Scientific Opinion on Pyrrolizidine alkaloids in food and feed

Abstract

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...

Risks for human health related to the presence of pyrrolizidine alkaloids in honey, tea, herbal infusions and food supplements

“…Regarding the hazard characterisation, the CONTAM Panel confirmed the uncertainties already identified in the 2011 opinion (EFSA CONTAM Panel, 2011), and noted additional uncertainties in particular related to the data sets used for the dose-response analysis for the characterisation of the carcinogenic hazard (see Section 2.1). However, the Panel confirmed that the main uncertainties remain considering the lack of toxicological data on most of the PAs of relevance for food and feed contamination.…”

“…This is supported by a series of human cases of intoxication following the consumption of herbal remedies derived from PA-producing plants (EFSA CONTAM Panel, 2011). In view of the uncertainty on the possible toxicity levels of PAs in humans and of the severity of the effects, the CONTAM Panel concluded that exposure levels less than 100 times lower than the aforementioned dose range of 1-3 mg PA/kg bw per day may be associated with the risk of acute/short-term effects.…”

“…As already outlined in the previous EFSA opinion (EFSA CONTAM Panel, 2011), reported lasiocarpine levels administered in the diet were converted to doses by considering average body weight and daily food intake of 400 g and 20 g, respectively. This corresponds to the default conversion factor of 0.05 recommended by the EFSA Scientific Committee guidance (2012) for chronic rat studies.…”

Dietary exposure assessment to pyrrolizidine alkaloids in the European population

“…The acute/short-term toxicity of 1,2-unsaturated PAs in humans is characterised mainly by the onset of hepatic veno-occlusive disease (HVOD), associated with high mortality and, or possibly progressing to liver cirrhosis. In its 2011 scientific opinion on the presence of PAs in food and feed, from the evaluation of various human case reports, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) selected a lowest known PA dose associated with acute/short-term toxicity in humans of approximately 2 mg/kg bw per day for the assessment of acute risks (EFSA CONTAM Panel, 2011).…”

“…The formation of reactive pyrroles is considered to be the key step related to all the identified adverse effects (Fu et al, 2004). Therefore, the CONTAM Panel decided to focus on the risk assessment of 1,2-unsaturated PAs and their respective N-oxide forms (EFSA CONTAM Panel, 2011). Considering that all 1,2-unsaturated PAs share a common metabolic pathway leading to the formation of genotoxic and carcinogenic reactive pyrroles, the CONTAM Panel concluded that it was not appropriate to establish a health-based guidance value, and decided to adopt the Margin of Exposure (MOE) approach for genotoxic carcinogens to the sum of 1,2-unsaturated PAs, assuming equal potency.…”