2-methoxy-2-methylbutane

Exposure related observations in humans: other data

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: Comparable to guideline study with acceptable restrictions. Published in peer-reviewed literature.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Materials and methods

Endpoint addressed:

basic toxicokinetics

Principles of method if other than guideline:

toxicokinetic study with human volunteers

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methoxy-2-methylbutane

EC Number:

213-611-4

EC Name:

2-methoxy-2-methylbutane

Cas Number:

994-05-8

Molecular formula:

C6H14O

IUPAC Name:

2-methoxy-2-methylbutane

Method

Details on study design:

Six men per group were exposed in a 15 m3 exposure chamber to 0, 15 or 50 ppm TAME for 4 hours. The average age of these men was 24.2 years. The physical activity of the exposed subjects corresponded to light deskwork. Samples were taken from chamber air three times during each exposure. Biological samples were collected from the test subjects’ blood and exhaled air before, during and after exposure. In addition, the subjects collected all urine during 48 hours starting from the time before exposure. The exhaled air, blood and urine samples were analysed using headspace gas chromatography. Toxicokinetic parameters, such as absorption kinetics, metabolism and extraction were determined. The study also contained recording of acute toxicity symptoms (sensory irritation and pre-narcotic signs) and posturographic (steadiness of standing) and reaction time (response to visual signal) measurement.

Exposure assessment:

measured

Results and discussion

Results:

The blood-air-partition coefficient of TAME was 16.2. TAME blood concentration rapidly increased with a slowing at the end during the 4 hours of exposure period demonstrating an approaching steady state. At 50 ppm, TAME blood concentration reached 13.2 μmol/L and when the exposure was 15 ppm, the maximum blood concentration was 4.8 μmol/L.
Independent of the air concentration, the lung retention during the 4 h exposure was 51%. The retention was greater than average in the beginning and lower than average at the end of exposure due to lowered capacity of tissues approaching steady state.
The blood concentration of tert-amyl alcohol (TAA) rose to the same level as that of TAME but with a 1-hour delay. Assuming steady state at the end of the exposure a theoretical clearance of about 1 L/min can be calculated. However, based on the calculated half times, a steady state would be reached only after 25-30 hours from the start of exposure. In any case, the estimated clearance figure shows that the metabolism of TAME is not very efficient. Observing from a graph blood concentration vs. time, blood clearance appears to have 2-3 separate phases. The half-life of TAME was about 6.3 hours while for TAA it was approximately 5.5 hours. Significant individual differences were also noted between test subjects. Thirty-four percent of TAME was removed in exhaled air unchanged whereas about 2/3 was metabolised to other products. Only about 0.3% was excreted as the primary metabolite, TAA, to the urine.