Maruyama Wakae, Yoshida Kikuo, Tanaka Takayuki, Nakanishi Junko
Graduate School of Environment and Information Sciences, Yokohama National University, 79-7 Tokiwadai, Hodogaya, Yokohama, Kanagawa 240-8501, Japan.
Chemosphere. 2003 Oct;53(4):301-13. doi: 10.1016/S0045-6535(03)00015-8.
Polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofuran and dioxin-like polychlorinated biphenyl concentrations in human liver, kidney, fat, blood, muscle, richly perfused tissue (brain, lung etc.) and skin were simulated to assess the health risk for Japanese fetuses. A 40-year time course of dioxin accumulation via food ingestion was simulated using a physiologically based pharmacokinetic (PBPK) model. In richly perfused tissue, the concentration estimated by the PBPK model showed better agreement with measured concentrations than that calculated by the one-compartment model. Fetal dioxin concentration was simulated based on the assumption that the fetal concentration was almost equal to the concentration in the mother's richly perfused tissue. To assess the reproductive risk, the estimated concentration in human fetus was compared with that in rat fetus in which reproductive function showed signs of alteration by 2,3,7,8-TCDD in previous reports [Toxicol. Appl. Pharmacol. 114 (1992) 118; 146 (1997) 11; Toxicol. Sci. 53 (2000) 411; 57 (2000) 275]. The present daily intake of 2,3,7,8-TCDD is approximately 1/50 of the amount that leads to possible reproductive toxicity in the next generation. However, when 29 kinds of dioxin congeners are considered, the present level is 1/5 of the hazardous levels. For species extrapolation of dioxin risk, further study on tissue concentration versus toxicity is required.
模拟了人体肝脏、肾脏、脂肪、血液、肌肉、高灌注组织（脑、肺等）和皮肤中的多氯代二苯并 - 对 - 二噁英、多氯代二苯并呋喃以及类二噁英多氯联苯的浓度，以评估对日本胎儿的健康风险。使用基于生理的药代动力学（PBPK）模型模拟了通过食物摄入二噁英的40年时间进程。在高灌注组织中，PBPK模型估算的浓度与实测浓度的一致性比单室模型计算的结果更好。基于胎儿浓度几乎等于母亲高灌注组织中的浓度这一假设，模拟了胎儿二噁英浓度。为评估生殖风险，将估算的人类胎儿体内浓度与大鼠胎儿体内浓度进行了比较，在以往报告中，大鼠胎儿的生殖功能因2,3,7,8 - 四氯二苯并 - 对 - 二噁英而出现改变迹象[《毒理学与应用药理学》114 (1992) 118；146 (1997) 11；《毒理学科学》53 (2000) 411；57 (2000) 275]。目前2,3,7,8 - 四氯二苯并 - 对 - 二噁英的每日摄入量约为可能导致下一代生殖毒性剂量的1/50。然而，若考虑29种二噁英同系物，目前的水平是危险水平的1/5。对于二噁英风险的物种外推，需要进一步研究组织浓度与毒性的关系。
