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Pyrrolizidine Alkaloids
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Senecio spp. (riddelliine) are found in temperate to tropical climates and produce a high concentration of PAs in the seeds and flowering tops. Riddelliine is a component of gordolobo yerba, a folk cough medicine still used by Mexican Americans in the southwestern United States, despite showing tumorigenic activity similar to comfrey. In addition, S. jacobaea (ragwort) found in the rangelands of the western United States produces riddelliine and other PAs that can cause pyrrolizidine alkaloidosis in cattle, horses, and, less commonly, sheep upon ingestion, and leave toxin residues in meat, milk, and honey [19].
Risk characterisation of constituents present in jamu to promote its safe use
Published in Critical Reviews in Toxicology, 2021
Suparmi Suparmi, Dasep Wahidin, Ivonne M. C. M. Rietjens
Acute exposure to PAs can cause hepatic veno-occlusive disease (HVOD) with severe liver damage, in some cases with fatal outcome (Mohabbat et al. 1976; Tandon et al. 1976; Wiedenfeld and Roder 1991). Chronic exposure to PA-containing jamu may lead to liver cirrhosis and pulmonary arterial hypertension (EFSA 2011). Furthermore, 1,2-unsaturated PAs, including lasiocarpine, monocrotaline, and riddelliine, are considered as being possibly carcinogenic to humans (category 2B) (IARC 2012). A possible concern upon chronic exposure to PA-containing jamu is PA-induced liver injury (PA-ILI). Gynura segetum, a PA-producing plant ingredient in jamu (Suparmi et al. 2020) is reported as the cause of PA-ILI in 15 patients in China after consumption of Gynura segetum-containing Chinese herbal products for five days up to 2 years (Lin et al. 2011).
Risk assessment of herbal supplements containing ingredients that are genotoxic and carcinogenic
Published in Critical Reviews in Toxicology, 2019
Gerhard Prinsloo, Francois Steffens, Jacques Vervoort, Ivonne M.C.M. Rietjens
PAs are found in hundreds of plant species including various Symphytum spp, such as Comfrey (Symphytum officinale) (Hirono et al. 1978; Elvin-lewis 2001; Stewart and Steenkamp 2001), Senecio spp. such as Senecio longilobus, (containing riddelline) (Steenkamp et al. 2001; Zuckerman et al. 2002), grain contaminated with PA containing weeds (Elvin-lewis 2001; Knutsen et al. 2017) and various Crotoloria spp. (Prinsloo et al. 2018). PA exposure due to consumption of herbal remedies is associated with hepatotoxicity especially veno-occlusive disease (VOD) in humans (Stewart and Steenkamp 2001; Zuckerman et al. 2002; Robertson and Stevens 2017) with clinical symptoms that include vomiting, enlargement of the liver and bleeding diarrhea (Chen et al. 2010). Daily PA intake of 10 μg/kg bw may lead to VOD in humans and a dose of 1 μg/kg bw per day was suggested for this toxic effect to not occur (Dreger et al. 2009). The levels reported by EFSA for PAs at 2 mg/kg bw per day for short term exposure (Knutsen et al. 2017) might raise a concern becasue of induction of VOD and even death. In some case studies deaths resulting from PA intake were reported, probably linked to a high concentration intake for only a limited exposure duration as observed in traditional use of PA containing plants. When evaluating carcinogenicity as an endpoint, as done in the present study, it appears that an intake of 1.3 µg/kg bw per day for 2 weeks every year over a 70 year lifespan, which is in the range of the 1 μg/kg bw per day that was suggested to exclude occurence of VOD (Dreger et al. 2009), resulted in an MOE of 5450, indicating a concern because of the genotoxic and carcinogenic properties of the PAs. The 95th percentile exposure levels obtained in the probablistic intake estimates of the present study resulted in levels of 701 µg/kg bw per day which were remarkably higher than the level of 1 μg/kg bw per day considered to be safe for acute exposure preventing VOD. Thus, the results of the present study corroborate the fact also reported by EFSA that PA containing food supplements present a risk for acute adverse effects. Thus it is concluded that the chronic risks of exposure to PAs via food supplements with respect to their genotoxic carcinogenicity does not always raise a concern (MOEs >10,000), while potential acute toxicity resulting in VOD induced by even short time exposure to food supplements at the high range of the PA contamination level, may be a major concern.