1,3-ジヒドロキシ-2-(ヒドロキシメチル)アントラキノン

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Lucidin has been identified in plants from Rubia (R. tinctorum, R. iberica), Coprosma (C. lucida, C. rotundifolia, C. acerosa), Morinda (M. citrifolia, M. umbellata), Galium (G. fagetorum, G. mollugo, G. dasypodum), Hymenodictyon (H. excelsum) and Commitheca (C. liebrechtsiana) species.

/HUMAN EXPOSURE STUDIES/ The largest outbreak reported to date occurred in the Gulran district of Herat Province in northwest Afghanistan, close to the border of the USSR. ...The outbreak, was estimated to have affected a population of approximately 35,000 in 98 villages. Examination of 7,200 inhabitants of the affected villages showed evidence of disease in 22.6%, which was more serious in 15%. Thus, it was estimated that approximately 8,000 subjects suffered from the disease including 5,000 who were seriously affected. All age groups were affected, but 46% of subjects were below 14 years of age. However, no sign of disease was found in children below 2 years of age. A detailed report concerning the pathological material obtained from 14 liver biopsies and 8 autopsies was made... /although/ the time interval between the onset of symptoms and the biopsy/autopsy was not indicated. Pathological findings were characteristic, ranging from acute disease with characteristic veno-occlusion to non-portal cirrhosis, which was observed in 5 of the above 22 cases. The outbreak was ascribed to massive contamination of wheat, the staple food crop, following 2 years of drought, with the seeds of Heliotropium popovii H. Riedl subsp. gillianum H. Riedl, which had been growing profusely among the wheat crop. The seeds contained pyrrolizidine alkaloids at concentrations reported by 2 laboratories to be 7.2 and 13.2-14.9 g/kg, identified mainly as the N-oxide of heliotrine (74%)..., and one or two other compounds similar in character to lasiocarpine. Samples of wheat from several villages contained an average of 40 seeds/kg, i.e., 0.03% by weight. It was estimated that an adult consumed at least 700 g flour/day, containing approximately 2 mg alkaloid (based on a mean of the seed analyses). /Pyrrolizidine alkaloids/

/HUMAN EXPOSURE STUDIES/ The two main sources of pyrrolizidine alkaloid poisoning reported in human beings are the consumption of cereal grain contaminated by weeds containing the alkaloids and the use of alkaloid-containing herbs for medicinal and dietary purposes. ...Three of the largest outbreaks of the disease have been reported from South Asia, two from the same site in central India and one from North-West Afghanistan. The first Indian outbreak... occurred in a group of 5 tribal villages in central India in 1972-73. ...Out of a total population of 2,060 in these villages, 71 households with 366 members were investigated. Among these, 39 cases had developed and 19 had died before commencement of the investigations. The incidence rate was 1.1% and the case fatality rate was 50%. All cases occurred among 20 households. In many households, several members were affected. In one household, 4 out of 5 cases died. ...The etiological factor of this outbreak was not established, though dietary contamination with pyrrolizidine alkaloids was considered. A second outbreak occurred at the same site in 1975... . A total population of 486 was affected, 67 cases were reported, of whom 28 (46%) had died. There was a strong family history... . In a later survey, 108 patients were studied and the mortality rate was estimated to be 63%. This time the etiological factor was identified as the plant Crotalaria nana Burm, which had been growing in the fields of millet (Panicum miliare), their staple food crop. The seeds of this plant became mixed with the cereal grain during harvesting. The toxic seeds contained pyrrolizidine alkaloids that were identified as a macrocyclic ester closely similar to monocrotaline. The total alkaloid content was estimated to be 5.3 g/kg of seed, expressed as monocrotaline. The levels of contamination of the millet with seeds were reported to be 0-3.4 g/kg in the unaffected and 0-19 g/kg in the affected households... . /Pyrrolizidine alkaloids/

/SIGNS AND SYMPTOMS/ After intake of madder root, occasional cases of red coloration of the urine, saliva, perspiration, and milk have been observed.

Madder root (Rubia tinctorum)

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 82: (2002) Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene

2002

2002

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of 15-20 male and female ACI rats, weighing 150-200 g, were fed a standard diet containing 0, 1 or 10% madder root (Rubia tinctorum) for 780 days. This root contained lucidin (0.34%) but also large amounts of alizarin (0.67%; 1,2-dihydroxyanthraquinone) and the primeverosides of both compounds. All surviving animals were killed and necropsied at 780 days. In the groups receiving 10% madder root diet, 2/16 males and 3/17 females developed hepatocellular adenomas, whereas none were observed in the controls or the 1% madder root group of either sex. In addition, renal tubule-cell adenomas were observed in 1/16 males and 2/16 females in the 10% madder root group and a renal tubule-cell carcinoma in 1/14 males in the 1% madder root group. No renal tumors were seen in the control groups.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Madder root, Rubia tinctorum L., is a traditional herbal medicine used against kidney stones. Recently /it was/ reported that lucidin, a hydroxyanthraquinone derivative present in this plant, is mutagenic in bacteria and mammalian cells. ...The formation of DNA adducts in tissue culture and mice /were also demonstrated/ after treatment with this compound. To elucidate the possible carcinogenicity of madder root, three groups of male and female ACI rats received either a normal diet or a diet supplemented with 1 or 10% drug for a total period of 780 days. Weight gain and morbidity were not different among the three groups. Non-neoplastic lesions related to the treatment were evident in the liver and kidneys of both sexes. Moreover, dose-dependent increases in benign and malignant tumor formation were observed in the liver and kidneys of treated animals. 32P-post-labelling analysis showed an increase in the overall level of DNA adducts observed in the liver, kidney and colon of rats treated with 10% madder root in the diet for 2 weeks. HPLC analysis of 32P-labelled DNA adducts revealed a peak co-migrating with an adduct obtained after in vitro treatment of deoxyguanosine-3'-phosphate with lucidin.

/GENOTOXICITY/ The genotoxic activity of lucidin (1,3-dihydroxy-2-hydroxymethyl-9,10-anthraquinone), ... was tested in a battery of short-term tests. The compound was mutagenic in five Salmonella typhimurium strains without metabolic activation, and the mutagenicity was increased after addition of rat liver S9 mix. In V79 cells, lucidin was mutagenic at the hypoxanthine-guanine phosphoribosyl transferase gene locus and active at inducing DNA single-strand breaks and DNA-protein cross-links as assayed by the alkaline elution method. Lucidin also induced DNA repair synthesis in primary rat hepatocytes and transformed C3H/M2-mouse fibroblasts in culture.

/GENOTOXICITY/ Mutagenicity of anthraquinone aglycones from Rubia tinctorum L. (Rubiaceae) was examined using the somatic mutation and recombination test in Drosophila melanogaster. Larvae heterozygous for recessive wing trichome mutations, multiple wing hairs (mwh), and flare (flr3) were exposed to test compounds and wings of emerged mwh/flr3 females were inspected for the presence of phenotypically mutant mosaic spots. No significant increase in the frequency of mutant spots was observed after the treatment of Drosophila larvae with pure lucidin.

Evaluation: There is limited evidence in experimental animals for the carcinogenicity of madder root (Rubia tinctorum). Overall evaluation: Madder root (Rubia tinctorum) is not classifiable as to its carcinogenicity to humans (Group 3). /Madder root (Rubia tinctorum)/

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

A mutagenic anthraquinone, lucidin, occurring in Rubiaceae plants, reacted with nucleic bases under physiological conditions to form adducts. ... The isolated purine base adducts were identified as condensed reactants at the benzylic position of 1 with a nitrogen atom of a purine base.

A hydroxyanthraquinone component of Rubia tinctorum (madder root) and several other plants; Used in traditional herbal medicines; [IARC]

The /IARC/ Working Group was not aware of any commercial use of purified lucidin.

Lucidin has been identified in plants from Rubia (R. tinctorum, R. iberica), Coprosma (C. lucida, C. rotundifolia, C. acerosa), Morinda (M. citrifolia, M. umbellata), Galium (G. fagetorum, G. mollugo, G. dasypodum), Hymenodictyon (H. excelsum) and Commitheca (C. liebrechtsiana) species.