Pyrrolizidine alkaloids in food: a spectrum of potential health consequences

References

• Allen , JR , Carstens , LA and Olson , BE . 1967 . Veno-occlusive disease in Macaca speciosa monkeys . Am J Pathol , 50 : 653 – 667 .
   PubMedGoogle Scholar
• Allen , JR and Chesney , CF . 1972 . Effect of age on development of cor pulmonale in non-human primates following pyrrolizidine alkaloid intoxication . Exp Mol Pathol , 17 : 220 – 232 .
   PubMedGoogle Scholar
• Allen , JR , Hsu , I-C and Carstens , LA . 1975 . Dehydroretronecine induced rhabdomyosarcomas in rats . Cancer Res , 35 : 997 – 1002 .
   PubMed Web of Science ®Google Scholar
• Alston , NS , Morris , PA , Tanner , MS and Variend , S . 1998 . An animal model for copper-associated cirrhosis in infancy . J Pathol , 186 : 215 – 221 .
   PubMedGoogle Scholar
• Altaee , MY and Mahmood , MH . 1998 . An outbreak of veno-occlusive disease of the liver in northern Iraq . Eastern Mediterr Health J. , 4 : 142 – 148 . ; [cited 2010 Apr 9]. Available from: http://www.emro.who.int/publications/emhj/0401/22.htm/
   Google Scholar
• Anon . 2001 . Besluit van 19 januari 2001, houdende vaststelling van het Warenwetbesluit Kruidenpreparaten . Staatsblad van het Koninkrijk der Nederlanden , 56 : 1 – 12 .
   Google Scholar
• Australian Bureau of Statistics . 1995 . National Nutrition Survey , Canberra, ACT : Australian Bureau of Statistics .
   Google Scholar
• Azadbakht , M and Talavaki , M . 2003 . Qualitative and quantitative determination of pyrrolizidine alkaloids of wheat and flour contaminated with Senecio in Mazandaran Province farms . Iranian J Pharm Res , 2 : 179 – 183 .
   Google Scholar
• Beales , K , Betteridge , K , Boppré , M , Cao , Y , Colegate , SM and Edgar , JA . 2007 . “ Hepatotoxic pyrrolizidine alkaloids and their N-oxides in honey and pollen ” . In Poisonous plants: global research and solutions , Edited by: Panter , K , Wierenga , T and Pfister , J . 94 – 100 . Wallingford : CABI .
   Google Scholar
• Beales , KA , Betteridge , K , Colegate , SM and Edgar , JA . 2004 . Solid phase extraction and LCMS analysis of pyrrolizidine alkaloids in honeys . J Agric Food Chem , 52 : 6664 – 6672 .
   PubMed Web of Science ®Google Scholar
• Betteridge , K , Cao , Y and Colegate , SM . 2005 . An improved method for extraction and LCMS analysis of pyrrolizidine alkaloids and their N-oxides in honey: Application to Echium vulgare honeys . J Agric Food Chem , 53 : 1894 – 1902 .
   PubMed Web of Science ®Google Scholar
• Boppré , M , Colegate , SM and Edgar , JA . 2005 . Pyrrolizidine alkaloids of Echium vulgare honey found in pure pollen . J Agric Food Chem , 53 : 594 – 600 .
   PubMed Web of Science ®Google Scholar
• Boppré , M , Colegate , SM , Edgar , JA and Fischer , OW . 2008 . Hepatotoxic pyrrolizidine alkaloids in pollen and drying-related implications for commercial processing of bee pollen . J Agric Food Chem , 56 : 5662 – 5672 .
   PubMed Web of Science ®Google Scholar
• Bras , G , Brooks , SEH and Watler , DC . 1961 . Cirrhosis of liver in Jamaica . J Pathol Bacteriol , 82 : 503 – 512 .
   PubMedGoogle Scholar
• Bull , LB , Culvenor , CCJ and Dick , AJ . 1968 . The pyrrolizidine alkaloids. Their chemistry, pathogenicity and other biological properties , Amsterdam, , the Netherlands : North Holland .
   Google Scholar
• Bull , LB and Dick , AT . 1959 . The chronic pathological effects on the liver of the rat of the pyrrolizidine alkaloids heliotrine, lasiocarpine and their N-oxides . J Pathol Bacteriol , 78 : 483 – 502 .
   PubMedGoogle Scholar
• Bundesamt für Risiokobewertung (BfR). 2007. Salatmischung mit pyrrolizidinalkaloid-haltigem Greiskraut verunreinigt; Stellungnahme Nr. 028/2007 des BfR vom 10. January 2007 [cited 2010 Apr 9]. Available from: http://www.bfr.bund.de/cm/208/salatmischung_mit_pyrrolizidinalkaloid_haltigem_geiskraut_verunreinigt.pdf/
   Google Scholar
• Bundesanzeiger . 1992 . 17 June, 4805; cited by Dtsch Apoth Ztg . 132: , : 1406 – 1408 .
   Google Scholar
• Bundesgesetzblatt. 1994. Verordnung des Bundesministers für Gesundheit und öffentlicher Dienst vom 5. Mai 1989 betreffend Arzneimittel, die nicht in Verkehr gebracht werden dürfen. 555/1994. Vienna (Austria): Bundesgesetzblatt
   Google Scholar
• Burkhardt , A and Klöppel , G . 1977 . Unusual obliterative disease of the hepatic veins in an infant . Virchow Arch A Path Anat Histol , 375 : 225 – 232 .
   PubMedGoogle Scholar
• Burns , J . 1972 . The heart and pulmonary arteries in rats fed on Senecio jacobaea . J Pathol , 106 : 187 – 194 .
   PubMedGoogle Scholar
• Candrian , U , Zweifel , U , Ruthy , J and Schlatter , C . 1991 . Transfer of orally administered [3H] seneciphylline into cow's milk . J Agric Food Chem , 39 : 930 – 933 .
   Web of Science ®Google Scholar
• Cao , Y , Colegate , SM and Edgar , JA . 2008 . Safety assessment of food and herbal products containing hepatotoxic pyrrolizidine alkaloids: interlaboratory consistency and the importance of N-oxide determination . Phytochem Anal , 19 : 526 – 533 .
   PubMed Web of Science ®Google Scholar
• Chan , PC , Haseman , JK , Prejean , JD and Nyska , A . 2003 . Toxicity and carcinogenicity of riddelliine in rats and mice . Toxicol Lett , 144 : 295 – 311 .
   PubMed Web of Science ®Google Scholar
• Chen , EP , Bittner , HB , Craig , DM , Davis , RD and van Trigt , P . 1997 . Pulmonary hemodynamics and blood flow characteristics in chronic pulmonary hypertension . Ann Thorac Surg , 63 : 806 – 813 .
   PubMedGoogle Scholar
• Chesney , CF and Allen , JR . 1973a . Monocrotaline induced pulmonary vascular lesions in non-human primates . Cardiovasc Res , 7 : 508 – 518 .
   PubMed Web of Science ®Google Scholar
• Chesney , CF and Allen , JR . 1973b . Endocardial fibrosis associated with monocrotaline induced pulmonary hypertension in non-human primates (Macaca arctoides) . Am J Vet Res , 34 : 1577 – 1581 .
   PubMed Web of Science ®Google Scholar
• Chou , MW , Wang , JY , Yang , Y-C , Beger , RD , Williams , LD , Doerge , DR and Fu , PP . 2003 . Riddelliine N-oxide is a phytochemical and mammalian metabolite with genotoxic activity that is comparable to the parent pyrrolizidine alkaloid riddelliine . Toxicol Lett , 145 : 239 – 247 .
   PubMed Web of Science ®Google Scholar
• Committee on Toxicity (COT). 2008. Committee on Toxicity of chemicals in food, consumer products and the environment. COT statement on pyrrolizidine alkaloids in food; [cited 2010 Apr 9]. Available from: http://cot.food.gov.uk/pdfs/cotstatementpa200806.pdf/
   Google Scholar
• Coulombe , RA . 2003 . Pyrrolizidine alkaloids in food . Adv Food Nutr Res , 45 : 61 – 99 .
   PubMedGoogle Scholar
• Craig , AM , Pearson , EG , Meyer , C and Schmitz , JA . 1991 . Serum liver enzyme and histopathologic changes in calves with chronic and chronic-delayed Senecio jacobaea toxicosis . Am J Vet Res , 52 : 1969 – 1978 .
   PubMedGoogle Scholar
• Crews , C , Berthiller , F and Krska , R . 2010 . Update on analytical methods for toxic pyrrolizidine alkaloids . Anal Bioanal Chem , 396 : 327 – 338 .
   PubMed Web of Science ®Google Scholar
• Crews , C , Startin , JR and Clarke , PA . 1997 . Determination of pyrrolizidine alkaloids in honey from selected sites by solid phase extraction and HPLC-MS . Food Addit Contam , 14 : 419 – 428 .
   PubMedGoogle Scholar
• Culvenor , CCJ . 1983 . Estimated intakes of pyrrolizidine alkaloids by humans: a comparison with dose rates causing tumours in rats . J Toxicol Environ Health , 11 : 625 – 635 .
   PubMed Web of Science ®Google Scholar
• Culvenor , CCJ , Clarke , M , Edgar , JA , Frahn , JL , Jago , MV , Peterson , JE and Smith , LW . 1980 . Structure and toxicity of the alkaloids of Russian comfey (Symphytum × uplandicum Nyman), a medicinal herb and item of human diet . Experientia , 36 : 377 – 389 .
   PubMedGoogle Scholar
• Culvenor , CCJ , Edgar , JA , Jago , MV , Outteridge , A , Peterson , JE and Smith , LW . 1976 . Hepato-toxic and pneumotoxicity of pyrrolizidine alkaloids and derivatives in relation to molecular structure . Chem Biol Interact , 12 : 299 – 324 .
   PubMed Web of Science ®Google Scholar
• Culvenor , CCJ , Edgar , JA and Smith , LW . 1981 . Pyrrolizidine alkaloids in honey from Echium plantagineum L . J Agric Food Chem , 29 : 958 – 960 .
   PubMed Web of Science ®Google Scholar
• Culvenor , CCJ , Edgar , JA , Smith , LW and Tweedale , HJ . 1969 . Dihydropyrrolizine analogues of pyrrolizidine alkaloids . Aust J Chem , 41 : 3599 – 3602 .
   Google Scholar
• Culvenor , CCJ , Edgar , JA , Smith , LW and Tweedale , HJ . 1970 . Dihydropyrrolizines III. Preparation and reactions of derivatives related to pyrrolizidine alkaloids . Aust J Chem , 23 : 1853 – 1867 .
   Web of Science ®Google Scholar
• Curtain , CC and Edgar , JA . 1976 . The binding of dehydroheliotridine to DNA and the effect of it and other compounds on repair synthesis in main and satellite band DNA . Chem Biol Interact , 13 : 243 – 256 .
   PubMedGoogle Scholar
• Danks , DM . 1991 . Copper and liver disease . Eur J Pediatr , 150 : 142 – 148 .
   PubMed Web of Science ®Google Scholar
• Daughton , CG . 2005 . Overlooked in Fallon? . Environ Health Perspect , 113 : A224
   Google Scholar
• De Jonge , ME , Huitema , ADR , Beijnen , JH and Rodenhuis , S . 2006 . High exposures to bioactivated cyclophosphamide are related to the occurrence of veno-occlusive disease of the liver following high-dose chemotherapy . Br J Cancer , 94 : 1226 – 1230 .
   PubMed Web of Science ®Google Scholar
• Deinzer , ML , Arbogast , BL and Buhler , DR . 1982 . Gas chromatographic determination of pyrrolizidine alkaloids in goat's milk . Anal Chem , 54 : 1811 – 1814 .
   Web of Science ®Google Scholar
• Deinzer , ML , Thomson , PA , Burgett , DM and Isaacson , DL . 1977 . Pyrrolizidine alkaloids: their occurrence in honey from tansy ragwort (Senecio jacobaea L.) . Science , 195 : 497 – 499 .
   PubMed Web of Science ®Google Scholar
• Dickinson , JO , Cooke , MP , King , RR and Mohamed , PA . 1976 . Milk transfer of pyrrolizidine alkaloids in cattle . J Am Vet Med Assoc , 169 : 1192 – 1196 .
   PubMed Web of Science ®Google Scholar
• Dickinson , JO and King , RR . 1978 . “ The transfer of pyrrolizidine alkaloids from Senecio jacobaea into the milk of lactating cows and goats ” . In Effects of poisonous plants on livestock , Edited by: Keeler , RF , Van Kampen , KR and James , LF . 201 – 208 . New York, NY : Academic Press .
   Google Scholar
• Dübecke , A , Beckh , G and Lüllmann , C . 2011 . Pyrrolizidine alkaloids in honey and bee pollen . Food Addit Contam , 28 ( 3 ) : 348 – 358 .
   Web of Science ®Google Scholar
• Eastman , DF , Dimenna , GP and Segall , HJ . 1982 . Covalent binding of two pyrrolizidine alkaloids, senecionine and seneciphylline, to hepatic macromolecules and their distribution, excretion, and transfer into milk of lactating mice . Drug Metabol Dispos , 10 : 236 – 240 .
   PubMed Web of Science ®Google Scholar
• Edgar , JA . 2003 . Pyrrolizidine alkaloids and food safety . Chem Austral , 70 : 4 – 7 .
   Google Scholar
• Edgar , JA , Roeder , E and Molyneux , RJ . 2002 . Honey from plants containing pyrrolizidine alkaloids: a potential threat to health . J Agric Food Chem , 50 : 2719 – 2730 .
   PubMed Web of Science ®Google Scholar
• Edgar , JA and Smith , LW . 2000 . “ Transfer of pyrrolizidine alkaloids into eggs: food safety implications ” . In Natural and selected synthetic toxins, biological implications. ACS Symposium Series 745 , Edited by: Tu , AT and Gaffield , W . 118 – 128 . Washington, DC : American Chemical Society .
   Google Scholar
• Eröksüz , H , Eröksüz , Y , Özer , H , Yaman , I , Tosun , F , Akyüz Kizilay , C and Tamer , U . 2003 . Toxicity of Senecio vernalis to laying hens and evaluation of residues in eggs . Vet Hum Toxicol , 45 : 76 – 80 .
   PubMedGoogle Scholar
• European Food Safety Authority (EFSA). 2007. Opinion of the scientific panel on contaminants in the food chain on a request from the European Commission related to pyrrolizidine alkaloids as undesirable substances in animal feed. EFSA J. 447:1–51; [cited 2010 Apr 9]. Available from: http://www.efsa.europa.eu/en/scdocs/doc/447.pdf/
   Google Scholar
• Farrington , KJ and Gallagher , CH . 1960 . Complexes of copper with some pyrrolizidine alkaloids and with some of their esterifying acids . Aust J Biol Sci , 13 : 600 – 603 .
   Google Scholar
• Fishman , AP . 1974 . Dietary pulmonary hypertension . Circ Res , 35 : 657 – 660 .
   PubMed Web of Science ®Google Scholar
• Fletcher , MT , McKenzie , RA , Reichmann , KG and Blaney , BJ . 2011 . Risks from plants containing pyrrolizidine alkaloids for livestock and meat quality in northern Australia , In : Riet-Correa F, Pfister J, Schild AL, Wierenga T, editors. . Poisonings by plants, mycotoxins and related toxins. Wallingford, UK: CAB International. p. 208–218
   Google Scholar
• Food Standards Australia New Zealand (FSANZ). 2001. Pyrrolizidine alkaloids in food. A toxicological review and risk assessment. Technical Report Series No. 2. Canberra (ACT): FSANZ; [cited 2010 Apr 9]. Available from: http:www.foodstandards.gov.au/_srcfiles/TR2.pdf/
   Google Scholar
• Food Standards Australia New Zealand (FSANZ). 2004. Consumers advised to limit consumption of Paterson's Curse/Salvation Jane honey, Fact sheet 9 February 2004, Canberra (ACT): FSANZ; [cited 2010 Apr 9]. Available from: http://www.foodstandards.gov.au/scienceandeducation/factsheets/factsheets2004/consumersadvisedtoli2347.cfm/
   Google Scholar
• Györika , S and Stricker , H . 2009 . Severe pulmonary hypertension possibly due to pyrrolizidine alkaloids in polyphytotherapy . Swiss Med Wkly , 139 : 210 – 211 .
   PubMedGoogle Scholar
• Harding , JDJ , Lewis , G , Done , JT and Allcroft , R . 1964 . Experimental poisoning by Senecio jacobaea in pigs . Pathol Vet , 1 : 204 – 220 .
   Google Scholar
• Hartmann , T . 1999 . Chemical ecology of pyrrolizidine alkaloids . Planta , 207 : 483 – 495 .
   Web of Science ®Google Scholar
• Heath , D , Shaba , J , Williams , A , Smith , P and Kombe , A . 1975 . A pulmonary hypertension-producing plant from Tanzania . Thorax , 30 : 399 – 404 .
   PubMedGoogle Scholar
• Heberer , T , Lahrssen-Wiederholt , M , Schafft , H , Abraham , K , Pzyrembel , H , Henning , KJ , Schauzu , M , Braeunig , J , Goetz , M , Niemann , L , Gundert-Remy , U , Luch , A , Appel , B , Banasiak , U , Böl , GF , Lampen , A , Wittkowski , R and Hensel , A . 2007 . Zero tolerances in food and animal feed – are there any scientific alternatives? A European point of view on an international controversy . Toxicol Lett , 175 : 118 – 135 .
   PubMed Web of Science ®Google Scholar
• Hirono , I , Mori , H and Haga , M . 1978 . Carcinogenic activity of Symphytum officinale . J Natl Cancer Inst , 61 : 865 – 869 .
   PubMed Web of Science ®Google Scholar
• Hirono , I , Shimizu , M , Fushimi , K , Mori , H and Kato , K . 1973 . Carcinogenic activity of Petasites japonicus Maxim, a kind of coltsfoot . Gann Monogr Cancer Res , 64 : 527 – 528 .
   PubMedGoogle Scholar
• Howell , JM , Deol , HS , Thomas , JB and Dorling , PR . 1991 . Experimental copper and heliotrope poisoning in sheep: morphological changes . J Comp Pathol , 105 : 49 – 74 .
   PubMedGoogle Scholar
• Huxtable , RJ . 1989 . “ Human health implications of pyrrolizidine alkaloids and herbs containing them ” . In Toxicants of plant origin , Edited by: Cheeke , PR . Vol. 1 , 42 – 86 . Boca Raton, FL : CRC Press .
   Google Scholar
• Huxtable , RJ and Awang , DVC . 1990 . Pyrrolizidine poisoning . Am J Med , 89 : 547 – 548 .
   PubMedGoogle Scholar
• Huxtable , RJ , Ciaramitaro , D and Eisenstein , D . 1978 . The effect of a pyrrolizidine alkaloid, monocrotaline and a pyrrole, dehydroretronecine, on the biochemical functions of the pulmonary endothelium . Mol Pharmacol , 14 : 1189 – 1203 .
   PubMed Web of Science ®Google Scholar
• Integrated Regional Information Networks (IRIN). 2008. ‘Charmak’ still killing people, livestock in West. 16 December. Kabul (Afghanistan): IRIN, UN Office for the Coordination of Humanitarian Affairs; [cited 2010 Apr 9]. Available from: http://www.irinnews.org/Report.aspx?ReportId=81971/
   Google Scholar
• International Programme on Chemical Safety (IPCS). 1988. Pyrrolizidine alkaloids. Environmental Health Criteria 80. Geneva (Switzerland): WHO; [cited 2010 Apr 9]. Available from: http://www.inchem.org/documents/ehc/ehc/ehc080.htm/
   Google Scholar
• Jago , MV . 1969 . The development of the hepatic megalocytosis of chronic pyrrolizidine alkaloid poisoning . Am J Pathol , 56 : 405 – 422 .
   PubMed Web of Science ®Google Scholar
• Jago , MV , Edgar , JA , Smith , LW and Culvenor , CCJ . 1970 . Metabolic conversion of heliotridine-based pyrrolizidine alkaloids to dehydroheliotridine . Mol Pharmacol , 6 : 402 – 406 .
   PubMed Web of Science ®Google Scholar
• Johnson , AE . 1976 . Changes in calves and rats consuming milk from cows fed chronic lethal doses of Senecio jacobaea (tansy ragwort) . Am J Vet Res , 37 : 107 – 110 .
   PubMed Web of Science ®Google Scholar
• Kay , JM , Heath , D , Smith , P , Bras , G and Summerell , J . 1971 . Fulvine and pulmonary circulation . Thorax , 26 : 249 – 261 .
   PubMed Web of Science ®Google Scholar
• Kazumoto , M , Shimizu , A , Takase , K , Nakano , T and Tameda , Y . 1997 . Asymptomatic primary pulmonary hypertension associated with liver cirrhosis . J Gastroenterol , 32 : 102 – 104 .
   PubMedGoogle Scholar
• Kempf , M , Beuerle , T , Bühringer , M , Denner , M , Trost , D , von der Ohe , K , Bhavanam , BR and Schreier , P . 2008 . Pyrrolizidine alkaloids in honey: risk analysis by gas-chromatography-mass spectrometry . Mol Nutr Food Res , 52 : 1193 – 1200 .
   PubMed Web of Science ®Google Scholar
• Kempf , M , Heil , S , Hasslauer , I , Schmidt , L , von der Ohe , K , Theuring , C , Reinhard , A , Scheier , P and Beulerle , T . 2010 . Pyrrolizidine alkaloids in pollen and pollen products . Mol Nutr Food Res , 54 : 1 – 9 .
   Google Scholar
• Krell , R . 1996. Value-added products from beekeeping. FAO Agricultural Service Bulletin No. 124; [cited 2010 Apr 9]. Chapter 3. Available from: http://www.fao.org/docrep/w0076E/w0076e00.HTM/
   Google Scholar
• Lanigan , GW . 1976 . Peptococcus heliotrinreducans sp. nov., a cytochrome-reducing anaerobe which metabolizes pyrrolizidine alkaloids . J Gen Microbiol , 94 : 1 – 10 .
   PubMedGoogle Scholar
• Lüthy , J , Heim , TH and Schlatter , CH . 1983 . Transfer of [3H] pyrrolizidine alkaloids from Senecio vulgaris L. and metabolites into rat milk and tissues . Toxicol Lett , 17 : 283 – 288 .
   PubMed Web of Science ®Google Scholar
• Mattocks , AR . 1986 . Chemistry and toxicology of pyrrolizidine alkaloids , London, , UK : Academic Press .
   Google Scholar
• Mattocks , AR and Driver , HE . 1983 . A comparison of the pneumotoxicity of some pyrrolic esters and similar compounds analogous to pyrrolizidine alkaloid metabolites given intravenously to rats . Toxicol , 27 : 159 – 177 .
   PubMedGoogle Scholar
• Mattocks , AR and White , INH . 1976 . The distribution of [3H] synthanecine A bis-N-ethylcarbamate and its metabolites in the rat . Chem Biol Interact , 15 : 173 – 184 .
   PubMed Web of Science ®Google Scholar
• Mayer , F and Lüthy , J . 1993 . Heliotrope poisoning in Tadjikistan . Lancet , 342 : 246 – 247 .
   PubMedGoogle Scholar
• McDonnell , PJ , Toye , PA and Hutchens , GM . 1983 . Primary pulmonary hypertension and cirrhosis: are they related? . Am Rev Respir Dis , 127 : 437 – 441 .
   PubMed Web of Science ®Google Scholar
• McLean , EK . 1970 . The toxic actions of pyrrolizidine (Senecio) alkaloids . Pharmacol Rev , 22 : 429 – 483 .
   PubMedGoogle Scholar
• Ministry of Agriculture, Fisheries and Food (MAFF). 1995. Surveillance of pyrrolizidine alkaloids in honey. Joint Food Safety and Standards Group Food Surveillance Information Sheet 52. London (UK): MAFF; [cited 2010 Apr 10]. Available from: http://archive.food.gov.uk/maff/archive/food/infsheet/1995/no52/52honey.htm/
   Google Scholar
• Molyneux , RJ , Gardner , DL , Colegate , SM and Edgar , JA . 2011. Pyrrolizidine alkaloid toxicity in livestock: a paradigm for human poisoning? Food Addit Contam. 28(3):293–307
   Google Scholar
• Molyneux , RJ and James , LF . 1990 . Pyrrolizidine alkaloids in milk: thresholds of in toxication . Vet Hum Toxicol , 32 ( suppl. ) : 94S – 103S .
   PubMedGoogle Scholar
• Molyneux , RJ , Johnson , AE , Olson , JD and Baker , DC . 1991 . Toxicity of pyrrolizidine alkaloids from Riddell groundsel (Senecio riddellii) to cattle . Am J Vet Res , 52 : 146 – 151 .
   PubMed Web of Science ®Google Scholar
• Molyneux , RJ , Johnson , AE and Stuart , LD . 1988 . Delayed manifestation of Senecio-induced pyrrolizidine alkaloidosis in cattle: case reports . Vet Hum Toxicol , 30 : 201 – 205 .
   PubMedGoogle Scholar
• Morris , P , O’Neil , D and Tanner , S . 1994 . Synergistic liver toxicity of copper and retrorsine in the rat . J Hepatol , 21 : 735 – 742 .
   PubMed Web of Science ®Google Scholar
• Müller , T , Müller , W and Feichtinger , H . 1998 . Idiopathic copper toxicoses . Am J Clin Nutr , 67 ( suppl. ) : 1082S – 1086S .
   Google Scholar
• Müller-Höcker , J , Weiss , M , Meyer , U , Schramel , P , Wiebecke , B , Belohradsky , BH and Hübner , G . 1987 . Fatal copper storage disease of the liver in a German infant resembling Indian childhood cirrhosis . Virchows Arch A , 411 : 379 – 385 .
   Web of Science ®Google Scholar
• National Toxicology Program (NTP). 2008. Final report on carcinogens background document for riddelliine. Washington (DC): US Department of Health and Human Services, National Toxicology Program; [cited 2010 Apr 9]. Available from: http://ntp.niehs.nih.gov/files/Riddelliine-FINAL_%2811_Aug_2008%29_508.pdf/
   Google Scholar
• National Toxicology Program (NTP). 2009. Candidate substances for 12th RoC. Washington (DC): US Department of Health and Human Services, National Toxicology Program; [cited 2010 Apr 9]. Available from: http://ntp.niehs.nih.gov/index.cfm?objectid=BD1A20B5-F1F6-975E-7CF8CBFACF0FC7EF
   Google Scholar
• Newberne , PM and Rogers , AE . 1973 . Nutrition, monocrotaline and aflatoxin B1 in liver carcinogenesis . Plant Food Man , 1 : 23 – 31 .
   Google Scholar
• Nolan , JP , Scheig , RL and Klatskin , G . 1966 . Delayed hepatitis and cirrhosis in weanling rats following a single small dose of the Senecio alkaloid, lasiocarpine . Am J Pathol , 49 : 129 – 151 .
   PubMedGoogle Scholar
• Percy , J and Pierce , AE . 1971 . Immunosuppressive activity of the pyrrolizidine alkaloid metabolite dehydroheliotridine . Immunology , 21 : 273 – 280 .
   PubMedGoogle Scholar
• Peterson , JE , Jago , MV , Reddy , JK and Jarrett , RG . 1983 . Neoplasia and chronic disease associated with the prolonged administration of dehydroheliotridine to rats . J Nat Cancer Inst , 70 : 381 – 386 .
   PubMed Web of Science ®Google Scholar
• Peterson , JE , Samuel , A and Jago , MV . 1972 . Pathological effects of dehydroheliotridine, a metabolite of heliotridine-based pyrrolizidine alkaloids in the young rat . J Pathol , 107 : 175 – 189 .
   PubMedGoogle Scholar
• Porter , H . 1966 . “ The tissue copper proteins: cerebrocupien, erythrocuprein, hepatocuprein, and neonatal hepatic mitochondrocuprein ” . In The biochemistry of copper. Proceedings of the Symposium on Copper in Biological Systems , Edited by: Peisach , J , Aisen , P and Blumberg , WE . 159 – 174 . New York, NY : Academic Press .
   Google Scholar
• Prakash , AS , Pereira , TN , Reilly , PEB and Seawright , AA . 1999 . Pyrrolizidine alkaloids in human diet . Mutation Res , 443 : 53 – 67 .
   PubMed Web of Science ®Google Scholar
• Price , LA , Walker , NI , Clague , AE , Pullen , ID , Smits , SJ , Ong , T-H and Patrick , M . 1996 . Chronic copper toxicosis presenting as liver failure in an Australian child . Pathol , 28 : 316 – 320 .
   PubMed Web of Science ®Google Scholar
• Rabinovitch , M . 2001 . Pathology of pulmonary hypertension . Prog Ped Cardiol , 12 : 223 – 247 .
   Google Scholar
• Rasenack , R , Müller , C , Kleinschmidt , M , Rasenack , J and Wiedenfeld , H . 2003 . Veno-occlusive disease in a fetus caused by pyrrolizidine alkaloids of food origin . Fetal Diagn Ther , 18 : 223 – 225 .
   PubMed Web of Science ®Google Scholar
• Rijksinstituut voor Volksgezondheid en Milieu (RIVM). 2007. Risicobeoordeling inzake de Aanwezigheid van Pyrrolzidine Alkaloiden in Honing. Wageningen (the Netherlands): RIVM; [cited 2010 Apr 9]. Available from: http://www.vwa.nl/actueel/bestanden/fileitem/22703
   Google Scholar
• Roitman , JN . 1983 . “ Ingestion of pyrrolizidine alkaloids: a health hazard of global proportions ” . In Xenobiotics in foods and feeds , Edited by: Findlay , JW and Schwass , DE . 345 – 376 . Washington, DC : American Chemical Society .
   Google Scholar
• Roth , RA and Ganey , PE . 1988 . Platelets and the puzzles of pulmonary pyrrolizidine poisoning . Toxicol Appl Pharmacol , 93 : 463 – 471 .
   PubMedGoogle Scholar
• Roulet , M , Laurini , R , Rivier , L and Calame , A . 1988 . Hepatic veno-occlusive disease in newborn infant of a woman drinking herbal tea . J Pediatr , 112 : 433 – 436 .
   PubMed Web of Science ®Google Scholar
• Scheinberg , IH and Sternlieb , I . 1994 . Is non-Indian childhood cirrhosis caused by excess dietary copper? . Lancet , 344 : 1002 – 1004 .
   PubMed Web of Science ®Google Scholar
• Schoental , R . 1959 . Liver lesions in young rats suckled by mothers treated with the pyrrolizidine (Senecio) alkaloids, lasiocarpine, and retrorsine . J Pathol Bacteriol , 77 : 485 – 504 .
   PubMedGoogle Scholar
• Schoental , R . 1963 . Liver disease and ‘natural’ hepatotoxins . Bull Wld Hlth Org , 29 : 823 – 833 .
   PubMed Web of Science ®Google Scholar
• Schoental , R . 1968 . Toxicology and carcinogenic action of pyrrolizidine alkaloids . Cancer Res , 28 : 2237 – 2246 .
   PubMed Web of Science ®Google Scholar
• Seawright , AA . 1994 . “ Toxic plant residues in meat ” . In Plant-associated toxins; agricultural, phytochemical and ecological aspects , Edited by: Colegate , SM and Dorling , PR . 77 – 84 . Wallingford, , UK : CAB International .
   Google Scholar
• Seibold-Weiger , K , Vochem , M , Mackensen-Haen , S and Speer , C . 1997 . Fatal hepatic veno-occlusive disease in a newborn infant . Am J Perinatol , 14 : 107 – 111 .
   PubMedGoogle Scholar
• Sergi , C , Beedgen , B , Linderkamp , O and Hofmann , WJ . 1999 . Fatal course of veno-occlusive disease of the liver (Endophlebitis Hepatica obliterans) in a preterm infant . Pathol Res Pract , 195 : 847 – 851 .
   PubMedGoogle Scholar
• Shevchenko , NK and Fakhrutdinova , SS . 1971 . Assessment of meat and milk in cases of Trichodesma poisoning . Veterinariya , 8 : 104 – 105 .
   PubMedGoogle Scholar
• Shumaker , RC , Robertson , KA , Hsu , IC and Allen , JR . 1976 . Neoplastic transformation in tissues of rats exposed to monocrotaline or dehydroretronecine . J Natl Cancer Inst , 56 : 787 – 789 .
   PubMed Web of Science ®Google Scholar
• Simonneau , G , Galie , N , Rubin , LJ , Langleben , D , Seeger , W , Domenighetti , G , Gibbs , S , Lebrec , D , Speich , R , Beghetti , M , Rich , S and Fishman , A . 2004 . Clinical classification of pulmonary hypertension . J Am Coll Cardiol , 43 ( suppl. S ) : 5 – 12 .
   PubMedGoogle Scholar
• Smith , LW and Culvenor , CCJ . 1981 . Plant sources of hepatotoxic pyrrolizidine alkaloids . J Nat Prod , 44 : 129 – 152 .
   PubMed Web of Science ®Google Scholar
• St George-Grambauer , TD and Rac , R . 1962 . Hepatogenous chronic copper poisoning in sheep in South Australia due to consumption of Echium plantagineum (Salvation Jane) . Aust Vet J , 30 : 288 – 293 .
   Google Scholar
• Steyn , DG . 1933 . Poisoning of human beings by weeds contained in cereals (Bread Poisoning) . Onderstepoort J Vet Sci Anim Indust , 1 : 219 – 266 .
   Google Scholar
• Stuart , KL and Bras , G . 1957 . Veno-occlusive disease of the liver . Queensland J Med , 26 : 291 – 315 .
   Google Scholar
• Sun , PS , Hsia , M-TS , Chu , FS and Allen , JR . 1977 . Inhibition of yeast alcohol dehydrogenase by dehydroretronecine . Food Cosmet Toxicol , 15 : 419 – 422 .
   PubMedGoogle Scholar
• Svoboda , DJ and Reddy , JK . 1972 . Malignant tumors in rats given lasiocarpine . Cancer Res , 32 : 908 – 912 .
   PubMed Web of Science ®Google Scholar
• Tandon , BN , Tandon , RK , Tandon , HD , Narndranathan , M and Joshi , YK . 1976a . An epidemic of veno-occlusive disease of liver in central India . Lancet , ii : 271 – 272 .
   Google Scholar
• Tandon , RK , Tandon , BN , Tandon , HD , Bhatia , ML , Bhargava , S , Lal , P and Arora , RR . 1976b . Study of an epidemic of venoocclusive disease in India . Gut , 17 : 849 – 855 .
   PubMedGoogle Scholar
• Tanner , MS . 1998 . Role of copper in Indian childhood cirrhosis . Am J Clin Nutr , 67 ( suppl. ) : 1074S – 1081S .
   Google Scholar
• Trollmann , R , Neureiter , D , Lang , T , Dörr , HG and Behrens , R . 1999 . Late manifestation of Indian childhood cirrhosis in a 3-year-old German girl . Eur J Pediatr , 158 : 375 – 378 .
   PubMed Web of Science ®Google Scholar
• Van Egmond H, Schothorst R, van den Top H. Forthcoming 2011. Pyrrolizidine alkaloids: the Afghanistan incident. Paper presented at: The meeting on pyrrolizidine alkaloids; Brussels. Submitted for publication in Food Addit Contam
   Google Scholar
• Walker-Smith , J and Blomfield , J . 1973 . Wilson's disease or chronic copper poisoning? . Arch Dis Childhood , 48 : 476 – 479 .
   PubMed Web of Science ®Google Scholar
• Wang , Y-P , Yan , J , Fu , PP and Chou , MW . 2005 . Human liver microsomal reduction of pyrrolizidine alkaloid N-oxides to form the corresponding carcinogenic parent alkaloid . Toxicol Lett , 155 : 411 – 420 .
   PubMed Web of Science ®Google Scholar
• Wiedenfeld , H , Roeder , E , Bourauel , T and Edgar , J . 2008 . Pyrrolizidine alkaloids. Structure and toxicity , Göttingen, Germany : V&R Unipress, Bonn University Press .
   Google Scholar
• Xia , Q , Chou , MW , Kadlubar , FF , Chan , P and Fu , PP . 2003 . Human liver microsomal metabolism and DNA adduct formation of the tumorigenic pyrrolizidine alkaloid, riddelliine . Chem Res Toxicol , 16 : 66 – 73 .
   PubMed Web of Science ®Google Scholar
• Yee , SB , Kinser , S , Hill , DA , Barton , CC , Hotckkiss , JA , Harkema , JR , Ganey , PE and Roth , RA . 2000 . Synergistic hepatotoxicity from coexposure to bacterial endotoxin and the pyrrolizidine alkaloid monocrotaline . Toxicol Appl Pharmacol , 166 : 173 – 185 .
   PubMed Web of Science ®Google Scholar