Benomyl
Encyclopedia
Benomyl is a fungicide
which was introduced in 1968 by DuPont
. It is a systemic benzimidazole
fungicide that is selectively toxic to microorganisms and to invertebrate
s, especially earthworm
s. Benomyl binds to microtubule
s, interfering with cell functions such as meiosis
and intracellular transportation. The selective toxicity of benomyl as a fungicide is possibly due to its heightened effect on fungal
rather than mammal
ian microtubules.
Due to the resistance
of parasitic fungi to benomyl which had developed and is now prevalent worldwide benomyl and similar pesticide compounds became largely ineffective. Because of high legal costs associated with it in 2001 DuPont ceased production of benomyl after 33 years on the market and voluntarily requested cancellation for its registration. However, as DuPont's patents expired long ago and in some countries benomyl's registration has not been revoked, other manufacturers still produce it.
In a laboratory study, dogs fed benomyl in their diets for three months developed no major toxic effects but did show evidence of altered liver function
at the highest dose (150 mg/kg). With longer exposure, more severe liver damage occurred including cirrhosis
.
The US Environmental Protection Agency
classified benomyl as a possible carcinogen
. Carcinogenic studies have produced conflicting results. A two year experimental mouse study has shown it "probably" causes an increase in liver tumours. The British Ministry of Agriculture Fisheries and Food
took the view that this was brought about by the hepatotoxic effect of benomyl.
In 1993, the Observer, a UK national newspaper, published a series of articles alleging a possible link between exposure of pregnant mothers to benomyl and their children being born without eyes (anophthalmia) or with related syndromes including reduced eyes and blindness
due to severe damage of the optic stem
. The newspaper cited a number of suspected clusters in the UK that may have corresponded to areas of benomyl use. Studies have shown that eye defects can occur at relatively high doses. A test in which rats were dosed orally demonstrated evidence of microphthalmia at dose levels of 62.5 mg/kg and above.
.
In October 2008, DuPont paid confidential settlements to two New Zealand families whose children were born with either anophthalmia or other birth defects. The mother of one of the children had been exposed to Benlate while working as a Christchurch
parks worker before his birth.
A Benlate compensation case involving an English boy from Essex
born without eyes is also due to be heard shortly in the US.
in turf
of three to six months, and in bare soil
, a half-life of six months to one year.
In 1991, DuPont issued a recall of its Benlate 50DF formula due to suspected contamination with the herbicide Atrazine. In the wake of the recall, many US growers blamed Benlate 50DF for destroying millions of dollars worth of crops. Growers filed over 1900 damage claims against DuPont, mostly involving ornamental crops in Florida. Subsequent testing by DuPont determined that the recalled product was not contaminated with atrazine. The reason for the alleged crop damage is unclear. The Florida Department of Agriculture and Consumer Services
suggested Benlate was contaminated with dibutylurea and sulfonylurea
herbicides.
After several years of legal argument DuPont paid out about US$750 million in damages and out-of-court settlements. By 1993, a coalition of farm worker and environmental groups came together to form "Benlate Victims Against DuPont", a group which called for a nation-wide boycott of DuPont products.
After carrying out tests, DuPont denied that Benlate was contaminated with dibutylurea and sulfonylureas and stopped compensation pay-outs. In 1995, a Florida judge rejected a complaint from the Florida Department of Agriculture that had alleged such a link.
Fungicide
Fungicides are chemical compounds or biological organisms used to kill or inhibit fungi or fungal spores. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality and profit. Fungicides are used both in agriculture and to fight fungal infections in animals...
which was introduced in 1968 by DuPont
DuPont
E. I. du Pont de Nemours and Company , commonly referred to as DuPont, is an American chemical company that was founded in July 1802 as a gunpowder mill by Eleuthère Irénée du Pont. DuPont was the world's third largest chemical company based on market capitalization and ninth based on revenue in 2009...
. It is a systemic benzimidazole
Benzimidazole
Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound consists of the fusion of benzene and imidazole. The most prominent benzimidazole compound in nature is N-ribosyl-dimethylbenzimidazole, which serves as an axial ligand for cobalt in vitamin B12. Benzimidazole, in...
fungicide that is selectively toxic to microorganisms and to invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
s, especially earthworm
Earthworm
Earthworm is the common name for the largest members of Oligochaeta in the phylum Annelida. In classical systems they were placed in the order Opisthopora, on the basis of the male pores opening posterior to the female pores, even though the internal male segments are anterior to the female...
s. Benomyl binds to microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
s, interfering with cell functions such as meiosis
Meiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....
and intracellular transportation. The selective toxicity of benomyl as a fungicide is possibly due to its heightened effect on fungal
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
rather than mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian microtubules.
Due to the resistance
Drug resistance
Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance. More commonly, the term is used...
of parasitic fungi to benomyl which had developed and is now prevalent worldwide benomyl and similar pesticide compounds became largely ineffective. Because of high legal costs associated with it in 2001 DuPont ceased production of benomyl after 33 years on the market and voluntarily requested cancellation for its registration. However, as DuPont's patents expired long ago and in some countries benomyl's registration has not been revoked, other manufacturers still produce it.
Toxicity
Benomyl is of such a low toxicity to mammals that it has been impossible to administer doses large enough to establish an . It has an arbitrary LD50 that is "greater than 10,000 mg/kg/day for rats". Skin irritation may occur through industrial exposure, and florists, mushroom pickers and floriculturists have reported allergic reactions to benomyl.In a laboratory study, dogs fed benomyl in their diets for three months developed no major toxic effects but did show evidence of altered liver function
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
at the highest dose (150 mg/kg). With longer exposure, more severe liver damage occurred including cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
.
The US Environmental Protection Agency
United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...
classified benomyl as a possible carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
. Carcinogenic studies have produced conflicting results. A two year experimental mouse study has shown it "probably" causes an increase in liver tumours. The British Ministry of Agriculture Fisheries and Food
Ministry of Agriculture, Fisheries and Food
The Ministry of Agriculture, Fisheries and Food was a United Kingdom government department created by the Board of Agriculture Act 1889 and at that time called the Board of Agriculture, and then from 1903 the Board of Agriculture and Fisheries, and from 1919 the Ministry of Agriculture and Fisheries...
took the view that this was brought about by the hepatotoxic effect of benomyl.
In 1993, the Observer, a UK national newspaper, published a series of articles alleging a possible link between exposure of pregnant mothers to benomyl and their children being born without eyes (anophthalmia) or with related syndromes including reduced eyes and blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...
due to severe damage of the optic stem
Optic nerve
The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...
. The newspaper cited a number of suspected clusters in the UK that may have corresponded to areas of benomyl use. Studies have shown that eye defects can occur at relatively high doses. A test in which rats were dosed orally demonstrated evidence of microphthalmia at dose levels of 62.5 mg/kg and above.
Birth defects
In 1996 a Miami jury awarded US$4 million to a child whose mother was exposed in pregnancy to Benlate. The child was born without eyes. The mother had been exposed to an unusually high dose of Benlate through her occupation, during pregnancy. An important issue in the case was whether the timing of exposure - during the formation of the optic nerve in the foetus - was critical as well as the magnitude of exposure. The case was prosecuted by The Ferraro Law FirmThe Ferraro Law Firm
The Ferraro Law Firm, P.A. is an American law firm that is best known for multi-mullion dollar mass tort litigation for victims of asbestos-induced mesothelioma and toxic exposure. Founded in 1985 by Jim Ferraro, the firm is based in Miami, Washington, D.C., and New York City. The firm has...
.
In October 2008, DuPont paid confidential settlements to two New Zealand families whose children were born with either anophthalmia or other birth defects. The mother of one of the children had been exposed to Benlate while working as a Christchurch
Christchurch
Christchurch is the largest city in the South Island of New Zealand, and the country's second-largest urban area after Auckland. It lies one third of the way down the South Island's east coast, just north of Banks Peninsula which itself, since 2006, lies within the formal limits of...
parks worker before his birth.
A Benlate compensation case involving an English boy from Essex
Essex
Essex is a ceremonial and non-metropolitan county in the East region of England, and one of the home counties. It is located to the northeast of Greater London. It borders with Cambridgeshire and Suffolk to the north, Hertfordshire to the west, Kent to the South and London to the south west...
born without eyes is also due to be heard shortly in the US.
Environmental effects
Benomyl binds strongly to soil and does not dissolve in water to any great extent. It has a half-lifeHalf-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
in turf
Sod
Sod or turf is grass and the part of the soil beneath it held together by the roots, or a piece of thin material.The term sod may be used to mean turf grown and cut specifically for the establishment of lawns...
of three to six months, and in bare soil
Soil
Soil is a natural body consisting of layers of mineral constituents of variable thicknesses, which differ from the parent materials in their morphological, physical, chemical, and mineralogical characteristics...
, a half-life of six months to one year.
In 1991, DuPont issued a recall of its Benlate 50DF formula due to suspected contamination with the herbicide Atrazine. In the wake of the recall, many US growers blamed Benlate 50DF for destroying millions of dollars worth of crops. Growers filed over 1900 damage claims against DuPont, mostly involving ornamental crops in Florida. Subsequent testing by DuPont determined that the recalled product was not contaminated with atrazine. The reason for the alleged crop damage is unclear. The Florida Department of Agriculture and Consumer Services
Florida Department of Agriculture and Consumer Services
The Florida Department of Agriculture and Consumer Services is an executive department of the government of Florida.The Commissioner of Agriculture is the head of the department...
suggested Benlate was contaminated with dibutylurea and sulfonylurea
Sulfonylurea
Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide...
herbicides.
After several years of legal argument DuPont paid out about US$750 million in damages and out-of-court settlements. By 1993, a coalition of farm worker and environmental groups came together to form "Benlate Victims Against DuPont", a group which called for a nation-wide boycott of DuPont products.
After carrying out tests, DuPont denied that Benlate was contaminated with dibutylurea and sulfonylureas and stopped compensation pay-outs. In 1995, a Florida judge rejected a complaint from the Florida Department of Agriculture that had alleged such a link.
Cellular Biology
Benomyl is used in molecular biology to study the cell cycle in yeast, in fact the name of the proteins Bub1,2,3 comes from their mutant in which budding was uninhibited by Benomyl.Further reading
- Tomlin, C., (Ed.) The Pesticide Manual, 10th Edition, British Crop Protection Council/Royal Society of Medicine, 1994.
- Benomyl, Extoxnet, Pesticide Management Education Program, Cornell University, NY, May 1994.
- World Health Organisation, WHO/PCS/94.87 Data sheet on benomyl, Geneva, 1994.
- Whitehead, R (Ed) The UK Pesticide Guide, British Crop Protection Council/CAB International, 1996.
- Thomas, M.R. and Garthwaite, D.G., Orchards and Fruit Stores in Great Britain 1992, Pesticide Usage Survey Report 115, Central Science Laboratory, 1994.
- Thomas, M.R. and Garthwaite, D.G., Outdoor Bulbs and Flowers in Great Britain 1993, Pesticide Usage Survey Report 121, Central Science Laboratory, 1995.
- Garthwaite, D.G., Thomas, M.R., Hart, M.J, and Wild, S, Outdoor vegetable crops in Great Britain 1995, Pesticide Usage Survey Report 134, Central Science Laboratory, 1997.
- Thomas, M.R. and Garthwaite, D.G., Hardy Nursery Stock in Great Britain 1993, Pesticide Usage Survey Report 120, Central Science Laboratory, 1995.
- Benomyl evaluation No. 57, MAFF, July 1992, pp109–111.
- More problems for Benlate? Agrow, 13 March 1992, p13.
- List of Chemicals Evaluated for Carcinogenic Potential, US EPA Office of Pesticide Programs, Washington, US, 1996.
- Benomyl, Environmental Health Criteria No 148, World Health Organisation, Geneva, Switzerland, 1993.