Benomyl

Benomyl (also marketed as Benlate) is a fungicide which was introduced in 1968 by Du Pont. It is a systemic benzimidazole fungicide that is selectively toxic to micro-organisms and to invertebrates, especially earthworms. Benomyl binds to microtubules, 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 mammalian microtubules.

Toxicity
Benomyl is of such a low toxicity to mammals that it has been impossible to administer doses large enough to establish an LD50. 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 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 bought about by the hepatoxic 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 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. A Benlate compensation case involving an English boy from Essex 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-life 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 Benlate50DF for destroying millions of dollars worth of crops. Growers filed over 1,900 damage claims against Du Pont, 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 suggested Benlate was contaminated with dibutylurea and sulfonylurea herbicides. After several years of legal argument Du Pont 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 Du Pont", a group which called for a nation-wide boycott of Du Pont products. After carrying out tests, Du Pont 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.