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Toxicological information

Basic toxicokinetics

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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

Reference
Name:
Unnamed
Type:
Constituent
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 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 parametersopen allclose all
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:
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:
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:
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.