Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
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: 201-148-0 | CAS number: 78-83-1
- 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 in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Objective of study:
- metabolism
- Principles of method if other than guideline:
- In an effort to understand the elimination kinetics of aliphatic alcohols found in alcoholic beverages, research was conducted with human subjects.
Test subjects consumed isobutanol in an ethanol/water vehicle over a two hour time period. Blood and urine samples were collected prior to consumption, at the end of the two-hour consumption period, at one, two, eight (urine only), and nine hours after the end of the exposure period. - GLP compliance:
- not specified
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Isobutanol
- Species:
- human
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- oral: drinking water
- Vehicle:
- other: orange juice
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Orange juice was prepared containing 40 % (v/v) ethan-1-ol and 3.75 mg/l 2-methylpropan-1-ol - Duration and frequency of treatment / exposure:
- 2 hours followed by 9 hours of post exposure
- No. of animals per sex per dose / concentration:
- not specified
- Control animals:
- not specified
- Metabolites identified:
- yes
- Details on metabolites:
- isobutyraldehyde and isobutyric acid
Reference
The blood concentrations of isobutanol, isobutyraldehyde, and isobutyric acid were approximately 4, 4, and 17 µmol/L at the end of the consumption period, clearly demonstrating that isobutyric acid was the major metabolite of isobutanol metabolism. While the addition of ethanol to the test beverage definitely altered the rate of isobutanol metabolism (via a competition for metabolic enzymes), the presence of ethanol did not affect how isobutanol was metabolized. Blood levels of isobutanol decreased over the next two hours while the isobutyraldehyde levels slowly increased in the blood. Isobutyric acid levels also decreased after the end of the consumption period. Urinary concentrations of isobutanol peaked at the one-hour postexposure time point. Urinary levels of isobutyraldehyde peaked at the eight hour post-exposure time point. Urinary levels of isobutyric acid peaked at the end of the two-hour exposure period. Urinary levels of propionaldehyde roughly followed those for isobutyraldehyde with peak levels of approximately 8 µmol/L. Urinary levels of propionic acid rose after the exposure period ended with plateau levels between 2 and 8 hours of approximately 60 µmol/L. Urinary levels of succinic acid roughly followed the propionic acid urinary elimination curve with peak levels of approximately 30 µmol/L. A diagram was provided in the paper describing the further metabolism of isobutyric acid, ending with propionic acid. The formation of succinic acid from propionic acid is proposed based on the known intermediate metabolism of propionic acid via the citric acid cycle.
Description of key information
Short description of key information on bioaccumulation potential result:
Absorption
Rapid absorption after inhalative exposition in rats (measurable blood levels after 5 min; Poet 2003) and after oral exposition in rabbits (Saito et al. 1975).
Metabolism
Rapid metabolism to isobutyric acid in rats (blood level of the metabolite peaked 10 min after isobutanol; Poet 2003).
Class I Alcohol Dehydrogenase (ADH) isozymes appear to be the most active for isobutanol metabolism in animals and humans (Sinclair et al. 1990)
Isobutyric acid, isobutyraldehyde and a not fully characterized urinary metabolite coeluted with isovaleric acid were known metabolites of isobutanol (several authors, i.e. Rüdell et al. 1983)
Excretion
Rapid excretion after inhalative exposition in vivo in rats (blood level peaked after 15 min; Poet 2003) and in rabbits (Saito et al. 1975) and in situ/ in vitro (Hedlund and Kiessling 1969) in rats.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
Isobutanol is rapidly absorbed following oral administration and inhalation exposures. Isobutanol is metabolised to isobutyraldehyde and isobutyric acid in rats and humans, primarily by alcohol and aldehyde dehydrogenases.
Discussion on bioaccumulation potential result:
Non-human information
In vitro Studies
The Class I Alcohol Dehydrogenase (ADH) isozymes appear to be the most active for isobutanol metabolism. The alcohol dehydrogenase reaction was studied in rat and chick embryo liver homogenates (Sinclair et al., 1990). The clearance of isobutanol in rats was investigated using in situ liver perfusions and in vitro liver homogenates (Hedlund and Kiessling 1969; Val. 4). Clearance of isobutanol was very rapid in both test systems.
In vivo Studies
Respiratory bioavailability studies conducted with isobutanol have correlated airborne isobutanol levels with internal blood levels of isobutanol and isobutyric acid (ACC, 2003). Inhalation of 2000 ppm (ca. 6.0 mg/L) isobutanol in a closed chamber resulted in isobutanol levels up to 278 µM after 15 min and isobutyric acid levels up to 93 µM after 25 min. Blood levels of isobutanol decreased to 155 µM by ninety minutes and isobutyric acid levels were not detectable. The clearance of isobutanol in rats was investigated using intraperitoneal injections (Hedlund and Kiessling; 1969). Clearance of isobutanol was very rapid. Oral administration of isobutanol to rabbits was reported by Saito et al. (1975), with blood and urinary analysis for isobutanol and metabolites. The metabolism proceeded as expected although the analytical procedures employed detected an urinary metabolite that coeluted with isovaleric acid but was not fully characterized. Plapp (2015) investigated the kinetics of ADH in rats and stated, that isobutanol was eliminated with zero-order kinetic at a dose of 10 mmol/kg.
Human information
In vitro Studies
Metabolism of isobutanol to isobutyraldehyde and isobutyric acid is via the alcohol and aldehyde dehydrogenase enzymes (as was demonstrated in vitro by Ehrig et al., 1988). The Class I ADH isozymes appears to be the most active for isobutanol metabolism. The kinetic constants for the alcohol dehydrogenase reaction was determined to have a Km of 0.04 - 0.11 µM and a Vmax of 0.68 - 0.86 µmol min-1 g wet wt.-1 in human liver homogenates (Sinclair, et al., 1990).
In vivo Studies
Studies in humans demonstrated that isobutanol was rapidly metabolized to isobutyric acid (main metabolite) and isobutyraldehyde; the renal elimination of isobutanol and its main metabolite isobutyric acid peaked within one hour after dosing (Ruedell et al. 1983). Isobutanol is rapidly absorbed and eliminated from blood following oral administration to humans (Bilzer et al., 1990).
Furthermore, volunteers that were exposed via breathing masks to concentrations up to 200 ppm n-butanol for 2 hours did not feel adverse effects (Astrand et al. 1976).
Summary
Isobutanol is rapidly absorbed following oral administration and inhalation exposures. Isobutanol is metabolised to isobutyraldehyde and isobutyric acid in rats and humans, primarily by alcohol and aldehyde dehydrogenases.
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.