Registration Dossier

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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1987
Report date:
1986

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The rates of hydrolysis were determined for several carboxylic acid esters (acetic acid esters) using S-9 homogenates from various respiratory tract tissues and livers of rats, rabbits and Syrian hamsters
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
N-butyl acetate
EC Number:
204-658-1
EC Name:
N-butyl acetate
Cas Number:
123-86-4
Molecular formula:
C6H12O2
IUPAC Name:
butyl acetate
Details on test material:
- Name of test material (as cited in study report): n-butyl acetate
- Analytical purity: highes purity available from Aldrich Chemical Co., Milwaukee, WI, USA
Radiolabelling:
no

Test animals

Species:
other: rats, rabbits and hamster
Strain:
other: male F344/N rats; male New Zealand white rabbits; male Syrian hamsters
Sex:
male

Results and discussion

Any other information on results incl. tables

The hydrolysis rate of n-butyl acetate in rat ethmoturbinate S-9 homogenate was determined to be 77 ± 2.13 nmol/mg S-9 protein /min (n = 3 to 5). Hydrolysis rates for other tissues are not reported.

 

As demonstrated with pentyl and phenyl acetate, liver S-9 homogenate had the highest catalytic activity of all rat tissues tested (nasal, trachea, lung tissues). S-9 mix from hamster tissues had higher activities than the respective rat tissue S-9 mixes and the S-9 mixes from hamster maxilloturbinates and ethmoturbinates had even higher activities than hamster liver S-9 mix. The values for rabbits were somewhere inbetween.

 

For saturated linear alkyl acetates (C1 to C6 and C8) hydrolysis rates were determined with rat ethmoturbinate preparations. Rates increased from 15 nmol/mg S-9 protein/min for methyl acetate up to a maximum of 94 nmol/mg S-9 protein/min for pentyl acetate. For the longer chain hexyl and octyl acetate decreasing hydrolysis rates were found (64 and 47 nmol/mg S-9 protein/min respectively):

Applicant's summary and conclusion

Conclusions:
The study results revealed no bioaccumulation potential of the test substance.
n-Butyl acetate seems to be rapidly hydrolyzed by esterases of the respiratory tract.
Executive summary:

The hydrolysis rates of several acetic acid esters were determined in vitro using S-9 homogenate preparations from various tissues of rats, rabbits and hamsters. For each assay 50 µL of a 0.5 M solution of ester in ethanol were incubated at 37°C for 30 min with 2 - 5 mL S-9 homogenate in 0.01 M Tris buffer at pH 7.4 containing 0.7 to 2.5 mg protein. The amount of acetic acid/acetate resulting from hydrolysis was analyzed by ion chromatography.

The hydrolysis rate of n-butyl acetate in rat ethmoturbinate S-9 homogenate was determined to be 77 ± 2.13 nmol/mg S-9 protein /min.

As demonstrated with pentyl acetate and phenyl acetate, liver S-9 homogenate had the highest catalytic activity of all rat tissues tested (nasal, trachea, lung tissues). Higher activities were observed for hamster S-9 preparations.

For linear alkyl acetates (C1 to C6 and C8), hydrolysis rates with rat ethmoturbinate preparations increased with chain length up to a maximum for pentyl acetate (94 nmol/mg S-9 protein/min). Longer chain acetates (hexyl and octyl) showed again decreasing hydrolysis rates (Dahl et al., 1987).