EFSA Compendium of Botanicals

Draft - work in progress

Xanthium strumarium L.

Family:: Asteraceae
Approval state:: Approved
Number of articles retrieved:: 2229
Number of processed references:: 12

Compositions

#1: protocatechuic acid in fruits #2: sesquiterpene lactones (xanthinin, xanthanol, xanthatin, xanthumin, xanthumanol, xanthinosin) in leaves #3: Xanthanolide sesquiterpene lactones (8-epi-xanthine and 8-epi-xanthine epoxide) in leaves #4: Atractyloside in fruits #5: cyanogenic glucosides in seeds

Endpoint Studies

Genotoxicity

#1: significant increase of Sister Chromatid Exchanges (mutagenicity) #2: increase in the percentage of chromosomal aberrations (genotoxicity) #3: hedgehog or apoptotic-like cells observed, DNA primary damage (both single- and double-strand breaks)(genotoxicity)

Composition #1: Hwang, Seung Hwan., Wang, Zhiqiang., Yoon, Ha Na., Lim, Soon Sung. Xanthium strumarium as an Inhibitor of alpha-Glucosidase, Protein Tyrosine Phosphatase 1beta, Protein Glycation and ABTS(+) for Diabetic and Its Complication. . molecules (basel, switzerland), 2016, vol. 21, no. 9 . DOI: 10.3390/molecules21091241. [DOI link]

Language:

English (en)
Plant part:

Fruit unspecified (as part-nature) (A067D)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

CH2Cl2
Substance:

3,4-Dihydroxybenzoic acid (RF-00008853-PAR)
Analytical method code:

Nuclear Magnetic Resonance (NMR) (F061A)
Analytical method - additional description:

LC-ESI-MS
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

protocatechuic acid in fruits

Composition #2: McMillan, C., Chavez, P.I., Mabry, T.J. Sesquiterpene lactones of Xanthium strumarium in a texas population and in experimental hybrids. biochemical systematics and ecology, 1975, vol. 3, no. 3, p. 137–141. DOI: 10.1016/0305-1978(75)90017-4. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

CHCL3
Substance:

Sesquiterpene lactones (RF-00004319-PAR)
Additional substance description:

xanthinin, xanthanol, xanthatin, xanthumin, xanthumanol, xanthinosin
Analytical method code:

Nuclear Magnetic Resonance (NMR) (F061A)
Analytical method - additional description:

TLC and NMR
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

sesquiterpene lactones (xanthinin, xanthanol, xanthatin, xanthumin, xanthumanol, xanthinosin) in leaves

Composition #3: Kim, YS., Kim, JS., Park, SH., Choi, SU., Lee, CO., Kim, SK., Kim, YK., Kim, SH., Ryu, SY. Two cytotoxic sesquiterpene lactones from the leaves of Xanthium strumarium and their in vitro inhibitory activity on farnesyltransferase . planta medica, 2003, vol. 69, no. 4, p. 375–377. DOI: 10.1055/s-2003-38879. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

Sesquiterpene lactones (RF-00004319-PAR)
Additional substance description:

Xanthanolide sesquiterpene lactones (8-epi-xanthine and 8-epi-xanthine epoxide)
Analytical method code:

Nuclear Magnetic Resonance (NMR) (F061A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Xanthanolide sesquiterpene lactones (8-epi-xanthine and 8-epi-xanthine epoxide) in leaves

Composition #4: Chu, Chien-Hua., Chiu, Chi-Ming., Hu, Anren., Wu, Hui-Chung., Ye, Shu-Ping., Ho, Kuo-Chieh., Chen, Liang-Yu. Toxicity attenuation of atractyloside in traditional chinese medicinal herbs after hydrothermal processing . botanical studies, 2012, vol. 53, no. 4, p. 459–465. .

Language:

English (en)
Plant part:

Fruit unspecified (as part-nature) (A067D)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

water
Substance:

atractyloside (RF-00004170-PAR)
Analytical method code:

GC-MS (F046A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Atractyloside in fruits

Composition #5: ESASHI, Y., MATSUYAMA, S., ASHINO, H., OGASAWARA, M., HASEGAWA, R. BETA-GLUCOSIDASE ACTIVITIES AND HCN LIBERATION IN UNIMBIBED AND IMBIBED SEEDS, AND THE INDUCTION OF COCKLEBUR SEED-GERMINATION BY CYANOGENIC GLYCOSIDES . physiologia plantarum, 1991, vol. 83, no. 1, p. 34–40. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Additional extraction description:

upper and lower seeds
Substance:

Cyanogenic glycosides (RF-00004375-PAR)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

cyanogenic glucosides in seeds

Endpoint study #1: Hwang, Seung Hwan., Wang, Zhiqiang., Yoon, Ha Na., Lim, Soon Sung. Xanthium strumarium as an Inhibitor of alpha-Glucosidase, Protein Tyrosine Phosphatase 1beta, Protein Glycation and ABTS(+) for Diabetic and Its Complication. . molecules (basel, switzerland), 2016, vol. 21, no. 9 . DOI: 10.3390/molecules21091241. [DOI link]

Study relevance:

Human health
Plant part:

Fruit unspecified (as part-nature) (A067D)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

CH2Cl2 extract, EtOAc fraction
Type of toxicological test:

in vitro (CHD061TT)
Limit test:

Not applicable
Sex:

No data
Control groups used:

no data
Endpoint measured:

Enzyme inhibition (CHD067EP)
Concentration unit:

Microgram/millilitre (G052A)
Effect concentration:

399.66
Critical effect:

Other toxicities (TOX19A)
Target tissue:

Digestive (TT002A)
Effect description:

EtOH fraction was found to exhibit a similar activity to the positive control, a known α-glucosidase inhibitor (377.19 µg/mL)
Effect or parameter linked to the endpoint:

enzyme inhibition (CHD032BE)
Internal remarks:

alpha-glucosidase inhibition (EtOAc fraction)

Endpoint study #2: Masvingwe, C., Mavenyengwa, M. Toxicological evaluation of the plant Xanthium strumarium in pigs in Zimbabwe . journal of venomous animals and toxins, 1998, vol. 4, no. 2 CITED APRIL 18, 2000, p. 1–8. .

Study relevance:

Animal (target species) health
Plant part:

Sprout (as part-nature) (A067R)
Additional plant/substance description:

fed with either crushed burs (fruits) 2 animals or the leaf seedling 4 animals
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

No
Tested organism:

Pig (as animal) (A057F)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

96.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

6
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

Neurologic (TT004A)
Effect description:

depression, vomiting, abdominal pain, weakness, recumbency, paddling convulsions terminating in death from 6 to 96 hours after ingestion (among 100% of pigs)
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

neurotoxicity and mortality in pigs fed with either crushed burs (fruits) 2 animals or the leaf seedling 4 animals

Endpoint study #3: Masvingwe, C., Mavenyengwa, M. Toxicological evaluation of the plant Xanthium strumarium in pigs in Zimbabwe . journal of venomous animals and toxins, 1998, vol. 4, no. 2 CITED APRIL 18, 2000, p. 1–8. .

Study relevance:

Animal (target species) health
Plant part:

Sprout (as part-nature) (A067R)
Additional plant/substance description:

fed with either crushed burs (fruits) 2 animals or the leaf seedling 4 animals
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

No
Tested organism:

Pig (as animal) (A057F)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

96.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

6
Control groups used:

no
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent (G138A)
Effect concentration:

2
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

acute hepatic congestion and hemorrhage, centrilobular hepatocyte necrosis at 2% of the total body weight
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

hepatotoxicity and mortality in pigs fed with either crushed burs (fruits) 2 animals or the leaf seedling 4 animals

Endpoint study #4: Masvingwe, C., Mavenyengwa, M. Toxicological evaluation of the plant Xanthium strumarium in pigs in Zimbabwe . journal of venomous animals and toxins, 1998, vol. 4, no. 2 CITED APRIL 18, 2000, p. 1–8. .

Study relevance:

Animal (target species) health
Plant part:

Sprout (as part-nature) (A067R)
Additional plant/substance description:

fed with either crushed burs (fruits) 2 animals or the leaf seedling 4 animals
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

No
Tested organism:

Pig (as animal) (A057F)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

96.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

6
Control groups used:

no
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent (G138A)
Effect concentration:

2
Critical effect:

NEPHROTOXICITY (TOX03A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

renal tubular degeneration at 2% of the total body weight
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

nephrotoxicity and mortality in pigs fed with either crushed burs (fruits) 2 animals or the leaf seedling 4 animals

Endpoint study #5: Islam, Mohammad Rashedul., Uddin, Mohammad Zashim., Rahman, Mohammad Sharifur., Tutul, Ershad., Rahman, Mohammed Zakiur., Hassan, Md Abul., Faiz, M A., Hossain, Moazzem., Hussain, Maleeha., Rashid, Mohammad Abdur. Ethnobotanical, phytochemical and toxicological studies of Xanthium strumarium L. . bangladesh medical research council bulletin, 2009, vol. 35, no. 3, p. 84–90. .

Study relevance:

Human health
Plant part:

Aerial part of plants (as part-nature) (A166F)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

methanol extracts of seedlings and mature plants
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

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

Long-Evans (CHD010ST)
Sex:

Male/Female
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

14.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

20
Control groups used:

yes, concurrent no treatment
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent (G138A)
Effect concentration:

0.1 - 0.5
Critical effect:

NEPHROTOXICITY (TOX03A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

infiltration of moderate number of lymphocytes in the stroma and tubules of kidney in the experimental rats fed with 0.1 -0.5% bw of methanol extract from seedings and plants. Besides, necroses of tubules also observed.
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Nephrotoxicity and mortality in rats

Endpoint study #6: Islam, Mohammad Rashedul., Uddin, Mohammad Zashim., Rahman, Mohammad Sharifur., Tutul, Ershad., Rahman, Mohammed Zakiur., Hassan, Md Abul., Faiz, M A., Hossain, Moazzem., Hussain, Maleeha., Rashid, Mohammad Abdur. Ethnobotanical, phytochemical and toxicological studies of Xanthium strumarium L. . bangladesh medical research council bulletin, 2009, vol. 35, no. 3, p. 84–90. .

Study relevance:

Human health
Plant part:

Aerial part of plants (as part-nature) (A166F)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

methanol
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

Yes
Tested organism:

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

Long-Evans (CHD010ST)
Sex:

Male/Female
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

14.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

20
Control groups used:

yes, concurrent no treatment
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent (G138A)
Effect concentration:

0.1 - 0.5
Critical effect:

Other toxicities (TOX19A)
Target tissue:

Neurologic (TT004A)
Effect description:

doses from 0.1 to 0.5% of body weight produced significant changes in behavior, movement and pattern of food intake in experimental rats. These effects
Effect or parameter linked to the endpoint:

behaviour (CHD001BE)
Internal remarks:

changes in behavior, movement and pattern of food intake in rats

Endpoint study #7: Islam, Mohammad Rashedul., Uddin, Mohammad Zashim., Rahman, Mohammad Sharifur., Tutul, Ershad., Rahman, Mohammed Zakiur., Hassan, Md Abul., Faiz, M A., Hossain, Moazzem., Hussain, Maleeha., Rashid, Mohammad Abdur. Ethnobotanical, phytochemical and toxicological studies of Xanthium strumarium L. . bangladesh medical research council bulletin, 2009, vol. 35, no. 3, p. 84–90. .

Study relevance:

Human health
Plant part:

Aerial part of plants (as part-nature) (A166F)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

methanol extracts of seedlings and mature plants
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

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

Long-Evans (CHD010ST)
Sex:

Male/Female
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

14.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

20
Control groups used:

yes, concurrent no treatment
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent (G138A)
Effect concentration:

0.1 - 0.5
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

generalized edema hypertrophy of the hepatocytes resulting in widespread, sinusoidal congestion. 60% of hepatocytes showed cytoplasmic compaction and disintegration, with apoptotic bodies indicating a degenerative necrotic process on liver cells.
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Hepatotoxicity and mortality in rats

Endpoint study #8: Turgut, M., Alhan, CC., Gurgoze, M., Kurt, A., Dogan, Y., Tekatli, M., Akpolat, N., Aygun, D. Carboxyatractyloside poisoning in humans. annals of tropical paediatrics, 2005, vol. 25, no. 2, p. 125–134. DOI: 10.1179/146532805X45728. [DOI link]

Study relevance:

Human health
Substance:

carboxyatractyloside (RF-00003728-PAR)
Plant part:

Seed (as part-nature) (A066P)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

8.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

9
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

Digestive (TOX18A)
Target tissue:

Digestive (TT002A)
Effect description:

abdominal pain, nausea and vomiting, drowsiness
Effect or parameter linked to the endpoint:

other (CHD003BE)
Internal remarks:

gastrointestinal toxicity in humans (case reports)

Endpoint study #9: Turgut, M., Alhan, CC., Gurgoze, M., Kurt, A., Dogan, Y., Tekatli, M., Akpolat, N., Aygun, D. Carboxyatractyloside poisoning in humans. annals of tropical paediatrics, 2005, vol. 25, no. 2, p. 125–134. DOI: 10.1179/146532805X45728. [DOI link]

Study relevance:

Human health
Substance:

carboxyatractyloside (RF-00003728-PAR)
Plant part:

Seed (as part-nature) (A066P)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

8.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

9
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

Neurologic (TT004A)
Effect description:

palpitations, sweating, dyspnoea among all, and convulsion, loss of consciousness and death (3/9). permeability and microvascular haemorrrage in the cerebrum and cerebellum.
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

neurotoxicitiy and mortality in humans (case reports)

Endpoint study #10: Turgut, M., Alhan, CC., Gurgoze, M., Kurt, A., Dogan, Y., Tekatli, M., Akpolat, N., Aygun, D. Carboxyatractyloside poisoning in humans. annals of tropical paediatrics, 2005, vol. 25, no. 2, p. 125–134. DOI: 10.1179/146532805X45728. [DOI link]

Study relevance:

Human health
Substance:

carboxyatractyloside (RF-00003728-PAR)
Plant part:

Seed (as part-nature) (A066P)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

8.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

3
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

liver confirmed centrilobular hepatic necrosis
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

hepatotoxicity and mortality in humans (case reports)

Endpoint study #11: Turgut, M., Alhan, CC., Gurgoze, M., Kurt, A., Dogan, Y., Tekatli, M., Akpolat, N., Aygun, D. Carboxyatractyloside poisoning in humans. annals of tropical paediatrics, 2005, vol. 25, no. 2, p. 125–134. DOI: 10.1179/146532805X45728. [DOI link]

Study relevance:

Human health
Substance:

carboxyatractyloside (RF-00003728-PAR)
Plant part:

Seed (as part-nature) (A066P)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Male/Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

8.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

3
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

NEPHROTOXICITY (TOX03A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

renal proximal tubular necrosis
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

nephrotoxicity and mortality in humans (case reports)

Endpoint study #12: Saidi, Hossein., Mofidi, Mani. TOXIC EFFECT OF XANTHIUM STRUMARIUM AS AN HERBAL MEDICINE PREPARATION. excli journal, 2009, vol. 8, p. 115–117. .

Study relevance:

Human health
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

water (leaves, stalks and seeds)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Female
Route of exposure:

ORAL: DRINKING WATER (OECD2229PL)
Exposure duration:

3.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligram (G155A)
Effect concentration:

30 -40
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

hepatic injury, symptomatic hypoglycemia
Effect or parameter linked to the endpoint:

haematology (CHD023BE)
Internal remarks:

hepatotoxicity in human

Endpoint study #13: Saidi, Hossein., Mofidi, Mani. TOXIC EFFECT OF XANTHIUM STRUMARIUM AS AN HERBAL MEDICINE PREPARATION. excli journal, 2009, vol. 8, p. 115–117. .

Study relevance:

Human health
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

water (leaves, stalks and seeds)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Female
Route of exposure:

ORAL: DRINKING WATER (OECD2229PL)
Exposure duration:

3.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Gram (G148A)
Effect concentration:

30- 40
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

Neurologic (TT004A)
Effect description:

altered mental status and seizure
Effect or parameter linked to the endpoint:

neurology (CHD027BE)
Internal remarks:

neurotoxicity in human

Endpoint study #14: Botha, Christo J., Lessing, Dries., Roesemann, Magda., van Wilpe, Erna., Williams, June H. Analytical confirmation of Xanthium strumarium poisoning in cattle. journal of veterinary diagnostic investigation, 2014, vol. 26, no. 5, p. 640–645. DOI: 10.1177/1040638714542867. [DOI link]

Study relevance:

Animal (target species) health
Substance:

carboxyatractyloside (RF-00003728-PAR)
Plant part:

Seed (as part-nature) (A066P)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Cattle (as animal) (A057E)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Number of organisms dosed:

150
Control groups used:

no
Endpoint measured:

Concentration level (CHD013EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

2.5
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

Neurologic (TT004A)
Effect description:

recumbency, apparent blindness, and hypersensitivity to convulsive seizures among dead cows (3/150)
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

neurotoxicity and death in cows (seeds)

Endpoint study #15: Botha, Christo J., Lessing, Dries., Roesemann, Magda., van Wilpe, Erna., Williams, June H. Analytical confirmation of Xanthium strumarium poisoning in cattle. journal of veterinary diagnostic investigation, 2014, vol. 26, no. 5, p. 640–645. DOI: 10.1177/1040638714542867. [DOI link]

Study relevance:

Animal (target species) health
Substance:

carboxyatractyloside (RF-00003728-PAR)
Plant part:

Seed (as part-nature) (A066P)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Cattle (as animal) (A057E)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Number of organisms dosed:

150
Control groups used:

no
Endpoint measured:

Concentration level (CHD013EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

2.5
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

distinctive microscopic lesions were severe, bridging centrilobular to midzonal hepatocyte necrosis and hemorrhage
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

hepatotoxicity in cows (seeds)

Endpoint study #16: Botha, Christo J., Lessing, Dries., Roesemann, Magda., van Wilpe, Erna., Williams, June H. Analytical confirmation of Xanthium strumarium poisoning in cattle. journal of veterinary diagnostic investigation, 2014, vol. 26, no. 5, p. 640–645. DOI: 10.1177/1040638714542867. [DOI link]

Study relevance:

Animal (target species) health
Substance:

carboxyatractyloside (RF-00003728-PAR)
Plant part:

Sprout (as part-nature) (A067R)
Additional plant/substance description:

seedlings
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Cattle (as animal) (A057E)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Number of organisms dosed:

150
Control groups used:

no
Endpoint measured:

Concentration level (CHD013EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

2.5
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

distinctive microscopic lesions were severe, bridging centrilobular to midzonal hepatocyte necrosis and hemorrhage
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

hepatotoxicity in cows (seedlings)

Endpoint study #17: Botha, Christo J., Lessing, Dries., Roesemann, Magda., van Wilpe, Erna., Williams, June H. Analytical confirmation of Xanthium strumarium poisoning in cattle. journal of veterinary diagnostic investigation, 2014, vol. 26, no. 5, p. 640–645. DOI: 10.1177/1040638714542867. [DOI link]

Study relevance:

Animal (target species) health
Substance:

carboxyatractyloside (RF-00003728-PAR)
Plant part:

Sprout (as part-nature) (A067R)
Additional plant/substance description:

seedlings
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Cattle (as animal) (A057E)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Number of organisms dosed:

150
Control groups used:

no
Endpoint measured:

Concentration level (CHD013EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

2.5
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

Neurologic (TT004A)
Effect description:

recumbency, apparent blindness, and hypersensitivity to convulsive seizures among dead cows (3/150)
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

neurotoxicity and death in cows (seedlings)

Endpoint study #18: STUART, BP., COLE, RJ., GOSSER, HS. COCKLEBUR (XANTHIUM-STRUMARIUM, L VAR STRUMARIUM) INTOXICATION IN SWINE - REVIEW AND REDEFINITION OF THE TOXIC PRINCIPLE . veterinary pathology, 1981, vol. 18, no. 3, p. 368–383. .

Study relevance:

Animal (target species) health
Substance:

carboxyatractyloside (RF-00003728-PAR)
Plant part:

Sprout (as part-nature) (A067R)
Type of toxicological test:

other (CHD008TT)
Limit test:

Yes
Tested organism:

Pig (as animal) (A057F)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

1.0
Unit of exposure duration:

single (food/feed) (G203A)
Number of organisms dosed:

24
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent (G138A)
Effect concentration:

0.75 - 3
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

13/23 pigs fed cotyledonary seedlings at 0.75% to 3.0% of their body weight (140 to 478 g of fresh plant) had acute diffuse centrilobular hepatic necrosis.
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Hepatotoxicity and mortality (cotyledonary)

Endpoint study #19: STUART, BP., COLE, RJ., GOSSER, HS. COCKLEBUR (XANTHIUM-STRUMARIUM, L VAR STRUMARIUM) INTOXICATION IN SWINE - REVIEW AND REDEFINITION OF THE TOXIC PRINCIPLE . veterinary pathology, 1981, vol. 18, no. 3, p. 368–383. .

Study relevance:

Animal (target species) health
Substance:

carboxyatractyloside (RF-00003728-PAR)
Plant part:

Seed (as part-nature) (A066P)
Type of toxicological test:

subchronic (CHD013TT)
Limit test:

Yes
Tested organism:

Pig (as animal) (A057F)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

42.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

12
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent (G138A)
Effect concentration:

10 - 30
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

3/12 pigs fed ground bur had clinical signs and convulsions within 24 hours and died. Serofibrinous ascites, gallbladder wall edema, and acute, diffuse, centrilobular and paracentral hepatic necrosis were present in the three clinically affected pigs
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Hepatotoxicity and mortality (burs)

Endpoint study #20: ESASHI, Y., MATSUYAMA, S., ASHINO, H., OGASAWARA, M., HASEGAWA, R. BETA-GLUCOSIDASE ACTIVITIES AND HCN LIBERATION IN UNIMBIBED AND IMBIBED SEEDS, AND THE INDUCTION OF COCKLEBUR SEED-GERMINATION BY CYANOGENIC GLYCOSIDES . physiologia plantarum, 1991, vol. 83, no. 1, p. 34–40. .

Study relevance:

Human health
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

ethanol
Type of toxicological test:

in vitro (CHD061TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

No data
Endpoint measured:

Concentration level (CHD013EP)
Concentration unit:

Millimol/100 Gramm (G193A)
Effect concentration:

0.00013 - 0.00024
Critical effect:

NONE (TOX14A)
Target tissue:

Digestive (TT002A)
Effect description:

beta-Glucosidase activity in upper and lower seeds of cocklebur at 1.3 -2.4 nmol HCN ( per g FW) per h
Effect or parameter linked to the endpoint:

enzyme inhibition (CHD032BE)
Internal remarks:

beta-Glucosidase activity in seeds

Genotox #1: Piloto Ferrer, Janet., Cozzi, Renata., Cornetta, Tommaso., Stano, Pasquale., Fiore, Mario., Degrassi, Francesca., De Salvia, Rosella., Remigio, Antonia., Francisco, Marbelis., Quinones, Olga., Valdivia, Dayana., Gonzalez, Maria L., Perez, Carlos., Sanchez-Lamar, Angel. Xanthium strumarium L. extracts produce DNA damage mediated by cytotoxicity in in vitro assays but does not induce micronucleus in mice. . biomed research international, 2014, vol. 2014, p. 575197–575197. DOI: 10.1155/2014/575197. [DOI link]

Study category:

Mutagenicity
Type of toxicological test:

sister chromatid exchange assay in mammalian cells (CHD039TT)
Method type:

in vitro
Tested organism:

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

CHO (CHD034ST)
Sex:

No data
Exogenous metabolic activation applied:

without
Route of exposure:

OTHER (OECD0PL)
Control groups used:

yes, concurrent vehicle
Endpoint measured:

chromosome aberration
Is genotoxic:

Positive
Remarks on genotox study:

A significant increase of SCE per cell was observed at 15 𝜇g/mL when cells were exposed to the extract for 3 h. When a continuous treatment of 27 h was applied, a statistically significant increase in SCE was observed at 5 𝜇g/mL of X. strumarium extract. Dose response increase in both treatments.
Internal remarks:

significant increase of Sister Chromatid Exchanges (mutagenicity)
Internal ID:

MEDLINE:25025061

Genotox #2: Piloto Ferrer, Janet., Cozzi, Renata., Cornetta, Tommaso., Stano, Pasquale., Fiore, Mario., Degrassi, Francesca., De Salvia, Rosella., Remigio, Antonia., Francisco, Marbelis., Quinones, Olga., Valdivia, Dayana., Gonzalez, Maria L., Perez, Carlos., Sanchez-Lamar, Angel. Xanthium strumarium L. extracts produce DNA damage mediated by cytotoxicity in in vitro assays but does not induce micronucleus in mice. . biomed research international, 2014, vol. 2014, p. 575197–575197. DOI: 10.1155/2014/575197. [DOI link]

Study category:

Genotoxicity
Type of toxicological test:

chromosome aberration assay (CHD047TT)
Method type:

in vitro
Tested organism:

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

CHO (CHD034ST)
Sex:

No data
Exogenous metabolic activation applied:

without
Route of exposure:

OTHER (OECD0PL)
Control groups used:

yes, concurrent vehicle
Endpoint measured:

chromosome aberration
Is genotoxic:

Positive
Remarks on genotox study:

the highest tested concentration of extract, 45 𝜇g/mL produced a significant increase in the percentage of CA with the mitotic index lower than 50% of the controls, indicating occurrence of cell toxicity from the extract; mitoses stopped after 18 h of treatment with 45 𝜇g/mL
Internal remarks:

increase in the percentage of chromosomal aberrations (genotoxicity)
Internal ID:

MEDLINE:25025061

Genotox #3: Piloto Ferrer, Janet., Cozzi, Renata., Cornetta, Tommaso., Stano, Pasquale., Fiore, Mario., Degrassi, Francesca., De Salvia, Rosella., Remigio, Antonia., Francisco, Marbelis., Quinones, Olga., Valdivia, Dayana., Gonzalez, Maria L., Perez, Carlos., Sanchez-Lamar, Angel. Xanthium strumarium L. extracts produce DNA damage mediated by cytotoxicity in in vitro assays but does not induce micronucleus in mice. . biomed research international, 2014, vol. 2014, p. 575197–575197. DOI: 10.1155/2014/575197. [DOI link]

Study category:

Genotoxicity
Type of toxicological test:

single cell gel/comet assay in mammalian cells for detection of DNA damage (CHD040TT)
Method type:

in vitro
Tested organism:

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

CHO (CHD034ST)
Sex:

No data
Exogenous metabolic activation applied:

without
Route of exposure:

OTHER (OECD0PL)
Control groups used:

yes, concurrent vehicle
Endpoint measured:

DNA damage and/or repair
Is genotoxic:

Positive
Remarks on genotox study:

hedgehog or apoptotic-like cells were observed at the highest tested concentration, that is, 45 𝜇g/mL. Dose-response increase in the percentage of unviable cells above 20 percent observed in the measured endpoint.
Internal remarks:

hedgehog or apoptotic-like cells observed, DNA primary damage (both single- and double-strand breaks)(genotoxicity)
Internal ID:

MEDLINE:25025061