EFSA Compendium of Botanicals

Draft - work in progress

Cycas circinalis L.

Family:: Cycadaceae
Approval state:: Approved
Number of articles retrieved:: 239
Number of processed references:: 9

Compositions

#1: Methylazoxymethanol #2: Cycasin in seed #3: BMAA in seed #4: Cardiac glycosides in male coni of Cycas circinalis (qualitative data) #5: Alkaloids in male coni of Cycas circinalis (qualitative data)

Endpoint Studies

#1: Extensive liver toxicity. #2: Dietary administration of cycasin resulted in an increased occurrence of renal tumors #3: Neurotoxicity (degeneration of motor neurons) #4: Hemorrhages in the gastrointestinal tracts leading to death #5: LD50 is higher than 2000 mg/kg b.w. #6: Washed cycad flour induced symptomatic features of ALS-Parkinsonism Dementia Complex in CD-1 male mice after 30 days feeding.

Genotoxicity

#1: Mutagenicity of Cycasin Aglycone (Methylazoxymethanol)

Composition #1: Smith, David W. E. Mutagenicity of cycasin aglycon (methylazoxymethanol), a naturally occurring carcinogen. Science (Washington, DC, United States), 1966, p. 1273–1274. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Substance:

Methylazoxymethanol (RF-00011525-PAR)
Additional substance description:

resulting from deglucosylation of cycasin present in seeds
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Methylazoxymethanol

Composition #2: Kisby, Glen E., Ellison, Mike., Spencer, Peter S. Content of the neurotoxins cycasin (methylazoxymethanol β-D-glucoside) and BMAA (β-N-methylamino-L-alanine) in cycad flour prepared by Guam Chamorros. neurology, 1992, p. 1336–1340. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

80% ethanol
Substance:

Cycasin (RF-00011099-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Result unit:

Microgram/gram (G049A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.004-75.93
Internal remarks:

Cycasin in seed

Composition #3: Kisby, Glen E., Ellison, Mike., Spencer, Peter S. Content of the neurotoxins cycasin (methylazoxymethanol β-D-glucoside) and BMAA (β-N-methylamino-L-alanine) in cycad flour prepared by Guam Chamorros. neurology, 1992, p. 1336–1340. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

80% ethanol
Substance:

Beta-N-Methylamino-L-alanine Beta-N-Methylamino-L-alanine (RF-00010852-PAR)
Additional substance description:

BMAA
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Result unit:

Microgram/gram (G049A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.00-18.39
Internal remarks:

BMAA in seed

Composition #4: Senthil Kumar, B., Vijaya Kumar, J. GCMS analysis of bioactive constituents from cycas circinalis.L and Ionidium suffruticosum. Ging. international journal of pharmaceutical sciences review and research, 2014, vol. 28, no. 2, p. 197–201. .

Language:

English (en)
Plant part:

Flower (as part-nature) (A067B)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

ethanol
Substance:

cardiac glycosides (RF-00010823-PAR)
Analytical method code:

Phytochemical screening (F604A)
Analytical method - additional description:

GC-MS
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Cardiac glycosides in male coni of Cycas circinalis (qualitative data)

Composition #5: Senthil Kumar, B., Vijaya Kumar, J. GCMS analysis of bioactive constituents from cycas circinalis.L and Ionidium suffruticosum. Ging. international journal of pharmaceutical sciences review and research, 2014, vol. 28, no. 2, p. 197–201. .

Language:

English (en)
Plant part:

Flower (as part-nature) (A067B)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

ethanol
Substance:

Alkaloids (RF-00004360-PAR)
Analytical method code:

Phytochemical screening (F604A)
Analytical method - additional description:

CG-MS
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Alkaloids in male coni of Cycas circinalis (qualitative data)

Endpoint study #1: Matsumoto, Hiromu., Strong, F. M. Occurrence of methylazoxymethanol in Cycas circinalis. archives of biochemistry and biophysics, 1963, p. 299–310. .

Study relevance:

Human health
Substance:

Methylazoxymethanol (RF-00011525-PAR)
Plant part:

Seed (as part-nature) (A066P)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

ethyl-ether
Type of toxicological test:

chronic/long term toxicity (CHD004TT)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

9.0
Unit of exposure duration:

Month (G206A)
Number of organisms dosed:

3
Control groups used:

no
Endpoint measured:

Concentration level (CHD013EP)
Concentration unit:

Percent (G138A)
Effect concentration:

2.5
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

liver damage
Effect or parameter linked to the endpoint:

gross pathology (CHD022BE)
Internal remarks:

Extensive liver toxicity.

Endpoint study #2: Gusek, Wilfried., Buss, Harro., Lacqueur, G. L. Histological-histochemical tests in "interstitial cycasin tumor" in rat kidneys. beitraege zur pathologischen anatomie und allgemeinen pathologie, 1967, p. 53–74. .

Study relevance:

Human health
Substance:

Cycasin (RF-00011099-PAR)
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

21.0
Unit of exposure duration:

Day (G134A)
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

500
Critical effect:

NEPHROTOXICITY (TOX03A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

Increased occurrence of renal tumors
Effect or parameter linked to the endpoint:

Carcinogenic (CHD036BE)
Internal remarks:

Dietary administration of cycasin resulted in an increased occurrence of renal tumors

Endpoint study #3: Kurland, L.T. Amyotrophic lateral sclerosis and parkinson's disease complex on Guam linked to an environmental neurotoxin. trends in neurosciences, 1988, vol. 11, no. 2, p. 51–54. DOI: 10.1016/0166-2236(88)90163-4. [DOI link]

Study relevance:

Human health
Substance:

Beta-N-Methylamino-L-alanine Beta-N-Methylamino-L-alanine (RF-00010852-PAR)
Plant part:

Seed (as part-nature) (A066P)
Preparation/Extraction method:

Raw, no heat treatment (A07HS)
Type of toxicological test:

subchronic (CHD013TT)
Tested organism:

Rhesus monkey (as animal) (A0CNQ)
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

13.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

13
Control groups used:

yes
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

Neurologic (TT004A)
Effect description:

Cortico-neuronal dysfunction, Parkinsonian features and behavioral changes with chromatolysis and degeneration of motor neurons
Effect or parameter linked to the endpoint:

neurology (CHD027BE)
Internal remarks:

Neurotoxicity (degeneration of motor neurons)

Endpoint study #4: Yang, M.G., Mickelsen, O. Cycad husk from Guam: Its Toxicity to rats. economic botany, 1968, vol. 22, no. 2, p. 149–154. DOI: 10.1007/BF02860558. [DOI link]

Study relevance:

Human health
Plant part:

Husk (as part-nature) (A166J)
Additional plant/substance description:

seed husk
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

Rat (as animal) (A0CNV)
Strain of test organism:

Sprague-Dawley (CHD012ST)
Sex:

Male
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

10.0
Unit of exposure duration:

Day (G134A)
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent (G138A)
Effect concentration:

6-24
Critical effect:

Digestive (TOX18A)
Target tissue:

Digestive (TT002A)
Effect description:

Hemorrhages in the gastrointestinal tracts leading to death
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Hemorrhages in the gastrointestinal tracts leading to death

Endpoint study #5: Babu, S.K., Jagadesan, V.K., Ramasamy, S. An acute oral toxicity study of Cycus circinalis L and Ionidium suffruticosum (Ging) in Wister albino rats. international journal of pharmaceutical sciences review and research, 2012, vol. 17, no. 2, p. 97–100. .

Study relevance:

Human health
Plant part:

Live plants (as part-nature) (A0BA0)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

ethanol
Type of toxicological test:

acute toxicity (CHD016TT)
Guideline:

OECD Guideline 401 (Acute Oral Toxicity) (OECD718PL)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

48.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

6
Control groups used:

yes
Endpoint measured:

Lethal dose rate in 50% of experimental organisms (CHD029EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

>2000
Critical effect:

Other toxicities (TOX19A)
Effect description:

acute toxicity - LD50
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

LD50 is higher than 2000 mg/kg b.w.

Endpoint study #6: Wilson, JMB., Khabazian, I., Wong, MC., Seyedalikhani, A., Bains, JS., Pasqualotto, BA., Williams, DE., Andersen, RJ., Simpson, RJ., Smith, R., Craig, UK., Kurland, LT., Shaw, CA. Behavioral and neurological correlates of ALS-parkinsonism dementia complex in adult mice fed washed cycad flour . neuromolecular medicine, 2002, vol. 1, no. 3, p. 207–221. .

Study relevance:

Human health
Plant part:

Seed (as part-nature) (A066P)
Preparation/Extraction method:

Powder (A06JD)
Additional plant/substance description:

washed flour
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

House mouse (as animal) (A0CNT)
Strain of test organism:

CD-1 (CHD003ST)
Sex:

Male
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

30.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

7
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Grams per day (G233A)
Effect concentration:

0.5
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

neurologic: Central Nervous System (TT035A)
Effect description:

behavioural effects and neuronal degeneration (ALS-Parkinsonism Dementia Complex)
Effect or parameter linked to the endpoint:

neurology (CHD027BE)
Internal remarks:

Washed cycad flour induced symptomatic features of ALS-Parkinsonism Dementia Complex in CD-1 male mice after 30 days feeding.

Genotox #1: Smith, David W. E. Mutagenicity of cycasin aglycon (methylazoxymethanol), a naturally occurring carcinogen. Science (Washington, DC, United States), 1966, p. 1273–1274. .

Study category:

Mutagenicity
Type of toxicological test:

bacterial reverse mutation assay (CHD028TT)
Method type:

in vitro
Tested organism:

Salmonella typhimurium (as organism) (A0CPZ)
Control groups used:

yes
Endpoint measured:

DNA damage and/or repair
Is genotoxic:

Positive
Remarks on genotox study:

Mutagenicity of Cycasin Aglycone (Methylazoxymethanol)
Internal remarks:

Mutagenicity of Cycasin Aglycone (Methylazoxymethanol)
Internal ID:

CAPLUS_1966:431742