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Diss Factsheets
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EC number: - | CAS number: -
- 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 in vivo
- Type of information:
- experimental study
- Remarks:
- Performed with metabolic degradation product
- Adequacy of study:
- supporting study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 975
Materials and methods
- Objective of study:
- other: ADME
- Principles of method if other than guideline:
- Oral rat ADME studies using [14]C-2-EH
- GLP compliance:
- no
Test material
- Reference substance name:
- 2-ethylhexan-1-ol
- EC Number:
- 203-234-3
- EC Name:
- 2-ethylhexan-1-ol
- Cas Number:
- 104-76-7
- Molecular formula:
- C8H18O
- IUPAC Name:
- 2-ethylhexan-1-ol
Constituent 1
- Specific details on test material used for the study:
- - Analytical purity: not speciifed
- Specific activity (if radiolabelling): not speciifed
- Locations of the label: 2-ethyl[1-14C]hexan-1-ol
- The test item 2-ethylhexan-1-ol is a metabolic degradation product of the substance to be registered. - Radiolabelling:
- yes
- Remarks:
- [14]C
Test animals
- Species:
- rat
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 300 g
- Individual metabolism cages: not speciifed
- Diet: ad libitum
- Water: ad libitum
- Housing: The animals were held in metabolism cages
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: cottonseed oil, 0.4 mL
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Low dose: 1µCi, 8.8 µg of labelled [14C]-2-EH dissolved in 0.4 mL cottonseed oil
High dose: 1µCi, 8.8 µg of labelled [14C]-2-EH dissolved in 0.4 mL cottonseed oil, additionally 0.1 mL (83.3 mg) of unlabeled 2-EH.
VEHICLE
Amount of vehicle (if gavage): 0.4 mL
- Duration and frequency of treatment / exposure:
- Single dose
Doses / concentrationsopen allclose all
- Dose / conc.:
- 29 other: µg/kg bw
- Remarks:
- labelled 2-EH/ low dose group
- Dose / conc.:
- 278 mg/kg bw/day (actual dose received)
- Remarks:
- unlabelled 2-EH plus 29 µg/kg bw labelled 2-EH/ high dose group
- No. of animals per sex per dose / concentration:
- 2 male rats per dose level
- Control animals:
- no
- Details on dosing and sampling:
- SAMPLING:
CO2 was collected in ethanolamine: cellososolve (1:8). Urine and faeces were collected at hourly intervals. The excreta, an ethanol wash of the cages, the rat hearts, brains, livers, kidneys and the carcass were examined for the radiolabel.
PROCESSING OF URINE:
2 mL of urine were passed through a Dowex 50-H column, 200-400 mesh and eluted with deionised water. Fractions were collected and monitored for radioactivity. Urine fractions from the high dose animals covering the first 18 hours after administration were pooled, made basic and extracted with diethyl ether, then adjusted to pH1 and extracted with diethyl ether. The two extracts were dried and used for characterisation of metabolites.
ANALYSES:
metabolites were separated by GC using FID. Mass spectrometry: chemical ionisation mass spectra and electron impact spectra were taken.
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- 2-Ethylhexanol was efficiently absorbed following oral administration to rats. There were no differences between the low dose (27 µg/kg bw) and the high dose ( 278 mg/kg bw) group.
- Details on excretion:
- - There were no differences between the low dose (27 µg/kg bw) and the high dose ( 278 mg/kg bw) group regarding excretion
- 14C associated with 2-ethyl[1-14C]-hexanol was rapidly excreted in respiratory CO2 (6-7%). The radioactivity reached a peak in less than 2 hours, logarithmic decrease witzh t1/2= 3.5 hrs
- Faeces: nearly complete within 20 hrs; a total of 8.6% of the administered dose eliminated by this route.
- Urine: 25% was excreted within 8 to 10 hrs, approx. 80% after 28 hrs
- Total: 96.1% were excreted after 28 hrs. Cage wash accounted for 2.7%. Only 1.4% was found in the carcasses.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- IDENTIFIED METABOLITES:
2- heptanone, 4-heptanone, CO2. 2-ethyl-5-hydroxyhexanoic acid, 2-ethyl-5-keto-hexanoic acid, 2-ethyl-1,6-hexanedioic acid. unchanged 2-ethylhexanol (approx. 3%)
ADDITIONAL INFORMATION ON METABOLISM
- The amount of label recovered in CO2 matched the amount of unlabelled 2-heptanone plus 4-heptanone recovered from urine, suggesting that both types of metabolites may have been derived from the major urinary metabolite, 2-ethylhexanoix acid, by decarboxylation following partial beta-oxidation. The 14CO2 appeared not to be derived from acetate or by reductive decarboxylation.
- There were no differences between the low dose (27 µg/kg bw) and the high dose ( 278 mg/kg bw) group regarding metabolism
OTHER INFORMATION ON METABOLIC PATHWAYS
- Ethylhexanol was a competitive inhibitor of yeast alcohol dehydrogenase, but a good substrate for the mammalian horse alcohol dehydrogenase.
- Metabolic pathways were suggested as follows:
(i) first step: oxidation of 2-ethyl-hexanol via alcohol dehydrogenase and aldehyde dehydrogenase to 2-ethyl-hexanoic acid (2-EHA)
(iia) omega-oxidation of 2-EHA, leading to the di-acid
(iib) omega-1 -oxidation of 2-EHA, leading to 5-hydroxy and 5-keto-2-ethylhexanoic acid
(iic) ß-oxidation, leading to the 2-keto- and 4-keto-pentanones and CO2.
Any other information on results incl. tables
Excretion of [14-C] within 28 hrs after oral administration to rats (% of dose) |
|
CO2 |
6-7 |
Urine |
80-82 |
Faeces |
8-9 |
Total excreted |
96.1 |
Cage wash |
2.7 |
Carcass |
1.4 |
Applicant's summary and conclusion
- Conclusions:
- 2-EH was rapidly absorbed, metabolised, and excreted mainly via urine within 28 hours after oral administartion to rats. Accumulation of 2-EH or its metabolites is unlikely to occur.
- Executive summary:
2-Ethylhexanol was efficiently absorbed following oral administration to rats. 14C associated with 2-ethyl[1-14C]-hexanol was rapidly excreted in respiratory CO2 (6-7%), faeces (8-9%) and urine (80-82%), with essentially complete elimination by 28 h after administration. There was no difference between the low or high dose (9 µg/kg bw and 278 mg/kg bw, resp.). The major metabolite is 2-ethylhexanoic acid, which appears in urine; alternatively it may also be further metabolised by either ß-oxidation or omega and omega-1 oxidation. Only 3% of the 2-ethylhexanol are excreted unchanged. Overall, 2-EH was rapidly absorbed, metabolised, and excreted mainly via urine within 28 hours following the oral administration to rats. Accumulation of 2-EH or its metabolites is unlikely to occur (Albro, 1975).
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