A physiologically based pharmacokinetic (PBPK) model for di-isononyl phthalate (DiNP) was developed by adapting the existing models for di(2-ethylhexyl) phthalate (DEHP) and di-butylphthalate (DBP). Both pregnant rat and human time-course plasma and urine data were used to address the hydrolysis of DiNP in intestinal tract, plasma, and liver as well as hepatic oxidative metabolism and conjugation of the monoester and primary oxidative metabolites. Data in both rats and humans were available to inform the uptake and disposition of mono-isononyl phthalate (MiNP) as well as the three primary oxidative metabolites including hydroxy (7-OH)-, oxo (7-OXO)-, and carboxy (7-COX)-monoisononyl phthalate in plasma and urine. The DiNP model was reliable over a wide range of exposure levels in the pregnant rat as well as the two low exposure levels in humans including capturing the nonlinear behavior in the pregnant rat after repeated 750 mg/kg/day dosing. The presented DiNP PBPK model in pregnant rat and human, based upon an extensive kinetic dataset in both species, may provide a basis for assessing human equivalent exposures based upon either rodent or in vitro points of departure.

通过修改邻苯二甲酸二（2-乙基己基）酯（DEHP）和邻苯二甲酸二丁酯（DBP）的现有模型，开发了邻苯二甲酸二异壬酯（DiNP）的基于生理的药代动力学（PBPK）模型。怀孕大鼠和人类随时间变化的血浆和尿液数据都用于解决肠道，血浆和肝脏中DiNP的水解以及肝氧化代谢以及单酯和主要氧化代谢产物的结合。可利用大鼠和人类的数据来说明邻苯二甲酸单异壬酯（MiNP）以及三种主要的氧化代谢产物（包括羟基（7-OH）-，氧代（7-OXO）-和羧基（血浆和尿液中的7-COX）-邻苯二甲酸单异壬酯 DiNP模型在妊娠大鼠的广泛暴露水平以及人类的两个低暴露水平中都是可靠的，包括在重复750 mg / kg /天的剂量后捕获妊娠大鼠的非线性行为。基于这两个物种广泛的动力学数据集，在妊娠大鼠和人类中提出的DiNP PBPK模型可以为基于啮齿动物或人类评估人类等效暴露提供基础。体外出发点。