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EC number: 211-776-7 | CAS number: 694-83-7
- 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
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.25 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 37.5
- Dose descriptor:
- LOAEC
- AF for dose response relationship:
- 3
- Justification:
- starting point is LOAEC instead of NOAEC
- AF for differences in duration of exposure:
- 1
- Justification:
- no additional factor is required for time duration since the effect observed is not dependent on the time of exposure
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- no allometric scaling foreseen
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 5
- AF for the quality of the whole database:
- 1
- Justification:
- no deficiencies
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.5 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.5 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
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- no data on the dermal absorption of the members of the amine heads category are available, in a conservative manner it is assumed that dermal absorption does not exceed oral absorption; therefore no correction for absorption has to be made for route-to-route extrapolation
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 2
- Justification:
- sub-chronic to chronic; factor of 2 is thought to be sufficiently conservative as the starting NOAEL was obtained in an oral gavage study with DCH, in studies with other category members and other ways of oral application the effect level was at least 4fold higher
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 5
- AF for the quality of the whole database:
- 1
- Justification:
- no deficiencies
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Additional information - workers
Worker DNELLong-termfor dermal route, systemic effects
No long-term toxicity study with dermal exposure is available for the members of this category. Therefore the DNEL long-term, dermal exposure, systemic effects is derived by route-to-route extrapolation from a toxicity study with oral exposure. The most sensitive NOAEL for this category was the NOAEL of 150 mg/kg bw/day identified in the Combined repeated dose reproduction and developmental toxicity study (OECD 422) with oral exposure to DCH. In the high dose group (500 mg/kg bw/d) several adverse effects were observed like reduced body weights and body weight gain, haematological and clinical biochemistry findings, macroscopic and microscopic findings in liver, lung and adrenal glands. No mortality was observed during the study (highest dose tested 500 mg/kg bw/day).
DNEL derivation:
Basis NOAEL: 150 mg/kg bw/day from combined repeated dose reproduction/developmental screening oral toxicity study (OECD422; males 31 and females approx. 45 days of oral application)
As no specific values on dermal and oral absorption are available-->therefore default assumption for oral absorption: 100 %
Assumption: no data on the dermal absorption of the members of the amine heads category are available, in a conservative manner it is assumed that dermal absorption does not exceed oral absorption; therefore no correction for absorption has to be made for route-to-route extrapolation
Assessment factors:
· Interspecies differences: 4 (allometric scaling); 2.5 (remaining differences)
· Intraspecies differences: 5
· Differences in duration of exposure : 2 (sub-chronic to chronic; factor of 2 is thought to be sufficiently conservative as the starting NOAEL was obtained in an oral gavage study with DCH, in studies with other category members and other ways of oral application the effect level was at least 4fold higher)
· Issues related to dose-response: 1 (none)
· Quality of whole database: 1 (no deficiencies)
--> Overall assessment factor: 100
DNEL = 150 mg/kg bw/day/100
DNEL = 1.5 mg/kg bw/day
Worker DNELLong-termfor inhalation route, local effects
In a subacute inhalation toxicity study male rats were exposed for 6 hours per day and overall 10times within two weeks to an aerosol/vapour mixture of the test material (i.e. MPMD). Concentrations used were 0, 9.2, 59 and 250 mg/m³ (analytical). Systemic effects and macroscopic lesions of the lung were obvious in the lung were observed in the high dose group. Microscopically exposure-related lesions were confined to the respiratory tract and were dose related. In the 50 and 250 mg/m3groups, lesions were observed in the nose, trachea, larynx/pharynx, and lung. These lesions were mainly minimal to mild in the 50 mg/m3group and mild to moderate in the 250 mg/m3group. Within the low dose group minimal to mild inflammation of the nasal epithelium was observed. Due to the fact that local effects on the respiratory tract were seen in all concentration groups tested and these effects were clearly concentration related a no observed adverse effect level could not be determined. The LOAEC of this study with MPMD was established to be 9.2 mg/m³. The results of this study where confirmed using another amine of the Amine heads category (i.e. DCH). In a study with the same study design, the local irritating effects on the upper respiratory effect were obvious also at the lowest dose group tested, thus the LOAEC = 10 mg/m³. In a subchronic study with HMD-dihydrochloride (HDDC = salt of HMD, which is another member of the amine heads category; inhalation exposure of rats 6h/day, 5d/week for 13 weeks) also local respiratory effects were critical. Under the test conditions, the NOAEC (HDDC) = 16 mg/m³/day for local respiratory damage (nasal respiratory epithelium degeneration), corresponding to a NOAEC (HMD) = 10 mg/m³/day. In another subchronic inhalation toxicity study with rats, the animals were repeatedly exposed to aqueous Hexamethylene Diamine (HMD) aerosol for six hours per day, five days per week at mean analytical concentrations of 0, 12.8, 51 and 215 mg/m³. Under the test conditions, no systemic effects were observed related to the treatment with HMD. The significant local irritation of respiratory tract, inducing clinical signs, was observed at the two highest concentrations tested. The NOAEC in male and female rats exposed by whole-body inhalation was 12.8 mg HMD/m³.
The NOAEC of the study with HMD-dihydrochloride is not considered adequate as starting point for DNEL derivation as the study was conducted with the less irritating HMD-dihydrochloride instead of the amine. However it can be used as supporting evidence for verifying the local irritating nature of all members of the amine heads category and that the effect is not crucially time dependent either - therefore no assessment factor was used for differences in duration of exposure.
DNEL derivation:
Basis LOAEC: 9.2 mg/m³ from 14 days toxicity study after aerosol/vapour exposure
Effects: dose dependent effects seen on the upper respiratory tract (e.g. nasal lesions) which were from minimal to moderate severity and were reversible within the 14-day recovery period
No correction of LOAEC was performed as local irritating effects are concentration dependent and are independent of the absorbed dose.
Assessment factors:
· Interspecies differences: no allometric scaling, 2.5 (remaining differences)
· Intraspecies differences: 5
· Differences in duration of exposure: 1 (no additional factor is required for exposure duration since the effect observed is not dependent on the time of exposure)
· Issues related to dose-response: 3 (starting point is LOAEC instead of NOAEC)
· Quality of whole database: 1 (no deficiencies)
--> Overall assessment factor: 37.5
DNEL = 9.2 mg/m³/37.5
DNEL = 245.3 µg/m³ = 0.245 mg/m³ ~ 0.25 mg/m³
Worker DNELacute/short termfor inhalation route, local effects
As an acute toxicity hazard has been identified (leading to C&L) a DNEL for peak exposure has to be derived. Ideally sub-lethal toxicity should be the starting point rather than mortality. In our case from the acute inhalation toxicity studies only information on mortality could be extracted as there were no detailed descriptions on pathological findings included. Therefore repeated-dose data from the sub-acute inhalation studies is thought to better characterize the acute hazard originating from the toxicological profile of the substances building this category.
Effects after repeated application of the submission substance by inhalation to rats were restricted to the respiratory tract. Therefore, an acute DNEL inhalation for local effects was established from the WORKER DNEL LONG-TERM FOR INHALATION ROUTE, LOCAL EFFECTS by using a multiplying factor of 2 considering that the observed adverse effects are mainly driven by the exposure concentration of the submission substance with respect to its corrosive properties.
DNEL: 245 µg/m³ *2 = 490 µg/m³ = 0.49 mg/m³ ~ 0.5 mg/m³
General Population - Hazard via inhalation route
Systemic effects
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.125 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Dose descriptor:
- LOAEC
- AF for dose response relationship:
- 3
- Justification:
- starting point is LOAEC instead of NOAEC
- AF for differences in duration of exposure:
- 1
- Justification:
- no additional factor is required for time duration since the effect observed is not dependent on the time of exposure
- AF for interspecies differences (allometric scaling):
- 1
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- Justification:
- no deficiencies
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.25 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.75 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):
- 200
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- no data on the dermal absorption of the members of the amine heads category are available, in a conservative manner it is assumed that dermal absorption does not exceed oral absorption; therefore no correction for absorption has to be made for route-to-route extrapolation
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 2
- Justification:
- sub-chronic to chronic; factor of 2 is thought to be sufficiently conservative as the starting NOAEL was obtained in an oral gavage study with DCH, in studies with other category members and other ways of oral application the effect level was at least 4fold higher
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- Justification:
- no deficiencies
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.75 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):
- 200
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 2
- Justification:
- sub-chronic to chronic; factor of 2 is thought to be sufficiently conservative as the starting NOAEL was obtained in an oral gavage study with DCH, in studies with other category members and other ways of oral application the effect level was at least 4fold higher
- AF for interspecies differences (allometric scaling):
- 4
- AF for other interspecies differences:
- 2.5
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- Justification:
- no deficiencies
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Oral
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Additional information - General Population
General population DNELLong-termfor dermal route, systemic effects
No long-term toxicity study with dermal exposure is available for the members of this category. Therefore the DNEL long-term, dermal exposure, systemic effects is derived by route-to-route extrapolation from a toxicity study with oral exposure. The most sensitive NOAEL for this category was the NOAEL of 150 mg/kg bw/day identified in the Combined repeated dose reproduction and developmental toxicity study (OECD 422) with oral exposure to DCH. In the high dose group (500 mg/kg bw/d) several adverse effects were observed like reduced body weights and body weight gain, haematological and clinical biochemistry findings, macroscopic and microscopic findings in liver, lung and adrenal glands. No mortality was observed during the study (highest dose tested 500 mg/kg bw/day).
DNEL derivation:
Basis NOAEL: 150 mg/kg bw/day from combined repeated dose reproduction/developmental screening oral toxicity study (OECD422; males 31 and females approx. 45 days of oral application)
As no specific values on dermal and oral absorption are availableàtherefore default assumption for oral absorption: 100 %
Assumption: no data on the dermal absorption of the members of the amine heads category are available, in a conservative manner it is assumed that dermal absorption does not exceed oral absorption; therefore no correction for absorption has to be made for route-to-route extrapolation
Assessment factors:
· Interspecies differences: 4 (allometric scaling), 2.5 (remaining differences)
· Intraspecies differences: 10
· Differences in duration of exposure: 2 (sub-chronic to chronic)
· Issues related to dose-response: 1 (none)
· Quality of whole database: 1 (no deficiencies)
--> Overall assessment factor: 200
DNEL = 150 mg/kg bw/day / 200
DNEL = 0.75 mg/kg bw/day
General population DNELlong-termfor inhalation route, local effects
In a subacute inhalation toxicity study male rats were exposed for 6 hours per day and overall 10times within two weeks to an aerosol/vapour mixture of the test material (i.e. MPMD). Concentrations used were 0, 9.2, 59 and 250 mg/m³ (analytical). Systemic effects and macroscopic lesions of the lung were obvious in the lung were observed in the high dose group. Microscopically exposure-related lesions were confined to the respiratory tract and were dose related. In the 50 and 250 mg/m3groups, lesions were observed in the nose, trachea, larynx/pharynx, and lung. These lesions were mainly minimal to mild in the 50 mg/m3group and mild to moderate in the 250 mg/m3group. Within the low dose group minimal to mild inflammation of the nasal epithelium was observed. Due to the fact that local effects on the respiratory tract were seen in all concentration groups tested and these effects were clearly concentration related a no observed adverse effect level could not be determined. The LOAEC of this study with MPMD was established to be 9.2 mg/m³. The results of this study where confirmed using another amine of the Amine heads category (i.e. DCH). In a study with the same study design, the local irritating effects on the upper respiratory effect were obvious also at the lowest dose group tested, thus the LOAEC = 10 mg/m³. In a subchronic study with HMD-dihydrochloride (HDDC = salt of HMD, which is another member of the amine heads category; inhalation exposure of rats 6h/day, 5d/week for 13 weeks) also local respiratory effects were critical. Under the test conditions, the NOAEC (HDDC) = 16 mg/m³/day for local respiratory damage (nasal respiratory epithelium degeneration), corresponding to a NOAEC (HMD) = 10 mg/m³/day.
In another subchronic inhalation toxicity study with rats, the animals were repeatedly exposed to aqueous Hexamethylene Diamine (HMD) aerosol for six hours per day, five days per week at mean analytical concentrations of 0, 12.8, 51 and 215 mg/m³. Under the test conditions, no systemic effects were observed related to the treatment with HMD. The significant local irritation of respiratory tract, inducing clinical signs, was observed at the two highest concentrations tested. The NOAEC in male and female rats exposed by whole-body inhalation was 12.8 mg HMD/m³.
The NOAEC of the study with HMD-dihydrochloride is not considered adequate as starting point for DNEL derivation as the study was conducted with the less irritating HMD-dihydrochloride instead of the amine. However it can be used as supporting evidence for verifying the local irritating nature of all members of the amine heads category and that the effect is not crucially time dependent either - therefore no assessment factor was used for differences in duration of exposure.
DNEL derivation:
Basis LOAEC: 9.2 mg/m³ from 14 days toxicity study after aerosol/vapour exposure
Effects: dose dependent effects seen on the upper respiratory tract (e.g. nasal lesions) which were from minimal to moderate severity and were fully reversible within the 14-day recovery period
No correction of LOAEC was performed as local irritating effects are concentration dependent and are independent of the absorbed dose.
Assessment factors:
· Interspecies differences: no allometric scaling, 2.5 (remaining differences)
· Intraspecies differences: 10
· Differences in duration of exposure: 1 (no additional factor is required for exposure duration since the effect observed is not dependent on the time of exposure)
· Issues related to dose-response: 3 (starting point is LOAEC instead of NOAEC)
· Quality of whole database: 1 (no deficiencies)
--> Overall assessment factor: 75
DNEL = 9.2 mg/m³/75
DNEL = 123 µg/m³ ~ 125 µg/m³ = 0.125 mg/m³
General population DNELacute/short termfor inhalation route, local effects
As an acute toxicity hazard has been identified (leading to C&L) a DNEL for peak exposure has to be derived. Ideally sub-lethal toxicity should be the starting point rather than mortality. In our case from the acute inhalation toxicity studies only information on mortality could be extracted as there were no detailed descriptions on pathological findings included. Therefore repeated-dose data from the sub-acute inhalation studies is thought to better characterize the acute hazard originating from the toxicological profile of the substances building this category.
Effects after repeated application of the submission substance by inhalation to rats were restricted to the respiratory tract. Therefore, an acute DNEL inhalation for local effects was established from the GENERAL POPULATION DNEL LONG-TERM FOR INHALATION ROUTE, LOCAL EFFECTS by using a multiplying factor of 2 considering that the observed adverse effects are mainly driven by the exposure concentration of the submission substance with respect to its corrosive properties.
DNEL: 125 µg/m³ *2 = 250 µg/m³ = 0.25 mg/m³
General population DNELLong-termfor oral route, systemic effects
The DNEL long-term, oral exposure, systemic effects is derived from a toxicity study with oral exposure. The most sensitive NOAEL for this category was the NOAEL of 150 mg/kg bw/day identified in the Combined repeated dose reproduction and developmental toxicity study (OECD 422) with oral exposure to DCH. In the high dose group (500 mg/kg bw/d) several adverse effects were observed like reduced body weights and body weight gain, haematological and clinical biochemistry findings, macroscopic and microscopic findings in liver, lung and adrenal glands. No mortality was observed during the study (highest dose tested 500 mg/kg bw/day).
DNEL derivation:
Basis NOAEL: 150 mg/kg bw/day from combined repeated dose reproduction/developmental screening oral toxicity study (OECD422; males 31 and females approx. 45 days of oral application)
As no specific values on oral absorption are availableàtherefore default assumption for oral absorption: 100 %
Assessment factors:
· Interspecies differences: 4 (allometric scaling), 2.5 (remaining differences)
· Intraspecies differences: 10
· Differences in duration of exposure: 2 (sub-chronic to chronic)
· Issues related to dose-response: 1 (none)
· Quality of whole database: 1 (no deficiencies)
-->Overall assessment factor: 200
DNEL = 150 mg/kg bw/day / 200
DNEL = 0.75 mg/kg bw/day
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

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