•x*~ ~,x, US Environmental Protection Agency
Office of Pesticide Programs
.*
Petition for Spiromesifen
November 14, 2007
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Bayer CropScience
November 14, 2007
Document Processing Desk
Office of Pesticide Programs (7504C)
U.S. Environmental Protection Agency
One Potomac Yard
2777 South Crystal Drive (7505P)
Arlington, VA 22202
Attention: Mr. Tom Harris, RD
Re: Petition for 3 Years Extension of Exclusive Data Use for Spiromesifen
(EPA Reg. No. 264-718) as provided for Under FIFRA Section 3(c) (1) (F)
Dear Mr. Harris,
Bayer CropScience hereby petition EPA to extend the period of exclusive data use for
spiromesifen insecticide by 3 years, by applying the provision of FIFRA Section 3(c)
Bayer CropScience believe that spiromesifen meets all of the criteria required for this
provision based on currently registered uses.
Spiromesifen has been classified as a reduced risk compound by EPA. Residue studies
supporting registration are available for 1 1 minor crops, thus qualifying for 3 additional
year data exclusivity (1 year for 3 minor uses up to a maximum of 3 years) providing
the other criteria listed in FIFRA Section 3{c) (1) (F) (ii) are met. Details of how
spiromesifen meets each of these criteria is described in attached petition.
I copied Robert Perlis of the Office of General Counsel, as instructed by Barbara
Madden e-mail to Jamin Huang on 8/25/05. If this petition needs to be forwarded to
any other person/division within the Agency, would you please see that it can be done.
If you have any question, please contact me either by telephone at 919-549-2156 or
email at sherry.movassaghi@bayercropscience.com.
Sincerely,
Sherry Movassaghi, Ph.D.
Registration Product Manager
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Petition for 3 Years Extension of Exclusive Data Use for
Spiromesi'fen as Provided for Under FIFRA Section 3(c) (1) (F) Hi)
Bayer CropScience hereby petition EPA to extend by 3 years the period of exclusive
data use for spiromesifen insecticide by applying the provision of FIFRA Section 3(c) (1)
(F) (ii).
FIFRA Section 3(c) (1) (F) (ii) states that:
The period of exclusive data use provided under clause (i) shall be extended 1
additional year for each 3 minor uses registered after the date of enactment of
this clause and within 7 years of the commencement of the exclusive use period,
up to a total of 3 additional years for all minor uses registered by the
Administrator if the Administrator, in consultation with the Secretary of
Agriculture, determines that, based on information provided by an applicant for
registration or a registrant, that -
(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 pesticide plays or will play a significant part in an
integrated pest management program.
Bayer CropScience consider that spiromesifen meets ali of the criteria listed above as
described in this doci^neTfTbased-eciXurrently registered uses. Spiromesifen and its
formulated products QBERON® 2 SC Insecticide/Mitictde, OBERON® 4 SC
Insecticide/Miticide and Forbid 4F-1fTsecticide/Miticide has brought a new mode of action
to the crops on which it is registered and has the unique property of controlling both
mites and whiteflies. Formulated spiromesifen was first registered by U.S. EPA on May
3, 2005 following tolerances having been set on the crops and crop groups below on
April 27, 2005:
• Cotton
« Field corn
• Strawberries
• Tuberous and corm vegetables (EPA crop subgroup 1-C)
• Vegetable, leafy greens subgroup (EPA crop subgroup 4-A)
• Vegetables, brassica, head and stem subgroup (EPA crop subgroup 5-A)
« Vegetables, brassica, leafy greens subgroup (EPA crop subgroup 5-B)
« Fruiting vegetables (EPA crop group 8)
• Cucurbit vegetables and melons (EPA crop group 9)
To support the above registrations residue trials were conducted in the major use crops
of corn, cotton, tomatoes and potatoes and on a wide range (eleven) of minor crops to
support the numerous minor use crops on which spiromesifen is currently registered.
The minor use crops for which residue data is available are listed in Table 1.
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Table 1
Minor Use Crops on which Residue Studies Have Been Conducted
Crop
Strawberries
Head Lettuce
Leaf Lettuce
Spinach
Broccoli
Cabbage
Mustard Greens
Peppers
Cantaloupe,
Cucumbers
^Summer Squash
MRIDf
45819411
45819427
45819427
45819427
45819426
45819426
45819431,46722301
45819417
45819414
45819414
45819414
Crop
Group/Subgroup
none
4-A
4-A
4-A
5-A
5-A
5-B
8
9
9
9
Residue studies supporting registration are, therefore available for 11 minor crops, thus
qualifying for 3 years data exclusivity (1 year for 3 minor uses up to a maximum of 3
years) providing the other criteria listed above are met. Details of how spiromesifen
meets each of these criteria is described below. On November 28, 2006 EPA's Reduced
Risk Committee granted, retrospectively after review of the complete package, reduced
risk status to spiromesifen for use on all registered crops, namely cotton, cucurbits, field
corn, fruiting vegetables, Brassica leafy vegetables, leafy vegetables (non-Brassica),
strawberry, tuberous vegetables and greenhouse, landscape, and nursery ornamentals.
Thereduced risk submission (Kelly, I. et al., 2006; Arthur, E. et al., 2003a; Buckelew, L.
and J. Mixson. 2003) and the supplementary response (Arthur, E. et al., 2003b) provides
supporting documentation to the information below.
Criterion I; There are insufficient efficacious alternative registered pesticides
available for the use
In the reduced risk document a summary of major competitor insecticides/miticides
registered for mite and/or whitefly control at the time of submission was listed.
Spiromesifen is a unique compound that controls both whiteflies and mites. While this
confers reduced risk advantages, it means that the competitors are very different
dependent on the pest being controlled. Competitors (by active ingredient) were
selected that accounted for more than 5% of the foliar treated acres in a particular
crop/crop group for either whitefly~oFmTfe"control. Soil applied systemic chemistries
such as aldicarb (Temik®) in the mite market and imidacloprid (Admire®) and
thiamethoxam (Platinum®) in the whitefly market were not included as spiromesifen will
not compete in or affect these markets. Generally, competitors were only selected if
they are labeled for the same pests that are on the spiromesifen (OBERON®) label. In
addition to products that were used in greater than 5% of treated acres, recently
registered products that were anticipated to capture significant market share were
included. Buprofezin (Courier®), hexythiazox (Savey®) and acetamiprid (Assail®) fell into
this category. The competitors are listed in Table 2.
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Table 2
Competitors to Spiromesifen in Minor Use Crops
Crop/
Crop Group
Strawberry
Melon/Cucurbit
Vegetables,
Fruiting
Vegetables,
leafy
(Non- Brassica)
Vegetables,
leafy (Brassica)
Pest
Mites
Whiteflies
Whiteflies
Mites
Whiteflies
Whiteflies
Whiteflies
Active
Ingredient
Spiromesifen
Abamectin
Hexythiazox
Spiromesifen
Spiromesifen
Buprofezin
Endosulfan
Spiromesifen
Abamectin
Dicofol
Spiromesifen
Acetamiprid
Buprofezin
Endosulfan /
Pyriproxyfen /
Spiromesifen
Acephate
Acetamiprid
Buprofezin
Spiromesifen
Endosulfan
Product Name
OBERON® 2 SC
Agri-Mek®0,15EC
Savey® 50 DF
OBERON® 2 SC
OBERON® 2 SC
Courier*'" IGR
Thiodan® SEC
OBERON® 2 SC
Agri-Mek®0.15EC
Kelthane® MF
OBERON* 2 SC
Assail®'" 70WP
Courier®"* IGR
Thiodan® 3EC
Knack® IGR
OBERON® 2 SC
Orthene® 75 S
Assail® 70WP
Courier®*" IGR
OBERON® 2 SC
Thiodan® 3EC
Chemical
Class/Family
Cyclic ketoenol
Avermectin,
macrocyclic lactone
Carboxamide
Cyclic ketoenol
Cyclic ketoenol
Substituted
thtdiazinone
Chlorinated
hydrocarbon
Cyclic ketoenol
Avermectin,
macrocyclic lactone
Organochlorine
Cyclic ketoenol
Chloronicotinyl
Substituted
thidiazinone
Chlorinated
hydrocarbon
Juvenile hormone
mimic
Cyclic ketoenol
Organophosphate
Chloronicotinyl
Substituted
thidiazinone
Cyclic ketoenol
Chlorinated
hydrocarbon
As can be seen in Table 2 there are a limited number of competitors for each use and in
some cases such as Whiteflies in strawberries, essentially no viable alternatives. Mites
are the larger market for Spiromesifen and abamectin alone generally dominates this
market. In addition field and laboratory tests have shown that Spiromesifen provides
consistent, long lasting pest control and other performance attributes which $ makes it
superior to major competitors as shown in Table 3.
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Table 3: Comparison of Spirotnesifen Control to Malor Competitive Products
Parameter
Active
Ingredient
Trade Name
Company
Mode of
Action
Residual Time
Pest /Benefit
Whitefly
Spider Mite
Product
Spiromesifen
Oberon*
Bayer
CropScience
Lipid
biosynthesis
inhibitor
30-45 days
Abamectin
Zephyr" &
Agri-Mek®
Syngenta
GABA
receptor
protein
inhibitor
30-40 days
Dicofol
Kelthane®
Dow
GABA-
gated Cl
channel
antagonist
21 days
Hexythiazox
Savey®
Gowan
Electron
transport
inhibitor
30 days
Pyriproxyfen
Knack®
Valent
Juvenile
hormone
mimic
21-31 davs
Pest /Benefit
•*•++
•*•++
+++
++ | ++
+++•
Acetamipricl
Intruder™
DuPont
Inhibition of
nicotinergic
acetylcholine
receptors
14-21 days
+++
Excellent control
Good control
Criterion II; The alternatives to the minor use pesticide pose greater risks to the
environment or human health
Spiromesifen is a reduced risk compound. The toxicological findings of the Health
Effects Division when registering spiromesifen were:
• Technical spiromesifen shows low acute toxicity (Toxicity Category III, IV) via the
oral, dermal and inhalation routes of exposure.
• It is neither an eye nor dermal irritant (Toxicity Category IV), but showed
moderate potential as a contact sensitizer in a Magnusson and Kligman
maximization assay.
• An acute endpoint of concern attributable to a single exposure (dose) was not
identified from the oral toxicity studies including infants and children
• Spiromesifen shows no significant developmental or reproductive effects
• Spiromesifen is not neurotoxic
« Spiromesifen is classified as "not likely to be carcinogenic to humans"
The reduced risk packages submitted to EPA provide supporting details as to why the
alternatives to spiromesifen pose greater risks to both human health and the
environment as summarized below.
Alternatives Pose Greater Risk to Human Health
Spiromesifen introduces newer, safer chemistry to control mite and whitefly infestations.
Spiromesifen showed no evidence of oncogenicity and is classified as "unlikely to be a
human carcinogen" (i.e. Class E oncogen). In the larger mite market, spiromesifen
competitors are abamectin, dicofol, and hexythiazox. Of these products, only abamectin
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has an E classification. The others are class C carcinogens with hexythiazox being
regulated by linear extrapolation (Q1*). Spiromesifen showed no evidence of being a
primary reproductive or developmental toxicant. Abamectin is a possible primary
reproductive and/or neonatal toxicant. The end-use products of spiromesifen carry the
signal word "Caution" being in Toxicity Category 111. Abamectin carries the signal word
"Warning" (Toxicity Category II).
In the whitefly market, spiromesifen competes with acephate. acetamiprid, buprofezin,
endosulfan and pyriproxyfen. Acephate is classified'as a possible C carcinogen,
buprofezin is a possible primary reproductive and/or neonatal toxicant, endosulfan
resulted in evidence of developmental toxicity at doses below that at which maternal
toxicity was observed. Endosulfan formulation (Thiodan®) is Category I based on eye
irritation potential carrying the signal word "Danger".
Alternatives Pose Greater Risk to the Environment
Risk assessments demonstrate that spiromesifen and its primary metabolites pose
minimal risk to non-target organisms. Tier 1 risk quotients are generally below all levels
of concern or can be easily refined to demonstrate negligible risk. Table 4 is a
comparison based on Tier 1 risk quotients taken from the reduced risk submission in
which quantitative values of these risk quotients are provided.
Table 4: Summary of Ecological Risk for Spiromesifen and Major
Competitors
No data available
= No Tier 1 LOC exceedences
= Between the endangered species LOC and the high risk LOC for acute risk. Between 1 and 2 times the LOC for chronic risk
= Greater than the high risk LOC for acute risk. Greater than 2 times the LOC for chronic risk.
Of the competitors only pyriproxyfen and acetamiprid in the whitefly market and possibly
hexythiazox in the mite market have a potentially more favorable profile. In the larger
mite market hexythiazox is a significant competitor only in strawberries where there are
very few alternates, the only significant one being abamectin which has a much less
favorable prgfL|e__WJaite,pyri£roxyfen generally has a very safe overall profile, it poses a
•20-fold_greater chronicjisk te-^aphnia than spiromesifen (Arthur, E. etal., 2003a). A
"strong case can therefore be made that spiromesifen has the safest overall ecological
profile with the exception of the minor hexythiazox use in strawberries.
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Spiromesifen has minimal effects on predacious bugs and other beneficials at typical
use rates. It is practically non-toxic to pollinators.
Criterion III and IV: the minor use pesticide plays or will play a significant Dart in
managing pest resistance (III): or the minor use pesticide plays or will play a
significant part in an integrated pest management program ((IV)
The USDA defines IPM as, "A sustainable approach to managing pests by combining
biological, cultural, physical, and chemical tools in a way that minimizes economic,
health, and environmental risks". Spiromesifen brings a new mode of action to all the
crops it is registered on and has the unique property of controlling both mites and
whiteflies. Resistance management is a critical component for whitefly and mite control
and Spiromesifen is an excellent fit.
Integrated pest management is improving in the crops on which Spiromesifen will be
used as newer "softer" products such as abamectin for mite control and the
chloronicotinyls/neonicotinoids and insect growth regulators for whitefly control are
established in the market. These newer products fit better with biological control
methods and have precipitated substantial reductions in the use of organophosphates,
pyrethroids and organochlorines in these crops. Control of spider mites with
organophosphates and pyrethroids, particularly, has been problematic because these
chemicals can stimulate mite reproduction and change plant physiology to make it a
more suitable host. Additionally, in some areas resistance has developed to these
insecticides.
Spiromesifen is an essential part of resistance management in regions where multiple
crops are grown that are becoming increasingly dependent on the use of chforonicotinyls
for whitefly control. The chloronicotinyl/neonicotinoid (CNI) class of chemistry has been
used effectively for whitefly control in vegetables and melons since 1993, and it is an
extremely important component to their production. In these crop complexes, insect
growth regulators are the main products used to relieve the pressure towards
chloronicotinyl resistance development.
Chloronicotinyls/neonicotinoids facing a particular threat for resistance development,
particularly in the southwest, which will be a major use area for Spiromesifen. Whitefly
populations and subsequent generations of whiteflies occur across a diverse range of
crops in the southwest. This presents a difficult problem for insecticide resistance
management when similar chemistries are used in different commodities for the same
pest. The University of Arizona has developed cross-commodity guidelines for this class
of chemistry which emphasize the importance of chemical class rotation, where possible,
to minimize selection pressure by the chemistries.
Furthermore, the discovery of the Q-biotype whitefly in the U.S could dramatically shift
regional whitefly pest management. The Q-biotype whitefly is a new strain of Bemisia
tabaci which is more commonly known as Sweetpotato whitefly or Silverleaf whitefly.
This strain is visually indistinguishable from B-biotype whitefly but is known to be
exceptionally less susceptible to the most common whitefly control products such as
acetamiprid, buprofezin, imidacloprid, and thiamethoxam. However, lab studies have
shown that Spiromesifen is one, if not the only, very effective product on this very difficult
to control pest (Guthrie, F. et a!., 2003). Biological surveys of whiteflies from different
regions of the U.S. have now confirmed detections of Q-biotype in the following states:
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Alabama, Arizona, California, Connecticut, Florida, Georgia, Indiana, Kentucky,
Louisiana, Michigan, New Jersey, New York, Oregon, Pennsylvania, and Vermont. So,
Spiromesifen has a strong role in resistance management of whitefly, particularly the
difficult to control Q-biotype.
Integrated pest management strategies clearly require additional chemical modes of
action in the mite and whitefly market that fit with the objective of minimizing economic,
health, and environmental risks if it is to be sustainable. The registration of spiromesifen
has brought many desirable benefits, which fit with this objective.
Conclusions
In conclusion spiromesifen meets all the criteria for granting a 3 year extension of the
exclusive data use period. Residue data is available for eleven minor use crops
exceeding the required number of nine. The mite and whitefly market for the minor crops
on which it is registered have very few valid alternatives and its adoption in the market
place is showing that it is a valuable tool. EPA has granted it reduced risk status for all
registered minor crops. It has no attributes of concern for human health in contrast to
most competitors. It poses less risk to non-target organisms with the potential exception
of hexythiazox in strawberries in which it is a valuable complementary tool.
Spiromesifen brings a completely new mode of action for both mite and whitefly control
to all minor use product listed on label, including: strawberry, cucurbits/melons and
vegetables (tuberous, fruiting and leafy, both non-brassica and brassica). Its level of
control and residual efficacy is equal to or better than present standards. With its low
use rate, long residual activity and dual pest activity, chemical use is minimized.
Spiromesifen will minimize resistance development to miticides for which there are very
few effective competitors. Its use for whitefly control will minimize the development of
resistance to the soil applied chloronicotinyls/neonicotinoids, a chemical class that is
critical to growers. It will complement currently applied whitefly products such as insect
growth regulators and pyrethroids that have already shown resistance development. It
will also ensure that organophosphates and organochlorines, whose use has been
diminishing, will not be re-introduced to combat this resistance. Spiromesifen has
minimal effects on predacious bugs and other beneficials at typical use rates. It is
practically non-toxic to pollinators.
References
Kelly, I., Bowers L, Christenson R, Arthur E., and Buckelew L. 2006. Justification for Designating
Spiromesifen as a Reduced Risk Compound on Currently Registered Crops, EPA Pesticide
Regulation Notice 93-7, Bayer CropScience, Research Triangle Park, NC. Report Number
G201515. May 4, 2006, 8 pages. MRID # 46835601
Arthur E., L. Bowers L., Buckelew R., Christenson, V. Dorr, F. Duah, J. Fisher, T. Gould, I. Kelly,
C. Lenz, J. Mixson, L. Russo, K. Shearer, V. Standart and L. Stocky, 2003a. Reduced Risk
Rationale for the Use of Spiromesifen on Field Corn, Cotton, Vegetable and Fruit Crops, Cucurbit
Vegetables, Fruiting Vegetables, Leafy Vegetables, Tuber Vegetables, Strawberry and Nursery,
Greenhouse and Landscape Ornamentals. Bayer CropScience Report Number 200565
Arthur E., L. Bowers L., Buckelew R., Christenson, V. Dorr, F. Duah, J. Fisher, T. Gould, I. Kelly,
C. Lenz, J. Mixson, L. Russo, K. Shearer, V. Standart and L. Stocky, 20035. Response to EPA's
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Reduced Risk Decision (Dated 10/17/2003} on Spiromesifen Use on Field Corn, Cotton,
Vegetable and Fruit Crops, Cucurbit Vegetables, Fruiting Vegetables, Leafy Vegetables, Tuber
Vegetables, Strawberry and Nursery Greenhouse and Landscape Ornamentals. Bayer
CropScience Report Number G 200753.
Buckelew, L. and J. Mixson, 2003. Resistance Management, Comparative Performance, and
Market Analysis for Spiromesifen: Oberon® 2 SC Insecticide/Miticide
Addendum Number 1 7b:Reduced Risk Rationale for the Use of Spiromesifen on Field Corn,
Cotton, Vegetable and Fruit Crops, Cucurbit Vegetables, Fruiting Vegetables, Leafy Vegetables,
Tuber Vegetables, Strawberry and Nursery, Greenhouse and Landscape Ornamentals. Bayer
CropScience Report Number 200566
Guthrie. F., I. Denholm and G.J. Devine, 2003. Rothamsted Research, Harpenden, Hertfordshire,
UK. And R. Nauen. BCS, Leverkusen, Germany. Proceedings of the BCPC Conference - Pest
and Diseases (2003) 795. Biological Evaluation of Spiromesifen against Bemisia (abaci and an
Assessment of Resistance risks.
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