Allyl hexanoate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Pre-GLP and pre-OECD test guideline study, but a good documentation

Data source

Reference

Reference Type:

publication

Title:

The hydrolysis of flavouring esters by artificial gastrointestinal juices and rat tissue preparations

Author:

Longland RC

Year:

1977

Bibliographic source:

Toxicology 8, 197-204

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

To show that allyl hexanoate is hydrolysed by artificial gastrointestinal juices (gastric and pancreatic juice).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Allyl hexanoate

EC Number:

204-642-4

EC Name:

Allyl hexanoate

Cas Number:

123-68-2

Molecular formula:

C9H16O2

IUPAC Name:

allyl hexanoate

Details on test material:

- Name of test material (as cited in study report): Allyl caproate
- Analytical purity: >99%

Radiolabelling:

no

Administration / exposure

Details on study design:

The artificial gastric and pancreatic juices were prepared as described in Pharmacopoeia Helvetica VI, modified in the case of the pancreatic juice
by increasing the ionic strength of the phosphate buffer to maintain the pH at 7.5 during the hydrolysis of the esters. The artificial gastric juice consisted of: sodium chloride 2.0 g, in 1 N HCI 80.0 mL and pepsin 3.2 g made up to one litre with distilled water and adjusted to pH 1.2. The artificial pancreatic juice consisted of: pancreatin 10.0 g, sodium taurocholate 0.5 g, disodium hydrogen phosphate 50.5 g and sodium dihydrogen phosphate dihydrate 15.6 g, made up to one litre with distilled water and adjusted to pH 7.50.
The artifical juice (110 mL) was placed in a stoppered 250-mL flask in a shaking incubator at 37 °C. A measured quantity of ester, a little less than that required to give a saturated solution, was added, the flask shaken vigorously for 2 min and returned to the incubator. At intervals, 20-mL portions of solution were pipetted into 25-mL stoppered flasks containing 5 ml of 0.16% solution of standard in solvent, cooled in ice, shaken vigorously for 2 min and left on ice to separate. As soon as sufficient solvent phase had separated, a sample was injected into the gas chromatograph.
Generally, samples were withdrawn from the hydrolysis flask at 0.5, 1, 2 and 4 h, but the intervals were decreased when the ester was found to hydrolyse quickly.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parameters

Toxicokinetic parameters 1

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 1120 min (artificial gastric juice)

Toxicokinetic parameters 2

Test no.:

#2

Toxicokinetic parameters:

half-life 1st: 1.98 min (artificial pancreatic juice)

Metabolite characterisation studies

Metabolites identified:

no

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Allyl hexanoate is rapidly hydrolysed in artificial pancreatic juice (half life t1/2=1.98 min) and slowly hydrolysed in artificial gastric juice (half life t1/2=1120 min).

Executive summary:

Artificial gastric and pancreatic juices were prepared and placed in a flask in a shaking incubator. Test compound was added and at designated intervals, portions of the solution were pipetted into flasks containing a solution of standard in solvent, cooled, shaken and left on ice to separate. As soon as sufficient solvent phase had separated, a sample was injected into a gas chromatograph for analysis. Nearly complete hydrolysis of allyl hexanoate in pancreatic juice required less than 10 minutes (5 half lifes = 9.9 min).