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[三氯乙烯体内外剂量之间的关系。使用生理药代动力学模型的模拟研究]

[The relationship between external and internal doses of trichloroethylene. A simulation study using a physiological pharmacokinetic model].

作者信息

Kaneko T, Endoh K, Sato A

机构信息

Department of Environmental Health, Medical University of Yamanashi.

出版信息

Sangyo Igaku. 1989 Sep;31(5):342-7. doi: 10.1539/joh1959.31.342.

DOI:10.1539/joh1959.31.342
PMID:2585813
Abstract

The relationship between external dose and internal dose of trichloroethylene (Tri) was analyzed by using a physiological simulation model. The external dose of Tri was represented by the time-weighted average (TWA) concentration in inhaled air or by the product of exposure concentration and exposure duration, and the internal dose by the area under the curve (AUC) of Tri blood concentration or by the cumulative amount of total trichloro compounds (TTC) in urine. If TWA concentrations were equal, the internal doses were also equal irrespective of whether Tri exposure was continuous, intermittent, or random. Both AUC of Tri and cumulative amounts of urinary TTC increased linearly with increase of Tri concentration in inhaled air up to 100 ppm. The increase at exposure concentrations between 100 and 500 ppm was non-linear. At concentrations above 500 ppm where Tri metabolism was saturated, AUC increased linearly again but much more sharply than the increase at concentrations below 100 ppm. In contrast, the increase of cumulative amounts approached a plateau along with Tri exposure concentration. If the exposure concentration was below the level when saturation of Tri metabolism did not occur, equal products of Tri concentration and exposure duration resulted in almost the same internal dose. In general, however, the AUC of blood concentration in a high-concentration, short-duration exposure was larger than that of a low-concentration, long-duration exposure, whereas the cumulative amount of TTC was larger in the latter than in the former.

摘要

利用生理模拟模型分析了三氯乙烯(Tri)的外剂量与内剂量之间的关系。Tri的外剂量用吸入空气中的时间加权平均(TWA)浓度或暴露浓度与暴露持续时间的乘积表示,内剂量用Tri血药浓度曲线下面积(AUC)或尿中总三氯化合物(TTC)的累积量表示。如果TWA浓度相等,无论Tri暴露是连续的、间歇的还是随机的,内剂量也相等。在吸入空气中Tri浓度高达100 ppm时,Tri的AUC和尿中TTC的累积量均随Tri浓度的增加呈线性增加。在100至500 ppm的暴露浓度下,增加是非线性的。在Tri代谢饱和的500 ppm以上浓度时,AUC再次呈线性增加,但比100 ppm以下浓度时的增加更为急剧。相比之下,累积量的增加随着Tri暴露浓度的增加接近平稳状态。如果暴露浓度低于Tri代谢未饱和时的水平,Tri浓度与暴露持续时间的相等乘积会导致几乎相同的内剂量。然而,一般来说,高浓度、短时间暴露时血药浓度的AUC大于低浓度、长时间暴露时的AUC,而TTC的累积量在后者大于前者。

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