## Regi s tration Decision for a New Method of Delivery (First Foliar Spray Use) of Methyl S alicylate U pd ate t o th e Prev i o us l y I ss u ed M e th y l Sa l i cy late R er eg is trat io n El ig ibili ty D ec is ion ( RE D ) ofNove mb e r, 2 00 5

A pproved b y :

**~** Ro bert M cN all y, D ir ec to r Bi ope s t i c ide s a n d P

o llu t i o n P reve nt io n Di v i s i o n D a t e :1.0 B ac k g r o und On March 20 , 2014. the U.S
. Env ironmental Protection Agency (EPA) received a r egistration application from Valent Biosciences Corporation (Va l ent) for a new use of LEAP® Biologica l Insect i cide Emulsifiable Suspens i on (LEA P ® ) , fo rmerly VBC

- 60347 B i ological l nsec t ic i de Emulsifiable Suspens ion. to contr o l army and pod wo rms in tomatoes and bell peppers in agricultural fie l ds and gree nhouses. LEAP ® is formu l ated as an emu l s ifiab le suspens i on wh i ch contai n s 5.95% of the active ingredient (a.i.) methy l sal i cylate (CAS Number 11 9

- 36

- 8)
. Methy l sal icy l ate is c lassified as a b i ochemical pestic i de and i s th e primary constituent in oil of w intergreen , a natura ll y frag r ant o il. It is character i z ed as a co l orless, yellowish o r redd ish. oi ly liqu i d with the di s tinct odor and taste of winte r green o r gaultheria. Met h yl salicy l ate is naturally extracted via stea m distil l at ion of mace rated l eaves from th e low growing plant, Gaultheria procumhens L ime . (fam. Ericaceae) or from the ba rk of Betula lenta (Sweet Birch). Methyl s a li cylate can a l so be manufactured sy n thetica ll y. Methy l sal i cylate was fi r st registered in 1 972 for use as an ani ma l repel lant in imp r egnated twist tabs to be hung on plants to repe l dogs and cats f r om tlower gardens. A subseq u ent registration of methy l sal i cy l ate fol l owed in 1996 as an insect r epellen t to be used as a constituent of food and feed packaging mate rial to r epe l insects in stored commod i ties. This registration was cons i dered to be a ·'food use,'' and thus necess i tated the estab l ish m ent of an exemption from the requ irement of a tolerance (see 40 CF R § 180. 11 89)
. Methyl sa li cy late a l so has a l ong h i story of use in consumer products as a counte r irritant and as a n analges i c fo r the management of ach ing and painful muscles and joints as well as suntan lot i ons (as an UV

- absorber) and perfume r y as a mod i fie r of blossom frag rances (EPA, 2005). The new use put forth by Valent (LEA P ® B i ologica l Insect i cide Emuls ifiable Suspens i on) i s intended for use as a fo li a r appl i cat i on to tomatoes and be ll peppers up to the flower ing stage of g rowth. and is therefore a non-food use. LEA P ® is a highly select ive in sect i c ide for use aga inst listed caterpil lar s (la rvae) of Lep idopterous insects. LEAP® i s intended fo r application as fo l iar spray using ground or handheld equ ipment to bell peppers and t omatoes in fie l ds and or greenhouses at an app li cation r ate of 1.0 to 4.0 p ints/ acre, up to a total of 16 p ints per ac r e per s ea s on . App l icat i ons are to be appl ied up to the tlower ing s tage of growth and must not be app l ied more frequent l y t han eve r y 5 days. T he personal protect ive equ ipment (P PE) statement on the label indicates that all app l ica t ors and other hand l ers must wear l ong s l eeved sh irt and lon g pants. chem ical res i stant g l oves, socks and shoes
. Mixer / loaders and app l icators m ust wear a dust / mist fi lt ering r esp ira t or meeting N IOS H standards of at least N

- 95, R

- 95, or P-95
. Repeated exposure to high concentr at i ons of microbia l pr oteins from the second act ive ingredient , Bacillus thuringie nsis, s ubsp. kurstaki , stra in ABTS-35 1 , listed on the label can cause an al le rg i c s ensitiza tion
. This new use of methy l sa l icy late rep r esents the first use of m ethyl sa li cy late as de l ivered in a manner where it is not enclosed in ma ter i als
. A copy of the product label a nd information relevant to EPA ' s ri sk assessment is ava i lab l e in Docket 10 EPA -H Q

- O PP -2014-0898.

Page 2 of62.0 Eva lu atio n In eva lu a tin g a pe s ticid e reg is trati o n applicati o n. th e EPA assesses a w id e va ri ety o f pesticide s pecific inf o rmati o n in c ludin g where and h ow the p es ticide is us ed. e nviro nmental fate (i.e
.. what happen s to th e pe s ti c id e o nce it' s applied ). and t ox icity s tudie s (i.e
. . ha 7.a rd s ) t o determine the likelihood o fad ver e effec ts (i.e
.. ri sk) fr o m exposu res assoc iated with th e u sc of the product. The e n v iro nmental fate properties o f th e pe s ticide arc c har acte rized by EPA. A l so . ri sk assessme nt s are devel o ped to eva lu ate th e compound as to h ow it might affect a wide r a n ge or non-target o r ga ni s m inc ludin g human s and t e rrestr i a l a nd aq uatic w ildlife (p l a nt and a nim als). On the ba s i s of th ese as c ss m e nts, EPA evaluate s a nd d eve lops lan g u age l o r each pesticide l abel to e ns ure the dir ec ti o n s fo r u sc a nd sa fet y mea s ures arc appropriate t o miti ga te any ri sks of concern . In thi s way. th e pe s ticide l ab e l communicat es to th e use r the esse nti al limit at ions and miti g ation measure s t o ens ur e n o unreaso nabl e adve r se effec ts o n hum an h ea lth o r the e n v ir o nment. Add iti o na lly, it is a F IFR A v io l ation t o use a pesticide in a way th a t in inc o nsis t e nt with the lab e l.
2. 1 Assess m e n t o f Ri s k t o Hum a n Hea lth 2
. 1.1 T ox ic ity E PA requi res a w i de ran ge of stud i es in o rder t o assess a pestic i de
. For me thyl sa licy late, the tox icolog ical databa se i s adequate to support th e a ssess ment of risk to hum a n hea lth from pe s ti cidal use o n tomatoe s a nd pepper s. pre-n owe rin g :
• Methyl sa li cy late i s moderate l y acutel y t ox i c by the oral route. but no n-t ox ic by th e dermal r o ute. It i s a sev ere s kin and eye irritant ( Toxic it y Category II )
. • S ub c hr o ni c s tudi es indicate no toxic ef f ec t s in 90 -da y o ral. dermal o r inh alat i o n stud ie s. H

oweve r . a No Ob se rv ed Adverse E ff ec t Level (NOAE L) for rep rod u c ti ve effec t s wa s estab li s hed at 250 m i ll i grams per k il ogram s (mg / kg) and a L owes t Ob s erved Adverse Effec t Lev e l (LOAEL) was establ i s hed at 500 mg/ kg ba se d on the d ec r ease d number of l itter s per br ee din g pa ir and reduced liv e litter s ize . T h e avai lab l e mut age nicit y s tud ies were ne ga tiv e . • The eval uati o n o f th e c hr o nic toxicity s tudi es indic a tes that methy l s alic y late i s no t carcinogenic. 2 .1. 2 E xp os u r c I n the new use of meth y l s alicy l ate a s a f o liar s pray o n fi el d and greenhou se pre-flowering to matoe s and pepp e r s, th e potent ial for d i eta r y exposure i s neg li gible and th i s i s cons idered by the Agency to be a n o n-f oo d u se based on the foll o wing:
• Residue data indi cate that me th yl sa lic y lat e w iII n ot be present on th e crop at time of harv est. • Methy l sa li cylate ha s a h a lf-lif e of le ss th an two and a half h o ur s o n f o li age.

P age 3 of 6• Methyl sa li cylate i s r ead il y biodegradable in sc r ee ning tests and may be ex p ec t e d to biodegrade in so il s a nd s urfa ce wate rs. • Methyl sa li cy lat e i s lik e l y to hydro lyze in water, espec iall y at a lk a lin e pH
. Residential and occupa t iona l ex p os ure are al so expected to be neg li g ibl e fo r the new use:
• Th e LEAP ® label is for agricu ltur a l u se o nl y. Th e product is not f o r u se in res id en ti a l s ites. • The exposure t o humans from the pe s ticidal use of meth y l sa l ic y late i s expected to be minimal. compared wi th the w id esp r ead u se of m e th yl sa li cy l a te as a n avo rin g in g redient in food s . • The low l eve l of p o t e ntial exposures (dermal and inhalati o n) durin g th e mixin g/ loadin g and app li ca ti o n process of this bi oc h e mi ca l are mo re than adequately miti ga ted by th e u se of persona l prot ec tive eq uipment a nd precaut ionary language stateme nt s placed o n e nd

use product labels. 2.1.3 Human Health Concl u s ion s Although rep r oduction effects we r e seen for methyl sa li cy late at a LO AEL of 500 mg/kg, sig nificant human ex pos ure to this biochemical is not expec ted und e r th e condit i o n s of approved past o r new prod u c t u se. Pr ev i o u s ly approved r eg is t ered product s are r eady to use, sel f-cont a in e d impregnated twi st tab s a nd f oo d packin g mat e rial. The n ew product is a f o li a r s pra y for pe ppers and t o mat oes pre-n owe rin g w ith PPE required o n the product lab e l a nd appropriate precautionary language s t ate ments, ·which miti gates the low l eve l of potential expos ure for the new use. Acute toxicity s tudi es p e rformed on the end-use product (E P ) LE A P ® Bi o l og ical I nsect icide Emulsifiable Suspension (ai. Bacillus thurin giens i s s ubsp. kurstaki, Strain AB T S-35 1 , 26.55 % and Methyl Sal i cy l a t

e, 5 .9 %) demonstrate l abe ling precauti o n ar y s igna l word mu st be "CAU TIO N:· B ased o n the se co n s id era ti o n s and th ose I i ste d in th e pr evio us l y de sc rib ed ha za rd assessments. an assessmen t of a n agg r egate exposure f o r al l pe s ti cida l u ses of m eth y l sa li cylate wo uld re s ult in minima l additi o nal exposure beyond what consumers a lready receive from o ther uses. Ex p ected expos ure levels from the se uses would be well below defi n ed acceptable l eve ls. even considering me th y l sa lic yl ate se n si ti v it y to infant s and children. 2.2 Ecological Exposure and Risk T h e batte ry of t es t s req uir ed t o assess th e e nviro nm e ntal fa t e a nd eco l og i ca l effec t s of methyl sa li cylate i s co mpl e te. Th e b ioc hemical i s rea dil y biodegradable in sc r een in g t es t s and ma y b e expec t ed t o b iodeg r ade in so il s and s urfac e wa t ers ( HS DB , 1996 ) . Mo r eove r , m e th y l sa li cy l ate i s li kely to hydro lyze in wa t e r. especia ll y at alk al in e p H ( HS DB , 1996). At p H 7.5. it s hy dro lysis half

- life i s estimated to be 14.1 days ( HSDB. 1996). Methyl sal i cylate absorbs UV rad iati on > 2990 nm and theref ore ma y undergo di r ect photolysis under env ir o nm enta l cond iti o n s ( HS DB. 1996); the ph o tolys is half- life was reported t o be 48 minutes in one s tud y ( HS DB , 1996). In th e Page 4 of 6atmosp h e re , methyl sa licylate r eacts with phot oc hemically produced hydroxy l radical s w ith a n es tim a t ed r ate cons tant of 11. 6 x I

## o·' 2cm 3 / m olecu l e. Assu mi n g a h yd r oxy l rad i cal co nce ntration of 5 x I

## o- s radi ca l s/c m3 • the ha l f-l i fe o f m ethyl sa l i cyla t e in the atmosphere wo u l d be 1.4 days ( HS OB , 1996). Ecotox icity data on methyl sal icylate s how that th e compo und is: • slightly to prac t icall y non-tox ic to avian species; • slight ly to practically n o n-toxic to fi sh: • s li ght toxicity t o aquatic invertebrates; • not ph y t otox i c; A co nt act toxic ity s tudy o n h o n ey bees u s in g th e n ew E P s h owed n o t ox i c effec ts (24 -hr a nd 48- hr 

### LD so for co nt act tox ici ty was g reater than 1 25 11 g a i /bee)
. Non -t arge t plant data req uire ments were add ressed w ith approved wa iver rationa les based upon 1) meth y l salicylate· s hi g h vapor pressu r e. which results in vo la t il izati on and rapid l osses from s ur faces. 2) its demonstrated nont ox icity of the compo und t o plant s in the applicant-sub mi tted efficacy studies. and 3) it s natural occurances in many plant species. Mo reover, w ith r ega rd s t o ecologica l toxicity , methyl sa li cy late is cur r en tl y released to the e nvi r o nment in effl ue nt s and emiss i o n s as a r es ult o f it production , dispo sa l a nd use as a fl avor in g in foods and beverages , as a fragrance age nt in cos m etics and perfume s, as a pharmaceutical age nt (counte rirrit a nt) in o intm e nt s and o r al rin ses, as a UV-abso rb er in suntan lo ti ons. as a carrier for fabric dyes , and as a UV-stabil i ze r in acryl ic re s in s. The Agency estimates that pesticidal use of meth y l salicylate i s ve r y sma ll in compa ri son t o it s current non pesticidal u ses. Th erefore. the Agency believes th at pe s ticidal use of methyl sa lic y l ate . includin g the new use a s a f o liar sp ra y, wi ll not contribute s i g nificant l y to eco l ogica l expos ure of this biochem i cal. Furtherm o r e. ba sed on low toxicit y and thi s the l ack of a sig nifi ca nt increa se in eco l og i cal expos ure. the Agency co n cludes a ''No E ff ect" determinati o n for di r ec t a nd indirect effects to listed species and th ei r hab itats . 3.0 A lter na t ives Methyl sal icylate can be u sed alone or a lo ngs ide currently registered biochemical or co nve ntional animal or in sec t r epellents and plan t g row th regulato rs; methyl sa lic y late can be an important component of an I ntegrated P est Management ( IPM ) system. The u se of this bioche mic a l a nim a l and in sec t r epellent a nd in sec ti cide may displace an d r e duc e th e amount o f co nve nti o na l act ive in g r ed i e nts r eq uired for the se purposes. Growe rs ma y pr efe r to u se m eth y l s alicylate as a v i able a lt ernat iv e to co nv e nti o nal products s inc e methyl sa li cy l a te prod u c t s co nt a in s horte r R e-E ntry I nterva ls ( RE I ) a nd s ho rt ha l f- lif e ( l ess than tw o and a ha lf hours on fo li age).

P age 

### 5 of 64.0 Benefits and Public Comments By definit i on alone, biochemicals are favorable whe n compared to currently registered convent i ona l alternat ives because biochemicals are natura l ly-occurring substances (or substances structura ll y-similar and functiona l ly id en ti ca l to na tu rall y-occurring substances) with a history of exposu re to humans and the environ m ent demonstrating minimal toxic ity and a non-toxic mode of action to the target pest(s). Benefits of biochemical pesticides as compared t o conventional pesticides typically include l owe r toxicity profi l es for humans a nd non -target o r ga ni sms , and faster degradation in the environment. As out lined above , methy l sa li cy l ate is a viab le alternative to conventional animal and insect r epe l lents and plant growth regulators due to it s l ow tox i city pr o file and half-life of le ss than two and a half hours on foliage
. On January 14, 20 IS , EPA publ i shed in the Federal Register a Not i ce of Receipt of th e Valent application for registrat i on of methy l salicylate as a foliar spray and annou nced a public comment period of 30 days. No comments were r eceived in response to this Not i ce of R ece ipt. EPA announced the proposed decision of the unconditional registration of methyl sa lic y late as a foliar spray on tomatoes and peppers pre-flowering on September I 0 , 20 1 5 , and held a publ i c c o mment period for IS days , closing Septembe r 24 , 20 1 5 , at I I :59 pm. No comments were received to the docket (Docket ID: EPA- I-I Q-OPP-2014-0898). 5.0 Regulatory Decision The Agency ' s methyl sal ic ylate database , w hi ch includes guidel in e studi es and scientific lite r ature reviews , is complete. T h e new use of methyl sa l icylate as a foliar sp ra y on tomatoes and bell peppers in agr i cu ltura l fields a nd g r een hou se is well supported by this database. In cons i der ing the assessed ri sk to human hea lth and the environment , the Agency concludes that methyl salicy late meets the re gulato ry standa rd under the Federal Insecticide, Fungic i de and R

odent icid e Act (F IFRA ). T here are no outstanding data requirements for this biocbemical. Therefore, the EPA is grant ing the unconditional registration ofth i s use of methyl salicy l ate under Sect i on 3(c)(S) of FIFRA. One product wi ll be r egistered: ·'LEAP ® Biological Insecticide Emulsifiable S u spension ' " is an end-use product (EP) conta ining the active ingredient Bacillus thuringiensis subsp
. kurstaki s train ABTS

- 351 in add iti on to methyl sa l icy l ate. Application of this product is app r oved for use outdoors on tomato and pepper plants, pre-flowering. The appl i cation rate is 1 .0 -4 .0 p ints of product per acre. up to a total of 16 p ints per acre per season . Appl icat i on must not be made more frequently than every 5 days. The ri sk assessments supporting this decision can be found at EPA -I-IQ-OPP- 20 14 -08 98; Document 10 : EPA-I-IQ -OPP- 2014 -0898-000 2 a nd Document ID: EPA-I-IQ-OPP-2014-0898- 0003 ; htt p :// , , ww .cp a . gov / pc s ti c ides/ r e r

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