Traditional Knowledge in the Safety Assessment of Botanical Food Supplements

Traditional Knowledge in the Safety Assessment of Botanical Food Supplements

I. Introduction

The safety assessment of botanicals has been sub-ject of a number of publications and recommenda-tions in recent years. These publications have pro-posed flow charts for the safety assessment ofbotanicals and identified data that would berequired to perform such risk assessments.1,2,3 Animportant element, often ignored or undervalued inthe various systems proposed for the safety assess-ment, is information and experience from the tradi-tional use of the plant or plant preparation.

This paper explores the various systems proposedand aims to identify the critical and essentialrequirements that manufacturers of botanical foodsupplements should observe to verify and assurethe safety of their products.

It must be emphasized that absolute safety doesnot exist. Due to the complex nature of botanicalsand the preparations thereof, in some cases, inher-ent toxins (e.g. thujones, estragole, …) can be pres-ent. This is also well known for conventional food,which moreover is eaten in a much higher amountand on a more regular basis than botanical supple-ments. However, food is generally recognized assafe which is the consequence of knowledge gath-ered over a long time on the basis of safe use and insome cases due to specific risk management proce-dures that have evolved or been established overtime. The same applies to botanicals and botanicalpreparations for which evidence exist of a long his-tory of use. Also here, the plant part, the prepara-tion, the conditions of use, the target populationand where necessary appropriate warnings haveresulted in the safe use of these products, notwith-standing the presence of inherent toxins.

This paper is intended to provide an overview ofthe requirements for manufacturers and to demon-strate the role that traditional use can play in theassessment of the safety of botanicals or botanicalpreparations.

EFFL 5|2012 241

The role of Traditional Knowledge in the SafetyAssessment of Botanical Food Supplements –Requirements for Manufacturers

Robert Anton*, Mauro Serafini** and Luc Delmulle***

The safety assessment of botanicals has been subject of a number of publications and

recommendations in recent years. These publications have proposed flow charts for the

safety assessment of botanicals and identified data that would be required to perform

such risk assessments. An important element, often ignored or undervalued in the various

systems proposed for the safety assessment, is information and experience from the

traditional use of the plant or plant preparation.

This paper explores the various systems proposed and aims to identify the critical and

essential requirements that manufacturers of botanical food supplements should observe

to verify and assure the safety of their products.

* Faculty of Pharmacy, University of Strasbourg , Illkirch, France.Contact: Prof Dr. Em. R. Anton, 9, allée de la Robertsau F-67000Strasbourg. Email: <[email protected].>

** Department of Environmental Biology, Sapienza University Rome,Italy.

*** IFAO Proform education, Troisvierges, Luxembourg.

1 Partial agreement in the social and public health field. 2005.Guidelines on the quality, safety and marketing of plant – basedfood supplements. Council of Europe.

2 B. Schilter et al. 2003. Guidance for the safety assessment ofbotanicals and botanical preparations for use in food and foodsupplements. Food and Chemical Toxicology 41, 1625–1649.

3 European Food Safety Authority. 2009. Advice on the EFSAguidance document for the safety assessment of botanicals andbotanical preparations intended for use as food supplements,based on real case studies. EFSA Journal 7(9): 280.

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The verification process of safety and quality con-sists of five important steps:1. Characterisation of the botanicals and prepara-

tions2. Collection of bibliographic data3. Collection of information from traditional use4. Interpretation of the data5. Identification of appropriate risk management

measures to control the risk(s) identified

II. Characterisation of the botanicaland preparations.

Characterisation of the botanical is the first stepbefore data collection can be performed. This char-acterisation includes at least identification of thefamily, the botanical scientific name: genus andspecies, author name, and were relevant also thevariety, hybrid or chemotype. Also vernacularnames and synonyms must be identified. Whenpossible, information on the place of harvesting,collection date, the processing undergone (drying,fermentation, storage, treatments, ...) should beavailable as this might influence the presenceand/or the amount of specific secondary metabo-lites. For preparations, the characterisation shallamong others also include information on theextraction solvents, the ratio botanical/solvent, andon the possible addition of additives (e.g. preserva-tives, carriers, …).

Identification of the botanical and the prepara-tion should be performed in relation to the standardreferences as described for example in National orEuropean Pharmacopoeias, including morphologi-cal, microscopical and chemical identification. Thechemical profile should be defined not only forthe supposed active compounds (if known) and/ormarkers but also for those compounds which mighthave some undesirable effects. The importance ofthe family is often omitted although the plantfamily may give an indication on the possible pres-ence of potential compounds of concern typical tothat family. A list of the families and compounds isgiven in annex 1. Also the EFSA compendium4 listscompounds of concern which might be present insome plants. The compendium being only indica-tive as no assessment of the collected informationhas been done, gives nevertheless a good overviewof compounds which might be expected in someplants.

The characterisation process and criteria have ex-tensively been described in detail in different scien-tific publications.5

III. Bibliographic data collection

Manufacturers should start with a search for avail-able documentation on the botanical and botanicalpreparation) and its various uses (food, food supple-ment, herbal medicinal products).1. Documents which can be issued by national or

international regulatory bodies or competentadvisory organizations can be a good source ofinformation:

Examples:– EFSA compendium– Safety assessment reports from safety assess-

ment bodies (e.g. AFSSA, …)– National lists with allowed or prohibited botani-

cals – Reference monographs by the Council of Europe– Monographs (WHO, ESCOP, EMA, Kommission

E, American Herbal Pharmacopeia, …)– FEEDAP monographs

2. Recognized standard reference text books alsocontain substantial information on the use andsafety of botanicals

Examples:– Bruneton J. 2005. Plantes toxiques6

– Cheeke P.R. (Ed.). 1989. Toxicants of plant origin7

– Frohne D., Pfänder H.J. and Anton R. 2009.Plantes à risques8

Traditional Knowledge in the Safety Assessment of Botanical Food Supplements 242 EFFL 5|2012

4 European Food Safety Authority. 2012. Compendium of botanicalsreported to contain naturally occurring substances of possible con-cern for human health when used in food and food supplements.EFSA Journal 10(5):2663.

5 Quality Guide for Botanical Food Supplements. 2011. Guidancefor the manufacture of safe and high quality botanical foodsupplements across the EU. European Botanical Forum, 50 rue del’Association, 1000 Brussels – Belgium. ISBN: 9789081760201.

6 Bruneton J. 2005. Plantes toxiques (Végétaux dangereux pourl’homme et les animaux), Ed. Tec & Doc, Lavoisier, Paris, 3ème édition, 618 pages, ISBN: 2-7430-0806-7.

7 Cheeke P.R. (ed.). 1989. Toxicants of plant origin. Volume IV.Phenolics. CRC Press, Inc. ISBN 0-8493-6693-2.

8 Frohne D., Pfänder HJ and Anton R. 2009. Plantes à risques,Ed.Tec&Doc, Lavoisier, Paris , 460 pages, ISBN: 978-2-7430-0907-1.

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– Hagers Handbuch der Pharmazeutischen Praxis19989

– Leung A.Y. and Foster S. 1996. Encyclopedia ofcommon natural ingredients used in food, drugsand cosmetics10

– Wichtl M. and Anton R. 2003. Plantes thérapeu-tiques11

3. An extensive systematic literature search in var-ious scientific databases should be performed toidentify further information on risks, casereports of adverse effects and toxicological dataavailable. When available, pharmacological data(kinetics, dynamics) can serve as additional sup-portive information. To ensure relevant results,also a search on synonyms and common namesas well as on the relevant substances present inthe plant, must be performed. A methodologyand examples of databases that can be used inliterature search are described in the Danishdraft on ‘Guideline for safety assessment of foodsupplements, annex 2: “guideline for search cri-teria in databases etc. for safety assessments,2011”.12

Examples of databases:– Pubmed or Medline– FSTA (Food Science and Technology Abstracts)– BIOSIS Previews (BioSciences Information Ser-

vice of Biological Abstracts)– GOOGLE SCHOLAR– EFSA website– Toxnet

– MeSH database (Medical Subject Headings)– REACH (Registration, Evaluation, Authorisation

and Restriction of Chemical)– RTECS (Registry of Toxic Effects of Chemical

Substances)– GESTIS (Germans dangerous substance data-

base)– Eurofir (BioActive Substances in Food Informa-

tion System)

IV. Collection of information on thetraditional use of the botanical

The term ‘traditional use’ refers to the body of infor-mation available on how the botanical has beenused over time. This includes information on howthe botanical has been collected and treated afterharvesting, which parts have been used, how it hasbeen prepared for human consumption and theconditions under which it has been used and theevolution of these conditions over time. A frame-work on how to collect and assess the data ontraditional use has been extensively described in‘Traditional Knowledge for the Assessment ofHealth Effects for Botanicals – A Framework forData Collection’.13

Information of traditional use will only be validfor botanicals that are used in similar forms (e.g.plant part and nature of preparation) and undercomparable conditions of use. The more the pre-paration and/or the conditions of use differ fromthe one for which traditional use has been recorded,the more additional evidence on safety will berequired.

Information of traditional use is a valuable ele-ment in the safety assessment of traditionally usedbotanicals. It obviously cannot exclude that newsafety issues can emerge that have not yet beenidentified. Post marketing surveillance is thereforean essential tool, being organised by some MemberStates in a systematic way. In France, ANSESlaunched a ‘nutrivigilance’ system in 2010.14

V. Interpretation of the collected data

On the basis of the results of the data collectionstep, the manufacturer must perform an assessmentof the data in relation to a possible risk. The out-come of this assessment may be either:

EFFL 5|2012 243

9 Hagers Handbuch der Pharmazeutischen Praxis 1998. SpringerVerlag. ISBN 3-540-52688-9.

10 Leung A.Y. and Foster S. 1996. Encyclopedia of common naturalingredients used in food, drugs and cosmetics. John Wiley & Sons,Inc. ISBN 0-471-50826-8.

11 Wichtl M. and Anton R. 2003. Plantes thérapeutiques (Tradition,pratique officinale, science et thérapeutique), Ed. Tec & Doc,Lavoisier, Paris, 2ème édition, 692 pages, ISBN: 2-7430-0631-5.

12 EC Enterprise and Industry, GUIDELINE FOR SAFETY ASSESS-MENTS OF FOOD SUPPLEMENTS. 2011. Notification Number:2011/142/DK. Erhvervs- og Byggestyrelsen, Langelinie Allé 17,2100 København Ø.; available on the Internet athttp://ec.europa.eu/enterprise/tris/pisa/app/search/index.cfm?fuseaction=pisa_notif_overview&iYear=2011&inum=142&lang=EN&sNLang=EN (last accessed on 27 September 2012).

13 Robert Anton, Mauro Serafini and Luc Delmulle, “TraditionalKnowledge for the Assessment of Health Effects for Botanicals –A Framework for Data Collection”, 2 EFFL (2012), pp. 74–80.

14 ANSES. 2010. Dispositif de nutrivigilance; available on theInternet at <http://www.anses.fr/index.htm> (last accessed on27 September 2012).

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– No risk has been identifiedWhen the totality of the data does not indicatethat a specific risk has been identified, this doesnot necessarily mean that no risk exists. Thenature of the data available and the history of useneed to be assessed to ascertain that the absenceof identified risk is not linked to the absence ofdata rather than to the absence of risk.

– A defined risk has been establishedThe level of the risk and its relevance for theintended product must be assessed. Risk manage-ment measures must be identified that are able tominimize or eliminate the particular risk duringproduct development or manufacturing of theproduct.

– A defined risk has not been established, but thereare indications of potential riskIt is possible that the totality of the informationcollected gives no strong indication of a specificrisk but gives rise to uncertainty and possibilityof a potential risk.

The manufacturer must also identify potential gapsthat may exist in the overview of data collected. Ifessential information is lacking, the judgment onthe safety status of the botanical and the prepara-tion must be addressed with care and the necessarymeasures should be undertaken to complement thedata.

An assessment of the relevance of the availabledata for the product under consideration can onlybe performed in the light of information on expo-sure. The manufacturer must assess or estimateintake of the botanical, the preparation or the com-pounds of concern to assess the impact of his prod-uct on exposure from all sources, including foods,other food supplements and herbal medicinal prod-ucts.

1. No risk has been identified

In such case the quality and availability of the datawill determine if it is acceptable to conclude on thesafety of the botanical and the preparation underconsideration.

If the evidence is judged to be sufficient, thepreparation that will be marketed must be similarand its conditions of use comparable to the datapresented in the literature. In case of any change it

must be ascertained that the same data remainapplicable.

The more the preparation or conditions of usediffer from the original and/or traditional data, theless acceptable they become to support the safety ofthe preparation.

In case the data is found to be absent, insuffi-cient, anecdotal or of low quality, a full risk assess-ment is required.

2. A defined risk has been established

In case a defined risk has been established, the man-ufacturer should assess if the risk is controllableand identify appropriate risk management meas-ures. If not, the botanical, the specific plant part orpreparation should not be used in the manufactur-ing of food supplements.

In many cases, regulatory limitations mayalready be in place (e.g. maximum levels, condi-tions/restrictions of use, labeling requirements, etc).

In addition, quality assurance measures maybe applied during production to control the riskin appropriate ways (by appropriate manufacturingprocesses, by removing plant parts and/or ingredi-ents eliminated, by inactivating compounds, etc).

The control of the risk is more straightforward inthose cases where the compounds of concern can beeffectively removed or reduced to acceptable safelevels.

It is more complex in those cases where the com-pounds of concern cannot be removed, where theirremoval is not possible without losing the associ-ated beneficial effects or where the compoundscausing the risk are not known.

In such cases the nature and level of risk must beassessed in the risk assessment process.

3. A defined risk has not been established,but there are indications of a potentialrisk

Indications of the possibility of adverse effects maycome from in vitro and animal, experimental orhuman research, observational evidence or fromcase reports. In such cases there are often insuffi-cient data to confirm the nature or severity of therisk because of a number of reasons:


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– the uncertainties related to the extrapolation ofexperimental or animal data to humans;

– the uncertain relevance of challenge studiesobtained in animals with non-physiological andunrealistic amounts of the botanical, the botani-cal preparation or their compounds;

– the difficulty to ascertain that the observedadverse effects are causally linked to the intake ofthe botanical under consideration;

– the confounding factors, such as contaminantspresent, cross contamination, underlying ill-nesses, intake of medicines, etc making suchcause and effect relationship determination diffi-cult;

– the absence of matrix effects of complex plantpreparations or the botanical itself in studyresults obtained for isolated or purified com-pounds.

In such cases an appropriate risk assessment wouldneed to be performed.

Such risk assessment needs to address the natureof the data and their relevance for the human situa-tion. For adverse effects reported in case-reports,a probable cause and effect relationship must beestablished between the intake of the plant, cor-rectly identified and fully characterized, and theobserved adverse effect.

Different causality algorithms can be used. Exam-ples are the Naranjo scale,15 the Jones scale,16 theKramer scale,17 the WHO causality method18 andthe RUCAM score (Roussel Uclaf Causality Assess-ment method).19,20 The different algorithms allhave their strengths and limitations and the moredetailed the information available, the more accu-rate and reliable they are.

VI. Identification of appropriate riskmanagement measures to controlthe risks identified

Manufacturers are bound by the requirements ofthe food legislation to assure that their products aresafe.

Many safety issues can easily be controlled andeliminated by quality assurance measures when theappropriate processing and analytical controls areapplied. The following approach can be proposed toidentify these measures.

1. The compound(s) of concern is (are)known and can be eliminated.

In case a risk is flagged and the compound isknown, the chemical profile of the preparationmust be well established to identify the presenceand level of the compound(s) of concern.

If data is available on the general toxicologicalprofile of the compound(s) under consideration, thelevel of risk can be assessed and risk managementmeasures proposed where necessary.

In such a case, primary quality assurance meas-ures should be applied by avoiding the use of thebotanical part containing the compound(s) or byremoving the compound(s) by processing.

This can be achieved by various techniques, suchas drying, selective extraction, physical, chemical orenzymatic inactivation or separation techniques,etc. The absence or threshold of the toxic or unde-sirable compound(s) should be analytically verifiedwhere appropriate.

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15 Naranjo et al. 1981. A method for estimating the probability ofadverse drug reactions. Clin. Pharmacol. Ther. 30 (2): 239–245.

16 Jones, Judith K. MD,PhD . 1982. Adverse drug reactions in thecommunity health setting: approaches to recognizing, counsel-ing, and reporting. Family & Community Health, 5 (2): 58–67.

17 Kramer S. M. et al. 1979. An algorithm for the operationalassessment of adverse drug reactions. JAMA, 242 (7): 623-632.

18 WHO – UMC causality report. 2012. The use of the WHO-UMCsystem for standardised case causality assessment; available on

the Internet at http://www.who-umc.org/DynPage.aspx?id=97224&mn1=7347&mn2=7252&mn3=7257 (last accessed on27 September 2012).

19 Danan G, Benichou C. Causality assessment of adverse reactionsto drugs-I. A novel method based on the conclusions of Inter-national Consensus Meeting: application to drug-induced liverinjuries. J Clin Epidemiol 1993; 46: 1323-30.

20 Benichou C, Danan G, Flahault A. Causality assessment ofadverse reactions to drugs-II. An original model for validation ofdrug causality assessment methods: case reports with positiverechallenge. J Clin Epidemiol 1993; 46: 1331-6.

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2. The compound(s) of concern is knownand cannot be removed.

a. Legal requirements in relation to the possiblesafety concern are applicable

Such information can come from national andEuropean regulatory framework as: – National list of botanicals and their preparations

that can be used in food supplements. These listsare usually based on scientific evaluations andrisk assessments made by national agencies thatmay establish, for some of the permitted botani-cals, daily intake limits and health warnings.

– Existing labelling provisions such as composi-tional statements or compulsory indications.

– Maximum levels laid down in EU legislation(contaminants, residues, …).

When legal requirements are set, the botanicalproducts must comply with the applicable legisla-tion.

b. No legal requirements in relation to thepossible safety concern are applicable

i. The level of safety can be deduced from literature

If no legal requirements have been established,the risk assessment of a botanical or botanicalpreparation will need to be based on the followingelements:– the assessment of the data compiled, including

the quality and amount of data available• Toxicological data• Pharmacological data;

– the presence of data on the history of safe use ina sufficiently large population over a sufficientlylong time;

– the presence/absence of adverse effects describedin case reports, assessed as probably attributed tothe intake of the botanical (preparation);

– consensus in expert reports on the level of safety(presence/absence of safety concerns);

– the gaps in the data identified;– estimation of exposure;– knowledge on the profile of compounds poten-

tially present in members of the same plant fam-ily;

– the degree of similarity between the botanicalpreparation and its conditions of use with thetraditionally described ones.

The assessment of these data and information canserve as a basis for establishing the level of safety ofthe botanical or botanical preparation.

Botanical preparations can rely on informationon history of safe use when used in similar formsand under comparable conditions of use as describ-ed in the traditional information.

In principle, this implies that the botanical prepa-ration would need to be manufactured under com-parable conditions as the traditional counterpart,in terms of processing, use of solvents, extractratio, etc. When the final product is manufacturedaccording all conditions as the traditional counter-part but presented in a different galenic form(e.g. dried aqueous extract versus aqueous extract),the equivalence of that preparation to the tradi-tional one in terms of the chemical profile must bedemonstrated.

It should be noted that the principle of equiva-lence also applies to the presence of active com-pounds, if known, when traditional use is used assupportive evidence for the beneficial effect.

ii. The level of safety cannot be deduced from the literature

In case the data is found to be absent, insufficient,anecdotal or of low quality, a full risk assessmentis required. This should be done by appropriatetoxicological tests. This may include:– genotoxicity testing– subchronic toxicity testing– other studies depending on the outcome of the

genotoxicity and subchronic toxicity studies orthe nature of the risk identified (e.g. reproductivetoxicity, developmental toxicity, neurotoxicity,immunotoxicity, chronic toxicity/carcinogenicity)

Which data will be needed will depend on the dataalready available and the botanical or preparationunder consideration and will need to be addressedon a case-by-case basis. Different approaches havebeen described in the literature.

The flowchart gives a schematic representationon how to identify appropriate management meas-ures.


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Traditional Knowledge in the Safety Assessment of Botanical Food SupplementsEFFL 5|2012 247

Figure 1 Flowchart for the determination of the Risk Management Measures that need to be considered for the safe use ofbotanicals or botanical preparations in food supplements

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VII. The specific case of mixtures

A specific case is the mixtures. Traditionally, it wascommon practice to use mixtures of botanicalsrather than using one single plant. This was not fortaste or flavorings purposes but fitted in the holisticapproach where a physiological function was notseen as a stand alone function but as part of abroader system which also has to be balancedor kept in balance. As a consequence, traditionalinformation on botanical mixtures should also besearched for and taken into account.

As a general rule, when different botanicals orbotanical preparations are used together in a finalproduct a safety file must be established by themanufacturer both on the individual botanicals ason the final combination. The effects of potentialinteractions between the plants should also beaddressed. In case of safety concerns, additionaldata might be required on a case-by-case basis (seeabove). This is in particular the case when thecombination of the botanicals is likely to lead toan increased intake of specific compounds of con-cern.

VIII. Conclusion

Traditional experience is a crucial source of infor-mation to demonstrate the safety of many botani-cals and botanical preparations. It has advantagesfor both manufacturers and regulators. Whenbotanicals are used in equivalent forms and undercomparable conditions of use as described in thetraditional information and after analysis of all datagathered, it provides assurance that the botanicalor the preparation used in food supplements willnot endanger consumer health. In the absence ofreports or further information describing safetyconcerns, it may be used to avoid the need forfurther toxicological testing.

Nevertheless, when traditional use cannot suf-ficiently be justified or more recent reports ofinformation exist that has identified safetyconcerns, appropriate risk management measure-ments should be taken to eliminate or minimizea risk in order to guarantee the safety of a givenproduct. The safety assessment methodology asdescribed above is an essential part of quality asin that process the necessary measures are defined

to avoid or control an eventual botanical relatedrisk. However, to guarantee a safe and consistentproduct it must be produced according well definedspecifications at all stages of the production processfrom raw material on towards the final productand must comply with all relevant aspects of foodlegislation in terms of composition, manufactureand control.

Annex 1

Most important Plant Families, some species ofwhich are known to contain compounds, the uncon-trolled use of which might pose a risk to humanhealth. (List and compounds non exhaustive).– Acoraceae: essential oil with

methylchavicol/asarones– Aizoaceae: indole alkaloids– Amaryllidaceae: isoquinoline alkaloids– Anacardiaceae: alkenylphenols (urushiols) and

anacardic acids– Annonaceae: acetogenins/isoquinoline alkaloids– Apiaceae: polyines/furanocoumarins/carboline

and piperidine alkaloids– Apocynaceae: cardenolide glycosides/mono-

terpene indole alkaloids– Araceae: asarones– Arecaceae: pyridine and phenylethylamine

alkaloids– Aristolochiaceae: isoquinoline alkaloids/

aristolochic acids– Asclepiadaceae: cardenolides/pregnane

derivatives/steroidal alkaloids– Asparagaceae: cardenolide glycosides– Asteraceae: essential oil with bicyclic mono-

terpenes: thuyones/sesquiterpenelactones/acetylenic compounds/pyrrolizidinealkaloids

– Berberidaceae: aporphine and isoquinolinealkaloids

– Bignoniaceae: naphtoquinones– Boraginaceae: pyrrolizidine alkaloids – Brassicaceae: cucurbitacins/imidazole and

quinoline alkaloids/cardenolides/glucosinolates– Buxaceae: steroidal alkaloids with amines– Cactaceae: phenylethylamine alkaloids– Calycanthaceae: bisbenzylisoquinoline alkaloids– Campanulaceae: piperidine alkaloids/saponins– Cannabaceae: cannabinoids – Caryophyllaceae: triterpenoid saponins


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– Celastraceae: phenethylamines orarylalkylamines/cardenolides

– Chenopodiaceae: essential oil withperoxygenated monoterpene/pyridine alkaloids

– Combretaceae: cis-stilbenes/pyrrolidine alkaloids– Convolvulaceae: indolizidine and pyrrolizidine

alkaloids/lysergic derivatives/glucoresins– Crassulaceae: bufadienolides/piperidine

alkaloids– Cucurbitaceae: oxygenated tetracyclic triterpene

derivatives: cucurbitacins– Cupressaceae: lignanes and esters of diterpene

acids/essential oil: thujones– Cycadaceae: azoxymethanol derivatives/amine

oxides– Cyperaceae: sesquiterpene pyridine

alkaloids/possible contamination withergopeptines

– Dioscoreaceae: pyrridinal alkaloids/steroidalsaponins

– Ericaceae: hydroquinone derivatives/diterpenes/essential oil with methylsalicylate

– Ephedraceae: phenylethylamine alkaloids– Equisetaceae: piperidine alkaloids– Euphorbiaceae: diterpene esters/cyanogenic

glycosides/piperidine and isoquinoline alkaloids/lectins

– Fabaceae: lectins and neurotoxins/dimethyl-tryptamine derivatives/cyanogenic glycosides/isoquinoline, pyrrolizidine, indole and quino-lizidine alkaloids/rotenoids/steroidal saponins

– Fagaceae: cyanogenic glycosides/xanthinederivatives/tannins

– Gelsemiaceae: quinolizidine alkaloids/indoleand oxindole alkaloids

– Illiciaceae: sequiterpene lactones– Iridaceae: benzoquinone derivatives– Juglandaceae: naphtoquinones– Lamiaceae: pyrrolidine alkaloids/diterpenes/

essential oil with methylchavicol, camphor,1,8-cineole and methyleugenol

– Lauraceae: phenanthrenic, aporphine andisoquinoline alkaloids/essential oil withmethyleugenol/tetrahydrofuran lignans

– Liliaceae: steroidal alkaloids/essential oil withmethylchavicol/cardenolides and bufadienolides

– Loganiaceae: indole alkaloids/mono andditerpene alkaloids

– Lycopodiaceae: quinolizine and pyridinealkaloids

– Lythraceae: macrocyclic polypeptide andbiphenylquinolizidine alkaloids/naphtoquinones

– Magnoliaceae: biphenol derivatives/isoquinolinealkaloids/essential oil with methyleugenol

– Malpighiaceae: indole and tryptamine alkaloids– Meliaceae: tetranortriterpenes and alkaloids– Menispermaceae: isoquinoline and

bisbenzylisoquinoline alkaloids andfuroditerpene lactones

– Monascaceae: possible contamination withmycotoxins

– Monimiaceae: isoquinoline and aporphinealkaloids/essential oil with methyleugenol,camphor

– Moraceae: cardenolide glycosides/furanocoumarins

– Moringaceae: benzylamine alkaloids– Myoporaceae: essential oil with

furanosesquiterpenes– Myristicaceae: essential oil with myristicin

and safrole/tryptamine alkaloids/lignanes– Myrtaceae: essential oil with methylchavicol

and methyleugenol– Nyctaginaceae: quinolizidine alkaloids– Orchidaceae: phenanthraquinones– Papaveraceae: isoquinoline and

benzophenanthridine alkaloids– Passifloraceae: lectins– Piperaceae: essential oil with apiole,

methylchavicol, methyleugenol/butenolides/cyanogenic glycosides/styrylpyrones/piperidineamides/pyridine and isoquinoline alkaloids

– Poaceae: pyrrolizidine alkaloids– Punicaceae: piperidine alkaloids– Ranunculaceae: diterpenes/isoquinoline and

benzylisoquinoline alkaloids/cardenolides– Rosaceae: cyanogenic glycosides/phloroglucinol

derivatives– Rubiaceae: indolo-monoterpenic alkaloids/

anthraquinones– Rutaceae: quinoline and imidazole alkaloids/

essential oil with methylchavicol– Santalaceae: thionin proteins– Simarubaceae: anthracene derivatives/indole

alkaloids/quassinoids– Sapindaceae: xanthine derivatives/essential oil

with methylchavicol– Schizandraceae: lignans – Solanaceae: tropane, nicotinic and steroidal

alkaloids

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– Thymeleaceae: diterpenes and daphnetoxins– Verbenaceae: essential oil with methyleugenol/

diterpenes/naphtoquinones– Viscaceae: viscotoxins and lectins

– Zingiberaceae: essential oil with methyleugenoland 1,8-cineole

– Zygophyllaceae: harmane alkaloids


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