Linalool

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

not indicated publication

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

An OECD guideline does not exist for this type of study

Data source

Reference

Reference Type:

publication

Title:

Preparation, characterization and pharmacokinetic studies of linalool-loaded nanostructured lipid carriers

Author:

Feng Shi*, Yingying Zhao*, Caleb Kesse Firempong and Ximing Xu

Year:

2016

Bibliographic source:

PHARMACEUTICAL BIOLOGY, 2016 VOL. 54, NO. 10, 2320–2328 http://dx.doi.org/10.3109/13880209.2016.1155630

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Linalool was suspended in 0.5% carboxymethylcellulose and applied via oral gavage to SD rats. Blood was drawn at several timepoints to prepare plasma. The concentration of Linalool in the plasma was analysed using a HPLC-UV method. The toxicokinetic parameters were calculated using BAPP 2.3 software package.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Linalool

EC Number:

201-134-4

EC Name:

Linalool

Cas Number:

78-70-6

Molecular formula:

C10H18O

IUPAC Name:

3,7-dimethylocta-1,6-dien-3-ol

Details on test material:

- Name of test material (as cited in study report): Linalool
- Substance type: Unsaturated racemic monoterpene alcohol

Specific details on test material used for the study:

Linalool (98%) from J&K Scientific Ltd. (Beijing, China)

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on species / strain selection:

Healthy male Sprague-Dawley rats (weight 300 ± 20 g) were obtained from Laboratory Animal Center of Jiangsu University (Jiangsu, China).

Sex:

male

Details on test animals or test system and environmental conditions:

The rats were fed with standard food pellets and maintained under standard laboratory conditions with a dark/light cycle of 12 h. All rats were fasted overnight before the experiments, but allowed access to water ad libitum. The use and care protocols of rats were reviewed and approved by the Ethic Committee of Jiangsu University.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on exposure:

Six male Sprague-Dawley rats received Linalool as a suspension in 0.5% (w/v) sodium carboxymethylcellulose at a dose level of 300 mg/kg bw.

Duration and frequency of treatment / exposure:

single dose

Doses / concentrations

Dose / conc.:

300 mg/kg bw (total dose)

No. of animals per sex per dose / concentration:

6

Control animals:

no

Positive control reference chemical:

No details given

Details on study design:

Six healthy male Sprague-Dawley rats (weighing approximately 300 g) were given Linalool via oral gavage using 0.5% CMC as vehicle.

Details on dosing and sampling:

After oral administration, blood samples (0.6 mL) were collecated at several time points (5, 10, 15, 20, 30, 40, 50, 60, 120, 180, 240, 300, 360 and 480 min) into heparinized centrifuge tubes. Plasma was prepared and analysed for Linalool using a HPLC-UV method. The HPLC apparatus included a pump (LC-10ADVP; Shimadzu), an UV detector (SPD-20A; Shimadzu) and a Symmetric C18 column (5 microm, 4.6x150 mm) at a detection wavelength of 210nm at 30 °C, and the injection volume was 20 microL. The mobile phase consisted of acetonitrile-water (47:53) at a flow rate of 1.0mL/min.

Statistics:

n.a.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

not investigated

Details on distribution in tissues:

not investigated

Details on excretion:

not investigated

Toxicokinetic parameters

Toxicokinetic parameters 1

Key result

Toxicokinetic parameters:

AUC: 76003.40 ng/min/mL

Toxicokinetic parameters 2

Key result

Toxicokinetic parameters:

Cmax: 1915.45 ng/mL

Toxicokinetic parameters 3

Key result

Toxicokinetic parameters:

Tmax: 40 min

Toxicokinetic parameters 4

Key result

Toxicokinetic parameters:

half-life 1st: 44.72 min

Metabolite characterisation studies

Metabolites identified:

not measured

Enzymatic activity

Enzymatic activity measured:

not measured

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

not investigated

Applicant's summary and conclusion

Conclusions:

Linalool is rapidly taken up upon oral bolus administration even at relatively high doses with the Cmax being observed already after 40 min. Linalool is rapidly eliminated from plasma with a half-life of approximately 45 min. Linalool could not be detected anymore in the plasma after 240 min.

Executive summary:

Six healthy male Sprague-Dawley rats (weighing approximately 300 g) were given Linalool via oral gavage using 0.5% CMC as vehicle. After oral administration, blood samples (0.6 mL) were collected at several time points into heparinized centrifuge tubes: 5, 10, 15, 20, 30, 40, 50, 60, 120, 180, 240, 300, 360 and 480 min. Plasma was prepared and analysed for Linalool using a HPLC-UV method. The HPLC apparatus included a pump (LC-10ADVP; Shimadzu), an UV detector (SPD-20A; Shimadzu) and a Symmetric C18 column (5 microm, 4.6 x 150 mm) at a detection wavelength of 210 nm at 30 °C, and the injection volume was 20 µL. The mobile phase consisted of acetonitrile-water (47:53) at a flow rate of 1.0mL/min. Toxicokinetic parameters were investigated using BAPP 2.3 pharmacokinetic software package (supplied by the Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University).

Linalool is rapidly taken up upon oral bolus administration even at relatively high doses with the Cmax (1915.45 ng/mL) being observed already after 40 min. Linalool is rapidly eliminated from plasma with a half-life of approximately 45 min. Linalool could not be detected anymore in the plasma after 240 min. The AUC(0 -t) was 76003.40 ng/min/mL.