Body burden measurements and models to assess inhalation exposure to methyl tertiary butyl ether (MTBE)

Biomarkers of methyl tertiary butyl either (MTBE) exposure and the partitioning of inhaled MTBE into the body were investigated in a human chamber study. Two subjects were exposed to an environmentally relevant nominal 5,011 micrograms/m3 (1.39 ppm) MTBE for 1 hour, followed by clean-air exposure for 7 hours. Breath and blood were simultaneously sampled, while total urine was collected at prescribed times before, during, and after the exposure. Mass-balance and toxicokinetic analyses were conducted based upon the time series measurement of multiple body-burden endpoints, including MTBE in alveolar breath, and MTBE and tertiary butyl alcohol (TBA) in venous blood and urine. The decay of MTBE in the blood was assessed by fitting the post-exposure data to a 2- or 3-exponential model that yielded residence times(tau) of 2-3 min, 15-50 min, and 3-13 h as measured by alveolar breath, and 5 min, 60 min, and 32 h as evaluated from venous blood measurements. Based on observations of lower than expected blood and breath MTBE during uptake and a decreasing blood-to-breath ratio during the post-exposure decay period, we hypothesize that the respiratory mucous membranes were serving as a reservoir for the retention of MTBE. The decay data suggest that 6-9% of the MTBE intake may be retained by this non-blood reservoir. The compartmental modeling was further used to estimate important parameters that define the uptake of inhaled MTBE. The first of these parameters is f, the fraction of C(air) exhaled at equilibrium, estimated as 0.60 and 0.46 for the female and male subject, respectively. The second parameter is the blood-to-breath partition coefficient (P) estimated as approximately 18. The product of these parameters provides an estimate of the blood concentration at equilibrium as 8-11 times the air concentration. Blood TBA lagged MTBE levels and decayed more slowly (tau = 1.5-3 h), providing a more stable indication of longer term integrated exposure. The concentration ranges of MTBE and TBA in urine were similar to that of the blood, ranging from 0.37 to 15 micrograms/L and 2 to 15 micrograms/L, respectively. In urine, MTBE and TBA by themselves bore little relationship to the exposure. However, the MTBE:TBA ratio followed the pattern of exposure, with peak values occurring at the end of the exposure (20- and 60-fold greater than pre-exposure values) before decaying back to pre-exposure levels by the end of the 7-h decay period. Urinary elimination accounted for a very small fraction of total MTBE elimination (< 1%).