Frontiers in toxicology最新文献

{"title":"E-cigarette exposure causes early pro-atherogenic changes in an inducible murine model of atherosclerosis.","authors":"Bayan Alakhtar, Cynthia Guilbert, Nivetha Subramaniam, Vincenza Caruana, Kiran Makhani, Carolyn J Baglole, Koren K Mann","doi":"10.3389/ftox.2023.1244596","DOIUrl":"10.3389/ftox.2023.1244596","url":null,"abstract":"<p><p><b>Introduction:</b> Evidence suggests that e-cigarette use (vaping) increases cardiovascular disease risk, but decades are needed before people who vape would develop pathology. Thus, murine models of atherosclerosis can be utilized as tools to understand disease susceptibility, risk and pathogenesis. Moreover, there is a poor understanding of how risk factors for atherosclerosis (i.e., hyperlipidemia, high-fat diet) intersect with vaping to promote disease risk. Herein, we evaluated whether there was early evidence of atherosclerosis in an inducible hyperlipidemic mouse exposed to aerosol from commercial pod-style devices and e-liquid. <b>Methods:</b> Mice were injected with adeno-associated virus containing the human protein convertase subtilisin/kexin type 9 (PCSK9) variant to promote hyperlipidemia. These mice were fed a high-fat diet and exposed to room air or aerosol derived from JUUL pods containing polyethylene glycol/vegetable glycerin (PG/VG) or 5% nicotine with mango flavoring for 4 weeks; this timepoint was utilized to assess markers of atherosclerosis that may occur prior to the development of atherosclerotic plaques. <b>Results:</b> These data show that various parameters including weight, circulating lipoprotein/glucose levels, and splenic immune cells were significantly affected by exposure to PG/VG and/or nicotine-containing aerosols. <b>Discussion:</b> Not only can this mouse model be utilized for chronic vaping studies to assess the vascular pathology but these data support that vaping is not risk-free and may increase CVD outcomes later in life.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"5 ","pages":"1244596"},"PeriodicalIF":0.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10757938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139076087","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":"Prenatal exposure to bisphenol A and/or diethylhexyl phthalate alters stress responses in rat offspring in a sex- and dose-dependent manner","authors":"Amrita Kaimal, Jessica M. Hooversmith, A. Cherry, Jillian T. Garrity, Maryam H. Al Mansi, N. Martin, Hannah E. Buechter, Philip V. Holmes, P. MohanKumar, S. MohanKumar","doi":"10.3389/ftox.2023.1264238","DOIUrl":"https://doi.org/10.3389/ftox.2023.1264238","url":null,"abstract":"Background: Prenatal exposures to endocrine disrupting chemicals (EDCs) are correlated with adverse behavioral outcomes, but the effects of combinations of these chemicals are unclear. The aim of this study was to determine the dose-dependent effects of prenatal exposure to EDCs on male and female behavior.Methods: Pregnant Sprague-Dawley rats were orally dosed with vehicle, bisphenol A (BPA) (5 μg/kg body weight (BW)/day), low-dose (LD) diethylhexyl phthalate (DEHP) (5 μg/kg BW/day), high-dose (HD) DEHP (7.5 mg/kg BW/day), a combination of BPA and LD-DEHP (B + D (LD)), or a combination of BPA and HD-DEHP (B + D (HD)) on gestational days 6–21. Adult offspring were subjected to the Open Field Test (OFT), Elevated Plus Maze (EPM), and Shock Probe Defensive Burying test (SPDB) in adulthood. Body, adrenal gland, and pituitary gland weights were collected at sacrifice. Corticosterone (CORT) was measured in the serum.Results: Female EDC-exposed offspring showed anxiolytic effects in the OFT, while male offspring were unaffected. DEHP (HD) male offspring demonstrated a feminization of behavior in the EPM. Most EDC-exposed male offspring buried less in the SPDB, while their female counterparts showed reduced shock reactivity, indicating sex-specific maladaptive alterations in defensive behaviors. Additionally, DEHP (LD) males and females and B + D (LD) females displayed increased immobility in this test. DEHP (LD) alone and in combination with BPA led to lower adrenal gland weights, but only in male offspring. Finally, females treated with a mixture of B + D (HD) had elevated CORT levels.Conclusion: Prenatal exposure to BPA, DEHP, or a mixture of the two, affects behavior, CORT levels, and adrenal gland weights in a sex- and dose-dependent manner.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"20 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139004073","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":"Prediction and assessment of xenoestrogens mixture effects using the in vitro ERα-CALUX assay","authors":"M. Elskens, I. Boonen, Steven Eisenreich","doi":"10.3389/ftox.2023.1252847","DOIUrl":"https://doi.org/10.3389/ftox.2023.1252847","url":null,"abstract":"Introduction: Many natural or synthetic compounds used in foods, dietary supplements, and food contact materials (FCMs) are suspected endocrine disruptors (EDs). Currently, scientific evidence to predict the impacts on biological systems of ED mixtures is lacking. In this study, three classes of substances were considered: i) phytoestrogens, ii) plant protection products (PPP) and iii) substances related to FCMs. Fourteen compounds were selected based on their potential endocrine activity and their presence in food and FCMs.Methods: These compounds were evaluated using an in vitro gene expression assay, the ERα-CALUX, to characterize their responses on the estrogen receptor alpha. Cells were exposed to fixed ratio mixtures and non-equipotent mixtures of full and partial agonists. The concentration-response curves measured for the three classes of compounds were characterized by variable geometric parameters in terms of maximum response (efficacy), sensitivity (slope) and potency (median effective concentration EC50). To account for these variations, a generic response addition (GRA) model was derived from mass action kinetics.Results: Although GRA does not allow us to clearly separate the concentration addition (CA) and independent action (IA) models, it was possible to determine in a statistically robust way whether the combined action of the chemicals in the mixture acted by interaction (synergy and antagonism) or by additive behavior. This distinction is crucial for assessing the risks associated with exposure to xenoestrogens. A benchmark dose approach was used to compare the response of phytoestrogen blends in the presence and absence of the hormone estradiol (E2). At the same time, 12 mixtures of 2–5 constituents including phytoestrogens, phthalates and PPPs in proportions close to those found in food products were tested. In 95% of cases, the response pattern observed showed a joint and independent effect of the chemicals on ER.Discussion: Overall, these results validate a risk assessment approach based on an additive effects model modulated by intrinsic toxicity factors. Here, the CA and IA approaches cannot be distinguished solely based on the shape of the concentration response curves. However, the optimized GRA model is more robust than CA when the efficacy, potency, and sensitivity of individual chemical agonists show large variations.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138586172","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":"Refinement of the acute inhalation limit test for inert, nano-sized dusts by an in silico dosimetry-based evaluation: case study for the dissolution of a regulatory dilemma","authors":"Heidi Stratmann, Lan Ma-Hock, Simone Tangermann, Richard A. Corley","doi":"10.3389/ftox.2023.1258861","DOIUrl":"https://doi.org/10.3389/ftox.2023.1258861","url":null,"abstract":"This case study aims to describe the dilemma faced when exposing rats to very high concentrations of fine, pulverulent materials for acute inhalation studies and to address the regulatory question of whether the effects seen here are relevant to humans and the subject of classification according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS). Many powders match the definition of nanomaterials in the EU; therefore, information on acute inhalation testing of powders up to the GHS cutoff of 5 mg/L is required. However, testing rats at such a high aerosol concentration can cause physical obstruction of the airways and even mortality by suffocation. Therefore, to evaluate whether the physical effects on airway obstruction in rats exposed to 5 mg/L for 4 hours and alternative exposures to 1 and 2 mg/L are relevant for humans, an in silico evaluation of aerosol deposition was conducted using the multiple-path particle dosimetry (MPPD) model. For this evaluation, actual exposure conditions for an organic, nano-sized pigment which produced 100% lethality in rats at 5 mg/L, but not at 1 mg/L, were used to assess the potential for airway obstruction in rats and accordingly in humans. As an indicator of the potential for airway obstruction, the ratio of the diameter of the deposited, aggregated aerosol to airway diameter was calculated for each exposure condition. For rats exposed to 5 mg/L for 4 h, approximately 75% of tracheobronchial and 22% of pulmonary/alveolar airways were considered vulnerable to significant or complete obstruction (ratios >0.5). In humans, an equivalent exposure resulted in just over 96% of human tracheobronchial airways that received deposited mass to airway diameter ratios between 0.3 and 0.4 (nasal) or 0.4 and 0.5 (oral), with no airways with ratios >0.5. For the pulmonary/alveolar region, ∼88% of the airways following nasal or oral breathing were predicted to have deposited aerosol diameter to airway diameter ratios <0.1, with no airways with ratios >0.5. Thus, the in silico results obtained for rats are in line with the pathological findings of the animal test. The predicted results in humans, however, affirm the hypothesis of a rat-specific high dose effect which does not justify a classification according to GHS.","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"24 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138600850","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":"Commentary: Considering intrauterine location in a model of fetal growth restriction after maternal titanium dioxide nanoparticle inhalation","authors":"J. DeSesso, L. D. Wise","doi":"10.3389/ftox.2023.1293873","DOIUrl":"https://doi.org/10.3389/ftox.2023.1293873","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"17 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138603834","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":"Acute exposure to diesel particulate matter promotes collective cell migration in thyroid cancer cells.","authors":"Sheena Yi-Hsin Cheng, Shih-Yuan Huang, Shih-Ping Cheng","doi":"10.3389/ftox.2023.1294760","DOIUrl":"https://doi.org/10.3389/ftox.2023.1294760","url":null,"abstract":"<p><p>Several ecological studies suggest that ambient air pollution is associated with the occurrence of thyroid cancer. In this study, we used certified diesel particulate matter as a proxy for fine particulate matter. Human thyroid cancer cell lines 8505C and TPC-1 were incubated with different concentrations of NIST1650b for 5 days and subjected to functional assays. We found that NIST1650b treatment did not affect short-term cell growth but reduced colony formation at high concentrations. Notably, NIST1650b-treated cells showed altered morphology toward cluster coalescence following treatment. Wound healing assays revealed that leading-edge cells formed protruding tips while maintaining cell-cell adhesion, and a significantly higher ratio of wound closure following treatment at 10 μg/mL was seen in both cell lines. A weak stimulatory effect on transwell cell migration was observed in 8505C cells. Taken together, our results suggest that fine particulate matter induced a coherent phenotype accompanied by augmented collective cell migration in thyroid cancer cells.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"5 ","pages":"1294760"},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10720445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814624","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":"Environmental chemical exposures and mental health outcomes in children: a narrative review of recent literature.","authors":"Ashley A James, Katherine L OShaughnessy","doi":"10.3389/ftox.2023.1290119","DOIUrl":"https://doi.org/10.3389/ftox.2023.1290119","url":null,"abstract":"<p><p><b>Background:</b> Mental health is an important factor for children's overall wellbeing. National health statistics show that millions of children are diagnosed with mental health disorders every year, and evidence from studies on chemical pollutants like lead and bisphenols indicate that environmental exposures are linked to mental health illnesses in youth. However, the relationship between children's mental health and the environment is not well understood. This paper aims to review recent literature on prenatal and/or childhood environmental chemical exposures and mental health problems related to mood, anxiety, and behavior. This work also identifies areas of insufficient data and proposes suggestions to fill the data gaps. <b>Methods:</b> A narrative review was performed by searching Google Scholar and PubMed for literature published in the last 6 years (2017-2022), using search terms related to children, mental health, and environmental chemical exposure. Additional relevant studies were identified by screening the references in these papers. <b>Results:</b> A total of 29 studies are included in this review and results are summarized by chemical category: heavy metals, endocrine-disrupting chemicals, and pesticides. The majority of studies reported positive and significant associations between chemical exposures and child mental health outcomes including internalizing and externalizing behaviors. <b>Conclusion:</b> This review demonstrates that there is a growing body of literature that suggests developmental exposure to some environmental chemicals increases a child's risk of mood, anxiety, and behavior problems. Future research should expand on these findings to understand cumulative impacts, chemical mixtures, neurotoxic mechanisms, sex differences, and windows of vulnerability.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"5 ","pages":"1290119"},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10720725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138814633","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":"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":"5 ","pages":"1250943"},"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":"5 ","pages":"1272368"},"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":"5 ","pages":"1280230"},"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}