Dicofol

Dicofol is a organochlorine acaricide (a chemical that kills mites) that is structurally similar to DDT. It is highly toxic to aquatic life and can cause egg-shell thinning in some bird species.

Production
Dicofol first appeared in the scientific literature in 1956(1), and was introduced onto the market by the US-based multinational Rohm & Haas in 1957(2). Other current manufacturers include Hindustan (India), Lainco (Spain) and Makhteshim-Agan (Israel)(3). It is sold under a number of trade names, including Kelthane and Acarin.
   
DDT is one of the intermediate products produced during dicofol manufacture. In 1986, the US Environmental Protection Agency (EPA) temporarily cancelled the use of dicofol because relatively high levels of DDT contamination were ending up in the final product. Modern processes can produce technical grade dicofol that contains less than 0.1% DDT(4).

Uses
Dicofol is used to kill crop-feeding mite pests such as the red spider mite. It is a contact poison which kills the pest after being ingested and picked up from the surface of the crop. In many countries, dicofol is also used in combination with other pesticides such as the organophosphates parathion-methyl, and dimethoate(5).
   
Application figures are not generally available as most countries do not record usage data according to particular active ingredients. The UK data show the average amount of dicofol active ingredient used between 1994 and 1997 was 1,143 kg per year(6). It is approved for use on apples, pears, blackcurrants, hops, strawberries, and protected crops of cucumbers, tomatoes and ornamentals(7).
   
In the US dicofol is mostly used on cotton, apples and citrus crops. Other crops include strawberries, mint, beans, peppers, tomatoes, pecans, walnuts, stonefruit, cucurbits, and non-residential lawns/ornaments(8). During 1998 the manufacturers voluntarily cancelled all residential turf uses(9). Based on available US data from 1987 to 1996, total annual domestic agricultural usage of dicofol averaged 390,000 kg of active ingredient for 290,000 hectares treated. The largest markets for dicofol in the US are cotton (over 50%) and citrus (almost 30%). Most of the usage is in California and Florida(10).

Acute toxicity
The acute oral LD50 (the dose required to kill half a population of laboratory test animals) for dicofol is 595-690 mg/kg for rats. It is classified by the World Health Organisation as a Class III, 'slightly hazardous' pesticide(11).
   
Like many insecticides and acaricides, dicofol is a nerve poison. The exact mode of action is not known, although in mammals it causes hyperstimulation of nerve transmission along nerve axons (cells). This effect is thought to be related to the inhibition of certain enzymes in the central nervous system(12).
   
Symptoms of ingestion and/or respiratory exposure include nausea, dizziness, weakness and vomiting; dermal exposure may cause skin irritation or a rash; and eye contact may cause conjuctivitis. Poisoning may affect the liver, kidneys or the central nervous system. Very severe cases may result in convulsions, coma, or death from respiratory failure(13).
   
Dicofol can be stored in fatty tissue. Intense activity or starvation may mobilise the chemical, resulting in the reappearance of toxic symptoms long after actual exposure(14).

Occupational exposure
The US EPA reviewed dicofol under its reregistration eligibility decision (RED) programme in 1998 which raised some strong concerns over hormonal and development toxicity for mixers, loaders, applicators, and field workers(15). In particular the EPA is concerned about exposures to handlers during the treatment of crops by ground and aerial equipment, and during treatment of ornamentals using hand-held equipment(16).
   
There are very few accurate estimates of occupational ill health from exposure to pesticides. Some figures are available from the US and the UK.
   
The California Department of Food and Agriculture has one of the world's most extensive incident reporting systems. Between 1982 and 1992, 38 incidents involving dicofol alone were reported: systemic 19 (50%); skin 10 (26%); eye 8 (21%); and eye/skin 1 (3%). The number of incidents per 1,000 applications for all illnesses ranged from 0.11 to 0.21.
   
The US National Pesticides Telecommunications Network database collected reports from 1984 to 1991 showing 91 human, 9 animal and 31 other poisoning incidents for a total of 131 incidents involving dicofol from 571 phone calls made to the hotline(17).
   
In the UK two cases in recent years were confirmed by the Pesticides Incident Appraisal Panel, although this does not necessarily reflect the true number of incidents involving dicofol. In one incident, a woman suffered inflammation and irritation to the skin around her left eye after exposure to dicofol and tetradifon. In another case, a four-year-old boy developed a cough after the field of hops adjacent to his garden was sprayed with a number of pesticides, including dicofol(18).

Neurotoxicity
Dicofol produced neurotoxic effects in adult rats in neurotoxicity tests. The US EPA has also identified that a postnatal development neurotoxicity study in rats is required in order to fill current data gaps(19).

Chronic effects
Tests on laboratory animals show that the primary effects after long term exposure to dicofol include increases in liver weight and enzyme induction in the rat, mouse and dog. There are also effects relating to altered adrenocorticoid metabolism (part of the hormonal system). In the rat hormonal changes were accompanied by the histological observation of vacuolation (empty cavities) of the cells of the adrenal cortex(20).
   
The US EPA has classified dicofol as a Group C, possible human carcinogen. There is limited evidence that it may cause cancer in laboratory animals, but there is no evidence that it causes cancer in humans. This classification was based on animal test data that showed an increase in the incidence of liver adenomas (benign tumour) and combined liver adenomas and carcinomas in male mice(21).

Residues in food and water
An assessment of dicofol by the UK Pesticides Safety Directorate in 1996 found that residues in apples, pears, blackcurrants and strawberries were higher than expected. The assessors considered it likely that the acceptable daily intake may be breached under normal conditions of use. Because of data gaps, they also found that implications are not clear for data on the transfer of residues from hops into beer, from blackcurrants into blackcurrant juice and apples into apple puree(22).
   
There is no established US maximum contaminant level (MCL) or health advisory levels for residues of dicofol in drinking water(23). In the European Union, the maximum level is the same for all active ingredients 0.1 mg/litre (parts per billion [ppb])(24).

Cumulative effects
As part of the RED review, US regulators have to assess all available information concerning the cumulative effects of pesticide residues and other substances that have a common mechanism of toxicity.
   
Dicofol is classed as an organochlorine pesticide. Other members of this class include DDT, methoxychlor, chlorbenzilate and ethylan. Less closely related members include lindane, dieldrin, endrin, chlordane, heptachlor, aldrin, endosulfan, kepone and toxaphene(25). Currently the US EPA does not have available data to determine whether dicofol has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment(26).

Endocrine disruption
The US RED review concludes that evidence for dicofol to cause endocrine disruption is suggestive, but not definitive. It has reproductive effects in some species (see below), although they appear to differ somewhat from its close analogues DDT and/or DDE. Whether the difference is due to the ability of dicofol to be metabolised to less toxic chemicals, its relatively short half-life (compared to DDT/DDE), or the reduced potency of the parent compound, is not currently known(27).
   
In 1980, an accident at the US Tower Chemical Company led to a release of dicofol into Lake Apopka in Florida. Ten years later Dr Guillette of Florida University linked this incident to a subsequent decline in the fertility of alligators in the lake. The US EPA is still not clear whether dicofol is involved in the reproductive failure of the alligator population following the accidental spill(28).
   
In 1993, US scientists reported the presence of dicofol in water samples from the western San Joaquin Valley in California. The highest concentration 2,500 ng/litre (2.5 ppb) was found at Orestimba Creak following agricultural spraying in the area. The researchers were concerned about these levels and called for further research into the endocrine-disruption toxicology of chemicals dissolved in water at low concentrations(29).

Environmental fate
According to the US Department of Agriculture, dicofol has a half-life in the environment of 60 days(30). Other US EPA laboratory and field studies show that dicofol has a half-life ranging from days to months. In ecological monitoring studies conducted in New York, Florida and California, dicofol dissipated from the soil surface with a half-life ranging from two to four months. The chemical is likely to be more persistent in acidic than neutral or alkaline soils or waters(31).
   
Dicofol and DDT are similar chemical structures, and the US EPA considers that dicofol has to a lesser degree some ability to accumulate in the environment(32).

Wildlife
Analytical screening of wildlife tissue samples for organochlorine chemicals rarely includes dicofol, and this may explain why, compared with other organochlorines, the relative hazard of dicofol to wildlife populations is poorly known(33).
   
Dicofol is 'highly' to 'very highly' toxic to a range of aquatic organisms, including fish, invertebrates and estuarine/marine organisms(34). The 96 hour LC50 for Channel catfish is 0.30 mg/litre (parts per million [ppm]), 0.51 mg/l for bluegill, 0.183 mg/l for fathead minnow, and 0.12 mg/l for rainbow trout(35). It also causes early life stage toxicity at levels of 19 ppb for fathead minnow and 1 ppb for rainbow trout(36). Little information is available on bioaccumulation in fish species(37).
   
Estuarine/marine organisms are particularly susceptible to dicofol. The 96 hour LC50 for the eastern oyster embryo larvae is 15.1 mg/l ppb, 0.14 mg/l (ppm) for mysid shrimp, and 0.37 ppm for sheepshead minnow(38).
   
In birds, dietary concentrations of dicofol between one and 10 mg/g (wet weight) fed to captive adult females caused eggshell thinning, reduced hatching success, or reduced fertility in American kestrels (Falco spar-veruis) and eastern screech-owls (Otus asio)(39). Similar effects have also been noted in the mallard duck and ring dove(40). Researchers in the US are concerned that there have been no intensive field investigations of possible reproductive effects, despite the results from these laboratory findings(41). Because of its potential to bioaccumulate in the environment, the US EPA has requested that chronic reproduction testing is required(42).

Regulation
In 1990, the use of dicofol was suspended in Sweden for environmental reasons(43). In Switzerland its use is permitted for research purposes only(44). Throughout the European Union dicofol containing less than 78% pp'-dicofol or more than lg/kg (0.1%) of DDT or DDT related compounds cannot be used(45).
    The 1998 US EPA review of dicofol recommended a number of changes in order to protect the environment and wildlife. Dicofol applications are limited to no more than one per year. In the UK, the maximum number of treatments permitted is two per year for apples and hops, and two per crop for strawberries, protected crops and tomatoes(46).
   
When the UK Advisory Committee on Pesticides reviewed dicofol in 1995, it was also concerned about occupational exposure, and made some recommendations:

Conclusion
Environmental concerns have prompted progressive countries like Sweden to ban dicofol, and other countries are following suit by imposing severe restrictions on its use.
   
Nevertheless dicofol is one of the world's last organochlorines still in widespread use. It has perhaps survived because its environmental persistence is low relative to DDT, although this is not the case when compared with the vast majority of other pesticides on the market. DDT is after all one of the lowest of all common denominators.

References
1. WHO/Food and Agriculture Organisation, Fact Sheet on dicofol, No 81, 1996, 14pp.
2. US EPA RED FACTS, Dicofol, Office of Pesticide Programs, US EPA, Washington, 1998, 7pp.
3. Tomlin, CDS, The Pesticide Manual, BCPC, 1997, p380-382.
4. Extension Toxicology Network, (EXTOXNET), Dicofol, Cornell University, US, 1992, 5pp.
5. Op. cit. 3.
6. Pers. Comm. Miles Thomas, Pesticide Usage Survey Group, Central Science Laboratory, 1999.
7. Evaluation on: Review of dicofol, Ministry of Agriculture, Fisheries and Food, York, 1996, 105pp. p. 8.
8. Op. cit. 2.
9. Dicofol, Reregistration Eligibility Decision, Environmental Protection Agency, Office of Pesticides Programs, 1998, 238pp.
10. Op. cit. 9.
11. WHO Classification of Pesticides by Hazard 1996-1997, International Programme on Chemical Safety, WHO/IPCS/96.3.
12. Op. cit. 1.
13. Op. cit. 4.
14. OP cit. 4.
15. Op. cit. 2.
16. Op. cit. 9.
17. Op. cit. 9.
18. Review of Dicofol, Ministry of Agriculture Fisheries and Food, September 1996, 105pp.
19. Op. cit. 9.
20. Op. cit. 18.
21. OP cit. 4.
22. Op. cit. 18.
23. Op. cit. 9.
24. EU Drinking Water Directive, 80/778/EEC.
25. Ware, G.W., Fundamentals of Pesticides, Thomson Publications, 1982.
26. Op. cit. 9.
27. Op. cit. 9.
28. Op. cit. 9.
29. Domagalski, J., Occurrence of dicofol in the San Joaquin River, California, Bulletin of Environmental Contamination and Toxicology, 1996, 57:284-291.
30. Op. cit. 4.
31. Op. cit. 9.
32. Op. cit. 9.
33. Clark, D.R., and Flickinger, Dicofol and DDT residues in lizard carcasses and bird eggs from Texas, Florida and California, Bulletin of Environmental Contamination and Toxicology, 1995, 54:817-824.
34. Op. cit. 2.
35. Op. cit. 9.
36. Op. cit. 9.
37. Op. cit. 9.
38. Op. cit. 9.
39. Op. cit. 33.
40. Rohm and Haas, Material Safety Data Sheet, 1999.
41. Op. cit. 33.
42. Op. cit. 9.
43. Emmerman, Anders, Pesticides News No. 34, December 1996.
44. Dicofol, Decision Guidance Document, FAO/UNEP, 1993.
45. EC Prohibition Directive of 21 December 1978.
46. R. Whitehead (Ed.), UK Pesticide Guide 1999, BCPC, Farnham, Surrey, UK.
47. Op. cit. 18.

[This article first appeared in Pesticides News No.43, March 1999, p20-21]