Frontiers in toxicology最新文献

{"title":"Source, distribution, and risk assessment of polycyclic aromatic hydrocarbons in sediment and fish samples from River Owan, Edo State, Nigeria.","authors":"Akinyinka Akinnusotu, Justina E Ukpebor, Felix E Okieimen","doi":"10.3389/ftox.2023.1250943","DOIUrl":"https://doi.org/10.3389/ftox.2023.1250943","url":null,"abstract":"<p><p>Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental contaminants that present several environmental risks including human health. The 16 priority PAHs including its 1-methylnaphthalene, and 2-methylnaphthalene were determined in sediment and fish samples (<i>Clarias anguillaris and Oreochromis niloticus</i>) of River Owan, Edo State, Nigeria using gas chromatography (GC) equipped with flame ionization detector (FID) and other standard laboratory protocols. The isomeric ratio was used for source diagnosis, sediment quality guidelines, and risk models of incremental lifetime cancer were used for risk assessment. 1-methylnaphthalene and 2-methylnaphthalene were most predominant in all sediment samples analysed. The ∑LMW PAHs ranged between 0.093-0.250 μg/kg; ∑HMW PAHs were 0.107-0.579 μg/kg. The sediment samples range for ∑PAHs was 0.280-0.810 μg/kg with concentration order of increase: SE5>SE4>SE3>SE6>SE1>SE2>SE7 for the seven sampling locations. The ∑PAHs for <i>Oreochromis niloticus</i> was 0.190 μg/kg, which is higher than the value of <i>Clarias anguillaris</i> 0.080 μg/kg, and these values were greatly lesser when compared to the European Commission limit of 12.00 μg/kg. The diagnostic ratio indicates that the sources are more pyrogenic than petrogenic, revealing combustion from grass, wood, and bush burning. Sediment quality assessment showed that the ∑PAHs were lower than the regulatory values of sediment quality guidelines (SQG) assessment suggesting no ecotoxicological effects on the benthic organisms in this area at present. The Incremental Life Cancer Risk results were in the range of 9.15 × 10^-12-1.46 × 10^-6 for children, and 7.78 × 10^-12-1.76 × 10^-6 for adults considering the three routes of exposure. The incremental life cancer risk assessment showed a negligible risk.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10711100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of the evaluation of endocrine-disrupting chemicals in the Japanese medaka (<i>Oryzias latipes</i>) fish.","authors":"Asok K Dasmahapatra, Charmonix B Williams, Anitha Myla, Sanjay K Tiwary, Paul B Tchounwou","doi":"10.3389/ftox.2023.1272368","DOIUrl":"10.3389/ftox.2023.1272368","url":null,"abstract":"<p><p>Japanese medaka (<i>Oryzias latipes</i>) is an acceptable small laboratory fish model for the evaluation and assessment of endocrine-disrupting chemicals (EDCs) found in the environment. In this research, we used this fish as a potential tool for the identification of EDCs that have a significant impact on human health. We conducted an electronic search in PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and Google Scholar (https://scholar.google.com/) using the search terms, Japanese medaka, <i>Oryzias latipes</i>, and endocrine disruptions, and sorted 205 articles consisting of 128 chemicals that showed potential effects on estrogen-androgen-thyroid-steroidogenesis (EATS) pathways of Japanese medaka. From these chemicals, 14 compounds, namely, 17β-estradiol (E2), ethinylestradiol (EE2), tamoxifen (TAM), 11-ketotestosterone (11-KT), 17β-trenbolone (TRB), flutamide (FLU), vinclozolin (VIN), triiodothyronine (T3), perfluorooctanoic acid (PFOA), tetrabromobisphenol A (TBBPA), terephthalic acid (TPA), trifloxystrobin (TRF), ketoconazole (KTC), and prochloraz (PCZ), were selected as references and used for the identification of apical endpoints within the EATS modalities. Among these endpoints, during classification, priorities are given to sex reversal (masculinization of females and feminization of males), gonad histology (testis-ova or ovotestis), secondary sex characteristics (anal fin papillae of males), plasma and liver vitellogenin (VTG) contents in males, swim bladder inflation during larval development, hepatic vitellogenin (<i>vtg</i>) and choriogenin (<i>chg</i>) genes in the liver of males, and several genes, including estrogen-androgen-thyroid receptors in the hypothalamus-pituitary-gonad/thyroid axis (HPG/T). After reviewing 205 articles, we identified 108 (52.68%), 46 (22.43%), 19 (9.26%), 22 (17.18%), and 26 (12.68%) papers that represented studies on estrogen endocrine disruptors (EEDs), androgen endocrine disruptors (AEDs), thyroid endocrine disruptors (TEDs), and/or steroidogenesis modulators (MOS), respectively. Most importantly, among 128 EDCs, 32 (25%), 22 (17.18%), 15 (11.8%), and 14 (10.93%) chemicals were classified as EEDs, AEDs, TEDs, and MOS, respectively. We also identified 43 (33.59%) chemicals as high-priority candidates for tier 2 tests, and 13 chemicals (10.15%) show enough potential to be considered EDCs without any further tier-based studies. Although our literature search was unable to identify the EATS targets of 45 chemicals (35%) studied in 60 (29.26%) of the 205 articles, our approach has sufficient potential to further move the laboratory-based research data on Japanese medaka for applications in regulatory risk assessments in humans.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10711633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential transcriptomic alterations in nasal versus lung tissue of acrolein-exposed rats.","authors":"Devin I Alewel, Thomas W Jackson, Katherine M Rentschler, Mette C Schladweiler, Anna Astriab-Fisher, Stephen H Gavett, Paul A Evansky, Urmila P Kodavanti","doi":"10.3389/ftox.2023.1280230","DOIUrl":"https://doi.org/10.3389/ftox.2023.1280230","url":null,"abstract":"<p><p><b>Introduction:</b> Acrolein is a significant component of anthropogenic and wildfire emissions, as well as cigarette smoke. Although acrolein primarily deposits in the upper respiratory tract upon inhalation, patterns of site-specific injury in nasal <i>versus</i> pulmonary tissues are not well characterized. This assessment is critical in the design of <i>in vitro</i> and <i>in vivo</i> studies performed for assessing health risk of irritant air pollutants. <b>Methods:</b> In this study, male and female Wistar-Kyoto rats were exposed nose-only to air or acrolein. Rats in the acrolein exposure group were exposed to incremental concentrations of acrolein (0, 0.1, 0.316, 1 ppm) for the first 30 min, followed by a 3.5 h exposure at 3.16 ppm. In the first cohort of male and female rats, nasal and bronchoalveolar lavage fluids were analyzed for markers of inflammation, and in a second cohort of males, nasal airway and left lung tissues were used for mRNA sequencing. <b>Results:</b> Protein leakage in nasal airways of acrolein-exposed rats was similar in both sexes; however, inflammatory cells and cytokine increases were more pronounced in males when compared to females. No consistent changes were noted in bronchoalveolar lavage fluid of males or females except for increases in total cells and IL-6. Acrolein-exposed male rats had 452 differentially expressed genes (DEGs) in nasal tissue <i>versus</i> only 95 in the lung. Pathway analysis of DEGs in the nose indicated acute phase response signaling, Nrf2-mediated oxidative stress, unfolded protein response, and other inflammatory pathways, whereas in the lung, xenobiotic metabolism pathways were changed. Genes associated with glucocorticoid and GPCR signaling were also changed in the nose but not in the lung. <b>Discussion:</b> These data provide insights into inhaled acrolein-mediated sex-specific injury/inflammation in the nasal and pulmonary airways. The transcriptional response in the nose reflects acrolein-induced acute oxidative and cytokine signaling changes, which might have implications for upper airway inflammatory disease susceptibility.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10712669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress in occupational exposure to styrene vapors and dangerous chemicals in the shipbuilding industry.","authors":"Daniela Pigini, Enrico Paci, Rachele Guglielmetti, Giovanna Tranfo, Mariangela Spagnoli, Annarita Fetoni, Laura Tricarico, Renata Sisto","doi":"10.3389/ftox.2023.1319896","DOIUrl":"https://doi.org/10.3389/ftox.2023.1319896","url":null,"abstract":"<p><p><b>Introduction:</b> In the shipbuilding industry, workers are exposed to a variety of dangerous chemicals, styrene being one of them. The International Agency for Research on Cancer classified styrene as a chemical belonging to group 2A, which means it is probably carcinogenic to humans. This study aimed at evaluating the oxidative stress effects due to occupational exposure to styrene and other chemicals. <b>Materials and methods:</b> Styrene urinary metabolites, such as mandelic acid and phenylglyoxylic acid, and the urinary biomarkers of oxidative stress, i.e., oxidation products of DNA and RNA and of proteins, were measured in a group of 17 workers and compared to the concentrations found in a group of 17 healthy volunteers who had not been exposed to chemicals. <b>Results and discussion:</b> Statistically significant differences were found for 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxo-7,8-dihydro-2'-deoxiguanosine (8-oxodGuo) concentrations that are higher in workers than in the control group. The workers performing the tasks of painting are the most exposed to styrene and show higher concentrations of 8-oxo-7,8-dihydroguanosine (8-oxoGuo). Workers performing the tasks of wood refining and welding are less exposed to styrene but have higher concentrations of 8-oxoGua and 8-oxodGuo. <b>Conclusion:</b> The exposure scenario in shipbuilding is a complex one, in which different xenobiotics are simultaneously present. The oxidative stress effect biomarkers, obtained from the oxidation product of RNA and DNA, are promising, sensitive, but not specific.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10702960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binary mixtures of imidacloprid and thiamethoxam do not appear to cause additive toxicity in fathead minnow larvae (<i>Pimephales promelas</i>).","authors":"Anya J Jeninga, Nicole Kooij, Elisabeth Harrahy, Tisha C King-Heiden","doi":"10.3389/ftox.2023.1282817","DOIUrl":"10.3389/ftox.2023.1282817","url":null,"abstract":"<p><p><b>Introduction:</b> Considerable use of neonicotinoid insecticides has resulted in their detection in surface waters globally, with imidacloprid (IM) and thiamethoxam (TM) frequently found together. Neonicotinoids are selective agonists for invertebrate nicotinic acetylcholine receptors (nAChR) leading to paralysis and death. While not overtly toxic to vertebrates, growing evidence suggests that chronic exposure to individual neonicotinoids can cause adverse health effects in fish. This work examined whether chronic exposure to binary mixtures of imidacloprid (IM) and thiamethoxam (TM) would be more toxic to fathead minnow (<i>Pimephales promelas</i>) larvae than either insecticide alone. <b>Materials and Methods:</b> Embryos were exposed to a 1:1 mixture of IM and TM (0.2, 2, 20, 200 or 2,000 μg/L of each pesticide) or a 1:5, 1:10, or 1:20 mixture of IM and TM (0.02 μg/L of IM with 0.1, 0.2, or 0.4 μg/L of TM) for a total of 8 days. Survival, developmental toxicity, embryonic motor activity, and startle escape responses were quantified. <b>Results:</b> Survival and growth were reduced, and hatching induced by exposure to a 1:1 mixture containing > 2 μg/L of each insecticide, but not following exposure to mixtures containing environmentally-relevant concentrations. Acute exposure to a 1:1 mixture did not alter embryonic motor activity; however, chronic exposure to these mixtures resulted in a slight but significant decrease in embryonic movements. Only 1:1 mixtures of high concentrations of IM and TM altered the startle escape response by increasing latency of response; however, a significant proportion of fish exposed to 1:1 mixtures had altered latency and burst speed. Taken together, these behavioral indicators of nAChR activation suggest that in mixtures, neonicotinoids could interfere with nAChR signaling despite their low affinity for the nAChR. <b>Conclusion:</b> Our findings suggest that toxicity of binary mixtures of IM and TM is primarily driven by IM, and that mixtures of IM with TM do not appear to cause significant additive toxicity when compared with our previous studies evaluating each neonicotinoid alone. Given the limited toxicological data available for mixtures of neonicotinoid insecticides in fish, further study is required to better understand the ecological risks these insecticides may pose to aquatic ecosystems.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138489477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SciRAPnano: a pragmatic and harmonized approach for quality evaluation of <i>in vitro</i> toxicity data to support risk assessment of nanomaterials.","authors":"Gen Shao, Anna Beronius, Penny Nymark","doi":"10.3389/ftox.2023.1319985","DOIUrl":"10.3389/ftox.2023.1319985","url":null,"abstract":"<p><p>Large amounts of nanotoxicity data from alternative non-animal (<i>in vitro</i>) test methods have been generated, but there is a lack of harmonized quality evaluation approaches for these types of data. Tools for scientifically sound and structured evaluation of the reliability and relevance of <i>in vitro</i> toxicity data to effectively inform regulatory hazard assessment of nanomaterials (NMs), are needed. Here, we present the development of a pragmatic approach to facilitate such evaluation. The tool was developed based on the Science in Risk Assessment and Policy (SciRAP) tool currently applicable to quality evaluation of chemical toxicity studies. The approach taken to develop the tool, referred to as SciRAPnano, included refinement of the original SciRAP <i>in vitro</i> tool through implementation of identified NM-relevant criteria, and further refined based on a set of case studies involving evaluation of 11 studies investigating <i>in vitro</i> toxicity of nano-sized titanium dioxide. Parameters considered cover key physicochemical properties as well as assay-specific aspects that impact NM toxicity, including NM interference with test methods and NM transformation. The final SciRAPnano tool contains 38 criteria for reporting quality, 19 criteria for methodological quality, and 4 guidance items to evaluate relevance. The approach covers essential parameters for pragmatic and harmonized evaluation of NM <i>in vitro</i> toxicity studies and allows for structured use of <i>in vitro</i> data in regulatory hazard assessment of NMs, including transparency on data quality.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mining toxicogenomic data for dose-responsive pathways: implications in advancing next-generation risk assessment.","authors":"A Rasim Barutcu, Michael B Black, Andy Nong","doi":"10.3389/ftox.2023.1272364","DOIUrl":"10.3389/ftox.2023.1272364","url":null,"abstract":"<p><p><b>Introduction:</b> While targeted investigation of key toxicity pathways has been instrumental for biomarker discovery, unbiased and holistic analysis of transcriptomic data provides a complementary systems-level perspective. However, in a systematic context, this approach has yet to receive comprehensive and methodical implementation. <b>Methods:</b> Here, we took an integrated bioinformatic approach by re-analyzing publicly available MCF7 cell TempO-seq data for 44 ToxCast chemicals using an alternative pipeline to demonstrate the power of this approach. The original study has focused on analyzing the gene signature approach and comparing them to <i>in vitro</i> biological pathway altering concentrations determined from ToxCast HTS assays. Our workflow, in comparison, involves sequential differential expression, gene set enrichment, benchmark dose modeling, and identification of commonly perturbed pathways by network visualization. <b>Results:</b> Using this approach, we identified dose-responsive molecular changes, biological pathways, and points of departure in an untargeted manner. Critically, benchmark dose modeling based on pathways recapitulated points of departure for apical endpoints, while also revealing additional perturbed mechanisms missed by single endpoint analyses. <b>Discussion:</b> This systems-toxicology approach provides multifaceted insights into the complex effects of chemical exposures. Our work highlights the importance of unbiased data-driven techniques, alongside targeted methods, for comprehensively evaluating molecular initiating events, dose-response relationships, and toxicity pathways. Overall, integrating omics assays with robust bioinformatics holds promise for improving chemical risk assessment and advancing new approach methodologies (NAMs).</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing food safety risk assessment in China: development of new approach methodologies (NAMs).","authors":"Daoyuan Yang, Hui Yang, Miaoying Shi, Xudong Jia, Haixia Sui, Zhaoping Liu, Yongning Wu","doi":"10.3389/ftox.2023.1292373","DOIUrl":"10.3389/ftox.2023.1292373","url":null,"abstract":"<p><p>Novel techniques and methodologies are being developed to advance food safety risk assessment into the next-generation. Considering the shortcomings of traditional animal testing, new approach methodologies (NAMs) will be the main tools for the next-generation risk assessment (NGRA), using non-animal methodologies such as <i>in vitro</i> and <i>in silico</i> approaches. The United States Environmental Protection Agency and the European Food Safety Authority have established work plans to encourage the development and application of NAMs in NGRA. Currently, NAMs are more commonly used in research than in regulatory risk assessment. China is also developing NAMs for NGRA but without a comprehensive review of the current work. This review summarizes major NAM-related research articles from China and highlights the China National Center for Food Safety Risk Assessment (CFSA) as the primary institution leading the implementation of NAMs in NGRA in China. The projects of CFSA on NAMs such as the Food Toxicology Program and the strategies for implementing NAMs in NGRA are outlined. Key issues and recommendations, such as discipline development and team building, are also presented to promote NAMs development in China and worldwide.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico approaches in carcinogenicity hazard assessment: case study of pregabalin, a nongenotoxic mouse carcinogen","authors":"Douglas A. Keller, Arianna Bassan, Alexander Amberg, Leigh Ann Burns Naas, Jon Chambers, Kevin Cross, Frances Hall, Gloria D. Jahnke, Amarjit Luniwal, Serena Manganelli, Jordi Mestres, Amy L. Mihalchik-Burhans, David Woolley, Raymond R. Tice","doi":"10.3389/ftox.2023.1234498","DOIUrl":"https://doi.org/10.3389/ftox.2023.1234498","url":null,"abstract":"In silico toxicology protocols are meant to support computationally-based assessments using principles that ensure that results can be generated, recorded, communicated, archived, and then evaluated in a uniform, consistent, and reproducible manner. We investigated the availability of in silico models to predict the carcinogenic potential of pregabalin using the ten key characteristics of carcinogens as a framework for organizing mechanistic studies. Pregabalin is a single-species carcinogen producing only one type of tumor, hemangiosarcomas in mice via a nongenotoxic mechanism. The overall goal of this exercise is to test the ability of in silico models to predict nongenotoxic carcinogenicity with pregabalin as a case study. The established mode of action (MOA) of pregabalin is triggered by tissue hypoxia, leading to oxidative stress (KC5), chronic inflammation (KC6), and increased cell proliferation (KC10) of endothelial cells. Of these KCs, in silico models are available only for selected endpoints in KC5, limiting the usefulness of computational tools in prediction of pregabalin carcinogenicity. KC1 (electrophilicity), KC2 (genotoxicity), and KC8 (receptor-mediated effects), for which predictive in silico models exist, do not play a role in this mode of action. Confidence in the overall assessments is considered to be medium to high for KCs 1, 2, 5, 6, 7 (immune system effects), 8, and 10 (cell proliferation), largely due to the high-quality experimental data. In order to move away from dependence on animal data, development of reliable in silico models for prediction of oxidative stress, chronic inflammation, immunosuppression, and cell proliferation will be critical for the ability to predict nongenotoxic compound carcinogenicity.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136352167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing chemical safety assessment through an omics-based characterization of the test system-chemical interaction","authors":"Giusy del Giudice, Giorgia Migliaccio, Nicoletta D’Alessandro, Laura Aliisa Saarimäki, Marcella Torres Maia, Maria Emilia Annala, Jenni Leppänen, Lena Mӧbus, Alisa Pavel, Maaret Vaani, Anna Vallius, Laura Ylä‐Outinen, Dario Greco, Angela Serra","doi":"10.3389/ftox.2023.1294780","DOIUrl":"https://doi.org/10.3389/ftox.2023.1294780","url":null,"abstract":"Assessing chemical safety is essential to evaluate the potential risks of chemical exposure to human health and the environment. Traditional methods relying on animal testing are being replaced by 3R (reduction, refinement, and replacement) principle-based alternatives, mainly depending on in vitro test methods and the Adverse Outcome Pathway framework. However, these approaches often focus on the properties of the compound, missing the broader chemical-biological interaction perspective. Currently, the lack of comprehensive molecular characterization of the in vitro test system results in limited real-world representation and contextualization of the toxicological effect under study. Leveraging omics data strengthens the understanding of the responses of different biological systems, emphasizing holistic chemical-biological interactions when developing in vitro methods. Here, we discuss the relevance of meticulous test system characterization on two safety assessment relevant scenarios and how omics-based, data-driven approaches can improve the future generation of alternative methods.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135293318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}