Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study is conducted according to well established method, but not a GLP guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In vitro absorption across everted gut sac measured as estimation of absorption from the small intestine via the oral route.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
Intestinal gut sacs were harvested from rats.
Animal: Male Han Wistar rats. Age: approx. 8-12 weeks old obtained from: Charles River, Research Models and Services, Margate, UK.

Administration / exposure

Route of administration:
other: in vitro test
Vehicle:
other: Fed State Simulated Intestinal Fluid

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
There was no detectable rat small intestinal absorption of Farnesane using the everted rat intestinal sacs. The limit of detection by GC-FID was estimated to be 0.01mM.

The results from the everted rat intestinal sacs incubations with the control mix of alkanes show good absorption of decane with concentrations in the serosal fluid calculated at 0.79mM from Rat 1 intestinal sacs and 0.47mM from Rat 2 intestinal sacs. These concentrations are approximately 20% and 12% respectively of the original incubation conditions of 3.85mM.

Decreased absorption was detected with the increased carbon chain length of the alkanes in the control mix with concentrations of dodecane in the serosal fluid calculated at 0.24mM and 0.14mM (8% and 5% respectively of the original incubation concentration of 3.01mM). Tetradecane concentrations in the serosal fluid were minimal at 0.06mM and 0.03mM (2% and 1% respectively of the original incubation concentration of 2.67mM).
No absorption of the hexadecane and octadecane into the serosal fluid could be detected.

These results are consistent with previous studies performed in this laboratory which have shown an inverse correlation between carbon chain length and the rat small intestinal absorption potential using everted rat intestinal sacs.

Any other information on results incl. tables

Calculated concentration of Farnesane in serosal fluid and external media

Sample

Calculated concentration of Farnesane in serosal fluid and external media (mM)

Mean (mM)

±SD

 

 

 

 

Serosal fluid 1 Rat 1

0 (0%)

 

 

Serosal fluid 2 Rat 1

0 (0%)

 

 

Serosal fluid 3 Rat 1

0 (0%)

-

-

 

 

 

 

Serosal fluid 1 Rat 2

0 (0%)

 

 

Serosal fluid 2 Rat 2

0 (0%)

 

 

Serosal fluid 3 Rat 2

0 (0%)

-

-

 

 

 

 

External fluid 1 Rat 1

5.22

 

 

External fluid 2 Rat 1

5.23

 

 

External fluid 3 Rat 1

5.27

5.24

0.02

 

 

 

 

External fluid 1 Rat 2

5.14

 

 

External fluid 2 Rat 2

5.75

 

 

External fluid 3 Rat 2

5.68

5.52

0.34

Applicant's summary and conclusion

Conclusions:
Interpretation of results: no bioaccumulation potential based on study results
No gut sac absorption
Executive summary:

The aim of this study was to determine the rat, small intestinal absorption potential of Farnesane and using everted rat intestinal sacs.

 

The results of this study have shown that there was no detectable rat small intestinal absorption of Farnesane using the everted rat intestinal sacs. The limit of detection by GC-FID in FeSSIF media was estimated to be 0.01mM.

 

The results from the everted rat intestinal sacs incubations with the control mix of alkanes show good absorption of decane with concentrations in the serosal fluid calculated at 0.79mM from Rat 1 intestinal sacs and 0.47mM from Rat 2 intestinal sacs. These concentrations are approximately 20% and 12% respectively of the original incubation conditions of 3.85mM.

 

There was diminishing absorption detected with increased carbon chain length of the alkanes in the control mix with concentrations of dodecane in the serosal fluid calculated at 0.24mM and 0.14mM (8% and 5% respectively of the original incubation concentration of 3.01mM). Tetradecane concentrations in the serosal fluid were minimal at 0.06mM and 0.03mM (2% and 1% respectively of the original incubation concentration of 2.67mM). No absorption of the hexadecane and octadecane into the serosal fluid could be detected.

 

Reference - “The use of everted rat small intestinal sacsin-vitroto estimate relative absorption potential of a series of alpha olefins” M. Penman, R. H. Powrie and C. R. Elcombe, Society of Toxicology 2014 Meeting, poster presentation #1593