Daily exposure to xenobiotics affects human health, especially the nervous system, causing neurodegenerative diseases. The nervous system is protected by tight junctions present at the blood–brain barrier (BBB), but only molecules with desirable physicochemical properties can permeate it. This is why permeation is a decisive step in avoiding unwanted brain toxicity and also in developing neuronal drugs. In silico methods are being implemented as an initial step to reduce animal testing and the time complexity of the in vitro screening process. However, most in silico methods are ligand based, and consider only the physiochemical properties of ligands. However, these ligand-based methods have their own limitations and sometimes fail to predict the BBB permeation of xenobiotics. The objective of this work was to investigate the influence of the pharmacophoric features of protein–ligand interactions on BBB permeation. For these purposes, receptor-based pharmacophore and ligand-based pharmacophore fingerprints were developed using docking and Rdkit, respectively. Then, these fingerprints were trained on classical machine-learning models and compared with classical fingerprints. Among the tested footprints, the ligand-based pharmacophore fingerprint achieved slightly better (77% accuracy) performance compared to the classical fingerprint method. In contrast, receptor-based pharmacophores did not lead to much improvement compared to classical descriptors. The performance can be further improved by considering efflux proteins such as BCRP (breast cancer resistance protein), as well as P-gp (P-glycoprotein). However, the limited data availability for other proteins regarding their pharmacophoric interactions is a bottleneck to its improvement. Nonetheless, the developed models and exploratory analysis provide a path to extend the same framework for environmental chemicals, which, like drugs, are also xenobiotics. This research can help in human health risk assessment by a priori screening for neurotoxicity-causing agents.

Seafood, one of the most important food commodities consumed worldwide, is considered a high-quality, healthy, and safe food option. However, marine ecosystems are the ultimate destination for a large group of chemicals, including contaminants of emerging concern, and seafood consumption is a major pathway of human exposure. With growing awareness of food safety and food quality, and increased demand for information on the risk of contaminants of emerging concern, there is a need to assess food safety issues related to harmful contaminants in seafood and ensure the safety of marine food resources. In this study, the risks of emerging compounds (endocrine disruptors, brominated flame retardants, pharmaceuticals and personal care products, and toxic elements) in fish and seafood were analyzed according to their PBT (persistence, bioaccumulation, toxicity) properties as well as in terms of their concentration levels in seafood. A hazard index (HI) was estimated for each compound by applying an artificial neural network (ANN) approach known as Self-Organizing-Maps. Subsequently, an integrated risk rank (IRI) was developed considering the values of HI and the concentrations of emerging compounds in seafood species gathered from the scientific literature. Current results identified HHCB, MeHg, NP, AHTN and PBDE209 as the top five highest ranked compounds present in seafood, according to the 50th percentile (mean) of the IRI. However, this ranking slightly changed when taking into account the 99th percentile of the IRI, showing toxic elements, methylmercury and inorganic arsenic, as having the highest risk. The outcome of this study identified the priority contaminants and should help in regulatory decision-making and scientific panels to design screening programs as well as to take the appropriate safety measures.

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