Frontiers in toxicology最新文献

{"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":"5 ","pages":"1282817"},"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":"5 ","pages":"1319985"},"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":"5 ","pages":"1272364"},"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":"5 ","pages":"1292373"},"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":"10 5","pages":"0"},"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":" 47","pages":"0"},"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}

{"title":"Assessment of glyphosate and its metabolites’ residue concentrations in cultured African Catfish offered for sale in selected markets in Ibadan, Oyo State, Nigeria","authors":"Selim Adewale Alarape, Adekemi Florence Fagbohun, Oladeni Adegoke Ipadeola, Anthony Ayodeji Adeigbo, Ridwan Olamilekan Adesola, Olanike Kudirat Adeyemo","doi":"10.3389/ftox.2023.1250137","DOIUrl":"https://doi.org/10.3389/ftox.2023.1250137","url":null,"abstract":"Introduction: Glyphosate is a non-targeted organophosphate insecticide whose solubility and mobility in hydrophilic solvents enable its rapid leaching into the soil and subsequent contamination of ground and surface water and possible build-up in the aquatic food chain. Based on the public health importance of glyphosate in fish through consumption, it is crucial to determine the current residue concentration in culture Clarias gariepinus species. The aim of the present study is to evaluate glyphosate’s residue concentrations and its metabolites in cultured African Catfish offered for sale in selected markets in Ibadan. Methods: A total of twenty-five (25) adult Clarias gariepinus (300 ± 50 g) were sourced from five (5) selected active fish markets (Ojoo, Iwo road, Eleyele, Challenge, and Apata) within the Ibadan metropolis. The collected fish tissue samples (liver, kidney, and spleen) were prepared for glyphosate residue concentration analysis using Liquid Chromatography (LC). Results: The results showed that glyphosate residues were recorded in all the seventy-five (75) fish tissue samples obtained from the selected fish markets in the Ibadan metropolis and all residue concentrations were above both the recommended Acceptable Daily Intake (ADI) of 1.0 mg/kg (1 × 10 −3 mg/L) and Maximum Residue Limits (MRL) of 0.01 mg/kg (1 × 10 −5 mg/L). Isopropylamine has the highest residue concentration followed by N-Phosphonomethyl and Aminomethylphosphonic Acid (AMPA), while N-Acetyl Glyphosate has the least residue concentration across the sampled markets. Discussion: The presence of residues of glyphosate and its metabolites in ready-to-eat fish calls for holistic, systematic, and effective risk management strategies towards monitoring pesticide/herbicide usage in aquaculture production and ensuring the provision of wholesome fish and fish products for the consumers.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"172 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135974586","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":"Ophthalmic manifestations and management considerations for emerging chemical threats.","authors":"Bryant A Menke, Christine Ryu, Grant A Justin, Rao V Chundury, Brent R Hayek, Matthew R Debiec, Steven Yeh","doi":"10.3389/ftox.2023.1281041","DOIUrl":"10.3389/ftox.2023.1281041","url":null,"abstract":"<p><p>Chemical agents have been utilized for centuries in warfare and pose a health threat to civilians and military personnel during armed conflict. Despite treaties and regulations against their use, chemical agent exposure remains a threat and measures to understand their effects and countermeasures for systemic and organ-specific health are needed. Many of these agents have ocular complications, both acute and chronic. This mini-review focuses on key chemical agents including vesicants (mustards, lewisite), nerve agents (sarin, VX), knockdown gasses (hydrogen cyanide), and caustics (hydrofluoric acid). Their ophthalmic manifestations and appropriate treatment are emphasized. Acute interventions include removal of the source and meticulous decontamination, as well as normalization of pH to 7.2-7.4 if alteration of the ocular pH is observed. Besides vigorous lavage, acute therapies may include topical corticosteroids and non-steroid anti-inflammatory therapies. Appropriate personal protective equipment (PPE) and strict donning and doffing protocols to avoid healthcare provider exposure are also paramount in the acute setting. For more severe disease, corneal transplantation, amniotic membrane graft, and limbal stem cell transplantation may be needed. Orbital surgery may be required in patients in whom cicatricial changes of the ocular surface have developed, leading to eyelid malposition. Multidisciplinary care teams are often required to handle the full spectrum of findings and consequences associated with emerging chemical threats.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"5 ","pages":"1281041"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71523577","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":"Using <i>in silico</i> tools to predict flame retardant metabolites for more informative exposomics-based approaches.","authors":"Breanne Kincaid, Przemyslaw Piechota, Emily Golden, Mikhail Maertens, Thomas Hartung, Alexandra Maertens","doi":"10.3389/ftox.2023.1216802","DOIUrl":"10.3389/ftox.2023.1216802","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; The positive identification of xenobiotics and their metabolites in human biosamples is an integral aspect of exposomics research, yet challenges in compound annotation and identification continue to limit the feasibility of comprehensive identification of total chemical exposure. Nonetheless, the adoption of &lt;i&gt;in silico&lt;/i&gt; tools such as metabolite prediction software, QSAR-ready structural conversion workflows, and molecular standards databases can aid in identifying novel compounds in untargeted mass spectral investigations, permitting the assessment of a more expansive pool of compounds for human health hazard. This strategy is particularly applicable when it comes to flame retardant chemicals. The population is ubiquitously exposed to flame retardants, and evidence implicates some of these compounds as developmental neurotoxicants, endocrine disruptors, reproductive toxicants, immunotoxicants, and carcinogens. However, many flame retardants are poorly characterized, have not been linked to a definitive mode of toxic action, and are known to share metabolic breakdown products which may themselves harbor toxicity. As U.S. regulatory bodies begin to pursue a subclass- based risk assessment of organohalogen flame retardants, little consideration has been paid to the role of potentially toxic metabolites, or to expanding the identification of parent flame retardants and their metabolic breakdown products in human biosamples to better inform the human health hazards imposed by these compounds. &lt;b&gt;Methods:&lt;/b&gt; The purpose of this study is to utilize publicly available &lt;i&gt;in silico&lt;/i&gt; tools to 1) characterize the structural and metabolic fates of proposed flame retardant classes, 2) predict first pass metabolites, 3) ascertain whether metabolic products segregate among parent flame retardant classification patterns, and 4) assess the existing coverage in of these compounds in mass spectral database. &lt;b&gt;Results:&lt;/b&gt; We found that flame retardant classes as currently defined by the National Academies of Science, Engineering and Medicine (NASEM) are structurally diverse, with highly variable predicted pharmacokinetic properties and metabolic fates among member compounds. The vast majority of flame retardants (96%) and their predicted metabolites (99%) are not present in spectral databases, posing a challenge for identifying these compounds in human biosamples. However, we also demonstrate the utility of publicly available &lt;i&gt;in silico&lt;/i&gt; methods in generating a fit for purpose synthetic spectral library for flame retardants and their metabolites that have yet to be identified in human biosamples. &lt;b&gt;Discussion:&lt;/b&gt; In conclusion, exposomics studies making use of fit-for-purpose synthetic spectral databases will better resolve internal exposure and windows of vulnerability associated with complex exposures to flame retardant chemicals and perturbed neurodevelopmental, reproductive, and other associated apical human health i","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"5 ","pages":"1216802"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429853","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":"Race, pigmentation, and the human skin barrier-considerations for dermal absorption studies.","authors":"Alec T Salminen,&nbsp;Prashiela Manga,&nbsp;Luísa Camacho","doi":"10.3389/ftox.2023.1271833","DOIUrl":"10.3389/ftox.2023.1271833","url":null,"abstract":"<p><p>A functional human skin barrier is critical in limiting harmful exposure to environmental agents and regulating the absorption of intentionally applied topical drug and cosmetic products. Inherent differences in the skin barrier between consumers due to extrinsic and intrinsic factors are an important consideration in the safety assessment of dermatological products. Race is a concept often used to describe a group of people who share distinct physical characteristics. The observed predisposition of specific racial groups to certain skin pathologies highlights the potential differences in skin physiology between these groups. In the context of the human skin barrier, however, the current data correlating function to race often conflict, likely as a consequence of the range of experimental approaches and controls used in the existing works. To date, a variety of methods have been developed for evaluating compound permeation through the human skin, both <i>in vivo</i> and <i>in vitro</i>. Additionally, great strides have been made in the development of reconstructed human pigmented skin models, with the flexibility to incorporate melanocytes from donors of different race and pigmentation levels. Together, the advances in the production of reconstructed human skin models and the increased adoption of <i>in vitro</i> methodologies show potential to aid in the standardization of dermal absorption studies for discerning racial- and skin pigmentation-dependent differences in the human skin barrier. This review analyzes the existing data on skin permeation, focusing on its interaction with race and skin pigmentation, and highlights the tools and research opportunities to better represent the diversity of the human populations in dermal absorption assessments.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"5 ","pages":"1271833"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54232733","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}