Renata Sano Lini, Deborah Thais Palma Scanferla, Nadya Garcia de Oliveira, Raul Gomes Aguera, Thais da Silva Santos, Jorge Juarez Vieira Teixeira, Alice Maria de Souza Kaneshima, Simone Aparecida Galerani Mossini
{"title":"Fungicides as a risk factor for the development of neurological diseases and disorders in humans: a systematic review.","authors":"Renata Sano Lini, Deborah Thais Palma Scanferla, Nadya Garcia de Oliveira, Raul Gomes Aguera, Thais da Silva Santos, Jorge Juarez Vieira Teixeira, Alice Maria de Souza Kaneshima, Simone Aparecida Galerani Mossini","doi":"10.1080/10408444.2024.2303481","DOIUrl":"10.1080/10408444.2024.2303481","url":null,"abstract":"<p><p>Although studies show that pesticides, especially insecticides, may be toxic to humans, publications on the neurological effects of fungicides are scarce. As fungicides are used widely in Brazil, it is necessary to gather evidence to support actions aimed at safely using of these chemicals. We investigated through a systematic review of publications on the use of fungicides and consequences of exposure related to nervous system diseases or neurological disorders in humans. The protocol review was registered on PROSPERO and followed the guidelines of the PRISMA-Statement. As far as it is known, there is no apparent systematic review in the literature on this topic. The search was comprised of the following databases: PubMed; Web of Science; Scopus and EMBASE, using groups of Mesh terms and strategies specific to each database. Thirteen articles were selected for this review. Regarding the substances analyzed in the studies, some reported the use of fungicides in general, without separating them by type, while others summarized the categories of all pesticides by their function (insecticides, herbicides, fungicides, etc.) or chemical class (dithiocarbamate, dicarboximide, inorganic, etc.). However, most of the articles referred to fungicides that contain the metal manganese (Mn) in their composition. As for neurological disorders, articles addressed Parkinson's disease (PD), neurodevelopmental outcomes, extrapyramidal syndrome resembling PD, cognitive disorders, depression, neural tube defects, motor neurone disease, and amyotrophic lateral sclerosis. Most investigations pointed to exposure to fungicides, mainly maneb and mancozeb, leading to the development of at least one neurological disease, which suggests the need for further multicentric clinical trials and prospective studies for greater clarity of the research problem.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"35-54"},"PeriodicalIF":5.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139575539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Grouping approaches based on structure alone are insufficient to conclude about toxicological properties-the example of monoamine-based chelates.","authors":"Josje H E Arts, Sina Bader, Steffen Bade","doi":"10.1080/10408444.2024.2303487","DOIUrl":"10.1080/10408444.2024.2303487","url":null,"abstract":"<p><p>Aminocarboxylic acid (monoamine-based) chelating agents such as GLDA, MGDA, NTA, and EDG are widely used in a variety of products and processes. In the European Union, based on the Green Deal and the Chemicals Strategy for Sustainability (CSS), there is an increasing tendency to speed up chemical hazard evaluation and to regulate chemicals by grouping substances based on molecular structure similarity. Recently, it was proposed to group <i>polycarboxylic acid monoamines, hydroxy derivatives and their salts with monovalent cations</i>, and to consider all group members as potential carcinogens based on the official CLP classification of one group member, viz. NTA, which is classified as suspected carcinogen Cat. 2. In this review, we show that a grouping approach for harmonized classification and labeling based on molecular structure alone, disregarding existing animal test data as well as current scientific and regulatory knowledge, would result in incorrect classification. Using such a simplistic, although considered pragmatic approach, classification of all group members upfront would not improve protection of human health. Instead, it could not only lead to unnecessary additional vertebrate animal testing but also to onerous and disproportionate restrictions being placed on the use of these valuable substances; some of these even being considered as green chemicals.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"55-67"},"PeriodicalIF":5.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohamed Kadry Taher, Franco Momoli, Jennifer Go, Shintaro Hagiwara, Siva Ramoju, Xuefeng Hu, Natalie Jensen, Rowan Terrell, Alex Hemmerich, Daniel Krewski
{"title":"Systematic review of epidemiological and toxicological evidence on health effects of fluoride in drinking water.","authors":"Mohamed Kadry Taher, Franco Momoli, Jennifer Go, Shintaro Hagiwara, Siva Ramoju, Xuefeng Hu, Natalie Jensen, Rowan Terrell, Alex Hemmerich, Daniel Krewski","doi":"10.1080/10408444.2023.2295338","DOIUrl":"10.1080/10408444.2023.2295338","url":null,"abstract":"<p><strong>Introduction: </strong>Fluoride is a naturally occurring substance that is also added to drinking water, dental hygiene products, and food supplements for preventing dental caries. Concerns have been raised about several other potential health risks of fluoride.</p><p><strong>Objective: </strong>To conduct a robust synthesis of evidence regarding human health risks due to exposure to fluoride in drinking water, and to develop a point of departure (POD) for setting a health-based value (HBV) for fluoride in drinking water.</p><p><strong>Methods: </strong>A systematic review of evidence published since recent reviews of human, animal, and <i>in vitro</i> data was carried out. Bradford Hill considerations were used to weigh the evidence for causality. Several key studies were considered for deriving PODs.</p><p><strong>Results: </strong>The current review identified 89 human studies, 199 animal studies, and 10 major <i>in vitro</i> reviews. The weight of evidence on 39 health endpoints was presented. In addition to dental fluorosis, evidence was considered strong for reduction in IQ scores in children, moderate for thyroid dysfunction, weak for kidney dysfunction, and limited for sex hormone disruptions.</p><p><strong>Conclusion: </strong>The current review identified moderate dental fluorosis and reduction in IQ scores in children as the most relevant endpoints for establishing an HBV for fluoride in drinking water. PODs were derived for these two endpoints, although there is still some uncertainty in the causal weight of evidence for causality for reducing IQ scores in children and considerable uncertainty in the derivation of its POD. Given our evaluation of the overall weight of evidence, moderate dental fluorosis is suggested as the key endpoint until more evidence is accumulated on possible reduction of IQ scores effects. A POD of 1.56 mg fluoride/L for moderate dental fluorosis may be preferred as a starting point for setting an HBV for fluoride in drinking water to protect against moderate and severe dental fluorosis. Although outside the scope of the current review, precautionary concerns for potential neurodevelopmental cognitive effects may warrant special consideration in the derivation of the HBV for fluoride in drinking water.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"2-34"},"PeriodicalIF":5.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evan M. Beckett, Anders Abelmann, Benjamin Roberts, Ryan C. Lewis, Drew Cheatham, Eric W. Miller, Ethan Hall, Jennifer S. Pierce
{"title":"An updated evaluation of reported no-observed adverse effect levels for chrysotile, amosite, and crocidolite asbestos for lung cancer and mesothelioma","authors":"Evan M. Beckett, Anders Abelmann, Benjamin Roberts, Ryan C. Lewis, Drew Cheatham, Eric W. Miller, Ethan Hall, Jennifer S. Pierce","doi":"10.1080/10408444.2023.2283169","DOIUrl":"https://doi.org/10.1080/10408444.2023.2283169","url":null,"abstract":"This analysis updates two previous analyses that evaluated the exposure-response relationships for lung cancer and mesothelioma in chrysotile-exposed cohorts. We reviewed recently published studies...","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":"31 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138824262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hepatotoxicity due to dietary supplements: state-of-the-art, gaps and perspectives","authors":"Fernando Rivero-Pino, Alfredo G. Casanova","doi":"10.1080/10408444.2023.2282415","DOIUrl":"https://doi.org/10.1080/10408444.2023.2282415","url":null,"abstract":"Food supplements are products intended to complement the normal diet and consist of concentrated sources of nutrients or other substances with a nutritional or physiological effect. Although they a...","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":"63 1","pages":""},"PeriodicalIF":5.9,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138552459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evidence and hypotheses on adverse effects of the food additives carrageenan (E 407)/processed Eucheuma seaweed (E 407a) and carboxymethylcellulose (E 466) on the intestines: a scoping review.","authors":"Mirlinda Tahiri, Celine Johnsrud, Inger-Lise Steffensen","doi":"10.1080/10408444.2023.2270574","DOIUrl":"10.1080/10408444.2023.2270574","url":null,"abstract":"<p><p>This scoping review provides an overview of publications reporting adverse effects on the intestines of the food additives carrageenan (CGN) (E 407)/processed Eucheuma seaweed (PES) (E 407a) and carboxymethylcellulose (CMC) (E 466). It includes evidence from human, experimental mammal and <i>in vitro</i> research publications, and other evidence. The databases Medline, Embase, Scopus, Web of Science Core Collection, Cochrane Database of Systematic Reviews and Epistemonikos were searched without time limits, in addition to grey literature. The publications retrieved were screened against predefined criteria. From two literature searches, 2572 records were screened, of which 224 records were included, as well as 38 records from grey literature, making a total of 262 included publications, 196 on CGN and 101 on CMC. These publications were coded and analyzed in Eppi-Reviewer and data gaps presented in interactive maps. For CGN, five, 69 and 33 research publications on humans, experimental mammals and <i>in vitro</i> experiments were found, further separated as degraded or native (non-degraded) CGN. For CMC, three human, 20 animal and 14 <i>in vitro</i> research publications were obtained. The most studied adverse effects on the intestines were for both additives inflammation, the gut microbiome, including fermentation, intestinal permeability, and cancer and metabolic effects, and immune effects for CGN. Further studies should focus on native CGN, in the form and molecular weight used as food additive. For both additives, randomized controlled trials of sufficient power and with realistic dietary exposure levels of single additives, performed in persons of all ages, including potentially vulnerable groups, are needed.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"521-571"},"PeriodicalIF":5.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxicity of chemical-based hand sanitizers on children and the development of natural alternatives: a computational approach.","authors":"Toshika Mishra, Suneetha Vuppu","doi":"10.1080/10408444.2023.2270496","DOIUrl":"10.1080/10408444.2023.2270496","url":null,"abstract":"<p><p>The unintended exposure of children to hand sanitizers poses a high risk of potentially fatal complications. Skin irritation, dryness, cracking, peeling, hypoglycemia, apnea, and acidosis are examples of unintended consequences of hand sanitizer. The sanitizer reportedly kills normal microbial flora on hands, which usually promotes innate immunity among children under 12. Children are more susceptible to the toxicity associated with the chemical constituents of marketed chemical-based hand sanitizers; however, the studies to develop sanitizer formulations for children are rudimentary. The adverse events limit the use of hand sanitizers specifically in children because of their sensitive and delicate skin. Additionally, it is reported that many chemical-based hand sanitizer formulations, especially alcohol-based ones may also contain contaminants like methanol, acetaldehyde, benzene, isopropanol, and ethyl-acetate. These contaminants are found to be hazardous to human health exhibiting toxicity on ingestion, inhalation, or dermal exposure, especially in children. Therefore, it is important to design novel, innovative, safer sanitizer formulations for children. The study aims to discuss the toxic contaminants in chemical-based sanitizer formulations and propose a design for novel herbal formulations with minimal toxicity and adverse effects, especially for children. The review focuses on ADMET analysis of the common contaminants in hand sanitizers, molecular docking, Lipinski's rule of five analysis, and molecular simulation studies to analyze the efficacy of interaction with the receptor leading to anti-microbial activity and drug-likeness of the compound. The <i>in silico</i> methods can effectively validate the potential efficacy of novel formulations of hand sanitizers designed for children as an efficient alternative to chemical-based sanitizers with greater efficacy and the absence of toxic contaminants.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"572-599"},"PeriodicalIF":5.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71421459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephen B Stanfill, Stephen S Hecht, Andreas C Joerger, Pablo J González, Luisa B Maia, Maria G Rivas, José J G Moura, Alpana K Gupta, Nick E Le Brun, Jason C Crack, Pierre Hainaut, Courtney Sparacino-Watkins, Robert E Tyx, Suresh D Pillai, Ghazi S Zaatari, S Jane Henley, Benjamin C Blount, Clifford H Watson, Bernd Kaina, Ravi Mehrotra
{"title":"From cultivation to cancer: formation of <i>N</i>-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications.","authors":"Stephen B Stanfill, Stephen S Hecht, Andreas C Joerger, Pablo J González, Luisa B Maia, Maria G Rivas, José J G Moura, Alpana K Gupta, Nick E Le Brun, Jason C Crack, Pierre Hainaut, Courtney Sparacino-Watkins, Robert E Tyx, Suresh D Pillai, Ghazi S Zaatari, S Jane Henley, Benjamin C Blount, Clifford H Watson, Bernd Kaina, Ravi Mehrotra","doi":"10.1080/10408444.2023.2264327","DOIUrl":"10.1080/10408444.2023.2264327","url":null,"abstract":"<p><p>Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific <i>N</i>-nitrosamines (TSNAs), such as <i>N</i>'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the <i>RAS</i> oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"658-701"},"PeriodicalIF":5.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chiu-Wing Lam, Vincent Castranova, Kevin Driscoll, David Warheit, Valerie Ryder, Ye Zhang, Patti Zeidler-Erdely, Robert Hunter, Robert Scully, William Wallace, John James, Brian Crucian, Mayra Nelman, Richard McCluskey, Donald Gardner, Roger Renne, Roger McClellan
{"title":"A review of pulmonary neutrophilia and insights into the key role of neutrophils in particle-induced pathogenesis in the lung from animal studies of lunar dusts and other poorly soluble dust particles.","authors":"Chiu-Wing Lam, Vincent Castranova, Kevin Driscoll, David Warheit, Valerie Ryder, Ye Zhang, Patti Zeidler-Erdely, Robert Hunter, Robert Scully, William Wallace, John James, Brian Crucian, Mayra Nelman, Richard McCluskey, Donald Gardner, Roger Renne, Roger McClellan","doi":"10.1080/10408444.2023.2258925","DOIUrl":"10.1080/10408444.2023.2258925","url":null,"abstract":"<p><p>The mechanisms of particle-induced pathogenesis in the lung remain poorly understood. Neutrophilic inflammation and oxidative stress in the lung are hallmarks of toxicity. Some investigators have postulated that oxidative stress from particle surface reactive oxygen species (psROS) on the dust produces the toxicopathology in the lungs of dust-exposed animals. This postulate was tested concurrently with the studies to elucidate the toxicity of lunar dust (LD), which is believed to contain psROS due to high-speed micrometeoroid bombardment that fractured and pulverized lunar surface regolith. Results from studies of rats intratracheally instilled (ITI) with three LDs (prepared from an Apollo-14 lunar regolith), which differed 14-fold in levels of psROS, and two toxicity reference dusts (TiO<sub>2</sub> and quartz) indicated that psROS had no significant contribution to the dusts' toxicity in the lung. Reported here are results of further investigations by the LD toxicity study team on the toxicological role of oxidants in alveolar neutrophils that were harvested from rats in the 5-dust ITI study and from rats that were exposed to airborne LD for 4 weeks. The oxidants per neutrophils and all neutrophils increased with dose, exposure time and dust's cytotoxicity. The results suggest that alveolar neutrophils play a critical role in particle-induced injury and toxicity in the lung of dust-exposed animals. Based on these results, we propose an adverse outcome pathway (AOP) for particle-associated lung disease that centers on the crucial role of alveolar neutrophil-derived oxidant species. A critical review of the toxicology literature on particle exposure and lung disease further supports a neutrophil-centric mechanism in the pathogenesis of lung disease and may explain previously reported animal species differences in responses to poorly soluble particles. Key findings from the toxicology literature indicate that (1) after exposures to the same dust at the same amount, rats have more alveolar neutrophils than hamsters; hamsters clear more particles from their lungs, consequently contributing to fewer neutrophils and less severe lung lesions; (2) rats exposed to nano-sized TiO<sub>2</sub> have more neutrophils and more severe lesions in their lungs than rats exposed to the same mass-concentration of micron-sized TiO<sub>2</sub>; nano-sized dust has a greater number of particles and a larger total particle-cell contact surface area than the same mass of micron-sized dust, which triggers more alveolar epithelial cells (AECs) to synthesize and release more cytokines that recruit a greater number of neutrophils leading to more severe lesions. Thus, we postulate that, during chronic dust exposure, particle-inflicted AECs persistently release cytokines, which recruit neutrophils and activate them to produce oxidants resulting in a prolonged continuous source of endogenous oxidative stress that leads to lung toxicity. This neutrophil-driven lung pathoge","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"441-479"},"PeriodicalIF":5.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10872584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}