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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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: Non-standard investigation; performed at a reputable laboratory and reported in detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
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 CAPA 3050 in vitro in a rat gut sac model
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
CAPA 3050
IUPAC Name:
CAPA 3050
Constituent 2
Chemical structure
Reference substance name:
ε-Caprolactone, oligomeric reaction products with propylidynetrimethanol
EC Number:
500-099-5
EC Name:
ε-Caprolactone, oligomeric reaction products with propylidynetrimethanol
Cas Number:
37625-56-2
Molecular formula:
(C6H14O3)x.C6H10O2 (x=0-6)
IUPAC Name:
2-Oxepanone, polymer with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol
Constituent 3
Reference substance name:
2-Oxepanone, polymer with 2-ethyl-2-(hydroxymethyl)-1, 3-propanediol
IUPAC Name:
2-Oxepanone, polymer with 2-ethyl-2-(hydroxymethyl)-1, 3-propanediol
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): CAPA 3050
- Substance type: Oligomer
- Physical state: Liquid
- Analytical purity: 100%
- Lot/batch No.: WCB000999
- Expiration date of the lot/batch: 23th August 2015
- Stability under test conditions: Stable for the duration of the study
- Storage condition of test material: Ambient
Radiolabelling:
no

Test animals

Species:
other: not relevant

Administration / exposure

Route of administration:
other: In vitro
Vehicle:
unchanged (no vehicle)
Details on exposure:
Gut (small intestine) sacs were prepated from male Han Wistar rats. The everted gut sacs were placed in a flask of 10 mL FeSSIF (Fed State Simulated Intestinal Fluid) medium containing 10 mM of CAPA 3050 at 37°C. The sacs from one rat were incubated in triplicate at 37°C for 1 hour. After 1 hour the individual sacs were removed, washed with running water and blotted dry.
Duration and frequency of treatment / exposure:
One hour incubation
Doses / concentrations
Remarks:
Doses / Concentrations:10 mM
No. of animals per sex per dose / concentration:
The sacs from one rat were incubated in triplicate at 37°C for 1 hour.
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 (male Han Wistar) rat proximal small intestine over a glass stirring rod, rinsing with TC-199 media and filling the everted intestine withoxygenated FeSSIF medium at 37°C and dividing it into sacs approximately 2.5 cm in length using braided suture silk. Each sac was placed in a flask of 10mL FeSSIF medium containing 10mM of CAPA 3050 at 37°C. The sacs from one rat were incubated in triplicate at 37°C for 1 hour. 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.
Details on dosing and sampling:
The contents of each sac and a sample of the external medium after incubation (400µL) were blown down to complete dryness under nitrogen at 90°C. 200µL of N,N-bis-trimethylsilyl-trifluoroacetamide (BSTFA) was added to each sample followed by 800 µL of pyridine and capped. The samples were then sonicated in a sonicating water bath for approximately 10 seconds to ensure mixing and reconstitution. The samples were then heated at 105°C for 30 minutes. A 150µL aliquot of the reconstituted sample was removed and placed in a crimp-top vial for analysis by Gas Chromatography Flame Ionisation Detection (GC-FID) to determine the concentration of the CAPA 3050 in each sample and compared against analytical standards.
Statistics:
Not required

Results and discussion

Preliminary studies:
The results of the study showed a different peak distribution in the serosal and external media compared to the standard. For Component 1 (TMP), the peaks in the serosal and external fluid were higher than the standard. For Component 2, the serosal fluid peak was slightly higher than the standard and the external fluid peak was comparable to the standard. For Component 3, the serosal peak was markedly lower than the external medium concentration. Components 4-8 were not detected in the serosal medium. Concentrations in the external medium were lower than the standard.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Although the study was not designed to assess metabolism, the change in peak profile is consistent with some hydrolysis of the CAPA 3050 oligomers to produce TMP [Component 1]

Any other information on results incl. tables

Summary of results

Component

Mean peak area

Standard

External medium

Serosal medium

#1

TMP

6742

10304

10601

#2

TMP + 1eCL

13256

13289

14725

#3

TMP + 2eCL

17515

15116

2749

#4

TMP + 3eCL

20634

6595

37

#5

TMP + 4eCL

8968

2486

-

#6

TMP + 5eCL

2952

307

-

#7

TMP + 6eCL

-

-

-

#8

TMP + 7eCL

-

-

-

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Executive summary:

The aim of this study was to determine the rat small intestinal absorption potential of CAPA 3050 using an in vitro everted gut sac model. From the results it can be concluded that the lower molecular weight components of CAPA 3050 (TMP > TMP+1ECL > TMP+2ECL > TMP+3ECL) were absorbed into the serosal fluid. This would imply a negative correlation between the molecular weight of the components of CAPA 3050 and the rat small intestinal absorption potential. It was also noted that the concentrations of components 4 to 6 were greatly reduced in the external medium after the 60 minute incubation at 37°C when compared to the 10 mM standard. The reasons for this drop in concentration are unclear, but it has been suggested that a possible reason could be hydrolysis of the higher molecular weight components of CAPA 3050 and conversion to TMP. Another possible reason could be the low water solubility of the higher molecular weight components.