Propyl acetate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with generally accepted scientific standards and described in sufficent detail (reliability adopted from OECD SIDS)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

In an effort to understand the respiratory bioavailability of aliphatic alcohols and esters, rats were placed into a whole-body plethysmograph. The wholebody plethysmograph is designed to measure (non-invasively) ventilatory movements on conscious rats. By collecting data on ventilatory movements, and chamber and venous blood propyl acetate concentrations, respiratory bioavailability determinations can be calculated.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Propyl acetate

EC Number:

203-686-1

EC Name:

Propyl acetate

Cas Number:

109-60-4

Molecular formula:

C5H10O2

IUPAC Name:

propyl acetate

Details on test material:

n-propyl acetate, spectroscopic grade (>99.9%)

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hilltop Lab Animals, Inc.
- Age at study initiation: no data
- Weight at study initiation: 270-350 g
- Fasting period before study: no data
- Housing: no data
- Individual metabolism cages: no data
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 1 °C
- Humidity (%): 50 +- 20 %
- Air changes (per hr): 15-20/h
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Details on exposure:

In an effort to understand the respiratory bioavailability of aliphatic alcohols and esters, a whole-body plethysmograph was installed in a gas-uptake
chamber. The rat has an indwelling jugular cannula implanted prior to study start and is placed in the plethysmograph. The plethysmograph
(containing the rat) is then placed in the gas-uptake chamber. The leads from the plethysmograph and the venous catheter are exteriorized from the
chamber for sample and data collection. The chamber is charged with 2000 ppm (= ca. 8.34 mg/L) propyl acetate and the chamber concentration decay curve is followed by gas chromatography. In addition, venous blood samples are taken at 0, 5, 10, 15, 20, 25, 30, 40, 50, 60, and 90 minutes. The wholebody plethysmograph is designed to measure (non-invasively) ventilatory movements on conscious rats. By collecting data on ventilatory
movements, and chamber and venous blood propyl acetate concentrations, respiratory bioavailability determinations can be calculated. Blood
samples from six animals were analyzed for n-propyl acetate and n-propyl alcohol concentrations.

Duration and frequency of treatment / exposure:

90 min, once

Doses / concentrations

Remarks:

Doses / Concentrations:
2000 ppm = ca. 8.34 mg/L (the chamber is charged with 2000 ppm propyl acetate and the concentration drops as the rat inhales the test article. Loss to chamber equipment and external surface of the rat is corrected for).

No. of animals per sex per dose / concentration:

6 males

Control animals:

no

Details on study design:

no data

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): blood
- Time and frequency of sampling: 5, 10, 15, 20, 25, 30, 40, 50, 60, and 90 min after injection of test material into the chamber

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Degradation product (CAS No./EC No./EINECS Name): 71-23-8/ 200-746-9/ propan-1-ol

Any other information on results incl. tables

The blood concentrations of n-propyl acetate and n-propyl alcohol during the exposure period are reported below.

Blood level concentrations following inhalation of propyl acetate vapor

Sampling time (min)	Propyl acetate*	Propyl alcohol*
0	0	0
5	17	88
10	29	102
15	36	110
20	31	101
25	32	94
30	33	85
40	25	80
50	20	70
60	14	49
90	6	46

*mean μM whole blood

The presence of propyl alcohol following propyl acetate inhalation exposure clearly demonstrates that propyl alcohol was the major

metabolite of propyl acetate metabolism. Blood levels of propyl alcohol (88 μM) exceeded those of propyl acetate (17 μM) at the first time point measured (5 minutes into the exposure). At the next time point (10 minutes into exposure), the levels of propyl alcohol in the blood were approximately 3-fold higher (102 μM) than the blood levels of propyl acetate (29 μM). Propyl acetate levels peaked at 15 minutes (36 μM) and remained fairly level over the next 15 minutes. Chamber concentrations decreased from time zero, both due to loss to chamber equipment surfaces as well as uptake by the rat (data not shown). Blood propyl alcohol levels were up to 2.5 to 8-fold higher than blood propyl acetate levels from 10 to 90 minutes after the start of the exposure.