Skip to main content
SpringerLink
Log in

Alkaloids in food: a review of toxicity, analytical methods, occurrence and risk assessments

  • Invited Review
  • Published:
Food Science and Biotechnology Aims and scope Submit manuscript

Abstract

Alkaloids have been utilized by humans for years. They have diverse applications in pharmaceuticals. They have been proven to be effective in treating a number of diseases. They also form an important part of regular human diets, as they are present in food items, food supplements, diet ingredients and food contaminants. Despite their obvious importance, these alkaloids are toxic to humans. Their toxicity is dependent on a range of factors, such as specific dosage, exposure time and individual properties. Mild toxic effects include nausea, itching and vomiting while chronic effects include paralysis, teratogenicity and death. This review summarizes the published studies on the toxicity, analytical methods, occurrence and risk assessments of six major alkaloid groups that are present in food, namely, ergot, glycoalkaloids, purine, pyrrolizidine, quinolizidine and tropane alkaloids.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

ARfD:

Acute reference dose

BMDL10 :

Benchmark dose at 10% extra risk

DNA:

Deoxyribonucleic acid

EFSA:

European food safety association

ELISA:

Enzyme-linked immunosorbent assay

FAB-MS:

Fast-atom bombardment mass spectrometry

FID:

Flame ionization detector

GC:

Gas chromatography

GC-EI-MS:

Gas chromatography-electron impact-mass spectrometry

GC–MS:

Gas chromatography–mass spectrometry

HPLC:

High-performance liquid chromatography

HRGC:

High-resolution gas chromatography

IARC:

International agency for research on cancer

LC–ESI–MS/MS:

Liquid chromatography-electrospray ionization-tandem mass spectrometry

LC-HRMS:

Liquid chromatography-high-resolution mass spectrometry

LC–MS/MS:

Liquid chromatography-tandem mass spectrometry

LC-Orbitrap-MS:

Liquid chromatography-orbitrap mass spectrometry

LD:

Lethal dose

LLE:

Liquid–liquid extraction

LOAEL:

Lowest-observed-adverse-effect-level

LOD:

Limit of detection

LOQ:

Limit of quantitation

MS:

Mass spectrometry

MS/MS:

Tandem mass spectrometry

NOAEL:

No-observed-adverse-effect-level

NTP:

National toxicology program

RP-HPLC:

Reverse-phase high-performance liquid chromatography

TDI:

Tolerable daily intake

TGA:

Total glycoalkaloid

UHPLC:

Ultra-high-performance liquid chromatography

UPLC-MS/MS:

Ultra-performance liquid chromatography-tandem mass spectrometry

UPLC-Q-TOF:

Ultra-performance liquid chromatography-quadrupole-time of flight

UV:

Ultraviolet

WHO:

World Health Organization

References

  • Acamovic T, Stewart CS, Pennycott TW (Eds.). Poisonous plants and related toxins. CABI. (2004).

    Google Scholar 

  • Aehle E, Dräger B. Tropane alkaloid analysis by chromatographic and electrophoretic techniques: an update. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 878: 1391-1406 (2010)

    Article  CAS  PubMed  Google Scholar 

  • Aeschbacher HU, Meier H, Jaccaud E. The effect of caffeine in the in vivo SCE and micronucleus mutagenicity tests. Mutation Research Letters. 174: 53-58 (1986)

    Article  CAS  Google Scholar 

  • Almeida AE, Cardoso CR, Almeida DV, Moreira RR, Silva M, Varanda EA. Mutagenic Activity of Glycoallkaloids from Solanum palinacanthum Dunal (Solanaceae) found in the Brazilian cerrado. Latin American Journal of Pharmacy. 29: 122-126 (2010)

    CAS  Google Scholar 

  • Aniszewski T. Alkaloids-Secrets of Life: Alkaloid Chemistry, Biological Significance, Applications and Ecological Role. Elsevier (2007)

    Google Scholar 

  • Aqel A, Almulla A, Al-Rifai A, Wabaidur SM, Alothman ZA Badjah-Hadj-Ahmed AY. Rapid and Sensitive Determination of Methylxanthines in Commercial Brands of Tea Using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry. International Journal of Analytical Chemistry (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  • Azadbakht M, Talavaki M. Qualitative and quantitative determination of pyrrolizidine alkaloids of wheat and flour contaminated with Senecio in Mazandaran Province farms. Iranian Journal of Pharmaceutical Research. 2: 179-83 (2022)

    Google Scholar 

  • de Aragão NM, Veloso MCC, Bispo MS, Ferreira SLC de Andrade JB. Multivariate optimisation of the experimental conditions for determination of three methylxanthines by reversed-phase high-performance liquid chromatography. Talanta. 67: 1007-1013 (2005)

    Article  PubMed  Google Scholar 

  • Azevedo RSA, Teixeira BS, Sauthier MC da S, Santana MVA, dos Santos WNL Santana D de A. Multivariate analysis of the composition of bioactive in tea of the species Camellia sinensis. Food Chemistry. 273: 39-44 (2019)

    Article  CAS  PubMed  Google Scholar 

  • Baek GH, Yang SW, Yun CI, Lee JG Kim YJ. Determination of methylxanthine contents and risk characterization for various types of tea in Korea. Food Control. 132: pp 108543 (2022)

    Article  CAS  Google Scholar 

  • Baker DC, Keeler RF, Gaffield W, Baker DC, Keeler RF Gaffield W. Pathology in Hamsters administered Solanum plant species that contain steroidal alkaloids. Toxicon. 27: 1331-1337 (1989)

    Article  CAS  PubMed  Google Scholar 

  • Ballester D, Yáñez E, Garcia R, Erazo S, Lopez F, Haardt E, Cornejo S, Lopez A, Pokniak J, Chichester CO. Chemical composition, nutritive value, and toxicological evaluation of two species of sweet lupine (Lupinus albus and Lupinus luteus). Journal of Agricultural and Food Chemistry. 28: 402-405 (1980)

    Article  CAS  PubMed  Google Scholar 

  • Baslé Q, Mujahid C Bessaire T. Application of a streamlined LC-MS/MS methodology for the determination of atropine and scopolamine in cereals from Asian and African countries. Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment. 37: 1744-1754 (2020)

    Google Scholar 

  • El Bazaoui A, Stambouli H, Bellimam MA Soulaymani A. Determination of tropane alkaloids in seeds of Datura stramonium L. by GC/MS and LC/MS. Annales de Toxicologie Analytique. 21: 183-188 (2009)

    Google Scholar 

  • Beyer J, Drummer OH, Maurer HH. Analysis of toxic alkaloids in body samples. Forensic science international. 185(1-3): 1-9 (2009)

    Article  CAS  PubMed  Google Scholar 

  • Birecka H, Catalfamo JL Eisen RN. A sensitive method for detection and quantitative determination of pyrrolizidine alkaloids. Phytochemistry. 20: 343-344 (1981)

    Article  CAS  Google Scholar 

  • Bispo MS, Veloso MC, Pinheiro HL, De Oliveira RF, Reis JO, De Andrade JB. Simultaneous determination of caffeine, theobromine, and theophylline by high-performance liquid chromatography. Journal of Chromatographic Science. 40: 45-48 (2002)

    Article  CAS  PubMed  Google Scholar 

  • Bodart P, Kabengera C Noirfalise A. Determination of a-Solanine and a-Chaconine in Potatoes by High-Performance Thin-Layer Chromatography/Densitometry. Journal of AOAC International. 83: 1468-1473 (2000)

    Article  CAS  PubMed  Google Scholar 

  • Bodi D, Ronczka S, Gottschalk C, Behr N, Skibba A, Wagner M, Lahrssen-Wiederholt M, Preiss-Weigert A These A. Determination of pyrrolizidine alkaloids in tea, herbal drugs and honey. Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment. 31: 1886-1895 (2014)

    CAS  Google Scholar 

  • Borré GL, Kaiser S, Pavei C, da Silva FA, Bassani VL Ortega GG. Comparison of methylxanthine, phenolics and saponin contents in leaves, branches and unripe fruits from ilex paraguariensis A. St.-Hil (mate). Journal of Liquid Chromatography and Related Technologies. 33: 362-374 (2010)

    Article  Google Scholar 

  • Boschin G, Annicchiarico P, Resta D, D’Agostina A Arnoldi A. Quinolizidine alkaloids in seeds of lupin genotypes of different origins. Journal of Agricultural and Food Chemistry. 56: 3657-3663 (2008)

    Article  CAS  PubMed  Google Scholar 

  • Breton D, Buret D, Clair P, Lafosse M. Chiral separation of atropine by high-performance liquid chromatography. Journal of Chromatography A. 1088(1-2): 104-109 (2005)

    Article  CAS  PubMed  Google Scholar 

  • Bushway RJ, McGann DF Bushway AA. Gas chromatographic method for the determination of solanidine and its application to a study of feed-milk transfer in the cow. Journal of Agricultural and Food Chemistry. 32: 548-551 (1984)

    Article  CAS  Google Scholar 

  • Butler WH, Fordt GP Creasy DM. A 90-day Feeding Study of Lupin (Lupinus angustifolius) Flour Spiked with Lupin Alkaloids in the Rat. Food and Chemical Toxicology. 34: 531-536 (1996)

    Article  CAS  PubMed  Google Scholar 

  • Cabello G, Valenzuela M, Vilaxa A, Durán V, Rudolph I, Hrepic N, Calaf G. A rat mammary tumor model induced by the organophosphorous pesticide parathion and malathion, possibly through acetylcholinesterase inhibition. Environmental Health Perspectives. 109:471-479 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caligiani A, Palla G, Bonzanini F, Bianchi A, Bruni R. A validated GC-MS method for the detection of tropane alkaloids in buckwheat (Fagopyron esculentum L.) fruits, flours and commercial foods. Food Chemistry. 127: 204-209 (2011)

    Article  CAS  Google Scholar 

  • Caniato R, Tabacchi R, Tsoupras G, Bicchi C. Capillary gas chromatography/positive and negative ion chemical ionization mass spectrometry on pyrrolizidine alkaloids of Senecio inaequidens using ammonia and hydroxyl ions as the reagent species. Journal of Natural Products. 52: 32-41 (1989)

    Article  Google Scholar 

  • Capasso A, Aquino R, de Tommasi N, Piacente S, Rastrelli L Pizza C. Neuropharmacology activity of alkaloids from South American medicinal plants. Current Medicinal Chemistry-Central Nervous System Agents. 2: 1-15 (2002)

    Article  CAS  Google Scholar 

  • Caprioli G, Logrippo S, Cahill MG James KJ. High-performance liquid chromatography LTQ-Orbitrap mass spectrometry method for tomatidine and non-target metabolites quantification in organic and normal tomatoes. International Journal of Food Sciences and Nutrition. 65: 942-947 (2014)

    Article  CAS  PubMed  Google Scholar 

  • Carpent G Desclin L. Effects of Ergocornine on the Mechanism of Gestation and on Fetal Morphology in the Rat. Endocrinology. 84: 315-324 (1969)

    Article  CAS  PubMed  Google Scholar 

  • Chami L al, Méndez R, Chataing B, O’Callaghan J, Usubillaga A, LaCruz L. Toxicological effects of α-solamargine in experimental animals. Phytotherapy Research. 17: 254-258 (2003)

    Article  PubMed  Google Scholar 

  • Chan PC, Haseman JK, Prejean JD Nyska A. Toxicity and carcinogenicity of riddelliine in rats and mice. Toxicology Letters. 144: 295-311 (2003)

    Article  CAS  PubMed  Google Scholar 

  • Chan PC, Mahler J, Bucher JR, Travlos GS Reid JB. Toxicity and carcinogenicity of riddelliine following 13 weeks of treatment to rats and mice. Toxicon. 32: 891-908 (1994)

    Article  CAS  PubMed  Google Scholar 

  • Chan P. NTP technical report on the toxicity studies of Riddelliine (CAS No. 23246-96-0) administered by gavage to F344 rats and B6C3F1 mice. Toxicity Report Series. 27: 1-D9 (1993)

    PubMed  Google Scholar 

  • Chen L, Mulder PP, Peijnenburg A, Rietjens IM. Risk assessment of intake of pyrrolizidine alkaloids from herbal teas and medicines following realistic exposure scenarios. Food and Chemical Toxicology. 130: 142-53 (2019)

    Article  CAS  PubMed  Google Scholar 

  • Choudhury RC, Palo AK. Modulatory effects of caffeine on methotrexate-induced cytogenotoxicity in mouse bone marrow. Environmental Toxicology and Pharmacology. 15: 79-85 (2004)

    Article  CAS  PubMed  Google Scholar 

  • Christen P, Bieri S, Veuthey JL. Analysis of tropane alkaloids in biological matrices. Wiley, Weinheim, Germany. Pp. 341-367 (2008)

    Google Scholar 

  • Cimpoiu C, Hosu A, Seserman L, Sandru M Miclaus V. Simultaneous determination of methylxanthines in different types of tea by a newly developed and validated TLC method. Journal of Separation Science. 33: 3794-3799 (2010)

    Article  CAS  PubMed  Google Scholar 

  • Conradie J, Stewart MJ, Steenkamp V. GC/MS identification of toxic pyrrolizidine alkaloids in traditional remedies given to two sets of twins. Annals of Clinical Biochemistry. 42: 141-144 (2005)

    Article  CAS  PubMed  Google Scholar 

  • de Cortes Sánchez M, Altares P, Pedrosa MM, Burbano C, Cuadrado C, Goyoaga C, Muzquiz M, Jiménez-Martínez C Dávila-Ortiz G. Alkaloid variation during germination in different lupin species. Food Chemistry. 90: 347-355 (2005)

    Article  Google Scholar 

  • Crews C, Anderson WAC, Rees G Krska R. Ergot alkaloids in some rye-based UK cereal products. Food Additives and Contaminants: Part B Surveillance. 2: 79-85 (2009)

    Article  CAS  PubMed  Google Scholar 

  • Crews C, Berthiller F Krska R. Update on analytical methods for toxic pyrrolizidine alkaloids. Analytical and Bioanalytical Chemistry. 396: 327-338 (2010)

    Article  CAS  PubMed  Google Scholar 

  • Culvenor CC, Edgar JA, Jago MV, Outteridge A, Peterson JE, Smith LW. Hepato-and pneumotoxicity of pyrrolizidine alkaloids and derivatives in relation to molecular structure. Chemico-Biological Interactions. 12: 299-324 (1976)

    Article  CAS  PubMed  Google Scholar 

  • Cushnie TPT, Cushnie B Lamb AJ. Alkaloids: An overview of their antibacterial, antibiotic-enhancing and antivirulence activities. International Journal of Antimicrobial Agents. 44: 377-386 (2014)

    Article  CAS  PubMed  Google Scholar 

  • Czapski GA, Szypuła W, Kudlik M, Wileńska B, Kania M, Danikiewicz W, Adamczyk A. Assessment of antioxidative activity of alkaloids from Huperzia selago and Diphasiastrum complanatum using in vitro systems. Folia Neuropathologica. 52: 394-406 (2014)

    Article  PubMed  Google Scholar 

  • Dalvi RR. Comparative assessment of the effect of solanine administered orally and intraperitoneally on hepatic dysfunction in male rats. The Japanese Journal of Veterinary Science. 47: 657-659 (1985)

    Article  CAS  PubMed  Google Scholar 

  • Dighe R Vaidya VG. Induction of Sister Chromatid Exchanges by Ergot Compounds in Chinese Hamster Ovary Cells In Vitro. Teratogenesis, Carcinogenesis and Mutagenesis. 8: 169-174 (1988)

    Article  CAS  PubMed  Google Scholar 

  • Dixit VP, Gupta RS. Antispermatogenic/antiandrogenic properties of solasodine (C27H43O2N) obtained from solanum xanthocarpum berries on the male genital tract of dog (Canis‐familiaris). A Histophysiological approach. International Journal of Andrology. 5: 295-307 (1982)

    Article  CAS  PubMed  Google Scholar 

  • Dixit VP, Gupta RS, Gupta S. Antifertility plant products: Testicular cell population dynamics following solasodine (C27 H43 O2 N) administration in Rhesus monkey (Macaca mulatta) andrologia. 21: 542-546 (1989)

    Article  CAS  PubMed  Google Scholar 

  • Drager B. Analysis of tropane and related alkaloids. Journal of Chromatography A. 978(1-2): 1-35 (2002)

    Article  CAS  PubMed  Google Scholar 

  • Dübecke A, Beckh G Lüllmann C. Pyrrolizidine alkaloids in honey and bee pollen. Food Additives and Contaminants - Part A. 28: 348-358 (2011)

    Article  Google Scholar 

  • Edgar JA, Smith LW. Transfer of pyrrolizidine alkaloids into eggs: food safety implications (2000)

  • EFSA Panel on Contaminants in the Food Chain (CONTAM). Knutsen HK, Alexander J, Barregård L, Bignami M, Brüschweiler B, Ceccatelli S, Cottrill B, Dinovi M, Edler L, Grasl‐Kraupp B. Risks for human health related to the presence of pyrrolizidine alkaloids in honey, tea, herbal infusions and food supplements. EFSA Journal. 15: e04908 (2017)

    PubMed  PubMed Central  Google Scholar 

  • EFSA Panel on Contaminants in the Food Chain (CONTAM). Schrenk D, Bignami M, Bodin L, Chipman JK, del Mazo J, Hogstrand C, Hoogenboom L, Leblanc JC, Nebbia CS, Nielsen E. Risk assessment of glycoalkaloids in feed and food, in particular in potatoes and potato‐derived products. EFSA Journal. 18: e06222 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  • EFSA Panel on Contaminants in the Food Chain (CONTAM). Schrenk D, Bodin L, Chipman JK, del Mazo J, Grasl‐Kraupp B, Hogstrand C, Hoogenboom L, Leblanc JC, Nebbia CS, Nielsen E. 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. EFSA Journal. 17: e05860 (2019)

    PubMed  PubMed Central  Google Scholar 

  • EFSA Panel on Contaminants in the Food Chain (CONTAM). Scientific opinion on ergot alkaloids in food and feed. EFSA Journal. 10: 2798 (2012)

    Article  Google Scholar 

  • EFSA Panel on Contaminants in the Food Chain (CONTAM). Scientific Opinion on Tropane alkaloids in food and feed. EFSA Journal. 11: 3386 (2013)

    Article  Google Scholar 

  • EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF). Silano V, Bolognesi C, Castle L, Cravedi JP, Engel KH, Fowler P, Franz R, Grob K, Gürtler R, Husøy T. Scientific opinion on flavouring group evaluation 49, Revision 1 (FGE. 49Rev1): Xanthine alkaloids from the priority list. EFSA Journal. 15: p.e04729 (2017)

    PubMed  PubMed Central  Google Scholar 

  • European Food Safety Authority. Arcella D, Gómez Ruiz JA, Innocenti ML, Roldán R. Human and animal dietary exposure to ergot alkaloids. EFSA Journal. 15: e04902 (2017)

    PubMed  PubMed Central  Google Scholar 

  • Fajardo J, Dexter J, Roscoe M, Nowicki T. Retention of ergot alkaloids in wheat during processing1,2. Cereal Chemistry. 72: 291-298 (1995)

    CAS  Google Scholar 

  • Fernandez LS, Sykes ML, Andrews KT, Avery VM. Antiparasitic activity of alkaloids from plant species of Papua New Guinea and Australia. International Journal of Antimicrobial Agents. 36: 275-279 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Fliniaux MA, Jacquin-Dubreuil A. A competitive solid-phase enzyme immunoassay for the evaluation of tropane alkaloids in plant material, using anti-DL-tropic acid antibodies. Planta Medica. 53: 87-90 (1987)

    Article  CAS  PubMed  Google Scholar 

  • Franzmann C, Wächter J, Dittmer N, Humpf HU. Ricinoleic acid as a marker for ergot impurities in rye and rye products. Journal of Agricultural and Food Chemistry. 58: 4223-4229 (2010)

    Article  CAS  PubMed  Google Scholar 

  • Frédérich M, Jacquier MJ, Thépenier P, de Mol P, Tits M, Philippe G, Delaude C, Angenot L, Zèches-Hanrot M. Antiplasmodial activity of alkaloids from various Strychnos species. Journal of Natural Products. 65: 1381-1386 (2002)

    Article  PubMed  Google Scholar 

  • Friedman M, Henika PR. Absence of genotoxicity of potato alkaloids α-chaconine, α-solanine and solanidine in the Ames Salmonella and adult and fetal erythrocyte micronucleus assays. Food and Chemical Toxicology. 30: 689-694 (1992)

    Article  CAS  PubMed  Google Scholar 

  • Friedman M, McDonald GM, Filadelfi-Keszi M. Potato glycoalkaloids: chemistry, analysis, safety, and plant physiology. Critical Reviews in Plant Sciences. 16: 55-132 (1997)

    Article  CAS  Google Scholar 

  • Friedman M, Roitman JN, Kozukue N. Glycoalkaloid and calystegine contents of eight potato cultivars. Journal of Agricultural and Food Chemistry. 51: 2964-2973 (2003)

    Article  CAS  PubMed  Google Scholar 

  • Gaffield W, Keeler RF. Implication of C-5, C-6 unsaturation as a key structural factor in steroidal alkaloid-induced mammalian teratogenesis. Experientia. 49: 922-924 (1993)

    Article  CAS  PubMed  Google Scholar 

  • Gaffield W, Keeler RF. Induction of terata in hamsters by solanidane alkaloids derived from Solanum tuberosum. Chemical Research in Toxicology. 9: 426-433 (1996)

    Article  CAS  PubMed  Google Scholar 

  • Ge Y, Liu P, Yang R, Zhang L, Chen H, Camara I, Liu Y, Shi W. Insecticidal constituents and activity of alkaloids from Cynanchum mongolicum. Molecules. 20: 17483-17492 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Gelder WMJ. Determination of the total C27-steroidal alkaloid com-position of Solanum species by high-resolution gas chromatography. Journal of Chromatography A. 331: 285-293 (1985)

    Article  Google Scholar 

  • Grauwiler J, Schon H. Teratological experiments with ergotamine in mice, rats, and rabbits. Teratology. 7: 227-235 (1973)

    Article  CAS  PubMed  Google Scholar 

  • Green BT, Lee ST, Welch KD, Gardner DR, Stegelmeier BL, Davis TZ. The serum concentrations of lupine alkaloids in orally-dosed Holstein cattle. Research in Veterinary Science. 100: 239-244 (2015)

    Article  CAS  PubMed  Google Scholar 

  • Green CR, Christie GS. Malformations in foetal rats induced by the pyrrolizidine alkaloid, heliotrine. British Journal of Experimental Pathology. 42: 369 (1961)

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gresta F, Abbate V, Avola G, Magazzà G, Chiofalo B. Lupin seed for the crop-livestock food chain. Italian Journal of Agronomy. 5: 333-340 (2010)

    Article  Google Scholar 

  • Griffith RW, Grauwiler J, Hodel C, Leist KH, Matter B. Ergot–toxicology considerations. Heffter-Heubner’s Handbook of Experimental Pharmacology. 805-851 (1978)

    Google Scholar 

  • Gupta RS, Dixit VP. Effects of short-term treatment of solasodine on cauda epididymis in dogs. Indian Journal of Experimental Biology. 40: 169-173 (2002)

    CAS  PubMed  Google Scholar 

  • Haynes P, Lambert TR, Mitchell ID. Comparative in-vivo genotoxicity of antiviral nucleoside analogues; penciclovir, acyclovir, ganciclovir and the xanthine analogue, caffeine, in the mouse bone marrow micronucleus assay. Mutation Research/Genetic Toxicology. 369(1-2): 65-74 (1996)

    Article  CAS  Google Scholar 

  • Hincks JR, Kim H-Y, Segall HJ, Molyneux RJ, Stermitz FR, Coulombe RA. DNA cross-linking in mammalian cells by pyrrolizidine alkaloids: Structure-activity relationships. Toxicology and Applied Pharmacology. 111: 90-98 (1991)

    Article  CAS  PubMed  Google Scholar 

  • Hirono I, Haga M, Fujii M, Matsuura S, Matsubara N, Nakayama M, Furuya T, Hikichi M, Takanashi H, Uchida E, Hosaka S. Induction of hepatic tumors in rats by senkirkine and symphytine. Journal of the National Cancer Institute. 63: 469-472 (1979)

    CAS  PubMed  Google Scholar 

  • Hirono I, Mori H, Yamada K, Hirata Y, Haga M, Tatematsu H, Kanie S. Carcinogenic activity of petasitenine, a new pyrrolizidine alkaloid isolated from Petasites japonicus Maxim. Journal of the National Cancer Institute. 58: 1155-1157 (1977)

    Article  CAS  PubMed  Google Scholar 

  • Hoogenboom LAP, Mulder PPJ, Zeilmaker MJ, van den Top HJ, Remmelink GJ, Brandon EFA, Klijnstra M, Meijer GAL, Schothorst R, van Egmond HP. Carry-over of pyrrolizidine alkaloids from feed to milk in dairy cows. Food Additives and Contaminants - Part A. 28: 359-372 (2011)

    Article  CAS  Google Scholar 

  • Hossain MB, Rai DK, Brunton NP. Optimization and validation of ultra-high-performance liquid chromatographic-tandem mass spectrometry method for qualitative and quantitative analysis of potato steroidal alkaloids. Journal of Chromatography B. 997: 110-115 (2015)

    Article  CAS  Google Scholar 

  • Houben RJ, Brunt K. Determination of glycoalkaloids in potato tubers by reversed-phase high-performance liquid chromatography. Journal of Chromatography A. 661 (1-2): 169-174 (1994)

    Article  CAS  Google Scholar 

  • IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, International Agency for Research on Cancer, & World Health Organization. Some traditional herbal medicines, some mycotoxins, naphthalene and styrene. World Health Organization (2002)

  • International Agency for Research on Cancer. Some naturally occurring substances. International Agency for Research on Cancer (1976)

  • International Agency for Research on Cancer. IARC Monographs evaluate drinking coffee, maté, and very hot beverages (2016)

  • Jankech T, Maliarová M, Martinka N. Determination of methylxanthines in tea samples by HPLC method. Nova Biotechnologica et Chimica. 18: 124-132 (2019)

    Article  CAS  Google Scholar 

  • Janssen GB, Beems RB, Elvers LH, Speijers GJA. Subacute toxicity of α-ergocryptine in Sprague-Dawley rats. 2: metabolic and hormonal changes. Food and Chemical Toxicology. 38: 689-695 (2000a)

    Article  CAS  PubMed  Google Scholar 

  • Janssen GB, Beems RB, Speijers GJA, van Egmond HP. Subacute toxicity of a-ergocryptine in Sprague-Dawley rats. 1: general toxicological effects. Food and Chemical Toxicology. 38: 679-88 (2000b)

    Article  CAS  PubMed  Google Scholar 

  • Jegorov A, Simek P, Heydova A, Cvak L, Minář J. Free and bonded homoisoleucine in sclerotia of the parasitic fungus Claviceps purpurea. Springer-Verlag Amino Acids. 12(1): 9-19 (1997)

    Article  CAS  Google Scholar 

  • Jeong SH, Choi EY, Kim J, Lee C, Kang J, Cho S, Ko KY. LC-ESI-MS/MS Simultaneous Analysis Method Coupled with Cation-Exchange Solid-Phase Extraction for Determination of Pyrrolizidine Alkaloids on Five Kinds of Herbal Medicines. Journal of AOAC International. 104: 1514-1525 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  • Jing H, Liu J, Liu H, Xin H. Histochemical investigation and kinds of alkaloids in leaves of different developmental stages in Thymus quinquecostatus. The Scientific World Journal (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  • John H, Binder T, Höchstetter H, Thiermann H. LC-ESI MS/MS quantification of atropine and six other antimuscarinic tropane alkaloids in plasma. Analytical and Bioanalytical Chemistry. 396: 751-63 (2010)

    Article  CAS  PubMed  Google Scholar 

  • Kakar F, Akbarian Z, Leslie T, Mustafa ML, Watson J, van Egmond HP, Omar MF, Mofleh J. An outbreak of hepatic veno-occlusive disease in Western Afghanistan associated with exposure to wheat flour contaminated with pyrrolizidine alkaloids. Journal of Toxicology. (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  • Kamel KA, Święcicki W, Kaczmarek Z, Barzyk P. Quantitative and qualitative content of alkaloids in seeds of a narrow-leafed lupin (Lupinus angustifolius L.) collection. Genetic Resources and Crop Evolution. 63: 711-719 (2016)

    Article  CAS  Google Scholar 

  • Karou D, Savadogo A, Canini A, Yameogo S, Montesano C, Simpore J, Colizzi V, Traore AS. Antibacterial activity of alkaloids from Sida acuta. African Journal of Biotechnology. 5: 195-200 (2006)

    CAS  Google Scholar 

  • Kempf M, Reinhard A, Beuerle T. Pyrrolizidine alkaloids (PAs) in honey and pollen-legal regulation of pa levels in food and animal feed required. Molecular Nutrition and Food Research. 54: 158-168 (2010)

    Article  CAS  PubMed  Google Scholar 

  • Khanchi AR, Khayatzadeh Mahani M, Hajihosseini M, Maragheh MG, Chaloosi M, Bani F. Simultaneous spectrophotometric determination of caffeine and theobromine in Iranian tea by artificial neural networks and its comparison with PLS. Food Chemistry. 103: 1062-1068 (2007)

    Article  CAS  Google Scholar 

  • Kim HY, Stermitz FR, Coulombe Jr RA. Pyrrolizidine alkaloid-induced DNA-protein cross-links. Carcinogenesis. 16: 2691-2697 (1995)

    Article  CAS  PubMed  Google Scholar 

  • Kokkonen M, Jestoi M. Determination of ergot alkaloids from grains with UPLC-MS/MS. Journal of Separation Science. 33: 2322-2327 (2010)

    Article  CAS  PubMed  Google Scholar 

  • Koleva II, van Beek TA, Soffers AE, Dusemund B, Rietjens IM. Alkaloids in the human food chain-natural occurrence and possible adverse effects. Molecular Nutrition and Food Research. 56: 30-52 (2012)

    Article  CAS  PubMed  Google Scholar 

  • Kozukue N, Han JS, Lee KR, Friedman M. Dehydrotomatine and α-Tomatine Content in Tomato Fruits and Vegetative Plant Tissues. Journal of Agricultural and Food Chemistry. 52: 2079-2083 (2004)

    Article  CAS  PubMed  Google Scholar 

  • Kraicer PF, Strauss JF. Ovulation block produced by an inhibitor of luteotrophin, ergocornine. European Journal of Endocrinology. 65: 698-706 (1970)

    Article  CAS  Google Scholar 

  • Krska R, Stubbings G, MacArthur R, Crews C. Simultaneous determination of six major ergot alkaloids and their epimers in cereals and foodstuffs by LC-MS-MS. Analytical and Bioanalytical Chemistry. 391: 563-576 (2008)

    Article  CAS  PubMed  Google Scholar 

  • Kuhara K, Takanashia H, Hirono I, Furuya T, Asada Y. Carcinogenic activity of clivorine, a pyrrolizidine alkaloid isolated from Ligularia dentata. Cancer Letters. 10: 117-122 (1980)

    Article  CAS  PubMed  Google Scholar 

  • Kuhlmann W, Fromme H-G, Heege E-M, Ostertag2 W. The mutagenic action of caffeine in higher organisms1. Cancer Research. 28: 2375–2389 (1968)

    CAS  PubMed  Google Scholar 

  • Kurek J. editor. Alkaloids: Their importance in Nature and Human life. BoD–Books on Demand; (2019)

  • Langer T, Möstl E, Chizzola R, Gutleb R. A competitive enzyme immunoassay for the pyrrolizidine alkaloids of the senecionine type. Planta Medica. 62: 267-271 (1996)

    Article  CAS  PubMed  Google Scholar 

  • Langkilde S, Mandimika T, Schrøder M, Meyer O, Slob W, Peijnenburg A, Poulsen M. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, α-solanine and α-chaconine in the Syrian Golden hamster. Food and Chemical Toxicology. 47: 1099-1108 (2009)

    Article  CAS  PubMed  Google Scholar 

  • Langkilde S, Schrøder M, Frank T, Shepherd LVT, Conner S, Davies H v., Meyer O, Danier J, Rychlik M, Belknap WR, McCue KF, Engel KH, Stewart D, Knudsen I, Poulsen M. Compositional and toxicological analysis of a GM potato line with reduced α-solanine content - A 90-day feeding study in the Syrian Golden hamster. Regulatory Toxicology and Pharmacology. 64: 177-185 (2012)

    Article  CAS  PubMed  Google Scholar 

  • Langkilde S, Schrøder M, Stewart D, Meyer O, Conner S, Davies H, Poulsen M. Acute toxicity of high doses of the glycoalkaloids, α-solanine and α-chaconine, in the Syrian Golden hamster. Journal of Agricultural and Food Chemistry. 56: 8753-8760 (2008)

    Article  CAS  PubMed  Google Scholar 

  • Lauber U, Schnaufer R, Gredziak M, Kiesswetter Y. Analysis of rye grains and rye meals for ergot alkaloids. Mycotoxin Research. 21: 258-262 (2005)

    Article  CAS  PubMed  Google Scholar 

  • Lee ST, Schoch TK, Stegelmeier BL, Gardner DR, Than KA, Molyneux RJ. Development of enzyme-linked immunosorbent assays for the hepatotoxic alkaloids riddelliine and riddelliine N-oxide. Journal of Agricultural and Food Chemistry. 49: 4144-4151 (2001)

    Article  CAS  PubMed  Google Scholar 

  • Logie CG, Grue MR, Liddell JR. Proton NMR spectroscopy of pyrrolizidine alkaloids. Phytochemistry. 37: 43-109 (1994)

    Article  CAS  Google Scholar 

  • Long Z, Wang C, Guo Z, Zhang X, Nordahl L, Zeng J, Zeng J, Liang X. A non-aqueous solid phase extraction method for alkaloid enrichment and its application in the determination of hyoscyamine and scopolamine. Analyst. 137: 1451-1457 (2012)

    Article  CAS  PubMed  Google Scholar 

  • López-Martínez L, López-de-Alba PL, García-Campos R, de León-Rodríguez LM. Simultaneous determination of methylxanthines in coffees and teas by UV-Vis spectrophotometry and partial least squares. Analytica Chimica Acta. 493: 83-94 (2003)

    Article  Google Scholar 

  • Luthy J, Zweifel U, Karlhuber B, Schlatter C. Pyrrolizidine alkaloids of Senecio alpinus L. and their detection in feeding stuffs. Journal of Agricultural and Food Chemistry. 29: 302-305 (1981)

    Article  CAS  PubMed  Google Scholar 

  • Magalhães SCQ, Fernandes F, Cabrita ARJ, Fonseca AJM, Valentão P, Andrade PB. Alkaloids in the valorization of European Lupinus spp. seeds crop. Industrial Crops and Products. 95: 286-295 (2017)

    Article  Google Scholar 

  • Marín-Sáez J, Romero-González R, Garrido Frenich A. Multi-analysis determination of tropane alkaloids in cereals and solanaceaes seeds by liquid chromatography coupled to single stage Exactive-Orbitrap. Journal of Chromatography A. 1518: 46-58 (2017)

    Article  PubMed  Google Scholar 

  • Matter ΒΕ. Failure to Detect Chromosome Damage in Bone-Marrow Cells of Mice and Chinese Hamsters Exposed in Vivo to Some Ergot Derivatives. Journal of International Medical Research. 4: 382-392 (1976)

    Article  CAS  PubMed  Google Scholar 

  • Matter BE. Heritable translocation test in mice with triethylenemelamine (TEM) and ergotamine. Mutation Research Letters. 104: 177-182 (1982)

    Article  CAS  Google Scholar 

  • Mattocks AR. Hepatotoxic Effects due to Pyrrolizidine Alkaloid N-Oxides. Xenobiotica, 1: 563-565 (1971)

    Article  CAS  PubMed  Google Scholar 

  • Mazur L, Peralta-Zamora PG, Demczuk B and Ribani RH. Application of multivariate calibration and NIR spectroscopy for the quantification of methylxanthines in yerba mate (Ilex paraguariensis). Journal of Food Composition and Analysis. 35: 55-60 (2014)

    Article  CAS  Google Scholar 

  • McCann J, Choi E, Yamasaki E, Ames BN, Jolley SB, Streitwieser D, Jen G, Donahue V, Stark G, Haroun L, Maron D, Keng T, Matsushima H, Bartsch E, Weisburger J, Miller E, Arcos J, Tomatis L, Rosenkranz H, Poirier L. Detection of carcinogens as mutagens in the Salmonella/microsome test: Assay of 300 chemicals. Proceedings of the National Academy of Sciences. 72: 5135-5139 (1975)

    Article  CAS  Google Scholar 

  • Merhoff GC, Porter JM. Ergot intoxication: Historical review and description of unusual clinical manifestations. Annals of Surgery. 180: 773 (1974)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller WC, Rice DL, Kreusel RG, Bedrossian CW. Monocrotaline model of noncardiogenic pulmonary edema in dogs. Journal of Applied Physiology. 45: 962-965 (1978)

    Article  CAS  PubMed  Google Scholar 

  • Moco S, Capanoglu E, Tikunov Y, Bino RJ, Boyacioglu D, Hall RD, Vervoort J, De Vos RC. Tissue specialization at the metabolite level is perceived during the development of tomato fruit. Journal of Experimental Botany. 58: 4131-4146 (2007)

    Article  CAS  PubMed  Google Scholar 

  • Mohamed R, Gremaud E, Richoz-Payot J, Tabet JC, Guy PA. Quantitative determination of five ergot alkaloids in rye flour by liquid chromatography–electrospray ionisation tandem mass spectrometry. Journal of Chromatography A.1114: 62-72 (2006)

    Article  CAS  PubMed  Google Scholar 

  • Molloy JB, Moore CJ, Bruyeres AG, Murray SA, Blaney BJ. Determination of dihydroergosine in sorghum ergot using an immunoassay. Journal of Agricultural and Food Chemistry. 51: 3916-3919 (2003)

    Article  CAS  PubMed  Google Scholar 

  • Morgan MR, Coxon DT, Bramham S, Chan HWS, van Gelder WMJ, Allison MJ. Determination of the glycoalkaloid content of potato tubers by three methods including enzyme-linked immunosorbent assay. Journal of the Science of Food and Agriculture. 36: 282-288 (1985)

    Article  CAS  Google Scholar 

  • Mroczek T, Głowniak K, Kowalska J. Solid-liquid extraction and cation-exchange solid-phase extraction using a mixed-mode polymeric sorbent of Datura and related alkaloids. Journal of Chromatography A. 1107: 9-18 (2006)

    Article  CAS  PubMed  Google Scholar 

  • Mulder PPJ, Beumer B, Oosterink E, de Jong J. Dutch survey pyrrolizidine alkaloids in animal forage. Dutch survey pyrrolizidine alkaloids in animal forage. Rikilt-Institute of Food Safety (2009)

  • Mulder PP, Van Raamsdonk LW, Voogt HJ, van Brakel MW, van der Horst GM, de Jong J. Dutch survey ergot alkaloids and sclerotia in animal feeds. Rikilt-Institute of Food Safety (2012)

  • Mulder PPJ, Pereboom-de Fauw DPKH, Hoogenboom RLAP, de Stoppelaar J, de Nijs M. Tropane and ergot alkaloids in grain-based products for infants and young children in the Netherlands in 2011–2014. Food Additives and Contaminants: Part B Surveillance. 8: 284-290 (2015)

    CAS  PubMed  Google Scholar 

  • Mulder P, de Nijs M. Determination of quinolizidine alkaloids in lupin flour by LC-MS/MS. A promising novel way of analysis. In Proceedings of the XIV International Lupin Conference, Milan, Italy. 21: 26-75 (2015)

  • Müller C, Kemmlein S, Klaffke H, Krauthause W, Preiß-Weigert A, Wittkowski R. A basic tool for risk assessment: A new method for the analysis of ergot alkaloids in rye and selected rye products. Molecular Nutrition and Food Research. 53: 500-507 (2009)

    Article  PubMed  Google Scholar 

  • Musita CN, Omayio DG, Abong’ GO, Okoth MW. Glycoalkaloids in commercial potato varieties traded in Nairobi, Kenya. F1000Research. 9: 423 (2020)

  • Nara A, Saka K, Yamada C, Kodama T, Takagi T. Forensic analysis using ultra-high-performance liquid chromatography–tandem mass spectrometry with solid-phase extraction of α-solanine and α-chaconine in whole blood. Forensic Toxicology. 37: 197-206 (2019)

    Article  CAS  PubMed  Google Scholar 

  • National Toxicology Program. Bioassay of lasiocarpine for possible carcinogenicity. National Cancer Institute Carcinogenesis Technical Report Series. 39: 1-66 (1978)

    Google Scholar 

  • National Toxicology Program. NTP Toxicology and Carcinogenesis Studies of Scopolamine Hydrobromide Trihydrate (CAS No. 6533–68–2) in F344 Rats and B6C3F1 Mice (Gavage Studies). National Toxicology Program Technical Report Series. 445: 1-277 (1997)

  • National Toxicology Program. NTP toxicology and carcinogenesis studies of theophylline (CAS No. 58–55–9) in F344/N rats and B6C3F1 mice (feed and gavage studies). National Toxicology Program Technical Report Series. 473: 1-326 (1998)

  • National Toxicology Program. Toxicology and carcinogenesis studies of riddelliine (CAS No. 23246–96–0) in F344/N rats and B6C3F1 mice (gavage studies). National Toxicology Program Technical Report Series. 508: 1-280 (2003)

  • Papadoyannis IN, Samanidou VF, Theodoridis GA, Vasilikiotis GS, van Kempen GJM, Beelen GM. A Simple and Quick Solid Phase Extraction and Reversed Phase HPLC Analysis of Some Tropane Alkaloids in Feedstuffs and Biological Samples. Journal of Liquid Chromatography. 16: 975-998 (1993)

    Article  CAS  Google Scholar 

  • Paradkar MM, Irudayaraj J. A rapid FTIR Spectroscopic Method for Estimation of Caffeine in Soft Drinks and Total Methylxanthines in Tea and Coffee. Journal of Food Science. 67: 2507-2511 (2002)

    Article  CAS  Google Scholar 

  • Pereira TN, Webb RI, Reilly PEB, Seawright AA, Prakash AS. Dehydromonocrotaline generates sequence-selective N-7 guanine alkylation and heat and alkali stable multiple fragment DNA crosslinks. Vol. 26. (1998)

    Article  PubMed  PubMed Central  Google Scholar 

  • Pelser PB, de Vos H, Theuring C, Beuerle T, Vrieling K, Hartmann T. Frequent gain and loss of pyrrolizidine alkaloids in the evolution of Senecio section Jacobaea (Asteraceae). Phytochemistry. 66: 1285-1295 (2005)

    Article  CAS  PubMed  Google Scholar 

  • Peterson JE, Jago MV. Comparison of the toxic effects of dehydroheliotridine and heliotrine in pregnant rats and their embryos. The Journal of Pathology. 131: 339-355 (1980)

    Article  CAS  PubMed  Google Scholar 

  • Peters-Volleberg GWM, Beems RB, Speijers GJA. Subacute toxicity of ergometrine maleate in rats. Food and Chemical Toxicology. 34: 951-958 (1996)

    Article  CAS  PubMed  Google Scholar 

  • Petry TW, Bowden GT, Buhler DR, Glenn Sipe KG. Genotoxicity of the pyrrolizidine alkaloid jacobine in rats. Toxicology Letters. 32: 275-281 (1986)

    Article  CAS  PubMed  Google Scholar 

  • Petry TW, Bowden GT, Huxtable RJ, Sipes IG. Characterization of hepatic DNA damage induced in rats by the pyrrolizidine alkaloid monocrotaline. Cancer Research. 44: 1505-1509 (1984)

    CAS  PubMed  Google Scholar 

  • Petterson DS, Ellis ZL, Harris DJ, Spadek ZE. Acute toxicity of the major alkaloids of cultivated lupinus angustifolius Seed to rats. Journal of Applied Toxicology. 7: 51-53 (1987)

    Article  CAS  PubMed  Google Scholar 

  • Philipov S, Berkov S. GC-MS Investigation of Tropane Alkaloids in Datura stramonium. Zeitschrift für Naturforschung C. 57: 559-561 (2002)

    Article  CAS  Google Scholar 

  • Phillips BJ, Hughes JA, Phillips JC, Walters DG, Anderson D, Tahourdint CSM. A Study of the toxic hazard that might be associated with the consumption of green potato tops. Food and Chemical Toxicology. 34: 439-448 (1996)

    Article  CAS  PubMed  Google Scholar 

  • Pothier J, Galand N, Dormeau C, Viel C. A Comparative study of the effects of sparteine, lupanine and lupin extract on the central nervous system of the mouse. Journal of Pharmacy and Pharmacology. 50: 949-954 (1998)

    Article  CAS  PubMed  Google Scholar 

  • Rao MS, Reddy JK. Malignant neoplasms in rats fed lasiocarpine. British Journal of Cancer. 37: 289-293 (1978)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reinhard H, Rupp H, Sager F, Streule M, Zoller O. Quinolizidine alkaloids and phomopsins in lupin seeds and lupin containing food. Journal of Chromatography A. 1112: 353-360 (2006)

    Article  CAS  PubMed  Google Scholar 

  • Reinhold L, Reinhardt K. Mycotoxins in foods in Lower Saxony (Germany): Results of official control analyses performed in 2009. Mycotoxin Research. 27: 137-143 (2011)

    Article  PubMed  Google Scholar 

  • Reinwaldt C, Bittner M, Kempe G, Glauner T. Quantitation of pyrrolizidine alkaloids in honey and herbal teas by UHPLC/MS/MS. Agilent Technologies Incorporation. (2017)

  • Renwick JH, Claringbold WDB, Earthy ME, Few JD, Caroline A, Mclean S. Neural-tube defects produced in Syrian hamsters by potato glycoalkaloids. Teratology. 30: 371-381 (1984)

    Article  CAS  PubMed  Google Scholar 

  • Resta D, Boschin G, D’Agostina A, Arnoldi A. Evaluation of total quinolizidine alkaloids content in lupin flours, lupin-based ingredients, and foods. Molecular Nutrition and Food Research. 52: 490-495 (2008)

    Article  CAS  PubMed  Google Scholar 

  • Robbins MC, Petterson DS, Brantom PG. A 90-Day Feeding Study of the alkaloids of Lupinus angustifolius in the Rat. Food and Chemical Toxicology. 34: 679-686 (1996)

    Article  CAS  PubMed  Google Scholar 

  • Roberts CA, Joost RE, Rottinghaus GE. Quantification of ergovaline in tall fescue by near infrared reflectance spectroscopy. Crop Science. 37: 281-284 (1997)

    Article  Google Scholar 

  • Roberts GT, Rand MJ. Chromosomal damage induced by some ergot derivatives in vitro. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 48: 205-214 (1977a)

    Article  CAS  PubMed  Google Scholar 

  • Roberts GT and Rand MJ. Effects of some ergot derivatives in bone marrow of mice. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 56: 59-67 (1977b)

  • Roberts GT, Rand MJ. The dominant lethal effects of some ergot alkaloids. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 50: 317-325 (1978)

  • Roeder E. Carbon-13 NMR spectroscopy of pyrrolizidine alkaloids. Phytochemistry. 29(1): 11-29. (1990)

    Article  CAS  Google Scholar 

  • Romera-Torres A, Romero-González R, Martínez Vidal JL, Garrido Frenich A. Simultaneous analysis of tropane alkaloids in teas and herbal teas by liquid chromatography coupled to high-resolution mass spectrometry (Orbitrap). Journal of Separation Science. 41: 1938-1946 (2018)

    Article  CAS  PubMed  Google Scholar 

  • Roseman DM, Wu X, Kurth MJ. Enzyme-linked immunosorbent assay detection of pyrrolizidine alkaloids: Immunogens based on quaternary pyrrolizidinium salts. Bioconjugate Chemistry. 7: 187-195 (1996)

    Article  CAS  PubMed  Google Scholar 

  • Saldaña MDA, Zetzl C, Mohamed RS, Brunner G. Extraction of methylxanthines from guaraná seeds, maté leaves, and cocoa beans using supercritical carbon dioxide and ethanol. Journal of Agricultural and Food Chemistry. 50: 4820-4826 (2002)

    Article  PubMed  Google Scholar 

  • Sanchez JM. Methylxanthine content in commonly consumed foods in Spain and determination of its intake during consumption. Foods. 6: 109 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  • Sánchez-Mata MC, Yokoyama WE, Hong YJ, Prohens J. α-Solasonine and α-solamargine contents of gboma (solanum macrocarpon l.) and scarlet (solanum aethiopicum l.) eggplants. Journal of Agricultural and Food Chemistry. 58: 5502-5508 (2010)

    Article  PubMed  Google Scholar 

  • Santiago Quiles MR, Oquendo-Jiménez I, Herreño-Saénz D, Antoun MD. Genotoxicity of alkaloid-rich extract from Lupinus termis seeds. Pharmaceutical Crops, 1(1) (2010)

    Article  Google Scholar 

  • Savary BJ, Dougall DK. Scopolamine radioimmunoassay for tissue cultures of datura. Phytochemistry. 29: 1567-1569 (1990)

    Article  CAS  Google Scholar 

  • Schmähl D, Habs M. Life-span investigations for carcinogenicity of some immune-stimulating, immunodepressive and neurotropic substances in Sprague-Dawley-rats. Zeitschrift fur Krebsforschung und Klinische Onkologie. Cancer Research and Clinical Oncology. 86: 77-84 (1976)

    PubMed  Google Scholar 

  • Schnitzius JM, Hill NS, Thompson CS, Craig AM. Semiquantitative determination of ergot alkaloids in seed, straw, and digesta samples using a competitive enzyme-linked immunosorbent assay. Journal of Veterinary Diagnostic Investigation. 13: 230-237 (2001)

    Article  CAS  PubMed  Google Scholar 

  • Schoeneberger H, Moron S, Gross R. Safety evaluation of water debittered Andean lupins (Lupinus mutabilis): 12-week rat feeding study. Plant Foods for Human Nutrition. 37: 169-182 (1987)

    Article  Google Scholar 

  • Schoental R. Liver lesions in young rats suckled by mothers treated with the pyrrolizidine (Senecio) alkaloids, lasiocarpine and retrorsine. Journal of Pathology and Bacteriology. 77: 485-495 (1959)

    Article  CAS  PubMed  Google Scholar 

  • Schoental R, Magee PN. Further observations on the subacute and chronic liver changes in rats after a single dose of various pyrrolizidine (Senecio) alkaloids. Journal of Pathology and Bacteriology. 78: 471-482 (1959)

    Article  CAS  PubMed  Google Scholar 

  • Shaar CJ, Clemens JA. Inhibition of lactation and prolactin secretion in rats by ergot alkaloids. Endocrinology. 90: 285-288 (1972)

    Article  CAS  PubMed  Google Scholar 

  • Sharma RP, Willhite CC, Shupe JL, Salunkhe DK. Acute toxicity and histopathological effects of certain glycoalkaloids and extracts of Alternaria solani or Phytophthora infestans in mice. Toxicology Letters. 3: 349-355 (1979)

    Article  CAS  Google Scholar 

  • Shrivas K, Wu HF. Rapid determination of caffeine in one drop of beverages and foods using drop-to-drop solvent microextraction with gas chromatography/mass spectrometry. Journal of Chromatography A. 1170: 9-14 (2007)

    Article  CAS  PubMed  Google Scholar 

  • Silva MR, Alvarez CM, García PM, Ruiz MA. Assessing the genotoxicities of sparteine and compounds isolated from Lupinus mexicanus and L. montanus seeds by using comet assay. Genetics and Molecular Research. 13: 10510-10517 (2014)

    Article  CAS  PubMed  Google Scholar 

  • Silva-Neto JP, Barreto RA, Pitanga BP, Souza CS, Silva VD, Silva AR, Velozo ED, Cunha SD, Batatinha MJ, Tardy M,Ribeiro CS. Genotoxicity and morphological changes induced by the alkaloid monocrotaline, extracted from Crotalaria retusa, in a model of glial cells. Toxicon. 55: 105-117 (2010)

    Article  CAS  PubMed  Google Scholar 

  • Sommer AF, Buchanan AR. Effects of ergot alkaloids on pregnancy and lactation in the Albino rat. American Journal of Physiology-Legacy Content. 180: 296-300 (1955)

    Article  CAS  Google Scholar 

  • Stanek M, Rotkiewicz T, Sobotka W, Bogusz J, Otrocka-Domagała I, Rotkiewicz A. The effect of alkaloids present in blue lupine (Lupinus angustifolius) seeds on the growth rate, selected biochemical blood indicators and histopathological changes in the liver of rats. Acta Veterinaria Brno. 84: 55-62 (2015)

    Article  Google Scholar 

  • Stanker LH, Kamps-Holtzapple C, Friedman M. Development and characterization of monoclonal antibodies that differentiate between potato and tomato glycoalkaloids and aglycons. Journal of Agricultural and Food Chemistry. 42: 2360-2366 (1994)

    Article  CAS  Google Scholar 

  • Stobiecki M, Blaszczyk B, Kowalczyk-Bronisz SH, Gulewicz K. The toxicity of seed extracts and their fractions from Lupinus angustifolius L. and Lupinus albus L. Journal of Applied Toxicology. 13: 347-352 (1993)

    Article  CAS  PubMed  Google Scholar 

  • Storm ID, Rasmussen PH, Strobel BW, Hansen HCB. Ergot alkaloids in rye flour determined by solid-phase cation-exchange and high-pressure liquid chromatography with fluorescence detection. Food Additives and Contaminants - Part A. 25: 338-346 (2008)

    Article  CAS  Google Scholar 

  • Svoboda DJ, Reddy JK. Malignant Tumors in Rats Given Lasiocarpine1. Cancer Research. 32: 908-913 (1972)

    CAS  PubMed  Google Scholar 

  • Tatsuta M, Iishi H, Baba M. Inhibition by neostigmine and isoproterenol and promotion by atropine of experimental carcinogenesis in rat stomach by N-methyl-N'-nitro-N-nitrosoguanidine. International Journal of Cancer. 44: 188-189 (1989)

    Article  CAS  PubMed  Google Scholar 

  • Topi D, Jakovac-Strajn B, Pavšič-Vrtač K, Tavčar-Kalcher G. Occurrence of ergot alkaloids in wheat from Albania. Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment. 34: 1333-1343 (2017)

    CAS  Google Scholar 

  • Tunali B, Shelby R, Morgan-Jones G, Kodan M. Endophytie Fungi and Ergot Alkaloids in Native Turkish Grasses. Phytoparasitica. 28: 375-377 (2000)

    Article  Google Scholar 

  • Urban J, Hamouz K, Lachman J, Pulkrábek J, Pazderů K. Effect of genotype, flesh colour and environment on the glycoalkaloid content in potato tubers from integrated agriculture. Plant, Soil and Environment. 64: 186-191 (2018)

    Article  CAS  Google Scholar 

  • Uysal UD, Aturki Z, Raggi MA, Fanall S. Separation of catechins and methylxanthines in tea samples by capillary electrochromatography. Journal of Separation Science. 32: 1002-1010 (2009)

    Article  CAS  PubMed  Google Scholar 

  • Vaněrková D, Marková L, Portychová L. Methodology for the safety assessment of lupin in terms of alkaloids content. In Horna A 14th International Nutrition & Diagnostics Conference 2014. pp. 7-82 (2014)

  • Vermeulen P, Fernández Pierna JA, van Egmond HP, Dardenne P, Baeten V. Online detection and quantification of ergot bodies in cereals using near infrared hyperspectral imaging. Food Additives and Contaminants - Part A. 29: 232-240 (2012)

    Article  CAS  Google Scholar 

  • Wagenvoort CA, Wagenvoort N, Dijk HJ. Effect of fulvine on pulmonary arteries and veins of the rat. Thorax. 29: 522-529 (1974)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang C, Li Y, Gao J, He Y, Xiong A, Yang L, Cheng X, Ma Y, Wang Z. The comparative pharmacokinetics of two pyrrolizidine alkaloids, senecionine and adonifoline, and their main metabolites in rats after intravenous and oral administration by UPLC/ESIMS. Analytical and Bioanalytical Chemistry. 401: 275-287 (2011)

    Article  CAS  PubMed  Google Scholar 

  • Wang YP, Fu PP, Chou MW. Metabolic activation of the tumorigenic pyrrolizidine alkaloid, retrorsine, leading to DNA adduct formation in vivo. International Journal of Environmental Research and Public Health. 2: 74-79 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waskell L. A study of the mutagenicity of anesthetics and their metabolites. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 57: 141-153 (1978)

    Article  CAS  PubMed  Google Scholar 

  • Wink M, Meibner C, Witte L. Patterns of quinolizidine alkaloids in 56 species of the genus Lupinus. Phytochemistry. 38: 139-153 (1995)

    Article  CAS  Google Scholar 

  • Winks M, Schmeller T, Latz-Brüning B. Modes of action of allelochemical alkaloids: interaction with neuroreceptors, DNA and other molecular targets. Journal of Chemical Ecology. 24: 1881-1937 (1998)

    Article  Google Scholar 

  • Witte L, Ernst L, Adam H, Hartmannt T. Chemotypes of two pyrrolizidine alkaloid-containing Senecio species. Phytochemistry. 31: 559-565 (1992)

    Article  CAS  Google Scholar 

  • Witters WL, Wilms RA, Hood RD. Prenatal effects of elymoclavine administration and temperature stress. Journal of Animal Science. 41: 1700-1705 (1975)

    Article  CAS  PubMed  Google Scholar 

  • Yovo K, Huguet F, Pothier J, Durand M, Breteau M, Narcisse G. Comparative pharmacological study of sparteine and its ketonic derivative lupanine from seeds of Lupinus albus. Planta Medica. 50: 420-424 (1984)

    Article  CAS  PubMed  Google Scholar 

  • Yu X, Bao Z, Zou J, Dong J. Coffee consumption and risk of cancers: A meta-analysis of cohort studies. BMC Cancer. 11: 1-11 (2011)

    Article  Google Scholar 

  • Zachariasova M, Cajka T, Godula M, Malachova A, Veprikova Z, Hajslova J. Analysis of multiple mycotoxins in beer employing (ultra)-high-resolution mass spectrometry. Rapid Communications in Mass Spectrometry. 24: 3357-3367 (2010)

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Zhang CR, Han YS, Wainberg MA, Yue JM. New Securinega alkaloids with anti-HIV activity from Flueggea virosa. RSC Advances. 5: 107045-107053 (2015)

    Article  CAS  Google Scholar 

  • Zou J, Li N. Simple and environmental friendly procedure for the gas chromatographic-mass spectrometric determination of caffeine in beverages. Journal of Chromatography A. 1136: 106-110 (2006)

    Article  CAS  PubMed  Google Scholar 

  • Zündorf I, Wiedenfeld H, Röder E, Dingermann T. Generation and characterization of monoclonal antibodies against the pyrrolizidine alkaloid retrorsine. Planta Medica. 64: 259-263 (1998)

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Dong-A University research fund.

Author information

Authors and Affiliations

  1. Department of Food and Biotechnology, Dong-A University, Saha-gu, Busan, 49315, Korea

    Adebayo J. Akinboye, Kiyun Kim, Seyun Choi & Joon-Goo Lee

  2. Department of Convergence Study on the Ocean Science and Technology, Korea Maritime and Ocean University, Busan, 49112, Korea

    Inho Yang

Authors
  1. Adebayo J. Akinboye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kiyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seyun Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Inho Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joon-Goo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Inho Yang or Joon-Goo Lee.

Ethics declarations

Conflicts of interest

There are no conflicts of interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Akinboye, A.J., Kim, K., Choi, S. et al. Alkaloids in food: a review of toxicity, analytical methods, occurrence and risk assessments. Food Sci Biotechnol 32, 1133–1158 (2023). https://doi.org/10.1007/s10068-023-01295-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-023-01295-0

Keywords

Search

Navigation