Toxicological safety assessment of a water extract of Lithocarpus litseifolius by a 90-day repeated oral toxicity study in rats.

Lithocarpus litseifolius although known as "Sweet Tea" (ST), has been traditionally accepted as a daily beverage and used as a folk medicine in southern China with little understanding of its potential toxicity. This study evaluated the safety of a water extract of ST by a subchronic toxicity study in Sprague-Dawley rats. A total of 80 rats were randomized divided into 4 groups with 10 males and 10 females in each group, treated with 2000, 1,000, 500 and 0 mg/kg body weight of ST extract by gavage for 90 days, respectively. The results of the study showed that ST extract did not induce treatment-related changes in the body and organ weight, food intake, blood hematology and serum biochemistry, urine indices, and histopathology in rats. The NOAEL of ST extract was observed to be 2000 mg/kg/day for rats of both sexes. These results indicated that ST extract was of low toxicity in the experimental conditions of the current study and had the potential for application in food-related products.

Subchronic Toxicity Evaluation of Idesia polycarpa Fruit Oil by 90-Day Oral Exposure in Wistar Rats.

Idesia polycarpa, belonging to the Flacourtiaceae family, is a tall deciduous tree, widely distributed in some Asian countries. It is famous for its high yield of fruit known as oil grape, which is rich of linoleic acid and linolenic acid, and so on. To provide evidences for its safe use as food, subchronic toxicity of I. polycarpa fruit oil and no observed adverse effect level were performed in male and female specific pathogen-free Wistar rats. Based on the Organization for Economic Co-operation and Development guidelines, the oil was orally administered to rats by gavage at 0, 1.0, 2.0, and 4.0mL/kg.bw/day for 90 days, followed by a 28-day recovery period. The results showed that no sign of oil-related toxicity, clinically or histologically, was observed in both male and female rats. Although there was a slight increase or decrease in some indicators such as hematology, serum chemistry, and so on, those changes were all within the normal ranges, and as presented in the 90-day study, the oil exhibited no toxic effect compared to the control rats. I. polycarpa might be a potential excellent and healthy vegetable oil resource.

Human Health Effects of Oral Exposure to Chromium: A Systematic Review of the Epidemiological Evidence.

The toxicity and carcinogenicity of hexavalent chromium via the inhalation route is well established. However, a scientific debate has arisen about the potential effects of oral exposure to chromium on human health. Epidemiological studies evaluating the connection between ingested chromium and adverse health effects on the general population are limited. In recent years, a wealth of biomonitoring studies has emerged evaluating the associations between chromium levels in body fluids and tissues and health outcomes. This systematic review brings together epidemiological and biomonitoring evidence published over the past decade on the health effects of the general population related to oral exposure to chromium. In total, 65 studies were reviewed. There appears to be an inverse association between prenatal chromium exposure and normal fetal development. In adults, parameters of oxidative stress and biochemical alterations increase in response to chromium exposure, while effects on normal renal function are conflicting. Risks of urothelial carcinomas cannot be overlooked. However, findings regarding internal chromium concentrations and abnormalities in various tissues and systems are, in most cases, controversial. Environmental monitoring together with large cohort studies and biomonitoring with multiple biomarkers could fill the scientific gap.

Biocide and other semi-volatile organic compound concentrations in settled indoor dust of CRESPI daycare centers and implication for public health.

This study investigates the presence of biocides and other semi-volatile organic compounds (SVOCs) in cleaning products used in daycare centers and health impact through ingestion of settled dust by young children. In Paris metropolitan area, 106 daycares area were investigated between 2019-2022. Fifteen substances were analyzed in settled indoor dust by gas chromatography-tandem mass spectrometry. Detection rates and concentrations ranged from 5 to 100%, and

Early Developmental Exposure to Triclosan Impacts Fecal Microbial Populations, IgA and Functional Activities of the Rat Microbiome.

Triclosan (TCS), a broad-spectrum antibacterial chemical, is detected in human urine, breast milk, amniotic fluid, and feces; however, little is known about its impact on the intestinal microbiome and host mucosal immunity during pregnancy and early development. Pregnant female rats were orally gavaged with TCS from gestation day (GD) 6 to postpartum (PP) day 28. Offspring were administered TCS from postnatal day (PND) 12 to 28. Studies were conducted to assess changes in the intestinal microbial population (16S-rRNA sequencing) and functional analysis of microbial genes in animals exposed to TCS during pregnancy (GD18), and at PP7, PP28 and PND28. Microbial abundance was compared with the amounts of TCS excreted in feces and IgA levels in feces. The results reveal that TCS decreases the abundance of Bacteroidetes and Firmicutes with a significant increase in Proteobacteria. At PND28, total Operational Taxonomic Units (OTUs) were higher in females and showed correlation with the levels of TCS and unbound IgA in feces. The significant increase in Proteobacteria in all TCS-treated rats along with the increased abundance in OTUs that belong to pathogenic bacterial communities could serve as a signature of TCS-induced dysbiosis. In conclusion, TCS can perturb the microbiome, the functional activities of the microbiome, and activate mucosal immunity during pregnancy and early development.

Assessment of acute and subacute toxicity, pharmacokinetics, and biodistribution of eugenol nanoparticles after oral exposure in Wistar rats.

The present study aimed to assess the safety, toxicity, biodistribution, and pharmacokinetics of eugenol nanoparticles (EONs) following oral administration in Wistar rat models. In the acute toxicity study, the rats were given a fixed dose of 50, 300, and 2000 mg/kg body weight per group orally and screened for 2 weeks after administration. In the subacute study, three different doses (500, 1000, and 2000 mg/kg BW) of EON were administered for 28 days. The results indicated no significant differences in food and water consumption, bodyweight change, hematological and biochemical parameters, relative organ weights, gross findings, or histopathology compared to the control. Additionally, no significant changes were observed in the expression profiles of inflammatory cytokines such as IL-1, IL-6, and TNFα in the plasma, confirming the absence of systemic inflammation. Biodistribution analysis revealed rapid absorption of eugenol and improved bioavailability due to gradual and sustained release, leading to a maximum eugenol concentration of 15.05 µg/mL (Cmax) at approximately 8 h (Tmax) in the blood plasma. Thus, the study provides valuable insights into the utilization of EON for enhancing the stability, solubility, and sustained release of eugenol and highlights its promising safety profile in vivo.

Health Risks for Consumers of Forest Ground Cover Produce Contaminated with Heavy Metals.

BACKGROUND: The activity of heavy metal (HM) mining and processing industries causes soils contamination with HM. The metals could be transferred from contaminated soils to edible plants and fungi. This study aimed to assess the content of Cd, Pb, Hg, As, and Ni in berries and edible mushrooms collected in the forests located near Miasteczko Slaskie zinc smelter and in the Lubliniec region, in the context of consumers' health risk. METHODS: The ET-AAS method was used to determine the content of Cd, Pb, Ni, and As. Mercury concentration was determined using the CV-AFS method. RESULTS: The studies showed high levels of Cd and Pb in the examined products. A statistically significant impact of the distance from the smelter on the Cd concentration in the berries was observed. Total non-cancer health risk from the combined exposure of adults to all HM in mushrooms and berries was significant when consuming the most heavily contaminated produce. The risk to children was significant, even when consuming products with moderate levels of the metals. Ingestion of Cd by children with mushrooms was related to a high cancer risk. The uncertainty of the results was determined. CONCLUSIONS: It is recommended to take action to increase awareness among residents of the areas adjacent to the forests regarding the existing health risk and to take possible measures to reduce exposure to HM.

Dust-phase phthalates in university dormitories in Beijing, China: pollution characteristics, potential sources, and non-dietary oral exposure.

This study aimed to determine dust-phase phthalate levels in 112 dormitories of 14 universities during autumn and winter, investigate their potential sources, and estimate phthalate exposure via dust ingestion. Twelve phthalates were detected, among which di-(2-ethylhexyl) phthalate (DEHP) and dicyclohexyl phthalate (DCHP) were the most abundant, followed by di-isobutyl phthalate (DiBP) and di-n-butyl phthalate (DnBP). The median concentrations and contributions of DCHP and DEHP were the highest. The contributions of di-n-octyl phthalate and di-nonyl phthalate were higher in winter than in autumn. Potential sources included iron furniture, chemical fiber textiles, clothes, and personal care products. Medium-density fiberboard furniture is a potential sink for phthalates. In two seasons, DEHP, DCHP, DiBP, and DnBP were the main phthalates ingested by college students . The median oral exposure of ten phthalates was higher in females than in males. College students have a high risk of exposure to DEHP in dormitories.

Mapping domestic water use to quantify water-demand and water-related contaminant exposure in a peri-urban community, Indonesia.

Water use of domestic activities was quantified by interviewing 217 people in a peri-urban community near Bandung, Indonesia. Resulting in data on domestic water demand and data needed for exposure modelling of domestic activities: drinking, cooking, brushing teeth, swimming, bathing, laundry, dishwashing, religious cleansing, washing hands and cleaning food. Average total domestic water usage was 117 l/person/day, topping the WHO guidelines for basic needs (50-100 l/person/day). This water use level is comparable with higher income countries for the same set of activities but 100% higher than water use in an Indonesian traditional rural community. The final dataset provides insight in quantity of water used for domestic activities, as well as the use-frequency, duration and water sources used. These data are scarce for Indonesia and other low-middle income countries but necessary for water demand studies and estimating risks through exposure to pathogens and emerging contaminants in human exposure modelling.

Uptake and elimination of methylsiloxanes in hens after oral exposure: Implication for risk estimation.

Methylsiloxanes are accumulated easily in aquatic organisms and may pose potential risks. However, available information on their uptake and accumulation in terrestrial species remains scarce. This study investigated the uptake, elimination and accumulation of eight typical methylsiloxanes in hens after a single oral exposure. At 1440 min after oral exposure, methylsiloxanes were mainly accumulated in kidney, liver and ovary, representing for 29.5 %, 20.4 % and 17.4 % of the summed methylsiloxanes in all tissues, respectively; all investigated chemicals were also detected in brains and unformed yolks. We found much higher mass uptake fractions (MUFs) of cyclic (27.5-66.5 %) than linear chemicals (9.9-17.3 %) by hens via this exposure, and the observed MUFs of individual cyclic congeners were comparable to the higher values of those reported for rats or fish previously. However, the metabolic half-life (t1/2) of these chemicals in hen tissues were in the range of 1.04-57.5 h based on kinetic analyses, indicating higher clearances in comparison with those reported for fish and rats. More research is needed on the metabolic mechanism of these chemicals in hens. Our findings provide important information for further understanding of transportation and transformation of these chemicals in terrestrial organisms and the associated potential risks.

The relevance of oral exposure in the workplace: a systematic review and meta-analysis.

Introduction: The inclusion of all relevant exposure routes in the exposure assessment is essential for the protection of workers. However, under European chemical regulations but also for workplace risk assessments according to occupational safety and health (OSH) requirements, the quantitative assessment of oral exposure is usually neglected assuming good occupational hygiene. In contrast, several studies point to the importance of unintentional ingestion in the workplace. To our knowledge, there is no systematic analysis of the extent of this exposure route. Methods: Therefore, the aim of this study was to assess systematically the current knowledge on the relevance of occupational oral exposure using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) method. Five electronic databases and nine institutional websites were searched for all publications on the relevance. The data were extracted into a concept matrix. In the subsequent meta-analysis, the identified conclusions on the relevance were analyzed. In addition, the measurement methods or modeling approaches that were described for occupational oral exposure were determined as well as the potentially relevant workplaces and substances. Results: In total, 147 studies were included in this analysis that contain a general or several, differentiated assessments of the relevance of occupational oral exposure. Nine of these studies assessed this exposure route as irrelevant. However, 123 studies considered oral exposure as potentially contributing and 80 studies explicitly identified it as relevant. 78 and 94 of the publications described modeling and measurement approaches, respectively. The workplaces frequently identified as potentially or explicitly relevant were other indoor, other industrial or recycling workplaces. Analogously, metals, dust and powders or pesticides were the most frequently investigated substance groups. Discussion: As several studies assessed occupational oral exposure as relevant in the context of different workplaces and substances, further investigation of this exposure route is needed. This systematic review and meta-analysis serve as a basis for further development of feasible assessment methods for this route of exposure.

Continuous oral exposure to micro- and nanoplastics induced gut microbiota dysbiosis, intestinal barrier and immune dysfunction in adult mice.

Micro/nanoplastics in the environment can be ingested by organisms and spread throughout the food chain, ultimately posing a threat to human health. However, the risk of continuous oral exposure in mammals remains unresolved. In this study, we utilized a continuous gavage mouse model to investigate the potential intestinal risks associated with oral exposure to polystyrene micro/nanoplastics (PS-MNPs) with environmentally relevant concentrations. The effects of PS-MNPs with different particle sizes on the gut microbiota, intestinal barrier, and intestinal immune function were evaluated. PS-MNPs can accumulate in the intestine after oral exposure and alter the composition of the gut microbiota. Exposure to PS-MNPs significantly reduced the ratio of Firmicutes to Bacteroidetes as well as the number of potentially beneficial bacteria in the gut, while the number of potentially harmful bacteria significantly increased. The short-chain fatty acids metabolized by gut microbiota were significantly changed by PS-MNPs. Exposure to PS-MNPs disrupts the function of the intestinal barrier and leads to inflammation in the intestines. The levels of secretory immunoglobulin A in the intestine and the differentiation of CD4+ and CD8+ T cells in mesenteric lymph nodes were significantly decreased by PS-MNPs. Moreover, the impact of PS-MNPs on mammalian intestinal health is influenced by the exposure duration and particle size, rather than the concentration. It also suggests that nanoplastics may pose more severe environmental risks.

Sensitivity of the Neotropical Solitary Bee Centris analis F. (Hymenoptera, Apidae) to the Reference Insecticide Dimethoate for Pesticide Risk Assessment.

Currently, only Apis mellifera is used in environmental regulation to evaluate the hazard of pesticides to pollinators. The low representativeness of pollinators and bee diversity in this approach may result in insufficient protection for the wild species. This scenario is intensified in tropical environments, where little is known about the effects of pesticides on solitary bees. We aimed to calculate the medium lethal dose (LD50) and medium lethal concentration (LC50) of the insecticide dimethoate in the Neotropical solitary bee Centris analis, a cavity-nesting, oil-collecting bee distributed from Brazil to Mexico. Males and females of C. analis were exposed orally to dimethoate for 48 h under laboratory conditions. Lethality was assessed every 24 h until 144 h after the beginning of the test. After the LD50 calculation, we compared the value with available LD50 values in the literature of other bee species using the species sensitivity distribution curve. In 48 h of exposure, males showed an LD50 value 1.33 times lower than females (32.78 and 43.84 ng active ingredient/bee, respectively). Centris analis was more sensitive to dimethoate than the model species A. mellifera and the solitary bee from temperate zones, Osmia lignaria. However, on a body weight basis, C. analis and A. mellifera had similar LD50 values. Ours is the first study that calculated an LD50 for a Neotropical solitary bee. Besides, the results are of crucial importance for a better understanding of the effects of pesticides on the tropical bee fauna and will help to improve the risk assessment of pesticides to bees under tropical conditions, giving attention to wild species, which are commonly neglected. Environ Toxicol Chem 2023;42:2758-2767. © 2023 SETAC.

Toxicokinetic and mass balance of morpholine in rats.

Morpholine (MOR) has a broad spectrum of use and represents high risk of human exposure. Ingested MOR can undergo endogenous N-nitrosation in the presence of nitrosating agents forming N-nitrosomorpholine (NMOR), classified as possible human carcinogen by the International Agency for Research on Cancer.In this study, we evaluated the MOR toxicokinetics in six groups of male Sprague-Dawley rats orally exposed to 14C-radiolabelled MOR and NaNO2. The major urinary metabolite of MOR, N-nitrosohydroxyethylglycine (NHEG), was measured through HPLC as an index of endogenous N-nitrosation. Mass balance and toxicokinetic profile of MOR were determined by measuring radioactivity in blood/plasma and excreta.MOR reached maximum blood concentration 30 minutes after administration. Elimination rate was rapid (70% in 8h). Most of the radioactivity was excreted in the urine (80.9 ± 0.5%) and unchanged 14C-MOR was the main compound excreted in the urine (84% of the dose recovered). 5.8% of MOR is not absorbed and/or was not recovered.Endogenous nitrosation of MOR was demonstrated by the detection of NHEG. The maximum conversion rate found was 13.3 ± 1.2% and seems to be impacted by the MOR/NaNO2 ratio.These results help refining our knowledge of the endogenous production of NMOR, a possible human carcinogen.

Natural History of Nonhuman Primates After Oral Exposure to Ebola Virus Variant Makona.

BACKGROUND: The primary route of infection by Ebola virus (EBOV) is through contact of mucosal surfaces. Few studies have explored infection of nonhuman primates (NHPs) via the oral mucosa, which is a probable portal of natural infection in humans. METHODS: To further characterize the pathogenesis of EBOV infection via the oral exposure route, we challenged cohorts of cynomolgus monkeys with low doses of EBOV variant Makona. RESULTS: Infection with 100 or 50 PFU of EBOV Makona via the oral route resulted in 50% and 83% lethality, respectively. Animals that progressed to fatal disease exhibited lymphopenia, marked coagulopathy, high viral loads, and increased levels of serum markers of inflammation and hepatic/renal injury. Survival in these cohorts was associated with milder fluctuations in leukocyte populations, lack of coagulopathy, and reduced or absent serum markers of inflammation and/or hepatic/renal function. Surprisingly, 2 surviving animals from the 100- and 50-PFU cohorts developed transient low-level viremia in the absence of other clinical signs of disease. Conversely, all animals in the 10 PFU cohort remained disease free and survived to the study end point. CONCLUSIONS: Our observations highlight the susceptibility of NHPs, and by extension, likely humans, to relatively low doses of EBOV via the oral route.

Titanium dioxide nanoparticles: revealing the mechanisms underlying hepatotoxicity and effects in the gut microbiota.

Numerous studies in recent years have questioned the safety of oral exposure to titanium dioxide nanoparticles (TiO2 NPs). TiO2 NPs are not only likely to accumulate in the gastrointestinal tract, but they are also found to penetrate the body circulation and reach distant organs. The liver, which is considered to be a target organ for nanoparticles, is of particular concern. TiO2 NPs accumulate in the liver and cause oxidative stress and inflammatory reactions, resulting in pathological damage. The impact of TiO2 NPs on liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was studied using a meta-analysis. According to the findings, TiO2 NPs exposure can cause an elevation in AST and ALT levels in the blood. Furthermore, TiO2 NPs are eliminated mostly through feces, and their lengthy residence in the gut exposes them to microbiota. The gut microbiota is also dysbiotic due to titanium dioxide's antibacterial capabilities. This further leads to changes in the amount of microbiota metabolites, which can reach the liver with blood circulation and trigger hepatotoxicity through the gut-liver axis. This review examines the gut-liver axis to assess the effects of gut microbiota dysbiosis on the liver to provide suggestions for assessing the gut-hepatotoxicity of TiO2 NPs.

Intestinal Toxicity of Metal Nanoparticles: Silver Nanoparticles Disorder the Intestinal Immune Microenvironment.

Albeit numerous studies have been conducted on the toxicity evaluation of engineered metal nanoparticles (NPs), significant knowledge gaps remain regarding the influence of oral exposure to metal NPs on the intestine system, especially the effects on the intestinal immune microenvironment. Herein, we examined the long-term effects of representative engineered metal NPs on the intestine through oral exposure and identified silver NPs (Ag NPs) that resulted in severe damage. Oral Ag NP exposure damaged the epithelial structure, reduced the thickness of the mucosal layer, and altered the intestinal microbiota. Particularly, the reduced thickness of the mucosal layer increased the phagocytosis of Ag NPs by dendritic cells (DCs). Comprehensive animal and in vitro experiments unraveled that Ag NPs directly interacted with DCs, resulting in the abnormal activation of DCs by generating reactive oxygen species and inducing uncontrolled apoptosis. Furthermore, our data unveiled that the interactions between Ag NPs and DCs reduced the proportion of CD103+CD11b+ DCs and induced Th17 cell activation with inhibition of regulatory T-cell differentiation, resulting in the disordered immune microenvironment in the intestine. Collectively, these results represent a new point of view on the cytotoxicity of Ag NPs on the intestine system. This study provides additional insights into the health risks of engineered metal NPs, especially Ag NPs.

Exposure to MoS2 nanosheets or bulk activated Kruppel-like factor 4 in 3D Caco-2 spheroids in vitro and mouse intestines in vivo.

MoS2 nanosheets (NSs) are novel 2D nanomaterials (NMs) being used in many important fields. Recently, we proposed the need to evaluate the influences of NMs on Kruppel-like factors (KLFs) even if these materials are relatively biocompatible. In this study, we investigated the influences of MoS2 NSs or bulk on KLF4 signaling pathway in 3D Caco-2 spheroids in vitro and mouse intestines in vivo. Through the analysis of our previous RNA-sequencing data, we found that exposure to MoS2 NSs or bulk activated KLF4 expression in 3D Caco-2 spheroids. Consistently, these materials also activated KLF4-related gene ontology (GO) terms and down-regulated a panel of KLF4-downstream genes. To verify these findings, we repeatedly exposed mice to MoS2 NSs or bulk materials via intragastrical administration (1 mg/kg bodyweight, once a day, for 4 days). It was shown that oral exposure to these materials decreased bodyweight, leading to relatively higher organ coefficients. As expected, exposure to both types of materials increased Mo elements as well as other trace elements, such as Zn, Fe, and Mn in mouse intestines. The exposure also induced morphological changes of intestines, such as shortening of intestinal villi and decreased crypt depth, which may result in decreased intestinal lipid staining. Consistent with RNA-sequencing data, we found that material exposure increased KLF4 protein staining in mouse intestines and decreased two KLF4 downstream proteins, namely extracellular signal-regulated kinase (ERK) and serine/threonine kinase (AKT). We concluded that MoS2 materials were capable to activate KLF4-signaling pathway in intestines both in vivo and in vitro.

Transformation, Absorption and Toxicological Mechanisms of Silver Nanoparticles in the Gastrointestinal Tract Following Oral Exposure.

Oral exposure is known as the primary way for silver nanoparticles (AgNPs), which are commonly used as food additives or antibacterial agents in commercial products, to enter the human body. Although the health risk of AgNPs has been a concern and extensively researched over the past few decades, there are still numerous knowledge gaps that need to be filled to disclose what AgNPs experience in the gastrointestinal tract (GIT) and how they cause oral toxicity. In order to gain more insight into the fate of AgNPs in the GIT, the main gastrointestinal transformation of AgNPs, including aggregation/disaggregation, oxidative dissolution, chlorination, sulfuration, and corona formation, is first described. Second, the intestinal absorption of AgNPs is presented to show how AgNPs interact with epithelial cells and cross the intestinal barrier. Then, more importantly, we make an overview of the mechanisms underlying the oral toxicity of AgNPs in light of recent advances as well as the factors affecting the nano-bio interactions in the GIT, which have rarely been thoroughly elaborated in published literature. At last, we emphatically discuss the issues that need to be addressed in the future to answer the question "How does oral exposure to AgNPs cause detrimental effects on the human body?".

Impact of polystyrene microplastic exposure on gilthead seabream (Sparus aurata Linnaeus, 1758): Differential inflammatory and immune response between anterior and posterior intestine.

Plastics are the most widely discharged waste into the aquatic ecosystems, where they break down into microplastics (MPs) and nanoplastics (NPs). MPs are ingested by several marine organisms, including benthic and pelagic fish species, contributing to organ damage and bioaccumulation. This study aimed to assess the effects of MPs ingestion on gut innate immunity and barrier integrity in gilthead seabreams (Sparus aurataLinnaeus, 1758) fed for 21 days with a diet enriched with polystyrene (PS-MPs; 1-20 µm; 0, 25 or 250 mg /kg b.w./die). Physiological fish growth and health status were not impacted by PS-MPs treatments at the end of experimental period. Inflammation and immune alterations were revealed by molecular analyses in both anterior (AI) and posterior intestine (PI) and were confirmed by histological evaluation. PS-MPs triggered TLR-Myd88 signaling pathway with following impairment of cytokines release. Specifically, PS-MPs increased pro-inflammatory cytokines gene expression (i.e., IL-1ß, IL-6 and COX-2) and decreased anti-inflammatory ones (i.e., IL-10). Moreover, PS-MPs also induced an increase in other immune-associated genes, such as Lys, CSF1R and ALP. TLR-Myd88 signaling pathway may also lead to the mitogen-activated protein kinases (MAPK) signaling pathway activation. Here, MAPK (i.e., p38 and ERK) were activated by PS-MPs in PI, following the disruption of intestinal epithelial integrity, as evidenced by reduced gene expression of tight junctions (i.e. ZO-1, Cldn15, Occludin, and Tricellulin), integrins (i.e., Itgb6) and mucins (i.e., Muc2-like and Muc13-like). Thus, all the obtained results suggest that the subchronic oral exposure to PS-MPs induces inflammatory and immune alterations as well as an impact on intestinal functional integrity in gilthead seabream, with a more evident effect in PI.