Paraquat

Paraquat is one of the most widely used herbicides in the world. It has had a tarnished reputation because of its acute oral toxicity and ill-health associated with operators - particularly in the plantation sectors of many developing countries.

What is paraquat?
Paraquat is one of the most widely used herbicides, and held the largest share of the global herbicide market until recently overtaken by glyphosate. Paraquat is sold in about 130 countries for use on large and small farms, plantations and estates and in non-agricultural weed control. It is a quick acting, non-selective herbicide, which destroys green plant tissue on contact and by translocation within the plant.
   
Paraquat was first synthesized in 1882. Its herbicidal properties were discovered only in 1955 in the ICI (now Zeneca) laboratories, who produced it commercially in 1961. This chemical type of herbicide - a bipyridyl - is shared with few other pesticides. One, the related diquat, is also a Zeneca product.
   
Although the patent protection on paraquat has expired, Zeneca remains the world's major producer. The raw bipyridyl and paraquat production take place in the UK (where a new £40 million production plant at Huddersfield replaced the original Widnes plant in 1995), in the US (Bayport, Texas) and Japan (Tal, 50% owned by Zeneca). Huddersfield is Zeneca's main plant, producing 8,000 tonnes a year, of which 95% is exported(1). In addition paraquat production takes place in Brazil and India. Final stage manufacture takes place in Thailand and Kelang, Malaysia (Zeneca now has a minority interest in the latter). The company has planned a US$80m. joint venture in China (north of Shanghai) to come on stream in 1998 and has recently said it will double the size of this plant to 6,000 tonnes a year(2). Paraquat is made by other basic producers in Argentina, China, India, Spain, Taiwan and the US.
   
Zeneca markets paraquat as Gramoxone for agricultural use in formulations ranging between 24-36% active ingredient and for home and garden use under the trade names Weedol and Pathclear in formulations of about 2.5% paraquat. The biggest markets for the company's paraquat products are the US, Japan, Malaysia, Thailand, Mexico, France and Brazil and annual sales are still increasing(3). For many years paraquat accounted for a big part of Zeneca's agro-chemical sales (24% in 1987(4) ) and is still a major product in the agrochemical portfolio.

Uses and usage
Paraquat is used to control broad-leaved weeds and grasses, being less effective on deep rooted plants such as dandelions. It does not harm mature bark, and is thus widely used for weed control in fruit orchards and plantation crops, including coffee, cocoa, coconut, oil palms, rubber, bananas, vines, olives and tea, ornamental trees and shrubs and in forestry. Other uses include weed control in alfalfa, onion, leeks, sugar beet, asparagus. It is used for weed control on non-crop land and can be used as a defoliant for cotton and hops before harvesting. Paraquat is used as a desiccant for pineapples, sugar cane, soya beans and sunflower(5). In pineapples, for example, paraquat is applied after harvest to accelerate the drying out process and enabling plants to be burnt after 3-5 weeks, compared to 13 weeks after the alternative cutting and natural drying. 
   
Paraquat is increasingly used to destroy weeds in preparing land for planting in combination with no-till agricultural practices which minimise ploughing and help prevent soil erosion. Although toxic to fish, it is used as an aquatic herbicide where it is absorbed by plant matter and silt.

Toxic effects
Acute toxicity
Paraquat is highly toxic to animals and has serious and irreversible delayed effects if absorbed. As little as one teaspoonful of the active ingredient is fatal. Death occurs up to 30 days after ingestion. Absorbed paraquat is distributed via the bloodstream to practically all areas of the body. The lungs selectively accumulate paraquat, and therefore contain higher concentrations than other tissues. This develops into pulmonary oedema and other lung damage, leading to fibrosis. Liver damage occurs and renal failure may follow as the kidneys remove absorbed paraquat.
   
At spray strength paraquat is of relatively low acute toxicity. It is classified as a solid and with an acute oral LD50 for rats of 157 mg/kg, which puts it into WHO as Class II 'moderately hazardous'(6). Paraquat is also toxic if absorbed through the skin, see 'health issues' below. The minimum lethal dose by oral ingestion in human beings is about 35 mg/kg body weight, although less could be lethal without treatment. In dogs the lethal dose is 25-50 mg/kg and in cows and sheep 50-75 mg/kg(7). There is no vapour toxicity, but it can cause nose bleeding if inhaled.
   
No antidote for poisoning exists although it is recommended that the highly absorbent Fuller's Earth is administered. Hospital care must be sought without delay.

Carcinogenicity
The US EPA has classified paraquat as a possible human carcinogen, but has concluded that the risks posed to individual applicators are minimal and of no concern(8).

Mutagenicity
The EPA requested additional studies on mutagenicity for re-registration in 1987. Of the studies of gene mutation accepted eight were negative, four weakly positive and four were positive. Based on these the EPA concluded that paraquat is weakly genotoxic.

Ecotoxicity
Paraquat is less toxic to birds than to mammals. Its toxicity to fish varies with the species, size of fish and the softness or hardness of the water. Aquatic plants can concentrate high levels of paraquat, and a recent study indicates that significant tadpole mortality results from when they feed on paraquat-contaminated plant material. It also resulted in tadpole tail abnormalities and affected swimming behaviour feeding activity(9).

Key health issues
Being less acutely toxic at spray strength, the greatest risk to workers of fatal and serious accidents is during mixing and loading. Studies show high incidence of paraquat-related ill-health. For example a study in Guápiles, one of the main plantation regions of Costa Rica, identified 284 accident cases caused by paraquat between 1988 and 1990, including 123 cases of systemic poisonings, burns, eye injuries and fingernail damage(10).
   
Conditions of use in many developing countries mean it is difficult to follow label instructions and recommendations for use. Sprayers generally have no or inadequate protective clothing, lack training, and have little knowledge of the specific effects of products they use. Workers on estates are frequently employed as sprayers for 10 months of the year, six days a week.
   
In occupational use the main route of exposure is through the skin and the worst cases of exposure occur during knapsack spraying. Continued exposure, as encountered by spray operators on plantations, is reported to affect the skin, eyes, nose and finger nails. Skin problems include mild irritation, blistering and ulceration, desquamation (peeling of the outer layer of the skin), necrosis (cell-death in skin tissue), dermatitis of the hands and in some cases scrotal areas (from leaking spray machines soaking trousers)(11). Severe exposure on hands has resulted in nail damage, ranging from localised discoloration to temporary nail loss(12). Eye splashes can result in irritation and inflamed eyelids (blepharitis) and visual acuity can decrease(13). A study in Thailand found clear indications of caustic burns on the feet after working with spinning disk applicators(14).
   
While small farmers face some of the same problems as estate workers (lacking training, distant washing medical facilities), they are exposed to paraquat less regularly. A study of small farmers in Kenya found no protective clothing was worn (the cost of a pair of rubber gloves was equivalent to a day's wage)(15).
   
Intact human skin is relatively impermeable to paraquat, although a number of fatalities resulting from dermal exposure to intact skin have been documented(16). The presence of scratches, cuts, sores or severe dermatitis on the skin substantially increase the risks. Furthermore dermal exposure to paraquat can lead to skin injury including severe dermatitis, second degree burns and itching rash on the face, neck, hands or all over the body(17). A study of Malaysian plantation sprayers cited health problems after exposure to paraquat(18). An education worker with banana plantation workers in Honduras sent reports of common nose bleeds, diminishing eye sight, burning of skin, thinning of hair, nausea, loss of toe and finger nails(19).
   
Incidents also occur in the North. In 1992, a UK agricultural worker died after being splashed in the face with paraquat when he dropped an open container(20). In 1994, a farmworker in the UK suffered a severe rash and infection to his groin after applying paraquat with a knapsack sprayer(21). A similar incident was confirmed in 1992.

Poisoning: suicides and accidents
Accidental or deliberate ingestion of paraquat has been responsible for a large number of pesticide-related deaths. It is a major suicide agent in many developing countries. In Sri Lanka a 1989 study of 669 poison incidents indicated that agrochemicals were responsible for 59% and paraquat was the commonest poisoning agent with a fatality rate of 68%(22). Paraquat poisonings are still common in the UK, where a study of pesticide poisoning between 1990-1991 indicates 44 deaths with paraquat responsible for 75%(23). Many of these may be suicides. There is concern in developing countries that the easy availability of pesticides leads to suicides which might not otherwise occur. Most cases are self-poisoning, but not all intend to die(24).
   
To prevent accidental deaths, Zeneca added three alerting agents in the formulations. A stenching agent, was added to some formulations in 1975, an emetic to induce vomiting in 1977, and a blue dye to prevent confusion with cola, black coffee or other beverages was added from 1977. These are included in most but not all formulations depending on cultural acceptance and product registration.

Wildlife incidents
Incidents in the UK do include paraquat (14 cases [11%] in 1994)(25), some of which are deliberate baiting of animals, while others involve exposure during or after spraying.

Measures to reduce exposure
In the US paraquat is a restricted use pesticide, and may be purchased and used only by certified applicators. In the UK there are no such restrictions and Pathclear and Weedol are allowed for amateur use in household gardens. Professional users should wear a protective face shield, wash splashes immediately, avoid spray drift and remove contaminated clothes immediately. The WHO Health and Safety Guide adds that normal personal protection and hygienic measures should be rigorously observed; paraquat should not be sprayed with inadequate dilution, nor used by people suffering dermatitis or with wounds(26).

Food residues
Residues in food are generally not detectable, except when it is used as a pre-harvest desiccant in food crops (e.g. cereals) where levels of up to 0.2 mg/kg of plant matter have been reported(27). The Acceptable Daily Intake is recommended as 0.004 mg/kg/day body weight(28).

Environmental effects
Paraquat binds rapidly and tightly to clay materials in soils, and when adsorbed it is biologically inactive. It also binds to humus and other organic material: this results in no, or very low soil residues or leaching into water sources.
   
Multiple spray trials showed paraquat residues in soil from 22-58 mg/kg. Under field conditions, the residual paraquat is slowly redistributed. Long-term field studies have shown degradation rates of 5-10% per annum, which is thought to prevent saturation of the carrying capacity of the soil and to prevent adverse effects on microflora and other soil organisms or on crop growth. In sandy soils with a low organic content paraquat may be more readily released into ground water(29) .
   
The German federal biological institute (BBA) asserted in 1983 that repeated treatments of paraquat led to an accumulation in the soil and damage to crops. It refused to re-register paraquat products, but this was challenged in the courts by ICI. In 1992 the Court ruled that the BBA was justified but also ruled that registration should be granted to a new ICI formulation of only 10% paraquat, which was re-approved later that year. Field crop applications are permitted only once every four years, and only in areas at risk from erosion. Wider registrations were refused because of effects on the environment(30).

Resistance
In contrast to less widely used herbicides, resistance has only occurred in 18 minor species on 50 sites, and nowhere is it of any agronomic or economic significance(31).

Conclusion
As paraquat is absorbed and binds quickly to soil, leaching into water sources is not generally a problem and its use as a herbicide does not lead to food residues. A major concern centres on accidental and deliberate ingestion of the active ingredient, where even small quantities are fatal. Exposure to the concentrated active ingredient is a problem during mixing and loading sprayers. In developing countries the conditions of use make safe use very difficult. Although not fatal at spray strength, regular use, such as required on plantations, leads to health problems.

Regulatory status
Finland and Sweden banned paraquat because of its high toxicity.
Austria banned because of high toxicity and high frequency of poisonings(32).
Hungary severely restricted because accidental poisoning rate was unacceptably high(33).
Norway voluntary cancellation.
Limited registration in Germany. Concern with residues in soil has led to registration for field crop applications only once every four years, and only in areas at risk from erosion.
US Restricted use pesticide - purchase and use only by certified applicators.
Europe Under EC Registration Directive 91/414 the UK will review paraquat on behalf of Member States by mid 1997(34).

 References
1. 'Zeneca points to strong results', Agrow, No. 225, 3 February 1995.
2. 'Zeneca to boost herbicide plant, Financial Times, 22 May 1996.
3. 'Zeneca defends independence as agrochemicals advance', Agrow, No. 252, 15 March 1996.
4. Dinham, Barbara, ICI Limited, Paraquat Production - Starting the Chain, a report for Greenpeace International, December 1989.
5. Tomlin, Clive (ed), The Pesticide Manual, incorporating The Agrochemicals Handbook, Tenth Edition, British Crop Protection Council and the Royal Society of Chemistry, Farnham UK, 1994.
6. WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classification 1996-97,WHO/PCS/96.3, WHO, Geneva, Switzerland, 1996.
7. Bismuth, C., et. al., 'Prognosis and treatment of paraquat poisoning. A review of 28 cases', Journal of Toxicol. Clinical. Toxicol. 19, pp 461-474, 1982, quoted in International Programme on Chemical Safety, Environmental Health Criteria 39, Paraquat and Diquat, WHO, Geneva, 1984.
8. EPA, Paraquat Fact Sheet No. 131, 1987.
9. Bauer Dial, C.A. and Dial, N.A., 'Lethal effects of the consumption of field levels of paraquat-contaminated plants on frog tadpoles', Bulletin of Environmental Contamination and Toxicology, 1995, 55:870-877.
10. Vergara, A. Accidentes con productos agroqu'micos reportados al Instituto Nacional de Seguros durante 1990, cant - n de Pococ' y Guácimo: un análisis preliminar: Ajuste Estructural: Mujer, Salud y Empleo, Jan José, Costa Rica, 1991.
11. Ongom et al 1994, Binns 1976, Newhouse et al 1978, Waight and Wheather 1979, Levin et al 1979, Horiuchi et al 1980 cited in EHC 39.
12. Samman and Johnston 1969, Howard 1979b, cited in EHC39 p89.
13. Studies reported in EHC39, p. 90.
14. Howard, J.K., Paraquat spraying. Comparative risks from high and low volume application methods. In Proceedings of 10th Asian Conference on Occupa-tional Health, Singapore, pp. 1-7. (EHC39, p86).
15. Craig, Ian and Chris Mbevi, 'Contamination in the Tropics', Pesticides News, 19, March 1993, p. 5.
16. Smith, J.G., Paraquat poisoning by skin absorption:a review', Human Toxicology, 7:15-19, 1988.
17. Ibid.
18. Arumugam, V., Victims Without Voice, Tenaganita and PAN Asia Pacific, 1992.
19. Brady, Christopher, US worker on a health and literacy project, Honduras, interview material and letter to the Pesticides Trust [now PAN UK], 18 March 1992.
20. Health and Safety Executive, Pesticide Incidents Investigated in 1992/93, UK.
21. Health and Safety Executive, Pesticide Incidents Investigated in 1994/95, UK.
22. Hettiarachchi, J. and G.C.S. Kodithuwakku, 'Pattern of Poisoning in Rural Sri Lanka', International Journal of Epidemiology, Vol 18 No 2, UK.
23. Pesticide Monitoring Unit, Surveillance of Human Acute Poisoning from Pesticides 1 October 1990-30 September 1993, National Poisons Information Service (Birmingham Centre).
24. Hettiarachchi, J. and G.C.S. Kodithuwakku, 'Self-poisoning in Sri Lanka: factors determining the choice of the poisoning agents', Human Toxicology, 8, 1989, pp 507-510.
25. Report of the Environmental Panel of the Advisory Committee on Pesticides, Pesticide Poisoning of Animals in 1994, Investigations of Suspected Incidents in the UK (and for 1993), MAFF, and Scottish agricultural Science Agency, UK, 1995.
26. International Programme on Chemical Safety, Paraquat Health and Safety Guide No. 51 WHO, Geneva, 1991.
27. Draft Decision Guidance Document for paraquat, FAO, 10 April 1993.
28. JMPR/CODEX, established in 1986.
29. Op. cit 26 and EHC39, op cit.
30. 'German paraquat decision endorsed but ICI to gain new registration', Agrow, 166, 28 August 1992, p. 1 and Agrow 175 8 January 1993, p. 9.
31. Holt, et al, Mechanisms and agronomic aspects of herbicide resistance, Annual Review of Plant Physiology & Molecular Biology, 1993, vol.44:203-229.
32. UNEP/FAO Information exchange on banned and severely restricted chemicals in international trade, control actions to ban or severely restrict chemicals, 1996.
33. Ibid.
34. Pesticide Safety Directorate, UK, 10 May 1996, pers. comm.

[This article first appeared in Pesticides News No.32, June 1996, p20-21]