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EC number: 411-700-4 | CAS number: 140921-24-0 HÄRTER VERSUCHSPRODUKT LS 2959E; HÄRTER VP LS 2959E
- 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

Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics, other
- Type of information:
- other: Expert statement
- Adequacy of study:
- key study
- Study period:
- 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Expert statement, no study available
Data source
Reference
- Reference Type:
- other: Expert statement
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Expert statement
- GLP compliance:
- no
Test material
- Reference substance name:
- 1,6-hexanediyl-bis(2-(2-(1-ethylpentyl)-3-oxazolidinyl)ethyl)carbamate
- EC Number:
- 411-700-4
- EC Name:
- 1,6-hexanediyl-bis(2-(2-(1-ethylpentyl)-3-oxazolidinyl)ethyl)carbamate
- Cas Number:
- 140921-24-0
- Molecular formula:
- C32H62N4O6
- IUPAC Name:
- 2-[3-(heptan-3-yl)-1,2-oxazolidin-2-yl]ethyl N-{6-[({2-[3-(heptan-3-yl)-1,2-oxazolidin-2-yl]ethoxy}carbonyl)amino]hexyl}carbamate
- Test material form:
- liquid
Constituent 1
Test animals
- Details on test animals or test system and environmental conditions:
- not applicable
Administration / exposure
- Details on exposure:
- not applicable
- Duration and frequency of treatment / exposure:
- not applicable
- No. of animals per sex per dose / concentration:
- not applicable
- Positive control reference chemical:
- not applicable
- Details on study design:
- not applicable
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Incozol EH was shown to immediately hydrolyse when getting in contact with water. Therefore, bioavailability after oral exposure was assessed only for the hydrolysis products 2-ethylhexanal and “fully hydrolysed Incozol EH”. Based on physico-chemical properties especially water solubility and log Pow value of “fully hydrolysed Incozol EH”, dissolution in the gastro-intestinal fluids and contact with the mucosal surface might occur and may allow direct uptake into the systemic circulation through aqueous pores or via carriage of the molecules across the membrane with the bulk passage of water. Passive diffusion might be a preferred entry route of 2-ethylhexanal into systemic circulation as it has lipophilic properties and a low water solubility. Clinical signs after a single administration of 2000 mg Incozol EH/kg bw in 1,2-propanediol in an acute oral toxicity study performed on rats were considered to be treatment-related and not associated to bioavailability of the test item. However, long-term administration of high doses of Incozol EH in a 28-day repeated dose toxicity study on rats indicated that the compound or rather its hydrolysis products became bioavailable.
Based on the vapour pressure of approximately 0.001 Pa at 20 °C Incozol EH is not expected to become airborne in its vapour form. However, if Incozol EH is degraded hydrolytically, inhalation exposure of 2-ethylhexanal, one of the hydrolysis products, could not be excluded due to its higher vapour pressure in comparison to Incozol EH itself. If the substance would reach the lungs, absorption directly across the respiratory tract epithelium by passive diffusion is likely to occur due to its log Pow value (3.07) and water solubility (450 mg/L).
Based on the molecular weight and physico–chemical properties of Incozol EH dermal penetration of the substance might be slow. It is general accepted that if a compound’s molecular weight is above 500 g/mol and water solubility falls between 1-100 mg/L, absorption can be anticipated to be low to moderate. These assumptions based on the physico-chemical properties are further supported by the results achieved from a GPMT which revealed that Incozol EH has skin sensitising properties and is, thus, absorbed dermally to a certain extent. - Details on distribution in tissues:
- Assuming that 2-ethylhexanal as one of the hydrolysis products is absorbed into the body following oral intake, it may be distributed into the interior part of the cells by passive diffusion due to its lipophilic properties and in turn the intracellular concentration may be higher than extracellular concentration particularly in adipose tissues. Direct transport through aqueous pores is likely to be an entry route to the systemic circulation of “fully hydrolysed Incozol EH” due to its higher water solubility compared to 2-ethylhexanal.
Based on its log Pow and BCF value Incozol EH might have a weak bioaccumulation potential. However, as it immediately hydrolyses when getting in contact with water bioaccumulation in the human body can be excluded. This assumption is supported by the lower BCF values of the hydrolysis products compared to Incozol EH.
- Details on excretion:
- As discussed above, Incozol EH will be hydrolysed after being in contact with an aqueous solution and will probably not be excreted in its non-hydrolysed form. The degradation product “fully hydrolysed Incozol EH” might be biliary excreted due to its molecular weight (>300 g/mol in rat). Renal excretion might be a preferred excretion pathway of degradation products of “fully hydrolysed Incozol EH” described above. Oxidation and conjugation products of 2-ethylhexanal were shown to be excreted via urine (English et al, 1998).
Metabolite characterisation studies
- Details on metabolites:
- Based on the structure of the molecule, Incozol EH immediately degraded hydrolytically after being in contact with an aqueous solution. The first degradation product “fully hydrolysed Incozol EH” may be further degraded hydrolytically to a certain extend to diethanolamine, 1,6-hexanediamine and carbon dioxide under basic conditions. 2-ethylhexanal is estimated to be oxidised to 2-ethylhexanoic acid which was shown to be conjugated with glucuronic acid or further oxidised to 2-ethyl-1,6-hexanedioic acid, 2-ethyl-6-hydroxyhexanoic acid and 2-ethylketohexanoic acid (English et al, 1998). No metabolic activation of Incozol EH and its hydrolysis products is expected as indicated by the negative in vitro genotoxicity assays in the presence of S9 mix.
Bioaccessibility (or Bioavailability)
- Bioaccessibility (or Bioavailability) testing results:
- Taken together, physico-chemical properties and experimental data indicate a low bioavailability of Incozol EH via oral and dermal route. Bioavailability after inhalation exposure is considered to be unlikely due to the low vapour pressure of the non-hydrolysed compound.
Applicant's summary and conclusion
- Conclusions:
- Based on physico-chemical characteristics, particularly water solubility and octanol-water partition coefficient absorption via oral and inhalation route is expected to be low. However, slow dermal absorption could not be excluded. Incozol EH is immediately hydrolysed into “fully hydrolysed Incozol EH” and 2-ethylhexanal. If absorbed, passive diffusion and active transport through aqueous pores is likely to be an entry routes to the systemic circulation. No metabolic activation of Incozol EH and its hydrolysis products is expected. Excretion via faeces is assumed to be the main excretion pathway of “fully hydrolysed Incozol EH” due to its molecular weight. Oxidation and conjugation products of 2-ethylhexanal were shown to be excreted via urine. Based on hydrolytical conversion of Incozol EH bioaccumulation is not likely to occur based on physico-chemical properties of the hydrolysis products.
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