US Environmental Protection Agency
Office of Pesticide Programs

Petition for Cyazofamid

April 2014


-------
APPLICATION FOR EXTENSION OF EXCLUSIVE USE PERIOD FOR

CYAZOFAMID

DATA SUPPORTING THE REGISTRATIONS OF
CYAZOFAMID TECHNICAL (EPA REGISTRATION NUMBER 71512-2)
RANMAN 400SC (EPA REGISTRATION NUMBER 71512-3)

SUPPORTING MINOR CROPS:

CROP GROUP 5 (BRASSICA (COLE) LEAFY VEGETABLES)
CROP GROUP 8 (FRUITING VEGETABLES) AND OKRA
CROP GROUP 9 (CUCURBITS VEGETABLES)
CARROT

GRAPES (EAST OF ROCKY MOUNTAINS)
TOMATO (GREENHOUSE TRANSPLANT)
SPINACH
HOP

AUTHORS

Melvin D. Grove, Ph.D., Gregory A. Leyes, Ph.D.,
Noriko Nakada, Max Parks, Michael A. Peplowski

SUBMITTER

ISK Biosciences Corporation
7470 Auburn Road, Suite A
Concord, OH 44077

DATE
SEPTEMBER 4, 2013

1


-------
STATEMENT OF NO CLAIM OF CONFIDENTIALITY*

No claim of confidentiality, on any basis whatsoever, is made for any information contained in this
document. I acknowledge that information not designated as within the scope of FIFRA sec. 10(d)(1)(A), (B),
or (C) and which pertains to a registered or previously registered pesticide is not entitled to confidential
treatment and may be released to the public, subject to the provisions regarding disclosure to multinational
entities under FIFRA 10(g).

COMPANY:	ISHIHARA SANGYO KAISHA, LTD.

Gregory A. Leyes

COMPANY AGENT:		

(Submitter)	Typed Name

Agent for ISHIHARA SANGYO KAISHA, LTD.
Vice President, Regulatory Affairs
ISK Biosciences Corporation

Title

* We submitted this material to the United States Environmental Protection Agency specifically under provisions contained in FIFRA as
amended, and thereby consent to use and disclosure of this material by EPA according to FIFRA. Notwithstanding the wording of our marking
{either as "Property of ISK BIOSCIENCES CORPORATION" or "Property of ISHIHARA SANGYO KAISHA, LTD."), this marking by itself conveys no
supplemental claims of confidentiality under FIFRA Sections 10(a) or 10(b). In submitting this material to the EPA according to the method and
format requirements contained in PR Notice 86-5 and PR Notice 2011-3, we do not waive any protection or right involving this material that
would have been claimed by ISK BIOSCIENCES CORPORATION or by ISHIHARA SANGVO KAISHA, LTD. or agents of these companies anywhere
else in the world, if this material had not been submitted to the EPA.

2


-------
COMPLIANCE STATEMENT

ISK Biosciences Corporation

This report is a compilation of information and is not subject to the principles of Good Laboratory Practice
Regulations set forth in Title 40, Part 160 of the Code of Federal Regulations of the United States of
America,

^	-¦ ^

Author

Noriko Nakada

ISK BIOSCIENCES CORPORATION



/ •• . "/

Date

Gregory A -Ceyes

Vice President, Regulatory Affairs
ISK BIOSCIENCES CORPORATION
Agent for STUDY SPONSOR
ISHIHARA SANGYO KAISHA, LTD.





Michael A. Peplowski
Manager, Product Registrations & Quality
Assurance, Regulatory Affairs
ISK BIOSCIENCES CORPORATION, APPLICANT

Dati

¦Tfr/3

T	

3


-------
TABLE OF CONTENTS

TITLE PAGE	1

STATEMENT OF NO CLAIM OF CONFIDENTIALITY	2

COMPLIANCE STATEMENT	3

TABLE OF CONTENTS	4

LIST OF ABBREVIATIONS	6

PURPOSE	7

INTRODUCTION AND BACKGROUND	7

PROFILE FOR CYAZOFAMID	8

RATIONALE AND DISCUSSION SUPPORTING THE EXTENSION REQUEST	10

1.	Minor Uses for Consideration	10

2.	Alternative Fungicides Considered	11

3.	Method Used To Identify Available Resistance Management, Pest Management, and Efficacy Information .... 17

4.	CROP GROUP 5: BRASSICA (COLE) LEAFY VEGETABLES	18

5.	CROP GROUP 8 (FRUITING VEGETABLES) AND OKRA	21

6.	CROP GROUP 9: CUCURBIT VEGETABLES	25

7.	CARROT	28

8.	GRAPE - EAST OF THE ROCKY MOUNTAINS	30

9.	TOMATO GREENHOUSE TRANSPLANT	32

10.	SPINACH	35

11.	HOP	37

CONCLUSIONS	40

REFERENCES	41

1.	FRAC CODE LIST2013: FUNGICIDES SORTED BY MODE OF ACTION, FUNGICIDE RESISTANCE ACTION
COMMITTEE, PAGE 3	42

2.	FRAC LIST OF PLANT PATHOGENIC ORGANISMS RESISTANT TO DISEASE CONTROL AGENTS,

JANUARY 2013, PAGES 9-11	53

3.	DAMICONE, JOHN, AND DAMON SMITH. FUNGICIDE RESISTANCE MANUAL. OKLAHOMA
COOPERATIVE EXTENSION SERVICE, OKLAHOMA STATE UNIVERSITY, PAGE 7	122

4.	BRENT, KEITH J., DEREK W. HOLLMAN. FUNGICIDE RESISTANCE IN CROP PATHOGENS: HOW CAN IT

BE MANAGED? FUNGICIDE RESISTANCE ACTION COMMITTEE, 2007, PAGE 55	131

5.	"ABOUT FRAC." FRAC. FUNGICIDE RESISTANCE ACTION COMMITTEE	191

6.	DU TO IT, LINSEY. PLANT DISEASE: CLUB ROOT OF CABBAGE AND OTHER CRUCIFERS. WASHINGTON
STATE UNIVERSITY EXTENSION. 2004. PAGE 2	194

7.	"MUSTARD GREENS (BRASSICA JUNCEA)-ClUBROOJ." AN ONLINE GUIDE TO PLANT DISEASE
CONTROL, OREGON STATE UNIVERSITY. OREGON STATE UNIVERSITY EXTENSION SERVICE	199

8.	"DISEASES OF CRUCIFERS: CLUBROOT." UNIVERSITY OF RHODE ISLAND LANDSCAPE HORTICULTURE
PROGRAM, GREENSHARE FACTSHEETS. UNIVERSITY OF RHODE ISLAND COOPERATIVE EXTENSION	203

9.	UMASS EXTENSION VEGETABLE PROGRAM	206

10.	APSNET, PHYTOPHTHORA BLIGHT: A SERIOUS THREATTO CUCURBIT INDUSTRIES	209

11.	BRITISH COLUMBIA, AGRICULTURE, PEST MANAGEMENT	222

4


-------
TABLE OF CONTENTS - CONTINUED

12.	VEGETABLE DISEASES CAUSED BY PHYTOPHTHORA CAPSICI IN FLORIDA, PLANT PATHOLOGY FACT
SHEET SP-159	 231

13.	UMASSAMHERST, CENTER FOR AGRICULTURE, UMASSEXTENSION	237

14.	HTTPy/WWW.GRAPES.MSU.EDU/DOWNYMILDEW.HTM 	240

15.	PENNSTATE COLLEGE OF AGRICULTURAL SCIENCES	243

16.	BRITISH COLUMBIA, MINISTRY OF AGRICULTURE, PYTHIUM DISEASES OF GREENHOUSE VEGETABLE
CROPS	246

17.	ONTARIO MINISTRY OF AGRICULTURE, FOOD AND RURAL AFFAIRS	254

18.	CONTROL OF DOWNY MILDEW OF HOPS, PLANT DISEASE/NOVEMBER 1983, PAGES 1183-1185	 256

19.	MANAGING DOWNY MILDEW IN HOPS IN THE NORTHEAST, UNIVERSITY OF VERMONT EXTENSION,

JUNE 2012	 260

20.	UNIVERSITY OF IDAHO, DEPARTMENT OF PLANT, SOIL, & ENTOMOLOGICAL SCIENCES	270

APPENDICES	273

Appendix 1: ISKBC EPA Stamped Label (EPA Reg. No. 71512-3)	274

Appendix 2: FMC Supplemental Label (EPA Reg. No. 71512-3-279)	292

Appendix 3: USDA NASS Information for Cyazofamid Labeled Crops	301

5


-------
LIST OF ABBREVIATIONS

CAA: Carboxylic Acid Amides

EPA: United States Environmental Protection Agency
FRAC: Fungicide Resistance Action Committee
IPM: Integrated Pest Management
PA: Phenylamides

PMSP: Pest Management Strategic Plans
Qol: Quinone Outside Inhibitors
NASS: National Agricultural Statistics Program
USDA: United States Department of Agriculture

6


-------
APPLICATION FOR EXTENSION OF EXCLUSIVE USE PERIOD FOR CYAZOFAMID DATA
SUPPORTING THE REGISTRATION OF CYAZOFAMID TECHNICAL (EPA REG. NO. 71512-2),
AND RANMAN 400SC (EPA REG. NO. 71512-3), A CYAZOFAMID-CONTAINING END-USE PRODUCT

PURPOSE

The purpose of this submission is to support the request of ISK Biosciences Corporation (ISKBC) for the
US Environmental Protection Agency (EPA or the Agency) to extend the exclusive use period for
Cyazofamid data for an additional three years. This request for a three-year extension is based on the
facts that Cyazofamid is registered and marketed for use on more than nine minor crops, these uses
were registered within the required time period, and the registered uses meet one or more of the four
criteria necessary to support the request.

INTRODUCTION AND BACKGROUND

The 1996 Food Quality Protection Act (FQPA) amendments to the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA) provide additional exclusive use data protection for minor use registrations.
FIFRA defines minor use as a use on a crop with acreage of less than 300,000 acres or, in the alternative,
when EPA and the US Department of Agriculture (USDA) determine that a use does not provide sufficient
economic incentive to support the registration of a pesticide for such use. If EPA determines that one of
four statutory criteria below are met by the minor use registrations, the period for exclusive use data
protection can be extended one year for every three minor uses registered during the first seven years of
the original registration. The maximum time period that the exclusive use period can be extended is
three years. The four criteria for extension of the exclusive use period in FIFRA Sec. 3(c)(l)(F)(ii) are:

(I)	there are insufficient efficacious alternative registered pesticides available for the use;

(II)	the alternatives to the minor use pesticide pose greater risks to the environment or human
health;

(III)	the minor use pesticide plays or will play a significant part in managing pest resistance; or

(IV)	the minor use pesticides plays or will play a significant part in an integrated pest
management program.

Before EPA considers any request to extend an exclusive use period, the Agency must determine that
there are, in fact, data entitled to exclusive use. FIFRA and its supporting regulations define data that are
entitled to exclusive use protection. Briefly, exclusive use data are: (1) data that pertain to a new active
ingredient (or new combination of active ingredients) initially registered after September 30, 1978; (2)
the data must have been submitted in support of the first registration of the new active ingredient or an
amendment to add a new use to the initial registration; and (3) the data must not have been submitted
to satisfy a requirement under Section 3(c)(2)(B) of FIFRA.

7


-------
EPA granted the initial registration for the RANMAN 400SC end use product (EPA Reg. No. 71512-3)
containing Cyazofamid on November 12, 2004 and for Technical Cyazofamid (EPA Reg. No. 71512-2) on
November 9, 2004. The initial registration included Cucurbit Vegetables (Crop Group 9); and potatoes
and field tomatoes. Potatoes and tomatoes are not part of the submission supporting the requested
exclusive use period extension. On August 1, 2008, EPA amended the RANMAN 400SC registration to
add Carrot. On July 29, 2009, EPA amended the RANMAN 400SC registration to add Grapes, East of the
Rocky Mountains; and Fruiting Vegetables (Crop Group 8) and Okra. Further, on August 13, 2010, EPA
amended the RANMAN 400SC registration to add Brassica (Cole) Leafy Vegetables (Crop Group 5) and
Turnip Greens; Spinach; and Hops.1 Note that these uses were registered within seven years of the initial
Cyazofamid registration. Minor uses included in the 2004, 2008, 2009 and 2010 registration actions are
thus eligible for consideration in a request to extend the exclusive use period. On September 14, 2012,
EPA further amended the RANMAN 400SC registration to add basil; succulent-podded and succulent-
shelled beans; and expanded label from spinach to leafy greens (Crop Subgroup 4A) including lettuce;
and expanded from potatoes to tuberous and corm vegetables (Crop Subgroup 1C) and expanded
fruiting vegetables crop Group 8 to Group 8-10. However, the crops added in September 14, 2012
amendment are not within the scope of this requested extension of the exclusive use period as the
amendment was not within 7 years of the initial Cyazofamid registration. We will discuss below the
minor crop qualification for extension of the exclusive use period with the crops registered within the
qualified registration period of 7 years from the initial Cyazofamid registration.

Based on these registrations and the data ISKBC submitted to support the registrations, EPA can
conclude that there are data supporting the registration of a new active ingredient first registered after
September 30, 1978 entitled to exclusive use protection. The exclusive use period for Cyazofamid data
currently exists until November 9, 2014. This submission requests that the exclusive use period be
extended through November 9, 2017.

For EPA to grant the requested extension of the exclusive use period, ISKBC must further demonstrate
that the uses registered in 2004, 2008, 2009 and 2010 include the number of minor crops necessary for
the extension, and that the registration of Cyazofamid for use on these minor crops meets one of the
required statutory criteria needed to support the extension of the exclusive use period. The remainder
of this submission documents that the conditions for extending exclusive use have been met.

Profile for Cyazofamid

Cyazofamid is a unique, locally systemic fungicide from a new class of chemistry, the cyanoimidazoles,
and is active at low seasonal use rates for control of late blight, Phytophthora blight, downy mildews,
clubroot, Pythium spp. and white rust in several vegetables, potatoes, carrots, grapes and hops.
Cyazofamid has been proven to kill Oomycete fungi by respiratory inhibition, specifically at Complex III in
the mitochondria of Oomycete fungi. Cyazofamid inhibits Qi (ubiquinone-reducing site) of Complex III of
the said fungi, which has only been reported for one other fungicide (amisulbrom) which is not
registered in the U.S. The unique mode of action of Cyazofamid on these fungi makes Cyazofamid

1 Office of Prevention, Pesticides and Toxic Substances. "RANMAN 400SC EPA Registration No. 71512-3 Issuance and Amendments Accepted
Dated: November 12, 2004, August 1, 2008, July 29, 2009 and August 13, 2010." Environmental Protection Agency, Washington, DC.

8


-------
particularly useful for resistance management to alternate or combine with application of several other
"single-site" fungicides, such as cymoxanil, mandipropamid, fluopicolide, propamocarb HCI, mefenoxam
and dimethomorph which have been registered for use for control of these diseases. This high level of
efficacy and significantly lower seasonal application rate will lead to replacement of older, high use rate
fungicides (such as chlorothalonil, maneb, mancozeb, etc.). Cyazofamid also effectively prevents
infection from Oomycete diseases to the crops listed above and leaves low residue on the crop at
harvest.

The commercial label for an end-use product containing Cyazofamid (i.e., EPA Reg. No. 71512-3-279)
includes resistance management labeling in the directions for use section of the label as recommended
by Pesticide Registration (PR) Notice 2001-5 "Guidance for Pesticide Registrants on Pesticide Resistance
Management Labeling." PR Notice 2001-5 language is most relevant to fungicides that are prone to
developing resistance. Fungicide Resistance Action Committee (FRAC) lists Cyazofamid as "Resistance
risk unknown but assumed to be medium to high (mutations at target site known in model organisms)"
and indicated "Resistance management required." Preventing resistance is important to ISK, and the
resistance language tailored to Cyazofamid is on the label below. In addition, Cyazofamid is an excellent
fit with many Integrated Pest Management (IPM) programs and therefore the IPM language for
Cyazofamid is given below as well.

GROUP 21 FUNGICIDE

RESISTANCE MANAGEMENT

Some plant pathogens are known to develop resistance to products used repeatedly for disease control.
RANMAN 400SC's mode/target site of action is complex III of fungal respiration: ubiquinone reductase, Qi
site, FRAC code 21. A disease management program that includes alternation or tank mixes between
RANMAN 400SC and other labeled fungicides that have a different mode of action and/or control pathogens
not controlled by RANMAN 400SC is essential to prevent disease resistant pathogens populations from
developing. RANMAN 400SC should not be utilized continuously nor tank mixed with fungicides that have
shown to have developed fungal resistance to the target disease.

Since pathogens differ in their potential to develop resistance to fungicides, follow the directions outlined in
the "Directions For Use" section of this label for specific resistance management strategies for each crop.
Consult with your Federal or State Cooperative Extension Service representatives for guidance on the proper
use of RANMAN 400SC in programs that seek to minimize the occurrence of disease

INTEGRATED PEST MANAGEMENT

RANMAN 400SC is an excellent disease control agent when used according to label directions for control of
several Oomycete fungi. Although RANMAN 400SC has limited systemic activity, it should be utilized as a
protectant fungicide and applied before the disease infects the crop. Depending upon the level of disease
pressure, good protection of the crop against disease can be expected over a period of 7 to 10 days. RANMAN
400SC is recommended for use as part of an Integrated Pest Management (IPM) program, which may include
the use of disease-resistant crop varieties, cultural practices, crop rotation, biological disease control agents,
pest scouting and disease forecasting systems aimed at preventing economic pest damage. Practices known to
reduce disease development should be followed. Consult your state cooperative extension service or local
agricultural authorities for additional IPM strategies established in your area. RANMAN 400SC may be used
in State Agricultural Extension advisory (disease forecasting) programs that recommend application timing
based upon environmental factors that favor disease development.

9


-------
RATIONALE AND DISCUSSION SUPPORTING THE EXTENSION REQUEST
1. Minor Uses for Consideration

As stated earlier, EPA registered multiple uses for Cyazofamid on November 12, 2004, followed
by additional crop registrations in August 1, 2008, July 29, 2009, August 13, 2010 and September
14, 2012, although the crops added in September 14, 2012 amendment are not within a scope of
this requested extension of the exclusive use period as the amendment was not within 7 years of
the initial Cyazofamid registration. A copy of the latest EPA-stamped label (i.e., EPA Reg. No.
71512-3) is provided as Appendix 1. FMC Corporation distributes Cyazofamid 400SC for ISKBC.
FMC holds a supplemental registration for RANMAN 400SC (i.e., EPA Reg. No. 71512-3-279). A
copy of the current commercial label is provided as Appendix 22; the label demonstrates that
ISKBC through FMC is marketing Cyazofamid for each of the uses approved by EPA in 2004, 2008,
2009, 2010 and 2012.

ISKBC has verified that 48 crops, specifically in the following crops, meet the less than 300,000
acre criterion and within 7 years period from the initial Cyazofamid registration for classification
as a minor use:

•	18 minor crops listed in Crop Group 5: Brassica (Cole) Leafy Vegetables, including Turnip
Greens (Crop Group 2)

•	11 minor crops listed in Crop Group 8 (Fruiting Vegetables and Okra

•	14 minor crops listed in Crop Group 9: Cucurbit Vegetables

•	Carrot

•	Grape, East of the Rocky Mountains

•	Tomato, Greenhouse Transplant

•	Spinach

•	Hop

ISKBC examined the USDA National Agricultural Statistics Service (NASS) and the OPPTS
Guideline 860.1500 Crop Field Trials to determine the total acreage of all the target crops
planted in the United States.3,4The NASS data is based on the 2007 Census of Agriculture. The
information from these sources is summarized by crop in the discussion sections for each
respective crop or crop group. For crops where there was available data, the major/minor status
was verified. Crops not individually surveyed in the U.S. Census of Agriculture were assumed to
be below the 300,000 acre threshold, and therefore considered minor crops.

2	This label was the most recent label in the marketplace priorto the newest EPA-approved label (i.e., 10/01/12). (Appendix 2)

3	United States, Environmental Protection Agency. Prevention, Pesticides and Toxic Substances. Residue Chemistry Test Guidelines OCSPP
860.1500 Crop Field Trials. Pages 60-62. EPA, August 1996.

4	2007 Census of Agriculture. United States Department of Agriculture, National Agricultural Statistics Service.
http://www.agcensus.usda.gov/Publications/2007/Full Report/usvl.pdf

10


-------
2. Alternative Fungicides Considered

Method for determining Alternative Fungicides

In order to determine the alternative fungicides used on these crops for the target pathogens,
competitor products and labels were evaluated. Sulfur, fumigant, petroleum oil and biological
products were excluded as they were not considered to be viable products based on efficacy or
market penetration, while the remaining products were considered viable alternatives. In
addition, to confirm the competitor products, data from GfK Kynetec5 were reviewed for as
many crops as were available in the database. Based on this research, the alternative fungicides
were divided by crop group and by pathogen, and are listed in Tables 2A through 2H. A brief
discussion for each alternative fungicide is also included. It must be noted that a distinction was
made between fungicides registered for use on various crops for various target pathogens, and
fungicides actually labeled for use on these crops and pathogens. This distinction was made
because, although many fungicides may be registered for specific use sites, they may not
currently be labeled and marketed for those use sites. Many of the documents used to support
this petition refer to and discuss as alternatives fungicides that have been registered with EPA,
but ISK does not believe these can be considered viable alternatives if they are not currently
used or available on the market.

Alternative Fungicides (active ingredients) by Use Sites. Target Pathogens, and FRAC Category
TABLE 2A: CROP GROUP 5 {BRASSICA (COLE) LEAFY VEGETABLES) ALTERNATIVE FUNGICIDES

Path oxen

Active Incredients

FRAC Cateiorv

Clubroot
[Phsmodiophora

brasskae)

Fluazinam

29

Downy mildew
(.Peronospora
parasitica)

Mefenoxam

4

Fenamidone

11

Phosphoric Acid

33

Dimethomorph

40

Mandipropamid

40

Maneb

M3

Chlorothalonil

M5

5 GfK Kynetec, St. Louise, MO.

11


-------
TABLE 2B: CROP GROUP 8 (FRUITING VEGETABLES) AND OKRA ALTERNATIVE FUNGICIDES

Pathogen

Active Ingredients

FRAC Category

Late blight
f.Phytophthora
infestans)

Fenamidone

11

Famoxadone+Cymoxanil

11/27

Fluopicolicle

43

Cuprous Oxide

Ml

Copper Hydroxide

Ml

Copper Sulfate

Ml

Copper Oxych lor ides

Ml

Phytophthora blight
(Phytophthora capsici)

Fenamidone

11

Famoxadorie+Cymoxa n i I

11/27

Mandipropamid

40

Fluopicolide

43

Copper

Ml

Maneb

M3

TABLE 2C: CROP GROUP 9

{CUCURBITS VEGETABLES)

ALTERNATIVE FUNGICIDES

Pathoeen

Active Ingredients

FRAC Cateeorv

Downy mildew
(Pseudoperonospora

cubemis),

Fenamidone

11

Famoxadone+Cymoxanil

11/27

Zoxamide

22

tymoxanil

27

Propamocarb HCI

28

Fosetyl-AI

33

Phosphoric Arid

33

Dimethomorph

40

Fluopicolide

43

Copper

Ml

Copper Hydroxides

Ml

Cuprous Oxide

Ml

Cuprous Oxych loride

Ml

Copper Sulfate

Ml

Mancozeb

M3

Maneb

M3

Chlorothalonil

M5

12


-------
TABLE 2C: CROP GROUP 9 (CUCURBITS VEGETABLES) ALTERNATIVE FUNGICIDES - CONTINUED

Pathogen

Active Ingredients

FRAC Category

Phytophthora blight
(Phytophthora capsici)

Mefenoxam

4

Famoxadone

11

Cymoxanil

27

Phosphorous Acid

33

Dimethomorph

40

Mandipropamid

40

Fluopicolide

43

TABLE 2D; CARROT ALTERNATIVE FUN

GIC1DES

Pathogen

Active Ingredients

FRAC Category

Cavity Spot
(Pythium ultimum)

Mefenoxam

4

Fenamidone

11

Root Oieback (P.
violae, P, sulcatum)

Mefenoxam

4

Forking {P. Irregulate,

P. splendens)

Mefenoxam

4

TABLE 2E: GRAPE, EAST

Of

THE ROCKY MOUNTAINS, A

LTERNATIVE FUNGICIDES

Pathogen

Active Ingredients

FRAC Category

Downy mildew
(;Plasmopara viticola)

Fenamidone

11

Famoxadone+Cymoxanil

11/27

Phosphorous Acid

33

Mandipropamid

40

Fluopicolide

43

Copper Oxychlorides

Ml

Copper Sulfate

Ml

Mancozeb

M3

Ziram

M3

13


-------
TABLE 2F: TOMATO GREENHOUSE TRANSPLANT ALTERNATIVE FUNGICIDES

Pathogen

Active Ingredients

FRAC Category

Pythium Damping off
[Pythium spp.)

Mefenoxam

4

Propamocarb HQ

28

Fosetyl-AI

33

TABLE

?G: SPINACH ALTERNATIVE FUN

GICIDES

Pathogen

Active Ingredients

FRAC Category

White rust
(Albugo occidentalis)

Mefenoxam

4

Aioxystrobin

11

Feriamidone

11

Pyraclostrobin

11

Famoxadone/Cymoxanil

11/27

Fosetyl-AI

33

Copper Hydroxide

Ml

TABL

E 2H: HOP ALTERNATIVE FUNGI

CIDES

Pathogen

Active Ingredients

FRAC Category

Downy mildew
(Pseudoperonospora
humuli)

Mefenoxam

4

Metaiaxyi

4

Famoxadone/Cymoxanil

11/27

Cymoxanil

27

Fosetyl-AI

33

Phosphorous Acid

33

Dimethomorph

40

Mandipropamid

40

Copper Sulfate, Copper
Oxide

Ml

Folpet

M4

14


-------
Alternative Fungicide Profiles

The different use sites and target pathogens of Cyazofamid can be treated (in most cases) with
many common fungicides and classes of fungicides. Below are brief profiles of the different
compounds organized by mode of action and chemical class. This information is provided as
general background information on resistance issues, which will serve as a basis for further
discussion in each crop group section.

Phenvlamides (PA)

The PA fungicide class, which includes mefenoxam (= metalaxyl), has well known resistance
and cross resistance in various Oomycetes, though mechanism is unknown. This class, listed
under FRAC Code 4, has high risk of resistance and has known resistant pathogens.6

Quinone outside Inhibitors (Qol)

Qol fungicides, also known as strobilurins, are "synthetic analogues of a naturally occurring
compound produced by a wood rotting fungus." Qols (FRAC Code 11) share a common anti-
fungal mode of action, inhibiting respiration in cells by targeting the cytochrome bc-1
protein that is encoded by a gene in the mitochondria. Comprised of many fungicides,
including four alternatives to Cyazofamid (azoxystrobin, famoxadone, fenamidone,
pyraclostrobin), Qols are broad spectrum with activity against major fungal pathogens.7
Many have developed a high level of resistance, caused by single mutation (G143A) in the
cytochrome bc-1 gene, and to a lesser extent by single mutation (F129L). FRAC guidelines for
Qols recommend instructions to apply the fungicides at specified intervals, to limit the
number of applications, and to alternate or mix with applications of effective fungicides from
other groups.8 This group has known resistance in various fungal species and cross
resistance is shown between all members of the Qol group. Resistance risk is high and FRAC
has Qol Guidelines for resistance management.9

Toluamides

Toluamides, chemicals of the Benzamide group, which includes zoxamide and are listed
under FRAC Code 22, have low to medium risk of resistance and resistance management is
required. 10

6	FRAC Code List 2013: Fungicides sorted by mode of action, Fungicide Resistance Action Committee. Page 3. (Reference 1) FRAC list of plant
pathogenic organisms resistant to disease control agents, January 2013, Pages 9-11. (Reference 2)

7	Damicone, John, and Damon Smith. Fungicide Resistance Manual. Oklahoma Cooperative Extension Service, Oklahoma State University,

Page 7. (Reference 3)

8	Brent, Keith J., Derek W. Hollman. Fungicide Resistance in Crop Pathogens: How Can It Be Managed? Fungicide Resistance Action Committee,
2007, Page 55. (Reference 4)

9	FRAC Code List 2013 Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 4. (Reference 1)

10	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 3. (Reference 1)

15


-------
Cvanoacetamideoxime

Cyanoacetamideoxime fungicides, which include cymoxanil, listed under FRAC Code 27, have
low to medium risk of resistance and have known resistant pathogens. Resistance
management is required11

Carbamates

Carbamate fungicides, which include propamocarb, are listed under FRAC Code 28 and have
low to medium risk resistance and have known resistant pathogens. Resistance management
is required12

Phosphonates

Phosphonates group (FRAC Code 33), which includes fosetyl-AI and Phosphorous acid/salts,
has few resistance cases reported in few pathogens. This group has low resistance risk but
has known resistant pathogens.13

Carboxvlic Acid Amides (CAA)

CAA fungicides are listed under FRAC Code 40 and include dimethomorph and
mandipropamid. This group has known resistance in Plasmopara viticola but not in
Phytophthora infestans and has low to medium risk of resistance. There are known
pathogens for resistance to this group. Cross resistance exists between all members of the
CAA group. FRAC has resistance management guidelines for CAA fungicides.14

Benzamides

Benzamides fungicides (FRAC Code 43), which include fluopicolide, have no known resistance
or resistant pathogens to date.15

Multi-site contact activity

Some alternatives have multi-site contact modes of actions. Multi-site fungicides interfere
with many metabolic processes of the fungus and are usually protectant fungicides. "Once
taken up by fungal cells, multisite inhibitors act on processes such as general enzyme activity
that disrupt numerous cell functions. Numerous mutations affecting many sites in the fungus
would be necessary for resistance to develop. Typically, these fungicides inhibit spore
germination and must be applied before infection occurs. Multi-site fungicides form a
chemical barrier between the plant and fungus. The risk of resistance to these fungicides is

FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 9. (Reference 1) FRAC list of plant
pathogenic organisms resistant to disease control agents, January 2013, Page 41. (Reference 2)

12	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 6. (Reference 1) FRAC list of plant
pathogenic organisms resistant to disease control agents, January 2013, Page 34. (Reference 2)

13	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 9. (Reference 1) FRAC list of plant
pathogenic organisms resistant to disease control agents, January 2013, Page 41. (Reference 2)

14	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 8. (Reference 1) FRAC list of plant
pathogenic organisms resistant to disease control agents, January 2013, Page 39. (Reference 2)

15	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 3. (Reference 1) FRAC list of plant
pathogenic organisms resistant to disease control agents, January 2013, Page 20. (Reference 2)

16


-------
low."16 Alternative multi-site fungicides include inorganics (various copper salts like copper
hydroxide, copper oxychloride, copper sulfate and cuprous oxide, FRAC Code Ml),
dithiocarbamates (mancozeb and maneb, FRAC Code M3), phthalimides (folpet, FRAC Code
M4), and chlorothalonil (FRAC Code M5). Generally considered as a low resistance risk group,
no signs of resistance to these fungicides have been noted, and there is no known cross
resistance between group members.17

3. Method Used To Identify Available Resistance Management, Pest Management, and
Efficacy Information

In order to determine that Cyazofamid satisfies the statutory criteria for the extension of the
exclusive use period, ISKBC followed a rigorous research and analysis methodology. The process
described below was used to find resistance management, integrated pest management, and
efficacy information for each of the labeled use sites. The findings from this process are detailed
in sections 4 through 11. The various resources provide a significant amount of information to
support that Cyazofamid meets the eligibility criteria for many minor crops.

After having confirmed the acreage and the major/minor crop status in the 2007 Census of
Agriculture and OPPTS 860.1500, the pathogens and alternative fungicides were evaluated for
each individual crop within the group.18 The primary analysis consisted of reviewing three major
documents from the Fungicide Resistance Action Committee: the FRAC Pathogen Risk List
December 2005, the FRAC List of Plant Pathogenic Organisms Resistant to Disease Control Agents
Revised January 2013, and the FRAC Code List 2013: Fungicides sorted by mode of action
(including FRAC Code numbering). The purpose of FRAC is to "provide fungicide resistance
management guidelines to prolong the effectiveness of 'at risk' fungicides and to limit crop
losses should resistance occur."19 The documents provide general information about the risk
levels for certain fungal diseases of developing resistance to individual or certain classes of
fungicides. The relevant information on modes of action and resistance levels for the respective
pathogens and the previously determined alternative active ingredients were extracted and
included in this petition.

16	Damicone, John, and Damon Smith. Fungicide Resistance Manual. Oklahoma Cooperative Extension Service, Oklahoma State University.
Page 3. (Reference 3)

17	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 10. (Reference 1)

18	United States, Environmental Protection Agency. Prevention, Pesticides and Toxic Substances. Residue Chemistry Test Guidelines OCSPP
860.1500 Crop Field Trials. Pages 60-62. EPA, August 1996.

19	"About FRAC." FRAC. Fungicide Resistance Action Committee, http://www.frac.info/frac/index.htm (Reference 5)

17


-------
4. CROP GROUP 5: BRASSICA (COLE) LEAFY VEGETABLES

CYAZOFAMID IS A HIGHLY EFFICACIOUS REGISTERED PESTICIDE AGAINST CLUBROOT AND
DOWNY MILDEW ON BRASSICA AND CYAZOFAMID PLAYS OR WILL PLAY A SIGNIFICANT PART IN
INTEGRATED PEST MANAGEMENT AND MANAGING PEST RESISTANCE TO DOWNY MILDEW AND
CLUBROOT ON BRASSICA

Cyazofamid was registered for use against clubroot (Plasmodiophora brassicae) and downy
mildew (Peronospora parasitica) on 18 minor crops (Table 4A) in Crop Group 5 (Brassica (Cole)
Leafy Vegetables) on August 13, 2010.20 United States Production statistics from USDA NASS for
each of these crops are listed in Appendix 3. The crops for which there is no information in the
NASS database or OPPTS 860.1500 are assumed to be below the 300,000 acre threshold and
thus considered minor crops. The statistics illustrate that the use sites qualify as minor use crops
under the FIFRA Sec. 2 (II). Cyazofamid was registered on Brassica within the first seven years
after the initial registration, and is eligible for extended exclusive use. ISK has evaluated the
literature available on Brassica and alternative pesticides, and believes that there are insufficient
efficacious alternatives available, thus meeting the exclusive use FIFRA Sec. 3(c)(l)(F)(ii) Criterion
I (Insufficient Efficacious Alternatives) for Cyazofamid. In addition, ISK believes that exclusive use
FIFRA Sec. 3(c)(l)(F)(ii) Criteria III (Resistance Management) and IV (Integrated Pest
Management) are met for Cyazofamid as well. All criteria are discussed further below.

Clubroot is a disease that affects most plants in the cruciferous vegetable family (Brassicaceae)
including the 18 minor crops registered for Cyazofamid. The disease is caused by the fungus
Plasmodiophora brassicae producing a resting spore, as well as a motile spore that can swim in
wet soils.21 It can spread by any means that moves soil: wind and water, footwear and
equipment, and in infected transplants. Soils that are cool, wet (70 to 80% water-holding
capacity) and acidic favor the pathogen.22

"It infects susceptible host plants through root hairs. Once in the tissue, it stimulates
abnormal growth of affected parts, resulting in a swollen club. Infection is favored by
excess soil moisture and low pH, although it can occur over a wide range of
conditions. Once a plant is infected, numerous resistant spores of the fungus are
produced in the "clubbed" tissues. As these tissues decay, spores are released into
the soil where they can remain infectious for at least 10 years. Contaminated soil
moved by wind or water can serve as a source of infestation of nearby fields, causing
outbreaks of disease in areas where susceptible crops are planted for the first time.
Numerous races of the pathogen have been identified."23

20Office of Prevention, Pesticides and Toxic Substances. "RANMAN 400SC EPA Registration No. 71512-3 Amendments and Submissions Dated:
August 1, 2008 (Added use for Carrot); July 29, 2009 (Added use for Grapes, East of the Rocky Mountain and Fruiting Vegetables and Okra); and
August 13, 2010 (Added use for Brassica (Cole) Leafy Vegetables, Hops and Spinach.)" Environmental Protection Agency, Washington, DC.

21	Du Toit, Lindsey. Plant Disease: Club Root of Cabbage and Other Crucifers. Washington State University Extension. 2004. Page 2. (Reference 6)

22	"Mustard Greens (Brassica juncea)-Clubroot." An Online Guide to Plant Disease Control, Oregon State University. Oregon State University
Extension Service, Oregon State University, http://pnwhandbooks.org/plantdisease/mustard-greens-brassica-iuncea-clubroot (Reference 7)

23	"Diseases of Crucifers: Clubroot." University of Rhode Island Landscape Horticulture Program, GreenShare Factsheets. University of Rhode
Island Cooperative Extension, http://www.uri.edu/ce/factsheets/prints/clubrootcrucifer.html (Reference 8)

18


-------
Fluazinam is the only alternative fungicide currently labeled for use on clubroot in Brassica.
Fluazinam is a contact, broad-spectrum fungicide, with a unique, multi-site mode of action that is
used to control clubroot on brassica (cole) leafy vegetables, and listed under 2,6-dinitroanilines
FRAC Code 29. Fluazinam has low risk of resistance, but there is resistance claimed in Botrytis in
Japan.24 Cyazofamid is registered and labeled for use against clubroot in 18 Brassica minor crops.
Other than fluazinam, Cyazofamid is the only fungicide registered for use against clubroot in
brassica (cole) vegetables, and therefore satisfies FIFRA exclusive use Criteria I, i.e. "there are
insufficient efficacious alternative registered pesticides available for use".

In regard to FIFRA Sec. 3(c)(l)(F)(ii) Criterion III (Resistance Management),Table 4B below shows
that there is only one other product on the market at this time for the control of clubroot on
Brassica. Therefore, Cyazofamid plays a significant role in managing resistance and therefore
Criterion III (in addition to Criterion I - discussed above) is met for Cyazofamid.

Downy mildew occurs wherever brassica crops are grown and infects cabbage, Brussels
sprouts, cauliflower, broccoli, kale, kohlrabi, Chinese cabbage, turnip, radish, and mustard
as well as cruciferous weed species. The disease caused by Peronospora parasitica is
particularly important on seedlings but can also cause poor growth and reduced yield and
quality of produce at later plant stages.25

Further, as stated in "Profile for Cyazofamid" section, Cyazofamid has IPM language in its label
and is an excellent disease control agent when used according to label directions for control of
downy mildew of brassica leafy vegetables. RANMAN 400SC, formulated commercial product of
Cyazofamid, is recommended for use as part of an IPM program, which may include the use of
disease-resistant crop varieties, cultural practices, crop rotation, biological disease control
agents, pest scouting and disease forecasting systems aimed at preventing economic pest
damage.

Due to unique mode of action, Cyazofamid is an integral part of disease resistance management
through rotation of fungicide with different mode of action.

BRASSICA (COLE) LEAFY VEGETABLES CONCLUSION:

Based on the information presented above, ISKBC believes that Cyazofamid meets FIFRA Sec.
3(c)(l)(F)(ii) Criteria I ("there are insufficient efficacious alternative registered pesticides
available for the use"), III ("the minor use pesticide plays or will play a significant part in
managing pest resistance") and IV ("the minor use pesticide plays or will play a significant part in
an integrated pest management program") for all 18 crops in Crop Group 5 (Brassica (Cole) Leafy
Vegetables) as listed below in Table 4A. Cyazofamid meets these criteria because it has a

24	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 4. (Reference 1)

25	UMass Extension Vegetable Program, https://extension.umass.edu/vegetable/diseases/brassica-downv-mildew (Reference 9)

19


-------
different mode of action, a moderate level of risk of developing resistance in the target
pathogens, and is highly efficacious, particularly when compared to the alternative registered
and marketed fungicides.

TABLE 4A; CYAZOFAMID CROP GROUP 5 (BRASSICA (COLE) LEAFY VEGETABLES)

MINOR CROP QUALIFICATION -18 CROPS QUALIFIED

Commodity

Under 300,000 Acres*"

Broccoli

Yes

Broccoli, Chinese fgai Ion)

Yes

Broccoli, raab (rapini)

Yes

Brussels sprouts

Yes

Cabbage

Yes

Chinese cabbage, (bok choy)

Yes

Chinese cabbage, (napa)

Yes

Chinese mustard cabbage
(gai choy)

Yes

Cauliflower

Yes

Cavalo broccolo

Yes

Collards

Yes

Kale

Yes

Kohlrabi

Yes

Mizuna

Yes

Mustard greens

Yes

Mustard spinach

Yes

Rape greens

Yes

Turnip greens

Yes

*USOA MASS Database, Unless otherwise noted, data retrieved from the 2007 Agricultural Census.

20


-------
TABLE 4B: CYAZOFAMID WILL PLAY A ROLE IN MANAGING PEST RESISTANCE
TO THE ALTERNATIVE ACTIVE INGREDIENTS FOR CLUBROOT AND DOWNY MILDEW TREATMENT

Pathogen

Alternative Active

Ingredients

Competitor FRAC
Category

Alternative
Resistance Risk*

Will Cyazofamid

manage resistance to
this fungicide?* *

Clubroot
(Plasmodiophora
brassicae)

Fluazinam

29

Low

Yes

Downy mildew
(Peronospora

parasitical

Mefenoxam

4

High

Yes

Fenamidone

11

High

Yes

Phosphoric Acid

33

Low

Yes

Dimethomorph

40

Low Medium

Yes

Mandipropamid

40

Low - Medium

Yes

Maneb

M3

Low

No

Chlorotbaloni!

MS

Low

No

* FftAC Code List 2013; Fungicides sorted by mode of action

•• This was determined primarily on the basis of the FRAC codes arid modes of actions for the alternatives: if the risk of resistance (based
on the FRAC code) for an alternative active ingredient is classified as M (multi-site), it was concluded that Cyazofamid would not serve as a
resistance management tool; if the risk of resistance (based on the FRAC code) for an alternative active ingredient was l ow to Medium or
High, Cyazofamid was considered to be a resistance management tool.

5, CROP GROUP B (FRUITING VEGETABLES) AND OKRA

CYAZOFAMID IS A HIGHLY EFFICACIOUS REGISTERED PESTICIDE AGAINST LATE BLIGHT AND
PHYTOPHTHORA ON FRUITING VEGETABLES AMD CYAZOFAMID PLAYS OR WILL PLAY A
SIGNIFICANT PART IN INTEGRATED PEST MANAGEMENT AMD MANAGING PEST RESISTANCE TO
LATE BLIGHT AND PHYTOPHTHORA BLIGHT ON FRUITING VEGETABLES

Cyazofamid was registered for use against late blight (Phytophthora infestans) and Phytophthora
blight (Phytophthora capsici) on a total of 11 minor use crops (Table 5A) in Crop Group 8 and
Okra on July 29, 2009.26 Cyazofamid was registered on the crops within the first seven years
after the initial registration, and therefore is eligible for extended exclusive use. United States
Production statistics from USDA NASS for each of these crops are listed in Appendix 3. The crops
for which there is no information in the NASS database or OPPTS 860.1500 are assumed to be
below the 300,000 acre threshold and thus considered minor crops. The statistics illustrate that
most of the use sites qualify as minor use crops under the statutory definition in FIFRA Sec. 2 (II).
Production of Tomato was 442,425 acres in 2007, thus this crop does not qualify for minor use
criteria, as it exceeds the maximum production limit, but information on the pesticide and
resistance management practices, and pathogen impacts for these crops were researched as
parallel and representative of the other 11 crops, which are eligible for exclusive use

M Office of Prevention, Pesticides and Toxic Substances. "RANMAN 400SC EPA Registration No. 71512-3 Amendments and Submissions Dated:
August 1, 2008 (Added use for Carrot); July 29, 2009 (Added use for Grapes, East of the Rocky Mountain and Fruiting Vegetables and Okra); and
August 13, 2010 (Added use for Brassiea (Cole) Leafy Vegetables, Hops and Spinach.)" Environmental Protection Agency, Washington, DC.

21


-------
consideration. ISK has evaluated the literature available on alternative pesticides, the
representative crops, and the entire crop group, and believes that Cyazofamid meets the
exclusive use criteria III (Resistance Management) and IV (Integrated Pest Management) under
FIFRA Sec. 3(c)(l)(F)(ii).

Cyazofamid is a unique, locally systemic fungicide from a new class of chemistry, the
cyanoimidazoles, having no known resistance risk, though the resistance risk is assumed to be
medium to high.27 As discussed above in Section 1, the label for the end-use product RANMAN
400SC includes resistance management language in the directions for use section. Cyazofamid
can be included in a resistance management rotation with the alternative active ingredients
registered for use on fruiting-vegetables. Table 5B lists the alternative active ingredients with
the corresponding level of resistance risk established by FRAC, and if Cyazofamid serves as a
resistance management tool. Below, a discussion by pathogen illustrates the important role
Cyazofamid plays to manage both Phytophthora infestans and Phytophthora capsici in this crop
group.

Phytophthora infestans

Late blight is caused by the fungus-like Oomycete pathogen, Phytophthora infestans. It can
infect and destroy the leaves, stems, and fruit. Severe late blight epidemics occur when the
pathogen grows and reproduces rapidly host crops. Late blight has the potential to cause
total crop loss.

Aside from Cyazofamid, the currently approved and labeled fungicides in these crop groups
include fenamidone (FRAC Category 11) and famoxadone+cymoxanil (FRAC 11/27) mixture
product which has high resistance risk due to high resistance of famoxadone28. Although
cymoxanil only presents low to medium resistance risk, it is used as mixture with
famoxadone for this fungus so that the resistance risk to the mixture is high. Other
alternatives are Benzamides fungicides (FRAC 43), which include fluopicolide, and various
copper salts like copper hydroxide, copper oxychloride, copper sulfate and cuprous oxide
(FRAC Ml). As was discussed in the alternative fungicide profiles, Benzamides fungicides
have no known resistance or resistant pathogens. In order to limit the potential for
developing resistance to Benzamides fungicides, rotation of fungicides is generally
recommended. Cyazofamid is the only fungicide with moderate resistance risk, other than
various copper salts, registered for Late blight control in fruiting vegetables. Therefore,
Cyazofamid will act as a significant tool in managing the resistance of Phytophthora infestans
in the crops listed within each crop group.

27	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 4. (Reference 1)

28	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 4. (Reference 1)

22


-------
Phytophthora capsici

Phytophthora capsici is an Oomycete plant pathogen that causes Phytophthora blight and
fruit rot of peppers and other important commercial crops. It is highly destructive disease
that can become a serious problem during the period of heavy rainfall; the pathogen can
spread rapidly through the crop resulting in severe losses within a short time. The pathogen
can infect the roots, crown, stem and fruit. The alternatives to Cyazofamid used on Crop
Group 8 (Fruiting vegetables) and Okra, include fenamidone, a Qol fungicide. Classified as
FRAC group 11, Qol fungicides are known to be high risk for resistance and fungicide cross
resistance. 29 In addition to fenamidone, the alternative fungicides include
famoxadone+cymoxanil (FRAC11/27), mandipropamid (FRAC 40), fluopicolide (FRAC 43),
copper (FRAC Ml) and maneb (FRAC M3).

Further, as stated in "Profile for Cyazofamid" section, Cyazofamid has IPM language in its label
and is an excellent disease control agent when used according to label directions for control of
several Oomycete fungi. RANMAN 400SC, formulated commercial product of Cyazofamid, is
recommended for use as part of an IPM program, which may include the use of disease-resistant
crop varieties, cultural practices, crop rotation, biological disease control agents, pest scouting
and disease forecasting systems aimed at preventing economic pest damage.

CROP GROUP 8 AND OKRA CONCLUSION:

Considering the information about the pathogens, the alternative fungicides and the available
crop information, ISKBC believes that Criteria III ("the minor use pesticide plays or will play a
significant part in managing pest resistance") and IV ("the minor use pesticide plays or will play a
significant part in an integrated pest management program") have been met for all of the 10
crops in Table 5A below with less than 300,000 planted acres. Cyazofamid meets this criterion
because it has a different mode of action, a moderate level of risk of developing resistance in the
target pathogens, and is highly efficacious, particularly when analyzed in comparison to the
alternative registered and marketed fungicides.

29 FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 4. (Reference 1)

23


-------
TABLE 5A: CYAZOFAMID CROP GROUP 8 {FRUITING VEGETABLES) AND OfCRA
MINOR CROP QUALIFICATION -11 CROPS QUALIFIED

Commodity

Under 300,000 Acres*

Tomato

No

Eggplant

Yes

Ground cherry

Yes

Okra

Yes

Pepino

Yes

Bell pepper

Yes

Chili pepper

Yes

Cooking pepper

Yes

Pimento

Yes

Sweet pepper

Yes

Tomatillo

Yes

*USDA MASS Database, Unless otherwise noted, data retrieved from the 2007 Agricultural Census,

TABLE SB: CYAZOFAMID WILL PLAY A ROLE IN MANAGING PEST RESISTANCE TO THE ALTERNATIVE

ACTIVE INGREDIENTS

Pathogen

Active Ingredients

FRAC Category

Alternative Resistance
Risk *

Will Cyazofamid
manage resistance
to this
fungicide?**

Late blight
(Phytophthora

infestans)

Fenamidone

11

High

Yes

Famoxadone+Cymoxan if

11/27

Fiigh/l ow Med

Yes

Fluopicolide

43

Resistance not known

Yes

Cuprous Oxide

Ml

Low

No

Copper Hydroxide

Ml

Low

No

Copper Oxychloride

Ml

Low

No

Copper Sulfate

Ml

Low

No

Phytophthora

Blight
(Phytophthora
capsici)

Fenamidone

11

High

Yes

Famoxadone+Cymoxanil

11/27

High/ Low - Medium

Yes

Mandipropamid

40

low - Medium

Yes

Fluopicolide

43

Resistance not known

Yes

Copper

Ml

Low

No

Maneb

M3

Low

No

• FRAC Code list 2013: fungicides sorted by mode of action

** This was determined primarily on the basis of the FRAC codes and mode* of actions for the alternatives: if the risk of resistance {based
on the FRAC code) for an alternative actfwe Ingredient is classified as M (muiti site), it was concluded that Cysurofamid would not serve as a
resistance management tool; if the risk of resistance (based on the FRAC code) for an alternative active ingredient was Low to Medium or
High, Cyazofamld was considered to be a resistance management tool.

24


-------
6. CROP GROUP 9: CUCURBIT VEGETABLES

CYAZOFAMID IS A HIGHLY EFFICACIOUS REGISTERED PESTICIDE AGAINST DOWNY MILDEW AND
PHYTOPHTHORA BLIGHT ON CUCURBIT VEGETABLES AND CYAZOFAMID PLAYS OR WILL PLAY A
SIGNIFICANT PART IN INTEGRATED PEST MANAGEMENT AND MANAGING PEST RESISTANCE TO
DOWNY MILDEW AND PHYTOPHTHORA BLIGHT ON CUCURBIT VEGETABLES

Cyazofamid was registered for use against downy mildew (Pseudoperonospora cubensis) and
Phytophthora blight (Phytophthora capsici) on total of 12 minor crops in Crop Group 9 on
November 12, 2004 and additional 2 minor crops (citron melon and Gherkin) in Crop Group 9
(Table 6A) on August 1, 2008.30 United States Production statistics from USDA NASS for each of
these crops are listed in Appendix 3. The crops for which there is no information in the NASS
database or OPPTS 860.1500 are assumed below the 300,000 acre threshold and thus
considered minor crops. The statistics from the USDA NASS database illustrate that the use sites
qualify as minor use crops under the statutory definition in FIFRA Sec. 2 (II). Cyazofamid was
registered on the crops within the first seven years after the initial registration, and therefore is
eligible for an extended exclusive use period. ISK has evaluated the literature available on
alternative pesticides, the representative crops, and the entire crop group, and believes that
Cyazofamid meets the exclusive use criteria III (Resistance Management) and IV (Integrated Pest
Management) under FIFRA Sec. 3(c)(l)(F)(ii).

Cyazofamid is a unique, locally systemic fungicide from a new class of chemistry, the
cyanoimidazoles, having no known resistance risk, though the resistance risk is assumed to be
medium to high.31 As discussed above in Section 1 above, the label for the end-use product
RANMAN 400SC includes resistance management language in the directions for use section.
Cyazofamid can be included in a resistance management rotation with the alternative active
ingredients registered for use on Crop Group 9, Cucurbit Vegetable, most of which have high
risks of developing resistance other than various copper salts. Table 6B lists the alternative
active ingredients with the corresponding level of resistance risk established by FRAC, and
whether Cyazofamid serves as a resistance management tool. Below, a discussion by pathogen
illustrates the important role Cyazofamid plays to manage both Phytophthora capsici and
Pseudoperonospora cubensis in this crop group.

30	Office of Prevention, Pesticides and Toxic Substances. "RANMAN 400SC EPA Registration No. 71512-3 Amendments and Submissions Dated:
August 1, 2008 (Added use for Carrot); July 29, 2009 (Added use for Grapes, East of the Rocky Mountain and Fruiting Vegetables and Okra); and
August 13, 2010 (Added use for Brassica (Cole) Leafy Vegetables, Hops and Spinach.)" Environmental Protection Agency, Washington, DC.

31	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 4. (Reference 1)

25


-------
Phytophthora capsici

Phytophthora blight of cucurbits is caused by the Oomycete Phytophthora capsici, which
infects more than 50 plant species in more than 15 families, and has become one of the
most serious threats to production of cucurbits and peppers as these are the most
susceptible hosts32. It is a fast spreading, aggressive disease, capable of causing complete
crop failures. The disease has been increasing in severity in the United States in recent years,
where outbreaks have threatened the survival of the processing pumpkin industry33.

The alternatives to Cyazofamid for Phytophthora capsici control are mefenoxam (FRAC
Category 4) and famoxadone+cymoxanil (FRAC 11/27), both of which have high risk of
resistance and cross resistance34. Further, dimethomorph and mandipropamid (FRAC 40) are
also alternatives, which have low to medium resistance risk. Although phosphorous acid
(FRAC 33) and fluopicolide (FRAC 43) are also alternatives with low risk or resistance risk not
known, it is essential that fungicides with different modes of action be rotated to prevent
the buildup of fungicide resistance in Phytophthora capsici.35 As Cyazofamid has a unique
mode of action, it can play a significant role in resistance management in Cucurbit vegetable
crop group.

Pseudoperonospora cubensis

Downy mildew caused by Pseudoperonospora cubensis is one of the most important
foliar diseases of cucurbits. It occurs worldwide where conditions of temperature and
humidity allow its establishment and can result in major losses to cucumber, melon,
squash, pumpkin, watermelon, and other cucurbits. Pseudoperonospora cubensis
infects only members of the cucurbit family and is an obligate parasite. Its survival
depends on the presence of cucurbit hosts, either in climates which permit their
growth year round or in greenhouse culture.36 Since 2004, the resurgence in virulence
has caused growers great concern and substantial economic losses necessitating
increased use of fungicides.

The alternatives to Cyazofamid to control Pseudoperonospora cubensis include famoxadone
(FRAC Category 11) and famoxadone+cymoxanil. FRAC has classified group 11 fungicides as a
class known to be high risk for resistance development and cross resistance occurs between
all members of group 11 fungicides.37 Further, resistance of Pseudoperonospora cubensis to

32	APSnet, Phytophthora Blight: A Serious Threat to Cucurbit Industries.

http://www.apsnet.org/publications/apsnetfeatures/Pages/PhvtophthoraBlight.aspx (Reference 10)

33	British Columbia, Agriculture, Pest Management, http://www.agf.gov.bc.ca/cropprot/pcapsici.htm (Reference 11)

34	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Pages 3, 4 & 9. (Reference 1)

35	Vegetable Diseases Caused by Phytophthora capsici in Florida, Plant Pathology Fact Sheet SP-159 (Reference 12)

36	UmassAmherst, Center for Agriculture, UMassExtension. http://extension.umass.edu/vegetable/diseases/winter-squash-downv-mildew
(Reference 13)

37	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 4. (Reference 1)

26


-------
FRAC 11 fungicides has been identified38 and is of such magnitude that this class of
fungicides is no longer recommended. In addition to the Qol compounds, other fungicides
used for treatments of cucurbit vegetables include zoxamide (FRAC 22), cymoxanil (FRAC 27),
propamocarb HCI (FRAC 28), and dimethomorph (FRAC 40), all of these have low to medium
resistance risk. Fosetyl-AI and phosphorous acid (FRAC 33), fluopicolide (FRAC 43), various
copper salts (FRAC Ml), mancozeb and maneb (FRAC M3) and chlorothalonil (FRAC MS) are
also alternatives and have low or no known resistance risk. With its unique mode of action,
Cyazofamid serves as an effective alternative in resistance management strategies.

In addition to playing a significant role in resistance management, Cyazofamid will also play a
significant role in Integrated Pest Management programs. As stated in "Profile for Cyazofamid"
section, Cyazofamid has IPM language in its label and is an excellent disease control agent when
used according to label directions for control of several Oomycete fungi. RANMAN, formulated
commercial product of Cyazofamid, is recommended for use as part of an IPM program, which
may include the use of disease-resistant crop varieties, cultural practices, crop rotation,
biological disease control agents, pest scouting and disease forecasting systems aimed at
preventing economic pest damage.

CROP GROUP 9 CONCLUSION:

Based on the discussion above, Cyazofamid meets the Criterion III ("the minor use pesticide
plays or will play a significant part in managing pest resistance") and Criterion IV ("the minor use
pesticide plays or will play a significant part in an integrated pest management program") for the
14 crops listed in Table 6A below. Cyazofamid meets these criteria because it has a unique mode
of action, a low to medium level of risk of developing resistance in the target pathogens.

TABLE 6A; CYAZOFAMID CROP GROUP 9 CUCURBIT VEGETABLES MINOR CROP QUALIFICATION -

14 CROPS QUALIFIED

Commodity

Under 300,000 Acres*

Cantaloupe

Yes

Chayote

Yes

Chinese waxgourd (Chinese preserving melon)

Yes

Citron melon

Yes

Cucumber

Yes

Gherkin

Yes

Gourd

Yes

Honeydew melon

Yes

Momordica spp.

Yes

Muskmelon

Yes

Watermelon

Yes

Pumpkin

Yes

Squash

Yes

Zucchini

Yes

~tJSDA MASS Database, Unless otherwise noted, data retrieved from the 200/ Agricultural Census.

** FRAC List af plant pathogenic organisms resistant to disease control agents, January 2013, Page 25. (Reference 2)

27


-------
TABLE 6B: CYAZOFAMID WILL PLAY A ROLE IN MANAGING PEST RESISTANCE
TO THE ALTERNATIVE ACTIVE INGREDIENTS

Pathogen

Active Ingredients

FRAC Category

Alternative
Resistance Risk *

Will Cyazofamld

manage
resistance to this
fungicide?**

Downy mildew
(Pseudoperonospora

cubemis)

Fenamidone

11

High

Yes

Famoxadone+Cymoxanil

11/27

High/Low-Medium

Yes

Zoxamidc

22

Low-Medium

Yes

Cymoxanil

27

Low-Medium

Yes

Proparnocarb HCI

28

Low-Medium

Yes

Fosetyl-Al

33

Low

Yes

Phosphorous Acid

33

Low

Yes

Dimethomorph

40

tow Medium

Yes

Fluopicolide

43

Resistance not known

Yes

Copper

Ml

Low

No

Copper Hydroxide

Ml

Low

No

Copper Oxide

Ml

Low

No

Copper Oxychlorides

Mi

Low

No

Copper Sulfate

Ml

Low

No

Maneb

MB

Low

No

Chlorothalonil

Mi

Low

No

Phytophthora Blight
(Phytophthora

capsici)

Mefenoxam

4

High

Yes

Famoxadone

11

High

Yes

Cymoxanil

27

Low Medium

Yes

Phosphorous Acid

33

Low

Yes

Dimethomorph

40

Low-Medium

Yes

Mandtpropamid

40

Low Medium

Yes

Fluopicolide

43

Resistance not known

Yes

* FRAC Code list 2013: Fungicides sorted by mode of action

•* This was determined primarily on the basis of the FRAC codes and modes of actions for the alternatives: if the risk of resistance {based
on the FRAC code) for an alternate active ingredient is classified as M {multi-site), it was concluded that Cya/ofamid would not serve as a
resistance management tool; if the risk of resistance (based on the FRAC code) for an alternative active ingredient was tow to Medium or
High, Cyarofamid was considered to be a resistance management tool.

7, CARROT

CYAZOFAMID IS A HIGHLY EFFICACIOUS REGISTERED PESTICIDE AGAINST CAVITY SPOT. ROOT
DIEBACK AND FORKING ON CARROT AND CYAZOFAMID PLAYS OR WILL PLAY A SIGNIFICANT
PART IN INTEGRATED PEST MANAGEMENT AND MANAGING PEST RESISTANCE '0 ITY SPOT.
ROOT DIEBACK AND FORKING ON CARROT

28


-------
Cyazofamid was registered for use against 3 fungal diseases (cavity spot, root dieback, and
forking) on Carrot on August 1, 2008.39 United States Carrot Production from USDA NASS was
90,292 acres in 2007, qualifying it as minor crop under FIFRA Sec. 2 (II) (Table 7A). Cyazofamid
was registered on carrot within the first seven years after the initial registration, and is eligible
for extended exclusive use. ISK has evaluated the literature available on carrot and alternative
pesticides, and believes that Cyazofamid meets the exclusive use criteria I (Insufficient
Efficacious Alternatives), III (Resistance Management) and IV (Integrated Pest Management)
under FIFRA Sec. 3(c)(l)(F)(ii).

Carrot diseases caused by Pythium spp. are intractable problems for both growers and scientists.
Carrots may be rejected at grading with only one or two visible lesions or any forking and if
disease incidence exceeds a relatively low threshold it becomes uneconomical to harvest the
crop.

Cyazofamid is registered for use in control of Cavity Spot (Pythium ultimum), Root Dieback (P.
violae, P. sulcatum) and Forking (P. irregulare, P. splendens) in carrot. As shown in Table 7B,
there are only 2 alternatives available for control of these diseases in carrot. Mefenoxam (FRAC
Category 4) is the only other fungicide labeled for all these pathogens in carrot. Other than
mefenoxam, fenamidone (FRAC 11) is labeled for Cavity Spot control in carrot. Both FRAC
Categories 4 and 11 have high risk of resistance and cross resistance40. Cyazofamid is registered
and labeled for use against Cavity Spot, Root Dieback and Forking in carrot and it is highly
efficacious. Therefore, Cyazofamid satisfies FIFRA exclusive use criteria I.

As discussed above in Section 1, the label for the end-use product RANMAN 400SC includes
resistance management language, and Cyazofamid can be included in a resistance management
rotation with the other products labeled for use on carrot. Table 7B lists the alternatives with
the corresponding level of resistance risk established by FRAC, and whether Cyazofamid serves
as a resistance management tool. All the alternatives have high risk of resistance. Cyazofamid
serves as an effective alternative to these compounds in resistance management strategies.

CARROT CONCLUSION:

In addition to the information from FRAC, data have been provided for carrot to demonstrate
that Criterion I ("there are insufficient efficacious alternatives"), Criterion III ("the minor use
pesticide plays or will play a significant part in managing pest resistance") and Criterion IV ("the
minor use pesticide plays or will play a significant part in an integrated pest management
program") have been met. Cyazofamid meets these criteria because it has a different mode of

39	Office of Prevention, Pesticides and Toxic Substances. "RANMAN 400SC EPA Registration No. 71512-3 Amendments and Submissions Dated:
August 1, 2008 (Added use for Carrot); July 29, 2009 (Added use for Grapes, East of the Rocky Mountain and Fruiting Vegetables and Okra); and
August 13, 2010 (Added use for Brassica (Cole) Leafy Vegetables, Hops and Spinach.)" Environmental Protection Agency, Washington, DC.

40	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Pages 3-4. (Reference 1)

29


-------
action and is highly efficacious, particularly when compared to the alternative registered and
marketed fungicides,

TABLE 7A: CYAZOFAMID CARROT, MINOR CROP QUALIFICATION

I Commodity

Acres Below 300,000* 1

| Carrot

Yes |

*USDA NASS Database, Unless otherwise noted, data retrieved from the 2007 Agricultural Census,

TABLE 7B: CYAZOFAMID WILL PLAY A ROLE IN MANAGING PEST RESISTANCE
TO THE ALTERNATIVE ACTIVE INGREDIENTS

Pathogen

Active Ingredients

FRAC Category

Alternative Resistance
Risk*

Will Cyazofamid

manage resistance
to this
fungicide?**

Cavity Spot

(Pythium

ultimum)

Mefenoxam

4

High

Yes

Fenamidone

11

High

Yes

Root Dieback

(P, violae, P.
sulcatum)

Mefenoxam

4

High

Yes

Forking (P.
Irregulate, P.
splendens)

Mefenoxam

4

High

Yes

* FRAC Code List 2013: Fungicides sorted by mode of action

*• This was determined primarily on the basis of the FRAC codes and modes of actions for the alternatives: if the risk of resistance (based
on the FRAC code) for an alternative active ingredient is classified as M (mufti-site), it was concluded that Cyazofamid would not serve as a

resistance management toot; if the risk of resistance (based on the FRAC code) for an alternative active ingredient was Low to Medium or
High, Cyazofamid was considered to be a resistance management tool.

8. GRAPE - EAST OF THE ROCKY MOUNTAINS

CYAZOFAMID IS A HIGHLY EFFICACIOUS REGISTERED PESTICIDE AGAINST DOWNY MILDEW ON
GRAPE EAST OF THE ROCKY MOUNTAIN AND CYAZOFAMID PLAYS OR WILL PLAY A SIGNIFICANT
PART IN INTEGRATED PEST MANAGEMENT AND MANAGING PEST RESISTANCE TO DOWNY
MILDEW ON GRAPE EAST Of THE ROCKY MOUNTAIN

Cyazofamid was registered for use against downy mildew (Plasmopara viticola) on grapes (East

of the Rocky Mountain) on July 29, 2009,41 United States total grape production from USDA NASS
was 1,051,407 acres in 2007 but excluding California State (868,330 acres), Washington State
(61,056 acres) and Oregon State (18,192 acres), grape production area in East of the Rocky
Mountains is 102,829 acres; hence qualifying it as minor crop under FIFRA Sec. 2 (II) (see Table
8A). Cyazofamid was registered on the crop within the first seven years after the initial

" Office of Prevention, Pesticides and Toxic Substances. "RAHMAN 4O0SC EPA Registration No. 71512-3 Amendments and Submissions Dated:
August 1, 2008 (Added use for Carrot); July 29, 2009 (Added use for Grapes, East of the Rocky Mountain and Fruiting Vegetables and Okra); and
August 13, 2010 (Added use for Brassita (Cole) Leafy Vegetables, Hops and Spinach,}"* E nvironmental Protection Agency, Washington, DC.

30


-------
registration, and is eligible for extended exclusive use. ISKBC has evaluated the literature
available on grapes and alternative pesticides, and believes that Cyazofamid meets the exclusive
use criteria III (Resistance Management) and IV (Integrated Pest Management) under FIFRA Sec.
3(c)(l)(F)(ii).

Downy mildew is a widespread, serious disease of grapevines.42 Downy mildew is caused by the
fungus Plasmopara viticola, which overwinters as dormant spores within infected leaves on the
vineyard floor which become active in the spring. The fungus Plasmopara viticola can infect
berries, leaves and young shoots. It occurs wherever it is wet and warm during the growing
season. Fungicides, however, are the most important control measure, especially on susceptible
varieties.43

Alternatives listed in Table 8B include fenamidone (FRAC 11), which has high risk of resistance
development, and famoxadone+cymoxanil (FRAC 11/27), which also have high resistance risk as
a mixture, and mandipropamid (FRAC 40), which has low to medium risk of resistance.
Plasmopara viticola in vines has known resistance to Cyanoacetamideoximes, which include
cymoxanil and CAA fungicides, which includes mandipropamid44. Further, fluopicolide (FRAC 43)
is also an alternative with resistance risk not known. Besides these and various copper salts
(RFAC Ml), phosphorous acid (FRAC 33), mancozeb and ziram (FRAC M3) have low risk of
resistance. Although there are some low resistance risk alternatives or an alternative with no
known resistance risk, rotational use of different mode of action fungicide is an important
practice in resistance management. Cyazofamid can serve as an effective alternative to these
compounds in resistance management strategies.

As discussed above in Section 1, the label for the end-use product RANMAN 400SC includes
resistance management language, and Cyazofamid can be included in a resistance management
rotation with the other products labeled for use on grapes. Table 8B lists the alternatives with
the corresponding level of resistance risk established by FRAC, and whether Cyazofamid serves
as a resistance management tool. All the alternatives have high risk of resistance. Cyazofamid
can serve as an effective alternative to these compounds in resistance management strategies.

GRAPE - EAST OF ROCKY MOUNTAINS CONCLUSION:

Considering the information about the pathogen, the alternative fungicides and the available
crop information, ISKBC believes that Criteria III ("the minor use pesticide plays or will play a
significant part in managing pest resistance") and IV ("the minor use pesticide plays or will play a
significant part in an integrated pest management program") have been met for grapes in East of
Rocky Mountains in Table 8A below with less than 300,000 planted acres. Cyazofamid meets
these criteria because it has a different mode of action, a moderate level of risk of developing
resistance in the target pathogen, and is highly efficacious, particularly when compared to the
alternative registered and marketed fungicides.

42	http://www.grapes.msu.edu/downv mildew.htm (Reference 14)

43	PennState College of Agricultural Sciences, http://agsci.psu.edu/fphg/grapes/disease-descriptions-and-management/downv mildew
(Reference 15)

44	FRAC List of plant pathogenic organisms resistant to disease control agents. January 2013, Pages 39 & 41. (Reference 2)

31


-------
TABLE 8A: CYAZOFAMID GRAPE EAST OF THE ROCKY MOUNTAIN,
MINOR CROP QUALIFICATION

Commodity

Acres Below 300,000*

Grape, East of the Rocky

Mountain

102,829 = 1,051,407 (US total) -
868,330 (California) - 61,056
(Washington) -18,192 (Oregon)

*USDA MASS Database, Unless otherwise noted, data retrieved from the 2007 Agricultural Census.

TABLE SB; CYAZOFAMID WILL PLAY A ROLE IN MANAGING PEST RESISTANCE
TO THE ALTERNATIVE ACTIVE INGREDIENTS

Pathogen

Alternative Active
Ingredients

Competitor FRAC
Category

Alternative Resistance
Risk*

Will Cyazofamld

manage
resistance to this
fungicide?**

Downy mildew
[Plasmopara
viticola)

Fenamidone

11

High

Yes

Famoxadone+Cymoxanil

11/27

High/Low-Medium

Yes

Phosphorous Acid

33

Low

Yes

Mandipropamid

40

Low - Medium

Yes

Fluopicolide

43

Resistance not known

Yes

Copper Oxychlorides

Ml

Low

No

Copper Hydroxide

Ml

Low

No

Copper Sulfate

Ml

Low

No

Mancozeb

M3

Low

No

Ziram

M3

Low

No

* f RAC Code list 2013: Fungicides sorted by mode of action

** This was determined primarily on the basis of the FRAE codes and modes of actions for the alternatives: if the risk of resistance {based
on the FRAC code) for an alternative active ingredient is classified as M {multi-site), it was concluded that Cyazofarmid would not serve as a
resistance management tool; if the risk of resistance {based on the F RAC code) for an alternative active ingredient was Low to Medium or
High, Cyaiofamid was considered to be a resistance management tool.

9. TOMATO GREENHOUSE TRANSPLANT

CYAZOFAMID IS A HIGHLY EFFICACIOUS REGISTERED PESTICIDE AGAINST PHYTHIUM DAMPING-
OFF ON TOMATO GREENHOUSE TRANSPLANT AND CYAZOFAMID PLAYS OR WILL PLAY A
SIGNIFICANT PART IN INTEGRATED PEST MANAGEMENT AND MANAGING PEST RESISTANCE TO
PHYTHIUM DAMPING-OFF ON TOMATO GREENHOUSE TRANSPLANT

32


-------
Cyazofamid was registered for use against Pythium Damping Off (Pythium spp.) on July 29,
2009.45 United States Tomato Greenhouse Transplant Production from USDA NASS was 1,009
acres (43,947,871 sqft) in 2007, qualifying it as minor crop under FIFRA Sec. 2 (II) (see Table 9A).
Cyazofamid was registered on tomato greenhouse transplant within the first seven years after
the initial registration, and is eligible for extended exclusive use. ISK has evaluated the literature
available on tomato greenhouse transplant and alternative pesticides, and believes that
Cyazofamid meets the exclusive use Criteria I (Insufficient Efficacious Alternatives), III (Resistance
Management), and IV (Integrated Pest Management) under FIFRA Sec. 3(c)(l)(F)(ii).

Damping Off (Pythium sppj

Pythium species are fungal-like organisms (Oomycetes), commonly referred to as water molds,
which naturally exist in soil and water as saprophytes, feeding on organic matter. Some Pythium
species can cause serious diseases on greenhouse vegetable crops resulting in significant crop
losses. Pythium infection leads to damping off in seedlings and crown and root rot of mature
plants. In Canada, several Pythium species, including P. aphanidermatum, P. irregulare and P.
ultimum, are known to cause damping-off and crown and root rot in greenhouse cucumber,
pepper and tomato crops. There are no Pythium resistant varieties available although some
varieties may have disease tolerance. Over watering, poor root aeration, root injury and
improper root zone temperatures can weaken the crop and, thus, trigger Pythium outbreaks.
Saturated growing media that are either too cold or too warm can be conducive to Pythium build
up and spread in water and recirculating nutrient solution. Plants grown under optimal
environmental conditions are less susceptible to Pythium than plants grown under poor
conditions.46

There are no marketing data available specifically for greenhouse tomatoes. ISKBC has done a
vigorous search for fungicides used for damping off on greenhouse tomatoes and found a few
alternatives as shown in Table 9B. Resistance and cross resistance are well known in various
Oomycetes with acylalanines chemical group (FRAC Category 4), which includes Mefenoxam, and
has high risk of resistance47. Propamocarb HCI (FRAC 28) has known resistance with Pythium spp.,
particularly in glasshouse48, although general resistance risk is low to medium49. Although
fosetyl-AI has low risk of resistance, rotation of registered fungicides with different chemical
groups is recommended to avoid resistance development in Pythium spp.50 Cyazofamid is

45	Office of Prevention, Pesticides and Toxic Substances. "RANMAN 400SC EPA Registration No. 71512-3 Amendments and Submissions Dated:
August 1, 2008 (Added use for Carrot); July 29, 2009 (Added use for Grapes, East of the Rocky Mountain and Fruiting Vegetables and Okra); and
August 13, 2010 (Added use for Brassica (Cole) Leafy Vegetables, Hops and Spinach.)" Environmental Protection Agency, Washington, DC.

46	British Columbia, Ministry of Agriculture, Pythium Diseases of Greenhouse Vegetable Crops, www.agf.gov.bc.ca/cropprot/pythium.htm
(Reference 16)

47	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 3. (Reference 1)

48	FRAC List of plant pathogenic organisms resistant to disease control agents, January 2013, Page 34. (Reference 2)

49	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Page 6. (Reference 1)

50	British Columbia, Ministry of Agriculture, Pythium Diseases of Greenhouse Vegetable Crops, www.agf.gov.bc.ca/cropprot/pythium.htm
(Reference 16)

33


-------
efficacious against damping-off and can serve as an effective alternative to these compounds in
resistance management strategies.

Further, as stated in "Profile for Cyazofamid" section, Cyazofamid has 1PM language in its label
and is an excellent disease control agent when used according to label directions for control of
several Oomycete fungi. RANMAN 400SC, formulated commercial product of Cyazofamid, is
recommended for use as part of an IPM program, which may include the use of disease-resistant
crop varieties, cultural practices, crop rotation, biological disease control agents, pest scouting
and disease forecasting systems aimed at preventing economic pest damage.

TOMATO GREENHOUSE TRANSPLANT CONCLUSION:

Considering the information about the pathogen, the alternative fungicides and the available
crop information, ISKBC believes that Criteria 1 (Insufficient Efficacious Alternatives), III ("the
minor use pesticide plays or will play a significant part in managing pest resistance") and IV ("the
minor use pesticide plays or will play a significant part in an integrated pest management
program") have been met for tomato greenhouse transplant in Table 9A below with less than
300,000 planted acres. Cyazofamid meets these criteria because it has a different mode of
action, a moderate level of risk of developing resistance in the target pathogen, and is highly
efficacious, particularly when compared to the alternative registered and marketed fungicides.

TABLE 9A: CYAZOFAMID TOMATO GREENHOUSE TRANSPLANT,

MINOR CROP QUALIFICATION

Commodity

Acres Below 300,000*

Tomato Greenhouse

Transplant

Yes

*USDA MASS Database. Unless otherwise noted, data retrieved from the 2007 Agricultural Census.

TABLE 9B: CYAZOFAMID WILL PLAY A ROLE IN MANAGING PEST RESISTANCE
TO THE ALTERNATIVE ACTIVE INGREDIENTS

Pathogen

Alternative Active

Ingredients

Competitor FRAC
Category

Alternative
Resistance Risk*

Will Cyazofamid
manage resistance to

this fungicide?1, *

Pythium

Damping-off
(Pythium spp )

Mefenoxam

4

High

Yes

Proparrtocarb HCI

28

Low - Medium

Yes

Fosetyl-AI

33

Low

Yes

* FRAC Code list 2013: Fungicides sorted by mode of action

" This was determined primarily on the basis of the FRAC codes and modes of actions for the alternatives; if the risk of resistance (based
on the FRAC code) for an alternative active ingredient is classified as M {multi-site}, it was concluded that Cyazofamid would not serve as a
resistance management tool; if the risk of resistance (based on the FRAC code) for an alternative active Ingredient was low to Medium or
High, Cyazofamid was considered to be a resistance management tool.

34


-------
10. SPINACH

CYAZOFAMID IS A HIGHLY EFFICACIOUS REGISTERED PESTICIDE AGAINST WHITE RUST ON
SPINACH AND CYAZOFAMID PLAYS OR WILL PLAY A SIGNIFICANT PART IN INTEGRATED PEST
MANAGEMENT AND MANAGING PEST RESISTANCE TO WHITE RUST ON SPINACH

Cyazofamid was registered for use against white rust (Albugo occidentalis) on spinach on August
13, 2010.51 United States Spinach Production from USDA NASS was 44,071 acres in 2007,
qualifying it as minor crop under FIFRA Sec. 2 (II) (see Table 10A). Cyazofamid was registered on
spinach within the first seven years after the initial registration, and is eligible for extended
exclusive use. ISK has evaluated the literature available on spinach and alternative pesticides,
and believes that Cyazofamid meets the exclusive use criteria III (Resistance Management) and
IV (Integrated Pest Management) under FIFRA Sec. 3(c)(l)(F)(ii).

White rust (Albugo occidentalis) is a major fungal disease of spinach in the United States. When
it does appear it has the potential to cause economic damage by making the spinach
unmarketable. Symptoms of the disease first appear as yellow spots on the upper side of the leaf
similar to downy mildew. However when the leaf is flipped over to expose the underside of the
leaf, a cluster of white pustules are observed instead of a mat of grey or purplish downy growth
as seen in downy mildew.52

Alternatives to Cyazofamid with low resistance risk are very limited (Table 10B). Most of
alternatives have high resistance risk. Mefenoxam (FRAC Category 4) and Qol fungicides (FRAC
11), which include azoxystrobin, fenamidone, pyraclostrobin and famoxadone, have high risk of
resistance and cross resistance within each group.53 Although famoxadone is sold and used as a
mixture with cymoxanil, which has low risk of resistance, due to the high resistance risk of
famoxadone, this mixture would have high resistance risk. Fosetyl-AI and copper hydroxide are
low risk alternatives.

Further, as stated in "Profile for Cyazofamid" section, Cyazofamid has IPM language in its label
and is an excellent disease control agent when used according to label directions for control of
several Oomycete fungi. RANMAN, formulated commercial product of Cyazofamid, is
recommended for use as part of an IPM program, which may include the use of disease-resistant
crop varieties, cultural practices, crop rotation, biological disease control agents, pest scouting
and disease forecasting systems aimed at preventing economic pest damage.

51	Office of Prevention, Pesticides and Toxic Substances. "RANMAN 400SC EPA Registration No. 71512-3 Amendments and Submissions Dated:
August 1, 2008 (Added use for Carrot); July 29, 2009 (Added use for Grapes, East of the Rocky Mountain and Fruiting Vegetables and Okra); and
August 13, 2010 (Added use for Brassica (Cole) Leafy Vegetables, Hops and Spinach.)" Environmental Protection Agency, Washington, DC.

52	Ontario Ministry of Agriculture, Food and Rural Affairs, http://onvegetables.com/2011/05/09/white-rust-in-spinach/ (Reference 17)

53	FRAC Code List 2013: Fungicides sorted by mode of action. Fungicide Resistance Action Committee, Pages 3-4. (Reference 1)

35


-------
SPINACH CONCLUSION;

Considering the information about the pathogen, the alternative fungicides and the available
crop information, ISKBC believes that Criteria III ("the minor use pesticide plays or will play a
significant part in managing pest resistance") and IV ("the minor use pesticide plays or will play a
significant part in an integrated pest management program") have been met for spinach in Table
10A below with less than 300,000 planted acres. Cyazofamid meets these criteria because it has
a different mode of action, a moderate level of risk of developing resistance in the target
pathogen, and is highly efficacious, particularly when compared to the alternative registered and
marketed fungicides.

TABLE 10A: CYAZOFAMID SPINACH, MINOR CROP QUALIFICATION

I Commodity

Acres Below 300,000* 1

I Spinach

Yes 1

*USOA MASS Database. Unless otherwise noted, data retrieved from the 200/ Agricultural Census.

TABLE 10B: CYAZOFAMID WILL PLAY A ROLE IN MANAGING PEST RESISTANCE
TO THE ALTERNATIVE ACTIVE INGREDIENTS

Pathogen

Alternative Active
Ingredients

Competitor FRAC
Category

Alternative
Resistance Risk*

Will Cyazofamid
manage resistance

to this fungicide?**

White Rust

{Albugo
occidentals)

Mefenoxarm

4

High

Yes

Azoxystrobin

11

High

Yes

Fenamidone

11

High

Yes

Pyraclostrobin

11

High

Yes

Famoxadone/Cymoxanil

11/27

High/Low-Medium

Yes

Fosetyl-AI

33

Low

Yes

Copper Hydroxide

Ml

Low

No

* FRAC Code List 2013: Fungicides sorted by mode of action
" This was determined primarily on the basis of the FRAC codes and modes of action', for the alternatives: if the risk of resistance (based on the
FRAC code) for an alternative active ingredient is classified as M (mufti-site), it was concluded that Cyazofamid would not serve as a resistance
management tool; if the risk of resistance {based on the FRAC code) for an alternative active ingredient was Low to Medium or High, Cfazofamtd
was considered to be a resistance management tool.

36


-------
11. HOP

CYAZOFAMID IS A HIGHLY EFFICACIOUS REGISTERED PESTICIDE AGAINST DOWNY MILDEW ON
HOP AND CYAZOFAMID PLAYS OR WILL PLAY A SIGNIFICANT PART IN INTEGRATED PEST
MANAGEMENT AND MANAGING PEST RESISTANCE TO DOWNY MILDEW ON HOP

Cyazofamid was registered for use against downy mildew (Pseudoperonospora humuli) on hop
on August 13, 2008.54 United States Hop Production from USDA NASS was 31,145 acres in 2007,
qualifying it as minor crop under FIFRA Sec. 2 (II) (see Table 11A). Cyazofamid was registered on
hop within the first seven years after the initial registration, and is eligible for extended exclusive
use. ISK has evaluated the literature available on hops and alternative pesticides, and believes
that Cyazofamid meets the exclusive use criteria III (Resistance Management) and IV (Integrated
Pest Management) under FIFRA Sec. 3(c)(l)(F)(ii).

The hop plant (Cumulus lupus L.) is a perennial with clockwise twining vine that dies back to the
ground each year. The male and female flowers are borne on separate plants. The papery bracts
and bracteoles of mature hop corns are used almost exclusively to flavor fermented malt
beverages. Hop downy mildew, caused by Pseudoperonospora humuli (P. humuli) is a major
disease in many hop-growing areas.55 P. humuli is closely related to the downy mildew that we
can find on crops such as cucumbers and watermelons, but is not so closely related that the
downy mildew from squash will infect hops and vice versa. Downy mildew can cause the
complete loss of marketable hop yield, and even hill death in sensitive varieties. It is a very
serious hindrance to successful hops production, but diligent integrated pest management can
help reduce disease infection.56

Losses due to downy mildew occur at several points in the disease cycle. Crown infections can
result in crown rot and plant death. Bud infections do not cause plant death, but do contribute
to poor plant vigor. Vine infections reduce vine before and may spike the growing point
necessitating retraining and increasing labor costs. Downy mildew thrives in environments with
moderate temperature, high humidity, and frequent precipitation. Whenever possible, resistant
varieties should be planted in fields known to have conditions favoring disease development.
Cultural practices that increase air movement, decreases relative humidity, and increase summer
temperatures will also help control downy mildew. When conditions favoring disease
development prevail, cultural practices and plant resistance may fail to provide adequate control.
Under these conditions, chemical fungicides are used for downy mildew control.57

54	Office of Prevention, Pesticides and Toxic Substances. "RANMAN 400SC EPA Registration No. 71512-3 Amendments and Submissions Dated:
August 1, 2008 (Added use for Carrot); July 29, 2009 (Added use for Grapes, East of the Rocky Mountain and Fruiting Vegetables and Okra); and
August 13, 2010 (Added use for Brassica (Cole) Leafy Vegetables, Hops and Spinach.)" Environmental Protection Agency, Washington, DC.

55	Control of Downy Mildew of Hops, Plant Disease/November 1983, Pages 1183-1185. (Reference 18)

56	Managing Downy Mildew in Hops in the Northeast, University of Vermont Extension, June 2012 (Reference 19)

57	University of Idaho, Department of Plant, Soil, & Entomological Sciences.
http://www.cals.uidaho.edU/pses/Research/r ent hoppest downvmildew.htm (Reference 20)

37


-------
Alternatives include mefenoxam (FRAC Category 4) and famoxadone+cymoxanil mixture (FRAC
11/27) which have high resistance risk. Other alternatives are cymoxanil (FRAC 27); fosetyl-al
and phosphorous acid (FRAC 33); dimethomorph and mandipropamid (FRAC 40); copper sulfate
and oxide salts (FRAC Ml); and folpet (FRAC Ml), all of which have low or low to medium
resistance risk. Although Cyazofamid has medium to high resistance risk, it is a good rotation
fungicide to these alternatives (see Table 11B).

Further, as stated in "Profile for Cyazofamid" section, Cyazofamid has IPM language in its label
and is an excellent disease control agent when used according to label directions for control of
several Oomycete fungi. RANMAN, formulated commercial product of Cyazofamid, is
recommended for use as part of an IPM program, which may include the use of disease-resistant
crop varieties, cultural practices, crop rotation, biological disease control agents, pest scouting
and disease forecasting systems aimed at preventing economic pest damage.

HOP CONCLUSION:

Considering the information about the pathogen, the alternative fungicides and the available
crop information, ISKBC believes that Criteria III ("the minor use pesticide plays or will play a
significant part in managing pest resistance") and IV ("the minor use pesticide plays or will play a
significant part in an integrated pest management program") have been met for hop in Table
11A below with less than 300,000 planted acres. Cyazofamid meets these criteria because it has
a different mode of action, a moderate level of risk of developing resistance in the target
pathogen, and is highly efficacious, particularly when analyzed in comparison to the alternative
registered and marketed fungicides.

TABLE 11A: CYAZOFAMID HOP, MINOR CROP QUALIFICATION

I Commodity

Acres Below 300,000* 1

1 Hop

1 Yes 1

*USDA MASS Database. Unless otherwise noted, data retrieved from the 2007 Agricultural Census.

38


-------
TABLE 11B: CYAZOFAMID WILL PLAY A ROLE IN MANAGING PEST RESISTANCE
TO THE ALTERNATIVE ACTIVE INGREDIENTS

Pathogen

Alternative Active
Ingredients

Competitor
FRAC Category

Alternative
Resistance Risk*

Will Cyazofamid
manage resistance
to this fungicide?**

Downy mildew
(Pseudoperonospora
humuli)

Mefenoxam (Metalaxyl)

4

High

Yes

Famoxadone+Cymoxanil

1.1/27

High/Low-
Medium

Yes

Cymoxanil

27

Low - Medium

Yes

Fosetyl-Al

33

Low

Yes

Phosphorous Add

33

low

Yes

Dimethornorph

40

Low - Medium

Yes

Mandipropamid

40

Low - Medium

Yes

Copper Suifate/Oxide

Ml

Low

No

Folpet

M4

Low

No

• FRAC Code List 2013; Fungicides sorted by mode of action

" This was determined primarily on the basis of the FRAC codes and modes of actions for the alternatives: if the risk of resistance {based
on the FRAC code) for an alternative active ingredient is classified as M {multi-site), it was concluded that Cyazofamtd would riot serve as a
resistance management tool; if the risk of resistance (based on the FRAC code) for an alternatiwe active ingredient was Low to Medium or
High, Cfazofamld was considered to be a resistance management tool.

39


-------
CONCLUSIONS

ISKBC, after rigorous review and analysis of many different data sources has confirmed that the following
Cyazofamid minor crops meet the following FIFRA Sec, 3(c)(l)(F)(ii) exclusive use criteria:

CROP

NUMBER OF MINOR USES

EXCLUSIVE USE CRITERIA MET

Crop Group 5 (Brassica (cole)
leafy vegetables)

18 (see Table 4A)

Criteria 1, III and IV

Crop group 8 (FRUTING VEGETABLE)
ANDOkRA

11 (see Table 5A)

Criteria III and IV

Crop group 9
(CUCURBIT VEGETABLE)

14 (see Table 6A)

Criteria III and IV

CARROT

1

Criteria 1, III and IV

GRAPE,EAST OF THE ROCKY
MOUNTAINS

1

Criteria III and IV

TOMAIO GREENHOUSE

TRANSPLANT

1

Criteria I, III and IV

SPINACH

1

Criteria III and IV

HOP

1

Criteria III and IV

FIFRA Sec. 3(c)(l)(F)(ii) states that for each 3 minor uses registered within 7 years of the commencement
of the exclusive use period that 1 additional year (up to a maximum of 3 years) of exclusive use data
protection can be granted assuming that the minor uses meet one of the four exclusive use criteria. The
exclusive use period for Cyazofamid commenced November 9, 2004 when Cyazofamid technical was
registered and all of the above uses were granted on November 12, 2004, August 1, 2008, July 29, 2009
and August 13, 2010, which are within the 7 year requirement. Therefore, all of the uses above are
eligible to be counted towards the three year extension as long as they meet at least one of the exclusive
use criteria. As this document has shown (and as the table above summarizes), all of the uses meet at
least one criteria, which gives a total of 48 minor uses. As only 9 uses are needed to obtain the
maximum of 3 years of exclusive use data protection, ISKBC requests that three years of exclusive use
data protection be granted for the following Cyazofamid registrations: 71512-2 (Cyazofamid Technical)
and 71512-3 (RANMAN 400SC).

40


-------
REFERENCES (ORDER of APPEARANCE)

1.	FRAC Code List 2013: Fungicides sorted by mode of action, Fungicide Resistance Action
Committee, Page 3.

2.	FRAC List of Plant Pathogenic Organisms Resistant to Disease Control Agents, January 2013,

Pages 9-11.

3.	Damicone, John, and Damon Smith. Fungicide Resistance Manual. Oklahoma Cooperative
Extension Service, Oklahoma State University, Page 7.

4.	Brent, Keith J., Derek W. Hollman. Fungicide Resistance in Crop Pathogens: How Can it be
Managed? Fungicide Resistance Action Committee, 2007, Page 55.

5.	"About FRAC." FRAC. Fungicide Resistance Action Committee.

6.	Du Toit, Linsey. Plant Disease: Club Root of Cabbage and Other Crucifers. Washington State
University Extension. 2004. Page 2.

7.	"Mustard Greens (Brassica juncea)-C\ubroot." An Online Guide to Plant Disease Control, Oregon
State University. Oregon State University Extension Service.

8.	"Diseases of Crucifers: Clubroot." University of Rhode Island Landscape Horticulture Program,
GreenShare Factsheets. University of Rhode Island Cooperative Extension.

9.	UMass Extension Vegetable Program.

10.	APSnet, Phytophthora Blight: A Serious Threat to Cucurbit Industries.

11.	British Columbia, Agriculture, Pest Management.

12.	Vegetable Diseases Caused by Phytophthora capsici in Florida, Plant Pathology Fact Sheet SP-159.

13.	UmassAmherst, Center for Agriculture, UMassExtension.

14.	http://www.grapes.msu.edu/downy mildew.htm

15.	PennState College of Agricultural Sciences.

16.	British Columbia, Ministry of Agriculture, Pythium Diseases of Greenhouse Vegetable Crops.

17.	Ontario Ministry of Agriculture, Food and Rural Affairs.

18.	Control of Downy Mildew of Hops, Plant Disease/November 1983, Pages 1183-1185.

19.	Managing Downy Mildew in Hops in the Northeast, University of Vermont Extension, June 2012.

20.	University of Idaho, Department of Plant, Soil, & Entomological Sciences.

41


-------
Reference 1

Footnotes: 6, 9,10,11,12, 13,14,15,17, 24, 27, 28, 29, 31, 34, 37,

40,47,49, and 53

42


-------
FRAC

FUNGICIDE RESISTANCE
ACTION COMMITTEE

FRAC Code List s*2013: Fungicides sorted by mode of action
(including FRAC Code numbering)

INTRODUCTION

The following table lists commercial fungicides according to their mode of action and resistance
risk. The most important bactericides are also included.

The Table headings are defined as:

MOA Code

Different letters (A to I, with added numbers) are used to distinguish fungicide groups according to
their biochemical mode of action (MOA) in the biosynthetic pathways of plant pathogens. The
grouping was made according to processes in the metabolism starting from nucleic acids synthesis
(A) to secondary metabolism, e.g. melanin synthesis (I) at the end of the list, followed by host plant
defence inducers (P), recent molecules with an unknown mode of action and unknown resistance
risk (U, transient status, mostly not longer than 8 years, until information about mode of action and
mechanism of resistance becomes available), and multi-site inhibitors (M).

Target Site and Code

If available, the biochemical mode of action is given. In many cases the precise target site is not
known. However, a grouping can be made due to cross resistance profiles within a group or in
relation to other groups.

Group Name

The Group Names listed are based on chemical relatedness of structures which are accepted in
literature (e.g. The Pesticide Manual). They are based on different sources (chemical structure, site
of action, first important representative in group).

Chemical Group

Grouping is based on chemical considerations. Nomenclature is according to IUPAC and Chemical
Abstract name.

Common name

BSI/ISO accepted (or proposed) common name for an individual active ingredient expected to
appear on the product label as definition of the product.

FRAC Code List® 2013

Page 1 of 10

43


-------
Comments on Resistance

Details are given for the (molecular) mechanism of resistance and the resistance risk. If field
resistance is known to one member of the Group, it is most likely but not exclusively valid that
cross resistance to other group members will be present. There is increasing evidence that the
degree of cross resistance can differ between group members and pathogen species or even within
species. For the latest information on resistance and cross resistance status of a particular pathogen /
fungicide combination, it is advised to contact local FRAC representatives, product manufacturer's
representatives or crop protection advisors. The intrinsic risk for resistance evolution to a given
fungicide group is estimated to be low, medium or high according to the principles described in
FRAC Monographs 1, 2 and 3. Resistance management is driven by intrinsic risk of fungicide,
pathogen risk and agronomic risk (see FRAC pathogen risk list).

Similar classification lists of fungicides have been published by T. Locke on behalf of FRAG - UK
(Fungicide Resistance, August 2001), and by P. Leroux (Classification des fongicides agricoles et
resistance, Phytoma, La Defense des Vegetaux, No. 554, 43-51, November 2002).

FRAC Code

Numbers and letters are used to distinguish the fungicide groups according to their cross resistance
behaviour. The numbers were assigned primarily according to the time of product introduction to
the market. The letters refer to P = host plant defence inducers, M = multi-site inhibitors, and U =
unknown mode of action and unknown resistance risk. Reclassification of compounds based on new
research may result in codes to expire. This is most likely in the U - section when the mode of
actions gets clarified. These codes are not re-used for new groups; a note is added to indicate
reclassification into a new code.

Last update: February 2013

Next update decisions: December 2013

* Disclaimer

The FRAC Code List is the property of FRAC and protected by copyright laws. The FRAC Code
List may be usedfor educational purposes without permission from FRAC. Commercial use of this
material may only be made with the express, prior and written permission of FRAC. Inclusion to the
FRAC Code List is based on scientific evaluation of the mode of action of the active ingredients; it
does not provide any kind of testimonial for the use of a product or a judgement on efficacy.

FRAC Code List® 2013

Page 2 of 10

44


-------
MOA

TARGET SITE
AND CODE

GROUP NAME

CHEMICAL GROUP

COMMON NAME

COMMENTS

FRAC
CODE

CO

"55
a)
.c

A1:

RNA polymerase I

PA - fungicides
(PhenylAmides)

acylalanines

benalaxyl
benalaxyl-M
(=kiralaxyl)
furalaxyl
metalaxyl
metalaxyl-M
(=mefenoxam)

Resistance and cross resistance
well known in various
Oomycetes but mechanism
unknown.

High risk.

See FRAC Phenylamide
Guidelines

4



oxazolidinones

oxadixyl



c

>
(0

(0
T3

O
(0

o

o

o





butyrolactones

ofurace

for resistance management



A2:

adenosin-
deaminase

hydroxy-
(2-amino-)
pyrimidines

hydroxy-
(2-amino-) pyrimidines

bupirimate
dimethirimol
ethirimol

Medium risk Resistance and
cross resistance known in

powdery mildews.
Resistance management
required.

8

3
C

<

A3:

heteroaromatics

isoxazoles

hymexazole

Resistance not known.

32



DNA/RNA synthesis
(proposed)

isothiazolones

octhilinone



A4:

DNA topoisomerase
type II (gyrase)

carboxylic acids

carboxylic acids

oxolinic acid

Bactericide. Resistance known.
Risk in fungi unknown.
Resistance management
required.

31



B1:

MBC -

fungicides
(Methyl
Benzimidazole
Carbamates)

benzimidazoles

benomyl
carbendazim
fuberidazole
thiabendazole

Resistance common in many
fungal species. Several target

site mutations, mostly
E198A/G/K, F200Y in (B-tubulin
gene.



C

o
"55
¦>

B-tubuline
assembly in mitosis

thiophanates

thiophanate
thiophanate-methyl

Positive cross resistance
between the group members.
Negative cross resistance to N-
Phenylcarbamates.

High risk. See FRAC
Benzimidazole Guidelines
for resistance management.

1

"D

a)
o

T3

c

(0

B2:

B-tubulin
assembly in mitosis

N-phenyl
carbamates

N-phenyl
carbamates

diethofencarb

Resistance known. Target site
mutation E198K. Negative cross
resistance to benzimidazoles.
High risk. Resistance
management required.

10

CO

"55
o

E

(id

B3:

benzamides

toluamides

zoxamide

Low to medium risk.
Resistance management
required.

22

B-tubulin assembly
in mitosis

thiazole
carboxamide

ethylamino-thiazole
carboxamide

ethaboxam



B4:













cell division

phenylureas

phenylureas

pencycuron

Resistance not known

20



(proposed)













B5:













delocalisation of
spectrin-like
proteins

benzamides

pyridinylmethyl-
benzamides

fluopicolide

Resistance not known

43

FRAC Code List® 2013

Page 3 of 10

45


-------
MOA

TARGET SITE
AND CODE

GROUP NAME

CHEMICAL GROUP

COMMON NAME

COMMENTS

FRAC
CODE



C1:

pyrimidinamines

pyrimidinamines

diflumetorim

Resistance not known.

39



complex I NADH
Oxido-reductase

pyrazole-MET1

pyrazole-5-
carboxamides

tolfenpyrad







phenyl-benzamides

benodanil

flutolanil

mepronil











phenyl-oxo-ethyl
thiophene amide

isofetamid

Resistance known for several









pyridinyl-ethyl-
benzamides

fluopyram

fungal species in field
populations and lab mutants.
Target site mutations in sdh
gene, e.g. H/Y (or H/L) at 257,
267, 272 or P225L, dependent
on fungal species.
Resistance management
required.

Medium to high risk.

See FRAC SDHI Guidelines
for resistance management.









furan- carboxamides

fenfuram





C2:

SDHI (Succinate

oxathiin-
carboxamides

carboxin
oxycarboxin





complex II:
succinate-dehydro-

dehydrogenase
inhibitors)

thiazole-
carboxamides

thifluzamide

7



genase



pyrazole-4-
carboxamides

benzovindiflupyr
bixafen
fluxapyroxad
furametpyr
isopyrazam
penflufen
penthiopyrad
sedaxane



C. respiration





pyridine-
carboxamides

boscalid









methoxy-acrylates

azoxystrobin
coumoxystrobin
enoxastrobin
flufenoxystrobin
picoxystrobin
pyraoxystrobin

Resistance known in various
fungal species. Target site
mutations in cyt b gene (G143A,



C3:

complex III:
cytochrome bc1
(ubiquinol oxidase)
at Qo site (cyt b
gene)

Qol-fungicides
(Quinone outside
Inhibitors)

methoxy-carbamates

pyraclostrobin
pyrametostrobin
triclopyricarb

F129L) and additional
mechanisms.

Cross resistance shown
between all members of the Qol





oximino acetates

kresoxim-methyl
trifloxystrobin

11



oximino-acetamides

dimoxystrobin
fenaminstrobin
metominostrobin
orysastrobin

group.

High risk.

See FRAC Qol Guidelines
for resistance management.









oxazolidine-diones

famoxadone









dihydro-dioxazines

fluoxastrobin









Imidazolinones

fenamidone











benzyl-carbamates

pyribencarb







C4:

complex III:

Qil - fungicides
(Quinone inside
Inhibitors)

cyano- imidazole

cyazofamid

Resistance risk unknown but
assumed to be medium to high
(mutations at target site known

21



cytochrome
bc1 (ubiquinone
reductase) at Qi site

sulfamoyl-triazole

amisulbrom

in model organisms).
Resistance management
required.



C5:

uncouplers of
oxidative phos-
phorylation



dinitrophenyl
crotonates

binapacryl
meptyldinocap
dinocap

Resistance not known.
Also acaricidal activity.

29





2,6-dinitro-
anilines

fluazinam

Low risk. However, resistance
claimed in Botrytis in Japan.





(pyr.-hydrazones)

(ferimzone)

Reclassified to U 14 in 2012.



FRAC Code List® 2013

Page 4 of 10

46


-------
MOA

TARGET SITE
AND CODE

GROUP NAME

CHEMICAL GROUP

COMMON NAME

COMMENTS

FRAC
CODE

C: respiration (continued)

C6:

inhibitors of
oxidative phos-
phorylation, ATP
synthase

organo tin
compounds

tri phenyl tin
compounds

fentin acetate
fentin chloride
fentin hydroxide

Some resistance cases
known. Low to medium risk.

30

C7:

ATP production
(proposed)

thiophene-
carboxamides

thiophene-
carboxamides

silthiofam

Resistance reported. Risk low.

38

C8:

complex III:
cytochrome bc1
(ubiquinone
reductase) at
Q x (unknown) site

Qxl - fungicide

(Quinone x
Inhibitor)

triazolo-pyrimidylamine

ametoctradin

Resistance risk assumed to
be medium to high
(single site inhibitor).
Resistance management
required.

45

D: amino acids and protein synthesis

D1:

methionine
biosynthesis
(proposed)
(cgs gene)

AP - fungicides
(Anilino-
Pyrimidines)

anilino-pyrimidines

cyprodinil
mepanipyrim
pyrimethanil

Resistance known in Botrytis
and Venturis, sporadically in
Oculimacula.

Medium risk.
See FRAC Anilinopyrimidine

Guidelines
for resistance management.

9

D2:

protein synthesis

enopyranuronic
acid antibiotic

enopyranuronic acid
antibiotic

blasticidin-S

Low to medium risk.
Resistance management
required.

23

D3:

protein synthesis

hexopyranosyl
antibiotic

hexopyranosyl
antibiotic

kasugamycin

Resistance known in fungal
and bacterial (P. glumae)
pathogens. Medium risk.
Resistance management
required.

24

D4:

protein synthesis

glucopyranosyl
antibiotic

glucopyranosyl
antibiotic

streptomycin

Bactericide. Resistance

known. High risk.
Resistance management
required.

25

D5:

protein synthesis

tetracycline
antibiotic

tetracycline antibiotic

oxytetracycline

Bactericide. Resistance

known. High risk.
Resistance management
required.

41

E: signal transduction

E1:

signal transduction
(mechanism
unknown)

aza-
naphthalenes

aryloxyquinoline

quinoxyfen

Resistance to quinoxyfen

known. Medium risk.
Resistance management
required. Cross resistance
found in Erysiphe (Uncinula)
necator but not in Blumeria
graminis.

13

quinazolinone

proquinazid

E2:

MAP/Histidine-
Kinase in osmotic
signal transduction
(os-2, HOG1)

PP-fungicides
(PhenylPyrroles)

phenylpyrroles

fenpiclonil
fludioxonil

Resistance found sporadically,
mechanism speculative.

Low to medium risk.
Resistance management
required.

12

FRAC Code List® 2013

Page 5 of 10

47


-------
MOA

TARGET SITE
AND CODE

GROUP NAME

CHEMICAL GROUP

COMMON NAME

COMMENTS

FRAC
CODE

E: signal

transduction (continued)

E3:

MAP/Histidine-
Kinase in osmotic
signal transduction
(os-1, Dafl)

dicarboximides

dicarboximides

chlozolinate
iprodione
procymidone
vinclozolin

Resistance common in Botrytis
and some other pathogens.
Several mutations in OS-1,
mostly I365S.

Cross resistance common
between the group members.

Medium to high risk.
See FRAC Dicarboximide

Guidelines
for resistance management.

2



F1:

formerly
dicarboximides











F2:

phospholipid
biosynthesis,
methyltrans-ferase

phosphoro-
thiolates

phosphoro-thiolates

edifenphos
iprobenfos (IBP)
pyrazophos

Resistance known in specific
fungi. Low to medium risk.
Resistance management
required if used for risky
pathogens.

6

>

'E

O)
a)

c

a)
c

(0

dithiolanes

Dithiolanes

isoprothiolane

F3:

lipid peroxidation
(proposed)

AH-fungicides

(Aromatic
Hydrocarbons)
(chlorophenyls,
nitroanilines)

aromatic hydrocarbons

biphenyl
chloroneb
dicloran
quintozene (PCNB)
tecnazene (TCNB)
tolclofos-methyl

Resistance known in some
fungi.

Low to medium risk.
Cross resistance patterns
complex due to different
activity spectra.

14

n

E
a)

F

heteroaromatics

1,2,4-thiadiazoles

etridiazole



T3
C
(0

(0

"55
a)
.c

c

>
(0

T3

a

F4:

cell membrane
permeability, fatty
acids (proposed)

carbamates

Carbamates

iodocarb
propamocarb
prothiocarb

Low to medium risk.
Resistance management
required.

28

F5:

formerly CAA-

fungicides















Bacillus
amyloliquefaciens
strain QST713





LL

F6:

microbial disrupters
of pathogen cell
membranes

microbial

Bacillus sp. and the
fungicidal lipopeptides
produced

Bacillus
amyloliquefaciens
strain FZB24

Resistance not known.

44



(Bacillus sp.)

Bacillus
amyloliquefaciens
strain MBI600

Induction of host plant defence
described as additional mode
of action for strain FZB24









Bacillus
amyloliquefaciens
strain D747







F7:

cell membrane
disruption
(proposed)

plant extract

terpene hydrocarbons
and terpene alcohols

extract from
Melaleuca alternifolia
(tea tree)

Resistance not known

46

FRAC Code List® 2013

Page 6 of 10

48


-------
MOA

TARGET SITE
AND CODE

GROUP NAME

CHEMICAL GROUP

COMMON NAME

COMMENTS

FRAC
CODE







piperazines

triforine











pyridines

pyrifenox
pyrisoxazole











pyrimidines

fenarimol
nuarimol

There are big differences in the
activity spectra of DMI
fungicides.

Resistance is known in various









imidazoles

imazalil
oxpoconazole
pefurazoate
prochloraz
triflumizole



G: sterol biosynthesis in membranes

G1:

C14- demethylase
in sterol
biosynthesis
(erg11/cyp51)

DMI-fungicides
(DeMethylation
Inhibitors)

(SBI: Class I)

triazoles
triazolinthiones

azaconazole

bitertanol
bromuconazole
cyproconazole
difenoconazole
diniconazole
epoxiconazole
etaconazole
fenbuconazole
fluquinconazole
flusilazole
flutriafol
hexaconazole
imibenconazole
ipconazole
metconazole
myclobutanil
penconazole
propiconazole
simeconazole
tebuconazole
tetraconazole
triadimefon
triadimenol
triticonazole
prothioconazole

fungal species. Several
resistance mechanisms are
known incl. target site mutations

in cyp51 (erg 11) gene, e.g.
V136A, Y137F, A379G, 1381V;
cyp51 promotor; ABC
transporters and others.

Generally wise to accept that
cross resistance is present
between DMI fungicides active
against the same fungus.

DMI fungicides are Sterol
Biosynthesis Inhibitors (SBIs),
but show no cross resistance to
other SBI classes.

Medium risk.

See FRAC SBI Guidelines
for resistance management.

3

G2:

A1 ^reductase
and
A8->A7-
isomerase
in sterol
biosynthesis
(erg24, erg2)

amines

morpholines

aldimorph
dodemorph
fenpropimorph
tridemorph

Decreased sensitivity for

powdery mildews.

Cross resistance within the
group generally found but not to





("morpholines")
(SBI: Class II)

piperidines

fenpropidin
piperalin

other
SBI classes.

5





spiroketal-amines

spiroxamine

Low to medium risk.
See FRAC SBI Guidelines
for resistance management.





G3:

3-keto reduc-tase,
C4- de-methylation
(erg27)

(SBI: Class III)

hydroxyanilides

fenhexamid

Low to medium risk.
Resistance management
required.

17



amino-pyrazolinone

fenpyrazamine



G4:

squalene-epoxidase

(SBI class IV)

thiocarbamates

pyributicarb

Resistance not known,
fungicidal and herbicidal activity

18



in sterol
biosynthesis
(erg1)

allylamines

naftifine
terbinafine

Medical fungicides only

FRAC Code List® 2013

Page 7 of 10

49


-------
MOA

TARGET SITE
AND CODE

GROUP NAME

CHEMICAL GROUP

COMMON NAME

COMMENTS

FRAC
CODE

H: cell wall biosynthesis

H3:

trehalase and
inositol-biosynthesis

glucopyranosyl
antibiotic

glucopyranosyl
antibiotic

validamycin

Resistance not known

26

H4:

chitin synthase

polyoxins

peptidyl pyrimidine
nucleoside

polyoxin

Resistance known.
Medium risk.
Resistance management
required.

19

H5:

cellulose synthase

CAA-fungicides
(Carboxylic Acid
Amides)

cinnamic acid amides

dimethomorph
flumorph
pyrimorph

Resistance known in
Plasmopara viticola but not in

Phytophthora infestans.
Cross resistance between all
members of the CM group.
Low to medium risk.
See FRAC CAA Guidelines for
resistance management

40

valinamide
carbamates

benthiavalicarb
iprovalicarb
valifenalate

mandelic acid amides

mandipropamid

1: melanin synthesis in
cell wall

11:

reductase in

melanin
biosynthesis

MBI-R

(Melanin
Biosynthesis
Inhibitors -
Reductase)

isobenzo-furanone

fthalide

Resistance not known

16.1

pyrrolo-quinolinone

pyroquilon

triazolobenzo-
thiazole

tricyclazole

12:

dehydratase in

melanin
biosynthesis

MBI-D

(Melanin
Biosynthesis
Inhibitors -
Dehydratase)

cyclopropane-
carboxamide

carpropamid

Resistance known.
Medium risk.
Resistance management
required.

16.2

carboxamide

diclocymet

propionamide

fenoxanil

P: host plant defence induction

P1:

salicylic acid
pathway

benzo-
thiadiazole
BTH

benzo-thiadiazole
BTH

acibenzolar-S-
methyl

Resistance not known

P

P2

benzisothiazole

benzisothiazole

probenazole
(also antibacterial
and antifungal
activity)

Resistance not known

P3

thiadiazole-
carboxamide

thiadiazole-
carboxamide

tiadinil
isotianil

Resistance not known

P4

natural
compound

polysaccharides

laminarin

Resistance not known

P5

plant extract

complex mixture,
ethanol extract

extract from
Reynoutria
sachalinensis
(giant knotweed)

Resistance not known

FRAC Code List® 2013

Page 8 of 10

50


-------
MOA

TARGET SITE
AND CODE

GROUP NAME

CHEMICAL GROUP

COMMON NAME

COMMENTS

FRAC
CODE

Unknown mode of action

(U numbers not appearing in the list derive from reclassified fungicides)

unknown

cyanoacetamide-
oxime

cyanoacetamide-
oxime

cymoxanil

Resistance claims described.
Low to medium risk.
Resistance management
required.

27

unknown

phosphonates

ethyl phosphonates

fosetyl-AI

Few resistance cases reported
in few pathogens.
Low risk

33



phophorous acid
and salts

unknown

phthalamic acids

phthalamic acids

teclofthalam
(Bactericide)

Resistance not known

34

unknown

benzotriazines

benzotriazines

triazoxide

Resistance not known

35

unknown

benzene-
sulfonamides

benzene-
sulphonamides

flusulfamide

Resistance not known

36

unknown

pyridazinones

pyridazinones

diclomezine

Resistance not known

37

unknown

thiocarbamate

thiocarbamate

methasulfocarb

Resistance not known

42

unknown

phenyl-
acetamide

phenyl-acetamide

cyflufenamid

Resistance in Sphaerotheca.
Resistance management
required

U6

actin disruption
(proposed)

aryl-phenyl-
ketone

benzophenone

metrafenone

Less sensitive isolates detected
in wheat powdery mildew.

Medium risk.
Resistance management
required.

U8

benzoylpyridine

pyriofenone

Cell membrane
disruption
(proposed)

guanidines

guanidines

dodine

Resistance known in
Venturia inaequalis.
Low to medium risk.
Resistance management
recommended.

U12

unknown

thiazolidine

cyano-methylene-
thiazolidine

flutianil

Resistance not known

U13

unknown

pyrimidinone-
hydrazones

pyrimidinone-
hydrazones

ferimzone

Resistance not known
Reclassified from C5 in 2012

U14

not
clas-
si-
fied

unknown

diverse

diverse

mineral oils,
organic oils,
potassium
bicarbonate,
material of
biological origin

Resistance not known

NC

FRAC Code List® 2013

Page 9 of 10

51


-------
MOA

TARGET SITE
AND CODE

GROUP NAME

CHEMICAL GROUP

COMMON NAME

COMMENTS

FRAC
CODE





inorganic

inorganic

copper
(different salts)



M1





inorganic

inorganic

sulphur



M2





dithiocarbamates
and relatives

dithio-carbamates
and relatives

ferbam
mancozeb
maneb
metiram
propineb
thiram
zineb
ziram



M3

>

>
"5

O
(0



phthalimides

phthalimides

captan
captafol
folpet

Generally considered as a low
risk group without any signs of
resistance developing to the
fungicides

M4

+•>
o
(0

c

multi-site
contact
activity

chloronitriles
(phthalonitriles)

chloronitriles
(phthalonitriles)

chlorothalonil

M5

o

o

a)

sulfamides

sulfamides

dichlofluanid
tolylfluanid

M6

CO
"5
3



guanidines

guanidines

guazatine
iminoctadine



M7





triazines

triazines

anilazine



M8





quinones
(anthraquinones)

quinones
(anthra-quinones)

dithianon



M9





quinoxalines

quinoxalines

chinomethionat/
quinomethionate



M10





maleimide

maleimide

fluoroimide



M11

FRAC Code List® 2013

Page 10 of 10

52


-------
Reference 2

Footnotes; 6,11,12,13,14,15, 38,44, and 48

53


-------
FRAC

FUNGICIDE RESISTANCE

ACTION COMMITTEE

FRAC

LIST OF PLANT PATHOGENIC
ORGANISMS RESISTANT TO DISEASE

CONTROL AGENTS

Revised January 2013

Source: www.frac.info
January 2013

54


-------
Important notes

The scope of the list.

The FRAC codes used in this document refer to those used in the FRAC Code List. The entries are listed by their Mode of Action code, with the
Chemical Group Codes and Group Names also being given for reference. For more information please refer to the latest edition of the FRAC
Code list.

This list is extensive in identifying those plant pathogens that have shown some form of resistance to the modes of action given and to the
respective chemical groups. Where a FRAC Code is not listed, no resistance has been reported.

Entries have generally been selected as the first confirmed, published, case of resistance of the particular mode of action against the pathogen
listed. Subsequent references for the same mode of action and host-pathogen combination are only included if the information is considered by
FRAC to be of special merit e.g. information on the molecular mode of resistance. Inclusion of cases of a known pathogen but a new host e.g.
Botrytis cinerea are considered on their merits. Similarly, references reporting a known case but in a different geographical region are also
considered on merit and may not be included.

Take care in using this list.

Care must be taken in using the information because:

1.	Inclusion of a pathogen in this list only demonstrates that it can become resistant. It does not indicate that pathogen populations in specific
geographical areas or locations are resistant. Seek local advice for specific localities. Information may also be found at the FRAC web page for
specific chemical Working Groups. See www.frac.info

2.	Resistance in plant pathogens can take many forms and it is important to realise the differences when consulting this list. The 'Remarks'
column gives guidance on the form of resistance found and can be interpreted as:

Source: www.frac.info
January 2013

55


-------
Laboratory mutation / selection. Indicates that the resistance has been selected for using various techniques including mutation by UV
light, or chemical mutagenesis. Such research illustrates that resistance can happen and can provide information on the resistance mechanism,
but is not a reliable indicator of the probability that resistance will happen when the chemical is used in the field.

Field trial: Indicates that resistance has been found in limited field trials. Very often such trials use application schedules that are
different to commercial practice and/or are designed to pressurise pathogen populations into becoming resistant in an attempt to quantify the
resistance risk. Such trials show that resistance can be generated but do not give reliable indications that resistance will occur if products are
used as recommended.

Field: Indicates that resistant isolates have been found in commercially treated fields. This does not mean that the resistance was always
extensive enough to cause complete disease control failure, but does indicate a need for active resistance management.

3. For pathogens capable of infecting several host genera / species e.g. Botrytis cinerea, the list does not include reference to all known crops.
For such pathogens it is reasonable to assume that if resistance is known, all areas of use are at risk and resistance management strategies should
be used.

Cross - resistance between chemicals in a particular group.

Resistance and cross-resistance between molecules in a particular group is not always absolute due to different activity spectra shown by group
members. Be careful when making assumptions about cross-resistance patterns and if in any doubt refer to FRAC or the manufacturer.

A note on taxonomy

This list has been compiled using the taxonomy in use at the time the report was made. In some cases organisms have been reclassified since the
original report and names have changed. Where names have changed recently, users of this list are advised to search using the old name as well
as the new one.

Further guidance

Please see information published by FRAC and contained in the FRAC Monographs, available for download from the FRAC webpage
www.frac.info

Source: www.frac.info
January 2013

56


-------
Updates

FRAC welcomes suggestions for inclusion in this list; please send information, including full Journal reference, to the Secretary. Note that only
cases of confirmed resistance will be included, supported by a published report from an accredited source. Reports of rumours of resistance or
unverified reports will not be included. The decision on inclusion rests with FRAC. New entries in the 2013 edition of the list are marked in blue.

A note on mercury:

Mercury was a traditional seed treatment for cereals. It is no longer used and, as such, does not appear in the FRAC list of fungicides. Resistance
did develop to it in Pyrenophora avenae on oats, Noble et al. (1966), and for Pyrenophora graminea on barley, Clark (1985).

Source: www.frac.info
January 2013

57


-------
Mode of Action Code and
Target Site

Group Name

FRAC Group
Code

A: NUCLEIC ACID SYNTHESIS

Al: RNA polymerase I

PA Fungicides Phenylamides

4

A2: Adenosine deaminase

Hydroxy - (2-amino) pyrimidines

8

A3: DNA/RNA synthesis (proposed)

Heteroaromatics

32

A4: DNA topoisomerase type II (gyrase)

Carboxylic acids

31

B: MITOSIS AND CELL DIVISION

Bl: P-tubulin assembly in mitosis

MBC fungicides, Methyl
Benzimidazole Carbamates

1

B2: P-tubulin assembly in mitosis

N-phenylcarbamates

10

B3: P-tubulin assembly in mitosis

Benzamides

22

B4: Cell division (proposed)

Phenylureas

20

B5: Delocalisation of spectrin like proteins

Benzamides

43

C: RESPIRATION

CI

Complex I, NADH oxidoreductase

Pyrimidinamines

39

C2

Complex II, succinate-dehydrogenase

SDHI fungicides

7

C3

Complex III, cytochrome bcl (ubiquinol
oxidase at Qo site (cyt b gene)

Qol fungicides, Quinone Outside
Inhibitors

11

C4: Complex III, cytochrome bcl (ubiquinone
reductase) at Qi site

Qil fungicides (Quinone Inside
Inhibitors)

21

C5: Uncouplers of oxidative phosphorylation

-

29

C6: Inhibitors of oxidative phosphorylation. ATP
synthase

Organo tin compounds

30

C7: ATP production (proposed)

Thiophene carboxamides

38

C8: Complex III, cytochrome bcl (ubiquinone
reductase) at Qx (unknown) site

Triazolo-pyrimidylamine

45

Source: www.frac.info
January 2013

58


-------
Mode of Action Code and
Target Site

Group Name

FRAC Group
Code

D: AMINO ACIDS AND PROTEIN SYNTHESIS

Dl: Methionine biosynthesis (proposed) (cgs gene)

AP fungicides. Anilinopyrimidines

9

D2: Protein synthesis

Enopyranuronic acid antibiotic

23

D3: Protein synthesis

Hexapyranosyl antibiotic

24

D4: Protein synthesis

Glucopyranosyl antibiotic

25

D5: Protein synthesis

Tetracycline antibiotic

41

E: SIGNAL TRANSDUCTION

El: Signal transduction (mechanism unknown)

Aza-naphthalenes

13

E2: MAP/Histidine-kinase in osmotic signal
transduction (os-2, HOG1)

PP fungicides. Phenylpyrroles

12

E3: MAP/Histidine-kinase in osmotic signal
transduction (os-1, Dafl)

Dicarboximides

2

F: LIPIDS AND MEMBRANE SYNTHESIS

F1

Formerly dicarboximides



F2: Phospholipid biosynthesis, methyl transferase

Phosphoro thiolates and dithiolanes

6

F3: Lipid peroxidation (proposed)

AH fungicides (Aromatic
Hydrocarbons)( chlorophenyls,
nitroanilines and heteroaromatics)

14

F4: Cell membrane permeability, fatty acids
(proposed)

Carbamates

28

F5: Moved to H5

CAA fungicides. Carboxylic Acid
Amides

40

F6: Microbial disrupters of pathogen cell
membranes

Bacillus subtilis and the fungicidal
lipopeptides produced

44

F7: Membrane disruption (proposed)

Plant extract

46

Source: www.frac.info
January 2013

59


-------
Mode of Action Code and
Target Site

Group Name

FRAC Group
Code

G: STEROL BIOSYNTHESIS IN MEMBRANES

Gl: C14 demethylase in sterol biosynthesis
(ergl l/cyp51)

DMI fungicides. DeMethylation
Inhibitors. SBI Class 1

3

G2: A14 reductase and A8 - A'isomerase in sterol-
biosynthesis (erg24, erg2)

Amines ('morpholines'). SBI class II

5

G3: 3-keto reductase, C4-demethylation (erg27)

Hydroxyanilides. SBI class III

17

G4: Squalene epoxidase in sterol biosynthesis
(ergl)

SBI class IV

18

H: CELL WALL BIOSYNTHESIS

H3

: Trehalase and inositol biosynthesis

Glucopyranosyl antibiotic

26

H4

: Chitin synthase

Polyoxins

19

H5

: Cellulose synthase

CAA fungicides. Carboxylic Acid
Amides

40

I: MELANIN SYNTHESIS IN CELL WALL

11: Reductase in melanin biosynthesis

MBI-R Melanin Biosynthesis
Inhibitors - Reductase

16.1

12: Dehydratase in melanin biosynthesis

MBI-D Melanin Biosynthesis
Inhibitors - Dehydratase

16.2

P: HOST PLANT DEFENCE INDUCTION

PI

Salicylic acid pathway

Benzo-thiadiazole BTH

P

P2

Benzisothiazole

Benzisothiazole

P

P3

Thi adi azol e-carb oxami de

Thiadiazole-carboxamide

P

P4



Natural compound

P

Source: www.frac.info
January 2013

60


-------
Mode of Action Code and
Target Site

Group Name

FRAC Group
Code

UNKNOWN MODE OF ACTION

Unknown

Cyanoacetamide-oxime

27

Unknown

Phosphonates

33

Unknown

Phthalamic acids

34

Unknown

Benzotriazines

35

Unknown

Benzene-sulfonamides

36

Unknown

Pyridazinones

37

Unknown

Thiocarbamate

42

Microtubule disruption (proposed)

Thiazole carboxamide

U5

Unknown

Phenyl-acetamide

U6

Actin disruption (proposed)

Benzophenone

U8

Cell membrane disruption (proposed)

Guanidines (dodine)

U12

Unknown

Thiazolidine

U13

Unknown

Pyrimidinone-hydrazones

U14

NOT CLASSIFIED

Unknown

Diverse

NC

MULTI-SITE CONTACT ACTIVITY

Multi-site contact activity

Inorganic (copper)

Ml

Inorganic (sulphur)

M2

Dithiocarbamates and relatives

M3

Phthalimides

M4

Chloronitriles (phthalonitriles)

M5

Sulfamides

M6

Guanidines

M7

Triazines

M8

Quinones

M9

Source: www.frac.info
January 2013

61


-------
LIST OF RESISTANT PATHOGENS

MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





A NUCLEIC ACID SYNTHESIS

A1

4

PA Fungicides (PhenylAmides). RNA polymerase 1





Bremia lactucae

Downy mildew

Lettuce

Crute et al. 1987;
Crute & Harrison
1988

field, genetics





Peronospora destructor

Downy mildew

Onion

Wright 2004

-





Peronospora hyoscyami (syn. P
tabacina)

Blue mold

Tobacco

Bruck et al. 1982

field





Peronospora tabacina

Blue mold

Tobacco

Bruck et al. 1981

field





Peronospora viciae

Downy mildew

Pea

Falloon et al. 2000

field





Phytophthora cactorum

Crown rot /
leather rot

Strawberry
American ginseng

Bal et al. 1987

Hill & Hausbeck
2008

field
field





Phytophthora capsici

Stem rot

Lima bean pods

Davey et al. 2008

field





Phytophthora cinnamomi

Root rot

Avocado

Darvas & Becker
1984

field





Phytophthora citricola

Rot / die back



Joseph & Coffey
1984

in-vitro mutation





Phytophthora citrophthora

Collar rot / foot
rots



Serrhini etal. 1985

in-vitro





Phytophthora citrophthora

Collar rot / foot
rots



Angeles Diaz Borras
& Vila Aguila 1988

in -vitro





Phytophthora erythroseptica

Pink rot

Potato

Lambert & Sal as
1994

Taylor etal. 2002

field
field

Source: www.frac.info
January 2013

62


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Phytophthora infestans

Late blight

Potato

Davids eetal. 1981
Hartill et al. 1983
Davids eetal. 1983

field
field
field





Phytophthora infestans

Late blight

Poroporo

Hartill et al. 1983

field





Phytophthora megasperma f.sp.
glycinea

Root rot

Soybean in-vitro

Lamboy & Paxton
1992

laboratory
selection





Phytophthora megasperma f.sp.
medicaginis

Root rot

Lucerne

Davidse 1981

laboratory
selection





Phytophthora melonis

Foot rot

Cucurbits

Wu etal. 2011

field (China)





Phytophthora nicotianae

Root rot

Ornamentals

Hu et al. 2008

field





Phytophthora palmivora

Root rot

-

Lucas etal. 1990

laboratory
induction





Phytophthora parasitica

Downy mildew

Periwinkle

Ferrin & Kabashima
1991

field / laboratory





Phytophthora parasitica var.
nicotianae

Black shank

Tobacco

Shew 1985

laboratory





Phytophthora porri

Downy mildew

Leek

Locke et al. 1997

field





Phytophthora sojae (syn. P
megasperma)

Stem / root rot

Soybean

Bhat etal. 1993

laboratory





Phytophthora sp.

Root rot

African violet

Romano &
Edgington 1985

field





Plasmopara halstedii

Downy mildew

Sunflower

Albourie et al. 1998

field





Plasmopara obducens

Downy mildew

Impatiens (Busy lizzy)

FRAC 2011
FRAG UK 2011







Plasmopara viticola

Downy mildew

Grapevine

Staub & Sozzi 1981
Bosshard & Schuepp
1983

Leroux & Clerieau
1985

field
field

Source: www.frac.info
January 2013

63


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Pseudoperonospora cubensis

Downy mildew

Cucumber

Reuveni et al. 1980

field





Pythium aphanidermatum

Damping off

-

Sanders & Soika
1988

field





Pythium aphanidermatum



Not specified / creeping bent
grass

Sanders et al. 1990

in-vitro mutation /
field





Pythium aphanidermatum

Damping off

Ornamentals

Moorman et al. 2002

field





Pythium cylindrosporum

Damping off

Ornamentals

Moorman et al. 2002

field





Pythium dissotocum

Root rot

Carrot

White et al. 1988

field





Pythium dissotocum

Root rot

Ornamentals

Moorman et al. 2002

field





Pythium heterothallicum

Damping off

Ornamentals

Moorman et al. 2002

field





Pythium irregular

Damping off

Ornamentals

Moorman et al. 2002

field





Pythium splendens

Damping off

Ornamentals

Moorman et al. 2002

field





Pythium spp.

Cavity spot
various

Carrot
Potato

White et al. 1988
Porter et al. 2009

field / laboratory
field





Pythium ultimum

Watery wound
rot

Potato

Taylor et al. 2002

field





Pythium ultimum

Damping off

Ornamentals

Moorman et al. 2002

field

A2

8

Hydroxy (2 amino) pyrimidines: Adenosine-deaminase





Erysiphe graminis f.sp. hordei

Powdery
mildew

Barley

Hollomon 1978

field





Sphaerotheca fuliginea

Powdery
mildew

Cucurbits

Schepers 1984
O'Brien et al. 1988

field

A3

32

Heteroaromatics DNA / RNA synthesis (proposed)

No resistance recorded

Source: www.frac.info
January 2013

64


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks

A4

31

Carboxylic acids





Erwinia amylovora

Fire blight

Pear

Manulis etal. 2003,
Kleitman et al. 2005

field survey





B MITOSIS AND CELL DIVISION

B1

1

MBC fungicides (Methyl Benzimidazole Carbamates)





Alternaria alternata

Alternaria rot

Citrus

Sitton & Pierson
1982

field





Ascochyta byj

Ascochyta
blight

Vegetables

Steekelenburg 1973

laboratory





Ascochyta pinodes

Leaf spot

Pea

Molinero etal. 1993

laboratory





Ascochyta pisi

Leaf spot

Pea

Molinero etal. 1993

laboratory





Aspergillus nidulans

Bearings rot

Banana

Hasti &
Georgopoulos 1971

laboratory





Botryodiplodia theobromae

Botryodiplodia
rot

Fruits (Mango)

Spalding 1982

Laboratory





Botrytis allii

Neck rot

Onion

Vilj anen-Rollinson
etal. 2007

Field (New
Zealand)





Botrytis cinerea

Grey mold

cyclamen

Bollen & Scholten
1971

laboratory





Botrytis cinerea

Chocolate spot

Beans

Harrison J G 1984

field





Botrytis cinerea

Grey rot

Grapes / Vines

Ehrenhardt et al.
1973 Lerouxetal.
1982

Elad etal. 1988

field

cross resistance to
phenylcarbamates,
Group 10





Botrytis cinerea

Grey mould

Lisianthus

Elad et al. 2008

field

Source: www.frac.info
January 2013

65


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Botrytis elliptica

Grey rot

Lily

Chastagner & Riley
1987

Hsiang &
Chastagner 1990

field





Botrytis squamosa

Leaf blight

Alliacea

Presly &
Maude 1982

laboratory





Botrytis tulipae

Fire blight

Tulip

Chastagner & Riley
1987

field





Ceratocystis ulmi

Dutch elm
disease

Elm

Brasier & Gibbs
1975

laboratory





Cercospora apii

Early blight

Celery

Berger 1973

field





Cercospora arachidicola

Leafspot

Peanut

Clarke et al. 1974;
Littrell 1974

field





Cercospora beticola

Leafspot

Sugar beet

Georgopoulos &
Dovas 1973

field





Cercospora musae

Leafspot

Banana

See Mycosphaerella
musicola







Cercosporidium personatum

Late Leafspot

Peanut

Clarke et al. 1974

field





Cladobotryum dendroides

Cobweb disease

Mushrooms

McKay et al. 1998

laboratory





Cladosporium carpophilum

Scab

Peach, Nectarine

Chandler et al. 1978

field





Cladosporium cladosporioides

Fruit rot

Fruits

Dekker 1972

review





Cladosporium cucumerinum

Cladosporium

Cucurbits

Dekker 1972

review





Cladosporium fulvum

Flower rot

Fruits

Staunton 1975

field





Coccomyces hiemalis

Cherry leaf spot

Cherry

Jones & Ehret 1981

field





Colletotrichum cereal

Anthracnose

Turfgrass

Wong et al. 2008

field





Colletotrichum coffeanum

Coffee berry
disease

Coffee

Cook & Pereira

field





Colletotrichum gloeosporioides

Anthracnose

Pome fruit

Spalding 1982

laboratory





Colletotrichum lindemuthianum

Anthracnose

Bean

Meyer 1976

review

Source: www.frac.info
January 2013

66


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Colletotrichum musae

Anthracnose

Banana

Griffee 1973

field





Corynespora cassicola

target spot

tomato

Date et al. 2004

field





Cryptocline cyclaminis

Anthracnose

Cyclamen

Garibaldi et al. 1987

field





Cylindrocladium scoparium

Stem canker

Eucalyptus

Callistemon sp., Pistacia
lentiscus

Prest &Poppe 1988
Vitale et al. 2009

field
field





Cylindrocladium scoparium

Stem canker

Eucalyptus

Prest &Poppe 1988

field





Didymella bryoniae

Gummy stem
blight

Cucurbits

Malathrakis &
Vakalounakis 1983
Steekelenburg 1987

field





Didymella lycopersici

Stem rot

Tomato









Drechslera oryzae

Brown spot

Rice

Annamali &
Lalithakumari 1987

laboratory





Elsinoe fawcetti

Scab

Citrus

Whiteside 1980a
Ieki 1994

field





Elsinoe veneta

Anthracnose

Raspberry

Munro etal. 1988

field





Erysiphe dehoracaerum

Powdery
mildew

Cucurbits

Abelentsev &
Savchenko 1980

field





Erysiphe graminis

Powdery
mildew

Cereals

Vargas 1973

field





Erysiphe polygoni

Powdery
mildew

Cowpeas

Rodriguez &
Melendez 1984

field





Erythronium spp.

Yellow fawn

Lily

Duineveld &
Beijersbergen 1975

field





Fulviafulva also see
Cladosporium fulvum

Leaf mold

Tomato

Miao & Higgins
1986

laboratory





Fusarium culmorum

Fusariose

Potato / Pink

Seppanen 1983
Hanson et al. 1996

field

Source: www.frac.info
January 2013

67


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Fusarium graminearum

Fusarium head
blight

Cereals

Chen et al. 2009

Laboratory /
mutation study





Fusarium nivale

Pink snow mold

Wheat

Tanaka etal. 1983

field





Fusarium oxysporium f. sp.

Fusariose

Oeillet

Tramier &

field





dianthi





Bettachini 1974







Fusarium oxysporium f sp.

Fusariose

Gladiolus

Magie & Wilfret

field





gladioli





1974







Fusarium oxysporium f sp.
lycopersici

Fusariose

Tomato

Thanassoulopoulos
etal. 1970

laboratory





Fusarium oxysporium f. sp.
tulipae

Fusariose

Tulip

Valaskova 1983

laboratory





Fusarium oxysporium f. sp.
Melonis

Fusariose

Melon

Bastels-Schooley &
MacNeil 1971

laboratory





Fusarium roseum

Fusariose

Rosa, turf

Smiley & Howard
1976

field





Fusarium roseum var.

Dry rot

Potato

TwoWetal. 1986

field





sambucinum













Fusarium solani f. sp. pisi

Fusariose

Solanaceae

Richardson 1973

field, laboratory





Fusarium sulphureum

dry rot

Potato

Hanson et al. 1996

field





Fusicladium effusum

Scab

Pecan

Littrell 1977







Gibberella fujikuroi

Fusariose

Rice

Ogawa 1988

field





Gibberella zeae



Rice

Liu etal. 2010

lab analysis





Gloeosporium spp.

Fruit rot

Apple









Glomerella acutata

Storage rot

Apple

Weber & Palm 2010

field isolates





Guignardia citricarpa

Black spot

Citrus

Herbert & Grech
1985

field





Helminthosporium solani

Silver scurf

Potato

Geary et al. 2007

field (USA)





Hypomyces rosellus

Cobweb disease

Mushrooms

Fletcher & Yarham
1976

field

Source: www.frac.info
January 2013

68


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Leveillula taurica

Powdery
mildew

Tomato

Jones & Thompson
1982

field





Monilinia cinerea

Brown rot

Rosa

Abelentsev &
Golyshin 1973

laboratory





Monilinia jructicola

Brown rot

Pome fruit

Jones & Ehret 1976

field





Monilinia fructigena

Brown rot

Pome fruit

Abelentsev &
Golyshin 1973

laboratory





Monilinia laxa

Brown rot

Pome fruit

Ogawae^a/. 1981

field





Mycogone perniciosa

Wet bubble

Mushrooms

Fletcher & Yarham
1976

field





Mycosphaerella brassicicola

Ring spot

Brassicas









Mycosphaerella citri

Greasy spot

Citrus

Whiteside 1980b

field





Mycosphaerella fijiensis

Black spot

Banana

Stover 1979

field





Mycosphaerella fragariae

Leaf spot

Strawberry

Remiro & Kimati
1974

field





Mycosphaerella melonis

Leaf spot /
gummy stem
blight

Strawberry

Kato etal. 1984

field





Mycosphaerella musicola

Yellow spot

Banana

JoyaC 1982

field





Neofabraea alba

Storage rot

Apple

Weber & Palm 2010

field isolates





Neofabraea perennans

Storage rot

Apple

Weber & Palm 2010

field isolates





Neonectria galligena

Storage rot

Apple

Weber & Palm 2010

field isolates





Neurospora crassa

Red mold

Bread

Sisler 1971

laboratory





Oidiopsis taurica

Powdery
mildew

Artichoke









Oidium begonia

Powdery
mildew

Begonia









Penicillium brevicompactum





Bollen & Scholten
1971

laboratory

Source: www.frac.info
January 2013

69


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Penicillium corymbiferum

Rot

Crocus

Bollen & Scholten
1971

Jarvis & Hargreaves
1973

laboratory
field





Penicillium digitatum

Green rot

Citrus / Pome fruit

Wild 1983

field





Penicillium expansum

Blue mold

Pome fruit / pear

Wicks 1977

field





Penicillium fructigenum



various

IidaW 1975

field





Penicillium italicum

Blue rot

Citrus

Muirhead 1974; Yu
1981

field





Penicillium oxalicum

Stem rot

Cucurbits









Penicillium sclerotigenum



Yellow yam

Plumbley et al. 1984

field





Pestalotiopsis kmgiseta

y blight

Tea

Omat.su et al. 2012

field





Pezicula alba

Ripe spot

Pome fruits

Bielenin 1986

field





Phoma clematidina

Wilt

Clematis

*







Phoma tracheiphila

Malsecco

Citrus

Gilmenez & Luisi.
1978

field





Phytophthora citricola

Dieback

Azalea

Ferrin & Kabashima
1991

field / laboratory





Phomopsis citri

Stem-end rot

Citrus

Spalding 1982

laboratory





Podosphaera leucotricha

Powdery
mildew

Fruit trees

Suta & Radulescu
1986

laboratory





Pseudocercosporella
herpotrichoides

Eyespot

Cereals

Griffin et al. 1982

field





Pyrenopeziza brassicae

Light leaf spot

Oilseed rape

Ilott et al. 1987

laboratory





Rhyncosporium secalis

Leaf

blotch/scald

Barley









Rhizoctonia solani

Brown
Rhizoctonia

Solanaceae

Martinet al. 1984

laboratory





Sclerotinia jructicola

Brown rot

Stone fruits

Whan J H 1976

field

Source: www.frac.info
January 2013

70


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Sclerotinia homeocarpa

Dollar spot

Grass

Cole 1974

Detweiler et al. 1983
Wong S P 2003

field





Sclerotinia sclerotorium

Sclerotiniose

Oilseed rape









Sclerotium spp.

Stem rot

Alliacea/Potato/Carrot









Septoria apiicola

Leaf spot

Celery









Septoria leucanthemi

Leaf spot

Chrysanthemum

Pauluse^a/. 1976

field





Septoria tritici

Leaf spot

Cereals

Griffin & Fisher
1985

laboratory





Sphaerotheca fuliginea

Powdery
mildew

Cucurbits

Schroeder &
Providenti 1971;
Naegler et al. 1977

field





Sphaerotheca humuli

Powdery
mildew

Ornamental flowers

Iida 1975

field





Sphaerotheca pannosa

Powdery
mildew

Rosa / Peach tree

Jarvis & Slingsby
1975

field





Sporobolomyces roseus

Pink yeast

Rosa (mutation)

Nachmias & Barash
1976

laboratory





Stagonospora curtisii

Leaf scorch

Ornamental flowers /
Narcisssus

Saniewska 1985

field





Talaromyces flavis



Fruits

Katanga/. 1984

laboratory





Tapesia yallundae

Eyespot

Cereals

see

P. herpotrichoides

field





Tapesia acuformis

Eyespot

Cereals

see

P. herpotrichoides

field





Trichoderma harzianum

Green mold

Soil / Mushrooms

Eastburn & Butler
1986

field

Source: www.frac.info
January 2013

71


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Uncinula necator (now Erysiphe
necator)

Powdery
mildew

Grapes / Vines

Naeglere^a/. 1977;
Pearson 1980
Pearson &
Taschenberg 1980

field





Ustilago hordei

Barley covered
smut

Barley

Ben-Yephet Y etal.
1975

laboratory





Venturia inaequalis

Scab

Pome fruit

Kiebacher &
Hoffmann 1976

field





Venturia nashicola

Scab

Pome fruit

Ishii & Yamaguchi
1981

field





Venturia pirina

Scab

Pome fruit

Shabi & Ben-Yephet
1976

field





Verticillium albo-atrum

Verticillium

Pome fruits

Ververke 1983

laboratory





Verticillium dahlia

Verticillium

Pome fruit / Solanacea

Locke & Thorpe
1976

McHugh &
Schreiber 1984

field





Verticillium fungicola

Verticillium

Mushrooms

Fletcher & Yarham
1976;

Samuels & Johnston
1980

field





Verticillium malthousei (= V

Verticillium

Mushrooms

Lambert & Wuest

field





fungicola)





1973







Verticillium tricorpus

Wilt

Tomato





Source: www.frac.info
January 2013

72


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks

B2

10

N-phenyl carbamates: P tubulin assembly in mitosis





Botrytis cinerea

Grey mold

Grapevine

Elad et al. 1988

Katan etal. 1989
Elad et al. 1992

cross resistance to

phenylcarbamates,

Group 10

field

field





Corynespora cassiicola

Target spot

Tomato

Date et al. 2004

field





Neurospora crassa





Fujimura etal. 1994

resistance
mechanism





Verticillium fungicola

Dry bubble

Mushroom

Bonnen & Hopkins
1997

field isolates

B3

22

Benzamides P tubulin assembly in mitosis

No resistance recorded

B4

20

Phenylureas cell division (proposed)





Rhizoctonia solani

Seedling
damping-off

Various vegetables and
ornamentals

Chen etal. 1996

laboratory

B5

43

Methyl-benzamides De-localisation of spectrin like proteins

No resistance recorded





C: RESPIRATION

CI

39

Pyrimidineamines: Complex 1 NADH Oxido-reductase

No resistance reported

Source: www.frac.info
January 2013

73


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code











C2

7

SDHI fungicides (Succinate dehydrogenase inhibitors) Complex II succinate dehydrogenase





Alternaria alternata

Alternaria late
blight

Pistachio

Avenot &
Michallides 2007
Avenot et al. 2008

field

resistance
mechanism





Aspergillus nidulans





White &

Georgopoulos 1986

mutant study





Coprinus cinereus





Ito et al. 2004

mutation study
and genetic
analysis





Botryotiniafuckeliana (Botrytis
cinerea)

Grey mould



Angelini et al. 2010

Laboratory
genetic analysis





Botrytis cinerea

Grey mould

Grapevine
Strawberry
Kiwi fruit

Apple

FRAC 2007
FRAC 2007
Bardas et al.2010

Yin et al. 2011

field

field

multiple

resistance

field





Botrytis elliptica

Grey mould

Lilly

FRAC 2007

field





Corynespora cassiicola

Corynespora
leaf spot

Cucumber

Miyamoto et al.
2007

Ishii et al. 2007

Miyamoto et al.
2009

Miyamoto et al.
2010b

field

(greenhouses)
molecular
mechanism
full field report

field

Source: www.frac.info
January 2013

74


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Didymella bryoniae

Gummy stem
blight

Cucurbits

FRAC 2007
Stevenson et al.
2008

field
field





Mycosphaerella graminicola

Leaf spot

Wheat

Skinner et al. 1998

laboratory
mutation study





Podosphaera xanthii

Powdery
mildew

Melon
Cucumber

FRAC 2007

Miyamoto et al.
2010a

field

field (Japan,
glasshouses)





Ustilago maydis

Smut

Maize

Keone^a/. 1991

laboratory
mutation study





Ustilago nuda

Loose smut

Barley

Leroux & Berthier
1988

field

C3

11

Qol fungicides (Quinone outside Inhib.) Complex III cytochrome bcl (ubiquinol oxidase) at Qo site (cyt b gene)





Alternaria alternata

Alternaria late
blight

Pistachio

Ma et al. 2003
Avenot &
Michallides 2007

field / laboratory
field





Alternaria alternata

Alternaria
blotch

Apple

Ishii 2008

field





Alternaria alternata

Alternaria
brown spot

Citrus

Mondal et al. 2009

field





Alternaria alternata

Leaf spot

Potato

FRAC 2011

field, G143A,
Europe





Alternaria arborescens

Alternaria late
blight

Pistachio

Ma et al. 2003

field / laboratory





Alternaria mali

Alternaria
blotch

Apple

Lu et al. 2003

field

Source: www.frac.info
January 2013

75


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Alternaria solani

Leaf spot

Potato

Pasche et al. 2002,
2004,

Pasche et al. 2005
Pasche &
Gudmestad 2008

field

resistance
mechanism
fitness of F129L





Alternaria tenuissima

Alternaria late
blight

Pistachio

Ma et al. 2003

field / laboratory





Ascochyta rabiei

Ascochyta
blight

Chickpea

Wise et al. 2009

field. Northern
Great Plains /
Pacific N West





Blumeria graminis, see Erysiphe













graminis













Botrytis cinerea

Grey mold

Strawberry

Strawberry, citrus
Kiwi fruit

Markoglou et al.
2006

FRAC 2007

Ishii 2008
Bardas et al. 2010

mutation study

Field, G143A,
Germany
Field, Japan
Multiple
resistance





Cercospora beticola

Leaf spot

Sugar beet

Keshav Burl a et al.

2012

Bolton et al. 2013

Field Italy

Field
USA





Cercospora sojina

Frogeye spot

Soya

FRAC 2011

Field, G143A,
USA





Colletotrichum graminicola

Leaf spot

Annual bluegrass / bent grass

Avila-Adame et al.
2003

field





Colletotrichum gloeosporioides

Anthracnose

Strawberry

Ishii 2008

field

Source: www.frac.info
January 2013

76


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Corynespora cassiicola

Leaf spot, target
spot

Cucumber

Ishii 2004
FRAC Brea
2012

field

field





Didymella bryoniae

Gummy stem
blight

Cucurbits
Watermelon

Olaya & Holm 2001
Langston 2002
Stevenson et al.
2002

field
field
field





Didymella rabiei

Ascochyta
blight

Chickpea

Gossen & Anderson
2004

field





Erysiphe graminis tritici

Powdery
mildew

Wheat

Heaney et al. 2000
Sierotzki et al.
2000a

field

resistance
mechanism





Erysiphe graminis hordei

Powdery
mildew

Barley

Heaney et al. 2000

field





Erysiphe necator: see also
Uncinula necator













Fusicladium carpophilum

Leaf spot

Almond

Foerster et al. 2009

California
orchards





Glomerella cingulata
(Colletotrichum gloeosporioides)

Anthracnose

Strawberry

Ishii 2004







Magnaporthe oryzae

Leaf spot

Lolium perenne (perennial
ryegrass)

Ma & Uddin 2009

Study on 1 field
isolate





Microdochium nivale

Stem / head

Wheat

Walker et al. 2009

isolates from seed





Microdochium majus

blight.











Microdochium nivale

Head blight

Wheat

FRAC 2011

FRAC Japan
report





Microdochium spp.

Stem / head
blight

CeStempeals

FRAC 2008

field, France,
G143A confirmed

Source: www.frac.info
January 2013

77


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Monilinia laxa
M. fructigena
M. jructicola

Brown rots

Fruit

Meissner &
Stammler 2010

Not resistance but
evidence of an
intron





Mycosphaerella fijiensis

Black Sigatoka

Banana

Heaney et al. 2000
Sierotzki et al.
2000b

Chin et al. 2001

field

resistance

mechanism

field





Mycosphaerella graminicola
See also Septoria tritici

Leaf spot

Wheat

Armand et al. 2003
Clark 2005
Fraaije et al. 2005
Gisi et al. 2005

field

field, review

field

field





Mycovellosiella nattrassii

Leaf mold

Eggplant / aubergine

Yano & Kawada
2003

Ishii 2004

field / laboratory
field





Pestalotiopsis kmgiseta

y blight

Tea

Omat.su et al. 2012

field





Phaeosphaeria nodorum

Leaf blotch

Wheat

Blixt et al. 2009

field, molecular
data





Pseudoperonospora cubensis

Downy mildew

Cucumber

Heaney et al. 2000

field





Plasmopara viticola

Downy mildew

Grapevine

Heaney et al. 2000
Gullino et al. 2004
Sierotzki et al. 2005

field
field
review





Podosphaera fusca

Powdery
mildew

Cucumber

Ishii et al. 2001
Fernandez-Ortuno et
al. 2006

Fernandez-Ortuno et
al. 2008

Field

Resistance
mechanism





Podosphaera xanthii

Powdery
mildew

Cucurbits

McGrath &
Shi shkoff 2003 a, b

field trial

Source: www.frac.info
January 2013

78


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Pseudoperonospora cubensis

Downy mildew

Cucumber

Heaney et al. 2000
Ishii et al. 2001

field
field





Pyrenophora teres

Net blotch

Barley

FRAC

Semar et al. 2007

field

molecular
analysis (F129L)





Pyrenophora tritici-repentis

Tan spot

Wheat

Reimann & Dei sing

2005

FRAC

field
field





Pyricularia grisea

Gray leaf spot

Perennial ryegrass

Vincelli & Dixon
2002

Kim et al. 2003

field

field / resistance
mechanism





Pyricularia oryzae

Blast

Rice

FRAC Japan

field (G143A)





Pythium aphanidermatum

Damping off

Turf

Gisi et al. 2002
Olaya et al. 2003

laboratory
field / resistance
mechanism





Ramularia colli-cygni

Necrotic leaf
spot

Barley

FRAC 2006

field





Rhizoctonia solani

Sheath spot

Rice

FRAC 2011

field, F129L,
USA





Rhynchosporium secalis

Scald, leaf
blotch

Barley

FRAC 2008

field, single
isolate, Picardie





Saccharomyces cerevisiae





DiRagoe^a/. 1989

resistance
mechanism





Septoria nodorum, see
Sphaeosphaeria nodorum













Septoria tritici

See also Mycosphaerella

graminicola

Leaf spot

Wheat

Fraaije & Lucas
2003

field

Source: www.frac.info
January 2013

79


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Sphaerotheca aphanis var.
aphanis

Powdery
mildew

Strawberry

Ishii 2008

field





Sphaerotheca fuligenea

Powdery
mildew

Cucumber

Heaney et al. 2000
Ishii et al. 2001

field
field





Stemphylium vesicarium

Brown spot

Pears

FRAC 2006
Alberoni et al. 2010a

field

as above, field





Stemphylium vesicarium

Purple spot /
sand blast

Asparagus

FRAC 2006

field





Uncinula necator (see also
Erysiphe necator)

Powdery
mildew

Grapevine

Wilcox et al. 2003

field





Ustilago maydis

Smut

Maize

Ziogas et al. 2002

laboratory
mutants





Venturia inaequalis

Scab

Apple

Zheng et al. 2000

Farbere^a/. 2002
Steinfeld et al. 2002
Dux et al. 2005

laboratory
mutants
field trial
field
field

C4

21

Qil fungicides (Quinone inside Inhibitors) Complex III cytochrome bcl (ubiqinone reductase) at Qi site





Phytophthora capsici

Stem / fruit rot

General

Kousik & Keinath
2008

Not specified





Saccharomyces cerevisiae





Di Rago & Col son
1988

the basis of
resistance

C5

29

Oxidative phosphorylation uncouplers





Botrytis cinerea

Grey mold

Adzuki bean

Tamura 2000

field (fluazinam)

Source: www.frac.info
January 2013

80


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks

C6

30

Organo tin compounds Inhibitors of oxidative phosphorylation, ATP synthase





Cercospora beticola

Leaf spot

Sugar beet

Giannopolitis 1978,
Giannopolitis &
Chrysayi-
Tokousbalides M
1980



C7

38

Thiophene carboxamides ATP production (proposed)





Gaeumannomyces graminis

Take-all

Wheat

Joseph-Horne et al.
2000

Russell et al. 2001
Freeman et al. 2005

field

field / laboratory
field





D AMINO ACIDS AND PROTEIN SYNTHESIS

D1

9

AP fungicides (Anilinopyrimidines) Methionine biosynthesis (proposed) (cgs gene)





Botrytis cinerea (Botryotinia
fuckeliana)

Grey mold

Grapevine

Forster & Staub
1996

Chapeland et al.
1999

Sergeeva et al. 2002
Baroffio et al. 2003

field experiments

field

field

field experiments





Botrytis cinerea

Grey mould

Lisianthus

Elad et al. 2008

field





Penicillium expansum

Blue mould

Apple

Apple (stored prod.)

Li & Xiao 2008
Xiao etal. 2011

Mutation study
Samples from
stores

Source: www.frac.info
January 2013

81


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks

D2

23

Enopyranuronic acid antibiotic. Protein synthesis





Streptomyces lividans





Nomura et al. 1991

laboratory





Pyricularia oryzae

Rice blast

Rice

Sakurai & Naito
1976

laboratory cross
resistance study

D3

24

Hexopyranosyl antibiotic. Protein synthesis





Bacillus subtilis



Not specified

Tominaga &
Kobayashi 1978

Mutation





Pyricularia oryzae

Rice blast

Finger millet

Taga et al. 1979

field isolates





Pyricularia oryzae

Rice blast

Rice

Ito & Yamaguchi
1977

Sakurai et al. 1977
Sakurai & Naito
1976

field
field

laboratory cross
resistance study

D4

25

Glucopyranosyl antibiotic (streptomycin). Protein synthesis





Erwinia amylovora

Fire blight

Pear
Pear
Various

Pear, apple, quince

Moller etal. 1972
Schroth et al. 1979
Basim et al. 2001
Manulis et al. 2003

field surveys





Erwinia caratovora

Bacterial stalk
rot

Maize

Chakravarti &
Anilkumar 1969.

In-vitro





Pseudomonas cichorii



Lettuce

Matsuzaki et al.
1981

field





Pseudomonas lapsa

Bacterial stalk
rot

Maize

Chakravarti &
Anilkumar 1969.

In-vitro





Pseudomonas syringae pv.
syringae

Blossom blast,
canker

Pear

Spotts & Cervantes
1995

field

Source: www.frac.info
January 2013

82


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Pseudomonas syringae pv.
tomato

Bacterial speck

Tomato

Silva & Lopes 1995

field





Pseudomonas viridiflava



Lettuce

Matsuzaki et al.
1981

field





Xanthomonas campestris pv.
vesicatoria



Pepper and tomato

Minsavage et al.
1990



D5

41

Tetracycline antibiotic. Protein synthesis





Erwinia amylovora

Fire blight

Apple, pear

Lacy et al. 1984
Basime^a/. 2001

field strain

selection

field





Pseudomonas syringae pv.
tomato

Bacterial speck

Tomato

Silva & Lopes 1995

field





Pseudomonas syringae pv.
syringae

Blossom blast,
canker

Pear

Spotts & Cervantes
1995

field





E: SIGNAL TRANSDUCTION

El

13

Aza-naphthalenes. Signal transduction, mechanism unknown





Blumeria graminis f.sp. tritici
Erysiphe necator

Powdery
mildew

Wheat
Grapevine

Genet & Jaworska
2009

Baseline, cross
resistance studies





Erysiphe graminis f. sp. hordei

Powdery
mildew

Barley

Hollomon et al.
1997

mutation

E2

12

PP fungicides (Phenylpyrroles). MAP / Histidine-kinase in osmotic signal transduction (os-2, HOG1)





Alternaria brassicicola

Leaf spot

Brassicas

Avenot et al. 2005

field / laboratory

resistance

mechanism

Source: www.frac.info
January 2013

83


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Aspergillus parasiticus



Artificial media

Markoglou et al.
2008

mutation study





Botryotinia fuckeliana

Grey mold

Grapevine

Faretra & Pallastro
1993

mutation





Fusarium spp.

Seed piece
decay

Potato

Peters et al. 2008

Not specified





Penicillium digitatum

Green mould

Not specified

Kanetis et al. 2008

Isolates from
packing houses
but no crop losses





Penicillium expansum

Blue mould

Apple

Li & Xiao 2008

Mutation study

E3

2

Dicarboximides. MAP / Histidine-kinase in osmotic signal transduction (os-1, Dafl)





Alternaria alternata

Leaf spot

Passion fruit

Hutton D G

laboratory / field





Alternaria spp. alternata,
tenuissima, arborescens group

late blight

Pistachio

Ma & Michailides
2004

field / induced





Alternaria brassicicola

Leaf spot

Brassicas

Avenot et al. 2005

field / laboratory

resistance

mechanism





Alternaria daucii

Leaf spot /
blight

Carrot

Strandberg 1984
Fancelli & Kimati
1991

laboratory





Botryosphaeria dothidea

Panicle / shoot
blight

Pistachio

Ma et al. 2001

laboratory / field





Botrytis cinerea

Grey mold

Cucumber

Steekelenburg 1987

field





Botrytis cinerea

Grey mold

Grapevine

Holz 1979
Lerou xetal. 1982

field

Source: www.frac.info
January 2013

84


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Botrytis cinerea

Grey mold

Strawberry

Davis & Dennis
1979

field





Botrytis cinerea

Grey mould

Lisianthus

Elad et al. 2008

field





Botrytis elliptica

Grey mold

Bulbs

Hsiang & Chastener
1990

field





Botrytis squamosa

Leaf blight

Onion

Tremblay etal. 2003

laboratory





Botrytis tulipae

Tulip fire

Tulip

Chastagner & Riley
1987

field





Didymella bryoniae

Grey mold

Cucumber

Steekelenburg 1987

field





Microdochium nivale

Snow mold

Grass / golf course

Pennucci etal. 1990

field





Monilinia fructicola

Brown rot /
twig/ blossom
blight

Stone fruit

Penrose et al. 1985
Elmer & Gaunt 1994

field





Monilinia laxa

Brown rot

Apple

Katan & Shabi 1981

laboratory





Neurospora crassa





Grindle 1984

laboratory
mutation





Pyrenopeziza brassicae

Light leaf spot

Oilseed rape / brassicas

Ilott & Ingram 1987

laboratory
selection /
mutation





Sclerotinia homeocarpa

Dollar spot

Agrostispalustris (bent
grass)

Detweiler et al. 1983

field





Sclerotinia minor

Basal rot

Lettuce

Hubbard et al. 1997

field





Sclerotinia minor

Sclerotinia
blight

Peanut

Brenneman et al.
1987

Smithed al. 1995

laboratory
field





Stemphylium vesicarium

Brown spot

Pear

Alberoni et al. 2005
Alberoni et al.
2010b

field

Resistance
mechanism

Source: www.frac.info
January 2013

85


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Ustilago maydis

Smut

Maize

Orth etal. 1994

laboratory
mutation





F LIPIDS AND MEMBRANE SYNTHESIS

F1

Formerly
dicarbox-
imides

Reclassified into E3









F2

6

Phosphoro-thiolates and dithiolanes. Phospholipid biosynthesis, methyltransferase





Bipolaris oryzae

Rice

Rice blast

Annamalai &
Lalithakumari 1992

mutagenisis and
field





Pyricularia oryzae

Rice

Rice blast

Uesugi 1981

mutation and field

F3

14

AH fungicides (Aromatic Hydrocarbons, chlorophenyls, nitroanilines, and heteroaromatics). Lipid peroxidation
(proposed)





Botrytis cinerea

Grey mold

Glasshouse vegetables

Esuruoso & Wood
1971

Hartill etal. 1983

laboratory / field

cross resistance
studies with
dicarboximides,
Group 2





Phytophthora drechsleti





Zhu Zhi-feng el al.
2006

Laboratory UV

mutation,

etridiazole

Source: www.frac.info
January 2013

86


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Rhizoctonia solani





Anilkumar &
Pandourange Gowda
1981

Van Bruggen &
Arneson 1984

PCNB in-vitro
adaptation

T ol cl ofo s-m ethyl,

in-vitro

adaptation





Sclerotium rolfsii

Southern blight
/ stem rot

Peanut

Shim etal. 1998

field

F4

28

Carbamates. Cell membrane permeability, fatty acids (proposed)





Pythium spp. (propamocarb)
P. aphanidermatum
P cylindrosporium
P. dissotocum
P heterothalicum group F
P. irregulare
P. splendens
P. ultimum

Damping off

Not specific but tested on
geranium seedlings

Moorman et al.
2002, Moorman and
Kim 2004

Glasshouse
isolates





G: STEROL BIOSYNTHESIS IN MEMBRANES

G1

3

DMI Fungicides (DeMethylation Inhibitors) SBI Class I. C14-demethylase in sterol biosynthesis (ergll / cyp 51)



IMPORTA

molecules
to another
activity be1

NT NOTE: The DMI group includes several areas of chemistry (See FRAC Code List) and many molecules. Individual
can differ widely in their activity spectrum. Cases are known where resistance to one molecule does not always lead to resistance
molecule. Reasons for this phenomenon are not always clear but appear to be linked to differences in the intrinsic levels of
ween molecules. If in any doubt assume that cross resistance can happen.





Aspergillus nidulans

"

"

De Waard & van
Nistelrooy 1979

genetic study





Blumeriella jaapii

Leaf spot

Cherry

Proffer et al. 2006

field

Source: www.frac.info
January 2013

87


-------
MOA

FRAC

Pathogen

Common name

Crop

Reference

Remarks

Code

Group
Code















Botrytis cinerea

Grey mold

Vegetables
Various

Elad 1992
Stehmann & De
Waard 1996

field

laboratory
investigation of
lack of intrinsic
activity





Cercospora beticola

Leaf spot

Sugar beet

Henry & Trivellas
1989

Karaoglanidis et al.
2000

Laboratory
mutants
Field isolates





Cladosporium caryigenum

Scab

Pecan

Reynolds et al. 1997

cross resistance,
laboratory





Colletotrichum gloeosporioides

Anthracnose

Mango

Gutierrez-Alonso et
al. 2003

postharvest /
laboratory





Erysiphe graminis f.sp. hordei

Powdery
mildew

Barley

Fletcher & Wolfe
1981

field





Erysiphe graminis f.sp. tritici

Powdery
mildew

Wheat

De Waard et al.
1986

field





Fusarium asiaticum

Fusarium head

Wheat

Yin et al. 2009

Lab study on





Fusarium graminearum

blight





isolates from
China





Fusarium fujikuroi





Zhao Zhi-hua et al.
2007

Laboratory

mutation

(prochloraz)





Fusarium solani. See Nectria

Cucurbits

Foot rot

Kalamarakis et al.

genetic study





haematococca var. cucurbiae





1991







Microdochium (Fusarium) nivale

"

"

Cristani & Gambogi
1993

Laboratory





Monilinia fructicola

Twig blight,
brown rot

Stone fruit

Nuninger-Ney et al.
1989

Laboratory
Field

Source: www.frac.info
January 2013

88


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks











Elmer et al. 1992







Mycosphaerella fijiensis

Sigatoka

Banana

Anonymous 1992







Mycosphaerella graminicola

Leaf spot

Wheat

Metcalfe et al. 2000
Mavroedi & Shaw
2005

HGCA 2005
Cools et al. 2005

field experiments
field experiments

field

laboratory





Mycovellosiella nattrassii

Leaf mold

Eggplant

Yamaguchi et al.
2000

field





Nectria haematococca var.
cucurbiae

Cucurbits

Foot rot

Kalamarakis et al.
1991

laboratory
genetics





Penicillium digitatum

Citrus

Green mold

Eckert 1987

Laboratory
selection





Penicillium italicum

-

Blue mold

De Waard et al.
1982

laboratory





Pseudocercosporella
herpotrichoides Lente or R type

Eyespot

Wheat

Leroux &
Marchegay 1991

field





Puccinia horiana

White rust

Chrysanthemum

Cevat 1992
Cook 2001

field
field





Puccinia striiformis

Yellow / stripe
rust

Wheat

Bayles et al. 2000
Napier et al. 2000

sensitivity shift
laboratory





Pyrenophora teres

Net blotch

Barley

Sheridan et al. 1985

field





Pyrenophora tritici-repentis

Tan spot

Wheat

Reimann & Dei sing
2005

field





Rhynchosporium secalis

Leaf blotch,
scald

Barley

Hunter et al. 1986
Kendall & Hollomon
1990

Kendall etal. 1993
Cooke et al. 2004

Glasshouse
field

Field isolates
field

Source: www.frac.info
January 2013

89


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Sclerotinia homoeocarpa

-

-

Vargases al. 1992

laboratory





Septoria tritici







See

Mycosphaerella
graminicola





Sphaerotheca fuligenea

Powdery
mildew

Cucumber

Schepers 1983,
1985a, 1985b

field





Sphaerotheca mors-uvae

Powdery
mildew

Blackcurrant

Goszczynski et al.
1988

field





Sphaerotheca pannosa

Powdery
mildew

Nectarine

Reuveni 2001

field





Trichoderma koningii

-

-

Figueras-Roca et al.
1996

Laboratory





Uncinula necator

Powdery
mildew

Grapevine

Steva et al. 1990
Reidi & Steinkellner
1996

Miller & Gubler
2003

field
field

field





Ustilago avenae

Loose smut

Oats

Hippe & Koller
1986

laboratory





Ustilago maydis

Smut / blister
smut

Maize

Walsh & Sisler 1981

laboratory





Venturia inaequalis

Scab

Apple

Stanis & Jones 1985;
Koller et al. 1991

field

laboratory





Venturia nashicola

Japanese pear
scab

Pear

Tomita&Ishii 1998

field

G2

5

Amines (Morpholines) SBI Class II. A14 reductase and A8 - A7 isomerase in sterol biosynthesis (erg24/ ergl)





Erysiphe graminis tritici

Powdery
mildew

Wheat

Napier et al. 2000

sensitivity shift

Source: www.frac.info
January 2013

90


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Erysiphe graminis hordei

Powdery
mildew

Barley

Napier et al. 2000

sensitivity shift





Nectria haematococca





Lasseron-De
Felandre et al. 1999

laboratory
mutants





Ustilago maydis

Smut

Maize

Markoglou & Ziogas
1999, 2000, 2001

laboratory
mutants

G3

17

Hydroxyanilides (SBI class III). 3-keto reductase C4-demethylation (erg27)





Botrytis cinerea (Botryotinia
fuckeliana)

Grey mold

Grapevine

Baroffio et al. 2003
Ziogas et al. 2003
Saito etal. 2011

field experiments
mutants

field (New York)





Botrytis cinerea

Grey mould

Lisianthus

Elad et al. 2008

field (low
frequency)

G4

18

SBI Class IV. Squalene epoxidase in sterol biosynthesis (ergl)

No resistance recorded





H: GLUCAN SYNTHESIS

H3

26

Glucopyranosyl antibiotic (validamycin). Trehalase and inositol biosynthesis





Coprinus cinereus





Shim et al. 1994



H4

19

Polyoxins. Chitin synthase





Cochliobolus heterostrophus





Gafur etal. 1998

laboratory
mutation





Alternaria alternata

Black leaf spot

Pear

Gasonshi &
Takanashi



Source: www.frac.info
January 2013

91


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Alternaria kikuchiana

Alternaria leaf
blotch

Apple, pear

Hori et al. 1976

laboratory study
on resistance
mechanism





Alternaria mali

Black leaf spot

Apple

Hwang & Yun 1986

field isolates





Alternaria solani



Not specified

Maria & Sullia 1986

laboratory
adaptation study





Sclerotium rolfsii



Not specified

Maria & Sullia 1986

laboratory
adaptation study

H5

40

CAA fungicides (Carboxylic acid amides). Cellulose synthase





Phytophthora capsici

Stem and fruit
rot

Peppers

Young et al. 2001
Young et al. 2005
Lu et al. 2010

laboratory

selection

cross resistance

study

field





Phytophthora infestans

Late blight

Potato

Dereviagina et al.
1999

Stein & Kirk 2003
Yuan et al. 2006

unstable field
isolates
mutation
mutation





.Phytophthora melonis

Foot rot

Cucumber/cucurbits

Lei Chen et al. 2012

mutation





Phytophthora parasitica

Black shank

Tobacco

Chabane et al. 1993

mutation





Plasmopara viticola
Pseudoperonospora cubensis

Downy mildew
Downy mildew

Vines
Cucurbits

Gisi et al. 2007
Blum et al. 2010
Blum etal. 2011

inheritance of

resistance

resistance

mechanism

resistance

mechanism

Source: www.frac.info
January 2013

92


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





11 MELANIN SYNTHESIS IN CELL WALL

11

16.1

MBI-R (Melanin biosynthesis Inhibitors: Reductase). Reductase in melanin biosynthesis





Magnaporthe grisea /
Pyricularia oryzae

Rice blast

Rice

Zhang et al. 2006

UV light

generated mutants

12

16.2

MBI-D (Melanin biosynthesis Inhibitors: Dehydratase). Dehydratase in melanin biosynthesis





Magnaporthe grisea /
Pyricularia oryzae

Rice blast

Rice

Yamaguchi et
al. 2002 Sawada et
al. 2004

Takagaki et al. 2004
Yamada et al. 2004

Field
field

resistance

mechanism

field





P: HOST PLANT DEFENCE INDUCTION

PI

P

Benzo-thiadiazole BTH. Salicylic acid pathway

No resistance recorded

P2

P

Benzisothiazole

No resistance recorded

P3

P

Thiadiazole-carboxamide

No resistance recorded

P4

P

Natural compound (Laminarin)

No resistance recorded

Source: www.frac.info
January 2013

93


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





U: UNKNOWN MODE OF ACTION

U

27

Cyanoacetamide oximes





Plasmopara viticola

Downy mildew

Grapevine

Gullino et al.
1997

field

U

33

Phosphonates





Bremia lactucae

Downy mildew

lettuce

Brown et al. 2004

field





Phytophthora citrophthora

Collar rot / foot
rots



Angeles Diaz Borras
& Vila Aguila 1988

in -vitro





Plasmopara viticola

Downy mildew

Grape vine

Khilare et al. 2003

field





Pythium aphanidermatum



Not specified

Sanders et al. 1990

in-vitro mutation

IT

34

Phthalamic acids

No resistance recorded

IT

35

Benzotriazines

No resistance recorded

IT

36

Benzene-sulfonamides

No resistance recorded

IT

37

Pyradazinones

No resistance recorded

IT

42

Thiocarbamate

No resistance recorded

IT

U5

Thiazole carboxamides. Microtubule disruption (proposed)

No resistance recorded

IT

U6

Phenyl-acetamide





Sphaerotheca cucurbitae

Powdery
mildew

Cucumber Hosokawa et al. 2006

glasshouses, Japan

Source: www.frac.info
January 2013

94


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks

U

U7

Cancelled: See El

Actin
disruption
(proposed)

U8

Benzophenone





Blumeria graminis

Powdery
mildew

wheat

Top Agrar, Dec. 2009
Felsenstein et al. 2010
(as above)

field, Germany
field, Germany

U

U10

Acrylonitrile

No resistance recorded





NC: NOT CLASSIFIED

Not
known

diverse

Various mineral oils, organic oils, potassium bicarbonate, material of biological origin.





Botryotinia fuckeliana

Resistant to
Bacillus subtilis
strain CL27



Li & Leifert 1994

Lab study





M: MULTISITE CONTACT ACTIVITY

Ml

Inorganics, copper



Pseudomonas species:
P. cepacia
P. gladioli

P. syringae pv. actinidiae
Agrobacterium species:
A. radiobacter
A. tumefaciens



Not specified, laboratory
isolates

Goto et al. 1994

in-vitro tests

Source: www.frac.info
January 2013

95


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Xanthomonas axonopodis pv.
citri

Citrus canker

Grapefruit

Canteros 2002

Field

M2

Inorganics, sulphur

No resistance recorded

M3

Dithiocarbamates and relatives



Botrytis cinerea

Grey mold

Not specified Bara

198z

ik & Edgington laboratory study



Helminthosporium halodes

Leaf spot

Sugar cane

Reddy & Anilkumar
1989

laboratory study



M4

Phthalimides



Botrytis cinerea

Grey mold

Not specified

Barak & Edgington
1984

laboratory study



Botrytis cinerea



Grapevine

Fourie & Holz 2001

laboratory



Botrytis cinerea

Grey mold

Glasshouse cucumber

Malathrakis 1989

glasshouse

M5

Chloronitriles (phthalonitriles)



Botrytis cinerea

Grey mold

Not specified

Barak & Edgington
1984

laboratory study



Botrytis cinerea

Grey mold

Glasshouse cucumber

Malathrakis 1989



M6

Sulphamides



Botrytis cinerea

Grey mold

Glasshouse cucumber

Malathrakis 1989



M7

Guanidines



Venturia inaequalis

Scab

Apple

Szkolnik &
Gilpatrick 1969,
1971

Dodine



Hypomyces

"

"

Kappas &
Georgopoulos

Dodine, induced
resistance

Source: www.frac.info
January 2013

96


-------
MOA
Code

FRAC
Group
Code

Pathogen

Common name

Crop

Reference

Remarks





Penicillium digitatum

Green mold

Citrus

Wild 1983





Penicillium italicum

Blue mold

Lemon

Hartill et al. 1983

in-vitro

M8

Triazines

No resistance recorded

Source: www.frac.info
January 2013

97


-------
References

A

Alberoni G, Cavallini D, Collina M, Brunelli A (2010a) Characterisation of the first Stemphylium vesicarium isolates resistant to strobilurins in

Italian pear orchards. European Journal of Plant Pathology 126 453-457
Alberoni G, Collina M, Lanan C, Leroux P, Brunelli A (2010b). Field strains of Stemphylium vesicarium with a resistance to dicarboximide

fungicides correlated with changes in a two-component histidine kinase. European Journal of Plant Pathology 128, 171-184
Angeles Diaz Borras M, Vila Aguilar R (1988). In-vitro resistance of Phytophthora citrophthora to metalaxyl and fosetyl-Al.

Anonymous (1992). Sterol biosynthesis inhibitors - risk of resistance and recommended antiresistance strategies. Recommendations of the

FRAC-DMI Working Group for 1992. Gesunde Pflanzen 44, 361 - 365
Abelentsev V I, Golyshin N M (1973). Adaptatsiya nekotorykh fitopatogennykh gribov k benomilu. Kimila v Sel'skom Khoz 11, 432-436
Abelentsev V I, Savchenko VI (1980). Resistance of the causative agent of powdery mildew of cucumbers to benzimidazole fungicides.

Khimiya v Sel'skrom Khozyaistve 18, 31 - 33
Alberoni G, Collina M, Pancaldi D, Brunelli A (2005). Resistance to dicarboximide fungicides in Stemphylium vesicarium of Italian pear

orchards. European Journal of Plant Pathology 113, 211-219
Albourie J-M, Tourville J, Tourviellie De Labrouhe D (1998). Resistance to metalaxyl in isolates of the sunflower pathogen Plasmopara

halstedii. European Journal of Plant Pathology 194, 235 - 242
Amand O, Calay F, Coquillart L, Legat T, Bodson B, Moreau J-M, Maraite H (2003). First detection of resistance to Qol fungicides in

Mycosphaerella graminicola on winter wheat in Belgium. Communications in Agricultural and Applied Biological Sciences 68, 519-531
Angelini R M C, Habib W, Rotolo C, Pollastro S, Faretra F (2010). Selection, characterisation and genetic analysis of laboratory mutants of

Botryotinia fuckeliana (Botrytis cinerea) resistant to the fungicide Boscalid. European Journal of Plant Pathology 128, 185-199
Anilkumar T B, Pandourange Gowda K T (1981). Growth and stability of penta chloronitro benzene resistant isolate of Rhizoctonia solani.
Zentralblattfuer Bakteriologie Parasitenkunde Infektionskrankheiten undHygiene Zweite Naturwissenschaftliche AbteilungMikrobiologie
der Landwirtschaft der TEchnologie unddes Umweltschutzes 136, 502-504
Annamalai P, Lalithakumari D (1987). Cross resistance in edifenphos resistant mutant of Dreschlera oryzae. Indian Phytopathology 40, 296
Annamalai P, Lalithakumari D (1992). Development of resistance in Bipolaris oryzae against edifenphos. Mycological Research 96, 454-460
Avenot H, Simoneau P, Iacomi-Vasilescu B, Bataille-Simoneau N (2005). Characterisation of mutations in the two component histidine kinase

gene AbNIKl from Alternaria brassicicola that confer high dicarboximide and phenylpyrrole resistance. Current Genetics 47, 234-243
Avenot H F, Michallides T J (2007). Resistance to pyraclostrobin, boscalid and Pristine (pyraclostrobin plus boscalid) in Alternaria alternate

isolates from California. Phytopathology 97, (7, Suppl. S) S5 Jul 2007.

Avenot H F, SellamA, Karaoglanidis G, Michailides T J (2008). Characterization of mutations in the iron-sulphur subunit of succinate
dehydrogenase correlating with boscalid resistance in Alternaria alternata from California pistachio. Phytopatholgy 98, 736-742

Source: www.frac.info
January 2013

98


-------
Avila-Adame C, Olaya G, Koller, W (2003). Characterisation of Colletotrichum graminicola isolates resistant to strobilurin related Qol
fungicides. Plant Disease 87, 1426-1432

B

Bal E, Gilles G, Creemers P, Vandergeten-Bollen J (1987). Mededelingen van de Faculteit Landbouwwetenschappen Universiteit Gent 52, 881 —
894

Barak E, Edgington L V (1984). Cross resistance of Botrytis cinerea to captan, thiram, chlorothalonil and related fungicides. Canadian Journal
of Plant Pathology 6, 318-320

Bardas G A, Veloukas T, Koutita O, Karaoglanidis G S (2010). Multiple resistance of Botrytis cinerea from kiwi fruit to SDHIs, Qols and

fungicides of other chemical groups. Pest Management Science 66, 967-973
Baroffio C A, Siegfried W, Hilber U W (2003). Long-term monitoring for resistance of Botryotinia fuckeliana to anilinopyrimidine,

phenylpyrrole and hydroxyanilide fungicides in Switzerland. Plant Disease 87, 662-666
Basim H, Ozturk S B, Unlu A, Yegen O, Zeller W (2001). Evaluation of Erwinia amylovora strains in Turkey for resistance to streptomycin,

oxytetracycline and copper. Phytopathology 91, S6
Bastels-Schooley J, MacNeil B H (1971). A comparison of the mode of action of three benzimidazoles. Phytopathology 61, 816-819
Bayles R A, Stigwood P L, Clarkson JDS (2000). Shifts in sensitivity of Puccinia striiformis to DMI fungicides in the UK. Acta

Phytopathologica et Entomologica Hungarica 35, 381 - 382
Ben-Yephet Y, Henis Y, Dinoor A (1975). Inheritance of tolerance to carboxin and benomyl in Ustilago hordei. Phytopathology 65, 563 - 567
Berger R D (1973). Disease progress of Cercospora apii resistant to benomyl. Plant Disease Reporter 57, 837 - 840
Bhat R G, McBlain B A, Schmitthenner A F (1993). The inheritance of resistance to metalaxyl and to fluorophenylalanine in mating of

homothallic Phytophthora sojae. Mycological Research 97, 865 - 870
Bielenin A (1986). Resistance to benzimidazole fungicides in Pezicula spp. Ochr. Rosl. 30, 16-17

Blixt E, Djurle A, Yuen J, Olson A (2009). Fungicide sensitivity in Swedish isolates of Phaeosphaeria nodorum. Plant Pathology 58, 655-664
Blum M, Waldner M, Gisi U (2010). A single point mutation in the novel PvCesA3 gene confers resistance to the carboxylic acid amide

fungicide mandipropamid in Plasmopara viticola. Fungal Genetics and Biology. 47, 499-510
Blum M, Waldner M, Olaya G, Cohen Y, Gisi U, Sierotzki H (2011). Resistance mechanism to carboxylic acid amide fungicides in the cucurbit

downy mildew pathogen Pseudoperonospora cubensis. Pest Management Science, 67, 1211-1214
Bollen G J, Scholten G (1971). Acquired resistance to benomyl and some other systemic fungicides in a strain of Botrytis cinerea in cyclamen.

Netherlands Journal of Plant Pathology 77, 83 - 90
Bonnen A M, Hopkins C (1997). Fungicide resistance and population variation in Verticillium fungicola, a pathogen of the button mushroom,

Agaricus bisporus. Mycological Research 101, 89-96
Bosshard E, Schuepp H (1983). Variability of selected strains of Plasmopara viticola with respect to their metalaxyl sensitivity under field
conditions. Zeitschriftfuer Pflanzenkrankheiten undPflanzenschutz 90, 449 - 459

Source: www.frac.info
January 2013

99


-------
Brasier C M, Gibbs J N (1975) Methyl benzimidazole-2-yl carbamate tolerance in aggressive and nonaggressive isolates of Ceratocystis ulmi.

Annals of Applied Biology 80, 231 - 236
Brenneman T B, Phipps P M, Stipes R J (1987). Sclerotinia blight of peanut relationship between in vitro resistance and field efficacy of

dicarboximide fungicides. Phytopathology 77, 1028-1032
Brown S, Koike S T, Ochoa O E, Laemmien F, Michelmore R W (2004). Insensitivity to the fungicide fosetyl-aluminum in California isolates of

the lettuce downy mildew pathogen Bremia lactucae. Plant Disease 88, 502-508
Bruck R, Gooding G V Jr, Main C E (1981). Evidence for resistance to metalaxyl in isolates of Peronospora tabacina. Phytopathology 71, 558
Bruck R, Gooding G V Jr, Main C E (1982). Evidence for resistance to metalaxyl in isolates of Peronospora hyoscyami. Plant Disease 66, 44 -
45

C

Canteros B (2002). Control of citrus canker caused by strains of Xanthomonas axonopodis pv. citri susceptible and resistant to copper.

Phytopathology 92, SI 16 (meeting abstract)

Cevat H (1992). Japanse roest terug van nooit weggeweest. nu maatregelen nemen om aantasting in najaar te voorkomen. Vakblad voor de
Bloemisterij 29, 32-33

Chabane K, Leroux P, Bompeix G (1993). Selection and characterisation of Phytophthoraparasitica mutants with ultraviolet induced resistance

to dimethomorph or metalaxyl. Pesticide Science 39, 325-329
Chakravarti B P, Anilkumar T B (1969). Hindustan Antibiotics Bulletin 12, 73-74

Chandler W A, Daniell J W, Littrell R H (1978). Control of peach diseases in annorchard having benomyl tolerant Cladosporium carpophilum.

Plant Disease Reporter 62, 783 - 786
Chapeland F, Fritz R, Lanen C, Gredt M, Leroux P (1999). Inheritance and mechanisms of resistance to anilinopyrimidine fungicides in Botrytis

cinerea (Botryotinia fuckeliana). Pesticide Biochemistry and Physiology 64, 85-100
Chastagner G A, Riley K (1987). Occurrence and control of benzimidazole and dicarboximide resistant Botrytis spp. on bulb crops in Western

Washington and Oregon USA. Phytopathology 77, 1237
Chen Y R, Huang J W, Chen L C (1996). In vitro inspection of pencycuron fungicide: Resistant Rhizoctonia solani Ag-4 and its interfering

factors. Plant Protection Bulletin (Taichung) 38, 313-328
Chen Yu, Zhou Ming-Guo (2009). Characterization of Fusarium graminearum isolates resistant to both carbendazim and a new fungicide
JS399-19. Phytopathology 99 441

Chin K M, Wirz M, Laird D (2001). Sensitivity of Mycosphaerella fijiensis from banana to trifloxystrobin. Plant Disease 85,1264-1270
Clark E M, Backman P A, Rodriguez-Kabana R (1974). Cercospora arachidicola and Cercosporidium personatum tolerance to benomyl and
related fungicides in Alabama peanut fields. Phytopathology 64, 1476 - 1477

Source: www.frac.info
January 2013

100


-------
Clark M R M (1985). Barley leaf stripe mercury resistance. In: British Crop Protection Council Monograph No. 31. Fungicides for Crop
Protection: 100 Years of Progress, Vol 2, Bordeaux Mixture Centenary Meeting. BCPC Publications, Croydon, England, pp. 351-354
Clark W (2005). Qol resistance i n Mycosphaerella graminicola in the UK: implications for future use of Qol fungicides. Proceedings of the

BCPC International Congress, Crop Science & Technology 283-290
Cole H, Warren C G, Sanders P L (1974). Fungicide tolerance - a rapidly emerging problem in turfgrass disease control. Proceedings

International Turfgrass Research Conference. 2D, 344-349
Cook R T A, Pereira J L (1976). Strains of Colletotrichum coffeanum the causal agent of coffee berry disease tolerant to benzimidazole

compounds in Kenya. Annals of Applied Biology 83, 365 - 379
Cooke L, Locke T, Lockley K D, Phillips A N, Sadiq M D S, Coll R, Black L, Taggart P J, Mercer P C (2004). The effect of fungicide

programmes based on epoxyconazole on the control and DMI sensitivity of Rhynchosporium secalis in winter barley. Crop Protection 23,
393-406.

Cools H J, Fraaje B A, Lucas J A (2005). Molecular mechanisms correlated with changes in triazole sensitivity in isolates of Mycosphaerella

graminicola. Proceedings of the BCPC International Congress, Crop Science & Technology 2005, 261-21A
Cristani C, Gambogi P (1993). Laboratory isolation of Microdochium (Fusarium) nivale mutants showing reduced sensitivity to sterol

biosynthesis inhibitors. Rivista di Patalogia Vegetale 3, 49 - 57
Crute IR, Norwood J M, Gordon P L (1987). The occurrence, characteristics and distribution in the United Kingdom of resistance to

phenylamide fungicides in Bremia lactucae (lettuce downy mildew). Plant Pathology 36, 297 - 315
Crute I, Harrison J M (1988). Studies on the inheritance of resistance to metalaxyl in Bremia lactucae and on the stability and fitness of field
isolates. Plant Pathology 37, 231 - 250

D

Darvas J M, Becker O (1984). Failure to control Phytophthora cinnamomi and Pythium splendens with metalaxyl after its prolonged use. Citrus

and Subtropical Fruit Journal 603, 9- 11.

Date H, Kataoka E, Tanina K, Sasaki S, Inoue K, Nasu H, Kasuyama S (2004). Sensitivity of Corynespora cassicola, causal agent of

Corynespora target spot of tomato, to thiophanate methyl and di ethofencarb ..Japanese Journal of Phytopathology 70, 7-9
Davey J F, Gregory N F, Mulrooney R P, Evans T A, Carroll RB (2008). First report of mefenoxam resistant isolates of Phytophthora capsici

from lima bean pods in the Mid-Atlantic region. Plant Disease 92, 656
Davidse L C (1981). Resistance to acylalanine fungicides in Phytophthora megasperma f. sp. medicaginis. The Netherlands Journal of Plant
Pathology 87, 11-24

Davidse L C, looijeu D, Turkenstein L J, Van Der Wal D (1981). Occurence of metalaxyl resistant strains of potato blight in Dutch potato fields.

The Netherlands Journal of Plant Pathology 87, 65 - 68
Davidse L C, Danial D L, Van Westen C J (1983). Resistance to metalaxyl in Phytophthora infestans in the Netherlands. The Netherlands
Journal of Plant Pathology 89, 1-20

Source: www.frac.info
January 2013

101


-------
Davis R P, Dennis C (1979). Use of dicarboximide fungicides on strawberries and potential problems of resistance in Botrytis cinerea.
Proceedings of the British Crop Protection Conference, Pests & Diseases 193 - 201

De Waard M A, Van Nistelrooy J G M (1979). Mechanisms of resistance to fenarimol in Aspergillus nidulans. Pesticide Biochemistry and
Physiology 10, 219 - 229

De Waard M A, Groeneweg H, Van Nistelrooy J G M (1982). Laboratory resistance to fungicides which inhibit ergosterol biosynthesis in
Penicillium italicum. Netherlands Journal of Plant Pathology 88, 99 - 112

De Waard M A, Kipp EMC, Horn N M, Van Nistelrooy J G M (1986). Variation in sensitivity to fungicides which inhibit ergosterol
biosynthesis in wheat powdery mildew. Netherlands Journal of Plant Pathology 92, 21-32

Dekker J (1972) In: Marsh R W, Systemic Fungicides. John Wiley & Son, New York, pp 156-174

Derevyagiana M K, Matskavichus G, D'Yakov Yu T (1995). Changes of resistance to dimethomorph of Phytophthora infestans (Mont.) D By.
isolates during cloning. Mikologiya i Fitopatologiya 29, 44-47

Dereviagina M K, Elanski S N, Diakov Yu T (1999). Resistance of Phytophthora infestans to the dimethomorph fungicide. Mikologiya i
Fitopatologiya 33, 208-213

Detweiler A R, Yargas J M Jr., Danneberger T K (1983). Resistance of Sclerotinia homoeocarpa to iprodione and benomyl. Plant Disease 67,
627 - 630

Di Rago J P, Colson A-M (1988). Molecular basis for resistance to antimycin and diuron Q-cycle inhibitors acting at the Q-I site in the
mitochondrial ubiquinol-cytochrome C reductase in Saccharomyces cerevisiae. Journal of Biological Chemistry 263, 12564-12570

Di Rago J-P, Coppee J-Y, Colson A-M (1989). Molecular basis for resistance to myxothiazol mucidin strobilurin A and stigmatellin cytochrome
B inhibitors acting at the center of the mitochondrial ubiquinol cytochrome C reductase in Saccharomyces cereviaiae. Journal of Biological
Chemistry 264, 14543-14548

Duineveld Th L J, Beijersbergen J C M (1975). On the resistance to benomyl of fungi isolated from bulbs and corms. Acta Horticulturae
(Wageningen) 47, 143-148

Dux H, Sierotzki H, Meier-Runge F, Gisi U (2005). Sensitivity of Venturia inaequalis populations to anilinopyrimidine, DMI and Qol

fungicides. In: Modern Fungicides and Antifungal Compounds IV. Eds. H-W Dehne, U Gisi, K-H Kuck, P E Russell, H Lyr. BCPC, Alton,
UK pp. 45-54

E

Eastburn D M, Butler E E (1986). The occurrence of benomyl resistant isolates of Trichoderma harzianum in Costa Rican soils. Phytopathology
76, 1066 (abstract)

Eckert J W (1987). Penicillium digitatum biotypes with reduced sensitivity to imazalil. Phytopathology 77, 1728

Elmer PAG, Gaunt R E (1994). The biological characteristics of dicarboximide resistant isolates of Monilinia fructicola from New Zealand
stone fruit orchards. Plant Pathology 43, 130 - 137.

Source: www.frac.info
January 2013

102


-------
Ehrenhardt H, Eichhorn K W, Thate R (1973). Zur Frage der Resistenzbildung von Botrytis cinerea gegenuber systemischen Fungiziden.

Nachrichtenblatt des Deutschen Pflanzenschutzdienstes (Braunschueig) 25, 49 - 50
Elad Y (1992). Reduced sensitivity of Botrytis cinerea to two sterol, biosynthesis inhibiting inhibiting fungicides: fenetrazole and fenethanil.
Plant Pathology 41, 47 - 54

Elad Y, Yunis H, Katan T (1992). Multiple fungicide resistance to benzimidazoles dicarboximides and diethofencarb in field isolates of Botrytis

cinerea in Israel. Plant Pathology 41, 41-46
Elad Y, Shpialter L, Korolev N, Mamiev M, Rav David D, Dori I, Ganot L, Shmuel D, Matan E, Messika Y. (2008) Integrated chemical and
cultural control for grey mould (Botrytis cinerea) management in Lisianthus. In: Modern Fungicides and Antifungal Compounds IV.
Proceedings of the 15th International Reinhardsbrunn Symposium. Eds. Dehne H-W, Gisi U, Kuck K-h, Russell P E, Lyr H. (in press)

Elmer PAG, Braithwaite M, Saville D J (1992). Changes in triforine sensitivity in populations of Monilinia fructicola from Hawkes Bay

orchards. Proceedings of the 45th. New Zealand Plant Protection Conference 45, 138 - 140
Esuruoso O F, Wood R K S (1971). The resistance of spores of resistant strains of Botrytis cinerea to quintozene tecnazene and dicloran. Annals
of Applied Biology 68, 271-279

F

Falloon R E, Follas G B, Butler R C, Goulder D S (2000). Resistance in Peronospora viciae to phenylamide fungicides: reduced efficacy of seed

treatments of pea (Pisum sativum) and assessment of alternatives. Crop Protection 19, 313 - 325
Fancelli M I, Kimati H (1991). Occurrence of iprodione resistant strains of Alternaria dauci. Summa Phytopathologica 17, 135-146
Farber R B K, Chin K M, Leadbitter N (2002). Sensitivity of Venturia inaequalis to trifloxystrobin. Pest Management Science 58, 261-267
Faretra F, Pollastro S (1993). Isolation, characterisation and genetic analysis of laboratory mutants of Botryotinia fuckeliana resistant to the

phenylpyrrole fungicide CGA-173506. Mycological Research 97, 620-624
Felsenstein F, Semar M, Stammler G (2010). Sensitivity of wheat powdery mildew (Blumeria graminis f.sp tritici) towards metrafenone.
Gesunde Pflanzen 62, 29-33

Fernandez-Ortuno D, Perez-Garcia A, Lopez-Ruiz F, Romero D, de Vicente A, Tores J A (2006). Occurrence and distribution of resistance to

Qol fungicides in populations of Podosphaera fusca in south central Spain. European Journal of Plant Pathology 115, 215 - 222
Fernandez-Ortuno D, Tores J A, de Vincente A, Perez-Garcia A (2008). Field resistance to Qol fungicides in Podosphaera fusca is not

supported by typical mutations in the mitochondrial cytochrome b gene. Pest Management Science 64, 694-702
Ferrin D M, Kabashima J N (1991). In-vitro insensitivity to metalaxyl of isolates of Phytophthora citricola and Phytophthoraparasitica from

ornamental hosts in Southern California USA. Plant Disease 75, 1041 - 1044
Figueras-Roca M, Cristani C, Vannacci G (1996). Sensitivity of Trichoderma isolates and selected resistant mutants to DMI fungicides. Crop
Protection 15, 615 - 620

Fletcher J T, Yarham D J (1976). The incidence of benomyl tolerance in Verticillium fungicola, Mycogone perniciosa and Hyphomyces rosellus
in mushroom crops. Annals of Applied Biology 84, 343 - 354

Source: www.frac.info
January 2013

103


-------
Fletcher J S, Wolfe M S (1981) Insensitivity of Erysiphe graminis f. sp. hordei to triadimefon, triadimenol and other fungicides. Proceedngs of

the Brighton Crop Protection Conference, Pests & Diseases 633 - 640
Foerster H, Connell J H, Adaskaveg J E (2009). Qol resistance in Fusicladium carpophilum populations from almond in California.
Phytopathology 99 S3 5

Forster B, Staub T (1996). Basis for use strategies of anilinopyrimidine and phenylpyrrole fungicides against Botrytis cinerea. Crop Protection
15, 529-537

Fourie P H, Holz G (2001). Incomplete cross-resistance to folpet and iprodione in Botrytis cinerea from grapevine in South Africa. South

African Journal ofEnology and Viticulture 22, 3-7
Fraaije B A, Burnett F J, Clark W S, Motteram J, Lucas J A (2005). Resistance development to Qol inhibitors in populations of Mycosphaerella

graminicola in the UK. In: Modern Fungicides and Antifungal Compounds IV. BCPC, Al;ton, UK pp. 63-72
Fraaije B A, Lucas J A (2003). Qol resistance development in populations of cereal pathogens in the UK. Proceedings of the BCPC

International Congress - Crop Science & Technology 689 - 694
FRAC. Where a reference is given as 'FRAC' please refer to the FRAC website: www.frac.info and the appropriate Working Group page. When

a date is given, this indicates the first report to the FRAC Working Group
FRAG UK. Indicates that a verified case was reported to the FRAG UK Committee

Freeman J, Ward E, Gutteridge R J, Bateman G L (2005). Methods for studying population structure, including sensitivity to the fungicide

siltthiofam, of the cereal take-all fungus, Gaeumannomyces graminis var. tritici. Plant Pathology 54, 686-698
Fujimura M, Kamakura T, Inoue K, Yamaguchi I (1994). Amino acid alterations in the beta-tubulin gene of Neurospora crassa that confer
resistance to carbendazim and diethofencarb. Current Genetics 25, 418-422

G

Gafur A, Tanaka C, Shimizu K, Ouchi S, Tsuda M (1998). Genetic analysis of Cochliobolus heterostrophus polyoxin resistant mutants.
Mycoscience 39, 155-159

Garibaldi A, Migheli Q, Gullino M L (1987). Evaluation of the efficacy of several fungicides against Cryptoclina cyclaminis on Cyclamen.

Meded. Fac. Landbouwwet. Rijksuniv. Gent 52, 859-865
Gasonshi K, Takanashi K (1973). Resistance of pear black spot pathogen to polyoxin. Annals of the Phytopathological Society of Japan 39, 173-
174

Geary B, Johnson D A, Hamm P B, James S, Rykbost K A (2007). Potato silver scurf affected by tuber seed treatments and locations, and

occurrence of fungicide resistant isolates of Helminthosporium solani. Plant Disease 91 315-320
Genet J L, Jaworska G (2009). Baseline sensitivity to proquinazid in Blumeria graminis f. Sp. Tritici and Erysiphe necator and cross resistance

with other fungicides. Pest Management Science 65 878-884
Georgopoulos S G, Dovas C (1973). A serious outbreak of strains of cercospora beticola resistant to benzimidazole fungicides in northern
Greece. Plant Disease Reporter 62, 205 - 208

Source: www.frac.info
January 2013

104


-------
Giannopolitis C N (1978). Occurrence of strains of Cercospora beticola resistant to tri-phenyl tin fungicides in Greece. Plant Disease Reporter
62, 205-208

Giannopolitis C N, Chrysayi-Tokousbalides M (1980). Biology of tri phenyl tin resistant strains of Cercospora beticola from sugar beet. Plant
Disease 64, 940 - 942

Gilmenez V I, Luisi N (1978). Tolerance to benomyl in Phoma tracheiphila. PhytopathogogiaMediterranea 17, 77 (abstract)

Gisi U, Pavic L, Stanger C, Hugelshofer U, Sierotzki H (2005). Dynamics of Mycosphaerella graminicola populations in response to selection

by different fungicides. . In: Modern Fungicides and Antifungal Compounds IV. BCPC, Al;ton, UK pp. 89-102
Gisi U, Sierotzki H, Cook A, McCaffery A (2002). Mechanisms influencing the evolution of resistance to Qo inhibitor fungicides. Pest
Management Science. 58, 859-867

Gisi U, Waldner M, Kraus N, Dubuis P H, Sierotzki H (2007). Inheritance of resistance to carboxylic acid amide fungicides in Plasmopara

viticola. Plant Pathology 56 199-208
Gossen B D, Anderson K L (2004). First report of resistance to strobilurin fungicides in Didymella rabiei. Canadian Journal of PLant Pathology
26,411

Goszczynski W, Cimanowski J, Bachnacki R (1988). First note on the occurrence of a strain of Sphaerotheca mors-uvae Schw. -Berk, with

decreased ensitivity to triadimefon. Fruit Science Reports (Skierniewice) 15, 181 - 184
Goto M, Hikota T, Nakajima M, Takikawa Y, Tsuyumi S (1994). Occurrence and properties of copper resistance in plant pathogenic bacteria.

Annals of the Phytopathological Society of Japan 60, 147-153
Griffee P J (1973). Resistance to benomyl and related fungicides in Colletotrichum musae. Transactions of the British Mycological Society 60,
433 -439

Griffin M J, Drummond M, Yarham D J, King J E, Brown M (1982). Benzimidazole resistance in Pseudocercosporella herpotrichoides, the

cause of eyespot disease of cereals. International Society for Plant Pathology, Chemical Control Newsletter 1, 7 - 8
Griffin M, Fisher N (1985). Laboratory studies on benzimidazole resistance in Septoria tritici. uelletin OEPP 15, 505 - 512
Grindle M (1984). Isolation and characterisation of vinclozolin resistant mutants of Neurospora crassa. Transactions of the British Mycological
Society 82, 635-644

Gullino M L, Mescalchin E, Mezzalama M (1997). Sensitivity to cymoxanil in populations of Plasmopara viticola in northern Italy. Plant
Pathology 46, 729-736

Gullino M L, Gilardi G, Tinivella F, Garibaldi A (2004). Observations on the behaviour of different populations of Plasmopara viticola resistant

to Qol fungicides in Italian vineyards. PhytopathologiaMediterranea 43, 341-350
Gutierrez-Alonso J G, Gutierrez-Alonso O, Nieto-Angel D, Teliz-Ortiz D, Zavaleta-Mejia E, Delgadillo-Sanchez F, Vaquera-Huerta H (2003).
Evaluation of resistance to imazalil, prochloraz, and azoxystrobin of Colletotrichum gloeosporioides (penz.) Penz. y Sacc. isolates and
control of Mango (Mangifera indica L.) anthracnosis during postharvest. Revista Mexicana de Fitopatologia 21,379-3 82

H

Source: www.frac.info
January 2013

105


-------
Hanson L E, Schwager S J, Loria R (1996). Sensitivity to thiabendazolwe in Fusarium species associated with dry rot in potatoes.
Phytopathology 86, 378-384

Harrison J G (1984). Botrytis cinerea as an important cause of chocolate spot in field beans. Transactions of the British Mycological Society 83,
631-638

Hartill W F T, Tompkins G R, Kleinshaw P J (1983). Development in New Zealand of resistance to dicarboximide fungicides in Botrytis cinerea
to acylalanines in Phytophthora infestans and to guazatine in Penicillium italicum. New Zealand Journal of Agricultural Research 26, 261 -
270

Hasti A C, Georgopoulos S G (1971). Mutational resistance to fungitoxic benzimidazole derivatives in Aspergillus nidulans. Journal of General
Microbiology 65, 371-374

Heaney S P, Hall A A, Davies S A, Olaya G (2000). Resistance to fungicides in the QoI-STAR cross resistance group: current perspectives.

Proceedings of the BCPC Conference - Pests & Diseases 755 -762
Henry M J, Trivellas A E (1989). Laboratory induced fungicide resistance to benzimidazole and azole fungicides in Cercospora beticola.

Pesticide Biochemistry and Physiology 35, 89 - 96
Herbert J A, Grech N M (1985). A strain of Guignardia citricarpa, the citrus black spot pathogen, resistant to benomyl in South Africa. Plant
Disease 69, 1007 (abstract)

HGCA (2005). Wheat Disease Management Guide - 2005 Update. Home Grown Cereals Authority, London UK

Hill S N, Hausbeck M K (2008). Virulence and fungicide sensitivity of Phytophthora cactorum isolated from American ginseng gardens in

Wisconsin and Michigan. Plant Disease 92, 1183-1189
Hippe S, Koller W (1986). Ultrastructure and sterol composition of laboratory strains of Ustilago avenae resistant to triazole fungicides.

Pesticide Biochemistry and Physiology 26, 209-219
Hollomon D W (1978). Competitive ability and ethirimol sensitivity in strains of barley powdery mildew. Annals of Applied Biology 90, 195-
204

Hollomon D W, Wheeler I, Dixon K, Longhurst C, Skylakakis G (1997). Defining the resistance risk of the new powdery mildew fungicide

quinoxyfen. Pesticide Science 51, 347-351
Holz B (1979). Uber eine resistenzersheinung von Botrytis cinerea an Reben gegen die neuen Kontaktbotrytizide im Gebeit der Mittelmosel.
Weinberg undKeller 26, 18-25

Hori M, Kakiki K, Misato T (1976). Mechanism of polyoxin resistance in Alternaria kikuchiana. Journal of Pesticide Science 1, 31-40
Hosokawa H., Yamanaka H., Haramoto M, Sano S, Yokota C, Hamamura H. (2006), Occurrence and biological properties of cyflufenamid-

resi stant Sphaerotheca cucurbitae. Japanese. Journal of Phytopathology 72: 260-261 (Japanese abstr.).

Hsiang T, Chastagner G A (1990). Parasitic fitness of benzimidazole and dicarboximide resistant isolates of Botrytis cinerea Botrytis elliptica

and Botrytis tulipae.Phytopathology 80, 978
Hu J H, Hong C X, Stomberg E L, Moorman G W (2008). Mefenoxam sensitivity and fitness analysis of Phytophthora nicotianae isolates from
nurseries in Virginia USA. Plant Pathology 57, 728-736

Source: www.frac.info
January 2013

106


-------
Hubbard J C, Subbarao, Koike S T (1997). Development and significance of dicarboximide resistance in Sclerotinia minor isolates from

commercial lettuce fields in California. Plant Disease 81, 148-153
Hunter T, Jordan V W, Kendall S J (1986). Fungicide sensitivity changes in Rhynchosporium secalis in glasshouse experiments. Proceedings of

the British Crop Protection Conference, Pests & Diseases 523 - 536
Hutton D G (1988). The appearance of dicarboximide resistance in Alternaria alternata in passionfruit in South-East Queensland Australia.

Australasian Plant Pathology 17, 34-36
Hwang B K, Yun J H (1986). Variability in sensitivity to polyoxin B of isolates of Alternaria mali and decreased fitness of polyoxin resistant
isolates. Journal of Phytopathology 115, 305-312

I

Ieki H (1994). Emergence of benzimidazole resistant strains of Elsinoe fawcetti Jenkins in citrus orchards in Japan. Annals of the

Phytopathological Society of Japan 60, 501 - 506
Iida W (1975). On the tolerance of plant pathogenic fungi and bacteria to fungicides in Japan. Japanese Pesticide Information 23, 13-16
Ilott T W, Ingram D S, Rawlinson C J (1987). Studies of fungicide resistance in Pyrenopeziza brassicae cause of light leaf spot disease of

oilseed rape and other brassicas. Transactions of the British Mycological Society 88, 515-523
Ishii H (2004). Fungicide resistance: a factor limiting integrated disease control. Proceedings of the 15th. International Plant Protection
Congress Ed. Guo Yu-yuan. p. 216

Ishii H, Yamaguchi A (1981). Resistance of Venturia nashicola to thiophanate-methyl and bonomyl existence of weakly resistant isolates and its

practical significance. Annals of the Phytopathological Society of Japan 4, 528 - 533
Ishii H, Fraaije B A, Sugiyama T, Noguchi K, Nishimura K, Takeda T, Amano T, Hollomon D W (2001). Occurrence and molecular

characteristics of strobilurin resistance in cucumber powdery mildew and downy mildew. Phytopathology 91, 1166-1171
Ishii H, Noguchi K, Tomita Y, Umemoto S, Nishimura K (1999). Occurrence of strobilurin resistance in powdery mildew and downy mildew on

cucumbers. . Annals of the Phytopathological Society of Japan 65, 655
Ishii, H., Fountaine J., Miyamoto, T., Nishimura, K. and Tomita, Y. (2007), Occurrence of a mutation in the succinate dehydrogenase gene
found in some isolates of cucumber Corynespora leaf spot fungus resistant to boscalid. Japanese Journal of Phytopathology 74: in press
(Japanese abstr.).

Ishii H (2008). Fungicide research in Japan, an overview. In: Modern Fungicides and Antifungal Compounds IV. Proceedings of the 15th

International Reinhardsbrunn Symposium. Eds. Dehne H-W, Gisi U, Kuck K-h, Russell P E, Lyr H. (in press)

Ito I, Yamaguchi T (1977). Occurrence of kasugamycin resistant rice blast fungus influenced by the application of fungicides. Annals of the

Phytopathological Society of Japan<\3, 301-303
Ito Y, Maraguchi H, Seshime Y, Oita S, Yanagi S O (2004). Flutolanil and carboxin resistance in Coprinus cinereus conferred by a mutation in
the cytochrome b560 subunit of succinate dehydrogenase complex (Complex II). Molecular Genetics and Genomics 272, 328 - 335

Source: www.frac.info
January 2013

107


-------
J

Jarvis W R, Hargreaves A J (1973). Tolerance to benomyl in Botrytis cinerea and Penicillium corymbiferum. Plant Pathology 22, 139-141
Jarvis W R, Slingsby K (1975). Tolerance of Botrytis cinerea and rose powdery mildew to benomyl. Canadian Plant Disease Survey 55, 44
Jones A L, Ehret G R (1976). Isolation and characterisation of benomyl tolerant strains of Monilinia fructicola. Plant Disease Reporter 60, 765 -
769

Jones A L, Ehret G R (1981). Resistance of Coccomyces hiemalis to benzimidazole fungicides. Plant Disease 64, 767 - 769
Jones W B, Thompson S V (1982). The effects of fungicide treatments on yield and quality of tomato plants infected with Leveillula taurica.
Phytopathology 72, 970 (abstract)

Joseph M C, Coffey M D (1984). Development of laboratory resistance to metalaxyl in Phytophthora citricola. Phytopathology 74, 1411 - 1414
Joseph-Horne T, Hollomon D W, Heppner C (2000). Silthiofam interferes with mitochondrial function in 'take-all' disease of wheat.

Proceedings of the Brighton Crop Protection Conference - Pests & Diseases 883-888
Joya C (1982). Identification of sigatoka pathogens and monitoring for benzimidazole resistance. Phytopathology 72, 453

K

Kalamarakis A E, De Waard M A, Ziogas B N, Georgopoulos S G (1991). Resistance to fenarimol in Nectria haematococca var cucurbitae.

Pesticide Biochemistry and Physiology 40, 212 - 220
Kanetis L, Forster H, Jones C A, Borkovich K A, Adaskaveg J E (2008). Characterization of genetic and biochemical mechanisms of fudioxonil

and pyrimethanil resistance in field isolates of Penicillium digitatum.Phytopathology 98 205-214.

Kappas A, Georgopoulos S G (1968). Radiation induced resistance to dodine fungicide in Hypomyces. Experietia (Basel) 24, 181 - 182
Karaoglanidis G S, Ionnidis P M, Thanossoulopoulos CC (2000). Reduced sensitivity of Cercospora beticola isolates to sterol demethylation

inhibiting fungicides. Plant Pathology 49, 567 - 572
Katan T, Shabi E (1981). REsistance to dicarboximide fungicides in laboratory isolates of Monilinia laxa. Phytoparasitica 9, 231-232
Katan T, Dunn M T, Papavizas G C (1984). Genetics of fungal resistance in Talaromyces flavus. Canadian Journal of Microbiology 30, 1079-
1087

Katan T, Elad Y, Yunis H (1989). Resistance to diethofencarb NPC in benomyl resistant field isolates of Botrytis cinerea. Plant Pathology 38,
86-92

Kato T, Suzuki K, Takahashi J, Kamoshita K (1984). Negatively correlated cross resistance between benzimidazole fungicides and methyl N-(3,

5-dichlorophenyl) carbamate. Journal of Pesticide Science 9, 489-495
Kendall S J, Hollomon D W (1990). DMI resistance and sterol 14-alpha demethylation in Rhychosporium secalis. Proceedings of the British

Crop Protection Conference Pests & Diseases 1129-1134
Kendall S J, Hollomon D W, Cooke L R, Jones D R (1993). Changes in sensitivity to DMI fungicides in Rhynchosporium secalis. Crop
Protection 12, 357 - 362

Source: www.frac.info
January 2013

108


-------
Keon J P R, White G A, Hargreaves J A (1991). Isolation, characterization and sequence of a gene conferring resistance to the systemic

fungicide carboxin from the maize smut pathogen, Ustilago maydis. Current Genetics 19, 475-481
Khilare V C, Deokate A S, Ganawane L V (2003). Occurrence of aluminium phosethyle (allitte) resistance in Plasmopara viticola causing

downy mildew of grapevine in Maharashtra. Journal of Phytological Research 16, 239-241
Kiebacher H, Hoffmann GM (1976). Benzimidazole resistance in Venturia inaequalis. Zeitschriftfuer Pflanzenkrankheiten undPflanzenschutz
83, 352-358

Kim Y-S, Dixon E W, Vincelli P, Farman M L (2003). Field resistance to strobilurin (Qol) fungicides in Pyricularia grisea caused by mutations

in the mitochondrial cytochrome b gene. Phytopathology 93, 891-900
Kleitman F, Shtienberg D, Blachinsky D, Oppenheim D, Zilberstaine M, Dror O, Manulis S (2005). Erwinia amylovora populations resistant to

oxolinic acid in Israel: prevalence, persistence and fitness. Plant Pathology 54, 108-115
Koller W, Smith F D, Reynolds K L (1991). Phenotypic instability of flusilazole sensitivity in Venturia inaequalis. Plant Pathology 40, 608 -
611

Kousik C S, Keinath A P (2008). First report of insensitivity to cyazofamid among isolates of Phytophthora capsici from the southeastern United
States. Plant Disease 92, 979

L

Lacy G H, Stromberg V K, Cannon N P (1984). Erwinia amylovora mutants and inplanta derived trans conjugants resistant to oxytetracycline.

Canadian Journal of Plant Pathology 6, 33-39
Lambert D H, Wuest P J (1973). Tolerance of Verticillium malthousii isolates to benomyl in relation to linear growth, gepgraphical origin, spray

volume or zineb tolerance. Phytopathology 63, 203 (abstract).

Lambert D H, Salas B (1994). Metalaxyl insensitivity of Phytophthora erythroseptica isolates causing pink rot of potato in Maine. Plant Disease
78,1010

Lamboy J S, Paxton J D (1992). Metalaxyl sensitivity selection within Phytophthora megasperma fsp. glycinea. Plant Disease 76, 932 - 936
Langston D (2002). Quadris resistance in Gummy Stem Blight confirmed. Georgia Extension Vegetable News. 2, 1

Lasseron-De Falandre A, Debieu D, Bach J, Malosse C, Leroux P (1999). Mechanisms of resistance to fenpropimorph and terbinafine, two sterol

biosynthesis inhibitors, in Nectria haematococca, a phytopathogenic fungus. Pesticide Biochemistry and Physiology 64, 167-184
Lei Chen, Shusheng Zhu, Xiaohong Itu, Zhili Pang, Meng Cai, Xili Liu (1	sssing the risk that 'Phytophthora melonis can develop a point

mutation (VI	A3 conferring resistance to carboxylic acid amide fungicides. Plos One 7 (7), e42069

Leroux P, Lafon R, Gredt M (1982). Resistance of Botrytis cinerea to benzimidazole and dicarboximide fungicides situation in Alsace Bordeaux

and Champagne vineyards France. Bulletin OEPP 12, 137 - 144
Leroux P, Clerjeau M (1985). Resistance of Botrytis cinerea and Plasmopara viticola to fungicides in French vineyards. Crop Protection 4, 137
- 160

Source: www.frac.info
January 2013

109


-------
Leroux P, Berthier G (1988). Resistance to carboxin and fenfuram in Ustilago nuda Jens. Rostr. the causal agent of barley loose smut. Crop
Protection 7, 16-19

Leroux P, Marchegay P (1991). Caracterisation des souches de Pseudocercosporella herpotrichoides agent du Pietin-verse des cereales,

resistantes au prochloraze, isolees en France sur ble tendre d'hiver. Agrononie 11, 767 - 776
Li H X, Xiao C L (2008). Characterization of fludioxonil resistant and pyrimethanil resistant phenotypes of Penicillium expansum from apple.

Phytopathology 98, 427-435

Li H, Leifert C (1994). Development of resistance in Botryotinia fuckeliana (de Barry) Whetzel against the biological control agent Bacillus

subtilis CL27. Zeitschriftfur Pflanzenkrankheiten undPjlanzenschutz 101, 414-8.

Littrell R H (1974). Tolerance in Cercospora arachidicola to benomyl and related fungicides. Phytopathology 64, 1377 - 1378
Littrell R H (1977) Population dynamics and control of benomyl tolerant and sensitive pecan scab strains. Proceedings of the American
Phytopathological Society 3, 1976

Liu X, Yin Y N, Wu J B, Jiang J H, Ma Z H (2010). Identification and Characterization of Carbendazim-Resistant Isolates of Gibberella zeae

Plant Disease 94, 1137-1142
Locke T, Thorpe I G (1976). Benomyl tolerance in Verticillium dahliae Kleb. Plant Pathology 25, 59
Locke T, Scrace J, Peace J M (1997). Resistance of Phytophthoraporri to metalaxyl. Pesticide Science 51, 371 - 374
Lu Y L, Sutton T B, Ypema H (2003). Sensitivity of Alternaria mali from north Carolina apple orchards to pyraclostrobin and boscalid.
Phytopathology 93, S54 (Abstract)

Lu X H, Zhu S S, Bi Y, Liu X L, Hao J J (2010). Baseline sensitivity and resistance risk assessment of Phytophthora capsici to iprovalicarb.

Phytopathology, 100, 1162-1168
Lucas J A, Bower L A, Coffey M D (1990). Fungicide resistance in soil-borne Phytophthora species. EPPO Bulletin 20, 199-206

M

Ma B, Uddin W (2009). Fitness and competitive ability of an azoxystrobin resistant G143 A mutant of Magnaporthe oryzae from perennial

ryegrass. Plant Disease 93 1044-1049
Ma, Z, Michailides T J (2004). Characterization of iprodione-resistant Alternaria isolates from pistachio in California. Pesticide Biochemistry
and Physiology 80, 75 -84

Ma Z, Felts D, Michailides T J (2003). Resistance to azoxystrobin in Alternaria isolates from pistachio in California. Pesticide Biochemistry and
Physiology 77, 66 - 74

Ma Z, Luo Y, Michailides T J (2001). Resistance of Botryosphaeria dothidea from pistachio to iprodione. Plant Disease 85, 183-188
Magie R O, Wilfret G J (1974). Tolerance of Fusarium oxysporum f sp. gladioli to benzimidazole fungicides. Plant Disease Reporter 58, 256 -
259

Malathrakis N E (1989). Resistance of Botrytis cinerea to dichlofluanid in greenhouse vegetables. Plant Disease 73, 138-141

Source: www.frac.info
January 2013

110


-------
Malathrakis N E, Vakalounakis D J (1983). Resistance to benzimidazole fungicides in the gummy stem blight pathogen Didymella bryoniae on

cucurbits. Plant Pathology 32, 395 - 400
Manulis S, Kleitman F, Shtienberg D, Shwartz H, Oppenheim D, Zilberstaine M, Shabi E (2003). Changes in the sensitivity of Erwinia

amylovora populations to streptomycin and oxolinic acid in Israel. Plant Disease 87, 650-654
Maria R, Sullia S B (1986). Acquired resistance of Alternaria solani and Sclerotium rolfsii to polyoxin D. Journal of Phytopathology 116, 60-66
Markoglou A N, Ziogas B N (1999). Genetic control of resistance to fenpropimorph in Ustilago maydis. Plant Pathology 48, 521-530
Markoglou AN, Ziogas B N (2000). Genetic control of resistance to tridemorph in Ustilago maydis. Phytoparasitica 28, 349-360
Markoglou AN, Ziogas B N (2001). Genetic control of resistance tothe piperidine fungicide fenpropidin in Ustilago maydis. Journal of
Phytopathology 149, 551-559

Markoglou A N, Malandrakis A A, Vitoratos A G, Ziogas B N (2006). Characterization of laboratory mutants of Botrytis cinerea to Qol

fungicides. European Journal of Plant Pathology 115, 149 - 162
Markoglou A N, Doukas E G, Ziogas B N (2008). Phenylpyrrole resistance and aflatoxin production in Aspergillus parasiticus Speare.

International Journal of Food Microbiology 127 268-275
Martin S B, Lucas L T, Campbell CL (1984). Comparative sensitivity of Rhizoctonia solani and Rhizoctonia like fungi to selected fungicides in-

vitro. Phytopathology 74, 778 - 781
Matsuzaki M, Azegami K, Chata K-I (1981). Streptomycin resistance in pathogenic bacteria isolated from diseased lettuce. Annals of the

Phytopathological Society of Japan 47, 297-300
Mavroedi V I, Shaw M W (2005). Sensitivity distributions and cross resistance patterns of Mycosphaerella graminicola to fluquinconazole,

prochloraz and azoxystrobin over a period of 9 years. Crop Protection 24, 259-266
McKay G J, Egan D, Morris E, Brown A E (1998). Identification of benzimidazole resistance in Cladobotryum dendroides using a PCR-based

method. Mycological Research 102, 671 - 676
McGrath M T, Shishkoff N (2003a). Resistance to strobilurin fungicides in Podosphaera xanthii associated with reduced control of cucurbit

powdery mildew in a research field. Phytopathology 93, S59
McGrath M T, Shishkoff N (2003b). First report of the cucurbit powdery mildew fungus (Podosphaera xanthii) resistant to strobilurin fungicides

in the United States. Plant Disease 87, 1007
McHugh J B, SchreiberJ R (1984). Tolerance of Verticillium dahliae to benzimidazoles. Plant Disease 68, 424 - 427
Meissner S, Stammler G. (2010). Monilinia laxa, M. fructigena andM. fructicola: Risk estimation of resistance to Qol fungicides and

identification of species with cytochrome b gene sequences. Journal of Plant Diseases and Protection. 117, 162-167
Metcalfe R J, Shaw M W, Russell P E (2000). The effect of dose and mobility on the strength of selection for DMI fungicide resistance in

inoculated field experiments. Plant Pathology 49, 546-557
Meyer E (1976). Resistance development against systemic fungicides benzimidazole derivatives in Colletorichum lindemuthianum. Mitteilungen
aus der Biologischen Bundesanstaltfur Land- undForstwirtschaft (166), 7-135

Source: www.frac.info
January 2013

111


-------
Miao V, Higgins V J (1986). Detection of induced susceptibility in tomato using mutants of Cladosporium fulvum tolerant to cycloheximide or

benomyl. Canadian Journal of Botany 64, 1299-1305
Miller T C, Gubler W D (2003). Uncinula necator retains high resistance levels to triadimefon in a survey of California populations despite

product absence for fourteen years. Phytopathology 93, SI 13
Minsavage G V, Cantero B I, Stall R E (1990). Plasmid mediated resistance to streptomycin in Xanthomonas campestris pv. vesicatoria.
Phytopathology 80, 719-723

Miyamoto T., Ishii H., Seko T., Tomita Y., Kobori S. Ogawara T. (2007). Occurrence of boscalid-resistant isolates of cucumber Corynespora

leaf spot fungus (C. cassiicola). Japanese Journal of Phytopathology 74: in press (Japanese abstr.).

Miyamoto T, Ishii H, Seko T, Kobori S, Tomita Y. (2009). Occurrence of Corynespora cassiicola isolates resistant to boscalid on cucumber in

Ibaraki prefecture, Japan. Plant Pathology 58, 1144-1151
Miyamoto T, Ishii H,Tomita Y (2010a). Occurrence of boscalid resistance in cucumber powdery mildew in Japan and molecular characterization

of the iron-sulfur protein of succinate dehydrogenase of the causal fungus. Journal of General Plant Pathology 76, 261-267
Miyamoto T, Ishii H, Stammler G, Koch A, Ogawara T, Tomita Y, Fountaine J M, Ushio S, Seko T, Kobori S. (2010b). Distribution and

molecular characterisation of Corynespora cassiicola isolates resistant to boscalid. Plant Pathology 59, 873-881
Molinero V, Leroux P, Tivoli B, Champion R, Said J (1993). Resistance to benzimidazole fungicides in pathogens of Ascochta diseases of peas.

Seed Science and Technology 21,531 -535
Moller W J, Beutel J A, Reil W O, Zoller B G (1972). Fire blight resistance to streptomycin in California. Phytopathology 62, 779
Mondal S N, da Silva A G, Dewdney M M (2009). Resistance to strobilurin fungicides in a population of Alternaria alternata causing

Alternaria brown spot of citrus. APS Meeting, S88
Moorman G W, AroraN, Kim S H (2002). Propamocarb resistance in species of Pythium. Phytopathology 92, S58 (meeting abstract)

Moorman G W, Kang S, Geiser D M, Kim S H (2002). Identification and characterisation of Pythium species associated with greenhouse floral

crops in Pennsylvania. Plant Disease 86, 1227 - 1231
Moorman G W, Kim S H (2004). Species of Pythium from greenhouses in Pennsylvania exhibit resistance to propamocarb and mefenoxam.
Plant Disease 88, 630-632

Muirhead T F (1974). Resistance to benzimidazole fungicides in blue mold of citrus in Queensland. Australian Journal of Experimental

Agriculture and Animal Husbandry 14, 698 - 701
Munro J M, Dolan A, Williamson B (1988). Cane spot (Elsinoe veneta) in red raspberry: infection periods and fungicidal control. Plant
Pathology 37, 390-396

N

Nachmias A, Barash I (1976). Decreased permeability as a mechanism of resistance to methylbenzimidazol-2-yl carbamate in Sporobolomyces
roseus. Journal of General Microbiology 94, 167 - 172

Source: www.frac.info
January 2013

112


-------
Naegler M, Diaconu V, Alexandria A A (1977). The resistance of powdery mildew vine Uncinula necatorand powdery mildew cucumbers

Sphaerotheca fuliginea to benzimidazole systemic fungicides. Analele Institutului de Cercetari Pentru Protectia Plantelor 12, 345 - 352
Napier B A S, Bayles R A, Stigwood P L (2000). Sensitivity of powdery mildew and yellow rust to DMI, morpholine and strobilurin fungicides

in England and Scotland. Proceedings of the BCPC Conference Pests & Diseases, 427-434
Noble M, Maggarvie Q D, Hams A F, Leaf L L (1966). Resistance to mercury of Pyrenophora avenae in Scottish seed oats. Plant Pathology 15,
23-28

Nomura H, Paik S-Y, Izuhara M, Sugiyama M (1991). Resistant mechanisms to blasticidin S in Streptomyces lividans. Korean Biochemical
Journal 24, 327-330

Nuninger-Ney C, Schwinn F J, Staub T (1989). In vitro selection of sterol biosynthesis inhibitor (SBI) resistant mutants in Moniliniafructicola
(Wint.) Honey. Netherlands Journal of Plant Pathology 95, 137 - 150

O

O'Brien R G, Vawdrey L L, Glass R J (1988). Fungicide resistance in cucurbit powdery mildew Sphaerotheca fuliginea and its effect on field

control. Australian Jounal of Experimental Agriculture 28, 417-424
Ogawa K (1988). Damage by Bakanae disease and its chemical control. Japanese Pesticide Information 52, 13-15
Ogawa J M, Manji B T, Bose E A (1981). Detection of benomyl resistant Monilinia laxa on apricots. Phytopathology 71, 893
Olaya G, Cleere S, Stanger C, Burbidge J, Hall A, Windass J (2003). A novel potential target site Qol fungicide resistance mechanism in

Pythium aphanidermatum. Phytopathology 93, S67
Olaya G, Holm A (2001). Sensitivity of Didymella bryoniae isolates to azoxystrobin. Phytopathology 91, S67-S68

Omat.su N, Tomihama T, Nonaka Y ( Incidence of strobilurin and benzimidazole resistant strains of Pestalotiopsis longiseta, causal agent

of gray blight, and practical control in tea field of Kagoshima Prefecture. Japanese Journal of 'Phytopathology, 78, 3-9
Orth A B, Sfarra A, Pell E J, Tien M (1994). Characterization and genetic analysis of laboratory mutants of Ustilago maydis resistant to
dicarboximide and aromatic hydrocarbon fungicides. Phytopathology 84, 1210-1214

P

Pasche J S & Gudmestad N C (2008). Prevalence, competitive fitness and impact of the F129L mutation in Alternaria solani from the United

States. Crop Protection 27, 427-435
Pasche J S, Piche L M, Gudmestad N C (2005). Effect of the F129L mutation in Alternaria solani on fungicides affecting mitochondrial

respiration. Plant Disease 89, 269-278
Pasche J S, Wharam C M, Gudmestad N C (2004). Shift in sensitivity of Alternaria solani to Qol fungicides. Plant Disease 88, 181 - 187
Pasche J S, Wharam C M, Gudmestad N C (2002). Shift in sensitivity of Alternaria solani (potato early blight) to strobilurin fungicides.

Proceedings of the BCPC Conference Pests & Diseases 841-846
Paulus A O, Nelson J, Besemer S (1976). Resistance of Septoria leucanthemi to benzimidazole fungicides. Plant Disease Reporter 60, 695 - 697

Source: www.frac.info
January 2013

113


-------
Pearson R C (1980). Occurrence of benomyl resistant strains of Uncinula necator on grapes in New York USA. Phytopathology 70, 467
Pearson R C, Taschenberg E F (1980). Benomyl resistant strains of Uncinula necator on grapes. Plant Disease 64, 677 - 680
Pennucci A, Beever R E, Laracy E P (1990). Dicarboximide resistant strains of Microdochium nivale in New Zealand. Australasian Plant
Pathology 19, 38-41

Penrose L J, Koffmann W, Nicholls M R (1985). Field occurrence of vinclozolin resistance in Monilinia fructicola. Plant Pathology 34, 228-234
Peters R D, Piatt H W, Drake K A, Coffin R H, Moorehead S, Clark M M, Al-Mughrabi K I, Howard R J (2008). First report of fludioxonil

resistant isolates of Fusarium spp. causing potato seed-piece decay. Plant Disease 92, 172
Plumbley R A, Hernandez M A, Thompson A K (1984). Benomyl tolerance in a strain of Penicillium sclerotigenum infecting yams and the use

of imazalil as a means of control. Tropical Agriculture 61, 182-185
Porter L D, Miller J S, Hamm P B, David N L, Gieck S L, Miller J S, Gunderson B, Inglis D A. (2009) Metalaxyl-M resistant Pythium species in

potato production areas of the Pacific Northwest of the USA. American Journal of Potato Research 86 315-326
Presly A H, Maude R B (1982). Tolerance in Botrytis squamosa to iprodione. Annals of Applied Biology 100, 117-127
Prest G de, Poppe J (1988). Efficacy of fungicides against Cylindrocladium scoparium and their influence on Azalea cuttings. Meded. Fac.

Landbouwwet. Rijksuniv. Gent 53, 643-650
Proffer T J, Berardi R, Ma Z, Nugent J E, Ehret G R, McManus P S, Jones A L, Sundin G W (2006). Occurrence, distribution, and polymerase
chain reaction-based detection of resistance to sterol demethylation inhibitor fungicides in populations of Blumeriella jaapii in Michigan.
Phytopathology 96, 709 - 717

QR

Reddy K P, Anilkumar T B (1989). Resistance development to mancozeb in Helminthosporium halodes. Mysore Journal of Agricultural
Sciences 23, 184-188

Redi H, Steinkellner S (1996). Proof of sensitivity reduction with oidium towards DMI fungicides in Austrian viticulture. Mitteilungen
Klosterneuburg 46, 181-188

Reimann S, Deising H B (2005). Inhibition of efflux mediated fungicide resistance in Pyrenophora tritici-repentis by a derivative of 4 '-

hydroxyflavone and enhancement of fungicide activity. Applied and Environmental Microbiology 71, 3269-3275
Remiro D, Kimati H (1974). Resistencia a benomil e tiofanato em Mycosphaerella fragariae (Tul.) Lind. Biologico 40, 22-24
Reuveni M (2001). Improved control of powdery mildew {Sphaerothecapannosa) of nectarines in Israel using strobilurin and polyoxin B

fungicides; mixtures with sulfur; and early bloom applications. Crop Protection 20, 663-668
Reuveni M, Eyal H, Cohen Y (1980). Development of resistance to metalaxyl in Pseudoperonospora cubensis. Plant Disease 64, 1108 - 1109
Reynolds K L, Brenneman T B, Bertrand P F (1997). Sensitivity of Cladosporium caryigenum to propiconazole and fenbuconazole. Plant
Disease 81, 163 - 166

Richardson L T (1973). Adaptive tolerance of Fusarium solani to benzimidazole derivatives in vitro. Canadian Journal of Botany 51, 1725-1732

Source: www.frac.info
January 2013

114


-------
Rodriguez R, Melendez P L (1984). Chemical control of cowpea powdery mildew and foliar spots. Journal of the Agricultural University P. R
68, 445-455

Romano M L, Edgington L V (1985). Resistance to metalaxyl in Phytophthora crown rot and root rot of African violet. Canadian Journal of
Plant Pathology 7, 448 - 449

Russell P E, Gaujard C, Creange P, Daniels A (2001). Aspects of take-all control by fluquinconazole. In: Modern Fungicides and Antifungal
Compounds III. Eds. H-W Dehne, U Gisi, K-H Kuck, P E Russell, H Lyr. AgroConcept GmbH, Bonn. pp. 91-102

S

Saito S, Cadie-Davidson L, Wilcox W F (2011). Practical resistance to fenhexamid Botrytis cinerea isolates from grapevines in New York.
Phytopathology, 101, SI58

Sakurai H, Naito H (1976). A cross resistance of Pyricularia oryzae to kasugamycin and blasticidin S. Journal of Antibiotics (Tokyoj 29, 1341-
1342

Sakurai H, Kwano M, Goh N, Yaoita T, Aoyaki K, Naito H (1977). Sensitivity distribution of physiologic races of Pyricularia oryzae to

kasugamycin. Journal of Antibiotics (Tokyo) 30, 607-609
Samuels G J, Johnston P R (1980) Benomyl and the Verticillium diseases of cultivated mushrooms. New Zealand Journal of Agricultural
Research 23, 155 - 157

Sanders P L, Soika M D (1988). Metalaxyl resistance frequency in overwintering populations of Pythium aphanidermatum from metalaxyl

control failure sites. Phytopathology 78, 1510
Sanders P L, Coffey M D, Greer G D, Soika M D (1990). Laboratory induced resistance to fosetyl aluminium in a metalaxyl resistant field

isolate of Pythium apahanidermatum. Plant Disease 74, 690-692
Saniewska A (1985). Red staining of Narcissi leaves. Ochr. Rosl. 29, 19-20
Sawada H, Sugihara M, Takagaki M, Nagayama K (2004). Pest Management Science 60, 777-785

Schabi E, Ben-Yephet Y (1976). Tolerance of Venturiapirina to benzimidazole fungicides. Plant Disease Reporter 60, 451 - 454
Schepers H T A M (1983). Decreased sensitivity of Sphaerotheca fuliginea to fungicides which inhibit ergosterol biosynthesis. Netherlands

Journal of Plant Pathology 89, 185 - 187
Schepers H T A M (1984). Persistence of resistance to fungicides in Sphaerotheca fuliginea. Netherlands Journal of PLant Pathology 90, 165-
171

Schepers H T A M (1985a). Development and persistence of resistance to fungicides in Sphaerotheca fuligenea in cucumbers in the Netherlands.

Doktorthesis Proefschrift van de Landbouwhogeschool te Wageningen
Schepers H T A M (1985b). Changes during a three year period in the sensitivity to ergosterol biosynthesis inhibitors of Sphaerotheca fuliginea

in the Netherlands. Netherlands Journal of Plant Pathology 91, 105 - 118
Schroedder W T, Providenti R (1969). Resistance to benomyl in powdery mildew in cucurbits. Plant Disease Reporter 53, 271 - 275
Schroth M N, Thomson S V, Moller W J (1979). Streptomycin resistance in Erwinia amylovora. Phytopathology 69, 565-568

Source: www.frac.info
January 2013

115


-------
Semar M, strobel D, Koch A, Klappach K, Stammler G. (2007). Field efficacy of pyraclostrobin against populations of Pyrenophora teres

containing the F129L mutation in the cytochrome b gene. Journal of Plant Diseases and Protection 114 117-119
Seppanen E (1983). Different tolerances of 14 Fusarium spp. to thiophanate-methyl. Annales Agriculturae Fenniae 22, 120-121
Sergeva V, Nair N G, Verdana J R, Shen C, Barchia I, Spooner-Hart R (2002). First report of anilinopyrimidine resistant phenotypes in Botrytis

cinerea on grapevines in Australia. Australasian Plant Pathology 31, 299-300
Serrhini N, Maraite M, Meyer J A (1985). In-vitro selection of strains of Phytophthora citrophthora resistant to metalaxyl. Bulletin OEPP 15,
443 - 450

Sheridan J E, Grbavac N, Sheridan M H (1985). Triadimenol insensitivity in Pyrenophora teres. Transactions of the British Mycological Society
85,338-341

Shim J-Y, Choi H-T, Yoon K-S (1994). Cell biological changes of validamycin resistant strain in Coprinus cinereus. Korean Journal of
Mycology 22, 31-35

Shew H D (1985). Response of Phytophthora parasitica var nicotianae to metalaxyl exposure. Plant Disease 69, 559 - 562
Shim M-Y, Starr J L, Neller K P, Woodard K E, Lee TA Jr. (1998). Distribution of isolates of Sclerotium rolfsii tolerant to

pentachloronitrobenzene in Texas peanut fields. Plant Disease 82, 103-106
Sierotzki H, Kraus N, Assemat P, Stanger C, Cleere S, Windass J, Gisi U (2005). Evolution of resistance to Qol fungicides in Plasmopara
viticola populations in Europe. In: Modern Fungicides and Antifungal Compounds IV. Eds. H-W Dehne, U Gisi, K-H Kuck, P E Russell, H
Lyr. BCPC, Alton, UK pp. 73-80

Sierotzki H, Wullschleger J, Gisi U (2000a). Point mutation in cytochrome b gene conferring resistance to strobilurin fungicides in Erysiphe

graminis f. sp. tritici field isolates. Pesticide Biochemistry and Physiology 68, 107-112
Sierotzki H, Parisi S, Steinfeld U, Tenzer I, Poirey S, Gisi U (2000b). Mode of resistance to respiration inhibitors at the cytochrome bcl enzyme

complex of Mycosphaere I la fijiensis field isolates. Pest Management Science 56, 833-841
Silva V L D, Loppes C A (1995). Pseudomonas syringae pv. tomato resistant to streptomycin and oxytetracycline in tomato plants treated or not

with agricultural antibiotics. Fitopatologia Brasileira 20, 80-84
Sisler H D (1971). Mode of action of benzimidazole fungicides. Proceedings of the 2nd International Congress of Pesticide Chemistry IUPAC,
Tel-Aviv, p. 323

Sitton J W, Pierson C F (1982). Interaction and control of Alternaria stem decay and blue mold in Anjou pears. Phytopathology 72, 1008
(Abstract)

Skinner W, Bailey A, Renwick A, Keon J, Gurr S, Hargreaves J (1998). A single amino-acid substitution in the iron-sulphur protein subunit of

succinate dehydrogenase determines resistance to carboxin in Mycosphaerella graminicola. Current Genetics 34, 393-398
Smiley R W, Howard, R J (1976). Tolerance to benzimidazole derivative fungicides by Fusarium roseum on Kentucky blue grass turf. Plant
Disease Reporter 60, 91-94

Smith F D, Phipps P M, Stipes R J, Brenneman T B (1995). Significance of insensitivity of Sclerotinia minor to iprodione in control of
Sclerotinia blight of peanut. Plant Disease 79, 517-523

Source: www.frac.info
January 2013

116


-------
Spalding D H (1982). Resistance of Mango pathogens to fungicides used to control postharvest diseases. Plant Disease 66, 1185-1186
Spotts R A, Cervantes L A (1995). Copper, oxytetracycline and streptomycin resistance of Psedomonas syringae pv. syringae strains from pear

orchards in Oregon and Washington. Plant Disease 79, 1132-1135
Staub T, Sozzi D (1981). Resistance au metalaxyl en pratique et les consequences pour son utilisation. Phytiatrie - Phytopharmacie 30, 283 -
291

Stanis V F, Jones A L (1985). Reduced sensitivity to sterol inhibiting fungicides in field isolates of Venturia inaequalis. Phytopathology 75,
1098- 1101

Starndberg J O (1984). Efficacy of fungicides against persistence of Alternaria dauci on carrot seed Daucus carota. Plant Disease 68, 39-42
Staunton W F, Kavanagh T (1975). Resistance of fungal pathogens to benomyl in Ireland and results of alternative spray programmes for disease

control. Proceedings of the British Insecticide and Fungicide Conference 8, 1-4
Steekelenburg NAM van (1973). Ascochya bij chrysant; resistent geworden tegen benomyl (Benlate). Vakbl. Bloemistrerij 28, 13
Steekelenburg NAM van (1987). Resistance to benzimidazole and dicarboximide fungicides in Botrytis cinerea and Didymella bryoniae in

cucumbers in the Netherlands. Medelingen van de Faculteit Landbouwwetenschappen Universiteit Gent 52, 875-880
Stehmann C, De Waard M A (1996). Sensitivity of populations of Botrytis cinerea to triazoles, benomyl and vincl ozolin. European Journal of
Plant Pathology 102, 171-180

Stein J M, Kirk W W (2003). The generation and quantification of resistance to dimethomorph in Phytophthora infestans. Plant Disease 88, 930
-934

Steinfeld U, Sierotzki H, Parisi S, Gisi U (2002). Comparison of resistance mechanisms to strobilurin fungicides in Venturia inaequalis. In:
Modern Fungicides and Antifungal Compounds III. Eds. H-W DEhne, U Gisi, K-H Kuck, P E Russell, H Lyr. AgroConcept GmbH, Bonn,
pp. 167-176

Steva H, Cartolaro P, Gomes da Silva M T (1990). Tolerance of powdery mildew of SBI fungicides: situation for 1989. Phytoma 419, 41 - 44
Stevenson K L, Langston D B, Seebold K W (2002). Resistance to azoxystrobin in the gummy stem blight pathogen in Georgia. Phytopathology
92, S79

Stevenson K L, Langston D, Sanders B F (2008). Baseline sensitivity and evidence of resistance to boscalid in Didymella bryoniae
Phytopathology 98: S151

Stover R H (1979). Field observations on benomyl tolerance in ascospores of Mycosphaerella fijiensis var. difformis. Transactions of the British
Mycological Society 72, 518-519

Suta V, Radulescu M (1986). Investigations on the integrated control of apple diseases in the orchards with biotypes of Venturia inaequalis and

Podosphaera leucotricha (Ell et Ev. ) Salm resistant to benzimidazolyc and triforine fungicides. Hortscience 23, 747 (abstract)

Szkolnik M, Gilpatrick J D (1969). Apparent resistance of Venturia inaequalis to dodine in New York apple orchards. Plant Disease Reporter 53,
861 - 864

Szkolnik M, Gilpatrick J D (1971). Resistance of Venturia inaequalis to N dodecyl guanidine acetate. Phytopathology 61, 132

Source: www.frac.info
January 2013

117


-------
T

Taga M, Nakagawa H, Tsuda M, Ueyama A (1979). Identification of 3 loci controlling kasugamycin resistance in Pyricularia oryzae.
Phytopathology 69, 463-466

Takagaki M, Kaku K, Watanabe S, Kawai K, Shimizu T, Sawada H, Kumakaru K, Nagayama K (2004). Mechanism of resistance to

carpropamid in Magnaporthe grisea. Pest Management Science 60, 921-926
Tamura O (2000). Fluazinam resistance in leguminous Botrytis cinerea and resistance management. Abstracts of the 10th. Symposium of

Research Committee on Fungicide Resistance pp 7-16
Tanaka F, Saito I, Miyajima K, Tsuchiya S, Tsuboki K (1983). Occurrence of thiophanate methyl tolerant isolates of Fusarium nivale synonymy

Gerlachia nivalis a causal fungus of snow mold of winter wheat in Japan. Annals of the Phytopathological Society of Japan 49, 565 - 566
Taylor R J, Sales B, Secor G A, Rivera V, Gumestad N C (2002). Sensitivity of North American isolates of Phytophthora erythroseptica and

Pythium ultimum to mefenoxam (metalaxyl). Plant Disease 86, 797 - 802
Thanassoulopoulos C C, Giannopilitis C N, Kitsos G T (1970). Evaluation of sensitiveness and development of resistance of Fusarium

oxysporum f.sp. lycopersici to benomyl. Phytopathologischea Zeitschrift 70, 114-120
Tivoli B, Deltour A, Molet D, Bedin P, Jouan B (1986). Isolation of thiabendazole resistant strains of Fusarium roseum var sambucinum from

potato tubers. Agronomie 6, 219 - 224
Tominaga A, Kobayashi Y (1978). Kasugamycin resistant mutants of Bacillus subtilis. Journal of Bacteriology 135, 1149-1150
Tomita Y, Ishii H (1998). Reduced sensitivity to fenarimol in Japanese field strains of Venturia nashicola. Pesticide Science 54, 150 - 156
Top Agrar (2009). Online article in Top Agrar December 2009. www.topagrar.com

Tramier R, Bettachini A (1974). A strain of Fusarium oxysporum f sp. dianthi resistant to systemic fungicides. Annales de Phytopathologie 6,
231 -236

Tremblay D M, Talbot B G, Carisse O (2003). Sensitivity of Botrytis squamosa to different classes of fungicides. Plant Disease 87, 573-578
U

Uesugi Y (1981). Resistance to fungicides in Pyricularia oryzae. Journal of pesticide Science 6, 239-246
V

Valaskova E (1983). The influence of various carbon and nitrogen sources on mycelium growth and resistance stability in a benomyl tolerant
strain of Fusarium oxysporum f sp. tulipae. Sbornik UVTIZ (Ustav Vedeckotechnickych Informaci pro Zemedelstvi) Ochrana Rostlin 19, 251
-260

Van Bruggen A H C, Arneson P A (1984). Resistance in Rhizoctonia solani to tolclofos methyl. Netherlands Journal of Plant Pathology 90, 95
- 106

Vargas J M Jr. (1973). A benzimidazole resistant strain of Erysiphe graminis. Phytopathology 63, 1366 - 1368

Source: www.frac.info
January 2013

118


-------
Vargas J M Jr., Golembiewski R, Detweiler A R (1992). Reduced sensitivity of Sclerotinia homoeocarpa to DMI fungicides. Phytopathology 82,
1069

Veverke K (1983). Resistance of Verticillium albo-atrum Reinke et Bert, to benomyl and trimorfamid. Zbl. Mikrobiol. 138, 565-568
Viljanen-Rollinson S L H, Marroni M V, Butler R C (2007). Reduced sensitivity to carbendazim in isolates of Botrytis allii. New Zealand Plant
Protection 60 108-113

Vincelli P, Dixon E (2002). Resistance to Qol (strobilurin-like) fungicides in isolates of Pyricularia grisea from perrenial ryegrass. Plant
Disease 86, 235-240

Vitale A, Aiello D, Castello I, Polizzi G (2009). First report of Benzimidazole resistant isolates of Cylindrocladium scoparium in Europe.

Plant Disease 93 110

W

Walker A S, Auclair C, Gredt M, Leroux P (2009). First occurrence of resistance to strobilurin fungicides in Microdochium nivale and

Microdochium majus from French naturally infected wheat grains. Pest Management Science 65 906-915
Walsh R C, Sisler H D (1981). Cross resistance patterns of fenarimol resistant isolates of Ustilago maydis. Phytopathology 71, 111 - 772
Weber R W S, Palm G (2010). Resistance of storage rot fungi Neofabraeaperennans, N. alba, Glomerella acutata and Neonectria galligena

against thiophanate-methyl in Northern German apple production. Journal of Plant Diseases and Protection. 117, 185-191
Whan J H (1976). Tolerance of Sclerotinia fructicola to benomyl. Plant Disease Reporter 60, 200 - 201

White G A, Georgopoulos S G (1986). Thiophene carboxamide fungicides structure activity relationships with the succinate dehydrogenase

complex from wild type and carboxin resistant mutants of Aspergillus nidulans. Pesticide Biochemistry and Physiology 25, 188-204
White J G, Stanghellini M E, Ayoubi L M (1988). Variation in the sensitivity to metalaxyl of Pythium spp isolated from carrot and other sources.

Annals of Applied Biology 113, 269 - 278
Whiteside J O (1980a). Detection of benomyl tolerant strains of Elsinoe fawcetti in Florida citrus groves and nurseries. Plant Disease 64, 871 -
872

Whiteside J O (1980b). Tolerance of Mycosphaerella citri to benomyl in Florida USA citrus groves. Plant Disease 64, 300 - 302
Wicks T (1977). Tolerance to benzimidazole fungicides in blue mold (.Penicillium expansum) on pears. Plant Disease Reporter 61, 447-449
Wilcox W F, Burr J A, Riegel D G, Wong F P (2003). Practical resistance to Qol fungicides in New York populations of Uncinula necator

associated with quantitative shifts in pathogen sensitivities. Phytopathology 93, S90
Wild B L (1983). Double resistance by citrus green mold Penicillium digitatum to the fungicides guazatine and benomyl. Annals of Applied
Biology 103, 237 - 242

Wise K A, Bradley C A, Pasche J S, Gudmestad N C (2009). Resistance to Qol fungicides in Ascochyta rabiei from chickpea in the Northern
Great Plains. Plant Disease 93 528-536

Source: www.frac.info
January 2013

119


-------
Wong F P, De la Carda K A, Hernandez-Martinez R, Midland S L ( 2008). Detection and characterization of benzimidazole resistance in

California populations of Colletotrichum cereale. Plant Disease 92, 239-246
Wong S P (2003). Past, current and future challenges for fungicide resistance management for turfgrass pathogens. Phytopathology 93
supplement6, SI 14

Wright P J (2004). Resistance of Peronospora destructor (onion downy mildew) to metalaxyl fungicides. New Zealand Plant Protection 57, 347.
(Conference Proceedings)

Wu Y, Lu S, Huang S, Fu G, Chen L, Xie D, L Q, Cen Z (2011). Field resistance of Phytophthora melonis to metalaxyl in South China.
Weishengwu Xuebo, 51, 1078-1086

XYZ

Xiao C L, Kim Y K, Boal, R J (2011). First report of occurrence of pyrimethanil resistance in Penicillium expansum from stored apples in

Washington State. Plant Disease 95, 72
Yamada N, Motoyama T, Nakasako M, Kagabu S, Kudo T, Yamaguchi I (2004). Enzymatic characterisation of scytalone dehydratase Val75Met
variant found in melanin biosynthesis dehydratase inhibitor (MBI-D) resistant strains of the rice blast fungus. Bioscience Biotechnology and
Biochemistry 68, 615-621

Yamaguchi J, Inada M, Matsuzaki M (2000). Occurrence of DMI fungicide resistant isolates of Mycovellosiella nattrassii Deighton, causal

fungus of leaf mold of eggplant. Japanese Journal of Phytopathology 66, 78 - 84
Yamaguchi J., Kuchiki F., Hirayae K., So K. (2002), Decreased effect of carpropamid for rice blast control in the west north area of Saga

prefecture in 2001. Japanese. Journal of Phytopathology 68: 261 (Abstr.).

Yano K, Kawada Y (2003). Occurrence of strobilurin-resistant strains of Mycovellosiella nattrassii, causal fungus of leaf mold of eggplants.

Japanese Journal of Phytopathology 69, 220-223
Yin Y, Liu X, Li B, Ma Z (2009). Characterization of sterol demethylation inhibitor resistant isolates of Fusarium asiaticum and F.

graminearum collected from wheat in China. Phytopathology 99 487-497
Yin Y N, Kim Y K, Xiao C L (2011). Molecular characterisation of boscalid resistance in field isolates of Botrytis cinerea from apple.
Phytopathology 101, 986-995

Young D H, Kemmitt GM, Owen J (2005). A comparative study of XR-539 and other oomycete fungicides: Similarity to dimethomorph and
amino acid amides in its mechanism of action. In: Modern Fungicides and Antifungal Compounds IV. Eds. H-W Dehne, U Gisi, K-H Kuck,
P E Russell, H Lyr. BCPC, Alton, UK pp. 145-152
Young D H, Spiewak S L, Slawecki R A (2001). Laboratory studies to assess the risk of development of resistance to zoxamide. Pest

Management Science 57, 1081-1087
Yu K-S (1981). Studies on the fungicide resistance of citrus blue mold fungus. Plant Protection Bulletin (Taichung) 23, 193 - 200
Yuan S K, Liu X L, Si N G, Dong J, Gu B G, Jiang H (2006). Sensitivity of Phytophthora infestans to flumorph: in vitro determination of
baseline sensitivity and the risk of resistance. Plant Pathology 55, 258-263

Source: www.frac.info
January 2013

120


-------
Zhang C Q, Zhu GN, Ma Z H, Zhou M G (2006). Isolation, characterization and preliminary genetic analysis of laboratory tricyclazole resistant

mutants of the rice blast fungus, Magnaporthe grisea. Journal of Phytopathology (Berlin) 154, 392 - 397
Zhao Zhi-hua, Mang Xi-ming, Fan Jie-ru, Liu Liang, Lfu Xi-Ii (2007). Effect of prochloraz on growth and development of prochloraz sensitive

strain and its resistant mutants in Fusarium fujikuroi. Nongyaoxue Xuebao 9 251-256
Zheng D, Olaya G, Koller W (2000). Characterization of laboratory mutants of Venturia inaequalis resistant to the strobilurin related fungicide

kresoxim-methyl. Current Genetics 38, 148-155
Zhu Zhi-feng, Pan Hong-yu, Zhang Hao, jiang Hui, Yuan Shan-kui, Qing-ping Yan (2006). Induction and characteristics of mutants of

Phytophthora drechsleti resistant to etridiazole. Nongyaoxue xuebao 8 (4) 323-326 (Chinese)

Ziogas B N, Markoglou AN, Tzima A (2002). A non-mendelian inheritance of resistance to strobilurin fungicides in Ustilago maydis. Pest
Management Science 58, 908-916

Ziogas B N, Markoglou A N, Malandrakis A A (2003). Studies on the inherent resistance risk to fenhexamid in Botrytis cinerea. European
Journal of Plant Pathology 109, 311-317

Source: www.frac.info
January 2013

121


-------
Reference 3

Footnotes: 7 & 16

122


-------
Oklahoma Co ope:Ft a ti ve: Extension Seifivii^e: EPP-7663

^mm m m mM

UIMII/ERSITY

John Damicone

Extension Plant Pathologist

Damon Smith

Extension Plant Pathologist

Oklahoma Cooperative Extension Fact Sheets
are also available on our website at:
http://osufacts.okstate.edu

Fungicides are important tools for managing diseases in
many crops. Unlike insecticides and some herbicides which kill
established insects or weeds, fungicides are most commonly
applied to protect healthy plants from infection by fungal plant
pathogens. To be effective, fungicides must be applied before
infections become established and in a sufficient spray volume
to achieve thorough coverage of the plant or treated area. Pro-
tection from fungicides is temporary because they are subject to
weathering and breakdown overtime. They also must be reapplied
to protect new growth when disease threatens. Poor disease
control with fungicides can result from several causes including
insufficient application rate, inherently low effectiveness of the
fungicide on the target pathogen, improper timing or application
method, and excessive rainfall. Resistance (lackofsensitivity)to
fungicides in fungal pathogens is another cause of poor disease
control. The development of fungicide resistance is influenced
by complex interactions of factors such as the mode of action of
the fungicide (how the active ingredient inhibits the fungus), the
biology of the pathogen, fungicide use pattern, and the cropping
system. Understanding the biology of fungicide resistance, how
it develops, and how it can be managed is crucial for ensuring
sustainable disease control with fungicides.

The problem of fungicide resistance became apparent
following the registration and widespread use of the systemic
fungicide (see fungicide mobility below) benomyl (Benlate) in
the early 1970s. Prior to the registration of benomyl, growers
routinely applied a protectant fungicide (see fungicide mobility
below) such as maneb, mancozeb, or copper to control diseases
withoutexperiencing resistance problems. Adistinctadvantage of
benomyl over the protectant fungicides was its systemic activity.
In addition to protecting plants from infection, systemic activity
conferred rainfastness and provided disease control when ap-
plied afterthe early stages of infection. Superior disease control
was often achieved with benomyl compared to the protective
dithiocarbamates. However, benomyl differed from the dithio-
carbamates in its site-specific mode of action (see Fungicide
Groups and Mode of Action below) which was readily overcome
by several fungal pathogens. Resistance problems appeared a
few years after benomyl was introduced where the fungicide was
used intensively. Sudden control failures occurred with diseases
such as powdery mildew, peanut leaf spot, and apple scab.

Many of the fungicides developed and registered since the
introduction of benomyl also are systemic, have a site-specific
mode of action, and are at increased riskfor resistance problems.
Fungicide resistance is now a widespread problem in global
agriculture. Fungicide resistance problems in the field have
been documented for more than 100 diseases (crop - pathogen
combinations), and within about half of the known fungicide
groups. Many more cases of resistance are suspected but have
not been documented. While resistance risks with many of fungi-
cides may not be as great as with benomyl, strategies to manage

the resistance risk have been developed and implemented to
avoid unexpected control failures and sustain the usefulness of
new products. As a result of resistance management strategies,
fungicides within all mode of action groups remain useful disease
management tools in at least some cropping systems. The pur-
pose of this bulletin is to describe the resistance phenomenon,
identify resistance risks in the different fungicide groups, and to
provide general guidelines for managing resistance. Since this
fact sheet was first written, many new fungicides have been
registered, and mode of action groups and specific resistance
management strategies are now specified on fungicide labels.
The listing of fungicides by mode of action group here is useful
for identifying appropriate fungicides for use in tank mixtures and
application schedules as part of the recommended resistance
management programs.

Fungicide Mobility

Understanding the mobility of fungicides on and in treated
plants, and how various fungicides are classified based on
mobility is important when making decisions pertaining to the
selection of the best fungicide for a particular disease and its
optimal application timing. Fungicides can be classified into two
basic mobility groups: protectant or penetrant. Regardless of
its mobility characteristics, no fungicide will be highly effective
after the development of disease symptoms and pathogen re-
production (spore production). Fungicides can slow or stop the
development of new symptoms if applied in a timely fashion, but
fungicides will not cure existing disease symptoms. Therefore,
understanding fungicide mobility, fungicide mode of action, and
the biology of the target pathogen are important so fungicide
applications are made before the disease becomes established
and more difficult to control.

Protectant fungicides are active on the plant surfaces
where they remain after application. There is no movement of
the fungicide into the plant. Because they remain on the plant
surface, protectant fungicides loose activity after being washed
off the plant and must be re-applied to new growth that develops
after application. Protectant fungicides typically prevent spore
germination, therefore they must be applied priorto infection and
have no effect once the fungus grows into the plant resulting in
infection.

Penetrant fungicides are absorbed into plants following
application. Because these fungicides are absorbed into plants,
they are generally considered systemic fungicides. However,
penetrant fungicides have different degrees of systemic move-
ment once inside the plant. Some fungicides are 'locally
systemic,' only moving a short distance such as through a few
layers of plant cells. Fungicides that move from one side of a
leaf to other have 'translaminar' movement. Translaminar and
locally systemic fungicides are not transported throughout the

Division of Agricultural Sciences and Natural Resources • Oklahoma State University

123


-------
plant. Highly mobile fungicides are either 'xylem-mobile' or 'true
systemics.' Xylem-mobile fungicides move upward in plants
and outward to the periphery of leaves with water through the
xylem, the water conducting tissue of the plant. True systemic
fungicides move both upward through the xylem, and downward
through the phloem, the food conducting tissue of the plant. Few
if any fungicides are fully systemic. Unlike protectant fungicides,
penetrant fungicides are rain fast within a few hours of applica-
tion and may require a less thorough application coverage to
be effective. In addition, many penetrant fungicides inhibit fun-
gal growth and sporulation and can be effective when applied
after the early stages of infection. Regardless of the level of
systemic movement, penetrant fungicides have limited 'curative'
ability. Generally they only stop or slow infections within the
first 24- to 72-hour period following fungal penetration into the
plant. Therefore, penetrant fungicides must be applied before or
shortly after infection, and are ineffective on existing symptoms.
Both protectant and penetrant fungicides provide good disease
control when applied before infection and are best applied on a
preventive schedule.

Development of Fungicide Resistance

Resistance is a genetic adjustment by afungusthat results in
reduced sensitivity to a fungicide. Reduced sensitivity is thought
to be a result of genetic mutations which occur at low frequencies
(one in a million or less) or of naturally occurring sub-populations
of resistant individuals. Individuals in a fungal population may
consist of the mycelium (the body of a fungus), sclerotia (large
survival structures), spores (small reproductive structures), or
the nucleus of single cells capable of reproduction and spread.
The resistance trait may result from single gene or multiple gene
mutations (see build-up of resistance below). Single-gene muta-
tions that confer resistance to site-specific fungicides are more
likely to develop than the simultaneous occurrence of mutations in
multiple genes needed to confer resistance to multi-site inhibiting
fungicides. Mechanisms of resistance differ depending on the
mode of action, but include alteration of the target site, reduced
fungicide uptake, active export of the fungicide outside fungal
cells, and detoxification or breakdown of the fungicide.

The level of resistance to afungicide can be measured in the
laboratory by exposing a collection of members of a field popula-
tion to the fungicide and measuring toxicity response. Toxicity
responses are usually measured as inhibition of fungus growth,
spore germination, or actual plant infection in cases where the
fungus cannot be cultured. The effective concentration which
inhibits growth, germination, or infection by 50 percent (EC50) is
then calculated for each sampled individual much in the same
way an LD50 (50 percent lethal dose) is calculated for assessing
the acute toxicity of a pesticide to rats or mice. Where many
members of a population are sampled and screened, a range
of sensitivity (or resistance) to the fungicide is usually observed.
The frequency distribution of the sensitivity of individuals in the
population is usually normal or bell-shaped, typical of many
biological responses in nature (Figure 1). Where the fungicide
is newly introduced or where the risk of resistance is low, the
population is distributed over a sensitive range. However, a
distribution consisting of two distinct sub-populations also may
occur where a small sub-population of resistant strains is present
along with a larger sub-population of sensitive strains (Figure
1A).

Build-up of Resistance

Resistance in a population becomes important when the
frequency of resistant strains builds up to dominate the popu-
lation. The build-up of resistant strains is caused by repeated
use of the fungicide which exerts selection pressure on the
population. The fungicide selectively inhibits sensitive strains,

but allows the increase of resistant strains. This shift toward
resistance occurs at different rates, depending on the number of
genes conferring resistance. When single gene mutations confer
resistance, a rapid shift toward resistance may occur, leading to
a population that is predominantly resistant and where control
is abruptly lost (Fig. 1A). When multiple genes are involved, the
shift toward resistance progresses slowly, leading to a reduced
sensitivity of the entire population (Fig. 1B). The gradual shift
with the multiple gene effect may result in reduced fungicide
activity between sprays, but the risk of sudden and complete
loss of control is low. It is difficult to clearly distinguish between
sensitive and resistantsub-populations with field sampling during
the early shifts towards reduced sensitivity because sensitivity
responses overlap. Large numbers of individuals must be tested
to identify the gradual type of resistance.

Assessing Resistance Risk

Many factors effect the development of resistance and
its build-up in the field, which makes it difficult to predict the
resistance riskfor new fungicides. Despite resistance problems
that have been identified following the introduction of some new
fungicides, many examples can be citedwheretheiruse continues
to be effective. Factors that must all be considered in assess-
ing resistance risk include the properties of the fungicide, the
biology of the pathogen, and the crop production system where
the fungicide is used.

Fungicide Groups and Mode of Action

Fungicides are grouped by similarities in chemical structure
and mode of action. Site-specific fungicides disrupt single meta-
bolic processes or structural sites of the target fungus. These
include cell division, sterol synthesis, or nucleic acid (DNA and
or RNA) synthesis. The activity of site-specific fungicides may be
reduced by single or multiple-gene mutations. The benzimidazole,
phenylamide, and strobilurin groups are subject to single-gene
resistance and carry a high risk of resistance problems. Other



A

control no control

B control

no controf



no fungicide | fungicide



no fungicide

fung)cid«



Cfl

to



r\ J '''
f) I j \



/ V *
/ \ '

j % t %
v \



>



1 / '



1 ' \ '
1 ' \ '

i\ \
t V 1



c







/ ' \'

\ 1 1 1



0

1

E

J

In



/ ' !
1 1 \
1 ' '\

/ ' ' V

kit 1
If 1 1

* I I
« \ \



2

/

\ * '



/ i ' \
i i \

' I 1 \
J 1 I 1





J





/ t tt
/it*
/ / / t

\ \ \
< \ \ V

\ V % \
\ V * *





high

tow

high

low





Fungicide sensitivity

Fungicide sensitivity

Figure 1. Depiction of the possible ways fungicide resistance
develops in population of a fungal pathogen. A) Abrupt
(qualitative) resistance development where an initially small,
subpopulation of resistant strains is present before fungicide
usage or develops as a result of a single gene mutation
occurring at low frequency (solid line). Following selec-
tion pressure of fungicide use, the frequency of resistant
individuals (broken line) becomes predominant and disease
control is rapidly lost. B) Gradual (quantitative) resistance
development arising from an accumulation of mutations in
multiple genes that leads to reduced sensitivity. The initial
population (solid line) is sensitive, but gradually shifts to-
wards reduced sensitivity under the selection pressure of
fungicide use (broken line).

EPP-7663-2

124


-------
fungicide groups with site-specific modes of action include dicar-

boximides and sterol demethylation inhibitors (DMIs), but resis-
tance to these fungicides appears to involve slower shifts toward
insensitivity because of multiple-gene involvement. Many of the
site-specific fungicides also have systemic mobility. However,
systemic mobility is not necessary for res-stance development.
Resistance problems have developed in the dicarboximide group
and with dodine, which are protectant fungicides.

Multi-site fungicides interfere with many metabolic processes
of the fungus and are usually protectant fungicides. Once taken
up by fungal cells, multisite inhibitors act on processes such as
general enzyme activity that disrupt numerous cell functions.
Numerous mutations affecting many sites in the fungus would be
necessary for resistance to develop. Typically, these fungicides
inhibit spore germination and must be applied before infection
occurs. Multi-site fungicides form a chemical barrier between
the plant and fungus. The risk of resistance to these fungicides
is low.

There are two codes currently used to classify fungicides by
mode of action (Table 1). The mode of action group (A, B, etc.)
refers to the general target site such as nucleic acid synthesis, cell
wall synthesis, respiration, etc. Sub-groups (A1, A2, etc.) within
a mode of action group refer to specific biochemical target sites
of fungicide activity. The FRAC (Fungicide Resistance Action
Committee) code is used on the fungicide label. The FRAC code
refers to fungicides that have same site-specific mode of action
and share the same resistance problems across members of the
group (cross-resistance). FRAC groups are currently numbered
from 1 to 43 in order of their introduction to the marketplace.
FRAC groups and mode of action subgroups are mostly the
same.

Fitness of Resistant Strains

Fitness isthe ability to compete and survive in nature. Strains
of pathogens resistant to some fungicides compete equally well
with sensitive strains and are still present after the fungicide in
question is no longer in use. For example, strains of Cercospora
arachidicola which causes early leaf spot of peanut are still
established in the southeastern U S. where benomyl resistance
was a problem more than 20 years ago. Therefore, fungicides
with resistance problems cannot be successfully reintroduced into
areas where resistant strains are highly fit. Fortunately, resistant
strains are sometimes less fit than wild-type sensitive strains.
This has been true for DMI resistance in powdery mildews and
for dicarboximide resistance in Botrytis diseases. Unfit strains
only compete well under the selection pressure of the fungicide.
Thus, the resistance is at least partially reversible when the
selection pressure of the fungicide is removed or minimized by
using resistance management.

Fungicide Use Pattern

Frequent and exclusive usage of at-risk fungicides increases
the risk of resistance problems. Selection pressure is increased
where repeated applications are required for disease control as
with many foliar diseases. Selection pressure and the risk of
resistance are low for seed treatments and for many soilborne
diseases which require only one or two applications per season.
The method and rate of application may also impact resistance
development. Poor disease control resulting from causes such
as improper application timing or inadequate spray coverage
may result in a need for a more intensive spray program and the
exposure of more individuals to the fungicide. Using adequate
rates in a manner that produces good disease control reduces
the reproductive capacity of fungal pathogens, thus reducing
selection pressure. Similarly, a preventive spray program is less
risky than a rescue program because select-on pressure is applied
to fewer individuals. Finally, an increase in selection pressure
results from an excessive number of applications where a real
need is not justified.

Pathogen Biology

Fungal pathogens with high rates of reproduction are most
prone to develop fungicide resistance. Because many individuals
(usually spores) are produced by these fungi, more individuals

are exposed to selection pressure and there is a greater prob-
ability of mutations that lead to reduced fungicide sensitivity.
Foliar diseases produce thousands of spores on the surface of
an individual leaf spot. Furthermore, these diseases typically
have several reproductive cycles per season. Under selection
pressure ofafungicide, resistant individuals may increase rapidly
and dominate the population after several cycles of infection and
reproduction.

Diseases with low reproduction rates generally complete

only one life cycle per season. Soilborne pathogens produce
fewer offspring per season than their foliar counterparts. Some
soilborne diseases reproduce by forming seed-like survival
structures called sclerotia. There may be fewer than a hundred
scierotia formed per plant. Where an at-risk fungicide is used
for soilborne disease control, resistance development is likely
to be slow because comparatively few individuals are exposed
to selection pressure.

Crop Production Practices

Production practices that favor increased disease pressure
also promote resistance development by increasing the number of
individuals exposed to selection pressure. Pathogens reproduce
at higher rates on susceptible varieties compared to resistant
or partially resistant varieties. Selection pressure also may be
reduced for resistant varieties because fewer applications should
be needed for effective disease control. Inadequate or exces-
sive fertilization with nitrogen may increase disease incidence
in some crops. For example, early blight of potato and tomato
and dollar spot of turf grass are favored by nitrogen deficiency.
Alternatively, the severity of spring dead spot of bermudagrass
and some foliar diseases of wheat is increased with intensive
nitrogen fertilization. Excessive irrigation or frequent irrigation
with small amounts of water increases the incidence of many
diseases by promoting disease spread, extended periods of leaf
wetness, and high soil moisture.

Continuous cropping and poor sanitation practices promote
severe early-season disease development. Closed cropping
systems such as greenhouses are particularly prone to resis-
tance problems because plants are grown in crowded conditions
that may favor severe disease development, rapid spread, and
high selection pressure. Permanently established plantings of
perennial crops such as orchards, nurseries, and vineyards are
particularly prone to resistance problems. Unlike annual crops
where crop rotation can be practiced, many pathogens survive
from year to year on plants and crop debris within permanent
plantings resulting in a local pathogen population exposed to
yearly selection pressures.

Resistance Management Strategies

Strategies for managing fungicide resistance are aimed at
delaying its development. Therefore, a management strategy
should be implemented before resistance becomes a problem.
The only way to absolutely prevent resistance is to not use an
at-risk fungicide. This is not a practical solution because many
of the modern fungicides that are at risk for resistance problems
provide highly effective, broad-spectrum disease control. By
delaying resistance and keeping its level under control, resis-
tance can be prevented from becoming economically important.
Because practical research in the area of fungicide resistance
management has been limited, many of the strategies devised
are based in the theory of expected responses of a pathogen
population to selection pressure. For the most part, evaluations
of the effectiveness of these strategies have not been based on

EPP-7663-3

125


-------
Table 1. Fungicides registered in the United States grouped by mode of action and relative risk for developing resistance
problems.

Mode of















action

Group1

Group name

Common name

Trade names

Mobility2

Uses3

Risk4

Nucleic acid

A1 (4)

Phenylamide

metalaxyl

Allegiance, MetaStar, Apron

S

ST, F, S

H

synthesis





mefenoxam or

Ridomil Gold, Apron XL,













metalaxyl-M

Subdue, Ultra Flourish,















Quali Pro

S

ST, F, S

H

Mitosis and

B1 (1)

Benzimidazole

thiabendazole

Mertect

s

ST, PH

H

cell division





thiophanate-methyl

Topsin M, Cleary's 3336,















T-Methyl, OHP 6672,















Thiophanate Methyl

s

ST, F, S

H



B3 (22)

Benzamide

zoxamide

Gavel (+ mancozeb)

s

F

M



B5 (43)

Acylpicoiide

fluopicolide

Presidio

s

F,S

M

Respiration

C2 (7)

Carboxamide

carboxin

Vitavax

s

ST

L







flutolanil

Contrast, Moncut, Pro Star,















Artisan (+ propiconazole)

s

ST, F, S

M







boscalid

Endura, Emerald,















Pristine (+ pyraclostrobin)

s

F, S

M



C3 (11)

Strobilurin (Quinone

azoxystrobin

Abound, Amistar, Heritage,











outside Inhibitor (Qoi))



Quadris, Protege, Dynasty,















Quilt (+ propiconazole)

s

F, S, ST

H







famoxidone

Tanos (+ curzate)

s

F

H







fenamidone

Reason

s

F

H







fluoxastrobin

Evito, Disarm

s

F, S

H







kresoxim-methyl

Cygnus, Sovran

s

F

H







pyraciost robin

Cabrio, Insignia, Headline,















Pristine (+ boscalid)

s

F, S

H







trifloxyst robin

Flint, Compass, Gem, Trilex,















Absolute (+ tebuconazole),















Stratego (+ propiconazole)

s

F, S, ST

H



C4 (21)

Quinone inside

cyazofamid

Ranman

s

F

M





Inhibitor (Qih













C5 (29)

Dinitroaniline

fiuazinam

Omega

P

F, S

L



C6 (30)

Organo tin

triphenyl tin hydroxideSuper Tin, Agri Tin

p

F

L

Amino acids

D1 (9)

Anilino-Pyrimidine

cyprodinil

Vanguard, Switch (+ fludioxanil)

s

F

M

and proteins





pyrlmethanil

Sea la

s

F

M



D4 (25)

Antibiotic (bactericide)

streptomycin

Agri-Mycin, Streptomycin,















Firevvaii

p

ST F

H



D5 (41)

Antibiotic (bactericide)

oxytetracycline

Mycoshield, Flameout

p

F

H

Signaling

E1 (13)

Quinoline

quinoxyfen

Quintec

p

F

M



E2 (12)

PhenylPyrrole

fludioxonil

Maxim, Scholar, Medallion,















Switch (+ cyprodinil)

p

ST, F, PH

L-M

Lipids and

F1 (2)

Dicarboximide

Iprodlone

Rovral, Chlpco 26019,







membranes







Iprodione, Chipco 26GT

p

F, S

M-H







vinclozolin

Ronilan, Curaian

p

F, 3

M-H



F3 (14)

Aromatic Hydrocarbon

chioroneb

Nu-F!ow D, Nu-Flow ND

p

ST

L







dichloran

Botran

p

F, S, PH, ST

L-M







PCNB

Terraclor, Turfcide

p

ST, S

L







etridiazole

Terrazoie, Terramaster

p

S

L-M



F4 (28)

Carbamate

propamocarb HC!

Previcur Flex, Banol

s

F, S

L-M



F5 (4CH

Carboxvlic Acid Amide

dimethomorph

Acrobat. Forum

s

F

L-M







mandipropamid

Revus







Sterol

G1 (3)

Demethylation

cyproconazole

Alto, Quadris Xtra







synthesis



Inhibitor (DMI)



(+azoxystrobin)

s

F









fenarimol

Rubigan

s

F, S

M







imazalil

Flo-Pro IMZ, Nu-Zone,















Fecundal

s

ST, PH

L







difenconazole

Dividend, Revus Top















(+ mandipropamid)

s

ST, F

L-M

EPP-7663-4

126


-------
Table 1. continued.

Mode of

action

Group1 Group name

Common name

Trade names

Mobility2

Uses3

Risk4



G1 (3) DMI (cont'd)

fenbuconazole

Enable, Indar

S

F

M





myQlob' '^3 I

Nova, Rally, Eagle, Systhane,













Laredo

S

F, S

M





metconazole

Caramba, Quash

S

F,S

M





propiconazole

Tilt, Orbit, Banner Maxx,













Propiconazole, Propimax,













Bumper, Propensity, Quilt













(+ azoxystrobin), Stratego













(+ trifloxystrobin)

Q

F, S

M





prothioconazole

Proline, Provost













(+ tebuconazole)

S

F.S

M





tebuconazole

Folicur, Raxil, Muscle, Trisum,













Tebuzol, Orius, Elite, Absolute













(+ trifloxystrobin)

3

F, S, ST

M





tetraconazole

Domark, Eminent

S

F

M





triadimefon

Bayleton

S

F, S

M





triadimenoi

Baytan

S

ST

L





triflumizole

Procure, Terraguard

S

F, S

M



G3(17) Hydroxyanilide

fenhexamid

Elevate, Captevate (+ captan)

p

F

L-M

Cell wall

H4 (19) Polyoxins

polyoxin

Endorse

s

F, S

M

synthesis













Plant defense

P1 (P) Benzo-thiadiazcle

acibenzolar-S-methyl Actigard, Blockade

s

F

L

activator













Unknown

U1 (27) Cyanoacetamideoxime cyrnoxanil

Curzate, Tanos (+ famoxadone)

s

F

M



U2 (33) Phosphonate

foseiyi-AL

Aiiette, Legion, Chipco













Signature

s

F

L





phosphorous acid

Phostroi, AgriFos

s

F

L





potassium phosphite

Fosphite, Prophyt

s

F

L

Multi-site

M1 (M1) Inorganic

copper salts

Kocide, Cuprofix, Tenn-Cop,







activity





Basic Copper, Champ, Champion,











Nu-Cop, Copper-Count-N

p

F

L



M2 (M2) Inorganic

sulfur

Microthiol, Suifur, Super Six,













Thioiux, Thiosperse

p

F

L



M3 (M3) Dithiocarbamate

ferbam

Ferbam

p

F

L





mancozeb

Dithane, Penncozeb, Manzate,













Fore, Mankocide (+ copper)

p

F, ST

L





maneb

Maneb, Manex, Pentathlon

p

F, ST

L





metiram

Poly ram

p

F

L





thiram

Thiram, Defiant

p

F, ST

L





ziram

Ziram

p

F

L



M4 (M4) Phthalimide

captan

Captan, Captec

p

F, ST

L



M5 (M5) Chloronitrile

chlorothalonil

Bravo, Equus, Echo, Daconil,













Chloronil, Chlorothalonil,













Initiate Concord So^otro

p

F, S

L



M7 (M7) Guanadine

dodine

Syllit, Dodine

p

F

M

Subgroups represent specific target sites within a mode of action, cross-resistance may occur within subgroups, FRAC group is in parenthesis. FRAC code is based
on time of product registration and potential for cross-resistance within subgroups.

2	P=protectant, S=systemic or penetrant.

3	S=soilborne diseases, F=foliar diseases, ST=seed treatment, PH=post-harvest treatment.

4	The resistance risk is assigned based on the worst case-scenario. For example, dicarboximide resistance is serious for some Botrytis diseases, but resistance
problems have not developed with other uses. Seed treatment uses are considered low-risk regardless of he fungicide's properties.

EPP-7663-5

127


-------
research, but rather on observations made where the fungicides
have been used commercially on a large scale.

Specific strategies for resistance management vary for

the different fungicide groups, the target pathogen(s), and the
crop. However, some strategies are generally effective (Table
2). Resistance management should integrate cultural practices
and optimum fungicide use patterns. The desired result is to
minimize selection pressure through a reduction in time of
exposure or the size of the population exposed to the at-risk
fungicide. Probably the most important aspect of optimizing
use patterns is the deployment of tank mixtures and alternating
sprays of the at-risk fungicide with a fungicide from a different
mode of action group. The comparative merits of tank-mixing
compared to alternating sprays have been debated. Some
theorize that tank-mixing reduces selection pressure only when
the partner fungicide is highly effective and good coverage is
achieved. Alternating fungicides is thought to act by reducing
the time of exposure. In practice, examples can be cited for
the effectiveness of both approaches. Both practices are more
effective when cultural practices are implemented to reduce
disease pressure. The alternation of blocks of more than one
spray is probably less effective in resistance management than
the other use patterns. For example, a block of four continuous
sprays of the DM! fungicide tebuconazole is recommended at
mid-season for peanut disease control. Despite the use of at
least one application of a non-DMI fungicide before and after
the 4-spray block, resistance to tebuconazole in both early and

Table 2. Cultural practices and fungicide use patterns
that reduce disease pressure and selection for fungicide
resistance.

Strategy

Result

Cultural practices
use resistant varieties

maintain proper soil fertility

avoid sites with high
disease pressure

crop rotation
sanitation

lower disease incidence and

rate of increase

reduces disease incidence
avoids high selection

reduces initial pathogen
population

reduces initial pathogen
population

Fungicide use patterns

use only when justified

use protectively

achieve good spray
coverage

use tank mixes with

protectants

alternate fungicides from
different fungicide groups

do not use soil applications

against foliar diseases

avoids unnecessary selection

hits small populations

reduces populations exposed
to selection

reduces populations exposed
to selection

reduces selection time
reduces selection time

late leaf spot diseases became a widespread problem in less
than 10 years.

The proper choice of a partner fungicide in a resistance
management program is critical. Generally, good partner fungi-
cides are multi-site inhibitors that have alow resistance risk (e.g.
chlorothalonil, mancozeb, etc.) and are highly effective against
the target pathogen. However, the use of an unrelated at-risk
fungicide with no potential for cross-resistance problems also
may be effective. Specific resistance management strategies
will be discussed for fungicide groups with the greatest history
and/or risk for resistance problems.

Benzimidazoles (FRAC Group 1; Mode of Action
Sub-Group B1)

Benzimidazoles are site-specific fungicides which interfere
with cell division. They have systemic mobility and have activ-
ity on many pathogens except water molds (e.g. Pythium and
Phytophthora) and darkly pigmented fungi (e.g. Alternaria).
Research has demonstrated that benzimidazole resistant
strains may be present at low frequencies in nature, even in the
absence of fungicide exposure. Under selection pressure, resis-
tance development is abrupt and rapid (Figure 1A). Resistant
strains cannot be controlled by increasing the application rate
or by shortening the spray interval. Resistant strains are often
fit and competitive in nature even without selection pressure.
Therefore, some populations have remained resistant where
benzimidazole use has been discontinued for 10 years. Resis-
tance to benzimidazoles has been documented for more than
60 diseases and cross-resistance exists within this fungicide
group. Benzimidazole resistance has received less recent at-
tention because the fungicide benomyl is no longer registered in
the U.S. However, resistance management remains important
for thiophanate-methyl, the other widely used benzimidazole
fungicide.

Management of benzimidazole resistance relies on reducing
the selection pressure by limiting fungicide exposure and using
tank mixtures or alternating sprays with a fungicide with a low
resistance risk (Table 3). Where multiple sprays are required
for disease control, avoid using benzimidazoles alone for an
extended period of time. In spite of the numerous resistance
problems with benzimidazoles, there are also many examples
where benzimidazoles have remained effective for more than
30 years with judicial use.

Strobilurins (FRAC Group 11; Mode of Action
Sub-Group C3)

Strobilurin fungicides, also know as quinine-outside inhibitor
(Qol)fungicides, are synthetic analogues of a naturally occurring

compound produced by a wood rotting fungus. Strobilurins inhibit

Table 3. Guidelines for reducing the risk of resistance to
benzimidazole fungicides (FRAC Group 1, Mode of Action
Group B1).

1.	Use cultural practices and pest management strategies
that reduce disease pressure.

2.	Do not exceed the allowable number of benzimidazole
applications on the label,

3.	Alternate or tank-mix benzimidazole applications with a
fungicide from a different mode of action group. In tank-
mixtures, both the benzimidazole and tank mix partner must
be applied at their labeled rate.

4.	Benzimidazoles should be use in preventive programs that
keep disease pressure low.

EPP-7663-6

128


-------
respiration in fungal cells bytargeting a protein (cytochrome bc-1)
that is encoded by a gene in the mitochondria. The fungicides
are broad-spectrum with activity against all the major types of
fungal pathogens Strobillurin fungicides penetrate plant leaves
and move from one side of the leaf to the other. This translaminar
mobility makes them rain-fast, but they lacktrue systemic move-
ment in the plant compared to some other systemic fungicides.
Strobilurins act on a broad range of fungal processes including
spore germination, fungal growth, and reproduction (sporulation).
Strobilurin fungicides have been registered on numerous crops
because of their broad-spectrum activity and excellent human and
environmental safety profiles. However, like the benzmidazoles,
resistance developed shortly after their introduction in the late
1990s. Three different single-gene mutations have been identi-
fied that abruptly confer resistance (Figure 1A) that has been
documented for more than 20 diseases. Resistant isolates are
cross-resistant to all other strobilurin fungicides, but not to other
mode of action groups including the closely related Qil (Group
C4 or 21) fungicides.

Resistance management programs rely on reducing selection
pressure by keeping disease pressure low, applying strobilurins
in mixtures or alternation with fungicide from a different mode of
action group, and limiting the number of applications per crop
season (Table 4). Several strobilurin fungicides are marketed in
pre-mixtures with non-strobilurin fungicides for use on certain
crops.

Dicarboximides (FRAC Group 2; Mode of Action
Sub-Group E3)

Dicarboximides inhibit both spore germination and fungal
growth. Resistance is thought to arise by mutations. The
frequency of resistant individuals and their level of resistance
increase gradually with prolonged selection pressure (Figure
1B). Resistance to dicarboximide fungicides has been identified
for more than 15 diseases including brown rot of stone fruits,
gray mold (Botrytis) on several crops, and important turf grass
diseases. Dicarboximide resistant strains of some pathogens are
less fit to survive than sensitive strains. Reduced exposure of
resistant strains to dicarboximide fungicides result in a decrease
in the frequency of resistant strains and possibly an overall shift
of the population back toward sensitivity. Thus, it has been pos-
sible to reintroduce dicarboximides into problem situations where
resistance management has been implemented.

Table 4, Guidelines lor reducing the risk of resistance to
strobilurin fungicides (FRAC Group 11; Mode of Action
Group C3),

1.	Use integrated pest management and cultural practices
known to reduce disease pressure. Strobilurin fungicides
may be used in extension-sponsored disease advisory (dis-
ease forecasting) programs, which recommend application
timing based on weather or risk factors favorable for disease
development.

2.	Limit the number of strobilurin applications to two to four per

season depending on the crop as specified on the label.

3.	Limit the number of sequential applications of strobilurin

fungicide to one or two, depending on the crop and or region
as specified on the label, before alternating with a fungicide
from a different mode of action group.

4.	Make preventative applications to keep disease pressure
low.

5.	Use pre-mixtures or tank mixtures of strobilurin fungicides
with fungicides from a different mode of action group. The
minimum labeled rates of each fungicide in the tank mix
should be used.

Table 5. Guidelines for preventing and managing resistance
to dicarboximide fungicides (FRAC Group 2, Mode of Action
Group E3).

1.	Use cultural practices that reduce the pathogen popula-
tion.

2.	Limitthe numberof dicarboximide applicationsto a maximum
of 2-3 per season and maintain regular prolonged times
without exposure to dicarboximides.

3.	Tank-mix or alternate dicarboximide applications with an ef-
fective non-dicarboximide fungicide having a low resistance
risk. Dicarboximide fungicides applied in tank mixtures count
toward season totals.

4.	Apply adequate rates as recommended on the label.

The primary goal of resistance management strategies
for dicarboximides is to limit selection time (Table 5). Delay the
first application as long as possible by using early-season ap-
plications of a protectant fungicide. This allows the deployment
of dicarboximides at a time when the population of resistant
strains is potentially the lowest. The possibility of resistance
problems is greatest where dicarboximides are used frequently
and exclusively. The number of applications made to a particular
site should not exceed three per season. This applies to multiple
crops grown in the same field. Resistance problems are likely to
be manifested by a partial loss of control and a need for a closer
spray interval. There is evidence that cross-resistance exists
between members of this group and one dicarboximide should
not be replaced with another where resistance is a problem.
Dicarboximide resistance appears to be a manageable problem.
These fungicides have remained useful for control of soilborne
diseases and have been successfully reintroduced into cropping
systems where resistance problems have arisen.

Demethylation Inhibitors (FRAC Group 3; Mode of
Action Sub-Group G1)

Demethylation inhibitor (DMI) fungicides (Table 1) are site-
specific fungicides that disrupt the synthesis of sterols. Sterols
are compounds required for growth of many plant pathogenic
fungi. DMIs are a large group of systemic fungicides that have a
broad range of activity against many types of foliar and soilborne
diseases exceptforthose caused by the water molds. Resistance
development issimilarto the dicarboximides. Typically, resistance
develops gradually and is at first difficult to detect (Figure 1B).
Resistant strains are thought to have reduced fitness; therefore,
reduced selection pressure through the use resistance manage-
ment strategies may partially shift the resistant populations back
toward sensitivity. DMI resistance has been documented for
more than 20 diseases including apple scab, powdery mildews,
gray mold, and brown rot of stone fruit.

Management strategies rely on the use of adequate rates
and limiting exposure by tank-mixing or alternating DMI ap-
plications with unrelated fungicides (Table 6). Using adequate
application rates is important because mildly resistant strains can
still be controlled. Avoid using DMI fungicides alone all season
long. Cross resistance is also a problem within this group so
replacement of one DMI with another is not practical. Premix-
iures of DMI fungicides with strobilurin or protectant fungicides
are being marketed for many crops to improve the spectrum of
diseases controlled and to comply with resistance management
guidelines.

Phenylamides (FRAC Group 4; Mode of Action
Sub-Group A1)

Phenylamides are highly systemic fungicides specifically
used to control diseases caused by water molds. Such dis-

EPP-7663-7

129


-------
Tables. Guidelines for preventing and managing resistance
to demithyiation inhibitor (DMI) fungicides (FRAC Code 3;
Mode of Action Group G1).

Table 7. Guidelines for preventing and managing resis-
tance to phenyiamide fungicides (FRAC Group 4; Mode of
Action Group A1).

1.	Use available cultural practices and resistant varieties to
reduce disease pressure.

2.	Apply according to label directions and do not use less than
the minimum label rate alone or in tank mixtures.

3.	Do not exceed the maximum allowed amount of a single
DMI fungicide per season. Extending the allowed amount
of one DMI fungicide with another will increase the risk of
resistance development.

4.	Keep the disease pressure low by using a preventive ap-
plication schedule.

5.	DMI fungicides are not recommended for season-long use
alone. Alternate sprays or blocks of sprays a fungicide from
a different mode of action group, use tank mixes of DMI
fungicides with an effective protective fungicide having a
low resistance risk.

1.	The phenylamides should be used in a preventive program
to keep disease pressure low.

2.	Forfoliar applications, phenylamides should be used in pre
mixtures with an unrelated (non-phenylamide) fungicide.

3.	Solo formulations for soil use should not be used for foliar
diseases and mixtures rather than straight phenylamides
should be used for seed treatments whenever possible.

4.	Soil treatments of phenylamides should not be used against
foliar diseases.

5.	The number of phenyiamide applications should not exceed
two to four per crop and year.

6.	Phenyiamide sprays are recommended early in season or
during the period of active vegetative growth of the crop
prior to switching to a non-phenylamide product later in
the season.

eases include damping off and root and lower stem rots caused
Pythium and Phytophthora, and foliar diseases such as late
blight, downy mildew, and white rust. Phenylamides inhibit fungal
growth by disrupting RNA synthesis. Resistance problems with

phenylamides, specifically metalaxyl, were observed shortly
after their introduction where they were used exclusively and
disease pressure was high. Resistance is governed by one or
two genes and a low frequency of resistant individuals may exist
in wild populations prior to use of these fungicides. Resistance
can increase rapidly through selection of the naturally occurring
strains (Figure 1A). Cross resistance occurs with other phe-
nyiamide fungicides, but not with fungicides from other mode
of action groups. Both resistant and sensitive strains survive in
the absence of phenyiamide fungicide use and their levels tend
to equilibrate over time. Resistance management is critical to
limit the proportion of resistant strains in a population.

Resistance management for phenyiamide fungicides is
most important for foliar diseases such as late blights and downy
mildews for which multiple sprays are required. Management
relies heavily on the use of premixes of phenylamides with pro-
tectant fungicides and limiting selection pressure (Table 7). The
manufacturer of metalaxyl-M markets premixes with mancozeb,
copper, and chlorothalonil for use against foliar pathogens.
Selection pressure is reduced by limiting the number of sprays
per crop and year. The marketing of pre-mixes of metalaxyl-M
with non-related protectant fungicides ensures compliance with
a resistance management strategy.

Conclusions

Fungicide resistance is one of several possible causes of

poor disease control. Fungicide resistance not only threatens

the usefulness of individual of fungicides, but also the farm
economy because of potential yield losses from poor disease
control. Unfortunately, registrations are being lost for older
broad-spectrum fungicides that have a low resistance risk.
Many of the newer replacement fungicides are more selective
in the number and types of diseases controlled and have site-
specific modes of action making them more prone to resistance
problems. Maintaining an array of effective fungicides is critical.
Resistance management strategies should be recommended by
crop advisors and implemented by growers to prolongthe active
life of at-riskfungicides. Fungicide groups have different levels of
resistance risk. Risk assessment is critical for newly developed
fungicides. Mode of action group and res-stance management
strategies are now clearly included on the registration labels of
most site-specific fungicides. However, itisdifficulttopredictthe
actual risk of resistance because of many interacting factors.
Experience with resistance indicates that resistance problems
are often manageable. Monitoring resistance levels in patho-
gen populations is essential for assessing risk and evaluating
management practices. Unfortunately, there is no coordinated
monitoring effort in place and growers will generally have to rely
on proven methods of resistance management.

References

1)	Beckerman, J. 2008. Understanding fungicide mobility.
Purdue Extension BP-70-W.

2)	Lyr, H. 1995. Modern selective fungicides: properties, ap-
plications, mechanisms of action. Jena, New York; Gustav
Fischer, Deerfield Beach, Fla.; 595 p.

3)	Fungicide Resistance Action Committee (http://www.frac.
i nfo/frac/i n dex. htm).

Oklahoma State University, in compliance with Title VI and VII of the Civil Rights Act of 1964, Executive Order 11246 as amended, Title IX of the Education Amendments of 1972, Americans
with Disabilities Act of 1990, and other federal laws and regulations, does not discriminate on the basis of race, color, national origin, gender, age, religion, disability, or status as a veteran in
any of its policies, practices, or procedures. This includes but is not limited to admissions, employment, financial aid, and educational services.

Issued in furtherance of Cooperative Extension work, acts of May 8 and June 30, 1914, in cooperation with the U.S. Department of Agriculture, Robert E. Whitson, Director of Cooperative Exten-
sion Service, Oklahoma State University, Stillwater, Oklahoma. This publication is printed and issued by Oklahoma State University as authorized by the Vice President, Dean, and Director of
the Division of Agricultural Sciences and Natural Resources and has been prepared and distributed at a cost of 42 cents per copy. 0409 GH

EPP-7663-8

130


-------
Reference 4

Footnote: 8

131


-------
FUNGICIDE RESISTANCE
IN CROP PATHOGENS:

HOW CAN IT BE MANAGED?

2nd, revised edition

KE1T11J BRENT and DEREK YV HOLLOMON

FRAC


-------
Cover:

Scanning electron
micrograph of 7-day-old
colony of powdery
mildew
(Blumeria graminis f.sp.
tritici) on a wheat leaf.

Insert shows a
2-day-old colony at
higher magnification.
Although the sensitivity
of mildew populations

towards certain
fungicides has changed
considerably over
the years,
implementation
of resistance
management strategies
has helped to sustain
an overall satisfactory
degree of control.
(Syngenta)

FUNGICIDE RESISTANCE ACTION COMMITTEE

a Technical Sub Group of

CROPLIFE INTERNATIONAL

Avenue Louise 143,1050 Brussels, Belgium
Telephone: + 32 2 542 04 10. Fax: +32 2 542 04 19

www.frac.info

133


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

FUNGICIDE RESISTANCE
IN CROP PATHOGENS:

HOW CAN IT BE MANAGED?

KEITH J BRENT

St Raphael, Norton Lane,
Chew Magna, Bristol BS18 8RX.UK

DEREK W HOLLOMON

School of Medical Sciences
Department of Biochemistry
University of Bristol, University Walk, Bristol, BS8 1TD, UK

Published by the Fungicide Resistance Action Committee 2007

FRAC Monograph No. 1 (second, revised edition)

ISBN 90-72398-07-6
Depot Legal: D/1995/2537/1

Design and production by Newline Graphics
Reprinted 2007


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

CONTENTS

Page No.

Summary	3

Introduction	5

Chemical Control of Crop Disease	6

Defining Fungicide Resistance	7

Occurrence of Resistance	9

Origins of Resistance	13

Resistance Mechanisms	16

Monitoring: Obtaining the Facts	18

Assessing the Risk	23

Management Strategies	27

Implementation of Management Strategies	34

Benzimidazoles	36

Phenylamides	37

Dicarboximides	39

SBIs (Sterol Biosynthesis Inhibitors)	40

Anilinopyrimidines	42

Qols (Quinone Outside Inhibitors)	42

CAAs (Carboxylic Acid Amides)	44

Resistance Management in Banana Production	45

The Future	46

Acknowledgement	50

References	50

135


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

SUMMARY

This publication gives a broad overview of efforts world-wide to combat

problems in crop protection that are caused by development of resistance to

fungicides. The following major points are emphasised:

•	Fungicide treatments are, and will remain, essential for maintaining healthy
crops and reliable, high-quality yields. They form a key component of
integrated crop management, and their effectiveness must be sustained as long
as possible.

•	Pathogen resistance to fungicides is widespread. The performance of many
modern fungicides has been affected to some degree.

•	Resistance problems could be much worse. All types of fungicide are still
effective in many situations. Current countermeasures are by no means
perfect, but they have proved to be necessary and beneficial.

•	Resistance builds up through the survival and spread of initially rare mutants,
during exposure to fungicide treatment. This development can be discrete
(resulting from a single gene mutation) or gradual (considered to be
polygenic). Resistance mechanisms vary, but mainly involve modification of
the primary site of action of the fungicide within the fungal pathogen.

•	Resistance risk for a new fungicide can be judged to some degree. High risk
indicators include: single site of action in the target fungus; cross-resistance
with existing fungicides; facile generation of fit, resistant mutants in the
laboratory; use of repetitive or sustained treatments in practice; extensive
areas of use; large populations and rapid multiplication of target pathogen; no
complementary use of other types of fungicide or non-chemical control
measures.

•	Monitoring is vital, to determine whether resistance is the cause in cases of
lack of disease control, and to check whether resistance management
strategies are working. It must start early, to gain valuable base-line data
before commercial use begins. Results must be interpreted carefully, to avoid
misleading conclusions.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

•	The main resistance management strategies currently recommended are: avoid
repetitive and sole use; mix or alternate with an appropriate partner fungicide;
limit number and timing of treatments; avoid eradicant use; maintain
recommended dose rate; integrate with non-chemical methods. Wherever
feasible, several strategies should be used together. Some are still based
largely on theory, and further experimental data are needed on the underlying
genetic and epidemiological behaviour of resistant forms, and on effects of
different strategies. Lowering dose may not be adverse in all circumstances.

•	The industrial body FRAC has been remarkably effective in its essential and
difficult role of coordinating strategy design and implementation between
different companies that market fungicides with a shared risk of cross-
resistance. Education and dissemination of information on resistance have also
been valuable activities. New types of fungicide continue to appear, and
receive close attention by FRAC.

•	Much research and formulation of advice on fungicide resistance have been
done by agrochemical companies. Public-sector scientists and advisers also
have contributed greatly to resistance management, in research and practice.
Their liaison with industry has been generally good, and there are
opportunities for further interaction.

•	The sustained supply of new and diverse types of chemical and biological
disease-control agents, and their careful introduction, are seen as key anti-
resistance strategies. This aspect of product development is now increasingly
recognised by national and international registration authorities, many of
which now require from applicants detailed information on the actual or
possible occurrence of resistance, on base-line data, and on proposed
monitoring activities and instructions for use.

4

137


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

INTRODUCTION

'A mutable and treacherous tribe' - this apt description of the fungi was written
by Albrecht von Haller in a letter to Carolus Linnaeus, ca. 1745.

For some 35 years now the agricultural industry has faced problems arising from the
development of resistance in fungal pathogens of crops, against the fungicides used to
control them. Since the first cases of widespread resistance arose, agrochemical
manufacturers, academic and government scientists, and crop advisers, have put a
great deal of effort into analysing the phenomenon and establishing countermeasures.
In 1994 the Fungicide Resistance Action Committee (FRAC), now affiliated to
CropLife International, commissioned a broad review of progress world-wide in
dealing with fungicide resistance, and of the outstanding difficulties that need to be
overcome.

This was published as FRAC Monograph No 1 (Brent 1995). The key tenets of
resistance management have not changed over the intervening years, but there have
been many developments in fungicide chemistry, in the incidence of fungicide
resistance, in knowledge of resistance mechanisms, and in resistance management
projects. As far as possible these have been incorporated into this Second Edition. As
before, this publication aims to be an informative article for all who are concerned
professionally with crop disease management, including biologists, chemists,
agronomists, marketing managers, registration officials, university and college
teachers, and students. It is meant to be read, or at least skimmed, as a whole. It is not
intended as a detailed work of reference for the specialist, although a limited number
of literature citations, out of the several thousand publications on this topic, are
provided for those readers with a deeper interest. Earlier reviews concerning fungicide
resistance management (Dekker, 1982; Brent, 1987; Schwinn and Morton, 1990;
Staub, 1991) were drawn upon freely in the original preparation of this monograph
and arc still of considerable value. A review paper by Kuck (2005) has provided more
recent information and comment. Where appropriate the authors have endeavoured to
discuss differing viewpoints, but conclusions are theirs and do not necessarily reflect
the views of FRAC.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN ft BE MANAGED?

Two further FRAC Monographs (No 2, Brent and Hollomon 1998; No.3, Russell,
2003), respectively address in more detail two major components of fungicide
resistance management: the assessment of risk, and the establishment of sensitivity
baselines. A second, revised edition of Monograph No. 2 is available.

CHEMICAL CONTROL OF CROP DISEASE

Modern spraying of
fungicides in cereal
fields in Europe.
Use of wide spray
booms and 'tram-lines'
aid timely and precise

application, but the
continued effectiveness
of the fungicides
themselves is a more
basic requirement.

(FRAC).

Fungicides have been used for over 200 years to protect plants against disease attack
by fungi. From small and primitive beginnings, mainly to protect cereal seeds and
grape-vines, the number of crops and crop diseases treated, the range of chemicals
available, the area and frequency of their use, and the effectiveness of treatments, have
increased enormously, especially since the second world war.

Remarkably, two very old-established remedies, copper-based formulations and
sulphur, are still used widely and effectively. Several 'middle-aged' fungicides
(phthalimides, dithiocarbamates, dinitrophenols, chlorophenyls) have been used
steadily for well over 40 years. A large number of more potent fungicides, of novel
structure and mostly with systemic activity not found in the earlier products, were
introduced in the late 1960s and 1970s. These included 2-amino-pyrimidines,
benzimidazoles, carboxanilides, phosphorothiolates, morpholines, dicarboximides,
phenylamides, and sterol demethylation inhibitors (DMIs). Introductions in the 1980s
mainly were analogues of existing fungicides, particularly DMIs, with generally
similar though sometimes improved properties. Over the past decade, however, a
number of novel compounds have been introduced commercially or have reached an
advanced stage of development - these include phenylpyrroles, anilinopyrimidines,
quinone outside inhibitors (Qols, including strobilurin analogues), benzamides and
carboxylic acid amides

The more recent fungicides are generally used in relatively small amounts, because of
their more potent action against plant pathogens. However, their margins of safety to
mammals and other non-target organisms are no smaller and are often greater, when
compared weight-for-weight with those of the older materials.

Spraying has always been the principal method of fungicide application, and the
conventional hydraulic sprayer still predominates. Reduction in spray volume, and
more stable and safer formulation, are probably the most significant advances that

139

6


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

have been made in application technology. The frequency and timing of spraying have
not changed a great deal from early recommendations, although the advent of the
systemic fungicides has permitted some greater latitude in these parameters and has
increased the feasibility of using disease threshold or forecast approaches. Roughly
half of the crop diseases treated require treatment only once or twice per season, and
the remainder require three or more (in some cases up to 20) applications. Systems of
integrated crop management involving minimum necessary chemical and energy
inputs, and use of complementary non-chemical protection measures wherever
possible, have been widely adopted and to some extent have led to a reduction in spray
number and dose in some situations.

At present some 150 different fungicidal compounds, formulated and sold in a several-
fold larger number of different proprietary products, arc used in world agriculture. The
total value of fungicide sales to end-users is approximately 7.4 billion US dollars
(source: Phillips McDougall, Industry Overview, 2005). Nearly half of the usage is in
Europe, where fungal diseases cause the most economic damage to crops. Most of the
recommended treatments generally provide 90% or greater control of the target
disease, and give the fanner a benefit: cost ratio of at least 3:1. Some diseases, e.g.
wheat bunt caused by Tilletia spp. or apple scab caused by Venturia inaequalis, require
an extremely high level of control for various commercial or biological reasons. For
some others, e.g. cereal powdeiy mildews (Blumeria graminis), the risks associated
with somewhat lower standards of control are smaller. Some fungicides control a
rather wide range of fungal diseases, whereas others have a limited spectrum of
activity against one or two specific groups of plant pathogens. Although many
fungicides are marketed, any one major crop disease typically is well controlled by
only three or four different types of fungicide, so that any fall in effectiveness of a
previously reliable fungicide through resistance development can be a veiy serious
matter for the grower.

DEFINING FUNGICIDE RESISTANCE

A potential new fungicide is identified in laboratory and glasshouse tests on different
types of fungal pathogen, and is then tested in field trials against an appropriate range


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

of crop diseases in different regions and countries. Only if it works uniformly well
against important crop diseases in a large number of trials over several seasons is it
considered for development and marketing. The pathogens it works against are
deemed to be 'sensitive', and those that it does not affect or hardly affects arc regarded
as 'naturally' or 'inherently resistant'. This pre-existing type of resistance is of no
further practical interest once it has been identified as a limitation to the range of use
of the fungicide. Reasons for natural resistance are seldom investigated, although
sometimes they can be deduced from mode of action studies.

The 'fungicide resistance' we are considering here is a different phenomenon,
sometimes called 'acquired resistance'. Sooner or later during the years of commercial
use of a fungicide, populations of the target pathogen can arise that are no longer
sufficiently sensitive to be controlled adequately. They generally appeal- as a response
to repeated use of the fungicide, or to repeated use of another fungicide which is
related to it chemically and/or biochemically through a common mechanism of
antifungal action. This emergence of resistant populations of target organisms, which
were formerly well controlled, has been widely known for antibacterial drugs (e.g.
sulphonamides, penicillin, streptomycin) and for agricultural and public health
insecticides (e.g. DDT) for almost sixty years.

Some people prefer to call this phenomenon 'insensitivity' or 'tolerance'. The former
term is preferred by some plant pathologists, because they believe that fungicide
resistance is easily confused with host-plant resistance to certain species or pathotypes
of fungi. Some agrochemical companies have also tended to use 'insensitivity', 'loss
of sensitivity' or 'tolerance', because these sound less alarming than 'resistance'. On
the other hand, two studies on terminology recommended that 'resistance' should be
the preferred term (Anon, 1979; Delp and Dekker, 1985). Also 'resistance' has been in
use for many years to describe precisely the same phenomenon in bacteriology and
entomology, and it is now veiy widely used with reference to fungicides also.

Workers within the agrochemical industiy have objected from time to time to the use
of 'resistance' to describe shifts in fungicide sensitivity occurring either in non-crop
situations such as the laboratory or experimental glasshouse, or in the field but to a
degree which is too small to affect disease control. They recommend that 'resistance'
should denote only situations where failure or diminution of crop disease control is
known to have resulted from a change in sensitivity. It is true that observations of
'resistance' generated in the laboratory, and detection of rare or weakly resistant

141

8


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

valiants in the field, have on occasions been misinterpreted by scientific authors, or by
commercial competitors, as indicating actual or impending failure of a product to
perform in practice, when in fact good control was still seemed.

However, attempts to restrict in this way the meaning of such a broadly used term as
'resistance' are bound to fail and to create more confusion. It is better to qualify the
term when necessary. 'Field resistance' (in contrast to 'laboratory resistance') has been
used sometimes to denote specifically a crop disease control problem caused by
resistance. However, detection of some signs of resistance in the field can still be a far
cry from having a control failure. It seems preferable to use 'field resistance' to
indicate merely the presence of resistant valiants in field populations (at whatever
frequency or severity), and 'practical resistance' to indicate consequent, observable
loss of disease control, whenever such precise terminology is necessary. 'Laboratory
resistance' or 'artificially induced resistance' also are useful, precise terms which arc
self-explanatory. Some authors have claimed to find 'field resistance' in studies where
the resistant valiants actually were detected only after the field samples were subjected
to subsequent selection by exposure to the fungicide in the laboratory. This is a
borderline case, which is ha I'd to categorise.

OCCURRENCE OF RESISTANCE

Table 1 gives a much condensed history of the occurrence of practical fungicide
resistance world-wide, and lists major fungicide groups for which resistance is well
documented. Leading examples arc given of the more important diseases affected, and
a few key literature references are cited. Up to 1970 there were a few sporadic cases of
fungicide resistance, which had occurred many years after the fungicide concerned
was introduced. With the introduction of the systemic fungicides, the incidence of
resistance increased greatly, and the time taken for resistance to emerge was often
relatively short, sometimes within two years of first commercial introduction. Many of
the fungicides introduced since the late 1960s have been seriously affected, with the
notable exceptions of the amine fungicides ('morpholines'), fosetyl-aluminium,
anilinopyrimidines, phenylpyrroles and some of the fungicides used to control rice
blast disease (e.g. probenazole, isoprothiolane and tricyclazole), which have retained
effectiveness over many years of widespread use. Some recently introduced fungicides


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?



Table 1







Occurrence of Practical Fungicide Resistance in Crops



Date first

Fungicide or Years of commercial

Main crop

Ref*

observed

fungicide use before resistance

diseases and



(approx.)

class observed (approx.)

pathogens affected



1960

Aromatic 20

Citrus storage rots.

1



hydrocarbons

Penicillium spp.



1964

Organo mercurials 40

Cereal leaf spot and stripe,

2





Pyrenophora spp.



1969

Dodine 10

Apple scab.

3





Venturia inaequalis



1970

Benzimidazoles 2

Many target pathogens,

4

1971

2 Amino pyrimidines 2

Cucumber and barley,

5





powdery mildews







Sphaerotheca fuliginea







& Blumeria graminis



1971

Kasugamycin 6

Rice blast,

6





Magnaporthe grisea



1976

Phosphorothiolates 9

Rice blast,

6





Magnaporthe grisea



1977

Triphenyltins 13

Sugar beet leaf spot.

7





Cercospora betae



1980

Phenylamides 2

Potato blight and

8





grape downy mildew.







Phytophthora infestans







& Plasmopara viticola



1982

Dicarboximides 5

Grape grey mould.

9





Botrytis cinerea



1982

Sterol Demethylation 7

Cucurbit and barley

10



inhibitors (DMIs)

powdery mildews.







S.fuliginea







& Blumeria graminis



1985

Carboxanilides 15

Barley loose smut.

11





Ustilago nuda



1998

Quinone outside 2

Many target diseases

12



Inhibitors (Qols;

and pathogens





Strobilurins)





2002

Melanin Biosynthesis 2

Rice blast,

13



Inhibitors (Dehydratase) (MBI D)

Magnaporthe grisea



~References:

. Eckert, 1982; 2. Noble el at. 1966; 3. Gilpatrick, 1982; 4. Smith, 1988; 5. Bient, 1982; 6. Kato, 1988; 7 Giaroiopolitis, 1978; 8

Staub, 1994:9. Loienz, 1988; lO.DeWaanl, 1994: 11. Locke, 1986; 12.Hcancy«a/.2000; 13. Kakuefo/,2003.



143


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

such as benzamides and carboxylic acid amides have not yet encountered serious
resistance problems, possibly because of the management precautions which have
been taken. Most of the older materials such as copper fungicides, sulphur,
dithiocarbamates (e.g. mancozeb), phthalimides (e.g. captan) and chlorothalonil, have
retained their full effectiveness in all their uses, despite their extensive and sometimes
exclusive use over many years.

Often the onset of resistance has been associated with total, or almost total, failure of
disease control. Indeed it was growers' observations of obvious and sudden loss of
effect that generally gave the first indication of resistance. Of course it was necessaiy
to show that resistance really was the cause, by checking for abnormally low
sensitivity of the pathogen in tests under controlled conditions. There was, and to
some extent still is, a temptation for growers and advisers to blame resistance for all
cases of difficulty of disease control. There arc many other possible reasons, such as
poor application, deteriorated product, misidentification of the pathogen, unusually
heavy disease pressure. However, there remained many examples where no other
explanation was found, and where serious loss of control was clearly correlated with
greatly decreased sensitivity of the pathogen population as revealed in laboratory tests
on representative samples.

Resistance of the kind just described, characterised by a sudden and marked loss of
effectiveness, and by the presence of clearcut sensitive and resistant pathogen
populations with widely differing responses, is variously referred to as 'qualitative',
'single-step', 'discrete', 'disruptive' or 'discontinuous' resistance (Fig.l). Once
developed, it tends to be stable. If the fungicide concerned is withdrawn or used much
less, pathogen populations can remain resistant for many years; a well-documented
example is the sustained resistance of Cercospora betae, the cause of sugar-beet
leafspot, to benzimidazole fungicides in Greece (Dovas et al., 1976). A gradual
recovery of sensitivity can sometimes occur, as in the resistance of Phytophthora
infestans, the potato late blight pathogen, to phenylamide fungicides (Cooke et al.,
2006). In such cases, resistance tends to return quickly if unrestricted use of the
fungicide is resumed, but re-entry involving also a partner fungicide has proved useful
in some instances.

Sometimes, as in the case of the DMI fungicides, and of the 2-amino-pyrimidine
fungicide ethirimol, resistance has developed less suddenly. In such cases, both a
decline in disease control and a decrease in sensitivity of pathogen populations as


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN ft BE MANAGED?

revealed by monitoring tests, manifest themselves gradually, and are partial and
variable in degree. This type of resistance is referred to as 'quantitative', 'multi-step',
'continuous', 'directional' or 'progressive' (Fig.l). It reverts rapidly to a more
sensitive condition under circumstances where the fungicide concerned becomes less
intensively used and alternative fungicides are applied against the same disease.
The first appearance of resistance in a particular fungicide-pathogen combination in
one region has almost always been accompanied, or soon followed, by parallel
behaviour in other regions where the fungicide is applied at a similar intensity.
Whether the fungicide also meets resistance in other of its target pathogens depends on
the individual case. Generally it does occur in other target pathogens that have a
comparable rate of multiplication, provided that the fungicide is used in an equally

Fig. 1

Diagrams showing the
bimodal and unimodal
distributions of degree
of sensitivity which are

characteristic of the
discrete and multi-step
patterns of resistance
development. Blue
shading indicates
original sensitive
population, and red
shading subsequent
resistant population.

12

145


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

intensive way. It is notable that rust fungi, despite their abundant spomlation and rapid
spread, appeal- to be low-risk, seldom producing resistance problems (Grasso et al.,
2006).

Pathogen populations that develop resistance to one fungicide automatically and
simultaneously become resistant to those other fungicides that are affected by the
same gene mutation and the same resistance mechanism. Generally these have proved
to be fungicides that bear an obvious chemical relationship to the first fungicide, or
which have a similar mechanism of fungitoxicity. This is the phenomenon known as
'cross-resistance'. For example, pathogen strains that resist benomyl are almost
always highly resistant to other benzimidazole fungicides such as carbendazim,
thiophanate-methyl or thiabendazole. Sometimes cross-resistance is partial, even when
allowance is made for the greater inherent activity of different members of a fungicide
group.

There is a converse phenomenon, 'negative cross-resistance', in which a change to
resistance to one fungicide automatically confers a change to sensitivity to another.
This is much rarer, but several cases are well characterised; one, involving
carbendazim and diethofencarb, has been of practical importance and is discussed
later.

Some pathogen strains arc found to have developed separate mechanisms of resistance
to two or more unrelated fungicides. These arise from independent mutations that arc
selected by exposure to each of the fungicides concerned. This phenomenon is totally
different from cross-resistance in its origin and mechanism, and is usually termed
'multiple resistance'. An example is the common occurrence of strains of Botrytis
cinerea that have become resistant to both benzimidazole and dicarboximide
fungicides.

ORIGINS OF RESISTANCE

Once it arises, resistance is heritable. It results from one or more changes in the
genetic constitution of the pathogen population. There is overwhelming circumstantial
evidence that a mutant gene that causes production of a particular resistance
mechanism pre-exists in minute amounts in the population. Before the fungicide was


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

ever used in the field, such a mutation would confer no advantage to the growth or
survival of the organism, and could well cause a slight disadvantage. Hence it would
remain at a very low frequency, probably dying out and re-appearing spontaneously
many times.

Spontaneous mutations of all kinds are continually occurring in all living organisms.
The rate of mutation can be increased greatly in the laboratory by exposing the
organism to ultra-violet light or chemical mutagenic agents, and thus resistant mutants
can be produced artificially. However, it cannot be assumed that such artificial mutants
are necessarily identical in resistance mechanism or in other respects to those that arise
in the field.

Typically, a resistant mutant might exist at an initial frequency of the order of 1 in
1000 million spores or other propagules of the pathogen. Amongst the survivors of a
fungicide treatment, however, the resistant forms will be in much higher proportion
('the survival of the fittest'). It is only when this reaches say 1 in 100 or even 1 in 10
in the population that difficulty of disease control and the presence of resistant
individuals will have become readily detectable. Thus the obvious onset of resistance
is often sudden, but prior to this the resistance will have been building up insidiously
at undetectable levels. If a fungicide treatment is very effective, with few survivors,
selection will be veiy rapid. If the fungicide is only 80% effective, then after each
treatment the number of variants will be concentrated only 5-fold and the build-up will
be slower.

Several fairly obvious but important deductions, which can influence assessment of
risk and design of avoidance strategies, can be made from consideration of this simple
process of mutation and selection. Accumulation of resistant mutants will be enhanced
by higher frequency of treatment with the fungicide concerned, by a more effective
application method or dose, by the presence of larger pathogen populations before
treatment, and by greater spore production and shorter generation times in the
pathogen.

The selection process outlined above is based on much genetic analysis of sensitive
and resistant strains, and on much field experience. However, it represents the simplest
form of resistance, the discrete pattern referred to earlier, which is also termed 'major
gene' resistance. One point mutation causing a single amino acid change in the target
protein is responsible for a high level of resistance, and the sensitive and resistant
forms fall into very distinct classes. This pattern is characteristic of resistance to

147

14


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

several major groups of fungicides including benzimidazoles, phenylamides,
dicarboximides and Qols. Other mutations in the target protein may give rise to lower
levels of resistance. For example, the F129L mutation in the
b-cytochrome target of Qols causes only low levels of resistance in many pathogens,
and hence is of little practical importance, in contrast to the G143A mutation which
causes a high degree of resistance, and consequent loss of disease control (Gisi et al.
2002).

A somewhat different 'polygenic' process of genetic change is thought to underlie the
'quantitative' or 'multi-step' pattern of resistance. Again resistance results from the
selection of mutants, but in this case a number of different genes, each with a partial
effect, appeal- to be involved. The more genes that mutate to resistance-causing forms,
the greater the degree of resistance. This would account for the gradual observable
development of resistance, and for the continuous range of sensitivity that can be
found (Fig.l). Although the theory of polygenic resistance is widely accepted, it must
be said that the genetic evidence for polygenic resistance in field isolates is rather thin.
The best known and most studied examples of continuous resistance in practice have
been in cereal powdeiy mildews, which arc rather hard to study genetically, and some
of the data are conflicting (Hollomon, 1981; Hollomon et al., 1984; Brown et al.,
1992). Biochemical evidence for polygenic resistance to azole (DMI) fungicides
indicates involvement of at least four resistance mechanisms which are discussed
below. However, Sanglard et al. (1998) studying the human pathogen Candida
albicans, found that different mutations in the same target-site gene may accumulate
in a single strain, and their individual effects may be additive, or possibly synergistic.
In this way poly allelic changes may contribute to multistep development of resistance.
Qols (strobilurins) are the first fungicide class to target a protein (cytochrome bc-1)
that is encoded by a mitochondrial gene. DNA repair mechanisms are less effective for
mitochondrial DNA than for nuclear DNA, and consequently mitochondrially encoded
genes are more liable to mutation. The frequency of DNA base changes in
mitochondrial DNA is further increased by its close proximity to reactive oxygen
species generated during respiration. Depending on the impact of these mutations on
fitness, resistance seems likely to develop quickly where target sites are encoded by
mitochondrial genes. Onset of resistance to Qols was in fact rapid in a number of
pathogens, although it must be noted that benzimidazole resistance, resulting from a
nuclear mutation, developed equally quickly.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

RESISTANCE MECHANISMS



Sampling barley
powdery mildew
(Blumeria graminis).
Leaves bearing pustules

are removed with
scissors, and the spores
are used as inoculum
for sensitivity tests in the
laboratory.

(Bayer CropScience)

Collecting samples of
Botrytis cinerea
from grapes by a
battery-driven, portable
spore-trapping device.

A vacuum deposits
spores on a fungicide
containing agar plate.

(MLGullino,
University of Turin)

A large amount of experimental effort has focussed on this subject, particularly in
academic laboratories. A broad outline of current information is given in Table 2.
Some of the information is derived from resistant strains generated in the laboratory
(e.g. for quinoxyfen) and not from field isolates. We now understand well the most
important mechanisms of resistance to the benzimidazole, carboxanilide,
phosphorothiolate, dicarboximide, and Qol fungicides. There is extensive information
concerning the DM1 fungicides, identifying four major resistance mechanisms that
may operate. However, there are still many gaps in our knowledge, not only for
established fungicide groups (e.g. anilinopyrimidines), but also for new fungicide
groups defined by cross-resistance (e.g. carboxylic acid amides, CAAs).

Many types of resistance mechanism are known. These include: alteration of the
biochemical target site so that it is no longer sensitive; increased production of the
target protein; developing an alternative metabolic pathway that bypasses the target
site; metabolic breakdown of the fungicide; exclusion or expulsion of the fungicide
through ATP-ase dependent transporter proteins.

By far the commonest mechanism appears to be an alteration to the biochemical target
site of the fungicide. This could explain why many of the older products have not
encountered resistance problems. Once they have penetrated the fungal cell, the older
fungicides act as general enzyme inhibitors, affecting many target sites (hence they are
sometimes called 'multi-site' inhibitors). They act selectively on fungi, rather than on
plants and animals, because they penetrate and accumulate much more readily in
fungi. Many sites in the fungus would have to change simultaneously in order to stop
the fungicide from working. The chances of the many necessary genetic changes
happening are negligible, and in any case an organism with so many alterations would
be highly unlikely to be pathogenic or even viable. The occasional cases of resistance
to multi-site fungicides presumably have resulted from other types of mechanism, not
involving the sites of action.

In contrast, modern fungicides act primarily at single target sites, and are often referred
to as 'single-site' or 'site-specific' fungicides. Thus just a single gene mutation can
cause the target site to alter, so as to become much less vulnerable to the fungicide.
The rapid development over the past 10 years of PCR-based diagnostic methods for

149

16


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN FT BE MANAGED?



Table 2

Mechanisms of Fungicide Resistance

Fungicide or fungicide class

Mechanism of resistance

Aromatic
hydrocarbons

Unknown, but show cross-resistance with dicarboximides
and phenylpyrroles

Organo-mercurials

*Detoxification by binding substances

Dodine

Unknown

Benzimidazoles

Altered target site (B-tubulin)

2-Amino-pyrimidines

Unknown

Kasugamycin

Altered target site (ribosomes)

Phosphorothiolates

Metabolic detoxification

Phenylamides

Possibly altered target site (RNA polymerase)

Dicarboximides and
Phenylpyrroles

*Altered target site (protein kinase involved
in osmoregulation)

DMIs

Increased efflux; altered target site; decreased demand
for target-site product; target-site over-production

Carboxanilides

Altered target site (succinate-ubiquinone oxidoreductase)

Qols (strobilurins)

Altered target site (ubiquinol-cytochrome c reductase)

Melanin Biosynthesis
Inhibitors (Dehydratase) MBI-D

Altered target site (scytalone dehydratase)

~Some doubt regarding occurrence in field isolates



Reviews by Leroux etai,2002; Yamaguchi and Fujimura, 2005; Brent and Hoi lomon, 2007; provide further information

detection of point mutations causing resistance has aided the identification of
resistance mechanisms, especially those involving target site changes. Several major
resistance genes have now been isolated and characterised. In each case a single point
mutation causes a change in a single amino acid in the target protein so that the
fungicide no longer binds so tightly. Different amino acid changes in a target protein
can cause different levels of resistance. For instance, as mentioned earlier, the G143A
mutation (causing glycine to be replaced by alanine) at amino acid position 143 in the
b-cytochrome of mitochondrial Complex EI, causes higher levels of resistance to Qols


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN ft BE MANAGED?

Wind impaction spore
trap, mounted on a car
roof. This has been used
to test for shifts in
sensitivity of aerial
cereal powdery mildew
spores. The trap
contains fungicide-
treated leaf pieces

(Syngenta)

Monilinia Brown Rot

Banomyl
0 ppm 1 ppm

Sensitive

Reilstant

*

Q

Radial-growth test on
two strains of Monilinia

fructicola (stone fruit
brown rot pathogen) on
split agar plates.
(Du Pont)

than the less common F129L mutation (replacing phenylalanine by leucine at position
129) (Sierotzki etal., 2005).

The way in which polygenic systems operate to give different degrees of resistance are
less clearly understood. The relatively low level of resistance caused by each gene
makes the mechanisms of resistance particularly hard to determine. In the case of the
DMI fungicides there is some evidence that mutation of different genes may elicit a
number of different resistance mechanisms listed in Table 2 (De Waard et al., 2006).
These are unrelated, but can act simultaneously and possibly in a synergistic way.

It is interesting that those few fungicides that are not directly fungitoxic, but which act
indirectly by affecting defence mechanisms in the host plant, e.g. probenazole, have
not encountered resistance. Reasons for this are not clear.

MONITORING: OBTAINING THE FACTS

By 'monitoring for fungicide resistance' we mean testing samples of field populations
of target pathogens for their degree of sensitivity to one or more fungicides. This is a
crucial area of resistance research, because virtually all our knowledge of the
distribution, evolution and impact of resistance in the field has depended on
monitoring. It was originally done in the early 1960s to investigate possible resistance
in seed-borne diseases of wheat and oats, and in storage mould on citrus fruit. A much
larger amount of monitoring is now routinely done world-wide.

Monitoring can be done to gain early warning of an impending resistance situation.
However, as discussed above, single-step resistance only becomes readily detectable in
field samples when a relatively high frequency of the resistant variants (>1%) is
reached. The next or next-but-one treatment would fail to give normal control.
Therefore useful early warning is unlikely to be obtained, unless unpractically large
numbers of samples are tested (300 samples are needed to give a 95% chance of
detecting resistance at 1% frequency).With multi-step resistance, partially resistant
strains can exist at high frequency before practical loss of disease control occurs.
Detection of these is feasible, so that in this case monitoring can indicate the risk of
more severe resistance developing and causing loss of control. If a molecular method
has been developed (see below) because a resistance problem has emerged elsewhere,

151

18


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN FT BE MANAGED?

and the mechanism involved identified, detection of a single step mutation can be
achieved at much lower frequencies, allowing earlier warning of the need to
implement anti-resistance strategies.

Another important reason for monitoring is to check that management strategies are
working. This involves monitoring regularly over large areas of use, an expensive
operation but one which has been justified by situations of high commercial risk.
Molecular diagnostics have been successfully used to monitor the degree of success of
anti-resistance strategies aimed at combating Qol resistance in powdery mildew and
septoria diseases of wheat (Fraaije et al„ 2002; 2005). Monitoring is also done at
specific sites in order to investigate complaints from growers of an apparent loss of
performance of the fungicide, and/or to give guidance on the selection of future
fungicide treatments at the site or in the district.

Many otherwise competent monitoring operations have, in the past, given
inconclusive results because one or both of two extremely important steps have been
omitted. The first of these is to develop monitoring methods early, and then to use
them to obtain base-line data on typical pathogen populations before they are exposed
to any widespread use of a new fungicide. This initial assessment of the 'natural'
range of sensitivity, which can be considerable, is an enormous help to the
interpretation of any later monitoring data in terms of possible shifts in sensitivity. It
also ensures that suitable sampling and assay methods have been worked out and
tested. Unfortunately, until recent years base-line data were all too rarely obtained.
However, largely because of registration requirements, the agrochemical industry is
now committing the resources needed to obtain such data prior to commercialisation.
FRAC Monograph No. 3 Sensitivity Baselines in Fungicide Resistance Research and
Management (Russell, 2003) gives a full account of the rationale and methodology of
baseline construction.

A second crucial activity to complement resistance monitoring, is to monitor practical
performance. Knowledge of the continued degree of effectiveness of field
performance is often surprisingly vague and badly recorded, and yet it is a critical
indicator of the occurrence of practical resistance. Systematic observations, year by
year, must be made on amounts of disease in commercial crops treated and untreated
with the at-risk fungicide, and also in any replicated plot trials that are done. In order
to confirm that practical resistance has appeared, it is essential to establish a clear
correlation, both in time and geographically, between the incidence of resistant



•5:

High throughput
micro-titre plate assay
for sensitivity to
azoxystrobin in
Mycosphaerella
graminicola.
Twelve isolates were
each tested against
eight different
azoxystrobin
concentrations, in the
presence of the growth
indicator dye,
Alamar Blue which
turns red where
pathogen growth

occurs.

This test shows
four azoxystrobin-
resistant isolates.

(B A Fraaije,
Rothamsted Research)

152


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

TT

/

JL

PGR Cyciffs

PCfl Cycles

Real-time PCR
detection of the G143 A
mutation causing
resistance to Qol

fungicides.
Different labelled
probes or primers are
used to identify
sensitive (left) or
resistant (right) alleles.
Tests can be formatted

to allow the
determination of the
frequency of resistant
alleles in a population.

(B A Fraaije,
Rothamsted Research)

Fig. 2

Results of a large-scale
monitoring programme
for resistance of wheat
powdery mildew to
triadimenol across
Europe. Values are
'resistance factors'
for 1993 (or 1992 for
Spain), i.e. ratios of the
fungicide concentrations
required to give 50%
inhibition of a field
sample and of a standard
wild-type strain).
Large regional
differences were found,
with resistance greatest
in the north-west where
DMI fungicide use had

been most intense.
(From Felsenstein, 1994)

biotypes and the deterioration of field performance of the fungicide. Evidence for the
latter should be recorded and collated, and not merely anecdotal.

Much experience has now been gained with regard to the reliability, logistics, costs
and necessity of monitoring. Timely and representative sampling is vital. It has been
found very revealing to obtain some samples of the pathogen early in the season
before treatment starts, if sufficient infection exists. The observation of a high
resistance level after treatment can actually be a sign of very successful control, the
resistant forms being concentrated in the small surviving population. Of course
practical problems would follow if the resistant population persisted and formed the
inoculum for the following year, but this is not necessarily the case. Experience has
also shown that the risk of resistance can vary greatly between regions where disease
pressures and fungicide use are high, and neighbouring areas where there is less
disease or where yields are too low to support widespread fungicide use. For example,
in Northern Europe several key cereal pathogens have developed resistance to a

153

201


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN FT BE MANAGED?

number of fungicide groups, whereas in southern Europe the same pathogens have
remained sensitive, and the requirement for monitoring is less important (Kuck, 2005).
Sensitivity testing methods must be able to give realistic, quantitative, reproducible
and readily understandable results. Standardisation of methods has been an aim of a
number of organisations, including EPPO and FRAC. Details of recommended
methods were published up to 1992 (Anon, 1991; Anon, 1992), and FRAC is now
planning to publish a catalogue of new methods on its webpage at www.frac.info.
Standardisation does enable direct comparisons to be made between results obtained
by different research centres, especially if an isolate of known sensitivity is tested at
each centre. On the other hand, pressure to conform must be applied with caution. If a
diversity of methods give similar results, as is generally the case, this actually
strengthens confidence in the results. Also it is often hard to judge the advantages and
problems of different methods until several years' experience of their use have been
gained. Different situations may be best suited by the use of different or modified
tests. A few examples of the wide range of methods that have been used are shown in
the photographs.

The cornerstone of monitoring remains some form of bioassay, so that a decrease in
sensitivity is identified regardless of the underlying mechanism. In recent years tests
have been miniaturised where possible. Spore germination assays are done in various
multi-well plate formats, permitting larger numbers of samples to be tested. Growth in
a liquid medium can be measured for some fungi directly in a spectrophotometer, or
by measuring respiration using reduction of a fluorophore (e.g. 4-methylumbelliferyl-
N-acetyl-B-D- glucosaminide) as an indicator (Fraaije et al., 2005). But bioassays can
be very resource-demanding, especially when applied to obligate parasites such as
downy and powdery mildews. Where molecular mechanisms of resistance are known,
and point mutations causing them defined, various PCR technologies can be applied to
detect Single Nucleotide Polymorphisms (SNPs, McCartney et al., 2003; Fraaije et al.,
2005). The early recognition of the correlation between a single amino acid change
(G143A) in the Qol target b-type cytochrome, provided the impetus for large-scale,
high-throughput monitoring of Qol resistance using allele-specific real-time PCR
(Collina et al., 2005; Kianianmomemi et al., 2007). Indeed, current monitoring for
Qol resistance is almost entirely dependent on real-time PCR diagnostic technologies,
which have proved capable of detecting point mutations at frequencies within field
populations as low as 1 in 10s .

Whole plant test on
sensitive strain of apple
powdeiy mildew
(Podosphaera
leucotricha).

Plants untreated (left)
or sprayed with
10Oppm benzimidazole
(right).

(From Anon, 1991)
(DuPont)

Potato leaf disc test on
Phytophthora infestans
(late blight pathogen)
with sensitive (left) and
resistant (right) spore
inocula. Discs are
floating on 1 pprn
metalaxyl solution.

(Syngenta)

154

21


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

When a point mutation causing resistance is identified in one pathogen, the
corresponding sequence can be determined in another pathogen, and a PCR diagnostic
assay developed even before practical resistance has been identified in that pathogen
(Windass et al., 2000). So far, PCR-based monitoring in this way has been restricted to
Qol resistance in a large number of pathogens, although application of PCR
technology to monitor resistance in other pathogen/fungicide combinations where
point mutations causing resistance are well known (e.g. resistance to benzimidazoles,
dicarboximides and carpropamid) would be technically feasible.

Interpretation of monitoring results has proved difficult in the past and at times it has
resulted in misleading over-prediction of resistance problems. There has been
exaggeration of the practical significance of slight variation in sensitivity between field
samples, or in the detection of resistant biotypes at low frequency or after a period of
artificial selection. This has partly arisen from a lack of rigorous reporting and
discussion of results in detailed scientific papers, in favour of verbal reports or brief
meeting abstracts. In general, however, careful monitoring, linked to good base-line
data and close observation of field performance, has yielded much information of
scientific and practical value, and will continue to do so.

Large-scale international programmes of monitoring for insecticide resistance have
been organised by FAO and WHO (cited in Brent, 1986). Comparable programmes
have not been conducted for fungicides, and it is questionable whether such large
schemes are appropriate. To date, the most extensive monitoring programmes for
fungicide resistance have been Huropc-widc surveys over a number of years of several
cereal and grape diseases. Funded by contracts with the agrochemical industry, these
surveys were initially carried out by workers at the Technical University of Munich,
Fig 2, and more recently by companies specialising in this type of work, such as
Epilogic, Biotransfer and Biorizon. More limited surveys within a country may be
funded mainly by agrochemical companies or grower organisations, and done either
by the agrochemical companies themselves, or by public sector or private research
organisations.

22

155


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

ASSESSING THE RISK

This is a matter of great importance to the chemical manufacturer who is about to
develop a new product. Knowledge of the risk of resistance will help to determine
whether the product should be developed and marketed, and, if so, of what nature and
how stringent should be the resistance management strategies and how much further
monitoring should be done.

The possibility that strains resistant to existing fungicides may be cross-resistant to the
candidate product is readily determined. The chemical structure of the potential
product, or its mode of action if known, may resemble those of existing fungicides,
and thus indicate a likelihood of cross-resistance. More direct guidance can be
obtained by testing the candidate against field isolates of the target pathogen that arc
known to resist other fungicides, and this is now done as a matter of routine. If cross-
resistance is not found in laboratory tests, and if the field trials are uniformly
successful, there still remains the risk of selection and build-up of initially rare
resistant mutants during commercial use. This risk is impossible to assess with any
precision, but some clues can be obtained, which permit a rough but useful estimation
of risk at low, moderate or severe levels. FRAC Monograph No. 2 Fungicide
Resistance: The Assessment of Risk (2nd revised edition, Brent and Hollomon, 2007)
addresses this topic in more detail.

Knowledge of the mechanism of action of a fungicide can be informative. For
example, a mechanism involving inhibition of tubulin assembly would, by analogy
with the benzimidazole fungicides, be considered a high risk indicator, whereas a
multi-site action would indicate relatively low risk.

The potential for mutation to resistance is best studied by treating target fungi with
mutagenic chemicals or ultra-violet light, exposing the treated cultures to the new
fungicide, and isolating and testing the survivors for resistance. It has long been
considered that failure to generate resistant mutants, with unimpaired fitness, in the
laboratory may indicate stability of performance in the field, as for example with
multi-site fungicides (Georgopoulos, 1994). Conversely the ready production of such
mutants could indicate a potential for practical resistance problems, as shown with
benzimidazoles, phenylamides and Qols.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

However, ease of mutant production has certainly not proved to be a totally reliable
indicator. Mutants that resist the amine (morpholine) fungicides arc easy to obtain in
the laboratory, but serious practical resistance problems have still not occurred over
the many years of extensive use of these fungicides. Mutants of several fungi which
were resistant to DMI fungicides were readily obtained in the laboratory, but these had
reduced growth rate and sporulation and their degree of resistance was inversely
proportional to pathogenicity. In view of these indications of decreased fitness in the
field it was concluded that practical resistance would be unlikely (Fuchs and
Drandarevski, 1976). Subsequently such resistance in fact appeared, although
relatively slowly. In a risk evaluation study on the phenylpyrrole fungicide fludioxonil,
resistant strains of Botrytis cinerea were obtained in the laboratory, and found to be
cross-resistant to dicarboximides. However, dicarboximide-resistant field isolates
proved to be sensitive to fludioxonil, and the latter did not select for dicarboximide
resistance in field experiments (Hilber et al., 1994).

Thus the reliability of genetic experimentation in predicting resistance risk is still a
matter of debate, although the consensus view is probably that it gives useful
indications for consideration along with other evidence. The degree of correlation
between the ease of production of resistant mutants in mutagenic and crossing
experiments, their fitness and pathogenicity, and the subsequent occurrence of field
and practical resistance, is an important and interesting topic which deserves more
research.

Repeated exposure of successive generations of a pathogen to sub-lethal
concentrations of a fungicide, sometimes called 'training' or forced selection, might be
expected to indicate practical resistance risk. This approach was used to study
potential resistance of Phytophthora infestans to phenylamides. Resistant strains could
be selected in vitro, but these either were not pathogenic or could not infect
phenylamide-treated plants. Selection on potato plants for 11 generations did not yield
any resistant strains (Staub et al., 1979). In contrast, exposure of a related fungus to a
mutagenic chemical (a nitrosoguanidine) yielded many highly phenylamide-resistant,
virulent strains which could infect treated plants (Davidse, 1981). These different
outcomes suggested that physically or chemically induced mutagenesis may be more
revealing than 'training' in resistance risk studies. Probably this is because stalling
populations in the laboratory are too small to include the range of spontaneous mutants
that occur in field populations. When mutagens are used it is important that

157

24


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

precautions are taken to avoid the risk of releasing resistant strains into host crops in
the locality. More research studies comparing mutagenesis and 'training' as predictors
are warranted, in relation both to discrete and multi-step resistance development in
practice.

The potential for selection of resistant mutants has from time to time been studied in
field-plot experiments in which a fungicide is applied repeatedly under conditions
which favour infection by a target pathogen. However there seem to be no recorded
instances of where such experimentation has yielded useful predictions of either future
field problems or their absence. If intensive treatments in the field do generate for the
first time fit, resistant pathogen strains then there is a danger that they could spread
and initiate problems of control, and suitable precautions must be taken.

As discussed earlier, classes of fungicide differ greatly in their basic vulnerability to
resistance arising in target pathogens. Indications of the degree of this intrinsic
fungicide risk, whether low, medium or high level, can emerge from mutagen
treatments or training experiments, or more reliably (although only after first
commercial introduction) from performance-checking and monitoring during early
years of commercial use, and from cross-resistance studies.

Different classes of pathogen also vary in their ability to become resistant to
fungicides. A number of biological factors arc involved in pathogen risk, and can be
considered to act together in an additive way (Gisi and Staehle-Csech, 1988a, b; Brent
et al., 1990). Higher pathogen risk is associated with a shorter life cycle, more
abundant spomlation of the pathogen, and rapid, long-distance dispersal of spores. For
example, resistance to the benzimidazole fungicides was much slower to develop in
cereal eyespot disease, where the pathogen (Oculimacula spp.) generally has only one
generation per year, with limited spore production and dispersal, and only one
fungicide application is made per year, than in cucurbit powdery mildew
(Sphaerotheca fuliginea) which has many short generations, abundant spomlation and
widespread dispersal, and requires repeated fungicide treatments. There are some
factors underlying the degree of pathogen risk, probably involving pathogen-specific
genomic behaviour, which arc not fully understood. For example, it is not clear why
rust fungi, despite abundant spomlation and short generation times, have caused no
major problems of fungicide resistance. The way in which 'fungicide risk' and
'pathogen risk' combine to determine the overall intrinsic risk of resistance problems
is illustrated in Fig. 3.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN ft BE MANAGED?

Fig. 3

Matrix diagram to
exemplify how
separate and
sometimes differing
degrees of resistance
risk are associated with
the use of a particular
fungicide class, and
with the control of a
particular target
pathogen.
Estimates are
approximate and based
on experience to date.
Blue shading indicates
lower risk, and red
shading higher risk.

Qols on rusts

Benzimidazoles on
cereal eyespot

Benzimidazoles and
Qols on cereal Septoria

Benzimidazoles on
grape Botrytis

Phenylamides on
soil-borne diseases

Phenylamides on
potato late blight

£

9

u
o
z

3

DMIs on

DMIs on

seed-borne diseases

1 barley Rhynchosporium 1

DMIs on
apple scab

Dicarboximides on
grape Botrytis

DMIs on
cereal powdery
mildew

Morpholines on
cereal powdery
mildew

Dithiocarbamates on
cereal rust

Pbthalimides on
apple scab

Dithiocarbamates
on potato late blight

Low

DISEASE RISK

High

Overall risks of resistance development in crop disease situations depend not only on
these intrinsic or inherent risks attached to particular types of fungicide or pathogen,
but also on the conditions of fungicide use. Unlike the intrinsic risks, the conditions of
use can vary much between regions and from farm to farm. They comprise
environmental factors, especially climatic and topographic conditions that affect the
severity and spread of crop disease, and a range of farmer-determined agronomic
factors. The latter include fungicide selection, application frequency and dose, use of
glass-houses or polythene tunnels (these tend to isolate pathogen populations and
prevent ingress of sensitive strains), pattern of crop rotation, choice of cultivar and its
degree of susceptibility to infection, and the extent of use of hygienic practices. If the
regional environment and farm practices tend not to favour disease development and

159

26


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

spread, and hence reduce the need for intensive fungicide use, and if the exclusive use
of the at-risk fungicide is restricted or avoided, then the overall risk of resistance
problems will be smaller.

Assessment of degree of risk of resistance development for a particular location must
take into account and integrate as far as possible all influential factors including the
intrinsic risk for each fungicide-pathogen combination, the environmental conditions
and their likely effects on disease incidence, and relevant agronomic practices which
should incorporate any specific fungicide use strategies recommended by the
fungicide manufacturer. Inevitably, such risk assessment can only be an approximate
estimate, at best indicating low, medium or high level, because many factors are
involved, and with our present state of knowledge their effects cannot be measured
precisely or given accurate weightings for relative importance.

MANAGEMENT STRATEGIES

Theoretical argument, experimental evidence and practical experience all indicate that
the build-up of resistance is greatly favoured by the sustained, sole use of fungicides
with specific mechanisms of action. Conversely, their occasional use, interspersed by
the use of other, unrelated products is unlikely to lead to resistance problems. In
practice, however, resistance management strategies must combine the long-term
conservation of fungicide effectiveness with an amount and pattern of use that are
sufficient both to satisfy the needs of the farmer and to provide a reasonable pay-back
to the manufacturer. It is not an easy task to design and implement such well-balanced
programmes.

Strategies must be applied uniformly over large areas in order to obtain their full
biological benefit, and also to ensure that any short-term commercial disadvantage and
long-term advantage are shared amongst all manufacturers of the same group of
fungicides. Thus to have a chance of success any strategy must be reached by
agreement and depend upon a commitment to implementation from all supply
companies involved. It must also be understandable and acceptable to the farmer. To
achieve all this, on the basis of limited data and understanding of the phenomenon, is
the difficult but important major aim of FRAC.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

The approaches taken for different groups of fungicides will be discussed later, but
first let us consider briefly the range of use strategies for resistance management that
are available. Although they are discussed individually, the integrated use of
combinations of different strategies is feasible, beneficial, and often implemented.

1. Do not use the product exclusively

Apply it as a mixture with one or more fungicides of a different type, or as one
component in a rotation or alternation of different fungicide treatments.

The 'companion' or 'partner' compounds applied in either of these ways will dilute
the selection pressure exerted by the at-risk fungicide and inhibit the growth of any
resistant biotypes that arise. The companion compound can be a multi-site compound
known to have a low risk of inducing resistance. Alternatively, it can be a single-site
fungicide that is known not to be related to its partner by cross-resistance or (in the
absence of known resistance) by a similar mode of action. Use of a mixture of two
single-site fungicides must carry some element of risk of selecting dual-resistant
strains. However, the chances of two mutations occurring simultaneously will be veiy
small compared to that of a single mutation (e.g. 1018 instead of 10"). Consecutive
development of double resistance could occur, but would seem much less likely to
develop than if the two components were used separately and repeatedly.

This type of strategy is widely recommended by industry and also by advisoiy bodies.
The use of formulated ('pre-packed') mixtures of two different fungicides has often
been favoured by manufacturers. If an at-risk fungicide is not sold alone, then use of
the mixture is the only use option open to the farmer and implementation of the
strategy is ensured. Also the control of many pathogens only requires one or two
treatments per annum so that the rotational approach is not appropriate. Mixtures arc
of course also marketed for other purposes, such as broadening the range of pathogens
which can be controlled or enhancing control by increasing the duration of protection.
Questions of what application rate is appropriate for each mixture component are
difficult and have been debated many times. Some reduction relative to the full
recommended separate rates has often been made, to keep down costs. This may
reduce selection pressure for the 'at risk' fungicide, but clearly it is vitally important to
maintain the companion compound at a level where it can still exert an effective
independent action against the target pathogens

Numerous mathematical models predicting rate of development of resistance in
relation to different regimes of fungicide use have been published, and arc discussed

161

28


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN FT BE MANAGED?

by Brent et al. (1990), Birch and Shaw (1997), and Brent and Hollomon (2007). They
reveal that two basic principles underlying resistance management are to reduce the
growth rates of both sensitive and resistant types, and to reduce the growth rate of the
resistant type relative to the sensitive type (Fry and Milgroom, 1990). Most of the
strategies that are used involve one or both of these effects. The models all indicate
that use of both mixtures and rotations can delay, but not prevent, the build-up of
resistant variants. They favour one or other of these two approaches to different
degrees depending on the various assumptions that are incorporated. Experimental
data relating to the effectiveness of mixture and rotation strategies are limited.
Growth-room and plastic-tunnel studies on Phytophthora infestans, showed that
applications of mixtures of a phenylamide fungicide with mancozeb or mancozeb plus
cymoxanil decreased the build-up of phenylamide resistance, compared with
phenylamide alone (Staub and Sozzi, 1984; Samoucha and Gisi, 1987). Selection for
Qol resistance in Plasmopara viticola was delayed by a mixture with folpet, fosetyl-
aluminium or mancozeb (Genet et al., 2006). Whilst small-scale studies such as these,
done under controlled conditions and with prepared inocula, can give clear and
reproducible results, there is also a need to test strategies against the much larger and
more diverse populations that occur in the field.

A recent modelling study (Pamell et al., 2006) has predicted that the regional spread
of single gene resistance over large distances will depend on the proportion of fields of
a particular crop that are sprayed, and not only on within-field use strategies. The
extent of any loss in fitness caused by the resistant mutation, and the effectiveness of
the fungicide against the wild-type sensitive pathogen, also influence the speed that
resistance will spread. It is suggested that some fields should be left untreated, or
treated with different, non-cross-resistant fungicides. Both verification of the model
and systematic commercialisation of such a 'patchwork' strategy will probably be
difficult to achieve, although the authors point out that analogous non-Bt-treated
refugia for Bt-sensitive insect populations have been established in Arizona through
legislation.

Field experimentation on resistance management strategies is always a difficult task,
requiring large, replicated plots, and sustained cropping, treatments and assessments
for several successive years. Variation in infection conditions and disease pressure
from year to year, irregular availability of adequate samples of the pathogen,
movement of inoculum between plots, ingress of external inoculum into the

Leaf segment test on

bariey powdery
mildew. Spores from
one field isolate are
dusted on segments
from plants grown from
seed treated with
different ethirimol
concentrations.

(Syngenta).

162

29


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN ft BE MANAGED?

Cucumber powdery
mildew caused by
Sphaerotheca fuliginea.
The healthy leaves were
on a plant treated with
dimethirimol via the
roots. In this instance
the mildew population
was sensitive to
dimethirimol, but
resistant populations
soon became common
in some countries.

(Syngenta)

experimental area, and other difficulties often render such work inconclusive. An early
field experiment on Cercospora beticola showed that alternation of benomyl and a tin
fungicide delayed the development of benomyl resistance (Dovas et al., 1976). In
several studies on cereal powdery mildews (Blumeria graminis f. sp. tritici and
hordei), field application of mixtures of triazoles with morpholine or aminopyrimidine
fungicides was found to hinder the development of resistance to one or to both of the
fungicides applied, which did occur after sequential applications of each fungicide
alone (Heaney et al., 1988; Brent et al., 1989; Lorenz et al., 1992). Effects of
fungicide alternation were less regular, giving either a similar or a smaller benefit
according to the particular study.

Development of resistance of Botrytis cinerea on tunnel-grown strawberries to
dicarboximides, and of Polyscytalum pustulans and Helminthosporium solani on
potatoes to thiabendazole, was shown to be delayed by the application of certain
fungicide mixtures (Hunter et al., 1987; Carnegie et al., 1994). In experiments on
grape powdery mildew (Uncinula necator) a mixture of triadimenol with sulphur or
dinocap at roughly half normal rates did not slow down the evolution of triadimenol
resistance; however, alternations, at full rates, did decrease resistance development
(Steva, 1994). Build-up of Qol resistance in Mycosphaerella graminicola in field plots
of wheat was much reduced by application of an azoxystrobin/epoxiconazole mixture,
compared with a solo azoxystrobin treatment (Gisi et al., 2005). Overall, field
experimentation does appear to support the adoption of mixture and rotation strategies,
but since there are some inconsistencies and the range of diseases and fungicides
worked on is rather limited, further work should be encouraged.

Practical experience also suggests that both mixture and rotation strategies have
delayed resistance development, and examples are discussed later. However, fully
conclusive evaluations of commercial-scale strategies are difficult to make because
comparable 'non-strategy' areas have seldom existed.

2. Restrict the number of treatments applied per season, and apply only when
strictly necessary. Use other fungicides both beforehand and subsequently

This approach, like rotation, reduces the total number of applications of the at-risk
fungicide and therefore must slow down selection to some extent. It can also favour
decline of resistant strains that have a fitness deficit. However, the treatments, which
are still applied consecutively, generally coincide with the most active stages of
epidemics when selection pressures are highest.

163

30'


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

Thus any delay in resistance may not be proportional to the reduction in spray number.
On the other hand a substantial break in use at a time when the pathogen is still
multiplying can allow a beneficial resurgence of more sensitive forms. Examples arc
considered later.

3. Maintain manufacturers' recommended dose

For many years farmers have often used reduced rates of application of fungicides,
mainly to reduce costs, especially in conditions where disease pressures arc usually
low, or where the risk of financial loss from reduced performance was not great. Also,
advisoiy services in pursuing lower-input approaches for economic and environmental
reasons, have recommended use of smaller doses for certain situations. On the other
hand it is the view of FRAC that recommended doses must be maintained, not only
because they will retain the built-in safety factor and secure the claimed levels of
performance under a wide range of conditions, but more particularly because it is
possible that reducing the dose could enhance the development of resistance.

However, relationships of fungicide dose to risks of resistance are not yet fully
established, and it seems likely that they may vary according to the fungicide in
question. Some of the models referred to above indicate that lowering the dose of the
at-risk fungicide (but retaining normal spray frequency) can delay build-up of major-
gene resistance by decreasing the overall effectiveness, increasing the numbers of
sensitive survivors and hence slowing down the selection of resistant forms that can
survive the full dose. With regard to multi-step resistance, it has been argued that
lowering dose can enhance resistance development by favouring the survival of low-
level resistant forms which would be inhibited by the full dose. The low-level resistant
forms could then mutate further or recombine sexually to give higher levels of
resistance. In practice the doses that actually reach the target organisms vary greatly
over space and time, giving very complex mixes of different exposure sequences.
Thus it can be argued equally that lowering the dose could hinder multi-step resistance
by giving a fore-shortened range of concentrations that would not provide the step-
ladder of selection pressure up to the highest levels. Moreover, as the dose rate
approaches zero there certainly will be no selection for resistance.

Experimental data regarding effects of different doses are still rather limited and
confusing. In a growth chamber experiment, selection for resistance to triazoles in
barley powdery mildew was slowed down by lowering fungicide concentrations
(Porras et al., 1990). Again the work is more difficult to do in the field, partly because


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN ft BE MANAGED?

Apple leaves bearing
lesions of scab disease,
caused by
Venturia inaequalis.

Resistance to
benzimidazoles and
dodine has caused
considerable problems
in the control of this
disease.

(KI Brent)

degrees of effectiveness, which must be critical, vary greatly between and within
growing seasons. Decreasing application rates appeared to slow down development of
resistance of triadimefon to barley powdery mildew (Hunter et al., 1984), but in other
experiments on strawberry Botrytis and wheat eyespot altering fungicide doses made
little difference to resistance build-up (Hunter et al., 1987; Hunter et al., 1993). When
a benomyl-mancozeb mixture was applied to control apple scab, build-up of benomyl
resistance was delayed by reducing the benomyl concentration and increasing the
mancozeb concentration (Lalancette et al., 1987). Halving the rate of triadimenol
enhanced development of resistance in grape powdery mildew in France (Steva,
1994), and 'split' (lower dose but more frequent) applications of fenpropimorph and
fenpropimorph-propiconazole mixtures led to significant decreases in fenpropimorph
sensitivity of wheat powdery mildew in Germany and Holland (Forster et al., 1994;
Engels and De Waard, 1994 ). However, reducing the dose of fenpropimorph did not
affect the sensitivity of barley powdery mildew in the UK (Zziwa and Burnett, 1994).
Decreasing the dose of DMI fungicides from one-quarter to one-eighth of the full
recommended dose was found to reduce resistance development in Mycosphaerella
graminicola (Metcalfe et al., 2000; Mavroeidi and Shaw, 2006).

It is now widely accepted, on theoretical grounds, limited experimental data and
practical experience, that risks of major-gene (single-step) resistance are unlikely to
increase, and may well decline as dose is lowered. The situation with regard to
polygenic resistance is still not at all clear, and more experimental work is justified in
order to obtain a sounder base for recommendations. Some of the published data refer
specifically to 'split' schedules, in which dose is lowered but frequency of application
is correspondingly increased, to give the same total mount applied each season. It is
important to distinguish these from reduced-dose applications made on normally timed
schedules so that the total dose per season is decreased. The use of more frequent
'split' applications could increase resistance risk and should be avoided.

4. Avoid eradicant use

One of the advantages of systemic fungicides is that they can eradicate or cure existing
infections. This property greatly assists their use on a 'threshold' basis, where
application is made only when a certain, economically acceptable, amount of disease
has already appeared, in order to prevent further spread. However, avoidance of the
use of systemic fungicides in this way has been recommended in two different
situations as an anti-resistance strategy.

165

32


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN FT BE MANAGED?

FRAC has recommended that eradicant use of phenylamides should be avoided. This
is because they are now always applied for control of foliage diseases as a mixture
with a multi-site companion fungicide. The latter does not work as an eradicant, so
that the phenylamide is acting alone when the mixture is applied to existing infections.
Avoidance of eradicant use could possibly delay resistance for another, more widely
applicable reason. To wait until a threshold population of the pathogen appears,
usually means that many sporulating lesions (occupying up to 5% of the foliar area)
are exposed to the fungicide. Opportunity for selection could be much greater than if
the fungicide had been applied prophylactically to keep populations permanently low.
Presumably it is with this risk in mind that FRAC discourages the eradicant use of
DMIs in some fruit crops. To the authors' knowledge there is no experimental
evidence comparing the resistance risks of prophylactic versus threshold-based
schedules, and research on this would be useful.

5.	Integrated disease management

This is a particular aspect of the concept more generally referred to as IPM (Integrated
Pest Management). The integrated use of all types of countermeasures against crop
disease is not only highly desirable on economic and environmental grounds, but is
also a major strategy for avoiding or delaying fungicide resistance. The use of disease-
resistant crop varieties, biological control agents, and appropriate hygienic practices,
such as crop rotation and removal of diseased parts of perennial crop plants, reduces
disease incidence and permits the more sparing use of fungicides, and in both these
ways decreases selection of fungicide-resistant forms. Equally of course the
application of fungicides reduces the risk of build-up of pathotypes with changed
virulence and the consequent 'breakdown' of disease-resistant varieties.
Unfortunately, non-chemical methods of disease control are often weak or not
available, so that fungicide application is the predominant or even the sole
countermeasure for many diseases (e.g. potato late blight, grape downy mildew,
Sigatoka disease of bananas, wheat bunt, stripe (yellow) rust of wheat, to name a few).

6.	Chemical diversity

The availability of a number of different types of fungicide for the control of each
major crop disease is highly beneficial both environmentally and in order to overcome
resistance problems. The continued use of one or a very few types of compound over
many years presents a much greater risk of side-effects and favours resistance in the

Storage rot of
oranges caused by
Penicillium digitatum.
Resistance to phenols,
benzimidazoles and
sec-butylamine has
caused problems, but
the advent of newer
fungicides and the
adoption of resistance
management
programmes have
enabled satisfactory

control to be
maintained overall.

(I W Eckeit,
University of California)

166

33


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN rr BE MANAGED?

Late blight on potato
foliage, caused by
Phytophthora infestans.
Although phenylamide
- resistant forms are

widespread,
phenylamides are still

used effectively in
mixture or rotation with
mancozeb and other
fungicides.

target organisms. Thus it is crucial that chemical invention and new product
development are sustained. Fortunately, registration authorities now accept the need
for diversity, in terms of pesticide chemistry and mechanisms of action, provided that
the new compounds maintain safety standards. A new fungicide does not necessarily
have to be superior to existing ones in order to be of value. It has to be effective, and,
in the resistance context, it should work against strains that are resistant to existing
fungicides. This latter property is usually associated with a new mode of action, and
ideally there should be more than one site of action to decrease the risk of evolution of
resistance to the new fungicide.

However, the development of new, highly active members of an existing fungicide
class, which retain the same primary mechanism of action, may also be of some use in
resistance management. This is exemplified by the latest tria/ole fungicide
prothioconazole, which is more potent generally and against which smaller resistance
factors are exhibited (Kuck and Mehl, 2004). Its introduction has to some extent
decreased problems of triazole resistance in cereal powdery mildews.

The withdrawal of fungicides, for example captafol and organo-tin fungicides, for
safety reasons has been necessary from time to time, but it has reduced options for
resistance avoidance strategies. It must be hoped that further de-registrations do not
occur. Restrictions on the use of ethylenebisdithiocarbamates (EBDCs), such as
mancozeb, already operate in several countries, and possibly these could become more
widespread and severe. This is a worrying prospect with regard to fungicide resistance
management. It is notable that in Sweden products based solely on EBDCs have been
prohibited, whereas products containing EBDCs together with other fungicides can
still be marketed and used.

IMPLEMENTATION OF MANAGEMENT STRATEGIES

Whilst public-sector research and advisory organisations have contributed greatly to
the establishment of countermeasures, the agrochemical industry has had to bear the
major responsibility of planning and implementation, and of course the associated
financial risks.

167

34


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN FT BE MANAGED?

When fungicide resistance first emerged as a major problem, the manufacturers
concerned had to respond as best they could against an unforeseen situation.
Resistance to benzimidazoles arose in 1969-70, only one to two years after first
introduction. The companies involved adopted a low-key approach, dealing with
complaints on an ad-hoc basis, and placing general warnings of the existence of
resistant strains and disclaimer notices on product labels. Results of any monitoring or
other studies done by them at this time were not published for 10 years, and no
recommendations regarding resistance management were issued.

Resistance to dimethirimol first appeared in Holland in 1970, the second year of use.
With hindsight, the year-round, almost universal use of this highly specific, systemic
fungicide, in glasshouses, to control the vigorous, abundantly sporulating cucumber
powdery mildew, was the ideal scenario for resistance build-up. The manufacturing
company mounted quickly a systematic monitoring programme (the first of its kind),
obtained clear evidence of practical resistance, withdrew the product from use in
affected regions, and published relevant data (Bent, et al., 1971).

Signs of resistance of barley mildew to the related compound ethirimol subsequently
were found in the UK, and the same manufacturer again published data as did the
Plant Breeding Institute (PBI) at Cambridge (Shephard et al., 1975; Wolfe and Dinoor,
1973). With advice from PBI, the company introduced a strategy of withdrawal of use
from winter bai ley, to break the year-round cycle of use. The resistance did not worsen
and a useful degree of disease control on spring barley was sustained. As more
alternative treatments came into use in the late 1970s ethirimol application to winter
barley was restored, and the level of resistance actually declined (Heaney et al., 1986).
Since the company concerned was the sole manufacturer of these two pyrimidine
fungicides, it was possible to implement major changes in use strategies uniformly and
without reference to other companies.

Carboxanilides and amines ('morpholines'), introduced at about the same time as the
benzimidazoles and 2-amino-pyrimidines, did not encounter the rapid onset of major
resistance problems. In 1980, however, strong resistance to metalaxyl, a relatively new
Oomycete fungicide, occurred in certain countries, and signs of resistance to
dicarboximides were also starting to appear. This situation of increasing concern
prompted a group of industrial scientists, who were attending a fungicide resistance
course at Wageningen in 1980, to propose the formation of an inter-Company Group
that would cooperate in investigating resistance problems and establishing

Grapes infested by
Botrytis cinerea.

Resistance to
benzimidazole and
dicarboximides
fungicides has affected
control seriously in
some regions. New
fungicides appear
promising.

168

35


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

countermeasures. At a meeting in Brussels in 1981, company representatives agreed a
draft constitution and modus operandi for FRAC.

Since then FRAC has been very active in sharing confidential company information on
the incidence of resistance, in planning relevant studies with agreed company inputs,
and in issuing consensus recommendations for the agrochemical industry and for
advisers and fanners (Russell, 2006).

FRAC decided to operate through Working Groups, one for each major class of
fungicides to which resistance is known, and which has more than one manufacturer,
or potential manufacturer with an announced development product. Currently there arc
four Working Groups, dealing with SBI (sterol biosynthesis inhibitor) fungicides,
anilinopyrimidines, Qol (quinone outside inhibitor) fungicides and CAA (carboxylic
acid amide) fungicides. These Groups collect and publish data on resistance status in
different crops, pathogens and countries, and issue and review annually resistance
management guidelines. Three former Working Groups, concerned with
benzimidazoles, dicarboximides and phenylamides, have now converted to Expert
Fora, giving relevant information and advice on request. The latest information and
guidelines from each Working Group are available on the FRAC website
(www.frac.info).

Benzimidazoles

Many pathogens adapted very quickly to benzimidazoles, for example Botrytis spp.
Others took about 10 years before being detected e.g. Oculimacula spp., cause of
cereal eyespot disease (Locke, 1986) or even 15 years (e.g. Rhynchosporium secalis,
cause of barley leaf-scald (Kendall et al., 1993).

Over the years the use of mixtures or alternations with non-benzimidazole fungicides
has been encouraged with varying degrees of vigour by the individual companies
concerned and by advisory services. Often this was done too late. When
benzimidazole resistance has already become established, it usually persists.
An example of the successful early use of a mixture strategy is the application of
benzimidazoles to control Cercospora leaf-spots of peanut in the USA. In the
southeastern states, where there was sole use of benomyl, practical resistance soon
appeared. In Texas, where benzimidazole-mancozeb mixtures were used from the start,
no resistance developed over many years except in trial plots where a benzimidazole

169

36


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

alone was applied repeatedly (Smith, 1988). The FRAC Working Group (now an
Expert Forum) supported the use of mixtures or alternation in a general way, and the
avoidance of eradicant use unless absolutely necessary, but did not make specific
recommendations or initiate major monitoring projects.

Use of benzimidazole fungicides worldwide is still substantial, despite the widespread
incidence of resistance since the early 1970s. In the absence of data it is hard to say to
what extent benzimidazole fungicides are now still effective, and whether use on the
present scale is fully justified. Monitoring in 1997-2003 in France revealed the
common occurrence at high frequency of benzimidazole-resistant strains of
Mycosphaerella graminicola and Oculimacula spp in wheat (Leroux et al., 2003,2005
a). A comprehensive, up-to-date survey of the situation world-wide regarding the
current use and effectiveness of benzimidazole fungicides would certainly be valuable.
One special and interesting approach to overcoming benzimidazole resistance has
been the application of a mixture of the benzimidazole fungicide carbendazim with
diethofencarb, to control Botrytis in grapes and other crops. Diethofencarb shows
negative cross-resistance with respect to benzimidazoles. Remarkably, it inhibits only
benzimidazole-resistant strains of the target pathogens and does not affect
benzimidazole-sensitive strains. In practice a formulated carbendazim-diethofencarb
mixture, introduced in 1987 initially gave good control of Botrytis, irrespective of
whether pathogen populations were benzimidazole-resistant or not. However, the
appearance and spread of strains resistant to both fungicides caused problems (Elad et
al., 1992; Leroux and Moncomble, 1994) and the product is no longer used.

Phenylamides

These fungicides were first introduced in 1977. They act specifically against oomycete
pathogens, having no effect on other classes of fungi.

In 1980 the first cases of resistance occurred, suddenly and seriously, against
metalaxyl applied to cucumbers for control of downy mildew (Pseudoperonospora
cubensis) in Israel and applied to potatoes in certain European countries for control of
late blight (Phytophthora infestans). In the following year resistance appeared also in
grape downy mildew (Plasmopara viticola) in France and South Africa and in tobacco
blue mould (Peronospora tabacina) in Central America. These events were
unexpected, since results of 'training' experiments done by the manufacturer (Staub et


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN ft BE MANAGED?

Black Sigatoka disease
of bananas caused by
Mycosphaerella fijiensis
var. difformis.
Strains resistant to
benzimidazoles, DMI
and Qol fungicides
have developed in
some countries and
have prompted the
international adoption
of agreed management
strategies.

(KJ Brent)

al., 1979) had appeared to indicate a low degree of risk. The dramatic occurrence in
1980 of practical resistance problems, in such a promising new fungicide class which
was beginning to involve other manufacturers, was perhaps the most compelling
influence underlying the formation of FRAC.

Recognising that resistance in Phytophthora infestans was associated with the solo use
of metalaxyl, and that it had not occurred in those countries where only formulated
mixtures with mancozeb were applied, the manufacturer immediately withdrew the
single product from use against foliar diseases and recommended that mixtures with
multi-site fungicides should be used. Subsequently the FRAC Phenylamides Working
Group produced a full set of guide-lines, hi abbreviated form, these are:

Use only as protectants; no curative or eradicant appl ications.

For foliar application use only pre-packed mixtures with residual partner
fungicide; the latter should be at 3/< to full dose, but the phenylamide dosage
depends on the intrinsic activity and is defined by the respective company.
Do not use soil treatments to control foliar disease.

Limit sprays to 2-4 consecutive applications per crop per year; do not exceed
14 day intervals.

Use in early season or period of active crop growth only, then switch to a non-
phenylamide product.

Do not use on seed potato crops or in nurseries.

Although not without difficult negotiation, FRAC secured uniform implementation of
these guide-lines by all the companies involved, and major use of this class of
fungicides continues against all target diseases. Since the problem of phenylamide
resistance first arose, several effective new oomycete-active fungicides have been
introduced, e.g. Qol fungicides, fluazinam, dimethomorph, cyazofamid and zoxamide,
so that many more options for diversified application programmes now exist.
Application of the FRAC recommendations did not in fact delay for long the
appearance and spread of resistant variants of P. infestans, which have become readily
detectable in many crops in most countries of use. Nevertheless there is evidence from
field experiments that phenylamide-mancozeb mixtures continue to perform better
than mancozeb alone (Staub, 1994), even in re-entry situations where a phenylamide
alone was originally used and then withdrawn (Dowley, 1994). The reasons for this are
not fully understood. The use of a leaf-disc test with a multiple spore inoculum may

171

38


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

have over-estimated the frequency of resistant mutants within crops. Since the
Oomycetes have multinucleate hyphal cells and sporangia, it is possible that the
proportion of nuclei with a resistant gene is a critical factor (Cooke et al., 2006).
The underlying reason for the sustained field activity of metalaxyl in mixtures, which
has also been observed in the control of lettuce downy mildew, Bremia lactucae
(Wicks et al., 1994), deserves more detailed study.

Against most Oomycete pathogens, chemical application is the only effective method
of control and there is not much scope for the IPM approach. An exception is the
downy mildew of lettuce. Metalaxyl-resistant populations of this fungus arc composed
only of one of a few particular pathotypes. Cultivars carrying genes for resistance
specifically against one of these pathotypes have been deployed in combination with
phenylamide treatment as a successful integrated control and resistance management
strategy (Cmte et al., 1994). Metalaxyl-resistant strains of a different pathotype do
arise from time to time, so that sustained surveillance and modification of
recommendations is necessary.

Dicarboximides

Fungicides of this class (iprodione, vinclozolin and procymidone) have been used
since the mid-1970s mainly to control fungi of the related genera Botrytis, Sclerotinia
and Monilinia. They largely replaced benzimidazole fungicides, which in many
situations were no longer effective because of resistance. Dicarboximide-resistant
variants appear frequently in laboratory cultures, and after about three years of
intensive use, resistant strains were detected also in the field. The field isolates have
shown differing degrees of resistance, and pathogenicity and other fitness factors tend
to decline as the degree of resistance increased. The proportion of resistant strains
varies greatly with time of year; they decline after dicarboximide treatment ceases and
increase again when it is resumed. Practical control problems, associated with
moderately resistant populations occurred, but at first were localised and variable in
degree. During the 1980s difficulties gradually increased, especially in grape-vines in
the parts of Europe where Botrytis is most prevalent, and even where mixtures were
used control was sometimes inadequate.

The FRAC Dicarboximide Working Group made the following recommendations:
- Do not apply more than two or three times per crop per season.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

Save applications for times when Botrytis infection pressure is high.

Leave prolonged periods without selection pressure.

Where resistance is established use mixtures to stabilise Botrytis control,

using the application rules given for a dicarboximide alone.

Despite extensive use of these guide-lines, practical resistance to different degrees
became widespread in grape-vines, especially in parts of France, and a sporadic
problem in some other crops. Earlier companion compounds such as captan, thiram,
dichlofluanid and chlorothalonil did not give fully adequate control, alone or in
mixture with a dicarboximide, but the restricted, once per year use of newer Botrytis-
active fungicides such as fluazinam, fludioxonil, fenhexamid and the
anilinopyrimidines, and also the dicarboximides, is now giving good levels of grape-
vine Botrytis control in France (Leroux et al., 2005 b).

SBIs (sterol biosynthesis inhibitors)

This large class of fungicides comprises three distinct groups: the sterol C14-
demethylation inhibitors (DMIs, e.g. triazoles, imidazoles, fenarimol, triforine);
amines (morpholines e.g. tridemorph, fenpropimorph, piperidines e.g. fenpropidin,
spiroketalamines e.g. spiroxamine); hydroxyanilides (e.g. fenhexamid).

DMIs were first used in the 1970s, triforine, triadimefon and imazalil being early
representatives. Since then at least 30 more DMIs have been used in agriculture. At the
time the FRAC Working Group formed, in 1982, there were veiy few reports of DMI
resistance. They have a site-specific mode of action, and resistant mutants were easily
obtained by mutagenic treatment in the laboratory. However, such mutants had
reduced pathogenicity and other fitness attributes, so that development of practical
resistance was deemed unlikely (Fuchs and Drandarevski, 1976). Practical resistance
did in fact develop in several pathogens during the 1980s (e.g. powdery mildews,
Venturia inaequalis, Mycosphaerella fijiensis var dijformis), but relatively slowly and
with fluctuating severity, as is considered to be characteristic of polygenic resistance.
Although amine fungicides have been used extensively for many years, they continue
to perform well. Considering the amount of use, their potency, the high multiplication
rates of the main target pathogens (e.g. powdery mildews and Mycosphaerella.
fijiensis var dijformis), and the ease of generating resistant mutants in the laboratory,
the stability of their performance has been remarkable. Some reports of decreased

173

40


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

sensitivity have appeared from time to time. The slightly resistant field isolates were
not cross-resistant to the DMI fungicides, which act at a different stage of sterol
biosynthesis.

Interestingly, several studies have revealed cross-resistance between isolates of bailey
and wheat powdeiy mildews with respect to fenpropimorph and fenpropidin, but little
cross-resistance to tridemorph appears to occur (Readshaw and Heaney, 1994). This
pattern correlates well with information on mechanisms of action, since
fenpropimorph and fenpropidin arc considered mainly to inhibit the A14-15 reduction
step, and tridemorph mainly the A8-7 isomerisation step, in sterol biosynthesis
(Hollomon, 1994). However, there is evidence for additional sites of action, and a
multi-site action, coupled with the flexible, multi-configurational nature of the carbon
chain, could account for the durability of action of the morpholine fungicides.
Hydroxyanilide fungicides inhibit yet another step in sterol biosynthesis, catalysed by
C3-keto-reductase. Fenhexamid, the sole hydroxyanilide in commercial use is applied
specifically for control of Botrytis spp. and related pathogens. During eight years of
use, no development of resistance to fenhexamid has been detected.

FRAC has made the following general recommendations regarding use of SBI
fungicides:

-	Do not use repeated applications of SBIs alone on the same crop in one season
against a high-risk pathogen in areas of high disease pressure for that pathogen.

-	For crop/pathogen situations requiring multiple spray applications, e.g. orchard
crops/powdery mildews, use mixtures or alternate (in block sprays or in
sequence) with effective non-cross-resistant fungicides.

-	If mixture or alternation is not possible, reserve SBI use for the critical part of
the season or critical crop growth stage.

-	If DMI or amine performance declines and less sensitive forms of the pathogen
arc detected, SBIs should only be used in mixture or alternation with effective
non-cross-resistant fungicides.

-	Complementary use of other fungicide classes with different modes of action
should be maximised.

-	Use as recommended on the label. Do not use reduced doses.

-	Use other measures such as resistant varieties, good agronomic practice, plant
hygiene.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

Recommendations for specific crop sectors have been made, and arc published on the
FRAC website. In general these confirm and amplify the above general
recommendations. Eradicant use is discouraged in apples and grapes.

These recommendations have been widely implemented, and in general the SB I
fungicides arc continuing to give good control of most target pathogens some 30 years
after their introduction. The warning against reduced rates could be open to debate
since, as discussed earlier, the relevant experimental data arc limited and conflicting.
This is clearly an important area for further research. However, it is of course always
necessaiy to use DMIs in amounts sufficient to ensure cost-effective disease control
under the particular conditions of use.

Anilinopyrimidines

These fungicides, which include cyprodinil, pyrimethanil and mepanipyrim, act
against a broad range of fungi. The FRAC Anilinopyrimidines Working Group has
focussed mainly on resistance management in Botrytis cinerea and Venturia inaequalis
on apple, which are high-resistance-risk pathogens and also important commercial
disease targets for this fungicide class. Resistant strains of both pathogens have been
detected in vineyards and apple orchards. These are cross-resistant to all the
anilinopyrimidine fungicides, but not to other fungicide classes. They have remained
at low frequency, and performance of anilinopyrimidines continues to be very good
after twelve years of commercial use.

Guidelines for use have been published by FRAC and implemented throughout this
period. These differ according to the crop disease, but the general approach is to
restrict the number of anilinopyrimidine treatments to be applied per crop and season.

Qols (Quinone outside Inhibitors, "strobilurins")

The class at present comprises twelve fungicides, from several different, but related
chemical groups (e.g. methoxyacrylates, oximino acetates) which have a common
mode of anti-fungal mode of action, inhibiting electron transfer at the Qo site in
mitochondrial complex III. They were first introduced ten years ago, and have been
widely used against a broad range of pathogens.

Within two years after their introduction, marked loss of action against powdery
mildew, associated with development of highly resistant populations was observed in

175

42


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

wheat crops in Germany, and soon after throughout north-west Europe (Chin et al.,
2001). Subsequently, serious resistant problems have been encountered in a range of
target pathogens, for example Mycosphaerella graminicola (cause of leaf spot of
wheat), Plasmopara viticola (downy mildew of grapes), Venturia inaequalis (cause of
apple scab) and Mycosphaerella fijiensis var. difformis (cause of black Sigatoka
disease of bananas). A full list, with literature citations is given by the Qol working
group on the FRAC website. In general, resistant forms have shown cross-resistance to
all the Qol fungicides. It is notable that resistance has not developed in Phytophthora
infestans (cause of potato late blight), a major target for some Qols. As with other
fungicide classes, the occurrence of resistant strains, and associated losses of Qol
performance, vary greatly between regions of use. For example, resistance of
Plasmopara viticola is much more prevalent in northern and south-western France,
than in Hungary or Spain where disease pressure and Qol use arc generally lower.
According to recent FRAC reports, in seventeen pathogens a high level of resistance
(resistance factor usually greater than 100) has been shown to be caused by a single
mutation (G143A) in the cytochrome bc-1 gene. Another single mutation (F129L),
generally causing a much lower degree of resistance, and little or no loss of control
provided recommended application rates are adhered to, has been detected in three
pathogens. Three further pathogens have produced strains with both these mutations.
It is noticeable that Qol resistant oomycete pathogens are sensitive to cyazofamid, a
Qil fungicide that blocks electron flow through the second quinone binding site of
cytochrome bc-1 which faces the inside of the mitochondrial matrix (Mitani et al.,
2005). Cyazofamid may be used as a partner to Qols in resistance management
programmes, although it should be recognised that both Qol and Qil fungicides
activate alternative oxidase, which causes low levels of resistance to both fungicide
groups (Wood and Hollomon, 2003; Hollomon et al., 2005; Gisi et al., 2005).

General FRAC guidelines for use of Qol fungicides include the following key
instructions:

-	Apply Qol fungicides at effective rates and intervals, according to
manufacturers' recommendations.

-	Limit the total number of applications within a total disease management
programme, whether applied solo or in mixture with other fungicides.

-	Alternate Qol applications, whether solo or in mixture, or whether single or
block treatments, with applications of effective fungicides from other cross-


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

resistance groups. Specific recommendation on size of blocks are given for specific
crops. Block applications of Qols must only be made in mixture with a non-cross-
resistant fungicide.

Specific recommendations for the use of Qols in cereal crops, grapes and bananas arc
published on the FRAC website, In cereals and bananas, Qols should always be used
in mixtures with non-cross-resistant fungicides.

CAAs (carboxylic acid amides)

A FRAC Working Group has been established recently to promote and co-ordinate
resistance management for the carboxylic acid amide (CAA) fungicides. At present
those used commercially arc dimethomoiph, flumorph, benthiavalicarb, iprovalicarb
and mandipropamid. They specifically act against oomycete pathogens, and probably
have a common mode of action.

Shortly after the first CAA (dimethomorph) was introduced in 1993, and despite
recommendations to always use in combination with multi-site fungicides, less
sensitive populations of Plasmopara viticola were observed in a number of vineyards
in France and Germany. Since then the frequency of less sensitive populations, and the
degree of loss of sensitivity have fluctuated, with no clear progressive build-up of
resistance in these or other regions. CAA resistance in P. viticola has been shown to be
inherited in a recessive way (Gisi et al., 2007). This could limit its spread since
oomycete fungi are diploid, or even polyploid, during much of their life cycle. Control
appears to remain good, with no complaints received from growers, although it cannot
be excluded that use of partner fungicides could in some situations mask a degree of
loss of performance. No instances of reduced sensitivity have been shown in other
oomycete pathogens, including Phytophthora infestans which has received extensive
monitoring.

Thus CAAs are regarded by FRAC as moderate-risk fungicides, which should
continue to perform well against all target diseases provided guidelines arc followed.
Key recommendations made by the Working Group for use against Plasmopara
viticola are:

Apply no more than four CAA sprays per season.

Apply always in mixture with effective multi-site or other non-cross-
resistant fungicides.

177

44


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN FT BE MANAGED?

No specific recommendations have yet been made for use against Phytophthora
infestans or other oomycete pathogens and users are encouraged to follow the
manufacturers' recommendations.

Resistance management in banana production

The crucial role of frequent fungicide applications in banana plantations, the serious
problems caused by benzimidazole resistance in the main pathogen, Mycosphaerella
fijiensis var. dijformis, and the importance of securing agreement regarding use
strategies between major production companies in different countries, were all
considerations that led to the formation of a special Working Group of FRAC
concerned with fungicide use and resistance management in bananas. The Group
includes a number of growers as well as agrochemical manufacturer members.





Table 3



Summary of FRAC recommendations for use of fungicides



on Banana to control black sigatoka

Updated during the FRAC working group meeting (Orlando, Florida, USA, 1 2. Feb.2006)

Chemical class

Solo or mixtures

Alternation or blocks

Maximum number Spra.v timing
of applicatioas

Demethylation

Both, mixtures

Only in full alternation

8; *

inhibitors (DMI)

preferred



not more than 50% of
total number of sprays

Amine fungicides

Both, mixtures

Block of maximum

15; No restrictions



preferred

2 consecutive sprays,
full alternation preferred

not more than 50% of
total number of sprays

Qo inhibitors (Qol)

Only in mixtures

Only in full alternation

3; **
not more than 33% of
total number of sprays

Anilinopyrimidines (AP)

Both, mixtures
preferred

Only in full alternation

6; No restrictions
not more than 50% of
total number of sprays

Benzimidazoles (BCM)

Only in mixtures

Only in full alternation

3; **
not more than 33% of
total number of sprays

* Applications starting preferably at onset of annual disease progression curve



** Preferably at lower disease pressure; sprays must be separated by at least 3 months




-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

Over the past twenty years the Group's guidelines have changed considerably, in
response to the introduction of new fungicide classes and to the development of
resistance to some classes of fungicides in certain countries, as shown by sensitivity
monitoring and performance checks. Monitoring is mainly done by germination tests,
performed locally, and for Qols additionally by PCR tests for the G143A mutation.
Resistance problems have arisen with benzimidazoles, in all regions, and to some
extent with DMI and Qol fungicides, mostly in Costa Rica and Panama. No problems
have arisen so far with amines and anilinopyrimidines.

Specific guidelines vary according to the fungicide class, and key recommendations
are given in Table 3. General guidelines, applicable to all groups, emphasise well-
established points of good resistance management discussed above, but one distinct
recommendation is that site-specific fungicides must be applied in oil or oil-water
emulsions. These enhance fungicidal action and also exert an independent effect on
black Sigatoka disease.

THE FUTURE

Whilst by no means fully successful, fungicide resistance management has
undoubtedly prevented or delayed potentially more serious losses of disease control
than those which have actually occurred. When practical resistance develops, it is now
recognised and acted upon promptly, so that the wasteful use of ineffective treatments
is avoided. Both FRAC and public-sector workers have had major roles to play in
developing and implementing resistance management and will continue to do so.
Important new fungicide groups continue to emerge from the industrial laboratories,
and of course it is vital to conserve their badly needed activities. It is also important
that resources are made available to support the search for new modes of action, which
will remain a cornerstone in resistance management. As fundamental research in
genetics, biochemistry and epidemiology increase understanding of factors that
influence risk, it should be possible to target the search for new modes of action
involving inhibition of metabolic processes that offer low risk of resistance
developing.

179

46


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN FT BE MANAGED?

It is heartening to know that baseline studies, and other appraisal and strategy-making
activities, are now firmly embedded in the evaluation and development of new
fungicides within the individual companies concerned. It is vital that FRAC Working
Groups for new fungicide classes should be formed at an early stage for all classes
where more than one company is involved. The formation of the anilinopyrimidine
and CAA Working Groups, before any practical resistance problems have arisen in
these classes of fungicides, are encouraging examples.

In Europe many registration authorities now require protocols for sensitivity test
methods, base-line data on the original range of sensitivity, and a statement on
resistance risk assessment and management strategy, as part of the registration
'package' (Heimbach et al„ 2002). Since such information should now be available,
and since evidence for efficacy is already a registration requirement, these
requirements seem quite reasonable. EU Directive 91-414 sets out the appropriate data
requirements and FRAC (and other RACs) have worked closely with EPPO to
produce a set of Guidelines (EPPO, 2002) to help in the gathering and interpretation of
the necessary data. Also, submission of protocols regarding resistance management is
a useful discipline for a company to undergo, and leads to an increased understanding
amongst authorities of the problems of resistance management and their avoidance.

There remains a danger, however, of inflexibility through over-emphasis on rigid
registration requirements. As experience of use of a new product grows, it may be
necessary to change the accepted strategy quickly, and it is essential that this is not
inhibited by bureaucratic delays. Any official categorisation of fungicide application
to crops, as low-risk, high-risk etc., should be avoided, in view of the present
uncertainty of knowledge regarding prediction of resistance development and
effectiveness of management strategies, and the known variations in resistance
development according to conditions of use in different regions. Of great help, as
discussed earlier, would be a more rapid and positive response of registration
authorities to new types of fungicides, which will increase diversity. A more positive
response of some authorities to applications for registration of pre-packed mixtures
will also help resistance management.

From time to time individual companies sponsor research projects concerning
fungicide resistance. However, there is scope for a stronger and more sustained
interaction between FRAC and public-sector researchers and advisers, and for
industrial funding of research projects. A difficulty regarding research projects is that

	¦	

* *

I

G





Germ-tube growth test
on sensitive strain of
Mycosphaerella fijiensis
var. difformis (banana
black Sigatoka disease
pathogen). Spores in the
top photograph exposed
to 5 ppm benomyl.
(FRAC)

180

'47


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

one company may not wish to fund jointly research in which the model compound
belongs to another company. Also a company may not wish its compound to be the
subject of an investigation in case undesirable results arc obtained. These difficulties
may prove ha I'd to overcome in some situations.

There arc also opportunities for funding of resistance research by growers through
levy-funded organisations, which is veiy appropriate and should be encouraged world-
wide. But national grower organisations can be waiy of supporting fungicide research
that may also aid production in other countries. It may be possible to obtain funds for
resistance management projects in developing countries through the international aid
agencies, provided that deserving proposals can be formulated.

Further research is still badly needed on the field behaviour or 'epidemiology' of
resistant biotypes, on the biochemical and genetic basis of resistance, and on their
interaction with different use strategies. This will provide a sounder basis for effective
resistance management, which still depends too much on opinion. Effects of altering
dose, both on normal and 'split' schedules particularly require more study, with respect
to discrete and multi-step resistance. Genetic evidence for the important concepts of
major-gene and polygenic resistance is based largely on studies of laboratory mutants,
and more work on field isolates remains a priority.

In the past much monitoring work, particularly that done by industry, has not been
fully published. Such information, including base-line data, is of long-term value and
is now more often published in scientific journals, or summarised on the FRAC web
site (www.frac.info/publ) where status reports and recommendations are also
published regularly. A Resistant Pest Management Newsletter is published by
Michigan State University (www.whalonlab.msu.com/ipmnews), but the emphasis is
strongly on insecticide resistance. Communication and discussion of results and
recommendations through occasional symposia, workshops and training courses on
fungicide resistance and its management must continue. The role of FRAC in this has
been important and one hopes that it will be sustained. Use of the internet to transmit
information rapidly to users world-wide, has quickly become a key component
keeping growers and users up-to-date with resistance management approaches.
The provision of crop varieties with improved disease resistance, and the development
of biological control agents will surely advance, and will strengthen the IPM approach.
Care will be needed to maintain the effectiveness of these biological components of
IPM, with use of similar strategies to those used for chemicals. The ability of

181

48


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

pathogens to overcome varietal resistance is well recognised, and the development of
resistance of a fungal pathogen (Botrytis cinerea) to a biological control agent
(.Bacillus subtilis CL27) has been observed (Li and Leifert, 1994).

Where resistance can be shown to result from specific DNA changes in resistant
isolates, various PCR diagnostic methods become the choice way to monitor
resistance. Management of Qol anti-resistance strategies relies almost entirely on PCR
diagnostics, and similar methods could be used to monitor resistance to
benzimidazoles, dicarboximides, DMIs, and MBI-D fungicides. It is not only
important that researchers keep abreast of advances in real-time PCR and array
technologies, but sufficient resources must be made available for laboratories involved
in routine monitoring to keep their instrumentation up-to-date in order to obtain the
benefits of these developments, such as the greatly increased sample throughput, and
rapid delivery of results. However, bioassay protocols, which can also be improved
(Fraaije et al., 2005), must remain a component of monitoring programmes, since
resistance may emerge through selection of different target site mutations, or
completely different mechanisms.

There is no doubt at all that chemical control methods will always be required to
maintain reliable crop yields of good quality. To conserve the fine fungicides we
already have, and to protect new arrivals, attention to resistance management, and
work to further improve it, must continue. Increased research effort, increased
interaction between industry, public-sector research and advisory services, and
registration authorities, and increased publication of information, will all be beneficial.
However, moderation should be the keynote, since the lion's share of tight R&D
budgets must go to new invention in chemical and biological crop protection.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

ACKNOWLEDGEMENT

We are grateful to all those people who have assisted in various ways in the preparation of this
second edition of this monograph. We must thank especially Professor Phil Russell, Professor
Ulrich Gisi and Dr Karl Heinz Kuck for their most helpful support and advice.

REFERENCES

Anon. (1979) Pest resistance to pesticides and crop loss assessments, FAO Plant Protection and
Production Paper 6/2 AGP: 1979/M/2, Rome, 41.

Anon. (1991) FRAC methods for monitoring fungicide resistance. EPPO Bulletin 21: 291 354.

Anon. (1992) FRAC methods for monitoring the sensitivity of fungal pathogens to phenylamide
fungicides. EPPO Bulletin 22: 297 322.

Bent, K J, Cole, AM, Turner, JAW and Woolner, M (1971) Resistance of cucumber powdery mildew
to dimethirimol. Proceedings 6th British Insecticide and Fungicide Conference, 274 282.

Birch, C P D and Shaw, M W (1997) When can reduced doses and pesticide mixtures delay the build
up of pesticide resistance? A mathematical model. Journal of Applied Ecology 34:
1032 1042.

Brent, K J (1982) Case study 4: Powdery mildews of barley and cucumber. In: Fungicide Resistance in
Crop Protection, Dekker, J and Georgopoulos, S G eds. Pudoc, Wageningen, 219 230.

Brent, K J (1986) Detection and monitoring of resistant forms: an overview. In: Pesticide Resistance:
Strategies and Tactics for Management. National Academy Press, Washington DC, 298 312.

Brent, K J (1987) Fungicide resistance in crops: its practical significance and management.
In: Rational Pesticide Use. Brent, K J and Atkin, R K eds. Cambridge University Press, 137 152.

Brent, K J (1995) Fungicide resistance in crop pathogens: How can it be managed? FRAC Monograph
No 1, GIFAP, Brussels, 48pp.

Brent, K J, Carter, G A, Hollomon, D W, Hunter, T, Locke, T and Proven, M (1989) Factors affecting
build up of fungicide resistance in powdery mildew in spring barley. Netherlands Journal of Plant
Pathology 95: 31 41.

Brent, K J and Hollomon, D.W (1998) Fungicide resistance: The assessment of risk FRAC Monograph
No 2, Global Crop Protection Federation, Brussels, 48pp.

Brent, K J, Hollomon, D W and Shaw M W (1990) Predicting the evolution of fungicide resistance. In:
Managing Resistance to Agrochemicals, Green, M B, LeBaron, H M and Moberg, W K eds. American
Chemical Society Washington DC, 303 319.

Brent, K J and Hollomon, D.W (2007) Fungicide resistance: The assessment of risk FRAC Monograph
No 2, second revised edition, FRAC, 52pp.

Brown, J K M, Jessop A C, Thomas, S and Rezanoor, H N (1992) Genetic control of the response of
Erysiphe graminis f.sp. hordei to ethirimol and triadimenol. Plant Pathology 41: 126 135.

50

183


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

Carnegie, S F, Cameron, A M, Hide, G A and Hall, S M (1994) The occurrence of thiabendazole
resistant isolates of Polyscytalum pustulans and Helminthosporium solani on seed potato tubers in
relation to fungicide treatment and storage. Plant Pathology 43: 961 971.

Chin, K M, Chavaillaz, D, Kasbohrer, M, Staub, T and Felsenstein, F g (2001) characterizing resistance
risk of Erysiphe graminis f. sp. tritici to strobilurins. Crop Protection 20: 87 96.

Collina, M, Landi, L, Guerrini, P, Branzanti, M B and Brunelli, A (2005) Qol resistance of Plasmopara
viticola in Italy: biological and quantitative real time PCR approaches. In: Modern fungicides and anti
fungal compounds IV. Dehne, H W, Gisi, U, Kuck, K H, Russell, P E and Lyr H eds. BCPC, Alton
UK, 81 88.

Cooke, L R, Carlisle, D J, Donaghy, C, Quinn, M, Perez, F M and Deahl, K L (2006) The Northern
Ireland Phytophthora infestans population 1998 2002 characterised by genotypic and phenotypic
markers. Plant Pathology 55: 320 330.

Crute, I R, Gordon P L and Moss, N A (1994) Variation for response to phenylamides in UK
populations of Bremia lactucae (lettuce downy mildew) and Peronospora parasitica (brassica downy
mildew). In: Fungicide Resistance, Heaney, S, Slawson, D, Hollomon, D W, Smith, M, Russell, P E
and Parry, D W eds. British Crop Protection Council, Farnham, Surrey, 155 162.

Davidse, L C (1981) Resistance to acylalanine fungicides in Phytophthora megasperma f.sp.
medicaginis. Netherlands Journal of Plant Pathology 87: 11 24.

Dekker, J (1982) Countermeasures for avoiding fungicide resistance. In: Fungicide 46 Resistance in
Crop Protection, Dekker, J and Georgopoulos, S G eds. Pudoc, Wageningen, Netherlands, 177 186.
Delp, C J and Dekker, J (1985) Fungicide resistance: definitions and use of terms. EPPO Bulletin 15:
333 335.

De Waard, M A (1994) Resistance to fungicides which inhibit sterol 14a demethylation, an historical
perspective. In: Fungicide Resistance, Heaney, S, Slawson, D, Hollomon, D W, Smith, M, Russell, P E,
and Parry, D W eds. British Crop Protection Council, Farnham, Surrey, 3 10.

De Waard, M A, Andrade, A C, Hayashi, K, Schoonbeek, H J, Stergiopoulos, I and Zwiers L H (2006)
Impact of fungal drug transporters on fungicide sensitivity, multidrug resistance and virulence. Pest
Management Science 62: 195 207.

Dovas, C, Skylakakis, G and Georgopoulos S G (1976) The adaptability of the benomyl resistant
population of Cercospora beticola in Northern Greece. Phytopathology 66:1452 1456.

Dowley, L J (1994) Practical aspects of phenylamide resistance management. In: Fungicide Resistance,
Heaney, S, Slawson, D, Hollomon, D W, Smith, M, Russell, P E, Parry, D W, eds. British Crop
Protection Council, Farnham, Surrey, 147 154.

Eckert, J W (1982) Case study 5: Penicillium decay of citrus fruits. In: Fungicide Resistance in Crop

Protection, Dekker, J and Georgopoulos, S G eds. Pudoc, Wageningen, 231 250.

Elad, Y, Yunis, H and Katan, T (1992) Multiple fungicide resistance to benzimidazoles, dicarboximides

and diethofencarb in field isolates of Botiytis cinerea in Israel. Plant Pathology 41: 41 46.

Engels, A J G and De Waard, M A (1994) Effect of different treatment schedules on the sensitivity of

Erysiphe graminis f.sp. tritici. to fenpropimorph. In: Fungicide Resistance, Heaney, S, Slawson, D,

Hollomon, D W, Smith, M, Russell, P E and Parry, D W eds. British Crop Protection Council, Surrey,

303 308.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

EPPO (2002) EPPO Standard PP 1/213(2) Efficacy evaluation of plant protection products: resistance
risk analysis.

Forster, B, Chavaillaz, D, Steden, C, Radtke, W, Kasbohrer, M and Kuhl, A (1994) Influence of split
application of fenpropimorph mixtures on disease control In: Fungicide Resistance, Heaney, S,
Slawson, D, Hollomon, D W, Smith, M, Russell, P E and Parry, D W eds. British Crop Protection
Council, Farnham, Surrey, 331 335.

Fraaije, B A, Butters, J A, Coelho, J M, Jones, D R and Hollomon, D W (2002) following the dynamics
of strobilurin resistance in Blumeria graminis f.sp. tritici using quantitative allele specific real time
PCR measurements with the fluorescent dye SYBR green. Plant Pathology 51: 45 54.

Fraaije, B A, Burnett, F J, Clark, W S, Motteram, J and Lucas, J A (2005) Resistance development to
Qol inhibitors in populations of Mycosphaerella graminicola in the UK. In: Modern fungicides and
anti fungal compounds IV. Dehne, H W, Gisi, U, Kuck, K H, Russell, P E and Lyr H eds. BCPC, Alton
UK, 63 71.

Fry, W E and Milgroom, M G (1990) Population biology and management of fungicide resistance. In:
Managing Resistance to Agrochemicals, Green, M B, LeBaron, H M and Moberg, W K eds. American
Chemical Society, Washington DC, 275 285.

Fuchs, A and Drandarevski, C A (1976) The likelihood of development of resistance to systemic
fungicides which inhibit ergosterol biosynthesis. Netherlands Journal of Plant Pathology 82: 85 87.
Genet, J L, Jaworska, G and Deparis, F (2006) Effect of dose rate and mixtures of fungicides on
selection for Qol resistance in populations of Plasmopara viticola. Pest Management Science 62:
188 194.

Georgopoulos, S G (1994) Early evaluation of fungicide resistance risk. In: Fungicide Resistance,
Heaney, S, Slawson, D, Hollomon, D W, Smith, M, Russell, P E and Parry, D W eds. British Crop
Protection Council, Farnham, Surrey, 389 396.

Giannopolitis, C N (1978) Occurrence of strains of Cercospora beticola resistant to triphenyltin
fungicides in Greece. Plant Disease Reporter 62: 205 208.

Gilpatrick, J D (1982) Case study 2: Venturia of pome fruits and Monilinia of stone fruits.
In: Fungicide Resistance in Crop Protection, Dekker, J and Georgopoulos, S G eds. Pudoc,
Wageningen, 195 206.

Gisi, U and Staehle Csech, U (1988a) Resistance risk evaluation of new candidates for disease control.
In: Fungicide Resistance in North America, Delp, C J ed. American Phytopathological Society, St Paul,
Minnesota, 101 106.

Gisi, U and Staehle Csech, U (1988b) Resistance risk evaluation of phenylamide and EBI fungicides.

Proceedings 1988 Brighton Crop Protection Conference Pests & Diseases, 359 366.

Gisi, U, Sierotzki, H, Cook, A and McCaffery, A (2002) Mechanisms influencing the evolution of

resistance to Qol inhibitor fungicides. Pest Management Science 58: 859 867.

Gisi, H, Pavic, L, Stanger, C, Hugelshofer, H and Sierotzki, H (2005) Dynamics of Mycosphaerella

graminicola populations in response to selection by different fungicides. In: Modern fungicides and

anti fungal compounds IV. Dehne, H W, Gisi, U, Kuck, K H, Russell, P E and Lyr H eds. BCPC, Alton

UK, 89 101.

52

185


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

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 Pathology 56: 199 208.

Grasso, V, Palermo, S, Sierotzki H, Garibaldi, A and Gisi,U (2006). Cytochrome b gene structure and
consequences for resistance to Qo inhibitor fungicides in plant pathogens. Pest Management Science
62:465 472.

Heaney, S P, Hutt, R T and Miles, V G (1986) Sensitivity to fungicides of barley powdery mildew
populations in England and Scotland; status and implications for fungicide use. Proceedings 1986
British Crop Protection Conference Pests & Diseases, 793 800.

Heaney, S P, Martin, T J and Smith, J M (1988) Practical approaches to managing anti resistance
strategies with DMI fungicides. Proceedings 1988 Brighton Crop Protection Conference Pests &
Diseases, 1097 1106.

Heaney, S P, Hall, A A, Davis, S A and Olaya, G (2000) Resistance to fungicides in the Qol STAR
cross resistance group: current perspectives. Proceedings British Crop Protection Conference Pests &
Diseases 755 762.

Heimbach, U, Krai, G and Niemann, P (2002) EU regulatory aspects of resistance risk assessment. Pest
Management Science 58: 935 938.

Hilber, U W, Schuepp, H and Schwinn, F J (1994) Resistance risk evaluation of fludioxonil, a new
phenylpyrrole fungicide. In: Fungicide Resistance, Heaney, S, Slawson, D, Hollomon D W, Smith, M,
Russell, P E and Parry D W eds. British Crop Protection Council, Farnham, Surrey, 397 402.

Hollomon, D W (1981) Genetic control of ethirimol resistance in a natural population of Erysiphe
graminis f.sp. hordei. Phytopathology 71: 536 540.

Hollomon, D W (1994) Do morpholine fungicides select for resistance? In: Fungicide Resistance,
Heaney, S, Slawson, D, Hollomon D W, Smith, M, Russell, P E and Parry D W eds. British Crop
Protection Council, Farnham, Surrey, 281 289.

Hollomon, D W, Butters, J and Clark, J (1984) Genetic control of triadimenol resistance in barley
powdery mildew. Proceedings 1984 British Crop Protection Conference, Pests & Diseases, 477 482.

Hollomon, D W, Wood, P M, Reeve, C and Miguez, M (2005) Alternative oxidase and its impact on
the activity of Qo and Qi site inhibitors. In Modern fungicides and anti fungal compounds IV. Dehne,
H W, Gisi, U, Kuck, K H, Russell, P E and Lyr H eds. BCPC, Alton UK, 55 62.

Hunter, T, Brent, K J and Carter G A (1984) Effects of fungicide regimes on sensitivity and control of
barley mildews. Proceedings 1984 British Crop Protection Conference Pests & Diseases, 471 476.

Hunter, T, Brent, K J, Carter, G A and Hutcheon, J A (1987) Effects of fungicide spray regimes on
incidence of dicarboximide resistance in grey mould (Botrytis cinerea) on strawberry plants. Annals of
Applied Biology 110: 515 525.

Hunter, T, Arnold, G, Jordan, V W L and Brent, K J (1993) Effects of different fungicide programmes
on infection of wheat crops by Pseudocercosporella herpotrichoides and on build up of fungicide
resistance, In: Proceedings 10th International Symposium on Systemic Fungicides and Antifungal
Compounds, Lyr, H and Polter, C eds. Ulmer, Stuttgart, 165 174.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

Kaku, K, Takagaki, M, Shimizu, T and Nagayama, K (2003) Diagnosis of dehydratase inhibitors in
melanin biosynthesis inhibitor (MBI D) resistance by primer introduced restriction enzyme analysis in
scylatone dehydratase gene of Magnaporthe grisea. Pest Management Science 59: 843 846.

Kato, T (1988) Resistance experiences in Japan. In: Fungicide Resistance in North America, Delp, C J
ed. American Phytopathological Society, St Paul, Minnesota, 16 18.

Kendall, S, Hollomon, D W, Ishii, H and Heaney, S P (1993) Characterisation of benzimidazole
resistant strains of Rhynchosporium secalis. Pesticide Science 40:175 181.

Kianianmomeni, A, Felsenstein, F, Schwarz, G and Wenzel, G (2006) Validation of a real time PCR
assay for the quantitative detection of strobilurin resistance in field isolates of Pyrenophora teres.
(2007) Pest Management Science 63: 219 224.

Kuck, K H and Mehl, H (2004) Prothioconazole: sensitivity profile and anti resistance strategy.
Pflanzenschutz Nachrichten Bayer 57: 225 236.

Kuck, K H (2005) Fungicide resistance management in a new regulatory environment. In: Modern
fungicides and anti fungal compounds IV. Dehne, H W, Gisi, U, Kuck, K H, Russell, P E and Lyr H
eds. BCPC, Alton UK., 35 43.

Lalancette, N, Hickey, K D and Cole, H (1987) Effects of mixtures of benomyl and mancozeb on build
up of benomyl resistant Venturia inaequalis. Phytopathology 77: 86 91.

Leroux, P and Moncomble, D (1994) Resistance of Botiytis cinerea to dicarboximides, benzimidazoles
and phenylcarbamates in the Champagne vineyards. In: Fungicide Resistance, Heaney, S, Slawson, D,
Hollomon, D W, Smith, M, Russell, P E and Parry, D W eds. British Crop Protection Council,
Farnham, Surrey, 267 270.

Leroux, P, Fritz, R, Debieu, Albertini, C, Lanen, C Bach, J, Gredt, M and Chapeland, F (2002)
Mechanism of resistance to fungicides in field strains of Botiytis cinerea. Pest Management Science 58:
876 888.

Leroux, P, Albertini, C, Arnold, A and Gredt, M (2003) Le pietin verse: caracteristiques et distribution
des souches de Tapesia acuformis et Tapesia yalundae resistantes aux fungicides. Phytoma 557: 8 13.
Leroux, P, Gredt, M, Walker, A S, Monard , J M and Caron, D (2005a) Resistance of the wheat leaf
blotch pathogen Septoria tritici to fungicides in France. In: Modern fungicides and anti fungal
compounds IV. Dehne, H W, Gisi, U, Kuck, K H, Russell, P E and Lyr H eds. BCPC, Alton, UK, 115
124.

Leroux, P, Gredt, M, Walker, A S and Panon, M L (2005b) Evolution of resistance of Botiytis cinerea
to fungicides in French vineyards.

Li, H and Leifert, C (1994) Development of resistance in Botryotinia fuckeliana (de Bary) Whetzel
against the biological control agent Bacillus subtilis CL27. Zeitschrift fur Pflanzenkrankheiten und
Pflanzenschutz 101: 414 418.

Locke, T (1986) Current incidence in the UK of fungicide resistance in pathogens of cereals.
Proceedings 1986 British Crop Protection Conference, Pests & Diseases, 781 786.

Lorenz, G (1988) Dicarboximide fungicides: history of resistance development and monitoring
methods. In: Fungicide Resistance in North America, Delp, C J ed. American Phytopathological
Society, St Paul, Minnesota, 45 51.

187

54


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

Lorenz, G, Saur, R, Schelberger, K, Forster, B, Kung, R, and Zobrist, P (1992). Long term monitoring
results of wheat powdery mildew sensitivity towards fenpropimorph and strategies to avoid the
development of resistance. Proceedings 1992 Brighton Crop Protection Conference Pests & Diseases,
171 176.

Mavroedi, V I and Shaw, M W (2006) Effects of fungicide dose and mixtures on selection for triazole
resistance in Mycosphaerella graminicola under field conditions. Plant Pathology 55:
715 725.

McCartney, H A, Foster, S J, Fraaije, B A and Ward E (2003) Molecular diagnostics for fungal plant
pathogens. Pest Management Science 59: 129 142.

Metcalfe, R J, Shaw, M W and Russell, P E. (2000) The effect of dose and mobility on the strength of
selection for DMI fungicide resistance in inoculated field experiments. Plant Pathology 49: 546 557.
Mitani, S, Araki, S, Takii, Y, Oshima, T, Matsuo, N and Takeda, R (2001) The biochemical mode of
action of the novel selective fungicide cyazofamid: specific inhibition of mitochondrial Complex III in
Pythium spinosum. Pesticide Biochemistry and Physiology 71: 107 115.

Noble, M, Maggarvie, Q D, Hams, A F and Leaf, L L (1966) Resistance to mercury of Pyrenophora
avenae in Scottish seed oats. Plant Pathology 15: 23 28.

Parnell, S, van der Bosch, F and Gilligan, C A (2006) Large scale fungicide spray heterogeneity and the
regional spread of resistant pathogen strains. Phytopathology 96: 549 555.

Porras, L, Gisi, U, and Staehle Csech, U (1990) Selection dynamics in triazole treated populations of
Erysiphe graminis. Proceedings 1990 Brighton Crop Protection Conference, Pests & Diseases, 1163
1168.

Readshaw, A E and Heaney, S P (1994) Fenpropimorph sensitivity in Erysiphe graminis f.sp. triticv,
survey of northern France 1991 1993. In: Fungicide Resistance, Heaney, S, Slawson, D,
Hollomon, D W, Smith, M, Russell, P E and Parry, D W eds. British Crop Protection Council,
Farnham, Surrey, 297 302.

Russell, P.E (2003) Sensitivity baselines in fungicide resistance research and management. FRAC
Monograph No 3. CropLife International, Brussels, 56 pp.

Russell, P E. (2006) Fungicide Resistance Action Committee (FRAC) Outlooks on Pest Management.
17:(3) 119 121.

Samoucha, Y and Gisi, U (1987) Use of two or three way mixtures to prevent build up of resistance to
phenylamide fungicides in Phytopkthora and Plasmopara. Phytopathology 77: 1405 1409.

Sanglard, D, Ischer, F, Koymans, L and Billie, J (1998) Amino acid substitutions in the cytochrome
P450 lanosterol 14a|31emethylase (CYP51A1) from azole resistant Candida albicans clinical isolates
contribute to resistance to anti fungal agents. Antimicrobial Agents and Chemotherapy 42: 241 253.
Sierotzki, H, Kraus, N, Assemat, P, Stanger, C, Cleere, S, Windass, J and Gisi, U (2005) Evolution of
resistance to Qol fungicides in Plasmopara viticola populations in Europe. In: Modern fungicides and
anti fungal compounds IV. Dehne, H W, Gisi, U, Kuck, K H, Russell, P E and Lyr H eds. BCPC,
Alton, UK, 73 88.


-------
FUNGICIDE RESISTANCE IN CROP PATHOGENS:
HOW CAN IT BE MANAGED?

Schwinn, F J and Morton, H V (1990) Antiresistance strategies: design and implementation in practice.
In: Managing Resistance to Agrochemicals, Green, M B. LeBaron, H M, and Moberg, W K eds.
American Chemical Society, Washington DC, 170 183.

Shephard, M C, Bent, K J, Woolner, M and Cole, A M (1975) Sensitivity to ethirimol of powdery

mildew from UK barley crops. Proceedings 8th British Crop Protection Conference, 59 60.

Smith, C M (1988) History of benzimidazole use and resistance. In: Fungicide Resistance in North

America, Delp, C J ed. American Phytopathological Society, St Paul, Minnesota, 23 24.

Staub, T (1991) Fungicide resistance: practical experience with antiresistance strategies and the role of

integrated use. Annual Reviews of Phytopathology 29: 421 442.

Staub, T (1994) Early experiences with phenylamide resistance and lessons for continued successful
use. In: Fungicide Resistance, Heaney, S, Slawson, D, Hollomon, D W, Smith, M, Russell, P E,
Parry, D W eds. British Crop Protection Council, Farnham, Surrey, 131 138.

Staub, T, Dahmen, H, Urech, P A and Schwinn, F (1979) Failure to select for in vivo resistance in
Phytophthora irtfestans to acylalanine fungicides. Plant Disease Reporter 64: 385 389.

Staub, T and Sozzi, D (1984) Fungicide resistance: a continuing challenge. Plant Disease 68:1026 1031.
Steva, H (1994) Evaluating anti resistance strategies for control of Uncinula necator. In: Fungicide
Resistance, Heaney, S, Slawson, D, Hollomon, D W, Smith, M, Russell, P E and Parry, D W eds.
British Crop Protection Council, Farnham, Surrey, 59 66.

Wicks, T G, Hall, B and Pezzaniti, P (1994) Fungicidal control of metalaxyl insensitive strains of
Bremia lactucae on lettuce. Crop Protection 13: 617 624.

Windass, J D, Heaney, S P, Renwick, A, Whitcombe, D M, Little, S, Gibson, N J, Theaker, J and
Stanger, C P (2000) Methods for detecting low frequencies of mutations in mitochondrially encoded
genes. International patent WO 00/66773.

Wolfe, M S and Dinoor, A (1973) Pathogen response to fungicide use. Proceedings 7th British
Insecticide and Fungicide Conference, 813 822.

Wood, P M and Hollomon, D W (2003) A critical evaluation of the role of alternative oxidase in the
performance of strobilurin and related fungicides acting at the Qo site of complex III.
Pest Management Science 59: 499 511.

Yamaguchi, J and Fujimura, M (2005) Recent topics on action mechanisms of fungicides. Journal of
Pesticide Science 30 : 67 74.

Zziwa, M C N and Burnett, F J (1994) The effect of reduced doses on the sensitivity of powdery
mildew to fenpropimorph in barley field trials. In: Fungicide Resistance, Heaney, S, Slawson, D,
Hollomon, D W, Smith, M, Russell, P E and Parry, D W eds. British Crop Protection Council,
Farnham, Surrey, 303 308.

56

189


-------
Keith J Brent OBE PhD FIBiol FRAgS

After graduating at London University in Botany and Microbiology, Keith Brent worked for over
twenty years in ICI.now Syngenta. At first he studied the biochemistry of filamentous fungi, at the

Akers Research Laboratories, Welwyn.

In 1964 he moved to Jealott'sHiU Research Station where he led research on fungicides discovery
and development and tackled some of the initial problems of fungicide resistance. In 1979 he was appointed
Head of the Crop Protection Division at Long Ashton Research Station, University of Bristol,
where he also became Deputy Director.

During this period he continued to be involved in fungicide research, and also taught in
international courses on fungicide resistance in seven countries world wide.

Since 1992 he has worked as an international consultant in crop protection and agricultural research
management and in 1995 he authored the first FRAC Monograph.

Derek W Hollomon PhD

Having gained a degree in Agricultural Botany at Reading University, Derek Hollomon
started his plant pathology research at Hull University and was awarded a doctorate in 1965.

After several years of post doctoral research in Canada, Australia and the USA,
he returned to the UK to initiate research at Rothamsted on the mode of action of the systemic fungicides
that were then beginning to be used for cereal disease control. His research soon extended to resistance problems,
and these have continued to be a major interest since he moved to the Long Ashton Research Station in 1985.
His work has involved much collaboration with the agrochemical industry, and also has kept him in
close contact with the growers. He was awarded the British Crop Protect ion Council Medal in 1995.

Sinoe 2002. he has been a visiting fellow in the Biochemistry department of the
University of Bristol researching the pathway of respiration in pathogenic fungi.

He is technical editor of the journal Pest Management Science.

190


-------
Reference 5

Footnote: 19

191


-------
FRAC

FUNGICIDE RESISTANCE
ACTION COM Ml FT EE

Purpose

FRAC is a Specialist Technical Group of CropL'rfe International
(Formerly Global Crop Protection Federation, GCPF).

The purpose of FRAC is to provide fungicide resistance management guidelines to prolong the effectiveness of "at
risk" fungicides 3ndto limit crop losses should resistance occur.

The main aims of FRAC are to:

1.	Identify existing and potential resistance problems.

2.	Collate information and distribute it to those involved with
fungicide research, distribution, registration and use.

3.	Provide guidelines and advice on the use of fungicides to reduce
the risk of resistance developing, and to manage it should it occur.

4.	Recommend procedures for use in fungicide resistance studies.

5.	Stimulate open liason and collaboration with universities,

government agencies, advisors, extension workers, distributors and farmers.

Organisation Structure

FRAC is comprised of a Central Steering Committee, five Working Groups and three Expert Fora. The chairperson of
each working group and expert forum are automatic members of Steering Committee.

Why FRAC ?

Fungicides have become an integral part of efficientfood production. The loss of a fungicide to agriculture through
| resistance is a problem that affects us all. It may lead to unexpected and costly crop losses to farmers causing local
shortages and increased food prices. Manufacturers lose revenue vital for funding the enormous development costs of
new products. Without reinvestment the re would be no new compounds. This would cause serious disease
management problems that would endanger the world food supply.

The problem of resistance has increased since the advent of highly effective compounds with specific sites of action.
Although representing marked improvements in performance, including systemic and therapeutic properties,
experience has shown that these compounds may be prone to resistance. As reliance on these fungicides grows,
action is required to safeguard their effectiveness.

i Industry recognises its responsibilityin safeguarding new chemistries that are brought to market. Through FRAC and
| the Working Groups it coordinates, companies are striving to establish more effective communications to alert all
I people involved in the research, production, marketing, registration and use of fungicides to the problems of
i resistance.

\ With an enlightened attitude, effective strategies can be conceived and adopted. Cooperative action is essential if we
; are to preserve the option of chemical disease control for our crops.

192


-------
History of FRAC	j

FRAC and its Wsrtcinf: Groups ortgmated as a result of a course an ftmgtcJde rssistance In 1980, anil developed at an !
miustri seminar In Brussels in 1981.	j

The seminar attracted 68 scientists and martcefing managers torn 35 major agrocbemtasi companies worldwide.«	!

the meeting it was apparent frtal there was an urgsrii need for ccfeborafien. Ihs Fungicide Resistance Mm	|

Conwnfflee was feus &om as an organisation designed Is discuss res (stance pro&tems and formulate plans for	j

cooperative efforts Is avoid or manage fungicide resistance. FRAC became incorporated wiitta GfFAP, the internafionat	j

Group of Naffonal Assoc -	• .	stwcal Products. This organisafion was later renamed	j

Gtotet. Crop Protection Federation (GCPF). Throughout 200® and 2081, GCPF has worked to evolvs into CropLffe	1

International, the new global federation to represent Ihs plant science industry.	|

Working Groups for benamMazflles, dicar&oximides, demethylaSon inhibitors piffs) and phenyl amides were

organised and companies were soon cooperating in iwmlwfng studies and other technical projects, Fungicide use	j

guidelines designed to reduce the risk of resistance deve&phig or to manage it if It was present, wars produced and	j

have been refined as knowledge grew. The DMI Worthing Group was sxpanslsti to cow all Stem! Biosynthesis	1

inhibitors, and renamed the SSI Fungicides Worsting Sreup.	I

The introduction of the aniinopyrfmidines in 1995 and STAR fungicides (StoMurfn Type Actios and Resistance) in j

193? (now renamed Qol Fungicides Wortctng Group) and more recertify the intreduclton of new carbolic acid amides j

(CAA fungicides) ted to lie formation of war Sting groups for these new areas.	j

!
:

in comparison to tie aiKRM-imenffened 'Al-basedr wofliof groups, the Banana Working Group cleats win a single crop j

and several chemical groups. Tile Banana Waiting Qtmp,. which was created in 20®, is comprised of banana grower
associations, research institutions and chemical manufeeturers. The oS|eel»s of tils worfcing group are simitar to the
oilier FRAC groups.

CuG.r !ii~ Esrizi'^ioszo-e Di£3i JO'S"*'39 31VJ	-''or;iog Gret.pi ¦? r?.3;3 anise ji E-'ysitFor5 T'r.ise

res are constructed 35 n'or-ial n*t.vor'-s of iecnnical s.psrrs around the ,.*/or;c Ths; pr.-i.-i.-j?. s gsisrsi g.j;ai
•3' nfih% i9sista"C5 s Nation for'hsse gicuip; ana sre '.•eaatsa on an as	?ssi? 5S n mfc-i "nal,?1

;sc^i<= a1'., a; I a g ' e

193


-------
Reference 6

Footnote: 21

194


-------
EB1049

PLANT DISEASE

CLUB ROOT OF CABBAGE AND OTHER CRUCIFERS

Club root probably affects
most plants in the crucifer
(mustard) family worldwide,
including cabbage, cauliflower,

Brussels sprouts, broccoli,
kohlrabi, kale, col lards, Chinese
cabbage, mustard, and some
varieties of turnips, radishes,
and rutabagas. Alyssum and
stock are also susceptible, as are
many native and weed species
in the mustard family. Horse-
radish and winter cress are
resistant. Several non-crucifer-
ous species can be infected with
club root, including members of
the rose family (Rumex spp.,
e.g., sorrel and dock), poppy
family (Papaver spp.), and grass
family (Agrostis spp. = bentgrass,

Dactylis spp. = orchard grass,

Holcus spp. = velvetgrass, and
Lolium spp. = ryegrass). How-
ever, these species rarely show
typical symptoms of club root.

Causal agent

Club root is caused by the
fungus Plasmodiophora brassicae,
which produces a resting spore
that can survive in the soil for
18 years or longer, as well as a
motile spore (zoospore) that

Washington State University
^ Extension

195

can "swim" in wet soils. At
least 9 pathogenic types
(pathotypes) of the fungus have
been identified.

Symptoms

The most distinctive symp-
tom of club root is abnormally
large, distorted roots. Clubs
(swellings) may form on the
fine roots, secondary
roots, tap root, or
even the under-
ground stem, with
larger clubs (up to 5"
to 6" wide) usually
forming on larger
roots just below the
soil surface. On
crops in which the
fleshy root is an
enlarged hypocotyl
(e.g., radish, turnip,
and rutabaga), clubs
form on the tap root
or on secondary
roots and are usually
globular or spherical.

For hosts with more
fibrous root systems
(e.g., cabbage,
cauliflower, and
broccoli), the

spindle-shaped clubs form on
individual roots. Root swellings
are usually not observed until
about 3 weeks after infection.

If susceptible plants are
infected as seedlings, they may
die. However, often there are no
symptoms on the top growth of
seedlings, only small clubs on
the roots. Club root rarely kills

Spindle-shaped clubs on the roots of a cabbage plant
infected with Plasmodiophora brassicae.


-------
plants infected at a later stage.
Severe distortion of the roots
reduces the ability of plants to
absorb water and minerals,
resulting in stunted top growth,
yellowing of the lower leaves,
and reduced yields. Infected
plants may wilt during warm
weather, but recover at night,
and may bolt (produce a flower
stem) prematurely in hot
weather. Top growth may
appear normal during cool,
overcast conditions when the
transpiration demand is low. As
infection progresses, the clubs
may be invaded by secondary
organisms, resulting in decay of
the roots and death of the plant.

Some plant species suscep-
tible to club root (e.g., turnip,
rutabaga, and rapeseed/canola)
may form non-infectious hy-
bridization nodules of an un-
known cause that are easily
confused with club root symp-
toms. Herbicide injury to the

roots can also be mistaken for
club root (particularly
dinitroaniline herbicides such as
treflan).

Disease cycle

Plasmodiophora brassicae is
most active in cool, wet, acidic
soils such as those found west
of the Cascade Mountains. In
the presence of roots of a
susceptible host, resting spores
of the fungus germinate to
produce motile spores
(zoospores) that penetrate root
hairs or at wound sites on
thickened roots and under-
ground stems. Underground
stems may also be infected
through leaf scars. Soil mois-
ture levels of 50 to 70% of the
maximum water-holding
capacity (about -20 to -15 kPa)
are required for infection to
occur, and club root is more
severe in soils with a pH <7.0.
Germination of resting spores

occurs when soil temperatures
reach >60°F.

Once a plant is infected, the
fungus causes plant cells in the
roots to enlarge and divide
repeatedly, leading to gall
(club) formation. The fungus
produces masses of resting
spores in these clubs. The
resting spores are released into
the soil when the clubs rot, and
may remain viable in the soil
for more than 18 years.
Plasmodiophora brassicae is
spread by movement of in-
fested soil clinging to farm
equipment, tools, and shoes.
The pathogen can spread on
infected transplants and in
contaminated manure, irriga-
tion water, and drainage water.
Repeated production of cruci-
fers on the same land leads to
rapid buildup of the pathogen
in fields.

Management

Cultural control. Cultural
practices play a very important
role in effective long-term
control of club root:

1.	Purchase disease-free
transplants from a reputable
dealer and transplant
seedlings into well-drained
soils free from P. brassicae.

2.	If producing transplants,
sanitation is very important
for effective control of club
root. Use only non-infested
seedbeds and clean trans-
plant media, trays, and
equipment. Do not lime
seedbeds or transplant
media heavily as this may
mask symptoms of club root
and symptoms could be-
come severe after seedlings

Root system of a plant infected with club root, showing clump- or fist-like galls
(clubs) which eventually rot and release resting spores of Plasmodiophora
brassicae into the soil.

196


-------
are transplanted into soil
with a lower pH.

3. Do not allow water to drain
from an infested field into
an irrigation source, and
avoid using irrigation water
contaminated with P.
brassicae.

4.	If some crops are infected
and others are free from
club root, work in club root-
free crops before moving
people and machinery into
infected crops to avoid
spreading infested soil to
non-infested areas. Clean
soil thoroughly from ma-
chinery and equipment
before moving from an
infested field into a clean
field. Use soap and water to
wash tools used to handle
infected plants.

5.	Control wild mustards in
crucifer crops.

6.	Practice long-term (6+ years)
crop rotation to help prevent
buildup of inoculum of P.
brassicae.

7.	Dispose of infected plants in
the garbage or a dump. Do
NOT put infected culled
plants in a compost pile.

8.	Do not use manure from
animals fed infected culled
plants or from animals
pastured in infected crops.

9.	Good soil drainage and
maintenance of a high soil
pH by regular application of
lime help control club root.
The degree of control is
influenced by soil pH, and
different soil types vary in
their response to altering pH
with lime. High concentra-
tions of calcium and magne-
sium may provide control of

club root when the soil pH
is <7.2. Conversely, low
calcium and magnesium
may permit club root to
develop if the soil pH is
>7.2. If susceptible crops are
to be planted into suspect or
infested fields, incorporate
limestone at least 6 weeks
prior to planting to raise the
soil pH >7.0. Late summer
or fall applications of lime,
when the soil is dry, are
more effective than spring
applications. Use lime that
will increase both soil pH
and soil calcium, i.e., calcitic
lime is usually more effec-
tive than dolomitic lime
unless soils are low in
magnesium. Mix the hy-
drated lime thoroughly into
the soil (1,500 lbs/acre) for
maximum disease control.
Finely-ground lime alters
the pH more rapidly than
coarse granules. Lime will
not prevent development of
club root if the concentra-
tion of spores of P. brassicae
in the soil is high. Periodi-
cally monitor changes in soil
pH in subsequent years to
determine the stability of
the pH change. Be aware
that increasing the soil pH
of coarse-textured soils may
lead to boron deficiency,
which can be alleviated with
foliar applications of boron
or inclusion of boron in the
transplant water. In addi-
tion, some non-crucifer
crops have problems with
high lime content in the soil,
which should be taken into
consideration if a non-
crucifer crop will follow the

crucifer crop. For example,
scab of potatoes is made
worse by liming.

10.	Nitrogen fertilization can
affect development of club
root. Fertilization with
calcium nitrate may result in
less disease compared with
applications of ammonium
sulfate or urea. Research
done in Canada (by
Elmhirst and Zimmerman,
as reported in the 2001 Pest
Management Research
Report for Agriculture and
Agri-Food Canada) showed
that side-dressing brassica
crops with calcium nitrate 3
weeks after transplanting
significantly reduced root
clubbing.

11.	If club root develops in a
crop, hilling the plants
promotes production of
adventitious roots which
may help the infected crop
yield better.

12.	Cabbage cultivars with
resistance to multiple lines
of the club root fungus are
available, e.g., "Badger
Shipper" and "Richelain."
Some cultivars are resistant
to select races of the fungus.

Chemical control. For home
gardeners, no fungicides are
registered for control of club
root. For commercial growers,
several fungicides have shown
efficacy for control of club root
and can be incorporated into an
effective integrated disease
management program with the
cultural practices described
above.

1. Seedbeds can be fumigated
if pathogen-free soils are not

197


-------
available. Preplant soil
treatment with PCNB
(Terraclor 75 WP or Terraclor F)
does not prevent develop-
ment of club root, but
reduces the number of clubs
formed as well as secondary
root rots. PCNB can be
broadcast or banded into the
soil at planting, or applied in
the transplant water.

2. Soil fumigation with metam
sodium (e.g., Vapam or
Sectagon) applied by
rotovate-and-roll or spray-
blade fumigation effectively
controlled club root when
evaluated in a cauliflower
crop in western Washington.

3.	Researchers in British
Columbia, Canada, demon-
strated that cyazofamid
(Ranman) provided excel-
lent control of club root
when applied in-furrow
with a surfactant. There was
no evidence of phytotoxicity
from cyazofamid (Elmhirst
and Zimmerman, 2001 Pest
Management Research
Report for Agriculture and
Agri-Food Canada). This
product is currently not
registered for this use in
Washington State.

4.	In Canada, application of
fluazinam (Omega) in-
furrow in the transplant

water provided good control
of club root on cauliflower
in organic soils (Elmhirst
and Zimmerman, 2001 Pest
Management Research
Report for Agriculture and
Agri-Food Canada). How-
ever, fluazinam was phyto-
toxic to cauliflower on
mineral soils. This product is
currently not registered for
this use in Washington State.

Follow label directions and
precautions when applying any
pesticide. Only use pesticides
legally registered in your state
for the particular crop on which
you wish to make the application.

By Lindsey J. du Toit, Vegetable Seed Pathologist, WSU Northwest Washington REC, Mount Vernon, WA. Original
bulletin prepared in November 1990 by Roy M. Davidson, Jr., Agricultural Research Technologist, and Ralph S. Byther,
Emeritus Extension Plant Pathologist, WSU Puyallup REC, Puyallup, WA.

~Warning. Use pesticides with care. Apply them only to plants, animals, or sites listed on the label. When mixing and
applying pesticides, follow all label precautions to protect yourself and others around you. It is a violation of the law to
disregard label directions. If pesticides are spilled on skin or clothing, remove clothing and wash skin thoroughly. Store
pesticides in their original containers and keep them out of the reach of children, pets, and livestock.

The law requires that pesticides be used as label directs. Uses against pests not named on the label and low application
rates are permissible exceptions. If there is any apparent conflict between label directions and the pesticide uses sug-
gested in this publication, consult your county Extension agent.

Issued by Washington State University Extension and the U.S. Department of Agriculture in furtherance of the Acts of
May 8 and June 30, 1914. Extension programs and policies are consistent with federal and state laws and regulations
on nondiscrimination regarding race, color, gender, national origin, religion, age, disability, and sexual orientation. Trade
names have been used to simplify information. No endorsement is intended. Revised April 2004. Subject codes 270,
356. A.	EB1049

198


-------
Reference 7

Footnote: 22

199


-------
http://pnwhandbooks.org/plantdisease/mustard-greens-brassica-juncea-downy-mildew-staghead

PNW Plant Disease Management Handbook

Printed page URL: pnwhandbooks.org/plantdisease/node/3554

Mustard Greens (Brassicajuncea)-Clubroot

Cause The disease is caused by Plasmodiophora brassicae, a fungus-like microorganism that
can survive in soil 18 years or more after an infected crop. It can be spread through any means
that moves soil: wind and water, footwear and equipment, and in infected transplants. Soils
that are cool, wet (70 to 80% water-holding capacity) and acidic favor the pathogen.

Clubroot probably affects all species of the Crucifer family, including wild mustard. The
microorganism that causes clubroot occurs worldwide and also infects plants in the rose, poppy,
and grass families including Agrostis, Dactylis, Holcus, and Lolium spp. However, these plants
rarely show typical symptoms of the disease.

Symptoms Plants wilt in hot weather but partly recover at night. Top growth maybe stunted,
yellowish, and likely to prematurely bolt or to wilt in hot weather. The distinctive symptom is
abnormally large roots-fine roots, secondary roots, the taproot, or even on the underground
stem. Roots develop clubs (swellings) that can be 5 or 6 inches wide. The largest clubs usually
are just below the soil surface on the larger roots. Affected seedlings will not show any root
swellings until about 3 weeks after infection. When susceptible plants are attacked in the
seedling stage, they can die. When plants are attacked at a later stage, the disease rarely kills,
but roots that are severely distorted have a reduced capacity to absorb minerals and water from
soil. But even with extensive root clubbing, top growth maybe nearly normal, depending on
environmental conditions and cultural practices.

Cultural control

•	Grow susceptible plants in clubroot-free fields, which are difficult to find in the
Willamette Valley of Oregon.

•	Control wild mustards if they are a weed problem.

•	If growing susceptible crops in suspect or infested fields, incorporate enough finely
ground limestone the year before planting to raise the soil pH above 7. Use lime

200


-------
applications that increase soil pH as well as level of soil calcium. Thoroughly mix lime
into the soil to maximize potential disease control. Lime inhibits disease development,
but will not prevent a disease outbreak if the spore load in the soil is sufficiently high.
Different soil types vary considerably in their response to efforts to alter the pH with
lime. Therefore, measure the initial soil pH, follow Soil Moisture Potential (SMP) test
recommendations, and monitor the changes after application. Periodically monitor the
pH in subsequent years to determine the stability of the change.

•	If planting in a suspect or infected field, incorporating hydrated lime (1,500 lb/A) at
least 6 weeks before planting, whether pH is neutral or alkaline, gives additional disease
control.

•	The form of nitrogen fertilizer can also influence disease. Using calcium nitrate may
result in less disease compared to ammonium sulfate or urea.

•	Early infection of seedlings can result in severe symptoms, so it is important to use only
uninfected seedbeds and clean transplant media, trays, and equipment. Do not lime
seedbeds or transplant-growing media heavily. It may mask the disease, which could
flare up once seedlings are transplanted to a soil of lower pH.

•	Never allow drainage water or soil from an infested field to enter an irrigation source.
Spores are moved easily in irrigation water.

•	Work in pathogen-free fields before moving people and machinery into infested fields.
Thoroughly clean soil from machinery and equipment before moving from an infested
field to a clean one.

•	Long rotations (6 years or longer) help prevent a pathogen buildup and reduce disease.

•	If clubroot occurs, hilling-up plants can encourage production of adventitious roots,
which may result in a better yield.

Chemical control

•	Preplant soil treatment with PCNB (Terraclor 75 WP or Terraclor F). PCNB does not
control clubroot completely but reduces the number of clubs and secondary root rots so
that the crop is nearly normal size. 12-hr reentry.

o Broadcast: For transplant or direct-seeded fields, use 40 lb/A Terraclor 75 WP or
7.5 gal/A Terraclor F, depending on soil type. Disk or rototill the PCNB into the
top 4 inches of soil. The treatment is effective for two (2) seasons if the soil is only
rototilled and cultivated, not plowed,
o Bands: For transplanted or direct-seeded fields. Although a savings in chemical
may be made the first year by applying it in bands before planting and cultivating

201


-------
it into the top 4 inches of soil, the second-year benefit from this application of
chemical is lost.

o Use starter solutions at 1 cup/plant at planting: PCNB at 2 lb/100 gal water of the
75 WP formulation or Terraclor F at 3 pints/100 gal water. Recommended only
for commercial growers.

• Omega 500F at 6.45 fl oz/100 gal water as a transplant drench or 2.6 pt/A for soil
incorporation. Product may cause plant stunting or delay and shorten harvest.
Preharvest interval is 50 days. 48-hr reentry.

Pscheidt, J.W., and Ocamb, C.M. (Senior Eds.). 2013. Pacific Northwest Plant Disease Management Handbook.
© Oregon State University.

Use pesticides safely!

•	Wear protective clothing and safety devices as recommended on the label. Bathe or shower after each use.

•	Read the pesticide label—even if you've used the pesticide before. Follow closely the instructions on the
label (and any other directions you have).

•	Be cautious when you apply pesticides. Know your legal responsibility as a pesticide applicator. You may
be liable for injury or damage resulting from pesticide use.

Trade-name products and services are mentioned as illustrations only. This does not mean that the participating
Extension Services endorse these products and services or that they intend to discriminate against products and
services not mentioned.

202


-------
Reference 8

Footnote: 23

203


-------
http7/www.uri.edu/ce/factsheets/prints/clubrootcrucifer.html

University of Rhode Island GreenShare Factsheets

Diseases of Crucifers: Clubroot

Clubroot is a worldwide problem of temperate climates in the production of cruciferous vegetables such as cabbage, broccoli,
cauliflower, radishes, kale, brussels sprouts and turnips, as well as field crops such as mustard and rape. The disease was
known as early as the 13th century in England where it was called "finger and toe" disease because of the shape of infected
roots.

Symptoms:

The most striking symptom of clubroot is an abnormal enlargement of the root system, with clubs often thickest at the center,
tapering spindle-like towards the ends. In radishes, clubroot causes distorted swellings on the base of the bulb and along the
tap root. In severe cases, entire plantings are destroyed. Clubroot-infected plants often wilt on sunny days and permanent
wilting may accompany advanced decay of infected roots. Severe stunting may be evident if infection occurs early and the
disease progresses rapidly. The malformed and greatly enlarged roots are the key symptom of this disease.

Causal Organism:

Clubroot is caused by the soil-borne fungus Plasmodiophora brassicae, which only infects plants in the crucifer family. It
infects susceptible host plants through root hairs. Once in the tissue, it stimulates abnormal growth of affected parts, resulting
in a swollen club. Infection is favored by excess soil moisture and low pH, although it can occur over a wide range of
conditions. Once a plant is infected, numerous resistant spores of the fungus are produced in the "clubbed" tissues. As these
tissues decay, spores are released into the soil where they can remain infectious for at least 10 years. Contaminated soil
moved by wind or water can serve as a source of infestation of nearby fields, causing outbreaks of disease in areas where
susceptible crops are planted for the first time. Numerous races of the pathogen have been identified.

Mangement:

Clubroot is a very difficult disease to manage, and heavily infested areas may have to be abandoned for future crucifer
production. Some control may be achieved with the following measures:

•	A good crop rotation program, growing crucifers on the same soil no more than every third or fourth year, is essential to
retard development of a large population of spores on land not already heavily infested.

•	Remove weeds in the crucifer (Brassicaceae) family.

•	Since clubroot is favored by a low pH, liming soil to pH 7.2 or above may be helpful. Raising soil pH too high, however,
may interfere with the growth of succeeding crops other than crucifers. Calcitic lime is usually preferable to dolomitic lime,
except for soils low in magnesium, where dolomitic lime is more effective. In course-textured soils, increasing the pH can
result in boron deficiency. This may be alleviated by application of boron in transplant water or as a foliar spray.

•	With transplanted crops, the use of pathogen-free seedbeds and uninfected plants is essential to prevent introduction of the
disease.

204


-------
•	Application of an appropriate fungicide in transplant water prior to planting may help to reduce disease development.

•	Clean and disinfect all machinery before moving it from infested to non-infested land.

•	Some resistant cultivars are available. However, plant resistance has not been very useful in clubroot control because of
rapid development of new races of the fungus.

•	Grow your own transplants to ensure that the disease does not enter from infested areas on new plants.

Adapted from Sally A. Miller, Randall C. Rowe and Richard M. Riedel, Ohio State University Extension, 2000

Pesticides are poisonous! Read and follow all safety precautions on labels. Handle carefully and store in original containers out of reach of children, pets
or livestock. Dispose of empty containers immediately, in a safe manner and place. Pesticides should never be stored with foods or in areas where
people eat.

When trade names are used for identification, no product endorsement is implied, nor is discrimination intended against similar materials. Be sure that
the pesticide you intend to use is registered for the state of use.

The user of this information assumes all risk for personal injury or property damage.

For more information, call the URI CE Gardening and Food Safety Hotline at 1-800-448-1011 or (401)874-2929 from
outside Rhode Island; Monday-Thursday between 9 am and 2 pm.

205


-------
Reference 9

Footnote: 25

206


-------
Source URL: https://extension.uinass.edu/veqetable/diseases/brassica-downv-mildew

Brassica Downy Mildew

Halyoperonospora
parasitica

Downy Mildew occurs wherever brassica crops are grown and infects cabbage, Brussels sprout, cauliflower,
broccoli, kale, kohlrabi, Chinese cabbage, turnip, radish, and mustard as well as cruciferous weed species.
The disease caused by Hyaloperonospora parasitica is particularly important on seedlings but can also cause
poor growth and reduced yield and quality of produce at later plant stages.

Identification:

Small, angular lesions develop on leaves and inflorescences. These lesions enlarge and become irregular,
yellow to orange necrotic patches, with dense sporulation on leaf undersides. Heavy sporulation gives leaf
undersides a gray to purple, downy appearance.

Life Cycle:

Downy mildew overwinters on winter-sown host crops or cruciferous weeds. Infection of leaves and
inflorescences results from sporangia produced on living hosts. Secondary sporangia are spread by wind and
splashing water. Oospores, if produced, survive in crop residues and in the soil. There is some evidence
that H. parasitica may be seed borne. The pathogen is favored by cool, moist conditions.

Crop Injury:

207


-------
On seedlings, cotyledons and hypocotyls may become infected and seedling loss can occur. In more mature
plants, small, angular lesions develop on leaves and inflorescences. A pale brown to gray discoloration
occurs on the surface of heads or curds and black streaks may develop on the stems. Affected tissues
become susceptible to attack by secondary rotting organisms. Downy mildew also attacks the taproots of
turnip and radish and infected organs develop a black, epidermal blotch and an internal discoloration.
Cultural Controls & Prevention:

•	Removal of crop debris and weed hosts may reduce inoculum.

•	Practice rotation with non-brassica crops.

•	Manage Downy Mildew on transplants in the seedling bed by improving air circulation, irrigating early
in the day, and applying fungicides.

•	Plant resistant or tolerant cultivars.

Chemical Controls & Pesticides:

For Current information on disease recommendations ins specific crops including information on chemical
control & pesticide management, please visit the New England Vegetable Management Guide website [3],

Crops that are affected by this disease:

Cabbage. Broccoli. Cauliflower, and Other Brassica Crops [4]

Radish [5]

Rutabaga and Turnip [6]

Links:

[1]	https://extension.umass.edu/vegetable/sites/vegetable/files/diseases/broccoli_downey_mildew_head.jpg

[2]	https://extension.umass.edu/vegetable/sites/vegetable/files/diseases/broccoli_downey_mildew_leaf.jpg

[3]	http://www.nevegetable.org/

[4]	https://extension.umass.edu/vegetable/crops/cabbage-broccoli-cauliflower-and-other-brassica-crops

[5]	https://extension.umass.edu/vegetable/crops/radish

[6]	https://extension.umass.edu/vegetable/crops/rutabaga-and-turnip

208


-------
Reference 10

Footnote: 32

209


-------
Feature Story April 2004

Phytophthora Blight:
A Serious Threat to
Cucurbit Industries

Mohammad Babadoost

University of Illinois
Department of Crop Sciences
AW-101 Turner Hall
1102 S. Goodwin Ave.

Urbana, IL 61801
Email: babadoos@uiuc.edu

Introduction

Phytophthora blight, caused by the oomycete Phytophthora
capsici, has become one of the most serious threats to production of
cucurbits and peppers, both in the United States and worldwide
(2,6,8,9,11,17,18,22,27,30). Phytophthora capsici was first described
by Leonian on pepper in New Mexico in 1922 (20). In 1931, Tucker
(38) classified it as a species of the genus Phytophthora and
considered P. capsici as a host-specific fungus pathogenic on pepper.
Subsequently, taxonomists (23,36,37) studied Phytophthora isolates
from various hosts in the world and re-described the taxonomy of P.
capsici.

Recently, the incidence of Phytophthora blight on cucurbits has
dramatically increased in Illinois (2,32) and other cucurbit-growing
areas in the world (8,9,17,18), causing up to 100% yield loss.

Cucurbit industries, particularly processing industries, are seriously
threatened by heavy crop loss resulting from Phytophthora blight. For
example, outbreaks of Phytophthora blight have threatened the
processing pumpkin and other cucurbit industries in Illinois, where
90% of processing pumpkins produced in the US are grown (2,3)

(Figs. 1 and 2). Similarly, the pickling cucumber industry of Michigan
is jeopardized by the increased occurrence of Phytophthora blight (8).
Because of heavy crop losses the growers often have to abandon their
own farms for cucurbit production and move into different areas,
sometimes traveling more than 50 miles, to find fields not infested
with P. capsici.

Fig. 1. A processing pumpkin field (and	Fig. 2. A cucurbit fruit showcase at a farm in

pumpkins, inset) at harvest in Illinois.	Illinois.

APSnet Feature

210

April 2004


-------
At present, no single method provides adequate control of P.
capsici on cucurbits. No cucurbit cultivar with measurable resistance
is available. In addition, crop rotation is virtually ineffective because
the pathogen can survive for several years in the soil (8,40), and it
can infect more than 50 plant species, including several weed species
(6,32). Research is clearly needed to develop effective strategies for
the management of Phytophthora blight caused by P. capsici on
cucurbits and other vegetables.

Geographical Distribution

Phytophthora capsici on cucurbits was first reported in 1937 in
Colorado and California (15,33). Since then Phytophthora blight has
been observed in cucurbit growing areas throughout the world
(4,5,6,7,40). Phytophthora capsici infection commonly occurs in
temperate, subtropical, and tropical environments.

Host Range

In 1996, Erwin and Ribeiro (6) reported that 49 plant species can
be infected by P. capsici. Among the major hosts are red and green
peppers (Capsicum annuum), watermelon (Citruilum ianatus),
cantaloupe (Cucumis melo), honeydew melon (C. meio), cucumber
(Cucumis sativus), blue Hubbard squash (Cucurbita maxima), acorn
squash (Cucurbita moschata), gourd (C. moschata), processing
pumpkin (C. moschata), yellow squash (Cucurbita pepo), (C. pepo),
zucchini squash (C. pepo), tomato (Lycopersicon esculentum ), black
pepper (Piper nigrum ), and eggplant (Solarium meiongena ). In
2004, Tian and Babadoost (32) reported five crop species/varieties —
beet (Beta vulgaris), Swiss chard (Beta vulgaris var. cicla), lima
beans (Phaseolus lunatus), turnip (Brassica rapa), and spinach
(Spinacia olerace) ~ and one weed species, velvetleaf (Abutilori
theophrasti), as hosts of P. capsici for the first time.

Symptoms and Signs

Phytophthora capsici can strike cucurbit plants at any stage of
growth. The infection usually appears first in low areas of the fields
where the soil remains wet for longer periods of time (Fig. 3A). The
pathogen infects seedlings, vines, leaves, and fruit (Fig. 4).

M .JT ¦ . -7 7 mmmLMU •	r i

Fig. 3. Post-emergence damping-off of pumpkin seedlings: (A) a low area in a pumpkin field
with severe seedling death; (B) damping-off of a seedling.


-------
Fig. 4. Phytophthora blight symptoms on cucurbits: (A) post-emergence damping-off of a
pumpkin seedling; (B) crown infection of a summer squash plant; (C) lesions on an immature
processing pumpkin fruit; (D) fruit rot of watermelon.

Damping-off. Phytophthora capsici causes pre- and post-
emergence damping-off in cucurbits in wet and warm (20 to 30°C)
soil conditions (5,6,12,40) (Fig. 3). In seedlings, a watery rot
develops in the hypocotyls at or near the soil line, resulting in plant
death (Fig. 3B). Post-emergence seedling death is preceded by plant
wilting. Mature plants show symptoms of crown rot (Fig. 4B). Initial
symptoms include a sudden, permanent wilt of infected plants without
a change in color (40) (Fig. 5). The wilt of leaves progresses from the
base to the extremities of the vines. Often plants die within a few
days of the first appearance of symptoms or after the soil is saturated
by excessive rain or irrigation. The stem near the soil line turns light
to dark brown and becomes soft and water-soaked. Infected stems
collapse and die. Tap and lateral roots of infected processing pumpkin
plants usually do not exhibit any symptoms. Following death of the
foliage, roots may give rise to new vines if environmental conditions
become less conducive for disease development. Phytophthora
damping-off may result in partial to total loss of the crop.

Fig. 5. Wilt of a pumpkin plant as a result of
crown infection with P. capsici.

Vine blight. Vines can be affected at any time during the growing
season (2,6,40). Water-soaked lesions develop on vines (Fig. 6). The
lesions are dark olive in the beginning (Fig. 6A) and become dark
brown in a few days (Fig. 6B). The lesions girdle the stem, resulting in
rapid collapse and death of foliage above the lesion site (Figs. 6C, 6D,
and 7). Unaffected parts of the vine continue to grow if no girdling
lesion develops along the vine.

212

APSnet Feature

April 2004


-------
Fig. 6. Vine symptoms of Phytophthora blight on pumpkin: (A) lesions on a newly infected
vine; (B) a fully-developed lesion; (C) a girdling lesion affecting a part of a vine; (D) crown
infection-

Fig. 7. Death of a muskmelon plant as a
result of crown infection with P. capsici.

Leaf symptoms. Phytophthora capsici can infect both the petiole
and leaf blade (2,40). Dark brown, water-soaked lesions develop on
petioles (similar to lesions on vines), resulting in a rapid collapse and
death of leaves. Infection of the leaf blade results in development of
leaf spots ranging from 5 mm to more than 5 cm in diameter (Fig. 8)
Infected areas are chlorotic at first and then become necrotic with
chlorotic to olive-green borders in a few days. Under wet and warm
conditions, leaf spots expand rapidly, coalesce, and may cover the
entire leaf. Under dry conditions, expansion of leaf spots may cease.

Fig. 8. Phytophthora spots, caused by P.
capsici, on a pumpkin leaf. Note chlorosis
and necrosis.

APSnet Feature

213

April 2004


-------
Fruit rot. Fruit rot can occur from the time of fruit set until
harvest (2,17,40) (Figs. 9 and 10). Fruit rot generally starts on the
side of the fruit that is in contact with the soil (Fig. 9B). However,
when an infected leaf or vine comes in contact with a fruit, fruit rot
will start at the point of contact (Fig. 9C). Also, symptoms on the
upper surface of the fruit develop following rain or overhead
irrigation, which provides splashing water for pathogen dispersal.

Fruit rot also can develop after harvest, during transit or in storage.
Fruit rot typically begins as a water-soaked lesion (Fig. 9A), which
expands, eventually covering the fruit with white mold (2,17) (Figs. 9
and 10). The pathogen produces numerous sporangia on infected fruit
(Figs. 9 and 10). Fruit infection progresses rapidly, resulting in
complete collapse of the fruit (Figs. 9D, IOC, and 10D). Phytophthora
foliar blight and fruit rot may result in total loss of the crop (2).

Fig. 9. Fruit rot of processing pumpkin caused by P. capsici: (A) a lesion on a fruit; (B) fruit rot
developed on the side contacting the soil; (C) fruit rot as a result of falling an infected leaf on
fruit; (D) severely infected and collapsed fruit.		

rtf?	M¥*"» - I

Fig. 10. Fruit rot caused by P. capsici on cucurbit crops in commercial fields in Illinois: (A)
cucumber; (B) jack-o-lantem pumpkin; (C) acorn squash; (D) zucchini.

APSnet Feature

214

April 2004


-------
Pathogen Identification

Identification of Phytophthora capsici is mainly based on the
morphology of sporangia (6). Sporangia of P. capsici are variable in
shape and are papillate with long pedicels (Fig. 11). Sporangial
shapes are influenced by light and other cultural conditions, and are
subspherical, ovoid, obovoid, ellipsoid, fusiform, and pyriform.
Sporangia are tapered at the base and are caducous with long
pedicels. Length x width of sporangia varies from 32.8 to 65.8 x 17.4
to 38.7 pm (6). Length/breath ratios of sporangia range from 1.3:1 to
2.1:1. Pedicel lengths are highly variable among the isolates, ranging
from 35 to 138 (jm.

Fig. 11. Sporangia and zoospores of P. capsici: (A)
sporangia and zoospores; (B) a sporangium releasing
zoospores.

Fig. 12. Growth pattern of P. capsici colonies
from processing pumpkin fields on lima bean
agar, 5-day-old cultures.

Fig. 13. Oospores of P. capsici.

Fig. 14. An oospore of P. capsici with an
amphigynous antheridium.

APSnet Feature

215

April 2004


-------
Other characteristics of P. capsici isolates from cucurbits are: (i)
colonies grow at temperatures from 10 to 36°C, with optimum
temperatures of 24 to 33°C: (ii) growth patterns of colonies are
cottony, petaloid, rosaceous, and stellate (Fig. 12); (iii) oospore
diameters range from 22 to 34 pm (Fig. 13); and antheridia are
amphigynous (Fig. 14). Phytophthora capsici is heterothallic, and both
A: and A2 types may exist in the same field.

Pathogenic and Genetic Diversity of P. capsici

Cucurbit isolates of P. capsici have been reported to be pathogenic
on cucurbits, pepper, and tomato (12,15). Polach and Wenster (25)
reported distinct pathogenic strains among isolates of P. capsici from
tomato, pepper and squash. In North Carolina, Ristaino (26)
evaluated the relative virulence of isolates of P. capsici from
cucumber and squash on pepper and found differences in virulence
among the isolates. In Italy, Tamietti and Valentino (30) grouped P.
capsici isolates into 13 classes depending on their ability to infect
different plant species (pepper, tomato, eggplant, melon, squash,
pea, and French bean). In South Korea, Lee, et al. (18) studied
aggressiveness of P. capsici isolates from pepper and pumpkin on
pumpkin cultivars and reported significant pathogen-host interactions.
In Illinois, Tian and Babadoost (31) reported significant differences
among isolates of P. capsici from different locations.

Genetic variation among P. capsici isolates has been reported in
vegetable growing areas in the world (10,16,19,31). Different
methods have been used to study the genetic variation of fungi (16,
21,28,34,35,39). Internal transcribed spacer (ITS) regions have been
used to determine genetic differences among species of Phytophthora
(28). Inter-simple sequence repeats (ISSR) amplification is a new
technique that could rapidly differentiate closely related individuals
within a fungal species (31,39). Amplified fragment-length
polymorphism (AFLP) is a recently developed polymerase chain
reaction (PCR) technique that provides genetic markers for
fingerprinting, mapping, and studying genetic relationships among
populations within fungal species (1). Tian and Babadoost (31) used
ISSR and AFLP tests to determine genetic differences among isolates
of P. capsici from Illinois (Fig. 15). They reported that cluster analysis
separated the isolates into four distinct groups, representing four
different locations from which they had been collected.

Fig. 15. Products of inter-simple sequence repeats (ISSR) test of P. capsici using primer
(GTC)7. Marker is a 1-kb ladder (Promega, Inc. Madison, Wl).

3000bp

APSnet Feature

216

April 2004


-------
|	' -	, r —

Phytophthora capsici is a soilborne pathogen and survives between
crops as oospores in soil or mycelium in plant debris (6,8,24,40). An
oospore is a thick-walled sexual spore (Figs. 13 and 14) and is formed
when mycella of two opposite mating types (At and A,) grow

together. Oospores are resistant to desiccation, cold temperatures,
and other extreme environmental conditions, and can survive in the
soil, in the absence of a host plant, for many years (8,40). Oospores
germinate and produce sporangia and zoospores (asexual spores)

(Fig. 11). Zoospores are released in water (Fig. 11B) and are
dispersed by irrigation or surface water. Zoospores are able to swim
for several hours and infect plant tissues. Abundant sporangia are
produced on Infected tissues, particularly on affected fruit (Figs. 9 and
10), and dispersed by water or through the air. Sporangia can either
germinate and infect host tissues directly, or they can release
zoospores, which can then infect the plant. If the environmental
conditions are conducive, the disease develops very rapidly.

Soil moisture conditions are important for disease development
(8,40). Sporangia form when the soil is at field capacity and they
release zoospores when soit is saturated. The disease is usually
associated with heavy rainfall, excessive-irrigation, or poorly drained
soil. Frequent irrigation increases the incidence of the disease.

! " ¦ " , ¦ ,	¦

No single method currently available provides adequate control of
Phytophthora blight. A combination of measures should be practiced
to reduce the damage caused by P. capsici on cucurbits
(2,8,12,13,14,40). The most effective practice in controlling P. capsici
is preventing the pathogen from being moved into a new field. The
following practices can help to manage Phytophthora blight in cucurbit
fields;

1.	Select fields with no history of Phytophthora blight.

2.	Select fields that did not have cucurbit, eggplant, pepper, or

tomato for at least 3 years. No rotation period has been
established for effective management of Phytophthora blight of
cucurbits.

3.	Select fields that are well isolated from fields infested with P.

capsici.

4.	Select well-drained fields, or do not plant the crop In the areas of

the field which do not drain well.

5.	Clean farm equipment of soil between fields.

6.	Plant non-vining crops (i.e., summer squash) on dome-shaped

raised beds (approximately 25 cm high).

7.	Plant resistant varieties, if available.

8.	Avoid excessive irrigation.

9.	Do not irrigate from a pond that contains water drained from an

infested field.

10.	Do not work In wet fields.

11.	Scout the field for the Phytophthora symptoms, especially after
major rainfall, and particularly In low areas.

12.	When symptoms are localized in a small area of the field, disk
the area.

13.	Discard infected fruit, but not in the field.

14.	Do not save seed from a field where Phytophthora blight
occurred.

15.	Remove healthy fruit from the infested area as soon as possible
and check them routinely.

217

APSnet Feature

April 2004


-------
16.	Do not display fruit for sale in an area that is infested with P.
capsici.

17.	Apply effective fungicides, when recommended. Seed treatment
with either mefenoxam (Apron XL LS at 0.42 ml per kg of seed)
or metalaxyl (Allegiance FL at 0.98 ml per kg of seed) can
protects seedlings of cucurbits until 5 weeks after sowing seed
(3), Applications of dimethomorph (Acrobat 50WP at 448 g/ha)
plus copper sulfate (i.e., Cuprofix Disperss at 2,25 kg/ha), at
weekly interwals, can provide effective protection against foliar
blight and fruit rot caused by P. capsici in cucurbit fields (13).
Crop losses resulting from Phytophthora blight in cucurbit fields
can be minimized by combining Apron 50WP seed-treatment
with applications of Acrobat plus copper.

Phytophthora blight, caused by P. capsici, is and will continue to be
a serious threat to cucurbit production In the US and worldwide. There
are no cucurbit cultivars with measurable resistance to Phytophthora
blight, the pathogen survives in soils for several years, and limited
chemical control of the disease is available. New strategies for
management of Phytophthora blight are essential. Along with cultural
management strategies, research is needed to assess the possibilities
of using induced resistance in plants, genetically modified cultivars,
biocontrol agents, and eradicant fungicides for control of P. capsici in
cucurbits and other crops.

e Cited

1.	Alonso, S., and Glenn, H. H. 1999. Modification of the AFLP protocol

applied to honey bee DNA. Biotech. 26:706-709.

2.	Babadoost, M. 2000. Outbreak of Phytophthora foliar blight and fruit rot

in processing pumpkin fields in Illinois. Plant Dis. 84:1345.

3.	Babadoost, M., and Islam, S. Z. 2003. Fungicide seed treatment effects

on seedling damplng-off of pumpkin caused by Phytophthora capsici.
Plant Dis. 87:63-68.

4.	C.M.I. 1985. C.M.I, description of pathogenic fungi and bacteria No. 836.

Phytophthora capsici, CAB, Kew, England.

5.	Erwin, D. C., Bartnlckl-Garcla, S., and Tsao, P. H. 1995. Phytophthora;

Its Biology, Taxonomy, and Pathology. American Phytopathological
Society, St. Paul, MN.

6.	Erwin, D. C., and Ribeiro, O. K. 1996. Phytophthora Diseases Worldwide.

American Phytopathological Society, St. Paul, MN.

7.	Farr, D. F., Bills, G. F», Chamuris, G. P., and Rossman, A. Y. 1995. Fungi

on Plants and Plant Products in the United States. American
Phytopathological Society, St. Paul, MN.

8.	Hausbeck, M. 2004. Phytophthora lessens learned: Irrigation water and

snap beans. The Vegetable Growers News 38:2829.

9.	Holmes, G. J., Lancaster, M. E,, Rodriguez, R. J., and Redman, R. S.

2001. Relative susceptibility of cucurbit and solanaceous drops to
Phytophthora blight. Phytopathology 91:S39. Publication no. P-2001-
0283-AMA.

10.	Hwang, B. K., Arthur, W. A., and Heitefuss, R. 1991. Restriction
fragment length polymorphisms of mitochondrial DNA among
Phytophthora capsici isolates from pepper (Capsicum annuum).

System. Appl. Micriobiol. 14:111-116.

APSnet Feature

218

April 2004


-------
11.	Hwang, B. K., and Kim, C. H. 1995. Phytophthora blight of pepper and
its control in Korea. Plant Dis. 79:221-227,

12.	Islam, S. Z., and Babadoost, M, 2002. Effect of red-light treatment of
seedlings of pepper, pumpkin, and tomato on the occurrence of

Phytophthora damping-off. HortSci 37:678-681.

13.	Islam, S. Z., and Babadoost, M. 2004. Evaluation of selected fungicides
for control of Phytophthora blight of processing pumpkin, 2004. Fung.

& Nemat. Tests 59:V129.

14.	Johnston, S. A. 1982. Control of the crown rot phase of Phytophthora

blight of bell pepper with fungicides. Fung. & Nemat. Tests 37:73.

15.	Kreutzer, W. A., Bodlne, E. W., and Durrell, t. W. 1940. Cucurbit
diseases and rot of tomato fruit caused by Phytophthora capsici.

Phytopathology 30:972-976.

16.	Lamour, K. H., and Hausbeck, M. K. 2002. The Spatiotemporal genetic
structure of Phytophthora capsici in Michigan and implications for
disease management. Phytopathology 92:681-684.

17.	Latin, R. X., and Rane, K. 1999. Identification and Management of
Pumpkin Diseases. BP-17, Purdue University, Lafayette, IN.

18.	Lee, B. K., Kim, B. S., Chang, S. W., and Hwany, B. K. 2001.

Aggressiveness of isolates of Phytophthora capsici from pumpkin and
pepper. Plant Dls. 85:797-800.

19.	Lee, S. B., White, T. J., and Taylor, J. W. 1993. Detection of
Phytophthora species by oligonucleotide hybridization to amplified
ribosomal DNA spacers. Phytopathology 83:177-181.

20.	Leonian, L. H. 1922. Stem and fruit blight of pepper caused by
Phytophthora capsici. Phytopathology 12:401-408.

21.	Majer, D. R., Mithen, B.G., Lewis, P. V., and Oliver, R. P. 1996. The use
of AFLP fingerprinting for the detection of genetic variation In fungi.

Mycol. Res. 100:1107-1111.

22.	Matheron, M. E., and Matejka, J. C. 1995. Comparative activities of
sodium tetrathiocarbonate and metalaxyl on Phytophthora capsici and
root and crown rot on chile pepper. Plant Disease 79:56-59.

23.	Mchau, G. R. A., and Coffey, M. D. 1995. Evidence for the existence of
two distinct subpopulations in Phytophthora capsici and a redescriptlon
of the species. Mycol. Res. 99:89-102.

24.	Papavizas, G. S., Bovvers, J. H., and Johnston, S. A. 1981. Selective
isolation of Phytophthora capsici from soils. Phytopathology 71:129-
133.

25.	Polach, F. J., and Wenster, R. K. 1972. Identification of strains and
Inheritance of pathogenclty in P. capsici. Phytopathology 62:20-26.

26.	Ristaino, J. B. 1990. Interspecific variation among isolates of
Phytophthora capsici from pepper and cucurbit fields In North Carolina.
Phytopathology 80:1253-1259.

27.	Ristaino, J. B., and Johnston, S. B. 1999. Ecologically-based
approaches to management of Phytophthora blight on bell pepper.

Plant Dis. 83:1080-1089.

28.	Ristaino, J. B., Trout, C. L., and Gregory, P. 1998. PCR amplification of
ribosomal DNA for species identification in the plant pathogen genus
Phytophthora. Appl. Environ. Microbiol. 64:948-954.

29.	Schmitthenner, A. F., and Hilty, 3. W. 1962. A modified dilution

technique for obtaining single-spore isolates of fungi from
contaminated material. Phytopathology 52:582-583.

219

APSnet Feature

April 2004


-------
30.	Tamletti, G. and Valentino, D, 2001. Physiological characterization of a
population of Phytophthora capsici Leon, from northern Italy. 3. Plant

Pathol. 33:1101,

31.	Tian, D., and Babadoost, M. 2003. Genetic variation among Isolates of
Phytophthora capsici from Illinois. Phytopathology 93:584, Publication
no. P-2003-0613-AMA.

32.	Tian, D., and Babadoost, M, 2004. Host range of Phytophthora capsici
from pumpkin and Pathogenicity of isolates. Plant Dis. 88:485-489.

33.	Tompkin, C. M., and Tucker, C. M. 1937. Phytophthora root rot of
honeydew melon. J. Agrtc. Res. 54:933-944,

34.	Tooley, P. W., Bunyard, B. A., Carras, M. M., and Hatziloukas, E. 1997.
Development of PCR primers from Internal transcribed spacer region II
for detection of Phytophthora species infecting potatoes. Appl. Environ.
Microbiol. 63:1467-1475.

35.	Trout, C. I., Ristaino, j, B., Madritch, M., and Wangsoomboondee, T.
1997. Rapid detection of Phytophthora infestans In late blight infected
potatoes and tomatoes using PCR. Plant DIs. 81:1042-1048.

36.	Tsao, P. H. 1991. The identities, nomenclature and taxonomy of
Phytophthora isolates from black pepper. Pages 185-211 in: Diseases
of Black Pepper. Proc. Int. Pepper Comm. Workshop on Black Pepper
Diseases. Goa, India. Y.R. Sarma and T. Premkumar, eds.

37.	Tsao, P. H., and Alizadeh, A. 1988. Recent advances in the taxonomy
and nomenclature of the so-called "Phytophthora palmivora" MF4
occurring on cocoa and other tropical crops. Pages 441-445 In: 10th
Int. Cocoa Res. Conf. Proc. Santo Domingo.

38.	Tucker, C. M. 1931. Taxonomy of the genus Phytophthora deBary,

Univ. MO, Agric. Exp. Stn. Res. Bull. 153.

39.	White, T. J,, Bruns, T., Lee, S., and Taylor, J. 1990. Amplification and
direct sequencing of fungal rlbosomal RNA genes for phylogenetics.

Pages 315-322 in: PCR protocols: a guide to methods and applications,
M. A. Innis, D.H. Gelfand, J.J. Sninsky, and TJ. White, ed. Academic

Press, Inc., New York, N.Y.

40.	Zitter, T. A., Hopkins, D. L., and Thomas, C. E. 1996. Compendium of
Cucurbit Diseases. American Phytopathologlcal Society, St. Paul, MN.

! ' ¦ . !„	" ' ' I! '	' " i " " . l"	„ " " "

http://vegetablemdonline.ppath.cornell.edu/PhotoPages/Impt_Dlseases/
Cucurbit/Cuc_Phytop.htrn (Phytophthora blight photos — from
Cornell's Vegetable MD Online)

http://veg-frult.cropscl.uiuc.edu/Vegetables/Main/vegetables.htm
(Vegetable diseases — from U of Illinois' Dept. of Crop Sciences)

http://www.ces.ncsu.edu/depts/pp/notes/Vegetable/vdin027/vdin027.htm
(Phytophthora Blight of Peppers and Cucurbits — from North Carolina
Cooperative Extension Service)

http://www.greeen.msu.edu/Aprll00updates/020GREEEN1999.pdf (An
Integrated Approach to Manage Phytophthora Blight on Michigan's
Vine Crops — PDF from Project GREEEN at Michigan State University)

http://digital.llbrary.okstate.edu/oas/oas pdf/v75/pl 5.pdf
(Phytophthora capsici Zoospore Infection of Pepper Fruit In Various
Physical Environments — from the Oklahoma Academy of Science)

APSnet Feature

220

April 2004


-------
http;//www,bitklsagllgi.net/Cucurbit Phytophthora capslct,htm
(Phytophthora capsici K6k Bofiazy ^QruklOdu)

http://www.apsnet.org/onllne/feature/pumpkln/phyto.html
(Phytophthora Fruit Rot — from an APSnet Feature, American

Phytopathological Society)

http://www.ces.purdue.edu/extmedia/BP/BP-17/BP-17.pdf

(Identification & Management of Pumpkin Diseases — PDF from
Purdue Cooperative Extension)

http://edis.ifas.ufl.edu/pdffiles/CV/CV12300.pdf (Cucurbit Production

in Florida — PDF from University of Florida's Institute of Food and

Agricultural Sciences (IFAS))

http://www.cfgrower.com/tlps/august/managing.html (Managing
Phytophthora Blight in Cucurbit Crops — from Country Folks Grower)

http://www.ag.uiuc.edu/~vista/abstracts/a945.html (Phytophthora
Blight of Cucurbits — from the VISTA infobase of the University of
Illinois)

yriqht 2004 by The American Phytopathological Society
American Phytopathological Society
3340 Pilot Knob Road
St, Paul, MN 55121-2097

e mail: apsgscisoc.orq

APSnet Feature

221

April 2004


-------
Reference 11

Footnote: 33

222


-------
http://www.agf.gov.bc.ca/cropprot/pcapsici.htm

Phytophthora Blight of Cucurbits and Pepper

Phytophthora blight, caused by the fungus-like pathogen Phytophthora capsici, was detected on
pepper, pumpkin, squash, gourds and eggplant in British Columbia, for the first time in 2004. It was
confirmed in two neighbouring market gardens in the Kelowna area, where it caused significant
damage.

Phytophthora blight is a serious threat to production of susceptible crops worldwide, particularly
cucurbits and solanaceous plants. It is a fast spreading, aggressive disease, capable of causing
complete crop failures. The disease has been increasing in severity in the United States in recent years,
where outbreaks have threatened the survival of the processing pumpkin industry. Many vegetable
growers are familiar with a close relative of this disease - late blight of potato and tomato, caused by
Phytophthora infestans.

Hosts

Crops that can be infected by Phytophthora capsici blight include pumpkin, many types of squash,
gourd, watermelon, cantaloupe, honeydew melon, cucumber, peppers, eggplant and tomato. In 2004,
US researchers reported that beet, Swiss chard, lima beans, turnip and spinach were also susceptible.
In total, there are over 50 susceptible species, including many common weeds.

Symptoms

223


-------
Infected pumpkin fruit covered with white cottony Infected pumpkin fruit turned completely white by
growth and sporangia of Phytophthora capsici.	growth of Phytophthora capsici

Phytophthora capsici may affect all parts of the plant, causing a wide variety of symptoms. It may
cause pre- and post-emergence damping-off, stem and vine blight, wilting or fruit rot. Symptoms can
appear as fast as 3 to 4 days after initial infection when temperatures are warm.

Damping-off may occur both before and after emergence of seedlings in susceptible crops in the
spring. Symptoms include a watery rot near the soil line, wilting, and subsequent plant death. White
fungal growth may appear on infected areas of blighted seedlings under moist conditions.
Damping-off is more likely to occur when soil conditions are wet and warm (20 to 30°C), and when the
disease is well established in the soil. Many other fungi and fungus-like organisms can also cause
damping-off, including Pythium, Rhizoctonia and Fusarium species. Damping-off caused by P. capsici
has not yet been found in British Columbia. It is possible that local spring soil temperatures may not
be warm enough to favour early infection.

Cucurbits

All cucurbits are susceptible to Phytophthora rot, but squash and pumpkin are the most commonly
affected. Cucumber and melon are considered to be somewhat tolerant.

Foliar symptoms on leaves and petioles appear as rapidly expanding, irregular, water-soaked
lesions, resulting in a rapid collapse and death of leaves. Leaf spots are chlorotic (yellow) at first and
then turn brown with yellow or light green borders.

224


-------
Vine blight appears as water-soaked lesions on the vines. Lesions turn brown and necrotic within a
few days, resulting in stem girdling, wilting and death of foliage above the lesions. Dieback of shoot
tips, wilting, shoot rot, and plant death quickly follow initial infection. P. capsici can devastate entire
squash plantings in a matter of days when conditions are warm and moist.

Fruit rot was the predominant symptom seen on pumpkin, squash and gourds during the Kelowna
outbreak in 2004. Fruit rot often starts on the underside of the fruit where it sits on the soil. It can also
develop on the upper side of the fruit following rain or overhead irrigation. Early symptoms include
large, water-soaked or slightly sunken, circular lesions, which expand to cover the fruit with white
mold. The mold consists of millions of sporangia (spores), which can spread with wind and rain to
cause further infections. The white fungal growth of P. capsici on the fruit should not be confused with
the white growth of powdery mildew, which is a common problem on cucurbit leaves. Fruit rot
progresses rapidly, resulting in complete collapse of the fruit and invasion of secondary rots. Fruit rot
can also develop after harvest.

Yellow scallop squash fruit covered with white Gourd fruit infected with Phytophthora capsici
cottony growth and sporangia of Phytophthora
capsici

Pepper

On pepper, infection of the stem near the soil line is common. Stem lesions start as dark,
water-soaked areas which become brown to black and result in girdling, wilting and plant death. P,
capsici may also cause root rot and foliar blight on pepper. On leaves, small, water soaked lesions
expand and turn a light tan colour. White moldy growth may be seen on leaves during wet periods.
Rapid blighting of leaves and shoots may occur. Pepper fruit can also be infected through the fruit

225


-------
stalk. Fruit rot appears as dark green, water-soaked areas that become covered with a white to gray
mold. Infected fruit dries, becomes shrunken and wrinkled, and remains attached to the stem.

Pepper plants killed by Phytophthora blight

Eggplant

Fruit rot is the most common symptom of phytophthora blight in eggplant. Symptoms appear as a
round, dark brown area on the fruit, which is surrounded by a rapidly expanding lighter tan zone. Fruit
lesions and eventually whole fruit may be covered with white to gray moldy growth during wet
periods.

Eggplant fruit showing symptoms of Phytophthora Infected eggplant fruit showing discolouration and
blight infection in the field.	light sporulation of Phytophthora capsici.

Tomato

226


-------
Infection of field tomatoes was not observed in B.C. in 2004, although tomato crops were grown near
infected peppers, pumpkins and squash. However P. capsici does cause serious problems in
tomatoes in other areas.

Phytophthora blight can cause crown rot, leaf spot, foliar blight and fruit rot in tomatoes. Fruit rot
begins as dark, water-soaked spots, often where fruit is touching the soil. The infected spot rapidly
expands during warm weather to cover most of the fruit surface with a brown, watery discoloration
that may appear as concentric rings. Under humid conditions, infected fruit may be covered with white
moldy growth and rot entirely following invasion by secondary microorganisms. Similar symptoms can
also be caused by the late blight pathogen, Phytophthora infestans.

Life Cycle

P. capsici is a soilborne pathogen which overwinters as oospores (thick-walled resting spores) in the
soil or in plant debris. Oospores are resistant to desiccation and cold temperatures, and can survive in
the soil for many years.

In the spring, oospores germinate to produce sporangia and zoospores (asexual spores) when soil
moisture is at field capacity. Sporangia are spread by wind and water through the air and are carried
with water movement in soil. Sporangia germinate to directly infect host tissue, or if conditions are
wet, they can also germinate to release zoospores. Zoospores are motile and swim to invade host
tissue. P. capsici can also be spread in infected transplants, seed, and through contaminated soil and
equipment.

Abundant sporangia are produced on infected tissues, particularly on infected fruit. Sporangia are
spread in water, by rainsplash, or in air currents. Wind-borne sporangia can be carried long distances.
If the environmental conditions are favourable, the disease develops very rapidly.

Phytophthora blight is favoured by high soil moisture, frequent rains or irrigation, and warm
temperatures (optimum 24-33 °C). The disease is usually associated with heavy rainfall,
excessive-irrigation, or poorly drained soil. P. capsici does not survive cold temperatures very well
unless oospores are present.

Pathogen variation and strains

227


-------
P. capsici shows considerable genetic variation. Different pathogenic strains may have the ability to
infect different crops, and there are also differences in virulence, or the ability to cause disease in host
plants. Some strains may be more aggressive than others on certain hosts.

Limited pathogenicity tests were conducted at the Pacific Agri-Food Research Centre using P. capsici
isolates collected from pumpkin and squash in Kelowna in 2004. The B.C. isolates were able to cause
infection of sweet pepper, winter squash and golden zucchini, but did not infect musk melon.

P. capsici has 2 mating types, A1 and A2. When both mating types are present in the same field, the
pathogen is able to reproduce sexually and produce oospores - a type of spore that can survive for
many years in the soil. To date, only one mating type has been detected in B.C. from the 2004
outbreak.

Prevention

P. capsici had never been reported in British Columbia before 2004, and the 2004 outbreak was very
small and localized. The disease was not detected in 2005. Some precautions can be taken to avoid
introducing it to your farm.

Seed Source: The disease may have been introduced to the Kelowna area on infected seed. Use a
reliable source for disease-free seed and transplants. Do not collect seed from an infected field.

Scouting: Early detection may help to avert serious losses. Scout your field regularly for disease
symptoms. Pay particular attention to low areas of the field where the soil remains wet for longer
periods of time.

Identification: Submit suspected P. capsici infected plants to the Plant Diagnostic Laboratory or
contact a Ministry of Agriculture Plant Pathologist for disease diagnosis. Proper identification of pests
and diseases is an important component of integrated pest management.

Biosecurity: Take precautions to prevent spreading diseases between fields, and to prevent possible
introductions of diseases from fields of other growers. Be aware that Phytophthora may be carried on
clothing, foot-ware and farm equipment. Refer to the publication: Biosecurity Guidelines for more
information.

Disease Management

228


-------
Phytophthora blight is a difficult disease to control, particularly once established in the soil as
oospores. Management strategies should combine cultural and chemical controls, along with other
disease prevention measures.

•	Crop rotation is an excellent disease management strategy for most vegetable diseases. Rotate
to non-susceptible or non-host crops for at least 2 years. Be sure there is no crop residue left
from previous infected crops before replanting. Note, crop rotation is not effective in areas where
oospores are present in the soil. When soil is infested, it may be best to move production of
susceptible crops to a field with no history of the disease. Currently it is not known whether the
disease has successfully overwintered in Okanagan soils.

•	Control volunteer crop plants and susceptible weeds such as nightshade during crop rotations.
Control weeds during the growing season.

•	Plant resistant varieties, if available. Some pepper varieties have tolerance to Phytophthora
blight. Check seed suppliers for resistance ratings. There are no cucurbit cultivars with
measurable resistance currently available.

•	Select well-drained fields, and avoid planting into low-lying areas. Raised beds are
recommended for non-vining cucurbits.

•	Do not over-irrigate. Discontinue overhead irrigation if the disease is present.

•	When symptoms are localized in a small area of the field, disk the area. This will help to prevent
movement of spores from infected plants to healthy plants during subsequent rainfalls.

•	Clean equipment before moving it from infested to clean areas.

•	Do not work in wet fields.

•	Do not keep cull piles. Bury or remove infected plant material from the vicinity of fields and
vegetable stands/display areas.

•	Remove healthy fruit from the infested area as soon as possible and check them periodically for
symptoms. Cull all fruit with symptoms, and do not leave culls on the field.

•	There are no fungicides registered for control of P. capsici blight in Canada, and fungicides have
not been highly effective in other areas. However fungicides applied for other diseases may
provide some level of control, particularly fungicides that are effective against late blight or
downy mildew. Preventive sprays are more effective than spray programs started after the
disease symptoms are already present. For best results, the use of fungicides should always be
combined with other disease management practices. Consult the Vegetable Production Guide for
current fungicide recommendations.

Links for Further Information

229


-------
Phytophthora Blight: A Serious Threat to Cucurbit Industries, by Mohammad Babadoost,
University of Illinois - APSnet

Scary Diseases Haunt Pumpkins and Other Cucurbits - APSnet

Phytophthora Blight of Cucurbits, Pepper, Tomato, and Eggplant - Thomas A. Zitter, Department
of Plant Pathology, Cornell University

Vegetable Diseases Caused by Phytophthora capsici in Florida, by P.D. Roberts, R.J. McGovern,
T.A. Kucharek, and D.J. Mitchell - University of Florida

Greenhouse and Field Evaluation of Bell Peppers for Resistance to Phytophthora Blight, by M.
Babadoost, S. Z. Islam, and M. Hurt - University of Illinois

230


-------
Reference 12

Footnote; 35

231


-------
Vegetable diseases caused by Phytophthora capsici in Florida

1

Plan! Pathology Fact Sleet	SIM 59

Vegetable Diseases Caused by Phytophthora
capsici in Florida

P.D. Roberts, R.J. McOovers, T.A. Kucharek, «nd D.J. Mitchell, respectively,

Assistant Professor, Southwest Florida Research and Education Center,

Immokalee, FL 34120 ; Associate Professor, Galf Coast Research and Education
Center, Bradeaton, PL 34203, Professors, Plant Pathology Department, Univer-
sity of Florida, Gainesville FL 32611. Revised 2000

Fti^nikusS-rvii-iV'	);w\i >»id A)9kiilinM$i&'m»V Uninvtsuy ,4 fhtiiU/ cJ»rr*u»-«•»*»#. Ifcwn

Introduction

Losses caused by PliytvfhHurni oifSiii
have consistently occurred in pepper produc-
tion an?,is on the east coast of Florida for the
pv white fun-
gal grow® during wet periods. Rapid blight-
ing of new leaves and the entire emerging shoot
may lake place (Figure 2),

http://ufdc.ufl.edu/UF00066805/00001 /print?options=OJ J*


-------
Vegetable diseases caused by Phytophthora capsici in Florida

Pepper fruit is infected through the fruit
stalk. Fruit rot appears as dark given, water-
soaked areas that become cov prod with a while
to gray mold (Figure 3). Infected fruit dries,
becomes shrunken, wrinkled, and hrtnvn, and
remains attached to the stem.

Eggplant

Although the entire plant may be sus-
ceptible, fruit rot is the prim,try symptom
caused by P. capsid in eggplant. It begins .is ,1
round, d centers of ixitted areas a re covered with
a grayish mold, while the outer margins of le-
siotts appear brown and water-soaked {Figure
7). The entire fruit eventually decays. Initial
symptoms of bacterial fruit blotch of water-
melon are similar to those caused by P. vtipskl

http://ufdc.ufl,edu/UF0OO668O5/OOOOl/print?eptions=GJJ*

233

6/27/2013


-------
Vegetable diseases caused by Phytophthora capsici in Florida

However, after lesions expand, the two diseases
can be easily separated because of llw presence
ol extensive rind cracking and absence; of fun-
gal growth wiili bacterial fruit blotch, while
Phvtophthora rot is characterized In abundant
fungal growth accompanied by little or no
cracking,

Other Cucurbits

Phifktjtfflhom atfmi causes rapid blight-
ing and death of chayote plants and a fruit rot

similar to that observed in watermelon. Angu*
lar, water-soaked lesions (figure 8), as well as
st rapid fruit rot which is covered with white
fungal growth, are produced in cut-amber.
Symptoms of Phytophthora Wight in canta-
loupe include leaf lesions and tip dieback of
vines.

Disease Cycle

Phyfophtlwra capski may survive in and
on seed and host plant debris in line soil by
means of thick-walled, sexually-produced
spores (oospores). Both mating types of the
pathogen necessary for oospore production are
present in Florida. The pathogen produces
spores of another type oiled zoospores thai are
tonlAined within s«k -li ke structures called, spo-
rangia, Zoospores are motile and swim to in-
vade host tissue. Plentiful surface moisture is
required for this activity. The sporangia «m>
spread by wind and water through tlx? air and
are carried with water movement in soil,
Ph^tofijth.m mpski is also moved ,i$ hyphae
(microscopic fungal strands) in infected trans-
plants and through contaminated soil and
equipment. Since water is integral lo the? dis-
persal and infection of P, cupski maximum dis-
ease occurs during m?l weather and in low or
waterlogged parts of fields, Excessive rainfall,
such as that which occurs during "1U \'uu>"
years, coupled with standing water creates
ideal conditions for epidemics caused by P.
atjimi. Growth of this pathogen can occur be-
tween 7-3/°C {4o-99i>£)r but temperatures be-
tween 27-32*C." (80-W1} Are oplima 1 for prodtie-
ing zoospores and Hie infection process. Un-

der ideal conditions, lite disease can progress
very rapidly ami symptoms can occur 3-4 days
after infection. Therefore, P. capsfc/can rapidly
affect entire fields.

Management

Management practices in transplant pro-
duction areas include the use of pathogen-free
and tungfeide-treateti seed, and sterile potting
media. Transplant trays, benches, seeding
equipment and plant bouse benches and other
structures should be disinfested using a so-
dium hypochlorite solution or other disinfes-
tant. Steam sterilization of transplant trays may
be useful. Transplant trays with infected plants
should be removed immediately from produc-
tion sit«s, Workers should disinfesl their hands
after contact with infected plants before resum-
ing their duties.

Planting sites should be well drained
and free of low-lying areas. Optimal water
management is essential lo prevent the occur-
rence of flooded field conditions that favor
Phytophthora blight The drainage ar&i of the
field should be kept free of weeds and volun-
tas* crop plants, particularly those in the
solan,ireous and cururbitac eous groups, A
preplant furnigant shoukl be used. Equip-
ment should be decontaminated before mov-
ing between infested and noninfested fields.
Infected fruit should be culled to prevent
spread in the packinghouse and during
shipment Effective, labeled fungicides
should be used preventiv ely according lo
label instructions. It Is essential that fungi-
cides with different modes of action be ro-
tated to prevent the buildup of tun guide
resistance in P. mpski; rotating or tank-mixing

-------
Vegetable diseases caused by Phytophthora capsici in Florida

4

Figure 1. Stem lesions at {he soil line and
root rot caused by Phtftaphthom aifrsici in
pepper.

Figure 2, Foliar blight of pepper caused by
I'hiftophthora mpsici

Figure 3. Fruit rot in pepper caused by	Pigmre 4, Fruit rot In eggplast caused by

Phytophthora capsici.	Phytophthoru cnpsict.

http://ufdc.ufl.edu/UF00066805/0000 l/print?options=0JJ*

235

6/27/2013


-------
Vegetable diseases caused by Phytophthora capsici in Florida

Figure 5, f ruit ml in tomato caused by
Phytoplflfitmt capsici.

Figure {>. Foliar blight and fruit rot of yellow
summer squash caused by Pfitjtophthmn
capsici.

\

figKC 7. Vafaas stages of fruit rot of water-
melon caused by PhytopMhom capski, Left,
early symptoms;right advanced symptoms.

Figure S. Foliar lesions caused by
PhytopMfwra capsici in cucumber.

http://ufdc.ufl.edu/UF00066805/0000 l/print?options=OJJ*

236

6/27/2013


-------
Reference 13

Footnote: 36

237


-------
Published on Vegetable Program (http://extensiori.umass.edu/veqetable)
Home > Winter Squash Downy Mildew

Winter Squash Downy Mildew

Pseudoperonospora
cubensis

Downy mildew caused by Pseudoperonospora cubensis is one of the most important foliar diseases of cucurbits. It
occurs worldwide where conditions of temperature and humidity allow its establishment and can result in major
losses to cucumber, melon, squash, pumpkin, watermelon, and other cucurbits. Downy mildew can begin to
develop at any time during cucurbit crop development in the northeastern US. Fortunately it has occurred
sporadically in this region, usually appearing late enough in the growing season that yield is not impacted.
Identification:

Symptoms of Downy mildew are confined to the leaves and their appearance varies widely among cucurbit species.
On most species, lesions are first visible on the upper leaf surface as small, irregular to angular, slightly chlorotic
areas. Symptoms appear first on older leaves and progress to younger leaves as they expand. When conditions
(leaf wetness and humidity) favor sporulation, the production of fruiting bodies (sporangia) on the lower leaf
surface gives the undersides of the lesions a downy appearance, varying in color from light gray to deep purple.
Lesions can coalesce and result in large areas of dead tissue which exposes the fruit to sunscald. Extensive
defoliation can occur when conditions are favorable.

Life Cycle:

Pseudoperonospora cubensis infects only members of the cucurbit family and is an obligate parasite. Its survival
depends on the presence of cucurbit hosts, either in climates which permit their growth year round or in
greenhouse culture. The source of primary inoculum in cold climates is windblown sporangia from areas where
plants survive the cold season. Generally, Downy mildew of cucurbits does not arrive in southern New England
until September. However, in some seasons it can move up the eastern seaboard early and arrive in July. The
progress of Downy mildew is tracked by the the Cucurbit Downy Mildew Alert System (http://cdm.ipmpipe.org
[2]/). Physiological specialization occurs in P. cubensis and at least five pathotypes have been described.
Cucumber and melon are susceptible to all pathotypes, while squash and melon cultivars vary in their reactions.
Spread of Downy mildew within a field can be by air currents, rain splash, workers, and tools.

'[1]

238


-------
Monitoring & Thresholds:

Inspect crops weekly for symptoms and have suspect samples confirmed by an extension specialist. Regularly
check the UMass Vegetable website (http://extension.umass.edu/veqetable/ [3D or Cucurbit Downy Mildew Alert
System ( http://cdm.ipmpipe.org [4] )for information about Downy mildew occurrence, forecasts, and risks of
disease development.

Cultural Controls & Prevention:

The main means of control are fungicide applications, the use of resistant cultivars, and cultural practices.
Maximum control can be achieved only with a combination of these measures.

•	Monitor disease occurrence and weather forecasts at http://cdm.ipmpipe.org/ [2]

•	Maximize the distance between cucurbit fields to limit potential inoculum sources.

•	Many commercial cultivars of cucumber have good levels of resistance to Downy Mildew. Watermelon

and melon cultivars are available with low levels of resistance. Squash and pumpkin cultivars are
resistant to some pathotypes but are very susceptible to compatible pathotypes. See variety tables
posted at http://vegetablemdonline.ppath.cornell.edu. [5]

•	Use plant spacings which reduce the density of the plant canopy. Avoid overhead irrigation. Both these

practices are aimed at minimizing the length of leaf wetness periods.

•	Choose planting sites with good air movement and without shading. Avoid overhead irrigation in early

morning when leaves are wet from dew or late in the day when leaves will not have an opportunity to dry
before dew forms.

•	Apply broad-spectrum protective fungicides before detection and systemic narrow-spectrum fungicides

when downy mildew occurs early in crop production.

Chemical Controls & Pesticides:

For Current information on disease recommendations ins specific crops including information on chemical control

& pesticide management, please visit the New England Vegetable Management Guide website [6],

Crops that are affected by this disease:

Cucumber. Muskmelon, and Watermelon [7]

Pumpkin. Sguash, and Gourds [8]

Source URL: http://extension.umass.edu/vegetable/diseases/winter-sguash-downv-mildew
Links:

[1]	http://extension.umass.edu/vegetable/sites/vegetable/files/diseases/winter_squash_downey_mildew_leaf.jpg

[2]	http://cdm.ipmpipe.org/

[3]	http://extension.umass.edu/vegetable/

[4]	http://cdm.ipmpipe.org

[5]	http://vegetablemdonline.ppath.cornell.edu.

[6]	http://www.nevegetable.org/

[7]	http://extension.umass.edu/vegetable/crops/cucumber-muskmelon-and-watermelon

[8]	http://extension.umass.edu/vegetable/crops/pumpkin-squash-and-gourds

239


-------
Reference 14

Footnote: 42

240


-------
httpV/www.grapes.msu.edu/downy mildew.htm

Downy mildew - Plasmopara viticola

Annemiek Schilder, MSU Plant Pathology

Home > Scouting guide> downy mildew

Downy mildew is a widespread, serious disease of grapevines. Initial leaf symptoms are light green to yellow
spots, called "oil spots" because they may appear greasy. Under humid conditions, white, downy spore masses
can be seen on the lower leaf surface. These spores are wind dispersed. The lesions eventually turn brown as the
infected tissue dies. Severely infected leaves drop prematurely, which can reduce winter hardiness of the vine.
Infected flower clusters dry up or become covered with white spores under humid conditions. Infected berries turn
a mottled dull-green or reddish purple and readily fall from the cluster. Although berries become resistant to
infection within three weeks after bloom, the rachis remains susceptible for several weeks longer.

Young lesions.	White downy spore masses on the lower Older lesions that have turned brown.

surface of the leaf.	Photos: A. Schilder

The pathogen overwinters in infected leaves on the ground. In spring, spores are carried by rain splash to new
leaves, where they require a film of water for infection. Lesions appear 5 to 17 days after infection. The disease can
spread rapidly under warm conditions with frequent rain or dew. Use the 10-10-10 rule to decide when to start
scouting for downy mildew: at least 10 cm (4 in.) of shoot growth, 10 mm (0.4 in.) rainfall and temperatures of 10°C
(50°F) during a 24-hour period.

241


-------
White spore masses develop On older leaves, lesions Young shoot covered with	Photo: t. zabadai

on infected berries.	are smaller and more spores. Photo: t zabadai

Photo: a. schiider	angular as they are

delimited by leaf veins.

Photo: A. Schiider

242


-------
Reference 15

Footnote: 43

243


-------
httpV/agsci.psu.edu/fphg/grapes/disease-descriptions-and-management/downy mildew

Extension » Plants and Pests » Home Lawn and Garden » ... » Disease Descriptions and
Management» Downy Mildew

Downy Mildew

Downy mildew is caused by a fungus that can infect berries, leaves and young
shoots. It occurs wherever it is wet and warm during the growing season. There is
some variety resistance, with V, vinifera varieties being the most susceptible and V.
rotundifolia being the most resistant.

Symptoms

The fungus attacks all green parts of the vine, especially the leaves. Lesions on
leaves are angular, yellowish, sometimes oily, and are located between the veins.
As the disease progresses, a white cottony growth can be observed on the lower
leaf surface. Severely infected leaves will drop. If enough defoliation occurs, the
overwintering buds will be more susceptible to winter injury. Infected shoot tips
become thick, curl, and eventually turn brown and die. Young berries are highly
susceptible, appearing grayish when infected. Berries become less susceptible
when mature. Infected berries remain firm compared to healthy berries, which
soften as they ripen. Infected berries will eventually drop

Disease Cycle

The disease is caused by the fungus Plasmopara viticola, which overwinters as

244


-------
dormant spores within infected leaves on the vineyard floor which become active in
the spring. This fungus has two types of spores, both germinating to give rise to
swimming spores. These spores swim to the stomates (breathing pores) of plants
and cause infection. Water is necessary for the spores to swim and to infect, so
outbreaks of the disease coincide with periods of wet weather. Downy mildew is
favored by all factors that increase the moisture content of soil, air, and the plant,
with rainfall being the principal factor for infection. The frequency of rain and the
duration of wet periods correlate with the number of additional infections during the
growing season. Downy mildew infection can become a severe problem when a wet
winter is followed by a wet spring and a warm summer with a lot of rainfall.

Disease Management

Some control can be achieved by preventative management practices. Spring
cultivation to bury fallen, infected leaves from the previous year may help reduce
early season disease pressure. Pruning out the ends of infected shoots and
practices that improve air circulation and speed drying within the vine canopy will
also help to control downy mildew. Fungicides, however, are the most important
control measure, especially on susceptible varieties. They should be applied just
before bloom, 7 to 10 days later (usually at the end of bloom), 10 to 14 days after
that, and, finally, 3 weeks after the third application. For varieties very susceptible to
downy mildew, or where the disease was severe the previous season, an additional
application is suggested about 2 weeks before the first blossoms open.

245


-------
Reference 16

Footnotes; 46 & 50

246


-------
www. agf. gov.bc.ca/cropprot/p ythium.htm

British Columbia, Ministry of Agriculture
Pythium Diseases of Greenhouse Vegetable Crops

Pythium species are fungal-like organisms (Oomycetes), commonly referred to as water molds, which naturally
exist in soil and water as saprophytes, feeding on organic matter. Some Pythium species can cause serious
diseases on greenhouse vegetable crops resulting in significant crop losses. Pythium infection leads to damping
off in seedlings and crown and root rot of mature plants. In Canada, several Pythium species, including P.
aphanidermatum, P. irregulare and P. ultimum, are known to cause damping-off and crown and root rot in
greenhouse cucumber, pepper and tomato crops. There are no Pythium resistant varieties available although
some varieties may have disease tolerance. Over watering, poor root aeration, root injury and improper root zone
temperatures can weaken the crop and, thus, trigger Pythium outbreaks. Saturated growing media that are either
too cold or too warm can be conducive to Pythium build up and spread in water and recirculating nutrient solution.
Plants grown under optimal environmental conditions are less susceptible to Pythium than plants grown under poor
conditions.

Disease cycle

Pythium can be introduced into a greenhouse in plug transplants, soil, growing media, plant refuse and irrigation
water. Greenhouse insects such as fungus gnats (Bradysia impatiens) and shore flies (Scateiia stagnaiis) can also
carry Pythium. Pythium spreads by forming sporangia, sack-like structures, each releasing hundreds of swimming
zoospores (Figure 1). Zoospores that reach the plant root surface encyst, germinate and colonize the root tissue by
producing fine thread-like structures of hyphae, collectively called mycelium. These hyphae release hydrolytic
enzymes to destroy the root tissue and absorb nutrients as a food source. Pythium forms oospores and
chlamydospores on decaying plant roots which can survive prolonged adverse conditions in soil, greenhouse
growing media and water, leading to subsequent infections.

247


-------
Fungus enters plant roots

Sexual

Reproduction

Figure 1. The disease cycle of Pythium damping-off and crown arid root rot of greenhouse vegetable crops.

Symptoms

'Pre-emergence' damping-off causes seeds and young seedlings to rot before they emerge from the growing
medium, while 'post-emergence' damping off kills newly emerged seedlings. In 'postemergence' damping-off, the
pathogen causes a water-soaked, soft brown lesion at the stem base, near the soil line, that pinches off the stem
causing the seedling to topple over and die. In mature plants, Pythium causes crown and root rot, where plants
suddenly wilt when weather turns warm and sunny and when plants have their first heavy fruit load. Often, upper
leaves of infected plants wilt in the day and recover overnight but plants eventually die. In the root system, initial
symptoms appear as brown to dark-brown lesions on root tips and feeder roots and, as the disease progresses,
symptoms of soft, brown stubby roots, lacking feeder roots, become visible (Figure 2). In larger roots, the outer root
tissue or cortex peels away leaving the string-like vascular bundles underneath. Pythium rot also occurs in the
crown tissue at the stem base. In cucumber, diseased crown turns orange-brown in colour, often with a soft rot at
the base; brownish lesions extending 10 cm up the stem base may be seen.

248


-------
Figure 2. Pythium crown and root rot in greenhouse cucumber showing orange discolouration of the crown area

and rotted roots and root tips.

Monitoring & Identification

Routinely monitor your crop for slightly wilted plants and check wet areas in the greenhouse where Pythium is
more likely to be present. Pythium occurs mostly in spring, at early fruit set and later in the season on mature
plants. In cucumber, Pythium can also occur in the summer on young plants brought in for the fall crop. Monitor
plants for wilting, and in cucumber, check the stem bases for discoloration. Always confirm Pythium diseases by
sending representative plant samples with roots, crowns and foliage to a plant diagnostic laboratory or the Ministry
of Agriculture's Plant Health Laboratory.

Integrated Disease Management

Disease management consists of a combination of cultural, biological and chemical tools to control and/or manage
crop diseases effectively. Cultural controls keep Pythium from reaching the roots while biological and chemical
controls inhibit or suppress Pythium in the root zone.

Cultural Controls

Sanitation: Field soil, debris, pond and stream water, and roots and plant refuse of previous crops can contain
Pythium. Follow a strict greenhouse sanitation program throughout the year and a thorough year-end clean up.
Clean and disinfest all interior greenhouse surfaces and equipment including tools, hoses, walkways, carts, totesT

249


-------
troughs, tanks and water supply lines. Use sterile propagating media. Remove dying plants by placing them
directly into plastic bags for disposal away from the greenhouse.

Irrigation water: Untreated water from rivers or streams poses great risk for Pythium introduction, while treated,
municipal water is considered safe from Pythium. Water storage and nutrient tanks need to be disinfected
periodically and covered to prevent Pythium contamination.

Nutrient Solution: Generally, greenhouse vegetables are raised on rockwool in plastic sleeves or bags containing
rooting medium (i.e. rockwool slabs, sawdust or coconut fibre) through which water and nutrient solution are
circulated. Since Pythium and other pathogens can build up in nutrient solution, periodically disinfest recirculating
nutrient solution using physical, biological or chemical methods (Marchuk, 2006).

Filtration methods:

Physical - slow sand filtration, ultrafiltration (membrane filters), micro-pore filtration (high pressure, rapid flow
membrane or sediment filters), heat pasteurization (95-97°C for 30 seconds or 85°C for 3 minutes), UV radiation,
sonic energy, magnetism, aeration (i.e. oxygenation), ozonation, etc.

Biological - biofiltration (slow sand or lava rock), water retention ponds.

Chemical: chlorine, chlorine dioxide, copper, hydrogen peroxide, electrochemical, soaps (wetting agents), iodine,
etc.

Resistant varieties: Although there are no resistant vegetable varieties, some vigorous varieties may have some
tolerance to Pythium. Contact your local seed/transplant agent for further information on Pythium tolerant varieties.

Seedlings & Transplants: Transplant in the morning or late afternoon/evening to avoid stress from high day time
temperatures. Allow for good air circulation around seedlings by proper plant spacing and good aeration of
irrigation water and re-circulating nutrient solution. Use healthy transplants and handle them carefully to avoid
wounding plants and roots and practice good sanitation when transplanting; do not let them dry when setting out.
Water seedlings in the morning so that plants are not wet overnight.

Plant growing conditions: Ensure that transplants have the proper root zone temperature and adequate moisture
when moved into the greenhouse. The growing media must be well drained as saturated bags with low oxygen
levels can predispose transplants to Pythium diseases.

Use warm, aerated irrigation water (18-22°C). Avoid low light levels, low pH, high salts and warm growing
conditions (above 28°C) which favour Pythium. In greenhouse cucumbers, the nutrient solution should be
delivered at pH 5.0 for approximately 5 weeks followed by adjusting the pH to a 5.8-6.2 regime for one week. (Tu,

250


-------
2004).

Target rock wool block wetness at 70-75% between watering.

Use white/colourless drip lines instead of black or place drip lines on the shaded side of the grow bags.

Disease monitoring: Plants must be monitored for any signs of Pythium diseases throughout the cropping cycle.
Remove and destroy severely infected plants and replant in new growing bags. Infected plant materials, including
grow bags, must be safely disposed away from the greenhouse by deep-burying, incinerating or composting.
Control fungus gnats (Eiradysia impatiens) and shore flies {Scatella stagnalis) which spread Pythium.

Biological and Chemical Control

Prevent Pythium diseases by practicing integrated disease management strategies based on cultural and
biological controls. Use fungicides as a last resort at the onset of disease.

Rotate registered fungicides with different chemical groups and strictly follow label directions to avoid resistance
development in Pythium.

Routinely monitor plants and evaluate the level of disease control if fungicides are used. Stop fungicide treatment
and get professional advice if fungicides fail.

Table 1. A summary of registered fungicides and label information (Please adhere to Product label
instructions when using each chemical)

Greenhouse cucumber, pepper & tomato

Mycoatop

propamocarb

Stmptomyces
Strain K61

Gllocladium

eatemlatum

28

preventative,
locally-
systemic

biological

non- systemic

12
hrs

NA

2 days for
cucumber 1
day for tomato
& pepper

0 clays

biological

suppressive

4 hrs

0 days

use preventative ly; maximum 2
applications per crop cycle after
lereafter 7-10 days
interval

use preventstivety: apply to growing
medium soon after transplanting,
thereafter every 3-6 weeks interval:
store unopened product In a cool
f<3°C), dry place.

use preventative^; apply to growing
medium soon after transplanting.

every 3-6 weeks interval;

251


-------


| |

j
|
|

store unopened product in a cool

(<4°C), dry place

RootShield
WP

Trichoderma

harzianum Rial,
strain KRL-AG2

biological

suppressive

|

:

4 hrs | 0 days

use preventative^; apply to growing
medium soon after transplanting,
repeat thereafter; store unopened
product in a cool (2-5°C). dry place

Greenhouse cucumber

Ridomil Gold
480EC or

480SL

metalaxyl-M, S
isomers

4

preventative.

systemic

12

\ 21 days

hrs |

use preventative^; one application
per crop cycle; apply as drench
immediately after transplanting

1REI - re-entry interval
ZPHI - pre-harvest interval
NA -Information is not available

For further information

1.	Chertf, M. et.al. 1994. Defense responses induced by soluble silicon in cucumber roots infected by Pythium
spp. Phytopathology 84: 236-242.

2.	Compendium of pepper diseases. 2003. K Pemezny, et. al. editors. The American Phytopathologies!
Society. httoi//www.apsnet.orq/apsstore/shopapspress/Paaes/43003.aspx

3.	Diseases and pests of vegetable crops in Canada. 1994. R. Howard et. al. editors. The Canadian
Phytopathological Society and the Entomological Society of Canada, http://ohvtopath.ca/dpvcc.html

4.	Growing greenhouse peppers in British Columbia. A production guide for commercial growers. 2005. BC
Greenhouse Growers' Association and B.C. Ministry of Agriculture, www.bcareenhouse.ca/publications.htm

5.	Growing greenhouse vegetables. 2005. Ontario Ministry of Agriculture, Food and Rural Affairs. Publication
order #371, Agdex #290. http://www.omafra.qov.on.ca/enqlish/products/newpubs.html or

products @omaf.qov.on.ca

6.	Jarvis, W.R. 1992. Managing diseases in greenhouse crops. American Phytopathological Society.
http://www.apsnet.orq/apsstore/shopapspress/Paqes/41221 .aspx

7.	Marchuk, R. 2006. Treatments for greenhouse recirculation water. Proceedings, 48th Annual Horticulture
Growers Short Course, 2006. Lower Mainland Horticultural Improvement Association, Pages 3-8.

8.	Pesticide label information for Canada: http://pr-rp.hc-sc.qc.ca/ls-re/index-enq.php

9.	Tu, J. C. 2004. An integrated control measure for Pythium root rot of hydroponically grown greenhouse
cucumbers. Acta Horticulturae 644: 571-574.

10.	Zamir, P.K. and R. Yip. 2003. Biological control of damping off and root rot caused by Pythium

252


-------
aphanidermatum on greenhouse cucumbers. Can. J. Plant Pathol. 25: 411-417.

Updated by:

Dr. Siva Sabaratnam

Plant Pathologist

Abbotsford Agriculture Centre

British Columbia Ministry of Agriculture

Iris Bitterlich

BC Greenhouse Growers' Association
May 2012

253


-------
Reference 17

Footnote; 52

254


-------
http7/onvegetables.com/2011/05/09/wliite-rust_in_spinach/

Information for commercial vegetable production in Ontario
White Rust in Spinach

May 9, 2011 by Janice LeBoeuf

Marion Paibomesai, Vegetable Crops Specialist, OMAFRA
Michael Celetti, Plant Pathology Program Lead, OMAFRA

White rust (Albugo occidentalis) is a major fungal disease of spinach in the United States that occurs
sporadically on spinach grown in Ontario, but when it does appear it has the potential to cause economic
damage by making the spinach unmarketable. Symptoms of the disease first appear as yellow spots on
the upper side of the leaf similar to downy mildew. However when the leaf is flipped over to expose the
underside of the leaf, a cluster of white pustules are observed instead of a mat of grey or purplish downy
growth as seen in downy mildew. Ideal conditions for white rust infection are wet and cool (16-21°C)
especially when warm days are followed by cool nights with the chance of dew. This disease frequently
shows up in Ontario spinach crops during August but can occur any time.

Management practices for white rust are similar to the practices used for downy mildew. There are some
varieties (i.e. Regal, Samish, etc.) that are tolerant to white rust. Avoid planting fall crops in or adjacent
to fields where an infected spring crop was grown and practice a 3-year crop rotation. Serenade ASO
(Bacillus subtilis) is registered for suppression of white rust on spinach in Ontario; however, other
products that are used to control downy mildew may also have activity on white rust. Please follow the
label for precautions and directions of use.

White rust on spinach leaf

255


-------
Reference 18

Footnote: 55

256


-------
C B. Skotland and Oennis A. Johnson

irrigated Agriculture Research and Extension Center

Washington State University, Prosser

Control of Downy Mildew of Hops

The hop plant (Humutus lupuhts I..) is

a perennial with clockwise twining vine
(bine) that dies hack to the ground each
year. The male and female flowers are
borne on separate plants. The papery
bracts and bracteoies of mature hop
cones (hg, I) are used almost exclusively
to flavor fermented malt beverages.

Hop downy mildew, caused by
Pseudopenntoxpora hitntuli (Miyubc &
Takah.l G. W, Wilson, is a major disease
in many hop-growing areas of the world.
It was first reported on wild hops in
Japan in 1905 and in Wisconsin in 1909
(12S. It wax found in England in 1920and
? years later had spread throughout the
hop-growing areas of Europe (12). Hop
dtrnnv mildew was reported in New York
State and western Washington's Puyallup
Valley in 1928. trt western Oregon in 1930,
in California in 1934, and in the Yakima
Valley of south central Washington in
1937, So tar. the disease has not been
found tn Australia. Tasmania, New
Zealand, or South Africa.

Downy mildew was a factor in the
decline and loss of hap production in
New York, Wisconsin, and the coastal
areas of California. and in occurrence in
the high-rainfall areas of western Oregon
and Washington led to the demise ol the
eultivars Early Cluster and I.ate Cluster
in those areas. In Oregon, the industry
survived by growing the more resistant
cultivar Fuggle, The susceptible Clustet
eultivars were shifted to the arid regions
of the Sacramento Valley ot California
and the Yakima and Boise valleys of the
Pacific Northwest. In 1982. of the
United States hop acreage was concen-
trated in the Yakima Valley (12.150 ha).
Boise Valley (1,518 ha), and Sacramento
Valley (199 hat. Approximately 3,007 ha
of hop are grown annually tn the
Willamette Valley of Oregon, where
environmental conditions in the spring
are conducive to mildew epidemics..

Downy mildew is a constant threat its
the European hop-growing areas and Is
controlled by use ol resistant eultivars.

The pubtical.oi costs of this arttcie were defrayed m put!
by page cnargs saymtnl This article must	fess

hereby marked "eritmiaameni" in «Mordiinc«s with IS
USC, 51734 solely to indicate this tact

'¦1963 American Phytopathologicai Society

rigid sanitation practices, and chemicals;
fungicides are often applied 8- 16 times in
England. Yugoslavia, and Germany {121
Epidemics occur even in the arid regions
of California. Idaho, and Washington. In
the Yakima Valley, the potential for an
epidemic exists every vcar because of the
extremely susceptible host and the
pathogen's method of overwintering,
with a serious epidemic occurring I year
out ol 3 (6).

Symptoms and Disease Cycle

The pathogen overwinters as mycelium
in infected buds and infected crowns, and
the mycelium spreads into developing
buds and shoots (1,2.13). The role of
oospores is not well understood, but in
New York (7) they were considered
important it! the overwintering ol the
pathogen. Oospores can be readily found
in inlected hop tissue in most ot the hop-
growmgareas of the world (1.7.10). In the
arid areas of California, Idaho, and
Washington, oospores are rare except in
infected cones, where considerable
numbers may be found. In the Yakima
Valley, infected cones are rare even in
mildew years because the dt), hot
summer weather prevents spread and
inlected tissue rapidly becomes necrotic.
In the spring, infected and healthy shoots
may be growing from the .same crown,
Miiny infected crowns have only healthy
shoots, while othcis have one to many
infected shoots (Fig, 21. I hese infected
shoots, with short internodesand vcllow-
green leaves. that cup downward (Fig. 3).
are called basal spikes and are the source
of the primary inoculum. I he Cluster
eultivars are particularly susceptible to
crown infection. Often, the crown is
killed or so weakened that many shoots
die before harvest.

Control Measures

Resistance. Ttie first hop eultivars
resistant to downy mildew were released
in Germany in 1962 (10). but the brewing
industrv is reluctant to accept new
eultivars. A cultivar accepted by the
industry in one area may be rejected bs
the industry when grown in another area.
Apparently, the environment affects the
organoleptic properties ot a cultivar in

some indefinable manner when the hop
cones are used directly in the brewing
process. The mildew-resistant eultivars
being grown in Europe are primarily the
"extract*" type, ie, the bittering agents are
extracted from the hop cones and the
extract is used. Some of these eultivars
require only two or three fungicide sprays
in wet environments <12). In the United
States, 75(~j ol the hops planted in arid
areas ate the extremely susceptible
Cluster eultivars. Fhe remaining 25'" j are
the eultivars Bullion, Brewers Gold, and
Cascade, which are tolerant to crown and
foliage infection but require fungicide
sprays to control foliage infection in high-
rainfall areas.

Sanitation. Removing the source ol
primary infection effectively reduced the
severity of epidemics in 1962 (14), In
Idaho, weekly spike removal reduced
mildew infections by 75'i and enhanced
control by spraying. In Washington, only
9- I0r
-------
Fig. 1. Mature hop (Humulus lupulus)
cones.

Fig. 2. Shoots growing from hop crown
infected with downy mildew (Pseudo•
peronospora humull).

Fig. 3. Infected shoots (basal spikes) with short internodes and yellow-green leaves
cupping downward.

Fig. 4. Hop vines with bases sprayed with
dinoseb to eradicate infected shoots.

were pruned early. By the first week of
May. when weather favored infection,
hops pruned early had spikes and hops
pruned late did not.

Chemicals. The first recorded control
measures systematic removal of spikes
and spraying with Bordeaux mixture—

1184 Plant Oisease/Vol. 67 No. 11

were in Japan in 1905. Bordeaux mixture
and various copper spray materials are
effective but must be coupled with
sanitation practices.

Zineb has been the primary fungicide
for downy mildew control in recent years.
Because the ethylenebisdithiocarbamates
decompose to ethylene thiourea (8).
however, the brewing industry has
requested that such residue beeliminated.
Even though health hazards do not exist
(4), the industry is concerned about
possible adverse publicity. In England,
zineb cannot be used within a month of
harvest (12).

In Oregon, calcium cyanamide dusted
over the top of the crown before shoots
emerged reduced the development of
basal spikes and also destroyed hop
seedlings, which often are infected,
presumably the result of oospore
germination. Similar success was achieved
in England with Bordeaux mixture and
captan (2). Streptomycin sulfate reduced
secondary infection and enabled shoots
to recover from systemic infection in
Oregon and England but has not been

effective in Washington and California.

Metalaxyl has been used commercially
in Europeand under emergency exemption
registration during 1981-1983 in the
United States. The compound has been
effective in controlling downy mildew in
experimental plots and growers' yards
(5). The incidence of downy mildew
during 1980 and 1981 in Washington
ranged from 0 to 3<,7 (percentage of hills
with spikes) in replicated field plots and
yards treated with metalaxyl and from 25
to 80% in adjacent plots, yards, and
sections of yards not treated with
metalaxyl.

Fungal resistance to metalaxyl has
been reported and precautions are being
taken to delay the selection and increase
of resistant populations of P. hamuli, A
formulation of metalaxyl containing
copper oxychloride is used in Europe as a
foliar spray. For use in the United States,
the manufacturer has suggested applying
metalaxyl over the hop crowns before
shoots emerge. When applied as a soil
drench, metalaxyl is taken up by the hop
roots. This application method has
worked well in Oregon and during wet
springs in Washington. In 1982. however,
rainfall in Washington was sufficient for
several infection periods but not
adequate to carry the chemical into the
root zones, so control was not effective.

Metalaxyl's success in controlling hop
downy mildew has been outstanding in
Oregon but not in Washington. The
explanations for this could be that: I) in
Oregon, the cultivars are less prone to
crown infection and the chemical acts on
the oospores, whereas in Washington, the
systcmically infected shoots growing
from the infected crown are the source of
primary infection; 2) under the high-
rainfall conditions of Oregon, metalaxyl
is readily moved to the root system; 3)
Oregon cultivars have a more developed
root system than Washington cultivars;
and 4) Washington grows more of the
extremely susceptible Cluster cultivars.
In Washington, spraying the foliage with
metalaxyl shortly before or after training
has been more effective than spraying the
soil surface over the crown.

Disease prediction. Disease prediction
models have been developed to strate-
gically time fungicide applications in
England. Germany. Yugoslavia, and
Czechoslovakia (12). In general, these
models use environmental factors, such
as rain wetness duration, amount of
rainfall, and relative humidity, and some
include an inoculum variable to identify
infection periods. Models in England
(11.12) couple infection periods with the
time delay of the subsequent incubation
period so fungicide applications can be
scheduled to protect against a second
infection cycle. This does not prevent the
first infection period of the season,
however, which could be costly where
cultivars are very susceptible to crown
infection and when initial inoculum levels

258


-------
are high. The model has accurately
predicted infection periods and aided
disease control in England (11) but
missed infection periods in Washington
during the 1980 and 1981 epidemics,
probably because of the susceptibility of
the Cluster cultivars.

A Washington model has been
developed that schedules protective
fungicide sprays based on the amount of
initial inoculum of P. humuli and the
likelihood of weather conditions favorable
for infection. During the spring, the
National Oceanic and Atmosphere
Administration provides daily weather
forecasts. Levels of primary inoculum arc
determined by visually monitoring hop
yards for spikes and by monitoring
environmental conditions forsporulation
on spikes. Inoculum potential is
estimated from the number of spikes,
night temperatures, and relative humidity.
Nights with temperatures higher than 5 C
and relative humidity above 70% favor
sporulation, whereas cool nights can
delay sporangia production on spikes for
several weeks. Rainy periods with
temperatures above 8 C favor infection
when sporangia are present.

The Washington model has had limited
testing, but forecasts during the severe
downy mildew epidemics in 1980 and
1981 allowed adequate scheduling of
fungicide applications. Final disease
incidences were 25-80% in yards where
the forecasts were not followed and 0-3%
in yards where they were.

Integrating the Components

Hop downy mildew exemplifies the
interactions of the va rious components
host, pathogen, and environment—of the
disease triangle. Satisfactory control in
wet environments requires sanitation
practices, resistant cultivars, and timely
application of fungicides. In arid
environments, sanitation practices and
either resistant cuitivars or timely
application of fungicides are needed. The
cultivars grown in arid environments are
susceptible to crown infection, so
production losses are due to crown rot
and death and rarely to infected cones.
The cultivars grown in wet environments
are mostly resistant to crown infection,
and losses result from cone infection.

In wet environments, oospores are
often abundant in infected leaves, shoots,
and especially cones. In dry environments,
oospores are rarely found in infected leaf
and stem tissue because the tissue of the
very susceptible cultivars becomes
necrotic, particularly when temperatures
are over 30 C. The overwintering role of
oospores is unclear, but in wet environ-
ments where cultivars resistant to crown
infection are grown, the germinating
oospore may be an important source of
primary inoculum. In arid environments,
P. humuli perennates as mycelium in
crowns of susceptible cultivars, and
oospores are not a means of overwintering.

Control measures may reflect the
overwintering method: Chemicals have
been used in high-rainfall areas to prevent
the development of basal spikes (3) but
have not been consistently effective in
arid areas on the extremely susceptible
cultivars.

Literature Cited

1.	Bressman. E. N.,and Nichols. R. A. 1933.
Germination of the oospores of Pseudo-
peronospora humuli. Phytopathology
23:485-486.

2.	Coley-Smilh, J. R. 1965. Infection of hop
rootstocks by downy mildew Pseudo-
peronospora humuli (Miy. et Tak.)
Wilson and its control by early-season
dusts. Ann. Appl, Biol. 56:381-388.

3.	Coley-Smith, J, R. 1966. Early-season
control of hop downy mildew Pseudo-
peronospora humuli (Miy. et Tak.)
Wilson with streptomycin and protectant
fungicides in severely infected plantings.
Ann. Appl. Biol. 57:183-191.

4.	Gowers, D. S.. and Gordon, C. F, 1979.
Some public health aspects of the
manufacture and use of zinc and
manganese ethylenebisdithiocarbamate
fungicides. Annu. Congr. Plant Prot. Inst.
Poznan, Poland, 19th, 1979. 13 pp.

5.	Hunger, R. M., and Horner, C. E. 1982.
Control of hop downy mildew with
systemic fungicides. Plant Dis.
66:1157-1159.

6.	Johnson, D. A., Skotland. C. B., and
Alldredge, J. R. 1983. Weather factors
affecting downy mildew epidemics of hops
in the Yakima Valley of Washington.
Phytopathology 73:490-493,

7.	Magie. R. O. 1942. The epidemiology and
control of downy mildew on hops. Tech.
Bull. N.Y. State Agric. Exp. Stn. 267:1-48.

8.	Marshall, W. D. 1977. Thermal decom-
position of ethylenebisdithiocarbamate
fungicides to ethylenethiourca in aqueous
media. J. Agric. Food Chem. 25:357-361.

9.	Romanko. R. R. 1964, Control of hop
downy mildew by chemical desiccants.
Phytopathology 54:1439-1442.

10.	Romanko, R. R.,Ogawa,.l. M., Skotland.
C. B., Horner. C. E.. and Brooks, S. N
1964. Hop downy mildew—a symposium.
Mod. Brew. Age 66:45-52.

11.	Royle. D.J. 1979. Prediction ol hop down\
mildew to rationalize fungicide use. Pages
49-56 in: Department of Hop Research.
Wye College, Annual Report for 1978.

12.	Royle, D. J., and Kremheller, H. T. H.
1981. Downy mildew of the hop. Pages
395-419 in: The Downy Mildews. D. M.
Spencer, ed. Academic Press, New York.

13.	Skotland, C. B. Infection of hop crowns
and roots by Pseudoperonospora humuli
and its relation to crown and root rot and
overwintering of the pathogen. Phyto-
pathology 51:241-244.

14.	Skotland. C. B.. and Romanko, R. R.
1964. Life history of the hop downy
mildew fungus. Wash. Agric. Exp. Stn.
Circ. 433. 6 pp.

C. B. Skotland

Dr. Skotland is a plant pathologist with
Washington State University, stationed
at the Irrigated Agriculture Research
and Extension Center in Prosser. He
obtained his B.S. degree from Utah
State University and his Ph.D. degree
in 1953 from the University of Wisconsin.
He investigated diseases of soybeans
with the USDA at North Carolina State
University, Raleigh, and has been with
Washington State University since
1956. His research is on diseases of
hops and mint.

Dennis A. Johnson

Dr. Johnson is extension plant pathol-
ogist and assistant plant pathologist at
the Irrigated Agriculture Research and
Extension Center in Prosser. After
receiving his Ph.D. in plant pathology
from the University of Minnesota, he
was an assistant plant pathologist at
the Texas Agricultural Experiment
Station in Vernon. In 1980 he moved to
Prosser, where he specializes in
epidemiology and integrated pest
management of irrigated crops.

Plant Disease/November 198^9 1185


-------
Reference 19

Footnote; 56

260


-------
1STW CROPS 8c SOILS PROGRAM

EXTENSION

CULTIVATING HEALTHY COMMUNITIES

Managing Downy Mildew in Hops in the Northeast

Rosalie Madden, Crop and Soils Technician & Dr. Heather Darby, UVM Extension Agronomist

Find us on the web: www.uvm.edti/extension/cropsoil/hops

Downy mildew (Pseudoperonospora hiimuli, Miyabe and Takali., Wilson) is a significant issue in hops in
the Northeast. Both Humulits htpuhts and H. jctponicas act as a host to P.humuli, as do certain nettles
(Uritca spp.) (Johnson et al. 2009). P. humuli is closely related to the downy mildew that you can find on
familiar crops such as cucumbers and watermelons, but is not so closely related that the downy mildew
from your squashes will infect your hops and vice versa (Johnson et al. 2009). Downy mildew can cause
the complete loss of marketable hop yield, and even hill death in sensitive varieties (Johnson et al. 2009).
It is a very serious hindrance to successful hops production, but diligent integrated pest management
(IPM) can help reduce disease infection, and/or help control downy mildew once the disease has reached
your hopyard. The goal of IPM practices is to integrate a multipronged approach that includes
prevention, observation, and various intervention strategies to reduce or eliminate the use of pesticides,
while at the same time managing pests at an acceptable level. This article will provide some guidelines
and strategies on how to control downy mildew in a sustainable manner.

Disease Symptoms

One of the most critical steps in IPM is proper pest identification. Downy
mildew produces characteristic diseased shoots, called "spikes" (Figures
1, 2, 4). Spikes will be stunted with short internodes, and appear chlorotic
with yellow-green, down curling or cupping leaves (Johnson et al. 2009).
The leaves will often be brittle, and will dry up starting at the base of the
spike. In the right conditions, necrosis will eventually move to the tip of
the spike. When these spikes emerge out of the crown, they are called
primary basal spikes (Figure 1). On a primary spike you will see
symptoms on the shoot tissue from the ground up.

Secondary spikes are
diseased shoots that
appear from an infected
apical meristem. An
apical meristem is the
growing point on a
plant; in the case of
hops this can either be
a sideann or the top of
the growing plant (Figure 2). With a secondary spike,
the plant tissue below the infection remains normal in
appearance, and the spike itself will usually become
necrotic and desiccated in dry weather. Compared to a
primary spike, the internodes may not be as noticeably

Figure 1. Primary basal spike.
Note short internodes, yellowing,
down-curled leaves, and leaf
necrosis at the base.

! University of Vermont Extension, June 2012

261


-------
Figure 3. Downy mildew infecting the apical
meristem at the top of the plant. Note how bine is
falling off the string.

Spikes are fairly characteristic of this disease, and once you
see it, it is hard to mistake them for anything else.
However, be forewarned that frost damage can sometimes
cause symptoms
similar to downy

mildew
(chlorosis, and,
in new growth,
necrosis of the
leaves and shoot
tips). As a result
of a late frost,
shoots may be
stunted and
older leaves may
have a rough, silvery appearance (Mahaffee et al. 2009b)
(Figure 4). Recent weather patterns should be taken into
consideration when evaluating your hopyard early in the
spring. Plants will usually recover from frost damage.

Figure 4. Frosted hops, note stunted shoots
and rough, silvery leaves.

Downy mildew will cause localized leaf lesions to appear on the
underside of a leaf. Downy mildew lesions are usually delimited by
leaf veins, appearing angular and water soaked (Figure 5). These
lesions will become necrotic and light to dark brown. Sporangia (the
structure in which spores are produced) may form a mass on the
underside of the leaf or spike and appear as a purple-grey or black
growth (Johnson et al. 2009).

shortened on a secondary spike. Trained bines that become
infected will often be developmentally arrested, and the
bines will fall off the string (Figure 3) (Johnson et al. 2009).

Inflorescences that become infected are dark brown, shriveled and
dried up, and can fall off the plant. Cones become brown and
hardened and, with an early infection, will stop developing.
Depending on when the infection occurred, the cone can either be
completely dark brown, or only have a few discolored bracts, giving a
striped or variegated appearance (Johnson et al. 2009).

Depending on the cultivar, the appearance of infected crowns can
vary. Infected crowns can appear reddish-brown to black, or have
streaks in the white crown tissue next to the bark. (Be sure to not
confuse the reddish-brown tissue found in the center of healthy
crowns that you will find in some cultivars!) Depending on the
cultivar, infected crowns can be completely rotted, appear healthy, or

Figure 3. Localized leaf lesions on
surface of leaf (top) and underside of
leaf (bottom). Note how lesions are
delimited by leaf veins.

262


-------
anywhere in between (Johnson et al. 2009).

If you would like to confirm that downy mildew has infected your hop plants, you can submit a sample to
your local University Extension Plant Diagnostic Laboratory. Visit their website or call them for
specifications on how to prepare and submit a sample. A diagnosis will cost between $15 and $30,
depending on the lab. Contact your local Plant Diagnostic Lab by following the links below or contacting
your local Extension office.

Cornell University Plant Disease Diagnostic Clinic
334 Plant Science Building
Ithaca, NY 14853

UMass Plant Diagnostic Lab
101 University Drive, Suite A7
Amherst, MA 01002

University of Vermont Plant Diagnostic Clinic

201 Jeffords Building

63 Carrigan Drive

University of Vermont

Burlington, VT 05405

Downy Mildew Lifecycle

Understanding a pest's lifecycle is important when developing a management plan. In order for a disease
outbreak to occur there must be a "disease triangle", consisting of a susceptible host, a conducive
environment, and the pathogen.

Like most mildews, P. humuli will thrive in warm, moist environments. Sporangia are usually produced
when the average relative humidity is greater than 71%, and the nightly minimum temperature is greater
than 41°F. The number of hours with a relative humidity greater than 80% is the greatest predictor of a
downy mildew outbreak. Plant tissue needs to be moist for spores to germinate. For shoot infection to
occur, water needs to be sitting for three hours with temperatures ranging from 66° -73°F or for six hours
at temperatures of 46°-50°F. Leaf infection doesn't require as long of a wetness period, and can occur in
1.5-2 hours, optimally at 59°-84°F, but will occur at temperatures as low as 41°F when the leaf is wet for
greater than 24 hours. A general rule of thumb is that appreciable leaf and shoot infection will occur if it
is wet at moderate temperatures for four to eight hours (Johnson et al. 2009).

Downy mildew can live on infected leaves, shoots, and cones, and will usually overwinter in infected
dormant buds and crowns as intercellular mycelium. Mycelium that overwinters in the crown will spread
into developing buds during winter and early spring, which is why shoots are already infected when
dormancy breaks, resulting in primary basal spikes. However, infected crowns don't always yield basal
spikes; sometimes infected crowns will yield both healthy shoots and infected basal spikes, and
sometimes infected crowns will only yield healthy shoots (Johnson et al. 2009).

Sporangia are produced on the underside of leaves at night when the temperature and humidity are
favorable. These spores are released in mid-morning to early afternoon, especially in rainy conditions.

263


-------
Sporangia land and germinate, producing spores that enter the plant through open stomata. The spores
can infect leaves, bud stipules, apical meristems, and cones if the conditions are favorable. As discussed,
infected leaves will result in localized leaf spots (Figure 5), which produce secondary inoculum to further
infect more shoots, leaves, and cones. Leaf lesions usually desiccate quickly in dry weather and don't last
long. Apical meristem infections, however, become systemic, producing secondary spikes and more
sporangia. With an apical meristem or a secondary spike infection, the mycelium will progress down the
shoot tissue toward the crown during the growing season. If the mycelium reaches the crown, hill death
can result, either immediately or over time, depending on the variety. The infected plant will often die as
a result of reduced carbohydrate reserves caused by the disease (Johnson et al. 2009).

Strategies for Controlling Downy Mildew

The pathogen can appear in your yard through various means. Spores can be swept in on the wind,
brought in on diseased root stock, or through the grower accidently carrying it into his or her field on their
clothes after visiting another hop-growing friend. Planting disease-free hop plugs is one way to be certain
that you are not bringing disease into your hopyard. The Northeast Hop Alliance has started a program to
propagate disease-free stock for members. Various other commercial sources can be found for disease-
free stock as well. Scouting for disease should be conducted on a regular basis (weekly) to determine the
degree of infection as well as to evaluate if the pathogen is spreading further. In addition, monitoring the
weather conditions will help to determine if the environment is right for disease infection. Control
options can be both preventative and remediative in nature. A multifaceted approach should be used to
have the best success.

Cultural/Mechanical Control

Planting resistant cultivars is the first important step in preventing a serious outbreak of downy mildew
(Table 1). Cultivars vary in susceptibility to crown rot and to cone, leaf, and shoot infection, but no
cultivars are immune. Cascade, Fuggle, Perle, Tettnang, and Willamette all display moderate resistance
to downy mildew. Cluster, Galena, Hallertauer Mittelfruh, Hersbrucker Spalt, and Nugget are all
susceptible to foliar infection (Johnson et al. 2009). Bullion, Brewer's Gold, and Cascade are considered
by Skotland and Johnson (1983) to be tolerant to crown and foliage infection, while still requiring
fungicides to control foliage infection. Crown rot susceptibility varies among cultivars, with Cluster
being extremely susceptible, which is the reason that Cluster is usually not grown in high-rainfall areas
(Johnson et al. 2009).

Strict sanitation is another important step in reducing the incidence of downy mildew in your yard.
Heavily diseased plants should be completely removed early in the season. Primary basal spikes should
be eliminated, either mechanically or chemically (Johnson et al. 2009). Spring pruning is usually done in
the late winter or early spring. The goal is to remove buds, shoots, and the previous season's bines.
Various levels of aggressiveness are often employed to do this. Pruning removes all shoots prior to
training. Crowning removes the top 0.75-2 inches of the crown prior to bud break. Scratching scratches
the soil surface, removing buds from the top 0.75-2 inches (Beatson et al. 2009). Removing the source of

264


-------
Variety

Usage

Disease Susceptibility0

Powdery Downy Verticilliuni
Mildew Mildew Wilt

Brewers Gold

Bittering

S

MR

MR

Bullion

Bittering

S

MR

R

Cascade

Aroma

MR

MR

MR

Centennial

Bittering

MR

S

U

Chinook

Bittering

MS

MR

R

Columbia

Aroma

MS

MR

S

Comet

Bittering

R

S

R

Crystal

Aroma

R

s

R

East Kent Golding

Aroma

S

s

MR

First Gold

Bittering

R

s

MR

Fuggle

Aroma

MS

R

S

Galena

Bittering

S

s

R

Glacier

Aroma

S

s

U

Hall. GoJd

Aroma

MS

R

s

Hall. Magnum

Bittering

S

R

MR

Hall. Mrttelfriih

Aroma

MS

S

S

Hall. Tradition

Aroma

MR

R

MR

Horizon

Bittering

MS

s

MR

Late Cluster

Aroma

S

S

R

Liberty

Aroma

MR

MR

U

Ml Hood

Aroma

MS

S

s

Newport

Bittering

R

R

u

Northern Brewer

Bittering

S

S

R

Nugget

Bittering

R

s

S

Olympic

Bittering

S

MS

R

Perte

Aroma

S

R

MR

Pioneer

Bittering

MR

MR

U

Saazer

Aroma

S

MS

S

Saazer 36

Aroma

S

MS

s

S palter

Aroma

S

R

MR

Sterling

Aroma

MS

MR

U

Teamaker

Aroma

MR

MR

s

Tettnanger

Aroma

MS

MS

S

Tolhurst

Aroma

S

S

U

U.S. Tettnanger

Aroma

MS

MS

S

Vanguard

Aroma

S

S

U

Willamette

Aroma

MS

MR

S

3 Disease susceptibility ratings are based on greenhouse and field observations in experimental
pilots and commercial yards in the Pacific Northwest as of 2009. Disease reactions may vary
depending on the strain of the pathogen present in some locations, environmental conditions,
and other factors, and should be considered approximate. S = susceptible; MS = moderately
susceptible; MR = moderately resistant; R = resistant; U= unknown

Table 1. Disease susceptibility and chemical characteristics of major hop
varieties. Reproduced from Field Guide for Integrated Pest Management
in Hops, a Cooperative Publication Produced by Oregon State University,
University of Idaho, U.S. Department of Agriculture - Agricultural
Research Service, and Washington State University, 2009.

primary infection can effectively
reduce the severity of the epidemic
(Skotland and Johnson 1983).
Skotland and Johnson (1983) advise
removing basal spikes weekly as it
reduces mildew infection by 75%,
and enhances the efficacy of spray
controls. In Washington, only 9-
10% of hills where spikes were
removed weekly had spikes at the
end of May. Where basal spikes
were not removed with the same
tenacity, 21-33% of hills displayed
signs of infection (Skotland and
Johnson 1983). Another option is
to prune later in the season, which
can reduce the severity of an
infection, particularly in areas with
shorter growing seasons. However,
if pruning is done too late in the
season, it will reduce yields
(Johnson et al. 2009), and some
argue that it may not be overly
effective in a damper climate
(Skotland and Johnson 1983).
Beatson et al. (2009) state that
pruning timing is cultivar-specific,
as it affects the training timing,
which in turn impacts yield.
Growers will often hill up around
the crown in mid-season as it
encourages the development of
roots and rhizomes near the top of
the crown. This helps to suppress
downy mildew in the current season
since the diseased shoots next to the
crown are buried (Beatson et al.
2009).

265


-------
After training, bines should be stripped.

Stripping removes the superfluous growth of
leaves and laterals from the lower five feet of the
trained bine (Beatson et al. 2009). Stripping
reduces inoculum density, and limits the
disease's spread into the upper canopy (Beatson
et al. 2009; Johnson et al. 2009). Stripping also
reduces the humidity around the base of the plant
by increasing airflow. Stripping can be done
either manually or chemically (Beatson et al.

2009). A desiccant spray can be used to
simultaneously take out basal spikes and strip,
but bines must be trained and at least seven feet
tall before a chemical desiccant can be used
without hurting the crop, and at this point it is
often too late to prevent serious infection
(Skotland and Johnson 1983). The date and
frequency of stripping can have a significant
effect on the carbohydrate reserves in the plant's root system. When you are stripping, it is important to
think of what will happen three months down the road at harvest. When the bine is harvested, there needs
to be enough leaf tissue left in the field so that the plant can continue to photosynthesize and accumulate
carbohydrates before winter dormancy. The deleterious effects of excessive stripping can be more severe
in early-maturing varieties, or plants that are already weakened by soil-borne disease (Beatson et al.
2009).

The success of your sanitation practices depends on your thoroughness, and can help delay an epidemic.
Aside from pruning and stripping, there are other practices that are critical to disease management, such
as avoiding excessive nitrogen fertilization. Using overhead irrigation should also be avoided, as it
increases leaf wetness. In cases with high disease incidence, an early harvest can be a tool to reduce cone
infection (Beatson et al. 2009; Johnson et al. 2009).

Chemical Control

When the weather conditions are favorable for downy mildew, spraying preventatively is key (Johnson et
al. 2009). Disease prediction models exist for downy mildew and hops in the Pacific Northwest and in
Europe. There are currently no disease prediction models for hops in the Northeast, but the Network for
Environment and Weather Applications has grape forecasting models in our region for grape downy
mildew, which will give you an idea of what to expect. Use four judgment in evaluating weather patterns
to determine when inoculum levels might be high. Based on the temperature and weather, it may not be
necessary to spray in the early spring if it is cool, below 41°F, or if there is low relative humidity.
However, low temperatures don't prevent spoliation for extended periods. Rainy weather will help
liberate the sporangia from spikes (Johnson and Skotland 1985), and it is still very important to keep on
top of spike removal.

Figure 4. Hops that have been stripped to 5', and all
untrained shoots and basal spikes removed.

266


-------
When using a fungicide, be sure to read the fungicide label in its entirety! It is illegal to use a chemical
on a crop or on a pest for which it is not specifically labeled, and it can often do more harm than good.
Keep in mind that not all chemicals are legal in every state; be sure to check with your local Extension or
Agency of Agriculture. It is also important to remember that while a chemical may be legal and labeled
for use in a state there is no assurance that the material is effective against a particular pest on a particular
crop, even if it is on the label. Also be sure to adhere to pre-harvest intervals and use proper personal
protection equipment. Downy mildew can develop resistance to fungicides fairly rapidly; it is very
important to vary the mode of action of the fungicides that you use in your yard (Johnson et al. 2009).
Each class should only be used a few times per season, which is usually specified on the label. If the
label permits, it can be very beneficial to tank mix fungicides that have a high risk for resistance
development with fungicides that have a low risk (Mahaffee et al. 2009a). Be sure to read the label
carefully, as some mixtures are phytotoxic to some crops but not others. For example, using both oil and
copper products in an apple orchard will result in phytotoxicity, but will work fine with tomatoes. It is
always advisable to try out a new fungicide or tank mix on a few plants to evaluate a crop's reaction
before spraying the whole yard. Also note that there are some varietal differences in reactions to certain
pesticides. The burr is very susceptible to mechanical damage during pesticide applications, so if at all
possible, try to avoid spraying during burr development. Instead spray a product that is a very effective
protectant with a long residual just prior to flowering. Basal growth should also be removed just prior to
flowering to minimize the spread of disease (Mahaffee et al. 2009a).

See Table 2 for a list of approved fungicides on hops in MA, NY and VT for 2012. This list is not
exhaustive; please check with your local Extension or Agency of Agriculture.

267


-------
Table 2. Approved fungicides on hops in, MA, NY, and VT for 2012.

Trade Name

EPA Reg. No.

Active ingredient

Group

Protectant

Systemic

Curative

OMRI
approved

Target pest

Registered

Powdery
mildew

Downy
mildew

Mites

Aphids

Other

MA

NY

VT

Actinovate AG

73314-1

Streptomyces lydicus
WYEC108



X



X

Y

X

X









X

X

Badge SC

80289-3

copperoxychloride,
copper hydroxide



X









X







X

X

X

BasicCopper50W HB

42750-168

basic copper sulfate

Ml

X





Y



X









X



Biocover UL

34704-806

petroleum oil

NC









X



X





X

X



Bonide Liquid Copper Fungicide Concentrate

67702-2-4

liquid copper

M

X







X

X





X

X

X

X

Bonide Liquid Copper Fungicide Ready to Use

67702-1-4

liquid copper

M

X







X

X





X





X

Carbon Defense

84846-1

potassium silicate

M

X







X



X

X

X



X



Champ DP Dry Prill (Agtrol)

55146-57

copper hydroxide

M

X









X







X

X

X

Champ Formula 2 Flowable (Agtrol)

55146-64

copper hydroxide

M

X









X







X

X

X

Champ WG

55146-1

copper hydroxide

M

X





Y



X









X

X

Champion Wettable Powder (Agtrol)

55146-1

copper hydroxide

M

X









X









X

X

C-O-C-S WDG

34704-326

copper oxychloride, basic
coppersulfate

Ml

X









X







X

X

X

Cueva Fungicide Concentrate

67702-2-70051

copper octanoate



X





Y

X

X





X

X

X

X

Cuprofix Ultra 40 Disperss

4581-413-82695

basic copper sulfate

Ml

X









X









X



Cuprofix Ultra 40 Disperss

70506-201

basic copper sulfate

Ml

X









X







X

X

X

Drexel Damoil

19713-123

petroleum oil

NC









X



X





X

X

X

DuPont Kocide 101

352-681

copper hydroxide

M

X









X







X

X

X

DuPont Kocide 2000

352-656

copper hydroxide

M

X









X







X

X

X

DuPont Kocide 3000

352-662

copper hydroxide

M

X









X







X

X

X

DuPont Kocide 4.5LF

352-684

copper hydroxide

M

X









X







X

X

X

DuPont Kocide DF

352-688

copper hydroxide

M

X









X







X

X

X

Ecomate Armicarb "0"

5905-541

potassium bicarbonate

NC





X



X

X





X

X

X

X

Flint Fungicide

264-777

trifloxystrobin

11

X



X



X

X







X

X

X

Fosphite Fungicide

68573-2

phosphorous acid mono-
and di-potassium salts

33

X



X



X

X





X

X

X

X

Fungi-phite

83472-1

phosphorous acid mono-
and di-potassium salts

33

X



X





X









X

X

Glacial Spray Fluid

34704-849

white mineral oil



X





Y

X



X





X

X

X

J MS Stylet Oil

65564-1

paraffinicoil

NC









X



X





X

X

X

JMS Stylet Oil, Organic

65564-1

paraffinicoil

NC







Y

X



X





X

X

X

Kaligreen

11581-2

potassium bicarbonate

NC

X





Y

X









X



X

Kentan DF

80289-2

copper hydroxide

M

X









X







X

X

X

Kphite 7LP Systemic Fungicide Bactericide (Ag Label)

73806-1

phosphorous acid mono-
and di-potassium salts

33

X



X



X

X







X

X

X

Kumulus DF

51036-352-66330

sulfur

NC

X





Y

X









X

X

X

MilStop Broad Spectrum Foliar Fungicide

70870-1-68539

potassium bicarbonate

NC

X







X









X

X

X

Monsoon

34704-900

tebuconazole

3

X

X





X









X



X

Nordox 75 WG

48142-4

cuprous oxide



X





Y



X









X



Nu-Cop 3L

42750-75

copper hydroxide

M

X









X







X

X

X

Nu-Cop 50DF

45002-4

cupric hydroxide

M

X









X







X

X

X

Nu-Cop 50WP

45002-7

copper hydroxide

M

X





Y



X







X

X

X

Nu-Cop HB

42750-132

cupric hydroxide

M

X









X







X

X



Nutrol

70644-1

potassium dihydrogen
phosphate



X







X









X

X

X

Omni Oil 6E

5905-368

mineral oil



X







X



X





X

X

X

Omni Supreme Spray

5905-368

mineral oil



X







X



X





X

X

X

Prev-AM Ultra

72662-3

sodium tetraborohyd rate
decahydrate











X



X







X



Pristine Fungicide

7969-199

boscalid, pyraclostrobin

7,11

X







X

X







X

X

X

Procure 480SC

400-518

triflumizole

3

X



X



X

X







X

X

X

Purespray 10E

69526-5

petroleum oil

NC









X



X





X

X

X

Purespray Green

69526-9

petroleum oil

NC







Y

X



X





X

X

X

Quintec

62719-375

quinoxyfen

13

X







X









X

X

X

Rally 40WSP

62719-410

myclobutanil

3

X

X

X



X









X

X

X

Rampart

34704-924

phosphorous acid mono-
and di-potassium salts

33

X



X



X

X







X

X

X

Regalia

84059-3

extract of Reynoutria
sachalinenis



X





Y

X

X







X

X

X

Saf-T-Side

48813-1

petroleum oil

NC

?



?

Y

X



X

X

X

X

X



Serenade ASO

69592-12

QST713strain Bacillus
subtilis



X





Y

X









X

X

X

Serenade Max

69592-11

QST713 strain of dried
Bacillus subtilis



X





Y

X









X

X

X

Sil-Matrix

82100-1

potassium silicate

M

X







X



X

X

X



X



Sonata

69592-13

Bacilluspumilus strain QST
2808



X





Y

X

X







X

X

X

Tebuzol 3.6F

70506-114

tebuconazole

3

X

X





X









X

X

X

Trilogy

70051-2

clarified hydrophobic
extract of neem oil

NC

X





Y

X









X

X



268


-------
References

Beatson, R.A., S.T. Kenny, S.J. Pethybridge, D. H. Gent. 2009. Hop Production. In W. Mahaffee, S. J.
Pethybridge, & D. H. Gent (Eds.), Compendium of Hop Diseases and Pests (pp. 5-8). St. Paul,
Minnesota: The American Phytopathological Society.

Gent, D., J.D. Barbour, A.J. Dreves, D.G. James, R. Parker, D.B. Walsh, eds. 2009. Field Guide for
Integrated Pest Management in Hops. Washington Hop Commission.

Johnson, D.A. & C.B. Skotland (1985). Effects of Temperature and Relative Humidity on Sporangium
Production of Pseudoperonospora humuli on Hop. Ecology and Epidemiology, 75 (2), 127-129.

Johnson, D.A., B. Engelhard, and D.H. Gent. 2009. Downy Mildew. In W. Mahaffee, S. J. Pethybridge,
& D. H. Gent (Eds.), Compendium of Hop Diseases and Pests (pp. 18-22). St. Paul, Minnesota:
The American Phytopathological Society.

Mahaffee, W., B. Engelhard, D.H. Gent, & G.G. Grove. 2009a. Powdery Mildew. In W. Mahaffee, S. J.
Pethybridge, & D. H. Gent (Eds.), Compendium of Hop Diseases and Pests (pp. 25-31). St. Paul,
Minnesota: The American Phytopathological Society.

Mahaffee, W., S.J. Pethybridge, D.H. Gent. 2009b. Injuries Caused by Environmental Factors. In W.
Mahaffee, S. J. Pethybridge, & D. H. Gent (Eds.), Compendium of Hop Diseases and Pests (pp.
73-74). St. Paul, Minnesota: The American Phytopathological Society.

Skotland, C.B. and D.A. Johnson. Control of Downy Mildew of Hops. Plant Disease, 67, 1183-1185.

269


-------
Reference 20

Footnote: 57

270


-------
http://www.cals.uidaho.edu/pscs/Research/r_ent_hoppest_dowriyraildew.htm
Description and life history

Hop downy mildew is caused by the organism Pseudoperonospora humuli, a fungus related to the
causal agents of hop black root and potato late blight. Like the powdery mildew fungus, hop
downy mildew is an obligate parasite and can live and reproduce only in living host tissue.
Cultivated hop, Humulus lupulus is its only host. Even the closely related annual or Japanese hop,
H. japonicus, appears immune.

The fungus overwinters either as bud infections or as a systemically infected crown. In the spring,
infected shoots, called primary spikes, emerge from the crown. Primary spikes are stunted,
pale-green to yellow, upright, and brittle with downward cupped leaves.

Under cool, moist, conditions, the stem and lower leaf surfaces may bear masses of gray to black
spores. These spores (zoosporangia) detach in response to mechanical agitation, raindrop
splashes, and changes in relative humidity, and may be bome by the wind or by water droplets to
healthy hop tissues. In the presence of free water, zoosporangia germinate releasing zoospores
that swim until they reach a leaf pore (stomata), where they encyst and develop a germ tube that
grows within the leaf and initiates an infection. The infection process, from zoosporangia!
germination to infection of the internal leaf cells, requires 2 to 3 hours at 70F. Zoosprangia will die
within two days if environmental conditions do not favor germination.

Sporangia landing on buds may initiate systemic infection of axillary or terminal buds. These
infected buds may in turn produce secondary spikes, which look much like primary spikes but,
arise from healthy vines instead of infected crowns and usually are bome higher on the plant.
Secondary infections are uncommon in the normally hot, dry climate in southern Idaho.

Damage to Hop

Losses due to downy mildew occur at several points in the disease cycle. Crown infections can
result in crown rot and plant death. Bud infections do not cause plant death, but do contribute to
poor plant vigor. Vine infections reduce vine vigor and may spike the growing point necessitating
retraining and increasing labor costs. Flower and cone infections directly reduce marketable yield,
but are uncommon in the hop growing area of southern Idaho, (back to top)

271


-------
Downy Mildew Management

Downy mildew thrives in environments with moderate temperatures, high humidity, and frequent
precipitation. Whenever possible, resistant varieties should be planted in fields known to have
conditions favoring disease development. Cultural practices that increase air movement,
decreases relative humidity, and increases summer temperatures will also help control downy
mildew. When conditions favoring disease development prevail, cultural practices and plant
resistance may fail to provide adequate control. Under these conditions chemical fungicides are
available for downy mildew control.

272


-------
APPENDICES

Appendix 1: ISKBC Latest EPA Stamped Label (9/14/12) (EPA Reg. No. 71512-3)
Appendix 2: FMC Current Supplemental Label (EPA Reg. No. 71512-3-279)
Appendix 3: USDA NASS Information for Cyazofamid Labeled Crops

273


-------
Appendix 1

ISKBC Latest EPA Stamped Label {9/14/12) {EPA Reg. No, 71512-3)

274


-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL, SAFETY
AND POLLUTION PREVENTION

Mike Peplowski

ISK Biosciences Corporation	SEP 1 4 2012

7470 Auburn Rd, Suite A
Concord, OH 44077

Subject: Addition of New Uses to Ranman 400SC and Supplemental Labeling for use on Basil
EPA Registration No. 71512-3
Decision No. 456370
Submission Date: 10/11 /11

Dear Mr. Peplowski:

The master label referred to above, submitted under the Federal insecticide, Fungicide, and
Rodenticide Act, as amended, to add the following uses: bean, succulent; bean, succulent, shelled; leafy
greens, subgroup 4A; basil, fresh and dried leaves; vegetable, tuberous and corm, subgroup 1C; and
vegetable, fruiting, group 8-10. is acceptable.

The supplemental labeling referred to above, submitted under the Federal Insecticide, Fungicide,
and Rodenticide Act, as amended, with directions for use on Basil, is acceptable, provided you make the
following changes:

1.	At the top of the page, add the following statement, "This supplemental label expires on 9/12/15
and must not be used or distributed after this date.''

2.	Revise the marketing statement, '"For control of diseases on basil," to read, "For control of listed
diseases on basil."

3.	Revise the warranty section to be identical to the master label.

A stamped copy of the master and supplemental labeling is enclosed for your records. Please
submit one (1) final printed copy for the above mentioned master label before releasing the product for
shipment. If you have any questions, please contact Dominic Schuler at (703) 347-0260 or via email at
schuler.dominic@epa.gov.

Product Manager 22
Fungicide Branch
Registration Division (7504P)

(A)

275


-------
BIOSCIENCES	.

RANMAN® 400SC

toEpfSS&	Supplemental Labeling

SEP 1 4 2012 SUPPLEMENTAL DIRECTIONS FOR THE USE OF

Under sfee Fed®?afl lasse^M®,	,nn„„

B^iuu. ^ BoJattoWe	Ranman 400SC

o» anended, for eto	(EPA Reg. No. 71512-3)

regas4©?©<& wu&er EPA IR©$J» No#

^ 	 FOR CONTROL OF DISEASES ON BASIL

Directions for Use:

It is a violation of Federal law to use this product in a manner inconsistent with its labeling.

CROP: BASIL

DISEASE

RATE PER ACRE

Downy mildew Peroriospora belbahrii

2.75 to 3.0 fl oz (0.071 to 0.078 lb a.i./A)

APPLICATION DIRECTIONS

Resistance Management:

DO NOT apply mere than 9 applications of RANMAN per crop. Alternate sprays of
RANMAN 400SC with a fungicide with a different mode of action. DO NOT make more than three
consecutive applications of RANMAN 400SC followed by at least three applications of fungicides
having different modes of action before applying additional RANMAN 400SC.

Application Instructions:

For control of downy mildew on basil make the applications on a 7- to 10-day schedule beginning
when disease conditions are favorable for disease development. Use the lower rate and longest
interval as disease preventative sprays or when disease conditions are low. Increase to the highest
rate and shortest interval under moderate to heavy disease pressure. RANMAN 400SC can be
applied on basil grown in a greenhouse.

RANMAN 400SC should be tank-mixed with an organosilicone surfactant when the disease infection
is severe, or a non-ionic surfactant or a blend of an organosilicone and a non-ionic surfactant when
disease infection is moderate or light, at the manufacturer's label recommendations for water
volumes up to 60 gallons per acre. Normal water volumes are 50 to 75 gallons per acre.

RANMAN 400SC may be applied through sprinkler irrigation equipment. See calibration directions
following this section.

Restrictions:

DO NOT apply more than 27 fluid ounces (0.7 lb a.i.) per acre per crop growing season.
The Pre-Harvest Internal (PHI) for this crop is 0-day.

Crops on this label may be planted immediately after the last treatment. Do not plant other crops not
registered for this product within 30 days after the last application.			

NOTE: Follow ail applicable directions, restrictions, and precautions on the Ranman 400SC label.

NOTE: This labeling must be in the possession of the user at the time of pesticide application.

ISK Biosciences Corporation
7470 Auburn Rd., Suite A
Concord. Ohio 44057

WarTanly and Limitation of Damages; Seller warrants to those persons lawfully acquiring title to this product that at the lime of the first sale of this product by
seller that this product conformed to its chemical description and is reasonably fit for the purposes stated on the label when used in accordance with Seller's
directions under normal conditions of use. and Buyers and users of this product assume the risk of any use contrary to such directions. SELLER MAKES NO
OTHER EXPRESS OR IMPLIED WARRANTY, INCLUDING ANY OTHER EXPRESS OR IMPLIED WARRANTY OF FITNESS OR OF
MERCHANTABILITY, AND NO AGENT OF SELLER IS AUTHORIZED TO DO SO. In no event shall Seller's liability for any breach of warranty
exceed the purchase price of the material as to which a claim is made. Buyers and users of this product are responsible for all loss or damage from use or
handling of this product which results from conditions beyond the control of Seller, including, but not limited to, incompatibility with products unless otherwise
expressly provided in the Directions for Use of this product, weather conditions, cultural practices, moisture conditions or other environmental conditions
outside of the ranges that are generally recognized as being conducive to good agricultural and/or horticultural practices.

09/12

AG-SUP-2012-0L0


-------
FIRST AID

If on skin

•	Take off contaminated clothing.

•	Rinse skin immediately with plenty of soap and
water for 15-20 minutes.

•	Call a poison control center or doctor for treatment
advice.

If in eyes

•	Hold eye open and rinse slowly and gently with
water for 15-20 minutes.

•	Remove contact lenses, if present, after the first 5 !
minutes, then continue rinsing eye.

•	Call a poison control center or doctor for treatment
advice.

If swallowed

•	Call a poison control center or doctor immediately
for treatment advice.

•	Have person sip a glass of water if able to swallow.

•	Do not induce vomiting unless told to do so by the
poison control center or doctor.

•	Do not give anything by mouth to an unconscious
^^erson^

If inhaled

® Move person to fresh air.

•	If person is not breathing, call 911 or an ambulance,
then give artificial respiration, preferably by mouth-
to-mouth, if possible.

•	Call a poison control center or doctor for further
treatment advice.

Have the product container or label with you when calling a poison control
center or doctor, or going for treatment.

HOT LINE NUMBER

For 24-Hour Medical Emergency Assistance (Human or Animal)
Call 1-888-484-7546.

For Chemical Emergency, Spill, Leak, Fire or Accident, Call
CHEMTREC 1-800-424-9300.

GROUP 1 21 | FUNGICIDE 1

fSKBIOSCIENCES

RANMAN® 400SC
AGRICULTURAL FUNGICIDE

ACTIVE INGREDIENT: Cyazofamid*	34.5%

OTHER INGREDIENTS:	65.5%

Total.	 100.0%

*4-chloro-2-cyano-Af/V-dimethyl-5-(4-methylphenyl)-l//-imidazole-1 -
sulfonamide (CA)

Contains 3.33 pounds Cyazofamid Per Gallon (400 grams per liter)

KEEP OUT OF REACH OF CHILDREN

CAUTION

See side panel for additional precautionary statements.
Read entire label carefully and use only as directed.

ISK Biosciences Corporation

7470 Auburn Road, Suite A
Concord, Ohio 44077 U.S.A.

EPA Reg. No. 71512-3 EPA Est. No.

Active Ingredient Made in Germany
Formulated in France

Net Contents: 2.5 Gallons

S C C E PTED

SEP 1 4 2012

Sfefcj flfes FW*fh1I

Mmd -*—iritto J
to 2feo psaSSdsS®

¦9HS2 V'2>


-------
PRECAUTIONARY STATEMENTS

HAZARDS TO HUMANS AND DOMESTIC ANIMALS

CAUTION

Harmful if absorbed through skin. Avoid contact with skin, eyes or
clothing. Avoid breathing spray mist. DO NOT take internally.

Personal Protective Equipment (PPE)

Applicators and other handlers must wear long-sleeved shirt and long pants,
socks, shoes, and chemical icsisUiii gloves made of any waterproof
material.

Remove PPE immediately after handling this product. Wash the outside of
gloves before removing. As soon as possible, wash thoroughly and change
into clean clothing. Do not allow contact of contaminated clothing with
unprotected skin. Follow manufacturer's instructions for cleaning/
maintaining PPE. If no such instructions for washables, use detergent and
hot water. Keep and wash PPE separately from other laundry.

Engineering Control Statements

When handlers use closed systems, enclosed cabs, or aircraft in a manner
that meets the requirements listed in the Worker Protection Standard (WPS)
for agricultural pesticides [40 CI R 170.240 (d) (4-6)], the handler PPB
requirements may be reduced or modified as specified in the WPS.

IMPORTANT: When reduced PPB is worn because a closed system is being
used, handlers must be provided all PPE specified above for "applicators
and other handlers" and have such PPE immediately available for use in an
emergency, such as a spill or equipment break-down.

User Safety Recommendations

Users should:

*	Wash thoroughly with soap and water after handling and before eating,
drinking, chewing gum. or using tobacco,

*	Remove and wash contaminated clothing before reuse.	

ENVIRONMENTAL HAZARDS	

DO NOT' apply directly to water, to areas where surface water is present or
to intertidal areas below the mean high water mark. DO NOT contaminate
waters when disposing of equipment wash waters or rinsate.

AVOIDING SPRAY DRIFT A! ITtE APPLICATION SITE IS THE
RESPONSIBILITY OF THE APPLICATOR. The interaction of many
cquipment-and-weather-rclatcd factors determine the potential for spray

drift. The applicator is responsible for considering all these factors when
making decisions, Where states have more stringent regulations, they
must be observed,

STORAGE AND DISPOSAL

DC) NOT contaminate water, food or feed by storage or disposal. Open
dumping is prohibited,

PESTICIDE STORAGE: Store in original container, in a secured, dry
place separate from fertilizer, food, and feed.

PESTICIDE DISPOSAL: Pesticide wastes are toxic. Improper disposal
of excess pesticide, pesticide spray or rinsate is a violation of Federal law,
If these wastes cannot be disposed of by use according to label
instructions, contact your State Pesticide or Environmental Control
Agency or the Hazardous Waste representative at the nearest EPA
Regional Office for guidance,

CONTAINER DISPOSAL: Nonreftllabie container. DO NOT reuse or
refill (his container. Triple rinse container (or equivalent) promptly after
emptying. Triple rinse as follows: Empty the remaining contents into
application equipment or a mix tank and drain for 10 seconds after the
flow begins to drip. Fill the container '/< full with waler and recap. Shake
for 10 seconds. Pour rinsate into application equipment or a tnix tank or
store rinsate for later use or disposal- Drain for 10 seconds after the flow
begins to drip. Repeat this procedure two more times. Then offer for
recycling if available, or puncture and dispose of in a sanitary landfill, or
by incineration or, if allowed by state and local authorities, by burning. If
burned, stay out of smoke.

DIRECTIONS FOR USE

it is a violation of Federal law to use this product in a manner inconsistent
with its labeling,

FAILURE TO fOLLOW iilh USE DIRECTIONS AND
PR EC A I.-1 IONS Q\ F11IS LABEL MAY RESUE'I IN PLAN! INJURY
OR POOR DISEASE CONTR01 .

Do not use for disease control on fruiting vegetables (other than tomato
transplants) or cucurbit vegetables grown for fruit production in
greenhouses.

ROTATIONAL CROP RESTRICTIONS

Crops on this label may be- planted immediately after the last treatment. Do

278


-------
not plant other crops not registered for this product within 30 days after the
last application.

DO NOT apply this product in a way that will contact workers or other
persons, either directly or through drift. Only protected handlers may he in
the area during application. For any requirements specific to your State or
Tribe, consult the agency responsible for pesticide regulation.

AGRICULTURAL USE REQUIREMENTS	

Use ibis product only in accordance with its labeling and with the Worker
Protection Standard", 40 C'FR Part 170. This Standard contains
requirements for the protection of agricultural workers on farms, forests,
nurseries, and greenhouses and handlers of agricultural pesticides. If
contains requirements for training, decontamination, notification, and
emergency assistance. It also contains specific instructions and exceptions
pertaining to the statements on this label about personal protective
equipment (PPF,), and restricted-entry interval. The requirements in this
box only apply to uses of this product that are covered by the Worker
Protection Standard.

DO NOT enter or allow worker entry into treated areas during the restricted
entry interval (REI) of twelve (12) hours.

PPE required for early entry to the treated areas that is permitted under the
Worker Protection Standard and that involves contact with anything that
has been treated, such as plants, soil, or water, is: coveralls, chemical
resistant gloves made of any waterproof material, shoes plus socks and
protective eyewear.	 	 _		

GENERAL INFORMATION
MIXING AND SPRAYING

RANMAN -100SC can be used effectively in dilute or concentrate sprays.
Thorough, uniform coverage is essential for disease control.

MOTR: Slowly invert container several times to assure uniform mixture of
formulation before adding this product to the spray tank.

Dosage rates on this label indicate fluid ounces of RANMAN 4Q0SC per
acre, unless otherwise stated. Under conditions favorable for disease
development, the highest rate specified and shortest application interval

should be used. For best product performance in all applications utilizing
water volumes up to 60 gallons per acre, an organosilicone surfactant
should be added according to the manufacturer's label recommendations
in order to improve spray coverage when the disease infection is severe.
However, a non-ionic surfactant or a blend of an organosilicone and a
non-ionic surfactant may be used according to the manufacturer"s label
when disease infection is moderate or light. Do not use a surfactant in
applications to grapes or tomato greenhouse transplant production.

RAMMAN 190SC may he applied with a!! types of spray equipment
normally used for ground and aerial applications.

The required amount of RANMAN 400SC should be added slowly into
the spray tank during filling. With concentrate sprays, pre-mix the
required amount of RANMAN 400SC in a clean container and add to the
spray tank as it is being filled. Keep agitator running when tilling spray
tank and during spray operations. DO NOT allow spray mixture to stand
overnight or for prolonged periods. Prepare only the amount of spray
required I or immediate use. Spraying equipment should be thoroughly
cleaned immediately after the application.

Apply RANMAN 4O0SC in sufficient watci to obtain adequate coverage
of the foliage. Galionage to be used will vary with crop and amount of
plant growth. Spray volume will usually range from 20 to 100 gallons per
acre {200 to 1000 liters per hectare) for dilute sprays, and 5 to 10 gallons
per acre (50 to 100 liters per hectare) for concentrate ground and aerial
sprays. For aerial applications, apply RANMAN 400SC in a minimum of
5 gallons of water per acre. Application through sprinkler irrigation
systems is not recommended unless specific directions are given for a
crop. See application and calibration instruction below.

TANK MIX COMPATIBILITY

RANMAN 4D0SC is physically compatible (no nozzle or screen

blockage) with many products recommended for control of diseases and
insects on vegetable crops. Read and follow all manufacturer's label

recommendations for the tank mix companion product. It is the
applicator's responsibility to ensure that the companion product is EPA
approved for use on the intended crop. RANMAN 400SC is generally
compatible with other insecticides, fungicides, fertilizers and
micronutrient products provided sufficient free water is available for
dispersion of all the tank mix products. However, the physical
compatibility of RANMAN 400SC with tank mix partners must be

279


-------
evaluated before use. Conduct ajar test with intended tank-mix pesticides
prior to preparation of large volumes. Use the following procedure: 1)
Pour the recommended proportions of the products into a suitable
container of water, 2) Mix thoroughly and 3) Allow to stand 5 minutes. If
the combination remains mixed or can be re-mixed readily, it is
considered physically compatible. Any physical incompatibility in the jar
test indicates that RANMAN 400SC should not be used in the tank-mix.

RANMAN 400SC is physically compatible (no nozzle or screen
blockage) with the following list of products:

Product

Active Ingredient

Acrobat

dimethomorph

Applaud

buprofczin

BT (several)

Bacillus thuringiensis

Cbiorothalonit (several)

chlorothalonil

C'urzatc

cymoxanil

Decis

deltamethrin

E1)BC (several)

mancoztb

Guthion

azinphos-methyl

Headline /Cabrlo

pyraclostrobin

Karate

lambda-cyhalothrin

La innate

methomyl

Mineral oils



Monitor / Tamaron

mcthamidophos

Omega

fluazinam

Previcur

Propamocarb hydrochloride

Provado

imidacloprid

Quadris /Abound

azoxystrobiri

Thiodan

endosulfan

Trigai d

cyromazine

CROP RESPONSE

RANMAN 400SC is not phytotoxic to the crop or succeeding crops when
applied according to label instructions.

INTEGRATED PEST MANAGEMENT

RANMAN 400SC is an excellent disease control agent when used
according to label directions for control of several Oomycete fungi.
Although RANMAN 400SC lias limited systemic activity, it should Sic
utilized as a protectant fungicide and applied before I lie disease infects
the crop. Depending upon the level of disease pressure, good protection
of the crop against disease can be expected over a period of 7 to 10 days.
RANMAN 400SC is recommended for use as part of an Integrated Pest
Management (1PM) program, which may include the use of disease-
resistant crop varieties, cultural practices, crop rotation, biological disease
control agents, pest scouting and disease forecasting systems aimed at
preventing economic pest damage. Practices known to reduce disease
development should be followed. Consult your state cooperative
extension service or local agricultural authorities for additional IPM
strategies established in your area. RANMAN 400SC may be used in
State Agricultural Extension advisory (disease forecasting) programs that
recommend application timing based upon environmental factors that
favor disease development.

RESISTANCE MANAGEMENT

Some plant pathogens are known to develop resistance to products used
repeatedly for disease control. RANMAN 400SCs mode/target site of
action is complex III of fungal respiration: ubiquinone reductase, Qi site.
I RAC code 21. A disease management program thai includes alternation
or tank mixes between RANMAN 400SC and other labeled fungicides
that have a different mode of action and/or control pathogens not
controlled by RANMAN 400NC i> essential to prevent disease resistant
pathogens populations from developing. RANMAN 400SC should not
be utilized continuously nor tank mixed with fungicides that have shown
to have developed fungal resistance to the target disease.

Since pathogens differ in their potential to develop resistance to
fungicides, follow the directions outlined in the "Directions For Use"
section of this label for specific resistance management strategies for
each crop. Consult with your Federal or State Cooperative Extension

280


-------
Service representatives for guidance on the proper use of RANMAN	resistance. RAN MAN 400SC. is not cross-resistant with other classes of

400SC in programs that seek to minimize the occurrence of disease	fungicides that have different modes of action.

DIRECTIONS FOR USE

Crop

Diseases

Use Rati*
PI. Oz. Product
Per Acre
(lb. at/A)

instructions

Basil

Downy mildew

(I'eromspom

bclbahru)

2.75 to 3.0
(0.071 to 0.078)

Resistance Management:

DO NOT apply more than 9 applications of RANMAN 400SC per crop. Alternate sprays, of RANMAN
4005C with a fungicide with a different mode of action. DO MOT make more than three consecutive
applications of RANMAN 400SC followed by at least three applications of fungicides having different
modes of action before applying additional RANMAN 400SC.

Application Instructions:

For control of downy mildew on basil, make die applications on a 7- to 10-day schedule beginning when
disease conditions are favorable for disease development. Use the lower rate and longest interval as
disease preventative sprays or when disease conditions are low. Increase to the highest rate and shortest
interval under moderate to heavy disease pressure.

RANMAN 400SC can be applied on basil grown in a greenhouse,

RANMAN 400SC should be lank-mixed with an organosilicone surfactant when the disease infection is
severe, or a non-ionic surfactant or a blend of organosilicone and a non-ionic surfactant when disease
infection is moderate or light, at the manufacturer's label recommendation for water volumes up to 60
gallons per acre. Normal water volumes arc 50 to 75 gallons per acre.

RANMAN 4Q0SC may be applied through sprinkler irrigation equipment. See calibration directions
elsewhere on the label.

Restrictions;

DO NOT apply more than 27 fluid ounces (0.7 lb a.i.) per acre per crop growing season.

The Pre-Harvest Interval (PHI) for this crop is 0 days.

Crops on this label may be planted immediately after the last treatment. Do not plant other crops not
registered for this product within 30 days after the last application.









281


-------
Crop

BRASSK'A

(COLE) LEAFY
VEGETABLES:
CROP GROUP 5

Broccoli;

CSiinese broccoli
/. Product
Per Acre
(lb. ai/A)

Transplant Soil
Drench:

12.9 to 25.75
(0.333 to 0.665
per 100 gallons

Instructions

Downy mildew
(Penmospora
parasitica)

Soil
incorporation:

20/ A
(0.52)

Foliar:
2.75 / A
(0.072)

Resistance Management:

DO NOT apply more than six (1 soil - 5 foliar) applications of RANMAN 4008C per crop. Alternate
foliar sprays of RANMAN 40QSC with a fungicide with a different mode of action. DO NOT make
more than three consecutive applications of RANMAN 400SC followed by at least three applications ot
fungicides having different modes of action before applying additional RANMAN 400SC.

Application Instructions:

Transplant Soil Drench fur control of club root: Immediately after transplanting, make a single

application within the rate range listed arid apply 1.7 fluid ounces of solution per plant as transplant
water. Use the lowest rate for fields with low soil infestation and increase to the higher rates when fields
have a history of moderate to high soil infestation.

Soil Incorporation: Alternatively, if desired and for soil with low infiltration rates, apply 20 fl oz per
acre in a minimum bandwidth of 9 inches along the planting row and incorporate to a soil depth of 6 to 8
inches with a precision incorporator in the same operation. Apply in a water volume of at least 50
gallons per acre, fransplant the seedlings into the treated band. If planting into a bed, a broadcast
application can be made prior to forming the bed.

Foliar sprays for downy mildew: Make fungicide applications on a 7- to 10-day schedule beginning
when disease is first seen or weather and downy mildew disease pressure are expected to initiate a
disease epidemic. Use the longest interval for preventative applications or very low disease pressure.
Shorten the interval as disease pressure and/or fast crop development increases, down to the shortest

interval.

RANMAN 400SC should be tank-mixed with an organosilicone surfactant when the disease infection is
severe, or a non-ionic surfactant or a blend of organosilicone and a non-ionic surfactant when disease
infection is moderate or light, at the manufacturer's label recommendation for water volumes up to 60
gallons per acre. Normal water volumes are 30 to 60 gallons per acre.

RANMAN 4Q0SC may be applied through sprinkler irrigation equipment. See calibration directions
elsewhere on the label

Restrictions:

DO NOT apply more than 39.5 11 o/ per acre per crop growing season. 11 soil application at a maximum
of 25.75 fl. oz./A and 5 foliar applications at 2.75 fl. oz./A (13.75 fl. oz./A) per application]
The Pre-Harvest Interval (PHI) for these listed crops is 0 days.

Crops on this label may be planted immediately after the last treatment. Do not plant other crops not
registered for this product within 30 days after the last application.

282


-------
Crop

Diseases

Carrot

Cavity spot.

Root DiebacK.

Forking

(Pythium ultimum,

P. violae,
P sulcatum
P. iiiuyulm.
P. splendens)

Use Rate	|

Kl. Oz. Product	J

Per Acre	I
(lb. ai/A)

6

(0.156)

Instructions

Resistance Management:

DO NOT apply more than 5 sprays of Ranman 400SC per crop,
with a fungicide with a different mode of action.

Alternate sprays of Ranman 400SC

Application instruct Kins:

Pre-plant incorporated {broadcast or band}: Apply in sufficient water to obtain adequate coverage within
3 days of planting and mechanically till into the soil to a depth of at least 2 inches or incorporate with at
least 1/4 inch of water.

Surface applications (broadcast or band): Subsequent applications may be made beginning at 14 days
atler plant emergence anil continue on a 14-21 day schedule. Apply in sufficient water to obtain
adequate coverage with the applications directed to the base of the plant, Ranman 400SC should be
incorporated into the soil with to 1 inch of water. If irrigation is not immediately available after the
application, then the application should be made in sufficient water to allow penetration into the soil.

Ranman 40QSC may be applied via any overhead irrigation system. Follow directions outlined in the
Application and Calibration Techniques For Sprinkler irrigation section of the label. Ranman 400SC
should be applied during the last 2 hours of the irrigation cycle to allow for adequate soil penetration,

I or banded applications a 6 to 8 inch band is recommended (See formula to calculate amount required in

the band).

Calculate the amount of*Ranman 400SC needed for band treatments by the formula:

band width in inches	broadcast rate	amount needed

row spacing in inches	^	Pcr acrc	= Per acrc

field

Restrictions

DO NOT use more than J0 II o/ per growing season.

DO NOT use any adjuvant when applying to carrots.

DO NOT apply within 14 days of harvest.

Crops on this label may be planted immediately after the last treatment. Do not plant other crops not
registered for this product within 30 days after the last application.

283


-------
Crop

CUCURBIT
VEGETABLE:

CROP GROUP 9

Cantaloupe

Chayotc

Chinese-

waxgourd
Citron Melon
Cucumbers
Gherkin
Gourds
1 loneydew
melons
Momordica spp.
Muskmelon
Watermelon
Pumpkin
Squash
Zucchini

Diseases

Downy mildew
( Pk tuit >{>eronospr>ra
cube us is)

Use Rale
H. ()/.. Product

Per Acre
(lb. ai/A)

2.) to 2 75
(0.054 to 0 071)

Phytophthora bhght
(Phytophthora cdpxtci)

2.75
(0.0711

Instructions

KcsisUmce Management:

IX) NOT apply more than six sprays of RANMAN 400SC per crop. Alternate sprays of RAN MAN
400SC with a fungicide with a different mode of action. 110 NOT make more than three consecutive
applications of RANMAN 400SC followed by at least three applications of fungicides having different
modes of action before applying additional RANMAN 400 SC.

Application Instructions:

For Downy mildew control, make fungicide applications on a 7- to 10-day schedule beginning with
initial flowering or when disease conditions are favorable for disease development, but prior to disease
development. Use the low rate and long interval as disease preventative sprays or when disease
conditions are low. Increase to highest rate and shortest interval under moderate to heavy disease
pressure.

For Phytophthora blight control, apply RANMAN 400SC to the base of the plants at the time of
transplanting. Alternatively, RANMAN 400SC may be applied in transplant water at the time of
transplanting. Apply 2.75 fl oz per acre in the transplant water. It is recommended that the water
volume for (his initial application be at least 50 gallons per acre. Additional applications should be made
on a 7- lo 10-day schedule beginning when conditions arc favorable for disease development.

RANMAN 400SC should be tank-mixed with an organosilicone surfactant when the disease infection is
severe, or a non-ionic surfactant or a blend of an organosilicone and a non-ionic surfactant when disease
infection is moderate or light, at the manufacturer's label recommendations for water volumes up to 60
gallons per acre. Normal water volumes are 20 to 50 gallons per acre.

RANMAN 400SC may be applied through sprinkler irrigation equipment. See calibration directions
following this section.

Restrictions

DO NOT apply more than 16.5 fluid ounces (0.43 lb a.i.) per acre per crop growing season.
The Pre-Harvest Interval (PHI) for this crop group is 0-day.

Crops on this label may be planted immediately after the last treatment. Do not plant other crops not
registered for this product within 30 days after the last application.

284


-------
Crop

Diseases

Use Rate
Fl, O/. Product
Per Acre
(lb. ml A)

Instructions

GRAPES

East of the Rocky

Mountains

Downy mildew
(Phismopura viticula)

2.1 to 2.75
(0,054 to 0.071)

Resisfanct' Manaucmcnt:

DO NOT apply more than six sprays of RANMAN 400SC per crop. Alternate sprays of RANMAN
400SC with a fungicide with a different mode of action. DO NOT make more than three consecutive
applications of RANMAN 400SC followed by at least three applications of fungicides having different
modes of action before applying additional RANMAN 400SC.

Application Instructions:

For Downy mildew control, make fungicide applications on a 10- to 14-day schedule beginning when
warning systems forecast disease infection periods or when disease conditions are favorable for disease
development. Lsc the lowest rate and longest interval for preventative applications or very low disease
pressure, increasing the rate and shortening the interval as disease pressure and/or fast crop
development increases up io the maximum rate and shortest interval. Do not use any surfactant with
this application.

Application water volumes for ground applications should be at (cast 100 gallons per acre.

RANMAN 400SC may be applied via aerial application using a minimum of 5 gallons of water volume
per acre.

Restrictions

DO NO'I apply more than 16.5 fluid ounces (0,43 lb. Al) per acre per growing season.

The P re-Harvest Interval (Pi ll) for this cr days.

HOPS

1

Downy mildew
(I'seuduperomispora
himulil

2.1 to 2.75
(0.054 to 0.071)

Resistance Management:

DO NO I apply more than six applications of RANMAN 400SC per crop. Alternate foliar sprays of
RANMAN 400SC with a fungicide with a different mode of action. DO NOT make more than three
consecutive applications of RANMAN 400SC followed by at least three applications of fungicides
having different modes of action before applying additional RANMAN 400SC.

Application Instructions

For downy mildew control, make fungicide applications on a 7- to 10-day schedule beginning when
disease is first seen or weather and downy mildew disease pressure are expected to initiate a disease
epidemic. Use the lowest rate and longest interval for preventative applications or very low disease
pressure, increasing the rate and shortening the interval as disease pressure and/or fast crop
development increases up to the maximum rate and shortest interval. Use water spray volume of at least
100 gallons per acre.

Restrictions;'

DO NOT apply more than 16.5 fl oz per acre per crop growing season.

The Pre-Harvest Interval for this listed crop is 3 days.

Crops on this label may be planted immediately after the last treatment. Do not plant other crops not
registered for this product within 30 days after the last application.

285


-------
Oop

Leafy Greens;
Crop Subgroup

! 4A

A ma ninth
(leafy amaranth,
Chinese spinach,
i.impala);
A rupuhi
(Rorjueitc);
Chervil;
Edible-leaved
chrysanthemum
Garland
chrysanthemum
Corn salad;
Garden cress;
Upland cress
(yellow rocket,
winter cress);
Dandelion;

Dock (sorrel);
Endive
(escarole);
l ettuce (head
and leaf):

Orach; Parsley;
Garden
purslane;

Winter
purslane;
Radirchio (red
chicory);
Spinach;
New Zealand
spinach;

Vine spinach
(Malabar
spinach, Indian
spinach).

Diseases

White rust

{Albugo oct'hknhilis)

Use Rale
Fl. Oz, Product
Per Acre
(lb. ai'A)

2.75

(0.07!)

Downy mildew
(Uremia Utctiwue)

Pythium Damping-ofT
[Pythium spp.)

2.75
(0.071)

2,75
(0.071)

Instructions

Resistance Management:

DO NOT apply more lhan six applications of RANMAN 400SC per crop. Alternate sprays of
RAN MAN 400 SC with a fungicide with a different mode of action. DO NOT make more than three
consecutive applications of RANMAN 400SC followed by at least three applications of fungicides
having different modes of action before applying additional RANMAN 400SC,

Application Instructions

For white rust control, make fungicide applications on a 7- to 10-day schedule beginning when disease
is first seen or weather and white rust disease pressure are expected to initiate a disease epidemic. Use
the longest interval for preventative applications or very low disease pressure, shortening the interval as
disease pressure and/or fast crop development increases up to the shortest interval.

For downy mildew control, make fungicide applications on a 7- to 10-day schedule beginning when
disease first appears or when disease conditions are favorable for disease development. Use the longest
interval for disease preventative sprays or when disease conditions are low. Increase application
frequency to the shortest interval under moderate to heavy disease pressure.

For Pythium control, make the first application to the soil as a directed, post transplant or post planting
application. Make this application within 24 hours of transplanting or seeding. The directed application
should be made as a band 4 to 6 inches wide over the seed line or transplants. Direct the entire per-acre
rate into the band. Calculate the application rate using the row width. Then, irrigate within 24 hours of
the first application with one half (1/2) to one (I) inch of water to properly move the product into the
root /one, Alternatively, RANMAN 400SC may be applied in transplant water at the time of
transplanting. Do not use a surfactant with this soil drench application, ft is recommended that the
water volume for this initial application be at least 50 gallons per acre. Additional applications should
be made on a 7- to 10-day schedule beginning when conditions arc favorable for disease development.

RANMAN 400SC should be tank-mixed with an organosilieone surfactant when the disease infection is
severe, or a non-ionic surfactant or a blend of organosilieone and a non-ionic sut lactam when disease

infection is moderate or light, at the manufacturer's label recommendation for water volumes up to 60
gallons per acre. Normal water volumes are 30 to 60 gallons per acre.

RANMAN 400SC may be applied through sprinkler irrigation equipment. See calibration directions

elsewhere on the label.

Restrictions;

DO NOT apply more than 16.5 fluid ounces (0.43 lb a.i.) per acre per crop growing season.
The Pre-Harvest interval (PHI) for this crop group is 0 days.

Crops on this label may be planted immediately after the last treatment. Do not plant other crops not
registered for this product within 30 days after the last application.

286


-------
< top

Diseases

Succulent-

Cottony leak

podded and

(Pythium

Succulent-

aphanidermatum)

shelled Beans;

Pythium ultimum)

Cfcer



arietinum



(chickpea,



garbanzo



bean);



Lupinus spp.



(including



sweet lupine,

Downy mildew

white sweet

fl'bytophthora

lupine, white

phaseotii

lupine, and



grain lupine).



Phamofm



spp. (including

Pbytophthora blight

kidney bean,

(Phytophthora capsici)

lima bean,



tnung bean,



navy bean,



pinto bean,



snap bean,



and waxbean);



Vicia faba



(broad bean,



fava bean);



Vigna spp.



(including



asparagus



bean,



btackeyed pea



and cowpea).



I'se Rate
FL Oz. Product
Per Acre
(lb, ai/A)

2,75
(0.071)

Instructions

Resistance Management:

DC) NOT apply more than six applications of RAN M AN 400SC per crop. Alternate sprays of
RANMAN 400SC with a fungicide with a different mode of action. DO NOT make more than
three consecutive applications of RANMAN 4Q0SC followed by at least three applications of
fungicides having different modes of action before applying additional RANMAN 400SC.

Application In strut' tio ns

I or cottony leak control, make the initial application ;ii ful! bloom (I" pods) and repeal on a 7- to

14-day schedule. Use the longest interval for disease preventative sprays or when disuse
condition* are low. Increase application frequency to the shortest interval under moderate Jo
heavy disease pressure.

For control of downy mildew on lima beans, make the applications on a 7- to 10-day schedule
beginning when disease first appears or when disease conditions are favorable for disease
development. Use the longest interval for disease preventative sprays or when disease conditions
are low. Increase the application frequency to the shortest interval under moderate to heavy
disease pressure.

For Phvtophtiioru blight control, make she P' application at 100% bloom-pin pod development

and a 2°d application at late pin-small pod development and repeat every 7 days as needed to
maintain disea>e control.

RANMAN 400SC should be tank-mixed with an organostlicone surfactant when the disease
infection is severe, or a non-ionic surfactant or a blend of orcanosiliconc and a non-ionic
surfactant when disease infection is moderate or light, at the manufacturer's label
recommendation for water volumes up Hi 60 callons per acre. Normal water volumes are 20 to 60
gallons per acre.

RANMAN 400SC may be applied through sprinkler irrigation equipment. See calibration
directions elsewhere on the label.

Restrictions:

DO NOT apply more than 16.5 fluid ounces (0.43 ib a.i.) per acre per crop growing season.

DO NOT apply to cowpeas used for livestock feed.

The Pre-ilarvest Interval (PHI) for this crop group is 0 days.

Crops on this label may be planted immediately after the last treatment. Do not plant other crops
not registered for this product within 3# days after the last application.

287


-------
Crop

I iiIii-rou< and
Corm
Vegetables:

Crop Subgroup

1C

Arracacha;

arrowroot;

Chinese

artichoke;

Jerusalem

artichoke;

Edible carina;

Bitter cassava;

Sweet

Cassava;

Chayote (root);

Chufa;

Dasheen

(taro);

Ginger;

LeriHi;

Pidati);

Sweet potato;

Tanler;
Turmeric;
Yam bean;

True yarn

Diseases

Lale blight
(Phytophihara
infestans)

Taro Leaf Blight

(Phytophthora

colocaseasei

Use Rale
Fl, O/, Product
Per Acre

	Cb- »'/A>	

Pink Rot

(Phytophthora

erythroseptica)

Pythium R001& Crown
Rot (Pythium xppj

Foliar
1.4 to 2.75
(0.036 to 0.071;

At Planting;
0.42 fl. ozJ
1000 linear ft
("Equivalent to
6.1 fl. oz./A on
36"row spacing]
(0.158)

Lay-by /Hilling:
2.75 fl. oz. /A
(0.071)

Instructions

Kesist;)act* Management:

DC) NOT apply more than 10 sprays of RANMAN 400SC per crop. Alternate sprays of RANMAN
400SC with a fungicide with a different mode of action. DO NOT make more than three consecutive
applications of RANMAN 400SC followed by at least three applications of fungicides having different
modes of action before applying additional RANMAN 400SC.

For pink rot Pythium root and crown rot control, do not use RANMAN 400SC at reduced rates as
incomplete control may occur promoting potential for development of resistant strains. Rotate other
fungicides with a different mode of action or tank-mix these fungicides with RANMAN 400SC to reduce
the chance of resistance occurring. Development of resistance cannot be predicted. If a treatment of
RANMAN 4U0SC is not effective, a resistant strain of fungi may be present. Accordingly, neither
RANMAN 400SC nor other fungicides with a similar mode of action will effectively control the disease.
Consult your local State University for alternative recommendations.

Application Instructions:

For foliar blight control, make fungicide applications on a 7- to 10-day schedule beginning when warning
systems forecast disease infection periods, generally at row closure or when conditions, are favorable for
disease development. Use the low rate and longest interval for preventative applications or very low
disease pressure, increasing the rate and shortening the interval as disease pressure and/or fast crop
development increases up to the maximum rale and shortest interval.

For Late blight tuber rot control, make the last 2 to 3 applications prior to desiccation with RANMAN
400SC at 2.75 11 07. applied weekly.

For pink rot, Pythium root and crown rot control at planting, apply 0.42 fluid ounces of product per 1000
linear foot of row in-furrow at planting using a minimum of 5 gallons of water per acre. Apply
RANMAN 4(10SC using a 6 to 8 inch band directly over the seed pieces prior to furrow closure, A side
dressing of RANMAN 4008C applied at hilling may be necessary for additional control. Where
mefenoxam-resistant strains of Phytophthora etythrosepticu and Pythium species are not present, a full
rate of RANMAN 400SC can be tank-mixed with mel'cnoxam containing fungicides tor additional
control.

For additional control of Pink Rot, Pythium root and crown rot in combination with an at-planting, in-
lurrow. RANMAN 40I»SC application, apply RANMAN 400SC as a broadcast spray at 2.75 tluid ounces

in a minimum of 20 gallons of finished spray solution per acre at hilling. Additional applications may be
needed depending on susceptibility of the crop to pink, root and/or crown rot disease, environmental
conditions conducive to favor severe disease development, or fields located in long growing season areas,

etc.

Follow the guidelines for disease resistance management listed above.

RANMAN 400SC should be lank-mixed with an organosilicone surfactant when the disease infection is
severe, or a non-ionic surfactant or a blend of an organosilicone and a non-ionic surfactant when disease
infection is moderate or light, at the manufacturer's label recommendations for water volumes up to 60
gallons per acre. Normal water volumes are 20 to 50 gallons per acre.	

288


-------




I sc Rate



Crop

Diseases

Fl. Oz. Product

Instructions



Per Acre







fib. ai/A)



INmtlo





RANMAN 400SC may be applied through sprinkler irrigation equipment. See calibration directions

(con tin tied)





following this section.







Restrictions







DO NOT apply more than 27.5 fluid ounces (0.71 lb a.i.j per acre per growning season.







DO NOT apply within 7 days of harvest.







Crops on this label may be planted immediately after the last treatment. Do not plant other crops not







registered tor this product within 30 days after the last application.

FRUITING

Late blight

2.1 to 2.75

Resistance Management:

VEGETABLES:

(Phytophthora

(0.05.4 to 0.071)

DO NOT apply more than six sprays of RANMAN 400SC per crop. Alternate sprays of RANMAN

Crop Group

infest anx)



4005C with a fungicide with a different mode of action. DO NOT make more than three consecutive

8-1©) includes:



applications of RANMAN 400SC followed by at least three applications of fungicides having different





modes of action before applying additional RANMAN 40OSC.

African eggplant:







BushTomato:





Application Instructions:

Bell pepper;





For Late blight control, make fungicide applications on a 7- to 10-day schedule beginning when warning

Concern;





.systems forecast disease infection periods, generally at (lower initiation or when conditions are favorable

Currant tomato:





for disease development. Use the lowest rate and longest interval for preventative applications or very

Eggplant;





low disease pressure, increasing the rate and shortening the interval as disease pressure and/or fast crop

Garden





development increases up to the maximum rate and shortest interval.

huckleberry;





For Phytophthora blight control, apply RANMAN 400SC to the base of the plants at the time of

Goji berry;

Phytophthora blight

2.75(0.071)

Ground Cherry:

{Phytophthora capsivi)



transplanting. Alternatively, RANMAN 400SC may be applied in transplant water at the time of

Martynia;





transplanting. Apply 2.75 fl oz per acre in She transplant water. It is recommended that the water volume

Naranjilta:





for this initial application be at least 5SS gallons per acre. Additional applications should be made on a 7-

Okra;





to 10-day schedule beginning when conditions are favorable for disease development.

Pea eggplant;







Pepino;





RANMAN 400SC should be tank-mixed with an organosiiicone surfactant when the disease infection is

Nonbell pepper;





severe, or a non-ionic surfactant or a blend of an organosiiicone and a non-ionic surfactant when disease

Roselle.





infection is moderate or light, at the manufacturer's label recommendations for water volumes up to 60

Scarlet eggplant;





gallons per acre. Normal water volumes are .^0 to 60 gallons per acre

Sunberry;





RANMAN 400SC may be applied through sprinkler irrigation equipment. See calibration directions

Tomatillo;





Tomato;





following this section.

Tree tomato;







Cultivars,





Restrictions

varieties, and/or





DO NOT apply more than 16.5 fluid ounces (0.43 lb a,i.) per acre per crop growing season ,

hybrids of these.





The P re-Harvest Interval (Pill) for these listed crops is 0 day.





Crops on this label may be planted immediately after the last treatment. Do not plan! other crops not







registered for this product within 30 days after the last application.

289


-------
Tomato
Greenhouse

Transplants
(Soil Drench}

Pythtum Damping-off

(Pylhimn spp )

3 n 0//100

gallons water
(oTo7S Iba.i./ 100
gallons water)

Tomato Greenhouse Transplant f reduction: For control of damping-off caused by fythium spp. make
a single fungicide application to the seedling tray at the time of planting or at any time thereafter up until
I week before transplanting. Apply the fungicide solution as a drench lo thoroughly wet the growing
medium. This results in the use of approximately 1 pint of solution per square foot if the growing
medium is 4 inches deep. Do not use any surfactant with this drench application,

APPLICATION AND CALIBRATION TECHNIQUES FOR
SPRINKLER IRRIGATION

Apply this product only through center pivot, motorized lateral move,
traveling gun, solid set or portable (wheel move, side roll, end tow, or
band move) irrigation system(s). DO NOT apply this product through any
other type of irrigation system.

Crop injury, lack of effectiveness, or illegal pesticide residues in the crop
can result from non-uniform distribution of treated water.

If you have questions about calibration, you should contact State
Extension Service specialists, equipment manufacturers or other experts.

DO NOT apply RANMAN 400SC through irrigation systems connected to
a public water system. "Public water system" means a system for the
provision to the public of piped water for human consumption if" such
system has at least 15 service connections or regularly serves an average
of at least 25 individuals daily at least 60 days per year.

Controls for both irrigation water and pesticide injection systems must be
functionally interlocked, so as to automatically terminate pesticide
injection when the irrigation water pump motor stops. A person
knowledgeable of the irrigation system and responsible for its operation
shall be present so as to discontinue pesticide injection and make
necessary adjustments, should the need arise.

The irrigation water pipeline must be fitted with a functional, automatic,
quick-closing check valve to prevent I he flow of treated irrigation water
back toward the water source. The pipeline must also be fitted with a

vacuum relief valve and low-pressure drain, located between the irrigation
water pump and the cheek valve, to prevent back-siphoning of treated
irrigation water into the water source.

Always inject RANMAN 400SC into irrigation water after it
discharges from the irrigation pump and after it passes through the

check valve. Never inject pesticides into the intake line on the suction
side of the pump.

Pesticide injection equipment must be fitted with a functional, normally
closed, solenoid-operated valve located on the intake side of the injection
pump. Interlock this valve to the power system, so as to prevent fluid
from being withdrawn from the chemical supply tank when the irrigation
system is either automatically or manually turned off.

The pesticide injection pipeline must contain a functional, automatic,
quick-closing check valve to prevent the flow of fluid back toward the
injection pump. The irrigation line or water pump must include a
functional pressure switch that will stop the water pump motor when the
water pressure decreases to the point where pesticide distribution is
adversely affected.

Spray mixture in the chemical supply tank must be agitated at all times,
otherwise settling and uneven application may occur. DO NOT apply
when wind speed favors drift beyond the area intended for treatment.

RANMAN 400SC may be used through Iwo basic types of sprinkler
irrigation systems as outlined in Sections A and B below. Determine
which type of system is in place, then refer to the appropriate directions
provided for each type.

A, Center Pivot, Motorized Lateral Move and Traveling Gun
Irrigation Equipment

For injection of pesticides, these continuously moving systems must use a
positive displacement injection pump of either diaphragm or piston type,
constructed of materials that are compatible with pesticides and capable
of being fitted with a system interlock and capable of injection at
pressures approximately 2-3 times those encountered within the irrigation
water line. Venturi applicator units cannot be used on these systems.

290


-------
Thoroughly mix recommended amount of this product for acreage to be
covered into the same amount of water used during calibration and inject
into system continuously for one revolution or run. Mixture in the
chemical supply tank must be continuously agitated during the injection
run. Shut off injection equipment after one revolution or run, but
continue to operate irrigation system until this product has been cleared
from the last sprinkler head.

B. Solid Set and Portable (Wheel Move, Side Moll, End Tow, or
Hand Move) Irrigation Equipment

With stationary systems, an effectively designed in-line venturi applicator
unit is preferred which is constructed of materials that are compatible with
pesticides; however, a positive-displacement pump can also be used.

Determine acreage covered by sprinkler. Fill tank of injection equipment
with water and adjust flow to use contents over a 30 to 45 minute period.
Mix desired amount of RANMAN 400SC for acreage to be covered with
water so that the total mixture of this product plus water in the injection
tank is equal to the quantity of water used during calibration.

Agitation is recommended. RANMAN 400SC can be injected at the
beginning or end of the irrigation cycle or as a separate application. Stop
injection equipment after treatment is completed and continue to operate
irrigation system until this product has been cleared from last spi inkier
head.

ISK Biosciences Corporation
7470 Auburn Road. Suite A

Concord, Ohio 44077 U.S.A.

WARRANTY AND LIMITATION OF DAMAGES

Seller warrants to those persons lawfully acquiring title to this product
that at the time of first sale of this product by Seller that this product
conformed to its chemical description and was reasonably tit for the
purposes stated on the label when used in accordance with Seller's
directions under normal conditions of use. To the extent consistent with
applicable law. Buyers and users of this product assume the risk of any
use contrary to such directions. EXCEPT AS PROVIDED
ELSEWHERE IN WRITING CONTAIMNC AN EXPRESS
REFERENCE TCI THIS WARRANTY AND LIMITATION OF
DAMAGES, SELLER MAKES NO OTHER EXPRESS OR
IMPLIED WARRANTY OR GUARANTY, INCLUDING ANY
OTHER EXPRESS OR IMPLIED WARRANTY OF FITNESS OR
OF MERCHANTABILITY, AND NO AGENT OF SELLER IS
AUTHORIZED TO DO SO. In no event shall Seller's liability for any
breach of warranty or guaranty exceed the purchase price of the product
as to which a claim is made. To the extent consistent with applicable law.
Buyers and users of this product are responsible for all loss or damage
from use or handling of this product which results from conditions beyond
the control of Seller, including, but not limited to, incompatibility with
other products unless otherwise expressly provided in Directions for Use
of this product, weather conditions, cultural practices, moisture conditions
or other environmental conditions outside of the ranges that are generally
recognized as being conducive to good agricultural and/or horticultural
practices.

Ranman® Is a registered trademark of Ishihara Sangyo Kaisha, Ltd.

291


-------
Appendix 2

FMC Current Supplemental Label (EPA Reg, No. 71512-3-279}

(This label was the most recent label in the marketplace prior to the newest EPA-approved label (i.e., 10/01/12)}

292


-------
GROUP

21

FUNGICIDE

RRNI

FUNGI

EPA Reg. No. 71512-3-279 EPA Est. No. 279-NY-1
Active Ingredient:

Cyazofamid*			34.5%

Other Ingredients: 	 65.5%

100.0%

*4-ch]oro-2-cyar>o-W,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide
(CA)

Contains 3.33 pounds Cyazofamid Per Gallon (400 grams per liter)

KEEP OUT OF REACH OF CHILDREN

CAUTION

See other panels for additional precautionary information.
Read entire label carefully and use only as directed.
MANUFACTURED IN FRANCE.

Manufactured for:

•FMC

FMC Corporation
Agricultural Products Group
1735 Market Street
Philadelphia PA 19103

Net Contents: 1 Gallon

Ml

C !

FIN

D E

FIRST AID

If on skin

•	Take off contaminated clothing.

•	Rinse skin immediately with plenty of soap and
water for 15-20 minutes.

¦ Call a poison control center or doctor for treat-
ment advice.

If in eyes

•	Hold eye open and rinse slowly and gently with
water for 15-20 minutes.

•	Remove contact lenses, if present, after the first
5 minutes, then continue rinsing eye.

•	Call a poison control center or doctor for treat-
ment advice.

If swallowed

•	Call a poison control center or doctor immedi-
ately for treatment advice.

¦ Have person sip a glass of water if able to swal-
low.

•	Do not induce vomiting unless told to do so by
the poison control center or doctor.

•	Do not give anything by mouth to an uncon-
scious person.

If inhaled

¦ Move person to fresh air.

•	If person is not breathing, call 911 or an ambu-
lance, then give artificial respiration, preferably
by mouth-to-mouth, if possible.

•	Call a poison control center or doctor for further
treatment advice

Have the product container or label with you when calling a poi-
son control center or doctor, or going for treatment.

HOTLINE NUMBER

For 24-Hour Medical Emergency Assistance (Human or
Animal) Call 1-800-331-3148.

For Chemical Emergency, Spill, Leak, Fire or Accident,

Call 1-800-331-3148.

PRECAUTIONARY STATEMENTS
Hazards to Humans (and Domestic
Animals)

CAUTION

Harmful if absorbed through skin. Avoid contact with skin, eyes or cloth-
ing. Avoid breathing spray mist. DO NOT take internally.

Personal Protective Equipment (PPE)

Applicators and other handlers must wear long-sleeved shirt and long
pants, socks, shoes, and chemical resistant gloves made of any water-
proof material.

Remove PPE immediately after handling this product. Wash the outside
of gloves before removing. As soon as possible, wash thoroughly and
change into clean clothing. Do not allow contact of contaminated clothing
with unprotected skin. Follow manufacturer's instructions for cleaning/
maintaining PPE. If no such instructions for washables, use detergent
and hot water. Keep and wash PPE separately from other laundry.

10-01-12

1

293


-------
Engineering Control Statements

When handlers use closed systems, enclosed cabs, or aircraft in a man-
ner that meets the requirements listed In the Worker Protection Standard
(WPS) for agricultural pesticides [40 CFR 170.240 (d) (4-6)], the handler
PRE requirements may be reduced or modified as specified in the WPS.
IMPORTANT: When reduced PRE is worn because a closed system is
being used, handlers must be provided all PPE specified above for "appli-
cators and other handlers" and have such PPE immediately available for
use In an emergency, such as a spill or equipment break-down.

User Safety Recommendations

Users Should:

•	Wash thoroughly with soap and water after handling
and before eating, drinking, chewing gum, or using
tobacco.

*	Remove and wash contaminated clothing before

reuse.

Environmental Hazards

DO NOT apply directly to water, to areas where surface water is pres-
ent or to intertidal areas below the mean high water mark. DO NOT
contaminate waters when disposing of equipment wash waters or rin-

sate.

AVOIDING SPRAY DRIFT AT THE APPLICATION SITE IS THE
RESPONSIBILITY OF THE APPLICATOR. The interaction of many
equipment-and-weather-related factors determine the potential for
spray drift. The applicator is responsible for considering all these fac-
tors when making decisions. Where states have more stringent reg-
ulations, they must be observed.

STORAGE AND DISPOSAL

DO NOT contaminate water, food or feed by storage or disposal.
Open dumping is prohibited.

Pesticide Storage: Store in original container, in a secured, dry
place separate from fertilizer, food, and feed.

Pesticide Disposal; Pesticide wastes are toxic. Improper dispos-
al of excess pesticide, pesticide spray or rinsate is a violation of
Federal law. If these wastes cannot be disposed of by use accord-
ing _ to label instructions, contact your State Pesticide or
Environmental Control Agency or the Hazardous Waste represen-
tative at the nearest EPA Regional Office tor guidance.

Container Disposal: Nonrefillable container. DO NOT reuse or
refill this container. Triple rinse container (or equivalent) promptly
after emptying. Triple rinse as follows: Empty the remaining con-
tents into application equipment or a mix tank and drain for 10 sec-
onds after the flow begins to drip. Fill the container 1/4 full with
water and recap. Shake for 10 seconds. Pour rinsate into applica-
tion equipment or a mix tank or store rinsate for later use or dis-
posal. Drain for 10 seconds after the flow begins to drip. Repeat
this procedure two more times. Then offer for recycling if available,
or puncture and dispose of in a sanitary landfill, or by incineration
or, if allowed by state and local authorities, by burning. If burned,
stay out of smoke.

DIRECTIONS FOR USE

It is a violation of Federal law to use this product In a manner incon-
sistent with its labeling.

FAILURE TO FOLLOW THE USE DIRECTIONS AND PRECAU-
TIONS ON THIS LABEL MAY RESULT IN PLANT INJURY OR
POOR DISEASE CONTROL.

Do not use for disease control on fruiting vegetables (other than
tomato transplants) or cucurbit vegetables grown for fruit production

in greenhouses.

ROTATIONAL CROP RESTRICTIONS

Crops on this label may be planted immediately after the last treat-
ment. Do not plant other crops not registered for this product within
30 days after the last application.

DO NOT apply this product in a way that will contact workers or other
persons, either directly or through drift. Only protected handlers may
be in the area during application. For any requirements specific to
your State or Tribe, consult the agency responsible for pesticide reg-
ulation.

AGRICULTURE USE REQUIREMENTS
Use this product only in accordance with its labeling and with
the Worker Protection Standard, 40 CFR Part 170. This
Standard contains requirements for the protection of agricultur-
al workers on farms, forests, nurseries, and greenhouses and
handlers of agricultural pesticides. It contains requirements for
training, decontamination, notification, and emergency assis-
tance. It also contains specific instructions and exceptions per-
taining to the statements on this label about personal protective
equipment (PPE), and restricted-entry interval. The require-
ments in this box only apply to uses of this product that are cov-
ered by the Worker Protection Standard.

DO NOT enter or allow worker entry into treated areas during
the restricted entry interval (REI) of twelve (12) hours.
PPE required for early entry to the treated areas that is permit-
ted under the Worker Protection Standard and that involves
contact with anything that has been treated, such as plants,
soil, or water, is: coveralls, chemical resistant gloves made of
any waterproof material, shoes plus socks and protective eye-
wear.

GENERAL INFORMATION
MIXING AND SPRAYING

RANMAN FUNGICIDE can be used effectively in dilute or concen-
trate sprays. Thorough, uniform coverage is essential for disease
control.

NOTE: Slowly invert container several times to assure uniform mix-
ture of formulation before adding this product to the spray tank.
Dosage rates on this label indicate fluid ounces of RANMAN FUNGI-
CIDE per acre, unless otherwise stated. Under conditions favorable
for disease development, the highest rate specified and shortest
application interval should be used. For best product performance in
all applications utilizing water volumes up to 60 gallons per acre, an
organosilicone surfactant should be added according to the manufac-
turer's label recommendations in order to improve spray coverage
when the disease infection is severe. However, a non-ionic surfactant
or a blend of an organosilicone and a non-ionic surfactant may be
used according to the manufacturer's label when disease infection is
moderate or light. Do not use a surfactant in applications to grapes or
tomato greenhouse transplant production.

RANMAN FUNGICIDE may be applied with all types of spray equip-
ment normally used for ground and aerial applications.

The required amount of RANMAN FUNGICIDE should be added
slowly into the spray tank during filling. With concentrate sprays, pre-
mix the required amount of RANMAN FUNGICIDE in a clean contain-
er and add to the spray tank as it is being filled. Keep agitator running
when filling spray tank and during spray operations. DO NOT allow
spray mixture to stand overnight or for prolonged periods. Prepare
only the amount of spray required for immediate use. Spraying equip-
ment should be thoroughly cleaned immediately after the application.
Apply RANMAN FUNGICIDE in sufficient water to obtain adequate
coverage of the foliage. Gallonage to be used will vary with crop and
amount of plant growth. Spray volume will usually range from 20 to
100 gallons per acre (200 to 1000 liters per hectare) for dilute sprays,
and 5 to 10 gallons per acre (50 to 100 liters per hectare) for concen-
trate ground and aerial sprays. For aerial applications, apply RAN-
MAN FUNGICIDE in a minimum of 5 gallons of water per acre.
Application through sprinkler irrigation systems is not recommended
unless specific directions are given for a crop. See application and
calibration instruction below.

TANK MIX COMPATIBILITY

RANMAN FUNGICIDE is physically compatible (no nozzle or screen
blockage) with many products recommended for control of diseases
and insects on vegetable crops. Read and follow all manufacturer's
label recommendations for the tank mix companion product. It is the
applicator's responsibility to ensure that the companion product is
EPA approved for use on the intended crop. RANMAN FUNGICIDE
is generally compatible with other insecticides, fungicides, fertilizers
and micronutrient products provided sufficient free water is available
for dispersion of all the tank mix products. However, the physical
compatibility of RANMAN FUNGICIDE with tank mix partners must
be evaluated before use. Conduct a jar test with intended tank-mix
pesticides prior to preparation of large volumes. Use the following
procedure: 1) Pour the recommended proportions of the products into
a suitable container of water, 2) Mix thoroughly and 3) Allow to stand
5 minutes. If the combination remains mixed or can be re-mixed read-
ily, it is considered physically compatible. Any physical incompatibili-
ty in the jar test Indicates that RANMAN FUNGICIDE should not be
used in the tank-mix.

294


-------
RANMAN FUNGICIDE is physically compatible (no nozzle or screen
blockage) with the following list of products;

Product

Active Ingredient

Acrobat

dimethomorph

Chlorothalonil (several)

chlorothalonil

Curzate

cymoxanil

ED8C (several)

mancozeb

Headline /Cabrio

pyraclostrobin

Mineral oils



Omega

fluazinam

Preview

Propamocarb hydrochloride

Quadris /Abound

azoxystrobin

CROP RESPONSE

RANMAN FUNGICIDE is not phytotoxic to the crop or succeeding
crops when applied according to label instructions.

INTEGRATED PEST MANAGEMENT
RANMAN FUNGICIDE Is an excellent disease control agent when
used according to label directions for control of several Oomycete
fungi. Although RANMAN FUNGICIDE has limited systemic activity, it
should be utilized as a protectant fungicide and applied before the
disease infects the crop. Depending upon the level of disease pres-
sure, good protection of the crop against disease can be expected
over a period of 7 to 10 days. RANMAN FUNGICIDE is recommend-
ed for use as part of an Integrated Pest Management (IPM) program,
which may include the use of disease-resistant crop varieties, cultur-
al practices, crop rotation, biological disease control agents, pest
scouting and disease forecasting systems aimed at preventing eco-
nomic pest damage. Practices known to reduce disease develop-
ment should be followed. Consult your state cooperative extension
service or local agricultural authorities for additional IPM strategies
established in your area. RANMAN FUNGICIDE may be used in
State Agricultural Extension advisory (disease forecasting) programs
that recommend application timing based upon environmental factors
that favor disease development.

RESISTANCE MANAGEMENT

Some plant pathogens are known to develop resistance to products
used repeatedly for disease control. RANMAN FUNGICIDE'S
mode/target site of action is complex III of fungal respiration:
ubiquinone reductase, Qi site, FRAC code 21. A disease manage-
ment program that includes alternation or tank mixes between RAN-
MAN FUNGICIDE and other labeled fungicides that have a different
mode of action and/or control pathogens not controlled by RANMAN
FUNGICIDE is essential to prevent disease resistant pathogens pop-
ulations from developing. RANMAN FUNGICIDE should not be uti-
lized continuously nor tank mixed with fungicides that have shown to
have developed fungal resistance to the target disease.

Since pathogens differ in their potential to develop resistance to
fungicides, follow the directions outlined in the "Directions For Use"
section of this label for specific resistance management strategies for
each crop. Consult with your Federal or State Cooperative Extension
Service representatives for guidance on the proper use of RANMAN
FUNGICIDE in programs that seek to minimize the occurrence of dis-
ease resistance. RANMAN FUNGICIDE is not cross-resistant with
other classes of fungicides that have different modes of action.

DIRECTIONS FOR USE

Crop

Diseases

Use Rate
Fl. Or Product
Per Acre
(lb. ai/AS

Instructions

Basil

Downy mildew

{Peronospom bet-
bahriij

2.75 to 3.0 (0.071
to 0.078)

Resistance Management:
DO NOT apply more than 9 applica-
tions of RANMAN Fungicide per
crop. Alternate sprays ol RANMAN
Fungicide with a fungicide with a
different mode of action. DO NOT
make more than three consecutive
applications of RANMAN Fungicide
followed by at least three applica-
tions ol fungicides having different
modes of action before applying
additional RANMAN Fungicide.
Application Instructions:
For control of downy mildew on
basil, mate the applications on a 7-
to 10-day schedule beginning when
disease conditions am favorable for
disease development. Use the
lower rats and longest interval as
disease preventative sprays or
when disease conditions are low.
Increase to the highest rate and
shortest interval under moderate to
heavy disease pressure.

RANMAN Fungicide can be applied
on basil grown in a greenhouse.
RANMAN Fungicide should be
tank-mixed with an organosilicone
surfactant when the disease infec-
tion is severe, or a non-ionic surfac-
tant or a bland of organosilicone
and a non-ionic surfactant when
disease infection is moderate or
light, at the manufacturer's label
recommendation for water volumes
up to 60 gallons per acre. Normal
water volumes are 50 to 75 gallons
per acre.

RANMAN Fungicide may be
applied through sprinkler irrigation
equipment. See calibration direc-
tions elsewhere on the label.
Restrictions:

DO NOT apply more than 27 fluid
ounces (0.7 lb a.i.) per acre per
crop growing season.
The Pre-Harvest Interval (PHI) for
this crop is 0 days.

Crops on this label may be planted
immediately after the last treat-
ment Do not plant other crops nol
registered for this product within 30
days after the last application. |

3

295


-------
Crop

BRASSICA

(COLE)
LEAFY VEG-
ETABLES:

CROP
GROUP 5

Broccoli;
Chinese broc-
coli (gai Ion);
broccoli raab
{rapini};
Brussels
sprouts; cab-
bage;

Chinese cab-
bags (bofc
choy); Chinese
cabbage
jnapa);
Chinese mus-
tard (gai choy):
cauliflower;
cavalo brocco-
lo; coilards:
tale;

kohlrabi; mizu-
na;

mustard
greens; mus-
tard spinach;
rape greens;
turnip greens

Diseases

Club root

(Ptasmxliophm
brasstcae)

Downy mildew

(Peronospom par
asitioa}

DsTRate
Fl. Oz. Product
Per Acre
(lb. al/A)

Transplant Soil
Drench;

12.9 to 25.75
(0.333 to 0.885
per 100 gallons

Soil Incorporation:

201A
(0.52)

Foliar;
2.75/A
(0.072)

Instructions

Resistance Management;

DO NOT apply more than six (1 soil
+ 5 foliar) applications ol RANMAN
Fungicide per crop. Alternate foliar
sprays of RANMAN Fungicide with
a fungicide with a different mods of
action. DO NOT make more than
three consecutive applications of
RANMAN Fungicide followed by at
least three applications of fungi-
cides having' different modes of
action before applying additional
RANMAN Fungicide.

Application Instructions;
Transplant Soil Drench for con-
trol of club root; Immediately after
transplanting, make a single appli-
cation within the rate range listed
arid apply 1.7 fluid ounces of solu-
tion per plant as transplant water,
Use the lowest rate far fields with
low soil infestation and increase to
the higher rates when fields have a
history of moderate to high soil
infestation.

Soil Incorporation; Alternatively, If
desired and for soil with low infiltra-
tion rates, apply 20 fl oz per acre in
a minimum bandwidth of 9 inches
along the planting row and incorpo-
rate to a soil depth of 6 to 8 inches
with a precision Incorporator in the
same operation. Apply in a water
volume of at least 50 gallons per
acre. Transplant the seedlings into
the treated band. If planting into a
bed, a broadcast application can be
made prior to forming the bed.
Foliar sprays for downy mildew;
Make fungicide applications on a 7-
to 10-day schedule beginning when
disease is first seen or weather and
downy mildew disease pressure are
expected to initiate a disease epi-
demic. Use the longest interval for
preventative applications or very
low disease pressure. Shorten the
interval as disease pressure and/or
fast crop development increases,
down to the shortest interval.
RANMAN Fungicide should be
tank-mixed with an organosilicone
surfactant when the disease infec-
tion is severe, or a non-ionic surfac-
tant or a blend of organosilicone
and a non-ionic surfactant when
disease infection Is moderate or
light, at the manufacturer's label
recommendation for water volumes
up to 80 gallons per acre. Normal
water volumes are 30 to 60 gallons
per acre.

RANMAN Fungicide may be
applied through sprinkler irrigation
equipment. See calibration direc-
tions elsewhere on the label.
Restrictions;

DO NOT apply more than 33.5 fl oz
per acre per crop growing season.
[1 soil application at a maximum of
25.75 fl, oz./A and 5 foliar applica-
tions at 2.75 fl, oz./A (13,76 fl.
oz./A) per application]
The Pre-Harvest Interval (PHI) for
these listed crops is 0 days.

Crops on this label may be planted
immediately after the last treat-
ment. Do not plant other crops not
registered for this product within 30
days after the last application.

Crop

Carrot

Diseases

Cavity spot, Root
Dieback, Forking

tihium ultimum,
riolse, R sul-
catum, R irregu-
Is re, Rsplsn-
densj

Use Rate
Fl. Oz Product
Per Acre (lb, al/A)

(0.156)

Instructions

Resistance Management:
DO NOT apply more than 5 sprays
of Ranman per crop. Alternate
sprays of Ranman with a fungicide
with a different mode of action.
Application instructions;
Pre-plant incorporated (broadcast
or band): Apply in sufficient water
to obtain adequate coverage within
3 days of planting and mechanical-
ly till into the soil to a depth of at
least 2 inches or Incorporate with at
least 1/4 inch of water.

Surface applications (broadcast or
band): Subsequent applications
may be made beginning at 14 days
after plant emergence and continue
on a 14-21 day schedule. Apply in
sufficient water to obtain adequate
coverage with the applications
directed to the base of the plant.
Ranman should be incorporated
into the soil with Vs to 1 inch of
water. If irrigation is not immediate-
ly available after the application,
then the application should be
made in sufficient water to allow
penetration into the soil.

Ranman may be applied via any
overhead irrigation system. Follow
directions outlined in the
Application and Calibration
Techniques For Sprinkler Irrigation
section of the label. Ranman
Fungicide should be applied during
the last 2 tours of the Irrigation
cycle to allow for adequate soil pen-
etration.

For banded applications a 6 to B
inch band is recommended (See
formula to calculate amount
required in the band).

Calculate the amount of Ranman
needed for band treatments by the
formula:

band width m

inches ^ broadcast rate
raw spacing in	per acre

amount needed
per acre of field

Restrictions:

DO NOT use more than 30 fl oz par
growing season.

DO NOT use any adjuvant when
applying to carrots,

DO NOT apply within 14 days of
harvest.

Crops on this label may be planted
immediately after the last treat-
ment Do not plant other crops not
registered for this product within 30
days after the last application.

4

296


-------
Crop

Diseases

Use Rate
Ft, Ot Product
Psr Acre
0b. al/Ai

Instructions

CUCURBIT VEG
ETABLE. CROP
GROUP 0

Cantaloupe
Chayote
Chinese wax-
gourd

Citron Melon
Cucumbers

Gherkin
Gourds

Honeydaw mel-
ons

Momordica spp.

Muskmc-Ion

Watermelon

Pumpkin

Squash

Zucchini

Downy mildew
{Pseudop&ronosp
ota cubsnsis)

Phytophthora
blight

(Phytophthora
capsici)

2.1 to 2.75
(0.054 to 0.071)

£75

(0.071)

Resistance Management:
DO NOT apply more than six
sprays of RANMAN FUNGICIDE
psr crop. Alternate sprays of RAN-
MAN FUNGICIDE with a fungicide
with a different mode of action. DO
NOT make more than three consec-
utive applications of RANMAN
FUNGICIDE followed by at least
three applications of fungicides
having different modes of action
before applying additional RAN-
MAN FUNGICIDE,

Application instructions;
For Downy mildew control, make
fungicide applications on a 7- to 10-
day schedule beginning with initial
flowering or when disease condi-
tions are favorable for disease
development, but prior to disease
development Use the low rate and
long interval as disease preventa-
tive sprays or when disease condi-
tions are low, Increase to highest
rate and shortest interval under
moderate to heavy disease pres-
sure,

For Phytophthora blight control,
apply RANMAN FUNGICIDE to the
base of the plants at the time of
transplanting. Alternatively, RAN-
MAN FUNGICIDE may be applied
in transplant water at the time of
transplanting. Apply 2,75 fl oz per
acre in the transplant water. It is
recommended that Ihs water vol-
ume for this initial application be at
(east 50 gallons per acre, Additional
applications should be made on a 7
to 10 day schedule beginning when
conditions are favorable far disease
development.

RANMAN FUNGICIDE should be
tank-mixed with an organosilicone
surfactant when the disease infec-
tion is severe, or a non-ionic surfac-
tant or a bland of an organosilicone
and a non-ionic surfactant when
disease Infection is moderate or
light, at the manufacturer's label
recommendations for water vol-
umes up to 60 gallons per acre.
Normal water volumes are 20 to 50
gallons per acre.

RANMAN FUNGICIDE may be
applied through sprinkler irrigation
equipment. See calibration direc-
tions preceding this section.
Restrictions:

DO NOT apply mora than 16,5 fluid
ounces (0.43 lb a,i.) psr acre per
crop growing season.
The Pre-Harvest Interval (PHI) for
this crop group is 0-day.

Crops on this label may be planted
Immediately after the last treat-
ment. Do not plant other crops not
registered for this product within 30
days after the last application,

Crop

Diseases

Use Rate
Fl. Oz. Product
Per Acre
(lb. ai/A)

Instructions

GRAPES

East of the

Rocky
Mountains

Downy mildew
{Plasmopara viti-
cola)

2.1 to 2.75
(0,064 to 0,071)

Resistance Management:

DO NOT apply more than six
sprays of RANMAN FUNGICIDE
per crop. Alternate sprays of RAN-
MAN FUNGICIDE with a fungicide
with a different mode of action, DO
NOT make more than three consec-
utive applications of RANMAN
FUNGICIDE followed by at least
three applications of fungicides
having different modes of action
before applying additional RAN-
MAN FUNGICIDE,

Application instructions:
For Downy mildew control, make
fungicide applications on a 10- to
14-day schedule beginning when
warning systems forecast disease
infection periods or when disease
conditions are favorable tor disease
development. Use the lowest rate
and longest interval for preventative
applications or very low disease
pressure, increasing the rate and
shortening the interval as disease
pressure and/or fast crop develop-
ment increases up to the maximum
rate and shortest interval. Do not
use any surfactant with this applica-
tion,

Application water volumes for
ground applications should be at
least 100 gallons per acre.
RANMAN FUNGICIDE may be
applied via aerial application using
a minimum of 5 gallons of water
volume per acre.

Restriction®

DO NOT apply more than 16.5 fluid
ounces (0,43 lb. Al) per acre per
growing season.

The Pre-HarvesI Interval (PHI) for
this crop is 30 days.

Crop

Diseases

Use Rate
Ff. Oz. Product
Per Acre
(lb. ai/A)

Instructions

HOPS

Downy mildew

fPseudoperonosp
om humulij

Z.I to2.75
(0,054 to 0.071)

Resistance Management:
DO NOT apply more than six appli-
cations of RANMAN Fungicide per
crop. Alternate foliar sprays of
RANMAN Fungicide with a fungi-
cide with a different mode of action,
DO NOT make mora than three
consecutive applications of RAN-
MAN Fungicide followed by at least
three applications of fungicides
having different modes of action
before applying additional RAN-
MAN Fungicide,

Application Instructions
For downy mildew control, make
fungicide applications on a 7- to 10-
day schedule beginning when dis-
ease is first seen or weather and
downy mildew disease pressure are
expected to initiate a disease epi-
demic. Use the lowest rate and
longest interval tor preventative
applications or very low disease
pressure, increasing the rate and
shortening the interval as disease
pressure and/or fast crop develop-
ment increases up to the maximum
rate and shortest interval, Use
water spray volume of at least 100
gallons per acre.

Restrictions;

DO NOT apply mom than 16.5 fl oz

per acre per crop growing season,
The Pre-Harvest Interval for this
listed crop is 3 days.

Crops on this label may be planted
immediately after the last treat-
ment. Do not plant other crops not
registered for this product within 30
days after the last application,

297


-------
Crop

Leafy Greens;
Crop

Subgroup 4 k

Amaranth
(leafy ama-
ranth,

Chinese
spinach, tarn-
pala); Aruguta
(Requeue);
Chervil;
Edible-leaved
chrysanthe-
mum Garland
chrysanthemu
mCorn ssfad;
Garden cress;
Upland cress
(yellow rocket,
winter cress};
Dandelion;
Dock (sorrel);
Endive (esca-
role); Lettuce
(head and
leaf); Orach;
Parsley;
Garden
purslane;
Winter
purslane;
Hadicchio (red
chicory);
Spinach;
New Zealand
spinach:

Vine spinach
{Malabar
spinach,

Indian
spinach).

Diseases

Whits rust

(Albugo occdun-
talis)

Use Rats
R, Oz. Product

Per Acre
jib. ai/A)

2.75
0.071)

Downy mildew

(Bremia lactacae)

Pythium

Damping-off
(Pythium spp.)

2.75
(0.071)

2,75
(0.071)

Instructions

Resistance Management;

DO NOT apply more than six sppli
cations ot RANMAN Fungicide per
crop. Alternate sprays of RANMAN
Fungicide with a fungicide with a
different mode of action. DO NOT
make more than three consecutive
applications of RANMAN Fungicide
followed by at feast three applica-
tions of fungicides having different
modes ot action before applying
additional RANMAN Fungicide,
Application Instructions
For white rust control, make fungi-
cide applications on a 7- to 10-day
schedule beginning when disease
is first seen or weather and white
rust disease pressure are expected
to initiate a disease epidemic. Use
the longest interval for preventative
applications or very low disease
pressure, shortening the interval as
disease pressure and/or fast crop
development increases up to Ihe
shortest interval.

For downy mildew control, make
fungicide applications on a 7- to 10-
day schedule beginning when dis-
ease first appears or when disease
conditions are favorable for disease
development. Use the longest inter-
val for disease preventative sprays
or when disease conditions are low.
increase application frequency to
the shortest interval under moder-
ate to heavy disease pressure.
For Pythium control, make the first
application to the soil as a directed,
post transplant or post planting
application. Mate this application
within 24 hours of transplanting or
seeding. The directed application
should be made as a band 4 to 6
inches wide over the seed line or
transplants. Direct the entire pet-
acre rate into the band. Calculate
the application rate using the row
width, Then, irrigate within 24 hours
of the first application with one half
(1/2) to one (1) inch of water to
properly move the product into Ihe
root zone. Alternatively, RANMAN
Fungicide may bs applied in trans-
plant water at the time of trans-
planting. Do not use a surfactant
with this soil drench application. It
is recommended that the water vol-
ume for this initial application be at
least 50 gallons per acre. Additional
applications should be made on a
7- to 10-day schedule beginning
when conditions are favorable for
disease development.

RANMAN Fungicide should be
tank-mixed with an organosilicone
surfactant when the disease infec-
tion is severe, or a non-ionic surfac-
tant or a blend of organosilicone
and a non-ionic surfactant when
disease infection is moderate or
light, at the manufacturer's label
recommendation for water volumes
up to 60 gallons per acre. Normal
water volumes are 30 to 60 gallons
per acre,

RANMAN Fungicide may be
applied through sprinkler irrigation
equipment, See calibration direc-
tions elsewhere on the label.
Restrictions:

DO NOT apply more than 16.5 fluid
ounces (0.43 lb a.i.) per acre per
crop growing season.
The Pre-Harvest interval (PHI) for
this crop group is 0 days.

Crops on this label may be planted
immediately alter the last treat-
ment Do not plant other crops not
registered for this product within 30
days alter the last application.

Crop

Succulent-
podded and
Succulent-
shelled
Beans;

Cicer ariesinum
(chickpea, gar-
banzo bean);
Lupinus spp,
(including
sweet lupine,
white sweet
lupine, white
lupine, and
grain lupine).
Phaseotus spp.
(including kid-
ney bean, lima
bean, mung
bean, navy
bean, pinto
bean, snap
bean, and
waxbean);

Vic'ta faba
(broad bean,
fava bean);
Vigna spp.
(including
asparagus
bean, black-
eyed pea and
cowpea).

Diseases

Cottony teak

(Pythium aphani-
dermatum)
Pythium uitimum)

Downy mildew

(Phytophthom

phassolij

Phytophthora

Might

{Phytophthora
eapsici)

Fl, Oz, Product
Per Acre
{lb. ai/A)

2.75
(0.071)

Instructions

Resistance Management.

DO NOT apply more than six appli-
cations of RANMAN Fungicide per
crop. Alternate sprays of RANMAN
Fungicide with a fungicide with a
different mode of action. DO NOT
make more than three consecutive
applications of RANMAN Fungicids
followed by at least three applica-
tions of fungicides having different
modes of action before applying
additional RANMAN Fungicide.
Application Instructions
For cottony leak control, make the
initial application at full bloom (1st
pods) and repeat on a 7- to 14-day
schedule. Use the longest interval
for disease preventative sprays or
when disease conditions are low.
Increase application frequency to
the shortest interval under moder-
ate to heavy disease pressure.
For control oi downy mildew on lima
beans, make the applications on a
7- to 10-day schedule beginning
when disease first appears or when
disease conditions are favorable for
disease development. Use the
longest interval for disease preven-
tative sprays or when disease con-
ditions are low. Increase the appli-
cation frequency to the shortest
interval under moderate to heavy
disease pressure.
For Phylophthora blight control,
make the 1st application at 100%
bloom-pin pod development and a
2nd application at late pin-small
pod development and repeat every
7 days as needed to maintain dis-
ease control,

RANMAN Fungicide should be
tank-mixed with an organosilicone
surfactant when the disease infec-
tion is severe, or a non-ionic surfac-
tant or a blend of organosilicone
and a non-ionic surfactant when
disease infection is moderate or
light, at the manufacturer's label
recommendation for water volumes
up to 60 gallons per acre. Normal
water volumes are 20 to 60 gallons
per acre,

RANMAN Fungicide may be
applied through sprinkler irrigation
equipment. See calibration direc-
tions elsewhere on the label.
Restrictions:

DO NOT apply more than 18,5 fluid
ounces (0,43 lb a.i.) per acre psr
crop growing season,

DO NOT apply to cowpess used for
livestock feed.

The Pre-Harvest Interval (PHI) tor
this crop group is 0 days.

Craps on this label may be planted
immediately after the last treat-
ment. Do not plant other crops not
registered for Ihis product within 30
days after Ihe last application.

6

298


-------
Use Rate
Fl. Oz. Product
Per Acre
(lb. ai/A)

Crop

Diseases

Instructions

Tuberous and
Corm

Vegetables:
Crop

Subgroup 1C

Arracacha;
arrowroot;
Chinese arti-
choke;

Jerusalem arti-
choke; Edible
canna; Bitter
cassava; Sweet
Cassava;
Chayote (root);
Chufa; Dasheen
(taro); Ginger;
Leren; Potato;
Sweet potato;
Tanier;

Turmeric; Yam
bean: True yam

Late blight

{Phytophihora

infssians)

Taro Leaf Blight

(Phytophihora

coiocaseass)

Foliar

1.4 to 2.75
(0.036 to 0.071)

Pink Rot
(Phytophihora
erythraseptica)
Pythiurn Root &
Crown Rot
(Pythium spp.)

At Planting:
0.42 fl. oz./1000

linear ft
[Equivalent to
6,1 fl. oz./A on
36"row spacing]
(0.158)

Lay-by/Hiding:

2.7S fl. oz./A
(0.071)

Resistance Management;

DO NOT apply moie than 10 sprays of
RANMAN FUNGICIDE per crop.
Alternate sprays of RANMAN FUNGI-
CIDE with a fungicide with a different
mode of action. DO NOT make more
than three consecutive applications of
RANMAN FUNGICIDE followed by at
least three applications of fungicides
having different modes o! action before
applying additional RANMAN FUNGI-

For pink rot, Pythium root and crown rot
control, do not use RANMAN FUNGI-
CIDE at reduced rates as incomplete
control may occur promoting potential
for development of resistant strains.
Rotate other fungicides with a different
mode of action or tank-mix these fungi-
cides with RANMAN FUNGICIDE to
reduce the chance of resistance occur-
ring. Development of resistance cannot
be predicted, (fa treatment of RANMAN
FUNGICIDE is not effective, a resistant
strain of fungi may be present.
Accordingly neither RANMAN FUNGI-
CIDE nor other fungicides with a similar
mods ol action will effectively control
the disease. Consult your local State
University for alternative recommenda-
tions.

Application instructions:

For foliar blight control, make fungicide
applications on a 7- to 10-day schedule
beginning when warning systems fore-
cast disease infection periods, general-
ly at row closure or when conditions are
favorable for disease development. Use
!hfl low rata and longest Interval for pre-
ventative applications or very low dis-
ease pressure, increasing the rate and
shortening the interval as disease pres-
sure and/or fast crop development
increases up to the maximum rate and
shortest interval.

For Late blight tuber rot control, make
the fast 2 to 3 applications prior to des-
iccation with RANMAN FUNGICIDE at
2.75 fl. oz. applied weekly.

For pink rol, Pythium root and crown rot
control at planting, apply 0.42 fluid
ounces of product per 1000 linear foot
of row in-furrow at planting using a min-
imum of 5 gallons ol water per acre.
Apply RANMAN FUNGICIDE using a 6
lo 8 inch band directly over the seed
pieces prior to furrow closure, A side
dressing of RANMAN FUNGICIDE
applied at hilling may be necessary for
additional control. Where mcfenoxam-
resistant strains of Phytophihora ery-
throseptlca and Pythium species are
not present, a full rate of RANMAN
FUNGICIDE can be tank-mixed with
mefenoxam containing fungicides for
additional control.

For additional control of Pink Rot,
Pythium root and crown rot in combina-
tion with an at-planting, in-furrow, RAN-
MAN FUNGICIDE application, apply
RANMAN FUNGICIDE as a broadcast
spray at 2.75 fluid ounces in a minimum
of 20 gallons of finished spray solution
per acre at hilling. Additional applica-
tions may be needed depending on
susceptibility of the crop to pink, root
and/or crown rot disease, environmen-
tal conditions conducive to favor severe
disease development, or fields located
in long growing season areas, etc.

Follow the guidelines for disease resist-
ance management listed above.
RANMAN FUNGICIDE should be tank-
mixed with an organosilicone surfaclant
when the disease Infection is severe, or
a non-ionic surfactant or a blend of an
organosilicone and a non-ionic surfac-
tant when disease infection is moderate
or light, at the manufacturer's label rec-
ommendations for water volumes up to
EO gallons per acre. Normal water vol-
umes are 20 to 50 gallons per acre.
RANMAN FUNGICIDE may be applied
through sprinkler irrigation equipment.
See calibration directions preceding :
this section.	:

Restrictions

DO NOT apply more than 27.5 fluid
ounces {0.71 lb a.i.) per acre per year
growning season.

DO NOT apply within 7 days of harvest.
Crops on this label may be planted
immediately after the las? treatment.
Do not plant other crops not registered
for this product within 30 days after the
last application.

Crop

Diseases

Use ftate
Fl. Oz. Product

Per Acre
(lb. ai/A)

Instructions

FRUITING
VEGETABLES
{Crop Group

8-10) and

QKRA,

includes:

African egg-
plant; Bush
Tomato; Bell
pepper;
Coneona;
Currant tomato
Eggplant;
Garden huckle-
berry; Qoji
berry; Ground
Cherry;
Martyniar
Naranjilia;

Okra;

Pea eggplant;
Pepino; Nonbel

K

Scarlel egg-
plant:

Sunberry;
Tomatiilo:
Tomato;

Tree tomato;
Cultivars, vari-
eties, and/or
hybrids of
these.

Late blight

{Pbyhphthom

iniestms)

Phytophihora
blight

(Phytophihora
eapsici)

2.1 to 2.75
(0.0S4 to 0.0710

2.75 (0.071)

Resistance Management;

DO NOT apply more than six
sprays of RANMAN FUNGICIDE
per crop. Alternate sprays of RAN-
MAN FUNGICIDE with a fungicide
with a different mode ol action. DO
NOT make more than three consec-
utive applications of RANMAN
FUNGICIDE followed by at least
three applications of fungicides
having different modes of action
before applying additional RAN-
MAN FUNGICIDE.

Application instructions:

For Late blight control, make fungi-
cide applications on a 7- to 10-day
schedule beginning when warning
systems forecast disease infection
periods, generally at flower initia-
tion or when conditions are favor-
able for disease development. Use
the lowest rate and longest interval
for preventative applications or very
low disease pressure, increasing
the rate and shortening the interval
as disease pressure and/or fast
crop development increases up to
the maximum rate and shortest
interval.

For Phytophthora blight control,
apply RANMAN FUNGICIDE to the
base of the plants at the time of
transplanting. Alternatively, RAN-
MAN FUNGICIDE may be applied
in transplant water at the time of
transplanting. Apply 2.75 fl oz per
acre in the transplant water. It is
recommended that the water vol-
ume for this initial application be at
least 50 gallons per acre. Additional
applications should be made on a 7
to 10 day schedule beginning when
conditions are favorable for disease
development.

RANMAN FUNGICIDE should be
tank-mixed with an organosilicone
surfactant when the disease infec-
tion is severe, or a non-ionic surfac-
tant or a blend of an organosilicone
and a non-ionic surfactant when
disease infection is moderate or
light, at the manufacturer's label
recommendations for water vol-
umes up to 60 gallons per acre.
Normal water volumes are 30 to 60
gallons per acre.

RANMAN FUNGICIDE may be
applied through sprinkler irrigation
equipment. See calibration direc-
tions preceding this section.
Restrictions

DO NOT apply more than 18.S fluid
ounces (0.43 lb a.i.) per acre per
crop growing season.
The Pre-Harvest Interval (PHI) for
these listed crops is 0-day.

Crops on this label may be planted
immediately after the last treat-
ment, Do not plant other craps not
registered tor this product within 30
days after the last application.

Tomato

Greenhouse
Transplants
(Soil Drench)

Pythium Damping-
oil (Pythium spp.}

3 It oz/100 gallons
water (0.078 lb a.i./
100 gallons water)

Tomato Greenhouse Transplant
Production: For control of darnp-
ing-ofl caused by Pythium spp,
make a single fungicide application
to the seedling tray at the time of
planting or at any time thereafter up
until 1 week before transplanting,
Apply the fungicide solution as a
drench to thoroughly wet the grow-
ing medium. This results in the use
of approximately 1 pint of solution
per square foot if the growing medi-
um is 4 inches deep. Do not use
any surfactant with this drench
application.

299


-------
APPLICATION AND CALIBRATION TECHNIQUES FOR
SPRINKLER IRRIGATION

Apply this product only through center pivot, motorized lateral move,
traveling gun, solid set or portable (wheel move, side roll, end tow, or
hand move) irrigation system(s). DO NOT apply this product through
any other type of irrigation system.

Crop injury, lack of effectiveness, or illegal pesticide residues in the
crop can result from non-uniform distribution of treated water.

If you have questions about calibration, you should contact State
Extension Service specialists, equipment manufacturers or other

experts.

DO NOT apply RAN MAN FUNGICIDE through irrigation systems

connected to a public water system. "Public water system" means a
system for the provision to the public of piped water for human con-
sumption if such system has at least 15 service connections or regu-
larly serves an average of at least 25 individuals daily at least 60 days
per year.

Controls for both irrigation water and pesticide injection systems must
be functionally interlocked, so as to automatically terminate pesticide
injection when the irrigation water pump motor stops, A person knowl-
edgeable of the irrigation system and responsible for its operation
shall be present so as to discontinue pesticide injection and make
necessary adjustments, should the need arise.

The Irrigation water pipeline must be fitted with afunctional, automat-
ic, quick-closing check valve to prevent the flow of treated irrigation
water back toward the water source. The pipeline must also be fitted
with a vacuum relief valve and low-pressure drain, located between
the Irrigation water pump and the check valve, to prevent back-
siphoning of treated irrigation water into the water source.

Always inject RANMAN FUNGICIDE into irrigation water after it
discharges from the irrigation pump and after it passes through
the check valve. Never inject pesticides into the intake line on
the suction side of the pump.

Pesticide injection equipment must be fitted with a functional, normal-
ly closed, solenoid-operated valve located on the intake side of the
Injection pump. Interlock this valve to the power system, so as to pre-
vent fluid from being withdrawn from the chemical supply tank when
the irrigation system is either automatically or manually turned off.
The pesticide injection pipeline must contain a functional, automatic,
quick-closing check valve to prevent the flow of fluid back toward the
injection pump. The irrigation line or water pump must include a func-
tional pressure switch that will stop the water pump motor when the
water pressure decreases to the point where pesticide distribution is
adversely affected.

Spray mixture in the chemical supply tank must be agitated at all
times, otherwise settling and uneven application may occur. DO NOT
apply when wind speed favors drift beyond the area intended for

treatment

RANMAN FUNGICIDE may be used through two basic types of sprin-
kler irrigation systems as outlined in Sections A and B below.
Determine which type of system is in place, then refer to the appro-
priate directions provided for each type.

A.	Center Pivot, Motorized Lateral Move and Traveling
Gun Irrigation Equipment

For injection of pesticides, these continuously moving systems must
use a positive displacement injection pump of either diaphragm or
piston type, constructed of materials that are compatible with pesti-
cides and capable of being fitted with a system interlock and capable
of injection at pressures approximately 2-3 times those encountered
within the irrigation water line. Venturi applicator units cannot be used
on these systems.

Thoroughly mix recommended amount of this product for acreage to
be covered into the same amount of water used during calibration
and inject into system continuously for one revolution or run. Mixture
in the chemical supply tank must be continuously agitated during the
injection run. Shut off injection equipment after one revolution or run,
but continue to operate irrigation system until this product has been
cleared from the last sprinkler head.

B.	Solid Set and Portable (Wheel Move, Side Roll, End
Tow, or Hand Move) Irrigation Equipment

With stationary systems, an effectively designed in-line venturi appli-
cator unit is preferred which is constructed of materials that are com-
patible with pesticides; however, a positive-displacement pump can
also be used.

Determine acreage covered by sprinkler. Fill tank of injection equip-
ment with water and adjust flow to use contents over a 30 to 45
minute period. Mix desired amount of RANMAN FUNGICIDE for
acreage to be covered with water so that the total mixture of this
product plus water in the injection tank is equal to the quantity of
water used during calibration.

Agitation is recommended. RANMAN FUNGICIDE can be injected at
the beginning or end of the irrigation cycle or as a separate applica-
tion. Stop injection equipment after treatment is completed and con-
tinue to operate irrigation system until this product has been cleared
from last sprinkler head

WARRANTY AND LIMITATION OF DAMAGES

Seller warrants to those persons lawfully acquiring title to this prod-
uct that at the time of first sale of this product by Seller that this prod-
uct conformed to its chemical description and was reasonably fit for
the purposes stated on the label when used in accordance with
Seller's directions under normal conditions of use. To the extent con-
sistent with applicable law, Buyers and users of this product assume
the risk of any use contrary to such directions.

EXCEPT AS PROVIDED ELSEWHERE IN WRITING CONTAINING
AN EXPRESS REFERENCE TO THIS WARRANTY AND LIMITA-
TION OF DAMAGES, SELLER MAKES NO OTHER EXPRESS OR
IMPLIED WARRANTY OR GUARANTY. INCLUDING ANY OTHER
EXPRESS OR IMPLIED WARRANTY OF FITNESS OR OF MER-
CHANTABILITY, AND NO AGENT OF SELLER IS AUTHORIZED
TO DO SO.

In no event shall Seller's liability for any breach of warranty or guar-
anty exceed the purchase price of the product as to which a claim is
made. To the extent consistent with applicable law, Buyers and users
of this product are responsible for all loss or damage from use or han-
dling of this product which results from conditions beyond the control
of Seller, including, but not limited to, incompatibility with other prod-
ucts unless otherwise expressly provided in Directions for Use of this
product, weather conditions, cultural practices, moisture conditions or
other environmental conditions outside of the ranges that are gener-
ally recognized as being conducive to good agricultural and/or horti-
cultural practices.

FMG -FMG Trademark

RANMAN® - is a registered Trademark of Ishihara Sangyo Kaisha, Ltd.

Acrobat, and Headline, - Registered Trademarks of BASF Corporation

Curzate, - Trademarks of E.I. DuPont de Nemours and Company

Cabrio - Tradmark of BASF AG

Omega - Trademark of Ishihara Sangyo Kaisha, LTD.

PREVICUR, - Registered Trademark of Bayer.

Abound, and Quadris, - Registered Trademarks of Syngenta Group Co.

300


-------
Appendix 3

USDA NASS Information for Cyazofamid Labeled Crops

301


-------
APPENDIX 3: USDA NASS INFORMATION FOR CYAZOFAMID LABELED CROPS

Commodity

Acreage*

Minor Use Eligibility

Crop Group 5





Broccoli

130,603

Yes

Broccoli, Chinese

N/A

Vpq

Broccoli, raab

N/A

Yes

Brussels sprouts

3,8/4

Yes

Chinese cabbage, (bok choy)

11,480

Yes

Chinese cabbage, {napa)

Yes

Chinese mustard cabbage

66

Yes

Cabbage

80,620

Yes

Cauliflower

39,515

Yes

Cavalo broccoli

N/A

Yes

Collarets

11,223

Yes

Kale

3,994

Yes

Kohlrabi

N/A

Yes

Mizuna

N/A

Yes

Mustard greens

8,323

Yes

Mustard spinach

N/A

Yes

Rape greens

1,600

Yes

Turnip greens

9,365

Yes

Crop Group i





Tomato

442,225

No

Eggplant

6038

Yes

Ground cherry

n/a

Yes

Okra

2,444

Yes

Pepino

n/a

Ypq

Bell pepper

Bell pepper
excluding
pimentos: 62,363

Yes

Chili pepper

Peppers other
than bell: 37,372

Yes

Cooking pepper

Peppers other
than bell: 37,372

Yes

Pimento

Peppers other
than bell: 37,372

Yes

Sweet pepper

Peppers other
than bell; 37,372

Yes

Tomatillo

N/A

Yes

302


-------
APPENDIX 3; USDA NASS INFORMATION FOR CYAZOFAMID LABELED CROPS - CONTINUED

Commodity

Acreage*

Minor Use Eligibility

Croo Group 9





Cantaloupe

84,290

Yes

Crop Group 9





Chayote

n/a

Yes

Chinese waxgourd (Chinese
preserving melon)

n/a

Yes

Citron-melon

n/a

Yes

Cucumber

Cucumber/ pickles:
151,759

Yes

Gherkin

n/a

Yes

Gourd

n/a

Yes

Honeydew melon

17,344

Yes

Momordica spp.

n/a

Yes

Muskmelon

n/a

Yes

Watermelon

142,359

No

Pumpkin

92,955

Yes

Squash

54,454

Yes

Zucchini

n/a

Yes

Carrot

90 292

Yes

Potato

1,131,963

No

Grape, East of the Rocky

Mountains

102,829=
1,051,407 (US
total) - 868,330
(California) -

61,056
(Washington) -
18,192 (Oregon)

Yes

Tomato, Greenhouse
Transplant

43,949,871 scjft =
1,009 acres

Yes

Spinach

44,071

Yes

Hop

31,145

Yes

*USDA NASS Database. Unless otherwise noted, data retrieved from the 2007 Agrrcuttursl Census,
N/A= Not Available, but assumed below the 300,000 acre threshold and thus considered minor crops.

303


-------