Diazinon

Diazinon is an organophosphate (OP) pesticide developed by Novartis in the early 1950s. Government regulators are increasingly likely to restrict its use because of concerns about neurotoxicity and data gaps.

What is diazinon?
Diazinon is an OP insecticide and acaricide (a chemical which kills mites and ticks), which acts as a contact stomach and respiratory poison. In common with other OPs, diazinon’s toxic action is achieved by inhibiting acetylcholinesterase, an enzyme essential for normal nerve impulse transmission. 
    It is used throughout the world to control a wide range of sucking and chewing insects and mites on a range of crops, including deciduous fruit trees, citrus fruit, bananas, vegetables, potatoes, beet, sugar cane, coffee, cocoa, tea, tobacco, cotton, and rice. It is also used to control agricultural soil-dwelling insects, and is applied as a sheep dip to control ectoparasites such as sheep scab and blow fly strike(1). Diazinon use in homes controls cockroaches, ants, and carpet beetles, and is in insecticidal pet collars(2). Trade names for diazinon include Knox-out, Dianon and Basudin(3).

Production and use
Diazinon was originally developed by JR Geigy (now Novartis) in the early 1950s. Manufacturers since include Aimco, Elf Atochem, Drexel, Makhteshim-Agan, Nippon Kayaku, and Novartis(4).  In many parts of the world, production and usage figures are not publicly available. Between 1987 and 1997, annual usage of diazinon in the US totalled about 6 million pounds (2.7 million kg). US states with significant use include California, Texas and Florida(5). US production figures for 1999 show 13.5 million pounds (6.1 million kg) of active ingredient were produced for sale(6). Up to 75% of the diazinon used in the US each year is for non-agricultural purposes, with 39% used by homeowners(7).
    A review of diazinon in 1991 by the UK’s Pesticide Safety Directorate raised concerns about sub-standard production resulting in the hazardous by-products monothiono-tetraethylpyrophosphate and sulfotepp(8).
    In California during 1998, 900,596 pounds (408,871kg) of diazinon active ingredient were used in both agricultural and some urban situations(9). 
    In the UK, diazinon has mostly been used either as a sheep dip, or to control ants and cockroaches around the home. Agricultural uses have been phased out since 1999 (see below). OP sheep dip use peaked in 1986 when in total 186 tonnes were sold. By 1998 sales had decreased to about 80 tonnes, largely because compulsory sheep dipping ended in 1992(10). Since December 1999 OP sheep dip use has been suspended in the UK (see below)(11). 

Acute toxicity
The World Health Organisation (WHO) classifies diazinon as a class II ‘moderately hazardous’ pesticide. The acute oral LD50 (the dose required to kill half a population of laboratory animals) for rats is 1,250 mg/kg, and for mice it is 80-135 mg/kg(12).
    Diazinon, as with other OPs and carbamates, poisons humans and insects through its effects on nerve enzymes. Diazinon combines chemically with the acetylcholinesterase enzyme and inactivates it. This enzyme is essential for the control of nerve impulse transmission. Loss of acetylcholinesterase allows the accumulation of acetylcholine, the substance secreted by nerves that activates muscles, glands, and other nerves. Accumulation of sufficient levels of acetylcholine at junctions between nerves muscles will cause muscle contractions or twitching. Accumulation of acetylcholine at junctions between nerves and glands results in gland secretion; and accumulation between nerves in the brain causes sensory and behavioural disturbances(13).
    The main symptoms of acute diazinon poisoning are headache, nausea, dizziness, pin-point pupils, blurred vision, tightness in the chest, difficulty in breathing, muscle weakness or twitching, difficulty in walking, vomiting, abdominal cramps, and diarrhoea. Effects on the central nervous system may include confusion, anxiety, drowsiness, depression, difficulty in concentrating, slurred speech, poor recall, insomnia, nightmares, and a form of toxic psychosis resulting in bizarre behaviour(14). The US Environmental Protection Agency (EPA) is concerned that poisoning due to unrecognised dermal absorption, and other routes of exposure can easily be misdiagnosed. This suggests that some individual cases of poisoning are missed(15).
    The US Poison Control Centre (PCC) has recently analysed its nationwide operations for the years 1985 to 1992(16). There were a total of 20,565 diazinon cases in the PCC database. Of these, 749 cases were occupational exposure – 519 (69.3%) included exposure to diazinon alone, and 230 (30.7%) involved exposure to multiple chemicals, including diazinon. There were a total of 10,079 adult non-occupational exposures – 9,060 (89.9%) involved the chemical alone and 1,019 (10.1%) concerned multiple chemicals(17). 
    California is one of the few places in the world that actively requires mandatory reporting of all occupational pesticide poisoning incidents from doctors. The California Pesticide Illness Surveillance Program (1982-1995) reported 521 cases where diazinon alone was judged responsible for adverse health effects. Only cases with a definite, probable, or possible relationship were reviewed. Diazinon ranked 5th as a cause of systemic poisoning in California from 1990 to 1994(18).
    In the UK there have been concerns about the effects of OP sheep dips (including diazinon) since they replaced the use of organochlorines in the mid-1980s. 

Chronic toxicity
Based on inhibition of the enzyme acetylcholinesterase, the daily administered no-observed-adverse-effect-level (NOAEL) for humans is 0.025 mg/kg body weight per day, according to WHO(19). Other reports suggest no-effect doses have ranged from 0.02 mg/kg/day in humans to 0.1 mg/kg/day in rats(20).
    In sub-chronic and chronic toxicity studies conducted in mice, rats and dogs, systemic toxicity occurred with decreases in body weight and body weight gains(21).
    There are also potential concerns about breakdown products. In animals diazinon is converted to diazoxon (where the sulphur molecule is substituted for oxygen), a compound that is a strong enzyme inhibitor(22).

Cancer 
Diazinon is not considered carcinogenic by agencies such as the International Agency for the Research on Cancer, or the US EPA(23). However, use of diazinon by farmers in Iowa and Minnesota has been linked to increased risk of non-Hodgkins lymphoma, a rare form of cancer(24). Similar links were found in the 1980s in Nebraska(25).

Neurological effects
Since the mid 1980s the health effects from exposure to low levels of OP sheep dip remain unclear and of great concern. Public interest groups in the UK such as the OP Information Network and the Pesticide Exposure Groups of Sufferers have campaigned for a ban on the use of diazinon because of these issues. Diazinon has played a major role in OP sheep dip use, along with propetamphos and chlorfenvinphos. Most methods of toxicological analyses for OPs have concentrated on measuring the indirect biological effects on humans, by measuring the degree of erythrocyte and plasma cholinesterase activity. However, people can have a wide variation in cholinesterase levels due to genetic factors and disease status, so measuring adverse effects can be difficult without baseline data(26).
    After years of concern, the UK government set up a Committee on Toxicity (COT) Working Group on OPs. Its terms of reference were: ‘To advise on whether prolonged or repeated low-level exposure to OPs, or acute exposure to OPs at a lower dose than causing frank intoxication, can cause chronic ill-health effects.’ The report went on to ‘advise regulatory agencies that any ill-effects remain unproven, although a question remains over whether there may be a small group of individuals particularly susceptible to OPs.’(27) Environmental groups say this ‘small group’ may include about 1,000 sheep dippers(28).
    Further work done at the Institute of Occupational Medicine identified the main risk of adverse effects from OP sheep dips as exposure to the concentrate. In December 1999 the government responded by withdrawing all OP sheep dip concentrate containers from the market until the introduction of containers which will minimise operator exposure to the OP(29).

Fate in the environment
A recent US paper reports that diazinon has been found in rivers across the US including the Mississippi and the Rio Grande. Diazinon is one of the most commonly detected insecticides in air, rain and fog(30).
    Analysis by the Environment Agency of Welsh rivers contaminated with OP and synthetic pyrethroid sheep dip revealed that during 1999, 57% of 111 river sites monitored recorded positive results for diazinon(31). 

Wildlife
The primary wildlife concern with diazinon results from its extremely high acute risk to birds. The acute oral LD50 for mallard ducklings is 3.5 mg/kg, and for young pheasants the figure is 4.3 mg/kg(32). In the US it has caused more documented avian deaths than any other pesticide except carbofuran(33). The majority of incidents on known sites have occurred on lawns and other turf, particularly on golf courses. In one US incident, diazinon applied at two pounds active ingredient per acre rate on turf caused the death of some 85 wigeons (a type of duck) after just 30/40 minutes of feeding(34).

Developing countries
The Food and Agriculture Organisation advises against using WHO class II pesticides like diazinon in developing countries, yet it is widely used in for example Senegal and Indonesia(35). 
    There is evidence that fish poisoning by pesticides occurs in Lake Victoria in East Africa. Between October 1997 and February 1999 six people were convicted and given prison sentences ranging from six months to 20 years after being caught on Lake Victoria with pesticides (endosulfan and diazinon)(36). 

Food residues
Diazinon is found in a range of fruit and vegetables including pears, soyabean, grain, strawberries, beans and tomatoes. The Consumers Union in the US is concerned that tolerance levels (maximum residue levels) for diazinon are too high, especially for children(37). In the UK, residues of the OPs diazinon and propetamphos are regularly found in sheep. Surveillance carried out in 1999 on 643 samples of kidney fat showed 20 contained OP residues, with diazinon detected in the range 21-150 µg/kg(38).

Regulatory action
The UK government is currently reviewing most uses of anticholinesterase pesticides (OPs and carbamates) (excluding sheep dips and other veterinary, and human medicines). In the case of diazinon, agricultural approvals were revoked in April 1999 because of a lack of data support by the manufacturers. Existing stocks can continue to be used for two years(39). The use of diazinon as a sheep dip is currently suspended (see above).
    The US also has an ongoing Review Process for all OPs to make sure that older pesticides such as diazinon meet current scientific and regulatory standards.
    The manufacturers are not supporting diazinon at the European Union level and it may be withdrawn by 2003(40).

Data gaps
Earlier this year the US EPA issued a Data-Call-In notice for a developmental neurotoxicity study for all OPs(41). Specifically for diazinon, it also announced data requirements for estimation of dermal and inhalation exposure for workers using the product(42). The US EPA has further listed a number of environmental fate data gaps including monitoring in reservoirs and lakes, drinking water supplies, air rain and fog; usage information in non-agricultural areas; freshwater fish acute toxicity study(43).
    A UK review of diazinon in 1991 identified a number of data gaps including a need for operator studies using emulsifiable concentrates, and for additional wildlife studies(44). 

Conclusions
Public interest groups around the world have raised concerns about the use of OPs in general, and diazinon in particular. In July this year the Consumers Union called on the US EPA to phase out all uses of diazinon within four years. It is concerned about exposure levels for children, and the threat to wildlife, especially many different species of birds. For many years, groups in the UK such as the OP Information Network and the Pesticide Exposure Groups of Sufferers have campaigned for a ban on the use of diazinon because of its impacts on sheep dippers. 
    After 50 years of use regulatory action over data gaps may see the end of diazinon. (By David Buffin)

References
1. C.D.S. Tomlin, The Pesticide Manual, British Crop Protection Council, 1997, pp354-356.
2. Diazinon, Environmental Health Criteria 198, International Programme on Chemical Safety, World Health Organisation, Geneva, 1998, p12.
3. Op. cit. 1.
4. Op. cit. 1.
5. Preliminary Human Health Risk Assessment Diazinon, US Environmental Protection Agency, Office on Prevention, Pesticides and Toxic Substances, 12 April 2000, p20.
6. Ibid.
7. Preliminary Environmental Risk Assessment for Diazinon, US Environmental Protection Agency, 5 May 1999, p10.
8. Diazinon, Evaluation Document, No. 35, Pesticides Safety Directorate, UK, April 1991. 
9. Trends in Use in Cholinesterase Inhibiting Pesticides, California Department of Pesticide Regulations, 2000, www.cdpr.ca.gov/docs/pur/pur98rep/table05.htm
10. Monitoring of pesticides in the environment, Report of the Pesticides in the Environment Working Group, Environment Agency, Bristol, 2000, p23.
11. Government Announces Four Point Plan on Organophosphates, MAFF press release, 455/99, 20 December 1999.
12. WHO Classification of Pesticides by Hazard 1998-1999, International Programme on Chemical Safety, WHO/IPCS/98.21.
13. Review of Diazinon Incident Reports, US EPA, Office on Prevention, Pesticides and Toxic Substances, 2 July 2000, p2.
14. Ibid, p3.
15. Op. cit. 13, p3.
16. Op. cit. 13, p18.
17. Op. cit. 13, p22-23.
18. Op. cit. 13, p28.
19. Op. cit. 2, p107.
20. Diazinon, Extoxnet, US, April 1992.
21. Op. cit. 5, p7.
22. Op. cit. 20.
23. www.atsdr.cdc.gov/tfacts86.htm.
24. K.B. Cantor, et. al., Pesticides and other risk factors for non-Hodgkin’s Lymphoma among men in Iowa and Minnesota, Cancer Research, 1992, 52, pp2447-2455. 
25. S.H. Zahm, et. al., A case-control study on non-Hodgkin’s lymphoma and agricultural factors in Eastern Nabraska, American Journal of Epidemiology, 1988, 128, p901. 
26. K.J.M. Niven, et. al., Occupational hygiene assessment of exposure to insecticides and the effectiveness of protective clothing during sheep dipping operations, Insitute of Occupational Medicine, February 1994.
27. Committee on Toxicity Working Group on OPs, 1998.
28. OP Sheep Dips and Human Health, seminar proceedings, National Farmers Union, UK, 2/6/95. p11.
29 Government announces four point plan on OPs, MAFF press release, 20 December 1999.
30. Op. cit. 7, p11.
31. Sheep Dip in Wales - 2000, Environment Agency, UK, 9 May 2000.
32. Op. cit. 1.
33. Op. cit. 7, p16.
34. Op. cit 7, p16.
35. The Pesticides Trail, The Pesticides Trust [now PAN UK], January 1995.
36. Assessing the Controls on Pesticide Residues in Fish Coming From Lake Victoria, Final Report, European Commission, DG24, 6 December 1999.
37. Adam Goldberg, Edward Groth and Charles Benbrook, letter to US EPA from Consumers Union, 17 July 2000.
38. Annual Report on Surveillance for Veterinary Residues in 1999, Veterinary Medicines Directorate, UK, 2000, p92.
39. Review of Anticholinesterase Compounds - Phase II, letter from the Pesticide Safety Directorate, 14 April 1999.
40. http://europa.eu.int/comm/dg24.
41. Op. cit. 5, p8.
42. Op. cit.5, p119.
43. Op. cit, 7, 26-28.
44. Op. cit. 8.

[This article first appeared in Pesticides News No.49, September 2000, p20]