Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Modern, high quality investigative study; non-GLP and non-guideline

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 available
Principles of method if other than guideline:
The study investigated the absorption of the submission sustance in an in vitro everted rodent intestinal sac model.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Di-pentaerythritol (Di-penta) 2,2,2',2'-tetrakis(hydroxymethyl)-3,3'-oxydipropan-1-ol
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
Intestinal sacs were prepared from male Han Wistar Rats, approximately 8-12 weeks of age. Rats were obtained from Harlan, Bicester, UK.

Administration / exposure

Route of administration:
other: in vitro
Vehicle:
other: 'Fed State' Simulated Intestinal Fluid (FeSSIF)
Details on exposure:
The sacs from two rats were incubated in triplicate at 37°C for 1 hour.
Duration and frequency of treatment / exposure:
Absorption was assessed over a period of one hour
Doses / concentrations
Remarks:
Doses / Concentrations:
A single concentration of 50 mM was used
No. of animals per sex per dose:
The sacs from two rats were used
Control animals:
no
Positive control:
Not required
Details on study design:
The everted intestinal sacs were prepared by gently everting a freshly excised rat proximal small intestine over a glass stirring rod, rinsing with TC-199 media and filling the everted intestine with oxygenated FeSSIF medium at 37°C and dividing it into sacs approximately 2.5 cm in length using braided suture silk.
Details on dosing and sampling:
After 1 hour the individual sacs were removed, washed with running water and blotted dry. The sacs were cut open and the serosal fluid drained into small tubes. Each tube was weighed before and after collection of the serosal fluid to accurately calculate the volume of medium collected from inside the sac.
Statistics:
Calculation of mean and standard deviation: no further statistical analyses required.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The calculated concentrations of Di-penta in the serosal fluid from the intestinal sac incubations were 6.148mM (±3.791) from Rat 1 and 7.700mM (±2.083) from Rat 2.

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables

Calculated concentration of Di-penta in serosal fluid.

 

Sample

Calculated concentration of Di-penta in serosal fluid (mM)

Mean (mM)

±SD

 

 

 

 

Serosal fluid 1 Rat 1

5.713

 

 

Serosal fluid 2 Rat 1

2.593

 

 

Serosal fluid 3 Rat 1

10.137

6.148

3.791

 

 

 

 

Serosal fluid 1 Rat 2

5.519

 

 

Serosal fluid 2 Rat 2

9.670

 

 

Serosal fluid 3 Rat 2

7.909

7.700

2.083

 

 

 

 

External media 60 min

35.895

 

 

 

Calculated amount of Di-penta absorbed into serosal fluid

 

Sample

Calculated amount of Di-penta absorbed into serosal fluid (µmoles/400µL)

Mean (µmoles)

±SD

 

 

 

 

Serosal fluid 1 Rat 1

2.285

 

 

Serosal fluid 2 Rat 1

1.037

 

 

Serosal fluid 3 Rat 1

4.055

2.459

1.516

 

 

 

 

Serosal fluid 1 Rat 2

2.208

 

 

Serosal fluid 2 Rat 2

3.868

 

 

Serosal fluid 3 Rat 2

3.164

3.080

0.833

 

 

 

 

External media 60 min

14.358

 

 

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: The results of the study indicate that di-Penta is absorbed in the everted rodent intestinal sac model
The results of the study indicate that di-Penta is absorbed in the everted rodent intestinal sac model; however the extent of absorption was less than for the other polyol substances investigated in this assay.
Executive summary:

The potential gastro-intestinal absorption of di-Penta was assessed in vitro, in the everted rodent gut sac model. The results of the study indicate that di-Penta is absorbed in the everted rodent intestinal sac model; however the extent of absorption was less than for the other polyol substances investigated in this assay.