Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The hydrolysis and degradation of Geranylacetat Extra in plasma, liver and gastrointestinal tract was investigated. To determine hydrolysis in either compartment, the test substance was incubated with plasma and liver-S9 fraction from rat as well as in gastric-juice simulant and intestinal-fluid simulant. After incubation, the proteins were precipitated and the amount of remaining substrate was analysed in the supernatant by GC/FID.
GLP compliance:
yes (incl. certificate)
Remarks:
Experimental Toxicology and Ecology

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Test Substance:
- Name of test material (as cited in study report): Geranylacetat Extra
- Physical state: liquid / yellowish, clear
- Analytical purity: 98.9 corr. area-%
- Test substance No.: 09/0294-3
- Batch No.: Ch 00006277L0
- Expiration date of the lot/batch: 04 Feb 2015
- Storage condition of test material: refrigerator(KS); under light exclusion ; air sensitive
- Homogeneity: given (vis)

Reference Substance 1:
- Name of reference material (as cited in study report): Geraniol Extra
- Physical state: liquid / yellowish, clear
- CAS No.: 106-24-1
- Analytical purity: 98.4 corr. area-%
- Test substance No.: 10/0046-2
- Batch No.: 00028577L0
- Expiration date of the lot/batch: 14 Aug 2013
- Storage condition of test material: ambient (RT); under light exclusion
- Homogeneity: given (vis)

Reference Substance 2:
- Name of reference material (as cited in study report): Benzyl benzoate
- Physical state: liquid / colorless, clear
- CAS No.: 120-51-4
- Analytical purity: 99.9%
- Test substance No.: 12/0416-1
- Batch No.: MKBG9990V
- Expiration date of the lot/batch: Apr 2016
- Storage condition of test material: ambient
- Homogeneity: given (vis)
Radiolabelling:
no

Test animals

Species:
other: not applicable (in vitro test)
Details on test animals and environmental conditions:
not applicable (in vitro test)

Administration / exposure

Route of administration:
other: not applicable (in vitro test)
Duration and frequency of treatment / exposure:
see "Any other information on materials an methods incl. tables"
Doses / concentrations
Remarks:
Doses / Concentrations:
see "Any other information on materials an methods incl. tables"
No. of animals per sex per dose:
not applicable (in vitro test)
Control animals:
other: not applicable (in vitro test)
Positive control:
see "Any other information on materials an methods incl. tables"
Statistics:
For calculation of the hydrolysis (turn over), peak areas of the substrates of active incubation (AI) and heat deactivated control (HDC) were used. Buffer controls were used to calculate the substrate recovery of the HDC and t=0 control.

Calculation of the turn over in plasma, liver- S9 fraction and intestine-fluid simulant:
% turn-over = 100 * (peak area (HDC) – peak area (AI)) / peak area (HDC)

Calculation of the turn-over in gastric-juice simulant:
% turn-over = 100 * (peak area (t=0) – peak area (AI)) / peak area (t=0)

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Geranylacetat Extra hydrolyzed within 0.5h completely in rat plasma (100%), liver S9 fraction of rats (100%) and intestinal-fluid simulant (100%) under the test conditions used. For gastric juice simulant the metabolic turn over that is related to t=0 control was calculated to be 25, 46 and 59% after an incubation period of 0.5, 1 and 2 h, respectively.

Applicant's summary and conclusion