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Toxicity Effects

CAS Registry Number: 117-10-2

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • 9,10-Anthracenedione, 1,8-Dihydroxy-
  • Antrapurol
  • Danthron

Human Toxicity Excerpts

  • ALTERNATIVE and IN VITRO TESTS: The comparative effects of the tumor promoter anthralin and its analog, danthron, on semiconservative DNA replication and DNA repair synthesis were studied in cultured human cells. Bromodeoxyuridine was used as density label together with 3H-thymidine to distinguish replication from repair synthesis in isopycnic CsCl gradients. Anthralin at 1.1 ug inhibited replication in T98G cells by 50%. In cells treated with 0.4 or 1.3 uM anthralin and additive effect was observed on the inhibition of replication by ultraviolet light (254 nm). In cells irradiated with 20 J/m2, 2.3 uM anthralin was required to inhibit repair synthesis by 50%. Thus there was no selective inhibitory effect of anthralin on repair synthesis. Danthron exhibited no detectable effect on either semiconservative replication or repair synthesis at concentrations below about 5.0 uM. Neither compound stimulated repair synthesis in the absence of ultraviolet irradiation. Thus, anthralin and danthron do not appear to react with DNA to form adducts that are subject to excision repair. Although both compounds appear to intercalate into supercoiled DNA in vitro to a limited extent, the degree of unwinding introduced by the respective drugs does not correlate with their relative effects on DNA synthesis in vivo. Therefore the inhibitory effect of anthralin on DNA replication and repair synthesis in T98G cells does not appear to result from the direct interaction of the drug with DNA.[Clark JM, Hanawalt PC; J Invest Dermatol 79 (1): 18-22 (1982). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract
  • CASE REPORTS: A woman developed deep discoloration of the skin following ingestion of large amounts of a laxative containing dantron. Such staining was also found in other studies, predominantly in elderly subjects, and was localized to the buttocks and thighs, with minor inflammatory symptoms. Contact of skin with feces or urine containing the drug seems to be a prerequisite for discoloration. Inflammation, when present, may result from reduction of the parent compound in the colon to the diol derivative, which irritates both the gut and skin, while the parent compound does not.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 270 (1990)] **PEER REVIEWED**
  • CASE REPORTS: An 18 year old girl presented with a leiomyosarcoma of the small bowel with widespread dissemination. Despite short term remissions after chemotherapy and surgery she died of the disease 10 months later. A history of prolonged exposure to danthron (an anthraquinone laxative) in childhood was obtained...[Patel PM et al; Postgrad Med J 65 (762): 216-7 (1989). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract Full text: PMC2429269
  • CASE REPORTS: Liver damage was reported in a woman who had used a laxative containing dantron and dioctyl calcium sulfosuccinate for one year. The symptoms disappeared after discontinuation of the medication but reappeared upon resumption; none of the compounds given alone had any effect on the results of hepatic function tests.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 270 (1990)] **PEER REVIEWED**
  • GENOTOXICITY: Dantron induced chromosomal aberrations in human peripheral lymphocytes in vitro in the absence of an exogenous metabolic system.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 270 (1990)] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: An eye irritant.[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1331] **PEER REVIEWED**
  • SIGNS AND SYMPTOMS: Melanosis coli, a state involving apoptosis and lipofuscin pigment accumulation in macrophages in colonic lamina propria, has been described in persons using anthraquinone laxatives.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 270 (1990)] **PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • GENOTOXICITY: ... A lettuce extract completely abolished the induction of micronuclei by the genotoxic anthraquinone danthron...[Mueller SO et al; Food Chem Toxicol 37 (5): 481-91 (1999). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract
  • GENOTOXICITY: /Dantron/ induced unscheduled DNA synthesis in hepatocytes from mice and rats but not in another study with rat hepatocytes. ... ln some studies, dantron inhibited gap-junctional intercellular communication in Chinese hamster V79 cells, but in other studies no such effect was found ... .[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 270 (1990)] **PEER REVIEWED**
  • GENOTOXICITY: 1,8-Dihydroxyanthraquinones ... (emodin, danthron and aloe-emodin) were tested in a number of in vitro assay systems. All three compounds induced tk-mutations in mouse lymphoma L5178Y cells. Induction of micronuclei also occurred in the same cell line, and was dose-dependent, with the potency ranking being danthron > aloe-emodin > emodin. In a DNA decatenation assay with a network of mitochondrial DNA of C. fasciulata, all three test compounds inhibited the topoisomerase II-mediated decatenation. Danthron and aloe-emodin, but not emodin, increased the fraction of DNA moving into comet tails when tested at concentrations around 50 uM in single-cell gel-electrophoresis assays (SCGE; comet assay). Comet assays were also used in modified form to determine whether pretreatment of the cells with the test compounds would reduce the effects of etoposide, a potent topoisomerase II inhibitor. All three test chemicals were effective in this pretreatment protocol, with danthron again being the most potent...[Muller SO et al; Mutat Res 371 (3-4): 165-73 (1996). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract
  • GENOTOXICITY: Danthron has been found to induce genetic damage in a limited number of prokaryotic, lower eukaryotic, and mammalian in vitro test systems.[DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Danthron (1,8-Dihydroxyanthraquinone) (117-10-2) (January 2005). Available from, as of September 18, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s055dant.pdf] **PEER REVIEWED**
  • GENOTOXICITY: Dantron induced respiration-deficient mutants in yeast.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 269 (1990)] **PEER REVIEWED**
  • GENOTOXICITY: Dantron was mutagenic to Salmonella tyhimurium TA1537 in the presence and absence of an exogenous metabolic system. It was also mutagenic to TA237, TA102 and TA104 in the presence of an exogenous metabolic system. In TA104, the results were not significantly changed by the addition of superoxide dismutase and catalase. In S. typhimurium TA100, TA1535, TA1538 and TA98, dantron was not mutagenIc in the presence or absence of an exogenous metabolic system.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 269 (1990)] **PEER REVIEWED**
  • GENOTOXICITY: The mutagenicity of /menadione, benzo[a]pyrene 3,6-quinone, 9,10-phenanthrenequinone, and danthron/ ... is demonstrated in the Salmonella TA104 tester strain. The metabolic pathways by which /the four compounds/ caused mutagenicity in this test system were investigated in detail as were the detoxification pathways. The two-electron reduction of these quinones by NAD(P)H-quinone oxidoreductase (DT-diaphorase) was not mutagenic, whereas the one-electron reduction, catalyzed by NADPH-cytochrome P-450 reductase, was mutagenic, except for danthron, which was only slightly mutagenic. The mutagenicity of the quinones via this pathway was ... attributable to the generation of oxygen radicals. The cytochrome P-450 monooxygenase also played a significant role in the detoxification and bioactivation of these quinones. For example, phenanthrenequinone was converted to a nonmutagenic metabolite in a cytochrome P-450-dependent reaction, whereas danthron was converted to a highly mutagenic metabolite... These studies show the complexity of metabolic pathways involved in the mutagenicity of quinones.[Chesis PL et al; Proc Natl Acad Sci USA 81 (6): 1696-700 (1984). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract Full text: PMC344985
  • GENOTOXICITY: The mutagenicity of anthracene, anthraquinone, and four structurally similar compounds of each was evaluated in the Ames/Salmonella microsome assay. Anthraquinone was shown to be mutagenic for strains TA1537, TA1538, and TA98 in the absence of rat liver homogenate. The four anthraquinone derivatives /including danthron/ were mutagenic for TA1537 exclusively. None of the anthracenes exhibited mutagenic activity.[Liberman DF et al; Appl Environ Microbiol 43 (6): 1354-9 (1982). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract Full text: PMC244239
  • GENOTOXICITY: Unsubstituted anthraquinone, 4 substituted anthraquinones (emodin, danthron, physcion, a new compound M-108-C) and 3 dimers (skyrin, rugulosin, rugulin) were tested using the Ames/Salmonella assay (strains TA98, TA100, TA1537 and TA102). Danthron and emodin were found to be mutagenic for TA1537 with or without metabolic activation, physcion only with metabolic activation. A significant difference was found between the mutagenic activities of emodin (16.2 His+/nmole) and danthron (6.5 His+/nmole) as well as a high specific mutagenic activity for physcion (11.6 His+/nmole). These results on structure-mutagenic activity relationships suggest that the 6-methyl group plays an important role in the mutagenic activity after metabolic activation...[Krivobok S et al; Mutat Res 279 (1): 1-8 (1992). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: 20 male C3H/HeN mice, eight weeks of age, was fed dantron (commercial grade; no impurity detected on thin-layer chromatography) at 20 mg/kg diet for 540 days, at which time the experiment was terminated. A group of 20 untreated male mice served as controls. Hepatocellular adenomas were found in 9/17 treated and 5/19 control mice. Hepatocellular carcinomas were found in 4/17 treated mice (all also had adenomas), an incidence that was significantly different (p<0.05; Fisher exact test) from that in controls (0/19). Adenomatous (polypoid) hyperplasia, occasionally associated with dysplastic changes, was observed in the cecum of 17/17 treated mice and in the remainder of the colon of 5/17 treated mice, but not in controls.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 267 (1990)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: A group of 18 male ACI rats, eight weeks of age, was fed dantron (purity unspecified) at 10,000 mg/kg diet for 16 months. A group of 15 untreated males served as controls. Twelve treated and 14 untreated rats survived more than one year. Nine tumors of the large intestine were found in 7/12 treated rats (three adenomas and four adenocarcinomas (p<0.02) of the colon and two adenomas of the cecum). In addition, focal epithelial hyperplasia was observed frequently in the mucosa of the colon and cecum of treated rats with and without intestinal tumors. No intestinal tumor or hyperplastic lesion was found in the 14 controls.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 268 (1990)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Groups of four male and four female beagle dogs received either a vehicle capsule or a capsule containing dantron at 5 or 15 mg/kg bw daily for one year. No adverse effect was observed. The doses employed were reported to be several-fold higher than the usual clinical dose.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 269 (1990)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Male rats given dantron at 600 or 2400 mg/kg diet for 26 weeks had enlarged lymph nodes in the mesocolon, which were brownish due to pigmentation of the accumulated mononuclear phagocytes. ln kidney, pigment deposition was seen in the cortical region.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 269 (1990)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: The carcinogenicity of chrysazin (1,8-dihydroxy-9,10-anthracenedione) was examined by dietary administration to C3H/HeN mice. All of the effective mice (17) which were given 0.2% chrysazin diet and which survived more than 500 days developed adenomatous hyperplasia with cystic glands of the cecum. Similar lesions were also seen in the colon of mice in this group. These intestinal lesions were not obtained in any effective mouse (19) of the control group. The incidence of hepatocellular carcinoma of mice given chrysazin (4/17) was significantly higher than that of the controls (0/19). These results indicate that chrysazin is carcinogenic in mice as well as in rats. Some mechanistic aspects of the causation of these intestinal lesions and liver neoplasms are also discussed.[Mori H et al; Jpn J Cancer Res 77 (9): 871-6 (1986). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: The modifying effects of chrysazin on 1,2-dimethylhydrazine (DMH)-induced colon and liver carcinogenesis were examined in male ICR/CD-1 mice. Starting at 6 weeks of age, mice were divided into four groups, two of which were treated with sc injections of DMH (20 mg/kg body wt) once a week for 12 weeks. A week after the final injection of DMH, one group was kept on the basal diet throughout the study (group I), and the other group was fed the diet containing chrysazin (mixed in basal diet at 0.2% concentration) alone for 42 weeks (group II). The other two groups were injected with normal saline and given the diet containing 0.2% chrysazin for 42 weeks (group III), or the basal diet during the experiment (group IV). The incidence and multiplicity of colon tumors of group II were significantly greater than those of group I (P < 0.05, P < 0.01). The incidence and multiplicity of the hepatocellular neoplasms of group II were larger than those of group I (P < 0.002, P < 0.02 respectively). In group III, colon tumors were not found, though a few liver neoplasms and severe inflammatory lesions of the colon were observed. The activity of ornithine decarboxylase of the colonic mucosa in mice exposed to chrysazin was stronger than that of animals without chrysazin. The results suggest that the promoting effect of chrysazin is probably related to an increase of cell proliferation in the target organ. A synergistic effect of DMH with chrysazin was also observed in liver tumorigenesis.[Sugie S et al; Carcinogenesis 15 (6): 1175-9 (1994). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: The tumor-promoting activity of the anthraquinone laxative danthron was studied by giving 3 groups of male rats a single subcutaneous injection of the colon tumor-inducing agent 1,2-dimethylhydrazine (DMH). After 1 week, the animals were fed diets containing 0, 600 or 2400 ppm of danthron for 26 weeks. Two other groups of rats were included in the study; one received no treatment while the other was given danthron only. Altogether 9 tumors were observed among animals given DMA with or without danthron. The incidence of colon tumors was higher in animals receiving DMH and danthron than in those given DMH only (5/60 vs. 0/30), but this difference was not statistically significant. The kidneys and lymph nodes of mesocolon were enlarged and showed a yellowish-red and brown discoloration, respectively. The pigment mostly displayed a PAS-positive reaction but contained no lipid as determined by several staining procedures. The available evidence suggests that the pigment is drug-derived.[Sjoberg P et al; Toxicol Lett 44 (3): 299-306 (1988). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: When administered in the diet to male rats, danthron induced adenomas and adenocarcinomas of the colon and adenomas of the cecum. When administered in the diet to male mice, danthron caused an increase in the incidence of hepatocellular carcinomas.[DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Danthron (1,8-Dihydroxyanthraquinone) (117-10-2) (January 2005). Available from, as of September 18, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s055dant.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: When administered in the diet without other chemicals, danthron caused a large increase in the incidence of a preneoplastic lesion, adenomatous polyploid hyperplasia of the cecum and colon in male mice.[DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Danthron (1,8-Dihydroxyanthraquinone) (117-10-2) (January 2005). Available from, as of September 18, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s055dant.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: When danthron was administered in the feed to mice that also received 1,2- dimethylhydrazine, the incidence and multiplicity of adenomas of the colon and liver were significantly increased.[DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Danthron (1,8-Dihydroxyanthraquinone) (117-10-2) (January 2005). Available from, as of September 29, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s055dant.pdf] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ln a two-stage carcinogenesis experiment, a group of 20 female ICR/Ha Swiss mice, seven weeks of age, received a single skin application of 7,12-dimethylbenz(a)anthracene at 20 ug in 0.1 mL acetone, followed two weeks later by applications three times a week of commercial-grade dantron at 170 ug in 0.1 mL acetone. A control group of 20 female mice received only skin applications of dantron at 170 ug in 0.1 mL acetone three times a week. Median survival time of animaIs in both groups was greater than 490 days, when the experiment was terminated. No skin tumor was found in either group.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 268 (1990)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ln a two-stage carcinogenicity study, groups of 30 male Sprague-Dawley rats, 50 days of age, received a single subcutaneous injection of 1,2-dimethylhydrazine (DMH) at 150 mg/kg bw. After one week they were fed dantron (purity, >97%) at 0, 600 or 2400 mg/kg diet; the average daily intakes were approximately 30 and 60 mg/kg bw. After 26 weeks, all animaIs were killed. Two additional groups of 30 male rats received either no treatment or were given the diet with the higher concentration of dantron alone. There was no significant difference in mean body weight gain between treated and control animaIs. ln the rats treated with DMH plus dantron, the combined incidences of intestinal adenomas and adenocarcinomas were 4/30 in the low-dose and 2/30 in the high-dose group. The incidences of intestinal adenocarcinomas were 0/30 in untreated controls, 0/30 in the group treated with dantron alone and 2/30 in the group treated with DMH alone. The difference in tumor incidence between animaIs treated with DMH alone and DMH plus dantron was not significant.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 268 (1990)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: ... Male F344 rats were fed a diet containing danthron, sennosid A, bisacodyl, 1-hydroxyanthraquinone (1-HAQ), magnesium sulfate (MgSO4), dextran sulfate sodium (DSS), pectin, carboxymethylcellulose sodium (CMC-Na) or sodium chloride (NaCl) for 7 days. The stimulant laxatives, danthron, sennosid A and bisacodyl, significantly induced cell proliferation in almost the entire intestinal epithelia in a clear dose-dependent manner. DSS also induced cell proliferation in some portions at high doses. Increase in BrdU-labelling indices was correlated well with the severity of inflammatory changes in the intestinal mucosa as well as with purging effects of stimulant laxatives and DSS. In contrast, the bulk-forming laxative CMC-Na did not consistently enhance cell proliferation nor cause apparent cytotoxicity in the intestine despite exerting remarkable purging effects. 1-HAQ and MgSO4 slightly induced cell proliferation in the cecum and the colorectum, although there was little or no intestinal cytotoxicity. Pectin and NaCl did not influence cell kinetics of the epithelia, nor cause any inflammatory changes in the mucosa. /These/ results thus indicate that diarrhea caused by laxatives is not necessarily correlated with induction of cell proliferation, as in the intestinal mucosa, and that inflammatory changes followed by regenerative process could be responsible for enhancing cell kinetics...[Toyoda K et al; Cancer Lett. 1994 Aug 15;83(1-2):43-9. Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: The effects of 1,8-dihydroxyanthraquinone (DHAQ), a stimulant laxative named danthron, on cell kinetics and prostaglandin (PG) biosynthesis in the gastrointestinal tract were investigated in male 8-week-old F344 rats divided into three groups, each consisting of 10 animals. The animals in groups one, two and three were respectively given diets supplemented with 0%, 0.1% and 0.2% DHAQ for 24 days. PGE2 levels in the colorectal mucosa were significantly (P < 0.05 and 0.001) elevated after DHAQ treatment and showed some evidence of a dependence of DHAQ dose, consistent with the plasma PGE2 levels. BrdU-labeling indices in the large intestinal epithelium were also significantly (P < 0.01) increased, although the other portions of the gut such as the stomach and small intestine were not significantly affected. Excretion of the main urinary metabolite of PGE (PGE-MUM) was significantly (P < 0.001 or 0.01) increased whereas the urinary PGE2 concentration and total PGE2 excretion were not changed. Thus the results of the ... study clearly indicate enhancement of cell proliferation by DHAQ in the large intestine epithelia, correlated with increased PGE2 levels in the large intestinal mucosa as well as the plasma, and possible support for the conclusion that quantitative analysis of urinary PGE-MUM, but not PGE2 itself, offer a useful approach for biomonitoring exposure to such stimulant laxatives.[Nishikawa A et al; Carcinogenesis 18 (6): 1259-63 (1997). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract
  • OTHER TOXICITY INFORMATION: Apoptosis together with accumulation of lipofuscin pigment in gut wall was noted in guinea-pigs given dantron orally at 25 mg/kg bw.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 269 (1990)] **PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Mouse ip 500 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1331] **PEER REVIEWED**
  • LD50 Mouse oral < 7 g/kg[The Merck Index, Fourteenth Edition (2006) [CD-ROM]] **PEER REVIEWED**

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Absorption, Distribution And Excretion

  • Following its administration within 24 hr of the induction of labor in 12 women, dantron was found in maternal urine, neonatal urine and amniotic fluide. Most of the drug appeared as a glucuronide in both mothers and babies.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 270 (1990)] **PEER REVIEWED**
  • Like other anthraquinone compounds, dantron is partially absorbed from the small intestine.[Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Co-danthramer capsules and Strong Co-danthramer capsules (Last updated February 2009). Available from, as of November 17, 2009: http://emc.medicines.org.uk/medicine/1219/SPC/Co-danthramer+capsules+and+Strong+Co-danthramer+capsules/#PRODUCTINFO] **PEER REVIEWED**
  • Male Wistar rats were given the sodium salt of dantron intravenously at 4.8, 22 or 58 umol/kg (1.2, 5.3 or 14 mg/kg) bw or at 12 umol/kg (28.8 mg/kg) bw by gastric tube. ... Following intravenous administration, about 80% of the dantron conjugates in bile were excreted after 1 hr; the dose fractions found after 5 hr represented about 20%, 30% and 40% of the low-; intermediate- and high-dose levels, respectively. The corresponding fractions in urine were 16%, 12% and 10%, giving rise to bile:urine excretion ratios of 1.3, 2.7 and 4.0, respectively. Only 30-50% of the dose could be accounted for by conjugates. Earlier studies also showed that after oral administration of dantron only 30-40% of the total dose administered could be recovered in feces and urine, mostly during the first 24 hr. /Dantron sodium salt/[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 268 (1990)] **PEER REVIEWED**
  • Rats were infused with danthron (I) at doses of 0.48, 2.2 and 5.8 umol/100 g body weight, or given 12 umol/100 g with gastric tube. TLC of bile and urine demonstrated a number of metabolites, at both administration routes. These included danthron monosulfate (II) and -glucuronide (III), two other phase 2 metabolites which behaved as the corresponding diconjugates, and several phase 1 metabolites (IV) in conjugated form. ... Following infusion, about 80% of the danthron conjugates in bile were excreted after 1 hour; the dose fractions found after 5 hours represented about 20%, 30%, and 40% at the low, intermediate and high dose level, respectively. The corresponding fractions in urine were 16%, 12% and 10%, giving rise to bile:urine excretion ratios of 1.3, 2.7 and 4.0, respectively. This change in excretion pattern was associated with changes in metabolite muster, which involved a decrease in the balance of IV:I conjugates, as well as an increase in III:II ratio. IV was more abundantly present in bile than in urine, and showed a more sustained excretion than the danthron conjugates. By intragastric administration, the cumulated excretion (bile + urine) of I conjugates were only 6%, 8% and 5% of dose, in three consecutive 6 hours' periods (0-6, 6-12 and 12-18 hours after dosing). The bile:urine excretion ratios seemed to decrease with time, as did the III:II ratio...[Sund RB; Pharmacol Toxicol 61 (2): 130-7 (1987). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract

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Metabolism/Metabolites

  • ... Everted sacs of rat jejunum and stripped colon were filled with Krebs-Henseleit solution (K-H) on the serosal (BL) side, and bathed at the mucosal (LU) side with K-H containing either danthron (3-4 nmol/mL) or rhein (10 nmol/mL). After 60 min incubation at 37 degrees C, LU and BL solutions and gut tissue were analysed for parent diphenol and metabolites by reverse-phase high-pressure liquid chromatography. Reference metabolites were isolated and purified from urine and bile of rats infused with danthron or rhein. The studies showed: (1) only small amounts of unchanged drug were present on the contraluminal side; (2) in both tissues, danthron was transformed into its monoglucuronide (G) and monosulfate (S); the ratio G:S was 6-8:1 in jejunum, and even greater in colon; (3) in jejunum, G and S were mainly secreted (LU:BL distribution ratios greater than 10:1); (4) in the colon, however, the main G fraction was absorbed (BL:LU ratios of 3:1), whereas a slight net secretion of S seemed to take place; (5) residuals (%) in gut tissue were small; (6) rhein was more slowly taken up and metabolized, but seemed otherwise to behave as danthron...[Sund RB, Elvegard SO; Pharmacology 36 Suppl 1:144-51 (1988). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract
  • Danthron infused intravenously in rats shows a complex dose-dependent pattern of metabolism and excretion. The metabolites, particularly the more polar ones, are in general excreted predominantly in bile, to a lesser extent in urine. ... /This/ paper describes a further study within a bile-derived metabolite group, which proved to be particularly heterogeneous. It contained more than a dozen metabolites, which were conjugates of four different aglycons including the parent danthron...[Sund RB et al; Pharmacology 47 Suppl 1:134-7 (1993). Available from, as of November 16, 2009:] **PEER REVIEWED** PubMed Abstract
  • In vitro, rat jejunum and colon transformed dantron into its monoglucuronide and monosulfate, the monoglucuronide being the major metabolite.[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 269 (1990)] **PEER REVIEWED**
  • Male Wistar rats were given the sodium salt of dantron intravenously at 4.8, 22 or 58 umol/kg (1.2, 5.3 or 14 mg/kg) bw or at 12 umol/kg (28.8 mg/kg) bw by gastric tube. Metabolites identified in the bile and urine following administration by either route included the monosulfate, beta-glucuronide and other unidentified metabolites. /Dantron sodium salt/[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: http://monographs.iarc.fr/ENG/Classification/index.php, p. V50 268 (1990)] **PEER REVIEWED**

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Tsca Test Submissions

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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