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EC number: 433-260-2 | CAS number: 168253-59-6
- 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:
- 50 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):
- 7
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 353 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- A factor 2 is suggested by the Guidance Document R.8 (ECHA, 2012) for the oral-to-inhalation extrapolation, but justified deviations are possible. Concerning inhalation, rats are in general more sensitive compared to humans as the rat’s ventilation frequency is higher. Also, anatomical differences as well as air flow patterns between rodents and humans are to be taken into account (e.g. in case of effects at the olfactory epithelium; see Frederick et. al., 1998, Harkema, 1991). Therefore a factor 1 is chosen for route extrapolation. This provides sufficient protection, taking additionally into account that the respiratory tract’s toxicity of the substance is characterised by a low potential for upper respiratory tract irritation and no systemic toxicity at all could be observed and that the acute studies that were performed with oral and inhalation route of exposure did not give evidence for a route specific systemic toxicity.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1.4
- Justification:
- For extrapolation of exposure duration subchronic to chronic: The suggested factor 2 for extrapolation of exposure duration subchronic (90 days) to chronic was corrected for difference in number of days of exposure per week (7 days/week in animal study versus 5 days/week for workers). Thus, the total AF is 2 * 0.7 = 1.4.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Already covered by correction of starting point. Correction was according to Figure R.8 in the Guidance Document R.8 (ECHA, 2012): Corrected inhalatory NOAEC = oral NOAEL * 1/0.38 kg/m³ * 6.7 m³/10 m³.
- AF for other interspecies differences:
- 1
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, but justified deviations are possible. The substance showed no evidence of systemic availability or toxicity in an acute oral or aerosol inhalation study. In a subacute (OECD 407) and a subchronic (OECD 408) study mild kidney effects (cortical tubular vacuolation) were seen at 1000 mg/kg. These findings were considered to be due to a storage process, and were shown to be be reversible in a two-weeks post exposure recovery in the subacute study. The DNEL derivation based on a NOAEL of 200 mg/kg bw/day with only mild effects at the next higher dose of 1000 mg/kg bw/day is already very conservative, therefore no correction for remaining interspecies differences has to be done, resulting in a factor 1.
- AF for intraspecies differences:
- 5
- AF for the quality of the whole database:
- 1
- Justification:
- The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 200 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
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:
- 7 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):
- 28
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 200 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Absorption oral compared to dermal assumed to be identical
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1.4
- Justification:
- For extrapolation of exposure duration subchronic to chronic: The suggested factor 2 for extrapolation of exposure duration subchronic (90 days) to chronic was corrected for difference in number of days of exposure per week (7 days/week in animal study versus 5 days/week for workers). Thus, the total AF is 2 * 0.7 = 1.4.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Differences rat vs. human
- AF for other interspecies differences:
- 1
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, but justified deviations are possible. The substance showed no evidence of systemic availability or toxicity in an acute oral or aerosol inhalation study. In a subacute (OECD 407) and a subchronic (OECD 408) study mild kidney effects (cortical tubular vacuolation) were seen at 1000 mg/kg. These findings were considered to be due to a storage process, and were shown to be be reversible in a two-weeks post exposure recovery in the subacute study. The DNEL derivation based on a NOAEL of 200 mg/kg bw/day with only mild effects at the next higher dose of 1000 mg/kg bw/day is already very conservative, therefore no correction for remaining interspecies differences has to be done, resulting in a factor 1.
- AF for intraspecies differences:
- 5
- AF for the quality of the whole database:
- 1
- Justification:
- The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
Acute/short term exposure
- Hazard assessment conclusion:
- no DNEL required: short term exposure controlled by conditions for long-term
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
The available studies show that the acute toxicity of aspartic acid, N,N'-(2-methyl-1,5-pentanediyl)bis-, 1,1',4,4'-tetraethyl ester is low (LD50 > 2000 mg/kg bw; LC50 > 4923 mg/m³). It is noteworthy that there does not appear to be any route-dependent systemic toxicity by reviewing the results of the acute oral (Stropp, 1999a) and inhalation (Pauluhn, 1999) studies for this substance.
Slight dermal (Leuschner, 1999a) and respiratory tract (Pauluhn, 1999) irritation were observed in the acute studies but are not considered sufficient to influence the determination of a DNEL. No dermal sensitisation potential was found (Stropp, 1999b).
Generally, repeated exposure studies are considered to be more reliable for defining the toxicity profile of chemicals and extrapolating the results to human exposure regimens. Because of the absence of any differentiating route-dependent systemic toxicity revealed by the acute studies, the low irritation potential, and their greater relevance in predicting human toxicity to chemicals, the subchronic oral toxicity study (Schladt, 2012) was chosen as key study for defining both the DNELs for inhalation and for dermal exposure. Thus, the NOAEL of 200 mg/kg bw/day was considered to be the point of departure.
The DNELlong-term, systemic for workers for oral/dermal exposure and for inhalative exposure is derived as follows:
DNELlong-term, systemic for oral/dermal exposure for workers using default extrapolation factors1:
Oral NOAEL (rat) from a subacute toxicity study: 200 mg/kg bw/day
Absorption oral compared to dermal assumed to be identical: 1
For interspecies differences rat vs. human (allometric scaling): 4
2For remaining interspecies differences: 1
For intraspecies differences in workers: 5
3For extrapolation of exposure duration subchronic to chronic: 1.4
For reliability of dose-response: 1
For quality of whole database: 1
Overall factor: 28
Worker DNELlong-term, systemic for oral/dermal exposure: 7 mg/kg bw/day
DNELlong-term, systemic for inhalative exposure for workers using default extrapolation factors1:
Oral NOAEL (rat) from a subacute toxicity study: 200 mg/kg bw/day
Correction of the starting point according to Figure R.8 -3 in the Guidance Document R.8 (ECHA, 2012):
Corrected inhalatory NOAEL = oral NOAEL * 1/0.38 m³/kg * 6.7m³/10m³
Corrected inhalatory NOAEL for workers = 353 mg/m³
4Absorption oral compared to inhalative: 1
For interspecies differences rat vs. human (allometric scaling): 1 (already covered by correction of starting point)
2For remaining interspecies differences: 1
For intraspecies differences in workers: 5
3For extrapolation of exposure duration subacute to chronic: 1.4
For reliability of dose-response: 1
For quality of whole database: 1
Overall factor: 7
Worker DNELlong-term, systemic for inhalative exposure: 50 mg/m³
1: default factors according to Guidance Document R.8 (ECHA, 2012)
2: A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, but justified deviations are possible. The substance showed no evidence of systemic availability or toxicity in an acute oral and an aerosol inhalation study. The DNEL derivation based on a NOAEL of 200 mg/kg bw/day with only mild effects at the next higher dose of 1000 mg/kg bw/day (limit dose) is already very conservative, therefore no correction for remaining interspecies differences has to be done, resulting in a factor 1.
3: The suggested factor 6 for extrapolation of exposure duration subchronic to chronic was corrected for difference in number of days of exposure per week (7 days/week in animal study versus 5 days/week for workers). Thus, the total AF is 2 * 0.7 = 1.4.
4: A factor 2 is suggested bythe Guidance Document R.8 (ECHA, 2012) for the oral-to-inhalation extrapolation, but justified deviations are possible. Concerning inhalation, rats are in general more sensitive compared to humans as the rat’s ventilation frequency is higher. Also, anatomical differences as well as air flow patterns between rodents and humans are to be taken into account (e.g. in case of effects at the olfactory epithelium; see Frederick et. al., Toxicol. Appl. Pharmacol. 152, 211 -231, 1998; Harkema, Toxicol. Pathol. 19, 4, 321 -336, 1991). Therefore a factor 1 is chosen for route extrapolation. This provides sufficient protection, taking additionally into account that the respiratory tract’s toxicity of the substance is characterised by a low potential for upper respiratory tract irritation and no systemic toxicity at all could be observed (Pauluhn, 1999) and that the acute studies that were performed with oral and inhalation route of exposure did not give evidence for a route specific systemic toxicity.
Due to the slight respiratory irritation potential of the substance shown in an acute inhalation study there is no need to derive an acute DNEL for local toxicity. It is proposed to limit exposure peaks to a factor of 4. This approach is in line with the regulatory procedure in Germany (see Technical Rule for Hazardous Substances 900, published by the German Federal Ministry of Labour and Social Affairs) and also with ECHA Guidance (2012), Chapter R.8., Appendix R.8 -8, box 6.
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:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 20
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 174 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- A factor 2 is suggested by the Guidance Document R.8 (ECHA, 2012) for the oral-to-inhalation extrapolation, but justified deviations are possible. Concerning inhalation, rats are in general more sensitive compared to humans as the rat’s ventilation frequency is higher. Also, anatomical differences as well as air flow patterns between rodents and humans are to be taken into account (e.g. in case of effects at the olfactory epithelium; see Frederick et. al., 1998, Harkema, 1991). Therefore a factor 1 is chosen for route extrapolation. This provides sufficient protection, taking additionally into account that the respiratory tract’s toxicity of the substance is characterised by a low potential for upper respiratory tract irritation and no systemic toxicity at all could be observed and that the acute studies that were performed with oral and inhalation route of exposure did not give evidence for a route specific systemic toxicity.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 2
- Justification:
- For extrapolation of exposure duration subchronic to chronic.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Already covered by correction of starting point. Correction was according to Figure R.8 in the Guidance Document R.8 (ECHA, 2012): Corrected inhalatory LOAEC = oral LOAEL * 1/1.15 m³/kg.
- AF for other interspecies differences:
- 1
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, but justified deviations are possible. The substance showed no evidence of systemic availability or toxicity in an acute oral or aerosol inhalation study. In a subacute (OECD 407) and a subchronic (OECD 408) study mild kidney effects (cortical tubular vacuolation) were seen at 1000 mg/kg. These findings were considered to be due to a storage process, and were shown to be be reversible in a two-weeks post exposure recovery in the subacute study. The DNEL derivation based on a NOAEL of 200 mg/kg bw/day with only mild effects at the next higher dose of 1000 mg/kg bw/day is already very conservative, therefore no correction for remaining interspecies differences has to be done, resulting in a factor 1.
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- Justification:
- The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
Acute/short 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:
- ECHA REACH Guidance
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:
- 2.5 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):
- 80
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 200 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Absorption oral compared to dermal assumed to be identical
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 2
- Justification:
- For extrapolation of exposure duration subchronic to chronic.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Differences rat vs. human
- AF for other interspecies differences:
- 1
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, but justified deviations are possible. The substance showed no evidence of systemic availability or toxicity in an acute oral or aerosol inhalation study. In a subacute (OECD 407) and a subchronic (OECD 408) study mild kidney effects (cortical tubular vacuolation) were seen at 1000 mg/kg. These findings were considered to be due to a storage process, and were shown to be be reversible in a two-weeks post exposure recovery in the subacute study. The DNEL derivation based on a NOAEL of 200 mg/kg bw/day with only mild effects at the next higher dose of 1000 mg/kg bw/day is already very conservative, therefore no correction for remaining interspecies differences has to be done, resulting in a factor 1.
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- Justification:
- The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
Acute/short 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:
- ECHA REACH Guidance
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:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 80
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 200 mg/kg bw/day
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 2
- Justification:
- For extrapolation of exposure duration subchronic to chronic.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Differences rat vs. human
- AF for other interspecies differences:
- 1
- Justification:
- A factor 2.5 is suggested by Guidance Document R.8 (ECHA, 2012) for remaining interspecies differences, but justified deviations are possible. The substance showed no evidence of systemic availability or toxicity in an acute oral or aerosol inhalation study. In a subacute (OECD 407) and a subchronic (OECD 408) study mild kidney effects (cortical tubular vacuolation) were seen at 1000 mg/kg. These findings were considered to be due to a storage process, and were shown to be be reversible in a two-weeks post exposure recovery in the subacute study. The DNEL derivation based on a NOAEL of 200 mg/kg bw/day with only mild effects at the next higher dose of 1000 mg/kg bw/day is already very conservative, therefore no correction for remaining interspecies differences has to be done, resulting in a factor 1.
- AF for intraspecies differences:
- 10
- AF for the quality of the whole database:
- 1
- Justification:
- The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
Acute/short 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:
- ECHA REACH Guidance
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
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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