Endosulfan

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IUPACName = 6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-
6,9-methano-2,4,3-benzodioxathiepine-3-oxide
OtherNames = Thiodan, Thionex, Phaser, Benzoepin
Formula = C₉H₆Cl₆O₃S
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CASNo = 115-29-7
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SMILES = ClC1(C(Cl)2Cl)C(COS(OC3)=O)C3C2(Cl)C(Cl)=C1Cl
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Endosulfan is a neurotoxic organochlorine insecticide of the cyclodiene family of pesticides. It is an endocrine disruptor, and it is highly acutely toxic. It is banned in the European Union, Cambodia, and several other countries, while its use is restricted in other countries, including the Philippines (where it will be banned after September 2008). It is still used extensively in many countries including India, New Zealand and the United States. It is made by Bayer CropScience, Makhteshim-Agan, and Hindustan Insecticides Limited among others, and sold under the tradenames Thionex, Thiodan, Phaser, and Benzoepin. Because of its high toxicity and high potential for bioaccumulation and environmental contamination, a global ban on the use and manufacture of endosulfan is being considered under the Stockholm Convention. [http://www.env-health.org/a/2627 "European Commission proposes to add endosulfan to the Stockholm POPs Convention"] , Environmental Health and Alliance, Aug 22, 2007.]

Uses

Endosulfan has been used in agriculture around the world to control insect pests including whiteflys, aphids, leafhoppers, Colorado potato beetles, cabbage worms, and other pests. It has also seen use in wood preservation, home gardening, and tse-tse fly control, though it is not currently used in any vector control campaigns. The World Health Organization estimated world wide annual production to be about 20 million pounds (9,000 metric tons) in the early 1980s.World Health Organization, [http://www.inchem.org/documents/ehc/ehc/ehc40.htm "Environmental Health Criteria 40"] , 1984.] In India, more endosulfan is produced than any other pesticide except mancozeb and monocrotophos, with almost 180 million pounds manufactured in the period 1999-2000. Saiyed H, Dewan A, Bhatnagar V, "et al.", [http://www.ehponline.org/members/2003/6271/6271.pdf Effect of Endosulfan on Male Reproductive Development] , "Environ. Health Perspect.", 2003, 111:1958-1962.] Because of its unique mode of action, it is useful in resistance management.

In the United States, endosulfan is only registered for agricultural use. It is used extensively on cotton, potatoes, tomatoes, and apples according to the Environmental Protection Agency (EPA). [ [http://www.panna.org/files/EPA-HQ-OPP-2002-0262-0062.pdf Benefits of Endosulfan in Agricultural Production: Analysis of Usage Information] , U.S. EPA, Docket ID NO. EPA-HQ-OPP-2002-0262-0062, 2007.] The EPA estimates that 1.38 million lb of endosulfan were used annually from 1987 to 1997.US EPA, [http://www.epa.gov/oppsrrd1/REDs/endosulfan_red.pdf "Reregistration Eligibility Decision for Endosulfan"] , November 2002.] In California, annual use of endosulfan dropped from 230,000 lb (104 t) in 1995 to just 83,000 lb (38 t) in 2005. [ "California Pesticide Use Reporting Data", California Department of Pesticide Regulation, 1997-2007, cited in [http://pesticideinfo.org/List_CA_Chem_Use.jsp?chk=259&cok=00&sk=00 "Pesticide Use in California"] , www.pesticideinfo.org.]

Chemistry

The IUPAC name for endosulfan is 6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepine-3-oxide. It is chemically similar to other cyclodiene pesticides like aldrin, chlordane, and heptachlor, and like its "cousins" it is synthesized from hexachlorocyclopentadiene. Specifically, it is produced by the Diels-Alder reaction of hexachlorocyclopentadiene with "cis"-butene-1,4-diol and subsequent reaction with thionyl chloride. Technical endosulfan is a mixture of steroisomers, designated "α" and "β," in a 7:3 ratio. The technical material may also contain small amounts endosulfan sulfate and related chemicals. α- and β-endosulfan are conformational isomers, and can be interconverted without breaking bonds. α-Endosulfan is the more thermodynamically stable of the two, and β-endosulfan slowly and irreversibly converts to the α form over time. [(a) Schmidt WF, Hapeman CJ, Fettinger JC, Rice CP, and Bilboulian S, " J. Ag. Food Chem.", 1997, 45(4): 1023–1026.
(b) Schmidt WF, Bilboulian S, Rice CP, Fettinger JC, McConnell LL, and Hapeman CJ, " J. Ag. Food Chem.", 2001, 49(11): 5372–5376.]

History

*Early 1950s Endosulfan developed.
*1954 Hoechst AG (now Bayer CropScience) registers endosulfan with the EPA, and US farmers begin using it.Agency of Toxic Substances and Disease Registry, [http://www.atsdr.cdc.gov/toxprofiles/tp41.html "Toxicological Profile for Endosulfan"] , 2000.]
*2000 Home and garden uses are terminated by agreement with the EPA.
*2002 The U.S. Fish and Wildlife Service recommends to the EPA that endosulfan should be cancelled. [Citation | last = Kay | first = Jane | title = A move to ease pesticide laws | newspaper = San Francisco Chronicle | pages = A1 | year = 2006 | date = March 2, 2006 | url = http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2006/03/02/MNG0JHH6NH1.DTL.] The EPA also determines that for young children, age 1-6, the risk of acute toxicity from endosulfan in food exceeds the agency's level of concern. The agency decides to allow endosulfan to stay on the market, but imposes more restrictions on endosulfan's agricultural uses. To mitigate its concerns over drinking water contamination and worker exposure, the EPA proposes additional label amendments.
*2007 The international community takes steps to restrict the use and trade of endosulfan. The Chemical Review Committee of the Rotterdam Convention on Prior Informed Consent recommends endosulfan for inclusion in the Convention, and the European Commission proposes to add it to the list of chemicals banned under the Stockholm Convention on Persistent Organic Pollutants. If approved, all use and manufacture of endosulfan would be banned globally. Meanwhile, Canada announces that endosulfan is under consideration for phase-out in that country, ["Canada to end endosulfan use?" [http://www.agrow.co.uk Agrow] , Oct 22, 2007.] and Bayer CropScience voluntarily pulls its endosulfan products from the U.S. market [ [http://www.panna.org/files/EPA-HQ-OPP-2002-0262-0057.pdf Note to Reader. Endosulfan: Request for Additional Information on Usage and Availability of Alternatives] , U.S. EPA, Nov. 16, 2007.] but continues to sell them abroad. [ [http://www.bayercropscience.com/BAYER/CropScience/cscms.nsf/id/endosulfan.htm?Open Our Products: Endosulfan] , BayerCropScience.com, Accessed 03/03/08.]
*2008 In February, environmental, consumer, and farm labor groups including the Natural Resources Defense Council, [ [http://docs.nrdc.org/health/hea_08021901A.pdf PETITION TO BAN ENDOSULFAN AND REVOKE ALL TOLERANCES AND COMMENTS ON THE ENDOSULFAN UPDATED RISK ASSESSMENT (OPP-2002-0262-0067) BY THE NATURAL RESOURCES DEFENSE COUNCIL] , National Resources Defense Council, Feb. 2008.] Organic Consumers Association, and the United Farm Workers [ [http://www.panna.org/newsroom/20080218 Thousands Tell EPA: Phase Out Endosulfan] , Pesticide Action Network, Feb. 18, 2008] call on the U.S. EPA to ban endosulfan. In May, coalitions of scientists,cite journal |author=Sass J, Janssen S |title=Open letter to Stephen Johnson, Administrator, U.S. Environmental Protection Agency: ban endosulfan |journal=Int J Occup Environ Health |volume=14 |issue=3 |pages=236–9 |year=2008 |pmid=18686727 |doi= |url=] environmental groups, and arctic tribes ask the EPA to cancel endosulfan, [cite journal|last=Erickson|first=Britt|date=MAY 21, 2008|title=Groups Petition EPA To Ban Endosulfan|journal=Chemical and Engineering News|url=http://pubs.acs.org/cen/news/86/i21/8621news5.html] and in July a coalition of environmental and workers groups file a lawsuit against the EPA alleging that the Agency illegally re-registered the pesticide. [cite news|url=http://www.mercurynews.com/breakingnews/ci_9985449|title=Group sues to ban DDT-related pesticide|first=The Associated Press|publisher=The Mercury News|accessdate=2008-08-11]

Health effects

Endosulfan is one of the more toxic pesticides on the market today, responsible for many fatal pesticide poisoning incidents around the world. [Pesticde Action Network North America, [http://www.panna.org/magazine/fall2006/featureSpeakingTruth.html Speaking the Truth Saves Lives in the Philippines and India] , "PAN Magazine", Fall 2006.] Endosulfan is also a xenoestrogen—a synthetic substance that imitates or enhances the effect of estrogens—and it can act as an endocrine disruptor, causing reproductive and developmental damage in both animals and humans. Whether endosulfan can cause cancer is debated.

Toxicity

Endosulfan is acutely neurotoxic to both insects and mammals, including humans. The US EPA classifies it as Category I: "Highly Acutely Toxic" based on a LD₅₀ value of 30 mg/kg for female rats, while the World Health Organization classifies it as Class II "Moderately Hazardous" based on a rat LD₅₀ of 80 mg/kg. [World Health Organization, [http://www.who.int/ipcs/publications/pesticides_hazard_rev_3.pdf "The WHO Recommended Classification of Pesticides by Hazard"] , 2005.] It is a GABA-gated chloride channel antagonist, and a Ca²⁺, Mg²⁺ ATPase inhibitor. Both of these enzymes are involved in the transfer of nerve impulses. Symptoms of acute poisoning include include hyperactivity, tremors, convulsions, lack of coordination, staggering, difficulty breathing, nausea and vomiting, diarrhea, and in severe cases, unconsciousness. Doses as low as 35 mg/kg have been documented to cause death in humans,International Programme on Chemical Safety, World Health Organization, [http://www.inchem.org/documents/pims/chemical/pim576.htm "Endosulfan (Poison Information Monograph 576)"] , July 2000.] and many cases of sub-lethal poisoning have resulted in permanent brain damage. Farm workers with chronic endosulfan exposure are at risk of rashes and skin irritation.

EPA's acute reference dose for dietary exposure to endosulfan is 0.015 mg/kg for adults and 0.0015 mg/kg for children. For chronic dietary expsoure, the EPA references doses are 0.006 mg/(kg·day) and 0.0006 mg/(kg·day) for adults and children, respectively.

Endocrine disruption

Theo Colborn, an expert on endocrine disruption, lists endosulfan as a known endocrine disruptor, [Colborn T, Dumanoski D, Meyers JP, Our Stolen Future : How We Are Threatening Our Fertility, Intelligence and Survival, 1997, Plume.] and both the EPA and the Agency for Toxic Substances and Disease Registry consider endosulfan to be a potential endocrine disruptor. Numerous "in vitro" studies have documented its potential to disrupt hormones and animal studies have demonstrated its reproductive and developmental toxicity, especially among males. A number of studies have documented that it acts as an anti-androgen in animals.cite journal |author=Wilson VS, LeBlanc GA |title=Endosulfan elevates testosterone biotransformation and clearance in CD-1 mice |journal=Toxicol. Appl. Pharmacol. |volume=148 |issue=1 |pages=158–68 |year=1998 |month=January |pmid=9465275 |doi=10.1006/taap.1997.8319 |url=http://linkinghub.elsevier.com/retrieve/pii/S0041-008X(97)98319-8] Environmentally relevant doses of endosulfan equal to the EPA's safe dose of 0.006 mg/kg/day have been found to affect gene expression in female rats similarly to the the effects of estrogen.cite journal |author=Varayoud J, Monje L, Bernhardt T, Muñoz-de-Toro M, Luque EH, Ramos JG |title=Endosulfan modulates estrogen-dependent genes like a non-uterotrophic dose of 17beta-estradiol |journal=Reproductive toxicology (Elmsford, N.Y.) |volume= |issue= |pages= |year=2008 |month=August |pmid=18790044 |doi=10.1016/j.reprotox.2008.08.004 |url=http://linkinghub.elsevier.com/retrieve/pii/S0890-6238(08)00209-8] It is not known whether endosulfan is a human teratogen (an agent that causes birth defects), though it has significant teratogenic effects in laboratory rats. [cite journal|journal=J Appl Toxicol|date=2007|volume=27|issue=2|pages=143–51|title=Citrinin and endosulfan induced teratogenic effects in Wistar rats|author=Singh ND, Sharma AK, Dwivedi P, Patil RD, Kumar M|doi=10.1002/jat.1185|pmid=17186572]

Reproductive and developmental effects

Several studies have documented that endosulfan can also affect human development. Researchers studying children from an isolated village in Kerala, India have linked endosulfan exposure to delays in sexual maturity among boys. Endosulfan was the only pesticide applied to cashew plantations in the hills above the village for 20 years and had contaminated the village environment. The researchers compared the villagers to a control group of boys from a demographically similar village that lacked a history of endosulfan pollution. Relative to the control group, the exposed boys had high levels of endosulfan in their bodies, lower levels of testosterone, and delays in reaching sexual maturity. Birth defects of the male reproductive system including cryptorchidism were also more prevalent in the study group. The researchers concluded that "our study results suggest that endosulfan exposure in male children may delay sexual maturity and interfere with sex hormone synthesis." Increased incidences of cryptorchidism have been observed in other studies of endosulfan exposed populations. [(a) Damgaard IN, Skakkebæk NE, Toppari J, "et al.", [http://www.ehponline.org/members/2006/8741/8741.pdf Persistent Pesticides in Human Breast Milk and Cryptorchidism] , "Environ. Health Perspect.", 2006, 114:1133-1138.
(b) Olea N, Olea-Serrano F, Lardelli-Claret P, "et al.", Inadvertent Exposure to Xenoestrogens in Children, "Toxicol. Ind. Health", 15:151–158.]

A 2007 study by the California Department of Public Health found that women who lived near farm fields sprayed with endosulfan and the related organochloride pesticide dicofol during the first eight weeks of pregnancy are several times more likely to give birth to children with autism. This is the first study to look for an association between endosulfan and autism, and additional study is needed to confirm the connection. [(a) cite journal |journal=Environ. Health Perspect. |date=2007 |volume=115 |issue=10 |pages=1482–9 |author= Roberts EM, English PB, Grether JK, Windham GC, Somberg L, Wolff C |title= Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley |doi=10.1289/ehp.10168 |pmid=17938740 |url=http://www.ehponline.org/members/2007/10168/10168.html
(b) Lay Summary: [http://www.ehponline.org/docs/2007/115-10/ss.html#auti Autism and Agricultural Pesticides] , Victoria McGovern, "Environ. Health Perspect." 2007, 115(10):A505]

Endosulfan and cancer

Endosulfan is not listed as known, probable, or possible carcinogen by the EPA, IARC, or other agencies. There are no epidemiological studies linking exposure to endosulfan specifically to cancer in humans, but "in vitro" assays have shown that endosulfan can promote proliferation of human breast cancer cells. [(a) Grunfeld HT, Bonefeld-Jorgensen EC, Effect of "in vitro" estrogenic pesticides on human oestrogen receptor alpha and beta mRNA levels, "Toxicol. Lett.", 2004, 151(3):467-80.
(b) Ibarluzea JmJ, Fernandez MF, Santa-Marina L, "et al", Breast cancer risk and the combined effect of environmental estrogens, "Cancer Causes Control", 2004, 15(6):591-600.
(c) Soto AM, Chung KL, Sonnenschein C, [http://www.ehponline.org/docs/1994/102-4/soto.html The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogensensitive cells] , "Environ. Health Perspect.", 1994, 102(4):380-383.] Evidence of cancinogenicity in animals is mixed.

Endosulfan in the environment

Endosulfan breaks down into endosulfan sulfate and endosulfan diol, both of which, according to the EPA, have "structures similar to the parent compound and are also of toxicological concern…The estimated half-lives for the combined toxic residues (endosulfan plus endosulfan sulfate) [range] from roughly 9 months to 6 years." The EPA concluded that, " [b] ased on environmental fate laboratory studies, terrestrial field dissipation studies, available models, monitoring studies, and published literature, it can be concluded that endosulfan is a very persistent chemical which may stay in the environment for lengthy periods of time, particularly in acid media." The EPA also concluded that " [e] ndosulfan has relatively high potential to bioaccumulate in fish."

Endosulfan can travel long distances from where it is used. For example, a 2008 report by the National Parks Service found that endosulfan commonly contaminates air, water, plants and fish of National Parks in the U.S. Most of the these parks are far from areas where endosulfan is used. [ [http://www.nature.nps.gov/air/Studies/air_toxics/wacap.cfm Western Airborne Contaminants Assessment Project] , National Parks Service.] Endosulfan has also been detected in dust from the Sahara Desert collected in the Caribbean after being blown across the Atlantic Ocean. [cite news | last = Ramnarine | first = Kristy| title = Harmful elements in Sahara dust | publisher = Trinidad & Tobago Express | date = May 12, 2008 | url = http://www.trinidadexpress.com/index.pl/article_news?id=161321883| accessdate = 2008-05-14]

In 2001, in Kerala, India, endosulfan spraying became suspect when linked to a series of abnormalities noted in local children. Initially endosulfan was banned, yet under pressure from the pesticide industry this ban was largely revoked. Achyuthan A studied the effects of the spraying. The situation there has been called "next in magnitude only to the Bhopal gas tragedy." [ [http://www.indiaenews.com/india/20070705/59179.htm 'Rain man' of Indian journalism makes sure wells stay full,] Frederick Noronha, IndiaENews.com, July 5th, 2007, accessed July 5th, 2007.] In 2006, in Kerala, compensation of Rs 50,000 was paid to the next kin of each of 135 people who were identified as having died as a result of endosulfan use. Chief Minister V S Achutanandan also gave an assurance to people affected by poisoning, "that the government would chalk out a plan to take care of treatment, food and other needs of the affected persons and that its promise of rehabilitation of victims would be honoured." [http://www.indiatogether.org/2006/sep/env-endosulf.htm]

A shipment of about 10 tonnes of endosulfan was illegally stowed on the ill-fated MV Princess of the Stars, a ferry that sank off the waters of Romblon (Sibuyan Island), Philippines during a storm in June 2008. Search, rescue, and salvage efforts were suspended when the endosulfan shipment was discovered, and blood samples from divers at the scene were sent to Malaysia for analysis. [cite news|url=http://www.gmanews.tv/story/103692/Divers-blood-samples-sent-to-Singapore-for-analysis|title=Divers' blood samples sent to Singapore for analysis|date=June 27, 2008|publisher=GMAnews.TV|accessdate=2008-06-27] The Department of Health of the Philippines has temporarily banned the consumption of fish caught in the area. [cite news|url=http://newsinfo.inquirer.net/breakingnews/nation/view/20080627-145172/DoH-bans-eating-of-fish-from-Romblon-waters|title=DoH bans eating of fish from Romblon waters |last=Aguilar|first=Ephraim|date=June 27, 2008|publisher=Inquirer.net|accessdate=2008-06-27] Endosulfan is classified as a "Severe Marine Pollutant" by the International Maritime Dangerous Goods Code.cite news|url=http://www.pic.int/incs/crc3/m13)/English/K0654774%20CRC-3-13.pdf|title=Draft Decision Guidance Document|last=Secretariat for the Rotterdam Convention on the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in International Trade|date=16 October 2007|publisher=United Nations Environment Programme|accessdate=2008-10-06]

References

External links

* [http://www.pmra-arla.gc.ca/english/pdf/rev/rev2007-13-e.pdf Health Canada: Preliminary Risk and Value Assessments of Endosulfan]
* [http://pesticideinfo.org/Detail_Chemical.jsp?Rec_Id=PC35085 Pesticideinfo.org: Endosulfan]
* [http://www.panna.org/campaigns/endosulfan Pesticide Action Network North America: Endosulfan]
* [http://www.cseindia.org/html/endosulfan/endosulfan_index.htm Endosulfan controversy in Kerala, India]
* [http://southasia.oneworld.net/article/view/157876/1 Endosulfan victims still suffer in India] , P.N. Venugopal, 15 February 2008, OneWorld South Asia.
* [http://www.eddenet.pmra-arla.gc.ca/4.0/4.1.2.asp?regn=15333.00 Thionex 50 WP US Product Label]
* [http://www.pan-germany.org/download/field_guide_without_endosulfan.pdf How to grow crops without endosulfan]
* [http://www.drexchem.com/ProductDetail.asp?ProductID=10038 Drexel - Product Detail: Endosulfan 3EC] - Information about endosulfan from an endosulfan manufacturer.