Computational assessment of the ADME-Tox profiles and harmful effects of the most common used phthalates on the human health

Abstract

In this study we consider 25 of the most commonly used phthalates and summarize the available data that support their effects on humans. For 15 of the 25 investigated phthalates (60%) there are no human hazard assessment data, neither from experimental nor from computational studies, which underlines the necessity of their risk assessment. Consequently, we have used various computational tools to predict their ADME-Tox profiles and assess their harmful effects on humans. The outcomes of our study reveal that the investigated phthalates have good bioavailability and skin permeability which are associated with toxicity, especially when they are inhaled. They are able to interact with important molecular targets in the human organism such as membrane receptors, cytochromes, kinases, phosphatases, transcription factors, or transporters. These interactions may conduct to predicted harmful effects of phthalates, such as toxicity and irritations of the respiratory and gastrointestinal tracts, skin and eye irritations, endocrine disruption potential, or non-genotoxic carcinogenicity. The investigated phthalates are not predicted to produce genotoxic carcinogenicity, mutagenicity and cardiotoxicity. Beside the investigated phthalates, the di(2-ethylhexyl) phthalate reflects the highest number of toxic effects, and the ditridecyl phthalate and the diisotrodecyl phthalate illustrate the smallest number of possible toxicological effects, namely skin irritation, non-genotoxic carcinogenicity and endocrine disruption potential.

Hydrosoluble and Liposoluble Vitamins: New Perspectives through ADMET Analysis

“…Prediction of ADMET profile is mainly based on models of the physicochemical properties of chemicals which influence much of their pharmacokinetics, but there are also prediction models of the endpoints in ADME that are based on both in vitro and in vivo assay results [23][24][25][26].…”

Computational Assessment of the Pharmacokinetics and Toxicity of the Intensive Sweeteners

“…Information acquired for every investigated sweetener has been synthetized and data are presented in Table I. In order to predict the pharmacokinetics and biological effects of these molecules we have used few accurate computational tools that were extensively used for assessing the biological or side effects of various chemicals: synthetic steroids [34], phthalates [10], oligomers of chitin, chitosan [35] and their derivatives [18], cosmetic ingredients and pesticides [2,16], low molecular weight oligomers of lactic acid [11] and of polydroxyalkanoates [36]. It highlights the applicability of these tools for predicting biological activity and toxicological endpoints for many classes of chemical compounds.…”

In silico Assessment of Pharmacological Profile of Low Molecular Weight Oligo-Hydroxyalkanoates

“…the pharmacological profiles and toxicological endpoints of water-soluble chitosan derivatives (Isvoran et al, 2017), steroids (Roman et al, 2018a), parabens (Roman et al, 2018b), chito-oligomers (Roman et al, 2019), phthalates (Craciun et al, 2019), pesticides (Alves et al, 2018b;Gridan et al, 2019), and low molecular weight oligomers of lactic acid (Dascalu et al, 2020). These methods are summarized in Table 2.…”