Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
01 to 14 Aug 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study (no data on GLP)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Objective of study:
other: hydrolysis in digestive fluid simulants
Test guideline
Qualifier:
according to
Guideline:
other: EFSA Note for Guidance for Food Contact Materials Annex 1 to Chapter III MEASUREMENT OF HYDROLYSIS OF PLASTICS MONOMERS AND ADDITIVES IN DIGESTIVE FLUID SIMULANTS (30 Jul 2008)
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate
- Appearance: Clear & bright liquid
- Analytical purity: 98% tri(nC7)/TMP (GC)
- Lot/batch No.: ES 110233
- Storage condition of test material: Room Temperature: (20±5 °C) in a closed and dark container
Radiolabelling:
no

Test animals

Species:
pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST DIGESTIVE SIMULANTS
INTESTINAL FLUID SIMULANT
- Description: The intestinal fluid simulant contains pancreatin from porcine pancreas as hydrolytic catalyst.
- Preparation: reported to have been done according to the guideline.
- Source of Pancreatin: Porcine pancreatin extract, activity equivalent to 8x SUP specification

SALIVA SIMULANT
- Description: carbonate buffer with a pH value of 9
- Preparation: reported to have been done according to the guideline.

GASTRIC JUICE SIMULANT
- Description: For more convenience, 0.1 M HCl were used for screening. As no hydrolysis with 0.1 M HCl was observed , it was considered not necessary to test 0.07 M HCl.
- Preparation: reported to have been done according to the guideline.

Administration / exposure

Route of administration:
other: mixing
Vehicle:
ethanol
Details on exposure:
- Preparation of sample solution
1. 200 mg of test material was weight to a 20 mL measuring flask.
2. The measuring flask was filled to the mark with ethanol.

- In vitro hydrolysis of sample solution
1. 100 µL of the sample solution was transferred to a 100 mL erlenmeyer flask.
2. The digestive fluid hydrolysis was carried out according to the guideline (see Duration and frequency of treatment / exposure).

Duration and frequency of treatment / exposure:
Intestinal fluid simulant: 1, 2 and 4 h
Saliva simulant: 0.5 h
Gastric juice simulant: 1, 2 and 4 h
Doses / concentrations
Remarks:
Doses / Concentrations:
10 mg/mL
No. of animals per sex per dose:
single determination
Control animals:
other: for GC: blank samples from test digestive simulants and samples of reference materials (parent substance and hydrolysis products)
Details on dosing and sampling:
DETERMINATION OF HYDROLYSIS PRODUCTS

- Calibration of the analytical method
It was checked, whether GC suited to determine the ester nC7/TMP (for 0 to 95% hydrolysis) and its hydrolysis products:
acid nC7 and TMP alcohol. Therefore a mix of acid nC7 and TMP alcohol and ester nC7/TMP in heptane was prepared to determine the retention time of each product. in addition a “blank” test using water as fluid simulant was performed in order to check that the ester amount is sufficient to be
measured by GC.

- sample preparation
At the end of hydrolysis test, products (ester, acid, alcohol) were extracted by adding:
- 1 mL of heptane in the 100 mL bottle for saliva and gastric-juice simulants
- 100 mL of heptane in a 250 mL bottle where the 100 mL of intestinal-fluid simulant test were also poured.
The bottle was shaken vigorously, and then the content was allowed to settle. The heptane fraction was recovered.
For saliva and gastric-juice simulants, this fraction was directly injected into the GC; for intestinal-fluid simulant, the
100 mL heptane were first concentrated to around 1 mL, with a rotary evaporator, and then injected into the GC.
It was also checked that no ester, acid or alcohol was remaining in water fraction after the heptane extraction.

Results and discussion

Main ADME resultsopen allclose all
Type:
other: ester hydrolysis in intestinal fluid simulant
Results:
no hydrolysis
Type:
other: ester hydrolysis in saliva simulant (test substance)
Results:
no hydrolysis
Type:
other: ester hydrolysis in gastric juice simulant (test substance)
Results:
no hydrolysis

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Not applicable
Details on distribution in tissues:
Not applicable
Details on excretion:
Not applicable

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The detection of acid nC7 and TMP and the parent substance ester nC7/TMP in intestinal fluid simulant, respectively:
nC7: 0%
TMP: 0%
ester nC7/TMP: 100%


Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: no hydrolysis in digestive fluid simulants observed