Hexachlorobenzene, or perchlorobenzene, is an

organochloride An organochloride, organochlorine compound, chlorocarbon, or chlorinated hydrocarbon is an organic compound containing at least one covalent bond, covalently bonded atom of chlorine. The chloroalkane class (alkanes with one or more hydrogens subst ...

with the molecular formula C₆Cl₆. It is a

fungicide Fungicides are biocidal chemical compounds or biological organisms used to kill parasitic fungi or their spores. A fungistatic inhibits their growth. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality, ...

formerly used as a seed treatment, especially on wheat to control the fungal disease

bunt Bunt may refer to: * Bunt (community), an elite social group from Karnataka, India * Bunt (baseball), a batting technique in baseball * Bunt (sail), a part of a ship's sail * Bunt Island, island in Antarctica * The Bunt, nickname of the Bunting ...

. It has been banned globally under the Stockholm Convention on Persistent Organic Pollutants.

Physical and chemical properties

Hexachlorobenzene is a stable, white, crystalline chlorinated hydrocarbon. It is sparingly soluble in organic solvents such as benzene, diethyl ether and alcohol, but practically insoluble in water with no reaction. It reacts violently above 65 °C with

dimethyl formamide Dimethylformamide is an organic compound with the formula ( CH3)2NC(O)H. Commonly abbreviated as DMF (although this initialism is sometimes used for dimethylfuran, or dimethyl fumarate), this colourless liquid is miscible with water and the major ...

and has a flash point of 468 °F. It is stable under normal temperatures and pressures. It is combustible but it does not ignite readily. When heated to decomposition, hexachlorobenzene emits highly toxic fumes of

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid Acid strength is the tendency of an acid, symbol ...

, other chlorinated compounds (such as

phosgene Phosgene is the organic chemical compound with the formula COCl2. It is a toxic, colorless gas; in low concentrations, its musty odor resembles that of freshly cut hay or grass. Phosgene is a valued and important industrial building block, espe ...

carbon monoxide Carbon monoxide (chemical formula CO) is a colorless, poisonous, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the simple ...

, and

carbon dioxide Carbon dioxide (chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is transpar ...

Synthesis

Hexachlorobenzene has been made on a laboratory scale since the 1890s, by the

electrophilic aromatic substitution Electrophilic aromatic substitution is an organic reaction in which an atom that is attached to an aromatic system (usually hydrogen) is replaced by an electrophile. Some of the most important electrophilic aromatic substitutions are aromatic ni ...

reaction of chlorine with benzene or chlorobenzenes. Large-scale manufacture for use as a fungicide was developed by using the residue remaining after purification of the mixture of isomers of hexachlorocyclohexane, from which the insecticide

lindane Lindane, also known as ''gamma''-hexachlorocyclohexane (γ-HCH), gammaxene, Gammallin and benzene hexachloride (BHC), is an organochlorine chemical and an isomer of hexachlorocyclohexane that has been used both as an agricultural insecticide and ...

(the γ-

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

) had been removed, leaving the unwanted α- and β- isomers. This mixture is produced when benzene is reacted with chlorine in the presence of ultraviolet light (e.g. from sunlight).

Usage

Hexachlorobenzene was used in

agriculture Agriculture or farming is the practice of cultivating plants and livestock. Agriculture was the key development in the rise of sedentary human civilization, whereby farming of domesticated species created food surpluses that enabled people to ...

to control the fungus ''

tilletia caries ''Tilletia caries'' (synonymous with ''Tilletia tritici'') is a basidiomycete that causes common bunt of wheat. The common names of this disease are stinking bunt of wheat and stinking smut of wheat. This pathogen infects wheat, rye, and various ...

'' (common bunt of wheat). It is also effective on

tilletia controversa ''Tilletia controversa'' is a plant pathogen. It is a fungus known to cause the smut disease TCK smut in soft white and hard red winter wheats. It stunts the growth of the plants and leaves smut balls in the grain heads. When the grain is mill ...

, dwarf bunt. The compound was introduced in 1947, normally formulated as a

seed dressing In agriculture and horticulture, a seed treatment is any additional material added to the seed. By the amount of material added, it can be divided into: * A seed dressing, typically containing a "protectant" ( pesticide) applied to the seed and po ...

but is now banned in many countries.

Safety

Hexachlorobenzene is an animal

carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...

and is considered to be a probable human carcinogen. After its introduction as a fungicide in 1945, for crop seeds, this toxic chemical was found in all food types. Hexachlorobenzene was banned from use in the United States in 1966. This material has been classified by the

International Agency for Research on Cancer The International Agency for Research on Cancer (IARC; french: Centre International de Recherche sur le Cancer, CIRC) is an intergovernmental agency forming part of the World Health Organization of the United Nations. Its role is to conduct and ...

(IARC) as a Group 2B carcinogen (possibly carcinogenic to humans). Animal carcinogenicity data for hexachlorobenzene show increased incidences of

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

(renal tubular tumours) and

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...

s. Chronic oral exposure in humans has been shown to give rise to a liver disease (

porphyria cutanea tarda Porphyria cutanea tarda is the most common subtype of porphyria. The disease is named because it is a porphyria that often presents with skin manifestations later in life. The disorder results from low levels of the enzyme responsible for the fift ...

), skin lesions with discoloration,

ulceration An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...

photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicity. ...

, thyroid effects, bone effects and loss of hair. Neurological changes have been reported in rodents exposed to hexachlorobenzene. Hexachlorobenzene may cause embryolethality and

teratogenic Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related t ...

effects. Human and animal studies have demonstrated that hexachlorobenzene crosses the placenta to accumulate in foetal tissues and is transferred in

breast milk Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates ( lacto ...

. HCB is very toxic to aquatic organisms. It may cause long term adverse effects in the aquatic

environment Environment most often refers to: __NOTOC__ * Natural environment, all living and non-living things occurring naturally * Biophysical environment, the physical and biological factors along with their chemical interactions that affect an organism or ...

. Therefore, release into waterways should be avoided. It is persistent in the environment. Ecological investigations have found that

biomagnification Biomagnification, also known as bioamplification or biological magnification, is any concentration of a toxin, such as pesticides, in the tissues of tolerant organisms at successively higher levels in a food chain. This increase can occur as a ...

up the food chain does occur. Hexachlorobenzene has a half life in the soil of between 3 and 6 years. Risk of

bioaccumulation Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance at a rate faster than that at which the substance is lost or eliminated ...

in an aquatic species is high.

Toxicology

* Oral LD50 (rat): 10,000 mg/kg * Oral LD50 (mice): 4,000 mg/kg * Inhalation LC50 (rat): 3600 mg/m³ Material has relatively low acute toxicity but is toxic because of its persistent and cumulative nature in body tissues in rich lipid content.

Unique Exposure Incident

Anatolia Anatolia, tr, Anadolu Yarımadası), and the Anatolian plateau, also known as Asia Minor, is a large peninsula in Western Asia and the westernmost protrusion of the Asian continent. It constitutes the major part of modern-day Turkey. The re ...

, Turkey between 1955 and 1959, during a period when bread wheat was unavailable, 500 people were fatally poisoned and more than 4,000 people fell ill by eating bread made with HCB-treated seed that was intended for agriculture use. Most of the sick were affected with a liver condition called

, which disturbs the metabolism of hemoglobin and results in skin lesions. Almost all breastfeeding children under the age of two, whose mothers had eaten tainted bread, died from a condition called "pembe yara" or "pink sore", most likely from high doses of HCB in the breast milk. In one mother's breast milk the HCB level was found to be 20 parts per million in lipid, approximately 2,000 times the average levels of contamination found in breast-milk samples around the world. Follow-up studies 20 to 30 years after the poisoning found average HCB levels in breast milk were still more than seven times the average for unexposed women in that part of the world (56 specimens of human milk obtained from mothers with porphyria, average value was 0.51 ppm in HCB-exposed patients compared to 0.07 ppm in unexposed controls),Gocmen, A., et al. Hexachlorobenzene Episode in Turkey, Biomedical Environmental Science 1989; 2(1): p. 36-43. and 150 times the level allowed in cow's milk.Peters, H.A., et al. Epidemiology of Hexachlorobenzene-induced Porphyria in Turkey: Clinical and Laboratory Follow-up After 25 Years, Archives of Neurology 1982; 39(12): p. 744-749. In the same follow-up study of 252 patients (162 males and 90 females, avg. current age of 35.7 years), 20–30 years' postexposure, many subjects had dermatologic, neurologic, and orthopedic symptoms and signs. The observed clinical findings include scarring of the face and hands (83.7%), hyperpigmentation (65%), hypertrichosis (44.8%), pinched faces (40.1%), painless arthritis (70.2%), small hands (66.6%), sensory shading (60.6%), myotonia (37.9%), cogwheeling (41.9%), enlarged thyroid (34.9%), and enlarged liver (4.8%). Urine and stool porphyrin levels were determined in all patients, and 17 have at least one of the porphyrins elevated. Offspring of mothers with three decades of HCB-induced porphyria appear normal.

References

Cited works Additional references *International Agency for Research on Cancer. In: ''IARC Monographs on the Evaluation of Carcinogenic Risk to Humans''. World Health Organisation, Vol 79, 2001pp 493–567 *''Registry of Toxic Effects of Chemical Substances''. Ed. D. Sweet, US Dept. of Health & Human Services: Cincinnati, 2005. *Environmental Health Criteria No 195; International Programme on Chemical Safety, World health Organization, Geneva, 1997. *Toxicological Profile for Hexachlorobenzene (Update), US Dept of Health & Human Services, Sept 2002. *''Merck Index'', 11th Edition, 4600

External links

* {{PPDB, 380 Obsolete pesticides Chloroarenes Endocrine disruptors Fungicides Hazardous air pollutants IARC Group 2B carcinogens Persistent organic pollutants under the Stockholm Convention Suspected teratogens Suspected embryotoxicants Persistent organic pollutants under the Convention on Long-Range Transboundary Air Pollution