Atrazine

The herbicide atrazine is used throughout the world for a varied range of uses. It is an environmental contaminant regularly found in rain, surface, marine, and ground water. Recent research has suggested a link between atrazine exposure and serious effects on the sexual development of frogs. 

Atrazine is a selective systemic herbicide(1) introduced in 1958(2) by J.R. Geigy (now part of Novartis)(3). Novartis is atrazine’s largest manufacturer(4); it is one of their best selling products(5) but it is also manufactured by a number of other companies and has a range of trade names including Marksman (Novartis), Coyote (Defensa), Atrazina (Cequisa), Atrazol (Sipcam) and Vectal (Aventis)(6). Atrazine is used for the pre and post-emergence control of annual and broad leaved weeds and perennial grasses(7); it inhibits photosynthesis and interferes with other enzymic processes(8). It is mainly absorbed through the plant roots, but can enter through the foliage, and accumulates in the apical meristems and leaves(9).

Usage
Globally, atrazine is used in the production of maize, sorghum, sugar cane, pineapples, chemical fallows, grassland, macadamia nuts, conifers, and for industrial weed control(10), with its biggest market in maize production(11). In Europe, its use is concentrated on maize, orchards and vineyards(12), and in the UK, it is mainly used for maize, forestry, roses, and grassland(13). Atrazine is also applied in combination with many other herbicides(14), for example with simazine, another triazine chemical(15).
    Atrazine is applied worldwide – in 1998 it was the most widely used maize herbicide in the US, applied to 69% of the maize acreage(16). The world market for atrazine is worth over $400 million at the user level(17). In Europe atrazine consumption has dropped markedly since 1989(18) due to restrictions on its use and competition from newer, less-persistent herbicides(19). In the UK, atrazine is not widely applied, however it does have significant uses in maize production for general weed control, for which there are no alternatives(20). For example, in 1997 atrazine was applied to 53% of the herbicide treated area of maize in the UK(21). Its use is on the increase, reflecting the expansion of maize cultivation: applications of atrazine to UK grassland and fodder crops rose from 24,120 spray hectares in 1989 to 109,602 in 1997(22). Atrazine is also an important pesticide for rose cultivation and the forestry industry – in 1997, from a total of 25,092 spray hectares on hardy nursery stock, atrazine accounted for 884 spray hectares(23).
    Another application of atrazine is for total weed control on non-crop land such as railways, roadsides and industrial areas(24). In the past, it was widely used for this purpose, however in recent years this use has been restricted in some countries. In the UK for example, approval for use of atrazine on non-cropped land was revoked in 1992 (with the exception of the home/garden situation) following concerns over residue levels in drinking water(25) (see below). 

Acute toxicity
Atrazine is classified by the WHO as a pesticide unlikely to present acute hazard in normal use(26). The acute oral LD50 (dose at which half the sample is dead) for rats is 1869-3090 mg/kg(27) and for mice it ranges from >1332-3992 mg/kg(28). These LD50 levels indicate atrazine’s low toxicity – the Advisory Committee on Pesticides (ACP) evaluation stated atrazine is of low oral, inhalational and percutaneous acute toxicity(29). Interestingly, ruminants seem to be much more sensitive to the acute toxic action than rodents, in one study, two doses of 250mg/kg caused death in both sheep and cattle(30). Atrazine is a mild skin irritant(31) and is moderately irritating to the eye(32); for example, Atrazine 90DF causes ‘substantial but temporary eye irritation’(33). 
    The highest likelihood of human exposure to atrazine is associated with its production and use in agriculture. The results of one study in the US showed that applicators of atrazine are experiencing detectable exposures during one-time application through dermal absorption, inhalation or both(34). Additionally, the public at large may be subject to exposure through the consumption of contaminated drinking water(35). 

Chronic effects
Teratogenicity (birth defects)
The International Programme on Chemical Safety (IPCS) concludes that ‘atrazine has no significant teratogenic action in rats, mice or rabbits’(36) and the ACP does not consider atrazine to be teratogenic(37). 

Reproductive effects
An in-depth review of the toxicology of atrazine states ‘studies of exposed people and laboratory tests show that atrazine and atrazine-containing herbicides reduce the ability to reproduce successfully’(38). The review examines a number of studies to validate this, for example one study found the incidence of premature birth in families in which the father applied atrazine on the farm was nearly double that of families in which the father was not exposed to pesticides(39).

Mutagenicity 
The ACP and the US Environmental Protection Agency (EPA) evaluations both concluded atrazine does not have a mutagenic effect(40). However, the Northwest Coalition for Alternatives to Pesticides (NCAP) believe that the EPA review omitted studies that raise serious concerns about atrazine’s mutagenicity, for example, one study found a significant increase in the percentage of chromosomal damage in the blood cells of workers in an atrazine production plant(41).

Carcinogenicity
The carcinogenicity of atrazine is a controversial subject that has been studied in both people and laboratory animals(42). From experiments on rats, the ACP concluded atrazine increased the occurrence of mammary gland carcinomas in the rat strain studied, but not in other species(43); from evaluating the available evidence the IPCS found there was no convincing evidence of carcinogenicity in rats or mice(44). In contrast, in human evaluations, one study on the incidence of breast cancer and ovarian cancers in Kentucky found the breast cancer risk was higher (1.1-1.2 fold) in counties with medium and high levels of triazine exposure than it was in counties with low exposure(45). However, a later study carried out with a similar design, did not find any association between atrazine and breast cancer, and indeed an inverse association with ovarian cancer(46). In 2001, the NCAP evaluated all the available studies on cancer. They came to the conclusion that the results of an IACR evaluation stating ‘atrazine is not classifiable as to its carcinogenicity to humans’ (due to inadequate evidence(47)) were appropriate(48).

Effects on wildlife
Atrazine is only slightly toxic to birds(49) – there is no mortality at 10,000 mg/kg diet(50). It is virtually non-toxic for bees(51) with an LD50 (contact) of >1000µg/bee. Atrazine is classified as moderately toxic for aquatic organisms (96-h LC50 range from 0.5-15mg/litre(52)) by the IPCS, the LD50 for catfish is 7.6 mg/l and 4.3 mg/l for guppies(53). It has been said that atrazine is degradable and has little tendency to bioaccumulate(54), thereby limiting possible long-term adverse effects on fish and wildlife(55). 
    However, recent research in the US has shown atrazine has serious effects on frogs’ sexual development. The research has found that atrazine at levels often found in the environment demasculinises tadpoles and turns them into hermaphrodites, with males having ovaries in their testes and much smaller vocal organs, and with ten times lower levels of testosterone than normal male frogs(56). The herbicide apparently modifies the steroid hormone balance in frogs at a sensitive time in their development(57). Researchers are now testing native leopard frogs from the American Mid-West with similar problems to determine whether the changes are due to atrazine(58). This research raises concern for all aquatic life that swims and breeds in atrazine-contaminated field runoff. 
    As it is an effective herbicide, in addition to direct toxic effects, the phytotoxicity of atrazine may constitute a problem in the case of uncontrolled applications(59) and indirectly affect aquatic animal populations by changes in water quality caused by their removal, for example decreased dissolved oxygen levels and reduced plant cover(60). 

Fate in the environment
Atrazine is a pervasive environmental contaminant(61). It is strongly persistent and is one of the most significant water pollutants in rain, surface, marine, and ground water(62). Its persistence (it has a half-life of 125 days in sandy soils(63)) and mobility in some types of soils because it is not easily absorbed by soil particles(64), means it often causes contamination of surface and ground waters(65). In the US for example, it has been found in the groundwater of all 36 river basins studied by the US Geological Survey(66) (USGS) and the USGS estimates that persistence in deep lakes may exceed 10 years. 

Resistance
Several weeds have developed resistance to atrazine. For example, atrazine resistant strains of the weeds Chenopodium and Amaranthus were collected from maize fields in the US that had been treated with atrazine for 12 years(67). In the UK rose industry, groundsel (Senecio vulgaris) has been identified as triazine resistant(68). As a result of this tendency for the development of resistance, there are restrictions on the number of applications that can be made to crops(69).

Regulatory status
In light of the widespread groundwater contamination highlighted above, concerns have arisen over atrazine residues in drinking water. These concerns have now led to bans in Austria, Slovenia, Germany, Denmark and Italy, and atrazine is subject to restrictions in several other European countries including France and the UK(70). However, in the UK, throughout the evaluation process, the ACP and the Ministry of Agriculture made a point of stressing that restrictions imposed on atrazine are not the result of any health risk, but only to keep residue levels in water within the legally imposed EC Drinking Water Directive limit of 0.1 µg/l for any single pesticide(71), a level which was not a level derived from toxicological studies. 
    In the US, the US EPA has established a Lifetime Health Advisory level for atrazine in drinking water of 3 µg/l, i.e. water containing atrazine at or below this level is acceptable for drinking every day over the course of one’s lifetime, and does not pose any health risk(72). 
    Some advocates of atrazine may feel the problem has been exaggerated. A Ciba-funded study in the US in 1996 showed that in 99.7% of drinking water supplies tested, atrazine residues were either not present or did not exceed the EPA’s standard. In those areas where the level exceeded the standard, Novartis is said to be co-operating with the local communities to reduce exposures(73). In fact, the company argues that ‘any ban on atrazine, based on political and other considerations rather than scientific argument, could set a dangerous precedent for the crop protection industry in its dealings with government authorities’.(74)
    In Europe atrazine is now pending review for inclusion on Annex 1 of the 91/414 directive on pesticides. The outcome of this process is likely to be controversial as if atrazine is included on Annex 1, some countries would have to re-permit atrazine use, but, for example, Germany has already indicated that it is reluctant to change its stance(75). By March 2000, atrazine had completed the peer review stage and entered one of the final stages of the EU review process. Two years later, the final Annex 1 decision is still awaited(76). 

Conclusions
Atrazine is a pesticide of major concern for a number of reasons including possible negative health effects, effects on aquatic organisms, levels in drinking water and the development of resistance. Whilst it is becoming less widely used, the effects of its long-term persistence may still cause health and environmental problems in the future. (HM)

References
1. Advisory Committee on Pesticides, Evaluation on Atrazine (2), Evaluation of Fully Approved or Provisionally Approved Products, No. 71, Ministry of Agriculture, Food and Fisheries, London, July, 1993.
2. IPSC International Programme on Chemical Safety, Atrazine Health and Safety Guide No. 47, WHO Geneva, 1990.
3. Hicks B, Generic Pesticides – The Products and Markets, Agrow Reports, PJB Publications, 1998.
4. Hicks, Ibid.
5. Dewar A, Agrow’s Top 25 – 2001 Edition, Agrow Reports, PJB Publications, April 1998.
6. Tomlin CDS (Ed), Pesticides Manual 12th Edition, British Crop Protection Council, 2000.
7. Tomlin, Op. cit. 6.
8. MAFF, Op. cit. 1.
9. MAFF, Ibid.
10. Tomlin, Op. cit. 6.
11. Hicks, Op. cit. 3
12. MAFF, Op. cit. 1.
13. MAFF, Ibid.
14. Tomlin, Op. cit. 6.
15. Pesticides Usage Survey Report, Hardy Nursery Stock, Number 152, Ministry of Agriculture, Fisheries and Food and Scottish Office Agriculture, Environment and Fisheries Department, 1997.
16. Dewar, Op. cit. 4.
17. Hicks, Op. cit. 3.
18. Hicks, Ibid.
19. Dewar, Op. cit. 4.
20. Davis M, Atrazine and Simazine: Restrictions now effective, Pesticides News, September 1993, Vol. 21, page 19, September 1993.
21. Pesticides Usage Survey Report, Grassland and Fodder Crops, Number 151, Ministry of Agriculture, Fisheries and Food and Scottish Office Agriculture, Environment and Fisheries Department, 1997.
22. Pesticides Usage Survey Report, ibid.
23. Pesticides Usage Survey Report, Op. cit. 15.
24. MAFF, Op. cit 1.
25. Advisory Committee on Pesticides Annual Report, Ministry of Agriculture, Food and Fisheries, 1992. 
26. IPCS, The WHO recommended classification of pesticides by hazard and guidelines to classification 1998-1999, WHO/IPCS/98.21.
27. Tomlin, Op. cit. 6
28. Tomlin, Ibid.
29. MAFF, Op. cit. 1.
30. IPCS, Op. cit. 2.
31. MAFF, Op. cit. 25
32. IPCS, Op. cit. 2.
33. Cox C, Herbicide Factsheet, Atrazine: Toxicology, Journal of Pesticide Reform, 2001, Vol 21, No. 2.
34. Perry M, et. al., Urinalysis of atrazine exposure in farm pesticide applicators, Toxicology and Industrial Health, 2000, vol. 16, 285-290.
35. IPCS, Op. cit. 2.
36. IPCS, Ibid.
37. MAFF, Op. cit. 25.
38. Cox, Op. cit. 33.
39. Savitz et. al., cited by Cox, Op. cit. 33.
40. MAFF, Op. cit. 1; Cox, Op. cit. 33.
41. Cox, Op. cit. 33.
42. Cox, Ibid.
43. MAFF, Op. cit. 1.
44. IPCS, Op. cit. 2.
45. Kettles et. al., cited by Cox, Op. cit. 33.
46. Hopenhayn-Rich C, Stump ML and Browning SR, Regional Assessment of Atrazine Exposure and Incidence of Breast Cancer and Ovarian Cancers in Kentucky, Archives of Environmental Contamination and Toxicology, 2002, 42, 127-136.
47. International Agency for Research on Cancer, cited by Hopenhayn-Rich et. al., ibid.
48. Cox, Op. cit. 33.
49. Pesticide Management Information Programme ‘Atrazine’ EXTOXNET Pesticide Information Notebook, Cornell University, New York, 1992.
50. IPCS, Op. cit. 2.
51. IPCS, Ibid.
52. IPCS, Ibid.
53. Tomlin, Op. cit. 6.
54. IPCS, Op. cit. 2
55. IPCS, Ibid.
56. Sanders R, University of California, Berkeley, Campus News, Media Relations, Press Release, Popular weed killer demasculinizes frogs, disrupts their sexual development, UC Berkeley study shows, www.berkeley.edu/news/media/releases/2002/04/15_frogs.html, April 2002.
57. Atrazine linked to endocrine disruption in frogs, Environmental Science and Technology, February 1, 2002.
58. Saunders, Op. cit. 56.
59. IPCS, Op. cit. 2.
60. MAFF, Op. cit. 1.
61. Cox C, Herbicide Factsheet, Atrazine: Environmental Contamination and Ecological Effects, Journal of Pesticide Reform, Fall 2001, Vol 21, No. 3.
62. Wiegand C, et. al., Toxicokinetics of Atrazine in Embryos of the Zebrafish (Danio rerio), Ecotoxicol. and Environmental Safety, 2001, 49, 199-205.
63. IPCS, Op. cit. 2.
64. ECOTOXNET, Op. cit. 49.
65. IPCS, Op. cit. 2.
66. US Geological Survey, cited by Cox, Op. cit 61.
67. Solymosi et, al,, cited by Cox, Op. cit. 61.
68. Pesticide Usage Survey Group, Op. cit. 21.
69. Whitehead R (Ed.), The UK Pesticide Guide 2002, British Crop Protection Council and CABI Publishing, 2002.
70. Hicks, Op. cit. 3
71. Davis, Op. cit. 20.
72. ECOTOXNET, Op. cit. 49.
73. Hicks, Op. cit. 3
74. Hicks, Ibid.
75. Hicks, Ibid.
76. Dewar, Op. cit. 5.

[This article first appeared in Pesticides News No. 56, June 2002, pages 20-21]