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Blancer707/Sandbox
Clinical data
Pregnancy
category
  • C
Routes of
administration		Topical
ATC code
Legal status
Legal status
  • In 2009, the Stockholm Convention banned agricultural uses but permitted pharmaceutical uses for 5 more years.[1] There are 152 ratified countries to the treaty[2].
Pharmacokinetic data
Protein binding91%
MetabolismHepatic cytochrome P-450 oxygenase system
Elimination half-life18 hours
Identifiers
  • (1r,2R,3S,4r,5R,6S)-1,2,3,4,5,6-hexachlorocyclohexane
CAS Number
PubChem CID
DrugBank
ChemSpider
Chemical and physical data
FormulaC6H6Cl6
Molar mass290.83 g/mol g·mol−1
3D model (JSmol)
  • Cl[C@H]1[C@H](Cl)[C@H](Cl)[C@@H](Cl)[C@H](Cl)[C@@H]1Cl
  (verify)

Lindane, also known as gamma-hexachlorocyclohexane, (γ-HCH), gammaxene, Gammallin and erroneously known as benzene hexachloride (BHC),[3] is an organochlorine chemical variant of hexachlorocyclohexane that has been used both as an agricultural insecticide and as a pharmaceutical treatment for lice and scabies.[4][5]

Lindane works as a neurotoxin by interfering with GABA neurotransmitter, specifically interacting with the GABAA receptor-chloride channel complex at the picrotoxin binding site. In humans, exposure to toxic amounts of lindane primarily affects the nervous system.[6][7] Lindane is not a mutagenic and data regarding carcinogenic potential have been conflicting.[6][8][9][10][11] It is unclear whether lindane is an endocrine disruptor.[8][9][10]

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.[12] In 2009 the production and agricultural use of lindane was banned under the Stockholm Convention on persistent organic pollutants in ratified countries. A specific exemption to that ban allows for its continued use as a second-line pharmaceutical treatment for lice and scabies. [13]

History and use

The use of lindane as an insecticide began in the 1940s. It has been used to treat food crops and forestry products, as a seed treatment, a soil treatment, and to treat livestock and pets. It has also been used as a pharmaceutical treatment for lice and scabies, formulated as a shampoo and lotion.[14][15][16] Notably, lindane-based agricultural products generally contain much higher concentrations of lindane compared with pharmaceutical treatments, often in combination with other agricultural chemicals. [17] It is estimated that roughly 600,000 tonnes of lindane were produced globally between 1950 and 2000; the vast majority of uses -- greater than 99% -- have been agricultural. [14] It has been manufactured in several countries, including the United States, China, Brazil, and several European countries, but as of 2007 only India and possibly Russia are still producing it.[14]

By 2006, the use lindane had been banned in 52 countries and restricted in 33. Seventeen countries, including the US and Canada, allow either limited agricultural or pharmaceutical use.[14] In 2009, a ban on the agricultural uses of lindane in agriculture was implemented under the Stockholm Convention on Persistent Organic Pollutants in ratified countries. A specific exemption to this treaty allows for the continued use of lindane-based medications for the second-line treatment of head lice and scabies for 5 more years. The production of the lindane isomers a- and ß-hexachlorocyclohexane, which are notably more toxic than lindane, was also banned.[18] Although the US has not ratified the Convention, it has similarly banned agricultural uses while allowing public health uses for the second-line treatment of lice and scabies.[18][13][19][20]

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 a pharmaceutical in 1951.[14] The EPA gradually began restricting its agricultural use in the 1970s due to concerns over its effects on human health and the environment.[21] By 2002, its use was limited to seed treatments for just 6 crops,[14] and in 2007 these last uses were cancelled.[22] The FDA continues to support approved medical uses.[23][24]

Pharmaceutical uses

Lindane medications are approved in the US for the treatment of scabies, head lice and pubic lice (“crabs”) and formulated as a 1% lotion and 1% shampoo for topical use. They are available by prescription only and were designated as second-line treatments in 1995, which means they are indicated when other "first-line" treatments have failed or cannot be used.[25] [25][26][27][28]

Resistance to lindane and other agents used to treat scabies and lice has been reported in the US and elsewhere, and is an important cause of treatment failure in areas where resistance has emerged. [26] [27] [29][30] [31] [32] [33] [34][35] [36][37] The actual rate of clinical resistance to lindane and other scabicides and pediculicides in the US is not known but varies geographically. [38] Because there are no recent controlled clinical studies evaluating the efficacy of lindane versus other approved treatments in the US, it is not known how lindane would compare with these agents today. Resistance to permethrin, in particular, is a growing concern because of its extensive use and availability as an over-the-counter first-line treatment. [39] [40] To this point, the most recent authoritative review of head lice treatments by a group of international experts ("The Cochrane Review") was withdrawn in 2007 for lack of current evidence of the comparative effectiveness of head lice treatments, noting that " The 'best' choice will now depend on local resistance patterns." [41]

In December 2007, the FDA sent a warning letter to Morton Grove Pharmaceuticals[42], requesting that the company correct misleading information about its lindane shampoo product that appeared on two websites developed by Alliant Pharmaceuticals as part of a contract marketing agreement, which the FDA believed minimized serious risks while over stating product benefits.[43] Morton Grove responded with corrective actions (http://www.lindane4lice.com/) and the contract with Alliant Pharmaceuticals terminated in May 2007. [44]

The State of California banned pharmaceutical lindane, effective 2002, and there are bills pending in the New York and Michigan state legislatures.[45] [46] The Michigan bill, which would restrict its use to doctors’ offices, passed the House on May 2008 and again in March 2009, but has not passed the Senate. [47] [48]

An analysis of the California ban concluded that the majority of pediatricians responding to a mail-in survey--78% of 135 respondents-- had not experienced problems treating lice or scabies since the ban took effect. By comparison, 22% of respondents did express concerns and cited resistance as the primary challenge following the ban. The study also documented a decrease in lindane wastewater contamination (i.e., water entering purification plants) and a decline in lindane poisoning incidents reported to Poison Control Centers. The report noted, however, that significant and steady declines in lindane poisonings had already occurred prior to the ban from 1998 to 2002. In addition, it is relevant to note that the study did not measure lindane levels in purified water released from treatment plants nor did it measure lindane in water sources used for drinking. [49] Regardless of these limitations, the authors stated that, "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." [49]

By contrast, the EPA published in 2002 the results of their own analysis, based in part on data from California water treatment plants, and concluded that lindane levels from use of pharmaceutical lindane was extremely low and not of concern.[16]

Morton Grove lawsuit

In 2006 Morton Grove Pharmaceuticals, the sole US manufacturer of lindane pharmaceuticals, sued the National Pediculosis Association, the Michigan Ecology Center, and two physicians, alleging that they disseminated defamatory materials regarding lindane and other charges. Morton Grove alleged more than $9.3 million in damages.[50] The defendants considered the legal action to be SLAPP suit and settled in 2008. The settlement did not require them to admit liability or make any payments to Morton Grove, but the Ecology Center did agree to clarify 7 of the statements it had published in its lindane factsheet.[45][51][52][53]

Human health effects

The EPA and WHO both classify lindane as "moderately" acutely toxic. It has an oral LD50 of 88 mg/kg in rats and a dermal LD50 of 1000 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.[54]

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.[6][55] Lindane has not been shown to affect the immune system in humans and, it is not considered to be genotoxic.[6] Limited data suggest that lindane may be an endocrine disruptor but the CDC has noted that additional research is needed to determine if there is any relevance to public health. [6]

Cancer risk

Assessments on the carcinogenic risk of lindane derived primarily from animal toxicology studies have been conflicting, though the most recent review of available evidence in 2004 by the Joint Commission of Pesticide Residues (JMPR) of the World Health Organization (WHO) and Food Agricultural Organization (FAO) of the United Nations concluded that “lindane is not likely to pose a carcinogenic risk to humans.”[10] In 2001, the Cancer Assessment Review Committee of the EPA issued a report on lindane in which they found “major deficiencies” with some of the earlier studies, prompting additional research and subsequent reclassification of lindane from “possibly carcinogenic” into the lesser category of “Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential.” The expert Committee further recommended that “quantification of human cancer risk is not required” because the evidence was limited to the finding of benign tumors in one species of female mice.[9] In 1987, the International Agency for Research on Cancer (IARC) classified the broader chemical class of hexachlorocyclohexanes (HCH) to which lindane belongs as group 2B "possible" human carcinogens, with the caveat that human evidence relating specifically to lindane was inadequate and that findings from animal cancer studies were equally limited.[8] Likewise, the U.S. Department of Health and Human Services (DHHS) determined that hexachlorocyclohexanes, including lindane, "may reasonably be anticipated to cause cancer in humans but similarly noted that “evidence for carcinogenicity in humans was inadequate.” The DHHS position was based on experimental animal studies reported by the IARC in 1979, 1982, 1987 and the National Cancer Institute in 1977.[9][10][56]

Adverse reactions to lindane pharmaceuticals

A variety of adverse reactions to lindane pharmaceuticals have been reported. The most common are nonserious reactions of the skin such as burning sensations, itching, dryness and rash. [57][58] Systemic effects have also been reported, including headache and dizziness and in rare instances seizures, and even more rarely death.[59] While serious effects are rare and have most often resulted from misuse, adverse reactions have occurred when used properly.[25][23][24][60] The FDA therefore requires a so-called black box warning on lindane products, which explains these risks and details proper use instructions.[59][61]

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 110 lbs (50 kg) as they may be at risk of serious neurotoxicity. [23][24]

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 chains, though it is rapidly eliminated when exposure is discontinued.[54]

The production and agricultural use of lindane are the primary causes of environmental contamination,[62] and levels of lindane in the environment have been decreasing in the U.S., consistent with decreasing agricultural usage patterns.[11] The production of lindane generates large amounts of waste hexachlorocyclohexane isomers, and it is estimated that "every ton of lindane manufactured produces about 9 tons of toxic waste."[63] Modern manufacturing standards for lindane involve the treatment and conversion of waste isomers to less toxic molecules, a process known as "cracking." [11] [64]

When lindane is used in agriculture, an estimated 12-30% of it volatilizes into the atmosphere, where it is subject to 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. [21] However, biotransformation and elimination are relatively rapid when exposure is discontinued. [14] 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 at: http://www.cdc.gov/nchs/nhanes/about_nhanes.htm ).[65] 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 U.S. will further reduce the amount of lindane introduced into the environment by more than 99%. [21][14]

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.[6] 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.[6] U.S. Geologic Survey teams concluded the same in 1999 and 2000.[66] 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.[16]

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).[67] By comparison, the state of California imposes a lower MCL for lindane of 19 ppt.[49] 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. [9][68][69][67] 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." [67] 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 difficultly in maintaining lindane levels below the 200 ppt MCL limit already in place. [67] Today, the legally enforceable MCL standard for lindane is 200 ppt while the national water criterion for lindane is 980 ppt. [67]

Isomers

Lindane is the gamma isomer of hexachlorocyclohexane ("γ-HCH"). In addition to the issue of lindane pollution are concerns 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.[6] 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.[64][dead link] Modern manufacturing standards for lindane involve the treatment and conversion of waste isomers to less toxic industrial chemicals, a process known as "cracking."[6][64] Today, only a few production plants remain active worldwide to accommodate public health uses of lindane and declining agricultural needs.[14] Lindane has not been manufactured in the U.S. since the mid-1970s but continues to be imported.

  • a-hexachlorocyclohexane
    a-hexachlorocyclohexane
  • ß-hexachlorocyclohexane
    ß-hexachlorocyclohexane

See also

References

  1. ^ Report of the Conference of the Parties of the Stockholm Convention on Persistent Organic Pollutants on the work of its fourth meeting. Convention on Persistent Organic Pollutants. Fourth meeting, Geneva, 4–8 May 2009. http://chm.pops.int/Portals/0/Repository/COP4/UNEP-POPS-COP.4-38.English.pdf
  2. ^ Stockholm Convention on POPs, Status of Ratification. Available at: http://chm.pops.int/Countries/StatusofRatification/tabid/252/language/en-US/Default.aspx
  3. ^ Brandenberger, Hans; Maes, Robert A. A. (1997). Analytical toxicology: for clinical, forensic, and pharmaceutical chemists. Berlin: Walter de Gruyter. p. 243. ISBN 9783110107319. Retrieved 2009-05-10.
  4. ^ Drugs.com Professional Drug Information: Lindane. Retrieved 2009-05-10
  5. ^ Commission for Environmental Cooperation. The North American Regional Action Plan (NARAP) on Lindane and Other Hexachlorocyclohexane (HCH) Isomers. 2005. Available at: http://www.cec.org/files/PDF/POLLUTANTS/Lindane-NARAP-Public-Comment_en.pdf.
  6. ^ a b c d e f g h i Agency for Toxic Substances and Disease Registry, U.S. Department of Health and Human Services. Toxicologic profile for alpha-, beta, gamma- and delta-hexachlorocyclohenxane. August 2005. http://www.atsdr.cdc.gov/toxprofiles/tp43.pdf
  7. ^ Lindane Voluntary Cancellation and RED Addendum Fact Sheet, US EPA, July name 2006.
  8. ^ a b c International Agency for Research on Cancer (IARC). Summaries & Evaluations: HEXACHLOROCYCLOHEXANES (Group 2B). Updated March 2, 1998. http://www.inchem.org/documents/iarc/suppl7/hexachlorocyclohexanes.html
  9. ^ a b c d e U.S. EPA. Evaluation of the Carcinogenic Potential of Lindane, PC. Code: 009001. 2001. http://www.lindane.com/pdf/EPA_Cancer_Assessment_of_Lindane2001.pdf
  10. ^ a b c d World Health Organization (WHO). Lindane in Drinking Water: Background Document for Development of WHO Guidelines for Drinking-Water Quality. 2004.
  11. ^ a b c United Nations Environment Programme. POPRC of the Stockholm Convention. Draft risk profile: Lindane. July 2006.
  12. ^ World Health Organization, The WHO Recommended Classification of Pesticides by Hazard, 2005.
  13. ^ a b Eliane Engeler, "UN: Treaty expanded by 9 more dangerous chemicals", Associated Press 2009-05-09
  14. ^ a b c d e f g h i Commission for Environmental Cooperation. North American Regional Action Plan (NARAP) on lindane and other hexachlorocyclohexane (HCH) isomers. November 30, 2006. http://www.cec.org/files/PDF/POLLUTANTS/LindaneNARAP-Nov06_en.pdf
  15. ^ "LINDANE: Risk Profile. UNEP/POPS/POPRC.2/17/Add.4". Stockholm Convention of Persistent Organic Pollutants. {{cite web}}: |access-date= requires |url= (help); Missing or empty |url= (help)
  16. ^ a b c U.S. Environmental Protection Agency (EPA). Lindane Reregistration Eligibility Decision (RED). 2002. http://www.regulations.gov/search/Regs/home.html#documentDetail?R=09000064800b449a
  17. ^ National Pesticide Information Retrieval System. Available at: http://ppis.ceris.purdue.edu/npublic.htm.
  18. ^ a b Report of the Conference of the Parties of the Stockholm Convention on Persistent Organic Pollutants on the work of its fourth meeting. Convention on Persistent Organic Pollutants. Fourth meeting, Geneva, 4–8 May 2009. http://chm.pops.int/Portals/0/Repository/COP4/UNEP-POPS-COP.4-38.English.pdf.
  19. ^ Persistent Organic Pollutants Review Committee http://www.pops.int/documents/meetings/poprc/chemreview.htm
  20. ^ Pesticide Action Network map of Lindane bans and restrictions http://www.panna.org/campaigns/docsLindane/lindaneBannedMap.pdf
  21. ^ a b c U.S. EPA. Addendum to the 2002 Lindane Reregistration Eligibility Decision (RED). July 2006. http://www.epa.gov/oppsrrd1/REDs/lindane_red_addendum.pdf
  22. ^ http://www.epa.gov/oppfead1/cb/csb_page/updates/2006/lindane-order.htm
  23. ^ a b c Lindane lotion, USP, 1% prescribing information. Updated March 28, 2003. http://www.fda.gov/cder/foi/label/2003/006309lotionlbl.pdf
  24. ^ a b c Lindane shampoo, USP, 1% prescribing information. Updated March 28, 2003. http://www.fda.gov/cder/foi/label/2003/006309shampoolbl.pdf.
  25. ^ a b c Food and Drug Administration. Lindane Assessment Memorandum. Posted 2003. http://www.fda.gov/cder/drug/infopage/lindane/lindanememoassessment.pdf.
  26. ^ a b McCarthy JS, Kemp DJ, Walton SF, Currie BJ (2004). "Scabies: more than just an irritation". Postgrad Med J. 80 (945): 382–7. doi:10.1136/pgmj.2003.014563. PMID 15254301.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ a b Thomas DR, McCarroll L, Roberts R; et al. (2006). "Surveillance of insecticide resistance in head lice using biochemical and molecular methods". Arch. Dis. Child. 91 (9): 777–8. doi:10.1136/adc.2005.091280. PMID 16774979. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  28. ^ FDA Public Health Advisory: Safety of Topical Lindane Products for the Treatment of Scabies and Lice. Availasble at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm110845.htm
  29. ^ Witkowski JA, Parish LC. Lindane-resistant scabies. J Am Acad Dermatol. 1992 Oct;27(4):648.
  30. ^ Parish LC, Witkowski JA, Kucirka SA. Lindane resistance and pediculosis capitis. Int J Dermatol. 1983 Dec;22(10):572-4.
  31. ^ Elston DM. Nit picking. J Am Acad Dermatol. 2005; 35:164.
  32. ^ Roberts RJ. Clinical practice. Head lice. N Engl J Med. 2002;346(21):1645–50.
  33. ^ Johnston G, Sladden M. Scabies: diagnosis and treatment. British Med J. 2005;331:619–622.
  34. ^ Chosidow O. Scabies and pediculosis. Lancet. 2000;355:819–826.
  35. ^ Currie BJ, Harumal P, McKinnon M, et al. First documentation of in vivo and in vitro ivermectin resistance in Sarcoptes scabiei. Clin Infect Dis. 2004;39:e8–e12.
  36. ^ Pollack RJ, Kiszewski A, Armstrong P, et al. Differential permethrin susceptibility of head lice sampled in the United States and Borneo. Arch Pediatr Adolesc Med. 1999;153:969–973.
  37. ^ Downs AM. Managing head lice in an era of increasing resistance to insecticides. Am J Clin Dermatol. 2004;5(3):169–177.
  38. ^ Kwon DH, Yoon KS, Strycharz JP, Clark JM, Lee SH. Determination of permethrin resistance allele frequency of human head louse populations by quantitative sequencing. J Med Entomol. 2008 Sep;45(5):912-20.
  39. ^ Clark JM. Determination, mechanism and monitoring of knockdown resistance in permethrin-resistant human head lice, Pediculus humanus capitis. Journal of Asia-Pacific Entomology 12 (2009) 1–7.
  40. ^ Burkhart CG, Burkhart CN.Safety and efficacy of pediculicides for head lice. Expert Opin Drug Saf. 2006 Jan;5(1):169-79.
  41. ^ Dodd CS.Withdrawn: Interventions for treating head lice. Cochrane Database Syst Rev. 2007 Jul 18;(4):CD001165.
  42. ^ Sciele Pharma Completes Acquisition of Alliant Pharmaceuticals. Press Release; June 12, 2007. http://phx.corporate-ir.net/phoenix.zhtml?c=120763&p=irol-newsArticle&ID=1014610&highlight
  43. ^ Warning Letter from the U.S. Food and Drug Administration to Morton Grove. (undated.)
  44. ^ Corrective information on lindane shampoo available at: http://www.lindane4lice.com/
  45. ^ a b Critics of drugs in for bad medicine, Laura Berman, The Detroit News, March 2, 2008.
  46. ^ Bill Summary - A06802
  47. ^ http://www.legislature.mi.gov/(S(qmov3e45chfz0w55ymrrcl45))/mileg.aspx?page=getObject&objectName=2009-HB-4402
  48. ^ HB-4569, As Passed House, May 15, 2008 Michigan Legislature website.
  49. ^ a b c Humphreys EH, Janssen S, Heil A, Hiatt P, Solomon G, Miller MD (2008). "Outcomes of the California ban on pharmaceutical lindane: clinical and ecologic impacts" (PDF). Environ. Health Perspect. 116 (3): 297–302. doi:10.1289/ehp.10668. PMC 2265033. PMID 18335094. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  50. ^ Morton Grove Pharmaceuticals, Inc. v. The National Pediculosis Association, et al., No. 06 C 3815 (N.D. Ill. June 18, 2007) (Bucklo, J.)
  51. ^ The Ecology Center's Clarification of Statements Regarding Lindane, Michigan Ecology Center, accessed March 3, 2008.
  52. ^ Ecology Center's lindane suit settled, Art Aisner, Ann Arbor News, March 15, 2008.
  53. ^ Ecology Center Retractions. Available at: http://www.lindane.com/retractions/ecologycenterrebuttal/
  54. ^ a b Persistent Organic Pollutant Review Committee (POPRC). Draft risk management evaluation for lindane. May, 2007. http://www.pops.int/documents/meetings/poprc/drprofile/drme/DraftRME_Lindane.pdf
  55. ^ "Unintentional topical lindane ingestions--United States, 1998-2003". MMWR Morb. Mortal. Wkly. Rep. 54 (21): 533–5. 2005. PMID 15931156..
  56. ^ IARC. Lindane (CAS No. 58-89-9) and Other Hexachlorocyclohexane Isomers. Report on carcinogens. 11th report. Available at: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s102lind.pdf.
  57. ^ Medication Guide Lindane Lotion USP, 1%. Updated March 28, 2003. Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM133687.pdf.
  58. ^ Medication Guide Lindane Shampoo USP, 1%. Updated March 28, 2003. Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM133688.pdf.
  59. ^ a b U.S. FDA Centers for Drug Evaluation and Research. Lindane lotion and lindane shampoo questions and answers. Updated April 15, 2003. http://www.fda.gov/cder/drug/infopage/lindane/lindaneQA.htm
  60. ^ U.S. FDA. Lindane Post Marketing Safety Review. Posted 2003. http://www.fda.gov/cder/drug/infopage/lindane/lindaneaeredacted.pdf
  61. ^ http://www.fda.gov/cder/drug/infopage/lindane/default.htm
  62. ^ U.S. EPA. Assessment of lindane and other hexachlorocyclohexane isomers. February 8, 2006
  63. ^ Life after Lindane in California: Water Concentrations, Poison Control Calls Drop Following Ban, Environmental Health Perspectives, Volume 116, Number 3, March 2008.
  64. ^ a b c International HCH & Pesticides Association. The legacy of lindane HCH isomer production. 2006. http://www.ihpa.info/docs/library/Lindane%20Main%20Report%20DEF20JAN06.pdf
  65. ^ US CDC. Third National Report on Human Exposure to Environmental Chemicals. 2005. Available at: http://www.cdc.gov/ExposureReport/pdf/thirdreport.pdf.
  66. ^ Kolpin DW, Furlong ET, Meyer MT, et al. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999–2000: A national reconnaissance. Environ Sci Technol. 2002;36(6):1202–1211.
  67. ^ a b c d e U.S. EPA. Announcem[ent of completion of EPA’s review of existing drinking water standards. Federal Register. 68(138): July 18, 2003.
  68. ^ California Public Health Goal for Lindane in Drinking Water. Available at: http://oehha.ca.gov/water/phg/pdf/lindan_f.pdf.
  69. ^ IPEN. Lindane: Agricultural and pharmaceutical alternatives to lindane. Available at: http://www.akaction.org/REPORTS/Alternatives%20to%20Lindane%20Report%204-29-09.pdf

Government and organizations

News stories and opinion articles

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