidney and the liver as slightly affected target organs at the limit dose level of 1000 mg/kg bw/day. For the observed minimal effects a low intraspecies variability for humans has to be expected.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 12.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH Guidance and ECETOC Technical Report No. 110
- Overall assessment factor (AF):
- 120
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 500 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- There are no relevant experimental data on repeated exposure by the dermal route
- 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:
- 6
- Justification:
- The default value for extrapolation from subacute to chronic exposure is used in order to cover the min. exposure duration for male animals.
- 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:
- 1
- Justification:
- Interspecies differences are fully covered by the allometric scaling. There is no additional evidence for species differences including toxicodynamics (ECETOC). Therefore, no additional factor is used.
- AF for intraspecies differences:
- 5
- Justification:
- The study used as point of departure for DNEL derivation indicates the kidney and the liver as slightly affected target organs at the limit dose level of 1000 mg/kg bw/day. For the observed minimal effects a low intraspecies variability for humans has to be expected.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA REACH Guidance and ECETOC Technical Report No. 110
- Overall assessment factor (AF):
- 120
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 6
- Justification:
- The default value for extrapolation from subacute to chronic exposure is used in order to cover the min. exposure duration for male animals.
- 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:
- 1
- Justification:
- Interspecies differences are fully covered by the allometric scaling. There is no additional evidence for species differences including toxicodynamics (ECETOC). Therefore, no additional factor is used.
- AF for intraspecies differences:
- 5
- Justification:
- The study used as point of departure for DNEL derivation indicates the kidney and the liver as slightly affected target organs at the limit dose level of 1000 mg/kg bw/day. For the observed minimal effects a low intraspecies variability for humans has to be expected.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- 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
Long-term exposure - systemic effects
Inhalation exposure
In the absence of an inhalation toxicity study with repeated exposure, the general population-DNEL long-term for inhalation route - systemic was derived from the NOAEL obtained in the key subacute oral repeated dose study in Wistar rats. A corrected inhalatory NOAEC (NOAECcorr) was calculated using a default respiratory volume for the rat (under the assumption of no difference in absorption between rat and human, and between routes). Using this NOAECcorr and considering the appropriate modification and assessment factors, the general population-DNEL (ong-term for inhalation route-systemic was calculated to be 8.7 mg/m³.
Calculation of the NOAECcorr
- Standard dose descriptor (NOAEL): 300 mg/kg bw
- Standard respiratory volume of the rat (sRVrat) for 24 hours: 1.15 m³/kg bw
- Oral absorption of the rat/inhalation absorption of humans (ABSoral-rat)/ABSinhal-human): 1/1
Corrected inhalatory NOAEC for general population:
= NOAEL * (1/sRVrat) * (ABSoral-rat/ABSinhal-human)
= 300 mg/kg bw/d * (1/1.15 m³/kg bw/d)* (1/1)
= 261 mg/m³
Dermal exposure
In the absence of a repeated dose toxicity study with dermal test substance application, the general population-DNEL long-term for dermal route - systemic was derived from the NOAEL obtained in the key subacute oral repeated dose study in Wistar rats. A corrected dermal NOAEL (NOAELcorr) was calculated under the assumption of a 5-times lower dermal absorption compared to oral absorption. Using this NOAELcorr and considering the appropriate modification and assessment factors, the general population-DNEL (long-term for dermal route-systemic) was calculated to be 12.5 mg/kg bw/d.
Calculation of the NOAELcorr
- Standard dose descriptor (NOAEL): 300 mg/kg bw/d
- Oral absorption of the rat/dermal absorption of humans (ABSoral-rat)/ABSdermal-human): 5/1
Corrected dermal NOAEL for the general population:
= NOAEL * (ABSoral-rat/ABSdermal-human)
= 300 mg/kg bw/d * (5/1)
= 1500 mg/kg bw/d
Oral exposure
The general population DNEL long-term for oral route - systemic was derived from the NOAEL of 300 mg/kg bw/day obtained in the key oral repeated dose toxicity study in rats. No modification of the dose descriptor is necessary. Using this NOAEL and considering the appropriate assessment factors, the general population-DNEL (long-term for oral route-systemic) was calculated to be 2.5 mg/kg bw/d.
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, ECHA-2012 -G-19 -EN.
ECETOC (2010). Guidance on assessment factors to derive a DNEL. ECETOC TR No. 110.
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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