View source for Lindane

{{hatnote|This compound is sometimes called benzene hexachloride. You may be looking for the similarly named aromatic compound [[hexachlorobenzene]].}}
{{short description|Organochlorine chemical and an isomer of hexachlorocyclohexane}}
{{infobox drug
| verifiedrevid = 457117932
| IUPAC_name = (1''r'',2''R'',3''S'',4''r'',5''R'',6''S'')-1,2,3,4,5,6-hexachlorocyclohexane
| image = Gamma-hexachlorocyclohexane.svg
| image_class = skin-invert-image
| width = 150px
| image2 = Lindane (chair) molecule ball.png
| width2 = 170
| alt2 = Ball-and-stick model of the lindane molecule (chair conformation)
<!--Clinical data-->
| Drugs.com = {{drugs.com|monograph|lindane}}
| MedlinePlus = a682651
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = C
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| legal_UK = <!-- GSL / P / POM / CD -->
| legal_US = <!-- OTC / Rx-only -->
| legal_status = Production and agricultural use is banned<ref name="Stockholm" >{{cite web |url = http://chm.pops.int/TheConvention/ThePOPs/ListingofPOPs/tabid/2509/Default.aspx |title = Listing of POPs in the Stockholm Convention |publisher = Stockholm Convention}}</ref> in the 182 countries that are Parties to the [[Stockholm Convention]], but pharmaceutical use is allowed as a second-line treatment for scabies and lice<ref name=Stockholm />
| routes_of_administration = Topical
<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 91%
| metabolism = Hepatic cytochrome P-450 oxygenase system
| elimination_half-life = 18 hours
| excretion =
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 58-89-9
| ATC_prefix = P03
| ATC_suffix = AB02
| ATC_supplemental = {{ATCvet|S02|QA01}} {{ATCvet|P53|AB52}}
| PubChem = 727
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00431
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 10481896
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 59NEE7PCAB
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C07075
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 32888
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 15891
<!--Chemical data-->
| C=6 | H=6 | Cl=6
| smiles = Cl[C@H]1[C@H](Cl)[C@@H](Cl)[C@@H](Cl)[C@H](Cl)[C@H]1Cl
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C6H6Cl6/c7-1-2(8)4(10)6(12)5(11)3(1)9/h1-6H/t1-,2-,3-,4+,5+,6+
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JLYXXMFPNIAWKQ-GNIYUCBRSA-N
}}

'''Lindane''', also known as '''''gamma''-hexachlorocyclohexane''' ('''γ-HCH'''), '''gammaxene''', '''Gammallin''' and '''benzene hexachloride''' ('''BHC'''),<ref name="bhc-misnomer">{{cite book |title= Analytical toxicology: for clinical, forensic, and pharmaceutical chemists | vauthors = Brandenberger H, Maes RA |year= 1997 |publisher= Walter de Gruyter |location= Berlin |isbn= 978-3-11-010731-9 |page= 243 |url= https://books.google.com/books?id=ZhYtynyC4kAC&pg=PA243 |access-date= 2009-05-10}}</ref> is an [[organochlorine]] chemical and an isomer of [[hexachlorocyclohexane]] that has been used both as an agricultural [[insecticide]] and as a [[pharmaceutical]] treatment for [[Pediculosis|lice]] and [[scabies]].<ref>{{cite web |url=https://www.drugs.com/mmx/lindane.html |title=Professional Drug Information: Lindane |access-date=2020-02-28 |archive-date=2018-08-20 |archive-url=https://web.archive.org/web/20180820005746/https://www.drugs.com/mmx/lindane.html |url-status=dead }}</ref><ref>{{cite web
|publisher=Commission for Environmental Cooperation |title=The North American Regional Action Plan (NARAP) on Lindane and Other Hexachlorocyclohexane (HCH) Isomers |year=2013 |url=http://www3.cec.org/islandora/en/item/11389-north-american-regional-action-plan-lindane-and-other-hexachlorocyclohexane-isomers-final-en.pdf |access-date=2020-02-28}}</ref>

Lindane is a [[neurotoxin]] that interferes with [[GABA]] [[neurotransmitter]] function by interacting with the [[GABAA receptor|GABA<sub>A</sub> 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]].<ref name="Agency">{{cite web | work = Agency for Toxic Substances and Disease Registry | publisher = U.S. Department of Health and Human Services | title = Toxicologic profile for alpha-, beta, gamma- and delta-hexachlorocyclohenxane. | date = August 2005 | url = http://www.atsdr.cdc.gov/toxprofiles/tp43.pdf }}</ref><ref name="VolRED">{{cite web | url = http://www.epa.gov/oppsrrd1/REDs/factsheets/lindane_fs_addendum.htm | title = Lindane Voluntary Cancellation and RED Addendum Fact Sheet | archive-url = https://web.archive.org/web/20061006133810/http://www.epa.gov/oppsrrd1/REDs/factsheets/lindane_fs_addendum.htm | archive-date=2006-10-06 | work = US EPA | date = July 2006 }}</ref> Whether lindane is an [[endocrine disruptor]] is unclear.<ref name="EPACA">{{cite web | work = U.S. EPA | title = Evaluation of the Carcinogenic Potential of Lindane, PC. Code: 009001 | date = 2001 | url = http://www.lindane.com/pdf/EPA_Cancer_Assessment_of_Lindane2001.pdf | archive-url = https://web.archive.org/web/20070928013800/http://www.lindane.com/pdf/EPA_Cancer_Assessment_of_Lindane2001.pdf | archive-date = 2007-09-28 }}</ref><ref>{{cite web |publisher=International Agency for Research on Cancer (IARC) |title=Summaries & Evaluations: HEXACHLOROCYCLOHEXANES (Group 2B) |date=1998-03-02 |url=http://www.inchem.org/documents/iarc/suppl7/hexachlorocyclohexanes.html}}</ref><ref>{{cite web |author=World Health Organization (WHO) |title=Lindane in Drinking Water: Background Document for Development of WHO Guidelines for Drinking-Water Quality |url=https://www.who.int/water_sanitation_health/dwq/chemicals/lindane.pdf |date=2004 |access-date=2020-02-28}}</ref>

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.<ref name="WHOClass">World Health Organization, [https://www.who.int/ipcs/publications/pesticides_hazard_rev_3.pdf ''The WHO Recommended Classification of Pesticides by Hazard''], 2005.</ref> In 2009, the production and agricultural use of lindane was banned under the [[Stockholm Convention]] on [[persistent organic pollutants]].<ref name=Stockholm /><ref name="COP4, 2009 Press release">[http://chm.pops.int/Convention/Pressrelease/COP4Geneva8May2009/tabid/542/language/en-US/Default.aspx Press Release - COP4 - Geneva, 8 May 2009: Governments unite to step-up reduction on global DDT reliance and add nine new chemicals under international treaty]</ref> A specific exemption to that ban allows it to continue to be used as a second-line pharmaceutical treatment for lice and [[scabies]].<ref name="engeler">Eliane Engeler, "UN: Treaty expanded by 9 more dangerous chemicals", Associated Press 2009-05-09</ref>

==History and use==
The chemical was originally synthesized in 1825 by [[Michael Faraday|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]].<ref>{{Cite book |title=The constant pest | vauthors = Ordish G |publisher=Peter Davies, London |year=1976 |isbn=9780432113004 }}</ref>  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 elliptica|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 [[Click beetle|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.<ref name=JH50>{{Cite book |title=Jealott's Hill: Fifty years of Agricultural Research 1928-1978 | veditors = Peacock FC, Newman JR |display-authors=etal |chapter=Chapter 5: Benzene hexachloride |pages=[https://archive.org/details/jealottshillfift0000peac/page/42 42]–48 |publisher=Imperial Chemical Industries Ltd. |year=1978 |isbn=0901747017 |url=https://archive.org/details/jealottshillfift0000peac|url-access=registration }}</ref> 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".<ref>{{cite web | work = U.S. EPA | title = Pesticide Product Label, NEW-CLEAR FREEWAX | date = 18 April 1974 | url = https://www3.epa.gov/pesticides/chem_search/ppls/003696-00032-19740418.pdf }}</ref><ref>{{cite web | url = https://www.floridamemory.com/items/show/45738 | work = Florida Memory | title = View showing the Feinberg brothers with their Freewax prod }}</ref> It has also been used as pharmaceutical treatment for lice and scabies, formulated as a [[shampoo]] or lotion.<ref name="Commission">{{cite web | work = Commission for Environmental Cooperation. | title = North American Regional Action Plan (NARAP) on lindane and other hexachlorocyclohexane (HCH) isomers | date = 30 November 2006 | url =  http://www.cec.org/files/PDF/POLLUTANTS/LindaneNARAP-Nov06_en.pdf | archive-url = https://web.archive.org/web/20070607020104/http://www.cec.org/files/PDF/POLLUTANTS/LindaneNARAP-Nov06_en.pdf | archive-date = 2007-06-07 }}</ref><ref>{{citation |title=LINDANE: Risk Profile. UNEP/POPS/POPRC.2/17/Add.4 |publisher=Stockholm Convention of Persistent Organic Pollutants}}</ref><ref name="EPARED">{{cite web | work = U.S. Environmental Protection Agency (EPA) | title = Lindane Reregistration Eligibility Decision (RED) | date = 2002 | url = http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2002-0202-0027 }}</ref> 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 [[Europe|European countries]].
By November 2006, the use of lindane had been banned in 52 countries and restricted in 33 others{{Outdated statistic}}. Seventeen countries, including the US and Canada, allowed either limited agricultural or pharmaceutical use.<ref name="Commission" /> 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.<ref name="POPS">{{cite conference | title = Report of the Conference of the Parties of the Stockholm Convention on Persistent Organic Pollutants on the work of its fourth meeting. | conference = Convention on Persistent Organic Pollutants. Fourth meeting. | location = Geneva | date = 4–8 May 2009 | url = http://chm.pops.int/Portals/0/Repository/COP4/UNEP-POPS-COP.4-38.English.pdf }}</ref> 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.<ref name="engeler" /><ref name="POPS" /><ref>{{cite web |author= Persistent Organic Pollutants Review Committee |url=http://www.pops.int/documents/meetings/poprc/chemreview.htm |title=Home |access-date=2020-02-05 |url-status=dead |archive-url=https://web.archive.org/web/20070927024722/http://www.pops.int/documents/meetings/poprc/chemreview.htm |archive-date=2007-09-27 }}</ref><ref>
{{cite web | title = Pesticide Action Network map of Lindane bans and restrictions |url=http://www.panna.org/campaigns/docsLindane/lindaneBannedMap.pdf  |access-date=2020-02-05 |url-status=dead |archive-url=https://web.archive.org/web/20070928110049/http://www.panna.org/campaigns/docsLindane/lindaneBannedMap.pdf |archive-date=2007-09-28 }}</ref>

===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 (United States)|Food and Drug Administration]] (FDA). It was registered as an agricultural insecticide in the 1940s, and as pharmaceutical in 1951.<ref name="Commission"/> The EPA gradually began restricting its agricultural use in the 1970s due to concerns over its effects on human health and the environment.<ref name="EPAREDADD">{{cite web | work = U.S. EPA | title = Addendum to the 2002 Lindane Reregistration Eligibility Decision (RED). | date = July 2006 | url = http://www.epa.gov/oppsrrd1/REDs/lindane_red_addendum.pdf |access-date=2007-09-05 |url-status=dead |archive-url=https://web.archive.org/web/20061006100023/http://www.epa.gov/oppsrrd1/REDs/lindane_red_addendum.pdf |archive-date=2006-10-06 }}</ref> By 2002, its use was limited to seed treatments for just six crops,<ref name="Commission"/> and in 2007, these last uses were cancelled.<ref>{{cite web |url=http://www.epa.gov/oppfead1/cb/csb_page/updates/2006/lindane-order.htm |title=Remaining Lindane Registrations Cancelled &#124; Pesticides &#124; US EPA |access-date=2010-01-14 |url-status=dead |archive-url=https://web.archive.org/web/20110604094216/http://www.epa.gov/oppfead1/cb/csb_page/updates/2006/lindane-order.htm |archive-date=2011-06-04 }}</ref>

====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.<ref name="AssessmentMemo">{{cite web |date=2003 |title=Lindane Assessment Memorandum. |url=https://www.fda.gov/cder/drug/infopage/lindane/lindanememoassessment.pdf |work=[[Food and Drug Administration (United States)|Food and Drug Administration]]}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref><ref name = "McCarthy">{{cite journal | vauthors = McCarthy JS, Kemp DJ, Walton SF, Currie BJ | title = Scabies: more than just an irritation | journal = Postgraduate Medical Journal | volume = 80 | issue = 945 | pages = 382–7 | date = July 2004 | pmid = 15254301 | pmc = 1743057 | doi = 10.1136/pgmj.2003.014563 | url = }}</ref><ref name="Thomas">{{cite journal | vauthors = Thomas DR, McCarroll L, Roberts R, Karunaratne P, Roberts C, Casey D, Morgan S, Touhig K, Morgan J, Collins F, Hemingway J | title = Surveillance of insecticide resistance in head lice using biochemical and molecular methods | journal = Archives of Disease in Childhood | volume = 91 | issue = 9 | pages = 777–8 | date = September 2006 | pmid = 16774979 | pmc = 2082909 | doi = 10.1136/adc.2005.091280 | url = }}</ref><ref name="FDATopical">{{cite web | work = FDA Public Health Advisory | title = Safety of Topical Lindane Products for the Treatment of Scabies and Lice. | url = https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm110845.htm }}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref> In December 2007, the FDA sent a [[FDA Warning Letter|Warning Letter]] to [[Morton Grove Pharmaceuticals]], the sole U.S. manufacturer of lindane products,<ref Name="scielePR">{{cite web | title = Sciele Pharma Completes Acquisition of Alliant Pharmaceuticals. | work = Press Release | date = 12 June 2007 | url = http://phx.corporate-ir.net/phoenix.zhtml?c=120763&p=irol-newsArticle&ID=1014610&highlight | access-date = 20 April 2021 | archive-date = 21 February 2013 | archive-url = https://archive.today/20130221092452/http://phx.corporate-ir.net/phoenix.zhtml?c=120763&p=irol-newsArticle&ID=1014610&highlight | url-status = bot: unknown }}</ref> 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."<ref name="FDAWarn">{{cite web | url = https://www.fda.gov/foi/warning_letters/s6604c.htm | title = Warning Letter | archive-url = https://web.archive.org/web/20080104154942/https://www.fda.gov/foi/warning_letters/s6604c.htm | archive-date=2008-01-04 | work = [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] | quote = to Morton Grove. (undated) }}</ref>

[[California]] banned the pharmaceutical lindane, effective 2002, and the [[Michigan House of Representatives]] passed a bill in 2009 to restrict its use to doctors' offices.<ref>{{Cite web | url=http://www.legislature.mi.gov/(S(qmov3e45chfz0w55ymrrcl45))/mileg.aspx?page=getObject&objectName=2009-HB-4402 | title=Michigan Legislature - House Bill 4402 (2009)}}</ref> 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."<ref name="CAOutcomes">{{cite journal | vauthors = Humphreys EH, Janssen S, Heil A, Hiatt P, Solomon G, Miller MD | title = Outcomes of the California ban on pharmaceutical lindane: clinical and ecologic impacts | journal = Environmental Health Perspectives | volume = 116 | issue = 3 | pages = 297–302 | date = March 2008 | pmid = 18335094 | pmc = 2265033 | doi = 10.1289/ehp.10668 | url = http://www.ehponline.org/members/2007/10668/10668.pdf | archive-url = https://web.archive.org/web/20080828105149/http://www.ehponline.org/members/2007/10668/10668.pdf | url-status = dead | archive-date = 2008-08-28 }}</ref>{{Primary source inline|date=November 2015}}

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."<ref name="r16"/>

==Other uses==
===Pest repellent===
Lindane is a [[bird repellent]].<ref name="Rudd-Genelly-1954-bundle">
   {{Unbulleted list citebundle
      |{{cite book | vauthors = Morrison FO | title=Residue Reviews / Rückstands-Berichte | chapter=A review of the use and place of lindane in the protection of stored products from the ravages of insect pests | journal=Residue Reviews | publisher=[[Springer New York]] | publication-place=[[New York, NY]], US | year=1999 | volume=41 | pages=113–180 | isbn=978-1-4615-8481-0 | doi=10.1007/978-1-4615-8479-7_5| pmid=4111922 }}{{rp|page=139}}
      |{{cite journal | vauthors = Rudd RL, Genelly RE | title=Lindane repellent to pheasants: Seed grain treated with high levels of lindane apparently avoided in favor of untreated grain | journal=[[California Agriculture]] | publisher=[[University of California Division of Agriculture and Natural Resources|UC Agriculture]] (UC ANR) | volume=8 | issue=5 | date=1954-05-01 | issn=0073-2230 | pages=13 | doi=10.3733/ca.v008n05p13 | doi-broken-date=12 July 2025 | s2cid=82736438 | id={{s2cid|131523930}}}}
   }}
</ref> Rudd & Genelly 1954 noticed that [[bird pest]]s seemed uninterested in treated seeds, specifically [[pheasant]]s and [[blackbird (disambiguation)|blackbird]]s around [[Davis, California|Davis, CA, US]].<ref name="Rudd-Genelly-1954-bundle" /> They tested its repellent effect on pheasants and found it effective, speculating that it may be usable as a general bird repellent.<ref name="Rudd-Genelly-1954-bundle" />

==Synthesis==
Lindane is not known to occur naturally.
[[Hexachlorocyclohexane]] (HCH) was discovered in 1825. Its insecticidal properties were not known until the 1940s. Technical grade HCH, as a mixture of [[isomer]]s is synthesized from [[benzene]] and [[chlorine]] in presence of [[ultraviolet light]]. The resulting product mixture comprises 65-70% α-HCH, 7-10% β-HCH, 14-15% lindane (γ-HCH), approximately 7% δ-HCH, 1-2% ε-HCH, and 1-2% other components.<ref>{{Cite web |title=Lindane (EHC 124, 1991) |url=https://www.inchem.org/documents/ehc/ehc/ehc124.htm |access-date=2024-11-09 |website=www.inchem.org}}</ref>

It can also be prepared by exposing a mixture of benzene and chlorine to [[alpha radiation]].<ref name="w711">{{cite journal | last=Alyea | first=Hubert N. | title=CHAIN REACTIONS PRODUCED BY LIGHT AND BY ALPHA RADIATION<sup>1</sup> | journal=Journal of the American Chemical Society | publisher=American Chemical Society (ACS) | volume=52 | issue=7 | year=1930 | issn=0002-7863 | doi=10.1021/ja01370a022 | pages=2743–2745}}</ref>

==Human health effects==
The EPA and WHO both classify lindane as "moderately" acutely toxic. It has an oral {{LD50}} of 88&nbsp;mg/kg in rats and a dermal LD<sub>50</sub> of 1000&nbsp;mg/kg. Most of the adverse human health effects reported for lindane have been related to agricultural uses and chronic, occupational exposure of seed-treatment workers.<ref name="r16">Persistent Organic Pollutant Review Committee (POPRC). Draft risk management evaluation for lindane. May, 2007. {{cite web |url=http://www.pops.int/documents/meetings/poprc/drprofile/drme/DraftRME_Lindane.pdf |title=Home |access-date=2007-09-05 |url-status=dead |archive-url=https://web.archive.org/web/20070927024713/http://www.pops.int/documents/meetings/poprc/drprofile/drme/DraftRME_Lindane.pdf |archive-date=2007-09-27 }}</ref>

Exposure to large amounts of lindane can harm the [[nervous system]], producing a range of symptoms from headache and dizziness to seizures, convulsions, and more rarely, death.<ref name="Agency"/><ref name="r17">{{cite journal | title = Unintentional topical lindane ingestions--United States, 1998-2003 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 54 | issue = 21 | pages = 533–5 | date = June 2005 | pmid = 15931156 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5421a2.htm | author1 = Centers for Disease Control Prevention (CDC) }}</ref> Lindane has not been shown to affect the [[immune system]] in humans, and it is not considered to be genotoxic.<ref name="Agency"/> Prenatal exposure to β-HCH, an [[isomer]] of lindane and production byproduct, has been associated with altered thyroid hormone levels and could affect brain development.<ref name="pmid18207242">{{cite journal | vauthors = Alvarez-Pedrerol M, Ribas-Fitó N, Torrent M, Carrizo D, Garcia-Esteban R, Grimalt JO, Sunyer J | title = Thyroid disruption at birth due to prenatal exposure to beta-hexachlorocyclohexane | journal = Environment International | volume = 34 | issue = 6 | pages = 737–40 | date = August 2008 | pmid = 18207242 | doi = 10.1016/j.envint.2007.12.001 }}</ref>{{Primary source inline|date=November 2015}}

The [[Occupational Safety and Health Administration]] and [[National Institute for Occupational Safety and Health]] have set occupational exposure limits ([[Permissible exposure limit|permissible exposure]] and [[Recommended exposure limit|recommended exposure]], respectively) for lindane at 0.5&nbsp;mg/m<sup>3</sup> at a time-weighted average of eight hours for skin exposure. People can be exposed to lindane in the workplace by inhaling it, absorbing it through their skin, swallowing it, and eye contact. At levels of 50&nbsp;mg/m<sup>3</sup>, lindane is [[IDLH|immediately dangerous to life and health]].<ref>{{Cite web|title = CDC - NIOSH Pocket Guide to Chemical Hazards - Lindane|url = https://www.cdc.gov/niosh/npg/npgd0370.html|website = www.cdc.gov|access-date = 2015-11-19}}</ref>

It is classified as an [[List of extremely hazardous substances|extremely hazardous substance]] in the United States as defined in section 302 of the U.S. [[Emergency Planning and Community Right-to-Know Act]] (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.<ref name="gov-right-know">{{Cite web | publisher = [[United States Government Publishing Office|Government Printing Office]] | title = 40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities | url = http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf | edition = July 1, 2008 | access-date = October 29, 2011 | archive-url = https://web.archive.org/web/20120225051612/http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf | archive-date = February 25, 2012 | url-status = dead }}</ref>

===Cancer risk===
Based primarily on evidence from animal studies, most evaluations of lindane have concluded that it may possibly cause cancer. In 2015, the [[International Agency for Research on Cancer]] classified lindane as a known human carcinogen,<ref>{{cite press release |url=https://www.iarc.fr/en/media-centre/pr/2015/pdfs/pr236_E.pdf |title=IARC Monographs evaluate DDT, lindane, and 2,4-D |author=The International Agency for Research on Cancer (IARC) |date=23 June 2015 |access-date=2015-11-19 }}</ref><ref>{{cite journal | vauthors = Loomis D, Guyton K, Grosse Y, El Ghissasi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Mattock H, Straif K | title = Carcinogenicity of lindane, DDT, and 2,4-dichlorophenoxyacetic acid | journal = The Lancet. Oncology | volume = 16 | issue = 8 | pages = 891–2 | date = August 2015 | pmid = 26111929 | doi = 10.1016/S1470-2045(15)00081-9 }}</ref> and in 2001 the EPA concluded there was "suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential."<ref name="EPACA" /> The [[U.S. Department of Health and Human Services]] determined that all isomers of hexachlorocyclohexane, including lindane, "may reasonably be anticipated to cause cancer in humans,"<ref name="Agency"/> and in 1999, the EPA characterized the evidence carcinogenicity for lindane as "suggestive ... of carcinogenicity, but not sufficient to assess human carcinogenic potential."<ref name="EPARED"/> Lindane and its isomers have also been on California's [[Proposition 65]] list of known carcinogens since 1989.<ref>{{cite web |url= http://oehha.ca.gov/prop65/prop65_list/files/P65single061110.pdf |title=Chemicals Known to the State to Cause Cancer or Reproductive Toxicity| publisher = State of California Environmental Protection Agency | work = Office of Environmental Health Hazard Assessment|date=June 11, 2010|access-date=23 September 2010|url-status=dead|archive-url=https://web.archive.org/web/20101008225026/http://www.oehha.ca.gov/prop65/prop65_list/files/P65single061110.pdf|archive-date=8 October 2010}}</ref> In contrast, the [[World Health Organization]] concluded in 2004 that "lindane is not likely to pose a carcinogenic risk to humans."<ref name="r19">World Health Organization (WHO). Lindane in Drinking Water: Background Document for Development of WHO Guidelines for Drinking-Water Quality. 2004. {{cite web |url=https://www.who.int/water_sanitation_health/dwq/chemicals/lindane/en/print.html |title=WHO &#124; Chemical hazards in drinking-water - lindane |access-date=2007-09-05 |url-status=dead |archive-url=https://web.archive.org/web/20080103184701/http://www.who.int/water_sanitation_health/dwq/chemicals/lindane/en/print.html |archive-date=2008-01-03 }}</ref> India's BIS considers Lindane a "confirmed carcinogen".<ref name=Hindu>{{cite news
|url=http://www.thehindu.com/todays-paper/article3084971.ece
|title='Pesticide levels in soft drinks too high' - Today's Paper - The Hindu
|date=August 3, 2006
|access-date=2015-12-27
|newspaper=The Hindu
}}</ref>

===Adverse reactions===
A variety of adverse reactions to lindane pharmaceuticals have been reported, ranging from skin irritation to [[seizure]]s, and, in rare instances, death. The most common side effects are burning sensations, itching, dryness, and rash.<ref name="QandA"/> While serious effects are rare and have most often resulted from misuse, adverse reactions have occurred when used properly.<ref name="AssessmentMemo"/><ref name="Prescribe">{{cite web | title = Lindane lotion, USP, 1% prescribing information. | website = [[Food and Drug Administration]] | date = 28 March 2003 | url = https://www.fda.gov/cder/foi/label/2003/006309lotionlbl.pdf }}
* {{cite web | title = Lindane shampoo, USP, 1% prescribing information. | website = [[Food and Drug Administration]] | date = 28 March 2003 | url = https://www.fda.gov/cder/foi/label/2003/006309shampoolbl.pdf }}</ref><ref name="Postmarketing">{{cite web | work = U.S. FDA | title = Lindane Post Marketing Safety Review | date = 2003 | url = https://www.fda.gov/cder/drug/infopage/lindane/lindaneaeredacted.pdf }}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref> The FDA, therefore, requires a so-called [[black box warning]] on lindane products, which explains the risks of lindane products and their proper use.<ref name="QandA">{{cite web | work = U.S. FDA Centers for Drug Evaluation and Research | title = Lindane lotion and lindane shampoo questions and answers. | date = 15 April 2003 | url = https://www.fda.gov/cder/drug/infopage/lindane/lindaneQA.htm }}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref><ref>{{cite web |url=https://www.fda.gov/cder/drug/infopage/lindane/default.htm |title=Lindane Information |website=www.fda.gov |url-status=dead |archive-url=https://web.archive.org/web/20030608220035/http://www.fda.gov/cder/drug/infopage/lindane/default.htm |archive-date=2003-06-08}}</ref>

The black box warning emphasizes that lindane should not be used on premature infants and individuals with known uncontrolled seizure disorders, and should be used with caution in infants, children, the elderly, and individuals with other skin conditions (e.g., [[dermatitis]], [[psoriasis]]) and people who weigh less than {{cvt|110|lb}}, as they may be at risk of serious [[neurotoxicity]].<ref name="Prescribe"/>

==Environmental contamination==
Lindane is a [[persistent organic pollutant]]: it is relatively long-lived in the environment, it is transported long distances by natural processes like [[global distillation]], and it can [[bioaccumulate]] in [[food chain]]s, though it is rapidly eliminated when exposure is discontinued.<ref name="r16"/>

The production and agricultural use of lindane are the primary causes of environmental contamination,<ref name="r23">U.S. EPA. Assessment of lindane and other hexachlorocyclohexane isomers. February 8, 2006</ref> and levels of lindane in the environment have been decreasing in the U.S., consistent with decreasing agricultural usage patterns.<ref name="r24">United Nations Environment Programme. POPRC of the Stockholm Convention. Draft risk profile: Lindane. July 2006.</ref> The production of lindane generates large amounts of waste hexachlorocyclohexane isomers, and "every ton of lindane manufactured produces about nine tons of toxic waste."<ref name="LifeAfter">{{cite journal | url = http://www.ehponline.org/docs/2008/116-3/ss.html#life | title = Life after Lindane in California: Water Concentrations, Poison Control Calls Drop Following Ban | archive-url = https://web.archive.org/web/20080515191544/http://www.ehponline.org/docs/2008/116-3/ss.html#life | archive-date= 2008-05-15 | journal = Environmental Health Perspectives | volume = 116 | issue = 3 | date = March 2008 }}</ref> Modern manufacturing standards for lindane involve the treatment and conversion of waste isomers to less toxic molecules, a process known as "cracking".<ref name="r24" /><ref name="IHPALegacy">{{cite web |publisher=International HCH & Pesticides Association |title=The Legacy of Lindane HCH Isomer Production A Global Overview of Residue Management, Formulation and Disposal |url=http://www.ihpa.info/projects/the-legacy-of-lindane-hch-isomer-production/ |access-date=2020-07-09 }}</ref>

When lindane is used in agriculture, an estimated 12–30% of it volatilizes into the atmosphere, where it is subject to [[global distillation|long-range transport]] and can be deposited by rainfall. Lindane in soil can leach to surface and even ground water, and can bioaccumulate in the food chain.<ref name="EPAREDADD"/> However, biotransformation and elimination are relatively rapid when exposure is discontinued.<ref name="Commission" /> Most exposure of the general population to lindane has resulted from agricultural uses and the intake of foods, such as produce, meats, and milk, produced from treated agricultural commodities. Human exposure has decreased significantly since the cancellation of agricultural uses in 2006. Even so, the CDC published in 2005 its Third National Report on Human Exposures to Environmental Chemicals, which found no detectable amounts of lindane in human blood taken from a random sampling of about 5,000 people in the US as part of the NHANES study (National Health and Nutrition Examination Survey.<ref>{{cite web | title = About the National Health and Nutrition Examination Survey | url = https://www.cdc.gov/nchs/nhanes/about_nhanes.htm | work = National Center for Health Statistics | date = 31 May 2023 | publisher = U.S. Centers for Disease Control and Prevention }}</ref><ref name="CDCReport3">{{cite web | work = US CDC | title = Third National Report on Human Exposure to Environmental Chemicals | date = 2005 | url = https://www.cdc.gov/ExposureReport/pdf/thirdreport.pdf | archive-url = https://web.archive.org/web/20070401141153/http://www.cdc.gov/exposurereport/pdf/thirdreport.pdf | archive-date=2007-04-01 }}</ref> The lack of detection of lindane in this large human "biomonitoring" study likely reflects the increasingly limited agricultural uses of lindane over the last two decades. The cancellation of agricultural uses in the United States will further reduce the amount of lindane introduced into the environment by more than 99%.<ref name="Commission" /><ref name="EPAREDADD" />

Over time, lindane is broken down in soil, sediment, and water into less harmful substances by algae, fungi, and bacteria; however, the process is relatively slow and dependent on ambient environmental conditions.<ref name="Agency"/> Lindane residues in honey and beeswax are reported to be the highest of any historical or current pesticide and to continue to pose a threat to honeybee health.<ref name="honey">{{cite journal | vauthors = Drummond J, Williamson SM, Fitchett AE, Wright GA, Judge SJ | title = Spontaneous honeybee behaviour is altered by persistent organic pollutants | journal = Ecotoxicology | volume = 26 | issue = 1 | pages = 141–150 | date = January 2017 | pmid = 27933553 | pmc = 5241328 | doi = 10.1007/s10646-016-1749-0 | bibcode = 2017Ecotx..26..141D }}</ref> The ecological impact of lindane's environmental persistence continues to be debated.

The US EPA determined in 2002 that the agency does not believe that lindane contaminates drinking water in excess of levels considered safe.<ref name="Agency"/> [[U.S. Geological Survey]] teams concluded the same in 1999 and 2000.<ref>{{cite journal |vauthors=Kolpin DW, Furlong ET, Meyer MT, etal | year = 2002 | title = Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999–2000: A national reconnaissance | url = http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1064&context=usgsstaffpub| journal = Environ Sci Technol | volume = 36 | issue = 6| pages = 1202–1211 | doi=10.1021/es011055j| pmid = 11944670 | bibcode = 2002EnST...36.1202K | url-access = subscription }}</ref> With regard to lindane medications, the EPA conducted "down-the-drain" estimates of the amount of lindane reaching public water supplies and concluded that lindane levels from pharmaceutical sources were "extremely low" and not of concern.<ref name="EPARED"/>

Note that the EPA has set the maximum contaminant level or "MCL" for lindane allowed in public water supplies and considered safe for drinking at 200 parts per trillion (ppt).<ref name="EPAReview03">U.S. EPA. Announcement of completion of EPA's review of existing drinking water standards. Federal Register. 68(138): July 18, 2003.</ref> By comparison, the state of California imposes a lower MCL for lindane of 19 ppt.<ref name="CAOutcomes" /> However, the California standard is based on a dated 1988 national water criterion that was subsequently revised by the EPA in 2003 to 980 ppt.<ref name="EPACA" /><ref name="EPAReview03" /><ref>
{{cite web | title = California Public Health Goal for Lindane in Drinking Water | url = http://oehha.ca.gov/water/phg/pdf/lindan_f.pdf | archive-url = https://web.archive.org/web/20091010001328/http://www.oehha.ca.gov/water/phg/pdf/lindan_f.pdf | archive-date=2009-10-10 }}</ref><ref>
{{cite web | vauthors = Hannon S, Keane C, Miller P |date=April 2009 |title=Lindane: Pharmaceutical and Agricultural Alternatives |url=http://www.ipen.org/documents/lindane-pharmaceutical-and-agricultural-alternatives |publisher=IPEN }}</ref> The EPA stated that the change resulted from "significant scientific advances made in the last two decades particularly in the areas of cancer and noncancer risk assessments."<ref name="EPAReview03" /> While the EPA considered raising the MCL standard for lindane to 980 ppt at that time, the change was never implemented because states had little difficulty in maintaining lindane levels below the 200 ppt MCL limit already in place.<ref name="EPAReview03" /> Today, the legally enforceable MCL standard for lindane is 200 ppt, while the national water criterion for lindane is 980 ppt.<ref name="EPAReview03" />

===Isomers===
Lindane is the gamma isomer of [[hexachlorocyclohexane]] ("γ-HCH"). In addition to the issue of lindane pollution, some concerns are related to the other isomers of HCH, namely [[alpha-HCH]] and [[beta-HCH]], which are notably more toxic than lindane, lack its insecticidal properties, and are byproducts of lindane production.<ref name="Agency" /> In the 1940s and 1950s, lindane producers stockpiled these isomers in open heaps, which led to ground and water contamination. The International HCH and Pesticide Forum has since been established to bring together experts to address the clean-up and containment of these sites.<ref name="IHPALegacy" /><ref>{{Cite report |url=http://www.ihpa.info/docs/library/reports/Lindane%20Main%20Report%20DEF20JAN06.pdf |title=The Legacy of Lindane HCH Isomer Production: Main Report: A Global Overview of Residue Management, Formulation and Disposal |last=Vijgen |first=John |date=January 2006 |publisher=International HCH & Pesticides Association |isbn=87-991210-1-8 |archive-url=https://web.archive.org/web/20070928164835/http://www.ihpa.info/docs/library/Lindane%20Main%20Report%20DEF20JAN06.pdf |archive-date=2007-09-28}}<!-- The 7 annexes are available at .../Lindane%20AnnexesDEF20JAN06.pdf --></ref> Modern manufacturing standards for lindane involve the treatment and conversion of waste isomers to less toxic industrial chemicals, a process known as "[[cracking (chemistry)|cracking]]".<ref name="Agency" /><ref name="IHPALegacy" /> Today, only a few production plants remain active worldwide to accommodate public-health uses of lindane and declining agricultural needs.<ref name="Commission" /> Lindane has not been manufactured in the U.S. since the mid-1970s, but continues to be imported.

<div class="skin-invert-image"><gallery>
File:Alpha-hexachlorocyclohexane.svg|α-hexachlorocyclohexane
File:Beta-hexachlorocyclohexane.svg|β-hexachlorocyclohexane
</gallery></div>

==See also==
* [[Benzene hexachloride (disambiguation)]]

== References ==
{{Reflist}}

== External links ==

===Government and organizations===
* [https://web.archive.org/web/20030608220035/http://www.fda.gov/cder/drug/infopage/lindane/default.htm FDA Information on Lindane]
* [https://archive.today/20121213095207/http://www.epa.gov/pesticides/reregistration/lindane/ EPA Information on Lindane]
* [https://web.archive.org/web/20061013061244/http://www.epa.gov/epaoswer/hazwaste/minimize/factshts/hexagama.pdf Gamma Hexachlorocyclohexane Fact Sheet]
* [http://www.atsdr.cdc.gov/toxprofiles/tp43.pdf Agency for Toxics and Disease Registry: Toxicological Profile for Hexachlorocyclohexane]
* {{PPDB|370}}
* [https://www.who.int/water_sanitation_health/dwq/chemicals/lindane.pdf World Health Organization Background Document on Lindane for Drinking-Water Quality Guidelines]
* [http://www.inchem.org/documents/pims/chemical/pim859.htm Lindane Chemistry and Uses]
* [http://www.inchem.org/documents/ehc/ehc/ehc124.htm World Health Organization: Lindane (EHC 124)]
* [http://www.lindane.com "Lindane Facts"] - Website run by Morton Grove Pharmaceuticals
*[https://www.nlm.nih.gov/toxnet/index.html U.S. National Library of Medicine: Hazardous Substances Databank &ndash; Lindane]

===News stories and opinion articles===
* [https://www.npr.org/templates/story/story.php?storyId=6556831 "Mom and Pros Tackle Lice"] - NPR story from 2006
* [https://web.archive.org/web/20070930230220/http://www.hindu.com/2006/08/03/stories/2006080322890100.htm Pepsi and Coca-Cola - Lindane in drinks in India] - news story from 2006
* [https://web.archive.org/web/20060528003323/http://www.panna.org/resources/gpc/gpc_200308.13.2.21.dv.html India - Pesticides in Coke & Pepsi drinks] - news story from 2003

{{Human lice}}
{{Anti-arthropod medications}}
{{insecticides}}
{{Consumer Food Safety}}
{{Xenoestrogens}}
{{GABAergics}}
{{Authority control}}

[[Category:Endocrine disruptors]]
[[Category:IARC Group 1 carcinogens]]
[[Category:Organochloride insecticides]]
[[Category:Persistent organic pollutants under the Stockholm Convention]]
[[Category:Persistent organic pollutants under the Convention on Long-Range Transboundary Air Pollution]]
[[Category:GABAA receptor negative allosteric modulators]]