Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 223-055-4 | CAS number: 3710-84-7
- 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

Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics, other
- Remarks:
- in silico
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- See enclosed files
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
- Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance on QSARs R.6
- Qualifier:
- according to guideline
- Guideline:
- other: REACH Guidance on IR&CSA, Chapter R.14, Occupational exposure assessment Update to change the scope of the guidance from exposure estimation to exposure assessment
- Version / remarks:
- August 2016
- Principles of method if other than guideline:
- pkCSM uses graph-based signatures to develop predictive models of central ADME properties. pkCSM performs as well or better than current methods.
- Specific details on test material used for the study:
- SMILES:
C(C)N(O)CC - Type:
- absorption
- Results:
- Intestinal absorption (human): 92.784%
- Type:
- distribution
- Results:
- VDss (human) (log L/kg): 0.242
- Type:
- distribution
- Results:
- Fraction unbound (human) : 0.382
- Type:
- distribution
- Results:
- BBB permeability (log BB): 0.571
- Type:
- distribution
- Results:
- CNS permeability (log PS): -3.485
- Type:
- excretion
- Results:
- Total Clearance (log ml/min/kg): 1.602
- Type:
- excretion
- Results:
- Renal OCT2 substrate: no
Reference
Property |
Model Name |
Predicted Value |
Unit |
Absorption |
Water solubility |
-0.005 |
Numeric (log mol/L) |
Absorption |
Caco2 permeability |
1.469 |
Numeric (log Papp in 10-6cm/s) |
Absorption |
Intestinal absorption (human) |
100 |
Numeric (% Absorbed) |
Absorption |
Skin Permeability |
-2.866 |
Numeric (log Kp) |
Absorption |
P-glycoprotein substrate |
Yes |
Categorical (Yes/No) |
Absorption |
P-glycoprotein I inhibitor |
No |
Categorical (Yes/No) |
Absorption |
P-glycoprotein II inhibitor |
No |
Categorical (Yes/No) |
Distribution |
VDss (human) |
-0.102 |
Numeric (log L/kg) |
Distribution |
Fraction unbound (human) |
0.751 |
Numeric (Fu) |
Distribution |
BBB permeability |
0.053 |
Numeric (log BB) |
Distribution |
CNS permeability |
-2.859 |
Numeric (log PS) |
Metabolism |
CYP2D6 substrate |
No |
Categorical (Yes/No) |
Metabolism |
CYP3A4 substrate |
No |
Categorical (Yes/No) |
Metabolism |
CYP1A2 inhibitior |
No |
Categorical (Yes/No) |
Metabolism |
CYP2C19 inhibitior |
No |
Categorical (Yes/No) |
Metabolism |
CYP2C9 inhibitior |
No |
Categorical (Yes/No) |
Metabolism |
CYP2D6 inhibitior |
No |
Categorical (Yes/No) |
Metabolism |
CYP3A4 inhibitior |
No |
Categorical (Yes/No) |
Excretion |
Total Clearance |
0.522 |
Numeric (log ml/min/kg) |
Excretion |
Renal OCT2 substrate |
No |
Categorical (Yes/No) |
Toxicity |
AMES toxicity |
No |
Categorical (Yes/No) |
Toxicity |
Max. tolerated dose (human) |
1.133 |
Numeric (log mg/kg/day) |
Toxicity |
hERG I inhibitor |
No |
Categorical (Yes/No) |
Toxicity |
hERG II inhibitor |
No |
Categorical (Yes/No) |
Toxicity |
Oral Rat Acute Toxicity (LD50) |
2.384 |
Numeric (mol/kg) |
Toxicity |
Oral Rat Chronic Toxicity (LOAEL) |
1.466 |
Numeric (log mg/kg_bw/day) |
Toxicity |
Hepatotoxicity |
No |
Categorical (Yes/No) |
Toxicity |
Skin Sensitisation |
No |
Categorical (Yes/No) |
Toxicity |
T.Pyriformistoxicity |
-0.937 |
Numeric (log ug/L) |
Toxicity |
Minnow toxicity |
2.611 |
Numeric (log mM) |
Description of key information
No in vivo/vitro data is available for the determination of toxicokinetics, metabolism and distribution of diethylhydroxylamine by the oral, dermal or inhalation routes.
Absorption
The assessment of the toxicokinetics of DEHA is based on the available toxicological data and its physicochemical properties as suggested by the REACH Guidance Chapter R.7c.
Diethylhydroxylamine is a liquid with a molecular weight of 89.16 g/mol and a vapour pressure of 5300 Pa (20°C). It soluble at 450 g/L at 20 °C in water, the log Kow is -0.17 and the pKa is 5.61 at 25°C. From its physico-chemical properties and the evidence for systemic availability from oral, dermal and/or inhalation acute and/or subacute studies, diethylhydroxylamine is expected to be absorbed by the oral, dermal and inhalation routes. However QSAR models were used below to evaluate the oral and dermal absorptions
.
Dermal absorption
DEHA have a water solubility above 10 g/L and a log P value below 0, therefore, DEHA may be too hydrophilic to cross the lipid rich environment of the stratum corneum and dermal uptake will be low. In addition, DEHA is too volatile (vapour pressures above 100-10,000 Pa) to penetrate further the stratum corneum. Therefore, the dermal rate of absorption of DEHA was estimated using the IH SkinPerm model (v2.04). For an instantaneous skin deposition of 1000 mg or a deposition over time of 1mg/cm²/h for 8 h, the absorption rates after 8 hours were estimated to be 5.5 and 8.8 %, respectively. Moreover the substance is not a skin irritant; therefore no increase of skin absorption is expected.
Therefore, according to the REACH Guidance, a default value of 10% dermal absorption will be used.
Oral absorption
DEHA molecule contains 2 ionisable groups (-OH and -NH2) which are favorable to an oral absorption. Based on the high solubility value in water and its low MW, DEHA may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. The log Kow is also favourable for absorption by passive diffusion.
The rate of oral absorbtion was estimated at 100% by the pkCSM method (Pires et al, 2015). The high absorption rate is further supported by the acute and repeated oral toxicity studies.
Therefore, according to the REACH Guidance, a default value of 100% oral absorption will be used.
Inhalation exposure
Based on the vapor pressure of DEHA, inhalation exposure is likely. The log Kow value is favourable for absorption directly across the respiratory tract epithelium by passive diffusion. The inhalation absorption is further supported by the signs of systemic toxicity observed in an inhalation 28-day study.
Therefore, according to the REACH Guidance, a default value of 100% inhalation absorption will be used.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
- Absorption rate - oral (%):
- 100
- Absorption rate - dermal (%):
- 10
- Absorption rate - inhalation (%):
- 100
Additional information
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.
