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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
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: 203-584-7 | CAS number: 108-45-2
- 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:
- 0.24 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
- Dose descriptor starting point:
- NOAEL
- Value:
- 6 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 0.24 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The NOAEL of 6 mg/kg was the concentration where no significant adverse effects were seen in a subchronic oral toxicity study.
Modification of starting point for rat respiratory volume (Allometric scaling); Value: 0.38 m3/kg bw (rat 8-hour respiratory volume); Remark: A modification of starting point for rat respiratory volume was applied per REACH guidance R.8.4.2.
Modification of starting point for differences in respiratory volumes;Value: 0.67 (6.7 m3/10 m3); Remark: A modification was applied to account for the increased respiratory volumes in active workers as compared to individuals at rest per REACH guidance R.8.4.2.
- AF for dose response relationship:
- 1
- Justification:
- A factor of 1 is appropriate since the dose descriptor is a NOAEL.
- AF for differences in duration of exposure:
- 1
- Justification:
- A factor of 1 is appropriate since the chronic study demonstrated no different or greater toxicity following chronic exposure compared to subchronic exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- A factor of 1 is appropriate since the adjusted start point was via mg/m3 (inhalation) and thus this assessment factor is not applicable per REACH guidance R.8.4.3.1.
- AF for other interspecies differences:
- 2.5
- Justification:
- A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
- AF for intraspecies differences:
- 5
- Justification:
- This is a default assessment factor for workers per REACH Guidance R.8.4.3.1.
- AF for the quality of the whole database:
- 4
- Justification:
- A factor of 4 is appropriate because of the lack of repeat dose inhalation data warrants an uncertainty factor of greater than 1.
- AF for remaining uncertainties:
- 2
- Justification:
- A factor of 2 is appropriate per REACH guidance R.8.4.2 (oral to inhalation).
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:
- 0.12 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):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 6 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Explanation for the modification of the dose descriptor starting point:
This is the concentration where no significant adverse effects were seen in a subchronic oral toxicity study.
Route–to-route extrapolation; Value: 1; Remark: A factor of 1 is appropriate since the animal exposure was via ingestion.
- AF for dose response relationship:
- 1
- Justification:
- A factor of 1 is appropriate since the dose descriptor is a NOAEL.
- AF for differences in duration of exposure:
- 4
- Justification:
- A factor of 4 is appropriate since the adjusted start point was via mg/kg per REACH guidance 8.4.3.1.
- AF for interspecies differences (allometric scaling):
- 2.5
- Justification:
- A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
- AF for other interspecies differences:
- 2.5
- Justification:
- A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
- AF for intraspecies differences:
- 5
- Justification:
- This is a default assessment factor for workers per REACH Guidance
R.8.4.3.1. - AF for the quality of the whole database:
- 1
- Justification:
- A high quality, robust toxicity database exists for this substance.
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:
- DNEL (Derived No Effect Level)
- Value:
- 0.49 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 250
- Dose descriptor starting point:
- other: LOAEL
- AF for dose response relationship:
- 2
- Justification:
- A factor of 2 is appropriate as an EC3 value can be considered as a LOAEL for induction of skin sensitization per REACH R.8 Appendix R.8-10.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- A factor of 1 is appropriate since the adjusted start point was via μg/cm2 (dermal) and thus this assessment factor is not applicable per REACH guidance R.8.4.3.1.
- AF for other interspecies differences:
- 10
- Justification:
- A default factor of 10 is appropriate per REACH guidance R.8.10.
- AF for intraspecies differences:
- 5
- Justification:
- This is a default assessment factor for workers per REACH Guidance R.8.4.3.1.
- AF for the quality of the whole database:
- 1
- Justification:
- A high quality, robust toxicity database exists for this substance.
- AF for remaining uncertainties:
- 2.5
- Justification:
- Route–to-route extrapolation; Value: 1; Remark: A factor of 1 is appropriate since the animal exposure was via the dermal route.
Other interspecies; Value: 2.5; Remark: A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Potential worker exposure would likely occur via the dermal or
inhalation routes.
This substance is classified as harmful via the acute oral, inhalation,
and dermal routes under REACH regulations and guidance. The rat oral
ALD is 450 mg/kg and the rat inhalation 4 -hour LC50 is 3.2 mg/L (3200
mg/m3). The rabbit dermal ALD for the structurally similar
substance, o-phenylenediamine (CAS 95-54-5), which was used as a
surrogate for acute dermal data, is 1500 mg/kg.
Male and female rats were exposed to 2, 6, and 18 mg/kg/d for 90 days by
oral gavage. Degenerative lesions of the liver, increased frequency of
pycnosis, and increased liver and kidney weights were observed in the
highest dose group. The NOEL for systemic
toxicity effects after 90 days was 6 mg/kg/day. The test
substance did not cause cancer in a 19-month drinking water study in
mice at any dose level tested. Based on this information, the NOAEL
for significant systemic effects was determined to be 6 mg/kg-bw/day and
can be used for development of a long-term DNEL for systemic effects.
Skin sensitization was observed in acute exposure studies; therefore a
short-term DNEL for local effects was derived.
In a local lymph node assay, this substance was found to be positive for dermal sensitization with an EC3 value of 0.49% (122.5 µg/cm2). As per REACH R.8 Appendix R. 8-10 Skin sensitization, an EC3 value can be considered as a LOAEL for induction (expressed in µg/cm2) and can be used for development of a short-term DNEL for local effects.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.03 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):
- 200
- Dose descriptor starting point:
- NOAEL
- Value:
- 6 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 5.217 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The NOAEL of 6 mg/kg is the concentration where no significant adverse effects were seen in a subchronic oral toxicity study.
Modification of starting point for rat respiratory volume (Allometric scaling); Value: 1.15 m3/kg bw (rat 24-hour respiratory volume); Remark: A modification of starting point for rat respiratory volume was applied per REACH guidance R.8.4.2.
- AF for dose response relationship:
- 1
- Justification:
- A factor of 1 is appropriate since the dose descriptor is a NOAEL.
- AF for differences in duration of exposure:
- 1
- Justification:
- A factor of 1 is appropriate since the chronic study demonstrated no different or greater toxicity following chronic exposure compared to subchronic exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- A factor of 1 is appropriate since the adjusted start point was via mg/m3 (inhalation) and thus this assessment factor is not applicable per REACH guidance R.8.4.3.1.
- AF for other interspecies differences:
- 2.5
- Justification:
- A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
- AF for intraspecies differences:
- 10
- Justification:
- This is a default assessment factor for the general population per REACH Guidance R.8.4.3.1.
- AF for the quality of the whole database:
- 4
- Justification:
- A factor of 4 is appropriate because of the lack of repeat dose inhalation data warrants an uncertainty factor of greater than 1.
- AF for remaining uncertainties:
- 2
- Justification:
- Route–to-route extrapolation: A factor of 2 is appropriate per REACH guidance R.8.4.2 (oral to inhalation).
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:
- 0.06 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:
- 6 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 6 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The NOAEL of 6 mg/kg is the concentration where no significant adverse effects were seen in a subchronic oral toxicity study.
- AF for dose response relationship:
- 1
- Justification:
- A factor of 1 is appropriate since the dose descriptor is a NOAEL.
- AF for differences in duration of exposure:
- 1
- Justification:
- A factor of 1 is appropriate since the chronic study demonstrated no different or greater toxicity than the subchronic study.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Remark: A factor of 4 is appropriate since the adjusted start point was via mg/kg per REACH guidance 8.4.3.1.
- AF for other interspecies differences:
- 2.5
- Justification:
- A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
- AF for intraspecies differences:
- 10
- Justification:
- is a default assessment factor for the general population per REACH Guidance R.8.4.3.1.
- AF for the quality of the whole database:
- 1
- Justification:
- A high quality, robust toxicity database exists for this substance.
- AF for remaining uncertainties:
- 1
- Justification:
- Route–to-route extrapolation: Value: 1; Remark: A factor of 1 is appropriate since the animal exposure was via ingestion.
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:
- DNEL (Derived No Effect Level)
- Value:
- 0.25 µg/cm²
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 500
- Dose descriptor starting point:
- other: LOAEL
- AF for dose response relationship:
- 2
- Justification:
- A factor of 2 is appropriate as an EC3 value can be considered as a LOAEL for induction of skin sensitization per REACH R.8 Appendix R.8-10.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- A factor of 1 is appropriate since the adjusted start point was via μg/cm2(dermal) and thus this assessment factor is not applicable per REACH guidance R.8.4.3.1.
- AF for other interspecies differences:
- 10
- Justification:
- A default factor of 10 is appropriate per REACH guidance R.8.10.
- AF for intraspecies differences:
- 10
- Justification:
- This is a default assessment factor for workers per REACH Guidance R.8.4.3.1.
- AF for the quality of the whole database:
- 1
- Justification:
- A high quality, robust toxicity database exists for this substance.
- AF for remaining uncertainties:
- 2.5
- Justification:
- Route–to-route extrapolation; Value: 1; Remark: A factor of 1 is appropriate since the animal exposure was via the dermal route.
Other interspecies; Value: 2.5; Remark: A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.06 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:
- 6 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The NOAEL of 6 mg/kg is the concentration where no significant adverse effects were seen in a subchronic oral toxicity study.
- AF for dose response relationship:
- 1
- Justification:
- A factor of 1 is appropriate since the dose descriptor is a NOAEL.
- AF for differences in duration of exposure:
- 1
- Justification:
- A factor of 1 is appropriate since the chronic study demonstrated no different or greater toxicity than the subchronic study.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- A factor of 4 is appropriate since the adjusted start point was via mg/kg per REACH guidance 8.4.3.1.
- AF for other interspecies differences:
- 2.5
- Justification:
- A default factor of 2.5 is appropriate per REACH guidance R.8.4.3.1.
- AF for intraspecies differences:
- 10
- Justification:
- This is a default assessment factor for the general population per REACH Guidance R.8.4.3.1.
- AF for the quality of the whole database:
- 1
- Justification:
- A high quality, robust toxicity database exists for this substance.
- AF for remaining uncertainties:
- 1
- Justification:
- Route–to-route extrapolation; Value: 1; Remark: A factor of 1 is appropriate since the animal exposure was via ingestion.
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
Potential general population exposure would likely occur via the dermal,
oral, or inhalation routes.
This substance is classified as harmful via the acute oral, inhalation,
and dermal routes under REACH regulations and guidance. The rat oral
ALD is 450 mg/kg and the rat inhalation 4 -hour LC50 is 3.2 mg/L (3200
mg/m3). The rabbit dermal ALD for the structurally similar
substance, o-phenylenediamine (CAS 95-54-5), which was used as a
surrogate for acute dermal data, is 1500 mg/kg.
Male and female rats were exposed to 2, 6, and 18 mg/kg/d for 90 days by
oral gavage. Degenerative lesions of the liver, increased frequency of
pycnosis, and increased liver and kidney weights were observed in the
highest dose group. The NOEL for systemic
toxicity effects after 90 days was 6 mg/kg/day. The test
substance did not cause cancer in a 19-month drinking water study in
mice at any dose level tested. Based on this information, the NOAEL
for significant systemic effects was determined to be 6 mg/kg-bw/day and
can be used for development of a long-term DNEL for systemic effects.
Skin sensitization was observed in acute exposure studies; therefore a
short-term DNEL for local effects was derived.
In a local lymph node assay, this substance was found to be positive for
dermal sensitization with an EC3 value of 0.49% (122.5 µg/cm2). As
per REACH R.8 Appendix R. 8-10 Skin sensitization, an EC3 value can be
considered as a LOAEL for induction (expressed in µg/cm2)
and can be used for development of a short-term DNEL for local effects.
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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