Safety and Drug Metabolism: Toward NCE and First in Human DOI
Jacob J. Briedé

Published: Jan. 1, 2024

Language: Английский

Retrospective analysis of carcinogenicity assessments within FDA-notified GRAS determinations DOI Creative Commons

Khatera Rahmani,

Yen-Ching Wu,

Neil Buck

et al.

Human & Experimental Toxicology, Journal Year: 2024, Volume and Issue: 43

Published: Jan. 1, 2024

Frameworks have been developed to standardize the assessment of carcinogenic potential in pharmaceutical and agrochemical industries, building upon decades research. Carcinogenicity is also evaluated during safety evaluation food substances, using a comprehensive approach unique each substance. To better understand these approaches, retrospective was conducted on publicly available database substances notified United States Food Drug Administration (US FDA) as being Generally Recognized As Safe (GRAS). The data contained within GRAS notifications (GRNs) were reviewed for methods used evaluate (genotoxicity studies, 2-year bioassays, other pre-clinical animal studies) identify patterns that could provide an understanding how this has different categories substances. While approaches required adapt all supported conclusion safety. must consider data, including identifying need when more be generated support evaluation. Due complexity food, ranging from defined chemical entities minimally processed agricultural commodities live microorganisms, conducting able most relevant scientifically approach. This paper illustrates commonly types proposes familiar product sectors.

Language: Английский

Citations

2

Assisting the Human Embryo Viability Assessment by Deep Learning for In Vitro Fertilization DOI Creative Commons

Muhammad Ishaq,

Salman Raza,

Hunza Rehar

et al.

Mathematics, Journal Year: 2023, Volume and Issue: 11(9), P. 2023 - 2023

Published: April 24, 2023

The increasing global infertility rate is a matter of significant concern. In vitro fertilization (IVF) significantly minimizes by providing an alternative clinical means becoming pregnant. success IVF mainly depends on the assessment and analysis human blastocyst components such as blastocoel (BC), zona pellucida (ZP), inner cell mass (ICM), trophectoderm (TE). Embryologists perform morphological for selection potential embryos to be used in process. Manual time-consuming, subjective, prone errors. Therefore, artificial intelligence (AI)-based methods are highly desirable enhancing efficiency IVF. this study, novel feature-supplementation-based segmentation network (FSBS-Net) has been developed deliver higher accuracy with less computational overhead compared state-of-the-art methods. FSBS-Net uses effective feature supplementation mechanism along ascending channel convolutional blocks accurately detect pixels minimal spatial loss. proposed method was evaluated using open database component segmentation, it outperformed terms both efficiency. segmented BC, ZP, ICM, TE, background intersections over union (IoU) values 89.15, 85.80, 85.55, 80.17, 95.61%, respectively. addition, achieved mean IoU all categories 87.26% only 2.01 million trainable parameters. experimental results demonstrate that could very helpful assisting embryologists components.

Language: Английский

Citations

5

Metabolites in the regulatory risk assessment of pesticides in the EU DOI Creative Commons
Olavi Pelkonen, Khaled Abass, Juan Manuel Parra Morte

et al.

Frontiers in Toxicology, Journal Year: 2023, Volume and Issue: 5

Published: Dec. 19, 2023

A large majority of chemicals is converted into metabolites through xenobiotic-metabolising enzymes. Metabolites may present a spectrum characteristics varying from similar to vastly different compared with the parent compound in terms both toxicokinetics and toxicodynamics. In pesticide arena, role metabolism increasingly recognised as significant factor particularly for design interpretation mammalian toxicological studies toxicity assessment pesticide/metabolite-associated issues hazard characterization risk purposes, including parts various residues ecotoxicological adversities. This particular relevance that are unique humans comparison found vitro or vivo animal studies, but also disproportionate (quantitative differences) between species. Presence underlie potential concerns. review aims current state-of-the-art comparative research assessment, One Health perspectives, future needs based on experiences gained at European Food Safety Authority.

Language: Английский

Citations

5

Toxicology of carbon nanomaterials in the Caenorhabditis elegans model: current status, characterization, and perspectives for testing harmonization DOI Creative Commons
Francine Côa, Leandro de Sá Bortolozzo, Daiana Silva Ávila

et al.

Frontiers in Carbon, Journal Year: 2023, Volume and Issue: 2

Published: Sept. 6, 2023

Carbon nanomaterials are promising advanced materials for novel technologies. Therefore, biosafety studies mandatory to support their safe development, uses, and disposal in sustainable innovation. Traditional toxicological assays typically expensive, time-consuming, have low throughput; they been replaced by new approach methodologies (NAMs) focused on vitro , chemico silico approaches, along with alternative models. Caenorhabditis elegan s has emerged as a complete model organism predictive toxicology due its transparent body, short reproductive life cycles, fully sequenced genome high homology the human genome. In this review, we discuss current status, state-of-the-art characterization techniques, scientific gaps nanotoxicity involving carbon C. elegans considering last two decades of research. Moreover, show existing supportive tools evaluate internalization biodistribution advantages limitations. Methodological experimental must still be discussed community; hence, bring discussion light point out future orientations perspectives. This review will contribute guiding research harmonization assays/protocols linked computational nanoinformatics approaches during development nanomaterials.

Language: Английский

Citations

4

Comparative toxicological assessment of 2 bisphenols using a systems approach: evaluation of the behavioral and transcriptomic responses of Danio rerio to bisphenol A and tetrabromobisphenol A DOI Creative Commons
Michael G. Morash, Morgan Kirzinger, John C. Achenbach

et al.

Toxicological Sciences, Journal Year: 2024, Volume and Issue: 200(2), P. 394 - 403

Published: May 10, 2024

Abstract The zebrafish (Danio rerio) is becoming a critical component of new approach methods (NAMs) in chemical risk assessment. As whole organism vitro NAM, the model offers significant advantages over individual cell-line testing, including toxicokinetic and toxicodynamic competencies. A transcriptomic not only allows for insight into mechanism action both apical endpoints unobservable adverse outcomes, but also changes gene expression induced by lower, environmentally relevant concentrations. In this study, we used larval to assess behavioral alterations caused subphenotypic concentrations 2 chemicals with same structural backbone, endocrine-disrupting bisphenol tetrabromobisphenol A. Following assessment toxicity, identify molecular pathways associated previously described phenotypes. We determined point departure each modeling as continuous systems which identification single concentration at toxic effects can be predicted. This then investigated confirmatory cell-based testing an integrated determine human health environment greater confidence. paper demonstrates impact using multi-faceted evaluating physiological neurotoxic exposure structurally related chemicals. By comparing phenotypic were able differentiate, characterize, rank toxicities bisphenols, methodological unique NAM.

Language: Английский

Citations

1

Use of Physiologically Based Kinetic Modeling to Predict Deoxynivalenol Metabolism and Its Role in Intestinal Inflammation and Bile Acid Kinetics in Humans DOI Creative Commons
Jingxuan Wang, Véronique de Bruijn, Ivonne M.C.M. Rietjens

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 72(1), P. 761 - 772

Published: Dec. 22, 2023

Current points of departure used to derive health-based guidance values for deoxynivalenol (DON) are based on studies in laboratory animals. Here, an animal-free testing approach was adopted which a reverse dosimetry physiologically kinetic (PBK) modeling is predict vivo dose response curves DON's effects intestinal pro-inflammatory cytokine secretion and bile acid reabsorption humans from concentration–effect relationships DON vitro. The calculated doses inducing 5% added effect above the background level (ED5) increasing IL-1β tissue amounts colon lumen glycochenodeoxycholic (GCDCA) were 246 36 μg/kg bw/day, respectively. These vitro–in silico-derived ED5 compared human dietary exposure levels, indicating that risk these end occurring various populations cannot be excluded. This silico provides novel strategy hazard assessment without using

Language: Английский

Citations

3

Hepatic cholesterol biosynthesis and dioxin-induced dysregulation: A multiscale computational approach DOI Creative Commons

Carla M. Kumbale,

Qiang Zhang, Eberhard O. Voit

et al.

Food and Chemical Toxicology, Journal Year: 2023, Volume and Issue: 181, P. 114086 - 114086

Published: Oct. 10, 2023

Language: Английский

Citations

2

Genetic variability in pathways associates with pesticide-induced nervous system disease in the United States DOI Creative Commons
Marissa B. Kosnik, Philipp Antczak, Peter Fantke

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 26, 2023

Abstract Nervous system disease development following pesticide exposure can vary in a population, but genetic susceptibility to chemicals is poorly characterized. We developed framework build Chemical – SNP (single nucleotide polymorphism) Disease linkages via biological pathways. integrated these with spatialized application data for the United States from 1992 2018 and nervous rates characterize variability pesticide-induced disease. found that number of SNPs implicated per US states positively correlates incidence prevalence Alzheimer’s disease, Parkinson multiple sclerosis. Further, only 2% sets used together over time overlapped between high occurrence low states, more pathways states. This supports pesticides contribute we priority lists SNPs, pesticides, further study.

Language: Английский

Citations

1

Boosting knowledge and harmonisation in the mycotoxin field through sustainable scientific alliances – MYCOBOOST DOI Open Access
Chiara Dall’Asta, Marthe De Boevre, Luca Dellafiora

et al.

EFSA Supporting Publications, Journal Year: 2023, Volume and Issue: 20(11)

Published: Nov. 1, 2023

The MYCOBOOST project was aimed to develop an integrated collaborative model for knowledge exchange and methodology harmonization in mycotoxin risk assessment. A specific focus given the identification of methodological data gaps mycotoxins field promote quality among community. More specifically, activities covered two main aspects, need a harmonisation lack extensive procedures field. Specific needs were identified through online survey interviews with experts, further analysed within consortium. gap analysis complemented by literature review assessment current available resources. As harmonisation, tasks molecular methods fungal identification, inclusion emerging occurrence data, use computational alternative/innovative food items monitoring plans. For all these relevant highlighted recommendations have been drawn. Concerning improvement quality, on revision resources database support impact left-censored exposure Moving from collected evidence, fit-for-purpose training outlined delivered physical workshops. materials (e.g. slides, video, exercises, handbooks) later uploaded ZENODO repository made scientific

Language: Английский

Citations

1

New approach methodologies to confirm developmental toxicity of pharmaceuticals based on weight of evidence DOI
Natasha R. Catlin,

Gregg D. Cappon,

Scott Davenport

et al.

Reproductive Toxicology, Journal Year: 2024, Volume and Issue: 129, P. 108686 - 108686

Published: Aug. 9, 2024

Language: Английский

Citations

0