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Diss Factsheets
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EC number: 244-848-1 | CAS number: 22224-92-6
- 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:
- 0.023 mg/m³
- Most sensitive endpoint:
- neurotoxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 12.5
- Dose descriptor starting point:
- NOAEL
- Value:
- 0.083 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 0.29 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Standard human bodyweight: 70 kg
Allometric scaling factor (ASF) dog: 1.4
Worker respiratory volume (wRV) for 8 hours with light physical activity per person: 10 m3
Oral absorption of the dog/ inhalation absorption of humans (ABS oral-dog / ABS inh.-human): 1/2
No correction for oral absorption is indicated as the test substance was shown to be completely absorbed from the gastro-intestinal tract (section 7.1). For inhalation absorption of humans a default value according to ECHA Guidance R.8 Dose- or concentration-response characterisation (2012) is used.
Correction for difference between human and experimental exposure conditions: 7 d dog/5 d worker
Corrected NOAEC (inhalation) for workers:
NOAECcorr = NOAELoral /ASF x 70 kg/10 m3 x 7d/5d x ABSoral/ABSinh
NOAECcorr = 0.083 mg/kg bw/day / 1.4 x 70 kg / 10m³ x 7d / 5d x ½
- 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:
- 1
- Justification:
- As a dose descriptor starting point is used from a chronic repeated dose toxicity study, no further extrapolation regarding duration is required.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- An assessment factor for allometric scaling has already been used for the modification of the dose descriptor starting point (NOAEC). No additional allometric scaling factor is required.
- 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 chronic toxicity study according to OECD No. 452 is considered to be conducted according to regulatory standards and not considered to contribute to uncertainty, hence it is 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:
- DNEL (Derived No Effect Level)
- Value:
- 0.53 mg/m³
- Most sensitive endpoint:
- neurotoxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 12.5
- Dose descriptor starting point:
- NOAEL
- Value:
- 0.25 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 6.64 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Standard human bodyweight: 70 kg
Allometric scaling factor (ASF) dog: 1.4
Correction for difference between human and experimental exposure conditions: 1
Worker respiratory volume (wRV) for 15 min: 0.31 m3
Oral absorption of the dog/ inhalation absorption of humans (ABS oral-dog / ABS inh.-human): 1/2
No correction for oral absorption is indicated as the test substance was shown to be completely absorbed from the gastro-intestinal tract (section 7.1). For inhalation absorption of humans a default value according to ECHA Guidance R.8 Dose- or concentration-response characterisation (2012) is used.
Corrected NOAEC (inhalation) for workers:
NOAECcorr = NOAELoral /ASF x 70 kg / 0.31 m3 x ABSoral/ABSinh
NOAECcorr = 0.083 mg/kg bw/day / 1.4 x 70 kg / 0.31 m³ x ½
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- An assessment factor for allometric scaling has already been used for the modification of the dose descriptor starting point (NOAEC). No additional allometric scaling factor is required.
- 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 acute neurotoxicity study is considered to be conducted according to regulatory standards and not considered to contribute to uncertainty, hence it is 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.
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.664 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
- Dose descriptor starting point:
- NOAEL
- Value:
- 0.083 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 11.62 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Oral absorption of the dog/ dermal absorption of humans (ABS oral-dog / ABS derm-human): 1/0.01
The human dermal absorption of 1% based on an in vitro model as given in the EFSA conclusion (2019) is used in the following calculation. No correction for oral absorption is indicated as the test substance was shown to be completely absorbed from the gastro-intestinal tract (section 7.1).
Correction for difference between human and experimental exposure conditions: 7 d dog/5 d worker
Corrected NOAEL (dermal) for workers:
NOAELcorr = NOAELoral x 7d/5d x ABSoral/ABSderm
NOAELcorr = 0.083 mg/kg bw/day x 7d/5d x 1/0.01
- 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:
- 1
- Justification:
- As a dose descriptor starting point is used from a chronic repeated dose toxicity study, no further extrapolation regarding duration is required.
- AF for interspecies differences (allometric scaling):
- 1.4
- Justification:
- The default allometric scaling factor for the differences between dogs and humans is applied.
- AF for other interspecies differences:
- 2.5
- Justification:
- The recommended AF for other interspecies differences is applied. 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 chronic toxicity study according to OECD No. 452 is considered to be conducted according to regulatory standards and not considered to contribute to uncertainty, hence it is 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:
- DNEL (Derived No Effect Level)
- Value:
- 1.43 mg/kg bw/day
- Most sensitive endpoint:
- neurotoxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 17.5
- Dose descriptor starting point:
- NOAEL
- Value:
- 0.25 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 25 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Oral absorption of the dog/ dermal absorption of humans (ABS oral-dog / ABS derm-human): 1/0.01
The human dermal absorption of 1% based on an in vitro model as given in the EFSA conclusion (2019) is used in the following calculation. No correction for oral absorption is indicated as the test substance was shown to be completely absorbed from the gastro-intestinal tract (section 7.1).
Correction for difference between human and experimental exposure conditions: 1
Corrected NOAEL (dermal) for workers:
NOAELcorr = NOAELoral x ABSoral/ABSderm
NOAELcorr = 0.25 mg/kg bw/day x 1/0.01
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for interspecies differences (allometric scaling):
- 1.4
- Justification:
- The default allometric scaling factor for the differences between dogs and humans is applied.
- 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 acute neurotoxicity study is considered to be conducted according to regulatory standards and not considered to contribute to uncertainty, hence it is 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.
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:
- low hazard (no threshold derived)
Additional information - workers
Systemic long-term DNEL for inhalation exposure
The respective NOAEC is based on a NOAEL of 0.083 mg/kg bw/day from a chronic oral dog (1 year feeding) study according to OECD No. 452, considering an oral bioavailability of 100%. No correction for oral absorption is indicated as the test substance was shown to be completely absorbed from the gastro-intestinal tract (section 7.1). It was modified using a standard human bodyweight of 70 kg, an allometric scaling factor (ASF) for the dog of 1.4, a worker respiratory volume (wRV) of 10 m³ for 8 hours with light physical activity, the default quotient of ½ for oral absorption of the rat and inhalation absorption of humans (ABS oral-rat / ABS inh-human) and a correction for difference between human and experimental exposure conditions (7 days exposure of the rats/5 days exposure of worker per week) to 0.29 mg/m3 using the equation provided in the Guidance Document on Information Requirement, Chapter R8:
NOAECcorr = NOAELoral /ASF x 70 kg/10 m3 x 7d/5d x ABSoral/ABSinh
Using assessment factors of (i) 2.5 for remaining species differences and (ii) 5 for intraspecies extrapolation, a DNEL of 0.023 mg/m3 for long-term, systemic inhalative exposure was calculated.
Systemic acute DNEL for inhalation exposure
In an acute inhalation toxicity study, the LC50 was 65 – 79 mg/m3 for 4 h (aerosol) exposure in male and female rats. Therefore, hazard could be identified and the determination of a DNEL for acute inhalation toxicity triggered. The DNEL was derived on the basis of an acute oral neurotoxicity study covering the test substance’s most relevant adverse effect (erythrocyte ChE inhibition) with a NOAEL of 0.25 mg/kg bw/d, considering an oral bioavailability of 100% (no correction for oral absorption is indicated as the test substance was shown to be completely absorbed from the gastro-intestinal tract (section 7.1)), and in accordance with ECHA Guidance R.8 Dose- or concentration-response characterisation (2012). The NOAEL was modified using a standard human bodyweight of 70 kg, an allometric scaling factor (ASF) for the dog of 1.4, a worker respiratory volume (wRV) of 0.31 m³ for 15 min with light physical activity and the default quotient of ½ for oral absorption of the rat and inhalation absorption of humans (ABS oral-rat / ABS inh-human) to 6.64 mg/m3 using the equation provided in the Guidance Document on Information Requirement, Chapter R8:
NOAECcorr = NOAELoral /ASF x 70 kg / 0.31 m3 x ABSoral/ABSinh
Using assessment factors of (i) 2.5 for remaining species differences and (ii) 5 for intraspecies extrapolation, a DNEL of 0.53 mg/m3 for acute systemic inhalation exposure was calculated.
Local long-term and acute DNELs for inhalation exposure
No study on respiratory irritation is available, but, due to the negative outcomes in in vitro skin irritation and no indication of respiratory irritation in available in vivo acute and subacute toxicity inhalation studies, long-term and acute local effects in the respiratory tract are not expected.
Systemic long-term DNEL for dermal exposure
The NOAEL of 0.083 mg/kg bw/day from a chronic oral dog (1 year feeding) study according to OECD No. 452 was used as POD, considering an oral bioavailability of 100%. No correction for oral absorption is indicated as the test substance was shown to be completely absorbed from the gastro-intestinal tract (section 7.1). The human dermal absorption of 1% based on an in vitro model as given in EFSA conclusion (2019) was used.
The POD was modified using a correction for difference between human and experimental exposure conditions (7 days exposure of the rats/5 days exposure of worker per week) and a dermal absorption of 1% to 11.62 mg/kg bw/day using the equation provided in the Guidance Document on Information Requirement, Chapter R8:
NOAELcorr = NOAELdermal x 7d/5d x ABSoral/ABSdermal
Using assessment factors of (i) 14 for interspecies differences (allometric scaling), (ii) 2.5 for remaining interspecies differences and (iii) 5 for intraspecies extrapolation, a DNEL of 0.664 mg/kg bw/day for long-term, systemic dermal exposure was calculated.
Systemic acute DNEL for dermal exposure
In an acute dermal toxicity study, the dermal LD50 was 72 – 92 mg/kg bw in male and female rats. Therefore, hazard could be identified and the determination of a DNEL for acute dermal toxicity triggered. The DNEL was derived on the basis of an acute oral neurotoxicity study covering the test substance’s most relevant adverse effect (erythrocyte ChE inhibition) with a NOAEL of 0.25 mg/kg bw/d, considering an oral bioavailability of 100%, and in accordance with ECHA Guidance R.8 Dose- or concentration-response characterisation (2012). No correction for oral absorption is indicated as the test substance was shown to be completely absorbed from the gastro-intestinal tract (section 7.1). The human dermal absorption of 1% based on an in vitro model as given in EFSA conclusion (2019) was used. The NOAEL was modified using the dermal absorption of 1% to 25 mg/kg bw/d with the equation provided in the Guidance Document on Information Requirement, Chapter R8:
NOAELcorr = NOAELoral x ABSoral/ABSderm
Using assessment factors of (i) 2.5 for remaining species differences and (ii) 5 for intraspecies extrapolation and (iii) for allometric scaling of 1.4, a DNEL of 1.43 mg/kg bw/d for acute systemic dermal exposure was calculated.
Local long-term and acute DNELs for dermal exposure
No hazards were identified in skin sensitisation and skin irritation studies. Thus, long-term and acute local dermal effects are not likely to occur.
Hazard to the eyes:
The test item is classified as eye damage Cat. 2. according to Regulation (EC) No 1272/2008 (CLP) and associated to the low hazard band. A qualitative risk assessment is conducted.
General Population - Hazard via inhalation route
Systemic 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
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:
- 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
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
General Population - Hazard via oral route
Systemic 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 for the eyes
Local effects
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Additional information - General Population
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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