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EC number: 225-004-1 | CAS number: 4602-84-0
- 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
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- The study was not of guideline design including just two treatment groups and a control, and was not conducted to GLP
Data source
Reference
- Reference Type:
- publication
- Title:
- Modulation of hepatic and renal drug metabolising enzyme activities in rats by subchronic administration of farnesol
- Author:
- Horn TL, Long L, Cwik MJ,Morrissey RL, Kapetanovic IM, McCormick DL
- Year:
- 2 005
- Bibliographic source:
- Chemico-Biological Interactions, 152, 79-99
Materials and methods
- Objective of study:
- absorption
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The study design was similar to an OECD 407 28-day repeated dose toxicity study although only two treated groups were included together with a standard vehicle control group. The numbers of animals per group complied with guideline requirements for studies of this type along with the experimental conditions. Half the animals from each group were terminated after 28 days of oral dosing whilst the remaining animals were terminated after a further 28-day period without treatment to assess recovery from any toxicities. Blood samples were taken from all animals at termination for the determination of plasma farnesol levels.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Farnesol
- EC Number:
- 225-004-1
- EC Name:
- Farnesol
- Cas Number:
- 4602-84-0
- Molecular formula:
- C15H26O
- IUPAC Name:
- farnesol
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Rats were individually housed in stainless steel cages suspended over absorbent cage boards, and were held in a temperature-controlled room maintained on a 12 h light/dark cycle. Rats were permitted free access to drinking water (supplied by automatic watering system) at all times during the study; rats were also allowed free access to Purina Certified Rodent Diet 5002 (PMI Nutrition International Inc., Brentwood, MO) throughout the study, except during an overnight fast prior to scheduled necropsies.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
- Dose levels of 500 or 1000 mg/kg/day were selected on the basis of a previous pre-clinical 28-day toxicity study without recovery
VEHICLE
- Justification for use and choice of vehicle (if other than water): Not stated
- Concentration in vehicle: Not stated
- Amount of vehicle (if gavage): 5 mL/Kg
- Lot/batch no. (if required): Not stated
- Purity: Not stated - Duration and frequency of treatment / exposure:
- 28 days followed by a 28-day recovery period
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 other: mg/mL
- Dose / conc.:
- 200 other: mg/mL
- No. of animals per sex per dose / concentration:
- 20 male and 20 female rats per group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose levels of 500 and 1000 mg/kg/day were selected by the National Cancer Institute on the basis of a previous preclinical 28-day toxicity study
- Rationale for animal assignment (if not random): animals randomly assigned to groups
- Rationale for selecting satellite groups: not stated
- Post-exposure recovery period in satellite groups: 28-day recovery period - Details on dosing and sampling:
- PHARMACOKINETIC STUDY
- Tissues and body fluids sampled: plasma
- Time and frequency of sampling: Blood samples taken from all animals killed at the end of 28-days of treatment
- Method type(s) for identification: Gas chromoatography/mass spectrometry
- Limits of detection and quantification: cis, cis-farnesol (0.233 umol/l); cis, trans-farnesol (0.527 umol/l); trans, cis-farnesol (0.516 umol/l); trans,
trans-farnesol (0.814 umol/l).
Results and discussion
Main ADME results
- Type:
- absorption
- Results:
- Plasma levels of total farnesol and individual farnesol isomers in rats receiving daily exposure to farnesol at doses of 500 or 1000 mg/kg/day
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Total plasma farnesol levels, and plasma levels of individual farnesol isomers in samples collected from study animals at approximately two hours post-dosing during the final week of farnesol administration are summarised in Table 1. As expected, plasma levels of total farnesol (all isomers) and individual farnesol isomers increased with increasing farnesol dose. Despite the fact that farnesol is an endogenous compound, plasma farnesol levels were not detectable in all animals in the vehicle control group (data not shown) as the levels were probably below the detection limit of the assay.
Any other information on results incl. tables
Table 1 - Plasma levels of total farnesol and individual farnesol isomers in rats receiving daily exposure to farnesol at doses of 500 or 1000 mg/kg/day
|
|
Concentration (µmol/L) |
|||
Male, 500a |
Male, 1000a |
Female, 500a |
Female, 1000a |
||
Total Farnesol |
Mean±SDb Rangec Nd |
3.75±2.02 1.29-6.68 8 |
7.82±1.60 5.12-9.64 10 |
5.89±3.38 2.76-11.3 9 |
8.75±2.91 5.74-13.6 10 |
cis,cisFarnesol |
Mean±SDb Rangec Nd |
0.676±0.267 0.283-0.931 5 |
1.09±0.393 0.603-1.57 10 |
0.485±0.178 0.234-0.729 5 |
0.929±0.336 0.576-1.57 10 |
cis,transFarnesol |
Mean±SDb Rangec Nd |
0.801 0.801 1 |
1.28±0.714 0.553-2.17 4 |
2.01 2.01 1 |
1.01±0.183 0.881-1.14 2 |
trans,cisFarnesol |
Mean±SDb Rangec Nd |
0.846±0.197 0.06-0.985 2 |
0.814±0.339 0.522-1.25 8 |
1.03±0.409 0.742-1.32 2 |
0.665±0.089 0.562-0.765 5 |
trans,transFarnesol |
Mean±SDb Rangec Nd |
3.02±1.44 1.29-4.95 8 |
5.57±1.00 4.08-6.97 10 |
5.18±2.64 2.76-10.0 9 |
7.29±2.27 4.90-11.6 10 |
Blood samples were collected approximately 2h post-dosing during the fourth week of farnesol administration. Plasma farnesol levels in all samples collected from vehicle controls were not detectable
a Sex and dose (mg/kg/day)
b Mean concentration (+/- standard deviation) for animals with quantifiable levels within the group
c Concentration range among animals with quantifiable levels within the group
d Number of animals (out of 10) with quantifiable levels within the group
Applicant's summary and conclusion
- Conclusions:
- Plasma concentrations of farnesol and associated isomers increased with increasing dose concentration following oral exposure in rats.
- Executive summary:
Male and female rats received daily exposure to farnesol at doses of 500 or 1000 mg/kg/day, alongside a vehicle control, for 28 days followed by a 28-day recovery period. Total plasma farnesol levels and plasma levels of individual farnesol isomers were analysed at approximately two hours post-dosing during the final week of farnesol administration. Plasma levels of total farnesol (all isomers) and individual farnesol isomers increased with increasing farnesol dose. This study is considered to be reliable with restriction (Klimisch 2) as it was a published study conducted similar to an OECD 407 28-day repeated dose toxicity study, with minor limitations in reporting.
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