An integrative translational framework for chemical induced neurotoxicity – a systematic review

Abstract

Many chemicals in day-to-day and industrial usage have ability to cross the blood brain barrier and develop neurotoxicity in human beings. There are numerous in vitro, in vivo, epidemiological and in silico studies developed to test the neurotoxicity of such chemicals. This systematic review summarized the endpoints and biochemical markers generated from in vitro models, organism-based models, human studies and in silico tools and how they are being used to translate the data for risk assessment of neurotoxic chemicals. With the advancement in experimental studies such as high throughput screening (e.g. proteomics, genomics), there is a huge potential of data generation related to genes and proteins facilitating deep understanding of molecular mechanisms of neurotoxicity. However, this demand a translational platform that can integrate the biological data from different studies mechanistically and thereby translated across intra and interspecies for neurotoxicity assessment. Further, this review proposed an integrative translational framework to assess the chemicals for neurotoxicity.

Tris(1,3-dichloro-2-propyl)phosphate Reduces Growth Hormone Expression via Binding to Growth Hormone Releasing Hormone Receptors and Inhibits the Growth of Crucian Carp

“…Furthermore, our results showed that the concentrations of TDCIPP in the brain were higher than those in the liver. Similarly, two previous studies reported that in carp and zebrafish, the bioconcentration factors of TDCIPP in the brain were higher than that in the liver. , Many chemicals that are subject to daily and industrial usages were reported to had the ability to cross the blood–brain barrier (e.g., BDE-47 and HBCDD), leading to the entrance of the chemicals into the brain and induction of toxic effects. , Collectively, these results indicated that TDCIPP might be able to cross the blood–brain barrier and highly accumulative in the fish brain, and the brain might be an important target organ for the exposure of TDCIPP.…”

“…51,53 Many chemicals that are subject to daily and industrial usages were reported to had the ability to cross the blood−brain barrier (e.g., BDE-47 and HBCDD), leading to the entrance of the chemicals into the brain and induction of toxic effects. 54,55 Collectively, these results indicated that TDCIPP might be able to cross the blood−brain barrier and highly accumulative in the fish brain, and the brain might be an important target organ for the exposure of TDCIPP.…”

Pharmacophore Modeling Using Machine Learning for Screening the Blood–Brain Barrier Permeation of Xenobiotics

“…Nonetheless, this model lays the groundwork for considering active transport along with passive diffusion for BBB permeation. The proposed framework can also support the 3Rs principle, and the use of such methods within read-across approaches [ 43 ] or in a wider integrative translational framework for chemical-induced neurotoxicity [ 44 ]. The current modeling pipeline is a generic framework that can be applied in the field of human risk assessment, as in silico methods for screening neurotoxic environmental chemicals have not yet been implemented.…”

“…The current modeling pipeline is a generic framework that can be applied in the field of human risk assessment, as in silico methods for screening neurotoxic environmental chemicals have not yet been implemented. Screened neurotoxic chemicals space can then be ranked according to their toxic potency by studying their kinetic properties and active concentration in CNS using dynamic modelling methods such as PBPK (physiology-based pharmacokinetics) [ 44 , 45 ]. This integrative approach of QSAR (quantitative structure activity relationship) and PBPK will ease the load of in vitro experiments and will also be helpful in revealing the adverse effects of these toxicants on different organs/system such as the liver, gut, and immune system in a mechanistic way [ 2 , 46 ].…”

EDC-induced mechanisms of immunotoxicity: a systematic review

“…Interspecies and intercell-type differences exist in different models (in-vitro, in-vivo, and human), leading to variation in the production of immune cells. Choice of models can result in similar or different outcomes depending on the cell type used in the study (Deepika et al 2020). Accordingly, as it was demonstrated with B cells, TCDD exposure results in an impaired IgM response both in mice and humans by affecting the Blimp-1-dependent differentiation toward plasmatic cell (Zhang et al 2013;Phadnis-Moghe et al 2015, 2016 and by impairing the LCK-dependent IgM secretion/trafficking, respectively (Zhou, Zhang, et al 2018).…”