### UNITED STATES ENVIRONMENTAL PROTECTION AGENC Y WASHINGTON , D

. C

. 20460



### M E MORAND UM Date: 22-AUG UST-2015 OFFICE OF CHEMICA L SAFETY AND POL L UTION PREVENTION



### SUBJECT: Roteno n e. Human Health Assessment Scopi n g D ocu m e nt in Support of Reg i strati o n Review. OP Barcodc: 042710 9 R eg is tratio n No.: NI A P C Co d e : 071003 Dec is ion No.: 503939 Petit io n No .: NI A R is k Ass e ss ment T y p e: N I A TXR No.: NI A Reg u lat ory Action: Re g is tration Review Scoping Document Ca se No .: N IA MRIO No.: NI A 

### FROM: CAS No.: 83- 79-4 40 CFR: N I A 

### B ri dgett Bobowiec , Bi o l og i st

## ~ Su mitr a B ose Biswas , Chemis t

## ~ Nancy McCarroll , Toxicolog i st .

## /V**~** 

# fJ, c.. l Ri s k Assessme nt Branch VI (RAB6) 

## I Health Effec t s Divis i on ( I

- JED) ( 7509P ) 

### THROUGH: Donna D avis , Acting Branch Chief Ri sk Assessment Branch V I Hea lth Effect s Divi s ion (7509 P) 

### TO: Kelly B a ll ard , C hem ical Review Manager Risk Manage m e nt and Impl eme ntation Br a nch I Pes ticide Re-Eval uati on Divi s io n ( PRO ) (750 8P ) \



### Att ached i s HED's hum a n health risk assessment scopi n g document for rotenone to support Reg i s trat ion R ev iew. The m ost recent quantitative human hea lth ri sk assessme nt was conducted in 2006 ( Memo , C. S mith , 28- J UNE

- 2006 ; 0328478).

Page I of 19Rotenone Re g is tration Review I luman H ealth A s sessment Scoping Document


### Tab l e o f Co nt e n ts 

### Exec uti ve Sum 1n ary ...... . ... ............ .. ........ . ............................................................ .. .............. . .. .. ...... 3 1.0 

### Introdu c ti o n ..... . .. .. .. .. ..... ..... . .. .. ..... .. . .. ... . ..... .. .... .. ... . .. .. . . .. .. .. . ..... .. .. . .... .. . .. .... .. . .. .. . . .. .. .. . .... ..... ... . . 4 2.0 

### H azard Characte ri zation/Assessment..
.. ... . ...... ........... . .. .... ....................................... . .. . ............ 5 3.0 Residue Chemistry and Dietary Exposure
. ... . ... ......... ... . . . .... .......... ........ .................................. 6 4.0 Re s id e nti a l Expos ure ............ . .. ....... . .. .. ..... ....... .. .. .............. .. . ...... ...... ... .. .. . .... . .. . .. . . .. . .. .. . ........... 7 5.0 Aggregate Risk Assessment.
.. ............... . ............... . ............ . ...... . ......... . . .................. .. . . .. ..... . .. . .. 7 6.0 Occupational Exposu re .................................. . ............... .. .. .. .. . ......... ... . .. . .. ......... .. . ..... .............. 8 7.0 Public He a lth a nd Pest ic id e Epid emi o logy Data
. ... . .. .. .... .. ................. .. . . ..... . .. . .... . .. .. ............... 8 8.0 Tolerance Assess ment a nd Inte rn ati ona l Harm onizat i o n . ....................................................... 9 9 .0 Environm e nta l Ju stice
...................................................... . ... .. ............ ...... . .. ........ . .. ..... . .. ......... . 9 I 0.0 

### C umul a ti ve ... .. .. .. .............. . .. .. .. . . .. .. .. ... . . . ... .. ............................................................ .. .. . . . .. . .. . ... 9 I 1.0 

### Hu1n an Studies
. .... .. .. ...... .. . ... . ... . ... ...... .. .. ...... .......... .. .. ...... .......... .. .. . ............ . ................ . ......... 9 12.0 

### Reference s ............................................................................................................................ 10 

### Att ac hment I: C hemic a l Id entit y and Di etary Tables
.. ...... .... .. .. . . . .. .. .. .. ... .. .. . . . ...... . .. . ... .. .. . . . .. .. . .. .. 11 

### A tt ac hm ent 2: Rotenone Acute , Subchronic , and C hro ni c Toxicity Profile
................... . .. .. . .... ... 13 

### Attachme nt 3: Toxicological Doses and Endpoints for Rotenone
............................................... 18 

### A tt achme nt 4: S ummary of R eg i s t ered Uses fo r R otc no ne . .. .. .. .. .. .. .. . . . .. .. . .. . ... ..... ..... . .. . . . ............ 1 9

Page 2 of 1 9Rotenone Registration R ev i ew Human Health Assessment Scop in g Document 

### Executive Summary HED has prepared a scoping document to support Registration Review of rotenone: a restricted use piscicidal chemical, applied directly to water by he li copters, c lo sed system aspirators , boats, and handheld equipment to manage fish populatio n s in lakes , ponds , reservoirs , riv e rs , and streams. R otenone i s formu lated as a suspension-concentrate (SC) and wettable powder (WP) in several end-use products ranging from 5 % to 7.4% active ingredient (ai) [2 pounds (lbs) 

### ail gallon; EPA Reg. No. 264

- 831]. Jn April of 2000 detailed standard operating procedures (SOPs) in the form of a management manual e ntitl ed 

### ROTE N ONE USE I N FISHERIES MANAGEMENT: Administrativ e and Technical Guidelines Manual, was produced by the American Fisheries Society. Registered rotenone label s s hould have langua ge to direct u sers to this manual , which in c lude s the most up-to-date restrictions , application methods and personal protection equipment (PPE) requirements. The manual was updated in 20 I 0. HED has considered all available data and human health risk assessments for rotenone with respect to its toxicity , exposure, and usage databases, and the most updated Agency science policy and ri sk assessment methodologies to determine th e scope of work necessary to support Re gistration Review. The toxicity database fo r roten one i s n ot complete as required by the 2007 revised 40 CFR Toxicology Data Requirements; however the data will not be required fo r registration review unles s there are changes in the limited rotenone use pattern. Th e toxicological data deficiencies identifi ed in the data call in (DC I) remain in rese rve at this point and include the fo ll owing; subchronic inhalation neurotoxicity study, an acute neurotoxicity s tudy as well as a chronic dog , developmental toxicity in non-rodents , a 21 -day dermal , a dermal penetration , a guideli ne metabolism, and an immunotoxicity study. In 2006 an additional I 

### OX ( leve l of concern (LOC) =1,000) was retained for all risk assessments to account for database uncertainty. Rotenone is classified as Toxicity Category I for oral and inh a lation routes of exposure and Toxicity Category IV via the derma l route of exposure. Rotenone is not an eye or sk in irritant nor i s it a skin sensi ti zer. The carcinogenic classification for rotenone is "not likel y to be carc ino genic in humans ," based on the lack of ev idence of carcinogenicity in rats and mice. Th e dietary expos ur e and residue chemistry databases are considered complete. Non -aquatic rotenone uses were terminated in spring of 2006 a nd therefore , dietary (food) exposure assessment is not required. Environmental Fate and Effects Divi s ion (EFE D ) provided HED with an acute est imated drinking water concentrati on (EDWC) of 200 ppb for surface water ( R. Da vid Jones , 0307383 , 5110 / 2006) based on the solub ilit y of rotenone in water. I n 2006, an acute and chronic dietar y exposure assessment was performed for rotenone considering exposures from drinking water only 

### (T. Goodlow, D328785 , 617/ 2006). Expos ure from the water was below the H E D 's le ve l of concern ( < I 00%). The rotenone fisheries management g uid e line manual has mandatory restrictions and SOPs to prevent consumption of treated fish. Rotenone i s exempt from the need to establ i sh tolerances. The Food Quality Protection Act (FQPA) of 1996 does not apply to rotenone and th erefore , HED does not need to aggregate pesticide exposures and ri sk from other sources of exposure (d rinking water and residential exposures). However , exposure from various routes and pathways may be combined in registration review if the toxicological effects are the same and expos ure i s expected to co-occur. There are no proposed or current residential uses for rotenone and therefore , a residential handler exposure assessment i s not requir ed for registration review at this time. However , res identi al Page 3of 19Rotenone Regi s tration Review Human Health Asses s ment Scoping Document exposure is possible through swimming and in gestion of previously treated water. In the 2006 risk estimates for short -tem1 post-application combined dermal and oral exposure to children (ages from I < 2 yea r s o ld ) from sw immin g in previously treated water were of co ncern ( margins of expos ure (MOE)s 

### < 1,000) a t day 0 afte r treatment. The ca lc ulated co ncentrati o n le ve l for incidental oral ingestion at which MOES exceeded 1 , 000 wa s 90 parts per billion (ppb) (0.24 lb ai / A 

### ft). From this calc ulati on , HED recomme nd ed sw immin g prohibition for at least thr ee days after the maximum application rate (250 ppb / 0.68 lb ai / A ft). There h ave been updates to the swimming exposure model since the 2006 ri sk assessmen t and the American fisheries rotenone manual. These updated expo s ure assumptions will be need to be in co rp orated as part of Registrat io n Revi ew. The R eg i stration Revie w process w ill also includ e consideration fo r rote n one bystander spray drift and volatilization assess m e nt s. The occupat ion al exposure database is adequate to support th e Registration Review process for r oteno n c. In the 2006 risk assessment , th ere w ere occ upati o nal handl e r risk estimates of co ncern ( MOEs < LOC) for scenarios that in volve d mixing/loading of liquid and wettab le powder rotenone formulations and for mixin g/loading/app lyi n g rotenone using boat aspirators and backpack sprayers d esp ite m ax imum miti gation p oss ibiliti es s uch as resp irator s and clo sed syste m s fo r mixing a nd lo ad in g. HED expec t s min im al occupationa l post-app li cation exposure from th e piscicidal use of rot e n one . As a result , no quant i tative occupational po s t- app li catio n assessment is expected, however an updated occupational handler assessment to reflect all regist e red u ses, m ax imum appl icat ion rates , and m ost up-to-d a te exposu r e polici es and toxicological points of departure ( PO Os) will be required for Registration Review 1.0 Introduction R otenone , or (6R , 6aS , l 2aS ) -I , 2 , 6 , 6a , 12 , I 2a -h exa h ydro

- 2-isopropeny l-8 , 9- dimetho

xyc hr omeny l[3 ,4- bfuro[2 , 3- h ]chrome n- 6

- one , is a naturally occurring compound that i s present in a number of plant s. This botanical pesticide d e rived from the roots of 

### Derris s pp. , 

### loncho catpus spp., and 

### Tephrosia spp ., found primarily in Malaysia , So uth America, and East Africa , i s registered b y E P A for piscicidal (fish kill ) uses. The last human health ri sk assessment was in 2006 and was the Final HED C h ap te r of th e R e re g i stration Eligibility Decision D ocument (RE D ) (Me mo , C. S mith , 28- J UNE

- 2006; D328478 )
. In add ition to th e RED , in 20 14 there was a Section 18 emergency use subm itted fo r an unregistered rotenone product (Memo , M. Sahafeyan. 07-AUG-2014; 0421308). Rotenone is app li ed directly to wate r to manage fish popul a ti o n s in lakes, ponds , rese rvoirs , rivers , and stream s . Rotenon e products are clas s ified as re s tricted use pest icid es due to high acute inhalation , acu t e oral, and aquatic toxicity. The chemical can rapidly degrade in soi l , water, and by s unli g ht , usually within 2

- 5 day s but may p e r sis t for as long as 6 months in colder weather. R egistered formulations of roteno ne include liquid and wettab le powder form ulati o ns w ith appl icatio n s made by helicopters and boats in lakes , reservoirs , and ponds ; with direct m ete rin g into mo v in g water suc h as strea m s; and with hand

- held equipment s u ch as ba ckpack spraye r s in difficult-to-reach aquatic areas. Current PP E for the va riou s handl e r sce nario s include , coveralls and g love s ove r baseline dermal protection , PFS and PF 10 respirators , and semi-c losed systems for diluting concentrate. Reentry is restricted unti I conce ntr at ion levels fall below 90 ppb. The application meth ods , PPE requirement s, reentry re s triction SO Ps are discussed in detail in the 

### ROTE NONE U SE JN F I SHE RI ES MANAGEMENT: Administrati ve and T ec hnical Guid e lines Manual produced by th e American Fisheries Society. T h e r e are no Page 4 of 19Rotenonc Regi st ration R ev iew Human Health Assessment Sco pin g Document 

### tolerances established for rote no ne b eca u se fi s h kill harv es ting practices , re stricti o n s on conc e ntration s prior to res tockin g are in place to prevent c onsumption of treated fi s h. 

### 2
. 0 Hazard Cha racte riz a tion / 

### Assessme nt Since the RED document was finalized (Smith 

### et al. , 2006) , no new studi es have bee n r eceived for rote none. T here fo r e , the toxicology d atab ase remain s incomplete ; however, because of the lim ite d use patte rn and accompanying u se manual for rot e none , the mi ss i ng s tudi es remain in re se rve but do n o t preven t regis tration review. T he re serve studies includ e a chronic dog , developmental tox icit y (no n- roden ts ) , dermal penetration, a 2 1-day dermal toxicit y s tud y , a g uid e line m e tabolism s tudy , as we ll as acute neurotoxicity study. Simi l arly , an inh a lation neuro tox ici ty s tud y w ith rote none , which was the s ubje ct of a D ata Call I n ( DCI ) (G D C I071003-20980), has never be e n satisfi ed a nd a s ubmitted data waive r was denied ( Locke , 2004)
. I n accordance with th e revis ed 2 007 40 CFR Part 1 58 T ox icolo gy Data Re quirem e nt s, an immunotoxicity study i s no w required for food a nd non- food use pesticides , ho weve r due to the limite d u se patt e rn , an ad dition a l DCI for this s tud y is not required at this time
. A toxico l ogy datab ase 1 

### OX uncertainty factor (UF ) i s s till in plac e for th e various point s of d eparture ( PO O s) selected fo r the dietary (wate r o nl y) , residential and occupational risk assess ment s. A d e finitive target organ ha s no t been id e ntified for ro te n o n e but numero u s publi s he d lite rature stud ies wi thin the pa st I 

### 0 years indicate that rotenone , v ia intra ve nous or subc ut aneous routes , indu ces behavioral , biochemical , and ne uropath olog ical effect s. While ne ith e r route of exposure is rele v ant to the risk assessment , th e intrav e nou s route m ay mimi c inhalation exposure , which i s a r ou t e of concern with rotenone. The o nl y available inh ala ti on tox ic ity study i s an acute LC so in the ra t (C atego r y I). H owever , none of th e presented s tudi es , which are s uitabl e fo r ri sk asse ss ment purposes , are adequate to address th e ne urot ox ic ity concerns o r the inh alation route of exposure. Minimal systemic toxicity ha s b ee n observed in the databa se and th e m ost common effec t in subc hronic o r chro ni c rat , d og , mou se , and/o r h ams ter o r a l st udi es , i s decreased body weight and/or body weight ga in
. Rat s a nd do gs a ppear to be equally sensitive and both are more sensitive than mice or h amsters; fema les app ea r to be m o re se n s iti ve than mal es to effects o n body we ight. No conclusions can be reached for e ithe r dermal or inhal atio n routes of administration s ince r o ute specific data i s not avai l able for these r outes of ex posure . In the dev e lop menta l s tudie s , matern a l toxicity occ urred either at lowe r do ses (rat s) or at a n equivalent dose in mou se maternal animals and th e pups ; no study was av ail ab le o n a no n- rode nt species
. In a two-g e neration r e producti ve toxicity s tudy (rat), adult and offspring tox icity were ob se rv ed at do ses g reat e r than 3 .0 m g/ k g/d ay . Th e main effec t in both pare ntal animals and pups was decreased body weight and body w ei gh t gai n . At this tim e , no quantitative o r qualitati ve ev id e n ce supports increase d s u sce ptibility ofrat or mou se fetuses or rat offspring. r t i s current ly unkn o wn ; how eve r , wh e ther 

### in utero exposure to ro ten o n e in the developing rabbit re s ult s in tox ic ity below o r at th e sam e dose re s ultin g in maternal tox ici ty. L ikewise , post-natal growt h and s urvival i s unknown for th e d eve lopin g rabbit. No evide nc e fo r carc in oge nici ty was seen in mice or r ats an d it i s not mut age nic in v itro or in vivo
. There fo re, roten o ne is c lassified as Group E ( evid e nce of non-carcinogenicity for humans) (Memo , 

### R. Gardner , 05-0CT-1988, TXR005 2673)
.

Pag e 5of19Rot enone Re gistration R eview Hum a n H ealth Assessment Scopi n g Document 

### In acute oral a nd inh a lat ion studies, rotenone is classified as Category I, seve rely toxic but is not toxic dermall y (Category IV ) or causes eye or derma l irritation (Category IV) , and it is a lso not a dermal sensitizer. An appropriate ac ut e e ndpoint for the ge ne ral p op ulation , includin g infant s and ch ildren , was not identified in the availab le toxicity stud ies . The acute dietary (drink in g wate r only) risk est imate calculated fo r females 1 3 -49 years of age i s based on a NOAEL of 15 mg/kg/day from the m ouse developmental s tud y. The chronic dietary (drinking water only) ri s k es timated was derived from the NOAEL of 0.375 mg/kg/day in the chronic /carcinogenic ity rat study. The short- and intermed iate- t erm (non

- cancer) dermal occupat ional and residential ri sk assessment for rotenone i s based on a N OAEL of 0
. 5 m g/kg/da y from a re producti o n study with a dermal ab so rption factor of 10 pe rc ent se lected. Long -term expos ure to rote no n e is not expected fo r cu rre nt registered uses. The dermal, inhalation, and incidental oral margins of exposure we re comb in ed for th e rotenone risk assess m e nt becau se the e ndpo int s are ba sed on the sa me toxicologica l effects. Effects were see n in both male and females so the body we ight of an average adult ( i. e., 80 kg) was u sed to es timat e exposure . Because of a s ign ifican t gaps in the toxicology database an additional l 

### OX UF ha s b ee n applied to the various p o ints of de parture ( PODs) se lec ted
. 

### Conclusions for Hazard Assessment: The toxicity d atabase for rote non e i s not complete; howeve r , d ata gaps are being he ld in re se rve and do not preclude registration review. As part of Registrati on Review. all e nd points used for rotenone ri sk assessment w ill be updated to reflect c urr en t H ED policy. Until the mi ssi ng data are presented to H ED , the addit ional 1 

### OX UF will be applied to a ll POD s . 

### 3.0 Resi du e C hemi s t ry a nd Die t ary Ex p os ur e The last residue chemistry review was completed for the RED in 2006 (Memo , C. Smith , 28- J UN E-2006; 0328478). Res idu e chemistry data deficiencies c ited in that memo have not been addresse d fo r rotenonc because all food uses hav e since been cancelled. Therefo r e, at prese nt time , there are no outstand in g deficiencies provided there is no request for a food use. T he re are no tolerances estab li s hed fo r rotenone because fish kill h arvest in g practices, restrictions o n concentrations prior t o r estoc kin g are in place t o preve nt consumption of tre at e d fi s h. The fate and tran sport p roperties of rotenone in the environment are not we ll understood. Rot c no ne hi sto ricall y has been c hara c t e ri ze d as immobile, non-persistent, a nd does not appear to bioaccumulate. This c h arac te ri zation i s true in so me circwnstances ( M e m o, R
. D av id Jon es, 05- MA Y-2006 , 0307383). Rotenone does degrade rapidly by aqueous photolysis (the photolysis hal f- life i s less than one day) o n warm sunn y d ays in clear water a nd m odera tel y at te mp erat ure s of25 ° C ( half-li ves of 1 2.6 days at a pH of 5 and 2 days at a pH of 9). How eve r , a quat ic fie ld studies s how that rotenone can persist in cold water at s u fficie nt concentrations to cause fish m o rt ality for at least 25 days , eve n in al kalin e cond ition s. EFED provided HED with an estim ated drinking water concentrati on (E D WC) of200 ppb for surface water (Memo , 

### R. D av id Jones , 05 -MA Y-2006, 0307383) based o n the so lubility of rotenone in wate r. It 

### is a lso worth no tin g that th e maximum application rate assessed 2006 250 ppb exceeds the solubility of rotenone. The suspended or emulsified roteno ne will be less available for m e tab o li sm o r hy dro l ys i s than that in th e dissolved ph ase. In 2006 a n ac ut e dietary exposure assess m ent was performed for r o ten o n e considering expos ures from drinkin g w a t e r only (T. Goodlow, 0328785 , 6/7/2006) using the Di etary Expos ure Eva lu ation Model (DEEMFCIDTM, Version 2.03)
. The ac ut e dietary exposure from drinking water co nc e ntration s were Page 6of19Rotenon e Regi s h·ation Review Human Health Assessment Sco pin g Docume nt below H E D ' s leve l of co nce rn ( < 100 % ac ute P A D ) for all popul at ion s ub gro up s. Us in g th e drinking wat e r leve l of co mpari s on (DWLOC) approach , H E D d e termin e d that chronic drinking water exposures greater than 40 ppb could pose a potential risk of co nc ern ( > I 00% c RfD ) to the mo st hi g hl y exposed population s ub gro up s, infan ts and c hildren. An updated di e t a ry assessmen t (wate r only) i s re quired as a part of th e r eg i strat ion revi ew. 

### 4.0 Res id enti a l Expos ure There are n o reg i stered or pro posed rotenone products that a ll ow fo r residential use. Rot enone is a restricted use ( RU ) pesticide; th e refore , a quantitative residen ti a l handl e r exposure assess m e n t is not ex pected. Howeve r , the re i s the potential fo r exposure to individual s in an e n v ironm e nt that has been previously treated with roteno n e. ln 2006 , HED comp let e d an assessment for residential p ost
- a pplic at ion exposure from re c reational swi mmin g in rotenone-treated waters . The calc ulated post-application sw immin g short-ter m d e rm al and in cidenta l ing es tion ri s k estim ates were of concern (MOEs < 1 , 000) for ch ildren (ages 1 t o < 2 yea r s o ld ). Acceptabl e combined risk es timat es were not of concern at 90 ppb co n centra t ion. Thi s back calculation l ead to a prohibiti o n of sw immin g fo r at least 2 da ys afte r completion of a 200 ppb (0
. 54 l b 

### ai l A 

### ft) rotenone application and at leas t 3 days after completion of a 250 ppb (0.68 lb ai/A 

### ft) rotenone. The aquat ic u se S OP swi mmin g mod e l ha s since been u pdat e d a nd a new sw immin g assessment will be nece ssary for R eg istration Re v i ew. Spray Drift a nd Volatili zation: Res id e ntial bystander expos ur es resulting fr o m off-site transport (e.g. , s pray drift or vol a tilizati o n ) ma y occur as a result of a pplic a tion s ofrote n one. The potential for sp ray drift will be quantitatively eva lu ated for each pest icid e during th e R egistrati on Rev iew process that ensures that all u ses of p es ticides w ill be co n s id ere d concurrentl y. The approach is o utlined in th e r ev i se d (2012) Standa rd Operating Pro cedures fo r R eside ntial Risk Assessment (SO P s)

- Resi denti al Exp osure Assessment Sta ndar d Operati n g P rocedures A d de nd a I: Cons iderati o n of Spray D rift. Th i s d oc um e nt outl in es the quantific atio n of indirect nonoccupational ex posure to drift
. In term s of volatilization , the agency has d eve lop ed a Volatilization Screenin g Tool and a subseque nt Vo latili zation Scree nin g Ana l ysis (http: //www .r eg ulati o n s.gov/#! docketD e tail;D = E PA-HQ-OPP- 20 14-0219 )
. Durin g Regi stration Re v i ew , th e agency will utili ze thi s ana lys i s to d ete rmine if data (i.e., flu x stu die s , route
- spec ific inh a lation t ox ico logical st udi es) o r further analyses are required for specific chemicals. 

### Conclus ions (o r R es id en tial Assess m en t: Th e r es idential expos ur e d atabase is considered comp lete . There are no proposed or current registrations for products containi n g rotenone that allow r esi denti a l use. T herefore , re s id e nti a l handl e r exposure assess ment s w ill not b e n ee d e d during R egistration R eview. Upd a ted res id e ntial post-application risk assess ment s will be r equired, however du e to the updated 2015 aquatic S OP and if significant changes are made t o the POD s and / o r U F s. The n eed for s pra y dri ft and vo l at ili zation ri s k assessment fo r r otenone will be co n s id e r ed durin g Re gist ration Re v iew
. 

### 5
. 0 Agg r egate Ris k A sse ssme n t In accord an ce with the Food Quality Protection Act ( FQP A) of 1996 , for c h e mic a l s h av i ng tol erances in foo d , HED mu s t co n s id e r a nd aggr egate pe st ic id e ex posures and risks from three major so urc es : foo d , drinkin g water, and r es id e nti a l exposures (o ra l , d ermal , and inh al a tion). A ll uses of rotenone o n food c rop s were cance lled and thu s , th e requirements of FQPA a re not applicab le, how ever, ba sed on th e curre ntl y regis te r ed u ses fo r rot e none , a dietary ( drinkin g Page 7of19Rot eno n e Re gistra ti o n R ev i ew Hum a n H ea lth Assessment Sco pin g Document 

### water only) assessme nt w ill be conduc ted
. Therefore , H ED will consider the aggregate exposu r es and risk s of the di e tar y (drinking water only ) as well as the res id e ntial post
- application exposures , as app ropriate, during Regis tration Review. 

### Conclusions (or Aggrega te Assessment: Durin g Regi s tration re v iew H ED w ill consider th e need for an aggregate assessme nt combining the drinking water (dietary) and nonoccupational exposures as appropriate. 

### 6 .0 Occ up ati onal E xposure Occupation a l handl e rs are anticipated to have s hort- and interm e diate-t e rm derm a l and inhalation exposures. Risk estimates of concern were identified for occupational h an dler s in the prev ious 2006 ri sk assessmen t. Occupational long-term ex po sures to rotenone are not expecte d fo r rotenone pi sc ic ide u ses . In th e 20 06 ri s k assessment, there were combined dermal and inhalati on risk estim ates of concern (MO Es< 1 , 000) for both liquid formulat ions and wettab le powder formulation s for mi xi n g and loading for boat app li cat ions even with maximum risk miti gation of a c losed system. Many of th e mixer / loa de r /ap plicator sce nario s fo r lake and pond s ites also exceeded HED's level of conce rn even at maximum ri sk mitigation using closed system s fo r mixing and load in g. R oteno ne ap pli ca ti on to moving water ( i. e. , streams) u s in g below wate r s urf ace drip bars resu lt ed in no risk es timates of concern with assumptions based o n no contact with rotenone o nc e loaded. In support of R egistrati on Review , an updated occ up at ional ex p os ure assessment fo r rotenone will be conducted for al l of the form ul at io n s types and possib le exposure sce n a rio s. New ri s k estimates will re fl ec t upd a te s to A m e rican F i s he rie s Rot e non e Manua l , HED ' s SOPs along with policy c han ges for body we ight assump tions, avai labl e chemical specific data , and c h anges to PODs or UF/ SFs. An 

### updated occupational dermal post-applicat io n assessment is not required during Registration Review. It is unlikely fo r occ up ation al workers to come into con tact with previously tre ated wate r except fo r water sa mpl e an d de ad fish co llection. H E D d oes not h ave data to assess these post-application activit ies , which are assumed to be negligible when compared to the occupational handler exposu re sce n a ri os. If 

### n ew policies or pro ced ur es a re de veloped, the Age ncy m ay rev i s it th e need fo r a qu antitat ive occ upati o nal de rm a l po st-ap plica tion e x po s ure assessme nt for rotenone. B ased on the Age n cy's c urr e nt practices , a quantitative occ up ationa l post-application inh a lati o n expos ure assess m en t was not performed for rotenone at this time. If 

### new po lici es or procedures are developed, th e Agency m ay rev i s it th e need for a qu antitati ve occ upational post
- application inhalation exposure a ssessme nt for rotenone. 

### Conclusions for Occupational Assessment: Th e occupationaJ ex po s ure d ataba se is adequate to support the Registration Review process for rotenone ; however, th ere were risk est imates of conce rn identified in 2006 assess men ts. S in ce occ up a ti onal handl e r ex p osure es tim ates were based o n su rroga te data fro m the P estic id e H a ndl e rs Expos ur e Database ( PHED ) , c hemic a l specific rotenone data o n the handler exposu re scenarios for could provide more refined wo rk er ri sk est imat es. 

### 7.0 Public Health a nd Pesticide Ep id em i ol ogy Data The Agency has rev iewe d the ava ilabl e incident data for rotenone (Me m o , E. Eva n s, S. R eco re , C. Ch ri ste n se n , 0l

- APRIL-2015 , D427 l 27) and based o n the low frequency and severity of cases re p o rted for rote non e in both ID S a nd SENSO R-P esticides, th e re does not appear to be a co ncern Page 8of19Rotenone R egis trati on Review Human Health Asses s ment Scoping Document 

### at this time that would warrant furthe r investigation for incid en t s. The Agency will continue to monitor the incident i nformation and if a concern is triggered , add iti onal analysis will be in cl u ded in the risk assessment. 

### 8.0 Toler a nce Assess m ent a nd Interna tion a l Ha rmoni za ti on An exempt io n from toleranc es was origi na ll y granted under 40 CFR 

### § 1 80. l 00 1 (b) for residues of rotenone ((2R,6aS, l 2aS) -1. 2.6,6a, 12, I2a

- hexahydro-2-isopropenyl-8.9

- dimethoxychromeno [3,4 -b)furo[2,3 -h]chromen - 6-one) in/on raw agricultural commodities. The exemption from tol erances i s currently li sted unde r 40 CF R 

### § 1 80.905
. In the las t RED, HE D reco mmend ed the tolerance exemp ti on be revoked s ince a ll food uses we re cancelled. 

### 9. 0 E nvironmental Justic e P otential areas of environmental justice concerns, to the extent possible , were considered in the most recent rotenone human-health risk assessment, in accordance with U.S. Executive Order 1 28 98 , " Federal Actions to Address Environmen tal J ustice in Minority Populat ions and Lowl ncome Population sa." The OPP typically considers the highest potential exposures from the legal use of a pesticide when conducting human health risk assessments, including. but not limited to , people who obtain drinking water from source s near agricultural areas , the variab ili ty of diets within the U.S
. , and peop le who may be exposed when harve s ting crops. S hould these highest exposures indicate potential risks of concern , OPP further refin es the risk assessments to ensure that the risk estimates are based on the best available information. 

### 10
. 0 C umulativ e Unlike other pesticides for which E P A has followed a cumulative ri sk approach based on a co mmon mechanism of toxici ty, E PA has not mad e a common mechanism of toxi c ity findin g for rotenone and any other s ub stances; and rotenone does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action , th erefo re , EPA has assumed that rotenone does not have a common mechanism of toxicity with other substances. F o r in formation re garding EPA 's efforts to dete rm ine which chem icals have a common mechanism of toxicity and to eval uate the cumu lati ve effects of such chem i cals. see the polic y statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and procedure s for c wn ul at in g effects from s ubstances fou nd to have a common mechanism on EPA 's website at http ://vvww.epa.gov/ pesticides/ cwnulative/
. 

### 11.0 Human Studi es Past rotenone risk assessme nt s rely in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Many such studie s, involving expos ure to many diffe r ent pest ic id es , comprise gene ri c pesticide exposure databases such as the Pest icide Handlers Ex posure Database ( PHED ), the Agricultural Handler Exposure Task Force (A HETF) Database, and the Agricultu ral Ree ntr y Task Force (ARTF) Database. EPA has rev iewed all the studies supporti n g these multi-pesticide generic exposure databases , a nd has fou nd no clear and conv in cing ev idence that the conduct of any of them was eithe r fundamentally unethical or s ignifi cantly deficient relative to the et hi cal

n http: //www.cpa.gov/ compl iance/cnvironmenta l justice / resources / pol icy/ exec_order
_ 1 2 898.pdf Page 9of19Rot enone Re g is tration Revi e w Human Health Assess ment Scoping Document 

### st andard s prev ailing at the tim e the research was conducted. All app li cable requirements of E PA's Rul e for the Protection of Hum a n Subject s of Research ( 40 CFR Part 26) have be en s at i sfied , a nd there i s no regulatory barrie r to conti nu ed rel iance on t hese studies. 

### 12
. 0 R e ference s

Memoranda Releva n t to Re2i s tration Rev iew . 1 Author Bar co de

P.Y. Barnes

Elizab eth E vans , Shanna 1 1 Rec ore , an d Carol Christensen

Ju dy Facey

Brian Fin l ayson. ct al.

R
. David Jon es

# sen Sahafeyan D34 3354

D4 27 1 27

D30 7384

http :// www. fish e ri essoc iety .o rg / rotenonc/ rot. pdf

03 07383

D4 2 130 8

D328478 Date
September I 1 , 2007

April I , 20 15

Febru ary 2 , 2006

20 10

M

ay 5 , 2006 August 7 , 2014

Jun e 28 , 2006 Title Rotenone : Revi sed Acute Aggre ga te Dietary and Drink in g Water Exposure and Risk Assessment for the Reregistra ti on Eligibility Deci sio n Rotenon e: Tier I R eview of Human In c idents Rotenon c (07 1003). Re sponse to Pha se I E rror Comments fro m Pr enti ss , I nc. on HED 's Pre liminary Human H ealt h Ri sk Assessm ent Plannin g a nd Standard Operatin g Procedures for the Use of R otenone in Fi sh 

## I Manage m en t Rotenone SO P Manual American Fisheries Soc iety Fish Managemenr Ch e micals Subcomm ittee



### - - - Drink in g Water and Swimmer Ex posure Assessment for Rot enone from th e Pi sc icid e Use Rotenon c. Section 1 8 Emergency Use for th e Presidi o Lake Rotenon e: Final HED C hapter of the R eregistratio n Eligibilit y Decis ion Document

# os Smi th RED). PC Co d e : 071003**~~~~~~~~~~~~~~~~~~~-'--'--- ~**  

### Atta chment s : Attac hm e nt 1: C he mical Id en tity and Di e tary Tables. Attachment 2: Rot e none Acute, Subchronic, and C hronic Toxicity Profile. Attachment 3: R otenone of Toxicological Dose s and Endpo int s for Rotenone. Attac hm e nt 4: Reg i ster ed Uses for Rot e no ne .

Page 10 of 19

### Attachment 1: C hemical Identity and Dietary Tables
. Table A.1.1: T est Com ound Nomenclature Chemical structure CK 3 0

0

..__ __**~c -"'CH2**  H ......._ CH3 Em irical formula C 23 H12 Ou 

# I t--"---------- ·

Co mmon nam e Rote non e . IUP AC name (2 R ,6 aS , 1 2aS)

- I .2,6,6a.12. I2a -h exahydro-2-isopropenyl-8. 9-**~- --** **---------1-- im** **ho y_** **'- ro** **o,( A-b]**  furo[2,3-h )chromen-6-o

_ n

_ e.__ _ CAS Reois

### r _ __ _,_83- 79-4

### ~ C hemical C lass Rote noid

Tabl e A
. 1.2: The Ph sicochemical Pro erties of Rotenone as e r ecor M t R d OPPTS Guideline Numb e r s Idcntification 830.1550 Prod uct ldentit )' and Com os1t1on 8 30. 1600 Desc ription of Material s Use d to Produce the Product 

### IMRIDI 4 44 1115-0 I

41 115-01 830.1620 Description of Production Process 4 830.1650 Desc ri tion of Formu lation Proce ss 4 41 11 5

- 01 46528

- 0 I 41 115-01 830. 1670 Discuss io n of Formation of 1 4 Im urities _[ 830.1700 Prelimin Analysis 4 '-------- 41386

- 0 1 830. 175 0 Ce rtifi e d Limits 830.1800 Enforcement Ana lyt ical Method 4 43953

- 0 1 447265-0 1 , 445 108-01 HPLC/UV Status 1 Re s ults or * Deficienc y A A

- A A A A A

830.1900 S ubmi ttal of Sa mple s E PA Repo si tory, A 44.2%

--- T IFA , In c. t------------
- --- --1- F

_ t

_ . Mea de, MD
. -1---- Ex piration Date: 02 /22

_ / 2

_ 0

_ 0

_ 6

_ ___ ---1**.6 30** **r** __________**80- 2**  __ -1-

A

__ -1-

T

_

an

____________ _ 830.6303 Ph xsical State 438180

-02 A Powder**~------------1--------,----.....----------------i** t- 8

_ 3

_

0.

_ 6

_

30

_ 4

_ 0

_ do

_

r __________ +

4

_

38 I 80

-02

- t- A Wet chalk Te mp (s) = No cha nge was obse rv ed: the 830.6313 Stabi lity to norma l**a~d** e levated 441237 _ 05 loss was less than 5%. M e tal s = No tempe<a'"<e s . metals and metal oon s 

# __J 

# -+-- I**~~nge** was obmved. the loss wa s about I 830 6
... 14 O 'd · /R d · C h mil 

## I 

# __L

. .) x 1 anon e UCllOll em1ca 438 180-02 A Incompatibilit y 830.6315 Flammabil ity_ 438 1 80

-02 A 830.6316 Explodability 438180

-02 A

.... ... 

### . . ... 

## - 

# 1s,o.6, 1 7 S tornge St ab oht y A None Not Aoolicable Not Anolicable Co ntain er I S tabilit y Temp
. Poly bag I Stable j 22EC 

# - I Duration I I 1.0 yr. I 

# _J

b The EPA 's Office of Wa t e r ha s established maximum conc ent ration levels (MCL) for trichloro e th y lene (5 ppb) and toluene 2000 ppb). However. recent env ironmental incidents have s hown trichloroethylene levels to exceed the MCL after applica t ions of rotenone to bodies of water. M o s t curre nt CSFs either do not list or do not quantify the impuriti es. T he refore, H ED is unab le to conduct a qualitativ e or quantit ative assessment of th e po te ntial ri s ks po sed by the im purit ies that may be pre se nt by any route of ex po s ure. Page 11of19Rotenone Regi s tration R eview Hum an Health Assessment Scoping Document Tab le A.1.2 : The Ph s i cochemical Pro ert i es o f Rotenon e M aste r R eco rd OPPTS G

## uid**li~n- 1**  b

_

e

_ r

_ s _____ -+- l

- d

- e n

_t

_ ifi

_ •c

_

a

_ t

_ io

_ n

--1- S

- t a

_

t

_ u

_ s 1

-1-

R

- e

- s u

_ 1

_ ts

_ o

_r

_ * D

_ efi

- 1c

- ie

_

n

_

c

_ y

__ _ ___

## ~ _ IMRIDI Pol y bag I Loss #5% I 0.5
. I 40EC 830.6319 Miscibilicy 441308

-01 A Not A licable 830.6320 Co rrosion Characteristics 441308 -0 I A None**---~---~----; ~--------!------~--~~---------------;**  830.632 1 Di e lectric Breakdown Voltage
__ +- 4

_ 4 1 308 -01 A Not App l icab

_ le

_________ ----<

, 830. 7000 pH --,..4

_ 4

_1

_ 3

_

08

_

-

_ 0

_

1
__ _,__

A

__**..,.. ot** **A~ li** **ab e**  _ _ (M RJD to be 830.7050 UVN IS absorption assioned 830. 7 100 Yi scos it )'. 44 1 308-0 I 830.7200 Melting Poin t/Me lting Ran ge 441237

-02 830.7220 Boilino Poin t/ Boilin o Point Ranoe 830.7300 Density/Relative Densicy/ Bu lk Dens it y 1830.7370 Dissociation Cons tant**~.7 550**  Partition coefficient (n-oc tanol ate r) shake flask method 830. 7560 Parti t ion coefficient (n-octanol /water) generator column method 830.7570 Partition coefficient (n-octanol / water) est im at io n by li quid chromatography 830.7840 Water Solubility: Column Elution Method; Shake Flask Method 830.7860 Water solubility, genera tor column method 830.7950 Vapor pressure 438 180-0 2 447181

- 01 44 1 237 -04

_ ............

............... 441237

- 03 

## I

# ~-~~~~**-9-0** I L 1 A = Acceptable; U = Unacce ptabl e (See *Deficiency) A Absorptivity at 235nm & 292 nm A Not A li cab le A 160

- 163 °C
A A A



### ----- -

... .. .

............ A 

# I : ----- - PAI is solid at room tern erature. Fluffy 0.2400 g/cm 3 ; 14
.70 lb/ c u . ft Com acted 0.4500g/cm 3 ; 2 8
. 10 lb/c u . ft PAI no dissociation constant at pH 2-12. (OEC D Method No. I 12
K o1w Log P = 4.16 See Guideline 830.7550 See Guid el in e 830.7550 Solvent = Water; Temperature = 20 °C; Avg. Solubility= 0.142 m g/

ml See Guideline 830.7840 Not App licab le
Tab le A.1.3: Acute Dietar y Exposure a nd Ri s k for Rot e none at the 95t1 • Percentile S urfa ce W ate r and Fis h Onl y

. I a PAD EDWC Expo s ur e % aPAD P o pu lat i on S u bgroup / k / d ) (ppb) ( mg/ kg / da y)**g** · gay Fema l es 1 3-49 years of 0.015 200 0.0 1111 7 74
Tab le A
. 1 .4: R es ults o f the Drinkin g Water Onl y Chroni c Dietary Exposure An a lysis for Rotenone Population S ub group

1 General U.S.

Popula ti on All In fant s(< I yea r old) c RfD (mg/kg/da).'.2 0.0004 0.0004 

## I Ex posure of Co ncern (ppb) 140 40 40 Children 1-2 yea" old**~004** 

# I Ch ;ld ccn 3-6 yem old
__ o

_ .0

_

0

_ 0

_ 4_-+----40 Number of Days that Exceed Exposure of Co ncern

4 in warm water



### ---- 53 in co ld 4-5 ° C wate r

27 in Lake Dav

_i

"'" s,

'- C

_A

_ ____ _.

# ::al91349~a~ __ o

_ .0

_

0

_ 0

_ 4
__

# ~ ____ 12

_

0
___

# ~----------------~

Page 12ofl9Rotenone Registration Revi ew Human Health Assessment Scoping Document 

### Attachment 2: Rotcnone Acu te , Subchronic, and C hroni c Toxicity Profile. T ec hnical Tabl e A.2.J: Test .Required for Nonfood Use P esticides 

### I S ati s fied R e quired 870.1100 Acute Oral Toxicity......
......... ........ ......... ........... ........... .. yes 

# I yes 870.1200 Acute Dermal Toxicity....
..... .............. ..... ....................... yes yes 

# I 870. 1300 Acute inhalation Toxicity...................
... ......................... yes yes 870.2400 Primary Eye Irritation..
.............................. ......... .......... .. yes yes 870.2500 Primary Dermal Irritation.................
.... ................. ... ...... yes yes 

# ---1

870.2600 Dermal Sensitization...................................................... y_ e

_ s ______ .._,._

y_

_ e

_ s .,...- 870.3100 Oral Subchronic (rat)...................................................... yes Ye s 1 870.3150 Oral Subchronic (dog)......................................
. ............ . no no 870.3200 21 /28-Day Dermal ( rat).................................................. no 870.3250 90-Day Dermal...............................
...... ........... ......... ...... yes 870.3465 28-Day Inh alation......................................
... .................. C R 870.3700a Developmental Toxicit y (rat)......................................... yes 870.3700b Developmental Toxicity (no nrod ent)
............................. yes 870.3800 Reproduction (rat}.......................................................... Y
. _ e

_ s __ 870.4 1 00a ChronicToxicity(rat)................................
... .................. yes 

## I Ye s' 870.4 1 OOb C hronic Toxicity (dog)..............................
. ................ . ... yes no 

# I 870.4200a Carcinogenicity (rat)....................................................... yes yes 870.4200b Carcinogenicity (mouse)
... ............. ......... ......... .............. yes yes 870.4300 Chronic/Carcinogenicity (rat)......................................... yes 

# -t yes 870.5 

# !00

### Mutagen~c~ty-Gene**Mulat~on** - bacterial :.... ............

### es**___** ye - s - - -----1 870.5.>00 Mutagenictty

- Gene Mutation

- mammalian
............:···· 

# I**~es** yes 870.5375 Mutagenicity

- Structural Chromosomal Aberrations.... yes yes 870.5395 Mutagenicity

- Mammalian Erythrocyte Micronucleus. 

# I yes 870.5450 Mutagenicity

- Rodent dominant lethal assay no 

# I 870.5500 Mutagenicit y - Bacterial DNA Dam age or Repair Test no**~** 870.5550 Mutagenicity

- Unscheduled D A Synthesis................. no 870.61 OOa Acu te Delayed Neurotoxicity. (hen)............................... no

1 870.61 OOb 90-Day Neuroto.xi.city (hen)...
... ................ ..... ................. no

870.6200a Acute Neurotox1c1ty Screen mg Bat1 ery (ra t).....
............. yes 870.6200b 90 Day Neurotoxicity Screening Battery (rat)................ yes 870.6300 Developmental Neurotoxicity (rat)................................. no 870.7485 General M e tabolism (rat)........
........... ..... ....... ............. ... yes no 

# _L

no 

# I no

n o n o 2 

# I**~o**

no 3 870.7600 Dermal Penetration, in vivo (male rat}.
.......................... yes 

## ------·--- 870. 7800 lmmunot oxicity (rat or mouse) yes 1 Rcquiremcnts for !his study arc fulfilled b) • the chronid oncogcnicity rat feeding study
. 1 An inhalation ncurotoxicity (ra t ) s ludy ( D C I G D C l- 071003-20980 was issued 9n006) no

- -- 

# I I _J

'CFR 158
. 340 (24) : Dermal absorption studies required for compounds havin g a se riou s 1oxic cffecl as idcn1ificd by ora l o r inhala1ion studies, for which a signili cam rou te of human exposure is dcnna l and for which the assumption of I00 percent absorption does 11 0 1 pr o duce an adequate margin of safety
. Registrants s hou ld wo rk closely with the Agency in developing an acceptable protocol and performing dennal absorption studies

Page 1 3of19Rot e no ne R eg i s tr at ion Rev ie w Hum an Health Assessment Sco pin g Document T ab le A
. 2.2: Ac ut e T ox i citv for R ote n o n e OPPT S G uid e lin e 

## I S tud y Ty p e 

## I 810.1100 99.23 % a . i. 

## I MIRD I R es ults LD so = I 02 mg/kg (M) LDso = 39.5 mg/kg (F) Toxic ity Cate2orv 

# I 81-1 I Acute oral [rat] 

# ___t

--- - - - , _ _ _ - - - - - - - --+- -- - -! 

# +- 00 145496
870.1200 

# I 81-2 Acute dermal**[rabbit ~**  43907501 

## I LDs 0 = > 5000mg/kg IV 

# + 97.9 %a .i
.

### ~ 

# - -1- - - -il 

# L 870.1300 81-3 Acute inhalation [rat] 

# I LC so 

## = 0.0212 mg/L combined J 4388260 I LC so = 0.0235 m g/L (M) 

# + 98 % a. i. L C." = 0.0194 m g/ L (F) 870.2400

81-4 

## I 43907503 conjunctiva! irritation , PIS 3.3 at I IV
'8 70.2500. 

# 1-- 81-5 Acute eye irr
. itation

# [rab**it)** 1 M11111nal 111 unwashed eyes 97.9 % a.i. hr ., c leared less than 24 hrs. te dermal irrita ti on [rabbit] 43907504 

# I P IS 0.08 at I h

- o - ur

_ \

_ v

_ h

-

ic

_ h

_ __._ __ l

_ V

_---1

_ _ 9

_ 7.9% a. i
.

## ~**ecreased** t o 0 at 72 ho

_ u

_ rs

_--+------1 870.2600 

# L 81-6 Skm scns; 1;za1;on [gu;nca p ; g] 1 

# I 

# I 43817903 ot a dermal se nsitizer 98%a. i. 

# _ __,__ - - - Ta bl e A.2.3: S ub ch r o ni c, C hro n ic , a n d Oth e r T ox ic ity Pr o fil e o f R ote n o n e G ui de lin e#/ S tu d y T y p e C M

I R l ? fi #

### (y~a**// D**  R es ult s 

# L- ass1 1 catio n oses 1 

## I 870. 3 100 

# I 1 82-la Sat is fi ed by MRIO 0 01 56739 , 4 1 657 1 0 1 (83-5) A**Da y**  oral toxicity ( rat ) 

# I 1 0014 1406 ( 1980 ) -..-N

- O

_ A

_ E

_

L

_

=

_

0

_

.4

_ m

_

g/k

_ g/

_

d

_ ay

-------------i 870.3150 LOA EL = 2 mg/kg/day based decreased body weight in mid82-1 b Acceptable / guideline d ti 1 (?Oo " ) d h. h d 1 d ti I (..,Oo " ) 

# I ose ema es _ / O an 1g

- ose ma es an ema es _, / O

1 90 D I . . ( d ) M&F: 0, 0.4, 2, I 0 d d
. . . (d . f 6 mg/kg/day - ay ora tox1c1ty og 

## I an treatment-relate 111 a111t 1 o n . urauon o treatment was 2**~** weeks) 1 870.3200 

### I

. 

### --- - ------------1

1 82-2 

# I No t Ava il a bl e

2 1

/28-Day dermal t oxicity

1 870.3 250

82-3 90 -D ay dennal toxicity 

## I No t Require d 

# I

# :~~/**465**

# t Required. 2 1/28

- D ay s tud y w i t h ne urol og ica l p ara m e t e r s i s r e quir e d ( O C I

- G D C l

- 07 1 003-20980 wa s i ss u ed 9 /2006). 1 90 -D ay ;nhalat;on tox;c;1y

870 .3700a 83-3a Developmental Toxicity (rat) 

# I 00144294 ( 198 2) Acceptable/ guideline F: 0, 0.75, 1.5 , 3. 6 

## I mg/kg/day

(GD 6- 19) 

## I Mate rn a l NOAEL = not id e ntifi ed LOA E L = 0.75 mg/kg/day , based o n clinical s i g ns oftoxiciry (sa livation , rubbing of face and paws on cage in all groups). 

# I D eve l op m e n ta l NOA EL = 3 m g/kg/day

LOA EL = 6 m g/ kg/d ay based on decreased fe tal body we ig ht 

## I (23%).

Pa ge 14of19Rote no ne R eg i s tra ti o n Review Hum an Hea lth Assess m e nt Scop ing D oc u me n t
T a b le A
. 2.3: S ub c h ron ic , C hro n ic , a nd Oth e r T ox ici ty P r o fil e o fR o t e n o n e G uid e l in e#/ S tud y T y p e

870.3700a 83-3a Developmental Toxicity (mouse)

870.3700b 83-3b Deve lo pm e nta l Tox i city (no n- rodent/rabbit) 870.3800 83-4 R

ep r o du ction (rat}

1 870.4 IOOa

83-la Chro ni c t ox i c it y ( r at) 870.4 I OOb 83-lb Chron ic toxici t y (dog) 8 70.42 0 0 83-2a Carcinogenici t y (ra t)

870.4200 

## I 83-2a

Carc in ogenic ity (rat) MRID # (y ear)/ C la s s ifi c a ti o n /Do s e s 00141707 (1981) ( m a in) 001 45049 ( 19 81 ) ( r ange-finding) Acceptable/gui d eline F: 0 , 3. 9, 15 , 24 m g/kg/day (G D 6- 17)

Not Ava i la bl e
0014 1408 (19 8 3) Acce pt ab le/g uid e lin e FO : M: 0, 0.5, 2.4, 4
. 8 mg/k g/d FO: F: 0, 0.6 , 3.0. 6 .2 m g/kg/day Fl ( M ):O. 0.6
. 3. 1
. 7 mg/kg/day Fl (F): 0, 0.7, 3.7, 8. 1 m g/kg/day 

# I R e s u lt s



## - - Ma terna l NOAEL

- I) mg/k g/day LOA E L = 24 mg/kg/day, based on decreased body weight ( 1 0 %) and bod y we ig ht g ain ( 4 1 %), fr o m r a nge findin g s tud y. D ev e lo pm e nt a l NOA EL = 15 mg/kg/day LO A EL = 24 mg/kg/day, based on inc r eased resorptions (3.8 vs. 0.5 con tro ls), from ra nge-fi n d ing study. Accep t a b l e w h e n ma i n a nd r a n ge- find in g s tud y c on s id e r e d toge th er.

# ---~ P a r e nt al/S ys te m ic NOAEL (M / F) = 0.51 0.6 mg/k g/day LOAEL ( M/ F) = 2.4/ 3.0 mg/kg/day based on dec reased body we ig ht ( 10 -1 3%) and b o dy we ig ht ga in ( 1 6-25%). R ep r o d u c t ive NOA E L (MIF) = 2.4 / 3.0 m g/ kg/ day LOA EL (M/ F) 

### = 4.8/ 6.2 mg/kg/day based on decrea se d live p ups/ liner in bo th gene r at ions (9. 7

- 9.9 vs. 1 1.4

- 11.8 co n tro ls). Off s prin g NO A EL ( M / F

) = 0.51 0.6 m g/kg/day LOA EL (M/F) 

### = 2.4 / 3.0 mg/k g/day based on dec reased F , and F2 pup body weight (8-18%) and body weight gain (mid 20- 26%; h igh 40

- 60 %)
. S ati s fi e d b y MRID # 00 1 56 7 39 , 4 1 65 7 10 1 ( 83-5 )

[ Not Ava i lab l e

4 01 79 8 0 I b /4627430 I (1986) NTP U n acccp t a b le/g u ide l i nc 0 , 38
. 75 pp m M: 0. 1.7. 3.4 mg/kg/day F: 0 , 1. 8, 3.6 mg/kg/day 00143257 (1979) Un acc e pt a b le / n o n g uideli n e M&F: 0. 1.7. 3.0 mg/kg/da y (i.p
.. 42 days, observed fo r 17 month s) M&F: 0 , 1.7, 3.0 N OAEL ( M / F) = 3.4 / 3.8 mg/kg/day LOAEL = not iden t ified Animals could have tolerated a hig h er dose. MTD no t achieved No ev id e n ce o f ca r c in oge nicit y

NOA EL = 3.0 mg/k g/ day L

OAEL = no t iden ti fi e d Anim a ls co uld h ave t o le r a t

ed a h ig he r d ose. MTD not achieved N o e v ide n ce o f ca r c in oge ni c i ty


# I mg/k g/ d (gavage. 42 days) 

# _,________ J Page 15of19Rotenone Registration Review Human Hea lth Assess ment Scop in g Docume!lt
Tab l e A.2.3: Subc hr o ni c, C hroni c, a nd Other Toxicity Profile of Rotc n o n e I 

# I

cu ; d e H"e # / Sindy T y p e 0 8.>-2b 

# I Ca rcin ogenicity (mouse)



### --- 1 870.4 200

83-2b Ca rcin ogenicity 

# I( ham s ter) 

# l I MRID# (year)/ C lass ifi ca tion / Do ses R es u l ts 40 17980 1 a/4627430 1 NOAEL = not identified (1986) LOAEL (M / F) = l 11 / 124mg/kg/day based on decreased body 

# INTP weight (low: (M) 6-12 %, (F) 12-20 %, high: (M) 1217 %, ( F)

Acceptable/ guide lin e 0 , 600, 1200 ppm No evi d e n ce o f carc in ogen ic it y 1 17- 26%. MoO, 111 ,242 

# l_ mg/k g/day F: 0 , 124 , 265 mg/kg/day

--- --- 00143256 (1979) 

# I Unacceptab l e / n o n g uideline



### - 

## - - 0. 12) , 2)0, :>00 , 1000 

## I ppm M&F: 0, 10 , 2 1 ,

42 , 83 mg/kg/day (food factor of 0.083) 

# I NOA EL = 42 mg/k g/day LOA EL = 83 mg/ kg/day ba sed on decreased weight gain. No ev id e n ce of carcinogen icit y Excessive mortality due to secondary inf ec ti on; additional 0 

### .. 

## - " .,,roups admini s tered :>00 and I 000 ppm for .> or 4 month s were mated re su ltin g in no viable offspring at I 000 ppm and maternal neg lec t and canniba li zation at 500 ppm 1 870.43

_ 0

_ 0

___ ___ , 00 1 56739 ( 1985 ) NOA EL = 0.3 75 m g/kg/day 83

- 5 4165710 1 (1989 LOAEL = 1.88 mg/kg/day, based on decrea sed body weight at 

# IChronic/ Oncogenicity amendment) termination [M:7 % ( mid) and 15 % ( high) ; F: 24% (mid) and 0 7 - 37 5 7- [M: 10% (mid) and 20% (h i gh); F: 3 1 % (m id) and 55% (high)] (rat) 

# I Acceptable/ guideline 4 2% (high)] and cumulative weight gain

, .) , . , :>ppm M&F : 

## o. 0.375, 1.88. and food con s umption in female s (9 % and 21 % in mid and

.., 7 , g/kg/d (ti d 

# I high , respectively] 

## I**:~~:":n** ay oo . . . . 

## I**of** 0.0 5) No ev idence of carc111o ge m c 1ty 

# -------1 Gene Mutation 40170506

## o evidence of induced mutant colonies over background for

1 84-2 870.5100 

# I ( 1988 ) NTP 

# I**y** rester s train at any concentration up co I 0,000 μ g/ plate with (Salmonella ry phimurium) st ud y 

# I and without metabolic activation; s trains TA 98 , TA 1 00 ,

___ j_A cceptable / guideline TA 1535 , TA 1537. 

# I Gene Mutation 

# I 40 170502 ( 1978 ) 

# I No e videnc e of induced mutant over back
. g round for any te s t
1 84-2 870.5100 Acceptable/ s tTain at any concentration up to I0 , 000 μ g/disk w ith a nd

(Sal111 0 11 e l/a 1 yphi 11111ri11111 ) guide lin e 

# I without metabolic activation; strains TA98 , TA I00 , TA 1535
.

. TA1537, TA1538.

# ne Mutation 40170505 ( 1984) Evidence of a concentration -relat ed positive response of 870.5300 Acceptable/ guideline 

# I induced mutant colonie s over background at 0.25 -8 .0 μ g/ mL 

# l 84-2 

## I without m e tabolic activation; s ig nificant cy totoxicity at 4 and 8 (mo u se ly mphom a ce ll s)**nL.** Cytog enetics 1 4017980 I c ( 1986 ) 

# I**N~.evidence** of chromo so me aberrations up to 100 μ g/ mL 870.5 375 Acceptab le/guideline 

# l without metabolic activation and 250 μg/mL w ith activation. 84-2 

# I ( Chine se ham s ter ovary)**~** Cytogenetics 

# I 00093702 ( 1981 ) 

# I Maxim um tolerated do se (MTD) was not achieved in either th e 

### l 870.5 385 U na cceptab l e / n o n- rat or mouse assays. No evide nc e of induc ed 84-2 g uid e lin e 

# I ch romatid/chromosome aberration s in rat bone marrow cells up 

# I

(mt ' "d mouse ) 

# I to 7.0 mg/k g; no s ignificant increase in frequency of
1 micronuclei in erythro cyte s from bone marrow of mice up to 80 mg/kg
. Pa ge 16of19Rotenon e Regi st ration Revi ew Human Hea lth Assessment Scop in g Document
Table A.2.3: Subchronic, C hroni c , a nd Other Toxicit y Profile of Rote n o n e 

# I MRID # (ye ar )/ 

# I G u ide lin e# / St ud y T yp e C lass ifi ca tion /Doses Re s ult s M icronucleus 00093702 ( 1981) Ne ga tive at oral doses ofO. 10 , o r 80 mg/kg 870.5395 Acceptable/ guideline 84-2 (mouse) No evide nc e of induced mutant colonies over background for 

# I Mitoti c gene conversion 00 1 44292 ( 1981) 870.5575 84

- 2 (Saccharomyces cerevisiae) 870.6200a 81

- 8 Acute ne uroto x ici ry screening battery 870.6200b

1 82- 7 Subchronic

neurotoxiciry screening 

# I bait•')' 6300 83

-6 Developmental neurotoxiciry 

# l 870.7485

85

- 1 Me t abolism and 

# I

phannacok;n<tk s (mt) 870.7600 85

-2 Denna! penetration (rat) 870.7800 lmmun otoxiciry S pecial s t11dies Subacute neurotoxiciry (rat) Acceptable/ guideline any test concentration up to I 0,000 ug/ plate with and without 

# I I metabolic ac t ivation. Limit dose 5000 μg/plate. Not Available



# __ J
Reque ste d , DCI 2 /9/04 (GDC l -07 1003-209 80)

- inhalation ( rat) in r ese rve

S tud y required pending result s of the subchronic inhalation neurotoxicity study.

00 145 496 ( 1984) 

# I Primary route of excretion is in feces; extensive enterohepatic 

# I Acceptable/ non- circulation; some urinary exc retion with females greater than

g uidelin e ma l es: polar metabolites reported in feces but metabolites not 0.01. 0.1. 5 mg/kg (o ral identified and iv) Not Avai l ab le

Not Ava il a bl e 4527950 I (Be tarb et et al.. 2000) Acceptable/nonguidel ine M: 2.5-2.75 mg/kg/day by i.v
. Behavioral. biochemical. and neuropath ological effects in humans: induction of specific neurodegenerative lesions in nigrostriatal dopaminergic neuron s I in fusion for 1-5 weeks**~~ ~~** **~~ ~** 

Page 17of19Rote none Regi s tration R ev iew Human Hea lth Assess me nt Sco pin g Docu me nt 

### Attachment 3 : Toxicological Do ses and Endpoints for Rotenone Ta bl e A.3: S umm ary of Toxicolog i ca l Points o f D e p arture a nd E ndp o ints fo r R ot en o ne for Use in Hum a n Risk Assess me nts Ex p os ure/ Point of Uncert a in Leve l o f Co n ce rn for S tud y a nd To x ico lo g i ca l E ffe cts Sce n a ri o D eo a rture t v Factors Ri sk A ssess me n t 15 mg&g/dav NOAEL = 15 UFA = I Ox NOA EL Developmental Toxicity

- mou se Acute Dietary mg/kg UFH = l Ox I000 (UF) MRID 00141707 (Fe male s 13-49 ) UFo = IOx LOA EL = 24 mg/k g/day , based on aRID = 0.015 inc reased resorption s mg/k g/ day Acute Dietary (General An appropriate endpoint attributable to a single dose was not identified in the available st udies , Population including the d eve lopmental toxicity s tudies includin g infant s and children) NOA EL= UF A= I Ox 0.375/kgLda):'. Chron ic / Carc in ogenicity (rat) Feed in g 0.375 UF11 = lOx NOA EL Tox ic ity MRJD41 657 1 0 1 Chronic Dierary mg/k g/day UFo = IOx l 000 (UF) LOA EL = 1.88 mg/kg/day , based on decreased body weight and food cRID = 0.0004 cons umpti o n in both sexes mg/k g/day UFA= IOx Reproductive Toxicity Study in Rats In cidental Ora l NOAEL = M RJD 00 141408 S hort- and 0.5 m g/k g/day UFii = J Ox R ec rea tion a l LOC = LOA EL = 2.4 / 3.0 mg/k g/d ay (M/F), I ntermediate

- Tenn UFo = IOx 1000 based on decreased parental (M&F) body weight and body weight gain Ora l NOAEL = 0.5 UF ,, = lOx Reproduc t ive Toxicity Study in Rats Dermal mg/k g/day UF11 = IOx Recreational/ MRID 00141408 All Duration s UFo = IOx Occupati onal LOC = LOAEL = 2.4/ 3.0 mg/kg/day (M/F), (Dermal 100 0 based on decreased parental ( M&F) Absorption body wei g ht and body weight gai n factor = l 0 %) Oral NOAEL = UFA = IOx R e produc tive Toxicity Study in Rat s Inhalation 0.5 m g/kg/day UF11 = lOx Recrearional / MRJD 00 1 4 1408 Short-and l 00 % inhalation UFo = lOx Occupational LOC = LOA EL = 2.4/3.0 mg/kg/day (M/F) , I ntermed iate-Terrn absorption 1000 based on decreased parental (M&F) factor body weigh t and b ody weight ga in Oral NOAEL = Chronic/ Carcinogenicity (rat) Feeding Inhalati on 0.5 mg/kg/day UFA= I Ox Recreational / Toxicity MRJ D 41657101 Long-Term I00 % inhalation UFH = IOx Occupa ti on al LOC = LOAEL = 1.88 mg/kg/day, based on absorption UF o= l Ox 1000 dec reased body we ight and food factor consumpt ion in both sexes Cancer (oral, dermal, C la ss ifi ca tion : No ev id ence of ca r c ino ge ni c it y inhalation)

NOA E L = no observed adverse effect level. LOAEL = lowe st obse r ved adverse effect level. RID = reference dose (a = acute: c = chronic). u1 : = uncertainty factor
. UF" = extrapo l a tion from animal to human ( inters pecies)
. U F11 = potentia l variation in sensi t ivity amon g members of the human populat i o n ( intraspccies). UFo = uncertainty in the da tabase beca use of mi ssi ng s tudi es. MO E margin of t:xposure. LOC = le vel of concern . N I A not applicab l e.

Pa ge 18of19Rotenonc Registration Review Human H ealth Assessment Scoping Document 

### Attachment 4: Summary of Reg i stered Uses for Rotenone
. Tab le A.4: Summary of Dir ect io n s for P r oposed Use for Rotenon e Company
3 POST ROAD FORE IG N DOMESTIC CHE MI CALS CORP DREXEL CHEM I CA L COMPANY

TIFA I NTERNATIO NAL LLC

CENTRAL GAR DEN & PET COMPANY Product Name a nd EPA R

eg ist rati on Number %a i ROTENON E RESIN FOR MANUFACTUR I NG USE 44.2 ONLY EPA Registration % Number: 6458-5 CU BE POWDER Fish I Toxicant 7.4 % EPA Registration Number: 6458-6 DREXEL 7.4% ROT ENONE WETTABL E POWDER EPA R egistratio n N umbe r : 7.4 % 19713-316



### - CHEM FI S H REGULA R EPA Reg1strat1on Number. 5 % Formulat Max. Use directions and limit at ion s based ion Type App. on c urr en t labels a lon e; not in cluding Rate reference t o gu idanc e manual This product may be formulated into en d-u se products for the pisicides uses (aquatic use s)

Wettable er Powd



## _ _, EC 0.68 l b ai

l A-ft & 0.54 lb ai/ A ft Restricted Use Pesticide. Do not use dead fish for food or feed. Do not use water trea ted to irrigate crops. Do not a ll ow sw immin g in treated water until throughly mixed. Restricted Use Pesticide. Do not use dead fish for food or feed. 82397-1**{_1439 -1** **7)** _______ _ 

### I CHEM SECT BRAND ROTENONE RESINS EPA R egis tration Number: 82397-4 CUBE POWDE R FISH TOXICANT EPA Regi s tr ation Number: 82397-5 ( 1439-260) PREN T OX CUBE POWDER EPA Registration umber: 89459-13 655-3**~-~ -----t**  P

RENTOX CUBE RESINS EPA R eg istra tion Number : 89459-15 655-69 PRENTOX PRENF I S l

-1 TOX I CANT EPA Re gistra tion Number: 89459-23 655-422 44 %

7.4 %

5.0% 44.2 %
5.0%

--'------1--- PRENT 0 X ROTENONE 8.74 % FISH TOX I CA T POWD ER EPA R egistration Number: 89459-32 (655 -691**-~-------+-** BR I IT LE EXTRACT OF CUBE ROO T EPA Regi s tratio n N umb e r : 44.2 % This product may be formulated into end-use products for th e pisicides uses (aquatic uses).

Wettabl e powder 0.68 lb ai/A-ft & 0.54 lb ai/A ft Re s trict ed Use P esticide. Do n ot use dead fish for food or feed. Do not use water treated to irrigate crops. Do not allow swimming in treated water until through! mixed. This product may be formulated into end-use products for th e pisicides uses (aquatic use s). This product may be formulated into end

- use product s for th e pisicides uses (aquatic uses).
EC

Powder 0.68 l b ailA-ft &0.54 lb ai/ A 

# I ft Re s tricted Use Pesticide. PPE li sted for m / l

/ a includes coveralls over baseline dermal. protec ti ve eyewear, and dus t/ mi s t respirator. Waterproof wader can be worn in place of 

# I coverall s. This product may be formulated into end-use products for th e pi s icides uses (aq uatic uses). 8 9459-43 (655-808**----!---!---~~-**
PRENTOX CFT LEGUMINE FISH TOXICANT EPA Re gistration Number:89459-48 (655 -899 ) 5.0 % EC 0.54 lb ai/ A ft R es tricted Use Pesticide. In strea m / ri vers/ lakes/ reservo i r / ponds no more than 0.5 ppm ai. PPE listed for mil/a includes coveralls over baseline dermal , protective eyewear. and du st/ mist respirator. Waterproof wader can be worn in place of coveralls. Sign s must be marked until less than I**.~m** formulation.**--4-- -~~--~--**  Pa ge 19of19