Emilio Benfenati

Emilio Benfenati
Mario Negri Institute for Pharmacological Research | Mario Negri · Department of Environmental Health Sciences

Chemistry

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664
Publications
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Publications

Publications (664)
Article
Azo dyes are broadly used in different industries through their chemical stability and ease of synthesis. However, these dyes are usually identified as critical environmental pollutants. Hence, a mathematical model for the adsorption affinity of azo dyes can be applied for solving tasks of medicine and ecology. Quantitative structure-property relat...
Article
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The risk-characterization of chemicals requires the determination of repeated-dose toxicity (RDT). This depends on two main outcomes: the no-observed-adverse-effect level (NOAEL) and the lowest-observed-adverse-effect level (LOAEL). These endpoints are fundamental requirements in several regulatory frameworks, such as the Registration, Evaluation,...
Preprint
The quantitative structure-property relationships for the dye affinity (DAF, kJ mol-1) of azo dyes were established using the Monte Carlo method by generating optimal SMILES-based descriptors. The index of ideality of correlation ( IIC ) and the correlation intensity index ( CII ) improved the model's predictive potential, specially when they were...
Preprint
Binding to acetylcholinesterase may cause toxic effects in humans. Organophosphates simultaneously are both dangerous and useful substances: dangerous since they are employed in chemical warfare; and useful when they are applied as pesticides. Here we suggest the models for organophosphates binding to acetylcholinesterase developed via representing...
Article
Carcinogenicity testing is necessary to protect human health and comply with regulations, but testing it with the traditionally used two-year rodent studies is time-consuming and expensive. In certain cases, such as for impurities, alternative methods may be convenient. Thus there is an urgent need for alternative approaches for reliable and robust...
Article
Checking the persistence of a chemical in the environment is extremely important. Regulations like REACH, the European one on chemicals, require the measurements or estimates of the half-life of the chemical in water, sediment, and soil. The use of non-testing methods, like quantitative structure-activity relationship (QSAR) models, is encouraged b...
Article
Evaluating the migration of chemicals from food contact materials (FCM) into food is a key step in the safety assessment of such materials. In this paper, a simple mechanistic model describing the migration of chemicals from FCM to food was combined with quantitative property-property relationships (QPPRs) for the prediction of diffusion coefficien...
Article
VEGAHUB ( www.vegahub.eu ) is a repository of freely available, downloadable tools based on computational toxicology methodologies. The main software tool available in VEGAHUB is VEGA QSAR software encoding more than 90 quantitative structure–activity relationship (QSAR) models for tens of endpoints for human toxicology, ecotoxicology, environmenta...
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Developmental and adult/ageing neurotoxicity is an area needing alternative methods for chemical risk assessment. The formulation of a strategy to screen large numbers of chemicals is highly relevant due to potential exposure to compounds that may have long-term adverse health consequences on the nervous system, leading to neurodegeneration. Advers...
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Amphibian populations are undergoing a global decline worldwide. Such decline has been attributed to their unique physiology, ecology, and exposure to multiple stressors including chemicals, temperature, and biological hazards such as fungi of the Batrachochytrium genus, viruses such as Ranavirus, and habitat reduction. There are limited toxicity d...
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Human aromatase, also called CYP19A1, plays a major role in the conversion of androgens into estrogens. Inhibition of aromatase is an important target for estrogen receptor (ER)-responsive breast cancer therapy. Use of azole compounds as aromatase inhibitors is widespread despite their low selectivity. A toxicological evaluation of commonly used az...
Article
Allergic contact dermatitis is increasingly of interest for the hazard characterization of chemicals. in vivo animal testing is usually adopted but in silico approaches are becoming the new frontier due to their swiftness and economic efficiency. Indeed, in silico models can rationalise the experimental outcomes besides having predictive ability. T...
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The system of self-consistent models is an approach to build up and validate quantitative structure-property relationships (QSPRs). This approach is a new conception of estimation of the predictive potential of different models. The reproducibility of the statistical quality of these models despite the differences in distributions is the criterion...
Chapter
Modeling developmental toxicity has been a challenge for (Q)SAR model developers due to the complexity of the endpoint. Recently, some new in silico methods have been developed introducing the possibility to evaluate the integration of existing methods by taking advantage of various modeling perspectives. It is important that the model user is awar...
Chapter
Screening compounds for potential carcinogenicity is of major importance for prevention of environmentally induced cancers. A large sequence of predictive models, ranging from short-term biological assays (e.g., mutagenicity tests) to theoretical models, has been attempted in this field. Theoretical approaches such as (Q)SAR are highly desirable fo...
Chapter
Many regulatory contexts require the evaluation of repeated-dose toxicity (RDT) studies conducted in laboratory animals. The main outcome of RDT studies is the identification of the no observed adverse effect level (NOAEL) and the lowest observed adverse effect level (LOAEL) that are normally used as point of departure for the establishment of heal...
Chapter
Industrial needs and regulatory requirements have played a significant role in accelerating the use of nontesting methods including in silico tools as alternatives to animal testing. The main interest is not solely on the use of in silico tools, or in read-across, but on better toxicological safety assessment of substances, and for this purpose mor...
Chapter
Information on genotoxicity is an essential piece of information in the framework of several regulations aimed at evaluating chemical toxicity. In this context, QSAR models that can predict Ames genotoxicity can conveniently provide relevant information. Indeed, they can be straightforwardly and rapidly used for predicting the presence or absence o...
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Endocrine-disrupting chemicals (EDCs) can inadvertently interact with 12 classic nuclear receptors (NRs) that disrupt the endocrine system and cause adverse effects. There is no widely accepted understanding about what structural features make thousands of EDCs able to activate different NRs as well as how these structural features exert their func...
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Abstract This guidance document provides harmonised and flexible methodologies to apply scientific criteria and prioritisation methods for grouping chemicals into assessment groups for human risk assessment of combined exposure to multiple chemicals. In the context of EFSA’s risk assessments, the problem formulation step defines the chemicals to be...
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To assess the impact of chemicals on an aquatic environment, toxicological data for three trophic levels are needed to address the chronic and acute toxicities. The use of non-testing methods, such as predictive computational models, was proposed to avoid or reduce the need for animal models and speed up the process when there are many substances t...
Chapter
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Traditional laboratory methods to evaluate the properties of chemicals involve a huge amount of animal testing, which represents a very important ethical impact and high costs. The EU Biocidal Products Regulation (BPR) includes specific provisions oriented to reduce animal testing, such as the Art 59, which establishes that the generation of inform...
Chapter
VEGA is a platform which is intended to offer to the user a series of tools for the assessment of property value of chemical substances. It includes more than 70 QSAR models for human toxicological, ecotoxicological, environmental, physicochemical, and toxicokinetic properties. Tools for read-across and screening are also provided. Here we will foc...
Chapter
Data mining (DM) and machine learning (ML) are ubiquitous in every area of human decision-making, from science, to commerce, to art. Their role in modeling the activity of chemicals is also increasing, as a plethora of data becomes available and traditional statistical tools are difficult to apply to it. In this chapter, the main methods of DM and...
Article
This read-across case study characterises thirteen, structurally similar carboxylic acids demonstrating the application of in vitro and in silico human-based new approach methods, to determine biological similarity. Based on data from in vivo animal studies, the read-across hypothesis is that all analogues are steatotic and so should be considered...
Article
Soil pollution is a critical environmental challenge: the substances released in the soil can adversely affect humans and the ecosystem. Several bioassays were developed to investigate the soil ecotoxicity of chemicals with soil microbes, plants, invertebrates and vertebrates. The 28-day collembolan reproduction test with the springtail Folsomia ca...
Article
Semi-correlation specifically assesses the correlation between a binary variable and a continuous variable. Semi-correlations were applied to develop binary models for various endpoints. We applied the semi-correlation to develop models of two kinds of skin sensitization one related to animals (local lymph node assay LLNA) and one to human beings (...
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The thyroid system plays a major role in the regulation of several physiological processes. The dysregulation of the thyroid system caused by the interference of xenobiotics and contaminants may bring to pathologies like hyper- and hypothyroidism and it has been recently correlated with adverse outcomes leading to cancer, obesity, diabetes and neur...
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Atom-pairs proportions are the transparent quality of a molecule: if a molecule has two atoms of oxygen and three atoms of nitrogen, the atom-pair atom1-atom2 can be expressed as a code “atom1-atom2-n1-n2,” indicating the different atoms and their numbers. These codes for a group of atoms (nitrogen, oxygen, sulfur, phosphorus, fluorine, chlorine, b...
Article
The 3Rs concept, calling for replacement, reduction and refinement of animal experimentation, is receiving increasing attention around the world, and has found its way to legislation, in particular in the European Union. This is aligned by continuing high-level efforts of the European Commission to support development and implementation of 3Rs meth...
Article
Cancer is a main concern for human health and there is a need of alternative methodologies to rapidly screen large quantitative of compounds that may represent a toxicological risk. Here a statistical analyses is performed on a benchmark database of experimental Ames data to identify chemical descriptors discriminating mutagens and non-mutagens. A...
Article
Growing interest in environmental toxicity assessment using Thamnocephalus platyurus as organism has led to an increased availability of acute toxicity data. Despite this growing interest in tests with this organism, however, to the best of our knowledge there are no computational models to predict the acute toxicity in T. platyurus. In view of the...
Article
It is usually held that good-quality models for the biological activity of peptides must take into account their 3D architecture and descriptors of quantum mechanics. However, the present study shows that it is possible to build up models without these complex calculations. The structure of tripeptides represented by sequences of one-symbol abbrevi...
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Background: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditi...
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Several tons of chemicals are released every year into the environment and it is essential to assess the risk of adverse effects on human health and ecosystems. Risk assessment is expensive and time-consuming and only partial information is available for many compounds. A consolidated approach to overcome this limitation is the Threshold of Toxicol...
Preprint
Full-text available
Atom-pairs proportions are the transparent quality of a molecule: if a molecule has two atoms of oxygen and three atoms of nitrogen, the atom-pair atom1-atom2 can be expressed as a code 'atom1-atom2-n1-n2', indicating the different atoms and their numbers. These codes for a group of atoms (nitrogen, oxygen, sulfur, phosphorus, fluorine, chlorine, b...
Article
The persistence of organic pollutants is an important environmental property due to the extended possibility to have an impact of corresponding substances. In many cases, the experimental values of the thousands of contaminants are missing. The object of the study is novel computational modeling for air pollutions. Quantitative structure-property r...
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Hydrolysis is one of the most important processes of transformation of organic chemicals in water. The rates of reactions, final chemical entities of these processes, and half-lives of organic chemicals are of considerable interest to environmental chemists as well as authorities involved in the controlling the processing and disposal of such organ...
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Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general a...
Article
The development of antiviral agents against SARS-CoV-2 is necessary. Specific drugs for SARS-CoV-2 are not available. Under such circumstances, the computational methods of drug discovery can be an attractive addition...
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Carcinogenicity is a crucial endpoint for the safety assessment of chemicals and products. During the last few decades, the development of quantitative structure–activity relationship ((Q)SAR) models has gained importance for regulatory use, in combination with in vitro testing or expert-based reasoning. Several classification models can now predic...
Article
The adipose tissue:blood partition coefficient is a key‐endpoint to predict the pharmacokinetics of chemicals in humans and animals, since other organ:blood affinities can be estimated as a function of this parameter. We performed a search in the literature to select all the available rat in vivo data. This approach resulted into two improvements t...
Article
Developmental toxicity refers to the occurrence of adverse effects on a developing organism as a consequence of exposure to hazardous chemicals. The assessment of developmental toxicity has become relevant to the safety assessment process of chemicals. The zebrafish embryo developmental toxicology assay is an emerging test used to screen the terato...
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Computational prediction of HIV-1 protease inhibitor via quantitative structure–activity relationships (QSARs) is a popular study in the field of computational chemistry. The aim of the present study was building up of QSAR models for anti-HIV activity by means of the CORAL software (http://www.insilico.eu/coral). Applying of correlation weights fo...
Article
Pesticides have an impact on the aquatic environment, with ecological effects. The regulation of this impact is of key importance. One of the components of the planning of agricultural and industrial activities is the development of databases and models in order to identify substances that may cause damage. In this study, a quantitative structure-a...
Article
Objective. Predictive models for toxicity to Tetrahymena pyriformis are an important component of natural sciences. The present study aims to build up a predictive model for the endpoint using the so-called index of ideality correlation (IIC). Besides, the comparison of the predictive potential of these models with the predictive potential of model...
Article
Repeated-dose toxicity (RDT) is a critical endpoint for hazard characterisation of chemicals, and is assessed to derive safe levels of exposure for human health. Here we present the first attempt to model simultaneously no-observed-(adverse)-effect-level) (NO(A)EL) and lowest-observed-(adverse)-effect-level (LO(A)EL). Classification and regression...
Article
Quantitative structure – activity relationships (QSARs) which are obtained with a representation of the molecular architecture via simplified molecular input-line entry system (SMILES) are applied to build up predictive models of acute toxicity of pesticides towards Daphnia magna. The acute toxicity towards Daphnia magna is an adequate measure of t...
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Abstract The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) was requested by the European Commission to review the substances for which a Specific Migration Limit (SML) is not assigned in Regulation (EU) No 10/2011. These substances had been covered by the Generic SML of 60 mg/kg food, but with Regulation (EU) 2016/1416 it...
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Read-across (RAX) is a popular data-gap filling technique that uses category and analogue approaches to predict toxicological endpoints for a target. Despite its increasing relevance, RAX relies on human expert judgement and lacks a reproducible and automated protocol. It also only relies on structural similarity for identifying the analogues, whil...
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Honey bees (Apis mellifera) provide key ecosystem services as pollinators bridging agriculture, the food chain and ecological communities, thereby ensuring food production and security. Ecological risk assessment of single Plant Protection Products (PPPs) requires an understanding of the exposure and toxicity. In silico tools such as QSAR models ca...
Article
The similarity is an important category in natural sciences. A measure of similarity for a group of various biochemical endpoints is suggested. The list of examined endpoints contains (1) toxicity of pesticides towards rainbow trout; (2) human skin sensitization; (3) mutagenicity; (4) toxicity of psychotropic drugs; and (5) anti HIV activity. Furth...
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Models for water solubility of pesticides suggested in this manuscript are important data from point of view of ecologic engineering. The Index of Ideality of Correlation (IIC) of groups of quantitative structure–property relationships (QSPRs) for water solubility of pesticides related to the calibration sets was used to identify good in silico mod...
Article
A large number of computer-based prediction methods to determine the potential of chemicals to induce mutations at the gene level has been developed over the last decades. Conversely, only few such methods are currently available to predict potential structural and numerical chromosome aberrations. Even fewer of these are based on the preferred tes...
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The uncertainty regarding the safety of chemicals leaching from food packaging triggers attention. In silico models provide solutions for screening of these chemicals, since many are toxicologically uncharacterized. For hazard assessment, information on developmental and reproductive toxicity (DART) is needed. The possibility to apply in silico tox...