Combined toxicokinetic and in vivo genotoxicity study on Alternaria toxins

Schuchardt, Sven; Ziemann, Christina; Hansen, Tanja

doi:10.2903/sp.efsa.2014.en-679

Cited by 40 publications

(53 citation statements)

References 3 publications

(7 reference statements)

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“…Studies on in vivo exposure are still scarce. In NMRI mice systemic bioavailability of AOH after oral application has been reported to be marginal (< 0.1% of the applied dose), with about 90% being eliminated via feces and around 9% subjected to a rapid metabolism to metabolites excreted via urine (Schuchardt et al 2014). These data indicate that in vivo concentrations of AOH in the higher micromolar range are unlikely to be reached in the bloodstream.…”

Section: Discussionmentioning

confidence: 99%

The mycotoxin alternariol suppresses lipopolysaccharide-induced inflammation in THP-1 derived macrophages targeting the NF-κB signalling pathway

et al. 2018

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Alternariol (AOH) is a secondary metabolite formed by black mold of the genus Alternaria alternata. Due to limited hazard and occurrence data, AOH is still considered as an “emerging mycotoxin” and, as such, not monitored and regulated yet. Recent studies indicate immunosuppressive effects in vitro by altering the expression of CD molecules and proinflammatory cytokines, which are indispensable in mounting an innate immune response. However, the mode of action by which AOH exerts its immunosuppressive effects has not been unraveled yet. The present study aimed to characterise the impact of AOH on the nuclear factor kappa B (NF-κB) pathway, the expression of NF-κB target cytokines and involved regulatory microRNAs (miRNAs). In THP-1 derived macrophages, AOH (1–20 µM) was found to suppress lipopolysaccharide (LPS)-induced NF-κB pathway activation, decrease secretion of the proinflammatory cytokines IL-8, IL-6, TNF-α and to induce secretion of the anti-inflammatory IL-10. Thereby, a distinct pattern of cytokine mRNA levels was monitored, varying between short- and long-term exposure. Concomitantly, AOH (2–20 µM) affected the transcription levels of miR-146a and miR-155 in LPS-stimulated THP-1 derived macrophages dose-dependently by down- and upregulation, respectively. In contrast, transcription of miR-16 and miR-125b, two other immune-related miRNAs, was not modulated. In the absence of a LPS stimulus, AOH (20 µM) did not affect basal NF-κB activity, but increased IL-10 transcription. Collectively, our results indicate, that AOH itself does not induce a proinflammatory immune response in human macrophages; however, in an inflamed environment it possesses the ability to repress inflammation by targeting the NF-κB signalling pathway and regulatory miRNAs.

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Section: Discussionmentioning

confidence: 99%

The mycotoxin alternariol suppresses lipopolysaccharide-induced inflammation in THP-1 derived macrophages targeting the NF-κB signalling pathway

et al. 2018

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“…ATX-II is significantly more genotoxic than AOH (Fleck et al, 2012;Schuchardt et al, 2014;Schwarz et al, 2012a), however, it has not been reported in naturally contaminated food so far. Due to the lack of commercially available reference material, it is not included in standard assays.…”

Section: Introductionmentioning

confidence: 91%

The fate of altertoxin II during tomato processing steps at a laboratory scale

Puntscher¹,

Marko²,

Warth³

2019

Preprint

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The emerging Alternaria mycotoxin altertoxin II demonstrated substantial genotoxicity in vitro. Ubiquitous Alternaria ssp. frequently infest various agricultural crops, leading to economic losses and also potential food safety issues caused by associated mycotoxin contaminations. Due to the lack of commercially available reference standards, data on the general chemical behavior, the occurrence and the biological/toxicological effects of altertoxin II are scarce. Since tomatoes are particularly prone to Alternaria infestations, we simulated the storage and food processing of intact tomatoes and purees after altertoxin II-addition. We observed significant decrease in altertoxin II concentrations during storage at room temperature and particularly under thermal stress, by employing a validated LC-MS/MS method. Moreover, the reduction to the compound’s epoxide group to the alcohol, i.e. the formation of altertoxin I, was determined at considerable ratios in intact tomato fruits suggesting effective enzymatic xenobiotic metabolism.

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“…The CONTAM Panel made several recommendations, and one of them led to a research project called 'Combined toxicokinetic and in vivo genotoxicity study on Alternaria toxins' (Schuchardt et al, 2014). The CONTAM Panel discussed the outcome of this project in November 2014 and concluded that the results did not bring full certainty nor did they increase concern regarding the potential in vivo genotoxicity of Alternaria toxins.…”

Section: Introductionmentioning

confidence: 99%

Dietary exposure assessment to Alternaria toxins in the European population

Arcella¹,

Eskola²,

Ruiz³

2016

EFS2

101

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Alternaria toxins are secondary metabolites produced by fungi that can contaminate cereals, oilseeds, fruits and vegetables. The chronic dietary exposure to four individual Alternaria toxins was estimated using 15,563 analytical results/4,249 samples (3,648 on alternariol (AOH), 3,654 on alternariol monomethyl ether (AME), 4,168 on tenuazonic acid (TeA) and 4,093 on tentoxin (TEN)). Most of the analytical results were left‐censored data (92%), with only 1,290 quantified results (mainly on ‘Oilseeds’ and ‘Grain milling products’). The highest exposure to AOH was estimated in ‘Toddlers’, with the mean exposure between 3.8 and 71.6 ng/kg body weight (bw) per day (minimum lower bound–maximum upper bound, (LB–UB)) and the 95th percentile exposure between 11.4 and 270.5 ng/kg bw per day (LB–UB). Overall, ‘Fruit and fruit products’ were the most important contributors to the dietary exposure to AOH. The highest exposure to AME was estimated in ‘Toddlers’, with mean exposure between 3.4 and 38.8 ng/kg bw per day (LB–UB) and 95th percentile exposure between 10.3 and 97.3 ng/kg bw per day (LB–UB). Overall, the main contributors to the dietary exposure to AME were ‘Vegetable oil’ and ‘Pome fruits’ (pears). The highest exposure to TeA was estimated in ‘Toddlers’ with mean exposure between 100 and 1,614 ng/kg bw per day (LB–UB), and in ‘Infants’ for the 95th percentile exposure estimations (98–3,603 ng/kg bw per day, LB–UB). ‘Cereal‐based food for infants and young children’ was the main contributor in ‘Infants’ and ‘Toddlers’, and tomatoes and tomato‐based products in other age classes. The highest exposure to TEN was estimated in ‘Toddlers’, with the mean exposure between 1.6 and 33.4 ng/kg bw per day (LB–UB), and the 95th percentile exposure around 55 ng/kg bw per day (UB) in different age classes. ‘Fruiting vegetables’ (tomatoes) were the major contributor to the dietary exposure to TEN. Although based on limited data, vegetarians seem to have higher dietary exposure to Alternaria toxins than the general population.

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Combined toxicokinetic and in vivo genotoxicity study on Alternaria toxins

Cited by 40 publications

References 3 publications

The mycotoxin alternariol suppresses lipopolysaccharide-induced inflammation in THP-1 derived macrophages targeting the NF-κB signalling pathway

The mycotoxin alternariol suppresses lipopolysaccharide-induced inflammation in THP-1 derived macrophages targeting the NF-κB signalling pathway

The fate of altertoxin II during tomato processing steps at a laboratory scale

Dietary exposure assessment to Alternaria toxins in the European population

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