Inhalation toxicokinetics of p-dichlorobenzene and daily absorption and internal accumulation in chronic low-level exposure to humans
Inhalation toxicokinetics of p-dichlorobenzene and daily absorption and internal accumulation in chronic low-level exposure to humans
复制标题
对二氯苯的吸入毒代动力学以及人体长期低水平接触时的日吸收和体内蓄积
DOI：
10.1007/s00204-002-0341-y
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发表时间：
2002
影响因子：
6.1
通讯作者：
M. Fukuhara
中科院分区：
文献类型：
--
作者：
Toshiaki Yoshida;K. Andoh;H. Kosaka;S. Kumagai;I. Matsunaga;Susumu Akasaka;Sei;H. Oda;M. Fukuhara
研究了对二氯苯(p-DCB)在人体内的吸入毒代动力学，估算了其日吸收和体内蓄积量，为一般人群慢性低水平暴露的风险评估提供了基础数据。7名男性受试者连续吸入约2.5ppm的p-DCB蒸气1h，测定呼气空气和血清中p-DCB的浓度-时间曲线和尿中p-DCB的主要代谢物2，5-二氯苯酚(2，5-DCP)。采用线性二房室模型对对-二氯苯的药代动力学进行了评价。利用估算的毒代动力学参数推算出慢性低水平暴露时p-DCB的日吸收量和体内蓄积量。排出体内的主要途径是尿液排泄，其次是代谢，而不是呼气。然而，在暴露开始后的9-11小时内，尿中排出的p-DCB仅为吸收总量的5%-16%。此外，根据毒代动力学分析，大多数被吸收的p-DCB似乎迅速分布到组织中，如脂肪。因此，p-DCB似乎需要很长时间才能从体内完全消除。在长期接触1ppb对二氯苯的受试者中，每日吸收和体内蓄积量平均分别为0.27亿毫克/天和2.9亿毫克。每天吸收的量与我们先前研究中吸入p-DCB的大鼠外推的量大致一致。
Inhalation toxicokinetics ofp-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 ofp-DCB vapor for 1 h, and the concentration-time courses ofp-DCB in their exhaled air and serum and of urinary 2,5-dichlorophenol (2,5-DCP), a major metabolite ofp-DCB, were examined. The toxicokinetics ofp-DCB was evaluated on the basis of the time courses using a linear two-compartment model. The amounts ofp-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 ofp-DCB excreted in urine was only 5–16% of the amount absorbed. Furthermore, most of the absorbedp-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 ofp-DCB. The amount absorbed daily agreed approximately with that extrapolated from rats which inhaledp-DCB in our previous study.