Azoxystrobin

Azoxystrobin is one of the first of a new class of fungicides, the strobilurins, to be commercialised. It is now the leading proprietary fungicide in the world, but there are already serious resistance concerns. 

What is azoxystrobin?
Azoxystrobin was first marketed in 1998 and is a systemic, broad-spectrum fungicide with activity against the four major groups of plant pathogenic fungi including Ascomcetes (eg powdery mildews), Basidiomycetes (eg rusts), Deutoromycetes (eg rice blast) and Oomycetes (eg downy mildew)(1). It inhibits spore germination and mycelial growth(2). It has worldwide uses on cereals, vines, rice, citrus, potatoes and tomatoes. In 1999, azoxystrobin was the leading proprietary fungicide worldwide with sales of US$415m(3) and is now a world market leader in cereals.
    It was given provisional approval for use in the UK on some fungal diseases of wheat and barley in 1997(4), subject to approval at EU level. It was given Annex 1 approval in the EU in 1998 as a fungicide for use on cereals and vines(5). In the UK it is marketed as Amistar, and in the US as Heritage. 
    In 1998, the first year of its use in the UK, azoxystrobin was the 17th most used active ingredient in arable crops by area. It was used on 882,676 ha(6). 86 tonnes of azoxystrobin were applied, making it the 36th product most used by weight. In the broad-spectrum cereal fungicide market strobilurins took a 42% share in 1999, which is expected to have increased to 60% in 2000 mainly at the expense of triazole fungicides(7). 

Acute toxicity
Azoxystrobin is classified by the World Health Organisation as ‘slightly hazardous’ (Class III)(8). The acute oral LD50 (the dose required to kill half a population of laboratory animals) is more than 5,000 mg/kg for rats. 
    It is an irritant to skin and may cause sensitization. It is also classed as toxic by inhalation(9). The UK Advisory Committee on Pesticides (ACP) noted that the uses for which approval was sought ‘did not include sprays which generated particles of a relevant size for inhalation’ and so the potential risk from inhalation was deemed acceptable. The ACP also noted that the active substance contained a co-formulant classifiable as having the potential to cause skin sensitization, and the company agreed to reformulate the product to reduce the amount of the co-formulant(10).

Chronic toxicity
The US EPA review concludes azoxystrobin is ‘unlikely to be a carcinogen’(11). The Pesticide Manual notes ‘Not oncogenic in rats or mice. No evidence of neurotoxicity, endocrine effects or teratogenicity’(12). 

Reproductive toxicity
Azoxystrobin was not teratogenic or mutagenic. ‘In vitro testing indicated clastogenic potential (ability to cause disruption to chromosomes), but negative results in vivo provided reassurance that azoxystrobin would not pose a genotoxic risk in practice’(13). 

Environmental fate
Azoxystrobin is labelled as dangerous to fish and other aquatic life(14) on the basis of toxicity of the product to algae. In addition, azoxystrobin partitioned into the sediment where it persisted with a half-life of greater than 100 days. This risk to sediment-dwelling species was assessed and a six-metre no-spray zone was considered sufficient to protect surface waters(15). The EU review also cautioned Member States who might approve specific uses of the compound to pay particular attention to impact on aquatic organisms and that authorisations should include appropriate risk mitigation measures(16). 
    According to the US Environmental Protection Agency, laboratory studies show azoxystrobin is moderately persistent in soil in the absence of light and potentially moderately mobile in coarse textured soils (sand and loamy sand soils); although field studies showed it was moderately immobile and relatively non-persistent in actual field conditions. Some degradation products had the potential to leach into ground water under some conditions, and a ‘groundwater advisory’ was placed on the label(17). 
    It is not thought that UK or European water companies or regulators have yet included azoxystrobin in analytical suites in spite of its widespread use.

Wildlife
The Pesticide Manual cites the International Organisation for Biological Control (IOBC) as authority for the statement that azoxystrobin is ‘harmless to non-target organisms including predatory mites and bugs, spiders, lacewings, hoverfly, ladybird, carabid beetle, parasitoid wasps and bees under field conditions at field application rates’(18). 

Food residues
The UK ACP endorsed an Acceptable Daily Intake of 0.2 mg/kg/bw/day based on an No Observable Adverse Effect Level from the 13-week dietary study in the rat, with a 100-fold safety factor. There are EU MRLs and draft UK MRLs. Azoxystrobin is included as one of 32 pesticides to be sought in apples, tomatoes, lettuce, strawberries and grapes in the next coordinated EU monitoring survey(19). 

Resistance
Although azoxystrobin is one of the first of the new strobilurin group of fungicides, certain wheat fungi have already developed resistance to it in Germany in 1998, which spread throughout Europe in 1999. In Japan resistance is widespread in cucumber fungi. Cross-resistance is also reported with two other non-strobilurin fungicides, famoxadone and fenamidone(20). 
    UK advice is now to avoid applying more than three foliar treatments of strobilurin products to the same crop to discourage resistance(21). 

Conclusions
Azoystrobin is a new strobilurin fungicide that is relatively non-toxic to humans and the environment, apart from dangers to aquatic species and groundwaters. However, in spite of the very short time since its introduction and widespread use resistance and cross-resistance are now common in two continents. (PB)

References
1. JM Clough, CRA Godfrey, et al, Azoxystrobin: A Novel Broad-spectrum Systemic Fungicide, Pesticide Outlook, 1996, 7:16-20.
2. CDS Tomlin (ed), The Pesticide Manual, British Crop Protection Council (BCPC) UK, 2000. 
3. SP Heaney, AA Hall, SA Davies and G Olaya, Resistance to fungicides in the Qol-STAR cross-resistance group:current perspectives, BCPC, Conference: Pests & Diseases 2000, UK, pp 755-62. 
4. Advisory Committee on Pesticides, Annual Report 1997, HMSO London, 1999.
5. EU Directorate General for Agriculture, DG VI-B-II-I, Review report for the active substance azoxystrobin, (Document 7581/VI/97-Rev.5) Brussels 22 April 1998 (and see website http://europa.eu.int/comm/food/fs/ph_ps/pro/eva/newactive/list2_en.htm).
6. DG Garthwaite, & MR Thomas, Arable Farm Crops in Great Britain 1998, Report 1, Pesticide Usage Survey Group, (PB 4808) MAFF Publications, York, 1999.
7. Agrow’s Complete Guide to Agrochemical Marketing Strategies in the EU, Agrow Report DS 19, August 2000, PJB Publications, UK.
8. World Health Organisation Recommended Classification of Pesticides by Hazard 1998-99 (ref: WHO/PCS/98.2), WHO, Geneva 1999.
9. Op. cit. 2. 
10. Op. cit. 4.
11. US EPA, Azoxystrobin, Pesticide Fact Sheet, Washington DC, February 1997.
12. Op. cit. 2. 
13. Op. cit. 4.
14. R. Whitehead (Ed.), The UK Pesticide Guide 2001. BCPC/CABI, UK, 2001.
15. Op. cit. 4.
16. Op. cit. 5.
17. Op. cit. 11.
18. Op. cit. 2. 
19. EU finalises MRL 2001 survey, Agrow 369, 2 February 2001.
20. Op. cit. 3.
21. Op. cit.14.

[This article first appeared in Pesticides News No.51, March 2001, p21]