Endosulfan is an off-patent organochlorine insecticide and acaricide.

This colourless solid has

emerged as a highly controversial agrichemical[1] due to its acute toxicity, potential for
bioaccumulation, and role as an endocrine disruptor. It is banned in more than 63 countries,
including the European Union, Australia and New Zealand, and other Asian and West African nations,
[2]
and being phased out in the United States, [3][4] Brazil[5] and Canada.[6] It is still used extensively in
many other countries including India and China. It is produced by Bayer CropScience, Makhteshim
Agan, and Government-of-India–owned Hindustan Insecticides Limited among others. Because of its
threats to the environment, a global ban on the manufacture and use of endosulfan and its isomers
worldwide was agreed,in the Stockholm Convention on 29th April 2011., subject to certain
exemptions proposed by India. The decision will not be binding on India unless specifically ratified by
the country.[7]

Uses
Endosulfan has been used in agriculture around the world to control insect pests including
whiteflys, aphids, leafhoppers, Colorado potato beetles and cabbage worms.[8] Because of its
unique mode of action, it is useful in resistance management; however, because it is non-
specific, it can negatively impact populations of beneficial insects.[9] It is, however,
considered to be moderately toxic to honey bees,[10] and it is less toxic to bees than
organophosphate insecticides.[11]

[edit] Production
The World Health Organization estimated world wide annual production to be about 9,000
metric tonnes (t) in the early 1980s.[12] From 1980–89, worldwide consumption averaged
10,500 t per year, and for the 1990s use increased to 12,800 t per year.

Endosulfan is a derivative of hexachlorocyclopentadiene and is chemically similar to aldrin,

chlordane, and heptachlor. Specifically, it is produced by the Diels-Alder reaction of
hexachlorocyclopentadiene with cis-butene-1,4-diol and subsequent reaction of the adduct
with thionyl chloride. Technical endosulfan is a 7:3 mixture of stereoisomers, designated α
and β. α- and β-endosulfan are conformational isomers arising from the pyramidal
stereochemistry of sulfur. α-Endosulfan is the more thermodynamically stable of the two,
thus β-endosulfan irreversibly converts to the α form, although the conversion is slow.[13][14]

[edit] History of commercialization and regulation

 Early 1950s: Endosulfan was developed.
 1954: Hoechst AG (now Bayer CropScience) won USDA approval for the use of
endosulfan in the United States.[15]
 2000: Home and garden use in the United States was terminated by agreement with
the EPA.[11]
 2002: The U.S. Fish and Wildlife Service recommended that endosulfan registration
should be cancelled,[16] and the EPA determined that endosulfan residues on food and
 in water pose unacceptable risks. The agency allowed endosulfan to stay on the US
market, but imposed restrictions on its agricultural uses.[11]
 2007: International steps were taken to restrict the use and trade of endosulfan. It is
recommended for inclusion in the Rotterdam Convention on Prior Informed Consent,
[17]
and the European Union proposed inclusion in the list of chemicals banned under
the Stockholm Convention on Persistent Organic Pollutants. Such inclusion would
ban all use and manufacture of endosulfan globally.[18] Meanwhile, the Canadian
government announced that endosulfan was under consideration for phase-out,[19] and
Bayer CropScience voluntarily pulled its endosulfan products from the U.S. market[20]
but continues to sell the products elsewhere.[21]
 2008: In February, environmental, consumer, and farm labor groups including the
Natural Resources Defense Council,[22] Organic Consumers Association, and the
United Farm Workers[23] called on the U.S. EPA to ban endosulfan. In May, coalitions
of scientists,[24] environmental groups, and arctic tribes asked the EPA to cancel
endosulfan,[25] and in July a coalition of environmental and workers groups filed a
lawsuit against the EPA challenging its 2002 decision to not ban it.[26] In October, the
Review Committee of the Stockholm Convention moved endosulfan along in the
procedure for listing under the treaty,[27] while India blocked its addition to the
Rotterdam Convention.[28]
 2009: The Stockholm Convention's Persistent Organic Pollutants Review Committee
(POPRC) agreed that endosulfan is a persistent organic pollutant and that "global
action is warranted", setting the stage of a global ban.[29] New Zealand banned
endosulfan.[30]
 2010: The POPRC nominated endosulfan to be added to the Stockholm Convention at
the Conference of Parties (COP) in April 2011, which would result in a global ban.[31]
The EPA announced that the registration of endosulfan in the U.S. will be cancelled[4]
[32]
Australia banned the use of the chemical.[33]

[edit] Health effects

Endosulfan is one of the most toxic pesticides on the market today, responsible for many fatal
pesticide poisoning incidents around the world.[34] 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. With regard to consumers intake of
endosulfan from residues on food, the Food and Agriculture Organization of United Nations
has concluded that long-term exposure from food is unlikely to present a public health
concern, but short term exposure can exceed acute reference doses.[35]

[edit] 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,[11] while the World Health Organization classifies it as Class II "Moderately
Hazardous" based on a rat LD50 of 80 mg/kg.[36] 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 hyperactivity, tremors,
convulsions, lack of coordination, staggering, difficulty breathing, nausea and vomiting,
diarrhea, and in severe cases, unconsciousness.[15] Doses as low as 35 mg/kg have been
documented to cause death in humans,[37] and many cases of sub-lethal poisoning have
resulted in permanent brain damage.[15] Farm workers with chronic endosulfan exposure are at
risk of rashes and skin irritation.[11]

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.[11]

[edit] Endocrine disruption

Theo Colborn, an expert on endocrine disruption, lists endosulfan as a known endocrine

disruptor,[38] 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.[11][15] A number of studies
have documented that it acts as an anti-androgen in animals.[39] 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 effects of estrogen.[40] 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.[41] A 2009 assessment concluded that
endocrine disruption occurs only at endosulfan doses that cause neurotoxicity.[42]

[edit] Reproductive and developmental effects

Several studies have documented that endosulfan can also affect human development.
Researchers studying children from many villages in Kasargod District, Kerala, India have
linked endosulfan exposure to delays in sexual maturity among boys. Endosulfan was the
only pesticide applied to cashew plantations in the villages 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."[43] Increased
incidences of cryptorchidism have been observed in other studies of endosulfan exposed
populations.[44]

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.[45] A 2009 assessment
concluded that epidemiology and rodent studies that suggest male reproductive and autism
effects are open to other interpretations, and that developmental or reproductive toxicity
occurs only at endosulfan doses that cause neurotoxicity.[42]

[edit] 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.[46] Evidence of cancinogenicity in animals is
mixed.[15]

[edit] Environmental fate

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."[11] It is also toxic to amphibians: low levels
have been found to kill tadpoles.[47]

Endosulfan is subject to long range atmospheric transport, i.e. it can travel long distances
from where it is used. For example, a 2008 report by the National Park Service found that
endosulfan commonly contaminates air, water, plants and fish of national parks in the U.S.
Most of these parks are far from areas where endosulfan is used.[48] Endosulfan has also been
detected in dust from the Sahara Desert collected in the Caribbean after being blown across
the Atlantic Ocean.[49] In 2009, the committee of scientific experts of the Stockholm
Convention concluded that "endosulfan is likely, as a result of long range environmental
transport, to lead to significant adverse human health and environmental effects such that
global action is warranted."[50]

[edit] Status by region

[edit] India

India the world's largest user of endosulfan,[8] and a major producer with three companies—
Excel Crop Care, Hindustan Insecticides Ltd, and Coromandal Fertilizers—producing 4,500
tonnes annually for domestic use and another 4,000 tonnes for export.[51]

In 2001, in Kerala, India, endosulfan spraying became suspect when linked to a series of
abnormalities noted in local children.[52] Initially endosulfan was banned, yet under pressure
from the pesticide industry this ban was largely revoked. The situation there has been called
"next in magnitude only to the Bhopal gas tragedy." [53]

The pesticide as banned in the State when A.K. Antony was Chief Minister following a report
by the National Institute of Occupational Health . The report had then stated that Endosulfan
was behind the dreadful state of farmers and children in Kasaragod.

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.
Achuthanandan 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."[54]

India's Second largest political party BJP Vice President Mukhtar Abbas Naqvi also
demanded the banning of Endosulphan [2].India is strongly opposed to adding endosulfan to
the Rotterdam[55] and Stockholm Conventions.[18] BJP demands ban on endosulfan " BJP is
with the people who are suffering due to the ill-effects of the pesticide in Kasaragod district,"
senior BJP leader and Leader of Opposition in Lok Sabha Sushma Swaraj said[56]

Madhya Pradesh, whose capital saw the world’s worst industrial disaster in 1984, made a
common cause with Kerala Chief Minister on seeking a ban on endosulfan.Writing separate
letters to the Kerala CM and Union Agriculture Minister Sharad Pawar, MP’s Agriculture and
Farmers’ Welfare Minister Ramkrishna Kusmaria said he fully supports the crusade against
toxic chemicals. “MP understands the dire consequences of manmade disaster,” Kusmaria
said in his letter to Achuthanandan, while referring to the Bhopal gas tragedy that took
thousands of lives. [57]

Karnataka government also banned the use of endosulfan, an insecticide, with immediate
effect. Briefing presspersons after the State Cabinet meeting, Minister for Higher Education
V.S. Acharya said the Cabinet discussed the harmful effects of endosulfan on the health of
farmers and people living in rural areas. The government will now invoke the provisions of
the Insecticides Act, 1968 (a Central act) and write a letter to the Union Government about
the ban. Minister for Energy, and Food and Civil Supplies Shobha Karandlaje, who has been
spearheading a movement seeking a ban on endosulfan, said, “I am grateful to Chief Minister
B.S. Yeddyurappa and members of the Cabinet for approving the ban.[58]

Rajendra Rajendra Singh Rana has written a letter to Prime Minister Manmohan Singh
demanding the withdrawal of the National Institute of Occupational Health (NIOH) study on
Endosulfan titled “Report Of The Investigation Of Unusual Illness” allegedly produced by
the Endosulfan exposure in Padre village of Kasargode district in north Kerala. In his
statement Mr. Rana said "The NIOH report is flawed. I'm in complete agreement with what
the workers have to say on this. In fact, I have already made representation to the Prime
Minister and concerned Union Ministers of health and environment demanding immediate
withdrawal of the report," as reported by The Economic Times and Outlook India [59][60]

Mrs. Vibhavari Dave, local leader and Member of Legislative Assembly (MLA), from
Bhavnagar, Gujarat voiced her concerns on the impact of ban of Endosulfan on families and
workers of Bhavnagar. She was a part of the delegation with Bhavnagar MP, Rajendra Singh
Rana, which submitted a memorandum to the district collector’s office to withdraw the NIOH
report calling for ban of Endosulfan.[61][62] The Pollution Control Board of the Government of
Kerala, prohihited the use of Endosulfan in the state of Kerala on 10 November 2010.[63] On
February 18, 2011, the Karnataka Government followed suit and suspended the use of
Endosulfan for a period of 60 days in the state.[64] Indian Union Minister of Agriculture
Sharad Pawar has ruled out implementing a similar ban at the national level despite the fact
that endosulfan has banned in 63 countries including European Union, Australia and New
Zealand.[65]

The Government of Gujarat had initiated a study in response to the workers rally in
Bhavnagar and representations made by Sishuvihar, an NGO based in Ahmadabad. The
committee constituted for the study also included former Dy.Director of NIOH, Ahmadabad.
The committee noted that the WHO, FAO, IARC and US EPA have indicated that endosulfan
is not carcinogenic, not teratogenic, not mutagenic and not genotoxic. The highlight of this
report is the farmer exposure study based on analysis of their blood reports for residues of
endosulfan and the absence of any residues. This corroborates the lack of residues in worker
exposure studies.[66]

[edit] New Zealand

Endosulfan was banned in New Zealand by the Environmental Risk Management Authority
effective January 2009[30] after a concerted campaign by environmental groups and the Green
Party.

See also: Pesticides in New Zealand

[edit] Philippines

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.[67] The Department of Health of the Philippines has
temporarily banned the consumption of fish caught in the area.[68] Endosulfan is classified as a
"Severe Marine Pollutant" by the International Maritime Dangerous Goods Code.[17]

[edit] United States

Endosulfan use in the US in pounds per square mile by county in 2002. (From [1])

In the United States, endosulfan is only registered for agricultural use, and these uses are
being phased out.[4] It has been used extensively on cotton, potatoes, tomatoes, and apples
according to the Environmental Protection Agency (EPA).[69] The EPA estimates that 1.38
million lb of endosulfan were used annually from 1987 to 1997.[11] The US exported more
than 300,000 lbs of endosulfan from 2001–2003, mostly to Latin America,[70] but production
and export has since stopped.

In California, endosulfan contamination from the San Joaquin Valley has been implicated in
the extirpation of the mountain yellow-legged frog from parts of the nearby Sierra Nevada
Mountains.[71] In Florida, levels of contamination the Everglades and Biscayne Bay are high
enough to pose a threat to some aquatic organisms.[72][73][74]

In 2007, the EPA announced it was rereviewing the safety of endosulfan.[75] The following
year, Pesticide Action Network and NRDC petitioned the EPA to ban endosulfan,[76] and a
coalition of environmental and labor groups sued the EPA seeking to overturn its 2002
decision to not ban endosulfan.[26] In June 2010, the EPA announced it was negotiating a
phaseout of all uses with the sole U.S. manufacturer, Makhteshim Agan and a complete ban
on the compound.[4]

An official statement by Makhteshim Agan of North America (MANA) states that "From a
scientific standpoint, MANA continues to disagree fundamentally with EPA's conclusions
regarding endosulfan and believes that key uses are still eligible for re-registration." The
statement adds, "However, given the fact that the endosulfan market is quite small and the
cost of developing and submitting additional data high, we have decided to voluntarily
negotiate an agreement with EPA that provides growers with an adequate time frame to find
alternatives for the damaging insect pests currently controlled by endosulfan," [77][78]

[edit] Australia

Australia banned endosulfan October 12, 2010[79][80][81] with a two year phase-out for stock of
endosulfan containing products.[79] Australia had, in 2008, announced endosulfan would not
be banned.[82] Citing New Zealand's ban, the Australian Greens called for "zero tolerance" of
endosulfan residue on food.[2]

[edit] Taiwan

US apples with endosulfan are now allowed to be exported to Taiwan although the ROC
government denied any U.S. pressure on it.[83]