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Administrative data

basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
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 Type:
other: Unpublished report

Materials and methods

Objective of study:
Principles of method if other than guideline:
Method: other
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
Vinyl neodecanoate
EC Number:
EC Name:
Vinyl neodecanoate
Cas Number:
Molecular formula:
vinyl neodecanoate
Details on test material:
Vinyl Neodecanoate IUCLID4 Test substance: as prescribed by 1.1 - 1.4

Test animals

Fischer 344

Administration / exposure

Route of administration:
other: In vitro
Details on exposure:
In vitro
Doses / concentrations
Doses / Concentrations:
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.
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:

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

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

Vinyl esters are a family of monomers used in the production of latex polymers. The following vinyl ester compounds were investigated in this study: vinyl acetate (CAS No. 108-05-04), vinyl propionate (CAS No. 105—38 -4), vinyl pivalate (CAS No. 3377-92-2), vinyl 2-ethylhexanoate (CAS No, 94-04 -2), divinyl adipate (CAS No. 4074-90—2), vinyl laurate (CAS No. 2146—71-6), vinyl neononanoate (CAS No. 54423-67-5), and vinyl neodecanoate (CAS No. 51000-52-3). The purpose of this study was to measure the rates of metabolism of these vinyl ester compounds in rat liver homogenates. The approach was to measure the disappearance of each of the compounds in F-344 male rat liver homogenates, as well as attempting to measure the appearance of the proposed metabolite, acetaldehyde. The auto-nonenzymatic degradation of selected compounds was also evaluated at pH 2, as was the effect of heat treatment on enzymatic degradation.

Gas chromatographic analysis of the vinyl ester compounds showed the required sensitivity for quantitation within the range of concentrations to be encountered in the study. Acetaldehyde was not detected in the liver incubation experiments for any of the vinyl ester compounds, as the use of acetonitrile in the experiment interfered with the identification and quantification of acetaldehyde. However, the inability to measure acetaldehyde production did not affect the measurements of vinyl ester metabolism rates, since these measurements were based solely on the disappearance rates of the vinyl ester substrate, and not on the appearance rates of the metabolic product(s).

Heat-inactivated incubations (70°C/20 min) inhibited metabolism, indicating that metabolism proceeded via enzymatic processes. The nonenzymatic degradation rate of vinyl acetate, vinyl pivalate and vinyl 2-ethylhexanoate at pH 2 was measured. It was found that this degradation rate at pH 2 was 2 to 3 orders of magnitude slower than the metabolic degradation rates measured using rat liver homogenates. The nonenzymatic degradation rate would, therefore, not be expected to substantially influence the overall breakdown of vinyl esters in vivo when compared to the enzymatic rates of degradation. The Michaelis-Menten, first-order rate constants (Km) and maximum velocities (V533) of metabolism of vinyl acetate, vinyl pivalate, vinyl 2-ethylhexanoate, vinyl neononanoate, divinyl adipate, vinyl neodecanoate, vinyl propionate, and vinyl laurate were measured in 3% (or less, w/w) rat liver homogenates with an incubation period of 1 minute or less. The vinyl esters were then ranked: using both values, according to their ability to be metabolized (greatest to least). The ranking of vinyl esters according to the Km value (for non—neo vinyl esters) was: vinyl propionate > vinyl 2-ethylhexanoate > vinyl acetate > divinyl adipate > vinyl laurate, and (for neo vinyl esters): vinyl pivalate > vinyl neononanoate > vinyl neodecanoate. The compounds were also ranked according to the V54: value: vinyl propionate > vinyl acetate > divinyl adipate > vinyl laurate > vinyl 2-ethylhexanoate, and (for neo vinyl esters): vinyl pivalate > vinyl neononanoate > vinyl neodecanoate. Regardless of the manner of ranking, results from these studies indicate that, of the vinyl esters tested in this study, vinyl propionate is the most readily metabolized vinyl ester not containing a neo group, and vinyl pivalate is the most readily metabolized of the neo-containing vinyl esters.

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.