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 as a pharmaceutical treatment for lice and scabies. Lindane is a neurotoxin that interferes with GABA neurotransmitter function by interacting with the GABAA receptor-chloride channel complex at the picrotoxin binding site. In humans, lindane affects the nervous system, liver, and kidneys, and may well be a carcinogen. Whether lindane is an endocrine disruptor is unclear. The World Health Organization classifies lindane as "moderately hazardous", and its international trade is restricted and regulated under the Rotterdam Convention on Prior Informed Consent. In 2009, the production and agricultural use of lindane was banned under the Stockholm Convention on persistent organic pollutants. A specific exemption to that ban allows it to continue to be used as a second-line pharmaceutical treatment for lice and scabies.
History and use The chemical was originally synthesized in 1825 by Faraday. It is named after the Dutch chemist Teunis van der Linden (1884–1965), the first to isolate and describe γ-hexachlorcyclohexane in 1912. The fact that mixtures of isomers of hexachlorocyclohexane have insecticidal activity is a case of multiple discovery. Work in the 1930s at the Jealott's Hill laboratories of Imperial Chemical Industries Ltd (ICI) led in 1942 to the realization that the γ isomer was the key active component in the mixture which had hitherto been tested. Development work in the UK was accelerated because at that time in World War II imports of derris containing the insecticide rotenone were restricted owing to the Japanese occupation of Malaya and alternatives were urgently needed. In trials in 1943 it was found that a five-fold increase in the yield of oats and wheat was achieved using a dust formulation of the available material, owing to its efficacy against wireworm pests. By the end of 1945, γ-hexachlorcyclohexane of 98% purity became available and ICI commercialised a seed treatment launched in 1949 as Mergamma A, containing 1% mercury and 20% lindane. Subsequently, lindane has been used to treat food crops and forestry products, as a seed or soil treatment, and to treat livestock and pets. It was used as a household pesticide as the active pesticide ingredient of an insecticidal floor wax product called "Freewax". It has also been used as pharmaceutical treatment for lice and scabies, formulated as a shampoo or lotion. Between 1950 and 2000, an estimated 600,000 tonnes of lindane were produced globally, and the vast majority of which was used in agriculture. It has been manufactured by several countries, including the United States, China, Brazil, and several European countries. By November 2006, the use of lindane had been banned in 52 countries and restricted in 33 others. Seventeen countries, including the US and Canada, allowed either limited agricultural or pharmaceutical use. In 2009, an international ban on the use of lindane in agriculture was implemented under the Stockholm Convention on Persistent Organic Pollutants. A specific exemption allows for it to continue to be used in second-line treatments for the head lice and scabies for five more years. The production of the lindane isomers α- and β-hexachlorocyclohexane was also banned. Although the US has not ratified the convention, it has similarly banned agricultural uses while still allowing its use as a second-line lice and scabies treatment.
United States In the US, lindane pesticide products were regulated by the U.S. Environmental Protection Agency (EPA), while lindane medications are regulated by the Food and Drug Administration (FDA). It was registered as an agricultural insecticide in the 1940s, and as pharmaceutical in 1951. The EPA gradually began restricting its agricultural use in the 1970s due to concerns over its effects on human health and the environment. By 2002, its use was limited to seed treatments for just six crops, and in 2007, these last uses were cancelled.
Pharmaceutical uses Lindane medications continue to be available in the US, though since 1995, they have been designated "second-line" treatments, meaning they should be prescribed when other "first-line" treatments have failed or cannot be used. In December 2007, the FDA sent a Warning Letter to Morton Grove Pharmaceuticals, the sole U.S. manufacturer of lindane products, requesting that the company correct misleading information on two of its lindane websites. The letter said, in part, that the materials "are misleading in that they omit and/or minimize the most serious and important risk information associated with the use of Lindane Shampoo, particularly in pediatric patients; include a misleading dosing claim; and overstate the efficacy of Lindane Shampoo." California banned the pharmaceutical use of lindane effective 2002, and the Michigan House of Representatives passed a bill in 2009 to restrict its use to doctors' offices. A recent analysis of the California ban concluded that a majority of pediatricians had not experienced problems treating lice or scabies since that ban took effect. The study also documented a marked decrease in lindane wastewater contamination and a dramatic decline in lindane poisoning incidents reported to poison control centers. The authors concluded, "The California experience suggests elimination of pharmaceutical lindane produced environmental benefits, was associated with a reduction in reported unintentional exposures and did not adversely affect head lice and scabies treatment." The Persistent Organic Pollutants Review Committee of the Stockholm Convention on Persistent Organic Pollutants considers the use of lindane in agriculture as largely redundant, with other, less toxic and less persistent pesticides. In the case of pharmaceutical use, the committee noted, "alternatives for pharmaceutical uses have often failed for scabies and lice treatment and the number of available alternative products for this use is scarce. For this particular case, a reasonable alternative would be to use lindane as a second-line treatment when other treatments fail, while potential new treatments are assessed."
Other uses
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