Scientific opinion on the risks for animal and human health related to the presence of quinolizidine alkaloids in feed and food, in particular in lupins and lupin‐derived products

Abstract

The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of quinolizidine alkaloids (QAs) in feed and food. This risk assessment is limited to QAs occurring in Lupinus species/varieties relevant for animal and human consumption in Europe (i.e. Lupinus albus L., Lupinus angustifolius L., Lupinus luteus L. and Lupinus mutabilis Sweet). Information on the toxicity of QAs in animals and humans is limited. Following acute exposure to sparteine (reference compound), anticholinergic effects and changes in cardiac electric conductivity are considered to be critical for human hazard characterisation. The CONTAM Panel used a margin of exposure (MOE) approach identifying a lowest single oral effective dose of 0.16 mg sparteine/kg body weight as reference point to characterise the risk following acute exposure. No reference point could be identified to characterise the risk of chronic exposure. Because of similar modes of action for QAs, the CONTAM Panel used a group approach assuming dose additivity. For food, the highest mean concentration of Total QAs (TotQAs) (i.e. the 6 most abundant QAs) was found in lupin seed samples classified as 'Lupins (dry) and similar-'. Due to the limited data on occurrence and consumption, dietary exposure was calculated for some specific scenarios and no full human health risk characterisation was possible. The calculated margin of exposures (MOEs) may indicate a risk for some consumers. For example, when lupin seeds are consumed without a debittering step, or as debittered lupin seeds high in QA content and when 'lupin-based meat imitates' are consumed. For horses, companion and farm animals, other than salmonids, the available database on adverse effects was too limited to identify no-observed-adverse-effect levels and/or lowest-observed-adverse-effect levels and no risk characterisation was possible. For salmonids, the CONTAM Panel considers the risk for adverse effects to be low.This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made.The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. Quinolizidine alkaloids in feed and food www.efsa.europa.eu/efsajournal 2 EFSA Journal 2019;17(11):5860 Quinolizidine alkaloids in feed and food www.efsa.europa.eu/efsajournal 3 EFSA Journal 2019;17(11):5860lupanine or 13a-OH-lupanine (each equivalent to 0.14 mg/kg bw for a person with a body weight of 70 kg). Human cases of poisoning with lupin seeds are infrequent and rarely lead to a fatal outcome. However, case reports of poisoning in children suggest that these are more susceptible to intoxication than adults, and doses of lupin alkaloids from 10 mg/kg bw onwards may be lethal. Intoxication have been associated with inadequate debittering of lupin seeds by consumers, while no case of poisoning has been...

Zearalenone Induces Apoptosis and Cytoprotective Autophagy in Chicken Granulosa Cells by PI3K-AKT-mTOR and MAPK Signaling Pathways

“…The toxicity of ZEA has attracted widespread attention due to the estrogenic effects of its metabolites. Over the past decade, both in vivo and in vitro studies have shown that ZEA has harmful effects on the reproductive systems of humans and animals [ 8 , 9 , 10 ]. Although studies have observed ZEA inducing autophagy and apoptosis in mammalian granulosa cells, the molecular mechanism of ZEA cytotoxicity remains unclear [ 3 , 11 ].…”

“…Many reports have shown that exposure to ZEA causes early puberty in children, endometrial adenocarcinoma, female breast cancer, and reduced testicular germ cells [ 5 , 6 ]. Meanwhile, in livestock production, low and high concentrations of ZEA have all been shown to have adverse effects, leading to hyperestrogenemia, abortion, and reproductive failure [ 7 , 8 , 9 ].…”

Investigations on the Transfer of Quinolizidine Alkaloids from Lupinus angustifolius into the Milk of Dairy Cows

“…However, the assessment revealed the possibility of exposures for some consumer groups, resulting in MoE values <1, indicating a potential risk for these consumers. Additionally, the EFSA stated that there is indirect evidence of a possible transfer of QAs from feed into milk, due to the QAs’ weak basic nature, which makes milk a possible additional exposure source . However, until now, there has only been one published case report of possible QA intoxication in a human infant after its mother drank goat milk in early pregnancy .…”

“…The QAs exert their toxicity by inhibiting acetylcholine receptors and voltage-dependent ion channels in the central nervous system, on motor endplates and the peripheral autonomic nervous system, where the individual QAs appear to have different levels of toxicity . Common acute toxic exposure symptoms in humans and mammals include respiratory depression, vomiting, and tachycardia. , Some QAs, such as anagyrine, also show teratogenic properties and have been associated with congenital skeletal malformations (crooked calf disease) in calves . Thus, to minimize the risk of QA intoxication in livestock animals, only sweet lupins are listed as feed for livestock species in the catalogue of feed materials…”

“…Most of the toxicological data originate from research on lupanine and sparteine, the latter compound was used as a pharmaceutical in the past . The European Food Safety Authority (EFSA) stated that “anticholinergic effects and changes in cardiac electric conductivity” are the relevant endpoints for risk assessment.…”