2,2'-[oxybis(methylene)]bis[2-ethylpropane-1,3-diol]

Basic toxicokinetics

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: High quality modern, 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 substance in an in vitro everted rodent intestinal sac model.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Di-TMP

IUPAC Name:

Di-TMP

Constituent 2

Reference substance name:

Di-Trimethylolpropane

IUPAC Name:

Di-Trimethylolpropane

Constituent 3

Reference substance name:

2,2'-[oxybis(methylene)]bis[2-ethylpropane-1,3-diol]

EC Number:

245-509-0

EC Name:

2,2'-[oxybis(methylene)]bis[2-ethylpropane-1,3-diol]

Cas Number:

23235-61-2

Molecular formula:

C12H26O5

IUPAC Name:

2-ethyl-2-{[2-ethyl-3-hydroxy-2-(hydroxymethyl)propoxy]methyl}propane-1,3-diol

Test material form:

other: liquid

Details on test material:

2,2'-[oxybis(methylene)]bis[2-ethylpropane-1,3-diol] Batch 4174037; supplied by Perstorp Holding AB

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system 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 / concentration:

The sacs from two rats were used

Control animals:

no

Positive control reference chemical:

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-TMP in the serosal fluid from the intestinal sac incubations were 36.52mM (±0.749) from Rat 1 and 38.173mM (±2.108) from Rat 2.

Metabolite characterisation studies

Metabolites identified:

not measured

Any other information on results incl. tables

Calculated concentration of Di-TMP in serosal fluid

 

Sample	Calculated concentration of Di-TMP in serosal fluid (mM)	Mean (mM)	±SD
Serosal fluid 1 Rat 1	37.133
Serosal fluid 2 Rat 1	35.685
Serosal fluid 3 Rat 1	36.741	36.520	0.749
Serosal fluid 1 Rat 2	36.485
Serosal fluid 2 Rat 2	37.499
Serosal fluid 3 Rat 2	40.536	38.173	2.108
External media 60 min	49.385

 

Calculated amount of Di-TMP absorbed into serosal fluid

 

Sample	Calculated amount of Di-TMP absorbed into serosal fluid (µmoles/400µL)	Mean (µmoles)	±SD
Serosal fluid 1 Rat 1	14.853
Serosal fluid 2 Rat 1	14.274
Serosal fluid 3 Rat 1	14.697	14.608	0.300
Serosal fluid 1 Rat 2	14.594
Serosal fluid 2 Rat 2	14.999
Serosal fluid 3 Rat 2	16.214	15.269	0.843
External media 60 min	19.754

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: The results of the study indicate that di-TMP is extensively absorbed in the everted rodent intestinal sac model.
The results of the study indicate that di-TMP is extensively absorbed in the everted rodent intestinal sac model.

Executive summary:

The potential gastro-intestinal absorption of di-TMP was assessed in vitro, in the everted rodent gut sac model. The results of the study indicate that di-TMP is extensively absorbed in the rat following oral dosing.