The Expert Forum is comprised of the following members:

Dietrich Hermann
Syngenta Crop Protection AG, Stein, Switzerland (Chair)
Alessandro Bermano Isagro S.p.A., Milano, Italy
Luigi Burri Isagro S.p.A., Milano, Italy
Duncan McKenzie Syngenta Crop Protection AG, Basel, Switzerland

The Phenylamide (PA) working group was formed in 1982 and held annual meetings until 1997. In 1999, the FRAC Steering committee decided to transform the working group to an expert forum. It was also decided to organise group meetings only on request and if more than one member company wishes to meet. The PA-FRAC Expert Forum represents an “information desk” for subjects related to phenylamide resistance and product performance; it is handled by the present chairman, Dr. Dietrich Hermann, Syngenta. Information on product performance, infringements of use recommendations and sensitivity of field populations are collected by the chairman and can be made available through the FRAC website.


The phenylamides are a highly active class of fungicides specifically controlling plant pathogens of the Oomycetes (the downy mildews of the Peronosporales and Sclerosporales, as well as most members of the Pythiales (e.g. Phytophthora and Pythium spp.) and Saprolegniales; Gisi, 2002). They penetrate the plant tissue rapidly, are translocated acropetally within the plant and inhibit rRNA biosynthesis (polymerase complex I) in the target pathogens. The mechanism of resistance may involve one (or two) major gene(s) and potentially several minor genes. The target gene and the site of mutation(s) in the genome have not been mapped so far. Therefore, there are no molecular methods available for the detection of resistance. Phenylamide fungicides are in commercial use since 1978. The following active ingredients are classified as phenylamides: metalaxyl, metalaxyl-M (mefenoxam), furalaxyl and oxadixyl (all Syngenta), benalaxyl and benalaxyl-M (kiralaxyl, Isagro) and ofurace (Bayer) (Gisi and Ziegler, 2002; Müller and Gisi, 2007).

The use strategies for PAs have been well established since long (see below) and do not create controversial issues amongst member companies, officials and advisors. No infringements of use strategies have been reported for many years. Current sensitivity monitoring data are produced by only a few research groups in industry and academia. The presence of resistant subpopulations at varying proportions is well documented in several plant pathogen species of Oomycetes on a range of crops worldwide (Gisi and Cohen, 1996; Gisi and Sierotzki, 2008; FRAC Resistance Survey List, However, sensitive subpopulations have not disappeared, even though PA-containing products have been used continuously in similar quantities and intensities over the past 30 years. This strongly suggests that the recommended anti-resistance strategies are successful and that biological processes (e.g. sexual reproduction, fitness) of the pathogens may contribute to equilibrate sensitivity in populations. Sampling and testing methods for resistance monitoring have been published through FRAC in 1992 (EPPO Bulletin 22, 297-322) and are still valid.

Sensitivity of field populations


Resistant isolates of Phytophthora infestans and Plasmopara viticola existed at low proportions in wild type populations already before PA fungicides were used commercially (1977/78) suggesting that recurrent mutations give rise to resistant individuals at different locations and time periods (Gisi and Cohen 1996). Resistant isolates have been selected through the use of PAs, increased in frequency, survived during over-wintering periods and migrated to other regions through transport of sporangia in rain droplets and infected plant material (tubers, seedlings). Resistant isolates can compete successfully with sensitive isolates even in the absence of PA treatments. Therefore, resistant isolates can be detected in current field populations that were treated with PAs or remained untreated.

Samples for sensitivity analyses should be taken as early in the epidemic cycle as possible. Those taken towards the end of the season will provide results which are a result of selection, migration, mating and competition occurring during epidemics. As a consequence, resistance frequencies are often overestimated. Standard sensitivity test methods (e.g. leaf disc assay) provide a fully resistant response to PAs (used as active ingredients) when as little as 1% of the sporangia in bulk samples of field populations are resistant (Sozzi et al., 1992). Since sensitivity tests are made with active ingredients of PAs but products are used for disease control in the field in mixture with multi-site fungicides (e.g. dithiocarbamates like mancozeb), there is no direct correlation between sensitivity test results in the laboratory and product performance in the field.

The current sensitivity test methods provide valuable information on the distribution of isolates over a certain time period in a given agronomic area but should not be used to predict product performance. In most cases mixed populations can be controlled adequately by PA-containing products if the proportion of resistant isolates is not too high and if the number of applications is limited (see use recommendations).

There is full cross resistance among all members of PA fungicides but there is no cross resistance between PAs and fungicides of other chemical classes like cyanoacetamide oximes (cymoxanil), QoIs (e.g. azoxystrobin, famoxadone), phosphonates (fosetyl-Al), carboxylic acid amide (CAA) fungicides (dimethomorph, iprovalicarb, mandipropamid), carbamates (propamocarb), dinitroanilines (fluazinam) and multisite inhibitors (e.g. dithiocarbamates like mancozeb).

Potato and tomato late blight (Phytophthora infestans)

The sensitivity of populations fluctuates from year to year and within the season. In many cases, sensitive isolates predominate early and resistant isolates late in the season for both PA-treated and untreated fields. In most countries of Western Europe (e.g. France, UK, Netherlands, Belgium, Germany, Switzerland), the proportion of resistant isolates have remained more or less stable for many years but increased recently again during 2003-2006 reaching high levels (50 to 80%) in 2007, except for Denmark, where it remained low (about 10%). Such results depend very much on the dynamics of epidemics and on when in the season the samples were collected (high frequency of resistance late in the season) and on how many samples were tested (more reliable results when more than 20 samples per agronomic area are tested). Resistance frequencies can change dramatically within few years as it was reported for Israel (Cohen, 2002) and Japan (FRAC), where the proportion of resistant isolates in field populations declined significantly over the last years and was very low in 2006.

Resistant isolates may be present in field populations in high proportions at the end of the season, and may be lower in frequency at the beginning of the next season. Therefore, over several years, resistant isolates may be in a “dynamic equilibrium” with sensitive isolates. Dynamics of resistance evolution are driven not only by selection through PA fungicides; equally important are biological processes during pathogen development (e.g. patchy occurrence of sexual recombination, effective migration of sporangia and infected plant material over large distances and changes in virulence, fitness and aggressiveness). The presence of resistant isolates has been confirmed in all parts of the world but the frequencies in populations are not well documented. The phenotypic and genotypic structures of current field populations suggest that they may emerge from local processes in addition to long distance transport. Isolates with an intermediate response to PAs can emerge through sexual recombination.

There is no genetic linkage between resistance to phenylamides and mating type (A1, A2). Sensitive, intermediate and resistant phenotypes can be represented in both the A1 as well as in the A2 mating types. The proportion of A2 mating type isolates collected from commercial potato fields has been low in many European countries (e.g. UK, France, Germany, Switzerland) until about 2000, whereas in other countries such as Mexico, the Netherlands and Scandinavia it reached 50% and more. However, since about 2004, the proportion of A2 mating type isolates increased significantly in Western Europe (except Denmark where A1 is still frequent) reaching 50 to 90% in 2007. By coincidence, the majority of these A2 isolates were resistant to PA fungicides. In Israel, the A1/A2 proportion changed in the last 30 years from initially almost 100/0 to 0/100 to again 100/0, the majority of recent isolates being A1 and PA-sensitive (Cohen, 2002 and pers. comm.).

On tomatoes in private gardens (e.g. France), the proportion of A2 mating type isolates has been much higher than on potato (Knapova and Gisi, 2002). Although populations from tomato and potato can be separated from each other genotypically (e.g. by SSR markers), there is a certain proportion of overlap in field populations. The aggressiveness of isolates is highest on the host of their origin and can be significantly lower for isolates collected from potato when tested on tomato. Tomato isolates can be rather aggressive on both hosts. Therefore, highly aggressive A2 isolates may jump easily from infected tomato to potato.

In countries outside Europe, e.g. the USA, Mexico and some Asian countries, P. infestans isolates have been tested for sensitivity to PA fungicides, mating type and molecular markers in the 1990’s (e.g. Fry et al., 1993). The “old” genotypes were reported to have been replaced in the USA, Canada and elsewhere by new genotypes (e.g. US 8 genotype, mostly A2 type), as a result of migration and recombination (Godwin et al., 1998). However, no relevant results on sensitivity of population have been published recently.

Major changes in the genotypic structure of P. infestans populations have occurred in Western Europe starting about in 2004. These changes became visible by using new molecular techniques, e.g. SSR (simple sequence repeats) also known as microsatellites (Knapova and Gisi, 2002; Cooke and Lees, 2004; Lees et al., 2006). When isolates collected in Europe in 1997 were compared with isolates from 2007, it can be demonstrated that the “old” A1 SSR genotypes (sensitive or resistant to PAs) significantly declined, two “new” A2 SSR genotypes (PA-resistant) emerged and became dominant (more than 50% in population), but also few PA-sensitive A1 SSR genotypes emerged in the same time period (Syngenta results and results collected by D. Cooke,

It is an ongoing discussion whether today’s P. infestans isolates in Europe are more aggressive than 10 years ago. Although a higher aggressiveness was claimed for recent P. infestans isolates in the Netherlands (e.g. Flier and Turkensteen, 1999), isolates collected in the UK, France and Switzerland in 2006 were not more aggressive than isolates from 1997 and 1979 (Syngenta results).

Several important questions about the driving forces for changes in recent P. infestans populations in Europe are still unsolved, e.g. which are the main selecting forces for new genotypes (cultivars, climate, fungicides?), how important are sexual and parasexual processes, and local and long distance transport (sporangia, infected seed tubers, tomato plants as inoculum)? However, P. infestans populations seem to remain largely clonal.

Grape downy mildew (Plasmopara viticola)

Much less information on resistance to PAs is available for this pathogen compared to P. infestans. In countries where sensitivity analyses have been conducted recently (e.g. France, Switzerland, Spain, Germany), the proportion of resistant P. viticola isolates has remained high (50 – 80%) but more or less stable since many years (Gisi and Sierotzki, 2008). In northern Italy, resistance was reported to be low. In many other countries, PA resistant isolates have been detected, although their proportion is not well documented. Since P. viticola undergoes sexual recombination every winter, the genetic diversity of the primary inoculum is very high (Gobbin et al., 2007) and resistance is inherited according to Mendelian rules, i.e. all F1 progeny isolates are intermediate (i) in sensitivity. The proportion of sensitive, intermediate and resistant isolates in F2 progeny should then be 1 : 2 : 1 (theoretical) but has been observed to be 1 : 3 : 2 (progeny of cross under laboratory conditions) and 1.5 : 2: 1 (selected field populations in France, Gisi et al., 2007). The sensitivity of field populations fluctuates from year to year and within the season (Gisi, 2002). Sensitive, intermediate and resistant isolates can be detected in fields that have been treated with PAs or remained untreated and are often in a “dynamic equilibrium” with each other. In general, the proportion of sensitive isolates declines during the epidemics every year (Gisi and Sierotzki, 2008). Dynamics of resistance evolution are driven not only by the selection through PA fungicides; equally important are the Mendelian type of inheritance and the genetic background of resistance, as well as high fitness and rate of migration of isolates.

Other pathogens:
The presence of resistant isolates in field populations has been confirmed in several other pathogens including Pseudoperonospora cubensis (e.g. Israel, USA, Australia), Peronospora tabacina (e.g. USA), Peronospora pisi (e.g. New Zealand), Bremia lactucae (e.g. USA, UK, Italy), Pythium spp. (turfgrass in USA) and other pathogens on a range of crops in several countries (Gisi 2002; FRAC Resistance Survey List, However, the proportion of resistant isolates in field populations is not well documented. Resistance levels are not uniform and do not necessarily correlate with product performance problems.

Use recommendations

The use recommendations for phenylamide-based products have remained unchanged since 1997. The key guidelines for use are as follows and they may be adapted to local needs:

The general use recommendations for phenylamide-based products have remained unchanged since 1997. The key (“umbrella”) guidelines for product use are as follows, they have to be adapted to local requirements and resistance levels:

1) The phenylamides should be used on a preventive and not curative or eradicative basis.

2) For foliar applications, the phenylamides should be used in pre-packed mixtures with an unrelated effective partner and used in a sound management programme. Where residual partners are used, it is recommended to use between three quarters and full recommended rates. The phenylamide dosage in the mixture depends on its intrinsic activity and is defined by the respective company.

3) The phenylamides should not be used as soil treatments against airborne diseases. When solo formulations are made available for soil use, strategies must be implemented which prevent any possibilities for foliar applications. For seed treatment, mixtures rather than straight phenylamides should be used whenever possible.

4) The number of phenylamide applications should be limited (two to four consecutive applications per crop and year). The application intervals should not exceed 14 days and may be shorter in cases of high disease pressure. If rates and application intervals are reduced, the total amount of the phenylamide fungicide used per season should not exceed that of the full rate, and the total exposure time should remain the same. The rate of the mixing partners should remain the same for both intervals.

5) Phenylamide sprays are recommended early season or during the period of active vegetative growth of the crop. The farmer should switch to non-phenylamide products not later than the normal standard application interval of the non- phenylamide product.

Recent relevant literature

COHEN, Y. 2002. Populations of Phytophthora infestans in Israel underwent three major genetic changes during 1983 – 2000. Phytopathology 92, 300-307. 

COOKE, D.E.L. and LEES, A.K. 2004. Markers, old and new, for examining Phytophthora infestans diversity. Plant Pathology53, 692-704.  

FLIER , WG and TURKENSTEEN LJ. 1999. Foliar aggressiveness of Phytophthora infestans in three potato growing regions in the Netherlands. European Journal of Plant Pathology105, 381-388. 

FRY, W.E. GOODWIN, S.B., DYER, A.T., MATUSZAK, J.M., DRENTH, A., TOOLEY, P.W., SUJKOWSKI, L.S., KOH, Y.J., COHEN, B.A., SPIELMAN, L.J., DEAHL, K.L., INGLIS, D.A. and SANDLAN, K.P. 1993. Historical and recent migrations of Phytophthora infestans: chronology, pathways and implications. Plant Disease77, 653-661.  

GISI, U. 1992. FRAC methods for monitoring the sensitivity of fungal pathogens to phenylamide fungicides. PA-FRAC of GIFAP. U. Gisi, ed., EPPO Bulletin22, 297-322:

Williams, R. and Gisi, U. Monitoring pathogen sensitivity to phenylamide fungicides: principles and interpretation, pp. 299-306.

Sozzi, D., Schwinn, F.J. and Gisi, U. Determination of the sensitivity of Phytophthora infestans to phenylamides: a leaf disc method, pp. 306-309.

Staehle-Csech, U. and Gisi, U. Determination of the sensitivity of Plasmopara viticola to phenylamides, pp. 314-316. 

GISI, U. 2002. Chemical control of downy mildews. pp.119-159 in P.T.N.Spencer, U. Gisi, A. Lebeda, eds., Advances in Downy Mildew Research, Kluwer, Dordrecht.

GISI, U. and COHEN, Y. 1996. Resistance to phenylamide fungicides: A case study with Phytophthora infestans involving mating type and race structure. Annual Review of Phytopathology34, 549-572.

GISI, U. and SIEROTZKI, H. 2008. Fungicide modes of action and resistance in downy mildews. European Journal of Plant Pathology122, 157-167.

GISI, U. and ZIEGLER, H. 2002. Phenylamides (acylalanines and related): Metalaxyl, metalaxyl-M, furalaxyl, benalaxyl, ofurace, oxadixyl. Pp. 609-616 in J.R. Plimmer, ed., Encyclopedia of Agrochemicals, John Wiley, New York.

GISI, U., HERMANN, D., OHL, L. and STEDEN, C. 1997. Sensitivity profiles of Mycosphaerella graminicola and Phytophthora infestans populations to different classes of fungicides. Pesticide Science51, 290-298.

GISI, U., WALDNER, M, KRAUS, N., DUBUIS, P.H. and SIEROTZKI, H. 2007. Inheritance of resistance to carboxylic acid amide (CAA) fungicides in Plasmopara viticola. Plant Pathology56, 199-208.

GOBBIN, D., RUMBOU, A. and GESSLER, C. 2007. Epidemiology and population genetics of grape vine downy mildew. Pp. 205-209 in A. Lebeda and P.T.N. Spencer-Phillips, eds., Advances in Downy Mildew Research, Vol. 3, Proceedings 2 nd International Downy Mildew Symposium, JOLA, Kostelec na Hané, Olomouc, Czech Republic

GOODWIN, S.B., SMART, C.D., SANDROCK, R.W., DEAHL, K.L., PUNJA, Z.K. and FRY, W.E. 1998. Genetic changes within populations of Phytophthora infestans in the United States and Canada during 1994-96: role of migration and recombination. Phytopathology88, 939-949.

KNAPOVA, G. and GISI, U. 2002. Phenotypic and genotypic structure of Phytophthora infestans populations on potato and tomato in France and Switzerland. Plant Pathology51, 641-653.

LEES, A.K., WATTIER, R., SHAW, D.S., SULLIVAN, L., WILLIAMS, N.A. and COOKE, D.E.L. 2006. Novel microsatellite markers for the analysis of Phytophthora infestans populations. Plant Pathology55, 311-319.

MÜLLER, U. and GISI, U. 2007. Newest aspects of nucleic acid synthesis inhibitors – metalaxyl-M. pp. 739-746 in W. Krämer and U. Schirmer, eds., Modern Crop Protection Compounds, Wiley-VCH, Weinheim, Germany.

For further information on phenylamides, contact Dr. Dietrich Hermann, Syngenta Crop Protection AG, Research Biology, WST 540-171, CH-4332 STEIN, Switzerland, Tel.: +41 62 8660159, e-mail:


Dietrich Hermann

Syngenta Crop Protection AG Research Biology
WST 540.1.71
CH 4332 Stein, Switzerland
Tel.: +41 62 8660159
Email: dietrich.hermann@




Copyright FRAC 2005