Hexyl acetate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published peer reviewed evaluation; in vitro assessment of metabolism

Data source

Reference

Reference Type:

publication

Title:

Carboxylesterases in the respiratory tracts of rabbits, rats and Syrian hamsters

Author:

Dahl AR, Miller SC & Petridou-Fischer J

Year:

1986

Bibliographic source:

Toxicology Letters, 36 (1987) 129-136

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Investigation into acetate ester hydrolysis by liver respiratory tract enzymes, in vitro.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

acetic acid hexyl ester

IUPAC Name:

acetic acid hexyl ester

Constituent 2

Reference substance name:

Hexyl acetate

EC Number:

205-572-7

EC Name:

Hexyl acetate

Cas Number:

142-92-7

Molecular formula:

C8H16O2

IUPAC Name:

hexyl acetate

Test material form:

not specified

Details on test material:

Acetate esters of methanol, ethanol, propanol, butanol, pentanol, hexanol, octanol, isobutyl alcohol, sec-butyl alcohol , tert-butyl alcohol and phenol;
ß-butyrolacetone and ß-propiolactone. All esters evaluated were obtained from Aldrich Chemical Co, including the two standards - acetic acid and 2-hydroxybutyric acid, at the highest purity available.

Radiolabelling:

no

Test animals

Species:

other: in vitro study

Administration / exposure

Route of administration:

other: in vitro

Vehicle:

not specified

Positive control reference chemical:

Not required for this type of study

Details on study design:

S9 fractions were prepared from samples of liver and respiratory tract tissues (turbinates, trachea, lung) from hamsters, rats and rabbits. The extent of hydrolyis of various esters was investigated in vitro. The esters tested were the acetates of methanol, ethanol, propanol, butanol, pentanol, hexanol, octanol, isobutyl alcohol, sec-butyl alcohol,tert-butylalcohol, and phenol; and ß-propiolactone and ß-butyro)actone. Pentyl acetate, phenylacetate, and ß-butyrolactone were selected for interspecies and intertissue comparisons.

Results and discussion

Preliminary studies:

None

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Not investigated

Details on distribution in tissues:

Not investigated

Details on excretion:

Not investigated

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

No data

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

No data

Any other information on results incl. tables

Pentyl acetate was the most readily hydrolyzed substrate among the straight chain aliphatic alcohol esters. Phenyl acetate was generally the most rapidly hydrolyzed of all the substrates. ß-Butyrolactone was essentially stable toward hydrolysis at pH 7.4 in the absence of S-9, whereas uncatalyzed hydrolysis of ß-propiolactone was extensive (t1/2 -20 min).  In rats, liver S-9 had the most catalytic activity toward all 3 test substrates, but in rabbits and hamsters the ethmoturbinates equalled or exceeded liver for all substrates except pentyl acetate with rabbit tissues. Lung S-9 consistently had less esterase activity than the other tissues, but trachea S-9 was usually nearly as active as nasal and liver tissues. The potential carcinogen ß-butyrolactone was a relatively poor substrate for rat and hamster S-9 enzymes but was comparable to pentyl acetate in the rabbit. An alcohol chain length of 5 atoms (pentyl acetate) with hydrophobicity constant 2.67 appeared to maximize rate of hydrolysis of acetate esters with the highly active ethmoturbinate-derived S-9. Straight chain alcohol esters were most rapidly hydrolyzed and tert-butyl alcohol had the slowest hydrolysis rate among 4-carbon alcohol acetates

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
The results of this study indicate the rapid hydrolysis of esters including hexyl acetate, following inhalation exposure.

Executive summary:

Data support the hypothesis that the metabolism of inhaled xenobiotics may occur extensively in the respiratory tract. Using the rat as an example, it is calculated that hydrolytic enzymes in the nasal cavity can hydrolyze a major portion of acetate esters inhaled at commonly encountered air concentrations.  Calculations, based upon the experimental results, indicate that inhaled esters may be largely converted to hydrolysis products in the nasal cavity.