Vinyl acetate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline in vitro experimental study, published in peer reviewed literature, minor restrictions in reporting but otherwise adequate for assessment.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1993

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The kinetic parameters for the hydrolysis of vinyl acetate in nasal respiratory and olfactory mucosa were determined.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Vinyl acetate

EC Number:

203-545-4

EC Name:

Vinyl acetate

Cas Number:

108-05-4

Molecular formula:

C4H6O2

IUPAC Name:

ethenyl acetate

Details on test material:

- Name of test material (as cited in study report): vinyl acetate
- Source: Aldrich Chemical Company, Milwaukee, WI, USA
- Purity >99%

Radiolabelling:

no

Test animals

Species:

other: rat and mouse

Strain:

other: CrlCD:BR rats and CD-1 mice

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Raleigh, NC, USA
- Weight: ~200-350 g (rats) and ~20-30 g (mice)
- Housing: individually in stainless steel wire-mesh cages
- Diet: Purina Certified Rodent Chow ad libitum
- Water: tap water ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- no data

IN-LIFE DATES: no data

Administration / exposure

Details on study design:

Animals were killed by carbon dioxide overdose. Nasal tissues were removed, pooled and then homogenised. Vinyl acetate was incubated with tissue homogenate and acetaldehyde was measured by HPLC.

Statistics:

Enzyme kinetic constants were calculated using EZ-FIT v2.0 (Perrella Scientific, Springfield, PA, USA).

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parameters

Toxicokinetic parameters 1

Toxicokinetic parameters:

other: respiratory tissue: Rat - Vmax= 22 and 23 µmol/min/mg protein in males and females respectively; mouse - Vmax = 30 and 46 µmol/min/mg protein in males and females respectively

Toxicokinetic parameters 2

Toxicokinetic parameters:

other: olfactory tissue: Rat - Vmax= 89 and 92 µmol/min/mg protein in males and females respectively; mouse - Vmax= 165 and 96 µmol/min/mg protein in males and females respectively

Toxicokinetic parameters 3

Toxicokinetic parameters:

other: respiratory tissue: Rat - Km= 0.43 and 0.30 mmol in males and females respectively; mouse - Km= 0.42 and 0.76 mmol in males and females respectively

Toxicokinetic parameters 4

Toxicokinetic parameters:

other: olfactory tissue: Rat - Km = 0.33 and 0.20 mmol in males and females respectively; mouse - Km for = 0.52 and 0.41 mmol in males and females respectively

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Acetaldehyde

Applicant's summary and conclusion

Conclusions:

Rat and mouse nasal respiratory and olfactory tissue contains carboxylesterases capable of hydrolysing vinyl acetate to acetaldehyde. There were no major sex differences in the kinetic parameters for the hydrolysis but there were differences between respiratory and olfactory mucosa. Vmax was significantly higher for olfactory mucosa; Km values were similar. Substrate inhibition occurred at high concentrations. The data do not explain the species differences in the carcinogenicity of vinyl acetate.