Publications by authors named "Isabelle P Oswald"

164 Publications

Versicolorin A enhances the genotoxicity of aflatoxin B1 in human liver cells by inducing the transactivation of the Ah-receptor.

Food Chem Toxicol 2021 Jul 10;153:112258. Epub 2021 May 10.

Toxalim (Research Centre in Food Toxicology), University of Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027, Toulouse, France.

Aflatoxins are a group of mycotoxins that have major adverse effects on human health. Aflatoxin B1 (AFB1) is the most important aflatoxin and a potent carcinogen once converted into a DNA-reactive form by cytochrome P450 enzymes (CYP450). AFB1 biosynthesis involves the formation of Versicolorin A (VerA) which shares structural similarities with AFB1 and can be found in contaminated commodities, often co-occurring with AFB1. This study investigated and compared the toxicity of VerA and AFB1, alone or in combination, in HepG2 human liver cells. Our results show that both toxins have similar cytotoxic effects and are genotoxic although, unlike AFB1, the main genotoxic mechanism of VerA does not involve the formation of DNA double-strand breaks. Additionally, we show that VerA activates the aryl hydrocarbon receptor (AhR) and significantly induce the expression of the CYP450-1A1 (CYP1A1) while AFB1 did not induce AhR-dependent CYP1A1 activation. Combination of VerA with AFB1 resulted in enhanced genotoxic effects, suggesting that AhR-activation by VerA influences AFB1 genotoxicity by promoting its bioactivation by CYP450s to a highly DNA-reactive metabolite. Our results emphasize the need for expanding the toxicological knowledge regarding mycotoxin biosynthetic precursors to identify those who may pose, directly or indirectly, a threat to human health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2021.112258DOI Listing
July 2021

Comparative sensitivity of proliferative and differentiated intestinal epithelial cells to the food contaminant, deoxynivalenol.

Environ Pollut 2021 May 25;277:116818. Epub 2021 Feb 25.

Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France. Electronic address:

The intestinal epithelium is a functional and physical barrier formed by a cell monolayer that constantly differentiates from a stem cell in the crypt. This is the first target for food contaminants, especially mycotoxins. Deoxynivalenol (DON) is one of the most prevalent mycotoxins. This study compared the effects of DON (0-100 μM) on proliferative and differentiated intestinal epithelial cells. Three cell viability assays (LDH release, ATP content and neutral red uptake) indicated that proliferative Caco-2 cells are more sensitive to DON than differentiated ones. The establishment of transepithelial electrical resistance (TEER), as a read out of the differentiation process, was delayed in proliferative cells after exposure to 1 μM DON. Transcriptome analysis of proliferative and differentiated exposure to 0-3 μM DON for 24 h revealed 4862 differentially expressed genes (DEG) and indicated an effect of both the differentiation status and the DON treatment. KEGG enrichment analysis indicated involvement of metabolism, ECM receptors and tight junctions in the differentiation process, while ribosome biogenesis, mRNA surveillance, and the MAPK pathway were involved in the response to DON. The number of differentially expressed genes and the amplitude of the effect were higher in proliferative cells exposed to DON than that in differentiated cells. In conclusion, our study shows that proliferative cells are more susceptible than differentiated ones to DON and that the mycotoxin delays the differentiation process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.116818DOI Listing
May 2021

Regulation of Secondary Metabolism in the Genus.

Int J Mol Sci 2020 Dec 12;21(24). Epub 2020 Dec 12.

Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France.

, one of the most common fungi occurring in a diverse range of habitats, has a worldwide distribution and a large economic impact on human health. Hundreds of the species belonging to this genus cause disastrous decay in food crops and are able to produce a varied range of secondary metabolites, from which we can distinguish harmful mycotoxins. Some species are considered to be important producers of patulin and ochratoxin A, two well-known mycotoxins. The production of these mycotoxins and other secondary metabolites is controlled and regulated by different mechanisms. The aim of this review is to highlight the different levels of regulation of secondary metabolites in the genus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21249462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763326PMC
December 2020

Effects of Wheat Bran Applied to Maternal Diet on the Intestinal Architecture and Immune Gene Expression in Suckling Piglets.

Animals (Basel) 2020 Nov 6;10(11). Epub 2020 Nov 6.

Precision Livestock and Nutrition Laboratory, TERRA Teaching and Research Centre, Gembloux Agro-Bio Tech, University of Liège, 5030 Gembloux, Belgium.

The strategy of improving the growth and health of piglets through maternal fiber diet intervention has attracted increasing attention. Therefore, 15 sows were conducted to a wheat bran (WB) group, in which the sows' diets included 25% of WB in gestation and 14% in lactation, and a control (CON) group, in which the sows' diets at all stages of reproduction did not contain WB. The results show that maternal high WB intervention seems not to have an impact on the growth of the offspring or the villus height of the duodenum, and the ratio of villi/crypts in the duodenum and jejunum were all higher in piglets born from WB sows, which may indicate that WB piglets had a larger absorption area and capacity for nutrients. The peroxisome proliferator-activated receptor gamma () and interleukin 6 () expression levels were notably upregulated in the ileal mucosa of WB piglets, while no immune-related genes in the colonic mucosa were affected by the maternal WB supplementation. In conclusion, adding a high proportion of wheat bran to the sow's gestation and lactation diet can affect the intestinal architecture and the expression of some inflammation genes, to some extent, in the ileal mucosa in the progeny.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani10112051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694546PMC
November 2020

The Gene Deletion Reveals That Patulin Biosynthesis Is Not Related to Conidiation in .

Int J Mol Sci 2020 Sep 11;21(18). Epub 2020 Sep 11.

Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France.

Dissemination and survival of ascomycetes is through asexual spores. The gene encodes a CH-type zinc-finger transcription factor, which is essential for asexual development. causes blue mold disease and is the main source of patulin, a mycotoxin that contaminates apple-based food. A PeΔ deficient strain was generated by homologous recombination. In vivo, suppression of completely blocked the development of conidiophores that takes place after the formation of coremia/synnemata, a required step for the perforation of the apple epicarp. Metabolome analysis displayed that patulin production was enhanced by suppression, explaining a higher in vivo aggressiveness compared to the wild type (WT) strain. No patulin was detected in the synnemata, suggesting that patulin biosynthesis stopped when the fungus exited the apple. In vitro transcriptome analysis of PeΔ unveiled an up-regulated biosynthetic gene cluster (PEXP_073960-PEXP_074060) that shares high similarity with the chaetoglobosin gene cluster of . Metabolome analysis of PeΔ confirmed these observations by unveiling a greater diversity of chaetoglobosin derivatives. We observed that chaetoglobosins A and C were found only in the synnemata, located outside of the apple, whereas other chaetoglobosins were detected in apple flesh, suggesting a spatial-temporal organization of the chaetoglobosin biosynthesis pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21186660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555563PMC
September 2020

Risk assessment of aflatoxins in food.

EFSA J 2020 Mar 9;18(3):e06040. Epub 2020 Mar 9.

EFSA was asked to deliver a scientific opinion on the risks to public health related to the presence of aflatoxins in food. The risk assessment was confined to aflatoxin B1 (AFB1), AFB2, AFG1, AFG2 and AFM1. More than 200,000 analytical results on the occurrence of aflatoxins were used in the evaluation. Grains and grain-based products made the largest contribution to the mean chronic dietary exposure to AFB1 in all age classes, while 'liquid milk' and 'fermented milk products' were the main contributors to the AFM1 mean exposure. Aflatoxins are genotoxic and AFB1 can cause hepatocellular carcinomas (HCCs) in humans. The CONTAM Panel selected a benchmark dose lower confidence limit (BMDL) for a benchmark response of 10% of 0.4 μg/kg body weight (bw) per day for the incidence of HCC in male rats following AFB1 exposure to be used in a margin of exposure (MOE) approach. The calculation of a BMDL from the human data was not appropriate; instead, the cancer potencies estimated by the Joint FAO/WHO Expert Committee on Food Additives in 2016 were used. For AFM1, a potency factor of 0.1 relative to AFB1 was used. For AFG1, AFB2 and AFG2, the data are not sufficient to derive potency factors and equal potency to AFB1 was assumed as in previous assessments. MOE values for AFB1 exposure ranged from 5,000 to 29 and for AFM1 from 100,000 to 508. The calculated MOEs are below 10,000 for AFB1 and also for AFM1 where some surveys, particularly for the younger age groups, have an MOE below 10,000. This raises a health concern. The estimated cancer risks in humans following exposure to AFB1 and AFM1 are in-line with the conclusion drawn from the MOEs. The conclusions also apply to the combined exposure to all five aflatoxins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2903/j.efsa.2020.6040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447885PMC
March 2020

The food contaminant, deoxynivalenol, modulates the Thelper/Treg balance and increases inflammatory bowel diseases.

Arch Toxicol 2020 09 2;94(9):3173-3184. Epub 2020 Jul 2.

Toxalim (Research Center in Food Toxicology), INRAE, ENVT, INP- PURPAN, UMR 1331, UPS, Université de Toulouse, 180 Chemin de Tournefeuille, BP93173, cedex 03, F-31027, Toulouse, France.

The incidence of inflammatory bowel diseases (IBD) is increasing in both Western and developing countries. IBD are multifactorial disorders involving complex interactions between genetic, immune, and environmental factors such as exposure to food contaminants. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food and induces intestinal breakdown and inflammatory response. To delineate the role of DON oral exposure in IBD, we used a Dextran sulfate sodium (DSS) colitis model in rats fed with a DON-contaminated diet or a control diet for 4 weeks. Colitis was induced in the 4th week by increasing concentrations of DSS in the drinking water (0, 2, 3 or 5%). DON exacerbated body weight loss and accelerated the appearance of symptoms in animals treated with DSS. DON increased morphological damage, pro-inflammatory markers (myeloperoxidase, CXCL-1 and IL-1β) and immune cell responses. In lamina propria of the rat with colitis, DON increased adaptive and innate immune responses after anti-CD3/28 or LPS stimulation, respectively. In the spleen, DON increased IFNγ secretion and reduced Treg populations. Interestingly, De-epoxy-DON (DOM-1) a detoxified form of DON did not have any consequences on colitis. These results suggest that DON is a risk factor in the onset of IBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00204-020-02817-zDOI Listing
September 2020

Proteome changes induced by a short, non-cytotoxic exposure to the mycoestrogen zearalenone in the pig intestine.

J Proteomics 2020 07 23;224:103842. Epub 2020 May 23.

Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France.

Intestinal epithelial homeostasis is regulated by a complex network of signaling pathways. Among them is estrogen signaling, important for the proliferation and differentiation of epithelial cells, immune signaling and metabolism. The mycotoxin zearalenone (ZEN) is an estrogen disruptor naturally found in food and feed. The exposure of the intestine to ZEN has toxic effects including alteration of the immune status and is possibly implicated in carcinogenesis, but the molecular mechanisms linked with these effects are not clear. Our objective was to explore the proteome changes induced by a short, non-cytotoxic exposure to ZEN in the intestine using pig jejunal explants. Our results indicated that ZEN promotes little proteome changes, but significantly related with an induction of ERα signaling and a consequent disruption of highly interrelated signaling cascades, such as NF-κB, ERK1/2, CDX2 and HIF1α. The toxicity of ZEN leads also to an altered immune status characterized by the activation of the chemokine CXCR4/SDF-1 axis and an accumulation of MHC-I proteins. Our results connect the estrogen disrupting activity of ZEN with its intestinal toxic effect, associating the exposure to ZEN with cell-signaling disorders similar to those involved in the onset and progression of diseases such as cancer and chronic inflammatory disorders. SIGNIFICANCE: The proteomics results presented in our study indicate that the endocrine disruptor activity of ZEN is able to regulate a cascade of highly inter-connected signaling events essential for the small intestinal crypt-villus cycle and immune status. These molecular mechanisms are also implicated in the onset and progress of intestinal immune disorders and cancer indicating that exposure to ZEN could play an important role in intestinal pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jprot.2020.103842DOI Listing
July 2020

Dietary exposure to mycotoxins in the French infant total diet study.

Food Chem Toxicol 2020 Jun 27;140:111301. Epub 2020 Mar 27.

Risk Assessment Department (DER), French Agency for Food, Environmental and Occupational Health & Safety, 14 rue Pierre & Marie Curie, F-94700, Maisons-Alfort, France.

The present study evaluated the exposure of children aged from one to 36 months to seven groups of mycotoxins, in the context of the infant French Total Diet Study (iTDS). Exposure was then compared to the health-based guidance values (HBGVs) for each mycotoxin. The value of the 90th percentile of exposure to nivalenol, patulin, fumonisins and zearalenone was less than 40% of the HBGV considered relevant for children. On the other hand, a risk could not be excluded for ochratoxin A and aflatoxins as exposure was close to the HBGV for ochratoxin A and the margin of exposure was much lower than the critical margin of 10,000 for aflatoxins. The HBGVs for toxins T2 and HT2, and for deoxynivalenol (DON) and its acetylated compounds were exceeded. Five percent to 10% of the children aged 5-12 months exceeded the HBGV considering the lower bound hypothesis for toxins T2 and HT2 and 7.5%-27% of the children aged 5 months and above exceeded the HBGV for DON. Consequently, the exposure of young children raises safety concerns for T2/HT2 and DON. Efforts should therefore be pursued to decrease their exposure to these molecules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2020.111301DOI Listing
June 2020

Reduced toxicity of 3-epi-deoxynivalenol and de-epoxy-deoxynivalenol through deoxynivalenol bacterial biotransformation: In vivo analysis in piglets.

Food Chem Toxicol 2020 Jun 16;140:111241. Epub 2020 Mar 16.

Toxalim, Research Center in Food Toxicology, Université de Toulouse, INRAe, ENVT, INP-Purpan, UPS, Toulouse, France.

Ingestion of deoxynivalenol (DON), one of the most common mycotoxin contaminants of cereals, leads to adverse effects for animal and human health. Bacterial biotransformation is a strategy to mitigate the toxicity of this mycotoxin. The present study aims to evaluate the toxicity of two bacterial biotranformation products of DON: 3-epi-deoxynivalenol (3-epi-DON) and de-epoxy-deoxynivalenol (DOM-1) through zootechnical, hematological, histological and immunological assays. Twenty-four 4-weeks-old piglets received a control diet or a diet contaminated with 3 mg kg DON, DOM-1, or 3-epi-DON for 7 days. Sample tissues were collected for histomorphometrical analysis, expression of cytokines and cell protein junctions. The zootechnical and hematological parameters were not modulated by any treatment. Ingestion of DON induced histological alterations in the intestine, liver and lymphoid organs, as well as an overexpression of pro-inflammatory cytokines, E-cadherin and occludin. These changes were not observed in piglets receiving the DOM-1 and 3-epi-DON contaminated diets. Pigs fed 3-epi-DON contaminated diet showed an increase in IgM levels in comparison with other diets, while no change was observed in IgA and IgG levels among the diets. Our results indicate that DOM-1 and 3-epi-DON are not toxic for piglets; thus bacterial biotransformation seems to be a sustainable alternative to reduce mycotoxin toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2020.111241DOI Listing
June 2020

H-NMR metabolomics response to a realistic diet contamination with the mycotoxin deoxynivalenol: Effect of probiotics supplementation.

Food Chem Toxicol 2020 Apr 4;138:111222. Epub 2020 Mar 4.

Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France. Electronic address:

Low-level contamination of food and feed by deoxynivalenol (DON) is unavoidable. We investigated the effects of subclinical treatment with DON, and supplementation with probiotic yeast Saccharomyces cerevisiae boulardii I1079 as a preventive strategy in piglets. Thirty-six animals were randomly assigned to either a control diet, a diet contaminated with DON (3 mg/kg), a diet supplemented with yeast (4 × 10 CFU/kg), or a DON-contaminated diet supplemented with yeast, for four weeks. Plasma and tissue samples were collected for biochemical analysis,H-NMR untargeted metabolomics, and histology. DON induced no significant modifications in biochemical parameters. However, lesion scores were higher and metabolomics highlighted alterations of amino acid and 2-oxocarboxylic acid metabolism. Administering yeast affected aminoacyl-tRNA synthesis and amino acid and glycerophospholipid metabolism. Yeast supplementation of piglets exposed to DON prevented histological alterations, and partial least square discriminant analysis emphasised similarity between the metabolic profiles of their plasma and that of the control group. The effect on liver metabolome remained marginal, indicating that the toxicity of the mycotoxin was not eliminated. These findings show that the H-NMR metabolomics profile is a reliable biomarker to assess subclinical exposure to DON, and that supplementation with S. cerevisiae boulardii increases the resilience of piglets to this mycotoxin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2020.111222DOI Listing
April 2020

Aflatoxin Biosynthesis and Genetic Regulation: A Review.

Toxins (Basel) 2020 02 28;12(3). Epub 2020 Feb 28.

Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRAE, ENVT, EI-Purpan, 31300 Toulouse, France.

The study of fungal species evolved radically with the development of molecular techniques and produced new evidence to understand specific fungal mechanisms such as the production of toxic secondary metabolites. Taking advantage of these technologies to improve food safety, the molecular study of toxinogenic species can help elucidate the mechanisms underlying toxin production and enable the development of new effective strategies to control fungal toxicity. Numerous studies have been made on genes involved in aflatoxin B1 (AFB1) production, one of the most hazardous carcinogenic toxins for humans and animals. The current review presents the roles of these different genes and their possible impact on AFB1 production. We focus on the toxinogenic strains and primary contaminants and major producers of AFB1 in crops. However, genetic reports on are also included because of the capacity of this fungus to produce sterigmatocystin, the penultimate stable metabolite during AFB1 production. The aim of this review is to provide a general overview of the AFB1 enzymatic biosynthesis pathway and its link with the genes belonging to the AFB1 cluster. It also aims to illustrate the role of global environmental factors on aflatoxin production and the recent data that demonstrate an interconnection between genes regulated by these environmental signals and aflatoxin biosynthetic pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/toxins12030150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150809PMC
February 2020

Versicolorin A, a precursor in aflatoxins biosynthesis, is a food contaminant toxic for human intestinal cells.

Environ Int 2020 04 24;137:105568. Epub 2020 Feb 24.

Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France. Electronic address:

Aflatoxin B (AFB) is the most potent carcinogen among mycotoxins. Its biosynthesis involves the formation of versicolorin A (VerA), whose chemical structure shares many features with AFB. Our data revealed significant levels of VerA in foodstuff from Central Asia and Africa. Given this emerging food risk, it was of prime interest to compare the toxic effects of the two mycotoxins against cells originating from the intestinal tract. We used human colon cell lines (Caco-2, HCT116) to investigate the cytotoxic process induced by the two mycotoxins. Contrary to AFB, a low dose of VerA (1 µM) disturbed the expression level of thousands of genes (18 002 genes). We show that the cytotoxic effects of low doses of VerA (1-20 µM) were stronger than the same low doses of AFB in both Caco-2 and HCT116 cell lines. In Caco-2 cells, VerA induced DNA strand breaks that led to apoptosis and reduced DNA replication of dividing cells, consequently inhibiting cell proliferation. Although VerA was able to induce the p53 signaling pathway in p53 wild-type HCT116 cells, its toxicity process did not mainly rely on p53 expression since similar cytotoxic effects were also observed in HCT116 cells that do not express p53. In conclusion, this study provides evidence of the risk of food contamination by VerA and shed light on its toxicological effect on human colon cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2020.105568DOI Listing
April 2020

Acute Exposure to Zearalenone Disturbs Intestinal Homeostasis by Modulating the Wnt/β-Catenin Signaling Pathway.

Toxins (Basel) 2020 02 11;12(2). Epub 2020 Feb 11.

Toxalim (Research Centre in Food Toxicology), University of Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France.

The mycotoxin zearalenone (ZEN), which frequently contaminates cereal-based human food and animal feed, is known to have an estrogenic effect. The biological response associated with exposure to ZEN has rarely been reported in organs other than the reproductive system. In the intestine, several studies suggested that ZEN might stimulate molecular changes related to the activation of early carcinogenesis, but the molecular mechanisms behind these events are not yet known. In this study, we investigated gene expression and changes in protein abundance induced by acute exposure to ZEN in the jejunum of castrated male pigs using an explant model. Our results indicate that ZEN induces the accumulation of ER but not ER, modulates Wnt/β-catenin and TGF- signaling pathways, and induces molecular changes linked with energy sensing and the antimicrobial activity without inducing inflammation. Our results confirm that the intestine is a target for ZEN, inducing changes that promote cellular proliferation and could contribute to the onset of intestinal pathologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/toxins12020113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076757PMC
February 2020

Integrative analysis of blood and gut microbiota data suggests a non-alcoholic fatty liver disease (NAFLD)-related disorder in French SLA minipigs.

Sci Rep 2020 01 14;10(1):234. Epub 2020 Jan 14.

Université Paris Saclay, INRAE, AgroParisTech, GABI, 78350, Jouy-en-Josas, France.

Minipigs are a group of small-sized swine lines, which show a broad range of phenotype variation and which often tend to be obese. The SLA (DD) minipig line was created by the NIH and selected as homozygous at the SLA locus. It was brought to France more than 30 years ago and maintained inbred ever since. In this report, we characterized the physiological status of a herd of French DD pigs by measuring intermediate phenotypes from blood and faeces and by using Large White (LW) pigs as controls. Three datasets were produced, i.e. complete blood counts (CBCs), microarray-based blood transcriptome, and faecal microbiota obtained by 16S rRNA sequencing. CBCs and expression profiles suggested a non-alcoholic fatty liver disease (NAFLD)-related pathology associated to comorbid cardiac diseases. The characterization of 16S sequencing data was less straightforward, suggesting only a potential weak link to obesity. The integration of the datasets identified several fine-scale associations between CBCs, gene expression, and faecal microbiota composition. NAFLD is a common cause of chronic liver disease in Western countries and is linked to obesity, type 2 diabetes mellitus and cardiac pathologies. Here we show that the French DD herd is potentially affected by this syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-57127-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959234PMC
January 2020

An in silico structural approach to characterize human and rainbow trout estrogenicity of mycotoxins: Proof of concept study using zearalenone and alternariol.

Food Chem 2020 May 23;312:126088. Epub 2019 Dec 23.

Department of Food and Drug, University of Parma, Area Parco delle Scienze 27/A, 43124 Parma, Italy. Electronic address:

The mycotoxins zearalenone and alternariol may contaminate food and feed raising toxicological concerns due to their estrogenicity. Inter-species differences in their toxicokinetics and toxicodynamics may occur depending on evolution of taxa-specific traits. As a proof of principle, this manuscript investigates the comparative toxicodynamics of zearalenone, its metabolites (alpha-zearalenol and beta-zearalenol), and alternariol with regards to estrogenicity in humans and rainbow trout. An in silico structural approach based on docking simulations, pharmacophore modeling and molecular dynamics was applied and computational results were analyzed in comparison with available experimental data. The differences of estrogenicity among species of zearalenone and its metabolites have been structurally explained. Also, the low estrogenicity of alternariol in trout has been characterized here for the first time. This approach can provide a powerful tool for the characterization of interspecies differences in mycotoxin toxicity for a range of protein targets and relevant compounds for the food- and feed-safety area.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2019.126088DOI Listing
May 2020

Co-occurrence of DON and Emerging Mycotoxins in Worldwide Finished Pig Feed and Their Combined Toxicity in Intestinal Cells.

Toxins (Basel) 2019 12 11;11(12). Epub 2019 Dec 11.

Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 180 Chemin de Tournefeuille, F- 31027 Toulouse CEDEX 3, France.

Food and feed can be naturally contaminated by several mycotoxins, and concern about the hazard of exposure to mycotoxin mixtures is increasing. In this study, more than 800 metabolites were analyzed in 524 finished pig feed samples collected worldwide. Eighty-eight percent of the samples were co-contaminated with deoxynivalenol (DON) and other regulated/emerging mycotoxins. The Top 60 emerging/regulated mycotoxins co-occurring with DON in pig feed shows that 48%, 13%, 8% and 12% are produced by Fusarium, Aspergillus, Penicillium and Alternaria species, respectively. Then, the individual and combined toxicity of DON and the 10 most prevalent emerging mycotoxins (brevianamide F, cyclo-(L-Pro-L-Tyr), tryptophol, enniatins A1, B, B1, emodin, aurofusarin, beauvericin and apicidin) was measured at three ratios corresponding to pig feed contamination. Toxicity was assessed by measuring the viability of intestinal porcine epithelial cells, IPEC-1, at 48-h. BRV-F, Cyclo and TRPT did not alter cell viability. The other metabolites were ranked in the following order of toxicity: apicidin > enniatin A1 > DON > beauvericin > enniatin B > enniatin B1 > emodin > aurofusarin. In most of the mixtures, combined toxicity was similar to the toxicity of DON alone. In terms of pig health, these results demonstrate that the co-occurrence of emerging mycotoxins that we tested with DON does not exacerbate toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/toxins11120727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950336PMC
December 2019

Unusual acute neonatal mortality and sow agalactia linked with ergot alkaloid contamination of feed.

Porcine Health Manag 2019 6;5:24. Epub 2019 Nov 6.

4ENVT, Toulouse, France.

Background: An increase in the occurrence of ergot alkaloid contamination has been observed in Europe in recent years. The typical clinical signs of pig ergot poisoning are impaired growth, agalactia and, sometimes, gangrene. Opportunities for reporting exposure doses associated with clinical signs in animals under field conditions are rare.

Case Presentation: In a farrow-to-finish pig farm with 160 sows, excessive acute neonatal mortality was reported in association with a loss of appetite and agalactia in sows. A herd examination was conducted and a high rate of piglet loss and agalactia in 13 sows out of the most affected batch of 20 were confirmed. Necropsy showed piglets with empty stomachs and intestines, with apparently normal mucosa. Gestating and lactating sow diet samples, as well as a wheat sample, were sent for analysis following feed mill inspection and a hypothesis of mycotoxin contamination of self-prepared feed. Liquid chromatography with mass spectrometry in tandem revealed an amount of total ergot alkaloids in all of the samples ranging from 3.49 mg/kg (gestating diet) to 8.06 mg/kg (lactating diet). The contaminated feed was removed and the situation returned to normal 3 weeks later (following batch of sows).

Conclusion: In the present case, the exposure of sows to 3.49 mg/kg ergot alkaloid for 10 to 15 days before the end of gestation and to 8.06 mg/kg ergot alkaloid over 3 to 4 days at the beginning of lactation - corresponding to a content of 10,146 mg of sclerotia/kg in the wheat of the diets- led to agalactia in 13 of 20 sows in a batch and to a high neonatal mortality rates for all litters. No clinical signs associated with vasoconstrictive effects were observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40813-019-0131-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833232PMC
November 2019

Fumonisins at Doses below EU Regulatory Limits Induce Histological Alterations in Piglets.

Toxins (Basel) 2019 09 19;11(9). Epub 2019 Sep 19.

Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, 31300 Toulouse, France.

Fumonisins (FBs) are mycotoxins produced by species that can contaminate human food and animal feed. Due to the harmful effects of FBs on animals, the European Union (EU) defined a recommendation of a maximum of 5 mg FBs (B1 + B2)/kg for complete feed for swine and 1 µg FBs/kg body weight per day as the tolerable daily intake for humans. The aim of this study was to evaluate the toxicity of dietary exposure to low doses of FBs, including a dose below the EU regulatory limits. Four groups of 24 weaned castrated male piglets were exposed to feed containing 0, 3.7, 8.1, and 12.2 mg/kg of FBs for 28 days; the impact was measured by biochemical analysis and histopathological observations. Dietary exposure to FBs at a low dose (3.7 mg/kg of feed) significantly increased the plasma sphinganine-to-sphingosine ratio. FBs-contaminated diets led to histological modifications in the intestine, heart, lung, lymphoid organs, kidney, and liver. The histological alterations in the heart and the intestine appeared at the lowest dose of FBs-contaminated diet (3.7 mg/kg feed) and in the kidney at the intermediate dose (8.1 mg/kg feed). At the highest dose tested (12.2 mg/kg feed), all the organs displayed histological alterations. This dose also induced biochemical modifications indicative of kidney and liver alterations. In conclusion, our data indicate that FBs-contaminated diets at doses below the EU regulatory limit cause histological lesions in several organs. This study suggests that EU recommendations for the concentration of FBs in animal feed, especially for swine, are not sufficiently protective and that regulatory doses should be modified for better protection of animal health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/toxins11090548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784023PMC
September 2019

Combination of Isotope Labeling and Molecular Networking of Tandem Mass Spectrometry Data To Reveal 69 Unknown Metabolites Produced by .

Anal Chem 2019 10 11;91(19):12191-12202. Epub 2019 Sep 11.

Toxalim (Research Centre in Food Toxicology) , Université de Toulouse, INRA, ENVT, INP-Purpan , UPS , F-31027 Toulouse , France.

The secondary metabolome of is poorly documented despite its frequent detection on contaminated food and its capacity to produce toxic metabolites such as ochratoxin A. To characterize metabolites produced by this fungi, we combined a full stable isotopes labeling with the dereplication of tandem mass spectrometry (MS/MS) data by molecular networking. First, the untargeted metabolomic analysis by high-resolution mass spectrometry of a double stable isotope labeling of enabled the specific detection of its metabolites and the unambiguous determination of their elemental composition. Analyses showed that infection of substrate by lead to the production of at least 92 metabolites and that 69 of them were completely unknown. Then, curated molecular networks of MS/MS data were generated with GNPS and MetGem, specifically on the features of interest, which allowed highlighting 13 fungisporin-related metabolites that had not previously been identified in this fungus and 8 that had never been observed in any fungus. The structures of the unknown compounds, namely, a native fungisporin and seven linear peptides, were characterized by tandem mass spectrometry experiments. The analysis of growing on its natural substrates, i.e. pork ham, turkey ham, and cheese, demonstrated that 10 of the known fungisporin-related metabolites and three of the new metabolites were also synthesized. Thus, the curation of data for molecular networking using a specific detection of metabolites of interest with stable isotopes labeling allowed the discovery of new metabolites produced by the food contaminant .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.9b01634DOI Listing
October 2019

In vitro and in vivo effects of a mycotoxin, deoxynivalenol, and a trace metal, cadmium, alone or in a mixture on the intestinal barrier.

Environ Int 2019 11 7;132:105082. Epub 2019 Aug 7.

Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.

Deoxynivalenol (DON), one of the most widespread mycotoxins in Europe, and cadmium (Cd), a widespread environmental pollutant, are common food contaminants. They exert adverse effects on different organs including kidney, liver, and intestine. The intestine is a common target of DON and Cd when they are ingested. Most studies have focused on their individual effects whereas their combined toxicity has rarely been studied. The aim of this study was thus to evaluate their individual and combined effects on the intestinal barrier function in vitro and in vivo. In vitro, Caco-2 cells were treated with increasing concentrations of DON and Cd (1-30 μM). In vivo, Wistar rats were used as controls or exposed to DON contaminated feed (8.2 mg/kg feed), Cd-contaminated water (5 mg/l) or both for four weeks. In Caco-2 cells, DON, Cd and the DON+Cd mixture reduced transepithelial electrical resistance (TEER) and increased paracellular permeability in a dose-dependent manner. Impairment of the barrier function was associated with a decrease in the amount of E-cadherin and occludin after exposure to the two contaminants alone or combined. A decrease in E-cadherin expression was observed in rats exposed to the two contaminants alone or combined, whereas occludin expression only decreased in animals exposed to DON and DON+Cd. Jejunal crypt depth was reduced in rats exposed to DON or Cd, whereas villi height was not affected. In vitro and in vivo results showed that the effects of exposure to combined DON and Cd on the intestinal barrier function in the jejunum of Wistar rats and in the colorectal cancer cell line (Caco-2) was similar to the effects of each individual contaminant. This suggests that regulations for each individual contaminant are sufficiently protective for consumers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2019.105082DOI Listing
November 2019

Combined hazard assessment of mycotoxins and their modified forms applying relative potency factors: Zearalenone and T2/HT2 toxin.

Food Chem Toxicol 2019 Sep 24;131:110599. Epub 2019 Jun 24.

Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.

This paper describes a methodology for hazard assessment of groups of related substances for which toxicity data are insufficient, and which utilises, next to conventional toxicological assessments and mechanistic information, the derivation of relative toxicity potency factors (RPFs). Zearalenone (ZEN) and T-2 toxin (T2) and HT-2 toxin (HT2) and their modified forms have been used as examples. A tolerable daily intake (TDI) for ZEN of 0.25 μg/kg bw was established. In vitro and in vivo studies suggested that modified forms of ZEN act via the same mode of action as ZEN (oestrogenicity). Results from in vivo uterotrophic assays were used to establish RPFs, allowing inclusion the different modified forms in a group TDI with ZEN. A TDI for the sum of T2/HT2 of 0.02 μg/kg bw per day and an acute reference dose (ARfD) of 0.3 μg/kg bw for the sum of T2/HT2 was established. In vitro studies show that phase I metabolites of T2/HT2 act via a similar mode of action as their parent compounds, namely protein synthesis inhibition with immune- and haematotoxicity. The phase I metabolites as well as conjugates of T2/HT2 and their phase I metabolites can be included in a group TDI with T2/HT2 applying RPFs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2019.110599DOI Listing
September 2019

Individual and combined mycotoxins deoxynivalenol, nivalenol, and fusarenon-X induced apoptosis in lymphoid tissues of mice after oral exposure.

Toxicon 2019 Jul 2;165:83-94. Epub 2019 May 2.

.Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, 10900, Thailand; Center for Advanced Studies for Agriculture and Food, KU Institute for Advanced Studies, Kasetsart University, CASAF, NRU-KU, Bangkok, 10900, Thailand. Electronic address:

Lymphocytes are involved in the adaptive immune response and are highly sensitive to type B trichothecenes. In grains and their products, deoxynivalenol (DON) is the most widely distributed trichothecene. It usually co-occurs with other type B members, such as nivalenol (NIV) and fusarenon-X (FX), because they are all produced by the same Fusarium fungi. However, the combined effects of mycotoxins are complex and cannot be predicted based on individual toxicity. Thus, the adverse effects of combined toxins are of increasing concern. The aim of this study was to compare the toxicity to lymphoid tissues of mice of DON alone or mixed with NIV or FX. Forty, 3-week-old male ICR mice were given a single oral administration of a vehicle control, one toxin, binary, or ternary mixtures and then sacrificed at 12 h after exposure. Mice treated with FX alone showed marked nuclear condensation and fragmentation of lymphocytes in the cortical thymus and germinal center of Peyer's patches and spleen. Similarly, these animals clearly displayed TUNEL- and Caspase-3-positive cells in the regions. In contrast, minimal changes were noticed in the lymphoid tissues of mice receiving combined toxins when compared to this toxin alone. In addition, oral exposure to FX alone significantly up-regulated the relative expression of Bax, Caspase-3, Caspase-9, and Trp53. These data increase our understanding of the toxic actions of DON, NIV, and FX alone or in combination to lymphocytes and can be used to assess the possible risk associated with their co-occurrences in foodstuffs to human and animal health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2019.04.017DOI Listing
July 2019

Morphologic, molecular and metabolic characterization of Aspergillus section Flavi in spices marketed in Lebanon.

Sci Rep 2019 03 27;9(1):5263. Epub 2019 Mar 27.

Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, 180 Chemin de Tournefeuille, F-31027, Toulouse, France.

Spices are used extensively in Lebanon not only to flavour foods but also for their medicinal properties. To date, no data are available regarding the nature of the toxigenic fungal species that may contaminate these products at the marketing stage in this country. Eighty samples corresponding to 14 different types of spices were collected throughout Lebanon to characterize the Aspergillus section Flavi contaminating spices marketed in Lebanon and the toxigenic potential of these fungal species. Most fungal genera and species were identified as belonging to Aspergillus section Flavi. Aspergillus flavus was the most frequent species, representing almost 80% of the isolates. Although identified as A. flavus by molecular analysis, some strains displayed atypical morphological features. Seven strains of A. tamarii and one A. minisclerotigenes were also isolated. Analyses of toxigenic potential demonstrated that almost 80% of strains were able to produce mycotoxins, 47% produced aflatoxins, and 72% produced cyclopiazonic acid, alone or in combination with aflatoxins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-41704-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437153PMC
March 2019

Effects of Mycotoxins on the Intestine.

Toxins (Basel) 2019 03 13;11(3). Epub 2019 Mar 13.

Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, 31027 Toulouse, France.

The gastrointestinal tract is the first physiological barrier against food contaminants, as well as the first target for these toxicants [...].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/toxins11030159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468410PMC
March 2019

Deoxynivalenol inhibits the expression of trefoil factors (TFF) by intestinal human and porcine goblet cells.

Arch Toxicol 2019 04 11;93(4):1039-1049. Epub 2019 Mar 11.

CNRS, Centrale Marseille, iSm2, UMR 7313, Aix Marseille University, 13397, Marseille, France.

Trefoil factors (TFFs) are bioactive peptides expressed by several epithelia, including the intestine, where they regulate key functions such as tissue regeneration, barrier function and inflammation. Although food-associated mycotoxins, including deoxynivalenol (DON), are known to impact many intestinal functions, modulation of TFFs during mycotoxicosis has never been investigated. Here, we analyzed the effect of DON on TFFs expression using both human goblet cells (HT29-16E cells) and porcine intestinal explants. Results showed that very low doses of DON (nanomolar range) inhibit the secretion of TFFs by human goblet cells (IC of 361, 387 and 243 nM for TFF1, 2 and 3, respectively) and prevent wound healing. RT-qPCR analysis demonstrated that the inhibitory effect of DON is related to a suppression of TFFs mRNA expression. Experiments conducted on porcine intestinal explants confirmed the results obtained on cells. Finally, the use of specific inhibitors of signal pathways demonstrated that DON-mediated suppression of TFFs expression mainly involved Protein Kinase R and the MAP kinases (MAPK) p38 and ERK1/2. Taken together, our results show for the first time that at very low doses, DON suppresses the expression and production of intestinal TFFs and alters wound healing. Given the critical role of TFFs in tissue repair, our results suggest that DON-mediated suppression of TFFs contributes to the alterations of intestinal integrity the caused by this toxin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00204-019-02425-6DOI Listing
April 2019

Individual and combined cytotoxicity of major trichothecenes type B, deoxynivalenol, nivalenol, and fusarenon-X on Jurkat human T cells.

Toxicon 2019 Mar 16;160:29-37. Epub 2019 Feb 16.

Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand; Center for Advanced Studies for Agriculture and Food, CASAF, KU Institute for Advanced Studies, NRU-KU, Kasetsart University, Bangkok 10900, Thailand. Electronic address:

Food and feed commodities are often contaminated by more than one mycotoxin. Among the several combinations that frequently occur, fusariotoxins are often mentioned. The multi-mycotoxins contamination is a serious threat for health. In the present study we investigated the toxic interactions between deoxynivalenol (DON), nivalenol (NIV), and fusarenon-X (FX) in Jurkat T cells by using the MTT assay. The tested mycotoxins alone or in combination had a dose dependent effect on proliferating lymphocytes. According to IC, it could be classified in decreasing order of toxicity: FX > NIV > DON > DON + FX > NIV + FX > DON + NIV > DON + NIV + FX. The type of mycotoxin interactions was assessed by calculating the combination index (CI) and the dose reduction index (DRI). Our data indicate that an antagonistic effect was strongly observed in binary combination between DON and NIV at higher concentrations and ternary mixtures. Meanwhile, the DON and FX mixtures generated moderate antagonism, while NIV and FX provoked different interactions. The effects of tested mycotoxins on apoptosis were also determined using a FACScan flow cytometer. At IC, the percentages of apoptotic cells in all treatment groups were significantly different when compared to control group but no significant differences among treatment groups was observed. Taken together, our data suggest that immunotoxicity among multi-mycotoxins contamination cannot be predicted based on individual effects but depends on the mixtures, ratio and/or concentrations in the product, as well as type of target cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2019.02.006DOI Listing
March 2019

Occurrence and Identification of Section in the Context of the Emergence of Aflatoxins in French Maize.

Toxins (Basel) 2018 12 7;10(12). Epub 2018 Dec 7.

ARVALIS Institut du Végétal, Station Expérimentale, 91720 Boigneville, France.

Aflatoxins (AFs) are secondary metabolites produced by section during their development, particularly in maize. It is widely accepted that AFB1 is a major contaminant in regions where hot climate conditions favor the development of aflatoxigenic species. Global warming could lead to the appearance of AFs in maize produced in Europe. This was the case in 2015, in France, when the exceptionally hot and dry climatic conditions were favorable for AF production. Our survey revealed AF contamination of 6% ( = 114) of maize field samples and of 15% ( = 81) of maize silo samples analyzed. To understand the origin of the contamination, we characterized the mycoflora in contaminated samples and in samples produced in the same geographic and climatic conditions but with no AFs. A special focus was placed on section . A total of 67 strains of section were isolated from the samples. As expected, the strains were observed in all AF+ samples and, remarkably, also in almost 40% of AF- samples, demonstrating the presence of these potent toxin producers in fields in France. was the most frequent species of the section (69% of the strains). But surprisingly, was also a frequent contaminant (28% of the strains), mostly isolated from AF+ samples. This finding is in agreement with the presence of AFG in most of those samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/toxins10120525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315360PMC
December 2018

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food.

EFSA J 2018 Dec 13;16(12):e05194. Epub 2018 Dec 13.

The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in food. Regarding PFOS and PFOA occurrence, the final data set available for dietary exposure assessment contained a total of 20,019 analytical results (PFOS n = 10,191 and PFOA n = 9,828). There were large differences between upper and lower bound exposure due to analytical methods with insufficient sensitivity. The CONTAM Panel considered the lower bound estimates to be closer to true exposure levels. Important contributors to the lower bound mean chronic exposure were 'Fish and other seafood', 'Meat and meat products' and 'Eggs and egg products', for PFOS, and 'Milk and dairy products', 'Drinking water' and 'Fish and other seafood' for PFOA. PFOS and PFOA are readily absorbed in the gastrointestinal tract, excreted in urine and faeces, and do not undergo metabolism. Estimated human half-lives for PFOS and PFOA are about 5 years and 2-4 years, respectively. The derivation of a health-based guidance value was based on human epidemiological studies. For PFOS, the increase in serum total cholesterol in adults, and the decrease in antibody response at vaccination in children were identified as the critical effects. For PFOA, the increase in serum total cholesterol was the critical effect. Also reduced birth weight (for both compounds) and increased prevalence of high serum levels of the liver enzyme alanine aminotransferase (ALT) (for PFOA) were considered. After benchmark modelling of serum levels of PFOS and PFOA, and estimating the corresponding daily intakes, the CONTAM Panel established a tolerable weekly intake (TWI) of 13 ng/kg body weight (bw) per week for PFOS and 6 ng/kg bw per week for PFOA. For both compounds, exposure of a considerable proportion of the population exceeds the proposed TWIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2903/j.efsa.2018.5194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009575PMC
December 2018

Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food.

EFSA J 2018 Nov 20;16(11):e05333. Epub 2018 Nov 20.

The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of dioxins (PCDD/Fs) and DL-PCBs in feed and food. The data from experimental animal and epidemiological studies were reviewed and it was decided to base the human risk assessment on effects observed in humans and to use animal data as supportive evidence. The critical effect was on semen quality, following pre- and postnatal exposure. The critical study showed a NOAEL of 7.0 pg WHO-TEQ/g fat in blood sampled at age 9 years based on PCDD/F-TEQs. No association was observed when including DL-PCB-TEQs. Using toxicokinetic modelling and taking into account the exposure from breastfeeding and a twofold higher intake during childhood, it was estimated that daily exposure in adolescents and adults should be below 0.25 pg TEQ/kg bw/day. The CONTAM Panel established a TWI of 2 pg TEQ/kg bw/week. With occurrence and consumption data from European countries, the mean and P95 intake of total TEQ by Adolescents, Adults, Elderly and Very Elderly varied between, respectively, 2.1 to 10.5, and 5.3 to 30.4 pg TEQ/kg bw/week, implying a considerable exceedance of the TWI. Toddlers and Other Children showed a higher exposure than older age groups, but this was accounted for when deriving the TWI. Exposure to PCDD/F-TEQ only was on average 2.4- and 2.7-fold lower for mean and P95 exposure than for total TEQ. PCDD/Fs and DL-PCBs are transferred to milk and eggs, and accumulate in fatty tissues and liver. Transfer rates and bioconcentration factors were identified for various species. The CONTAM Panel was not able to identify reference values in most farm and companion animals with the exception of NOAELs for mink, chicken and some fish species. The estimated exposure from feed for these species does not imply a risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2903/j.efsa.2018.5333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009407PMC
November 2018