"Dynamic" biological exposure indexes for n-hexane and 2,5-hexanedione, suggested by a physiologically based pharmacokinetic model.
Biological exposure index (BEI) of n-hexane was studied for accuracy using a physiologically based pharmacokinetic (PB-PK) model. The kinetics of n-hexane in alveolar air, blood, urine, and other tissues were simulated for different values of alveolar ventilations and also for constant and variable exposures. The kinetics of 2,5-hexanedione, the toxic n-hexane metabolite, were also simulated. The ranges of n-hexane concentrations in biological media and the urinary concentrations of 2,5-hexanedione are discussed in connection with a mean n-hexane exposure of 180 mg/m3 (50 ppm) (threshold limit value [TLV] suggested by American Conference of Governmental Industrial Hygienists [ACGIH] for 1988-89). The experimental and field data as well as those predicted by simulation with the PB-PK model were comparable. The physiological-pharmacokinetic simulations are used to propose the "dynamic" BEIs of n-hexane and 2,5-hexanedione. The use of simulation with PB-PK models enables a better understanding of the limits, advantages, and issues associated with biological monitoring of exposures to industrial solvents.
Perbellini
L
L
Institute of Occupational Medicine, University of Verona, Policlinico Borgo, Roma, Italy.
Mozzo
P
P
Olivato
D
D
Brugnone
F
F
D006586:Hexanes / Q000493:pharmacokinetics* / Q000652:urine; D006588:Hexanones / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D007659:Ketones / Q000493:pharmacokinetics*; D008452:Maximum Allowable Concentration; D008954:Models, Biological; D014018:Tissue Distribution
D006586:Hexanes; D006588:Hexanones; D007659:Ketones; C026385:n-hexane; C011269:2,5-hexanedione