Met h y l Eu geno l (ME) PC Code: 203900 

### Preliminary Work Plan and Summary Document Re g istration Review: Initial Docket March 2016 Case # 6203



### Approved b y :

# Robert**E~: ~**  Biope s ticide s and Pollution Prevention Di v i s ion 

### Date:Methy l E u geno l (ME)
T A BL E O F CO N T EN T S E P A-HQ-OPP

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I. PRE LIM INARY WO R K P LAN
................. . .................... .. ... .... .. .. .. . .. .. . . .. ... . . . .. .. .. ... ... ..... . ........ . ...... . .. . .4 A. O verv i ew . . ............... . ............ . . ...... . . ....... . ... ... .. ..... . ... . .. ... . .. . ...................... . ... . ....... . ......... . ..... ... . . .... 4 B . S t a tut ory a nd R egu l a to ry A uth o rit y . . . . ........ . ... . ..... . ....... . .. . .. . ... . .. . .. . .. .. ..... . . . . . .. . .......................... . . 

### .4 C . B ack gro un d a nd R e gul a tory Inf o rm at io n .. ..... . .. . .. ... ..... .. . . .. . . . ... .. .. . . ..... . ................. . ............ . ..... . .. 5 D . A n t i ci p a te d Dat a Nee d s a nd Ri s k Assess m e nt s . ... . ..... . ... . .. . ...... . ...... . .................... . . ... . . ...... . . .. .. . . .8 E. Ri s k to Threat ene d a n d E nd an gere d S p ecies
. . ..... . ................................... . ... ...... . . . . . .. . .. . . .... . .. . ... 1 4 F. E nd ocrine Effects
... . ...... . . . ... . ............. . .......................... . .. . . . . . . .. .. . . .. ... .... .. . .. . ............... . .. . ...... . ..... . 1 6 G. In c ide nt s ....... . ... . .. . .. . ...... .. .... . .. . . ... . . . . . ... . .. . ... ... . . ... . ... ...... . .. . ...... . ..... . ......... . ...... ... .. . ... .. ..... . ........ . . .. 1 7 H . T im e lin e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............... 1 7 I . G uid a n ce fo r Co mm e n ters .. . ..... . ..... ... ..... .. ...... . .... . .. . . ........... . .. . .............. . ....... . ............... . ........... 1 8 J . Nex t S te p s .. .. . .... . .... .. .... . ...... ..... .... . .. . . . ... . . ..................... . .. . .. . ... . .. . ...... . ..... . ................ .. . .. . . ... ..... .. . . 1 9 II
. BIB L IO G RAPH Y
......... . .......................................... . .. . ....... .. . . ... . .. . .. .. . . .. ... .... . .. . .............. . ... . . . .. .. ........ 20 A. S tudi es S upp o rtin g Reg i stra ti o n Rev iew of Me th y l E u ge n o l
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Page 2 of 23Methyl Eu ge no l (ME) EPA- H Q-OPP

- 20 1 5-054 7 www. regu / a t io ns . gov ACRONYMS AND ABBREVIATIONS AI or a.i. Active Ingre di e nt BPPD The EPA's Bi o p es ticid es and Pollution Preven ti on Divi s ion C.F. R
. Code of Federal Regulations D C I D a ta Call-In EDSP Endocrine Di s ruptor Screening Program EPA U
. S. Environmental Prot ec ti o n Agency FFDCA Federal Food, Dru g, and Cos metic Act FIFRA Federal In sec ticide , Fungicide , and Rodenticide Act FQPA Food Quality Protect ion Act FR Federal Regi s ter FWP Final Work Plan IDS In cide nt Data System MRIDNo. Master Record Id e ntific a ti o n N umber: The E PA' s sys t e m of recording and tracking s tudi es s ubmitte d t o th e Office of Pesticide Program s. MRL Maximum Resid u e Lim it OPP T h e EPA's Office of Pes ti cide Programs P C Code P es ti c id e chemica l code: a six -di gi t number assigned b y OPP to identify pesticide chemical s. PWP Prelimin ary W or

k Pl an TGAI Technical grade of th e active in gred ient TMDL Tota l Maximum Dail y Load 

# us U nited States

Page 3 of 23M e th y l Eu ge n o l (ME) I. PRELIMI N ARY WORK PLAN A. Overview EP A- H Q

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T he d oc k et (E P A -HQ-OPP- 20 15- 0 1 73) f or Me th y l E u ge no l (ME) i s n ow o p e n , i n iti a ting th e fi r s t publi c co mm e nt p eri o d fo r t hi s regis t ra ti on rev iew (case nu m b er 6203). T hree end u se p ro du c t s co nt ai nin g M e th y l Eu ge n o l are reg i s tered. T hi s p re li m in ary wo rk pl a n ( PWP ) ex pl a in s w h a t th e U
. S
. E n v iro nm e nt a l P rotecti o n Age n cy's (E P A ) Offi ce of P es ti c id e Program s (OP P ) kn ows ab o ut M eth y l E u ge n o l , hi g hli g htin g a nti c i pate d d a ta and assess m e nt nee d s, id e nt i fies t ypes of in fo rm ati o n tha t wo uld b e es p ec ia ll y u se ful t o th e E P A in co ndu c tin g th e rev i ew, an d provi des a n an ti ci p at e d t ime l i ne f or com pl et i ng t h e r egis tr at io n rev i ew proc e ss f or Me th y l Eu ge n o l. Th e regi s tra ti o n rev i ew process was des i gned to includ e a publi c p arti c ip a ti o n co mp o n e nt t o so li c it input fro m inte res te d s take ho ld ers. Th e EPA int e nd s , b y s h a rin g thi s inf o rm ati o n in th e doc ke t , to in fo rm th e p ubli c of w h a t it kn ows ab o ut Meth y l Eu ge no l , an d w h a t t ypes of n ew d at a or o th er informat ion wo uld b e he lpful f o r th e Age ncy to r ece ive as it moves towa rd a d ec i s io n o n th is co mp o un d. T h e EPA e n co u rage s all i nte res te d s t akeh o ld e rs to rev i ew th e PWP a nd to p rov i de co mm e nt s a nd additi o n a l inf o rm a ti o n th at w ill he lp th e E P A' s d ec i s i o n-m akin g process fo r thi s bi och e mi ca l p est i c id e. In ad di ti o n to ge n e ra l a reas o n w hich p e rso n s m ay w i s h t o co mm e nt , th e re ar e so m e areas id e nti fi e d in th e PW P ab o ut w hi c h th e E P A s p ec ifi ca ll y seek s com m e nt s and in fo rm ati o n . Inte res te d s ta k eho ld ers co uld inc lu de the f o ll owi n g: e n v i ro nmen ta l n o np rofi t or inte res t gro up s ; p e s ti c id e m a nu fac ture r s ; agric ultu ra l lab o r o r com mod ity gro up s; co mm e r c i a l , in s ti tuti o n a l , res ide nti a l , a nd o th er u s e rs of pe s ti cides ; or th e publi c a t l arge. T he PWP b egin s b y de s cr ib in g th e statut o ry a nd regu l ato r y a uth o ri t i e s for regi s t rat io n r ev iew. Nex t , it p rov id es b ac k gro und o n Me th y l Eu ge n o l , w hi c h includ es a d esc ri p ti o n of it s mo de of ac ti o n , c urre ntl y reg i s te red p e s t ici de p rod u c t s, ap pli cati on ra t es a nd me th o d s, u s e s ites, an d to lerance exempti o n in fo rm ati o n . Th e n , it li s t s th e a nti c ip ate d d ata n ee d s a nd ri s k as s ess m e nt s , a nd a p ro j ec ted r egis tr ati o n rev i ew tim e lin e f o r thi s case . Fin a ll y, th e PW P prov id es gu id a nce f o r co rnrn e nte rs , ex pl a in s th e nex t s t ep s E P A w ill b e t akin g , s umm ari z es b ac k gro und in fo rm a ti o n , a nd li sts s upp ort in g st udi es , ri s k assess me nt s , and o th er d oc um e nt s avail abl e for th e regi s tra ti o n rev i ew of Me th y l E u ge n o l. F urth e r in fo rm a ti o n a b o ut th i s ca s e , i n cl udin g b ackgro und a n d s upp o rtin g d oc um en t s , i s av a i labl e at 

### http : //

www.r egulations
. go v ( und er " SEAR CH f o r : Rul es , Co mm e nt s , A d j udi ca ti o n s or S upp o rtin g D oc um e nt s , " e nt er th e d ocke t id e ntifi ca ti o n numb e r, w hi c h i s indi cated above).
B. Sta tutory a nd Re g ulatory Authority Th e F oo d Qu a lity Pro tec ti on Ac t ( F Q P A) of 1 996 m a nd ate d a regi s tra ti o n rev i ew progra m . A ll p es ti c id es d i s tribut e d o r so l d in th e U nited S t at es (U. S
. ) mu s t g en e r a ll y b e r eg i s tered b y th e E P A , b ased o n sc i e ntifi c d at a s h ow in g th at th ey w ill n o t cau s e unreaso n abl e ri s k s t o hum a n h ealth o r th e e n v iro nm e nt w he n u se d a s dir ec te d o n th e pro du c t l ab e lin g. Th e regis trati o n rev iew program i s inte nd e d t o make s ure th at , as th e ability to a ssess ri s k evo l ve s and a s p o li c i es and pract ices c han ge , all regi s te r e d p es ti c id es co ntinu e to m eet th e s t atu to r y s t and ard of n o unreaso n abl e ad ve r s e effect s t o hum a n health o r th e e nv i ro nm e nt. C h an ge s in sc i ence, publi c p o li cy, and p e s t ic id e u se p ra c ti ces wi ll occ ur over t ime. Page 4 of 23M e th y l E uge n o l (ME ) E P A -H Q

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. gov Thro ugh th e r e gi s trati o n rev ie w pro gra m , the EPA p eri o di ca ll y reeva lu ate s p es ti c id es to make s ure that , as ch a n ge o c c ur s, produ c t s in th e m a rketpl ace a re sa f e to u se. Inf o rm a ti o n on thi s progra m i s prov id e d o n th e E PA 's web s ite 2

. T he Age n cy i s impl e m e ntin g the regi s tr ati o n r ev iew pr o gra m purs u a nt to F e dera l In sec ti c id e, Fun g i c ide , a nd R o d e nticid e A c t ( FIFRA) se ction 3(g), and will rev i ew e ac h regi s te re d p es ticid e ev e ry 15 yea rs to de te rmin e w h e th er it c o ntinu es to me e t th e F IFRA s ta ndard f o r re gis tra ti o n . Th e re gul ati o n s gov ernin g re gi s tra tion rev i e w b eg in at 40 C. F
. R
. 

### § 1 5 5.40
. Th e Age n c y will c o n s id e r b e n efit s inf o rm ati o n and dat a a s r e quire d b y F IFRA
. Th e public ph ase of re g i st rati o n r ev iew b egin s w he n th e initi a l d o ck e t i s o p e ne d f o r each case. T h e d oc k et i s th e A ge n c y 's o pp o rtunity to s tate wh at it kn ows ab o ut th e p es ti ci d e an d w h a t additi o n a l ri s k a nal yses a nd d at a o r inf o rm a ti o n it b eli eves are nee de d to mak e a r e gi s t ra ti o n re v ie w d ec i s i o n . Aft er rev i ew in g a nd r es pondin g to c o mm e nt s a nd dat a rece ive d in th e d oc k et durin g thi s initi al c omment p eri o d , th e EPA will dev el o p a fin a l wo rk pl a n ( FWP) an d th e a nti c ipate d sch e dule for th e reg i s tra ti o n r ev iew of Meth y l E u ge n o l. 

### C. Background and Regulatory Information i. 

### Summar y of the Active Ingredient, Usage and Associated Pesticide Products M eth y l E u ge n o l i s a n atur a l c on st itu e nt in a w id e r a nge of pl a nt s includin g m a ny of th ose c o n s um e d as foo d b y hum a n s a nd a nim al s. It h as a cl ove like fr agran ce a nd i s fo und in cl oves, c a rro t s , nutm eg, ros em ar y, b as il , l a ur e l , b a n a n as, walnut s , c itru s, bl ac k p e pp e r t ea tree, h yac inth , a nd s n a k eroo t. M eth y l E u ge n o l i s app roved in the U nite d St at es f o r u se in n atur a l or s ynth e ti c f o rm s as a fl avo rin g age nt in foo d s s u c h as i ce crea m , c oo ki es, candy, co l a so ft drink s, gum , a nd a s a fragra nce in p e rfum es a nd soa p s . In A pril 200 2, th e U S F oo d and Dru g Admini s tra ti o n (FDA) d e te rmin e d sy nth eti c form s of Meth y l E u ge n o l to b e "Ge n er all y R ega rd e d as S afe ( GRAS) " a nd m ay b e sa f e l y u se d in foo d in accord a nce w ith s p ec ifi c c o nditi o n s. In 2 00 6, th e EPA regi s te re d M e th y l E u ge n o l f or u s e as an in sect attrac ta nt. 

### It h as a n o n-tox ic mo re of ac ti o n. E nd u se pro du c t s ( EP ) c o nt a inin g M e th y l E u ge n o l a re u sed to a ttra ct a ran g e of ge nd er s p ec ific (m a l e) in sec t s a nd are f o rmul a te d into b a it s, lures, tr ap s , a nd c o n es. Th ese d e li very sys tem s a re ge n era ll y s ta ti o ne d o n a nd a ro und agri c ultur a l c ro p s, s tru ct ures , l a nd sc ap es, and r ig ht

- of

ways f o r u se in m o nito rin g and era di catin g in sec t p o pul a ti o n s in c ludin g th e M e dite iT a n ean a nd Ori e nt a l Fruit Fl y, thrip , l eaf min e r s, s pid er s, mites, m os quit oes , a nd a nt s. Two c urre ntl y r eg i s t ered pro duct s co nt a in Meth y l Eu ge n o l as th e so l e acti ve i n gre di e nt a t 5 8 a nd 7 6
. 9%, r esp ec ti ve l y, a nd an o th er regi s te re d pro du c t conta in ing M eth y l E u g en o l at 5 1 % i s c o mbin e d w ith s pin osa d , a co nve ntional in sec t ic id e b ase d o n n atur all y o c c urrin g c he mi ca l co mp o und s fo und in th e bac te ri a l s p e ci es 

### Sacc haro p o l yspora sp inosa. M e th y l E u ge n o l i s a n imp o rt ant p a rt of th e co ntr o l programs t a rge tin g m a ny s p e ci es of fruit fli es 

### (e.g
. , M e dit erran e an f ruit fl y, Ori e nt a l fruit fl y, m e l o n fl y, so la n aceo u s fruit fl y , and M ex i can fruit fl y) thro u g ho ut s t at es s u c h as H awa ii , Fl ori d a, a nd Ca lif o rni a. Cert a in s p ec ies o f fruit fli es c an c au se dev a s ta tin g dam age t o a wid e ra n ge of c o mm e rci a ll y grow n fruit a nd veg e tabl es. Wh e n fo rmul a te d as a Ju re, m eth y l e u ge n o l attrac t s m a le fruit fli es to trap s w here th ey di e o r a re r e m ove d f o r m o nit o rin g purp oses . Wh e n f o rmul a te d w ith th e in se cti c id e s pin osad , in sec t s (m al es) a ttrac te d b y the m e th y l e u ge n o l ex p eri e n ce irrever s ibl e tre m o r s, p ros tra te tre mbl i n g, p a ra l ys i s, a nd de ath fr o m ex p os ure to s pin osad th e re b y r e du c i n g th e am o unt of p es ticid es appli e d di rec tl y to plant s. Th e e ncl ose d n ature of it s a ppli cati o n ( tr ap s, lu res, s t ati o n a r y b a it s , a nd co nes ) limit s M e th y l E u ge n o l ' s ex p os ure p o te ntial t o hum an s as we ll as to n o n - tar ge t e d and li s ted orga ni s m s . Th e c h e mi ca l s tructure o f M e th y l E u ge n o l i s:

2 See http : // www2
. e p a.gov/p estic id e- reeva lu a ti o n . Page 5 of 2 3Methy l Eu geno l (ME)

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Tab le l. O pro v id es a s umm ary of t he c he mical facts fo r Met h y l E u ge nol : 

### Tabl e 1.0 C hemical Facts for Methyl E ugenol PC code 203900 Case N umb e r 6203 CAS N umb e r 93-15-2 Year fir s t reg i ste red 2006 Pesticide Ty p e In se ct A ttrac ta nt C hem ical cla ss Bioc he mic a l Reregistration E li gib ility D ec i s ion (RED) No To lera nce Reassess m e nt D ece mb er 2004; Fe bruar y 2 , 2005 (70F R 5440) E li g ibilit y D ec i s io n (TRE D ) C umul a tiv e group No t app li cab le. Met hy l E u ge n o l h as not b ee n id e ntifi e d as a member o f a c umul a ti ve g ro up that s h a res a common m ec h a ni s m of tox icity. 40 CFR C it a tion 40 CF R 1 80 .1 067 (Met hy l E u ge n o l a nd Ma la thion combi n a tion ) Non-pest ic id a l u ses Foo d F lavo rin g Age nt

Pa ge 6 of 23Methyl Eugeno l (ME) EPA-HQ

- OPP

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. gov The following t ab l e s ummari zes the u se and u sage in formation for Methyl Eu geno l : Table 2.0 Methyl Euge n o l Use and Usage Information Summary of Use In sec t attractan t/lure commonly u sed in tr aps and ba it s t ati o n s for monitorin g and eradicating insect popu l ations. Use Sites Agricultural fie ld s and orch ards, land scap es, right-of- ways Summary of Usage No usage inf ormati on has been reported. Formu l at ion Types Oily l iquid , co nes App li cati on Method Lures , in trap s a nd b a it s t at ions Technical Registrant Farma Tech Int ernatio nal Corp. No. of Registrations 3 R estri cted Use None

Tabl e 3
. 0 Sum m ary of Cur r ent ly R egistere d Meth y l E u geno l based Pesticide End-Use Products (EPs) EPA Product Name Registration (%Active Date Registered App lication Application Use Sites Number Ingredient; Rates Method s Formu lat ion Type) FTMETHYL Di sposa ble lure in EUGENOL SHORT 81325

- 3 LURE October 26, 2007 7.75g retrievable trap Tree canopies 58%
Cone/ lure in Buffer areas and 36638 -41 Sentry Methyl December I , l Og retrievable trap periphery of Eugeno l Cone 2007 fruit orchards 76.9% and crop field s No n- Crop Site s STATIC Spinosad Large droplet liquid On ly: sta kes 627 19

- 592 ME June 1 3, 2008 3.4

- 6.84 fl s pot app li cation posts , fence s, 51% oz ./ acre non-crop tree trunks or li mbs , telephone pole s,

Pa ge 7 of 23Methyl Eu ge n o l (ME) EPA-HQ -OPP

- 20 1 5-05 4 7 www. re gu l ati ons. gov ii. Tolerance Actions In March , 19 82, an exemption from the re quirem e nt of a tolerance was es tabli s h e d by the Agenc y for M eth y l Eugenol-Mal athion (3: 1 ratio ) combination impregnated on a c a rrier and u se d in United States Department of Agricu ltu re (USDA) Oriental Fruit Fl y Eradication Program s. Thi s exemption was modifi e d in April, 2004 to further define the carrier. An Experimental Use Permit (EUP) was granted in June , 1990 to the Tropical Fruit and Vegetable Re search Laboratory , USDA Agricultura l Research Station in Honolulu , HI to use Methyl Eugeno l and Malathion in pla s tic trap s pl aced on the p eriph e ry o f fruit orchards to mitigate Oriental Fruit Fl y population s. Thi s EUP ex pire d in October, 19 92. In April , 20 0 2, th e U.S. Food and Drug Administration (FDA) d e clare d sy nthetic forms of Methyl Eugeno l to be Generall y Regarded as Safe (GRAS) and may be safe l y used in food in accord a nce with s pecific conditions under 21 CFR 172
. 515
. In February , 2005 EPA publi s hed a Tolerance R eass e ss ment Eligibility Docume nt for Meth y l Eugeno l and concluded "
. .. th ere i s a rea so nable certainty that n o h arm to any population or s ubgroup will re s ult from the di e tary and water exposure to Methyl Eu geno l from u ses s p ec ified in th e ex i s tin g exe mption for the requirement s for tol erance f or Methyl Eugenol und er 40 CFR § 1 80.1067." Occupation a l and re s id e nti a l ex po s ure risks were not eva lu ated in thi s tol e ranc e rea ssess m e nt.

D. Anticipated Data Needs and Risk Assessments Pro v id e d be low are tabl es of th e current data requir e ment s f o r bioch e mic a l p es ti c id es as se t forth in 40 C.F. R. 

### § 15 8, s ubpart U. They a re arrayed b y sc ie ntifi c di sc ipline 

### (i.e ., prod uct ch e mi s try, hum a n h ea lth assessment, and non-t a rg et organism s ) a nd d esc ription s of how the d ata requirements ha ve be e n fulfill e d o r where d a ta h ave been waived. At thi s tim e, n o data gap s (anticipated dat a n ee d s) for Meth y l E u ge nol h ave been identifi e d
. Th e mo s t recent comprehensive ri s k assessment for Methyl Eugenol was completed September 20,2013, in s upport of an amendment to add unregi s tere d so urce s (U.S
. EPA, 2013). B eca u se there are no data gap s for Meth y l E ugen o l or anti c ip at e d d a ta nee d s, and no a dditional inf o rmation ha s been rece iv ed on thi s bi oc he mic a l s ince thi s most recent ri s k assess ment , th e A ge nc y doe s n o t a nticipat e the need to conduct a new ri s k ass e ss ment during registration rev i ew.
i. Product Chemistry (40 C.F.R. § 158
. 2030 )

Table 4.0 Summary of Product Analysis for Methyl Eugenol Harmonized Has Data Requirement MRIDNo. or

Guideline Data Requirement Number Been Addressed? How? Other Source 88 0.1100 Prod uct Id e ntity and Co mpo s iti o n Yes- Study 4 63 5 8 40 3 880. 1 200 Description of Sta rtin g Materials , Yes

- Study 4 9008903; Pro ducti on , a nd Formulation Process 4 900890 1 880. 1400 Discus s i on of Fo rmati o n of Impuriti es Yes

- Study 4 774 1901 ; Page 8 of 23Methy l Eugeno l (ME)

Harmonized

Guideline Number 830. 1700 830. 1 750 830. 1 800 EPA-HQ-OPP-20 15-0547 www. reg ula ti o n s .g ov
Table 4.0 Summary of Product Analysis for Methyl Eugenol Has Data Requirement MRIDNo. or Data Requirement Been Addressed? How? Other Source 47541903 Prelimin ary Analysis Yes

- Study 49008902 Certified Limit s Yes

- Study 49008902; 49008904 Enforcement Analytical Method Ye s - Study 49008903

Table 5.0 Summary of Physical and Chemical Characteristics for Methyl Eugeno l Harmonized Has Data Requirement MRID No. or

Guideline Data Requirement Number Been Addressed? How? Other Source 830.6302 Co l or Yes

- Study 46358403 830
. 6303 Phy s ical St ate Yes

- Study 4635 8 403 830
. 6304 Odor Ye s - Study 46358403 830.63 1 3 Stability to Norma l and Elevated Ye s - Stud y 46358403 Temperatures, Metal s and Metal I o n s 830.7000 pH Ye s - Stud y 4635 8 403 83 0.7050 UVNisib l e Li g ht Absorption Yes

- Study 4635 8 403 830
. 7200 Me lting Point/Melting Range Not required 2 830.7220 Boiling Point/Boiling Ran ge Ye s- Study 4635 8403 830.7300 Den s ity/Relative D e n s ity/ Bulk Den s ity Ye s - Study 46358403 (Specific Gravity) 8 30.7520 Particle Size , Fib e r Length , and No t requir ed

- s ub s tance is a liquid Diameter Distribution 830 .7 550 830.7560 Partition Coefficient (n-Octano l Water) Not require d 3 8 30.7570 830 .7840 W a ter Solubility Yes

- Stud y 46358403

2 Per 40 § CF R 1 58.2030 Test Note 1 6: Req uired f o r o rga ni c c hemi ca l s unl ess they di soc iate in water o r are partiall y or co mpl e te ly s o lubl e in M e th y l Eugenol is p artiall y so lubl e in water. 3 P er 40 § C FR 1 58.2030 Test Note 1 6: R e quir ed f o r o rgani c c h e mi ca ls unl ess th ey di ssociate in water o r are partiall y o r co mpl e t e l y so lubl e in water. Methyl e uge no l i s partiall y so lubl e in water. Page 9 of 23Me th y l E u ge n o l (ME) E P A -H Q

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Table 5
. 0 Summar y of Physical and Chemical Characteristics for Meth y l Eugenol Harmonized Ha s Data Re quire ment MRID No
. or

Guid e lin e Data Requirement Number B e en Addre ss ed? How? Oth e r Sourc e 830.7950 Vap o r Pre ss ure Yes

- S tudy 4 63 5 8 4 03

11. Human Health Asse s sment (40 C
. F
. R. § 158
. 2050 ) 

### Ha zard Chara ct e rization and Ri s k T he tox i co l og ic a l d at a b ase i s c o n s id ere d co mpl e te f or c harac ter i z in g h azard a nd assess in g ri sk fro m M eth y l Eu ge n o l. No additi o n a l s tudi es are a nti c ip a te d t o b e n ee d e d f o r reg i s t ra ti on rev iew . Ac ute tox ic ity s tu d i es h ave s h ow n s li g ht tox i c ity re l a t ive to o r al ( LD so > 1 , 179 m glkg) a nd d erm a l (LD so > 2
. 02 m glkg) ro utes o f ex p os ures (Tox. Catego r y III )
. T he inh a la ti o n L Cs o i s greate r th a n 4. 8 mg/L w ith n o d eath s o r a d ve r se s ig n s n o t e d (Tox. Catego ry I V)
. Meth y l E u ge n o l pro du c ed s kin irrit a ti o n in a prim ar y d etm a l irrit ati o n s tud y but thi s ef f

ec t cl eared b y 72 h our s ( Tox. Catego r y I V). S igni fica nt eye irrit ati o n was n o te d in a prim ary eye irr i t ati o n s tud y a t o ne h o ur p os t appli cati o n of Me th y l E u geno l bu t cl eared b y 2 4 h o ur s (Tox. Catego r y IV). M eth y l E u ge n o l i s n o t cl ass ifi e d as a s kin se n s iti zer. Sub c hro ni c tox ic ity s tudi es co ndu c t e d w ith M eth y l Eu ge n o l de mo n s tr ate d in c rease d li ve r we i ght s in b o th m a l e a nd f e m a le ra t s. In a pre n at a l tox ici ty s tud y, a re du c ti o n in th e av er age fe ta l b o d y we ight p er litt er an d an in c rease d in c id e n ce of un oss ifi e d s t ern eb ra ! was no t e d ; in c rease d li ve r we ig ht was n ote d in the m a te rn a l a ni mal s. In additi o n , a re pro du ct ive s tud y d e m o n s trate d th at M eth y l E u ge n o l i ndu ced a s i gn ifi can t in crease in t es ti s s i ze. C hro ni c tox i co l ogy s tu d ies de mo n s tr at e th at re l ative l y high

- b o lu s d oses o f M e th y l E u ge n o l admini s t e r

e d o r all y res ult in h ep a ti c n eo pl as m s in rat s a nd mi ce. R es ult s of mut age ni c it y s tudi es indi cat e d th at M e th y l E u ge n o l cau se d un sc h e dul e d DNA s ynth es i s a nd M e th y l Eu ge n o l met ab o lit es f o rm e d DNA addu c t s. M e th y l Eu ge n o l h as b ee n rev i ewe d b y th e Nati o n a l Tox ico l ogy P rogram (NTP, 200 5 ) and c l ass ifi e d as " reaso n a bl y a nti c ip a te d t o b e a hum a n carc inoge n "
. U nd e r th e c o nditi o n s of2 year ra t s tudi es, th er e was cl ear ev id e nce of carc in oge ni c ac ti v i ty o f M eth y l E u ge n o l w ith in cre a se inc id e nc es o f li ver ne o pl as m s and ne u roe nd oc rin e tum o r s of th e g l a n d ul ar s t o m ac h i n m a l e a nd fe m al e r at s a nd th e in c rease in c id e n ces of ki d ney n eo pl as m , m a li gnant m eso th eli o m a, m a mm ary g l and fibr oad e n o m a, s ub c ut a neo u s fibr o m a and fibr o m a o r fib rosa rco m a ( co mbin e d ) in m a l e r a t s . A co mp a rabl e mo u se s tud y a lso s h owed th at th er e w a s in c rease in in c id e n ces of li ve r n eo pl as m s a nd ne uroe nd ocrin e tum o r s of th e g l a ndul ar s to m ac h re l a t e d t o M e th y l Eu ge n o l ex p os ure. H owever, b ased o n th e n o n-f oo d u se of Meth y l E u ge n o l as a lure in trap s pl aced in cl ose prox im ity t o f oo d cro p s ( n o t o n f oo d ), n o d ie ta r y, o r al , de rm a l or inh a la ti o n ri sks o f ex p os ure ex i s t s (F arwe ll , 20 04 ).

Page 10 of 23Methyl Eu ge n o l (ME)



### D ie t a r

y an d O ccupationa l Exposu r e and Ri sk Assessment EPA- H Q-O PP- 20 1 5-05 4 7 www. re gulation s . gov

A l though there are hazardou s effect s found i n rodent to x icity s tudie s, the potential for hum a n dietary e x po s ure to thi s chemical i s be l ow a l evel o f quantitation. The in sec t attractant, Methy l Eugenol, i s n o t app l i e d to a ny food crops but i s o nly u sed near orc h ard s. Du e to it s vo lat ility and bec a u se of it s u se p attern s, i t is considered unlikely for Methy l Eugenol to contaminate food or drinking water. Thi s was confirmed b y a m o n i toring s tudy b y th e Ca lifornia Department of Food a nd Agricu l tura l , which did not det ect Meth y l Eugeno l in fruit co ll ected near s it es of Meth y l Eugenol trap s u se (Turner 

### e t al., 19 89). Therefore , there are no ri s k concern s for M et hyl Eugenol u se d as an i n sec t attractant in in sec t trap s . In addition , the retrie vable in sec t trap s are availab l e as r ead y to u se it e m s th ere b y significantly limiting the pote ntial f or applicator derm a l and inhalation ex po s ure . The p o tenti al for p os t-app l icati o n dermal and inhalation exposure re s ultin g from entry into trea ted a reas is anticipated to b e neg l i g ibl e. T he ready to u se retrie vabl e trap s ar e u sed in orchards and require no additional p os t-app l icati o n treatment or hand l in g other than to r e m ove th e m for di s p osa l or replacement approximately every 3-4 m o nth s. 4 Furthermore , the Ag e nc y h as r ece i ve d n o incid e nt re p o rt s r es ultin g from th e u se of p est icid a l produ c t s containing Methy l E u ge nol.

Tab l e 6
. 0 S u mmary of H u man Hea l th Assessment Data for Methy l E u ge n o l
Data Requirement Has Data MRIDNo. Harmonized Req ui rement Been So urce or Other

Guide li ne Addressed? How? Reference Number Acute Oral Toxicity- Rat Y es - Study U.S. E P A 44906304 870. 1100 870. 1 200 Acute Dennal T ox ic it y Yes- Study U.S. EPA 4490 6304 87 0.1300 Acute Inh a l a ti o n Toxicity Ye s - Study U.S. EPA 4490 6304 870 .2400 Primary Eye Irrit ati o n Yes

- Study U.S. E PA 44 906304 870.2600 Primary D e nn a l S ens iti za ti o n Yes

- Study U.S
. EPA 44 906304 870.2 50 0 Acute Dennal Irrit ati o n Yes - Study U.S. E P A 4490 6304 870.5 100 ; Mutagenicity: Moertelman s e t Moertelmans Bacterial R e verse Mutation Yes- S tud y a!. , (1986) e ta/
. , (19 86) Test NTP, (2000) NTP , (2000)

4 Me th y l Eugeno l Co n e labe l u se pattern. Page 1 1 o f 23Meth y l Eu ge no l (ME) E PA-HQ-OPP-20 1 5

- 0547 www. re gulation s . gov
Table 6.0 Summary of Human Health Assessment Data for Methyl Eugenol
Data Requirement Has Data MRID No
. Harmonized Requirement Been Source or Other

Guideline Addressed? How? Reference Number 870.5300 Euk aryotic R everse Mutation Moertelman s et Moertelman s Te s t Yes- Study a !. , ( 19 8 6) e t a !
. , (1986) NTP, (2000) NTP , (2000) 870 .3100 90-d ay Ora l

- rat Ye s - Study NTP , (2000) NTP, (2000) 870.3 100 90-day Oral - mo use Ye s - Study NTP, (2000) NTP , (2000) 870.3200 90-day Dermal Ye s -W aive d 5 4691 83 02 870.3250 90- d a y Inh a la tion

- rat Ye s - Wai v ed 6 4691 8 302

8 70.3700 Prenata l De v elopmental- rat Ye s - Study Price , (2004) Price , (2004) 87 0.3800 Reproductive To x ici ty -ra t Ye s - Study NTP, (2000) NT P , (2000) NTP, (2005) NT P , (2005) N rn , (2000) Carc in oge ni c it y- rat N rn , (2000) Abdo , K.M. 87 0.4200 Abdo , K.M. e t e ta!. , (200 1) a !. , (200 1) Aum a n , J
.T ., A um an, J.T. , e l e ta!
. (2004) Ye s - Stud y a !
. (2004) Miller E. C., Miller E
. C. , e t e ta!., ( 1 983)

a!., ( 19 83 ) Phillip s, Phillip s, D.H. , e t D
. H ., e t a ! ., a / ., (19 8 4) ( 1 984) 870.4200 Carcinogen i city -mo u se NTP, ( 2 005) NTP , (2005) Y es - St ud y 88 0.3550 G e n otoxicity (lmmun o toxicity) Ye s - Study NT P , (2000) NTP, (2000)
5Th e 90 da y Derm a l s tud y was wa ived as re p ea t d e rm a l ex p os ure t o M e th y l E u ge no l I s n o t expected ba s ed o n It s u se patt e rn as a r ea dy t o u se re trie vabl e in sec t trap . 6 The 90 day Inh a l ati o n s tudy was wa i ved as rep ea t inh a l ati o n exposure to M e th y l Euge nol is n o t ex p ec te d ba sed o n it s u se p attern as a ready t o u se r e trie vabl e in sec t trap .
Page 12 of 23M e th y l E u ge n o l (ME) EPA -H Q-O PP- 20 1 5-05 4 7 tVI V IV
. re gulati o n s . gov iii. Nontarget Organisms and Environmental Fate ( 40 C.F. R. § 158 . 2060) Expos ure of n on -t ar get avian and m amm a li an s p ec ies to Meth y l E ug e n o l i s hi gh l y unlik e l y b eca u se th e end prod u ct i s u se d as a fruit fl y a ttr act ant th at i s e nclo se d in contai n e rs o r traps for u se in o r c h a rd s (no gro und or aeria l spray) , d egrades qu ick l y (vapor degr a d es with h a lf-lif e of 5 h o ur s), and i s appli e d at a ma x imum ra te of I 0 gram AI p e r h ec t are , a mbient a ir re s idu e leve l s were rec orded at 

### 14 2.8

- 34
. 9 ppt o n day of a ppli cati o n and Day I p os t app li cation a nd s h owe d no detectable residue s at D ay 5 (Turner 

### et 

### a/. , 

### 1989). M e th y l E u ge nol i s r egis te r ed in ready to u se retrievable tr aps , which will s ignificantly limit potential expos ur e to bird s, fish , n o n-t a r ge t in sec t s , and aqu ati c o r gani s m s . There i s no gro und or ae ri a l s pra y a nd , th erefore, n o p o t e nti a l for runoff o r drift t o an aq u a ti c area.

Tabl e 7.0 Summary of Non-target Organism Data for Methyl Eugenol Harmoniz e d Ha s Data Requirement B ee n

Guideline Data Re quirement MRID Number Addressed? How? 850.2 100 Avian Acute Ora l Toxici ty Ye s - W aived 7 469 1 8 302 850.2200 Avian Di e t ary Tox ic it y Y es - Waived 8 469 1 83 02 850. 1075 Fi s h Ac ut e Tox ic ity , F re s h wa ter Yes

- Stud y 44906304 850. 10 10 Aqua t ic In ve rt e br a te A c ut e Ye s - Wa ived 9 469 1 8302 T ox icity, Fre s hw a ter 8 50.4100 Terrestria l Pl a nt Toxic ity, Y es - Waiv e d 1 0 469 1 8302 Seedling Emergence 850.4 1 50 Terre s tri a l P lant Tox ic ity , Yes

- Wa i ved 11 4 69 1 8302 Veget a t ive Vigor 88 0.4350 Nontarge t In sec t Te s t i n g Ye s - Study 47147604
7 T he Av t a n Ac ut e O ra l tox t c t

ty s tud y was wa 1 ve d as ex po s ure t s no t ex p ec ted t o occu r b ecaus e of M et h y l Eu ge n o l u se p atte m as a ready to u se re tri evabl e in sect trap. 8 The Av i a n Di e tary tox ic it y s tudy w a s wa i ve d as ex p os ure is n o t ex p ec t e d t o occ ur bec a u se o f Meth y l E uge n o l u se p a tt e m as a r

ea dy t o u se re tri e vab l e in sec t tra p . 9 T he A qu ati c In ve rte bra t e Ac ut e t oxic ity s tudy was wa i ve d as exposur e is n ot expec t e d to occ ur becau e o f Me th y l Eu ge n o l u e p att e m as a r ea dy t o u se re tri eva bl e in sec t trap . 1 0 T h e T e rres tri a l Pl a nt See dling Em e rg e n ce tox i c ity s tud y was wa ive d as expos ure i s no t ex p ec te d to occ ur becau se of Meth y l Eu ge n o l u se pattem as a r ea d y to u se re tri evab l e in sec t trap. 1 1

T h e Te rres tri a l Pl a nt Veg e t at ive Vigor tox ic ity s tud y was waived as ex p os ur e is no t ex p ec ted to occ ur be cau se of Methy l E u ge n o l u se patte m as a r eady to u se r e tri evab le insec t tr ap.

Page 1 3 of 23Methyl Eu geno l (ME)



### Harmonized

Guideline Number 850. 10 75
850. 10 75 850. 1010 850.2200 850.2 100 EPA-H Q-OP P- 20 1 5

- 05 4 7 www . re gu latio n s . gov 

### Table 8.0 Summary of Ecotoxicity Studies for Methyl Eugenol Species Results MRIDNo. Rainbow t ro ut 44906304 (On co rhynchus mykiss ) 96 hr LC so = 6.0 m g/ L (4.9

- 7.2 mg/ L) ; Moderate toxicity Bluegill s unfi s h 96 hr LC so = 8. 1 m g/ L (7.4 -9 .0 m g/L) 44906304 (Lepomis macro chirus) Moderate t ox icity Daphnia magna Waiver re qu es t granted becau se of l ow potential ex posure to terr est ri a l areas. Product i s enc losed in trap/ lure
. 12 Av ian Dietary Test Waiver request g ra nted becau se of low potential ex pos ure to terre st rial a r

eas. Product i s e ncl osed in trap/ lure. 13 A v ia n Acute Ora l Waiver r eq uest gra nted be ca u s e of low potential expos ure to te rrest ri a l areas. Prod u c t i s e ncl osed in trap/ lure . 14 1 2 Watve r req u es t grante d b ecau se of l ow potent t a l ex p osu re to terrestna l areas. Product ts e n c lose d tn tr ap / lure, te rrestnal expos ure n o t ex pe c t ed. 13 Wa i ve r r equest gr ant e d b eca u se of low po t e ntial ex po s ure t o terres tri a l areas. Pro du c t i s enc losed in trap/ lure, t errestri a l expos ure n o t ex pected
. 14 Waiver r eques t gra nt e d b eca u se of low pote nti a l ex p os ure t o t errestria l areas. Pro du c t i s enclosed in tr ap/ lure, t errest ri a l expos ure n ot expec ted.

E. 

### Threatened/E ndang e red Species Methyl E u geno l i s u se d as an at trac tant for fruit flie s in orchard b ai t tr ap s and i s also pro duc e d n aturall y in many pl a nt s. Acute tox icit y s tudi es o n freshwater fish s how th a t Methyl E u ge no l i s m o d erate l y toxic with LC so valu es ra ngin g from 6.0

- 8. 1 m g/ L. E nv ironmental ex p os ur e to this compound i s ex p ec ted to be limited bec a u se the pro duct i s to b e u se d only in th e m anuf acture of bait-trap s a nd lur es; an d therefore m ost of the require m e nt s f or n o n-tar ge t e d tes t s peci es and o th e r eco logical tes tin g were wai ve d
. The Cali fornia D epartm ent of Food and Agriculture (Turner 

### e t al., 1 989) monit ored r es idu e l eve l s of Methyl Eugenol in a mbient a ir aro und trap s at 14 2.8

- 34 .9 ppt on day of a pplicati o n a nd Day I p os t a ppli cati o n and s h owe d n o de tec tabl e r es idu es at Day 5 (Tabl e 9). Methy l E u ge n o l vapor rapidly d egrade s in th e e nv iro nm e nt with a half-lif e of 5 hours.



### Table 9.0 Methyl Eugeno l Concentration found in Air during Application of Oriental Fly Eradication Program ppt) 

### Days After Site 1 Site 2 Site 3 Site 4 Application 0 142.8 7 1. 9 ND 44
. 2 1 34.9 3 1. 9 ND 31.9 5 ND ND ND ND Field s tudie s h ave a l so s h ow n th at Methyl Eugenol i s a kairomone (Metcalf and Metcalf, 19 92) and i s a n attractant for m any s pecie s of th e Subfamily D ac inae 

### (i. e. fruit fly s ubfamily). Uc hida 

### et al. , (2006) concluded th at trap s with Methyl Eugenol attracted m a n y n o n-target in sec t s, m a ny of which were Page 14 of 23Me th y l E uge n o l (ME) EP A -H Q

- O P P

- 2 0 1 5

- 05 4 7 www .regulations
. gov sc ave n ge r flie s. Th e re se arch e r s co nclud e d , h owever, that th e prese n ce of th ese n o n-t arge t fli es m ay h ave res ulte d p a rti a ll y fr o m th e lures, as we ll as d ecay in g i n sec t s i n s id e th e tra p s. Bec a u se of the se findin gs, th ey c o nclud e d th at futur e s tudie s w ith M e th y l Eu g en o l s h o uld inclu de fr e qu e nt cl e anin g o f tra p s in o rd e r to avo id fa l se p os iti ve res ult s for e valu atin g M e th y l Eu ge n o l 's abilit y t o a ttra ct n o n-target in sec t s. Le bl a n c 

### et a l
. , ( 2 00 9) al so n o te d th at fruit fl y lures ( M e th y l Eu ge n o l) , w he n u se d ove r large a reas m ay attrac t a s m a ll numb e r of non-target in se ct s , includin g p o llin a to r s a nd a phid pre d at o r s , pl a nt feedin g Miridae , and S c i arida e , o r b y seco nd ar y att rac ti o n of l a rge numb er s of sa prop h ago u s s p ec i es to th e a cc umul ati o n o f d ead tra pp e d fli es . Th ey furth e r n o t e d th a t th ere w as a re l ati ve l y s m all numb er o f in sect p o llin at o r s (in c ludin g h o n ey b ees ) in M e th y l E u ge no l trap s ( 0
. 0 3 to 0
. 15 p e r trap p er d ay ) s u gges tin g th a t thi s a ttr ac ti o n i s like l y t o oc cur over s h o rt di s ta n ce and c an b e minimi ze d b y avo idin g th e appli cati o n o f M e th y l Eu ge n o l trap s to trees durin g the flo we rin g stage. L

e bl an c 

### e t a l
. , ( 2 0 09 ) ob served th a t , b ec au se m os t n ati ve H awa ii a n in sec t s p ecies a re r ath er un co mm o n in hi g hl y m o difi e d h abit a t s , th e ri s k of a ttr act in g l a rge numb e r s of e nd e mi c sa p ro ph ago u s n o n-t a r ge t s to d ecayin g fli es i s ve r y l ow in t he n o n-n a ti ve a nd agric ultura l h abit at s wh e re th e lures are prim a ril y u se d. Thi s wa s c o nfi rm e d in a pre limin ar y c o mp a ri so n (H awa ii ) o f catc h e s o fDr oso philid ae in trap s b a it e d with d ecayin g fli es in re l ati ve ly undi s turbed n ati ve f o rest , t wo e c o to ne f o res t s ite s adj ac e nt to n a"ti ve fo r es t a nd n o n-n a ti ve f o r es t a nd agri cultura l a reas . On M ay 9, 2 00 6 , in 7 1 F R 4 699 4-47 0 54 , the F i s h a nd Wildlife S erv ic e (FW S ) of th e D ep artm e nt of th e Int erio r (DOl ), pl ac ed 1 2 s p ec i es o f pi c ture - w in g fruit fli es fr o m th e H awa ii an i s la nd s o n th e e nd an ge r e d o r threate n e d li s t 

### (D roso phil a a gla ia, D
. diff e r

e n s, D
. h e m i p eza, D . h e t e ro n e u r a, D
. m o nt gom e t y i , D. m ulli, D
. musap hilia, D
. n e oclavise ta e, D . o b a ta i , D
. och robasis, D. subs t enop tera , and 

### D
. t arp h y tri c hia ). Sin ce M e th y l E u ge n o l i s an attr act a nt f o r fruit fli es, m a nu facture r s of e nd-u se pro du cts mu s t m ak e cert a in th a t pro du c t s are n o t u s e d in a reas wh er e th e s e fli e s m ay b e i mp a ct e d
. Th ese li s ted s p ec i es of f ruit fli es an d th eir c riti ca l h a bit a t a re pro t ec ted w ith nin e of the s p ec i es alread y o n fo res t reserves th a t a re p ro te cted S t ate Pa rk la nd , or p1i va t e l a nd pro tec t e d b y th e Nature Co n serva n cy . Th e re m a inin g s p ec ies a re o n s ites w ith n o agric ultural a cti v it y a nd s ites ow n e d and m a n age d b y th e C ity a nd Co unt y of H o n o lulu adj ace nt to Sta te c o n serv a ti o n di st ric ts ( Coo k , 2 00 7)
. A s e a rc h of th e U.S
. E P A's E n v i ro nm e nt al Incid e nt In fo rm a ti o n S ys te m ( E llS ) co nduct e d o n J a nuary 11 , 2 01 6 , revea l e d n o in c id e nt s as s oc ia te d w ith Meth y l E u ge n o l ; thi s d a t ab a s e co nt a in s info rm a ti o n d a tin g b a ck to th e 1 9 70 s. Th e E P A w ill c o n s id er a n y in c id e nt d ata o r co mm e nt s s ubmitte d in r es p o n se t o thi s Pre limin ary Wo rk Pl a n . B a s e d up o n th e res ult s of tox icit y te s t s o n n o n-t arge t s p ec i e s a nd th e l ow p ote nti a l fo r ex p o s ure n o te d prev io u s l y (n o t lik e l y to a tt rac t p o llin ato r s), th e ri s k s to e ndan ge red/ thre at e ne d s p ecies a nd th e ir d es ign a t e d c riti ca l h abi tat s, fr om M e th y l Eug e n o l as an ac ti ve in gredi e nt in p e s ti c id e pro du c t s a re ex p ec ted to b e ne gli g ibl e . Th e re f ore, E P A h as reach e d a " No Effec t " det e rmin ati o n f o r e nd a n ge re d/ threate n e d s p ec i es a nd d es ign a te d c riti ca l h abit at (R ex ro d e , 2 0 15).

Page 15 of 23Methyl E u ge n o l (ME) 

### F. Endocrine Effects EPA

- HQ-OPP-20 15-054 7 www. r e gulation s. go v

As required by the Administrator under the Federal Food, Drug , and Cosmetic Act (FFDCA) section 408(p), th e EPA has developed the Endocrine Di sru ptor Screening Program (EDSP) and ha s begun to implement the screening program that is to be us e d to test all pesticid es in order to determine whether certain s ubstances (i ncludin g pe s ticide active and other ingre dient s) ma y ha ve a n effect in hum a n s or wildlife similar to an effect produced by a " naturall y occurring estrogen, or other such endocrine effects as the Administrator may de s ignate." FFDCA section 408(p)(4) authorizes the Administrator , by order , to exempt fro m the requirements of the Estrogenic Substances Screening Program a biologic s ub s ta nc e or other substance if a determination is made that the s ub s tanc e i s not an ticipated to produce any effect in humans similar to an effect produced by a naturally occurring estrogenic substance. Between October 2009 and February 2010 , the EPA i ss ued te st orders / data call-in s for the fir s t group of 67 chemicals, w hich contains 58 pe s ticid e active ingredients and 9 in ert ingredients. A seco nd li s t of chemica ls id en tified for EDSP scree ning was published on June 14 , 2013 , and include s some p es ticides sc heduled for registration review and chemicals found in water. Methyl Eugenol wa s among th e group of p es ticide active ingredient s on the li s ts to be screened under the EDSP. E PA researchers developed the Endocrine Di s ruption Screening Program for the 21st Century Da s hbo ard (EDSP21 Da s hboard) to provide access to new chemical data on over 1 ,800 chemicals of intere st. The purpo se of this i s to help EPA evaluate chemicals for endocrine -r elated activ ity (EDSP21 Da s hboard). No data are available on the endocrine effect s of Methyl Eugeno l ; however , d ata are available for Eugenol. Because Eugenol i s s ignificantly s imilar to Methyl Eugenol in s tructure and environmental effects , E ugenol EDSP d a ta are u sed here as a surrogate for Methyl Eugenol data. Eugenol was tested b y EPA 's, Office of Re searc h and Development (ORD), National He a lth and Environmental Effects Research Laboratory (NHEERL) , and MED for chemical binding t o rainbow trout endocrine receptor (ER) as mea s ured 

### in vitro with relative bindin g affinity that ha s been es timated to be s imil ar to that of a very weak phenol binding
. Eugenol was not run in th e gene activation assay for confirmation, but the observed binding curve wa s believed to b e due t o competitive binding for the estrogen receptor based upon affirmative binding re s ult s f o r other similar methoxy phenol structures which induced detectable v itellog enin (Vtg) gene expression in liver s lic es of male rainbow trout 

### (Schmieder et. al. , 2004)
. The relation s hip of low binding affinity 

### in vitro and the abilit y to cause an adverse effect 

### in vivo i s not known. However, Eugenol was - 1.5 to 2.5 orders of magnitude les s in it s relative binding affinity for ER than chemicals that ha ve been tested and s hown t o have 

### in vivo effects in MED s tudies , and similar chemicals te s ted by others (Seki 

### e ta!., 2003a , b; Yokota 

### et al. , 2001 ).
In s ummary , Eugenol i s a very weak bind e r 

### in vitro; and i s unlikely to re s ult in an 

### in vivo effect of concern to human s o r wi l dlife given that it i s a component of mint , it s n a tural pre sence in the environment, and it s l o ng hi s tory of u se without reported effects. The EPA, as p art of thi s Preliminary Work Pl a n , belie ves that Methyl Eugenol is a s ub s tance that would not likely produce any effect in human s similar to an effect produced b y a natura ll y occurring estrogenic s ubst a nce . Re s ult s from the EDSP21 Da s hboard for Methy l Eugenol (AC so- AR, ACs o - ER , and ACsoThR bioassays) showed that the chemical was inacti ve (did not bind effectively) against estrogenic target s . As s uch , pursuant to Section 408(p) (4) , the EPA w ill detennine in the future whether it can Page 16 of 23Methyl Eugenol (ME) EPA-HQ-OPP

- 20 15-0547 Wlvw
. reg u lations
. gov exempt Methyl Eugeno l from the requirements of the Section 408(p) EDSP. ln the eve nt the EPA does determine to exempt this substance from the EDSP, an order w ill be issued. For further information on the status of the EDSP, the policies and procedures , the li sts of chem i ca l s, future lists , the test guidelines and the Tier 1 screening battery, please visit our website at 

### http :// www. e pa . g ov/en do/.
G. Incidents A search of the Office of Pesticide Programs' Incident Data System (IDS) from April 7 , 2006 , through December 2 , 20 15 , indicated that there are no individual reports of major incidents involving humans associated with the use of Methyl Eugeno l in insect traps. In addition, a search of OPP's Env ironmenta l Incident Information System (EllS) conducted on J anuary 11,2016 , revealed no incidents associated with Methyl Eugeno l ; thi s database contains information dating back to the 1 970 s . The EPA wi ll consider any incident data or comments subm itt ed in response to this Preliminary Work P l an. 

### H. Timeline Below i s the projected timeline for Registration Review case 6203: Methy l Eugenol: 

### Activities Estimated MonthNear Opening the Dock et Open Docket and 60-Day Public Comment Period for March 2016 C l ose Public Comment Period May 2016 

### Case Development Issue Final Work Plan September 20 1 6 Issue Data Call -in N / A Data Submission N / A Open 30-Day Public Comment Period for Draft Ri s k Assessments N / A Close Public Comment Period N / A 

### Registration Review Decision Open 60-Day Public Comment Period for Proposed Registration March 2017 Review

Decision Close Public Comment Period May 2017 Final Decision September 20 17 *Estimated Total (years) 1 year and 6 months 

## * This schedu l e i s s ubject to revi s ion should un fore seen i ss ue s ari s e during the regi s tration review proce ss . In the

ev e nt an issue ari s e s, s uch a s the fai lure to acquire an EDSP exemption , an amended Fina l Work Plan will be i s sued at that time that will s et forth a new timeline and , if applicable, any new dat a requirements will be included in the amended document and a Data Call-In Notice will be i ss ued
. Page 17 of 23Methyl Eugenol (ME)

I. Guidance for Commenters E P A-HQ-OPP-20 15-054 7 www.regu lations
. gov

The public is in v ited to comment on the EPA's preliminary work plan and rationale. The areas below highlight topics of special intere s t to the EPA where comments, data submissions, or reference to so urce s of additional information could be of particular use. The EPA will consider all comments , as well as any additional infonnation or data provid e d in a timely manner, prior to i ss uing a Final Work Plan for thi s case. i. Environmental Justice The EPA see ks to achie ve environmental ju s tice , the fair treatment and meaningful involvement of all p eo ple, r egardle ss of race, color, national origin, or income, in th e d eve lopm e nt, implementation , and enforcement of environmental laws , regulations, and policie s . To help address potential e nvironm e ntal ju stice i ss ue s , the EPA seeks information on any groups or segments of the popul ation who, a s a re s ult of their location , cultural practice s, or other factors , may hav e unusually high exposure to the pe s ticidal use of Methyl Eugenol, compared to the general population. Please comment if you are aware of any subpopulations that may have atypical, unusually high exposure compared to the general population . ii. Water Quality Methyl Eugenol i s not identified as a cause of impairment for a ny water bodie s li s ted as impaired und er Section 303(d) of th e Clean Water Act. 15 In addition, no Total Maximum Dail y Load s (TMDL s) have b ee n d eve loped for Methyl Eugenol. More inform ation on impaired water bodie s and TMDL s can be found on EPA's website. 16 The EPA invites submission of water quality data for this pesticide. To the extent possible, d a ta s hould conf01m to the quality standards in Appendix A of the 

### Office of Pesticide Programs (OPP) Standard Operating Procedure: Inclu s ion of Impair ed Water Body and Other Water Quality Data in R egistra tion R eview Risk Assessment and Management Proces 15 to e n s ure they can b e used quantitati ve l y or qualitativel y in pesticide risk assessments. iii. Trade Irritants Through the registration review proce ss , the EPA intend s to so licit information on tra de irrit a nt s and, to the extent feasible , take s tep s toward facilitating irritant re so lution. The EPA will work to harmoni ze tolerance and international Maximum R es idue Limits (MRLs) , and , if nece ssary, m ay modify tolerance level s to do so. Growers and other stakeholders are asked to comment on any trade irritant i ss ue s re s ulting fr o m lack ofMRLs or di s p aritie s between U.S. tolerance s, including exemptions and MRLs in key export m a rket s, providing as much specificity as po ss ible regarding the nature of the concern. There are no known MRL s for Methyl Eugenol. Therefore, th e EPA doe s not an ticip a te that current u ses of Methyl Eugenol will po se concerns as tr ade irritants.

1 5 Thi s is ba s ed on inf o nnati o n provided at http :// www.epa.gov /

owow /tmdl ! 1 6 Thi s do c um e nt ca n be found a t http :// www. epa. gov /opp s rrd//registration r ev iew /water qualitv sop.htm Page 18 of 23Met hy l E ugenol (ME)

iv . Additional Information E P A -H Q-OP P- 20 1 5

- 0547 \ VlVW
. r egu/ari o n s. g ov

S t akeho ld ers a re a l so s p ec ifi ca ll y aske d t o prov id e infom1at ion and d a ta th at w ill ass i s t th e E P A in refi nin g th e ri s k assess m e nt s . T h e E P A i s inte res te d in o bt a inin g th e f o ll ow in g in fo nn at io n rega rd i n g M e th y l Eu ge n o l: IJi> Co nfirm ati o n o n th e fo ll ow in g l ab e l in form a ti on:



### - Sites of app li cati o n -Formu l at i o ns

- App li catio n m e thods and equipme n t

- Maximum app l ication rat es

- Frequency of app li cation, app li ca tion interva l s, and maxim um number of app l ications

- Geographic li mi t ations on use IJi> Use o r p o te nti a l u se d is tri b uti o n (e.g. , ac reage and geographi ca l distribu t io n of r e l eva nt u se s ites)
1Ji> Me d ia n a nd 90 1 h p erce ntil e re p o rted u se r at es ( lb s ac ti ve i n gre d ie n t/ ! ,000 sq u a re f ee t) fro m u sage d at a- n ati o n a l , s ta t e , and co unt y 1Ji> A ppli ca ti o n timin g (date of fi rs t a ppl icati on a nd a ppli cati o n interva l s)

- n ati o n a l , s ta te , and co unty 1Ji> Usage/ u se inf o rm ati o n for n o n agric ultur a l u ses 1Ji> Typ i ca l a ppli ca ti o n in terva l ( d ays) IJi> S ta t e or loca l u se r es tri ct ion s 1Ji> Mo ni to rin g da ta 1Ji> Fo reig n techni ca l reg i s tr ant s not li s t ed above w h o s up pl y techni ca l Meth yl Eu ge n o l to th e US m a rket 

### J. N ext Steps After th e 60-day co mm e nt p eri o d c loses , th e E P A w ill r ev iew an d res p o nd t o a n y co mm e nt s re c e i ve d in a tim e ly m a nn e r , th e n i ss u e a Final W o rk Pl a n f o r M e th y l E u ge n o l.

Page 19 of 23Methy l Eugenol (ME) EPA-HQ-OPP-20 1 5-0547 w 1

vw . r e gula tion s. g ov 

### II
. BIBLIOGRAPHY A. Studies Supporting Registration Review of Methyl E ugenol Abdo, K.M. 

### eta !. , 200 1. 14-week tox i city and ce ll proliferation of Methyl Eu geno l adm ini stered by gavage to F344 rats and B6C3F1 mice Food Chern Toxicol39 (4): 303-16. Asquith, A. and Kido, M. 1 995. Nat i ve Hawaiian in sects attracted to the sem i ochemical Met h y l Eugeno l , used for male annihi l ation of the orienta l fruit fly (Diptera: Tephritidae). Environmenta l Entomo l ogy23: 1 397-1408. Auman , J
.T. , Fannin, R. D. , Sieber, S. 0., C unnin gham , M. L. , and Paule s, R. S. 2004. Earl y c h anges in hepatic gene express i on following expos ure t o th e rodent carc in ogen Methyl Euge n o l. Toxico logist 78 (1 -S) : 1 35. Beroza, M. , Inscoe , M.N. , Schwartz, P.H. , Kep lin ger , M
. L. , and Mastri , C.W. 1 975. Acute toxicity stud i es with in sect attractants. Tox i co l ogy and Applied pharmacology 3 1 : 421-429. (M RID 44906304 ). Cook, P
. 2002
. Ph ys i ca l and Chem i cal Properties: FT Meth y l E u ge n ol. Unp ubli shed study prepared by Farma Tech Internationa l Corp. 47 p . 

### (M RID 46358403 ). Cook, p. 2002. Phy s ical and C h em i ca l Properties Methy l Eugeno l. Farma Tech. Internationa l. 

### (MRID 46358403 ). Cook, R
. 2005. S u pp l ementa l Stud i es / Infonnation Submitted as Support for a Non- Target P l ant Waiver (40 CFR 15 8.540): The Environmental Monitoring of Methy l Eugenol, Na l ed an d Dichlorvo s During a Pest Trapping and Eradication Program: Monitoring of Methyl Eugenol and DDVP in Fruit Near Fruit F l y Trap s During a Pe s t Trapp in g Program: Methyl E u geno l /Nal ed Monitoring at Fru it F l y Trapping Location s. Unpub li shed study prepared by Farma Tech Inte rn ationa l Co rporation and State of Ca lif orn i a. 78 p . (MRID 46671001)
. Cook , R
. 2007. Non -T arget In sec t s: FT -M ethyl Eugeno l Short Lure. Unp ublished s tudy prepared by Farma Tech Internat iona l Corp. 130 p (MRID 47147604) Cook , P
. (2012) FT

- Methy l Euge n o l : Anal ys i s of Sample: Certified Limits. Unpub li s hed study prepared by Farma Tech International Corp. 1 9p. (MRID 49008902). Cook, P. (2012) FT Methyl Eu geno l : Analysis of Sa mpl e: Certified Limit s. Unpub li s hed s tudy prepared by Farma Tec h Int ernati onal Corp
. 16p. (M RID 49008904). Farwe ll , K. , (2004). D302237. Risk As sess ment for Meth yl Eugenol (Meth y l eugeno l ). Leblanc , 

### 1. , Rubinoff, D ., and Vargas, R. I. 2009. Attraction ofNontarget Specie s to Fruit Fly (Dipte r a: Tephritidae) Male Lures and Decaying Fruit Flies in Traps in Hawaii. Environ. Entomol. 38(5): 144 6

- 14 6 1. Page 20 of 23Methy l Eugeno l (ME) EPA-HQ-OPP-20 1 5-0547 www . re gulat i ons . gov Leblanc , 

### 1. , Rubinoff, D and Vargas, R.I. 2009
. Attraction ofNontarget Species to Fru it Fly (Diptera: Tephritidae) Male Lures and Decaying Fruit Fli es in Traps in Hawaii
. Environ. Entomo l. 38(5): 144 6- 1461. Metcalf, R. L. and E. R. Metca l f. 1992. Fruit flies of the family Tephritidae, pp . 109

- 15 2
. In Metcalf , R. L. and E
. R
. Metcalf, Plant kairomones in insect ecology and control. Chapman and Hall , New York, 1 68 pp . Mortelman s, K. , Haworth , S., Lawlor, T. , Speck , W., Tainer, B. , Zeiger, E. 1986. Sa lm onella mutagenicity tests: II. Re s ult s from the te s ting of 270 c h emicals. Environ Mutagen 8: 1-11 9 National In s titute of Health. 2000. N IH , 2000. Toxicology & Carcinogenesis Stud i es of Methyl Eugeno l in F344/N Rat s and B6C3Fl Mic e p .8 -1 0 Technical Report Series No. 491 NIH Publication No. 00

- 3950 U
. S. D e partment of Health and Human Services , National Toxicology Program , Nationa l In s titute of Environmental Health Scienc es, Re sea rch Triangle Park , NC 27709
. NTP (National Toxicology Program)
. 2000. Toxicology and carc in ogenesis studies of Methyl Eu genol (CAS No. 93-15-2) in F344/N r ats and B6C3F1 mice (gavage studies). NTP TR 491. 412 pp. NTP (Nationa l Toxico l ogy Program)
. 2005. E l eventh Report on Carcinogens: Methyl Eugenol (93-15- 2). OECD, 2009. Report of the Expert Cons ult at ion to Eva lu ate an Estrogen Receptor Binding Affinity Model for Haza rd Identification. Series on Testing and Assessment, No. 111. A u gust 2 1 , 2009
. ENV /JM/ MON0(2009)33. h ttp: // sea rc h .oecd
. org/offic i ald oc um e nt s/ di s pl ayd oc u men tpd f /? co te = e nv/ jrn/mo n o ( 2009)33& d o cl a n g u ag e = e n Phillip s, D
. H., Reddy, M.Y. , and Rand erath, K. 19 84
. 32P -p ost- l abe llin g ana l ys is of DNA adducts formed in the li ve rs of an im a l s treated with safrole , estrago l e and other naturally-occurring a lkenyl benzene s II. Newborn male B6C3F1 mice
. Carc in ogenesis 5 ( 1 2): 1 623-8. Price , C
. 2004. Final Study Report: Developmental toxicity evalu ation for Methy l Eugeno l (CAS No. 93 -1 5

- 2) administered by gavage to Sprague-Dawley (CD) rats on gestationa l day s 6 through 19
. NTP Study No.; TER-97-007
. 1-1 09. Rexrode , M. , (2015). Registration Review for Methyl Eugeno l. Rose, R. (2006) Scentry Methy l Eugeno l Biochemical Pesticide Registration Data Requirement s: Waiver Req u ests. Unpublished s tudy prepared by Scentry Biolo g i ca l s, In c . 10 p (MRID 46918302). Schm i eder, P.K. , Tapper, M.A., Denny, J.S. , Kolanc zyk , R .C., Sheedy, B.R. , Henry, T.R., Veith, G.D., 2004. Use of trout li ve r s li ces to enhance mechanistic interpretation of estrogen receptor binding for cost
- effective prioriti zation of chemica ls w ithi n large inventories. Environ. Sci. Techno!. 38 (23) , 6333

- 6342
. Page 21 of 23Methyl Eugenol (ME) EP A-H Q-OPP-20 15-054 7 www. r e gulation s . go v SAP, 2009. See http: //www.epa.gov/ scipoly / sap/ meetings/ 2009/ 082509meeting.html: cite both the EPA white paper and the SAP report. SAP, 2013. See http: //www . epa.gov/ scipoly / sap/ m eet ings/ 2013 / 012913meeting.html, cite both the EPA white paper and the SAP report. Seki, M. , Yokota , H., Matsubara, H. , Maeda, M. , Tadokoro, H ., Kobayashi , K. , 2003a. Fish full lifecycle testing for the weak estrogen 4-tert-pentylphenol on medaka (Oryzias latipes). Environ. Toxicol. Chern. 22, 1487-1496
. Seki, M., Yokota, H ., Maeda, M ., Tadokoro, H ., Kobayashi, K ., 2003b. Effect of 4-nonylphenol and 4- tert-octylphenol on the sex differentiation in medaka (Oryzias latipe s). Environ. Toxicol. Chern. 22 , 1507

- 1516. Turner, B. , Miller, N., Tran , D
. and Powell, S. 1989
. The environmental monitoring of Methyl E ugenol, naled, and dichlorvos during a pe st trapping and eradication program. California Department of Food and Agriculture. (MRID 488710-01) . Uchida , G. K. , Mackey, B. E. , Vargas , R
. I. , Beard s ley , J
. W, Hardy , D. E. , Goff, M. L., and Stark, J
. D
. Respon se of nontarget insects to Methyl Eugenol , cue-lure , trimedlure , and protein bait bucket traps on Kauai I s lan d , Hawaiian I s land s, USA. Proc. Hawaii Entomol. Soc. 38: 61-72. 2006. U.S. EPA (December 16 , 2004) Risk Assessment for Methyl Eugenol http ://www. regulations
. gov/# !documentDetai l ; D = EPA-HQ-OPP-2004-04 1 8-0003
. U.S. EPA (December 2004) Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progre ss and Risk Management Deci s ion (TRED) for Methyl Eugenol http: / 

### Iarchive. epa. gov / pesti ci des/reregi stration/web/ pdf / methyl_e ugeno l_tred. pdf U.S. EPA Approved Label for Scentry Methyl Eugenol Cone, EPA File Symbol 36638-41 , Decemb e r 11 , 2007 , http :/ / ofmpub
. epa.gov/ apex/pesticides/ f?p = PPLS : 8 : 1 7 14 8588 1 530 15 : : NO : : P8 PUID,P8 RINUM:4860 1 2,36638 -41
. U.S. EPA , 2013. Endocrine Di s rupter Screening Program: Final Second Li s t of Chemicals and Substances for Tier 1 Screening. EPA-HQ-2009-0477-0074
. U.S. Environmental Protection Agency Environmental Incident Information System (EllS) Version 2.1.1. 10 114/20 15. U.S. Environmental Protec tion Agency Da s hboard Overview. Endocrine Di s ruption Screening Program for the 21 st Century. http :// actor.epa.gov/ edsp21 

### I U.S. Fish and Wildlife Service. 2007. Endangered and thre a tened wildlife a nd plants: revised propo sed de s ignation of critical habitat s for 1 2 s pecies of picture-wing flie s from the Hawaiian Island s: propo se d rul e. Fed. Reg
. 72: 67427-67522. Page 22 of 23Methyl Eugenol (ME) EPA -H Q-OPP-20 15-054 7 www.regu la tions
. gov 

### Yokota , H., Seki , M. , Maeda , M. , Oshima , 

### Y., Tadokoro , H. , Honjo, T. , 

### Kobayashi, K. , 2001
. Life-cycle toxicity of 4-nonylphenol to medaka (Oryzias latip es). Environ. Toxicol. Chern. 20 , 2552

- 2560.

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