Chemicals with harmful effects

From DrugPedia: A Wikipedia for Drug discovery

Revision as of 04:59, 2 September 2008 by Ravi (Talk | contribs)
(diff) ←Older revision | Current revision (diff) | Newer revision→ (diff)
Jump to: navigation, search

Contents

Endosulfan

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 on 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.

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. 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. Because of its unique mode of action, it is useful in resistance management.

History

  • Early 1950s Endosulfan developed.
  • 1954 Hoechst AG (now Bayer CropScience) registers endosulfan with the EPA, and US farmers begin using it.
  • 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. 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, and Bayer CropScience voluntarily pulls its endosulfan products from the U.S. market but continues to sell them abroad.
  • 2008 In February, environmental, consumer, and farm labor groups including the Natural Resources Defense Council, Organic Consumers Association, and the United Farm Workerscall on the U.S. EPA to ban endosulfan. In May, coalitions of scientists,[16] environmental groups, and arctic tribes ask the EPA to cancel endosulfan, 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.

Health effects

Endosulfan is one of the more toxic pesticides on the market today, responsible for many fatal pesticide poisoning incidents around the world. 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. 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, 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.

Endocrine disruption

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

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 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.

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.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.Endosulfan has also been detected in dust from the Sahara Desert collected in the Caribbean after being blown across the Atlantic Ocean.

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." 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."

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 have been sent to Malaysia for analysis.The Department of Health of the Philippines has temporarily banned the consumption of fish caught in the area.