Inhalation toxicokinetics of p-dichlorobenzene and daily absorption and internal accumulation in chronic low-level exposure to humans
Inhalation toxicokinetics of p-dichlorobenzene (p-DCB) in humans was evaluated, and the amounts of daily absorption and internal accumulation were estimated in order to obtain fundamental data for the risk assessment of chronic low-level exposure in the general population. Seven male subjects continuously inhaled about 2.5 ppm of p-DCB vapor for 1 h, and the concentration-time courses of p-DCB in their exhaled air and serum and of urinary 2,5-dichlorophenol (2,5-DCP), a major metabolite of p-DCB, were examined. The toxicokinetics of p-DCB was evaluated on the basis of the time courses using a linear two-compartment model. The amounts of p-DCB absorbed daily and the internal accumulation in chronic low-level exposure were extrapolated using the estimated toxicokinetic parameters. p-DCB was transferred from inhaled air to the body with a constant high absorption rate during exposure. The major route for elimination from the body was urinary excretion followed by metabolism, not exhalation. However, during 9–11 h after the start of exposure, the fraction of p-DCB excreted in urine was only 5–16% of the amount absorbed. Furthermore, most of the absorbed p-DCB seemed to be distributed rapidly to the tissues, such as fat, according to toxicokinetic analysis. Consequently, p-DCB seems to require a long time to be completely eliminated from the body. The amounts of daily absorption and internal accumulation were extrapolated to average 0.27 mg/day and 2.9 mg, respectively, in the subjects exposed chronically to 1 ppb of p-DCB. The amount absorbed daily agreed approximately with that extrapolated from rats which inhaled p-DCB in our previous study.
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