EFSA Compendium of Botanicals

Draft - work in progress

Isocoma pluriflora (Torr. & A.Gray) Greene // Haplopappus heterophyllus (A.Gray) S.F.Blake

Family:: Asteraceae
Approval state:: Approved
Number of articles retrieved:: 33
Number of processed references:: 5

Compositions

#1: Benzofurans #2: L-Carvone #3: Dehydrotremetone #4: Tremetone #5: 3-oxyangeloyl-tremetone #6: Dehydrotremetone #7: Tremetone #8: 3-oxyangeloyl-tremetone #9: Tremetone #10: Dehydrotremetone #11: 3-Oxyangeloyltremetone

Endpoint Studies

#1: increased resting heart rate, decreased appetite, exercise intolerance, reluctance to stand, and swelling of the large appendicular muscles #2: myoglobinuria, heart lesions #3: Toxicity of benzofuran ketones - fatigue, elevated heart rate at the end of the 10 min recovery period, and increased creatine kinase activity #4: increased heart rate, decreased appetite, exercise intolerance, reluctance to stand, swelling of the large appendicular muscles, exophthalmia with slow pupillary reflexes

Genotoxicity

Composition #1: Zalkow, L. H., Ekpo, B. A., Gelbaum, L. T., Harris, R. N., III., Keinan, E., Novak, J. R., Jr., Ramming, C. T., Van Derveer, D. The benzofurans of Isocoma wrightii. Structure and stereochemistry. Journal of Natural Products, 1979, p. 203–219. .

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

Ethanol
Substance:

Benzofurans (RF-00010791-PAR)
Additional substance description:

Toxethol, Toxol, Toxyl angelate, 2,3-diacetylbenzofuran
Analytical method code:

Chromatographic tests (F015A)
Analytical method - additional description:

H NMR Spectra
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Benzofurans

Composition #2: Zalkow, L.H., Harris III, R.N., Burke, N.I. The lower terpenoids of Isocoma Wrightii. Journal of Natural Products, 1979, p. 96–102. .

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

Hexane and ether extraction
Substance:

Carvone (RF-0538-001-PPP)
Additional substance description:

L-carvone
Analytical method code:

Chromatographic tests (F015A)
Analytical method - additional description:

H NMR
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

L-Carvone

Composition #3: Davis, T. Z., Stegelmeier, B. L., Lee, S. T., Green, B. T., Hall, J. O. Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in horses. TOXICON, 2013, vol. 73, p. 88–95. DOI: 10.1016/j.toxicon.2013.06.018. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

hexane:ethyl acetate
Substance:

dehydrotremetone (RF-00004264-PAR)
Analytical method code:

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

Milligram/gram (G060A)
Result type:

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

1.34
Internal remarks:

Dehydrotremetone

Composition #4: Davis, T. Z., Stegelmeier, B. L., Lee, S. T., Green, B. T., Hall, J. O. Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in horses. TOXICON, 2013, vol. 73, p. 88–95. DOI: 10.1016/j.toxicon.2013.06.018. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

hexane:ethyl acetate
Substance:

tremetone (RF-00003609-PAR)
Analytical method code:

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

Milligram/gram (G060A)
Result type:

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

0.53
Internal remarks:

Tremetone

Composition #5: Davis, T. Z., Stegelmeier, B. L., Lee, S. T., Green, B. T., Hall, J. O. Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in horses. TOXICON, 2013, vol. 73, p. 88–95. DOI: 10.1016/j.toxicon.2013.06.018. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

hexane:ethyl acetate
Substance:

3-oxyangeloyl-tremetone (RF-00004122-PAR)
Analytical method code:

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

Milligram/gram (G060A)
Result type:

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

2.39
Internal remarks:

3-oxyangeloyl-tremetone

Composition #6: Davis, T. Zane., Green, Benedict T., Stegelmeier, Bryan L., Lee, Stephen T., Welch, Kevin D., Pfister, James A. Physiological and serum biochemical changes associated with rayless goldenrod (Isocoma pluriflora) poisoning in goats. TOXICON, 2013, vol. 76, p. 247–254. DOI: 10.1016/j.toxicon.2013.10.010. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

hexane:ethyl acetate
Substance:

dehydrotremetone (RF-00004264-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Dehydrotremetone

Composition #7: Davis, T. Zane., Green, Benedict T., Stegelmeier, Bryan L., Lee, Stephen T., Welch, Kevin D., Pfister, James A. Physiological and serum biochemical changes associated with rayless goldenrod (Isocoma pluriflora) poisoning in goats. TOXICON, 2013, vol. 76, p. 247–254. DOI: 10.1016/j.toxicon.2013.10.010. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

hexane:ethyl acetate
Substance:

tremetone (RF-00003609-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Tremetone

Composition #8: Davis, T. Zane., Green, Benedict T., Stegelmeier, Bryan L., Lee, Stephen T., Welch, Kevin D., Pfister, James A. Physiological and serum biochemical changes associated with rayless goldenrod (Isocoma pluriflora) poisoning in goats. TOXICON, 2013, vol. 76, p. 247–254. DOI: 10.1016/j.toxicon.2013.10.010. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

hexane:ethyl acetate
Substance:

3-oxyangeloyl-tremetone (RF-00004122-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

3-oxyangeloyl-tremetone

Composition #9: Lee, Stephen T., Cook, Daniel., Davis, T. Zane., Gardner, Dale R., Johnson, Robert L., Stonecipher, Clinton A. A Survey of Tremetone, Dehydrotremetone, and Structurally Related Compounds in Isocoma spp. (Goldenbush) in the Southwestern United States . journal of agricultural and food chemistry, 2015, vol. 63, no. 3, p. 872–879. DOI: 10.1021/jf505423h. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

hexane
Substance:

tremetone (RF-00003609-PAR)
Analytical method code:

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

Milligram/gram (G060A)
Result expression:

Dry matter (B002A)
Result type:

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

0.16-0.4
Internal remarks:

Tremetone

Composition #10: Lee, Stephen T., Cook, Daniel., Davis, T. Zane., Gardner, Dale R., Johnson, Robert L., Stonecipher, Clinton A. A Survey of Tremetone, Dehydrotremetone, and Structurally Related Compounds in Isocoma spp. (Goldenbush) in the Southwestern United States . journal of agricultural and food chemistry, 2015, vol. 63, no. 3, p. 872–879. DOI: 10.1021/jf505423h. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

hexane
Substance:

dehydrotremetone (RF-00004264-PAR)
Analytical method code:

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

Milligram/gram (G060A)
Result expression:

Dry matter (B002A)
Result type:

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

0.8-2.6
Internal remarks:

Dehydrotremetone

Composition #11: Lee, Stephen T., Cook, Daniel., Davis, T. Zane., Gardner, Dale R., Johnson, Robert L., Stonecipher, Clinton A. A Survey of Tremetone, Dehydrotremetone, and Structurally Related Compounds in Isocoma spp. (Goldenbush) in the Southwestern United States . journal of agricultural and food chemistry, 2015, vol. 63, no. 3, p. 872–879. DOI: 10.1021/jf505423h. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

hexane
Substance:

3-oxyangeloyl-tremetone (RF-00004122-PAR)
Analytical method code:

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

Milligram/gram (G060A)
Result expression:

Dry matter (B002A)
Result type:

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

1.9-4
Internal remarks:

3-Oxyangeloyltremetone

Endpoint study #1: Davis, T. Z., Stegelmeier, B. L., Lee, S. T., Green, B. T., Hall, J. O. Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in horses. TOXICON, 2013, vol. 73, p. 88–95. DOI: 10.1016/j.toxicon.2013.06.018. [DOI link]

Study relevance:

Animal (target species) health
Substance:

tremetone (RF-00003609-PAR)
Additional plant/substance description:

Tremetone and derivatives
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

Horse (as animal) (A0B9Z)
Sex:

Female
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

7.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

4
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

60
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Target tissue:

cardiovascular / haematological: Heart (TT011A)
Effect description:

increased resting heart rate, decreased appetite, exercise intolerance, reluctance to stand, and swelling of the large appendicular muscles
Effect or parameter linked to the endpoint:

mobility (CHD011BE)
Internal remarks:

increased resting heart rate, decreased appetite, exercise intolerance, reluctance to stand, and swelling of the large appendicular muscles

Endpoint study #2: Davis, T. Z., Stegelmeier, B. L., Lee, S. T., Green, B. T., Hall, J. O. Experimental rayless goldenrod (Isocoma pluriflora) toxicosis in horses. TOXICON, 2013, vol. 73, p. 88–95. DOI: 10.1016/j.toxicon.2013.06.018. [DOI link]

Study relevance:

Animal (target species) health
Substance:

tremetone (RF-00003609-PAR)
Additional plant/substance description:

Tremetone and derivatives
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

Horse (as animal) (A0B9Z)
Sex:

Female
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

10.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

4
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

60
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Target tissue:

cardiovascular / haematological: Heart (TT011A)
Effect description:

myoglobinuria, heart lesions - 60% of the myocardium was affected
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

myoglobinuria, heart lesions

Endpoint study #3: Davis, T. Zane., Green, Benedict T., Stegelmeier, Bryan L., Lee, Stephen T., Welch, Kevin D., Pfister, James A. Physiological and serum biochemical changes associated with rayless goldenrod (Isocoma pluriflora) poisoning in goats. TOXICON, 2013, vol. 76, p. 247–254. DOI: 10.1016/j.toxicon.2013.10.010. [DOI link]

Study relevance:

Human health
Substance:

tremetone (RF-00003609-PAR)
Additional plant/substance description:

Tremetone and derivatives
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

Goat (as animal) (A057P)
Sex:

Female
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

7.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

20
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

10-20
Critical effect:

MUSCLO-SKELETAL (TOX13A)
Target tissue:

Muscle, Skeletal (TT055A)
Effect description:

fatigue while exercising, elevated heart rate at the end of the 10 min recovery period, increased creatine kinase activity
Effect or parameter linked to the endpoint:

mobility (CHD011BE)
Internal remarks:

Toxicity of benzofuran ketones - fatigue, elevated heart rate at the end of the 10 min recovery period, and increased creatine kinase activity

Endpoint study #4: Davis, T. Zane., Green, Benedict T., Stegelmeier, Bryan L., Lee, Stephen T., Welch, Kevin D., Pfister, James A. Physiological and serum biochemical changes associated with rayless goldenrod (Isocoma pluriflora) poisoning in goats. TOXICON, 2013, vol. 76, p. 247–254. DOI: 10.1016/j.toxicon.2013.10.010. [DOI link]

Study relevance:

Human health
Substance:

tremetone (RF-00003609-PAR)
Additional plant/substance description:

Tremetone and derivatives
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

Goat (as animal) (A057P)
Sex:

Female
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

4.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

20
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

40-60
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Target tissue:

cardiovascular / haematological: Heart (TT011A)
Effect description:

increased heart rate, decreased appetite, exercise intolerance, reluctance to stand, swelling of the large appendicular muscles, exophthalmia with slow pupillary reflexes
Effect or parameter linked to the endpoint:

mobility (CHD011BE)
Internal remarks:

increased heart rate, decreased appetite, exercise intolerance, reluctance to stand, swelling of the large appendicular muscles, exophthalmia with slow pupillary reflexes