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Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline study, published in peer-reviewed literature, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Controlled ethyl tert-butyl ether (ETBE) exposure of male volunteers. I. Toxicokinetics.
Author:
Nihlén A, Löf A, Johanson G
Year:
1998
Bibliographic source:
Toxicol Sci.; 46(1):1-10

Materials and methods

Type of study / information:
information on inhalation absorption
Endpoint addressed:
basic toxicokinetics
Principles of method if other than guideline:
Studying the uptake and disposition of ETBE
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethoxy-2-methylpropane
EC Number:
211-309-7
EC Name:
2-ethoxy-2-methylpropane
Cas Number:
637-92-3
Molecular formula:
C6H14O
IUPAC Name:
2-ethoxy-2-methylpropane
Details on test material:
ETBE, technical grade, supplied by Ecofuel S.P.A, Italy. After redistillation the purity was 98.5%.

Method

Ethical approval:
other: The study was carried out according to the Declaration of Helsinki, after approval by the Regional Ethical Committee at the Karolinska Institute Stockholm, Sweden, and after written consent by the volunteers.
Details on study design:
Eight healthy male volunteers were exposed to ETBE vapour (0, 5, 25, and 50 ppm) during 2 h of light physical exercise. ETBE and the proposed metabolites tert-butyl alcohol (TBA) and acetone were analyzed in exhaled air, blood, and urine.
Exposure assessment:
measured
Details on exposure:
Exposure was to ETBE in an exposure chamber (20 m3) with controlled climate (average temperature 19°C, 43% relative humidity, 16 air exchanges/hr). The concentration of ETBE in the chamber air was analysed every 5 min during exposure and mean measured concentrations were 4.8, 25 and
50 ppm.

Results and discussion

Results:
The respiratory uptake of ETBE was 32-34% and the respiratory exhalation was 45-50% of absorbed ETBE.
The kinetic profile of ETBE could be described by four phases in blood (average half-times of 2 min, 18 min, 1.7 h, and 28 h) and two phases in urine (8 min and 8.6 h). Postexposure half-times of TBA in blood and urine were on average 12 and 8 h, respectively.
The 48-h pulmonary excretion of TBA accounted for 1.4-3.8% of the absorbed ETBE, on an equimolar basis.
Urinary excretion of ETBE and TBA was low, below 1% of the ETBE uptake, indicating further metabolism of TBA or other routes of metabolism and elimination.
The kinetics of ETBE and TBA were linear up to 50 ppm.

Applicant's summary and conclusion