1,8-Dihydroxyanthraquinone

Description

Danthron, a natural product, was originally extracted from the roots and rhizome of Polygonaceae plant, also called Da Huang in traditional Chinese herbal medicine. Now it is synthesized in many countries, such as Germany, India, Japan, Poland, the United Kingdom, and the United States. Danthron is reasonably anticipated to be a human carcinogen.
Danthron is an anthraquinone that exists at room temperature as a red or orange crystalline powder.It is practically insoluble in water, but soluble in a variety of solvents (acetone, chloroform, diethyl ether, ethanol) and alkaline hydroxide solutions. The stability of danthron is generally good. It is stable under room temperatures and normal pressures.

Chemical properties

orange-brown or brown powder

Chemical properties

Red-orange to orange crystalline powder or reddish-brown crystalline solid.

The Uses of 1,8-Dihydroxyanthraquinone

1,8-Dihydroxyanthraquinone can be used:

• To prepare an inclusion complex with β-cyclodextrin, applicable as a sensor in the estimation of Cu²⁺?ions in an aqueous solution.
• As a starting material in the synthesis of 1,4,5,8-tetramethoxyanthracene.
• As an aromatic scavenger in the modification of lignin, which acts as a corrosion inhibitor for steel.

The Uses of 1,8-Dihydroxyanthraquinone

Used as a stimulant laxative, though due to its carcinogenic properties, is not widely prescribed.

The Uses of 1,8-Dihydroxyanthraquinone

cathartic

The Uses of 1,8-Dihydroxyanthraquinone

Important intermediate in the manufacture of alizarin and indanthrene dyestuffs; forms insoluble Ca, Ba, Pb lakes. Antioxidant in synthetic lubricants; fungicide.

Background

Withdrawn from the Canadian, US, and UK markets in 1998 due to genotoxicity.

Definition

ChEBI: 1,8-Dihydroxyanthraquinone is a dihydroxyanthraquinone that is anthracene-9,10-dione substituted by hydroxy groups at positions 1 and 8. It has a role as an apoptosis inducer and a plant metabolite.

brand name

Dorbane (3M Pharmaceuticals); Istizin (Sterling Winthrop);Doss;Normax;Regulex-d.

World Health Organization (WHO)

Dantron, an anthroquinone derivative, has been available for over twenty years and is widely used as a laxative. The results of two chronic toxicity studies in rodents, published in 1985 and 1986, have shown that administration of high doses is associated with the development of intestinal and liver tumours.

General Description

Orange crystalline powder. Almost odorless and tasteless.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

1,8-Dihydroxyanthraquinone is incompatible with strong reducing substances such as hydrides, nitrides, alkali metals, and sulfides.

Fire Hazard

Flash point data for 1,8-Dihydroxyanthraquinone are not available; however, 1,8-Dihydroxyanthraquinone is probably combustible.

Side Effects

Liver injury may occur with 1,8-Dihydroxyanthraquinone when used as a laxative for one year. Symptoms disappeared after discontinuation of the drug, but recurred after resumption of the drug; none of the drugs administered alone had any effect on liver function test results. In addition, deep skin discolouration may occur with heavy use, mainly in elderly subjects, and is limited to the buttocks and thighs, with mild signs of inflammation. Skin contact with faeces or urine containing the drug appears to be a prerequisite for discolouration. Inflammation, if present, may be due to reduction of the parent compound in the colon to diol derivatives, which can irritate the intestine and skin in a way that the parent compound does not. There is also the possibility of colorectal melanosis.

Safety Profile

Confirmed carcinogen with experimental carcinogenic data. Moderately toxic by intraperitoneal route. An eye irritant. Questionable carcinogen with experimental carcinogenic and neoplastigenic data. Human mutation data reported. A laxative. When heated to decomposition it emits acrid smoke and irritating fumes.

Synthesis

1,8-Dihydroxyanthraquinone is prepared by replacing SO3H, by directly replacing nitro groups in sulfolane in the presence of calcium oxide , or, better, via 1,8-dimethoxyanthraquinone and subsequent hydrolysis of the ether .

Potential Exposure

A potential liver carcinogen and possible narcotic, this compound is no longer sold or marketed in the United States Nervous system toxin-acute effects; Respiratory toxin-acute effects other than severe or moderate irritation; Liver-acute effects; Eye irritant-mild.

Carcinogenicity

Danthron is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.

Environmental Fate

Danthron can cause DNA damage particularly at guanines in the 5'-GG-3', 5'-GGGG-3', 5'-GGGGG-3' sequences in the presence of Cu(II), cytochrome P450 reductase and the nicotinamide adenine dinucleotide phosphate (NADPH)-generating system. H2O2 and Cu(I) may also be involved because this DNA damage can be inhibited by catalase and bathocuproine. The further mechanism is danthron is reduced by P450 reductase and generate reactive oxygen species through the redox cycle, leading to extensive Cu(II)-mediated DNA damage. The DNA damage also comes from similar topoisomerase II inhibitor behavior of danthron.

Metabolism

Not Available

Shipping

UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.

Purification Methods

Crystallise Danthrone from EtOH and sublime it in a vacuum. [Beilstein 8 IV 3217.]

Toxicity evaluation

Danthron is discovered in several species of plants and insects. It has been isolated from dried leaves and stems of Xyris semifuscata harvested in Madagascar, and roots of Da Huang, a Chinese traditional herbal medicine. Danthron also appears to be biosynthesized by some insects. The presence of danthron in insects may be a way of protection from predators. Danthron can be manually synthesized by many countries. In the United States, danthron was available from 12 suppliers.
If released to the atmosphere, danthron will exist in both the vapor phase and the particulate phase. Vapor phase danthron has an estimated half-life of 11 days. Particulate phase danthron can be physically removed from air by wet and dry deposition. It is expected to biodegrade with 68% degradation within 3 months.
If released to water, danthron is expected to adsorb to the surface of solid particle and sediment. Biodegradation is also a major pathway processed in water. It was reported that 82% of the added danthron was degraded by fresh water within 3 days. If added to seawater, 91% of danthron was reported as degraded. Danthron may bioconcentrate in aquatic organisms, such as fish and shrimps.

Incompatibilities

Keep away from strong reducing agents, such as hydrides, nitrides, alkali metals, and sulfides.

Waste Disposal

It is inappropriate and possibly dangerous to the environment to dispose of expired or waste drugs and pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double- bagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to prop- erly 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.