Toxicokinetics of methyl tert-butyl ether (MTBE) and tert-amyl methyl ether (TAME) in humans, and implications to their biological monitoring.
Healthy male volunteers were exposed via inhalation to gasoline oxygenates methyl tert-butyl ether (MTBE) or tert-amyl methyl ether (TAME). The 4-hr exposures were carried out in a dynamic chamber at 25 and 75 ppm for MTBE and at 15 and 50 ppm for TAME. The overall mean pulmonary retention of MTBE was 43 +/- 2.6%; the corresponding mean for TAME was 51 +/- 3.9%. Approximately 52% of the absorbed dose of MTBE was exhaled within 44 hr following the exposure; for TAME, the corresponding figure was 30%. MTBE and TAME in blood and exhaled air reached their highest concentrations at the end of exposure, whereas the concentrations of the metabolites tert-butanol (TBA) and tert-amyl alcohol (TAA) concentrations were highest 0.5-1 hr after the exposure and then declined slowly. Two consecutive half-times were observed for the disappearance of MTBE and TAME from blood and exhaled air. The half-times for MTBE in blood were about 1.7 and 3.8 hr and those for TAME 1.2 and 4.9 hr. For TAA, a single half-time of about 6 hr best described the disappearance from blood and exhaled air; for TBA, the disappearance was slow and seemed to follow zero-order kinetics for 24 hr. In urine, maximal concentrations of MTBE and TAME were observed toward the end of exposure or slightly (< or = 1 hr) after the exposure and showed half-times of about 4 hr and 8 hr, respectively. Urinary concentrations of TAA followed first-order kinetics with a half-time of about 8 hr, whereas the disappearance of TBA was slower and showed zero-order kinetics at concentrations above approx. 10 micro mol/L. Approximately 0.2% of the inhaled dose of MTBE and 0.1% of the dose of TAME was excreted unchanged in urine, whereas the urinary excretion of free TBA and TAA was 1.2% and 0.3% within 48 hr. The blood/air and oil/blood partition coefficients, determined in vitro, were 20 and 14 for MTBE and 20 and 37 for TAME. By intrapolation from the two experimental exposure concentrations, biomonitoring action limits corresponding to an 8-hr time-weighted average (TWA) exposure of 50 ppm was estimated to be 20 micro mol/L for post-shift urinary MTBE, 1 mu mol/L for exhaled air MTBE in a post-shift sample, and 30 micro mol/L for urinary TBA in a next-morning specimen. For TAME and TAA, concentrations corresponding to an 8-hr TWA exposure at 20 ppm were estimated to be 6 micro mol/L (TAME in post-shift urine), 0.2 micro mol/L (TAME in post-shift exhaled air), and 3 micro mol/L (TAA in next morning urine).
Finnish Institute of Occupational Health, Helsinki, Finland. sinikka.vainiotalo@ttl.fi
Sinikka
S
Vainiotalo
Vesa
V
Riihimäki
Kaija
K
Pekari
Eija
E
Teräväinen
Antero
A
Aitio
D000328:Adult; D001944:Breath Tests; D004784:Environmental Monitoring; D006801:Humans; D019570:Inhalation Exposure; D008168:Lung / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000439:Pentanols / Q000097:blood / Q000652:urine*; D020002:tert-Butyl Alcohol / Q000097:blood / Q000652:urine*
D008738:Methyl Ethers; D000439:Pentanols; C043243:methyl tert-butyl ether; C032765:tert-amyl alcohol; C096680:tertiary-amyl methyl ether; D020002:tert-Butyl Alcohol