Isopropyl acetate

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

supporting 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:

Uptake of 10 polar solvents during short term respiration.

Author:

Kumagai S, Oda H, Matsunaga I, Kosada H, Akasaka S.

Year:

1999

Bibliographic source:

Tox Sci 48, 255-63

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

basic toxicokinetics

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Measurement of the exhaled concentration of the substance as a percentage of inhaled concentrations.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl acetate

EC Number:

205-500-4

EC Name:

Ethyl acetate

Cas Number:

141-78-6

Molecular formula:

C4H8O2

IUPAC Name:

ethyl ethanoate

Details on test material:

no data. Information from reliable handbook sources

Specific details on test material used for the study:

Source: Special grade, Wako Pure Chemical Industries Ltd, Osaka, Japan.

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 4
- Sex: Male
- Age: Mean 42 years (SD=3.2)
- Race: Japanese
- Demographic information: no data
- Known diseases: no data
- Other: Weight 60.5kg average (SD=13.5), height average 167cm (SD=8.8). Three of the volunteers were smokers but did not smoke for 3 hours before the study and all abstained from alcohol for 15 hours before the study.

Ethical approval:

confirmed, but no further information available

Route of exposure:

inhalation

Reason of exposure:

intentional

Exposure assessment:

measured

Details on exposure:

The volunteers were exposed to the substance (whole body in an inhalation chamber) for 10 minutes followed by a five minute recovery period breathing clean air. Exhaled air was collected from 1 min before exposure to the end of the exposure period. Subjects breathed through a mouthpiece with a one way valve. The inlet valve was connected to a 100L Tedlar bag containing the test concentration or room air. The outlet valve was connected to another 10L Tedlar valve to collect the exhaled air, which was changed every minute. The lines were heated to 40C to prevent internal condensation of the test substance. The inlet and outlet air was continuously monitored by GC/FID. Calibration curves were used to determine the concentrations. Test concentrations used were 50, 100 and 200ppm.. Air relative humdity was 50% and temperature 20C. The volunteers inhaled room air for at least 3 minutes to ensure equipment stability before each run was started. Concentrations in the Tedlar bags were later measured by GC/FID.

Results and discussion

Clinical signs:

None reported

Results of examinations:

The mean respiratory rate for each solvent was from 12.1 to 14 min-1. The mean tidal volume was from 470 to 530 ml, no differences were found among the solvents. The mean exhaled concentrations were ~33% of the inhalation concentration for the second five minutes of exposure, indicating an absorption of 67%. The concentration of ethyl acetate at the end of the exhalation cycle was ~10% of the inlet concentration, indicating elimination of ethyl acetate via exhaled air. On cessation of exposure, the concentration of ethyl acetate in exhaled air fell to zero within 30 seconds suggesting that there was no residual ethyl acetate in the blood stream by this time. The metabolite ethanol was detected in exhaled air in proportion to the inhalation concentration of ethyl acetate and equilibrated at ~2% f the inhalation concentration. The authors determined that these concentrations could only be seen via metabolisation in the respiratory tract wall tissue.

Applicant's summary and conclusion

Executive summary:

A study investigated the respiratory uptake of ethyl acetate in male volunteers using exposure concentrations of 50, 100 and 200ppm and established that over a 10 minute period of exposure, uptake is around 67% of the inhaled concentration. Upon cessation of exposure, exhaled ethyl acetate fell to undetectable levels after half a minute, suggesting rapid metabolism in vivo. End exhaled concentrations were around 10% of inhalation concentrations. Ethanol was detected in exhaled air at concentrations which could only be due to metabolism in the respiratory tract tissues prior to systemic absorption. The authors concluded that the results of this study (which examined a number of solvents) when correlated with partition co-efficients supports the hypothesis that solvent absorbed in the mucous layer of the respiratory tract is removed by the bronchial blood circulation.