LINDANE

Description

Lindane is one of eight different hexachlorocyclohexane (HCH), [58-89-9], C6H6Cl6, isomers and its Chemical Abstract name is 1α, 2α,3β,4α,5α,6β- hexachlorocyclohexane 58-89-9 (γ-HCH or γ -BHC, benzene hexachloride) (80). Commercial products containing lindane are marketed as either a mixture of isomers or as the pure γ -BHC isomer. Not unexpectedly, lindane is a highly stable lipophilic compound and it has been used extensively worldwide as an insecticide. In contrast, hexachloropentadiene, [77-47-4], C5Cl6, is an extremely reactive industrial intermediate used as a chemical intermediate in the synthesis of a broad range of cyclodiene-derived pesticides, which include endosulfan, endrin, heptachlor, and several different organohalogen flame retardants (81).

Chemical Properties

BHC is a white-to-brownish crystalline solid with a musty, phosgene-like odor.

Chemical Properties

white powder

Chemical Properties

Lindane is a white to yellow, crystalline powder with a slight, musty odor (pure material is odorless).

Physical properties

Colorless to yellow crystalline solid with a slight, musty, chlorinated-like odor. Odor threshold concentration is 12.0 mg/kg (Sigworth, 1964). Robeck et al. (1965) reported an odor threshold of 330 ppb.

Originator

Kwell,Reed Carnrick,US,1952

Uses

The only identified uses for hexachlorocyclohexane-containing products are based on the insecticidal activity of the γ isomer (lindane), which is considered to be the only insecticidally effective component (Extoxnet 1996). Lindane or technical-grade hexachlorocyclohexane containing the γ isomer is used primarily as an insecticide in the treatment of wood and wooden structures, seed grains, and livestock (ATSDR 2005, HSDB 2009). Other major uses are as an insecticide for several dozen fruit and vegetable crops, in baits and seed treatments for rodent control, and for treatment of scabies (mites) and lice. It is approved by the U.S. Food and Drug Administration foruse in three products for the treatment of lice and scabies (one lotionand two shampoos) (FDA 2009). Agricultural and pesticide uses accounted for about 270,000 kg (594,000 lb) of lindane and 450,000 kg (1 million pounds) of technical-grade hexachlorocyclohexane in 1974;the remaining uses were industrial or pharmaceutical (IARC 1979).

Uses

Pesticide and insecticide.

Indications

Lindane (Gamma benzene hexachloride, Kwell, Thionex) is a cyclic chlorinated hydrocarbon originally developed as an agricultural insecticide. It is absorbed through the chitinous exoskeleton and stimulates the nervous system, resulting in seizures and death of the insect. It is both a pediculicide and scabicide, with a 45% to 70% ovicidal effect. Resistance has been shown to Pediculosis capitis and Sarcoptes scabiei.
Lindane can be absorbed through intact skin following topical application and has the potential for CNS toxicity. It should therefore be used with great caution in infants, children <2 years of age, elderly patients, and pregnant and lactating women. It may be irritating to the eyes or mucous membranes; hence, these areas should be avoided. Irritant dermatitis may occur with use of excessive amounts or over prolonged periods. Toxicity, if overused, may result in nausea, vomiting, seizures, or even bone marrow suppression.
Lindane is an organochlorine with very slow onset of action and poor ovicidal activity; it takes over 3 hours to kill the lice during which increased lice crawling and twitching can cause increased pruritus for the patient. Lindane is available as a shampoo for the treatment of pediculosis capitis and/or pubis and in cream and lotion form for treating scabies and all forms of pediculosis. GBH also repels ticks and other arthropods and kills chiggers.

Definition

ChEBI: Beta-hexachlorocyclohexane is the beta-isomer of hexachlorocyclohexane. It has a role as a persistent organic pollutant. It is an organochlorine pesticide and a hexachlorocyclohexane.

Manufacturing Process

Chlorine gas was gradually passed into 660 parts of benzene contained in a lead-lined reaction vessel until 890 parts of the gas had been absorbed. The mixture was stirred continuously and the temperature maintained at 15°C to 20°C.
The supply of chlorine was then interrupted and the precipitated solid filtered off and dried. In weight, it was found to be equivalent to 900 parts. The mother liquid was then mixed with 330 parts of benzene and the mixture again treated with 890 parts of chlorine in the manner described.
After filtering the reaction mixture resulting from the second chlorination, the filtrate was again mixed with a smaller quantity of benzene and again chlorinated in a similar manner. In this way, a continuous process for the preparation of benzene hexachloride resulted.
That benzene hexachloride isomer mixture is then the raw material for lindane production. The production of lindane per se is not a chemical synthesis operation but a physical separation process. It is possible to influence the gamma isomer content of benzene hexachloride to an extent during the synthesis process. Basically, however, one is faced with the problem of separating a 99%-plus purity gamma isomer from a crude product containing perhaps 12 to 15% of the gamma isomer. The separation and concentration process is done by a carefully controlled solvent extraction and crystallization process. One such process is described by R.D. Donaldson et al. Another description of hexachlorocyclohexane isomer separation is given by R.H. Kimball.

brand name

Benhexachlor;Gamex;Gamma benzene;Hexachloride.

Therapeutic Function

Pediculicide, Scabicide

World Health Organization (WHO)

Lindane has been available for more than 25 years and is widely used as an agricultural and household pesticide.

General Description

Colorless solid with a musty odor; pure material is odorless. Used as a pesticide and scabicide.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

LINDANE is incompatible with strong bases. LINDANE is incompatible with powdered metals such as iron, zinc and aluminum. LINDANE is also incompatible with oxidizing agents. LINDANE can undergo oxidation when in contact with ozone. When exposed to alkalis, LINDANE undergoes dehydrochlorination.

Health Hazard

LINDANE is a stimulant of the nervous system, causing violent convulsions that are rapid in onset and generally followed by death or recovery within 24 hours. The probable human oral lethal dose is 50-500 mg/kg, or between 1 teaspoon and 1 ounce for a 150-lb (70 kg) person.

Health Hazard

High acute toxicity; symptoms — headache,dizziness, nausea, vomiting, diarrhea, tremor,cyanosis, epileptic convulsions; stimulant tonervous system, which can lead to violent convulsions; such convulsions may setrapidly that may either progress to recovery within 24 hours or could lead to death(Hayes 1982); ingestion of 2–10 g probably fatal to human; an irritant to eyeand skin; chronic exposure causes liverinjury; oral LD50 value (mice): 86 mg/kg;carcinogenic to animals, causing liver andlung tumors; exposure limit: TLV : TWA(skin) 0.5 mg/m³ (ACGIH, MSHA, andOSHA); RCRA Waste Number U120.

Fire Hazard

When heated to decomposition, LINDANE emits toxic fumes of chlorine, hydrochloric acid, and phosgene.

Agricultural Uses

Insecticide, Rodenticide: Lindane has been used against insects in a wide range of applications including treatment of animals, buildings, man for ectoparasites, clothes, water for mosquitoes, living plants, seeds and soils. Most applications have been canceled due to excessive residues, e.g., stored foodstuffs, that may cause cancer. Formulators, distributors and users of lindane represent a special risk group. The major use of lindane in recent years has been to pretreat seeds. Other uses include sunflowers, peas, wheat, barley and oats. Lindane is currently also used in lotions, creams and shampoos for the control of lice and mites in humans. Not approved for use in EU countries. A U.S. EPA restricted Use Pesticide (RUP). Lindane should be handled as a carcinogen, with extreme caution. Most applications have been canceled. It has not been produced in the U.S. since 1977; however, it is still imported into the U.S. and formulated to treat head lice, body lice and scabies.

Trade name

AALINDAN®; AFICIDE®; AGRISOL G-20®; AGROCIDE®; AGRONEXIT®; AMEISENATOD®; AMEISENMITTEL (MERCK)®; APARASIN®; APHTIRIA®; APLIDAL®; ARBITEX®; BEN-HEX®; BENTOX 10®; CELANEX®; CHLORESENE®; CODECHINE®; DELSANEX DAIRY FLY SPRAY®; DETMOL-EXTRAKT®; DETOX 25®; DEVORAN®; DOL GRANULE®; DRILL TOXSPEZIAL AGLUKON®; DUAL MURGANIC RPB SEED TREATMENT®; ENTOMOXAN®; EXAGAMA®; FORLIN®; GALLOGAMA®; GAMACID®; GAMAPHEX®; GAMENE®; GAMMA-COL®; GAMMALIN®; GAMMALIN 20; GAMMALEX®; GAMMASAN 30®; GAMMATERR®; GAMMAPHEX®; GAMMEX®; GAMMEXANE®; GAMMEXENE®; GAMMOPAZ®; GEXANE®; HECLOTOX®; HEXA®; HEXAFLOW®; HEXATOX®; HEXAVERM®; HEXICIDE®; HEXYCLAN®; HORTEX®; INEXIT®; ISOTOX®; JACUTIN®; KOKOTINE®; KWELL®; LENTOX®; LINDAGRAM®; LIDENAL®; LINDAFOR®; LINDAGAM®; LINDAGRAIN®; LINDAGRANOX®; LINDAPOUDRE®; LINDATOX®; LINDOSEP®; LINTOX®; LOREXANE®; MARSTAN FLY SPRAY®; MERGAMMA 30®; MILBOL 49®; MIST-O-MATIC LINDEX®; MSZYCOL®; NEXEN FB®; NEXIT®; NEXIT-STARK®; NEXOL-E®; NICOCHLORAN®; NOVIGAM®; OMNITOX®; OVADZIAK®; OWADZIAK®; PEDRACZAK®; PFLANZOL®; QUELLADA®; RODESCO INSECT POWDER®; SANG GAMMA®; SILVANO®; SPRITZ-RAPIDIN®; SPRUEHPFLANZOL®; STREUNEX®; TAP 85®; TRI- 6®; VITON®

Contact allergens

Lindane is a pesticide used for its antiinsect properties in agriculture, wood protection, in antiinsect paints and veterinary and human medicine against many and veterinary and human medicine against many and demodicidosis. Its use is controlled, particularlybecause of neurological toxicity

Clinical Use

Lindane is 1,2,3,4,5,6-hexachlorocyclohexane, -benzenehexachloride, or benzene hexachloride (Kwell, Scabene,Kwildane, G-Well). This halogenated hydrocarbon is preparedby the chlorination of benzene. A mixture of isomersis obtained in this process, five of which have been isolated:α, β, γ, δ, and ε. The γ-isomer, present to 10% to 13% inthe mixture, is responsible for the insecticidal activity. The -isomer may be separated by various extraction and chromatographictechniques.Lindane occurs as a light buff to tan powder with a persistentmusty odor, and it is bitter. It is insoluble in water butsoluble in most organic solvents. It is stable under acidic orneutral conditions but undergoes elimination reactions underalkaline conditions.The action of lindane against insects is threefold: it is a directcontact poison, it has a fumigant effect, and it acts as astomach poison. The effect of lindane on insects is similar tothat of DDT. Its toxicity in humans is somewhat lower thanthat of DDT. Because of its lipid solubility properties, however,lindane when ingested tends to accumulate in the body.Lindane is used locally as a cream, lotion, or shampoo forthe treatment of scabies and pediculosis.

Safety Profile

Confirmed carcinogen with experimental carcinogenic and neoplastigenic data. A human systemic poison by ingestion. Also a poison by ingestion, skin contact, intraperitoneal, intravenous, and intramuscular routes. Human systemic effects by ingestion: convulsions, dyspnea, and cyanosis. Experimental teratogenic and reproductive effects. Mutation data reported. See also BENZENE HEXACHLORIDE and other benzene hexachloride entries. When heated to decomposition it emits toxic fumes of Cl-, HCl, and phosgene.

Potential Exposure

The major commercial usage of BHC is based upon its insecticidal properties. α-BCH is used as an Agricultural chemical, pesticide, pharmaceutical, and veterinary drug. The 7-isomer has the highest acute toxic ity, but the other isomers are not without activity. It is gen erally advantageous to purify the 7-isomer from the less active isomers. The γ-isomer acts on the nervous system of insects, principally at the level of the nerve ganglia. As a result, lindane has been used against insects in a wide range of applications including treatment of animals, buildings, humans for ectoparasites, clothes; water for mosquitoes; living plants; seeds and soils. Some applications have been abandoned due to excessive residues, e.g., stored food stuffs. By voluntary action, the principal domestic producer of technical grade BHC requested cancellation of its BHC registrations on September 1, 1976. As of July 21, 1978, all registrants of pesticide products containing BHC voluntar ily canceled their registrations or switched their former BHC products to lindane formulations.

First aid

If this chemical gets into the eyes, remove anycontact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts theskin, remove contaminated clothing and wash immediatelywith soap and water. Seek medical attention immediately. Ifthis chemical has been inhaled, remove from exposure,begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR ifheart action has stopped. Transfer promptly to a medicalfacility. When this chemical has been swallowed, get medical attention. Give large quantities of water and inducevomiting. Do not make an unconscious person vomit.

Carcinogenicity

Lindane (as γ-hexachlorocyclohexane), hexachlorocyclohexan e (technical grade), and other hexachlorocyclohexane isomers are reasonably anticipated to be human carcinogens based on sufficient evidence of carcinogenicity from studies in experimental animals.

Environmental Fate

Biological. In a laboratory experiment, a strain of Pseudomonas putida culture transformed lindane to g-3,4,5,6-tetrachlorocyclohexane (g-TCCH), g-pentachlorocyclohexane (g-PCCH) and a-BHC (Benezet and Matsumura, 1973). g-TCCH was also reported as a product of lindane degradation by Clostridium sphenoides (MacRae et al., 1969; Heritage and MacRae, 1977, 1977a), an anaerobic bacterium isolated from flooded soils (MacRae et al., 1969; Sethunathan and Yoshida, 1973a). Lindane degradation by Escherichia coli also yielded g-PCCH (Francis et al., 1975). Evidence suggests that degradation of lindane in anaerobic cultures or flooded soils amended with lindane occurs via reductive dehalogenation producing chlorine-free volatile metabolites (Sethunathan and Yoshida, 1973a).
After a 30-day incubation period, the white rot fungus Phanerochaete chrysosporium converted lindane to carbon dioxide. Mineralization began between the third and sixth day of incubation. The production of carbon dioxide was highest between 3 to 18 days o
Beland et al. (1976) studied the degradation of lindane in sewage sludge under anaerobic conditions. Lindane underwent reductive hydrodechlorination forming 3,4,5,6-tetrachlorocyclohex- 1-ene (g-BTC). The amount of g-BTC that formed reached a maximum conc
When lindane was incubated in aerobic and anaerobic soil suspensions for 3 weeks, 0 and 63.8% was lost, respectively (MacRae et al., 1984). Using settled domestic wastewater inoculum, lindane (5 and 10 mg/L) did not degrade after 28 days of incubation at 25°C (Tabak et al., 1981).
Soil. In moist soils, lindane biodegraded to g-pentachlorocyclohexene (Elsner et al., 1972; Kearney and Kaufman, 1976; Fuhremann and Lichtenstein, 1980). Under anaerobic conditions, degradation by soil bacteria yielded g-BTC and a-BHC (Kobayashi

Metabolic pathway

The metabolic pathways of gamma-HCH are complex and more than 80 metabolites have been identified (Macholz and Kujawa, 1985). Dehydrohalogenation reactions are important. Gamma-HCH may be converted into other HCH isomers in the environment and also microorganisms and plants may convert gamma-HCH (1) into the alpha (2), beta (3), or delta (4) isomers (see Schemel). Bioisomerisation does not appear to be a significant pathway in mammals. In animals, metabolism of gamma-HCH generally leads to less-chlorinated, unsaturated metabolites. Chlorinated phenols may be formed and excreted as glucuronides. In a detailed discussion of the biodegradation of gamma-HCH, the reaction mechanisms involved were critically reviewed (Kurihara and Nakajima, 1980). Oxygenation or glutathione conjugation are important initial stages in metabolism. Key intermediates in the metabolic pathways are hexachlorocyclohexene (18), pentachlorocyclohexene (5) and tetrachlorocyclohexene (6) and these have been identified in a number of organisms (Macholz and Kujawa, 1985).

Solubility in water

Wt % at 20 °C: 30.31 in acetone, 22.42 in benzene, 19.35 in chloroform, 17.22 in ether, 6.02 in ethanol (Windholz et al., 1983)
9.76 and 13.97 g/L in hexane at 10 and 20 °C, respectively (shake flask-GC, Mills and Biggar, 1969)
92.8 g/kg in triolein at 25 °C (Chiou and Manes, 1986)

storage

Color Code—Blue: Health Hazard/Poison: Storein a secure poison location. Prior to working with thischemical you should be trained on its proper handling andstorage. Store in tightly sealed containers in a cool, dryplace away from light and incompatible materials. Protectcontainers against physical damage. A regulated, markedarea should be established where this chemical is handled,used, or stored in compliance with OSHA Standard1910.1045.

Shipping

UN2761 Organochlorine pesticides, solid, toxic, Hazard Class: 6.1; Labels: 6.1-Poisonous materials.

Purification Methods

Crystallise it from EtOH. Purify it also by zone melting. Possible CANCER AGENT, TOXIC. [: Beilstein 1 H 23, : Beilstein 5 I 8, many isomers : Beilstein 5 III 41, 5 IV 55.]

Degradation

Gamma-HCH is extremely stable to light, air, temperatures up to 180 °C, and to acids. It undergoes dechlorination in alkalis with DT₅₀ values (22 °C) of 191 days (pH 7) and 11 hours (pH 9). It is photodegraded in organic solvents (2-propanol or methanol) by UV irradiation (254 nm).

Toxicity evaluation

The acute toxicity of lindane depends on the age, sex, and animal species, and on the route of administration. The oral LD₅₀ in mice, rats, and guinea pigs is 86, 125–230, and 100–127 mg/kg, respectively. In contrast, most of the other isomers were considerably more toxic (94,95). Some of the other toxic responses caused by lindane in laboratory animals include hepato- and nephrotoxicity, reproductive and embryotoxicity, mutagenicity in some short-term in vitro bioassays, and carcinogenicity (80). The mechanism of the lindane-induced response is not known. Only minimal data are available on the mammalian toxicities of hexachlorocyclopentadiene.

Incompatibilities

Lindane decomposes on contact with powdered iron, aluminum, and zinc and with alkalis producing trichlorobenzene. Corrosive to metals

Waste Disposal

For the disposal of lindane, a process has been developed involving destructive pyrolysis @ 400-500℃ with a catalyst mixture which contains 5%-10% of either cupric chloride, ferric chloride; zinc chloride; or aluminum chloride on activated carbon. Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/mo) must conform with EPA regulations governing storage, transportation, treatment, and waste disposal.

Raw materials

Preparation Products