Modeling di (2-ethylhexyl) Phthalate (DEHP) and Its Metabolism in a Body’s Organs and Tissues through Different Intake Pathways into Human Body

Abstract

Phthalate esters (PAEs) are ubiquitous in indoor environments as plasticizers in indoor products. Residences are often exposed to indoor PAEs in the form of gas, particles, settled dust, and surface phases. To reveal the mechanism behind the accumulation of PAEs in different tissues or organs such as the liver and the lungs when a person exposed to indoor PAEs with different phases, a whole-body physiologically based pharmacokinetic model for PAEs is employed to characterize the dynamic process of phthalates by different intake pathways, including oral digestion, dermal adsorption, and inhalation. Among three different intake pathways, dermal penetration distributed the greatest accumulation of DEHP in most of the organs, while the accumulative concentration through oral ingestion was an order of magnitude lower than the other two doses. Based on the estimated parameters, the variation of di-ethylhexyl phthalate (DEHP) and mono (2-ethylhexyl) phthalate (MEHP) concentration in the venous blood, urine, the liver, the thymus, the pancreas, the spleen, the lungs, the brain, the heart, and the kidney for different intake scenarios was simulated. The simulated results showed a different accumulation profile of DEHP and MEHP in different organs and tissues and demonstrated that the different intake pathways will result in different accumulation distributions of DEHP and MEHP in organs and tissues and may lead to different detrimental health outcomes.

X-box binding protein 1 caused an imbalance in pyroptosis and mitophagy in immature rats with di-(2-ethylhexyl) phthalate-induced testis toxicity

“…DEHP and its biometabolite MEHP are known for their toxicity to main organs, especially the reproductive system. 36 , 38 , 39 Excess ROS generation, blood-testis barrier disintegration, and steroid synthesis may be triggered by DEHP exposure, as revealed in our previous studies. 22 , 40 However, the potential mechanism of DEHP-induced spermatogenic dysfunction in puberty remains unclear.…”

“…MEHP, the main biometabolite of DEHP, exerts a primary toxic effect on most organs. 36 , 37 Based on our previous study, MEHP was administered in vitro . 22 Scanning electron microscopy (SEM) was used to evaluate inflammasomes in MEHP-treated cell lines ( Fig.…”

Phthalate intake in Chinese homes and its contribution to total intake among children

“…Given the relatively heavy molecular weight phthalates with lower vapour pressures like DEHP, which has a tendency to be in dust 54 , it seems reasonable that DEHP had a dust ingestion contribution of > 90% to the indoor intake. The study by Li et al 55 indicated that dust ingestion of DEHP mainly accumulated in liver and had the greatest adverse in uence on liver compared to other humans' organs. On the other hand, low-molecular-weight phthalates such as DEP, DiBP, and DnBP tend to exist in the gas phase.…”