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.
Yoshida
Toshiaki
T
Osaka Prefectural Institute of Public Health, 1-3-69, Nakamichi, Higashinari-ku, Osaka 537-0025, Japan. tsyosida@iph.pref.osaka.jp
Andoh
Katashi
K
Kosaka
Hiroshi
H
Kumagai
Shinji
S
Matsunaga
Ichiro
I
Akasaka
Susumu
S
Nakamura
Sei-ichi
S
Oda
Hajime
H
Fukuhara
Morio
M
D000042:Absorption; D000328:Adult; D000393:Air Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine; D002722:Chlorobenzenes / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D013997:Time Factors
D000393:Air Pollutants; D002722:Chlorobenzenes; C018511:4-dichlorobenzene