EFSA Compendium of Botanicals

Draft - work in progress

Rubia tinctorum L.

Family:: Rubiaceae
Approval state:: Approved
Number of articles retrieved:: 611
Number of processed references:: 7

Compositions

#1: lucidine, alizarine, purpuroxanthine and rubiadine in roots #2: lucidin-3-o primeveroside in roots #3: lucidin in roots

Endpoint Studies

#1: non neoplastic and neoplastic lesion in rats #2: females/ males - mild toxicity, targeting liver, kidneys, RBC, WBC #3: males (5% in diet) chronic toxicity in liver, kidneys, blood cells #4: females (5% in diet) chronic toxicity in liver, kidneys, blood cells #5: males (1% in diet) chronic toxicity in liver, kidneys #6: females (1% in diet) chronic toxicity in liver, kidneys #7: histopathological changes in kidneys

Genotoxicity

#1: DNA adduct #2: mutagenic effect in TA100 with S9 #3: ethylacetate extract - mutagenicity to TA 98

Composition #1: Jaeger, Ismene., Hafner, Christoph., Welsch, Claudia., Schneider, Klaus., Iznaguen, Hassan., Westendorf, Johannes. The mutagenic potential of madder root in dyeing processes in the textile industry . mutation research-genetic toxicology and environmental mutagenesis, 2006, vol. 605, no. 1-2, p. 22–29. DOI: 10.1016/j.mrgentox.2006.01.007. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

ethyl acetate extracts
Substance:

anthraquinones (RF-00004343-PAR)
Additional substance description:

lucidine, alizarine, purpuroxanthine and rubiadine
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

lucidine, alizarine, purpuroxanthine and rubiadine in roots

Composition #2: Ishii, Yuji., Inoue, Kaoru., Takasu, Shinji., Jin, Meilan., Matsushita, Kohei., Kuroda, Ken., Fukuhara, Kiyoshi., Nishikawa, Akiyoshi., Umemura, Takashi. Determination of Lucidin-Specific DNA Adducts by Liquid Chromatography with Tandem Mass Spectrometry in the Livers and Kidneys of Rats Given Lucidin-3-O-primeveroside . chemical research in toxicology, 2012, vol. 25, no. 5, p. 1112–1118. DOI: 10.1021/tx300084p. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Additional extraction description:

unspecified
Substance:

anthraquinones (RF-00004343-PAR)
Additional substance description:

lucidin-3-o-primeveroside
Analytical method code:

HPLC-UV (F021A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

lucidin-3-o primeveroside in roots

Composition #3: WESTENDORF, J., POGINSKY, B., MARQUARDT, H., GROTH, G., MARQUARDT, H. THE GENOTOXICITY OF LUCIDIN, A NATURAL COMPONENT OF RUBIA-TINCTORUM L, AND LUCIDINETHYLETHER, A COMPONENT OF ETHANOLIC RUBIA EXTRACTS . cell biology and toxicology, 1988, vol. 4, no. 2, p. 225–239. DOI: 10.1007/BF00119248. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

ethylacetate
Substance:

lucidin (RF-00003909-PAR)
Analytical method code:

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

HPLC-MS
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

lucidin in roots

Endpoint study #1: Westendorf, J., Pfau, W., Schulte, A. Carcinogenicity and DNA adduct formation observed in ACI rats after long-term treatment with madder root, Rubia tinctorum L . carcinogenesis, 1998, vol. 19, no. 12, p. 2163–2168. DOI: 10.1093/carcin/19.12.2163. [DOI link]

Study relevance:

Human health
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Preparation/Extraction method:

Drying (dehydration) (A07KG)
Type of toxicological test:

chronic/long term toxicity (CHD004TT)
Limit test:

Not applicable
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

780.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

30
Control groups used:

yes, plain diet
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent/volume (G088A)
Effect concentration:

1
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

non-neoplastic lesions in liver, kudneys, benign and malignant tumour formation in kidneys and liver
Effect or parameter linked to the endpoint:

histopathology neoplastic (CHD024BE)
Internal remarks:

non neoplastic and neoplastic lesion in rats

Endpoint study #2: Inoue, Kaoru., Shibutani, Makoto., Masutomi, Naoya., Toyoda, Kazuhiro., Takagi, Hironori., Uneyama, Chikako., Nishikawa, Akiyoshi., Hirose, Masao. A 13-week subchronic toxicity study of madder color in F344 rats. food and chemical toxicology, 2008, vol. 46, no. 1, p. 241–252. DOI: 10.1016/j.fct.2007.08.002. [DOI link]

Study relevance:

Human health
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Type of toxicological test:

subchronic (CHD013TT)
Limit test:

Not applicable
Guideline:

OECD GUIDELINE 408 (REPEATED DOSE 90-DAY ORAL TOXICITY IN RODENTS) (OECD1256PL)
Tested organism:

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

Fischer344 (CHD009ST)
Sex:

Male/Female
Exposure duration:

13.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

20
Control groups used:

yes, plain diet
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent/volume (G088A)
Effect concentration:

0.6
Critical effect:

NEPHROTOXICITY (TOX03A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

lower body weight, weak anemia, increased platelet count, TP, conjugated bilirubin, Ca, IP, decreased A/G, histopathological changes in renal tubules, focal necrosis of hepatocytesincreased liver weight,
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

females/ males - mild toxicity, targeting liver, kidneys, RBC, WBC

Endpoint study #3: Inoue, Kaoru., Shibutani, Makoto., Masutomi, Naoya., Toyoda, Kazuhiro., Takagi, Hironori., Takahashi, Miwa., Fujimoto, Hitoshi., Hirose, Masao., Nishikawa, Akiyoshi. One-year chronic toxicity of madder color in F344 rats - Induction of preneoplastic/neoplastic lesions in the kidney and liver . food and chemical toxicology, 2008, vol. 46, no. 10, p. 3303–3310. DOI: 10.1016/j.fct.2008.07.025. [DOI link]

Study relevance:

Human health
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Preparation/Extraction method:

Drying (dehydration) (A07KG)
Type of toxicological test:

chronic/long term toxicity (CHD004TT)
Limit test:

Not applicable
Tested organism:

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

Fischer 344/DuCrj (CHD090ST)
Sex:

Male
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

53.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

10
Control groups used:

yes, plain diet
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent/volume (G088A)
Effect concentration:

5
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

Cardiovascular / Haematological (TT001A)
Effect description:

anemia, serum biochemical alterations, renal cell adenoma, glutathione S-transferase placental form-positive liver cell foci
Effect or parameter linked to the endpoint:

histopathology neoplastic (CHD024BE)
Internal remarks:

males (5% in diet) chronic toxicity in liver, kidneys, blood cells

Endpoint study #4: Inoue, Kaoru., Shibutani, Makoto., Masutomi, Naoya., Toyoda, Kazuhiro., Takagi, Hironori., Takahashi, Miwa., Fujimoto, Hitoshi., Hirose, Masao., Nishikawa, Akiyoshi. One-year chronic toxicity of madder color in F344 rats - Induction of preneoplastic/neoplastic lesions in the kidney and liver . food and chemical toxicology, 2008, vol. 46, no. 10, p. 3303–3310. DOI: 10.1016/j.fct.2008.07.025. [DOI link]

Study relevance:

Human health
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Preparation/Extraction method:

Drying (dehydration) (A07KG)
Type of toxicological test:

chronic/long term toxicity (CHD004TT)
Limit test:

Not applicable
Tested organism:

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

Fischer 344/DuCrj (CHD090ST)
Sex:

Male/Female
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

53.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

10
Control groups used:

yes, plain diet
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent/volume (G088A)
Effect concentration:

5
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

Cardiovascular / Haematological (TT001A)
Effect description:

anemia, serum biochemical alterations, glutathione S-transferase placental form-positive liver cell foci
Effect or parameter linked to the endpoint:

histopathology neoplastic (CHD024BE)
Internal remarks:

females (5% in diet) chronic toxicity in liver, kidneys, blood cells

Endpoint study #5: Inoue, Kaoru., Shibutani, Makoto., Masutomi, Naoya., Toyoda, Kazuhiro., Takagi, Hironori., Takahashi, Miwa., Fujimoto, Hitoshi., Hirose, Masao., Nishikawa, Akiyoshi. One-year chronic toxicity of madder color in F344 rats - Induction of preneoplastic/neoplastic lesions in the kidney and liver . food and chemical toxicology, 2008, vol. 46, no. 10, p. 3303–3310. DOI: 10.1016/j.fct.2008.07.025. [DOI link]

Study relevance:

Human health
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Preparation/Extraction method:

Drying (dehydration) (A07KG)
Type of toxicological test:

chronic/long term toxicity (CHD004TT)
Limit test:

Not applicable
Tested organism:

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

Fischer 344/DuCrj (CHD090ST)
Sex:

Male
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

53.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

10
Control groups used:

yes, plain diet
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent/volume (G088A)
Effect concentration:

1
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

increased weight of liver, kidneys, renal tubule hyperplasia, increased cell proliferative activity in tubules
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

males (1% in diet) chronic toxicity in liver, kidneys

Endpoint study #6: Inoue, Kaoru., Shibutani, Makoto., Masutomi, Naoya., Toyoda, Kazuhiro., Takagi, Hironori., Takahashi, Miwa., Fujimoto, Hitoshi., Hirose, Masao., Nishikawa, Akiyoshi. One-year chronic toxicity of madder color in F344 rats - Induction of preneoplastic/neoplastic lesions in the kidney and liver . food and chemical toxicology, 2008, vol. 46, no. 10, p. 3303–3310. DOI: 10.1016/j.fct.2008.07.025. [DOI link]

Study relevance:

Human health
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Preparation/Extraction method:

Drying (dehydration) (A07KG)
Type of toxicological test:

chronic/long term toxicity (CHD004TT)
Limit test:

Not applicable
Tested organism:

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

Fischer 344/DuCrj (CHD090ST)
Sex:

Female
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

53.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

10
Control groups used:

yes, plain diet
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent/volume (G088A)
Effect concentration:

1
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

increased weight of liver, renal tubule hyperplasia, increased cell proliferative activity in tubules
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

females (1% in diet) chronic toxicity in liver, kidneys

Endpoint study #7: Inoue, Kaoru., Yoshida, Midori., Takahashi, Miwa., Fujimoto, Hitoshi., Ohnishi, Kuniyoshi., Nakashima, Koichi., Shibutani, Makoto., Hirose, Masao., Nishikawa, Akiyoshi. Possible contribution of rubiadin, a metabolite of madder color, to renal carcinogenesis in rats . food and chemical toxicology, 2009, vol. 47, no. 4, p. 752–759. DOI: 10.1016/j.fct.2009.01.003. [DOI link]

Study relevance:

Human health
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Additional plant/substance description:

unspecified
Type of toxicological test:

short-term toxicity (CHD017TT)
Limit test:

Not applicable
Tested organism:

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

Fischer344 (CHD009ST)
Sex:

Male
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

1.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

6
Control groups used:

yes, plain diet
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Percent/volume (G088A)
Effect concentration:

1.5
Critical effect:

NEPHROTOXICITY (TOX03A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

cortical tubule degeneration, proliferative activity of tubule cells in the outer medulla
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

histopathological changes in kidneys

Genotox #1: Westendorf, J., Pfau, W., Schulte, A. Carcinogenicity and DNA adduct formation observed in ACI rats after long-term treatment with madder root, Rubia tinctorum L . carcinogenesis, 1998, vol. 19, no. 12, p. 2163–2168. DOI: 10.1093/carcin/19.12.2163. [DOI link]

Study category:

Genotoxicity
Type of toxicological test:

other (CHD008TT)
Method type:

in vivo
Guideline used:

No guideline followed
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Exogenous metabolic activation applied:

without
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration for in vivo:

2.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

5
Control groups used:

yes, plain diet
Endpoint measured:

DNA damage and/or repair
Is genotoxic:

Positive
Remarks on genotox study:

DNA adduct observed in liver, kidneys and colon
Internal remarks:

DNA adduct
Internal ID:

WOS:000077890600016

Genotox #2: Jaeger, Ismene., Hafner, Christoph., Welsch, Claudia., Schneider, Klaus., Iznaguen, Hassan., Westendorf, Johannes. The mutagenic potential of madder root in dyeing processes in the textile industry . mutation research-genetic toxicology and environmental mutagenesis, 2006, vol. 605, no. 1-2, p. 22–29. DOI: 10.1016/j.mrgentox.2006.01.007. [DOI link]

Study category:

Mutagenicity
Type of toxicological test:

bacterial gene mutation assay (CHD027TT)
Method type:

in vitro
Guideline used:

According to
Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay) (OECD1287PL)
Tested organism:

Bacteria (as organism) (A0CJR)
Strain of test organism:

TA 100 (CHD024ST)
Exogenous metabolic activation applied:

with and without
Control groups used:

yes
Endpoint measured:

gene mutation
Is genotoxic:

Positive
Remarks on genotox study:

strong mutagenic effect with induction rates of 5.7-13.9 (TA100 with S9 mix)
Internal remarks:

mutagenic effect in TA100 with S9
Internal ID:

WOS:000238401600004

Genotox #3: WESTENDORF, J., POGINSKY, B., MARQUARDT, H., GROTH, G., MARQUARDT, H. THE GENOTOXICITY OF LUCIDIN, A NATURAL COMPONENT OF RUBIA-TINCTORUM L, AND LUCIDINETHYLETHER, A COMPONENT OF ETHANOLIC RUBIA EXTRACTS . cell biology and toxicology, 1988, vol. 4, no. 2, p. 225–239. DOI: 10.1007/BF00119248. [DOI link]

Study category:

Genotoxicity
Type of toxicological test:

bacterial gene mutation assay (CHD027TT)
Method type:

in vitro
Guideline used:

No guideline followed
Tested organism:

Salmonella typhimurium (as organism) (A0CPZ)
Strain of test organism:

TA 98 (CHD029ST)
Exogenous metabolic activation applied:

no data
Control groups used:

no data
Endpoint measured:

gene mutation
Is genotoxic:

Positive
Remarks on genotox study:

mutagenicity to TA 98
Internal remarks:

ethylacetate extract - mutagenicity to TA 98
Internal ID:

WOS:A1988N878000007