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EC number: 242-362-4 | CAS number: 18479-58-8
- 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:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: An essentially well conducted study using accepted procedures of the time. Predates GLP requirements.
Data source
Reference
- Reference Type:
- publication
- Title:
- The Absorption, Distribution and Excretion of Linalool in the Rat
- Author:
- Parke, D.V., Quddusur Rahman, KH.M. and Walker, R.
- Year:
- 1 974
- Bibliographic source:
- Biochemical Society Transactions Vol. 2, pp. 612-615, 547th Meeting, London
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The rate and route of excretion of linalool was investigated in the rat after intragastric and intraperitoneal administrations. The extent of enterohepatic circulation after biliary excretion was determined.
- GLP compliance:
- no
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Details on test material:
- Linalool, labelled with 14C in positions 1 and 2, was synthesized by the method of Filip and Moravek (1959).
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals and environmental conditions:
- Male, 12-week old rats.
Administration / exposure
- Route of administration:
- other: intragastric and intraperitoneal
- Vehicle:
- propylene glycol
- Details on exposure:
- Labelled linalool (10 microCi) was administered by stomach tube to rats as a 25% (w/v) solution in propylene glycol at a dose of 500 mg/kg bwt.
The animals were individually caged in Metabowls (Jencon Ltd.) and urine and feces were collected over a period of 72 hours. Expired air was passed through traps containing ethanol:ethanolamine (2:1, v/v) and samples were collected from the traps over the same period.
Two rats with indwelling common bile duct cannulas were administered labelled linalool (1 microCi, 20 mg) intraperitoneally as a 10% solution in propylene glycol and bile collected at intervals over a period of 6 hours in one animal and 11 hours in the other.
In a separate experiment, two rats with bile ducts cannulated were treated as follows: a cannula from the bile duct of the first animal was inserted into the duodenal end of the bile duct cannula of the second animal; another cannula was inserted into the hepatic end of the bile duct of the second animal and the bile duct was ligated between the cannulae. Thus, bile from the first animal was introduced into the duodenum of the second while bile was collected from the second animal. The presence of radioactivity in this bile after intraperitoneal injection to the first animal was indicative of enterohepatic circulation.
At the end of the experiment, animals were killed and residual radioactivity in brain, lung, liver, heart, spleen, gastro-intestinal tract, kidney, skin and skeletal muscle was counted after digestion with hyamine. - Duration and frequency of treatment / exposure:
- Single administration
Doses / concentrations
- Remarks:
- Doses / Concentrations:
As indicated above
- No. of animals per sex per dose:
- As indicated above
- Control animals:
- no
- Positive control:
- None
- Details on dosing and sampling:
- See description above
Results and discussion
Main ADME results
- Type:
- other: DT50
- Results:
- Approximately 50% of the total administered dose was excreted within 18 hours.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Linalool is rapidly absorbed from the gut as evidenced by extensive and rapid urinary excretion of radioactivity over the first 36 hours with no significant delay between dosing and the appearance of radioactivity in the urine.
- Details on distribution in tissues:
- At the end of the 72 hour period following intragastric administration, only about 3% of the radioactivity remained in the tissues and this was located mainly in the liver (0.5%), gut (0.6%), skin (0.8%) and skeletal muscle (1.2%). Other organs including the kidney contained insignificant amounts of radioactivity.
- Details on excretion:
- Following intragastric intubation, nearly complete elimination (est. 97%) of linalool occurred by 72 hours. The majority of this was in urine (est. 58%) with 23% in expired air, primarily as 14^CO2 and not as exhaled linalool or other metabolites. Fecal excretion was delayed; occurring primarily between 36 and 48 hours and suggesting biliary excretion was involved. Approximately 50% of the administered total dose was excreted within 18 hours.
In bile duct cannulated rats, more than 25% of the intraperitoneal dose was excreted by this route in 6-11 hours (principally in the first 4 hours) and appearing as polar conjugates. The conjugates were partially hydrolyzed by beta-glucuronidase and more fully by a mixture of beta-glucuronidase and sulphatase. In the cross-over experiment with cannulated rats in which bile from a first rat was introduced into the duodenum of a second rat, radioactivity equivalent to 2.5% of the original dose appeared in the bile of the second rat over a 12 hour period with peak excretion at 7 to 9 hours.
Assuming that 25% of the original dose appears in the bile of the first animal over the period studies, and also that 25% of the conjugates that were hydrolyzed and reabsorbed by the second animal, it can be calculated that 40% of the biliary conjugates are hydrolyzed and reabsorbed in the first pass. This extensive enterohepatic circulation may account in part for the delayed fecal excretion.
Applicant's summary and conclusion
- Conclusions:
- The study suggests that large doses of linalool may be metabolized in the rat by conjugation and excretion in the urine and bile while a substantial amount of the dose may enter intermediary metabolism with eventual excretion as carbon dioxide. The rapid and complete excretion of linalool and its metabolites suggests no long-term hazard from tissue accumulation.
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