Mechanism of Action of TiO2: Recommendations to Reduce Uncertainties Related to Carcinogenic Potential.

The Risk Assessment Committee of the European Chemicals Agency issued an opinion on classifying titanium dioxide (TiO2) as a suspected human carcinogen upon inhalation. Recent animal studies indicate that TiO2 may be carcinogenic through the oral route. There is considerable uncertainty on the carcinogenicity of TiO2, which may be decreased if its mechanism of action becomes clearer. Here we consider adverse outcome pathways and present the available information on each of the key events (KEs). Inhalation exposure to TiO2 can induce lung tumors in rats via a mechanism that is also applicable to other poorly soluble, low-toxicity particles. To reduce uncertainties regarding human relevance, we recommend gathering information on earlier KEs such as oxidative stress in humans. For oral exposure, insufficient information is available to conclude whether TiO2 can induce intestinal tumors. An oral carcinogenicity study with well-characterized (food-grade) TiO2 is needed, including an assessment of toxicokinetics and early KEs.

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.

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.

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.

Oral Exposure to Sodium Chloride without Subsequent Consumption Does Not Alter Salt Taste Function in Adults: A Cross-Over Intervention Study.

BACKGROUND: Reduction in dietary sodium increases salt taste sensitivity; however, non-oral sodium supplementation does not, suggesting that oral exposure is more important for modulating taste perception than consumption without tasting. OBJECTIVE: Using psychophysical methods, we assessed the effect of a two-week intervention involving oral exposure to a tastant without consumption on modulating taste function. METHODS: In a cross-over intervention study, n = 42 adults (age, mean ± SD: 29.7 ± 8.0 years) completed 4 intervention treatments requiring participants to rinse their mouths with 30 mL of a tastant, 3 times daily for 2 weeks. Treatments included oral exposure to 400 mM sodium chloride (NaCl), monosodium glutamate (MSG), monopotassium glutamate, and sucrose. Participants' taste function for salty, umami, and sweet [detection threshold (DT), recognition threshold (RT), and suprathreshold (ST)], and the glutamate-sodium discrimination status was evaluated before and after the tastant treatments. Effects of the interventions on taste function were assessed by using linear mixed models including treatment, time, and treatment x time interactions as fixed effects; significance was set at P > 0.05. RESULTS: There was no treatment × time interaction on DT and RT for all tastes assessed (P > 0.05). The only change in ST was following the NaCl intervention, participants' salt ST decreased at the highest concentration (400 mM) compared with the pre-NaCl treatment taste assessment (mean difference (MD): -0.052 [95% CI: -0.093, -0.010] labeled magnitude scale, P = 0.016). Compared with the pre-MSG treatment taste assessment, participants improved their ability to perform the glutamate-sodium discrimination task after the MSG intervention (MD:1.64 [95% CI: 0.395, 2.878] correct discrimination tasks, P = 0.010). CONCLUSION: Saltiness of an adult's free-living diet is unlikely to influence salt taste function, as oral exposure without consumption to a salt concentration greater than normally found in food, only attenuated taste responses to highly salty stimuli. This provides preliminary evidence that regulating salt taste function may require a coordinated response between oral activation and consumption of sodium.

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.

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.

Histological, haematological, and thyroid hormones toxicity of female rats orally exposed to CuO/ZnO core/shell nanoparticles synthesized by Ar plasma jets.

Advancements in nanomedicine helped scientists design a new class of nanoparticles known as hybrid nanoparticles (core/shell) for diagnostic and therapeutic purposes. An essential requirement for the successful use of nanoparticles in biomedical applications is their low toxicity. Therefore, toxicological profiling is necessary to understand the mechanism of nanoparticles. The current study aimed to assess the toxicological potential of CuO/ZnO core/shell nanoparticles with a size of 32 nm in Albino female rats. In vivo toxicity was evaluated by oral administration of 0, 5, 10, 20, and 40 (mg/L) of CuO/ZnO core/shell nanoparticles to a female rate for 30 consecutive days. During the time of treatment, no deaths were observed. The toxicological evaluation revealed significant (p < 0.01) alteration in white blood cells (WBC) at a 5 (mg/L) dose. Also, increase in red blood cells (RBC) at 5, 10 (mg/L) doses, while hemoglobin (Hb) levels and hematocrit (HCT) increased at all doses. This maybe indicates that the CuO/ZnO core/shell nanoparticles stimulated the rate of blood corpuscle generation. The anaemia diagnostic indices (mean corpuscular volume MCV and mean corpuscular haemoglobin MCH) remained unchanged throughout the experiment for all the doses tested 5, 10, 20, and 40 (mg/L). According to the results of this study, exposure to CuO/ZnO core/shell NPs deteriorates the Triiodothyronine hormone (T3) and a Thyroxine hormone (T4) activated by Thyroid-Stimulating Hormone (TSH), which is generated and secreted from the pituitary gland. There is possibly related to an increase in free radicals and a decrease in antioxidant activity. Significant (p < 0.01) growth retardation in all groups treated due to rats' infection by Hyperthyroidism induced by thyroxine (T4) level increase. Hyperthyroidism is a catabolic state related to increased energy consumption, protein turnover, and lipolysis. Usually, these metabolic effects result in weight reduction and a decrease in fat storage and lean body mass. The histological examination indicates that the low concentrations of CuO/ZnO core/shell nanoparticles are safe for desired biomedical applications.

Can oral toxicity data for PFAS inform on toxicity via inhalation?

Per- and poly-fluoroalkyl substances (PFAS) are ubiquitous in the environment and are detected in wildlife and humans. With respect to human exposure, studies have shown that ingestion is the primary route of exposure; however, in certain settings, exposure via inhalation could also be a significant source of exposure. While many studies examined toxicity of PFAS via ingestion, limited information is available for PFAS toxicity via the inhalation route, translating into a lack of exposure guidelines. Consequently, this article examined whether route-to-route extrapolation to derive guidelines for inhalation exposure is appropriate for PFAS. Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) were used as exemplary PFAS given the abundance of toxicity data for these two compounds. Our evaluation determined that available toxicity and toxicokinetic data support route-to-route extrapolation for PFAS in order to derive inhalation-based standards. Results from this analysis suggest that an air concentration of 7.0 × 10-5  mg/m3 (or 0.07 µg/m3 ) would be an appropriate RfC for PFOA and PFOS assuming the 2016 EPA RfD of 0.00002 mg/kg-day, whereas use of the interim RfDs proposed in 2022 of 1.5 × 10-9 and 7.9 × 10-9  mg/kg would yield much lower RfCs of 5.25 × 10-9 and 2.77 × 10-8  mg/m3 (or 5.25 × 10-6 and 2.77 × 10-5 µg/m3 ) for PFOA and PFOS, respectively.

Glyphosate-based formulation affects Tetragonisca angustula worker's locomotion, behavior and biology.

Declining bee populations diminish pollination services, damaging plant and agricultural biodiversity. One of the causes of this decline is the use of pesticides. Pesticides with glyphosate as the main active ingredient are among the most used pesticides worldwide, being the most used in Brazil. This study determined the 24 and 48 h LD50 (median lethal dose) of the herbicide's glyphosate-based formulation by ingestion, identified sublethal doses, and investigated its effects on the locomotion and behavior of Tetragonisca angustula workers. The LD50 found indicates that a glyphosate-based formulation is highly toxic to T. angustula. The doses applied, including concentrations found in nature, caused death, motor changes (decreased speed and tremors), excessive self-cleaning, and disorientation (return to light and stop). Although we did not test for pollination effects, we can infer from our results that this formulation can negatively affect the pollination activity of T. angustula. Evaluation of the toxicity and sublethal effects of pesticides on bees contributes to a better understanding of their harmful effects on hives and allows for the development of strategies to reduce these impacts.

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.

Assessment of intestinal injury of hexavalent chromium using a modified in vitro gastrointestinal digestion model.

Intestinal injury assessment of hexavalent chromium (Cr-VI) in humans is crucial for quantifying assessment of adverse health risk posed by the intake of Cr (VI)-contaminated water. To overcome the deficiency in simulating human gastric reduction and intestinal absorption, we modified the constituents of simulated gastric fluid in in vitro digestion method by adding reductants glutathione (18 µM) and ascorbic acid (180 µM), which incorporated with human intestinal epithelial model to construct an in vitro gastrointestinal digestion (IVGD) model for intestinal injury assessment. Cr-VI bioaccessibility results from IVGD model showed that weak gastric acidity significantly increased the intestinal accessible Cr-VI dose by 22.41-38.43 folds. The time-course intestinal absorption indicated prolongation of intestinal exposure destroyed the intestinal epithelium, and 24 h after Cr-VI treatment was a good time point to perform intestinal absorption and toxicity assessment. A series of cell-based bioassays provided initial warning of adverse effect, suggesting that epithelial integrity exhibited greatest sensitivity to Cr-VI exposure and might be used as a sensitive marker for the toxicity assessment of oral exposure to Cr-VI. Notably, this study provides a feasible strategy for delineation of Cr-VI biotransformation and intestinal injury following ingestion exposure, which contributes to address the toxicity data gap of low-dose exposure in humans and puts forward a reference for intestinal toxicity assessment of other chemicals.

Effects of subchronic dietary exposure to the engineered nanomaterials SiO2 and CeO2 in C57BL/6J and 5xFAD Alzheimer model mice.

BACKGROUND: There is an increasing concern about the neurotoxicity of engineered nanomaterials (NMs). To investigate the effects of subchronic oral exposures to SiO2 and CeO2 NMs on Alzheimer's disease (AD)-like pathology, 5xFAD transgenic mice and their C57BL/6J littermates were fed ad libitum for 3 or 14 weeks with control food pellets, or pellets dosed with these respective NMs at 0.1% or 1% (w/w). Behaviour effects were evaluated by X-maze, string suspension, balance beam and open field tests. Brains were analysed for plaque load, beta-amyloid peptide levels, markers of oxidative stress and neuroinflammation. RESULTS: No marked behavioural impairments were observed in the mice exposed to SiO2 or CeO2 and neither treatment resulted in accelerated plaque formation, increased oxidative stress or inflammation. In contrast, the 5xFAD mice exposed to 1% CeO2 for 14 weeks showed significantly lower hippocampal Aß plaque load and improved locomotor activity compared to the corresponding controls. CONCLUSIONS: The findings from the present study suggest that long-term oral exposure to SiO2 or CeO2 NMs has no neurotoxic and AD-promoting effects. The reduced plaque burden observed in the mice following dietary CeO2 exposure warrants further investigation to establish the underlying mechanism, given the easy applicability of this administration method.

Ingestion of titanium dioxide nanoparticles: a definite health risk for consumers and their progeny.

Titanium dioxide (TiO2) is one of the most commonly used nanomaterials in the world. Additive E171, which is used in the food industry, contains a nanometric particle fraction of TiO2. Oral exposure of humans to these nanoparticles (NPs) is intensive, leading to the question of their impact on health. Daily oral intake by rats of amounts of E171 that are relevant to human intake has been associated with an increased risk of chronic intestinal inflammation and carcinogenesis. Due to their food preferences, children are very exposed to this NP. Furthermore, maternal-foetal transfer of TiO2 NPs during pregnancy, as well as exposure of the offspring by breastfeeding, have been recently described. In France, the use of E171 in the production of foodstuffs was suspended in January 2020 as a precautionary measure. To provide some answers to this public health problem and help global regulatory agencies finalize their decisions, we reviewed in vitro and in vivo studies that address the effects of TiO2 NPs through oral exposure, especially their effects on the gastrointestinal tract, one of the most exposed tissues. Our review also highlights the effects of exposure on the offspring during pregnancy and by breastfeeding.

In vivo toxicity assessment of eugenol and vanillin-functionalised silica particles using Caenorhabditis elegans.

The toxicological properties of different silica particles functionalised with essential oil components (EOCs) were herein assessed using the in vivo model C. elegans. In particular, the effects of the acute and long-term exposure to three silica particle types (SAS, MCM-41 micro, MCM-41 nano), either bare or functionalised with eugenol or vanillin, were evaluated on different biological parameters of nematodes. Acute exposure to the different particles did not reduce nematodes survival, brood growth or locomotion, but reproduction was impaired by all the materials, except for vanillin-functionalised MCM-41 nano. Moreover, long-term exposure to particles led to strongly inhibited nematodes growth and reproduction. The eugenol-functionalised particles exhibited higher functionalisation yields and had the strongest effects during acute and long-term exposures. Overall, the vanillin-functionalised particles displayed milder acute toxic effects on reproduction than pristine materials, but severer toxicological responses for the 96-hour exposure assays. Our findings suggest that the EOC type anchored to silica surfaces and functionalisation yield are crucial for determining the toxicological effects of particles on C. elegans. The results obtained with this alternative in vivo model can help to anticipate potential toxic responses to these new materials for human health and the environment.

Chronic exposure to low concentration of MC-LR caused hepatic lipid metabolism disorder.

Microcystin-LR (MC-LR), a potent hepatotoxin can cause liver damages. However, research on hepatic lipid metabolism caused by long-term exposure to environmental concentrations MC-LR is limited. In the current study, mice were exposed to various low concentrations of MC-LR (0, 1, 30, 60, 90, 120 µg/L in the drinking water) for 9 months. The general parameters, serum and liver lipids, liver tissue pathology, lipid metabolism-related genes and proteins of liver were investigated. The results show that chronic MC-LR exposure had increased the levels of triglyceride (TG) and total cholesterol (TC) in serum and liver. In addition, histological observation revealed that hepatic lobules were disordered with obvious inflammatory cell infiltration and lipid droplets. More importantly, the mRNA and proteins expression levels of lipid synthesis-related nuclear sterol regulatory element binding protein-1c (nSREBP-1c), SREBP-1c, cluster of differentiation 36 (CD36), acetyl-CoA-carboxylase1 (ACC1), stearoyl-CoA desaturase1 (SCD1) and fatty acid synthase (FASN) were increased in MC-LR treated groups, the expression levels of fatty acids ß-oxidation related genes peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) was decreased after exposure to 60-120 µg/L MC-LR. Furthermore, the inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were higher than that in the control group. All the findings indicated that mice were exposed to chronic low concentrations MC-LR caused liver inflammation and hepatic lipid metabolism disorder .

Preclinical In Vitro Model to Assess the Changes in Permeability and Cytotoxicity of Polarized Intestinal Epithelial Cells during Exposure Mimicking Oral or Intravenous Routes: An Example of Arsenite Exposure.

The gastrointestinal tract (GIT) is exposed to xenobiotics, including drugs, through both: local (oral) and systemic routes. Despite the advances in drug discovery and in vitro pre-clinical models, there is a lack of appropriate translational models to distinguish the impact of these routes of exposure. Changes in intestinal permeability has been observed in different gastrointestinal and systemic diseases. This study utilized one such xenobiotic, arsenic, to which more than 200 million people around the globe are exposed via their food, drinking water, work environment, soil, and air. The purpose of this study was to establish an in vitro model to mimic gastrointestinal tract exposure to xenobiotics via oral or intravenous routes. To achieve this, we compared the route (mimicking oral and intravenous exposure to GIT and the dose response (using threshold approach) of trivalent and pentavalent inorganic arsenic species on the permeability of in vitro cultured polarized T84 cells, an example of intestinal epithelial cells. Arsenic treatment to polarized T84 cells via the apical and basolateral compartment of the trans-well system reflected oral or intravenous routes of exposure in vivo, respectively. Sodium arsenite, sodium arsenate, dimethyl arsenic acid sodium salt (DMAV), and disodium methyl arsonate hydrate (MMAV) were assessed for their effects on intestinal permeability by measuring the change in trans-epithelial electrical resistance (TEER) of T-84 cells. Polarized T-84 cells exposed to 12.8 µM of sodium arsenite from the basolateral side showed a marked reduction in TEER. Cytotoxicity of sodium arsenite, as measured by release of lactate dehydrogenase (LDH), was increased when cells were exposed via the basolateral side. The mRNA expression of genes related to cell junctions in T-84 cells was analyzed after exposure with sodium arsenite for 72 h. Changes in TEER correlated with mRNA expression of focal-adhesion-, tight-junction- and gap-junction-related genes (upregulation of Jam2, Itgb3 and Notch4 genes and downregulation of Cldn2, Cldn3, Gjb1, and Gjb2). Overall, exposure to sodium arsenite from the basolateral side was found to have a differential effect on monolayer permeability and on cell-junction-related genes as compared to apical exposure. Most importantly, this study established a preclinical human-relevant in vitro translational model to assess the changes in permeability and cytotoxicity during exposure, mimicking oral or intravenous routes.

Internal dose of vanadium in rats following repeated exposure to vanadyl sulfate and sodium orthovanadate via drinking water.

Vanadium is a ubiquitous environmental contaminant that exists in multiple oxidation states. Humans are exposed to vanadyl (V4+) and vanadate (V5+) from dietary supplements, food, and drinking water and hence there is a concern for adverse human health. The current investigation is aimed at identifying vanadium oxidation states in vitro and in vivo and internal concentrations following exposure of rats to vanadyl sulfate (V4+) or sodium metavanadate (V5+) via drinking water for 14 d. Investigations in simulated gastric and intestinal fluids showed that V4+ was stable in gastric fluid while V5+ was stable in intestinal fluid. Analysis of rodent plasma showed that the only vanadium present was V4+, regardless of the exposed compound suggesting conversion of V5+ to V4+ in vivo and/or instability of V5+ species in biological matrices. Plasma, blood, and liver concentrations of total vanadium, after normalizing for vanadium dose consumed, were higher in male and female rats following exposure to V5+ than to V4+. Following exposure to either V4+ or V5+, the total vanadium concentration in plasma was 2- to 3-fold higher than in blood suggesting plasma as a better matrix than blood for measuring vanadium in future work. Liver to blood ratios were 4-7 demonstrating significant tissue retention following exposure to both compounds. In conclusion, these data point to potential differences in absorption and disposition properties of V4+ and V5+ salts and may explain the higher sensitivity in rats following drinking water exposure to V5+ than V4+ and highlights the importance of internal dose determination in toxicology studies.

Comparative toxicokinetics of bisphenol S and bisphenol AF in male rats and mice following repeated exposure via feed.

We investigated the plasma toxicokinetic behavior of free (parent) and total (parent and conjugated forms) of bisphenol S (BPS) and bisphenol AF (BPAF) in plasma of adult male rats and mice following exposure via feed for 7 days to BPS (338, 1125, and 3375 ppm) or BPAF (338, 1125, and 3750 ppm). In rats, the exposure concentration-normalized maximum concentration [Cmax/D (ng/mL)/(ppm)] and area under the concentration time curve [AUC/D (h × ng/mL)/(ppm)] for free was higher for BPS (Cmax/D: 0.476-1.02; AUC/D: 3.58-8.26) than for BPAF (Cmax/D: 0.017-0.037; AUC/D:0.196-0.436). In mice, the difference in systemic exposure parameters between free BPS (Cmax/D: 0.376-0.459; AUC/D: 1.52-2.54) and free BPAF (Cmax/D: 0.111-0.165; AUC/D:0.846-1.09) was marginal. Elimination half-lives for free analytes (4.41-10.4 h) were comparable between species and analogues. When systemic exposure to free analyte was compared between species, in rats, BPS exposure was slightly higher but BPAF exposure was much lower than in mice. BPS and BPAF were highly conjugated; total BPS AUC values (rats ≥18-fold, mice ≥17-fold) and BPAF (rats ≥127-fold, mice ≥16-fold) were higher than corresponding free values. Data demonstrated that there are analogue and species differences in the kinetics of BPS and BPAF.

A more secure and effective method for throat swab collection: The importance of adequate exposure of oral cavity in COVID-19 specimen collection.

OBJECTIVES: This study aims to propose a novel and effective throat swab collection method for coronavirus disease 2019 (COVID-19). METHODS: The subjects were randomly divided into two groups. The subjects were asked to open their mouth to make "ah" sound (traditional method) or simulate yawn (improved method) for throat swab collection. The usage of tongue depressor, collection time, adverse reactions and subjective discomfort (VAS score) were compared. The collection time, comprehensive indicators of adverse reactions and VAS score were also compared among three collectors. RESULTS: The tongue depressor was less used in the improved group (χ2 = 40.186, P < 0.01). The average collection time of the traditional group was 5.44 ± 2.97 and that of the improved group was 4.00 ± 2.31 (P < 0.01). The subjects in the improved group had fewer and milder adverse reactions. The VAS score of subjects in the improved group was lower than that in the traditional group (P < 0.01). Among different collectors, the collection time, comprehensive indicators of adverse reactions and VAS were the same as the overall trend. CONCLUSION: Simulating yawn is a safer and faster throat swab collection method.