US EPA

630433 

Dissertation 

The influences of exposure pattern and duration on elimination kinetics and exposure assessment of tetrachloroethylene in humans [PhD] 

Chien, YC 

1997 

Rutgers University 

New Brunswick, NJ 

Doctoral Dissertation 

English 

The influence of exposure duration and pattern on body's kinetics during and after environmental tetrachloroethylene exposure were examined using exhaled breath analysis. A subject was exposed to tetrachloroethylene in dry-cleaning stores for three durations, during which personal exposure (breathing-zone air) and alveolar breath samples were collected concurrently, and in a controlled environment facility for different exposure duration and pattern combinations, all of which had the same total exposures. Three dynamic processes that affect elimination were examined: absorption, distribution and elimination. Absorption kinetics were examined using the relationships between the exposure air and exhaled breath concentrations measured simultaneously. It was found that shorter exposure duration resulted in higher percent absorption and therefore higher internal dose The distributions of Perc within the body were studied using both compartment and pharmacokinetic models. Shorter exposure duration or higher exposure intensity resulted in higher Perc body burden, higher peak brain concentration and higher short-term metabolic burden than a longer exposure with lower exposure concentration. A shorter exposure (30-minute) also resulted in greater percent amounts expired, larger area under the postexposure curve and longer first elimination half-lives than longer (90-minute) exposures. The exposure pattern did not have a large influence on the elimination kinetics for 30-minute exposures, but showed significant effects for the longer, 90 minutes, exposures. These findings support the current hypothesis that exposure conditions affect body elimination kinetics. These measurements were also used to evaluate a pharmacokinetic model for tetrachloroethylene. The use of an integrated air concentration as the model input resulted in similar prediction as the actual exposure profiles. The pharmacokinetic model with optimized parameters effectively predicted the postexposure breath concentrations of short-term exposures with small fluctuation in exposure concentration, but is insufficient to predict under extreme exposure scenarios, especially for longer exposure duration. The results also indicated that the assumption of instantaneous exchange between alveolar air and blood may not be valid. The percent Perc metabolized in the liver was predicted to be 36% for the current exposure levels. 

Humans; Kinetics; Tetrachloroethylene