Among naturally occurring plant constituents, the 1,2-unsaturated pyrrolizidine alkaloids (in the following termed 'PAs') play a distinct role because of the large number of congeners occurring in nature and the pronounced toxicity of some congeners. Several PAs are hepatotoxic in humans, experimental and farm animals and were shown to be potent hepatocarcinogens in laboratory rodents. Although the general mode of action leading to toxicity has been elucidated, i.e., being mediated by metabolic conversion of the parent molecule into a highly reactive electrophile capable of attacking cellular target molecules, major questions related to the risk assessment of PAs remain unresolved. It was the aim of a workshop held in September 2018 to shed more light on the occurrence, exposure, mode of action, toxicokinetics and -dynamics of PAs to improve the scientific basis for an advanced toxicological risk assessment. The contributions in nine chapters describe the scientific progress using advanced analytical methods, studies in subcellular fractions, cell culture, experimental animals and humans and the use of PBPK modeling and structure-activity relationship considerations aiming at a better understanding of PA toxicity and genotoxicity. Since PAs differ considerably in their toxic potencies and substantial species differences in sensitivity towards PA exposure exist, a special emphasis was placed on these issues.

中文翻译：

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食品和植物药中的吡咯烷嗪生物碱：发生，接触，毒性，机理和风险评估-综述。

在天然存在的植物成分中，由于自然界中存在大量同类物，并且某些同类物具有明显的毒性，因此1,2-不饱和吡咯并立烷生物碱（以下称为“ PAs”）起着独特的作用。几种PA在人类，实验动物和农场动物中均具有肝毒性，并在实验室啮齿动物中被证明是有效的肝致癌物。尽管已经阐明了导致毒性的一般作用方式，即是通过将母体分子代谢转化为能够攻击细胞靶分子的高反应性亲电试剂来介导的，但仍未解决与PA风险评估有关的主要问题。这是2018年9月举行的研讨会的目的，是要进一步了解发生，暴露，行动方式，PA的毒物动力学和动力学，以改善进行高级毒理学风险评估的科学依据。共分九章的内容描述了使用先进的分析方法，在亚细胞级分，细胞培养，实验动物和人类中的研究以及PBPK建模和构效关系的使用，以更好地了解PA毒性和遗传毒性的科学进展。由于PA的毒性有很大不同，并且物种对PA暴露的敏感性也存在很大差异，因此特别强调了这些问题。实验动物和人类以及使用PBPK建模和构效关系的考虑，目的是更好地了解PA毒性和遗传毒性。由于PA的毒性有很大不同，并且物种对PA暴露的敏感性也存在很大差异，因此特别强调了这些问题。实验动物和人类以及使用PBPK建模和构效关系的考虑，目的是更好地了解PA毒性和遗传毒性。由于PA的毒性有很大不同，并且物种对PA接触的敏感性也存在很大差异，因此特别强调了这些问题。