1,8-디히드록시안트라퀴논

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Do not store above 30 °C.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No method should be applied ... until it has been thoroughly tested for its effectiveness & safety on material to be inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by reaction with 4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As a general technique ... treatment with sodium dichromate in strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 1-2 days is generally considered sufficient when freshly prepd reagent is used. ... Carcinogens that are easily oxidizable can be destroyed with milder oxidative agents, such as saturated soln of potassium permanganate in acetone, which appears to be a suitable agent for destruction of hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for 1,8-Dihydroxyanthraquinone (7 total), please visit the HSDB record page.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens are used ... should be marked distinctively with appropriate labels. Access ... limited to persons involved in expt. ... A prominently displayed notice should give the name of the Scientific Investigator or other person who can advise in an emergency & who can inform others (such as firemen) on the handling of carcinogenic substances. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has occurred, such as spillage, should be decontaminated by lab personnel engaged in expt. Design of expt should ... avoid contamination of permanent equipment. ... Procedures should ensure that maintenance workers are not exposed to carcinogens. ... Particular care should be taken to avoid contamination of drains or ventilation ducts. In cleaning labs, procedures should be used which do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner equipped with high-efficiency particulate filter on exhaust, which are avail commercially, should be used. Sweeping, brushing & use of dry dusters or mops should be prohibited. Grossly contaminated cleaning materials should not be re-used ... If gowns or towels are contaminated, they should not be sent to laundry, but ... decontaminated or burnt, to avoid any hazard to laundry personnel. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in lab could build up during conduct of expt, periodic checks should be carried out on lab atmospheres, surfaces, such as walls, floors & benches, & ... interior of fume hoods & airducts. As well as regular monitoring, check must be carried out after cleaning-up of spillage. Sensitive methods are required when testing lab atmospheres. ... Methods ... should ... where possible, be simple & sensitive. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for 1,8-Dihydroxyanthraquinone (10 total), please visit the HSDB record page.

6.7 [mg/m3]

73 [mg/m3]

440 [mg/m3]

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

Effective March 28, 1987, danthron containing products may no longer be marketed in the United States. The Food and Drug Administration has advised drug firms manufacturing laxatives containing the drug danthron to immediately discontinue their production and to recall them from retail store shelves. Detention without physical examination is indicated on all (Bulk, Rx and OTC) articles of drug offered for human use that contain danthron.

This final rule declares OTC laxative drug products containing danthron to be new drugs within the meaning of section 201(p) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321(p)), for which an application or abbreviated application (hereinafter called application) approved under section 505 of the act (21 U.S.C. 355) and 21 CFR part 314 is required for marketing. In the absence of an approved application, products containing these drugs for laxative use also would be misbranded under section 502 of the act (21 U.S.C. 352). The final rule amends part 310 (21 CFR part 310) to include danthron by adding new Sec. 310.545(a)(12)(iv)(B). Because a safety problem has been identified for OTC drug products containing danthron, this final rule is effective on the date of its publication in the Federal Register. Therefore, on or after January 29, 1999, no OTC drug products that are subject to this final rule may be initially introduced or initially delivered for introduction into interstate commerce unless they are the subject of an approved application.

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.

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.

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.

EC50; Species: Lemna gibba (Inflated duckweed); Conditions: freshwater, renewal, photomodified; Concentration: 500 ug/L for 7 days; Effect: decreased population growth /formulation/

EC50; Species: Lemna gibba (Inflated duckweed); Conditions: freshwater, renewal, simulated solar radiation; Concentration: 2500 ug/L for 7 days; Effect: decreased population growth /formulation/

EC50; Species: Lemna gibba (Inflated duckweed); Conditions: freshwater, renewal, photosynthetically active radiation; Concentration: 3000 ug/L for 7 days; Effect: decreased population growth /formulation/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 8,600(SRC), determined from a structure estimation method(2), indicates that 1,8-dihydroxyanthraquinone is expected to be immobile in soil(SRC). An estimated pKa value of 1,8-dihydroxyanthraquinone is 8.45(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of 1,8-dihydroxyanthraquinone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.4X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(5). 1,8-Dihydroxyanthraquinone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.6X10-10 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation data were not available(SRC, 2009).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 8,600(SRC), determined from a structure estimation method(2), indicates that 1,8-dihydroxyanthraquinone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.4X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 50(SRC), from an estimated log Kow of 3.9(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). 1,8-Dihydroxyanthraquinone is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Biodegradation data were not available(SRC, 2009).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1,8-dihydroxyanthraquinone, which has an estimated vapor pressure of 8.6X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase 1,8-dihydroxyanthraquinone may be removed from the air by wet or dry deposition(SRC). 1,8-Dihydroxyanthraquinone absorbs light at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).

/AQUATIC SPECIES/ The study on the acute, sublethal and chronic toxicity of 1,8-dihydroxyanthraquinone to Daphnia magna showed that the 48 hr LC50 was 0.37 mg/L, and the feeding behavior of Daphnia magna was severely affected by the compound. When exposed to 0.2 mg/L of 1,8-dihydroxyanthraquinone for 5 hr, the filtration and ingestion rate of Daphnia magna was inhibited by 97%. Chronic toxicity test results indicated that the reproduction ability decreased dramatically after exposing to sublethal concentration of 1,8-dihydroxyanthraquinone ...

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 1,8-dihydroxyanthraquinone can be estimated to be 8,600(SRC). According to a classification scheme(2), this estimated Koc value suggests that 1,8-dihydroxyanthraquinone is expected to be immobile in soil. An estimated pKa value of 1,8-dihydroxyanthraquinone is 8.45(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/1,8-Dihydroxyanthraquinone/ has been isolated from dried leaves and stems of Xyris semifuscata harvested in Madagascar. /1,8-Dihydroxyanthraquinone/ is the basic structure of the aglycones of naturally occurring laxative glycosides, in e.g., Cassia (senna), Aloe, Rheum and Rhamnus (cascara) species. /1,8-Dihydroxyanthraquinone/ has been identified in larvae of the elm-leaf beetle, Pyrrhalta luteola. The presence of a mixture of anthraquinones and anthrones was suggested to be a means of protection from predators, and these compounds appear to be biosynthesized by the insect.

/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.

/SIGNS AND SYMPTOMS/ An eye irritant.

/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.

/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.

For more Human Toxicity Excerpts (Complete) data for 1,8-Dihydroxyanthraquinone (7 total), please visit the HSDB record page.

Dantron (Chrysazin; 1,8-Dihydroxyanthraquinone)

Group 2B: Possibly carcinogenic to humans

Volume 50: (1990) Pharmaceutical Drugs

1990

1989

An estimated BCF of 50 was calculated in fish for 1,8-dihydroxyanthraquinone(SRC), using an estimated log Kow of 3.9(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

The Henry's Law constant for 1,8-dihydroxyanthraquinone is estimated as 5.4X10-11 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 1,8-dihydroxyanthraquinone is expected to be essentially nonvolatile from water surfaces(2). 1,8-Dihydroxyanthraquinone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.6X10-10 mm Hg(SRC), determined from a fragment constant method(3).

Important intermediate in the manufacture of alizarin and indanthrene dyestuffs; forms insoluble calcium, barium, and lead lakes. Antioxidant in synthetic lubricants; fungicide.

It is currently used as an antioxidant in synthetic lubricants, in the synthesis of experimental antitumor agents, and as a fungicide for control of powdery mildew ... It is also used, to a lesser extent, as an intermediate in the manufacture of dyes and forms lakes with calcium, barium, and lead.

Therapeutic category: Cathartic /Former use in USA/

Therapeutic category (Vet): Purgative /Former use in USA/

Dantron has been prepared by several processes, including the alkaline hydrolysis of 1,8-dinitroanthraquinone, the caustic fusion of 1,8-anthraquinonedisulfonic acid, the diazotization of 1,8-diaminoanthraquinone followed by hydrolysis of the bisdiazo compound, the acid hydrolysis of 1,8-dimethoxyanthraquinone in glacial acetic acid-sulfuric acid, the alkaline hydrolysis of 1,8-anthraquinonedisulfonic acid using calcium oxide, and the reaction of 1,8-dinitroanthraquinone with sodium formate or potassium formate.

Dantron is available commercially at a purity of 95-99%.

Altan

Antrapurol

Bancon

For more Formulations/Preparations (Complete) data for 1,8-Dihydroxyanthraquinone (37 total), please visit the HSDB record page.

9,10-Anthracenedione, 1,8-dihydroxy-: ACTIVE

Use was discontinued in Canadian, US and UK markets in 1998

In 1987, US manufacturers voluntarily withdrew production of all human drug products containing dantron.