Registration Dossier

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: 1. Study was an in vitro protocol which would detect and measure only some mechanisms of elimination. 2. Study was not conducted according to a valid and/or internationally accepted testing guideline.

Data source

Reference
Reference Type:
other: Unpublished report
Title:
Unnamed
Year:
1994

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
Method: other
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Vinyl Neodecanoate IUCLID4 Test substance: as prescribed by 1.1 - 1.4

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male

Administration / exposure

Route of administration:
other: In vitro
Vehicle:
acetone
Details on exposure:
In vitro
Doses / concentrations
Remarks:
Doses / Concentrations:
10
Details on study design:
This in vitro study was designed for the testing Vinyl Neodeconoate's disappearance from a buffered solution incorporating whole liver crude homogenate preparations, using Michaelis-Menten kinetics. Liver homogenate was prepared from livers of adult male Fischer 344 rats in sodium phosphate buffer (pH 7.4). Approximately 2 g of liver were minced and rinsed with buffer. Liver was homogenized using a Polytron Homogenizer (~ 15 sec) at a speed setting of 4. The homogenate was then diluted with 50 mM sodium phosphate buffer (pH 7.4) so as to provide concentrations of 3, 1, 0.3 and 0.1% (v/v) homogenate. The homogenates were spiked with test substance prepared in acetone (5 mM). Two hundred-five microliters (205 µl) of liver homogenate were used in all experiments. Standards solutions were prepared by using buffer instead of liver homogenate. Each experiment wasconducted in duplicate. Five microliters of spiking solution were introduced into the homogenate and blank tubes. Tubes were incubated at 37°C for a period of time (not specified in the study). The reaction was terminated by addition of 785 µl of acetonitrile. Tubes were centrifuged, supernatant was collected and analyzed by GC equipped with column (DB-1, Megabore, 30 m x 0.53 mm ID, 5 micrometer film thickness) and flame ionization detector and Hewlett Packard 3396 A Integrator.
Statistics:
Linear regression of Lineweaver-Burk plots served to establish Michaelis-Menten rate constants (Km) and maximum velocities (Vmax).

Results and discussion

Preliminary studies:
A preliminary test with vinyl adipate was conducted to determine the appropriate concentration of liver homogenate to be used in the definitive testing with Vinyl Neodeconate.

Metabolite characterisation studies

Metabolites identified:
no

Any other information on results incl. tables

There was no attempt to fractionate the liver homogenate, and no attempt to determine actual metabolites. There was no attempt to measure GSH depletion either. In general, no disappearance of vinyl neodecanoate was detected in 2 separate tests at any of the concentrations.

Applicant's summary and conclusion

Conclusions:
No dissipation kinetic constants were established for Vinyl Neodeconoate and no metabolites were identified.
Executive summary:

In vitro preparations of rat liver homogenate were used to assess the disappearance of Vinyl Neodecanoate as a function of time at five different concentrations. No disappearanve of Vinyl Neodecanoate was observed in two idependent studies over the concentration range employeed. Therefore, no in vitro dissipation kinetics were established for Vinyl Neodecanoate.