# Annex B



# Spirotetramat

B.3 Data on application and further information

Reviewed by:
AGES, Austria– 2 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

B.3 Data on application and further information
B.3.1 Data on application relevant to the active su bstance (Annex IIA 3.1 to 3.6)

B.3.1.1 Function (Annex IIA 3.1)
Spirotetramat is an insecticide.
B.3.1.2 Effects on harmful organisms (Annex IIA 3.2 )
Spirotetramat acts in the target pests mainly after oral ingestion and feeding from the plants.
B.3.1.2.1 Nature of the effects on harmful organism s (Annex IIA 3.2.1)
Spirotetramat is very effective against aphids, sca les, mealy bugs, psyllids, white flies and selected thrips. It has a slow initial but an excellent residual activi ty and acts mainly against immature stages and requ ires oral ingestion. In many cases it outperforms most of the currently used products, as for example control of the Californian red scale ( Aonidiella aurantii ) on citrus, or control of the sweet potato whitefl y ( Bemisia tabaci ) on vegetables. It is an important tool in resistance m anagement, as it has a new mode of action.
B.3.1.2.2 Translocation in plants (Annex IIA 3.2.2)
Spirotetramat is highly systemic and possesses not only xylem-, but also phloem-mobility. Once taken u p by the plant, the active substance moves acropetal in the xylem and acropetal and basipetal in the phloem

. After treatment, even the new shoots or the roots a re protected from sap-sucking pests due to this spe cific biological property.

B.3.1.3 Field of use (Annex IIA 3.3)
Spirotetramat is intended to be used as an insectic ide in agriculture on a range of crops such as citr us, pome and stone fruits; tree nuts, grape; strawberries, f ruiting and leafy vegetables (indoor and outdoor); brassica vegetables, hops but also on tubers vegetables and tropical fruits such as pineapple, mangoes, bananas and cotton. It is also considered, to use the product o n ornamentals and trees.
B.3.1.4 Harmful organisms controlled and crops or p roducts protected or treated (Annex

IIA 3.4)
The harmful organisms controlled comprise aphids, s cales, mealy bugs, psyllids, white flies and select ed thrips species.
B.3.1.4.1 Details of existing and intended uses (An nex IIA 3.4.1)
Spirotetramat is intended to be used especially in top fruit, citrus, grapes, berries, fruiting and le afy vegetable, and hops. The details of the intended us es are defined in Document D1. Some examples are listed below:– 3 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Citrus (Orange) Citrus (Lemon) Diaspididae Aonidiella aurantii Aspidiotus neri Apple, Pear Pemphigidae Aphididae

Psyllidae Eriosoma lanigerum Aphis pomi Dysaphis plantaginea Psylla pyri Cherries, plums, peaches, nectarines, apricots Aphididae Aphis pomi Dysaphis plantaginea Brachycaudus helichrysi Myzus cerasi Myzus persicae Fruiting vegetables Aleyrodidae

Aphididae Bemisia tabaci Trialeurodes vaporariorum Myzus persicae Aphis gossypii Cole crops Aphididae Brevicoryne brassicae Lettuce Aphididae Nasonovia ribis-nigri Hop Aphididae Phorodon humuli Strawberries Aphididae, Aleyrodidae Bemisia tabaci, Trialeurodes vaporariorum, Aphis ssp. Onions Thripidae Thrips tabaci Beans Aphididae, Aleyrodidae Aphis ssp., Trialeurodes vap
., Bemisia tabaci Grapes Pseudococcidae Planococcus ssp.

B.3.1.4.2 Details of harmful organisms against whic h protection is afforded (Annex IIA 3.4.2)
Spirotetramat provides excellent control of a broad number of sucking pests belonging to the Sternorrh yncha sub-order (whiteflies; psyllids; scales; mealybugs; aphids). These pests have generally a high reprodu ction potential and a lack of control of them can lead to considerable losses of crop value. Their short lif e cycle can contribute to the development of resistance to insecticides, as for example whiteflies and aphids. Sap-sucking pests are responsible for three types o f damage: direct damage (feeding on sap, which can weaken the plants; cause deformations and reduce th e yield); indirect damage (accumulation of honeydew produced by the insects, which serves as a substrat e for the growth of black sooty mold on leaves and fruit), transmission of viruses. For indoor fruiting vegetables, whiteflies, and amo ng them Bemisia tabaci , are major pests especially for Southern Europe countries. They have developed resi stance to insecticides from different chemical clas ses. 75 g a.i/ha/ m leafwall of spirotetramat, applied w ith a minimum of 7 days interval in case of multipl e applications, provide a very high level of control of B. tabaci (including resistant populations) offering at leas t 3 weeks of residual efficacy after the last applica tion. These applications will also be able to contr ol aphids populations which could infest the crop at the same time. The Californian red scale, A. aurantii is a difficult to control space species and is a m ajor pest on citrus (orange, mandarine) as infested fruits have a low m arketable value for fresh production. One applicati on at 60 g a.i/ha/m c.h of spirotetramat, targeted agains t the first generation, at crawlers movement, is ab le to provide a season-long control until maturity of the fruits. Additional spray may be requested however to control later occurring pests, such as Aleurothrixus floccosus (Homoptera: Aleyrodidae) at 75 g a.i/ha/ m c.h. On apple several aphids species can weaken the grow th of the trees (like Eriosoma lanigerum and Aphis pomi to a lesser extent). Dysaphis plantaginea can cause direct feeding damage on fruits. The wo oly apple aphid E. lanigerum

is a hard to reach insect as they produce filament ous wax (“wool”) which protect them and the full systemicity of spirotetramat contribut es greatly to its excellent efficacy against this p est. These– 4 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

aphids species can be effectively controlled by spi rotetramat, from 45 g a.i/ha/m c.h ( A. pomi; D. plantaginea ) to 75 g a.i/ha/m c.h ( E. lanigerum ). It has been also observed that one application a gainst E. lanigerum

(post-flower, at movement of crawlers) was able to provide sinificative control of later occurring A. pomi , infesting new growing shoots, thanks to its longe vity and its full systemicity. Psylla piri

on pear is the major sucking pest on pear; high po pulations of adults and nymphs feeding on new shoots can have a direct effect on the growth of tr ees; they also produce a vast amount of honeydew, damaging the leaves and the fruits. In the majority of situations , one application of spirotetramat a t 75 g a.i/ha/ m canopy height , targeted against the seco nd generation when eggs are at the yellow stage /fi rst larval stage visible is sufficient to provide a hig h level of control of the pear sucker populations f or at least 3 weeks.

B.3.1.4.3 Effects achieved (Annex IIA 3.4.3)
After having ingested spirotetramat, juvenile stage s of insects such as aphids, whiteflies cannot moul d properly and die within 2 to 5 days. The speed of l ethal effect is variable, depending on the life sta ges or on external parameters. Spirotetramat can also drastic ally reduce the number of viable larvae deposited b y adult aphids.

B.3.1.5 Mode of action (Annex IIA 3.5)
The mode of action of Spirotetramat is the suppress ion of the lipid synthesis. This novel MoA aims at a biochemical target and inhibits the proper formatio n of the ACCase. As a consequence, the total lipids in the target pests are significantly decreased and this l eads in the end to the death of the insect.
B.3.1.5.1 Mode of action, mechanism(s) and pathway( s) involved (Annex IIA 3.5.1)

Reference: Spirodiclofen: Mode of Action and Resistance Risk A ssessment in Tetranychid Pest Mites Author(s), year: Nauen R, 2005 Report/Doc. number: M-277046-01-1 Guideline(s): not relevant GLP: not relevant

Spirotetramat is a new insecticide and acaricide pa rticularly effective against a broad range of sucki ng pests of agronomic importance, including aphids and white flies. Its mode of action is similar to that of spi rodiclofen and spiromesifen, i.e. inhibition of lipid biosynth esis by acting on acetyl CoA carboxylase [see refer ence below]. Spirotetramat was shown to strongly reduce the lipid content in aphids feeding on leaves treat ed with the compound. More detailed investigations with 14C -acetate as a radiolabeled precursor of fatty acids revealed a full inhibition of de novo synthesis of lipids in aphids. Spirotetramat also showed excelle nt efficacy against insecticide resistant pests (including neon icotinoid resistant whiteflies) and will most likel y be classified within group 23 of the IRAC (Insecticide Resistance Action Committee) mode of action classification scheme, i.e. grouped together with s pirodiclofen and spiromesifen. Due to the lack of a ny cross-resistance to existing chemical classes of in secticides, spirotetramat will be an invaluable new tool to manage insecticide resistance in many crops and pes ts worldwide. Due to its physicochemical properties, spirotetrama t effectively acts on a broad spectrum of pests as mentioned above, e.g. it shows an excellent efficac y against different aphid species, including Myzus persicae, Aphis gossypii and Phorodon humuli. Due t o its mode of action as lipid biosynthesis inhibito r particularly juvenile stages of aphids are affected by spirotetramat, whereas adults are strongly affe cted in their fecundity, which from an applied point of vie w will drastically reduce population development un der field conditions. Spirotetramat applied foliarly exhibite d an excellent systemic efficacy against aphids and whiteflies, whereas its contact efficacy against th ese pests is rather limited. Once penetrated into t he plant spirotetramat will be readily hydrolyzed to its eno l form. The BYI08330-enol shows a water solubility of 150– 5 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

ppm and is a weak acid (pKa-value 5.2), rendering t he compound mobile within the symplast (phloem) of the plant according to the “weak acid hypothesis”. Henc e it can move acro- and basipetally, and even prote cts the roots when foliarly applied.
B.3.1.5.2 Details of active metabolites and degrada tion products (Annex IIA 3.5.2)
Spirotetramat (BYI08330) is transformed within the plant rapidly to the de-acylated BYI08330-enol. BYI08330-enol is the only major metabolite of spiro tetramat which exhibits a relevant insecticidal act ivity. Due to its weak acidity (pKa 5.2) BYI08330-enol is responsible for the phloem systemic properties of t he compound. In spite of this it has some advantages t o apply spirotetramat and not directly BYI08330-eno l since biological trials have shown a higher efficac y of spirotetramat.

N H O O

O O

O N H O H

O

O
Spirotetramat BYI08330-enol

B.3.1.5.3 Information relative to the formation of active metabolites and degradation products

(Annex IIA 3.5.3)

Please refer to B.3.1.5.2.
B.3.1.6 Information on possible occurrence of the d evelopment of resistance (Annex IIA 3.6)
Introduction – resistance risk analysis spirotetram at Resistance in arthropod pest species comprises a ch ange in the genetic composition of a population in response to selection by pesticides such that contr ol in the field may be impaired at recommended application rates. Selection for resistance in pest populations (including weed, fungi, mites, and ins ects) due to frequent applications of agrochemicals has been one of the major problems in modern agriculture for many years. Spirotetramat (BYI 8330) will be listed together wi th spirodiclofen and spiromesifen as a member withi n group 23 of the IRAC (Insecticide Resistance Action Committee) mode of action classification scheme (www.irac-online.org). It is listed as an inhibitor of lipid biosynthesis and can principally be used in alternation with any insecticide of other mode of action classe s. Due to the fact that the tetramic acid derivativ e spirotetramat belongs to a completely new chemical class of insecticides, cross-resistance to other insecticides is rather unlikely, and this was confi rmed by investigations carried out recently (Nauen, unpublished). The experimental results out of these studies are reported below. The efficacy of spirotetramat against several sucki ng pest species was tested with laboratory strains resistant and susceptible to conventional insectici des, e.g. organophosphates, carbamates, pyrethroids
, chlorinated hydrocarbons and neonicotinoids. Baseli ne susceptibility and resistance monitoring studies have been performed for those species considered as high risk organisms and targeted by the active ingredie nt mentioned above, and are mentioned below. The studi es were performed according to EPPO Guideline PP 1/213 (see Heimbach et al., 2000; OEPP/EPPO, 1999) whereever necessary. Species tested included the green peach aphid ( Myzus persicae ), the cotton aphid ( Aphis gossypii ), the damson hop aphid ( Phorodon humuli ), the cotton whitefly ( Bemisia tabaci ) and the greenhouse whitefly ( Trialeurodes vaporariorum ). Spirotetramat was particularly tested against bioch emically characterized, multi-resistant strains of B. tabaci derived from vegetables from different parts in the world incl. European areas such as southern Spain– 6 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

(Rauch & Nauen, 2003). The cotton whitefly was cons idered to be one of the most important pest species due to its pronounced multi-resistance to numerous insecticides including neonicotinoids. Several of t he neonicotinoid resistant strains show high monooxyge nase activity, elevated esterase and glutathione Stransferase levels, and target-site mutations leadi ng to acetylcholinesterase insensitivity and kdr (k nock down resistance) (Nauen and Denholm, 2005). Spirotetramat turned out to be highly active in bot h insecticide susceptible and resistant strains of several sucking pest species, and showed no cross-resistanc e to other chemical classes of insecticides tested in these strains. Our studies using for example B. tabaci
, T. vaporariourum

and M. persicae

(as aphid representative most prone to resistance development ) revealed that spirotetramat is a new chemical opt ion with a new mode of action for example in aphids to control multi-resistant sucking pests. It is an exc ellent partner of many known chemical classes of insectici des in resistance management strategies

Materials and methods Insecticides All reference insecticides (technical material) use d were either obtained in-house or purchased from Ehrenstorfer (Augsburg, Germany) and Riedel de Haen (Seelze, Germany), respectively. All technical insecticides used were of analytical grade (purity >97%).

Insects Aphids Myzus persicae

(strains NS, JR and F04-01) and Aphis gossypii (strain HS) were maintained on cabbage and cotton plants, respectively under the following conditions: day temperature 24°C, night temperatur e 20°C, 18 : 6 h light : dark and 65% RH. For all exp eriments aphids (nymphs) from synchronized populati ons were used. In order to obtain synchronized populations, leaf d iscs (30 mm in diameter) were cut from Chinese cabb age and placed on a bed of agar (10 g litre -1 ; 2 mL per well) in six-well tissue culture plates (Greiner Bio-One GmbH, Frickenhausen, Germany). Fifteen to 20 adult apterous aphids were placed in each well before the plates were covered with a ventilated lid. The plat es were stored upside down in the laboratory at 22° C and an ambient photoperiod. The aphids produced nymphs and after 24 h adult aphids were removed and nymphs within a similar age class were obtained. Th e leaf discs with the nymphs were placed onto a Chinese cabbage plant and maintained until they rea ched the stage which was needed for the respective test. Synchronised nymphs were kept in the greenhou se at a day temperature of 24°C, a night temperatur e of 20°C, 18 h : 6 h light : dark and 65% RH. Cotton aphids ( A. gossypii ) were synchronized in a similar manner, but using cotton leaf discs instead of cabb age leaf discs.

Whiteflies All strains were maintained on cotton plants ( Gossypium hirsutum ) at 25 ± 1°C, 60% RH and a photoperiod of L:D 16h:8h. Table 1 lists all different strains of B. tabaci and T. vaporariorum

used throughout the study. Strains CRE04-01, ISR-02 and ESP-00 are highly resi stant to neonicotinoid insecticides as well as to o ther, conventional whitefly compounds such as organophosp hates, carbamates, pyrethroids, pymetrozine and IGR ́s (Rauch & Nauen, 2003). The resistance pattern of the T. vaporariorum strains is not known in detail, but UH-06 and GrKS-05 were obtained from places wit h difficulties to control these pests.– 7 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Table 1. Whitefly strains tested.

Strain Origin Date Host plant Biotype Bemisia tabaci CRE04-01 Crete 2004 Tomato Q BR-JM03 Brazil 2003 Tomato B ISR-02 Israel 2002 Roses B MEX03-02 Mexico 2003 Tomato B ESP-00 Spain 2000 Pepper Q SUD-S Sudan 1994 Cotton - Trialeurodes vaporariorum UH-06 Germany 2006 Vegetables - GrKS-05 Greece 2005 Vegetables - HS-Ref Germany 1996 Ornamentals -

Bioassays useful to monitor resistance Leaf-dip bioassay aphids: A leaf-dip bioassay procedure was designed to test all compounds under the same conditions in 6-well tissue culture plates. Th e wells of the tissue culture plates were filled wi th 2 ml Agar (1% (w/v)). Several plates were usually prepar ed and stored at 4°C until used. Plates were equili brated to room temperature and leaf discs (Ø 30 mm) were c ut out of the first and second fully expanded true leaves from three-week old plants, for example Brassica olearacea for M. persicae or G. hirsutum for A. gossypii . The leaf discs were then dipped into serial aqueo us dilutions of active ingredient in 0.02 % (w/v) Triton X-100, and after drying the leaf discs were transferred to 6-well plates. In order to assess ba seline susceptibility using strains NS ( M. persicae ) and AGS ( A. gossypii ), respectively, spirotetramat was tested at least twice with up to six replicates per concentra tion. Ten 3-4d old nymphs from synchronized populat ions were confined to each well. Diagnostic concentratio ns for each insecticide, i.e. rounded LC 50 , 95 , 99 -values, were calculated from log-dose probit-mortality regr essions using Polo PC (LeOra Software, California) after 72h. Field strains collected can be tested at diagn ostic concentrations, i.e. a single plate consists of six replicates of one insecticide concentration. Aphids unable to move and showing strong symptoms of poisoning were scored as dead. The methodology has been published including results in more detail by Nauen and Elbert (2003). However, no serious case o f field resistance in any aphid species has yet bee n detected with spirotetramat.

Leaf-dip bioassay whiteflies: In leaf dip bioassays, cotton leaf discs (30 mm in diameter) were dipped for 5 sec in aqueous solutions of insecticides containing 0.2 g litre -1 Triton X-100 as a non-ionic wetting agent (Elbert & Nauen, 1996). Air-dried leaf discs were t hen placed with their adaxial surface downwards ont o a bed of agar (14 g litre -1 ) in a small Petri dish (40mm in diameter). Adult w hiteflies were collected from rearing cages by means of a vacuum-pump powered aspirator a nd after brief CO 2 anesthesia, 20 adults were placed onto the leaf-discs. Afterwards each Petri dish was sealed with a ventilated lid and stored upside dow n. Whiteflies were scored for mortality after 72 h.

Egg/larval-dip bioassay whiteflies: Due to the fact that spirotetramat is particularly effective against juvenile stages all tests were done using whitefly nymphs. One leaf of cotton plants with two true lea ves was removed and the remaining one was cut to a size of c. 12-15 cm2. These plants were infested with adult whiteflies (c. 300 per leaf) for 8h. Afterwards, th e whiteflies were removed and the infested leaves w ere dipped in serial dilutions of insecticide for 5 s. Each set of plants was dipped at appropriate time i ntervals after infestation to cover the correct developmenta l stages in the bioassays, i.e. eggs or 2nd/3rd ins tar nymphs. Percentage mortality was scored on represen tative leaf areas after the last larval instar has been reached (after 14-17 d at 25°C, 65% RH and 16h:8h ( L:D), starting from the egg stage). A typical exper iment with spirotetramat against 2 nd instar nymphs (both species) was assessed for effi cacy 8-10d after treatment.– 8 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Calculations LC 50 - and LC 95,99 -values and their 95% confidential intervals were c alculated from probit regressions using the computer program POLO-PC (LeOra Software, Berke ley, USA) or GrapPad Prism v4.0 (GraphPad Software, San Diego, USA).

Results Baseline susceptibility and cross-resistance studie s.

Aphids Spirotetramat (BYI 8330) showed excellent efficacy against all strains of aphids tested in a leaf-dip bioassay (Table 2).

Table 2. Log-dose probit-mortality baseline data of spirotetramat for some strains of M. persicae and A. gossypii. Leaf-dip bioassay, 3rd instar nymphs, 3d.

Species Strain LC 50 , ppm LC95, ppm LC99, ppm M. persicae NS 0.69 5.5 17.7 JR 0.59 4.1 12.3 F04-01 0.27 1.8 5.3 A. gossypii HS 3.5 21 58

Strain JR is known to be resistant against organoph osphates, carbamates and pyrethroids due to esteras e E4 over-expression and MACE (modified acetylcholine sterase), respectively. However, strain JR original ly derived from tobacco plants represents a typical R3 strain of M. persicae (Nauen & Elbert, 2003). Strain F04- 01 is a field strain collected in France and shows a similar resistance pattern as JR. Spirotetramat s howed excellent efficacy against both strains, which can be considered as representatives of the most resist ant strains of M. persicae

currently known. There is a max. 3-fold (natural) variation in response to spirotetramat between the three different M. persicae strains tested (Table 2), and never been exposed t o spirotetramat under field conditions. The insecticide susceptible reference strain HS of A. gossypii was about 3-4 times less susceptible than M. persicae NS. P. humuli

obtained from German hop (Hallertau) turned out to be as susceptible as M. persicae , so field samples of both species can be checked u sing the same diagnostic dose. For future resistance monitoring purposes it is sug gested to use a diagnostic dose of spirotetramat of 10 and 30 ppm in a leaf-dip bioassay for nymphs of M. persicae (P. humuli) and A. gossypii , respectively

.

Whiteflies Bemisia tabaci All strains of B. tabaci

tested responded quite susceptible to spirotetrama t with a maximum variation of 3.8- fold between strains, irrespective which biotype is considered (Table 3).– 9 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Table 3. Log-dose probit-mortality baseline data of spirotetramat on some strains of B. tabaci. Leafdip bioassay, 2 nd instar nymphs, 10d.

Strain LC 50 , ppm FL 95% RR SUD-S 0.26 0.11 – 0.59 CRE04-01 1.0 0.72 – 1.4 3.8 BR-JM03 0.64 0.30 – 1.4 2.5 ISR-02 0.72 0.25 – 2.0 2.8 MEX03-02 0.49 0.38 – 0.63 1.9 ESP-00 0.74 0.15 – 3.5 2.8

Composite
LC 50 , ppm 0.78 0.47 – 1.3
LC 95 , ppm 12 5.9 – 15 LC 99 , ppm 36 15 – 170
Abbreviations: FL = Fiducial Limits, RR = Resistance Ratio, Composite = all data combined

The highest concentration applied against nymphs wa s 200ppm and provides a 100% efficacy against all strains tested. A mean LC 99 -value of 36ppm was obtained and derived from all r esults combined (composite, Table 3). Therefore future monitoring activities fo r spirotetramat susceptibility in field populations will be carried out using two concentrations, i.e. 10ppm an d 40ppm representing the approx. LC 95 and LC 99 , respectively

.
Apart from spirotetramat also other insecticides be longing to different mode of action classes were te sted against some strains in order to check for possible , metabolically or target-site driven cross-resista nce. Especially the Q-type strains (ESP-00 and CRE04-01) and the B-type strain ISR-02 were highly resistant to neonicotinoi d insecticides and other insecticides when compared to SUD-S (Tables 4-7). No cross-resistance between spi rotetramat and any other insecticide was observed i n the experiments conducted.– 10 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Table 4. Cross resistance pattern of B. tabaci strain SUD-S. Leaf-dip bioassay using either 2 nd instar nymphs (*) or adults as described under materials a nd methods.

Table 5. Cross resistance pattern of B. tabaci strain ESP-00. Leaf-dip bioassay using either 2 nd instar nymphs (*) or adults as described under materials a nd methods.– 11 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Table 6. Cross resistance pattern of B. tabaci strain CRE04-01. Leaf-dip bioassay using either 2 nd instar nymphs (*) or adults as described under mate rials and methods.

Table 7. Cross resistance pattern of B. tabaci strain ISR-02. Leaf-dip bioassay using either 2 nd instar nymphs (*) or adults as described under materials a nd methods.– 12 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Trialeurodes vaporariorum In addition to B. tabaci

, three strains of the greenhouse whitefly were tes ted for their susceptibility against spirotetramat. Second instar nymphs of T. vaporariorum were in general somewhat less susceptible to spirotetramat when compared to B. tabaci nymphs. However, variation in LC 50 -values between strains was also 3-fold, and similar diagnostic doses will be u sed.

Table 8. Log-dose probit-mortality baseline data of spirotetramat on some strains of T. vaporariorum

. Leaf-dip bioassay, 2nd instar nymphs, 10d.

Strain LC 50 , ppm FL 95% UH-06 2.49 1.63 – 3.80 GrKS-05 1.76 1.40 – 2.20 HS-Ref 5.44 2.27 – 11.9

Abbreviations: FL = Fiducial Limits

RESISTANCE MANAGEMENT RECOMMENDATIONS Monitoring for resistance will be carried out routi nely (wherever possible even annually) with importa nt pests such as some aphid species and whiteflies and resul ts will be published regularly. According to EU dir ective 91/414/EEC national authorities have to consider re sistance risk associated with the introduction of p lant protection products as part of the authorization pr ocess (Heimbach et al., 2000). Guidelines for prope r resistance risk evaluation have recently been appro ved by the European and Mediterranean Plant Protect ion Organization (EPPO) and are taken into account duri ng the registration procedure (OEPP/EPPO, 1999; McNamara and Smith, 2000). The directives presented hereafter include a number of options. If possible , the first one should be used. So long-term a.i. rotatio n is considered better than short-term rotation; be ing better than a mixture; and the last one better than a spra ying sequence with only one active ingredient. Control practices for the mentioned pests differ co nsiderably between countries, crops, varieties and climatic conditions. Therefore a general strategy has to cov er a wide range of flexibility. Its concrete implem entation and adaptation to local conditions has therefore to be achieved by regional specialists.

Spirotetramat is a tetramic acid derivative with a similar mode of action as spirodiclofen and spirome sifen, and therefore a member of IRAC Group 23 within the IRAC Mode of Action Classification scheme (www.irac

online.org ). In order to prevent possible resistance developm ent against spirotetramat the following points should be considered as a preliminary guidance unti l further recommendations will be published:

• Long-term rotation act best against rapid selectio n of resistant populations. This means, that a change of active ingredient should take place when the next generation of the pest has to be treated to prevent a selection with the other chemical grou p within the same generation of the pest.

• Use effective doses of the individual components w hen applying tank mixtures and the full recommended rate of in co-formulations.

• Control should not be carried out with products of just one chemical class.

• The use of non-specific products helps to prevent the development of resistance.

• All possible cultivation techniques should be used alongside physical and biological pest control methods.

• Crop protection products should be used in such a way as to reduce the risk to beneficial organisms.

• Preparations should be used at the recommended dos es and spray intervals.

• Ensure that uniform spray coverage is achieved.

• If signs of diminished efficacy become evident, do not carry out a follow-up treatment with an active ingredient of the same chemical class.

• Monitor the situation wherever possible so as to d etect the first signs of resistance.– 13 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

B.3.2 Data on application relevant to the plant pro tection product (Annex IIIA 3)

B.3.2.1 Field of use (Annex IIIA 3.1)
Spirotetramat is an insecticide in agriculture for foliar application.
B.3.2.2 Effects on harmful organisms (Annex IIIA 3. 2)
Spirotetramat is very effective against aphids, sca les, mealy bugs, psyllids, white flies and selected thrips .It has a slow initial but an excellent residual activi ty and acts mainly against larvae. It requires oral ingestion. It outperforms most of the currently used products and is an important tool in resistance management, as it has a new mode of action.– 14 –Spirotetramat – Volume 3, Annex B.3, Data on application and further informationApril 2008B.3.2.3 Details of representative uses (Annex IIIA3.3)B.3.2.3.1 Summary of representative uses evaluated(Spirotetramat) (Annex IIA 3.3.1)Crop and/or situation(a)MemberState orCountryProductnameFGorI(b)Pests orGroup ofpestscontrolled(c)FormulationApplicationApplication rate per treatmentPHI(days)(l)Remarks:(m)Type(d-f)Conc.of as(i)methodkind(f-h)growthstage &season(j)numbermin max(k)intervalbetweenapplications (min)kg as/hLmin maxwater L/hamin maxkg as/hamin maxCitrusall typesEU-S Spirotetramat F scales,aphids,mealy bugs,mitesOD 150sprayBBCH 78 atlastapplication;Firstapplication notearlier thanmid of May2 21 0.00961000 L/haand m CH*,max 3000L/ha0.096 kgas./ha andm CH*,max0.288 kgas./ha(3 metres)14representative usefor the EUevaluationLettucehead andleafyEU-NEU-SSpirotetramat F aphids OD 150sprayBBCH 48 atlast applicationmax. 2 14 0.0072 -0.0144500-1000 0.072 7representative usefor the EUevaluationLettuce,head andleafyEU-NEU-SSpirotetramat G aphids OD 150sprayBBCH 48 atlast applicationmax. 2 14 0.0072 -0.0144500-1000 0.072 7representative usefor the EUevaluationRemarks:(a) For crops, the EU and Codex classifications (both) should be used; where relevant, theuse situation should be described (eg.fumigation of a structure)(b) Outdoor or field use (F), glasshouse application (G) or indoor application (I)(c) eg. biting and suckling insects, soil born insects, foliar fungi, weeds(d) eg. wettable powder (WP), emulsifiable concentrate (EC), granule (GR)(e) GCPF Codes - GIFAP Technical Monograph No 2, 1989(f) All abbreviations used must be explained(g) Method, eg. high volume spraying, low volume spraying, spreading, dusting, drench(h) Kind, eg. overall, broadcast, aerial spraying,row, individual plant, between the plants -type of equipment used must be indicated(i) g/kg or g/l(j) Growth stage at last treatment (BBCH Monograph,Growth Stages of Plants, 1997,Blackwell, ISBN 3-8263-3152-4), including where relevant, information on season attime of application(k) The minimum and maximum number of application possible under practical conditionsof use must be provided(l) PHI - minimum pre-harvest interval(m) Remarks may include: Extent of use/economic importance/restrictions– 15 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Details of existing and intended uses

Crops Crop Code citrus ssp.:

oranges mandarins lemons limes Pummelo Clementine CIDSS

CIDSI CIDRE CIDLI CIDAF CIDGR CIDCL lettuce LACSP

B.3.2.3.2 Harmful organisms against which protectio n is afforded (Annex IIIA 3.3.2)
Crops Crop Code Pest Pest Code citrus ssp.:

oranges mandarins

lemons limes CIDSS

CIDSI CIDRE

CIDLI CIDAF Aonidiella aurantii

Parlatoria pergandei Aleurothrixus floccosus Pseudococcus citri Aspidiotus nerii AONDAU PARLPE ALTHFL PSECCI ASPDNE

lettuce LACSP Nasonovia ribis-nigri (Myzus persicae (Hyperomyzus lactucae (Pemphigus bursarius NASORN MYZUPE) HYLEPA) PEMPBU)

B.3.2.3.3 Effects achieved (Annex IIIA 3.3.3)
After having ingested spirotetramat, juvenile stage s of insects such as aphids, whiteflies cannot moul t properly and die within 2 to 5 days. The speed of l ethal effect is variable, depending on the life sta ges or on external parameters. Spirotetramat can also drastic ally reduce the number of viable larvae deposited b y adults aphids.
B.3.2.4 Application rate (Annex IIIA 3.4)
Rate of application per unit treated:

Crop L product/ha kg as /ha citrus ssp: oranges, mandarins, lemons, limes 0.64 per m CH* max.:1.92 0.096 per m CH* max.: 0.288

lettuce, field 0.48 0.072 lettuce, glasshouse 0.48 0.072

*: CH: C anopy H eight

B.3.2.5 Concentration of active substance in materi al used (Annex IIIA 3.5)
Spirotetramat OD 150 contains 150 g active substanc e/L finished product.– 16 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

The concentration of active substance in the spray solution applied is as follows:

Citrus: 0.0096% Lettuce: 0.0072% - 0.0144%
B.3.2.6 Method of application (Annex IIIA 3.6)
Lettuce, field: Overall spray application with sta ndard tractor mounted field sprayers or Knappsacksp rayers with spray volume of 500-1000 L/ha

Lettuce, greenhouse: Overall spray application with Knappsacksprayers with spray volume of 500-1000 l/ha

Citrus: Overall spray application with standard tr actor mounted field sprayers or Knappsacksprayers with spray volume of 1000-5000 L/ha

B.3.2.7 Number and timing of application, timing, g rowth stages (of crop and harmful

organism) and duration of protection (Annex IIIA 3. 7)
Crop number of applications timing of applications duration of protection

citrus ssp: oranges, mandarins, clementines, lemons, limes 1-2 at movement of crawlers (scales, mealybugs); at beginning of infestation (whiteflies) min. 21 days

lettuce, field 1-2 at beginning of infestation min. 14 days lettuce, glasshouse 1-2 at beginning of infestation min. 14 days

B.3.2.7.1 Maximum number of applications and their timings (Annex IIIA 3.7.1)

Crop maximum number of applications timing of applications

citrus ssp: oranges, mandarins, clementines, lemons, limes 2

lettuce, field 2 lettuce, glasshouse 2 The spray is performed only when the relevant pest is present and when the Economic Threshold Level (ETL) is reached.

B.3.2.7.2 Growth stages of crops or plants to be pr otected (Annex IIIA 3.7.2)

Crop timing of applications citrus ssp: oranges, mandarins, clementines, lemons, limes BBCH 71-78

lettuce, field BBCH 42-43 lettuce, glasshouse BBCH 42-43– 17 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

B.3.2.7.3 Development stages of the harmful organis m concerned (Annex IIIA 3.7.3)
Spirotetramat is mostly active against juvenile sta ges. For scales control such as for A. aurantii the product should be targed at crawlers movement (which corres ponds to the first larval which is a mobile one. Fo r aphids , where populations are frequently composed of mixed development stages, Spirotetramat should be applied at beginning of infestations, when populati ons start to develop. For whiteflies, beginning of infestation is also the optimal timing as the product is mainly active against larvae and nymphs.

B.3.2.7.4 Duration of protection afforded by each a pplication (Annex IIIA 3.7.4)
Duration of the protection of at least 7 days up to 28 days is afforded.

B.3.2.7.5 Duration of protection afforded by the ma ximum number of applications

(Annex IIIA 3.7.5)
Duration of the protection of at least 7 days up to 28 days is afforded.
B.3.2.8 Necessary waiting periods or other precauti ons to avoid phytotoxic effects on

succeeding crops (Annex IIIA 3.8)
B.3.2.8.1 Minimum waiting periods or other precauti ons between last application and sowing or

planting succeeding crops (Annex IIIA 3.8.1)

Must be clarified.
B.3.2.9 Limitations on choice of succeeding crops ( Annex IIIA 3.8.2)

There is no such limitation.
B.3.2.9.1 Description of damage to rotational crops (Annex IIIA 3.8.3)
Rotational crops sown at the appropriate time will not be damaged.
B.3.2.10 Proposed instructions for use (Annex IIIA 3.9)
Please refer to attached label proposal.
B.3.2.11 Other/Special Studies (Annex IIIA 3.10)
No other special study was carried out.– 18 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

B.3.3 Summary of data on application
Spirotetramat (BYI 08330) is intended to be used as an insecticide in agriculture on a range of crops such as citrus, pome and stone fruits; grape; strawberries, fruiting and leafy vegetables (indoor and outdoor) ; brassica and bulb vegetables, hops but also on tube rs and tropical fruits such as pineapple, mangoes, bananas, tree nuts and cotton. In the EU the repres entative uses for Annex-1-inclusion consist of lett uce as a low crop and citrus as a high crop.

Spirotetramat is very effective against aphids, sca les, mealy bugs, psyllids, white flies and selected thrips. It has a slow initial but an excellent residual activi ty and acts mainly against immature stages and requ ires oral ingestion. In many cases it outperforms most of the currently used products, as for example control of the Californian red scale ( Aonidiella aurantii ) on citrus, or control of the sweet potato whitefl y ( Bemisia tabaci ) on vegetables. It is an important tool in resistance m anagement, as it has a new mode of action.

Spirotetramat is highly systemic and possesses not only xylem-, but also phloem-mobility. Once taken u p by the plant, the active substance moves acropetal in the xylem and acropetal and basipetal in the phloem

. After treatment, even the new shoots or the roots a re protected from sap-sucking pests due to this spe cific biological property.– 19 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

B.3.4 Further information on the active substance ( Annex IIA 3.7 - 3.9)
B.3.4.1 Recommended methods and precautions concern ing handling, storage, transport or

fire (Annex IIA 3.7)
A Safety Data Sheet for the technical material is p rovided.

Reference: Safety Data Sheet Author(s), year: Bayer CropScience Safety Data Shee t for Spirotetramat TC, Version 1, EU Document No. 102000009024 Guideline(s): not relevant GLP: not relevant

B.3.4.1.1 Handling and storage:
Handling: Advice on safe handling Use only in area provided with appropriate exhaust ventilation. Advice on protection against fire and explosion Dust may form explosive mixtures with air. Take measures to prevent the build up of electrosta tic charge. Keep away from heat and sources of ignition. Storage: Requirements for storage areas and containers Store in original container. Keep container tightly closed. Store in a place accessible by authorized persons o nly. Advice on common storage Keep away from food, drink and animal feedingstuffs

. Suitable materials Only use containers that are approved specifically for the product
B.3.4.1.2 Transport information:
Land transport - ADR/ RID/ ADNR: UN-No: 3077 Labels: 9 Packaging group III Hazard no 90 Description of the goods: UN 3077 ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (SPIROTETRAMAT) Sea transport - IMDG: UN-No: 3077 Class: 9 Packaging group: III EMS: F-A, S-F Marine pollutant: Marine pollutant Description of the goods: ENVIRONMENTALLY HAZARDOU S SUBSTANCE, SOLID, N.O.S. (SPIROTETRAMAT)– 20 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Air transport - IATA: UN-No: 3077 Class: 9 Packaging group: III Description of the goods: ENVIRONMENTALLY HAZARDOU S SUBSTANCE, SOLID, N.O.S. (SPIROTETRAMAT)

B.3.4.1.3 Fire fighting measures:
Suitable extinguishing media water spray foam carbon dioxide (C0 2 ) sand

Specific hazards during fire fighting In the event of fire the following can be released: hydrogen cyanide (hydrocyanic acid) carbon monoxide (CO) nitrogen oxides (NO x )

Special protective equipment for fire-fighters In the event of fire and/or explosion do not breath e fumes. Use breathing apparatus.

Further information Collect contaminated fire extinguishing water separ ately. This must not be discharged into drains.

B.3.4.2 Procedures for destruction or decontaminati on (Annex IIA 3.8)
B.3.4.2.1 Pyrolytic behaviour (Annex IIA 3.8.1)
Not applicable as the product contains no chlorine.

B.3.4.2.2 Detailed instructions for safe disposal ( Annex IIA 3.8.2)

Product: Do not dispose of waste into the sewerage system. D ispose of by incineration in an authorized special waste incineration plant. Comply with local legislation. For larger quantities, contact manufacturer.

Contaminated packaging: Packaging that cannot be cleaned should be disposed of as product waste. It must be incinerated in an authorized special was te incineration plant. Comply with local legislatio n.

B.3.4.2.3 Methods other than controlled incineratio n for disposal of the a.s., contaminated

packaging and contaminated materials (Annex IIA 3.8 .3)

No methods, other than controlled incineration are recommended for disposal.– 21 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

B.3.4.3 Emergency measures in case of accident (Ann ex IIA 3.9)

B.3.4.3.1 First aid measures:

General advice Move out of dangerous area. Place and transport vic tim in stable position (lying sideways). Remove contaminated clothing immediately and dispos e of safely.

Inhalation Keep patient warm and at rest. Move to fresh air. C all a physician or poison control center immediately.

Skin contact Wash off thoroughly with plenty of water and soap, if available with polyethyleneglycol 400, subsequently rinse with water.

Eye contact Remove contact lenses, if present, after the first 5 minutes, then continue rinsing eye.

Ingestion Do NOT induce vomiting. Call a physician or poison control center immediately. Rinse mouth.

Notes to Physician Treatment Elementary aid, decontamination and symptomatic tre atment.

B.3.4.3.2 Procedures for the decontamination of wat er in case of an accident:
In case of contamination of water with Spirotetrama t accidental spillage, always try to isolate and pr otect the contaminated area. Water should be used as sparingl y as possible to clean up the area. Where feasible, the contaminated water should be pumped out and isolate d for further appropriate treatment. The collected contaminated water must be burnt in a commercial in cinerator. If incineration facilities are inadequat e, obtain advice from the manufacturer on other decontaminati on methods. In any case, the contaminated water mus t not come in contact with surface water. If accident ally contaminated water is used to produce drinking water, ensure with the competent authorities that the leve l of contamination does not reach the parametric va lue for drinking water.
B.3.4.3.3 Other/Special Studies
No other or further special studies have been condu cted nor have they been considered necessary or triggered.– 22 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

B.3.5 Further information on the plant protection p roduct Movento  150 OD Insecticide

(Annex IIIA 4)
B.3.5.1 Packaging (type, materials, size, etc.), co mpatibility of the preparation with packaging

materials (Annex IIIA 4.1)
B.3.5.1.1 Specification of the packaging (Annex III A 4.1.1)
Specific Requirement Examples Material Bottle / Canister: HDPE PA / adhesive / HDPE EVOH / adhesive / HDPE, Capacity: Bottle / canister up to 10 liter, which may or may not be packed in an outer corrugated fibreboard case such as:

• 20 x 0.250 liter • 20 x 0.500 liter

• 12 x 1 liter • 4 x 3 liter

• 4 x 5 liter • 2 x 10 liter

Canister / IBC over 10 liter such as:

• 20 liter • 25 liter

• 50 liter • 200 liter

• 640 liter • 1000 liter

Type of closure and size of opening Screw cap 36-50-63 mm (with HF seal or internal wad ) - to fit container neck as defined in ECPA One Trip Container Guidelin es. Tri – Sure, S 56 x 4 mm, guarantees closure. Screw cap DN 50 guarantees closure and DN 150 guara ntees closure. Application devices None

B.3.5.1.2 Suitability of the packaging and closure (strength, leak proof and resistance to

transport and handling) (Annex IIIA 4.1.2)
Statement of compliance: The packaging complies with ADR regulations and it has been tested using the ADR test methods appropriate to the pack type and material and class ification of the contents. Appropriate UN certifica tes are issued.
B.3.5.1.3 Resistance of the packaging material to i ts content (Annex IIIA 4.1.3)
The resistance of the packaging material is address ed by the shelf-life study data submitted under Ann ex III (2.7.3) and has been found to be acceptable. The resistance of packaging material to its content s has been tested in accordance with GIFAP Technica l Monograph No 17 (May 1993); M-266311-01-1; M-266300 -01-1 and M-266306-01-1.– 23 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Issuer: Christian Jürgensen Date: 2006-Sep.-15 Job Title: Laboratory Manager Company Name: Bayer CropScience AG Address: BCS-IOP-TISS Packaging Technology Building 6820 40789 Monheim Telephone: +49 2173 / 38 - 4679 Fax: +49 2133 / 38 - 4761 e-mail address: christian.juergensen@bayercropscience.com

B.3.5.2 Procedures for cleaning equipment (Annex II IA 4.2)
All application equipment and contaminated protecti ve clothing should be washed/cleaned with water or a dilute detergent solution and thoroughly rinsed. Ca re should be taken not to spill the contaminated wa shings from application equipment into waste water channel s. Contaminated cleaning liquids should be disposed safely according to local regulations.
B.3.5.2.1 Procedures for cleaning application equip ment and protective clothing (Annex IIIA

4.2.1)
Application equipment Field spraying equipment should be sufficiently cle aned in order to avoid product left over. Cleaning of field spaying equipment is in general an essential part o f the recommendations for use of plant protection products. Empty the contents of the spraying equipment comple tely onto the field just sprayed. Remove all filter s and nozzles, scrub clean and rinse them with clean wate r. Put 10 % clean water into the tank to cover the agitator and add about 0.5% liquid detergent. Opera te a tank flushing system if fitted. Circulate wate r through the pump and controls for at least one minute. Drai n sprayer, collect washings. Repeat procedure once more. Pump last washing water out through boom feed hoses and pipes. Collect washings. Clean off the outside of the sprayer using minimum water volumes. Collect washings. Replace cleaned nozzles and filt ers. Collect and put all washings back into the tank and spray out onto the field headland, or otherwise sa fely dispose of them. Ensure the sprayer systems are com pletely drained before storage. Plant protection equipment should always be stored in a properly des ignated storage facility.

Protective clothing All contaminated clothing should be washed / cleane d with a dilute detergent solution and thoroughly r insed with clean water. Impermeable overalls, boots and face shields should be washed clean and dried. Permeable overalls should be laundered after use. Disposable overalls and gloves should be washed and disposed of as contaminated waste. Gloves and boots should be washed clean, if necessa ry on the insides as well.
B.3.5.2.2 Effectiveness of cleaning procedures (Ann ex IIIA 4.2.2)
The product is dispersible in water. Therefore it c an be removed from surfaces with water. Adding a di lute detergent solution will enhance the effectiveness o f the cleaning process. The OD-formulation contains considerable amounts of natural oil, due to which the formulation may adhe re to the wall of the container. Consequently, the rin sed residue of the OD-formulation will be somewhat higher– 24 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

than for the standard SC-formulations. Therefore, i n case that material has dried on surfaces, the use of heated water (25 °C) will improve the cleaning effe ctiveness also. Nevertheless, under practical conditions of use in the EU and given that the rinsing water is not cold er than 7 °C the rinsed residues will be negligible.

The general procedure for cleaning field sprayers i s described below. For spray equipment the manufacturer’s manual must describe how to clean an d/or flush the pumps and pipes and control gauges whilst spray mixture is still present in the tank o r the sprayer have to be cleaned for the next crop completely. The basic technical steps have to be defined for ev ery sprayer type separately by the manufacturer:

General requirements:

• The cleaning procedure has to be done immediately after spraying the product.

• Empty the sprayer down to the technical leftover

• The technical rest liquid have to be diluted with clear water (in minimum 10% of the total tank capacity) and have to be sprayed out - ensure that the inside walls of sprayer will be cleaned thoroughly – best option to use a rotating cleaning nozzle.

• This step have to be repeated in case of products will be sensitive regarding crop safety or residues in succeeded treated crops

• Filters have to be removed and cleaned separately.

• The cleaning procedure has to be done in an untrea ted part of the field.

• Personal protective clothing is required for the c leaning procedure.

According to Efficacy Guideline 302, proposed by PS D and published in December 2001 by the European and Mediterranean Plant Protection Organization as document 02/9740, specific studies to prove the cleaning efficacy of application equipment is not r equired, if the product is not expected to cause pl ant damage at recommended use rates. This holds true fo r almost all insecticides and fungicides and specif ically for the Spirotetramat OD 150. Therefore, further studies are not considered to be necessary.
B.3.5.3 Re-entry periods, necessary waiting periods or other precautions to protect man,

livestock and the environment(Annex IIIA 4.3)
B.3.5.3.1 Pre-harvest interval (in days) for each r elevant crop(Annex IIIA 4.3.1)

Crop Pre-harvest Interval (PHI)
citrus ssp: oranges, mandarins, clementines, lemons, limes 14

lettuce, field 7
lettuce, glasshouse 7

B.3.5.3.2 Re-entry period (in days) for livestock, to areas to be grazed(Annex IIIA 4.3.2)
Re-entry period needs not to be established as the representative crops are not grazed.– 25 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

B.3.5.3.3 Re-entry period (in hours or days) for ma n to crops, buildings or spaces

treated(Annex IIIA 4.3.3)
A safe re-entry or handling of treated crops is pos sible when spray deposit has dried. For detailed ca lculation see Annex III, Section 3, point 7.
B.3.5.3.4 Withholding period (in days) for animal f eeding stuffs(Annex IIIA 4.3.4)
Since a residue in feed items and the uptake of the se residues by animals is negligible, no residues i n animal matrices will occur if spirotetramat is use as reco mmend. Therefore, no withholding is deemed necessar y.
B.3.5.3.5 Waiting period (in days) between applicat ion and handling of treated products (Annex

IIIA 4.3.5)
Given the toxicological profile of the product and the residue levels at harvest in treated agricultur al commodities, there is no need to define a waiting p eriod between application and handling treated prod ucts.
B.3.5.3.6 Waiting period for sowing or planting suc ceeding crops (Annex IIIA 4.3.6)
As reported in point KIIA, section 4, point 6.6.3.2 “Magnitude of the residue in field rotational crop s”, neither Spirotetramat (BYI 08330) nor its metabolites appea r in concentrations above the LOQ in all rotational crop matrices (report no. RAFNY019). Therefore, no waiti ng period for sowing or planting succeeding crops i s required.
B.3.5.3.7 Conditions under which the preparation ma y or may not be used(Annex IIIA 4.3.6)
Product should not be used in windy conditions in o rder to avoid drift into water bodies.

B.3.5.4 Risks from recommended methods, precautions & procedures to minimize

Annex IIIA 4.4)

Reference: Bayer CropScience Safety Data Sheet for Spirotetram at OD 150 (06424376) Author(s), year: Anonymous, 2006 Report/Doc. number: M-276466-01-1 Guideline(s): EC Directive 2001/58/EC GLP: No

B.3.5.4.1 Warehouse storage (Annex IIIA 4.4.1)
Keep out of the reach of children. Keep away from food, drink and animal feeding stuff s. When using, do not eat, drink or smoke. Keep away from source of ignition. Store in the original container under usual warehou se conditions! Keep containers tightly closed in a cool, well-ventilated place. Store in a place accessible by authorized persons o nly! Keep away from direct sunlight and protect aga in frost. For more information see: Guidelines for the safe handling of pesticides duri ng their formulation, packing, storage and transpor t (GCPF). Guidelines for the safe warehousing of crop protect ion products (GCPF).

B.3.5.4.2 User level storage (Annex IIIA 4.4.2)
Keep out of the reach of children.– 26 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Keep away from food, drink and animal feeding stuff s. When using, do not eat, drink or smoke. Keep away from source of ignition.

B.3.5.4.3 Transport (Annex IIIA 4.4.3)
Risks during transport of product are minimal. Foll ow the general rules and good practice for transpor t and the Dangerous Goods regulations. Do not stow the pr oduct together with food, feed and consumable items

. Transport classification of the product in Europe i s: Road and rail (ADR and RID): UN3082 (environmentall y hazardous substance), Hazard No. 90.

B.3.5.4.4 Fire (Annex IIIA 4.4.4)
Extinguish fires with foam or carbon dioxide (CO2), sand or water spray. Do not allow run-off from fir e fighting to enter drains or water courses, e.g. by bundling the area with sand or earth. Wear a self-contained breathing apparatus. Remove p roduct from areas of fire or otherwise cool contain ers with water in order to avoid pressure being built u p due to heat. Water should be used as sparingly as possible and i f contaminated it must not come in contact with sur face water. It must be collected and burned in a commerc ial incinerator. If burning facilities are inadequa te, obtain the manufacturer's advice on decontamination method s.

B.3.5.4.5 Nature of protective clothing proposed (A nnex IIIA 4.4.5)
If product is handled such that there is a risk:

Respiratory protection: If product is handled while not enclosed, and if skin contact may occur: Full mask Multi-range filter ABEK/P2 Hand protection: PVC or other plastic material glov es Eye protection: Safety glasses with side-shields Hygiene measures: Avoid contact with skin, eyes and clothing. Keep working clothes separately. Wash hands before breaks and at the end of workday. Wash hands immediately after work, if necessary tak e a shower. Remove soiled or soaked clothing immediately and cl ean thoroughly before using again. Garments that cannot be cleaned must be destroyed ( burnt).

B.3.5.4.6 Characteristics of protective clothing pr oposed (Annex IIIA 4.4.6)
Respiratory protection If product is handled while not enclosed, and if skin contact may occur: Full mask Multi-range filter ABEK/P2 Hand protection PVC or other plastic material glov es Eye protection Safety glasses with side-shields

B.3.5.4.7 Suitability and effectiveness of protecti ve clothing and equipment (Annex IIIA 4.4.7)
Safety glasses with side-shields are recommended to protect eyes from contact with the product.– 27 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Protective clothing is recommended as routine hygie nic measure. Chemical resistant gloves are well kno wn to sufficiently protect hands from contact with the product handled.

B.3.5.4.8 Procedures to minimise the generation of waste (Annex IIIA 4.4.8)

Product To minimise product waste, users are required not t o prepare more than they will use for the treatment

.
Package To minimise package waste, empty and rinsed contain ers should be delivered to a local container collec tion programme, where available. Otherwise, they should be rendered unusable, e.g. by puncturing, and disposed in accordance with local regulations. Packaging that cannot be cleaned should be disposed of as product waste. It must be incinerated in an authorised special waste incineration plant. Comply with local legislation. To minimise generation of leftovers, users are reco mmended to store not more than will be consumed wit hin the shelf life period of the product.
B.3.5.4.9 Combustion products likely to be generate d in the event of fire (Annex IIIA 4.4.9)
The following can be released in case of fire: Carbon dioxide (CO 2 ) Carbon monoxide (CO) Nitrous gases (NOx) Hydrogen cyanide (hydrocyanic acid)
B.3.5.5 Emergency measures in case of an accident ( Annex IIIA 4.5)
B.3.5.5.1 Containment of spillages (Annex IIIA 4.5. 1)
Keep people and animals away.

Do not discharge into drains / surface water / grou ndwater. Cover any spilled liquid with absorbent ma terial such as sand, earth or a proprietary absorbent mate rial. After the liquid has been absorbed, carefully sweep it up into a disposable container and tightly seal. Dispose by incineration in an authorised special w aste incineration plant. Comply with local legislation. For larger quantities contact manufacturer.

If spillage enters drains leading to sewage works, inform local company immediately. If spillage enter s rivers or watercourses, inform the Environmental Agency.

B.3.5.5.2 Decontamination of areas, vehicles and bu ildings (Annex IIIA 4.5.2)
Take up with adsorbent material (e.g. sand, earth o r a proprietary absorbent material). Transfer collected material to heavy duty plastic d rums and keep safe for disposal. Clean contaminated floors and objects thoroughly, o bserving environmental regulations.
B.3.5.5.3 Disposal of damaged packaging, adsorbents and other materials (Annex IIIA 4.5.3)
After the liquid has been absorbed (sand, earth or proprietary absorbent material), carefully sweep it up into a disposable container and tightly seal. Damaged pa ckaging and adsorbents should be collected into hea vy duty plastic drums. Containers and drums can be taken to waste disposal site or incineration plant, after consultation wit h site operator and/or with the responsible authority. Dis pose of by incineration in an authorised special wa ste incineration plant. Comply with local legislation. For larger quantities, contact manufacturer.– 28 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

B.3.5.5.4 Protection of emergency workers and bysta nders (Annex IIIA 4.5.4)
Keep people and animals away. Avoid contact with sp illed product or contaminated surfaces and wear personal protective equipment (see B.3.5.4.6).

In the event of fire and/or explosion, do not breat he fumes. Wear self contained breathing apparatus f or fire fighting if necessary. Remove product from area of fire or otherwise cool containers with water in ord er to avoid pressure being built up due to heat.

When dealing with a spillage, do not eat, drink or smoke. Remove soiled or soaked clothing immediately

. Clean hands and face at work intervals and after wo rk.

B.3.5.5.5 First aid measures (Annex IIIA 4.5.5)
General advice: Move out of dangerous area. If the patient is likely to become unconscious, place and transport in stable sideways position. Remove s oiled or soaked clothing immediately. After inhalation: Move the patient to fresh air an d keep at rest. Call a physician immediately. After eye contact: In the case of contact with eye s, rinse immediately with plenty of water. Call a physician immediately. After skin contact: After contact with skin, wash immediately with soap and plenty of water. Call a physician immediately. After ingestion: Do not induce vomiting. Wash out mouth with water. Call a physician immediately.

B.3.5.6 Neutralisation procedures, pyrolytic behavi our and other methods (Annex IIIA 4.6)
B.3.5.6.1 Details of proposed procedures for small quantities (Annex IIIA 4.6.1)
No neutralization procedure (e.g. reaction with alk ali to form less toxic compounds) is suitable for spirotetramat OD 150.
B.3.5.6.2 Evaluation of products of neutralization (small quantities) (Annex IIIA 4.6.2)
No neutralization procedure (e.g. reaction with alk ali to form less toxic compounds) is suitable for spirotetramat OD 150.
B.3.5.6.3 Procedures for disposal of small quantiti es of neutralized waste (Annex IIIA 4.6.3)
No neutralization procedure (e.g. reaction with alk ali to form less toxic compounds) is suitable for spirotetramat OD 150.
B.3.5.6.4 Details of proposed procedures for large quantities (Annex IIIA 4.6.4)
No neutralization procedure (e.g. reaction with alk ali to form less toxic compounds) is suitable for spirotetramat OD 150.
B.3.5.6.5 Evaluation of products of neutralization (large quantities) (Annex IIIA 4.6.5)
No neutralization procedure (e.g. reaction with alk ali to form less toxic compounds) is suitable for spirotetramat OD 150.
B.3.5.6.6 Procedures for disposal of large quantiti es of neutralized waste (Annex IIIA 4.6.6)
No neutralization procedure (e.g. reaction with alk ali to form less toxic compounds) is suitable for spirotetramat OD 150.– 29 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

B.3.6 Pyrolytic Behaviour of the Active Substance ( Annex IIIA 4.7)
Not applicable as the product spirotetramat OD 150 does not contain chlorine.
B.3.7 Disposal Procedures for the Plant Protection Product (Annex IIIA 4.8)
B.3.7.1 Detailed instructions for safe disposal of product and its packaging (Annex IIIA 4.8.1)
Leftover quantities of the product have to be burne d in an authorised special waste incineration plant

. Comply with local legislation. As containers are combustible (HDPE): Burn these em ptied containers in an authorised special waste incineration plant. Comply with local legislation. Otherwise, they should be rendered unusable after c leaning, e.g. by puncturing, and disposed of in accordance with local regulations. Note that empty containers can be land filled after cleaning, when in compliance with local regulation s.

B.3.7.2 Methods other than controlled incineration for disposal (Annex IIIA 4.8.2)

No methods other than controlled incineration are r ecommended for disposal.
B.3.7.3 Other/Special Studies (Annex IIIA 4.9)
No other / special studies have been conducted.– 30 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

B.3.8 References relied on

Annex point/ reference number Author(s) Year Title Source (where different from company) Company, Report No GLP or GEP status (where relevant) Published or not Data Protection Claimed

Y/N-R/NR Owner

Annex II Data and Information KIIA 3.6 /06 Anonymous 2002 Efficacy evaluation of plan t protection products - Resistance risk analysis Publisher:European and Mediterranean Plant Protection Organization, Journal:Efficacy evaluation of plant protection products, Volume:1, Issue:PP1/213(2, Pages:76-93, Year:2004, Report No.: M-256143-01-1, Edition Number: M-256143-01-1 Non GLP, published No

KIIA 3.7 /01 Anonymous 2006 Spirotetramat TC Bayer CropScience AG, Report No.: M-276780-01-1, Edition Number: M-276780-01-1 Date: 01.09.2006 Non GLP, unpublished Yes BCS

KIIA 3.8.1 /01 Anonymous 2006 Spirotetramat TC Bayer CropScience AG, Report No.: M-276780-01-1, Edition Number: M-276780-01-1 Date: 01.09.2006 Non GLP, unpublished Yes BCS

KIIA 3.8.2 /01 Anonymous 2006 Spirotetramat TC Bayer CropScience AG, Report No.: M-276780-01-1, Edition Number: M-276780-01-1 Date: 01.09.2006 Non GLP, unpublished Yes BCS

KIIA 3.8.3 /01 Anonymous 2006 Spirotetramat TC Bayer CropScience AG, Report No.: M-276780-01-1, Edition Number: M-276780-01-1 Date: 01.09.2006 Non GLP, unpublished Yes BCS– 31 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Annex point/ reference number Author(s) Year Title Source (where different from company) Company, Report No GLP or GEP status (where relevant) Published or not Data Protection Claimed

Y/N-R/NR Owner

KIIA 3.6 /06 Anonymous 2002 Efficacy evaluation of plan t protection products - Resistance risk analysis Publisher:European and Mediterranean Plant Protection Organization, Journal:Efficacy evaluation of plant protection products, Volume:1, Issue:PP1/213(2, Pages:76-93, Year:2004, Report No.: M-256143-01-1, Edition Number: M-256143-01-1 Non GLP, published No

KIIA 3.7 /01 Anonymous 2006 Spirotetramat TC Bayer CropScience AG, Report No.: M-276780-01-1, Edition Number: M-276780-01-1 Date: 01.09.2006 Non GLP, unpublished Yes BCS

KIIA 3.8.1 /01 Anonymous 2006 Spirotetramat TC Bayer CropScience AG, Report No.: M-276780-01-1, Edition Number: M-276780-01-1 Date: 01.09.2006 Non GLP, unpublished Yes BCS

KIIA 3.8.2 /01 Anonymous 2006 Spirotetramat TC Bayer CropScience AG, Report No.: M-276780-01-1, Edition Number: M-276780-01-1 Date: 01.09.2006 Non GLP, unpublished Yes BCS

KIIA 3.8.3 /01 Anonymous 2006 Spirotetramat TC Bayer CropScience AG, Report No.: M-276780-01-1, Edition Number: M-276780-01-1 Date: 01.09.2006 Non GLP, unpublished Yes BCS

KIIA 3.9 /01 Anonymous 2006 Spirotetramat TC Bayer CropScience AG, Report No.: M-276780-01-1, Edition Number: M-276780-01-1 Date: 01.09.2006 Non GLP, unpublished Yes BCS– 32 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Annex point/ reference number Author(s) Year Title Source (where different from company) Company, Report No GLP or GEP status (where relevant) Published or not Data Protection Claimed

Y/N-R/NR Owner

KIIA 3.6 /01 Elbert, A.;

Nauen, R. 1996 Bioassays for Imidacloprid for resistance monitoring against the whitefly Bemisia Tabaci Publisher:Brighton Crop Protection Conference, Journal:Proceedings of the Brigthon Crop Protection Conference - Pests and Diseases, Issue:6D-8, Pages:731-738, Year:1996, Report No.: MO-01-021697, Edition Number: M-087913-01-1 Non GLP, published No

KIIA 3.6 /02 Heimbach, U.;

Kral, G.; Niemann, P. 2000 Implementation of resistance risk analysis of plant protection products in the German authorisation procedure Publisher:BCPC (British Crop Protection Council), Location:Farnham, Surrey, UK, Journal:The BCPC Conference - Pest & Diseases 2000 - Conference Proceedings, Volume:2 (7B-2), Pages:771 - 776, Year:2000, Report No.: M-256236-01-1, Edition Number: M-256236-01-1 Non GLP, published No

KIIA 3.6 /03 McNamara, D.

G.; Smith, I. M. 2000 Development of an international standard on resistance risk analysis Publisher:BCPC (British Crop Protection Council), Location:Farnham, Surrey, UK, Journal:The BCPC Conference - Pest & Diseases 2000 - Conference Proceedings, Volume:2 (7B-1), Pages:765 - 770, Year:2000, Report No.: M-256264-01-1, Edition Number: M-256264-01-1 Non GLP, published No– 33 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Annex point/ reference number Author(s) Year Title Source (where different from company) Company, Report No GLP or GEP status (where relevant) Published or not Data Protection Claimed

Y/N-R/NR Owner

KIIA 3.5.1 /01 Nauen, R. 2005 Spirodiclofen: Mode of a ction, resistance risk assessment in Tetranychid pest mites Publisher:Pesticide Science Society of Japan, Location:Anonymous, Journal:Journal of Pesticide Sciences, Volume:30, Issue:3, Pages:1-4, Year:2005, Report No.: M-277046-01-1, Edition Number: M-277046-01-1 Non GLP, published No

KIIA 3.6 /05 Nauen, R.,

Denholm, I. 2005 Resistance of insect pests to neonicotinoid insecticides: current status and future prospects Publisher:Wiley InterScience, Location:Wiley-Liss, Inc., Journal:Archives of Insect Biochemistry and Physiology, Volume:58, Issue:2005, Pages:200-215, Year:2005, Report No.: MO-05-007838, Edition Number: M-250577-01-1 Non GLP, published No

KIIA 3.6 /07 Nauen, R.;

Bretschneider, T.; Elbert, A.; Fischer, R.; Reckmann, U.;

van Waetermeulen, X. 2005 Biological and mechanistic considerations on the mode of action of Spirotetramat Publisher:Anonymous, Location:Anonymous, Journal:Journal of Pesticide Science, Volume:30, Issue:-, Pages:272, Year:2005, Report No.: M-277043-01-1, Edition Number: M-277043-01-1 Non GLP, published No– 34 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

Annex point/ reference number Author(s) Year Title Source (where different from company) Company, Report No GLP or GEP status (where relevant) Published or not Data Protection Claimed

Y/N-R/NR Owner

KIIA 3.6 /04 Nauen, R.;

Elbert, A. 2003 European monitoring of resistance to selected insecticides in Myzus persicae and Ahis gossypii (Homoptera: Aphididae) with special reference to imidacloprid Publisher:Bulletin of Etmological Research, Volume:93, Pages:47-54, Year:2003, Report No.: MO-03-004948, Edition Number: M-089162-01-1 Non GLP, published No

KIIA 3.6 /08 Rauch, N.;

Nauen, R. 2003 Identification of biochemical markers linked to neonicotinoid cross resistance in Bemisia tabaci (Hemiptera: aleyrodidae) Publisher:Wiley-Liss, Inc., Journal:Archives of Insect Biochemistry and Physiology, Volume:54, Pages:165 - 176, Year:2003, Report No.: MO-05-009326, Edition Number: M-252537-01-1 Non GLP, published No– 35 –

Spirotetramat – Volume 3, Annex B.3, Data on applic ation and further information April 2008

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Y/N-R/NR Owner

Annex III Data and Information
KIIIA1 4.2.1 /01
KIIIA1 4.2.2 /01
KIIIA1 4.4.1 /01
KIIIA1 4.4.2 /01
KIIIA1 4.4.3 /01
KIIIA1 4.4.4 /01
KIIIA1 4.4.5 /01
KIIIA1 4.4.6 /01
KIIIA 1 4.4.7 /01
KIIIA1 4.4.8 /01
KIIIA1 4.4.9 /01
KIIIA1 4.5.1 /01
KIIIA1 4.5.2 /01
KIIIA1 4.5.3 /01
KIIIA1 4.5.4 /01
KIIIA1 4.5.5 /01
KIIIA1 4.6.1 /01
KIIIA1 4.6.2 /01
KIIIA1 4.6.3 /01
KIIIA1 4.6.4 /01
KIIIA1 4.6.5 /01
KIIIA1 4.6.6 /01
KIIIA1 4.7 /01
KIIIA1 4 .8.1 /01
KIIIA 4.8.2 /01 Anonymous. 2006 Spirotetramat OD 150 G Bayer CropScience AG, Report No.: M-276466-01-1, Edition Number: M-276466-01-1 Date: 04.08.2006 Non GLP, unpublished Yes BCS

KIIIA1 4.2.2 /02 Anonymous 2001 Efficacy guideline 302, european and mediterranean plant protection organisation - Cleaning application equipment - Efficacy aspects Publisher:PSD, Location:Great Britain, Year:2001, Report No.: M-279919-01-1, Edition Number: M-279919-01-1 Non GLP, published No