# Proposed Registration Decision for the New Active Ingredient Male Sea Lamprey Mating Pheromone

. Hou se n ge r , Dir ector Office of Pe stic id e Program s Date : 

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### S umm ary This document announces that the Env ironm e ntal Protec tion Agency (EPA) ha s comp lete d it s in iti al eva luati o n of th e prop ose d new bioch e mic a l pheromone Male Sea Lamprey Mati ng Ph ero mone a nd has concluded tha t it meet s th e r eg ulatory and safety s tanda rd s under the Fed era l In sec ti c ide , Fungicid e and Rodenticide Act (FIFRA). Two products a r c propo se d to be r egis te r e d und e r Sect i o n 3(c)(5) of FIFRA : a Manufacturinguse Product (M P), Ma l e Sea La mpre y Mating Pheromo ne Tec hnic a l ; an d a n E nd-u se Produ ct (E P )

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### Male Sea Lamp rey M ati ng Pheromone. Th e reg i strant for these prod uc ts is the Un ited States f- i s h and Wi ldlif e Serv ic e (US FW S)

. the age ncy charged w ith co ntr o llin g th e spread of the pes t. Sea Lamprey. T he new act ive ingre di ent will be use d as an attractant to trap Sea Lampreys (Pet ro m yzo n marinm ) 

### durin g their spawning seaso n. T he E P is o nl y inte nd e d for use on th e up s tr ea m po11 ions of the tributari es of the Great Lakes, Lake C hampl a in , and the Finger Lake s areas ( i.e. th e Great Lakes Ba si n) , whe r e Sea Lamprey are an in vasive spec ies. wreaking ha voc o n the na ti ve fi s h eries. Du e to the international natur e of th e Sea Lamprey incurs ion , th e two Male Sea Lamprey Mating Ph eromone product s are being jointly reg i ste red with Canada ; a nd the EP will be applied in a coo rdin ate d effort by th e tw o gove rnm en tal agenc ies c harged with con tro lling thi s pest

- USfWS and Fi s heries and Ocea n s Canada. The reg i s trati o n of thi s ac ti ve ingredient i s considered by US FWS to be in the publ ic interes t, and is expec te d to be an imp o rtant tool in p ro t ec tin g o ur Great Lakes ecosys tem and fisheri es. Th e c hem ical nom enc latur e for Male Sea Lamprey Mating Ph ero mon e is 3- k etop etrom yzo nol s ulfat e, a mmonium sa lt (3 kPMZS). Th e co mp o und occ urs natura ll y as a ph ero mone excre t ed b y Sea La mpre y; howeve r, the sc al e of commercial pest i c id al app li cation n ecess it a t es sy nth et ic produc ti o n. In its co nce ntrated fo rm , the co mp o und is a c rys tallin e so lid , and is stabl e in lo n g term s torage. but dis soc iate s r ead il y in so lve nt s . a ll ow in g for effective di spe rsal in aquatic environmen ts. As 

### a b io pe s ticicl e, Male Sea Lamp re y M atin g Ph ero mo ne is cla ss ifi ed as a pheromone and serves primarily a s an attractan t for breeding female Sea Lamp r ey during s pawnin g seaso n. The EP i s tim e -re leased ou t of traps in tributaries wh ere Se a Lampre ys spawn. Li ke other federally regis t ere d ph ero mone s , Male Sea Lamprey Mat in g Pheromone is e fficaci o us in trace amount s . The E P contains 1 .06% w / w 3 -k etopetrom yzo no l s ulfat e, ammonium sa lt as it s active ingredi ent , and has an applied conce ntrati o n between 4.72 

### t o 0.0472 

### parts per trilli on (pp t). P es ti cida l app li cat io n s not with s tand in g , the total co ncen tratio n of 3 kPMZ S is n ot anticipated to exceed backgro und leve l s in place s where Sea Lampre y are naturall y fo und (concen trati o ns o f natura l 3k PMZS durin g th e middle of spawnin g season range from 33.4 ppt to 120.9 ppt). The EP is to be applie d onl y during s pawning seaso n . which occ ur s from Apri l throu gh Jun e . T he ph ero mo ne has a half-lif e o f 26 ho ur s, and is not det ec tab le w ith in a month o f the e nd of spawning season. No adve r se effects from 3 kMP ZS ha ve ever bee n observe d or reported in a n y aquatic e n v ironment s (to e ith er human s o r nont arge t o rga ni s ms) where Sea La mprey are native; and USFWS has no t obse r ved toxic effec ts from expos ure to th ese compound s in the Great Lakes area s ince the y first began moni to rin g the co mp ou nd th e r e in 2004. Th e control or Sea Lamprey is of critical imp o rt ance to USFWS a nd Fi s he rie s and Ocean s Canada

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### go , ·crnme ntal age nci es re s pon s ible for protec tin g th e aquatic env ironm en t in the Great Lakes re g ion. The Sea Lamp rey is a predatory fi sh th at attac hes to ho s t fi s h and feeds on Page 2 of 9the blood and body fluid s . A s in g l e Sea Lamprey kills 40 or m o re pounds of fi sh in it s life as a para s ite. Sea L amp r ey in vaded the G r ea t Lak es r eg io n in earnes t in the late 1 9 111 centu ry w h e n 

### a canal wen t arou nd N iagara Fall s and con n ec ted Sea Lampre y h ab itat in th e lower N iagara to the Sea Lamprey-free waters of the Great Lakes. B y the 1950 s . ca Lampre y predation in the Great Lakes region had caused po p u lation cras h es of the fo li o' in g native fish: Lake Trout. Salmon. Steel head. Whitefis h. Chubs. Burbot and Walleye. A coordinated program of mechanical trapping and lampric ide u se. begun in th e 1 950s, has r estored th ose fi sheries t o h eal th. and ha s reduced Sea Lamprey populations b y m o r e th an 90%

. USFWS is a nticip a tin g s ign ili ea nt ga in s in trapping (20%) w ith th e b roader u se of th e n ew ac ti ve in g r edie nt Male Sea Lampre y Mat i ng Pherom o ne. While Male Sea L amprey Mat in g Ph e romon e is co n si d e red a n ew active in gredie nt under Section 3 o f 

### FIFRA, it had b ee n pre v iou s ly approved in seve ra l Exp e rim e ntal Use Pe rmit s (75437-EU P -1 throu g h -4), th e fir st penn it b e ing i ss ued on Fe bruary 5 , 2004. T h e Agenc y ha s mor e th a n a d eca d e -lon g hi s tory with the active ingredient a nd i s in rece ipt of a s ub s tantial database. wh i c h s upp o rt s bo th th e human h ea lth risk assessme nt a nd the ecological ri sk assessment. The ri sk assessme nt c l ea rl y demonst ra tes that expos ure to this ph e romone wi ll be de minimus. and th a t , e x p os ure n otw iths tandin g, th e pheromone i s nonto x ic to hum ans a nd n o ntar ge t o rga ni s ms thrnu g h a n y route of e xp os ure. 

## Background Male Sea Lamprey Mating Pheromone was classified as a biochemica l pestic ide b y the Bi oche mi ca l C la ss ificati o n Co mmittee o n March 22, 2000, due to its natura l occur re nce , hi sto ry of exposu r e t o human s and th e envi ronm e nt w ith out tox ic ity and it s nontoxi c mod e of act ion as a pheromon e. With regard to toxico log ica l hi s to ry , there h ave b ee n no obse rved adve r se effects from Male Sea Lamprey Mat in g Ph e romon e in a n y aquatic environ ment where Sea L amp rey are indigenou s . On January 29, 2003, the U

.. E n v ironment a l Protec tion Agency (""E P A'.) rece i ved a n a ppli cati o n from Great Lak es F i s hery Co mmi ss ion for an Ex p e rim e ntal Use Pe rmit ( EUP ) containing the n ew activ e ingre d ie nt Ma le Sea L amp r ey Mat in g Ph e rom one. O n April 

### 9

. 2003. E P A announced receipt of an application for a n EU P contain ing th a t new ac ti ve in g re di e nt (Vo lum e 68. Nu mber 68. 

### FR page numb e r s 17374

- 1 7375). Six s upportin g documents. including a hum a n hea l th ri sk assess m e nt , an eco log ic a l ri sk assessme n t and a product c hemi s tr y assess m e nt were po s ted in Docket OPP-2 00 3-0080. No co mm e nt s were re ceived re lati ve to the a pplic at ion o r th ose a ssess m e nt s. Th e EUP u s in g this acti ve in g r e di e nt was i ss u e d on February 

### 9. 2004. On October 30. 20 1 3. E P A a nn o unc ed receipt of a Sect io n 3 ap pli cati o n to register two new products conta inin g th e new act ive in gre di e n t

- M ale Sea L a mpr ey Mati n g Ph e romo n e Technical and Male Sea Lamprey Mating Ph e romon e (Vo l ume 78, Number 2 1 0, 

### FR page numbers 64937

- 64938). Th e app li ca nt was U SF WS. A copy of that notice i s avai lable in Do c ke t 

## ro Numb e r EPA-HQ-OPP- 2 013-0538 via htto: llw1nr.reg11/utions.gor. No co mment s we re s ubmitted in respo n se t o th e announcement.

Pa ge 

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### Eva lu atio n In c, ·aluati n g a pesticide regi s tration application. th e E PA assesses a "v icl c varie ty of pesticicl e s peci !ic inf ormat ion in c ludin g w he re and h ow th e pestic ide i s use d

. e n v ironm e nt a l la te (i.e

.. \\hat happens to th e pcs ti c iu e o nc e it' s app li ed), and to x icity s tudi es (i .e .. e ff ec ts o n hum a n s a n d other nontarget organ i s m s) to determine the likelihood of adve r se effec t s (i.e

.. ri sk) from exposures assoc iated " ·ith th e proposed use of the prod uct. Risk assessments are developed to e\ aluate the em·ironmcn t a l fate 

# or th e compound as well as how it might affect a wide range o f nontargct organisms including humans and terre s trial and aquatic wildlife (plants and animals). On the basis 

# or the se assess ment s . EPJ\ evaluate s and approves lan g uage fo r eac h pesticide label to ensure the di rections fo r u se and safety mea s ures are appropriate to mitigate potential ri s k. In this \\'ay. the pe s ticide' s labd he lp s t o communica te esse ntial l imitations and miti ga tion s th a t arc nece ssary fo r public sa fety. It i s a F I FRA v io la ti o n t o u se a pe s ti c id e in a way that i s incon s i ste nt with the label. The human he a lth a nd e nvironmental ri s k assessments ( includin g a n e nd anger e d s p e cies a ssess ment ) suppo rtin g thi s dec i s ion a s we ll as the draft lab e lin g can be found in the regulatory docket ( D oc um e nt I D : E PA- HQ-OPP- 20 1 3

- 0538). Th e application for r eg i s tration of Male Sea Lamp rey Mating Ph eromone was r ev iewed jointly with Canada"s pe s ticidal regulatory agenc y, PMRA. All data requirement s for eac h agency were res pectively addres s ed ; a nd the agencies were ab le to sha re review s with eac h other , r es ultin g in a more robust ri s k assessme nt. The joint review and proposed re g i strati o n i s particularly notabl e as th e registration o f Ma l e Sea Lamprey Matin g Ph eromone i s bein g s ponsore d by governmen t a l age n c ie s in each country; and the E P is b e in g uniqu e ly employed as a to o l of e n v ironmental protectio n inte nd ed to redress the env i ronme nt al damage o f a particularl y h a rmful in vas ive s pecies

. w hich i s plaguing both countries. 

### Assess m e n t of Ri sk t o H uman Hea lth EPA requires a wide range of stud ies in o rd er to assess a pesticide. For M a le Sea Lamprey Mating Ph eromone, the database of stu di es a nd in format ion s upp o rtin g th e assess m en t of ri s k to hum an health i s s uffi c ient to s upp ort regi s tration of this non-food u se ph e romon e . There i s amp l e information indi catin g th a t the us e of Male Sea Lamprey Mating Pheromon e will not result in a n y meaningful n ew expos ure , and that , ex p os ure notwithstanding , th e co mp o und i s nont ox ic a nd does not pose a ri sk throu g h an y other route o f exposure. Du e to the ex tremel y hi g h cost of manufacturin g the te s t substance as well as the large quantitie s o f te s t s ub stance re quire d for limit do se te s tin g for Tier I human health d a t a requirements , USFWS propo sed s ubmittin g a lternativ e 

### in v itro tes ting st udie s to EPA (a nd PMRA) in fulfillment of man y of the human health testi n g data requi rem e nt s for both age nci es as part of the joint re v iew proc ess . A fter a review of the protoc o l s and the studies. EPA a nd PMRA , have detennined th a t all the hum an h ealth data r eq uire m e nt s for a biochemi ca l h ave been sa ti s fi ed a nd th at the hum a n h ea lth risk assess ment i s s uffi cie nt to s upp o rt r eg i s tra ti o n . All the information s ubmitted demonstrate th a t Male Sea L a mprey Mating Pheromon e i s n on to x ic t o human s.

P age 4 of 9

### With re g ard to ac ut e toxi c ity data requirem e nt s, non gu idelin e in vitro 

### t es tin g s tudi es were s ubmitt e d in s upp o rt o f tho se data require me nt s. In th e acute oral tox icity study. th e acute ora l LD so va lu e was determ in ed to be >20 00 m g/kg bw (Tox ic ity Ca t ego ry III ); and intrace ll ular AT P co ncen tration we re > 300 0 μM , indicatin g ve r y low cytotoxic i ty fo r Ma l e Sea La mpre y Matin g Ph eromo n e Tec hni ca l. An in vitro 

### st ud y for acu te dermal toxicity es tab li s hed an LD so > 2000 mg/kg bw (Toxi c ity Catego ry 111 ); 

### an d there was no observed cytotox ic ity. A no ng uidelin e in vitro 

### tes tin g st ud y in s upport of the acute inh a latio n t ox ic ity dat a req uire m ent was deemed supp lemen tal ; a nd a de te rmin ati o n was mad e that because of the l ack of inh alation exposure. further informati o n in support o f the re quire ment was no t nece ssa ry . T he acti ve in g r e di e nt i s no t a vo l at il e s ub s tanc e a nd it is app li ed in a n aq ueous e nv iro nm e nt ; as s uc h , no inh a lation exposu re is expec ted. A no ng uid e lin e in vitro 

### study s ubm itted in s upport of the primar y eye ir Titat ion data requirement in dicated that th e ac ti ve in gr ed ie nt is a mild ocu lar irrit ant ; acco rdin g l y , it was cla ss ifi ed as T ox ici t y Category Ill. 

### The no ng uidelin e in vitro 

### te s tin g s tud y was s ubmitted in s upp o rt of the pr imary dermal irritation r equ ire ment ; and the compound was c lass ifi ed as Toxic ity Catego ry JV. The no ng uideline in vitro 

### s tud y s ubmitted to fulfill th e de rma l se ns iti zat ion data requ irem e nt co nclud ed th at th e act i ve in g r e dient is a weak sens iti zer. T he in for matio n s ubmitt ed in s upp ort of the app li catio n fo r the ac ti ve in g redient Ma l e Sea Lamprey Matin g Ph ero m one indi cat e th a t it is not subchro ni ca ll y to x ic. Repeated exposure to Male Sea Lamprey Matin g Ph ero mone v ia ora l , dermal , and inhalati o n path ways is hi g hl y unlikely. Th e MP is manufactu re d in s ma ll batches rang in g from 10 to 100 g, no m ore th a n o nce o r tw ice per yea r wi th maximum annual production not excee din g I 

### k g . T he MP is manufactured in an e nclo se d e nvironm e nt u s in g pre sc rib e d pe rsonal protect ive eq uipm e nt , and i s packag e d in herm e ticall y se al ed v ia ls. Th e E P is then fo rmulat e d , u s in g 0 .1 0 g o f th e MP in I OmL 50 % so lve nt-ba se d mixture. The EP is then placed in trap s, which are pl aced in th e waters of the affected tributari es, w here th e active compound is s low ly time rel eased. No s ig nifi cant expo s ure to th e MP or E P is an ticip ated. S ubchroni c ora l to x icity data requir e m e nt s we re sa ti s fi ed tlu· o ug h rat io nal es and s upported by th e in vitro 

### s tud ies and by i nf o rmation fro m the open sc ientific literature

. With spec i fic rega rd to the 90-day o ra l toxicity r eq uire me nt. th e hum an hea lth assess me nt furth er not es : ( I ) 

### r epea t ed ex pos ure via drinking wa t e r is highly unlike ly due to a lack of c urTe nt use of the target s tream s as so urce s of municipal drinking water; a nd i f thi s u se did occ ur , it would no t be diff e re nt than u s in g wate r fro m Sea Lamp r ey infe s t ed s treams durin g spaw nin g : and (2), th e estimated acute sys t e mi c LD so was > 2000 mg/kg bw , which is far greate r th an the effect i ve a pplied ra t e of

- I0" 1 2 

### M. With rega rd to the 90-day de m 1 al tox ic it y data requireme n t , the human h ea lth assess me nt notes : ( 1 ) th e MP and EP a re not in tended for direct applicat io n to hum a n ski n and are not ma nu fac tured in a manner that wo uld res ult in pro longed or repeated derm a l contac t ; (2) th e estimated acu te syste mic LD so wa s > 2 000 mg/ kg bw in in vitro 

### test ing for acu t e sys t e mi c tox ic ity . w hi ch is far grea t er than the effec ti ve applied rat e of

- 1 

# o- 1 2 

### M; and (3) The TGA I was es timat ed t o be no n-irrit ati ng . With regard t o th e 90 -d ay inh ala ti o n toxicity data req uire me nt , th e assessment r e ite r ates that no inhalation ex p os ure is anti c ip ate d for e ith er the MP o r the EP. Th e M P is a non- vo latile so lid that is manufacture d in a manner that wo uld not res ult in r e peated inh a lation expos ure; and the 

### EP is an aq ueo u s so luti o n that is time-re leased into s tr eam s, w h ose resulting concentrations fall w ithin background leve ls. In s ho rt , no s ubchronic exposures are expected; and any ex posure would be within natural back gro und levels

. Mutagc nicity data requi rem en ts we re sati sfied s i mi la rl y by a rationale su pp or t ed by infom1ati o n from th e sc ient ifi c lite ra ture. Male Sea L amp r ey Mating Ph eromone is a non - food use P age 5 of 9pherom o n e that will be applied te mp o rall y, and whose use w ill res ult in concentrations that fa ll w ithin background leve ls . Accordingly, th e u se of th e activ e i ngredient will n o t result in r epeated exposu r e to human s v ia ora l , dermal , or inh a la tion routes of ex posure. T h e developme nt a l tox ic ity data r e quire me nt for Male Sea Lampre y Mating Pheromone was also sati sfied by a rational e, and was s upported by information from th e scie ntifi c lit erature. Th e b as i s of th e rationa le is that th e active ingredi e nt i s not intended fo r food us e, and th e u se of produ c t s containin g the compound wi ll not re su lt in a n y s ignificant expos ure s to hum a n s above background leve ls. Lastly, EPA has not found Ma le Sea Lamprey Mating Ph eromone to s h are a co mmon m ec h a ni s m of toxicity with any other s ub s tance s . In a dditi o n , Male Sea Lamprey Mating Pherom o n e does n ot appea r to produce a tox ic metabolite produced b y o th e r s ub s tan ces . Gi ve n th e de m o n st rated lack of adverse effec t s on hum a n s, a qualitative as sess men t of Mal e Sea Lamprey M a tin g Ph eromone i s considered s uf1i cient. Hum a n s are rare ly ex p osed to thi s nont ox ic pheromone an d there h ave been no observed or re ported adve r se effec t s on hum an s w h o are r egu lar l y prese nt in and aro und Sea Lamprey h a bitat. Th e act ive ingredient will be used a t low rat es in water, and it s u se w ill re s ult in concentrati o n s w ithi n natural background leve l s. A l so, th e E P will o n ly be u se d durin g spaw nin g seaso n , April

- Jun e . F urth e rmore , M a le Sea Lamprey Matin g Ph e romone i s e xp e cted to biode g rade rapidly. Inform ation s ubmitt ed by US FW S s h ows that th e ac ti ve compound ha s a half-life of26 h ours, and that trac es of th e com p o und are not fou nd i n the wa ter w ithin a m on th of the end of s pawnin g seaso n. Du e to th e infrequent a ppli cati o n s. low application rate , high biodegradabi li ty, th e pesticida l u se of Ma le Sea L amprey M a tin g Pheromone i s n o t a nticipated to con tribute s ig nifi cantl y to human ex po s ur e beyond exis tin g (bu t te mpora l) background leve l s . 

### Assessment of Ecologica l Risk E nvironm e ntal Fate E nvir o nm e nta l fate a nd g ro und wate r data are not required at thi s time b eca u s e th e result s of th e nonta rge t o rga nism toxicity assess m e nt (Tier I data req uire m e nt s) did n ot tri gge r these Tier II data requirements. H owever , a s referred to above , Male Sea La mprey Matin g Ph e romone i s n o t expected to persist in th e e n v ironment. Mal e Sea Lamprey Mating Ph e romone ha s a h alf -li fe of 26 hours; a nd USFWS m o nitoring , done in co njun ct ion w ith their Male Sea Lamp rey Matin g Ph ero m one EU P s, indi cate th at n o trac es of th e pheromone are detected w ithin a month of th e end of s pawning season . 

### Environmental E ff ec ts The nonta rge t o rga ni s m dat a requirement s fo r Male Sea Lamp rey Mating Pheromone we re sat i s fied throu g h rational es, which are s upported b y non g uid e lin e stu die s and information from the open sc i e ntific literature. Both E PA a nd PMRA have co n curre d on an eco l ogica l risk assessme nt : and both agencies find th at th e r e are no concerns for nontar ge t aq uatic o r terre s tri a l o rga ni s m s resulti n g from the use of Male Sea Lampre y Ma tin g Pherom o n e.

Pa ge 6 o f9The rationales for a ll the nontarge t organism data requirement s demonstrate that n o ntarge t o rga nism s will only be negligibl y exposed to the active ingredient and that tho se miniscule exposures are not toxic to n ontarget organisms

. With regard to aquatic nontarge t o rganisms , data indicate that the use of the ac ti ve ingredient will re s ult in concentrations of the compound that a re within background le ve ls where mal e Sea L amprey are n atura ll y prese nt durin g spawnin g periods. (USFWS monitoring ha s demonstrated that there is no addi ti o n al efficacy r e lative to any concentrat ions above natural background leve ls.) App li cat ion of the Male Sea Lamprey Mating Pheromone i s expected to result in treated water w ith concentrations of 

### 4. 72 to 

### 0.04 72 ppt. well within the range of concentrati on of the pheromone in native Sea Lamprey habit a t during spaw ning seaso n , which can reach concentrations of 

### 120

. 9 ppt. Applications of the act i ve in g redient are a l so both targeted a nd tempora l. Mal e Sea Lamprey Matin g Pherom o ne i s on ly to be u s ed in the upstream portion s of affected tributari es . and it i s only applied durin g s pawnin g se ason (Ap ril throu gh Jun e). Moreover, th e active compound does not p ers ist in th e e nvironm e nt. It h as a half-life of 

### 26 hours and i s not found in Sea Lamprey inh ab ited wate r s wi thin a month a fter application. With regard to toxic effects on aquatic nontarget organi sms, ther e have been no observed adverse effects from the use of th e compound in waters w h e re Sea Lamprey are indigenou s, and there have been no observed adverse effects by USFWS s taff , who have monitored s uch effect s since they began ex perimentin g with th e pheromone in 

### 2004. With regard to te rr estrial nontarget organisms. n o exposure i s anticipated. A pplication s of Male Sea Lamprey M a ting Ph ero mone are s pecificall y tar ge te d to aquatic e n v ironm e nts ; it i s to be applied in traps in s tr eams in miniscule amo unt s. In s hort , there are no plausib le expos ures fo r terre s trial o rganism s. Based on de minimu s exposures , and lack of observed toxicity for thi s naturall y occ urring compound. th e ecological risk assess ment concludes that th e re are no ri s ks to either aqua tic or te rrestrial n o ntarget organisms. 

### En d a ng ered S p ec i es Assessment An endangered spec ies assessment on Male Sea Lamprey Mating Pheromone fu11h e r quantifie s and eluc id ates Male Sea Lamprey Mating Pheromone 's nonto xic ity to nontarg e t o rga nism s and indicates that s ignificant exposure to nontarget organisms i s not anticipated. The active ingredient, 3- ketop e tromyzonol s ulfate (3-kPMZS), is not toxic to the targe t pe s t. It is a pheromone used to at tr act Sea Lamprey into trap s . When applied as a p es ticide in traps it re s ults in concentrations of 

### 4.72 to 

### 0.0472 ppt in the treated waters. Ex posure o f nontar ge t organisms to the active in gred ient i s anticipated to fall we ll with i n natural background l eve ls emitted by ca Lamprey du rin g spawning seaso n , which can range a s high as 

### 12 0. 9 ppl. The compou n d do es not persi s t in the env ironm ent and has an average half-life of 

### 26. 1 hours ± 

### 1 .8. Naturally occu rrin g Sea Lampre y ph eromones ha ve been observed in Great Lakes tributari es for over 

### 60 years and n o toxic effects from exposure to these compounds ha s ever been observed or r epo rt e d. The Agency a l so co nduc ted a search 

### ( 10 / 14 / 20 15) of the Eco log ical In c ident In format io n System ve r s ion 

### 2.1. I (E II S) and did not find any re port s of detrimental exposure of 3

- KPMZS or the inert, meth y l alcohol , to aquatic or terrestrial species. In add i tion , efficacy studies d emo n s trated that nontarge t species were not more likely to be captu red in Male Sea Lamprey Mating Ph e romon e- baited trap s w h en compared to unbaited traps. Due to its nontoxic mod e of action (as a pheromone / attractant/confusion agen t) and its low ex posure to nontarge t s peci es ( natural background l eve ls not ex ceeded) a Risk Quotient (RQ) is not t yp icall y calculated s ince the point estimates of e ith er toxicity and /o r expos ure wi ll u s u a ll y be at or near zero: and none was n ee d e d h e re. The e ndangered s peci es assessment concludes that Male Sea Lamprey Matin g Pherom one h as no kn own direct o r indirec t to x ic effects to n o nt arge t organisms: and EPA ha s determined Page 7 of 9that the use of the active in g redie nt Male Sea Lampre y Mat i ng Pheromone will res ult in

.. No Effect" to a ny current ly li s te d threatened o r e ndangered s p ecies o r any de s ignated critica l habitat. 

### A lte rn atives There are two conventional lampricide ac ti ve ingredients

- TFM (3-triflu oromethy l-4- nitrophenol) and Niclosamide (2',5-dichloro-4'-nitrosalicylanilide)

- that are cu rren tl y u se d in seve n registered product s fo r th e purpo se of Sea Lamprey co ntrol. Both TFM a nd Niclosamide products a r e u sed at hi g h er r ates and each has a hi g her to x ic o lo g ica l ri sk profile than Male Sea Lampre y Matin g Pheromone. Use data indicate an average of approximately 80.000 pounds of TFM active ingredient and ap proximatel y 300 pounds of Nic losamide active ingredient are appl ice! annua ll y . Wat er concentratio n s of TFM are typically 12 ppm through ou t treated areas: and l iclosam icle concentrations range from 25 to 35 ppb in treated areas. There are n o natural background l evels for eithe r convent ion al act ive ingredient. With regard to toxicity , TFM h as an acute ora l 

### LD 5o values of 141 and 160 m g/ kg fo r males and females , respectively. 

### It is a l so considered to be toxic to both lish and n o ntarget plants. icl osa mide is hi g hl y tox ic to both fi sh and nontarget aquat ic im ·ertebra tc s . 

### Benefits Sea Lamprey in the Great Lakes region are cu rre ntly contro ll ed by blocking th e ir access to spawning habitat through p h ysica l barriers and by deploying chemical pesticides ( lampricide s) where th ey suc cessfully rep roduce. In s p eci fie stream s, the number of young produced by adult Sea Lamprey can be reduced if most of th e adu lt s are trap p ed and removed befo re spaw nin g. A nd even i f that s tream must be treated w ith a la mpricid e s ub seque ntl y, a sma ller initial population will leave few e r s urv ivin g Sea Lamprey. The r efo re , improvem e nt s in trappin g technology can adva nc e Sea Lamprey co ntro ls expo n e nti a ll y. The addition of Male Sea Lamprey Mating Ph eromone to th e trapping arsenal has recentl y been shown to increase Sea Lamprey trap catch. I n large streams, es peciall y those w ith few adu lt Sea Lamprey, app lication of M a le Sea Lamprey Mating Ph e ro m o n e increased the re moval rate by 20-40%. Because th e ph e romone i s a natural compound r elease d by Sea Lamprey and very litt le is needed to induce a behavioral re s pon se, its app licati o n i s v iewed as a mu c h m ore environmentally benign means of chemically contro llin g Sea Lamprey populations than through the mer e u se of co n ve nti ona l lampricides. 

### It is further expected that the improved removal rat e. created th rough the use of Male Sea Lamprey Mating Ph ero m one, will result in a diminished and more targeted use of the m o re toxic conventional lampri c id es; and it w ill ha ve the further effect of res to rin g th e native ecosys te m and fi s h e ry by s ignificantl y reducing th e number s of thi s predatory invasive spec ies. Notably. Male Sea Lamp rey Mating Pheromone will be the first vertebrate pheromone ever regist e red as a biopesticide. Presently , over 40 registered pheromone active in gred ie nt s are safe ly u sed to contro l hundreds of pest insects. T hat t arge ted u se of these pheromone products o n in sects has been an imp o rtant tool in agricultura l pest control over the la s t two de cad es , successfu ll y reducing the use of more toxic co n ve ntion a l in sect ic ide s. 

### It i s expec ted that th e addi ti on of this new act i ve ingredient will help set the stage fo r the development of other vertebrate p h eromones.
Pa ge 8 of 9

### Public Co mm e nts On Apri l 9. 2003 , E PA announced receipt of an application for an EUP (sec 5) containing a new active ingredient Male Sea Lamprey Mating Ph eromone (Vo lum e 68, Number 68. 

### FR page numbers 17 374

- 17375). Six support in g documents. in cl udin g a human health ri sk assessment, an ecological risk assessment and a p roduct chemistry assessment were posted in Docket OPP

2003-0080

. No comments were received in conjunct i on wi th that application or those assessme nt s. On October 30. 20 1 3. EPA annou nc ed receipt of an applicatio n to register products (sec 3) containing a new ac ti ve ingredient

- Ma le Sea Lamprey Matin g Pheromone T echnical and Male Sea Lamprey Mating Pheromone (Vo lum e 78, N umb e r 2 10 , FR page numbers 64937

- 64938). Th e app li cant was a federal partn e r , US FW S

. A copy of that notice i s avai lab le in Docket I D Number EPA- H Q-O PP- 2013

- 0538 v ia 

### hllu : 1nrn '. r e r,,:u/01ions

. g<ff. No comments were submined in response to the announcement. 

### Proposed Re g ulatory Deci s ion The Male Sea Lamprey Mating Pheromone database

- wh ich includ es a battery ornonguideline 

### in vitro studies, open scientific literature and data from USFWS's monitoring or EUPs con taining Male Sea Lamprey Mating Ph e r omo n e - is adeq uate and su pport s the pest ic idal nonfood u se of Mal e Sea Lamp rey Mating Ph ero mon e. In considering the assessed ri sk to human health and the environmen t. the Age n cy conc lude s that Male Sea Lamprey Mating Pheromone meets the regulatory standard under the Fede ral Insecticide. Fungicide and Rodenticide Act 

### (FIFRA)

. There are n o outstanding data r equirements for thi s biochemical. The r efore. the E P A is prop os in g to gra nt th e u ncondi tio n al re gis tra tion of the M a l e Sea Lamprey Mat ing Pheromone as a new act ive in g redie nt (non-food use) under Section 3(c)(5) of FffRA. Two products are proposed to be reg i stered: Male Sea Lamprey Mating Pheromone Technical is a Manufactur in g- u se Product ( MP) and Mal e Sea Lamprey Matin g Pheromone is a n En d-u se Pr oduct (E P )

. Application s of th e EP are m ade in the tr ibutaries of the Great Lake Region during Sea Lamprey spawning season from April throu gh June. Applications are made in traps through a regularized drip, resulting in a n applied concentration be tween 4.72 to 0

. 0472 ppt during that time period. Resulting concentrations in those tributaries are ex p ected to be w ithin background leve ls in p laces w h e re Sea Lamprey are n a tura ll y found. Th e human health and ecolog ical ri sk assessmen t s suppor tin g thi s decision as wel l as the draft labeling can be found in the regulatory docket (Docket 

### ID EPA-H Q-OPP-2013

- 0538).

P age 9 of 9