Senecionine (Pyrrolizidine Alkaloid · Hepatotoxic · HVOD · Regulatory Reference)
| Compound | Senecionine |
| Chemical class | Alkaloid — Pyrrolizidine Alkaloid (Unsaturated macrocyclic PA; hepatotoxic) |
| CAS | 130-01-8 |
| Primary source | Senecio jacobaea (ragwort / tansy ragwort), Senecio vulgaris, multiple Senecio species |
| Key applications | Informational reference — hepatotoxic PA; veno-occlusive disease model compound; not a supplement ingredient |
| Claim strength | Not applicable (toxicological reference) |
| Typical form | Not a supplement ingredient — hepatotoxic contaminant of concern |
| Buy from Herbuno | Browse HerbIQ Compound Index → |
Name origin: From Senecio (the genus, Latin for “old man” referring to the white pappus). Senecionine is a macrocyclic unsaturated pyrrolizidine alkaloid — the prototype compound for the hepatotoxic PA class. Pyrrolizidine alkaloids (PAs) are a class of plant secondary metabolites distributed across approximately 6,000 plant species worldwide, most commonly in the Asteraceae (Senecio, Eupatorium), Boraginaceae (Symphytum/comfrey, Heliotropium, Borago), and Fabaceae (Crotalaria) families. The key structural feature conferring hepatotoxicity is the 1,2-unsaturated necine base (pyrroline ring) — present in senecionine and other hepatotoxic PAs but absent in saturated PAs which are less toxic. Food and supplement safety context: PAs are among the most significant natural botanical food safety concerns globally. PA contamination of herbal supplements, teas, honey, and food crops (from PA-containing weed seeds) has caused hepatic veno-occlusive disease (HVOD) outbreaks and individual cases worldwide. Senecionine is the primary PA marker compound used in PA toxicology research and regulatory monitoring. Regulatory context: The European Food Safety Authority (EFSA) and WHO have established PA intake limits and monitoring frameworks. PA-containing supplements (comfrey root internally, borage, coltsfoot) are restricted or banned in multiple markets. Senecionine and other PAs are regulated contaminants in herbal products.
Senecionine — Toxicological and Regulatory Context
Hepatic veno-occlusive disease (HVOD) — mechanism: Senecionine undergoes hepatic bioactivation via CYP3A4/3A5 to pyrrolic esters (dehydropyrrolizidine alkaloids) — highly reactive alkylating agents that cross-link DNA and proteins in hepatic sinusoidal endothelial cells and hepatocytes. HVOD results from obliteration of central hepatic venules, causing progressive centrilobular necrosis and hepatic failure. HVOD outbreaks have occurred in Afghanistan, Pakistan, India, and Central Asia from consumption of PA-contaminated grain (Heliotropium-contaminated wheat). Individual cases occur from comfrey root tea consumption and PA-contaminated supplements. Critical safety reference.
Genotoxicity and carcinogenicity: Unsaturated PAs are IARC Class 2B carcinogens (possibly carcinogenic to humans). Liver tumours are induced in animal carcinogenicity studies. Chronic low-level PA exposure below the threshold causing acute HVOD may nonetheless carry long-term carcinogenic risk. EFSA has applied a margin of exposure (MoE) approach for PA risk assessment — noting that current dietary PA exposure from herbal teas and honey is of concern for some population groups. Regulatory reference.
Supplement regulatory framework: Multiple regulatory actions on PA-containing supplements: (1) Germany banned internal use of comfrey root preparations >1985 due to PA content; (2) EU Commission Regulation 2020/2040 sets maximum PA limits in food supplements and tea; (3) WHO Technical Report 2017 provides PA risk assessment framework; (4) UK MHRA has taken action against PA-containing supplements. Formulators must test all relevant botanical raw materials for PA content using validated HPLC-MS/MS methods. Critical regulatory compliance reference for formulators.
This compound is documented for research and formulator education purposes. For commercially available botanical ingredients, explore the HerbIQ Compound Index →
Frequently Asked Questions — Senecionine
Which herbs contain hepatotoxic pyrrolizidine alkaloids?
Key commercial herbs of concern include: comfrey (Symphytum officinale) — high symphytine, echimidine, lycopsamine; borage (Borago officinalis) — lycopsamine, amabiline; coltsfoot (Tussilago farfara) — senkirkine, senecionine; life root/groundsel (Senecio species); “jin bu huan” and some Chinese herbal preparations. Also: honey, herbal teas, and grain from PA-weed-contaminated agriculture can be contaminated. Note: comfrey ROOT contains much higher PA levels than comfrey LEAF; topical comfrey use is generally considered lower risk than internal use.
What PA levels are acceptable in supplements?
EU Commission Regulation 2020/2040 (in force from 1 July 2022) sets maximum limits: 1.0 µg/kg for food supplements (dry) and 0.35 µg/kg for food supplements in liquid form (as sum of 35 regulated PAs). These are extremely low thresholds. Food supplements containing botanical ingredients known to have PA content (comfrey, borage, coltsfoot) must be tested by validated HPLC-MS/MS methods to confirm compliance. Violating these limits results in regulatory withdrawal of the product.
Is topical comfrey use safe despite the PA content?
Topical comfrey preparations (COMBUDORON, commercial wound-healing creams) have been studied for wound healing and joint pain with positive results. Transdermal PA absorption is significantly lower than oral absorption. The European Medicines Agency (EMA) Community Herbal Monograph for comfrey permits topical preparations with <1 µg PA per daily dose in finished product, for maximum 4–6 weeks duration. Herbuno’s Comfrey Root extract products are specifically for topical and external formulations; internal supplement use of comfrey root extract is not recommended.
How should formulators test for PA contamination?
PA testing requires HPLC-MS/MS (liquid chromatography-tandem mass spectrometry) with validated methods covering the 35 PAs regulated by EU Commission Regulation 2020/2040. Standard antioxidant and heavy metal testing does not detect PAs. Contract testing laboratories in Germany, Netherlands, and UK specialise in PA analysis. Formulators using borage oil, comfrey preparations, or any Boraginaceae/Senecio/Crotalaria-adjacent botanical should include PA panel testing in raw material release specifications.
Related compounds: Monocrotaline, Symphytine, Amygdalin, Linamarin
Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.
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