Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Toxicological information

Basic toxicokinetics

Currently viewing:

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
Justification for type of information:
refer to analogue justification provided in IUCLID section 13

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 fresh preparations of rat liver and small intestine
GLP compliance:
no

Test material

Constituent 1
Chemical structure
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
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Details on study design:
The animals were killed by cervical dislocation, the abdomen opened and the liver and approx. 10-cm length of small intestine within the region
between 10 and 30 cm from the pylorus removed. Liver homogenate (10%) was prepared in ice-cold 1.15% KCI 1 mM EDTA buffer pH 7.4. The small
intestine was flushed through with ice-cold Krebs—Ringer solution, slit along its length and the mucosal surface removed. Mucosal homogenate (10%) was prepared in ice-cold oxygenated Krebs—Ringer solution containing glucose (200 mg/100 ml). Hydrolysis studies were commenced immediately after the preparation of the tissue homogenates. The procedure used was similar to that described for the artificial gastrointestinal juices except that portions of samples were removed from the reaction flasks at shorter time intervals; 0, 10, 20 and 30 mM for liver homogenates and 0, 3, 6 and 10 min for intestinal mucosal preparations. Additionally, when ester hydrolysis was found to proceed extremely rapidly, the tissue assays were conducted with diluted tissue preparations.
The 5-mL aliquots removed from the reactions flasks were delivered into ice-cold tubes containing 1.5 g of NaCl, methanol (10 mL) and chloroform
(5 mL). After shaking the tubes vigorously for 2 min, 5 mL of chloroform containing the internal standard was added and the tube further shaken for
30 sec, 5 ml of saturated NaCl solution was then added and the shaking continued for 30 sec. The tube was centrifuged at 5000 rev./min for 10 min and the chloroform layer removed for gas chromatography. Gas—liquid chromatographic analysis was conducted on a Pye series 104 dual flame ionization chromatograph. The columns were 5 feet X 4 mm glass, packed with 100/120 mesh celite impregnated with 10% Carbowax 20 M or with polyethylene glycol adipate. The chromatographs were run isothermally, using nitrogen at 50 ml/rain as the carrier gas.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parametersopen allclose all
Test no.:
#1
Toxicokinetic parameters:
half-life 1st: 3.96 sec (Liver)
Test no.:
#2
Toxicokinetic parameters:
half-life 1st: 0.096 sec (small intestinal mucosa)

Applicant's summary and conclusion

Conclusions:
Allyl hexanoate is rapidly hydrolysed in tissue homogenates of rat liver (half life t1/2=3.96 sec) and rat small intestinal mucosa (half life t1/2=0.096 sec).
Executive summary:

Male Wistar albino animals were sacrificed, abdomen opened and the liver and approx. 10 cm lengths of small intestine within the region between 10-30 cm from the pylorus removed. Liver homogenate (10%) was prepared in ice-cold 1.15% KCl mM EDTA buffer at pH 7.4 and homogenate from mucosal surface of intestinal segment (10%) was prepared in ice-cold Krebs-Ringer solution containing 2 g glucose/L. Aliquots of homogenates were placed in flasks in a shaking incubator. Test compound was

added and at designated intervals, portions of solution were extracted with NaCl, methanol & chloroform. After extraction, samples were analyzed with gas chromatography. Liver hydrolysis constant = 630 per hour. Rat liver homogenates were found to be 30 times more efficient than artificial pancreatic juice for allyl heptanoate. Small intestinal mucosa hydrolysis constant = 26000 per hour. Hydrolytic activity in the small intestinal mucosa preparation was 1238 times that in artificial pancreatic juice.