Chronic Dietary Exposure Research Articles

Simultaneous determination and dietary risk assessment of clethodim and its metabolites in different fruits and vegetables

ABSTRACT Clethodim is one of the most widely used herbicides in agriculture and, after field application, is metabolised to several metabolites. The potential toxicological negative effects of these compounds are poorly understood. Thus, recently, within the risk assessment framework, the European Food Safety Authority (EFSA) proposed to include the minor metabolites in the definition of clethodim residue. In this work, an easy to use and reliable UHPLC method coupled with a triple quadrupole MS/MS was developed and validated for the detection and quantification of the herbicide clethodim and related metabolites clethodim sulphone, clethodim sulphoxide, metabolites M17R and M18R in apple, grape, olive and rice. The five analytes were extracted by using a modified QuEChERS procedure, while the active ingredients were determined in multiple reaction monitoring (MRM) ion-switching mode. The proposed method showed calibration curve linearity with r2 ≥ 0.990 for all active ingredients (a.is.) both in solvent and matrix extracts. Limits of quantitation (LOQ) of the five compounds ranged from 9.44 µg/kg for M17R in olive extract to 11.01 µg/kg for clethodim in apple extract. Recoveries values ranged from 86% to 119% at two concentration levels (LOQ and 10xLOQ), while the intraday and interday precisions of the method were both below 10% in all cases. The method was successfully used for the quantification of the five a.is. in different food matrices. Furthermore, chronic dietary risk was investigated using a hazard quotients (HQ) method based on European dietary habits. The chronic dietary exposure risk quotients ranged from 1.0 × 10−5 (lower bound scenario) to 2.7 × 10−4 (upper bound scenario) which were significantly lower than 1. Data obtained indicate that the dietary exposure risks were acceptable for clethodim and its major and minor metabolites applied in apple, table grape, rice and table olive.

Rat Tumour Histopathology Associated with Experimental Chronic Dietary Exposure to Ochratoxin A in Prediction of the Mycotoxin's Risk for Human Cancers.

Mammalian animal toxicity of ochratoxin A (OTA) has focused largely in the past half-century on pigs because of initial recognition of it as a principal cause of intermittent growth suppression and renal disease caused by mouldy feed. Subsequent classical toxicology has used laboratory rodents because renal pathology in pigs raised questions concerning possible involvement in the human idiopathic bilateral renal atrophy of Balkan endemic nephropathy for which OTA was a focus of attention for human nephropathy through 1980s and into 2000s. Emphasis on human nephropathy has more recently concerned the plant metabolite aristolochic acid. Recognition that agricultural management can often minimise food and feed-stuff spoilage by OTA-producing Aspergilli and Penicillia has moderated some of the risks for animals. Legislation for human food safety combined with sophisticated analysis generally provides safety in the developed world. Chronic experimental exposure of male rats, in the absence of clinical dis-ease, specifically causes renal cancer. The possibility of this as a unique model for the human has generated considerable experimental evidence which may be more directly relevant for carcinogenesis in the complex kidney than that obtained from biochemical toxicities in vitro. Nevertheless, there does not appear to be any case of human renal or urinary tract cancer for which there is verified etiological proof for causation by OTA, contrary to much claim in the literature. To contribute to such debate, histopathology review of OTA/rat renal cancers, augmented where appropriate by immune profiles, has been completed for all remaining tumours in our research archive. Overall consistency of positivity for vimentin, is matched with occasional positives either for CD10 or the cytokeratin MNF 116. The current situation is discussed. Suggestion that OTA could cause human testicular cancer has also been challenged as unsupported by any experimental findings in rats, where the Leydig cell tumour immune profile does not match that of human germ cell neoplasms.

Aflatoxicosis Dysregulates the Physiological Responses to Crowding Densities in the Marine Teleost Gilthead Seabream (Sparus aurata).

Simple SummaryA fungal toxin, aflatoxin B1 (AFB1), undermines growth and stress axes of gilthead seabream (Sparus aurata) with depletion of somatic carbohydrate and lipid reservoirs. The present study assessed the physiological consequences of high stocking density versus low stocking density in seabream juveniles, which had previously been fed with AFB1 supplementation. These stressors are likely to converge by inferring animal welfare and economic profitability in the food animal industry. Interestingly, AFB1 seems to cause physiological and molecular dysfunction in response to overcrowding densities. Our results might be relevant to elucidate a potential risk for fish farming that is often overlooked.Several studies in fish have shown that aflatoxin B1 (AFB1) causes a disparity of species-dependent physiological disorders without compromising survival. We studied the effect of dietary administration of AFB1 (2 mg AFB1 kg−1 diet) in gilthead seabream (Sparus aurata) juveniles in combination with a challenge by stocking density (4 vs. 40 g L−1). The experimental period duration was ten days, and the diet with AFB1 was administered to the fish for 85 days prior to the stocking density challenge. Our results indicated an alteration in the carbohydrate and lipid metabolites mobilization in the AFB1 fed group, which was intensified at high stocking density (HSD). The CT group at HSD increased plasma cortisol levels, as expected, whereas the AFB1-HSD group did not. The star mRNA expression, an enzyme involved in cortisol synthesis in the head kidney, presented a ninefold increase in the AFB1 group at low stocking density (LSD) compared to the CT-LSD group. Adenohypophyseal gh mRNA expression increased in the AFB1-HSD but not in the CT-HSD group. Overall, these results confirmed that chronic AFB1 dietary exposure alters the adequate endocrinological physiological cascade response in S. aurata, compromising the expected stress response to an additional stressor, such as overcrowding.

Responses of juvenile fathead minnow (Pimephales promelas) gut microbiome to a chronic dietary exposure of benzo[a]pyrene.

The microbiome has been described as an additional host "organ" with well-established beneficial roles. However, the effects of exposures to chemicals on both structure and function of the gut microbiome of fishes are understudied. To determine effects of benzo[a]pyrene (BaP), a model persistent organic pollutant, on structural shifts of gut microbiome in juvenile fathead minnows (Pimephales promelas), fish were exposed ad libitum in the diet to concentrations of 1, 10, 100, or 1000μg BaP g-1 food, in addition to a vehicle control, for two weeks. To determine the link between exposure to BaP and changes in the microbial community, concentrations of metabolites of BaP were measured in fish bile and 16S rRNA amplicon sequencing was used to evaluate the microbiome. Exposure to BaP only reduced alpha-diversity at the greatest exposure concentrations. However, it did alter community composition assessed as differential abundance of taxa and reduced network complexity of the microbial community in all exposure groups. Results presented here illustrate that environmentally-relevant concentrations of BaP can alter the diversity of the gut microbiome and community network connectivity.

Effects of Chronic Dietary Exposure to Phytoestrogen Genistein on Uterine Morphology in Mice.

Genistein is naturally occurring in plants and binds to estrogen receptors. Humans are mainly exposed through diet, but the use of supplements is increasing as genistein is claimed to promote health and alleviate menopausal symptoms. We analyzed diverse uterine features in adult mice chronically fed genistein for different times. The luminal epithelium height was increased in females treated with 500 and 1000 ppm at PND 95, and the width of the outer myometrium was increased in females treated with 1000 ppm at PND 65 compared to that in controls. An increase in proliferation was noted in the inner myometrium layer of animals exposed to 300 ppm genistein at PND 185 compared to that in controls. Luminal hyperplasia was greater in the 1000 ppm group at PND 65, 95, and 185, although not statistically different from control. These results indicate that genistein may exert estrogenic activity in the uterus, without persistent harm to the organ.

Differential gene expression profile of mice lung following chronic dietary exposure to chlorpyrifos and/or cypermethrin

Chlorpyrifos is an organophosphate and the cypermethrin is Type 2 pyrethroid insecticide that are frequently used for indoor and outdoor pest control. The combination of both chlorpyrifos and cypermethrin is commonly used to control pest and prolonged exposures of this combination results in chronic or persistent neurologic and teratogenic effects along with abortions and other reproductive failure. We have earlier reported that delay exposure to cypermethrin and chlorpyriphos results in lung injury, however, the molecular mechanism remains to be elucidated. The present study was designed to study differential transcriptional profiling to identify the candidate genes associated with lung injury after exposure to chlorpyriphos and/or cypermethrin in a mouse model. Swiss male albino mice (N=24) ageing 6-8 week were divided into one control group and three treatment groups (n=8each). Treatment group-І, ІІ and ІІІ were given orally chlorpyriphos (2.76 mg/kg), cypermethrin (2 mg/kg) and combination dissolved in corn oil for 90 days. Lung samples were collected and subjected to microarray analysis. The data revealed that 365 genes were dysregulated following exposure to chlorpyrifos, cypermethrin and their mixture. Treatment with chlorpyriphos upregulated 194 genes and downregulated 171 genes whereas cypermethrin treatment caused upregulation of 171 genes and downregulation of 152 genes while their combination upregulated 176 genes and downregulated 146 genes (minimum cut off of 12.0 log fold change). Atp5g2, Cox6a1, Tpt1, Hint1, Fau, Rps27, Fth1, Rplp0 Sftpd and Sftpa were among the top ten dysregulated genes in all the treatments groups. Protein-protein interaction analysis showed that Atp5g2, Cox6a1, Tpt1, Hint1, Fau, Rps27, Fth1 and Rplp0 forms a network with each other whereas Sftpd and Sftpa1 are co- expressed. Data taken together suggest that exposure to chlorpyrifos and/or cypermethrin may induce lung damage via dysregulating the expression of Atp5g2, Cox6a1, Tpt1, Hint1, Fau, Rps27, Fth1, Rplp0, Sftpd and Sftpa.. The findings of current study have significance as farm workers get frequent exposures to the cocktail of these pesticides in field situations.

Chronic dietary exposure to inorganic arsenic.

Following an official request to EFSA from the European Commission, EFSA assessed the chronic dietary exposure to inorganic arsenic (iAs) in the European population. A total of 13,608 analytical results on iAs were considered in the current assessment (7,623 corresponding to drinking water and 5,985 to different types of food). Samples were collected across Europe between 2013 and 2018. The highest mean dietary exposure estimates at the lower bound (LB) were in toddlers (0.30 μg/kg body weight (bw) per day), and in both infants and toddlers (0.61 μg/kg bw per day) at the upper bound (UB). At the 95th percentile, the highest exposure estimates (LB–UB) were 0.58 and 1.20 μg/kg bw per day in toddlers and infants, respectively. In general, UB estimates were two to three times higher than LB estimates. The mean dietary exposure estimates (LB) were overall below the range of benchmark dose lower confidence limit (BMDL 01) values of 0.3–8 μg/kg bw per day established by the EFSA Panel on Contaminants in the Food Chain in 2009. However, for the 95th percentile dietary exposure (LB), the maximum estimates for infants, toddlers and other children were within this range of BMDL 01 values. Across the different age classes, the main contributors to the dietary exposure to iAs (LB) were ‘Rice’, ‘Rice‐based products’, ‘Grains and grain‐based products (no rice)’ and ‘Drinking water’. Different ad hoc exposure scenarios (e.g. consumption of rice‐based formulae) showed dietary exposure estimates in average and for high consumers close to or within the range of BMDL 01 values. The main uncertainties associated with the dietary exposure estimations refer to the impact of using the substitution method to treat the left‐censored data (LB–UB differences), to the lack of information (consumption and occurrence) on some iAs‐containing ingredients in specific food groups, and to the effect of food preparation on the iAs levels. Recommendations were addressed to improve future dietary exposure assessments to iAs.

Organophosphate and carbamate pesticide residues and accompanying risks in commonly consumed vegetables in Kenya

ABSTRACT The current study was conducted to assess the levels of organophosphates and carbamates in vegetables in Kenya and to examine potential consumer health risks. A total of 90 samples were analysed by liquid chromatography/high-resolution tandem mass spectrometry. Residues of acephate, chlorpyrifos, methamidophos, omethoate and profenofos were found in 22% of the samples, ranging from 10 to 1343 μg/kg. The EU MRL was exceeded in 21%, 10%, 8% and 22% of the samples of French beans, kales, spinach and tomatoes, respectively. Chlorpyrifos in spinach had an acute HQ of 3.3 and 2.2 for children and adults, respectively, implying that potential health risks with respect to acute dietary exposure cannot be excluded. For chronic dietary exposure, all chronic HQs were below 1. The HI for the pesticides was 0.54 and 0.34 for children and adults. Routine monitoring of OPs and carbamates in vegetables is recommended to minimise consumer’s health risks.

Chronic dietary exposure to nickel from selected foods consumed in Belgium

ABSTRACT The risk assessment conducted by the European Food Safety Authority stated some concerns regarding the chronic exposure of the European population to nickel due to food intake. This study aimed to evaluate the extent of the Belgian population’s exposure to nickel via intake of different foods/drinks available in their market. Ni concentrations were measured in selected foods consumed in Belgium, and exposures from this limited group of foods were estimated for consumers of these foods. Legumes, soy products, breakfast cereals, and chocolate spreads were responsible for 26%, 14%, 11% and 8% of the overall exposure (overall chronic exposure through consuming all the included food types in this study except tap water) of children (3–9 years) to nickel. For adolescents (10–17 years), the highest percentage of overall chronic exposure again originated from legumes (19%). This was followed by breakfast cereals (14%), soy products (11%) and chocolate spreads (11%). For adults (18–64 years), major contributors to the overall chronic daily exposure were legumes (16%), dark chocolate (15%) and breakfast cereals (10%). The aggregate exposure assessment, including the highest contaminated foods, for different sub-populations, revealed mean exposure levels of 1.02, 0.60 and 0.34 μg kg−1 b.w. day−1 for children, adolescents, and adults respectively. The mean, P75, P90 and P95 values for aggregate chronic exposure of the overall consumer’s population were 0.62, 0.80, 1.5 and 210 μg kg−1 b.w. day−1 respectively. This study recommends controlling the intake of food products with elevated nickel content especially for the more vulnerable sub-population groups such as children with lower body weight and nickel sensitised individuals. It also demonstrates a shift in potential risk on human health to nickel exposure due to the transition towards a more plant-based diet.

Update of the risk assessment of nickel in food and drinking water.

The European Commission asked EFSA to update its previous Opinion on nickel in food and drinking water, taking into account new occurrence data, the updated benchmark dose (BMD) Guidance and newly available scientific information. More than 47,000 analytical results on the occurrence of nickel were used for calculating chronic and acute dietary exposure. An increased incidence of post‐implantation loss in rats was identified as the critical effect for the risk characterisation of chronic oral exposure and a BMDL 10 of 1.3 mg Ni/kg body weight (bw) per day was selected as the reference point for the establishment of a tolerable daily intake (TDI) of 13 μg/kg bw. Eczematous flare‐up reactions in the skin elicited in nickel‐sensitised humans, a condition known as systemic contact dermatitis, was identified as the critical effect for the risk characterisation of acute oral exposure. A BMDL could not be derived, and therefore, the lowest‐observed‐adverse‐effect‐level of 4.3 μg Ni/kg bw was selected as the reference point. The margin of exposure (MOE) approach was applied and an MOE of 30 or higher was considered as being indicative of a low health concern. The mean lower bound (LB)/upper bound (UB) chronic dietary exposure was below or at the level of the TDI. The 95th percentile LB/UB chronic dietary exposure was below the TDI in adolescents and in all adult age groups, but generally exceeded the TDI in toddlers and in other children, as well as in infants in some surveys. This may raise a health concern in these young age groups. The MOE values for the mean UB acute dietary exposure and for the 95th percentile UB raises a health concern for nickel‐sensitised individuals. The MOE values for an acute scenario regarding consumption of a glass of water on an empty stomach do not raise a health concern.

Dietary exposure of the Italian population to nickel: The national Total Diet Study

Dietary exposure of the Italian population to nickel has been assessed in the national Total Diet Study (TDS). Occurrence data were combined with national individual consumption data to estimate mean and high level dietary exposure of population subgroups according to age and gender, both at the national level and for the four main geographical areas of Italy. The mean chronic dietary exposure of infants and toddlers, children, adolescents, adults, and the elderly were 4.00, 4.57, 2.57, 1.55, and 1.47 μg/kg bw per day, respectively. These intakes lie in the intermediate range of exposure estimates from TDS carried out in other countries. Main contributors to the total nickel exposure for children and adolescents were ‘sweet products’ and ‘cereals and cereal products’. In adults and the elderly nearly 30% of the exposure was associated to the consumption of ‘cereals and cereal products’. Mean and 95th percentile chronic dietary exposure was below the TDI in all age groups. For the risk characterisation of acute oral exposure, exposure data for consumers only in the adult population were compared with the reference point for systemic contact dermatitis. Consumption of ‘cocoa’, ‘chocolate’, ‘crustaceans and molluscs’, ‘pulses’ had remarkable potential to elicit adverse effects in nickel-sensitised individuals.

Study on degradation behaviour, residue distribution, and dietary risk assessment of propiconazole in celery and onion under field application.

Propiconazole is widely used to control fungal diseases in field crops, including celery and onion. The potential risk to the environment and human health has aroused much public concern. Therefore, it is significant to investigate the degradation behaviour, residue distribution, and dietary risk assessment of propiconazole in celery and onion. A sensitive analytical method for determination of propiconazole residue in celery and onion was established and validated through high-performance liquid chromatography tandem mass spectrometry. The average recovery rate of propiconazole ranged from 85.7% to 101.8%, with a relative standard deviation of 2.1-6.3%. For the dissipation kinetics, the data showed that propiconazole in celery and onion was degraded, with half-lives of 6.1-6.2 days and 8.7-8.8 days respectively. In the terminal residue experiments, the residues of propiconazole were below 4.66 mg kg-1 in celery after application two or three times and were below 0.029 mg kg-1 in onion after application of three or four times with an interval of 14 days under the designed dosages. The chronic and acute dietary exposure assessments for propiconazole were valued by risk quotient, with all values being lower than 100%. Propiconazole in celery and onion was rapidly degraded following first-order kinetics models. The dietary risk of propiconazole through celery or onion was negligible to consumers. The study not only offers a valuable reference for reasonable usage of propiconazole on celery and onion, but also facilitates the establishment of maximum residue limits in China. © 2020 Society of Chemical Industry.

Dissipation and dietary risk assessment of tristyrylphenol ethoxylate homologues in cucumber after field application

The potential for tristyrylphenol ethoxylates (TSPEOs) residues to contaminate crops or be released into the environment is of increasing concern, as they are toxic to living organisms. This study determined the dissipation of TSPEO homologues in cucumber under field conditions. TSPEOn (n = 6–29) dissipated more rapidly in cucumber than in soil samples, with half-lives of 1.80–4.30 d and 3.73–6.52 d, respectively. Short-chain TSPEOn (n = 6–11) persisted for longer than other oligomers in soil. Concentrations of the final residues (∑TSPEOs) in cucumber and soil were 24.3–1349 μg/kg and 47.3–1337 μg/kg, respectively. TSP15EO or TSP16EO was the dominant oligomer, with concentrations of 2.30–150 μg/kg. The risk assessment showed that the acute and chronic dietary exposure risks of ∑TSPEOs in cucumber were 0.03–0.57% and 0.05–0.39%, respectively, suggesting little or no health risk to Chinese consumers.

Comparison of acute respiratory epithelial toxicity for 4-Methylimidazole and naphthalene administered by oral gavage in B6C3F1 mice

4-Methylimidazole (4MEI) is a contaminant in food and consumer products. Pulmonary toxicity and carcinogenicity following chronic dietary exposures to 4MEI is a regulatory concern based on previous rodent studies. This study examined acute pulmonary toxicity in B6C3F1 mice from 6 h to 5 days after oral gavage with a single dose of 150 mg/kg 4MEI, a double dose delivered 6 h apart, or vehicle controls. Oral gavage of 150 mg/kg naphthalene, a prototypical Club cell toxicant, was used as a positive control. Intrapulmonary conducting airway cytotoxicity was assessed in fixed-pressure inflated lungs using qualitative histopathology scoring, quantitative morphometric measurement of vacuolated and exfoliating epithelial cells, and immunohistochemistry. 4MEI treatment did not change markers of cytotoxicity including the mass of vacuolated epithelium, the thickness of the epithelium, or the distributions of epithelial proteins: secretoglobin 1A1, proliferating cell nuclear antigen, calcitonin gene-related peptide, and myeloperoxidase. 4MEI and vehicle controls caused slight cytotoxicity with rare vacuolization of the epithelium relative to the severe bronchiolar epithelial cell toxicity found in the naphthalene exposed mice at terminal bronchioles, intrapulmonary airways, or airway bifurcations. In summary, 4MEI caused minimal airway epithelial toxicity without characteristic Club Cell toxicity when compared to naphthalene, a canonical Club Cell toxicant.

Perinatal exposure to a dietary pesticide cocktail does not increase susceptibility to high-fat diet-induced metabolic perturbations at adulthood but modifies urinary and fecal metabolic fingerprints in C57Bl6/J mice

BackgroundWe recently demonstrated that chronic dietary exposure to a mixture of pesticides at low-doses induced sexually dimorphic obesogenic and diabetogenic effects in adult mice. Perinatal pesticide exposure may also be a factor in metabolic disease etiology. However, the long-term consequences of perinatal pesticide exposure remain controversial and largely unexplored. ObjectivesHere we assessed how perinatal exposure to the same low-dose pesticide cocktail impacted metabolic homeostasis in adult mice. MethodsSix pesticides (boscalid, captan, chlopyrifos, thiachloprid, thiophanate, and ziram) were incorporated in food pellets. During the gestation and lactation periods, female (F0) mice were fed either a pesticide-free or a pesticide-enriched diet at doses exposing them to the tolerable daily intake (TDI) level for each compound, using a 1:1 body weight scaling from humans to mice. All male and female offsprings (F1) were then fed the pesticide-free diet until 18 weeks of age, followed by challenge with a pesticide-free high-fat diet (HFD) for 6 weeks. Metabolic parameters, including body weight, food and water consumption, glucose tolerance, and urinary and fecal metabolomes, were assessed over time. At the end of the experiment, we evaluated energetic metabolism and microbiota activity using biochemical assays, gene expression profiling, and 1H NMR-based metabolomics in the liver, urine, and feces. ResultsPerinatal pesticide exposure did not affect body weight or energy homeostasis in 6- and 14-week-old mice. As expected, HFD increased body weight and induced metabolic disorders as compared to a low-fat diet. However, HFD-induced metabolic perturbations were similar between mice with and without perinatal pesticide exposure. Interestingly, perinatal pesticide exposure induced time-specific and sex-specific alterations in the urinary and fecal metabolomes of adult mice, suggesting long-lasting changes in gut microbiota. ConclusionsPerinatal pesticide exposure induced sustained sexually dimorphic perturbations of the urinary and fecal metabolic fingerprints, but did not significantly influence the development of HFD-induced metabolic diseases.

A preliminary assessment of dietary exposure of ochratoxin A in Central Anatolia Region, Turkey.

The aim of this study was to determine dietary exposure to ochratoxin A (OTA) in Turkish adults. In this study, 500 food samples (50 rice, 50 wheat bread, 50 pasta, 50 raisins, 50 dried figs, 50 pistachios, 50 hazelnuts, 50 almonds, 50 chilli, 25 coffee, and 25 cocoa) collected from Turkey were analysed with a high-performance liquid chromatography (HPLC) method. Moreover, a total of 370 analytical results (110 cereal-based snacks, 95 wine, 35 beer, and 130 chocolate) collected from our previous observations were also used in the evaluation of exposure estimates. OTA was found in 52% of cocoa, 42% of raisins, 40% of coffee, 34% of chilli, 14% of dried figs, 10% of pasta, 8% of pistachios, 6% of wheat bread, 4% of rice, and 4% of hazelnuts. The chronic dietary exposure to OTA for Turkish adults, using lower bound (LB) and upper bound (UB) concentrations, varied from 0.683 to 4.487 ng/kg body weight (b.w.) per week for mean estimate and from 3.976 to 5.760 ng/kg b.w. per week for the 95th percentile (P95) estimate. Cereals and cereal-based products made the largest contribution (75.3-85.7%) to OTA exposure. Both mean and P95 chronic exposure to OTA were greatly below the tolerable weekly intake of 120 ng/kg b.w. per week and thus not a health concern for Turkish adults.

Sex differences, growth, reproduction and zinc ion homeostasis of zebrafish after chronic dietary l-selenomethionine exposure

Several mechanisms regarding the developmental and reproductive toxicity of l-selenomethionine (SeMet) in freshwater fish have been widely reported. However, limited information was available on endocrine-disrupting effects of SeMet. In this study, zebrafish larvae (day 24 post-fertilization) were exposed to environmentally-relevant levels of dietary SeMet (control, 1.11 ± 0.11, 3.59 ± 0.20, 10.80 ± 0.52, 29.19 ± 0.46, and 58.63 ± 0.70 μg Se/g d.w. diet) for 90 days until sexual maturity. For the first time, a gender difference in the effect of SeMet on body mass of zebrafish was observed. The lowest observed adverse effect level (LOAEL) in male was 10.80 ± 0.52 μg Se/g d.w., while it was 29.19 ± 0.46 μg Se/g d.w. in female. Chronic exposure to dietary SeMet reduced the percentage of early vitellogenic oocyte in female and the percentage of spermatid in male by inhibiting the growth hormone/insulin-like growth factors (GH/IGFs) and hypothalamus-pituitary-gonad (HPG) systems, which was characterized by significant decreases in the transcriptional levels of gh, igf1, era, and ar. Se content in the liver of male was significantly higher than that in female when dietary Se level reached 10.80 ± 0.52 μg Se/g d.w.. Furthermore, the zinc content in the livers and gonads of both female and male treated with 29.19 ± 0.46 and 58.63 ± 0.70 μg Se/g d.w. diets was significantly reduced. Reduction of zinc ion not only led to the significantly upregulated transcriptional levels of zip1 and znt2, but also downregulated transcriptional levels of znf219l and sp7. In summary, this study provides a new evidence that chronic exposure to high level of dietary SeMet (≥10.80 μg Se/g d.w.) could impair the development and reproduction of zebrafish with gender difference by interfering the GH/IGFs and HPG systems. Moreover, disruption of zinc ion homeostasis might exacerbate the toxicity of Se to zebrafish.

Jejunal villus absorption and paracellular tight junction permeability are major routes for early intestinal uptake of food-grade TiO2 particles: an in vivo and ex vivo study in mice

BackgroundFood-grade TiO2 (E171 in the EU) is widely used as a coloring agent in foodstuffs, including sweets. Chronic dietary exposure raises concerns for human health due to proinflammatory properties and the ability to induce and promote preneoplastic lesions in the rodent gut. Characterization of intestinal TiO2 uptake is essential for assessing the health risk in humans. We studied in vivo the gut absorption kinetics of TiO2 in fasted mice orally given a single dose (40 mg/kg) to assess the ability of intestinal apical surfaces to absorb particles when available without entrapment in the bolus. The epithelial translocation pathways were also identified ex vivo using intestinal loops in anesthetized mice.ResultsThe absorption of TiO2 particles was analyzed in gut tissues by laser-reflective confocal microscopy and ICP-MS at 4 and 8 h following oral administration. A bimodal pattern was detected in the small intestine: TiO2 absorption peaked at 4 h in jejunal and ileal villi before returning to basal levels at 8 h, while being undetectable at 4 h but significantly present at 8 h in the jejunal Peyer’s patches (PP). Lower absorption occurred in the colon, while TiO2 particles were clearly detectable by confocal microscopy in the blood at 4 and 8 h after treatment. Ex vivo, jejunal loops were exposed to the food additive in the presence and absence of pharmacological inhibitors of paracellular tight junction (TJ) permeability or of transcellular (endocytic) passage. Thirty minutes after E171 addition, TiO2 absorption by the jejunal villi was decreased by 66% (p < 0.001 vs. control) in the presence of the paracellular permeability blocker triaminopyrimidine; the other inhibitors had no significant effect. Substantial absorption through a goblet cell (GC)-associated pathway, insensitive to TJ blockade, was also detected.ConclusionsAfter a single E171 dose in mice, early intestinal uptake of TiO2 particles mainly occurred through the villi of the small intestine, which, in contrast to the PP, represent the main absorption surface in the small intestine. A GC-associated passage and passive diffusion through paracellular TJ spaces between enterocytes appeared to be major absorption routes for transepithelial uptake of dietary TiO2.

Dietary risk assessment of pesticide residues on Tremella fuciformis Berk (snow fungus) from Fujian Province of China

ABSTRACT To assess the dietary exposure risks of pesticide residues in snow fungus for the general population and young children, 91 snow fungus samples were collected from major production areas in Fujian Province, China and the presence of 44 pesticides was determined. A total of thirteen pesticides were detected; 65.9% of the samples contained one or more pesticide residues. The most frequently found pesticide was carbofuran, followed by acetamiprid and then imidacloprid. Data obtained were used for chronic, acute, and chronic cumulative dietary exposure risk assessments. The chronic hazard quotient (cHQ) was extremely low for both the general population and young children. The %ADI values of cumulative dietary exposures to organophosphorus pesticides and carbamates ranged from 0.53% to 1.49%, and did not exceed their corresponding ADIs. However, the acute dietary risks from all 13 pesticides, especially carbofuran and methamidophos, were of concern due to the relatively high acute hazard quotient. The risk ranking scheme showed that carbofuran could pose a high risk to snow fungus consumers. Finally, suggestions are made about the potential use in snow fungus cultivation of the pesticides with detected residues.

Cumulative dietary risk assessment overarching different regulatory silos using a margin of exposure approach: A case study with three chemical silos

Risk assessment of chemicals occurring in our diet is commonly performed for single chemicals without considering exposure to other chemicals. We performed a case study on risk assessment of combined dietary exposure to chemicals from different regulatory silos, i.e. pesticides (PPRs), persistent organic pollutants (POPs) and food additives (FAs). Chemicals were grouped into the cumulative assessment group (CAG) liver steatosis using a component-based approach. Based on literature, the CAG included 144 PPRs, 49 POPS and 7 FAs for which concentration data were available.For each silo, chronic combined dietary exposure was assessed for adults and children of nine European countries following the most commonly used exposure methodologies in Europe and by using a relative potency factor approach. For risk characterization, a Margin of Exposure (MOE) was calculated. To overarch the risk across silos, a normalised combined margin of exposure (nMOET) approach was proposed.This case study demonstrated that risk assessment of combined exposure to chemicals can be performed within regulatory silos. It also highlighted important differences in the conservatism of exposure scenarios, the derivation of point of departures and the subsequent acceptable MOEs between the silos. To overarch the risk despite these differences, a nMOET approach can be used.