An Outbreak of Hepatic Veno-Occlusive Disease in Western Afghanistan Associated with Exposure to Wheat Flour Contaminated with Pyrrolizidine Alkaloids

Kakar, Faizullah; Akbarian, Zarif; Leslie, Toby; Mustafa, Mir Lais; Watson, John T.; Egmond, H. P. van; Mohammad, Omar; Mofleh, Jawad

doi:10.1155/2010/313280

Cited by 131 publications

(123 citation statements)

References 6 publications

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“…Genera of each of these plant families such as Senecio, Eupatorium, Heliotropium, and Crotalaria have been reported as toxic to livestock and humans (Mohabbat et al 1976;Tandon et al 1976;Harper et al 1985;Hill et al 1997;Prakash et al 1999;Shimshoni et al 2015b;Kakar et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Occurrence of pyrrolizidine alkaloids in animal- and plant-derived food: results of a survey across Europe

Mulder

López

Castellari

et al. 2017

Food Additives & Contaminants: Part A

112

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Pyrrolizidine alkaloids (PAs) are secondary metabolites of plant families such as Asteraceae or Boraginaceae and are suspected to be genotoxic carcinogens. Recent investigations revealed their frequent occurrence in honey and particularly in tea. To obtain a comprehensive overview of the PA content in animal-and plant-derived food from the European market, and to provide a basis for future risk analysis, a total of 1105 samples were collected in 2014 and 2015. These comprised milk and milk products, eggs, meat and meat products, (herbal) teas, and (herbal) food supplements collected in supermarkets, retail shops, and via the internet. PAs were detected in a large proportion of plant-derived foods: 91% of the (herbal) teas and 60% of the food supplements contained at least one individual PA. All types of (herbal) teas investigated were found to contain PAs, with a mean concentration of 460 µg kg −1 dry tea (corresponding to 6.13 µg L −1 in [herbal] tea infusion). The highest mean concentrations were found in rooibos tea (599 µg kg −1 dry tea, 7.99 µg L −1 tea infusion) and the lowest in camomile tea (274 µg kg −1 dry tea, 3.65 µg L −1 tea infusion). Occurrence of PAs in food supplements was found to be highly variable, but in comparable ranges as for (herbal) tea. The highest concentrations were present in supplements containing plant material from known PA-producing plants. In contrast, only 2% of the animalderived products, in particular 6% of milk samples and 1% of egg samples, contained PAs. Determined levels in milk were relatively low, ranged between 0.05 and 0.17 µg L −1 and only trace amounts of 0.10-0.12 µg kg −1 were found in eggs. No PAs were detected in the other animal-derived products.ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Occurrence of pyrrolizidine alkaloids in animal- and plant-derived food: results of a survey across Europe

Mulder

López

Castellari

et al. 2017

Food Additives & Contaminants: Part A

112

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“…Compared to wheat flour there was 1000 times less PAs in milk and whey. In water samples PAs were not detected (Kakar et al, 2010).…”

Section: Outbreaksmentioning

confidence: 90%

“…In particular, human poisoning with 1,2-unsaturated PAs is known to cause liver toxicity resulting in development of hepatic veno-occlusive disease (HVOD) (Chen and Huo, 2010). The latest documented outbreak was recorded in Afghanistan in 2008 (Kakar et al, 2010) where flour contaminated with seeds of Heliotropium (Boraginaceae) and milk from goats appeared to be the main cause for the health damage. In laboratory experiments, 1,2-unsaturated PAs showed the potential to induce genotoxicity in different model systems, and carcinogenicity was observed following chronic oral exposure to several 1,2-unsaturated PAs (Fu et al, 2004;.…”

Section: Terms Of Reference As Provided By the European Commissionmentioning

confidence: 99%

“…For example, the latest documented PA-outbreak (Kakar et al, 2010) could be tracked to wheat flour contaminated with Heliotropium seeds and qurut, a cheese common throughout Central Asia (here derived from goats milk) which also showed Heliotropium PAs and trichodesmine, a PA typical for Crotalaria spp. Recently, PAs were repeatedly detected in packed salads and the contamination could be traced back to the presence of accompanying Senecio vulgaris plant parts (BfR, 2007).…”

Section: Foodmentioning

confidence: 99%

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Scientific Opinion on Pyrrolizidine alkaloids in food and feed

2011

EFS2

226

130

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The European Food Safety Authority (EFSA) was asked by the European Commission to deliver a scientific opinion on pyrrolizidine alkaloids (PA) in food and feed. PAs are toxins exclusively biosynthesised by plants. To date, approximately 600 different PAs are known. Results for 13,280 bulk honey and 1324 retail honey samples were provided to EFSA by one Member State and 351 feed samples were provided by a second Member State. The EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) performed estimates of both acute and chronic exposure to PAs through honey for three different age groups. Although there might be other sources of PA exposure, due to lack of data the CONTAM Panel was not able to quantify dietary exposure from food other than honey. A number of PAs were identified as being of particular importance for food and feed. Based on the present knowledge of metabolism, activation, DNA adduct-formation, genotoxicity and carcinogenicity, the CONTAM Panel concluded that 1,2-unsaturated PAs may act as genotoxic carcinogens in humans. Therefore, the CONTAM Panel decided to apply the Margin of Exposure (MOE) approach. A benchmark dose lower confidence limit for a 10 % excess cancer risk (BMDL 10 ) of 70 µg/kg b.w. per day for induction of liver haemangiosarcomas by lasiocarpine in male rats was calculated as the reference point for comparison with the estimated dietary exposure. The CONTAM Panel concluded that there is a possible health concern for those toddlers and children who are high consumers of honey. There is generally a low risk of PA poisoning in livestock and companion animals in the EU as most PA poisonings reported recently are due to accidental exposure. © European Pyrrolizidine alkaloids in food and feedEFSA Journal 2011;9(11):2406 2 SUMMARYFollowing a request from the European Commission, the Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on the risks to human and animal health related to the presence of pyrrolizidine alkaloids (PA) in food and feed. PAs are toxins exclusively biosynthesised by plants. They are typical plant secondary metabolites against herbivores. It has been estimated that approximately 6000 plant species world wide, representing 3 % of all flowering plants, may contain pyrrolizidine alkaloids. PAs are mainly found in the distantly related angiosperm families of the Boraginaceae (all genera), Asteraceae (tribes Senecioneae and Eupatorieae) and Fabaceae (genus Crotalaria). The PA-content of plant material depends on a large number of factors (species, plant organ, harvest, storage, extraction procedures). Reported contents vary from trace amounts up to 19 % based on dry weight. The name pyrrolizidine is the chemical description of two-fused 5-membered rings with a nitrogen atom at the bridgehead. This motif is the central structure of a variety of PAs. PAs generally consist of an amino alcohol which is referred to as necine or necine base and an acid part which is called a necic acid. Most of the known PAs are este...

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“…It is unknown whether the applied heating and fermentation processes will lead to a reduction of the PA concentration and/or changes in the PA composition. A certain stability to processing can be assumed, given that Mulder et al (2015) detected PAs in heat-treated milk from retail in the EU and Kakar et al (2010) reported occurrence of PAs in qurut, a goat cheese from Afghanistan (Kakar et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Fate of pyrrolizidine alkaloids during processing of milk of cows treated with ragwort

Nijs

Mulder

Klijnstra

et al. 2017

Food Additives & Contaminants: Part A

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To investigate the fate of pyrrolizidine alkaloids (PAs) during milk processing, milk of cows treated via rumen fistula with a mixture of 84% (w/w) ragwort (Jacobaea vulgaris, syn. Senecio jacobaea) and 16% narrow-leaved ragwort (Senecio inaequidens) was processed using laboratory scale heating systems with industrial settings. Pasteurised and sterilised (UHT) milk were produced, as well as set-type yoghurt and cheese. Samples were analysed for 29 PAs using LC-MS/MS, of which 11 PAs were detected above LOQ in the samples (0.1 µg l −1). Alterations in the PA concentration and composition between the standardised milk and the corresponding end-product(s) were evaluated. The heat treatments applied for pasteurisation and UHT sterilisation to prepare semi-skimmed consumption milk did not affect the PA levels in the end-products. In yoghurt, after fermentation of standardised milk (6 h, pH 4.4), 73% of total PAs were recovered. The PA concentration, specifically dehydrojacoline, was decreased, although not quantifiable, during cheese production. A further decrease of 38% during 6 weeks of ripening was observed. The results show that the PA concentration of natural contaminated cow's milk is not affected by heat treatment applied for pasteurised and sterilised milk, but that microbial fermentation of the milk leads to a lowered PA concentration in yoghurt and cheese. This is probably due to microbiological degradation, since PAs are fairly stable under acidic conditions. ARTICLE HISTORY

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An Outbreak of Hepatic Veno-Occlusive Disease in Western Afghanistan Associated with Exposure to Wheat Flour Contaminated with Pyrrolizidine Alkaloids

Cited by 131 publications

References 6 publications

Occurrence of pyrrolizidine alkaloids in animal- and plant-derived food: results of a survey across Europe

Occurrence of pyrrolizidine alkaloids in animal- and plant-derived food: results of a survey across Europe

Scientific Opinion on Pyrrolizidine alkaloids in food and feed

Fate of pyrrolizidine alkaloids during processing of milk of cows treated with ragwort

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