1-HYDROXYANTRAQUINONE (Group 2B)
MADDER ROOT (RUBIA TINCTORUM) (Group 3)For definition of Groups, see Preamble Evaluation.
VOL.: 82 (2002) (p. 129)
5. Summary of Data Reported and Evaluation
5.1 Exposure data
Hydroxyanthraquinones are constituents of a number of plant species including Rubia tinctorum (madder root) and Morinda officinalis that are used in traditional herbal medicines. 1,3-Dihydroxy-2-hydroxymethylanthraquinone (lucidin) occurs in R. tinctorum in the form of glycoside conjugates, and 1-hydroxyanthraquinone similarly occurs in M. officinalis.
5.2 Human carcinogenicity data
Herbs containing anthraquinone derivatives
Herbs containing anthraquinone derivatives are used as laxatives and several studies have reported data relating indices of use of such laxatives to cancer outcomes. In an early British study, patients with gastrointestinal cancer reported higher past chronic use of senna than did patients with other diseases. Three German case–control studies on colorectal cancer using melanosis coli as an exposure indicator gave conflicting results. An Australian case–control study on colorectal cancer which assessed self-reported use of anthraquinone laxatives as an index of exposure found no excess risk. A study of urothelial cancer in Germany found elevated relative risks in relation to several types of laxative, including those containing anthraquinones. For all of these case–control studies, it is difficult to exclude bias and confounding from dietary habits, constipation or use of analgesics. Except for two studies (the Australian colorectal cancer and the German urothelial cancer studies), selection of controls is also a major concern.
5.3 Animal carcinogenicity data
1-Hydroxyanthraquinone was tested for carcinogenicity by oral administration in three studies in rats and induced adenocarcinomas of the large intestine in two studies.
No carcinogenicity tests have been carried out with 1,3-dihydroxy-2-hydroxymethylanthraquinone (lucidin) per se, although the herb madder root (Rubia tinctorum) (which contains this compound among others) was tested by oral administration in rats. Madder root caused an increase in hepatocellular adenomas and adenomas and carcinomas of the renal cortex in males and females in a single experiment.
5.4 Other relevant data
1-Hydroxyanthraquinone is metabolized by rats and excreted as alizarin (1,2-dihydroxyanthraquinone). When given orally to rats, it induced inflammatory changes in the colon. It is mutagenic in bacteria and causes unscheduled DNA synthesis in rat liver cells in vitro.
Lucidin primeveroside is hydrolysed in rats to the aglycones 1,3-dihydroxy-2-hydroxymethylanthraquinone (lucidin) and rubiadin, which are excreted in urine. Lucidin is mutagenic in bacteria, mutagenic and genotoxic in cultured mammalian cells and forms DNA adducts in mice.
There is inadequate evidence in humans for the carcinogenicity of laxatives containing anthraquinone derivatives.
There is sufficient evidence in experimental animals for the carcinogenicity of 1-hydroxyanthraquinone.
There is limited evidence in experimental animals for the carcinogenicity of madder root (Rubia tinctorum).
1-Hydroxyanthraquinone is possibly carcinogenic to humans (Group 2B).
Madder root (Rubia tinctorum) is not classifiable as to its carcinogenicity to humans (Group 3).
For definition of the italicized terms, see Preamble Evaluation.
See Also: Toxicological Abbreviations