Physiological poison metabolic kinetic model of adults orally exposed to DEHP

Abstract

The invention relates to the field of public health, in particular to chemical risk assessment, and particularly relates to a physiological poison metabolism kinetic model for adults orally exposed toDEHP. The construction method of the model comprises the following steps: S1, determining a kinetic process of absorption, distribution, metabolism and excretion of DEHP ingested orally in a human body; S2, determining a physiological poison metabolism kinetic model structure of an adult orally exposed to DEHP; S3, establishing a mathematical model, and compiling a differential equation; S4, acquiring human physiological parameters, DEHP biochemical parameters and DEHP toxicokinetic parameters; S5, simulating a physiological poison metabolism kinetic model of DEHP and optimizing parameters. The model and the method disclosed by the invention are helpful to establish DEHP internal and external exposure association of a human body, simulate the content level of DEHP in a target organ, and further clarify an effect mechanism and a dose-reaction relation of DEHP in combination with an effect index of DEHP; therefore, the health risk that people are orally exposed to DEHP can be evaluatedmore accurately, and important scientific basic data are provided for making and correcting DEHP limit values.

Description

technical field [0001] The invention relates to the field of public health, in particular to chemical risk assessment. In particular, it relates to a physiological toxicokinetic model of adult oral exposure to DEHP. Background technique [0002] Bis(2-ethylhexyl)phthalate (DEHP), CAS No. 117-81-7, is mainly used as a plasticizer in various plastic products, such as children's toys, floor tiles, wall coverings , furniture, paints, adhesives, food packaging containers, plastic pipes, medical equipment, etc. Oral ingestion was the main route of DEHP exposure for adults, while skin contact exposure and respiratory inhalation exposure contributed less. DEHP exposure is associated with a variety of health hazards. DEHP has an endocrine disrupting effect, and its primary metabolite MEHP can affect the lipid metabolism process in the human body; and DEHP is potentially carcinogenic, and animal experiments have found that chronic DEHP exposure increases the incidence of liver canc...

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Problems solved by technology

[0007] Chemicals and their metabolites often show specific toxic effects on biological targets such as specific cells, tissues or organs. Therefore, it is necessary to obtain the "target concentration" of the above-mentioned sites, and it is difficult to affect the internal organs of the human body only by experimental means. or tissue separation and extraction, and because human experiments are too complicated, it is usually necessary to extrapolate based on experimental data of other species (such as rodents), but the differences in physiological structure and function of species make this extrapolation more difficult Uncertainty

Due to the lack of correlation with human physiology, the traditional toxicokinetic model is difficult to accurately predict the internal exposure concentration of chemicals and their metabolites to the target, and it is also difficult to extrapolate the prediction results to different exposure scenarios, exposure routes and species

[0008] At present, most of the relevant research on DEHP is limited to the assessment of the external exposure level of DEHP in the population, and there are few studies on the correlation and mutual derivation between the external exposure dose of DEHP and the internal exposure dose of the population, and the health effects of DEHP and its metabolites in the human body depend on the blood The content levels of various metabolites in the body and their content levels in target organs and target tissues. The actual measurement of this level requires obtaining blood samples from the population and various organs and tissues for detection. This is an invasive operation with high costs and low cooperation among the population. , cannot be promoted and applied, and human organs and tissues cannot be sampled and tested

[0009] There are differences in the metabolic parameters of DEHP in animals and humans, so the DEHP physiological toxicokinetic model suitable for animals cannot be applied to humans

Moreover, the health effect of DEHP in the human body depends on the content of metabolites in the blood circulation system, and it is not advisable for the human body DEHP physiological toxicology kinetic model that cannot accurately estimate the content of metabolites such as MEHP in the blood.

In addition, after the human body is exposed to DEHP, a variety of metabolites can be detected in urine, the most important of which are MECPP, MEHHP, MEOHP, MCMHP, and MEHP. Human DEHP physiological toxicokinetic models that do not cover the above metabolites are not yet available. need to be further improved

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